Startseite Lebenswissenschaften Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy
Artikel Open Access

Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy

  • Yazhen Yuan , Chenjun Shao , Yongqing Guan EMAIL logo , Hongwei Lu , Dandan Wang und Shuangmei Zhang
Veröffentlicht/Copyright: 3. März 2023
Artikel downloaden (PDF)
Open Life Sciences
Aus der Zeitschrift Open Life Sciences Band 18 Heft 1

Abstract

This retrospective case–control study examined the association between the rs2071559 (-604T/C) single nucleotide polymorphism (SNP) in the vascular endothelial growth factor receptor (VEGFR)-2 gene and the risk of diabetic retinopathy (DR) in Northern Han Chinese. This study included patients diagnosed with diabetes mellitus (DM) in Shijiazhuang between 07/2014 and 07/2016. The healthy controls were unrelated individuals who received routine physical examinations. The diabetic patients were grouped as DM (diabetes but no fundus examination abnormalities), proliferative DR (PDR), and non-proliferative DR (NPDR). Finally, 438 patients were included: 114 controls and 123, 105, and 96 patients in the DM, NPDR, and PDR groups, respectively. In the multivariable analyses and all genetic models, the VEGFR-2 rs2071559 SNP was not associated with DR (among all diabetic patients) or with PDR (among the patients with DR) after adjustment for age, sex, duration of DM, blood glucose, systolic blood pressure, diastolic blood pressure, and body mass index (all P > 0.05). In conclusion, the VEGFR-2- 604T/C rs2071559 SNP is not associated with DR or PDR in the Han Chinese population of Shijiazhuang (China).

Keywords: type 2 diabetes; diabetic retinopathy; vascular endothelial growth factor receptor; gene polymorphism; VEGFR-2

1 Introduction

Diabetic retinopathy (DR) is a microvascular complication of type 2 diabetes mellitus (T2DM) and a leading cause of preventable blindness in adults [1–3]. DR is a spectrum that starts with non-proliferative DR (NPDR) that eventually progresses to proliferative DR (PDR) [1–3]. The worldwide prevalence of DR is 24.6% in patients with diabetes [4], the highest incidence rates are observed in African Americans, Hispanics, and South Asians [3]. In China, among patients with diabetes, the prevalence rates of DR and vision-threatening DR are 27.9 and 12.6%, respectively [5]. The management of DR includes glycemic control, lipidemia control, blood pressure control, laser therapy, intravitreal anti-vascular endothelial growth factor (VEGF) therapy, vitrectomy, and intravitreal steroids [2,6].

VEGF is a key molecule in the development of DR [7,8]. Intravitreal VEGF levels are high in diabetic patients and correlate with neovascularization [9], especially in patients with PDR [3,10]. In addition to VEGF levels, the expression and distribution of the VEGF receptor (VEGFR)-2 are also crucial in developing DR and progressing from NPDR to PDR [11–13]. Indeed, VEGFR-2 controls endothelial cell proliferation, migration, survival, and osmosis via its activation by VEGF [8].

Single nucleotide polymorphisms (SNPs) in the VEGFR-2 gene can affect the development and progression of multiple diseases by affecting the binding efficiency between VEGFR-2 with VEGF or by reducing the transcriptional activity of VEGFR-2 [14–16]. The involvement of some VEGF SNPs in the development of DR and response to treatment are well-known [17–20], but the role of VEGFR-2 SNPs in the development of DR is poorly known. The rs2071559 SNP is located in the promoter of VEGFR-2 and decreases the transcriptional activity of VEGFR-2 [14,21,22]. A previous study revealed that four SNPs in the VEGF gene and one (rs2071559 or -604T/C) in the VEGFR-2 gene were associated with the development of DR [23], but it did not examine the association of the rs2071559 SNP with PDR. There are several studies on the polymorphisms of VEGF in DR [17,23–25], but only one study of the rs2071559 SNP in VEGFR-2 was found [23]. Since DR is a complex trait affected by multiple genes and the environment, exploring the role of VEGFR-2 SNPs in various populations is relevant.

Therefore, the present study aimed to examine the association between the -604T/C locus polymorphism of the VEGFR-2 gene and the risk of DR among T2DM patients and then of PDR among DR patients in a Han population in North China.

2 Materials and methods

2.1 Study design and subjects

This retrospective case–control study included patients with T2DM who visited the Department of Ophthalmology and the Department of Endocrinology of the Fourth Hospital of Hebei Medical University between July 2014 and July 2016. T2DM was diagnosed according to the International World Health Organization (WHO) T2DM diagnostic criteria (1999) [26]. The healthy controls were unrelated individuals who received routine physical examinations between July 2014 and July 2016. All subjects were of Han ethnicity and from families living in Shijiazhuang, Hebei Province, China, for at least three generations.

The subjects were divided into four groups (one control group and three patient groups) according to the 2002 International Clinical Classification Criteria for DR [27]. The DM group included the T2DM patients without fundus examination abnormalities. The PDR group included the patients with one or more of the following: neovascularization, vitreous hemorrhage, and preretinal hemorrhage. The NPDR group included the patients with microangioma, intraretinal hemorrhage, and microvascular abnormalities, but without the PDR-specific findings.

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations and institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the ethics committee of The Fourth Hospital of Hebei Medical University.

2.2 Data collection

The data were obtained from the medical records and included sex, age, fasting blood glucose levels, body height, body weight, systolic blood pressure, diastolic blood pressure, and T2DM duration. The body mass index (BMI) was calculated as BMI = body weight (kg)/height (m2).

2.3 VEGFR-2 -604T/C polymorphism

DNA was routinely extracted from venous blood collected in sodium citrate tubes and stored at 4°C. Peripheral blood leukocyte DNA was extracted using the proteinase K digestion-saturated sodium chloride salting-out method within 1 week of blood collection [28].

The polymerase chain reaction-ligation detection reaction (PCR-LDR) method was used to determine the VEGFR-2 -604T/C polymorphism. The forward primer for the amplification of rs2071559 was 5′-AAA TAT TTT GGG AAA TAG CGG GAA TG-3′, and the reverse primer was 5′-TGG CGA ACT GGG CAA GTG CGT TTT C-3′. The forward and reverse primers for -604T/C were 5′-GAG CAC GAT GGA CAA AAG CCT-3′ and 5′-GGG AGA AGC GGA TAC TCA GCC-3′, respectively. The PCR product length was 255 bp, and the GC content was 47.5%. The LDR probe design included two probes. The sequences of the probes for rs2071559 were TC: 5′-TTT TTT TTA TAT TTT GGG AAA TAG CGG GAA TGC-3′, TT: 5′-TTT TTT TTT TTA TAT TTT GGG AAA TAG CGG GAA TGT-3′, and TR: 5′-P-TGG CGA ACT GGG CAA GTG CGT TTT CTT TTT T-FAM-3′.

The size of the ligated products was 64/C and 67/T. The LDR reaction consisted of cycling through the following conditions for 25 cycles: 94°C for 30 s and 56°C for 1 min.

Sterile distilled water was used as a negative control. In addition, 10% of the DNA samples were randomly selected for duplicate experiments. All repeated results were consistent with the original ones.

2.4 Statistical analysis

Statistical analysis was performed using SPSS 13.0 (SPSS, Chicago, IL, USA). The Hardy–Weinberg equilibrium was tested in all groups using the chi-square test. Normally distributed continuous variables were expressed as means ± standard deviations (and analyzed using one-way analysis of variance and the Bonferroni post hoc test. Non-normally distributed continuous variables were presented as medians (ranges) and compared using the Kruskal–Wallis test. Non-conditional logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs). P-values < 0.05 were considered statistically significant.

3 Results

3.1 Characteristics of the subjects

Finally, 438 subjects were included: 114 controls, 123 patients in the DM group, 105 in the NPDR group, and 96 in the PDR group. There were no significant differences in age and sex among the four groups (all P > 0.05) (Table A1).

3.2 Association between VEGFR-2 gene rs2071559 and DR

The three genotypes (CC, CT, and TT) were present in all four groups and met the Hardy–Weinberg equilibrium (all P > 0.05) (Table A2). The frequencies of CC, CT, and TT were 17.6, 45.6, and 36.8% in the control group, 12.2, 50.4, and 37.4% in the DM group, 7.6, 53.3, and 39.1% in the NPDR group, and 7.3, 46.9, and 45.8% in the PDR group. There were no significant differences among the four groups (P = 0.191) (Table 1).

Table 1

Distribution of genotype and allele frequencies of VEGFR-2 -604T/C

Control group N = 114 DM group N = 123 NPDR group N = 105 PDR group N = 96 P
Genotype, n (%) 0.191
 CC 20 (17.6%) 15 (12.2%) 8 (7.6%) 7 (7.3%)
 CT 52 (45.6%) 62 (50.4%) 56 (53.3%) 45 (46.9%)
 TT 42 (36.8%) 46 (37.4%) 41 (39.1%) 44 (45.8%)
Allele, n (%) 0.198
 C 92 (40.4%) 92 (37.4%) 72 (34.3%) 59 (30.7%)
 T 136 (59.6%) 154 (62.6%) 138 (65.7%) 133 (69.3%)

DM, diabetes mellitus without DR group; NPDR, non-proliferative DR group; PDR, PDR group.

The C and T allele frequencies were 40.4 and 59.6% in the control group, 37.4 and 62.6% in the DM group, 34.3 and 65.7% in the NPDR group, and 30.7 and 69.3% in the PDR group (P = 0.198) (Table 1).

3.3 Univariable and multivariable analyses in the T2DM patients

The rs2071559 genotypes were not associated with DR in the univariable analysis (P > 0.05) (Table 2). The duration of T2DM (OR = 1.064, 95% CI: 1.024–1.105, P = 0.002), blood glucose (OR = 1.801, 95% CI: 1.057–3.067, P = 0.030), systolic blood pressure (OR = 1.023, 95% CI: 1.009–1.038, P = 0.001), and diastolic blood pressure (OR = 1.047, 95% CI: 1.021–1.075, P < 0.001) were associated with DR. The rs2071559 SNP of the VEGFR-2 gene was not associated with DR after adjustment for age, sex, duration of DM, blood glucose, systolic blood pressure, diastolic blood pressure, and BMI (Table 3).

Table 2

Univariable logistic regression analysis for factors associated with DR among type 2 diabetic patients

OR 95% CI P
Risk factor
Age >60 vs ≤60 1.008 (0.643, 1.58) 0.971
Sex Female vs male 1.073 (0.684, 1.685) 0.759
Duration of DM Per one year 1.064 (1.024, 1.105) 0.002
Blood glucose >6.1 vs ≤6.1 mmol/L 1.801 (1.057, 3.067) 0.030
SBP Per one mmHg 1.023 (1.009, 1.038) 0.001
DBP Per one mmHg 1.047 (1.021, 1.075) <0.001
BMI 18.5–24 Ref. — —
≤18.5 1.063 (0.187, 6.047) 0.945
>24 vs 18.5-24 0.794 (0.496, 1.271) 0.337
Genotype
Dominant model (TC + CC) vs TT 0.815 (0.515, 1.292) 0.384
Recessive model (TC + TT) vs CC 0.581 (0.273, 1.234) 0.158
Co-dominant model TC vs TT 0.541 (0.243, 1.205) 0.133
CC vs TT 0.882 (0.546, 1.422) 0.606
Over-dominant model (TT + TC) vs TC 1.006 (0.642, 1.576) 0.978

DM, diabetes mellitus; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body weight index; OR, odds ratio; CI, confidence interval.

Table 3

Multivariable logistic regression analysis of the factors associated with DR among type 2 diabetic patients using different genetic models

Genetic models Genotype Adjusted OR 95% CI P
Dominant model TT Ref.
TC/CC 0.929 (0.567, 1.521) 0.769
Recessive model TT/TC Ref.
CC 0.495 (0.218, 1.121) 0.092
Co-dominant model TT Ref.
CC 0.506 (0.213, 1.204) 0.123
TC 1.041 (0.623, 1.74) 0.877
Over-dominant model TC Ref.
TT/CC 0.841 (0.519, 1.363) 0.483

Adjusted for age, sex, duration of diabetes mellitus, blood glucose, SBP, DBP, and BMI.

OR, odds ratio; CI, confidence interval.

3.4 Univariable and multivariable analyses among patients with DR

The rs2071559 genotypes were not associated with PDR in the univariable analysis (P > 0.05) (Table 4). Female sex (OR = 1.776, 95% CI: 1.010–3.125, P = 0.046), duration of T2DM (OR = 1.082, 95% CI: 1.032–1.134, P = 0.001), systolic blood pressure (OR = 1.018, 95% CI: 1.002–1.034, P = 0.032), and BMI > 24.0 kg/m2 (OR = 0.358, 95% CI: 0.198–0.645, P = 0.001) were associated with the development of PDR. The rs2071559 SNP of the VEGFR-2 gene was not associated with PDR in any genetic model after adjustment for age, sex, duration of DM, blood glucose, systolic blood pressure, diastolic blood pressure, and BMI (Table 5).

Table 4

Univariable logistic regression analysis for factors associated with PDR among DR patients

OR 95% CI P
Risk factor
Age >60 vs ≤60 0.842 (0.484, 1.466) 0.544
Sex Female vs male 1.776 (1.01, 3.125) 0.046
Duration of DM Per one year 1.082 (1.032, 1.134) 0.001
Blood glucose >6.1 vs ≤6.1 mmol/L 1.552 (0.743, 3.244) 0.242
SBP Per one mmHg 1.018 (1.002, 1.034) 0.032
DBP Per one mmHg 1.013 (0.986, 1.041) 0.349
BMI 18.5–24 Ref. — —
≤18.5 0.193 (0.019, 1.946) 0.163
>24 vs 18.5–24 0.358 (0.198, 0.645) 0.001
Genotype
Dominant model (TC + CC) vs TT 0.757 (0.432, 1.327) 0.331
Recessive model (TC + TT) vs CC 0.954 (0.332, 2.737) 0.930
Co-dominant model TC vs TT 0.815 (0.271, 2.449) 0.716
CC vs TT 0.749 (0.42, 1.336) 0.327
Over-dominant model (TT + TC) vs TC 1.295 (0.744, 2.256) 0.361

PDR, proliferative DR; DM, diabetes mellitus; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body weight index; OR, odds ratio; CI, confidence interval.

Table 5

Multivariable logistic regression analysis of the factors associated with PDR among DR patients in different genetic models

Genetic models Genotype Adjusted OR 95% CI P
Dominant model TT Ref.
TC/CC 0.868 (0.456, 1.651) 0.665
Recessive model TT/TC Ref.
CC 1.207 (0.355, 4.102) 0.763
Co-dominant model TT Ref.
CC 1.092 (0.303, 3.931) 0.893
TC 0.842 (0.435, 1.629) 0.609
Over-dominant TC Ref.
TT/CC 1.205 (0.641, 2.262) 0.563

Adjusted for age, sex, duration of diabetes mellitus, blood glucose, SBP, DBP, and BMI.

PDR, PDR; OR, odds ratio; CI, confidence interval.

4 Discussion

While the role of VEGF SNPs in the development of DR and response to treatment has been described [18,20], the role of VEGFR-2 SNPs in the development of DR is poorly known. Therefore, this study aimed to examine the association between the rs2071559 SNP of the VEGFR-2 gene and the risk of DR in a Han population in North China. The results suggest that the VEGFR-2 -604T/C polymorphism (rs2071559) is not associated with DR among T2DM patients or PDR among patients with DR in the Han population of Shijiazhuang (China).

DR is a complex trait affected by numerous genes and environmental factors [29,30], and the pathogenesis is still unclear. Of note, DR is a polygenic trait affected by numerous genes, and any polymorphisms within each of these genes will influence the development of DR [29,30]. VEGF is a key molecule in the development of DR [7,8]. Intravitreal VEGF levels are high in diabetic patients and correlate with neovascularization [9], especially in patients with PDR [3,10]. In addition to VEGF levels, the expression and distribution of the VEGF receptor (VEGFR)-2 are also important in developing DR and progressing from NPDR to PDR [11–13]. Indeed, VEGFR-2 controls endothelial cell proliferation, migration, survival, and osmosis via its activation by VEGF [8]. Still, other receptors are involved in DR. VEGFR belongs to the receptor tyrosine kinase superfamily and is a membrane mosaic protein. It contains three subtypes: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4) [31,32]. In addition, there are some related receptors, such as neuropilin 1 and 2 [33]. Among them, VEGFR-1 is mainly expressed in monocytes, trophoblast cells, renal mesangial cells, and vascular endothelial cells [31,32]. It is known that VEGF-A, VEGF-B, and PIGF can be combined with it, which is mainly related to the growth regulation of hematopoietic stem cells. VEGFR-2 is mainly distributed on the surface of endothelial cells [31,32]. Other cells include hematopoietic stem cells, retinal precursor cells, and megakaryocytes, which bind to VEGF-A, VEGF-C, VEGF-D, and VEGF-E [31,32]. Combined with VEGF, it stimulates endothelial cell proliferation, increases vascular permeability, and promotes angiogenesis [31,32]. VEGFR-3 is mainly expressed in lymphatic endothelial cells [31,32]. It is known that VEGF-C and VEGF-D combine with VEGFR-3 to regulate the survival and function of lymphatic endothelial cells [34]. NP-1 and NP-2 mainly exist in nerve axons and vascular endothelial cells. They can regulate the signal transduction of VEGFR-2 [35]. They are specific receptors of VEGF165.

At present, it has been recognized that the effect of VEGF on the proliferation and differentiation of endothelial cells is mediated by VEGFR-2. VEGFR-2 regulates the survival of endothelial cells. VEGF-A depends on VEGFR-2 and its subsequently activated PI3K (phosphatidylinositol 3-kinase) to regulate the survival of human umbilical vein endothelial cells, which is conducive to angiogenesis [31,32]. Second, VEGFR-2 regulates the migration of endothelial cells. The migration of endothelial cells is of great significance to angiogenesis. Endothelial cells can migrate along the concentration gradient of VEGF and other growth factors through the basement membrane hydrolyzed by protease, which plays a key role in metastasis [31,32]. Third, VEGFR-2 regulates the proliferation of endothelial cells. VEGF-A is the VEGF level of many endothelial cells. VEGFR-2 on the cell membrane combines with it to transmit extracellular signals to cells and activate a series of downstream signal pathways to regulate the proliferation of endothelial cells [31,32]. Fourth, VEGFR-2 regulates the permeability of endothelial cells. After VEGFR-2 is activated by VEGF binding, it stimulates vascular endothelial cells to release nitric oxide and causes changes in vascular permeability. The above effects are helpful to promote the survival, proliferation, and migration of endothelial cells and induce neovascularization [31,32].

Besides VEGFR-2, a previous genome-wide study revealed that the rs918519 SNP in LOC285626, rs1158314 in NRXN3, rs8004963 in NRXN3, rs11159428 in NRXN3, and rs918520 in LOC285626 are associated with PDR [36]. Another study revealed that the -634G>C SNP in VEGF is associated with PDR [19]. Churchill et al. [17] showed that the -160C, rs13207351, and rs1570360 SNPs in VEGF are associated with PDR. So far, no SNPs in VEGFR-2 have been associated with PDR. A previous study showed that the VEGFR-2 rs2071559 SNP was associated with DR [23], but that previous study did not examine the association of the rs2071559 SNP with PDR. The present study examined the rs2071559 SNP with PDR, and it was not associated with DR in all subjects or with PDR among patients with DR. DR is a complex trait affected by the clinical characteristics of the T2DM patient, genetic background, and living environment [30]. The impact of the rs2071559 on DR can be affected by various other SNPs in the VEGF pathway, as well as in other pathways interacting with the VEGF pathway since DR is a polygenic disorder [29,30]. The relationship between the rs2071559 SNP and the development of PDR in Chinese may be weakened by the influence of other polymorphisms found in the Chinese population, but it will have to be examined. A Spanish study reported no association between the rs2071559 SNP and age-related macular degeneration [37]. Nevertheless, this SNP has been associated with various conditions, including age-related macular degeneration, stroke, endometriosis, hepatocellular carcinoma, and recurrent spontaneous abortion [15,16,20,38–40], but not with lymphoma [41]. In patients with T2DM, the rs2071559 SNP is associated with the extent of carotid atherosclerosis and with myocardial infarction [42,43].

Anti-VEGF drugs have become the first-line treatment for many retinal neovascularization diseases, including age-related macular degeneration and PDR [44,45]. Anti-VEGFR-2 drugs, including the monoclonal antibody ramucirumab and a variety of small-molecule tyrosine kinase inhibitors, remain solely used for the systemic treatment of malignant tumors (e.g., gastric and gastroesophageal adenocarcinoma in the second-line setting) [46], and are only in early trials for eventual ophthalmologic applications [47,48]. Therefore, in the context of future applications of VEGFR-2-targeting drugs in ophthalmic diseases, understanding the factors related to VEGFR-2 that can influence the course of the diseases is of importance. Future studies should examine all SNPs in VEGFR-2 and the various proteins involved in its pathway.

Indeed, reliable SNPs could serve as predictive markers to make informed decisions about the management of specific diseases, the effectiveness of various drugs, and adverse reactions to specific drugs. The plasma sVEGFR-2 levels are elevated in severe DR, while plasma levels of sVEGFR-1 and sVEGFR-3 remain unaltered between patients and controls [49]. In this study, there were no associations between the VEGFR-2 rs2071559 SNP and DR of PDR. VEGFR-2 controls endothelial cell proliferation, migration, survival, and osmosis via its activation by VEGF [8]. VEGFR-2 expression is higher in diabetic eyes than in controls [50]. The activation of VEGFR-2 by VEGF leads to nitric oxide production, blood vessel permeability, and endothelial proliferation [50]. An animal study showed that the specific knockdown of VEGFR-2 in the retina led to decreased neovascularization and improved the morphology of the endothelial cells, highlighting the central role of VEGFR-2 in retinal diseases [51]. Hence, in the context of future anti-VEGFR-2 therapies, a better understanding of the potential effects of VEGFR-2 in DR is essential.

This study has limitations. The sample size was small and from a single center. In addition, only one SNP was analyzed in this study because it was not studied before. Other VEGFR-2 SNPs might yield different results.

This study showed no associations between the rs2071559 SNP and DR (among T2DM patients) or PDR (among DR patients). In the Han population in the Shijiazhuang area of China, the rs2071559 SNP of VEGFR-2 is not associated with the risk of developing DR or PDR.

tel: +86-13931982519, fax: +86-21-57643271

  1. Funding information: Authors state no funding involved.

  2. Author contributions: Y.Z.Y. and Y.Q.G. carried out the studies, participated in collecting data, and drafted the manuscript. D.D.W. and S.M.Z. performed the statistical analysis and participated in its design. C.J.S. and H.W.L. helped to draft the manuscript. All authors read and approved the final manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Appendix

Table A1

Baseline characteristics of the subjects

Controls N = 114 DM N = 123 NPDR N = 105 PDR N = 96
Age, years, median (range) 56.5 (43, 76) 61 (38, 82)a 62 (31, 81)a 60.5 (38, 79)
Male, n (%) 61 (53.5%) 56 (45.5%) 53 (50.5%) 35 (36.5%)
BMI, kg/m2, median (range) 24.5 (16.7, 35.8) 24.8 (16.8, 34.9) 25.4 (17.3, 48.9) 23.9 (18.3, 30.7)c
Systolic pressure, mmHg, median (range) 129.5 (95, 213) 128 (96, 180) 130 (80, 200) 140 (100, 200)a,b
Diastolic pressure, mmHg, median (range) 80 (40, 132) 80 (60, 100) 80 (50, 120) 80 (60, 110)b
Duration of DM, years, median (range) — 7 (0.5, 24) 8 (1, 30) 10 (0, 28)b,c
Fasting blood glucose, mmol/L, median (range) — 7 (4, 24) 7.5 (4.1, 19) 8 (3.52, 24)b

DM, diabetes mellitus without DR group; NPDR, non-proliferative DR group; PDR, proliferative DR group; BMI, body weight index.

Bonferroni post hoc test.

aCompared with control, P < 0.05.

bCompared with DM, P < 0.05.

cCompared with NPDR, P < 0.05.

Table A2

Hardy–Weinberg equilibrium

Group X 2 P
PDR 0.98 0.32
NPDR 3.54 0.06
DM 0.72 0.40
Control 0.31 0.58

DM, diabetes mellitus without DR group; NPDR, non-proliferative DR group; PDR, proliferative DR group.

References

[1] Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA. 2007;298(8):902–16.10.1001/jama.298.8.902Suche in Google Scholar PubMed

[2] American Diabetes Association. Microvascular complications and foot care: standards of medical care in diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S105–18.10.2337/dc18-S010Suche in Google Scholar PubMed

[3] Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376(9735):124–36.10.1016/S0140-6736(09)62124-3Suche in Google Scholar PubMed

[4] Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556–64.10.2337/dc11-1909Suche in Google Scholar PubMed PubMed Central

[5] Zhang G, Chen H, Chen W, Zhang M. Prevalence and risk factors for diabetic retinopathy in China: a multi-hospital-based cross-sectional study. Br J Ophthalmol. 2017;101(12):1591–5.10.1136/bjophthalmol-2017-310316Suche in Google Scholar PubMed PubMed Central

[6] American Academy of Ophthalmology. Preferred practice pattern: diabetic retinopathy. San Francisco: American Academy of Ophthalmology; 2014.Suche in Google Scholar

[7] Dvorak HF, Sioussat TM, Brown LF, Berse B, Nagy JA, Sotrel A, et al. Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels. J Exp Med. 1991;174(5):1275–8.10.1084/jem.174.5.1275Suche in Google Scholar PubMed PubMed Central

[8] Frank RN. Treating diabetic retinopathy by inhibiting growth factor pathways. Curr Opin Investig Drugs. 2009;10(4):327–35.Suche in Google Scholar

[9] Hata Y, Miura M, Nakao S, Kawahara S, Kita T, Ishibashi T. Antiangiogenic properties of fasudil, a potent Rho-Kinase inhibitor. Jpn J Ophthalmol. 2008;52(1):16–23.10.1007/s10384-007-0487-5Suche in Google Scholar PubMed

[10] Cheung N, Wong IY, Wong TY. Ocular anti-VEGF therapy for diabetic retinopathy: overview of clinical efficacy and evolving applications. Diabetes Care. 2014;37(4):900–5.10.2337/dc13-1990Suche in Google Scholar PubMed

[11] Nakao S, Zandi S, Hata Y, Kawahara S, Arita R, Schering A, et al. Blood vessel endothelial VEGFR-2 delays lymphangiogenesis: an endogenous trapping mechanism links lymph- and angiogenesis. Blood. 2011;117(3):1081–90.10.1182/blood-2010-02-267427Suche in Google Scholar PubMed PubMed Central

[12] Sun D, Nakao S, Xie F, Zandi S, Bagheri A, Kanavi MR, et al. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis. FASEB J. 2014;28(9):3942–51.10.1096/fj.14-251934Suche in Google Scholar PubMed PubMed Central

[13] Gupta N, Mansoor S, Sharma A, Sapkal A, Sheth J, Falatoonzadeh P, et al. Diabetic retinopathy and VEGF. Open Ophthalmol J. 2013;7:4–10.10.2174/1874364101307010004Suche in Google Scholar PubMed PubMed Central

[14] Wang Y, Zheng Y, Zhang W, Yu H, Lou K, Zhang Y, et al. Polymorphisms of KDR gene are associated with coronary heart disease. J Am Coll Cardiol. 2007;50(8):760–7.10.1016/j.jacc.2007.04.074Suche in Google Scholar PubMed

[15] Fang AM, Lee AY, Kulkarni M, Osborn MP, Brantley MAJr. Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration. Mol Vis. 2009;15:2710–9.Suche in Google Scholar

[16] Zhang W, Wang Y, Zheng Y, Sun K, Wan L, Tai Q. Association of polymorphism in vascular endothelial growth factor Receptor 2 gene and risk of stroke. Chin Circ J. 2009;22:227–30.Suche in Google Scholar

[17] Churchill AJ, Carter JG, Ramsden C, Turner SJ, Yeung A, Brenchley PE, et al. VEGF polymorphisms are associated with severity of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2008;49(8):3611–6.10.1167/iovs.07-1383Suche in Google Scholar PubMed

[18] Chen CF, Liou SW, Wu HH, Lin CH, Huang LS, Woung LC, et al. Regulatory SNPs alter the gene expression of diabetic retinopathy associated secretary factors. Int J Med Sci. 2016;13(9):717–23.10.7150/ijms.16345Suche in Google Scholar PubMed PubMed Central

[19] Errera FI, Canani LH, Silva ME, Yeh E, Takahashi W, Santos KG, et al. Functional vascular endothelial growth factor -634G>C SNP is associated with proliferative diabetic retinopathy: a case-control study in a Brazilian population of European ancestry. Diabetes Care. 2007;30(2):275–9.10.2337/dc06-1399Suche in Google Scholar PubMed

[20] Wu M, Xiong H, Xu Y, Xiong X, Zou H, Zheng M, et al. Association between VEGF-A and VEGFR-2 polymorphisms and response to treatment of neovascular AMD with anti-VEGF agents: a meta-analysis. Br J Ophthalmol. 2017;101(7):976–84.10.1136/bjophthalmol-2016-309418Suche in Google Scholar PubMed PubMed Central

[21] Shilpa P, Kaveri K, Salimath BP. Anti-metastatic action of anacardic acid targets VEGF-induced signalling pathways in epithelial to mesenchymal transition. Drug Discov Ther. 2015;9(1):53–65.10.5582/ddt.2014.01042Suche in Google Scholar PubMed

[22] Buysschaert I, Schmidt T, Roncal C, Carmeliet P, Lambrechts D. Genetics, epigenetics and pharmaco-(epi)genomics in angiogenesis. J Cell Mol Med. 2008;12(6B):2533–51.10.1111/j.1582-4934.2008.00515.xSuche in Google Scholar PubMed PubMed Central

[23] Yang X, Deng Y, Gu H, Ren X, Li N, Lim A, et al. Candidate gene association study for diabetic retinopathy in Chinese patients with type 2 diabetes. Mol Vis. 2014;20:200–14.Suche in Google Scholar

[24] Han L, Zhang L, Xing W, Zhuo R, Lin X, Hao Y, et al. The associations between VEGF gene polymorphisms and diabetic retinopathy susceptibility: a meta-analysis of 11 case-control studies. J Diabetes Res. 2014;2014:805801.10.1155/2014/805801Suche in Google Scholar PubMed PubMed Central

[25] Zeng Y, Dai F, Yang K, Tang Y, Xu M, Zhou Y. Association between a vascular endothelial growth factor gene polymorphism (rs2146323) and diabetic retinopathy: a meta-analysis. BMC Ophthalmol. 2015;15:163.10.1186/s12886-015-0155-3Suche in Google Scholar PubMed PubMed Central

[26] World Health Organization. Definition, diagnosis, and classification of diabetes mellitus and its complications. Geneva: World Health Organization; 1999.Suche in Google Scholar

[27] Wilkinson CP, Ferris FL 3rd, Klein RE, Lee PP, Agardh CD, Davis M, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110(9):1677–82.10.1016/S0161-6420(03)00475-5Suche in Google Scholar PubMed

[28] Watkins PJ. Retinopathy. BMJ. 2003;326(7395):924–6.10.1136/bmj.326.7395.924Suche in Google Scholar PubMed PubMed Central

[29] Cho H, Sobrin L. Genetics of diabetic retinopathy. Curr Diabetes Rep. 2014;14(8):515.10.1007/s11892-014-0515-zSuche in Google Scholar PubMed PubMed Central

[30] Cabrera AP, Mankad RN, Marek L, Das R, Rangasamy S, Monickaraj F, et al. Genotypes and phenotypes: a search for influential genes in diabetic retinopathy. Int J Mol Sci. 2020;21(8):2712.10.3390/ijms21082712Suche in Google Scholar PubMed PubMed Central

[31] Simons M, Gordon E, Claesson-Welsh L. Mechanisms and regulation of endothelial VEGF receptor signalling. Nat Rev Mol Cell Biol. 2016;17(10):611–25.10.1038/nrm.2016.87Suche in Google Scholar PubMed

[32] Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer. 2011;2(12):1097–105.10.1177/1947601911423031Suche in Google Scholar PubMed PubMed Central

[33] Guo HF, Vander Kooi CW. Neuropilin functions as an essential cell surface receptor. J Biol Chem. 2015;290(49):29120–6.10.1074/jbc.R115.687327Suche in Google Scholar PubMed PubMed Central

[34] Holmes K, Roberts OL, Thomas AM, Cross MJ. Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition. Cell Signal. 2007;19(10):2003–12.10.1016/j.cellsig.2007.05.013Suche in Google Scholar PubMed

[35] Neufeld G, Kessler O, Herzog Y. The interaction of Neuropilin-1 and Neuropilin-2 with tyrosine-kinase receptors for VEGF. Adv Exp Med Biol. 2002;515:81–90.10.1007/978-1-4615-0119-0_7Suche in Google Scholar PubMed

[36] Graham PS, Kaidonis G, Abhary S, Gillies MC, Daniell M, Essex RW, et al. Genome-wide association studies for diabetic macular edema and proliferative diabetic retinopathy. BMC Med Genet. 2018;19(1):71.10.1186/s12881-018-0587-8Suche in Google Scholar PubMed PubMed Central

[37] Cruz-Gonzalez F, Cieza-Borrella C, Cabrillo-Estevez L, Canete-Campos C, Escudero-Dominguez F, Gonzalez-Sarmiento R. VEGF A (rs699947 and rs833061) and VEGFR2 (rs2071559) gene polymorphisms are not associated with AMD susceptibility in a Spanish population. Curr Eye Res. 2013;38(12):1274–7.10.3109/02713683.2013.819926Suche in Google Scholar PubMed

[38] Galan A, Ferlin A, Caretti L, Buson G, Sato G, Frigo AC, et al. Association of age-related macular degeneration with polymorphisms in vascular endothelial growth factor and its receptor. Ophthalmology. 2010;117(9):1769–74.10.1016/j.ophtha.2010.01.030Suche in Google Scholar PubMed

[39] Cardoso JV, Abrao MS, Vianna-Jorge R, Ferrari R, Berardo PT, Machado DE, et al. Combined effect of vascular endothelial growth factor and its receptor polymorphisms in endometriosis: a case-control study. Eur J Obstet Gynecol Reprod Biol. 2017;209:25–33.10.1016/j.ejogrb.2016.10.046Suche in Google Scholar PubMed

[40] Wang W, Ma XP, Shi Z, Zhang P, Ding DL, Huang HX, et al. Epidermal growth factor receptor pathway polymorphisms and the prognosis of hepatocellular carcinoma. Am J Cancer Res. 2015;5(1):396–410.Suche in Google Scholar

[41] Kaddu-Mulindwa D, Rosolowski M, Ziepert M, Regitz E, Assmann G, Bewarder M, et al. VEGFR2 and VEGFA polymorphisms are not associated with an inferior prognosis in Caucasian patients with aggressive B-cell lymphoma. Eur J Haematol. 2021;106(1):100–4.10.1111/ejh.13526Suche in Google Scholar PubMed

[42] Merlo S, Starcevic JN, Mankoc S, Santl Letonja M, Cokan Vujkovac A, Zorc M, et al. Vascular endothelial growth factor gene polymorphism (rs2010963) and its receptor, kinase insert domain-containing receptor gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus. J Diabetes Res. 2016;2016:1482194.10.1155/2016/1482194Suche in Google Scholar PubMed PubMed Central

[43] Kariz S, Petrovic D. Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: case-control cross-sectional study. Clin Biochem. 2014;47(16–17):192–6.10.1016/j.clinbiochem.2014.08.004Suche in Google Scholar PubMed

[44] Tah V, Orlans HO, Hyer J, Casswell E, Din N, Sri Shanmuganathan V, et al. Anti-VEGF therapy and the retina: an update. J Ophthalmol. 2015;2015:627674.10.1155/2015/627674Suche in Google Scholar PubMed PubMed Central

[45] Adamis AP, Brittain CJ, Dandekar A, Hopkins JJ. Building on the success of anti-vascular endothelial growth factor therapy: a vision for the next decade. Eye (London). 2020;34(11):1966–72.10.1038/s41433-020-0895-zSuche in Google Scholar PubMed PubMed Central

[46] Khan U, Shah MA. Ramucirumab for the treatment of gastric or gastro-esophageal junction cancer. Expert Opin Biol Ther. 2019;19(11):1135–41.10.1080/14712598.2019.1656715Suche in Google Scholar PubMed

[47] de Moraes Neto JE, Pereira FD, Neves RL, Tenorio de Barros NM, Gil CD, Fernandes AG, et al. Preclinical assessment of intravitreal ramucirumab: in vitro and in vivo safety profile. Int J Retina Vitreous. 2020;6:40.10.1186/s40942-020-00243-ySuche in Google Scholar

[48] Falcon BL, Chintharlapalli S, Uhlik MT, Pytowski B. Antagonist antibodies to vascular endothelial growth factor receptor 2 (VEGFR-2) as anti-angiogenic agents. Pharmacol Ther. 2016;164(August 2016):204–25.10.1016/j.pharmthera.2016.06.001Suche in Google Scholar PubMed

[49] Paine SK, Mondal LK, Borah PK, Bhattacharya CK, Mahanta J. Pro- and antiangiogenic VEGF and its receptor status for the severity of diabetic retinopathy. Mol Vis. 2017;23:356–63.Suche in Google Scholar

[50] Witmer AN, Blaauwgeers HG, Weich HA, Alitalo K, Vrensen GF, Schlingemann RO. Altered expression patterns of VEGF receptors in human diabetic retina and in experimental VEGF-induced retinopathy in monkey. Invest Ophthalmol Vis Sci. 2002;43(3):849–57.Suche in Google Scholar

[51] Simmons AB, Bretz CA, Wang H, Kunz E, Hajj K, Kennedy C, et al. Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy. Angiogenesis. 2018;21(4):751–64.10.1007/s10456-018-9618-5Suche in Google Scholar PubMed PubMed Central

Received: 2021-09-14
Revised: 2022-03-18
Accepted: 2022-04-15
Published Online: 2023-03-03

© 2023 Yazhen Yuan et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Systemic investigation of inetetamab in combination with small molecules to treat HER2-overexpressing breast and gastric cancers
  3. Immunosuppressive treatment for idiopathic membranous nephropathy: An updated network meta-analysis
  4. Identifying two pathogenic variants in a patient with pigmented paravenous retinochoroidal atrophy
  5. Effects of phytoestrogens combined with cold stress on sperm parameters and testicular proteomics in rats
  6. A case of pulmonary embolism with bad warfarin anticoagulant effects caused by E. coli infection
  7. Neutrophilia with subclinical Cushing’s disease: A case report and literature review
  8. Isoimperatorin alleviates lipopolysaccharide-induced periodontitis by downregulating ERK1/2 and NF-κB pathways
  9. Immunoregulation of synovial macrophages for the treatment of osteoarthritis
  10. Novel CPLANE1 c.8948dupT (p.P2984Tfs*7) variant in a child patient with Joubert syndrome
  11. Antiphospholipid antibodies and the risk of thrombosis in myeloproliferative neoplasms
  12. Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C
  13. High glucose and high lipid induced mitochondrial dysfunction in JEG-3 cells through oxidative stress
  14. Pharmacological inhibition of the ubiquitin-specific protease 8 effectively suppresses glioblastoma cell growth
  15. Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1
  16. Age-related changes in peripheral T-cell subpopulations in elderly individuals: An observational study
  17. Single-cell transcription analysis reveals the tumor origin and heterogeneity of human bilateral renal clear cell carcinoma
  18. Identification of iron metabolism-related genes as diagnostic signatures in sepsis by blood transcriptomic analysis
  19. Long noncoding RNA ACART knockdown decreases 3T3-L1 preadipocyte proliferation and differentiation
  20. Surgery, adjuvant immunotherapy plus chemotherapy and radiotherapy for primary malignant melanoma of the parotid gland (PGMM): A case report
  21. Dosimetry comparison with helical tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy for grade II gliomas: A single‑institution case series
  22. Soy isoflavone reduces LPS-induced acute lung injury via increasing aquaporin 1 and aquaporin 5 in rats
  23. Refractory hypokalemia with sexual dysplasia and infertility caused by 17α-hydroxylase deficiency and triple X syndrome: A case report
  24. Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis
  25. 6-Phosphogluconate dehydrogenase inhibition arrests growth and induces apoptosis in gastric cancer via AMPK activation and oxidative stress
  26. Experimental study on the optimization of ANM33 release in foam cells
  27. Primary retroperitoneal angiosarcoma: A case report
  28. Metabolomic analysis-identified 2-hydroxybutyric acid might be a key metabolite of severe preeclampsia
  29. Malignant pleural effusion diagnosis and therapy
  30. Effect of spaceflight on the phenotype and proteome of Escherichia coli
  31. Comparison of immunotherapy combined with stereotactic radiotherapy and targeted therapy for patients with brain metastases: A systemic review and meta-analysis
  32. Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation
  33. Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy
  34. The role of IL-31 and IL-34 in the diagnosis and treatment of chronic periodontitis
  35. Triple-negative mouse breast cancer initiating cells show high expression of beta1 integrin and increased malignant features
  36. mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study
  37. The apatinib and pemetrexed combination has antitumor and antiangiogenic effects against NSCLC
  38. Radiotherapy for primary thyroid adenoid cystic carcinoma
  39. Design and functional preliminary investigation of recombinant antigen EgG1Y162–EgG1Y162 against Echinococcus granulosus
  40. Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial
  41. Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics
  42. Performance comparison of three scaling algorithms in NMR-based metabolomics analysis
  43. PI3K/AKT/mTOR pathway and its related molecules participate in PROK1 silence-induced anti-tumor effects on pancreatic cancer
  44. The altered expression of cytoskeletal and synaptic remodeling proteins during epilepsy
  45. Effects of pegylated recombinant human granulocyte colony-stimulating factor on lymphocytes and white blood cells of patients with malignant tumor
  46. Prostatitis as initial manifestation of Chlamydia psittaci pneumonia diagnosed by metagenome next-generation sequencing: A case report
  47. NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2
  48. Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis
  49. Exosomal HBV-DNA for diagnosis and treatment monitoring of chronic hepatitis B
  50. Shear stress leads to the dysfunction of endothelial cells through the Cav-1-mediated KLF2/eNOS/ERK signaling pathway under physiological conditions
  51. Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection
  52. Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves’ disease in children
  53. Cloning, subcellular localization and expression of phosphate transporter gene HvPT6 of hulless barley
  54. Coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome
  55. Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis
  56. Whole-exome sequencing applications in prenatal diagnosis of fetal bowel dilatation
  57. Gemella morbillorum infective endocarditis: A case report and literature review
  58. An unusual ectopic thymoma clonal evolution analysis: A case report
  59. Severe cumulative skin toxicity during toripalimab combined with vemurafenib following toripalimab alone
  60. Detection of V. vulnificus septic shock with ARDS using mNGS
  61. Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing
  62. The influence and mechanistic action of sperm DNA fragmentation index on the outcomes of assisted reproduction technology
  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
  64. ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis
  65. Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report
  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
  67. Collagen changes in rabbit conjunctiva after conjunctival crosslinking
  68. Effects of NM23 transfection of human gastric carcinoma cells in mice
  69. Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia
  70. Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation
  71. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling
  72. Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report
  73. Giant duplication of the transverse colon in an adult: A case report and literature review
  74. Ectopic thyroid tissue in the breast: A case report
  75. SDR16C5 promotes proliferation and migration and inhibits apoptosis in pancreatic cancer
  76. Vaginal metastasis from breast cancer: A case report
  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
https://doi.org/10.1515/biol-2022-0081
Schlagwörter für diesen Artikel
type 2 diabetes; diabetic retinopathy; vascular endothelial growth factor receptor; gene polymorphism; VEGFR-2
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Systemic investigation of inetetamab in combination with small molecules to treat HER2-overexpressing breast and gastric cancers
  3. Immunosuppressive treatment for idiopathic membranous nephropathy: An updated network meta-analysis
  4. Identifying two pathogenic variants in a patient with pigmented paravenous retinochoroidal atrophy
  5. Effects of phytoestrogens combined with cold stress on sperm parameters and testicular proteomics in rats
  6. A case of pulmonary embolism with bad warfarin anticoagulant effects caused by E. coli infection
  7. Neutrophilia with subclinical Cushing’s disease: A case report and literature review
  8. Isoimperatorin alleviates lipopolysaccharide-induced periodontitis by downregulating ERK1/2 and NF-κB pathways
  9. Immunoregulation of synovial macrophages for the treatment of osteoarthritis
  10. Novel CPLANE1 c.8948dupT (p.P2984Tfs*7) variant in a child patient with Joubert syndrome
  11. Antiphospholipid antibodies and the risk of thrombosis in myeloproliferative neoplasms
  12. Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C
  13. High glucose and high lipid induced mitochondrial dysfunction in JEG-3 cells through oxidative stress
  14. Pharmacological inhibition of the ubiquitin-specific protease 8 effectively suppresses glioblastoma cell growth
  15. Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1
  16. Age-related changes in peripheral T-cell subpopulations in elderly individuals: An observational study
  17. Single-cell transcription analysis reveals the tumor origin and heterogeneity of human bilateral renal clear cell carcinoma
  18. Identification of iron metabolism-related genes as diagnostic signatures in sepsis by blood transcriptomic analysis
  19. Long noncoding RNA ACART knockdown decreases 3T3-L1 preadipocyte proliferation and differentiation
  20. Surgery, adjuvant immunotherapy plus chemotherapy and radiotherapy for primary malignant melanoma of the parotid gland (PGMM): A case report
  21. Dosimetry comparison with helical tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy for grade II gliomas: A single‑institution case series
  22. Soy isoflavone reduces LPS-induced acute lung injury via increasing aquaporin 1 and aquaporin 5 in rats
  23. Refractory hypokalemia with sexual dysplasia and infertility caused by 17α-hydroxylase deficiency and triple X syndrome: A case report
  24. Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis
  25. 6-Phosphogluconate dehydrogenase inhibition arrests growth and induces apoptosis in gastric cancer via AMPK activation and oxidative stress
  26. Experimental study on the optimization of ANM33 release in foam cells
  27. Primary retroperitoneal angiosarcoma: A case report
  28. Metabolomic analysis-identified 2-hydroxybutyric acid might be a key metabolite of severe preeclampsia
  29. Malignant pleural effusion diagnosis and therapy
  30. Effect of spaceflight on the phenotype and proteome of Escherichia coli
  31. Comparison of immunotherapy combined with stereotactic radiotherapy and targeted therapy for patients with brain metastases: A systemic review and meta-analysis
  32. Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation
  33. Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy
  34. The role of IL-31 and IL-34 in the diagnosis and treatment of chronic periodontitis
  35. Triple-negative mouse breast cancer initiating cells show high expression of beta1 integrin and increased malignant features
  36. mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study
  37. The apatinib and pemetrexed combination has antitumor and antiangiogenic effects against NSCLC
  38. Radiotherapy for primary thyroid adenoid cystic carcinoma
  39. Design and functional preliminary investigation of recombinant antigen EgG1Y162–EgG1Y162 against Echinococcus granulosus
  40. Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial
  41. Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics
  42. Performance comparison of three scaling algorithms in NMR-based metabolomics analysis
  43. PI3K/AKT/mTOR pathway and its related molecules participate in PROK1 silence-induced anti-tumor effects on pancreatic cancer
  44. The altered expression of cytoskeletal and synaptic remodeling proteins during epilepsy
  45. Effects of pegylated recombinant human granulocyte colony-stimulating factor on lymphocytes and white blood cells of patients with malignant tumor
  46. Prostatitis as initial manifestation of Chlamydia psittaci pneumonia diagnosed by metagenome next-generation sequencing: A case report
  47. NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2
  48. Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis
  49. Exosomal HBV-DNA for diagnosis and treatment monitoring of chronic hepatitis B
  50. Shear stress leads to the dysfunction of endothelial cells through the Cav-1-mediated KLF2/eNOS/ERK signaling pathway under physiological conditions
  51. Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection
  52. Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves’ disease in children
  53. Cloning, subcellular localization and expression of phosphate transporter gene HvPT6 of hulless barley
  54. Coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome
  55. Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis
  56. Whole-exome sequencing applications in prenatal diagnosis of fetal bowel dilatation
  57. Gemella morbillorum infective endocarditis: A case report and literature review
  58. An unusual ectopic thymoma clonal evolution analysis: A case report
  59. Severe cumulative skin toxicity during toripalimab combined with vemurafenib following toripalimab alone
  60. Detection of V. vulnificus septic shock with ARDS using mNGS
  61. Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing
  62. The influence and mechanistic action of sperm DNA fragmentation index on the outcomes of assisted reproduction technology
  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
  64. ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis
  65. Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report
  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
  67. Collagen changes in rabbit conjunctiva after conjunctival crosslinking
  68. Effects of NM23 transfection of human gastric carcinoma cells in mice
  69. Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia
  70. Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation
  71. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling
  72. Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report
  73. Giant duplication of the transverse colon in an adult: A case report and literature review
  74. Ectopic thyroid tissue in the breast: A case report
  75. SDR16C5 promotes proliferation and migration and inhibits apoptosis in pancreatic cancer
  76. Vaginal metastasis from breast cancer: A case report
  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2026 De Gruyter Brill
Heruntergeladen am 27.1.2026 von https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0081/html
Button zum nach oben scrollen