Startseite Lebenswissenschaften Association study of CLDN14 variations in patients with kidney stones
Artikel Open Access

Association study of CLDN14 variations in patients with kidney stones

  • Ihsan Ullah , Khadijah Murtaza , Hafiza Ammara , Misbah , Munir Ahmad Bhinder , Amjad Riaz , Wasim Shehzad und Muhammad Yasir Zahoor EMAIL logo
Veröffentlicht/Copyright: 28. Februar 2022
Artikel downloaden (PDF)
Open Life Sciences
Aus der Zeitschrift Open Life Sciences Band 17 Heft 1

Abstract

Claudin-14 protein plays an essential role in regulating calcium ions in the kidney and ear. Two phenotypes, hearing loss and kidney stones, were reportedly associated with variations in the CLDN14 gene. This study aimed to understand CLDN14 mutations’ contribution to hearing loss and renal stone formation in a Pakistani cohort. We analyzed CLDN14 sequence variations in 100 patients, along with healthy individuals, to assess whether specific polymorphisms were associated with the disease. Also, we performed an in silico analysis using a mutation database and protein annotation. The rs219779’s genotype CT (p = 0.0020) and rs219780’s genotype AG (p = 0.0012) were significantly associated with kidney stones. We also found that a novel haplotype, “TA” associated with kidney stone formation, has moderate linkage disequilibrium. The TA haplotype was significantly correlated with a kidney stone risk formation of 3.76-fold (OR (CI 95%) = 3.76 (1.83–7.72)) and p = 0.0016 compared to other haplotypes. In silico analysis revealed that mutations associated with hearing loss were not correlated with renal stone formation but affected claudin-14 protein stability. We structurally mapped a novel TA haplotype of CLDN14 that, based on our analysis, likely contributes to the pathogenesis of renal stones.

Keywords: cell tight junction; calcium homeostasis; nephrolithiasis; hearing loss; gene association

1 Introduction

Tight junctions, also known as zonula occluden, play a significant role in cell-to-cell adhesion in epithelial or endothelial tissues. They act as a physical barrier, continuously sealing the cell–cell junction, allowing controlled transportation of water and solutes across the paracellular space in the renal tubule and epithelium [1]. Tight junctions consist of protein strands interwoven into the junction lipid bilayer, making strong contacts with protein strands of the adjacent cells [1]. Claudins are composed of four transmembrane domains, two extracellular loops, a short cytosolic N-terminus, and longer cytosolic C-terminus. The first extracellular domain is crucial for determining selectivity. Several claudin isoforms in the renal tubule of adults and neonates have been reported to determine the paracellular diffusion pathway’s capacity, selectivity, and permeability [2].

The claudin protein family comprises 27 members, each expressed in specific tissues [3]. The integral membrane protein claudin-14, encoded by the CLDN14 gene, is a part of tight junctions. The claudin-14 protein binds specifically to the Yes-associated protein (YAP), a novel transcriptional co-activator [4]. Claudin-14 is attached to a neighboring claudin-14 via an extracellular groove, controlling calcium transportation in the junction [5]. Claudin 14 regulates calcium reabsorption in the ascending limb [6,7,8]. Claudin proteins play a vital role in ion regulation; any abnormality in this protein might lead to dysregulation of calcium and other ions [9]. Hou [10] suggested that the tight junction complex at the apex of the reticular lamina requires claudin-14 as a cation-restrictive barrier to maintain the proper ionic composition of the fluid surrounding the basolateral surface of outer hair cells. The calcium-sensing receptor (CASR) and calcium intake may regulate the expression of claudin-14 [11,12,13,14]. Many synonymous variants in the CLDN14 gene were reportedly linked to kidney stone formation and reduced bone mineral density [15]. Previously, nonsynonymous homozygous mutations in CLDN14 were correlated with the autosomal-recessive nonsyndromic sensorineural deafness disease [16,17]. The precise role and regulatory mechanism of claudins are not fully explained, and a great deal of work remains [18]. CLDN14 mutations exhibit two phenotypes that are not reported together. This study aimed to determine the role of the CLDN14 gene in nephrolithiasis-affected individuals of the local Pakistani population. We performed an in silico analysis of CLDN14 variants by employing different databases for nephrolithiasis and hearing loss phenotypes to determine the role of CLDN14 variants on gene regulation and protein structural stability.

2 Material and methods

2.1 Enrolment of patients

One hundred patients from unrelated families were enrolled. Inclusion criteria: each had one or more kidney stones, with calcium being the main stone component. The diagnosis was made using ultrasound, chemistry, and analysis of urine and stone composition (if available). Exclusion criteria: Patients with other kidney and metabolic diseases, nephrosis, diabetes, and heart patients were excluded. Clinicians (physicians) from different districts of Punjab province performed patient enrolment. Patients were recruited from Shaikh Zahid Hospital Lahore, General Hospital Lahore, Services Hospital Lahore, Civil Hospital Bhawalpur, District Civil Hospital Hafizabad, District Civil Hospital Narowal, and some patients were recruited from home via different references. Patient information, such as diet, cast, age, weight, and history of other diseases, was obtained. The control sample was taken from healthy people with no family and personal history of stone or kidney diseases.

  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, institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the UVAS (Institutional Review Board) IRB Ref: IRB/217/12 and Ethical Review Board of Service Institute of Medical Sciences (SIMS), Lahore Ref No. IRB/2017/334/SIMS.

2.2 Sequencing

Genomic DNA was extracted from blood samples using the standard organic methods [19]. Exon 3 and the untranslated regions (UTRs) of the CLDN14 gene was amplified using a set of primers designed by Primer3 Software [20] ([forward: 5′-CTTGGCTTCATTAGGGCTCC-3′] 60.5°C; [reverse: 5′-GAACCCCTGCCTCCATTGA-3′] 59.5°C). Each amplicon was sequenced in both orientations using Sanger dideoxy chain termination chemistry. Sequencing polymerase chain reaction (PCR) products were separated using ABI PRISM 3700 Genetic Analyser (Foster City, CA, USA). PCR was carried out in the T100TM Thermal Cycler (Bio-Rad, Hercules, CA, USA) by using a 25 µL reaction mixture containing 50 ng DNA, 1× (NH4)2SO4 buffer, 250 µM of each dNTPs, 1.5 mM MgSO4, 10 µM of each primer and 2.0 U Taq DNA polymerase. All PCR amplifications were performed at an annealing temperature of 59°C.

2.3 Statistical analysis

The analysis of enrolled patients and control data, including allelic and genotypic frequencies expressed as counts (percentages), was performed using the statistical package for social sciences (SPSS) version 20. Using a Chi-square test, Hardy–Weinberg equilibrium (HWE) was performed, which served as a statistical control for systematic genotyping error and population stratification, where CLDN14 polymorphisms that violated HWE, as indicated by p  <  0.05 for in the control group, were not processed for further data analyses. Odds ratios (ORs) with associated 95% confidence intervals (CI) were determined to assess the strength of statistical association, if any, considering allelic, genotypic, recessive, dominant, and log-additive models by the same SNPstats program [21]. The pairwise linkage disequilibrium and haplotype analysis for CLDN14 polymorphisms were conducted using the Haploview program [22]. The Bonferroni correction for multiple testing was performed to calculate ORs and associated p-values for genotype and haplotype associations between CLDN14 polymorphisms and kidney stones.

2.4 In silico analysis

We performed an analysis of variants associated with renal stone formation and hearing loss using different resources: Human Genome Mutation Database (HGMD) [23], ClinVar, Exome Variant Server, and literature [24]. The amino acid conservation, mutation, and domain specificity analyses were carried out using Clustal Omega alignment of claudin-14 and orthologous sequences from human, mouse, chicken, and frog downloaded from the Ensemble database. The crystal structure of mouse claudin-14 large domain, claudin-19 (3X29:A), was obtained from the Protein Databank (https://www.rcsb.org/). PyMol [25] was used to analyze the claudin-19 structure by studying mutational interactions and structural stability.

3 Results

3.1 Cohort characteristics

The average age, body weight, and gender percentage of the groups are presented in Table 1. In the patient group, the average male age was 20.7 years compared to that of the female was 22.5 years. The average male weight was 62 kg compared to that of females at 57.2 kg. Overall, the patient’s weight and age were lower than those of controls, suggesting that the stone phenotype appears at a younger age (young-onset).

Table 1

Clinical and genetic characteristics of patients

Characteristic No. Average age (Year) Average weight (kg) Percentage
Normal (100) Male 63 29.42 66.1 63
Female 37 33.34 52.35 37
Patients (100) Male 72 20.7 62 72
Female 28 22.5 57.2 28

3.2 Sanger screening

We found two SNPs, rs219779 (C > T) and rs219780 (G > A), through Sanger sequencing of CLDN14 coding exon 3 and UTRs (Figure 1 and Table 2) in patients with kidney stones. The patients are heterozygous for specific alleles, i.e., the genetic score less than 1 [23] indicated the changes are polymorphisms and not monogenic and less pathogenic. The allelic and genetic frequencies for all the CLDN14 polymorphisms did not violate the HWE in the control group.

Figure 1 Sanger sequencing of CLDN14 in patients. Rows are annotated with coordinates of SNPs rs219779 and rs219780, respectively, in five samples: KS_11, KS_13, KS_9, KS_2, and KS_15.
Figure 1

Sanger sequencing of CLDN14 in patients. Rows are annotated with coordinates of SNPs rs219779 and rs219780, respectively, in five samples: KS_11, KS_13, KS_9, KS_2, and KS_15.

Table 2

Association of CLDN14 rs219779 and rs219780 variants with nephrolithiasis disorder considering allelic and genotype frequencies

Group Allele Case Control OR (CI 95%) p value*
rs219779 C 135 (0.68) 159 (0.80) Referent 0.0368
T 65 (0.32) 41 (0.20) 1.8672 [1.1867–2.9378]
rs219780 G 135 (0.68) 160 (0.80) Referent 0.0256
A 65 (0.32) 40 (0.20) 1.9259 [1.2211–3.0375]
rs219779 CC 35 (0.35) 60 (0.60) Referent
CT 65 (0.65) 39 (0.39) 2.8571 [1.6067–5.0809] 0.0020
TT 0 (0) 1 (0.01) 0 2.54
rs219780 GG 35 (0.35) 61 (0.61) Referent
AG 65 (0.65) 38 (0.38) 2.9812 [1.6742–5.3086] 0.0012
AA 0 1 (0.01) 0 (0) 2.556

OR: odds ratio; CI: 95% confidence interval; *p values reflect adjustment for age and gender. Bonferroni correction for multiple testing was applied (p value threshold= 0.01). Statistically significant p values (<0.01) and associated OR values are highlighted in bold.

The genotypes rs219779 CT (OR:2.8571, p: 0.0020) and genotypes rs219780 AG (OR:2.9812, p:0.0012) have significant association with kidney stones (Table 2). We have only genotype TT (rs219779) and AA (rs219780) in controls but not in patients. So, we cannot evaluate recessive and dominant genetic models.

3.3 Haplotype analysis and linkage disequilibrium

The haplotype analysis was conducted on genetic data of the patient and control groups using SNPstats software [21]. The promising candidate haplotype was TA as evidenced by the p-value of 0016, Odds Ratio of 3.76, and 95% CI [1.83–7.72] (Table 3). The other haplotypes exhibited higher allele frequencies in the control samples with a low p-value (Table 3). Furthermore, the TA haplotype frequency was 0.1146 in the control group and 0.2291 in patients, suggesting that the association between this haplotype and kidney stone disorders’ etiology was statistically significant. The global haplotype association p-value was 0.0019. Pairwise LD analysis and haplotype plot construction demonstrated moderately significant D’ measures between two pairs of both SNPs, suggesting that these two loci pairs may be linked together. Furthermore, the trend of association persisted for the haplotype to check the combined effect of LD analysis and shows a moderate effect of both SNPs because both fall in the same block with a score of 53 as shown in Appendix Figure A2.

Table 3

Association of kidney stone risk with CLDN14 genetic variants considering haplotype analysis

Haplotypes Case (freq.) Control (freq.) Odds ratio [95%CI] p-value*
CG 0.5791 0.7096 1.00 —
TA 0.2291 0.1146 3.76 (1.83–7.72) 0.0016
TG 0.0959 0.0904 2.13 (0.91–4.96) 0.328
CA 0.0959 0.0854 2.53 (1.04–6.16) 0.172

OR: odds ratio; 95% CI: 95% confidence interval; *p values reflect adjustment for age and gender. Bonferroni correction for multiple testing was applied (p value threshold= 0.01). Statistically significant p values (<0.01) and associated OR values are highlighted in bold.

3.4 Conservational annotation of reported mutations

Numerous mutations in CLDN14 were reportedly associated with hearing loss, and all exhibited higher genetic scores, according to the American College of Medical Genetics and Genomics guidelines. Herein, we conducted a conservation analysis of CLDN14 sequences with both hearing loss- and kidney stone-associated mutations using the HGMD database and the literature (Figure 2 and Figure A1). The CLDN14 orthologs were present up to fish and not in lower organisms. Importantly, we found almost all hearing loss-associated mutations located in the helical transmembrane domain, critical for protein stability and ion transport. In contrast, kidney stone-associated mutations were located in the regulatory regions and UTRs.

Figure 2 Clustal alignment of human, mouse, chicken, frog, and fish. Mutations are coloured according to their type, whereas domains are separated by lines.
Figure 2

Clustal alignment of human, mouse, chicken, frog, and fish. Mutations are coloured according to their type, whereas domains are separated by lines.

3.5 Protein structural analysis

The mouse claudin-19 (3X29:A) was used for protein structure analysis as it is closely related to claudin-14. Based on our amino acid alignment (Figure 2), the mutation is conserved in the structure. We found structural abnormalities in the mutated protein by comparing protein simulations and distance measurements of normal and mutated proteins (Figure 3). Strong interactions are indicated by bond lengths between 1.5 and 4.0 Å [26]. Using PyMol, we generated mutations in the following amino acids’ crystal structure: p.P20, p.R80, p.V85, p.A94, p.G101, and p.A163, all of which were present in the transmembrane region. In these mutants, amino acid interactions with neighboring amino acids changed. The most notable changes were found in the transmembrane region (amino acids 82-102), which interact with amino acids 50-56 (Figure 3). Kidney stone-associated mutations were not found in or around regions where hearing loss mutations were present.

Figure 3 Crystal structure mutation annotations using PyMol. Mutations (shown in dots) were mapped onto the structure of claudin-19 with distances in Å. Amino acid interactions are compared between wild type and mutants. The mutated amino acid is highlighted in green and is connected via dotted lines to the interacting amino acid.
Figure 3

Crystal structure mutation annotations using PyMol. Mutations (shown in dots) were mapped onto the structure of claudin-19 with distances in Å. Amino acid interactions are compared between wild type and mutants. The mutated amino acid is highlighted in green and is connected via dotted lines to the interacting amino acid.

4 Discussion

Claudin-14 is an integral membrane protein with a role in calcium regulation and ion homeostasis. Several CLDN14 variants have been associated with hearing loss and renal stone formation. Wilcox et al. [16] reported that recessive inheritance of CLDN14 variants was associated with hearing loss in a Pakistani cohort. Thorleifsson et al. [15] illustrated that the rs219780 SNP was linked to renal stone formation in patients from a large cohort study (p-value = 4.0 × 10 (−12) of Iceland and the Netherlands. Thorleifsson’s study also shows the association of rs219779 with kidney stones. Interestingly, rs219779 was reportedly involved in higher serum parathyroid hormone (PTH), which regulates calcium homeostasis [27]. Although these two SNPs were reported associated with kidney stone risk in the Indian population [28], the specific haplotype was not identified. In the Guha study, rs219780 allele and genotype frequency were p < 0.001 compared to our allele A (G referent) p = 0.0256 and genotype AG p = 0.0012. Their LD analysis of three SNPs (rs219777, rs219778, and rs219780) do not suggest any strong findings, but our findings suggest moderate association in one block (Figure A2). Furthermore, our study suggests that rs219779 have a stronger association with kidney stone compared to previous studies suggesting rs219780 [15,28]. We identified a novel TA haplotype of CLDN14 SNPs, rs219779 and rs219780, and its association with the renal stone formation, which is not previously studied in CLDN14 studies. The significant p-value (0.0016) of the TA haplotype in our study suggests a strong association with kidney stone risk formation. The present study’s findings confirmed those in previous work [6], showing that rs219779 and rs219780 were in linkage disequilibrium; this explains the predictive role of the TA haplotype.

This suggests that mutations in intergenic parts like UTRs and enhancer regions indirectly involved in cell signaling can lead to increased calcium levels in specific tissues and contribute to stone formation. Some studies have also described the role of somatic variation of CLDN14 in cancer [29].

We assumed stone-associated variations could make CLDN14 susceptible to microRNA silencing in the regions that control gene regulation. Calcium levels control the silencing function of two microRNAs (miR-9 and miR-374). miR-9 and miR-374 repressed the translation of claudin 14 protein by silencing the transcript in kidneys [30]. Nishi et al. [31] reported that this protein had a similar function in many species but the difference existed in ion regulation due to the molecular location of regulatory domains. These data indicated that protein function is evolutionarily adapted and can change depending on epigenetics and environmental factors like diet. These changes can affect the signaling cascade and gene regulation as observed in cancer [32].

Overall, we identified the TA haplotype and its association with kidney stone formation but no additional monogenic or genetically strong mutations in our cohort. We supplemented our study with an in silico analysis. We determined that amino acids 49-60 were crucial for extracellular and transmembrane interactions. Our structural analysis suggests that the transmembrane region is vital for structural stability and function (Figure 3) [32]. Also, our in silico studies showed that the mutations associated with hearing loss were highly conserved.

5 Conclusion

We found a novel TA haplotype (p = 0.0016) of rs219779 and rs219780 SNPs, both of which were previously reported to correlate with kidney stone formation in different populations in separate studies. Furthermore, our study suggested that hearing loss was associated with genetically strong monogenic mutations in CLDN14 causing protein instability, whereas stone-associated variations of CLDN14 affected gene regulation.

tel: +042-99211374, ext. 347

Acknowledgement

We are thankful to the patients who participated in the study and the clinicians for helping with the patients’ enrolment.

  1. Funding information: Departmental support was awarded to Ihsan Ullah as a Ph.D. scholar of the Institute of Biochemistry and Biotechnology, the University of Veterinary and Animal Sciences, Lahore, Pakistan.

  2. Author contributions: All authors made substantial contributions to the study’s conception and design and/or acquisition of the data and/or analysis and interpretation of the data. Each author participated in drafting the article or revising it critically for important intellectual content and gave the version’s final approval and any revised version.

  3. Conflict of interest: The 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

Figure A1 Genomic position of both SNPs and conservation of amino acid: (a) SNP rs219979, Chr21:37833751 C >T p.R 81; (b) rs219780 Chr21:37833307 G >A p.T 229.
Figure A1

Genomic position of both SNPs and conservation of amino acid: (a) SNP rs219979, Chr21:37833751 C >T p.R 81; (b) rs219780 Chr21:37833307 G >A p.T 229.

Figure A2 Linkage disequilibrium (LD) analysis of rs219979 and rs219780 SNPs of the CLDN14 gene.
Figure A2

Linkage disequilibrium (LD) analysis of rs219979 and rs219780 SNPs of the CLDN14 gene.

References

[1] Niessen CM. Tight junctions/adherens junctions: basic structure and function. J Invest Dermatol. 2007;127(11):2525–32.10.1038/sj.jid.5700865Suche in Google Scholar PubMed

[2] Angelow S, Alan SL. Claudins and paracellular transport: an update. Curr Opin Nephrolhy. 2007;16(5):459–64.10.1097/MNH.0b013e32820ac97dSuche in Google Scholar PubMed

[3] Furuse M, Tsukita S. Claudins in occluding junctions of humans and flies. Trends Cell Biol. 2006;16(4):181–8.10.1016/j.tcb.2006.02.006Suche in Google Scholar PubMed

[4] Wattenhofer M, Reymond A, Falciola V, Charollais A, Caille D, Borel C, et al. Different mechanisms preclude mutant CLDN14 proteins from forming tight junctions in vitro. Hum Mutat. 2005;25(6):543–9.10.1002/humu.20172Suche in Google Scholar PubMed

[5] Findley MK, Koval M. Regulation and roles for claudin‐family tight junction proteins. IUBMB life. 2009;61(4):431–7.10.1002/iub.175Suche in Google Scholar PubMed PubMed Central

[6] Arcidiacono T, Simonini M, Lanzani C, Citterio L, Salvi E, Barlassina C, et al. Claudin-14 gene polymorphisms and urine calcium excretion. Clin J Am Soc Nephrol. 2018;13(10):1542–9.10.2215/CJN.01770218Suche in Google Scholar PubMed PubMed Central

[7] Toka HR. New functional aspects of the extracellular calcium-sensing receptor. Curr Opin Nephrol Hypertens. 2014;23(4):352.10.1097/01.mnh.0000447016.21228.e0Suche in Google Scholar PubMed PubMed Central

[8] Sato T, Courbebaisse M, Ide N, Fan Y, Hanai JI, Kaludjerovic J, et al. Parathyroid hormone controls paracellular Ca2+ transport in the thick ascending limb by regulating the tight-junction protein Claudin14. Natl Acad Sci USA. 2017;114(16):E3344–53.10.1073/pnas.1616733114Suche in Google Scholar PubMed PubMed Central

[9] Angelow S, Alan SL. Structure-function studies of claudin extracellular domains by cysteine-scanning mutagenesis. J Biol Chem. 2009;284(42):29205–17.10.1074/jbc.M109.043752Suche in Google Scholar PubMed PubMed Central

[10] Hou J. The yin and yang of claudin‐14 function in human diseases. Ann NY Acad Sci. 2012;1258:185.10.1111/j.1749-6632.2012.06529.xSuche in Google Scholar PubMed PubMed Central

[11] Toka HR, Al-Romaih K, Koshy JM, DiBartolo S, Kos CH, Quinn SJ, et al. Deficiency of the calcium-sensing receptor in the kidney causes parathyroid hormone–independent hypocalciuria. J Am Soc Nephrol. 2012;23(11):1879–90.10.1681/ASN.2012030323Suche in Google Scholar

[12] Gong Y, Renigunta V, Himmerkus N, Zhang J, Renigunta A, Bleich M, et al. Claudin‐14 regulates renal Ca++ transport in response to CaSR signalling via a novel microRNA pathway. The EMBO Journal. 2012;31(8):1999–2012.10.1038/emboj.2012.49Suche in Google Scholar

[13] Gong Y, Hou J. Claudin-14 underlies Ca++-sensing receptor–mediated Ca++ metabolism via NFAT-microRNA–based mechanisms. J Am Soc Nephrol. 2014;25(4):745–60.10.1681/ASN.2013050553Suche in Google Scholar

[14] Gong Y, Himmerkus N, Plain A, Bleich M, Hou J. Epigenetic regulation of microRNAs controlling CLDN14 expression as a mechanism for renal calcium handling. J Am Soc Nephrol. 2015;26(3):663–76.10.1681/ASN.2014020129Suche in Google Scholar

[15] Thorleifsson G, Holm H, Edvardsson V, Walters GB, Styrkarsdottir U, Gudbjartsson DF, et al. Variants in the CLDN14 gene associated with kidney stones and bone mineral density. Nat Genet. 2009;41(8):926.10.1038/ng.404Suche in Google Scholar

[16] Wilcox ER, Burton QL, Naz S, Riazuddin S, Smith TN, Ploplis B, et al. Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29. Cell. 2001;104(1):165–72.10.1016/S0092-8674(01)00200-8Suche in Google Scholar

[17] Ben-Yosef T, Belyantseva IA, Saunders TL, Hughes ED, Kawamoto K, Van Itallie CM, et al. Claudin-14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration. Hum Mol Genet. 2003;12(16):2049–61.10.1093/hmg/ddg210Suche in Google Scholar PubMed

[18] Lal-Nag M, Morin PJ. The claudins. Genome biol. 2009;10(8):235.10.1186/gb-2009-10-8-235Suche in Google Scholar PubMed PubMed Central

[19] Grimberg J, Nawoschik S, Belluscio L, McKee R, Turck A, Eisenberg A. simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucleic Acids Res. 1989;17(20):8390.10.1093/nar/17.20.8390Suche in Google Scholar PubMed PubMed Central

[20] Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Bioinformatics methods and protocols. Totowa, NJ: Humana Press; 2000. p. 365–38610.1385/1-59259-192-2:365Suche in Google Scholar

[21] Solé X, Guinó E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928–9.10.1093/bioinformatics/btl268Suche in Google Scholar PubMed

[22] Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21(2):263–5.10.1093/bioinformatics/bth457Suche in Google Scholar PubMed

[23] Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, et al. Human Gene Mutation Database (HGMD®): 2003 update. Hum Mutat. 2003;21(6):577–81.10.1002/humu.10212Suche in Google Scholar PubMed

[24] Pérez-Palma E, Gramm M, Nürnberg P, May P, Lal D. Simple ClinVar: an interactive web server to explore and retrieve gene and disease variants aggregated in ClinVar database. Nucleic acids res. 2019;47(W1):W99–105.10.1093/nar/gkz411Suche in Google Scholar PubMed PubMed Central

[25] Schrödinger L, DeLano W. PyMOL [Internet]. 2020. Available from: http://www.pymol.org/pymol.Suche in Google Scholar

[26] Rowland RS, Taylor R. Intermolecular nonbonded contact distances in organic crystal structures: Comparison with distances expected from van der Waals radii. J phys chem. 1996;100(18):7384–91.10.1021/jp953141+Suche in Google Scholar

[27] Zanetti D, Rao A, Gustafsson S, Assimes T, Montgomery SB, Ingelsson E. Genetic variants associated with circulating parathyroid hormone. J Am Soc Nephrol. 2017;28(5):1553–65.10.1681/ASN.2016010069Suche in Google Scholar PubMed PubMed Central

[28] Guha M, Bankura B, Ghosh S, Pattanayak AK, Ghosh S, Pal DK, et al. Polymorphisms in CaSR and CLDN14 genes associated with increased risk of kidney stone disease in patients from the eastern part of India. PloS One. 2015;10(6):e0130790.10.1371/journal.pone.0130790Suche in Google Scholar PubMed PubMed Central

[29] Gunzel D, Yu AS. Claudins and the modulation of tight junction permeability. Physiol Rev. 2013;93(2):525–69.10.1152/physrev.00019.2012Suche in Google Scholar PubMed PubMed Central

[30] Hou J. The role of claudin in hypercalciuric nephrolithiasis. Curr Urol Rep. 2013;14(1):5–12.10.1007/s11934-012-0289-2Suche in Google Scholar PubMed PubMed Central

[31] Nishi H, Hashimoto K, Panchenko AR. Phosphorylation in protein-protein binding: effect on stability and function. Structure. 2011;19(12):1807–15.10.1016/j.str.2011.09.021Suche in Google Scholar PubMed PubMed Central

[32] Valle BL, Morin PJ. Claudins in cancer biology. Current Topics in Membranes. Vol. 65, Academic Press; 2010. p. 293–33310.1016/S1063-5823(10)65013-2Suche in Google Scholar
Received: 2021-05-27
Revised: 2021-10-08
Accepted: 2021-10-10
Published Online: 2022-02-28

© 2022 Ihsan Ullah 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. Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
  3. The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
  4. Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
  5. LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
  6. Association study of CLDN14 variations in patients with kidney stones
  7. Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
  8. Regulation of miR-30b in cancer development, apoptosis, and drug resistance
  9. Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
  10. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
  11. Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
  12. Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
  13. Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
  14. Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
  15. Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
  16. Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
  17. Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
  18. Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
  19. Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
  20. Nutrition intervention in the management of novel coronavirus pneumonia patients
  21. circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
  22. Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
  23. Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
  25. Comparison of axon extension: PTFE versus PLA formed by a 3D printer
  26. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
  28. Study on the mechanism of inhibiting patulin production by fengycin
  29. SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
  30. Relationship between blood clots and COVID-19 vaccines: A literature review
  31. Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
  32. Bioinformatics network analyses of growth differentiation factor 11
  33. NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
  34. Expression of Zeb1 in the differentiation of mouse embryonic stem cell
  35. Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
  36. Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
  37. Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
  38. Genetic susceptibility to high myopia in Han Chinese population
  39. Potential biomarkers and molecular mechanisms in preeclampsia progression
  40. Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
  41. Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
  42. The significance of PAK4 in signaling and clinicopathology: A review
  43. Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
  44. Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
  45. Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
  46. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
  47. MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
  48. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
  49. BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
  50. Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
  51. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
  52. A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
  53. Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
  54. Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
  55. Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
  56. A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
  57. β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
  58. Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
  59. BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
  60. Mucormycosis co-infection in COVID-19 patients: An update
  61. Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
  62. Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
  63. Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
  64. Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
  65. Nasopharyngeal tuberculosis: A case report
  66. Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
  67. Aberrant pulmonary immune response of obese mice to periodontal infection
  68. Bacteriospermia – A formidable player in male subfertility
  69. In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
  70. Effects of KCa channels on biological behavior of trophoblasts
  71. Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
  72. Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
  73. Prognostic signature related to the immune environment of oral squamous cell carcinoma
  74. Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
  75. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
  76. Role of MMP-2 and CD147 in kidney fibrosis
  77. Geometric basis of action potential of skeletal muscle cells and neurons
  78. Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
  79. Role of cerebellar cortex in associative learning and memory in guinea pigs
  80. Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
  81. Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
  82. Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
  83. Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
  84. Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
  85. Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
  86. Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
  87. Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
  88. One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
  89. S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
  90. Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
  91. Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
  92. Evaluation of prognostic markers in patients infected with SARS-CoV-2
  93. N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
  94. Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
  95. Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
  96. Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
  97. Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
  98. Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
  99. Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
  100. SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
  101. Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
  102. Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
  103. Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
  104. Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
  105. Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
  106. PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
  107. A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
  108. Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
  109. A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
  110. The role of erythrocytes and erythroid progenitor cells in tumors
  111. Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
  112. Abnormal methylation caused by folic acid deficiency in neural tube defects
  113. Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
  114. Plant Sciences
  115. Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
  116. Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
  117. Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
  118. Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
  119. Phytoremediation of pollutants from wastewater: A concise review
  120. Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
  121. Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
  122. Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
  123. Study on pecan seed germination influenced by seed endocarp
  124. Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
  125. The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
  126. Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
  127. Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
  128. Cloning and expression analysis of SERK1 gene in Diospyros lotus
  129. Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
  130. A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
  131. Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
  132. The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
  133. Food Science
  134. Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
  135. Binge eating disorder during COVID-19
  136. Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
  137. FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
  138. Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
  139. Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
  140. Functional constituents of plant-based foods boost immunity against acute and chronic disorders
  141. Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
  142. Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
  143. Ecology and Environmental Sciences
  144. Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
  145. Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
  146. Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
  147. Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
  148. Plant volatile organic compounds attractive to Lygus pratensis
  149. Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
  150. Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
  151. Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
  152. Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
  153. Bioengineering and Biotechnology
  154. Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
  155. Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
  156. Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
  157. Agriculture
  158. Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
  159. Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
  160. Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
  161. Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
  162. Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
  163. Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
  164. Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
  165. Animal Sciences
  166. Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
  167. Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
  168. SI: A Scientific Memoir
  169. Suggestions on leading an academic research laboratory group
  170. My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
  171. Erratum
  172. Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
https://doi.org/10.1515/biol-2021-0134
Schlagwörter für diesen Artikel
cell tight junction; calcium homeostasis; nephrolithiasis; hearing loss; gene association
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
  3. The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
  4. Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
  5. LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
  6. Association study of CLDN14 variations in patients with kidney stones
  7. Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
  8. Regulation of miR-30b in cancer development, apoptosis, and drug resistance
  9. Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
  10. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
  11. Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
  12. Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
  13. Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
  14. Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
  15. Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
  16. Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
  17. Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
  18. Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
  19. Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
  20. Nutrition intervention in the management of novel coronavirus pneumonia patients
  21. circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
  22. Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
  23. Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
  25. Comparison of axon extension: PTFE versus PLA formed by a 3D printer
  26. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
  28. Study on the mechanism of inhibiting patulin production by fengycin
  29. SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
  30. Relationship between blood clots and COVID-19 vaccines: A literature review
  31. Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
  32. Bioinformatics network analyses of growth differentiation factor 11
  33. NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
  34. Expression of Zeb1 in the differentiation of mouse embryonic stem cell
  35. Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
  36. Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
  37. Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
  38. Genetic susceptibility to high myopia in Han Chinese population
  39. Potential biomarkers and molecular mechanisms in preeclampsia progression
  40. Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
  41. Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
  42. The significance of PAK4 in signaling and clinicopathology: A review
  43. Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
  44. Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
  45. Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
  46. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
  47. MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
  48. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
  49. BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
  50. Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
  51. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
  52. A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
  53. Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
  54. Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
  55. Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
  56. A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
  57. β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
  58. Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
  59. BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
  60. Mucormycosis co-infection in COVID-19 patients: An update
  61. Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
  62. Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
  63. Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
  64. Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
  65. Nasopharyngeal tuberculosis: A case report
  66. Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
  67. Aberrant pulmonary immune response of obese mice to periodontal infection
  68. Bacteriospermia – A formidable player in male subfertility
  69. In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
  70. Effects of KCa channels on biological behavior of trophoblasts
  71. Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
  72. Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
  73. Prognostic signature related to the immune environment of oral squamous cell carcinoma
  74. Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
  75. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
  76. Role of MMP-2 and CD147 in kidney fibrosis
  77. Geometric basis of action potential of skeletal muscle cells and neurons
  78. Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
  79. Role of cerebellar cortex in associative learning and memory in guinea pigs
  80. Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
  81. Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
  82. Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
  83. Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
  84. Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
  85. Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
  86. Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
  87. Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
  88. One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
  89. S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
  90. Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
  91. Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
  92. Evaluation of prognostic markers in patients infected with SARS-CoV-2
  93. N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
  94. Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
  95. Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
  96. Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
  97. Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
  98. Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
  99. Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
  100. SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
  101. Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
  102. Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
  103. Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
  104. Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
  105. Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
  106. PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
  107. A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
  108. Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
  109. A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
  110. The role of erythrocytes and erythroid progenitor cells in tumors
  111. Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
  112. Abnormal methylation caused by folic acid deficiency in neural tube defects
  113. Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
  114. Plant Sciences
  115. Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
  116. Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
  117. Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
  118. Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
  119. Phytoremediation of pollutants from wastewater: A concise review
  120. Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
  121. Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
  122. Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
  123. Study on pecan seed germination influenced by seed endocarp
  124. Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
  125. The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
  126. Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
  127. Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
  128. Cloning and expression analysis of SERK1 gene in Diospyros lotus
  129. Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
  130. A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
  131. Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
  132. The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
  133. Food Science
  134. Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
  135. Binge eating disorder during COVID-19
  136. Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
  137. FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
  138. Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
  139. Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
  140. Functional constituents of plant-based foods boost immunity against acute and chronic disorders
  141. Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
  142. Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
  143. Ecology and Environmental Sciences
  144. Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
  145. Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
  146. Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
  147. Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
  148. Plant volatile organic compounds attractive to Lygus pratensis
  149. Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
  150. Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
  151. Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
  152. Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
  153. Bioengineering and Biotechnology
  154. Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
  155. Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
  156. Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
  157. Agriculture
  158. Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
  159. Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
  160. Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
  161. Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
  162. Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
  163. Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
  164. Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
  165. Animal Sciences
  166. Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
  167. Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
  168. SI: A Scientific Memoir
  169. Suggestions on leading an academic research laboratory group
  170. My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
  171. Erratum
  172. Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Gewinner des OpenAthens UX Award 2026
Gewinner des OpenAthens UX Award 2026
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2026 De Gruyter Brill
Heruntergeladen am 13.3.2026 von https://www.degruyterbrill.com/document/doi/10.1515/biol-2021-0134/html
Button zum nach oben scrollen