Home Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
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Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease

  • Ammar L. Hussein EMAIL logo , Dunia T. Nema and Gulboy A. Nasir
Published/Copyright: June 27, 2024

Abstract

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic fat accumulation in individuals consuming little or no alcohol, has become highly prevalent globally. Oxidative stress plays a central role in instigating inflammation and cell death pathways driving NAFLD progression. This case–control study aimed to elucidate the association between circulating levels of the pivotal non-enzymatic antioxidants – coenzyme Q10 and vitamins E and C – and liver injury parameters among 60 Iraqi NAFLD patients versus 30 healthy controls. NAFLD diagnosis entailed over 5% hepatic steatosis on ultrasound excluding other etiologies. Patients spanned three age groups: 20–29, 30–39, and 40–49. Substantially diminished antioxidant levels concurrent with elevated alkaline phosphatase enzyme were unveiled in NAFLD patients relative to controls (all p < 0.001). Age-based analysis reinforced widespread antioxidant depletion and liver enzyme augmentation across NAFLD patients. Significant correlations also emerged between antioxidants and liver parameters. Our novel observations confirm an antioxidant inadequacy likely perpetuating pathogenic oxidative reactions in NAFLD. Restoring such deficits through lifestyle or therapeutic interventions may confer preventative and disease-modifying value.

1 Introduction

Non-alcoholic fatty liver disease (NAFLD) represents the most frequent chronic liver disorder worldwide, with an approximate prevalence of 25% among the global adult population [1,2,3,4,5,6]. The condition is defined by excessive triglyceride accumulation within hepatocytes, prompting hepatic injury, in individuals consuming little or no alcohol [7,8,9,10]. Originally deemed a relatively benign state, simple steatosis can advance to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and ultimately hepatocellular carcinoma in a subset of patients over years to decades [11,12,13,14]. Nearly 30% of the general population may manifest some degree of NAFLD, rising over 50% among type 2 diabetics in reflection of the intimate pathogenic links with insulin resistance and metabolic dysfunction [1,15,16]. Mirroring the escalating global obesity epidemic, the prevalence of NAFLD is projected to increase markedly over forthcoming years, portending an immense future healthcare burden [1,17,18]. Developing preventative and therapeutic modalities for impeding disease onset and progression is therefore imperative.

A wealth of mechanistic evidence causally implicates oxidative stress in the pathogenesis of NAFLD [19]. Elevated generation of reactive oxygen species overwhelms endogenous antioxidant defenses, instigating inflammatory, fibrogenic, and cell death cascades that drive progressive liver injury [20,21]. Mitochondrial dysfunction, ER stress, immune activation, and other systems constitute sources of augmented reactive oxygen species among multiple preclinical NAFLD models and patients [22]. Accordingly, clinical studies demonstrate depletion of diverse enzymatic and non-enzymatic antioxidants encompassing superoxide dismutase, catalase, glutathione peroxidase, glutathione, vitamin E, vitamin C, and coenzyme Q10 in NAFLD subjects relative to healthy individuals [19,23,24]. Such redox imbalance is believed to arise due to the initial adaptive upregulation of antioxidants attempting to mitigate oxidative damage, followed by eventual overwhelm and decline of these defensive pathways [25]. Hence, strategies to bolster innate antioxidant capacity through lifestyle interventions or therapeutic supplementation represent a biologically rational approach to potentially retard NAFLD progression that warrants further exploration [26,27].

Vitamin E refers to eight structurally related compounds with the α-tocopherol isoform conveying the greatest bioavailability and antioxidant function [28]. Its phenolic hydroxyl moiety readily donates hydrogen to quench lipophilic radicals and reactive species, while other unique mechanisms like protein kinase C modulation elicit anti-inflammatory actions [29,30,31]. Animal studies of experimental NASH demonstrate vitamin E restoration of glutathione alongside reductions in oxidative damage, inflammation, stellate cell activation, and histological fibrosis versus disease controls [32]. The hydrophilic vitamin C directly scavenges diverse reactive oxygen species and also sparingly regenerates lipid-soluble antioxidants like vitamin E to disrupt deleterious oxidation reactions [33]. Epidemiological studies reveal an inverse relationship of vitamin C intake with human NAFLD severity, although occasional inconsistent outcomes have been reported [34,35,36]. Coenzyme Q10 is a crucial electron carrier that facilitates mitochondrial ATP generation and participates in membrane stabilization and beta-oxidation [37]. Through such properties, coenzyme Q10 elevation putatively suppresses lipotoxic liver injury, oxidative stress, and inflammation in NAFLD, with mixed clinical findings thus far [38,39,40].

In efforts to provide further human evidence regarding perturbations in redox homeostasis arising during NAFLD, we examined circulating levels of the above described, biologically active non-enzymatic antioxidants – coenzyme Q10 and vitamins E and C – alongside the hepatic injury marker alkaline phosphatase among 60 Iraqi NAFLD patients compared to 30 healthy controls. Determining whether antioxidant deficits associated with this high-risk condition could substantiate a basis for restoring such reserves nutritionally or pharmaceutically to mitigate pathogenic liver oxidative damage.

2 Materials and methods

2.1 Study design and participants

This case–control study enrolled 60 NAFLD patients alongside 30 healthy volunteers at Tikrit Teaching Hospital (Iraq) over a 3-month interval from October to December 2023. NAFLD diagnosis entailed ultrasonographic evidence of hepatic steatosis exceeding 5% of hepatocytes excluding secondary causes such as significant alcohol consumption, viral infection, or drugs per established criteria [39]. Patients spanned three age brackets: 20–29 years (n = 9), 30–39 years (n = 17), and 40–49 years (n = 34). Controls consisted of age-matched healthy adults without liver disease.

  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 Ethical Committee of College of Medicine, Tikrit University (203 on 06.02.2023).

2.2 Sample analysis

Overnight fasting blood samples were collected from participants and centrifuged to isolate serum. ELISA techniques quantified concentrations of coenzyme Q10, vitamin E, vitamin C (indices of antioxidant status), and alkaline phosphatase (marker of hepatic injury) per kit protocols.

2.3 Statistical analysis

Data were expressed as mean ± standard deviation. Significant between-group differences were evaluated by independent samples’ t-test or Mann–Whitney U test as appropriate, with p < 0.05 deemed statistically significant. Pearson’s correlation test determined linear associations between parameters. Statistical Package for Social Sciences software version 28.0 facilitated analyses.

3 Results

3.1 Demographic characteristics of study participants

Table 1 displays a comparative summary of demographic and clinical features between NAFLD patients and healthy controls. Most patients were middle-aged and obese in contrast to the young, normal-weight predominance among control adults.

Table 1

Demographic and anthropometric characteristics of NAFLD patients versus healthy controls

Variables Groups Patient Control Chi-square p value
Age groups 20–29 years 9 12 8.4 0.015
30–39 years 17 9
40–49 years 34 9
BMI Normal weight 2 18 47.8 0.00001
Overweight 13 10
Obesity 45 2
Sex Male 30 15 0 1
Female 30 15

3.2 Circulating antioxidants and liver enzyme among cases versus controls

As shown in Table 2, relative to healthy controls, Iraqi NAFLD patients displayed markedly reduced serum levels of coenzyme Q10 (29.5 ± 5.2 vs 18.3 ± 5.3 μmol/L), vitamin E (58.9 ± 18.2 vs 43.1 ± 22.0 μmol/L), and vitamin C (13.2 ± 2.7 vs 6.5 ± 2.7 mg/L) (all p < 0.001), indicating a gross systemic antioxidant deficit. Conversely, the hepatic injury indicator alkaline phosphatase was notably elevated among NAFLD patients compared to controls (101.7 ± 15.7 vs 74.4 ± 5.1 U/L, p < 0.001).

Table 2

Comparison of circulating antioxidants and alkaline phosphatase levels between NAFLD patients and healthy controls

Variable Patients, mean ± SD Control, mean ± SD p-value
CoQ10 18.32 ± 5.32 29.50 ± 5.18 p < 0.001
Vitamin E 43.14 ± 21.96 58.90 ± 18.20
Vitamin C 6.54 ± 2.71 13.20 ± 2.66
ALP 101.68 ± 15.72 74.30 ± 5.10

3.3 Stratified analysis of antioxidants and liver enzymes by age

Further age-wise scrutiny of cases versus controls, as delineated in Tables 35, reinforced widespread reductions in examined antioxidants among Iraqi NAFLD patients across all age groups, ranging from young adults to middle-aged individuals. Concurrently, alkaline phosphatase also remained markedly elevated in patients compared to controls across the age spectrum. The sole outlier was vitamin E in the youngest (20–29 years) patient subgroup, which did not significantly differ versus corresponding controls. Nevertheless, collectively these observations verify gross antioxidant deficits and liver enzyme augmentation manifesting quite ubiquitously from early in the natural history of NAFLD regardless of age.

Table 3

Comparison of circulating antioxidants and alkaline phosphatase among 20–29-year-old NAFLD patients versus controls

Variables Patients, mean ± SD, N = 8 Control, mean ± SD, N = 10 p-value
(20 – 29) years – G1
CoQ10 19.59 ± 6.48 28.96 ± 4.50 0.002
Vitamin E 61.28 ± 31.37 56.89 ± 15.92 0.724
Vitamin C 6.73 ± 1.74 13.13 ± 1.82 0.001
ALP 97.43 ± 12.82 75.25 ± 5.52 0.001
Table 4

Comparison of circulating antioxidants and alkaline phosphatase among 30–39-year-old NAFLD patients versus controls

Variables Patients, mean ± SD, N = 8 Control, mean ± SD, N = 10 p-value
(30–39) years – G2
CoQ10 19.089 ± 6.329 30.905 ± 5.248 0.001
Vitamin E 33.361 ± 8.672 62.730 ± 22.559 0.002
Vitamin C 6.73 ± 1.74 13.13 ± 1.82 0.001
ALP 97.43 ± 12.82 75.25 ± 5.52 0.001
Table 5

Comparison of circulating antioxidants and alkaline phosphatase among 40–49-year-old NAFLD patients versus controls

Variables Patients, mean ± SD, N = 15 Control, mean ± SD, N = 10 p-value
(40–49) years – G3
CoQ10 17.74 ± 4.65 28.61 ± 6.09 0.001
Vitamin E 43.19 ± 21.38 57.10 ± 16.85
Vitamin C 6.61 ± 3.24 13.53 ± 2.99
ALP 101.20 ± 15.37 75.25 ± 5.14

3.4 Interrelationships between oxidative stress markers and liver function

Correlation analysis, as shown in Figure 1, unveiled no significant linear association between coenzyme Q10 and alkaline phosphatase amongst Iraqi NAFLD patients (p = 0.45). However, circulating coenzyme Q10 manifested a robust inverse correlation with vitamin C levels (r = −0.7, p = 0.001). Significant positive correlations were apparent between coenzyme Q10 and vitamin E (r = 0.7, p = 0.001), alkaline phosphatase and vitamin C (r = 0.4, p = 0.03), alkaline phosphatase and vitamin E (r = 0.4, p = 0.03), along with vitamins C and E (r = −0.5, p = 0.04).

Figure 1 
                  Correlative analysis between circulating antioxidants and liver enzyme in Iraqi NAFLD patients. (a) Association between coenzyme Q10 and alkaline phosphatase levels. (b) Association between coenzyme Q10 and vitamin C levels. (c) Association between coenzyme Q10 and vitamin E levels. (d) Association between alkaline phosphatase and vitamin C levels. (e) Association between alkaline phosphatase and vitamin E levels. (f) Association between vitamin C and vitamin E levels.
Figure 1

Correlative analysis between circulating antioxidants and liver enzyme in Iraqi NAFLD patients. (a) Association between coenzyme Q10 and alkaline phosphatase levels. (b) Association between coenzyme Q10 and vitamin C levels. (c) Association between coenzyme Q10 and vitamin E levels. (d) Association between alkaline phosphatase and vitamin C levels. (e) Association between alkaline phosphatase and vitamin E levels. (f) Association between vitamin C and vitamin E levels.

4 Discussion

In this case–control study, we report markedly depleted circulating concentrations of the pivotal non-enzymatic antioxidants; coenzyme Q10, vitamin E, and vitamin C paralleling elevated alkaline phosphatase liver enzyme among Iraqi NAFLD patients relative to healthy controls. Age-stratified analysis reinforced pervasive antioxidant deficits and liver function abnormalities manifesting quite ubiquitously regardless of age variation. Significant inter-relationships were also unveiled between these redox homeostatic markers and hepatic parameter. Collectively, our novel observations verify perturbation of antioxidant capacity likely perpetuating pathogenic oxidative damage that drives NAFLD progression. Strategies to rectify such inadequacies nutritionally or pharmacologically may offer preventative and therapeutic value.

Excess intrahepatic lipid accumulation incites complex pathogenic cascades encompassing lipotoxicity, aberrant metabolites, mitochondrial dysfunction, ER stress, and immune activation that boost the production of reactive oxygen species and nitrogen species [22,41]. Resultant oxidative stress overwhelms endogenous antioxidant defenses to trigger inflammatory, apoptotic, and fibrogenic pathways critical to NASH and fibrosis development [20]. Accordingly, both experimental models and human studies demonstrate the depletion of diverse enzymatic and non-enzymatic antioxidants in NAFLD subjects [23,26,42,43]. Our observations confirm significant attrition of circulating coenzyme Q10, vitamin E, and vitamin C levels amongst Iraqi NAFLD patients, likely perpetuating such hepatic oxidative injury. Vitamin E demonstrates potent radical-scavenging activity and also enhances glutathione recycling, suppresses inflammatory signaling, and reduces oxidative damage, immune infiltration, and fibrosis progression in experimental NASH [32,44,45]. Vitamin C directly deactivates diverse reactive oxygen species and sparingly regenerates membrane antioxidant vitamin E following oxidative stress [33]. Coenzyme Q10 facilitates mitochondrial respiration and correspondingly lowers ROS generation, while also stabilizing membranes [37]. Augmenting the availability of such innate compounds through dietary or supplemental means may therefore confer preventative and therapeutic advantages by mitigating oxidative reactions underlying NAFLD pathogenesis – a premise warranting further scrutiny. In addition to the impact of coenzyme Q10 on liver, it carries potential beneficial effects against drug toxicity [46,47] or improvement of other chronic conditions [48,49,50].

Interestingly, whereas coenzyme Q10 did not associate with alkaline phosphatase levels, significant correlations existed between the vitamins and enzyme. Differential subcellular partitioning probably determines such divergent interrelationships. Nevertheless, collectively restoring depressed antioxidant reserves may impart broader therapeutic benefit. Our age-defined analysis notably reinforced an overt antioxidant deficit manifesting quite pervasively from younger adulthood onwards regardless of demographic variation. This suggests that redox imbalance arises relatively early in NAFLD and represents an integral component of pathogenic progression rather than solely a late secondary phenomenon. Addressing such inadequacies proactively could therefore offer advantage.

This study has certain limitations meriting consideration. Our cohort size was modest, preventing more nuanced patient stratification by gender, body mass index (BMI), or other factors. Dietary habits, physical activity profiles, smoking status, and comorbid conditions were not captured but may conceivably impact outcomes. The histological examination represents the gold standard for accurately staging NAFLD severity. Nevertheless, our findings provide clinical evidence substantiating the pronounced depletion of key non-enzymatic antioxidants and verifying oxidative stress contributions toward early NAFLD pathogenesis. Further studies in larger populations would valuably validate and extend these observations.

5 Conclusion

In conclusion, relative to healthy controls, Iraqi NAFLD patients exhibited significantly reduced circulating concentrations of the pivotal antioxidants coenzyme Q10, vitamin E, and vitamin C complementing elevated alkaline phosphatase liver enzyme. Age-stratified analysis reinforced pervasive antioxidant inadequacy and liver dysfunction progressing from young adulthood regardless of demographic variability. Significant inter-relationships were also unveiled between these redox-homeostatic markers and enzyme parameter. Collectively, our novel observations confirm perturbation of antioxidant capacity likely perpetuating pathogenic oxidative reactions underlying NAFLD onset and progression. Strategies to rectify such deficits through lifestyle and therapeutic interventions may offer preventative and disease-modifying value that warrants further evaluation.

Several limitations should be considered when interpreting findings from this study. The study is a case–control, which can only establish associations and not causality. Longitudinal studies or randomized controlled trials would provide stronger evidence for the role of antioxidants in NAFLD. The cohort size was modest, restricting extensive demographic-based stratifications. Detailed dietary information, smoking patterns, physical activity profiles, and comorbidity data were not captured. The study focused on the levels of coenzyme Q10 and vitamins E and C as non-enzymatic antioxidants. There are other antioxidants that could also play a role in NAFLD, and their inclusion in future studies would provide a more comprehensive understanding of antioxidant status in this condition. Moreover, only three age groups included in the study and other age groups need to be investigated. Histopathology represents the diagnostic gold standard for precisely staging NAFLD severity and inflammation, rather than relying exclusively on imaging criteria. Nonetheless, such limitations apply equally to cases and controls. Hence, this study provides novel clinical evidence substantiating oxidative stress mechanisms in early human NAFLD pathogenesis.

Acknowledgments

The authors are thankful to the staff of the Department of Biochemistry/College of Medicine/Tikrit University for technical assistance with sample analyses. Thanks are also in order for the staff of the Tikrit Teaching Hospital laboratory and all participants volunteering to contribute toward this research.

  1. Funding information: Authors state no funding involved.

  2. Author contributions: Conceptualization, A.L.H. and D.T.N.; methodology, A.L.H. and D.T.N.; software and validation, D.T.N.; formal analysis, investigation, resources, and data curation, A.L.H. and G.A.N.; writing – original draft preparation, A.L.H. and G.A.N.; writing – review and editing, G.A.N.; visualization, A.L.H.; supervision, G.A.N.

  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.

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Received: 2024-02-06
Revised: 2024-04-06
Accepted: 2024-05-06
Published Online: 2024-06-27

© 2024 the author(s), published by De Gruyter

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Articles in the same Issue

  1. Biomedical Sciences
  2. Constitutive and evoked release of ATP in adult mouse olfactory epithelium
  3. LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
  4. PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
  5. Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
  6. The role and mechanism of esketamine in preventing and treating remifentanil-induced hyperalgesia based on the NMDA receptor–CaMKII pathway
  7. Brucella infection combined with Nocardia infection: A case report and literature review
  8. Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
  9. Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
  10. PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
  11. Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
  12. Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
  13. Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
  14. A case of Trousseau syndrome: Screening, detection and complication
  15. Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
  16. Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
  17. Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
  18. Current research and evidence gaps on placental development in iron deficiency anemia
  19. Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
  20. Pheochromocytoma-induced myocardial infarction: A case report
  21. Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
  22. Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
  23. Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
  24. KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
  25. Current state of research on copper complexes in the treatment of breast cancer
  26. Exploring antioxidant strategies in the pathogenesis of ALS
  27. Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
  28. IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
  29. The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
  30. Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
  31. P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
  32. Probiotics for inflammatory bowel disease: Is there sufficient evidence?
  33. Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
  34. Microbial perspective on the skin–gut axis and atopic dermatitis
  35. Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
  36. Highly specific vaginal microbiome signature for gynecological cancers
  37. Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
  38. The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
  39. Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
  40. Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
  41. Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
  42. VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
  43. Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
  44. Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
  45. Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
  46. Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
  47. Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
  48. Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
  49. Cystic adenomyoma of the uterus: Case report and literature review
  50. Mesoporous silica nanoparticles as a drug delivery mechanism
  51. Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
  52. Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
  53. Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
  54. Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
  55. Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
  56. Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
  57. Embedded monitoring system and teaching of artificial intelligence online drug component recognition
  58. Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
  59. Yak meat content in feed and its impact on the growth of rats
  60. A rare case of Richter transformation with breast involvement: A case report and literature review
  61. First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
  62. Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
  63. Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
  64. Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
  65. The role of Phafin proteins in cell signaling pathways and diseases
  66. Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
  67. Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
  68. Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
  69. Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
  70. Imaging manifestations of ductal adenoma of the breast: A case report
  71. Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
  72. Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
  73. Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
  74. Circular RNAs as potential biomarkers for male severe sepsis
  75. Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
  76. The expression and biological role of complement C1s in esophageal squamous cell carcinoma
  77. A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
  78. Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
  79. HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
  80. IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
  81. Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
  82. Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
  83. Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
  84. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
  85. Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
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