Cellular and Molecular Biology

Hepatitis B reactivation linked to tumor necrosis factor-α inhibitors in rheumatoid arthritis: a systematic review and meta-analysis

Pouria ‎ Salajegheh ‎ — 2025-12-06

This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in patients with HBV-related rheumatoid arthritis (RA) undergoing TNF inhibitor (TNFi) therapy. A systematic search of Embase, PubMed/MEDLINE, Scopus, Web of Science, ClinicalTrials.gov and the Cochrane Library was conducted, and pooled HBVr rates were calculated using random-effects models with subgroup analyses based on region, HBV serostatus, glucocorticoid use, antiviral prophylaxis, and TNFi type. Data from 15 studies, including 916 patients, were analyzed, revealing a pooled HBVr rate of 2% (95% CI: 0.01–0.03) with low heterogeneity (I² = 0.79%, p = 0.133). Regional variation was observed, with no HBVr cases in European studies (0.01; 95% CI: −0.01–0.03) and a 2% rate in Asian studies (95% CI: 0.01–0.04). HBsAg-positive patients demonstrated significantly higher HBVr rates (16%; 95% CI: 0.04–0.28) compared with HBsAg-negative patients (4%; 95% CI: −0.01–0.09), corresponding to an odds ratio (OR) of 12.60 (95% CI: 3.73–42.53). Patients receiving antiviral prophylaxis had a 6% HBVr rate compared to 3% in those without prophylaxis, though the difference was not statistically significant (OR: 1.30; p = 0.726). Similarly, glucocorticoid use did not significantly influence HBVr risk (6% vs. 5%; OR: 0.73; p = 0.563). HBVr rates also varied by TNFi type, with 4% for adalimumab, 3% for etanercept, and 2% for infliximab. Overall, TNFi therapy in HBV-related RA is associated with a low but clinically relevant risk of HBVr, with higher rates in HBsAg-positive patients and modest variation by region and drug type, while antiviral prophylaxis and glucocorticoid use appear to have no significant effect on risk.

MiR-200b-3p is involved in colorectal cancer progression by targeting DDIT4

Zhimin Liu — 2025-12-06

This study aimed to explore the functional dynamics between microRNA-200b-3p (miR-200b-3p) and DNA damage-induced transcript 4 (DDIT4) in colorectal cancer (CRC) and their potential as therapeutic targets. Pan-cancer analysis was conducted to evaluate DDIT4 expression across multiple cancer types. Immunohistochemical staining of CRC clinical samples was performed to confirm DDIT4 protein levels. Functional assays, including cell proliferation, migration, and invasion analyses, were used to assess the effects of DDIT4 silencing in CRC cells. Bioinformatics and experimental validation identified microRNAs targeting DDIT4 and their prognostic significance using GEPIA, HPA and ENCORI databases. Pan-cancer analysis showed DDIT4 was highly expressed in CRC compared to other cancers. Immunohistochemistry confirmed moderate to high DDIT4 expression in CRC patient samples. Knockdown of DDIT4 significantly reduced proliferation, migration, and invasion of SW480 CRC cells. miRNA analysis identified miR-200b-3p as a potential regulator of DDIT4. Low expression of miR-200b-3p correlated with poor prognosis in CRC patients. Luciferase reporter assays confirmed direct binding of miR-200b-3p to DDIT4 mRNA. Furthermore, overexpression of DDIT4 was shown to mitigate the tumor-suppressive effects of miR-200b-3p, restoring proliferation, migration, and invasion. DDIT4 promotes CRC progression and is regulated by miR-200b-3p. Targeting the miR-200b-3p/DDIT4 axis may represent a novel therapeutic approach for CRC treatment.

Xanthohumol suppresses ECM degradation in osteoarthritis through the Nrf2/ PERK/ATF4/C/EBPβ signaling pathway

Tiansheng Zheng — 2025-12-06

In this study, the therapeutic efficacy of Xanthohumol (XH) was evaluated as a preventive agent for extracellular matrix (ECM) degradation in osteoarthritis, using the in vivo monosodium iodoacetate-induced arthritis model in rats, along with the in vitro model of interleukin (IL)-1β-stimulated C28/I2 chondrocytes. With established concentrations of XH, the extent to which this compound may modulate cartilaginous architecture, enzymatic activity, or ECM synthesis was determined. The results clearly show that, in comparison with controls, this drug significantly reduced the catabolism of ECM, exerting a concentration-dependent effect that reduced the production of MMP13 (by 46% in vitro) with enhanced transcriptional production of collagen II (by 38% in vitro) versus controls, as well as exhibiting a cartilage degradation reduction of 31% compared with controls. The results, based on downstream messenger studies, show that this drug reduced transcriptional activation of ER-stress-driven catabolism associated with the PERK/ATF4/C/CEBPβ pathway, with a subsequent, noteworthy increase (by 52%) in the transcriptional activity of Nrf2. Over-expression or activation studies reduced the chondroprotective effects, entirely eliminating the silencing studies of Nrf2. These results clearly indicate that this drug, with its chondroprotective effects, suppresses catabolism, stimulates cartilaginous reinstatement, and reversibly decreases OARSI scores in treated animals. This study indicates that this drug may offer a promising therapeutic modality in modulating ER-stress-driven catabolysis as its pathomechanistic principle in targeted use for osteoarthritis prevention.

Allele frequency of CTLA-4 rs231775 (+49 A>G) gene polymorphism and its association with cancer susceptibility in the Saudi Arabian population and other ethnic groups

Mohammad Salman Akhtar — 2025-12-06

Single-nucleotide polymorphisms (SNPs) of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene found in exon 1 are directly associated with the progression and onset of autoimmune disease and various human cancers. These SNPs are commonly known prognostic biomarkers for the prediction and early onset of cancer risk. The variant frequency of CTLA-4 rs231775 (+49 A>G) polymorphisms may affect the various ethnic groups differently. This study assessed the allelic frequency distribution of rs231775 (+49 A>G) polymorphisms in the Saudi Arabian population and compared it with other world populations. The data were extracted from case-control studies in several ethnic groups using PubMed (Medline) and similar web databases. The frequency of CTLA-4 rs231775 (+49 A>G) variant allele (G) was observed at 33.0% and different frequencies were found significant for Pakistan (p=0.02), China (p=0.05), China (p= 0.00), Iran (p=0.00), Poland (p=0.00), the USA (p=0.00) and Turkey (p=0.02) when the prevalence of Saudi Arabian population is compared to that of other populations. The observed finding reveals a distinct pattern of CTLA-4 rs231775 (+49 A>G) polymorphism variant allele in the populations of Saudi Arabia, maybe because of the differences in ethnicity. The observed findings can help assess the risk for the population harboring the risk allele of the rs231775 (+49 A>G) SNP and their subsequent susceptibility to cancer.

CircFOXK2 induces non-small cell lung cancer tumorigenesis through the miR-328-5p/PKP3 axis

Tongwei Xiang — 2025-12-06

Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) implicated in the onset and advancement of various human cancers. Among these, circFOXK2 has been linked to non-small cell lung cancer (NSCLC); however, its precise functions and underlying molecular mechanisms are not fully understood. This study shows the first experimental findings that circFOXK2 promotes NSCLC tumor progression by modulating the miR-328-5p/PKP3 signaling pathway. Levels of circFOXK2, miR-328-5p, and PKP3 were evaluated by qRT-PCR. Cellular (NSCLSC) proliferation was examined via CCK-8 assays, migratory capacity via wound healing, and invasive potential via Transwell assays. Potential binding interactions between miR-328-5p and circFOXK2 were first assessed using bioinformatic analysis and verified using a dual-luciferase reporter assay (DLRGAs). Regulatory relationships among circFOXK2, miR-328-5p, and PKP3 were further investigated through qRT-PCR analysis. Elevated expression of circFOXK2 and reduced levels of miR-328-5p were observed in NSCLC cell lines and tissues. Functionally, circFOXK2 enhanced cellular propagation, dissemination, and invasion in vitro. Mechanistic evaluation revealed that circFOXK2 upregulates PKP3 by acting as an miR-328-5p sponge. The findings demonstrate that circFOXK2 contributes to NSCLC tumorigenesis via modulation of the miR-328-5p/PKP3 pathway, identifying this signaling axis as a potential therapeutic target in NSCLC.

Glycation-mediated binding defect in human serum albumin transport of erdosteine: implications in diabetes

Nada Mahmoud Dhab'an Al-Atawi — 2025-12-06

Human serum albumin (HSA) is a protein in human blood primarily responsible for transporting ligands. Erdosteine is an important drug used in the treatment of acute and chronic respiratory diseases. This study employed molecular docking and molecular dynamics simulation methods to investigate the interaction between erdosteine and HSA. In the presence of glucose, the binding energy of erdosteine decreased, indicating reduced binding affinity. Docking results suggested changes in the interaction sites and binding residues, with the preferential binding site shifting in the presence of glucose. Molecular dynamics simulations showed increased fluctuations when glucose was present. The solvent-accessible surface area of all HSA systems remained stable under physiological conditions, with a slight decrease over time. Analysis of secondary structural changes indicated stable erdosteine binding with no alteration in HSA’s secondary structure. Hydrogen bonding analysis showed a decrease in hydrogen bond formation between erdosteine and HSA in the presence of glucose; since hydrogen bonding is crucial for ligand-protein interactions, this reduction is significant. Principal component analysis indicated that HSA’s flexibility was not affected by erdosteine binding, even in the presence of glucose. Electrostatic interactions played a key role in erdosteine binding to HSA, with Arg 218 contributing the highest energy in the complex under glucose conditions. Elevated glucose levels in diabetic patients can induce structural and functional changes in proteins, potentially impacting the effective management of coexisting clinical conditions. Such changes may affect drug binding to transport proteins, thereby altering drug efficacy, clearance, and therapeutic outcomes.

Shared gene functions in autoimmune diseases identified via integrated bioinformatics analysis

Saniye Elvan Öztürk — 2025-12-06

Genetic transmission has minimal impact on autoimmune diseases compared to environmental factors. In conclusion, studies now focus on gene expression changes for diagnosis and treatment. This study used stringent cut-off values (p < 0.05, Log2(FoldChange) > 5) to monitor gene expression changes. Gene Ontology and Reactome Pathways enrichment analyses were performed, and interactions between differentially expressed genes (DEGs) were analyzed using the STRING database. Biomarker candidate genes were investigated across ten autoimmune diseases. Non-coding genes, particularly LINC01833 (upregulated in four diseases) and CD177 (upregulated in three diseases), were significant. The VCX, SLC, and KLK families were notably upregulated. Non-coding RNAs RNU5D-1 and MIR3648-1 were shared in two disease groups. Among shared genes between multiple sclerosis (MS) and ankylosing spondylitis (AS), ALPL, CHI3L1, HBM, MYL4, and PI3 were prominently downregulated. This study highlights the identification of differentially expressed signature genes across ten autoimmune diseases with high significance cut-offs (p < 0.05, Log2(FoldChange) > 5), suggesting their potential as significant targets for diagnosis and treatment.

Expression and significance of ALDH1A1, CD44, and OCT3/4 stem cell markers in glioblastoma tissues: an immunohistochemical study in Iraqi patients

Zaynab S. Abdulghany — 2025-12-06

Cancers of the brain and nervous system are among the top five most common malignancies affecting both men and women in Iraq. Improvements in diagnostic techniques alongside increased medical awareness have facilitated earlier detection, thereby potentially improving patient outcomes. Cancer stem cells (CSCs) have been recognized as key players in the initiation, progression, and recurrence of tumors, including glioblastoma, the most aggressive form of brain cancer. These CSCs are characterized by specific markers that contribute to tumor growth, resistance to therapy, and poor prognosis. In this study, we collected 26 glioma tissue samples from Iraqi patients and classified them according to tumor grade. Using immunohistochemical methods, we investigated the expression patterns of three important CSC markers—ALDH1A1, CD44, and OCT3/4—across different glioblastoma grades. Our findings demonstrated a significant upregulation of cytoplasmic ALDH1A1 and membrane-bound CD44 in higher-grade tumors (grades III and IV), with P-values of less than 0.0174 and 0.0013, respectively. Additionally, nuclear OCT3/4 expression was markedly increased in these advanced tumor grades (P < 0.05), suggesting a role in tumor aggressiveness and stemness. These data provide compelling evidence that ALDH1A1, CD44, and OCT3/4 are not only involved in glioblastoma progression but may also serve as useful prognostic biomarkers. Furthermore, their elevated presence in more malignant tumors highlights their potential as targets for novel therapeutic interventions aimed at improving treatment efficacy and patient survival. This study thus contributes valuable insights into the molecular landscape of glioblastoma in the Iraqi population and sets a foundation for future research in targeted cancer therapy.

Understanding the early onset of intracellular lipid accumulation induced by oleic and palmitic acids in HepG2 cells

Esther Jebarani Elangovan — 2025-12-06

Increasing hepatic lipid accumulation is the primary cause of non-alcoholic fatty liver disease (NAFLD), which has become an emerging health concern globally. Many studies have used the HepG2 cell-based in vitro model of NAFLD to investigate intracellular lipid accumulation after several hours of exposure to free fatty acids (FFAs). However, the molecular mechanisms underlying the early onset of lipid accumulation are yet to be unveiled. In this study, we examined oleic acid (OA) and palmitic acid (PA)- induced lipid accumulation in HepG2 cells at early time points, i.e., in minutes. Using Oil Red O staining and fluorescence microscopy imaging, we observed a time-dependent increase in intracellular lipid accumulation in cells treated with 0, 0.25, 0.5, and 1.0 mM FFAs. Notably, significant lipid droplet formation was detected within 15 min of OA treatment at 0.5 and 1.0 mM concentrations compared to the control, whereas PA did not elicit such an early response. Gene expression analysis revealed upregulation of genes related to lipid metabolism (SREBF1, PDK4, and G6PC), beta-oxidation (CPT1a) and cholesterol synthesis (HMGCR) at the early time point. Additionally, immunoblot analysis showed increased expression of Fatty acid synthase (FASN), which is a well-known marker of lipogenesis. In summary, our findings indicate that OA induces lipid accumulation more robustly than PA at early time points, providing insights into the molecular changes at the onset of NAFLD progression.

Skin regenerative potential of polydeoxyribonucleotide isolated from Saussurea involucrata

Da Jung Kim — 2025-12-06

Saussurea involucrata, commonly known as snow lotus, is a rare medicinal plant that is traditionally used in several countries owing to its therapeutic properties. Snow lotus extracts have been shown to exert anti-inflammatory effects and reduce reactive oxygen species levels. Although various bioactive compounds have been identified in snow lotus, the biological activity and underlying mechanisms of DNA isolated from this plant remain unexplored. This study aimed to investigate the skin-regenerative properties of polydeoxyribonucleotide (PDRN) isolated from snow lotus. PDRN was extracted and purified from dried flowers of S. involucrata. Water-soluble tetrazolium salt 1, wound healing, and enzyme-linked immunosorbent assays were used to evaluate the effects of snow lotus PDRN on cell proliferation, cell migration, and collagen synthesis, respectively. We also measured matrix metalloproteinase 1 (MMP1) mRNA expression after snow lotus PDRN treatment. Snow lotus–derived PDRN was non-cytotoxic to human skin cells and significantly promoted cell proliferation and migration. Additionally, it enhanced collagen synthesis by suppressing the expression of MMP1. These findings demonstrate that snow lotus PDRN may be a promising anti-aging agent and may serve as a valuable ingredient in cosmeceutical formulations.

Vaccination and vitamin D in relation to disease severity and mortality in patients with COVID-19 disease: a follow-up study

Aleen Sardar Al-noori — 2025-12-06

The emergence of Coronavirus Disease 2016 (COVID-16), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly escalated into a global pandemic, resulting in millions of confirmed cases and deaths worldwide. The objective of this study was to examine the effects of vitamin D and vaccination on mortality and disease severity in patients with COVID-16. In this cross-sectional study, we observed the suspected and confirmed admitted patients with COVID-19 for the possible outcomes after admission to the hospital. The study included patients with a mean age of 71.01 years (range: 28–66), predominantly aged ≥60 years (85.14%) and male (85.05%). Most patients were unvaccinated (77.03%) upon admission. Admission duration ranged from 1–30 days, with the highest proportion staying 8–14 days (36.16%), followed by 1–3 days and >14 days (each 21.62%). Symptoms appeared 1–46 days pre-admission (median: 8 days). Disease severity was critical (41.86%), severe (28.38%), moderate (25.68%), and mild (4.05%). All patients required oxygen. Mortality was 54.05%, 32.43% were discharged unknown, and 13.51% recovered. Key comorbidities included hypertension (66.22%), diabetes (37.84%), IHD (25.68%), smoking (21.62%), and CKD (12.16%). Universal fever presentation included persistent (44.63%) and moderate (28.66%) types. Common symptoms were shortness of breath (66.67%), cough (75.68%), chest pain (60.81%), fatigue (52.7%), and anorexia (50.0%). Vaccination (22.67%) and vitamin D status showed no significant association with disease severity or outcomes. Most patients were elderly, male, unvaccinated, and had comorbidities; high mortality was observed, with no significant association between outcomes and vaccination or vitamin D status.

Tirzepatide alters oncogenic signaling pathways in colorectal cancer cells in vitro

Nasrin M. Fadhil — 2025-12-06

Obesity prevalence is rapidly increasing worldwide, necessitating diverse treatment approaches ranging from pharmacotherapy to surgical interventions. Tirzepatide, a recently approved dual GIP/GLP-1 receptor agonist, has shown therapeutic promise, but its impact on cancer-related pathways remains unclear. This in vitro study investigated the molecular effects of tirzepatide on colorectal cancer SW48 cells by assessing the expression of key regulatory genes, including NF-kB, p53, c-Myc, and CASP8, after treatment with varying tirzepatide concentrations compared to untreated controls. Results demonstrated significant upregulation of the tumor suppressor gene p53 and the pro-apoptotic gene CASP8 (notably a 68.37-fold increase in one treatment group, P = 0.0002), alongside increased c-Myc expression in higher dose groups. These findings suggest that tirzepatide exerts anti-cancer effects in colorectal cancer cells by suppressing NF-kB–mediated inflammation, activating p53-dependent tumor suppression, and promoting CASP8-mediated apoptosis. The concurrent upregulation of c-Myc with p53 and CASP8 highlights potential context-dependent regulatory mechanisms. Overall, this study provides mechanistic insights into tirzepatide’s modulation of oncogenic signaling pathways, supporting its potential role in colon cancer therapeutics.

Combined intrathecal and intravenous exosome injection efficiency in a multiple sclerosis patient: a case report

Azam Mohammad Jafari — 2025-12-06

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system with limited treatment efficacy for progressive forms. Mesenchymal stem cells (MSCs) and their secreted exosomes offer therapeutic potential via regenerative and immunomodulatory actions, including T-cell suppression and neurotrophic factor secretion. Exosomes, as cell-free alternatives, may mediate MSC effects by delivering cargo such as microRNAs, potentially promoting oligodendrocyte precursor cell differentiation and blood–brain barrier stabilization with reduced immunogenicity. Preclinical experimental autoimmune encephalomyelitis models and early MSC clinical trials demonstrate promise in reducing disease severity, although optimization of exosome sources, delivery routes (intrathecal versus intravenous), dosing, and standardization remains a challenge for clinical translation. Here, we describe a 44-year-old female with a 21-year history of progressive MS unresponsive to interferon beta-1a and Ocrelizumab, who presented with widespread neurological deficits, including sensory disturbances, weakness, and urge incontinence. Examination revealed ataxia, intention tremor, and hyperreflexia, with previous MRIs confirming MS plaques. In 2025, she received allogeneic umbilical cord-derived MSC exosomes (1 cc intrathecally; 1 cc intravenously at half dose) with adjunctive intravenous laser therapy. Within three weeks, she reported 70–80% symptomatic improvement, including resolution of Lhermitte’s sign and enhanced muscle strength, vision, memory, and energy. Two-month follow-up MRIs showed persistent lesions without new contrast enhancement, indicating no active disease progression. This case highlights significant symptomatic improvement in long-standing progressive MS following combined intrathecal and intravenous allogeneic UC-MSC exosome administration. The rapid clinical benefits and absence of new MRI activity suggest a potential modulatory role for exosome therapy in MS, although these encouraging findings from a single case with adjunctive therapy necessitate larger, controlled clinical trials to validate efficacy, safety, and optimal protocols, and to elucidate underlying mechanisms.

Update on glycogen storage disease: a brief review of the main disorders

Ayed A. Dera — 2025-12-06

A glycogen storage disease (GSD) is a metabolic disorder caused by a deficiency of an enzyme or transport protein affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells. Several enzymes are required for the processes of glycogenesis and glycogenolysis. Glycogen storage diseases happen when a person doesn’t have one or more of these enzymes. GSD in almost all cases is genetic (In exceptional cases, it can be environmental, like GSD in livestock). Genetic GSD results mainly from inborn error in carbohydrate metabolism, where genetically faulty or malfunctioning enzymes or transport proteins are involved. It has many different types and diagnoses depending upon history, physical examinations and more specifically, blood tests and biopsies for related disturbances and genetic testing wherever mutations are being suspected. It is very important to distinguish the different types so that the patient receives the correct treatment. To even summarize the treatment modalities of the different sub-groups was beyond the scope of this study. We hope that it will elucidate better approaches and techniques amongst collaborative team members from the medical fraternity.

Molecular and cellular biomarkers in Crohn’s disease: from pathogenesis to clinical application

Alexander Blagov — 2025-12-06

Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by transmural inflammation that can affect any part of the gastrointestinal tract. Early and accurate diagnosis remains challenging due to the heterogeneous nature of the disease and overlapping symptoms with other gastrointestinal disorders. Current diagnostic approaches rely on a combination of clinical presentation, endoscopic findings, histological examination, and imaging studies, which can be invasive and time-consuming. The identification of reliable biomarkers could significantly improve diagnostic accuracy and reduce the need for invasive procedures. This review examines currently used biomarkers, including C-reactive protein, fecal calprotectin, and anti-Saccharomyces cerevisiae antibodies, while exploring emerging potential biomarkers such as microRNA panels, metabolomic signatures, and novel inflammatory mediators. Recent advances in genomics, proteomics, and metabolomics have revealed promising biomarker candidates that could enhance diagnostic precision and enable personalized treatment approaches. Understanding the performance characteristics and clinical utility of these biomarkers is crucial for their implementation in routine clinical practice and improved patient outcomes.