Molecular Biology Reports最新文献

Background: Thyroid hormones are mainly concerning with regulation of organs metabolism. Hypothyroidism is a pathological condition characterized by decrease of T3 and T4 level that negatively impact various organs especially liver and lung. Dapagliflozin (DAPA) is an anti diabetic drug posses antioxidant and anti apoptotic properties AIM OF THE STUDY: The aim of this work is to identify the effect of DAPA on disturbance of liver and lung functions result from hypothyroidism MATERIALS AND METHODS: Twenty four rats (6 rats/group) were divided into four groups: control group, DAPA group that received DAPA (1 mg/kg/day for five weeks), PTU group that received propylthiouracil (15 mg/kg/day for five weeks), PTU+ DAPA group that received PTU and DAPA as described in the other groups RESULTS: Hypothyroidism induced oxidative stress associated mitophagy disturbance in both lung and liver with development of apoptosis in liver. DAPA avoided this effect CONCLUSION: DAPA protects against liver and lung injury result from hypothyroidism.

Dimethyl fumarate (DMF) is an electrophilic compound used clinically for multiple sclerosis and psoriasis. We elaborate here that the pharmacological effects of DMF extend beyond the well-known activation of the NRF2 antioxidative pathway. Indeed, DMF directly modifies reactive cysteine residues on multiple proteins in immune and neural cells, leading to diverse anti-inflammatory, immunomodulatory, and neuroprotective actions. Recent studies revealed that DMF may affect proteins involved in inflammasome activation, glycolysis, and cell signaling pathways, including JAK-STAT and NF-kB. These effects may expand the potential clinical applications of DMF in diverse pathologies, including neurodegenerative, cardiovascular, and pulmonary diseases. We summarize current findings on chemical reactivity, target proteins, and emerging clinical applications of DMF, highlighting new opportunities for DMF repurposing.

Background: ADAMTS-2 is a key extracellular matrix (ECM) remodeling enzyme increasingly implicated in osteosarcoma biology. Although ADAMTS-2 is known to participate in collagen processing and ECM turnover, the upstream inflammatory cues and transcriptional mechanisms regulating its expression in osteosarcoma remain unclear. Tumor necrosis factor-α (TNF-α), a dominant pro-inflammatory cytokine within the osteosarcoma microenvironment, represents a strong candidate regulator due to its ability to activate several pathways. This study aimed to elucidate the TNF-α-ADAMTS-2 regulatory axis at mechanistic levels.

Methods and results: Gene expression profiling revealed that ADAMTS-2 is significantly upregulated in osteosarcoma tissues compared with normal bone and is associated with ECM disassembly and collagen fibril organization pathways. Functional assays in Saos-2 cells demonstrated that TNF-α stimulation markedly increased ADAMTS-2 mRNA (~ 17-fold) and protein levels (~ twofold). Promoter activity assays showed strong TNF-α-mediated activation, with the highest induction in the - 180/ + 112 region. Pharmacological inhibition experiments revealed that MEK, PI3K, JNK, and NF-κB pathways are all required for TNF-α-induced ADAMTS-2 transcription. In silico motif analysis identified STAT3 and NF-κB binding elements within the promoter, and electrophoretic mobility shift assays supported the interaction of these transcription factors with specific promoter regions.

Conclusions: This study provides the first mechanistic evidence that TNF-α regulates ADAMTS-2 expression through the coordinated activation of multiple signaling pathways and the engagement of STAT3 and NF-κB transcription factors at the promoter. These findings uncover a previously uncharacterized inflammatory regulatory axis linking TNF-α signaling to ECM remodeling and highlight ADAMTS-2 as a potential mediator of osteosarcoma progression.

Introduction: Hepatocellular carcinoma (HCC) and chronic liver disease (CLD) are mostly linked to hepatitis C virus (HCV) infection, especially genotype 4. The advancement of liver cancer is significantly influenced by epigenetic mechanisms, such as DNA methylation and microRNA regulation.

Aim of the study: This study aimed to assess the expression of two tumor suppressor genes in patients infected with HCV genotype 4: glutathione S-transferase pi 1 (GSTP1) and E-cadherin 1 (CDH1). It also sought to investigate the regulatory interactions among these genes, microRNA152 (miRNA152), and DNA methyltransferase 1 (DNMT1) to assess their potential as biomarkers for hepatocellular carcinoma (HCC) development.

Methods: Quantitative real-time PCR was done to evaluate the gene expression levels of GSTP1, CDH1, miRNA152, and DNMT1 in CLD and HCC patients infected with HCV genotype 4. Correlation analyses were used to examine regulatory linkage.

Results: The results indicated a substantial inverse correlation between DNMT1 and miRNA152. Furthermore, DNMT1 expression exhibited a negative association with both GSTP1 and CDH1, while GSTP1 and CDH1 had a positive correlation. The results indicate that DNMT1 and miRNA152 govern the epigenetic inactivation of tumor suppressor genes.

Conclusion: In individuals with HCV genotype 4, the interplay of miRNA152, DNMT1, GSTP1, and CDH1 may contribute to the pathogenesis of HCC. These indicators demonstrate potential roles as therapeutic targets and noninvasive prognostic biomarkers for HCV-related liver disease.

Background: Foot-and-mouth disease (FMD) remains a major constraint to livestock productivity in Pakistan, particularly in Khyber Pakhtunkhwa (KP), where recurrent outbreaks cause substantial economic losses. Despite routine biannual vaccination, the continued circulation of FMD virus (FMDV) serotype A predominantly the A-Iran-05 lineage raises concerns regarding antigenic mismatch between field strains and vaccine formulations.

Methods: Results A total of 244 epithelial tissue samples were collected from clinically infected cattle and buffaloes across four districts of KP. Of these, 226 samples were confirmed positive for FMDV serotype A by RT-PCR, and 215 VP1 gene sequences were successfully obtained. Phylogenetic analysis revealed that all isolates clustered within the A-Iran-05 lineage and were genetically distinct from the vaccine strain A22/Iraq/64. Antigenic relationship analysis demonstrated low r₁-values (< 0.39), indicating poor antigenic matching and suggesting reduced vaccine effectiveness. Epidemiological analysis identified age (2-4 years) as a significant risk factor for infection, while no significant associations were observed with sex, species, vaccine brand, or clinical severity.

Conclusions: The dominance of antigenically divergent FMDV serotype A strains in KP highlights the limitations of current vaccine formulations. Continuous molecular surveillance and the development of region-specific vaccines are essential to improve FMD control strategies in endemic regions of Pakistan.

Background: Klebsiella pneumoniae exhibits a marked propensity for acquiring beta-lactam resistance genes. Among these, AmpC beta-lactamases are able to hydrolyze a broad spectrum of antibiotics including first- through third-generation cephalosporins, cephamycins, and aztreonam. The CIT, EBC, and DHA families are among the most clinically significant plasmid-mediated AmpC variants in this pathogen. Consequently, this study aimed to investigate the prevalence of genes encoding these specific enzymes among clinical isolates of K. pneumoniae in northern Iran.

Methods: One hundred clinical isolates were collected from hospitalized patients and identified using standard microbiological and biochemical assays. The antimicrobial resistance profile of each isolate was determined via the disk agar diffusion method. Subsequently, PCR test was employed to detect the presence of the bla_CIT, bla_EBC, and bla_DHA genes.

Results: The mean age of the patients (58 females and 42 males) was 50.31 years. Isolates were sourced from patients in general (41%), pediatric (45%), burn (7%), and infectious (7%) hospitals. The primary specimen sources were urine (64%), blood (10%), tissue (15%), wound (7%), and sputum (4%). The highest prevalence of resistance (93%) was observed against ampicillin-sulbactam, whereas 73% of isolates remained susceptible to ertapenem.

Conclusion: The high ampicillin-sulbactam resistance represents a serious concern for the management of hospital-acquired infections. Furthermore, while the presence of the investigated bla_CIT, bla_EBC, and bla_DHA genes did not show a statistically significant correlation with resistance to most tested antibiotics, their detection remains of potential clinical importance due to the risk of horizontal gene transfer to other bacterial species.

Purpose: Breast cancer is a significant global health issue, with resistance to doxorubicin (DOX) posing a major challenge to effective treatment. SUMOylation, a post-translational modification process, is linked to cancer progression and therapy resistance. PIAS4, a SUMO E3 ligase involved in maintaining genome stability and stress response, may play a role in these mechanisms. However, its function in breast cancer progression and DOX resistance remains uncertain. This study investigates the potential role of PIAS4 in mediating DOX resistance in breast cancer.

Methods and results: Naked mole-rats (NMRs) are cancer-resistant rodents with improved genome maintenance, yet the role of SUMOylation in this trait remains unclear. SUMOylation machinery gene expression levels are investigated using qPCR in NMR tissue in comparison with carcinogenic breast cancer (MCF-7) cell line. Functional studies are performed in MCF-7 cells overexpressing PIAS4 to demonstrate effects on proliferation, invasion, drug sensitivity, and protein expression in the presence and absence of DOX treatment. While most SUMOylation genes were expressed at low levels in NMR intestinal tissues, PIAS4 showed higher expression compared to MCF-7 cells. PIAS4 overexpression in MCF-7 cells significantly decreases colony formation, invasiveness, and resistance to DOX. Western blot analysis showed downregulated Bcl-2 protein levels after DOX treatment, indicating a potential role in apoptosis evasion.

Conclusion: PIAS4 expression level plays a role in breast cancer cell survival, invasiveness, and chemoresistance, partly by altering anti-apoptotic pathways. These findings position PIAS4 as a potential biomarker and therapeutic target for overcoming resistance to anthracycline-based therapies in breast cancer.