Molecular Biology Reports最新文献

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and highly fatal disease characterized by excessive accumulation of extracellular matrix (ECM), foci of myofibroblasts, and a usual pattern of interstitial pneumonia. As suggested by international guidelines, the treatment for this disease involves supportive therapies, as there is currently no effective treatment. Plant-derived nanovesicles have emerged as a new treatment for various diseases and have been tested in cellular and murine models.

Methods and results: This research aimed to test the use of Allium sativum nanovesicles (AS-NV) in a murine model of IPF induced by bleomycin. AS-NV reduced the amount of collagen and restored lung architecture in the mouse model. AS-NV was tested on human lung fibroblasts, which do not affect the viability of healthy cells. AS-NV treatment decreases the mRNA levels of genes related to fibrosis, inflammation, and ECM deposition (Mmp2,Timp-2,Vegf,Pcna,Col1a1,Tgf-β,α-Sma,IL-1β,and Hif1a) in bleomycin-induced idiopathic pulmonary fibrosis.

Conclusions: This research highlights the anti-inflammatory and antifibrotic activity of AS-NV, which contributes to plant nanovesicle mechanisms in IPF; however, more AS-NV studies are needed to identify alternative treatments for idiopathic pulmonary fibrosis.

Background: Oral cancer (OC) is a significant global health concern, with Pakistan ranking 5th worldwide in OC incidence. Given the poor prognosis, early detection of at-risk individuals is crucial. Genetic factors, particularly single nucleotide polymorphisms (SNPs) in metabolic genes, may influence OC susceptibility. This study investigated the association between SNPs in CYP1A1, COX2, SOD2, and HIF1a genes and OC risk in the Pakistani population.

Methods: A prospective study was conducted from October 2019 to March 2022, enrolling 215 newly diagnosed OC patients and 410 controls. Genetic variations were analyzed using High-Resolution Melting (HRM) analysis and Sanger sequencing, with protein expression evaluated by ELISA.

Results: No significant associations were found between the studied SNPs and OC risk. However, a non-significant trend was observed for the SOD2 variant (rs4880), where the G allele was associated with a higher OC risk than the A allele (p = 0.20). Elevated COX2 and HIF1α levels (p-values of 0.014 and < 0.001, respectively) and reduced SOD2 levels (p < 0.0001) were observed in OC patients, while CYP1A1 levels remained similar in both controls and cases.

Conclusion: Although SNPs in CYP1A1, COX2, SOD2, and HIF1α were not significantly associated with OC risk in the Pakistani population, altered protein expression levels of COX2, HIF1α and SOD2 suggest additional regulatory mechanisms. Further investigation into post-transcriptional modifications and epigenetic factors could lead to novel biomarkers and therapeutic targets for OC in Pakistan.

Background: SUN2 is a nuclear envelope protein associated with the nuclear lamina and with proteins linked to nuclear export, splicing, and nucleo-cytoskeleton communication. Studies of SUN2 in cancer have been limited but have suggested that it has tumor-suppressive activity in some carcinomas. Medulloblastoma is a pediatric tumor that develops in the cerebellum and is currently classified into four molecular groups: WNT (Wingless), SHH (Sonic Hedgehog), 3, and 4. SUN2 expression profiles appear to be altered in brain cancer but have not been previously evaluated in medulloblastoma.

Methods and results: The University of Alabama at Birmingham Cancer (UALCAN) data analysis portal, Gene Expression Profiling Interactive Analysis (GEPIA), the Oncopression gene expression compendium, and the R2 genomics analysis and visualization platform were used to analyze SUN2 expression in cancer, which was found to vary by cancer type; in particular, SUN2 expression was found to be upregulated in medulloblastoma. We also explored the effects of reduced SUN2 protein levels (by RNA interference) on gene expression profiles using a cDNA microarray in DAOY medulloblastoma-derived cells. We found that SUN2 protein is upregulated in medulloblastoma, mainly in the SHH group, which correlates with poor survival. Furthermore, the reduced SUN2 expression in medulloblastoma cells is associated with the downregulation of the expression of other genes, including members of the bitter taste-sensing type 2 receptor (TAS2R) family.

Conclusions: This study shows that SUN2 is upregulated in medulloblastoma-with molecular interplay in gene expression-which has group-dependent implications for medulloblastoma development. In particular, the upregulation of SUN2 is associated with a progression of the SHH group of medulloblastoma.

Background: Chronic Myeloid Leukemia (CML), accounting for 15-20% of adult leukemia cases, is marked by the Philadelphia chromosome, resulting from the t(9;22)(q34;q11) translocation. This leads to uncontrolled cell proliferation and survival. Imatinib therapy lowers BCR-ABL levels, influencing telomere-associated proteins and increasing telomerase accessibility, indirectly boosting its activity. This study investigates the effects of MST-312 and imatinib, both individually and combined, on a CML cell line.

Methods: The K562 cells were subjected to different doses of MST-312 and imatinib, including four combination concentrations. Cell viability and metabolic activity were measured using trypan blue and MTT assays at 24-, 36-, and 48-h post-treatment. Flow cytometry (AnnexinV/PI) assessed cell apoptosis after 36 h of treatment with MST-312 and imatinib, both individually and in combination. The expression levels of Bax, Bcl-2, hTERT, P21, P53, and c-Myc were determined via qRT-PCR.

Results: Both MST-312 and imatinib independently reduced cell viability in a dose- and time-dependent manner. Their combination further decreased cell viability compared to monotherapy. Treatment of K562 cells with MST-312 and imatinib for 36 h increased Bax expression and the Bax/Bcl-2 ratio while decreasing Bcl-2 expression. Combined treatment significantly reduced hTERT ansd P21 gene expression compared to imatinib alone.

Conclusions: The combination of MST-312 and imatinib shows potential as a CML therapy. However, further research and clinical trials are necessary to validate these findings and determine their clinical relevance.

Background: Pin2/TRF1 interacting protein X1 (PinX1), a telomerase inhibitor, is located at human chromosome 8p23. This region is important for telomere length maintenance and chromosome stability, both of which are essential for regulating human ageing and associated diseases.

Methods and results: We investigated the research progress of PinX1 in human cancers. In cancers, the expression levels of PinX1 mRNA and protein vary according to cancer cell types, and PinX1 plays a critical role in the regulation of cancer development and progression. Additionally, a review of the literature indicates that PinX1 is involved in mitosis and affects the sensitivity of cancer cells to radiation-induced DNA damage. Therefore, PinX1 has therapeutic potential for cancer, and understanding the function of PinX1 in the regulation of cancers is crucial for improving treatment. In this review, we discuss the expression level of PinX1 in a variety of cancers and how it affects the implicated pathways. Additionally, we outline the function of PinX1 in cancer cells and provide a theoretical basis for PinX1-related cancer therapy.

Conclusions: PinX1 has promising prospects in future cancer therapeutics. This review may provide theoretical support for researchers in this field.

Objective: Single nucleotide polymorphisms (SNPs) are linked to carcinogenesis. Pathogenic variants in the CDH1 gene are associated with gastric cancer. This study examines the genotype and allele frequencies of three SNPs (rs16260, rs13689, and rs9929218) in the CDH1 gene and their relationship with gastric cancer risk.

Materials and methods: The study involved 105 gastric cancer patients with pathology results and 105 healthy controls. Clinical, histopathological, and demographic data were collected and compared between the two groups.

Results: No significant differences were found for rs16260 (- 160 C > A) and rs9929218 (G > A) between patients and controls (p > 0.05). For rs13689 (T > C), the T allele frequency was 90% in patients versus 69% in controls, while the C allele frequency was 10% in patients versus 31% in controls. A significant difference was observed for this SNP, with a higher T allele frequency in patients (OR = 4.03 CI95% 2.4-6.7, p < 0.0001) compared with controls, suggesting a fourfold increased risk of gastric cancer. Genotype frequencies were 80% wild-type (TT) and 20% heterozygous-type (TC) in patients, and 58% TT, 22% TC, and 20% mutant-type (CC) in controls (p < 0.0001). The frequencies of non-C allele carriers (TT) were present in 80% of patients versus 58.1% of controls (OR = 2.88 CI95% 1.56-5.34, p = 0.0006).

Conclusion: This study is the first to link the rs13689 SNP's T allele and TT genotype with increased gastric cancer risk. Our results suggest that the rs13689 T allele may contribute significantly to disease susceptibility, while the rs16260 CC genotype and rs9929218 GG genotype may influence risk in smokers.

Background: Herbacetin, a flavonol abundant in traditional medicines, is documented as an anti-inflammatory agent. However, information regarding its attributes on lipopolysaccharide (LPS)-induced inflammatory immunopathies has not been delineated yet. The present study aimed to comprehend herbacetin effects on LPS-induced aspects of unwarranted, non-resolving inflammation, particularly via targeting the vicious circle of oxi-inflammatory stress, autophagy-apoptosis, macrophages polarization, impaired inflammasome activation, and inflammatory cascades.

Methods and results: In-vitro model of LPS-stimulated RAW 264.7 macrophage was recapitulated to investigate different inflammatory anomalies using enzyme-linked immunosorbent assay, qRT-PCR (Real-Time Quantitative Reverse Transcription PCR), immunoblotting. Concanavalin A challenged splenocytes and in silico studies were performed to measure Tregs population and binding affinity, respectively.

Results: Herbacetin administration caused remarkable reduction in nitric oxide, reactive oxygen species, mitochondrial membrane potential hyperpolarization, tumor necrosis factor-α, interferon-γ, interleukin-6, inducible nitric oxide synthase and ratio of M1/M2 markers (inducible nitric oxide synthase/arginase-1/macrophage scavenger receptor-1/mannose receptor C type-1) in in vitro model of persistent inflammation. Suppression of interleukins-5,17 and matrix metalloproteinases-2,3,9,13 and proliferating cell nuclear antigen, signifies its anti-inflammatory attributes. Noticeable decline in monodansylcadaverine-Lysotracker staining, caspase-6, and enhanced p62, B-cell lymphoma-2 expression indicates apoptosis-autophagosome accumulation inhibition and lysosomal destabilization. These were accompanied by reduced NLRP3 activation, caspase-1, AIM-2 expression, and interleukin-1β release. Subsequently, up-regulated activation of TLR-4, NF-κB, PI3K, Akt, ERK1/2, and JNK was decisively thwarted by herbacetin. In silico investigation signified the interaction of herbacetin with these targets. Decreased cytokines and enhanced Tregs conferred its role in extenuating inflammation facilitated by T-cells depletion.

Conclusion: Collectively, these findings comprehend attributes of herbacetin as an alternative therapeutic strategy in relieving LPS-associated chronic inflammatory disorders.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a ubiquitous neurotrophic factor that exhibits a variety of physiological functions and plays a critical role in the exploitation of therapeutic potential across a range of diseases, including cardiovascular disorders, nervous system diseases, metabolic imbalances, and cancers. In the context of cardiac diseases, MANF significantly promotes cardiomyocyte survival and improves cardiac functionality. Furthermore, MANF not only provides neuroprotection by shielding neurons from damage and promoting nerve regeneration in neurological disorders, but also involves in insulin resistance, lipid metabolism disturbances and fat-containing liver lesions. However, the oncogenic or tumor suppressive function of MANF in cancer remains unclear, requiring further investigation to elucidate its precise role in the process of cancer initiation and progression. This review aims to summarize the latest advancements in understanding the molecular pathways, intricate mechanisms, and therapeutic potential of MANF in the prevention and treatment of various diseases, emphasizing its multifaceted contributions to health and disease management.

The action of Corepressor for Element Silencing Transcription Factor 1 (CoREST) is primarily related to neural fate decisions. However, the molecular mechanisms linking neuroinflammation to the histone modifying complex remain unclear. CoREST is a hub for several cofactors that play important roles in epigenetic remodeling and transcriptional regulation. It allows us to question their functions during the inflammatory response in the Central Nervous System. The impact of LPS-induced neuroinflammation on the transcriptional epigenetic control of members with CoRest repressive complex in the hippocampus was investigated. Characterizing the basal transcriptional profile in the hippocampus of members with CoREST repressive complex showed that the Rcor3 is the most expressed gene, and the Rcor2 is the least expressed one. It was also demonstrated that the levels of Lsd1, CoREST1 (Rcor1), and CoREST2 (Rcor2) transcripts increased in the hippocampus after LPS i.p. administration, while for CoREST3 (Rcor3), no significant difference was observed. A significant increase was noticed in the percentages of the 5-meC mark (Hypermethylation) for the Rcor1 and Lsd1 genes with a positive Pearson correlation between methylation and expression. However, the correlation was directly proportional, ruling out DNA methylation as the main mechanism in transcriptional control.