Cellular and molecular biology最新文献

Colorectal cancer (CRC) is the most prevalent type of gastrointestinal cancer. Genetic, epigenetic, and lifestyle factors have been implicated in the development of CRC. Non-coding RNAs such as HOX transcript antisense RNA (HOTAIR) and miR-3117 have been associated with cell proliferation, progression, invasion, and metastasis, as well as poor survival in several cancer types. This study examines the potential association between the HOTAIR (rs920778 T>C) and miR-3117 (rs7512692 C>T and rs4655646 G>A) variants and the clinicopathological features of CRC in Mexican patients. The study included genomic DNA of peripheral blood samples from 557 individuals (296 CRC patients and 261 controls). The variants were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The association was calculated using the odds ratio (OR) test. P-values were adjusted using the Bonferroni test (0.016). Individuals carrying the T/C and C/C genotypes for the HOTAIR rs920778 variant exhibited a higher susceptibility to CRC (OR=1.73, 95% CI: 1.15-2.58, P=0.009 and OR=2.78, 95% CI: 1.74-4.45, P=0.001, respectively). Male patients older than 50 years and carrying the C/C genotype demonstrated an increased susceptibility to developing CRC (OR=2.77, 95% CI: 1.63-4.70, P=0.001). Additionally, C/C genotype carriers exhibited an association with the advanced TNM stage. Furthermore, for the rs7512692 variant of the miR-3117 gene, patients carrying the C/T genotype exhibited increased susceptibility to developing CRC (OR=1.92, 95% CI: 1.35-2.74, P=0.001). Male patients over 50 years of age and carrying the C/T genotype demonstrated increased susceptibility for early TNM stages and tumor location in the colon. The results obtained suggest that the HOTAIR rs920778 and miR-3117 rs7512692 variants play a significant role in colorectal cancer risk.

Mucopolysaccharidosis type IV also known as Morquio syndrome is a rare autosomal recessive lysosomal storage disorder due to deficiency of either N-acetyl-galactosamine-6-sulfatase (type A) or deficiency of beta-galactosidase (type B) which results in damages of bones, cartilages, eye corneas, skin and connective tissue. The objective of this study was to explore the relationship between specific gene mutations (c.860C>T, c.421T>A, c.1196delA) and clinical manifestations in patients with mucopolysaccharidosis type IV (MPS IV. The study was conducted at Heevi Tertiary Hospital in Duhok, Iraqi Kurdistan, till the period of September 2024, it involved 10 patients with confirmed MPS IV. Data on demographics, family history, consanguinity, skeletal, intelligence, and genetic mutations were collected. Results showed that mean age at diagnosis of 7.94 years, with females predominating. Consanguinity and family history were common. Short stature, macrocephaly, fatigue, generalized pain, and various skeletal abnormalities such as dysostosis multiplex and others. Hip dysplasia was present in 50% of patients, while intelligence was normal in most. The most frequent genetic mutation was c.860C>T, followed by c.421T>A and c.1196delA. Biochemical and hematological parameters were within normal ranges, but growth retardation was evident. Geographic clustering of mutations was noted, with c.860C>T prevalent in Zakho and c.1196delA exclusive to Akre. In conclusion, the study highlights the severe phenotypic expression associated with these mutations and underscores the influence of consanguinity and regional genetic predispositions. These findings emphasize the need for targeted genetic counseling and population screening programs in high-risk areas.

B lymphocyte cells have received considerable attention in recent studies regarding their role in tumor immunity. Tumor Infiltrating B cells (TIBs) are the name that describes the B lymphocyte cells that infiltrate a tumor tissue. Different cellular components interplay in the environment of tumor and modulate the response of antitumor immune dynamically.   A Dual role for TIBs is detected in tumor immunity regulation instead of just tumor promotion or inhibition. The present study was performed to evaluate the tumor-infiltrating B lymphocyte and the clinical outcome. Immunohistochemical analysis of B Lymphocytes in stromal/intratumoral regions was performed in 40 OSCC specimens by using CD20 antibodies. Expression of the markers and their relationship with clinicopathological parameters was evaluated by using of Independent t-test and Analysis of Variance (ANOVA) (two-tailed). Data analysis demonstrates a significant association of stromal and intratumoral CD20+ B lymphocyte infiltration with well-differentiated lesions (P < 0.05) and stage I cases (P>0.05). In addition to a significant correlation of stromal infiltration of CD20+B lymphocytes with lymph node metastasis (P=0.01). The results suggest that CD20+ B lymphocytes play an important role in OSCC, where higher infiltration of CD20+ B cells in stromal regions, particularly in cases with lymph node involvement, may be used as a prognostic indicator and may aid in determining whether the use of B lymphocyte as therapeutic targets in OSCC.

Insulin resistance (IR) is a key contributor to the development of metabolic diseases, and metformin has been shown to help mitigate IR. Long non-coding RNAs (lncRNAs) are emerging as important regulators in metabolic disorders. This study aimed to investigate the differential expression of lncRNAs in IR and assess the impact of metformin on these lncRNAs. Using the Huh7 cell line to model IR (Huh7-IR), we treated the cells with metformin (Huh7-IR+Metf). Microarray analysis, followed by bioinformatic analysis in RStudio, identified 127 downregulated and 109 upregulated lncRNAs, among which 60 showed reduced expression following metformin treatment in Huh7-IR cells. Notably, the upregulated lncRNAs HOX transcript antisense RNA (HOTAIR), long intergenic non-protein coding RNA, muscle differentiation 1 (LINCMD1) and Prader-Willi region non-protein coding RNA 2 (PWRN2) were found to be associated with genes involved in the insulin signaling pathway. These three lncRNAs were further validated using real-time RT-PCR. This study highlights the differential expression of lncRNAs in IR and their modulation by metformin. Specifically, metformin restores the expression of lncRNAs that were deregulated in IR, including HOTAIR, LINCMD1, and PWRN2, likely through the regulation of critical biological processes and signaling pathways associated with IR. In conclusion, our findings demonstrate that metformin modulates the expression of key lncRNAs, including HOTAIR, LINCMD1, and PWRN2, which are deregulated in insulin resistance. This regulation likely occurs through the modulation of critical signaling pathways, such as NFκB and AMPK, suggesting that targeting lncRNAs could offer new therapeutic avenues for managing IR and related metabolic disorders.

This study explores microbial dynamics in paper recycling, emphasizing the significance of sustainable practices for environmental preservation. Samples were collected from various urban waste sources in Erbil city, Kurdistan Region, Iraq, including materials such as pizza boxes, cigarette packets, and coffee cups. Pure bacterial colonies were isolated using standard methods, and their morphological and physiological traits were characterized through biochemical tests. Identification of bacterial species followed established protocols. The study identified diverse bacterial species associated with paper waste, highlighting potential hygiene concerns in the recycling process. The findings of this study contribute to understanding the microbial ecology associated with paper waste and recycling processes. By optimizing hygiene measures and gaining insights into the microbial communities present, this research underscores the importance of sustainable practices in paper recycling to mitigate environmental impacts and promote a healthier ecosystem. Policies for future waste management and reduction of environmental risks have been proposed.

The overexpression of tumor markers within Extracellular Vesicles (EVs), particularly in tumor-derived exosomes (TDEs), plays a pivotal role in metastasis in the context of colorectal cancer (CRC). Nonetheless, the precise role of EV content in CRC diagnosis and prognosis necessitates extensive validation through bioinformatics and clinical investigations. We explored molecular markers shared between TDEs and circulating tumor cells (CTCs) in the blood of cancer patients to identify candidate genes involved in metastasis. Common markers were analyzed in gene expression profiles of two studies (GSE31023 and GSE72577). The expression of candidate genes was assessed by RT-PCR in CTC, TDEs, and microvesicles (MVs), and was correlated with clinicopathological features. To further confirm, the expression of candidate genes was investigated in exosomes derived from the parental HT-29 colorectal cancer cell line (HT-29-EXOs), and cancer stem cells (CSCs) -enriched spheroids (CSC-EXOs) derived thereof.  Gene ontology (GO) analysis suggested platelet-derived growth factor A (PDGFA) and proto-oncogene, Serine/Threonine kinase Raf-1 (RAF1) as new CRC candidate markers in CTCs and TDEs. Expression of PDGFA (P=0.0086) and RAF1 (P=0.048) were upregulated in TDEs but significantly decreased (P=0.0001) in MVs. Furthermore, expression in CSC-EXOs (P=0.0004) was increased compared to HT-29-EXOs. PDGFA and RAF1 mRNA are higher in CSC-EXOs than in HT-29-EXOs, which correlates with higher expression in CSC than in the primary tumor. Notably, as no increase was observed in MVs, PDGFA and RAF1 mRNA appear to be actively recruited into TDE.

Endometrial cancer of the uterine corpus (ECUC) is a common malignancy among females. Disulfidptosis, a recently identified form of cellular death, is characterized by elevated SLC7A11 expression and limited glucose availability, making it a potential cancer treatment target. In this research, clinical data and transcriptome information from EC samples were accessed from the TCGA database. A disulfidptosis-related lncRNAs(DRLs) prognostic signature was developed by univariate/LASSO/multivariate regression analyses. Cellular pathways were identified through GO, KEGG, and GSEA analyses. Immune infiltration as well as tumor mutational burden (TMB) were evaluated. The TIDE algorithm and the GDSC database were utilized to predict how patients reacted to immunotherapy as well as anticancer drugs. Finally, the expressions of disulfidptosis-related lncRNAs were measured using RT-qPCR. Results: In this study, we identified 524 disulfidptosis-related lncRNAs and developed a prognostic signature consisting of five DRLs (AC022960.1, PRDX6-AS1, EMSLR, AL359715.3, AC103563.9). Our prognostic signature effectively stratified EC patients into high- and low-risk groups. Compared with the high-risk group, patients in the low-risk group exhibited better overall survival (OS). Additionally, ROC curves and concordance index (C-index) plots were used to assess the accuracy of our prognostic signature. The results demonstrated that the AUC values for 1-, 3-, and 5-year survival were 0.676, 0.712, and 0.722, respectively, indicating high predictive accuracy. Further analysis revealed significant differences between high- and low-risk groups in terms of TMB, drug sensitivity, and immune cell infiltration. PCR results showed that PRDX6-AS1, EMSLR, AL359715.3, and AC103563.9 were upregulated in EC cells, whereas AC022960.1 was downregulated. In conclusion, we developed a DRLs signature capable of predicting the TMB, prognosis, and immunological cell infiltration patterns, as well as the reactions to immunotherapy in EC patients.

This study investigates the effects of regular exercise on inflammation and mitochondrial biogenesis in the eye using a controlled experimental Alzheimer's disease (AD) model. Twenty-four male Wistar rats were divided into four groups: control, Alzheimer, exercise, and Alzheimer with exercise. Molecular markers, including Nuclear Factor Kappa B (NF-κB), Fibronectin Type III Domain-Containing Protein 5 (FNDC5), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (PGC-1α), Sirtuin 1 (SIRT1) were analyzed through real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) Matrix Metalloproteinase 2 (MMP-2), and Interleukin-1 Beta (IL-1β) were analyzed enzyme-linked immunosorbent assay (ELISA)  to evaluate exercise-induced changes in inflammation and mitochondrial function. NF-κB levels were significantly elevated in the Alzheimer group, reflecting neuroinflammation, while exercise partially mitigated these effects. Exercise increased FNDC5, PGC-1α, and SIRT1 levels, suggesting a role in promoting neuroprotection and mitochondrial biogenesis. However, MMP-2 and IL-1β effects were primarily observed at the gene expression level, without substantial changes in protein levels. The use of an Alzheimer-specific model reduced confounding factors, such as age-related pathologies, providing a clearer perspective on Alzheimer-associated ocular changes. These findings highlight the potential of exercise in modulating key molecular pathways involved in AD.

The present study aimed to investigate the effect of Sodium valproate (VAP) combined with methylprednisolone (MP) on spinal cord injury (SCI), and its underlying mechanism. Following the establishment of the SCI model using SD mice, VPA treatment group: 8 hours after the establishment of SCI model, VAP (dissolved in normal saline) was injected intraperitoneally at a dose of 300 mg/kg for 30 days. MP treatment group: 30min, 6 and 24 hours after successful establishment of SCI model, MP (dissolved in normal saline) was injected intraperitoneally at a dose of 30 mg/kg. Behavioral tests, Nissl staining, and H&E staining were employed to assess motor function recovery and neuronal cell death. Western blot was used to assess the apoptosis-associated proteins (Bcl-2, caspase-3, Bax). They showed VAP combined with MP can significantly improve the motor function of spinal cord and reduce neuronal death. Also, significant upregulation of Bcl-2 expressions, with the downregulation of Bax and caspase-3 expressions were found in the VAP combined with MP treated group. This study aims to explore the mechanism of VAP combined with MP in the treatment of SCI. The findings of this study the protective effect of MP combined with MP on SCI may be mediated by inhibition of NF- κ B signal pathway. These results demonstrate the therapeutic potential of VAP combined with MP in SCI.

Streptomyces strains are renowned for their ability to produce a wide array of secondary metabolites, which play crucial roles in ecological interactions and have significant pharmaceutical applications. The optimization of culture conditions is a key factor in maximizing the production of these bioactive compounds. This study investigated the growth patterns and bioactivity of a newly isolated Streptomyces gobitricini cultured on different media: R5, R5E, R2YE, and YEME. Data showed that R5 and R2YE media supported higher biomass accumulation, achieving peak dry weights of 225 mg/L and 175 mg/L, respectively, after 96 h-incubation, compared to R5E (52 mg/L) and YEME (48 mg/L). Growth phases, especially the exponential phases, were longer and more pronounced in nutrient-rich media like R5 and R2YE. Furthermore, the inherent antioxidant activities, enzyme inhibitory properties against α-amylase, α-glucosidase, lipase, and trypsin, as well as secreted phospholipase A2, cyclooxygenases and lipooxygenase, showed significant variations influenced by the growth media, with R5 exhibiting the highest overall bioactivity. Specifically, R2YE extracts demonstrated potent inhibitory effects on α-glucosidase and phospholipases, while YEME showed promising lipase inhibition. These findings emphasized the critical role of media composition in promoting secondary metabolite production in S. gobitricini, ultimately enhancing its potential medicinal applications for several human diseases such as obesity and inflammation. Consequently, optimizing bacterial culture conditions could significantly improve yield and efficiency of bioactive compounds.