Current molecular medicine最新文献

Background: The analysis of diabetic nephropathy (DN)-related gene dataset demonstrated that C-X-C motif chemokine ligand 3 (CXCL3) is highly expressed in DN. Exploring the impact of CXCL3 in the course of DN is the core goal of this study.

Methods: The cell model used in this study was CIHP-1 cells induced by high glucose (HG). qRT-PCR and western blot analysis were carried out to determine the expression difference of CXCL3. After down-regulating the CXCL3 level, we analyzed HG-induced CIHP-1 cell viability by MTT assay, proliferation by EdU staining, apoptosis by flow cytometry, and changes in related protein expression by western blot. In order to analyze the possible regulatory relationship between endothelial cellspecific molecule 1 (ESM-1) and CXCL3 in DN, we constructed an over-expressed ESM-1 plasmid and carried out a rescue experiment.

Results: CXCL3 and ESM-1 were highly expressed in HG-induced podocytes (p<0.05). Silenced CXCL3 (siCXCL3) increased the viability and proliferation of CIHP- 1 cells induced by HG, reduced the proportion of apoptosis, and produced corresponding protein changes (p<0.01). After the overexpression of ESM-1, the effects of siCXCL3 were partially offset (p<0.05).

Conclusion: In this study, ESM-1 increased HG-induced podocyte damage by promoting CXCL3 expression.

Background: Inflammation, infection, autoimmune diseases, or malignancy can cause the abnormal proliferation of lymphocytes; therefore, clinicians should always take detailed history and physical examination to screen the patient for lymphadenopathy.

Objectives: The aim and objective of the current study was to assess the pattern of diseases causing lymphadenopathies in the Pakistani Population.

Methodology: The current study was a cross-sectional study. Data were obtained from existing patient records from Dow Diagnostic Research and Reference Laboratory [DDRRL]-Dow University of Health Sciences [DUHS] from Jan 2020 to Dec 2022. Patients undergoing chemotherapy and biopsies with poor preservation and inconclusive diagnosis were excluded from the study, while patients of any age, gender, and various sites of lymphadenopathy were included in this study. Ethical approval was obtained from the ethical Review Board [IRB] of Dow University of Health Sciences [DUHS].

Results: A total of 675 FNAC and lymph node biopsies of lymph nodes were obtained. Age, location, and gender were taken into consideration when analyzing the lymph node biopsy materials of these patients. There were 200 [29.62%] males and 475 [70.37%] females. The age range of the patients was 1 year to 80 years, and the mean [SD] age of the patients was 33.76 ± 17.54 years.

Conclusion: In the current study, we aim to provide guidance to the clinician on initial diagnostic laboratory testing, imaging, and the potential need for biopsy by evaluating the pattern of diseases causing lymphadenopathy in our population.

Nowadays, the research of exhaled breath condensate (EBC) analysis is widely discussed in the scientific community. The growing interest in EBC analysis results is related to the ample advantages of non-invasive techniques in healthcare and related fields. In particular, EBC analysis can be used to diagnose respiratory diseases, monitor the disease's course during therapy, and monitor drug intake and metabolism. This review aims to systematize the accumulated knowledge on EBC collection, concentration, storage, and analysis methods and compare them with similar procedures for exhaled breath (EB). We proposed a generalized chemical classification of EBC compounds that are biomarkers for various diseases. The potential transformation of substances during EB condensation was considered, and EBC analysis methods were systematically categorized based on this classification. Methods for EBC analysis using chromatographic separation with mass spectrometric detection (hyphenated methods) were separately discussed as the most promising methods for future research applications.

Background: Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. However, a synthetic nine-coordinate bismuth (III) complex (complex 1) has never been assessed so far for its anticancer in the esophageal squamous cell carcinoma cell line (EC109).

Objective: This study aimed to investigate the apoptosis effect of a complex1 in the EC109 cells.

Methods: EC109 cells were treated with complex1. The MTT assay was employed to assess the viability of EC109 cells; the changes in apoptotic and morphological characteristics, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) were examined. The expression levels of proteins associated with apoptosis were assessed using western blotting.

Results: Complex1 was found to inhibit the growth of EC109 cells, exhibiting an IC50 of 0.654 μM through apoptosis depends upon complexation with bismuth(III). In addition, cells exposed to complex1 exhibited a significant increase in the level of intracellular ROS through the suppression of the antioxidant system and caused a reduction in mitochondrial membrane potential(MMP). Co-treatment with N-acetyl-Lcysteine( NAC), an antioxidant agent prevented accumulation of ROS and cell death. Complex1 also led to enhanced Bax expression, and reduced Bcl-2 expression in EC109 cells, thereby enhancing caspase-3/9 activity.

Conclusion: Our study confirmed that complex1 induced apoptosis via enhancing the generation of ROS along with a decline in levels of antioxidant enzymes, subsequently causing MMP loss.

Breast cancer is a heterogeneous disease and highly prevalent malignancy affecting women globally. Breast cancer treatments have been demonstrated to elicit significant and long-lasting effects on various aspects of a patient's life, including physical, emotional, social, and financial, highlighting the need for comprehensive cancer care. Recent research suggests that the composition and activity of the gut microbiota may play a crucial role in anticancer responses. Various compositional features of the gut microbial population have been found to influence both the clinical and biological aspects of breast cancer. Notably, the dominance of specific microbial populations in the human intestine may significantly impact the effectiveness of cancer treatment strategies. Therefore, the manipulation of the microbiota to improve the anticancer effects of conventional tumor treatments represents a promising strategy for enhancing the efficacy of cancer therapy. Emerging evidence indicates that alterations in the gut microbiota composition and activity have the potential to impact breast cancer risk and treatment outcomes. In this paper, we conduct a comprehensive investigation of various databases and published articles to explore the impact of gut microbial composition on both the molecular and clinical aspects of breast cancer. We also discuss the implications of our findings for future research directions and clinical strategies.

Background: Oxidative damage and apoptosis of lens epithelial cells (LECs) are the primary factors contributing to the development of age-related cataracts (ARC). The potential protective effects of epigallocatechin gallate (EGCG) on LECs remain unclear despite its remarkable antioxidant and anti-apoptotic properties. The aim of this study was to explore the role of serine/threonine-protein kinase (PAK1) in EGCG-mediated attenuation of H2O2-induced apoptosis of LECs in vivo and in vitro.

Methods: PAK1 expression was assessed in the anterior capsule of the lens from mice and patients with and without ARC using western blotting and immunohistochemistry. Human lens epithelial B3 (HLE-B3) cells were pre-treated with EGCG+H2O2 or H2O2 only, and PAK1 expression was determined using qRT-PCR and western blotting. Apoptosis (following PAK1 overexpression or silencing) and cell survival were assessed using Hoechst 33342 staining and a cell counting Kit-8 assay, respectively. Cleaved caspase-3 was measured in transected cells, aged/young mice, and mice treated with EGCG via western blotting.

Results: PAK1 expression was significantly lower in ARC LECs than in control LECs. In HLE-B3 cells, EGCG+H2O2 treatment upregulated PAK1 mRNA and protein expression when compared with H2O2 alone. PAK1 overexpression alleviated H2O2- induced apoptosis in LECs, while low expression weakened EGCG's protective effects. PAK1 overexpression reduced cleaved caspase-3 expression in H2O2-treated cells, whereas PAK1 silencing increased its expression in EGCG+H2O2-treated cells. EGCG decreased cleaved caspase-3 expression in H2O2-treated cells. These results suggest that PAK1 inhibits cleaved caspase-3 expression, thereby enhancing EGCG's attenuation of H2O2-induced LEC apoptosis.

Conclusion: The PAK1/cleaved caspase-3 pathway plays a key role in EGCG's protective effects on the development of ARC. This provides a new therapeutic target for the use of EGCG in preventing and treating ARC.

Background: This study focuses on exploring the impact of Astragaloside IV [AS-IV] on osteogenic differentiation.

Methods: Osteogenic differentiation was induced in rat osteoblasts, following which treatment with AS-IV at varied doses was performed. Using Alizarin red staining and alkaline phosphatase [ALP] detection assay, the osteogenic differentiation of the cells was investigated. The expressions of osteogenic differentiation-related genes were determined by quantitative real-time polymerase chain reaction [qRT-PCR]. The phosphatidylinositol 3-kinase [PI3K]/protein kinase B [Akt] signaling pathwayassociated protein expressions were examined using Western blot. After osteoblasts were transfected with protein tyrosine phosphatase non-receptor type 2 [PTPN2] overexpression plasmid, the impact of PTPN2 on osteoblasts treated with AS-IV was examined.

Results: AS-IV treatment enhanced osteogenic differentiation and up-regulated the expression of osteogenic differentiation-related genes, as well as the levels of p- PI3K/PI3K and p-AKT/AKT, while reducing PTEN protein production in osteoblasts. Overexpression of phosphatase and tensin homolog [PTEN] inhibited osteogenic differentiation, and PTPN2 overexpression counteracted the effects of AS-IV on osteogenic differentiation.

Conclusion: AS-IV contributing to osteogenic differentiation may be related to the PTPN2-mediated PTEN/PI3K/Akt pathway.

Colorectal cancer poses a major global health issue, profoundly affecting both mortality and morbidity rates across the world. A key obstacle in understanding the pathogenesis of colorectal cancer lies in its high inter-patient and spatial heterogeneity, making standard treatments ineffective. Commonly, the study on colorectal cancer relies on bulk RNA sequencing, offering an average gene expression profile for a heterogenous cell population. However, this approach obscures the heterogeneous characteristics of the cancer cells and hinders a comprehensive understanding of the complex interplay among different cell populations. Recently, the advent of single-cell RNA sequencing has been revolutionary, enabling researchers to analyze individual immune cells and overcome the limitations of bulk RNA sequencing. Through single-cell RNA sequencing, researchers have gained insights into the dynamic nature of the immune response to cancer and potential targets for immunotherapy. In this review, we discuss the technical aspects of single-cell RNA sequencing, the application of single-cell RNA sequencing in cancer immunology, and the potential of single-cell RNA in clinical settings. We believe that harnessing singlecell RNA sequencing in cancer research holds immense potential to drive the development of personalized immunotherapies, aiming to improve patient outcomes in colorectal cancer.

Antibiotic resistance remains a major challenge in the use of antimicrobial agents and poses a threat to public health worldwide. This review discusses the epigenetic mechanisms underlying antibiotic resistance. Significant attention is also given to gene expression patterns that promote microbial adaptability and survival in the context of antibiotic therapy, as well as epigenetic mechanisms that contribute to modifying the activity of resistance genes. The authors argue that epigenetics plays a key role in the development and spread of antibiotic resistance. By offering new perspectives on the complex interaction between genetic and epigenetic regulations in microbial populations using metal nanoparticles, the authors shed light on potential therapeutic targets and strategies to combat antibiotic resistance. Exploring the disclosure of epigenetic mechanisms when interacting with metal nanoparticles on resistant cultures is insufficiently covered in the literature. This review not only presents the latest scientific findings in this field but also opens up avenues for further research that will help address the growing problem of antibiotic resistance.