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.

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.

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.

Depression, which is emerging as one of the most widely prevalent neuropsychiatric disorders worldwide, has affected people across all age groups. However, it is currently primarily affecting adults aged 18 to 25. The condition is characterized by disrupted sleep cycles, diurnal variation, and disturbed core body temperature rhythms. Currently, the anti-depressant medications that are prescribed and authorized, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), benzodiazepines, anxiolytics, and antihistamines have demonstrated effective outcomes. However, the findings from the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study are disappointing. The results show that currently available antidepressants yield only minimal improvements in effectiveness for patients who did not respond to their initial medication. Melatonin has emerged as a promising option for tackling these issues. Moreover, due to its diverse abilities to regulate circadian rhythms and promote synchronization, melatonin offers an alternative therapeutic approach to alleviate the side effects and target the underlying causes of depression linked to an impaired circadian system. This review intends to provide a comprehensive overview of melatonin, including aspects such as its structural analysis, biosynthesis, regulation, catabolism, and involvement in various physiological processes, particularly highlighting its antidepressant activity.

Background: Osteoarthritis (OA) is a chronic joint disease characterized by the degradation of articular cartilage. Polyphyllin I (PPI) has anti-inflammatory effects in many diseases. However, the mechanism of PPI in OA remains unclear.

Methods: HC-a cells treated with IL-1β were identified by immunofluorescence staining and microscopic observation. The expression of collagen II and DAPI in HC-a cells was detected by immunofluorescence. The effects of gradient concentration of PPI on IL-1β-induced cell viability, apoptosis, senescence, and inflammatory factor release were detected by MTT, flow cytometry, SA-β-Gal assay and ELISA, respectively. Expressions of apoptosis-related genes, extracellular matrix (ECM)- related genes, and TWIST1 were determined by qRT-PCR and western blot as needed. The above-mentioned experiments were conducted again after TWIST1 overexpression in IL-1β-induced chondrocytes.

Results: IL-1β reduced the number of chondrocytes and the density of collagen II. PPI (0.25, 0.5, 1 μmol/L) had no effect on cell viability, but it dose-dependently elevated the inhibition of cell viability regulated by IL-1β. The elevation of cell apoptosis, senescence and expression of IL-6 and TNF-α were suppressed by PPI in a dosedependent manner. Additionally, PPI reduced the expression of cleaved caspase-3, bax, MMP-3, and MMP-13 and promoted the expression of collagen II. TWIST1 expression was diminished by PPI. TWIST1 overexpression reversed the abovementioned effects of PPI on chondrocytes.

Conclusion: PPI suppressed apoptosis, senescence, inflammation, and ECM degradation of OA chondrocytes by downregulating the expression of TWIST1.

Background: Neferine (Nef) has a renal protective effect. This research intended to explore the impact of Nef on hyperuricemic nephropathy (HN).

Methods: Adenine and potassium oxonate were administered to SD rats to induce the HN model. Bone marrow macrophages (BMDM) and NRK-52E were used to construct a transwell co-culture system. The polarization of BMDM and apoptosis levels were detected using immunofluorescence and flow cytometry. Renal pathological changes were detected using hematoxylin-eosin (HE) and Masson staining. Biochemical methods were adopted to detect serum in rats. CCK-8 and EDU staining were used to assess cell activity and proliferation. RT-qPCR and western blot were adopted to detect NLRC5, NLRP3, pyroptosis, proliferation, and apoptosis-related factor levels.

Results: After Nef treatment, renal injury and fibrosis in HN rats were inhibited, and UA concentration, urinary protein, BUN, and CRE levels were decreased. After Nef intervention, M1 markers, pyroptosis-related factors, and NLRC5 levels in BMDM stimulated with uric acid (UA) treatment were decreased. Meanwhile, the proliferation level of NRK-52E cells co-cultured with UA-treated BMDM was increased, but the apoptosis level was decreased. After NLRC5 overexpression, Nef-induced regulation was reversed, accompanied by increased NLRP3 levels. After NLRP3 was knocked down, the levels of M1-type markers and pyroptosis-related factors were reduced in BMDM.

Conclusion: Nef improved HN by inhibiting macrophages polarized to M1-type and pyroptosis by targeting the NLRC5/NLRP3 pathway. This research provides a scientific theoretical basis for the treatment of HN.

Most chronic respiratory diseases often lead to the clinical manifestation of pulmonary fibrosis. Inflammation and immune disorders are widely recognized as primary contributors to the onset of pulmonary fibrosis. Given that macrophages are predominantly responsible for inflammation and immune disorders, in this review, we first focused on the role of different subpopulations of macrophages in the lung and discussed the crosstalk between macrophages and other immune cells, such as neutrophils, regulatory T cells, NKT cells, and B lymphocytes during pulmonary fibrogenesis. Subsequently, we analyzed the interaction between macrophages and fibroblasts as a possible new research direction. Finally, we proposed that exosomes, which function as a means of communication between macrophages and target cells to maintain cellular homeostasis, are a strategy for targeting lung drugs in the future. By comprehending the mechanisms underlying the interplay between macrophages and other lung cells, we aim to enhance our understanding of pulmonary fibrosis, leading to improved diagnostics, preventative measures, and the potential development of macrophage-based therapeutics.