Acta biochimica Polonica最新文献

Mitochondrial investigations have extended beyond their traditional functions, covering areas such as ATP synthesis and metabolism. Mitochondria are now implicated in new functional areas such as cytoprotection, cellular senescence, tumor function and inflammation. The basis of these new areas still relies on fundamental biochemical/biophysical mitochondrial functions such as synthesis of reactive oxygen species, mitochondrial membrane potential, and the integrity of the inner mitochondrial membrane i.e., the passage of various molecules through the mitochondrial membranes. In this view transport of potassium cations, known as the potassium cycle, plays an important role. It is believed that K⁺ influx is mediated by various potassium channels present in the inner mitochondrial membrane. In this article, we present an overview of the key findings and characteristics of mitochondrial potassium channels derived from research of many groups conducted over the past 33 years. We propose a list of six fundamental observations and most important ideas dealing with mitochondrial potassium channels. We also discuss the contemporary challenges and future prospects associated with research on mitochondrial potassium channels.

Depression is a common psychiatric disorder. Due to the disadvantages of current clinical drugs, including poor efficacy and unnecessary side effects, research has shifted to novel natural products with minimal or no adverse effects as therapeutic alternatives. The ocean is a vast ecological home, with a wide variety of organisms that can produce a large number of natural products with unique structures, some of which have neuroprotective effects and are a valuable source for the development of new drugs for depression. In this review, we analyzed preclinical and clinical studies of natural products derived from marine organisms with antidepressant potential, including the effects on the pathophysiology of depression, and the underlying mechanisms of these effects. It is expected to provide a reference for the development of new antidepressant drugs.

Human chemokine receptor 8 (CCR8) is a promising drug target for immunotherapy of cancer and autoimmune diseases. Monoclonal antibody-based CCR8 targeted treatment shows significant inhibition in tumor growth. The inhibition of CCR8 results in the improvement of antitumor immunity and patient survival rates by regulating tumor-resident regulatory T cells. Recently monoclonal antibody drug development targeting CCR8 has become a research hotspot, which also promotes the advancement of antibody evaluation methods. Therefore, we constructed a novel engineered customized cell line HEK293-cAMP-biosensor-CCR8 combined with CCR8 and a cAMP-biosensor reporter. It can be used for the detection of anti-CCR8 antibody functions like specificity and biological activity, in addition to the detection of antibody-dependent cell-mediated cytotoxicity and antibody-dependent-cellular-phagocytosis. We obtained a new CCR8 mAb 22H9 and successfully verified its biological activities with HEK293-cAMP-biosensor-CCR8. Our reporter cell line has high sensitivity and specificity, and also offers a rapid kinetic detection platform for evaluating anti-CCR8 antibody functions.

Metformin has shown great promise in the treatment of HCC. Radiofrequency ablation (RFA) deficiency results in recurrence and metastasis of remaining HCC tumors. Here, we aimed to investigate the role and mechanism of metformin in HCC after RFA deficiency. HCC cell line Hep-G2 was selected to simulate RFA deficiency and named HepG2-H cells. After treating cells with different concentrations of metformin (2.5, 5, 10 μM) or transfecting related plasmids, cell proliferation, migration, invasion, apoptosis and angiogenesis were detected, in vitro permeability test was performed, and an angiogenesis-related protein VEGFA was analyzed. The residual HCC model after RFA deficiency was established in mice. Metformin was administered by gavage to detect changes in tumor volume and weight, and CD31 staining was used to observe microvessels. The targeting relationship between miR-302b-3p and TXNIP was demonstrated by the bioinformatics website, dual-luciferase reporter assay, and RNA pull-down assay. The results found that metformin inhibited RFA deficiency-induced growth and angiogenesis of HCC cells in vitro. miR-302b-3p counteracted the therapeutic effect of metformin on RFA deficiency. miR-302b-3p targeted regulation of TXNIP. The up-regulation of TXNIP reversed the effects of overexpression of miR-302b-3p on RFA-deficient HCC cells. Metformin inhibited RFA-deficiency-induced HCC growth and tumor vascular abnormalities in vivo. Overall, metformin promotes the normalization of abnormal blood vessels after RFA deficiency in HCC by miR-302b-3p targeting TXNIP, which can be used to prevent the progression of HCC after RFA.

Objective: To explore the dynamic changes of serum miR-105-3p expression after thyroid cancer surgery and its correlation with clinicopathological manifestations and to evaluate its clinical value as a potential biomarker after surgery.

Methods: A total of 100 thyroid cancer patients admitted to Shaanxi Provincial People's Hospital from November 2020 to August 2021 were selected as the research objects. The aim was to detect the expression of serum miR-105-3p in patients and its correlation with tumor pathological characteristics (pathological type, tumor differentiation, TNM stage, lymph node metastasis), and to detect the dynamic changes of postoperative serum miR-105-3p in patients to evaluate its prognostic value as a potential biomarker.

Results: The level of serum miR-105-3p increases in patients with well-differentiated thyroid cancer and lymph node metastasis; the level of serum miR-105-3p gradually decreases with the passage of time after surgery, and there is a significant difference between 4 d after surgery and before surgery; serum miR-105-3p level can significantly distinguish between patients with poor prognosis and good prognosis within 2 years after the operation, and it can predict the improvement of the prognosis of thyroid cancer after surgery.

Conclusions: The level of serum miR-105-3p is closely related to the degree of differentiation and lymph node metastasis in patients with thyroid cancer. Its level gradually decreases with the passage of time after surgery. It has a good diagnostic value for the prognosis of thyroid cancer after surgery and when it is expected to become a thyroid cancer surgery. Potential biomarkers for post-diagnosis.

Background: Prostate cancer is one of the most common cancers in men worldwide. This study aims to elucidate the roles of c-Jun N-terminal kinase (JNK) in the progression of castration-resistant prostate cancer (CRPC).

Methods: JNK overexpressing and knockdown cell lines were established on the PC-3 prostate cell line. qPCR and Western blotting were performed to determine the mRNA and protein levels of target genes in prostate tissues and cell lines. MTT and Matrigel invasion assays were conducted to evaluate the cell viability and invasive ability, respectively. The Kaplan-Meier estimator was performed to estimate the overall survival rate and second progression-free survival rate. Pearson's correlation coefficient was used to evaluate the relationship between JNK and prostate-specific antigen (PSA).

Results: Relative JNK expression was correlated with Gleason score and PSA value in patients with CRPC. Kaplan-Meier analysis revealed that patients with low JNK expression exhibited high overall survival and second progression-free survival rate. In vitro assays demonstrated that JNK overexpression promoted cell viability and invasion as well as the protein expressions of extracellular signal-regulated kinase (ERK) and matrix metalloproteinase 1 (MMP1) in PC-3 cell lines.

Conclusions: JNK overexpression promotes the development of CRPC via the regulation of ERK and MMP1.

LncRNA MIR31HG is involved in many types of cancers, while its roles in breast cancer are still unknown. The current study aimed to explore the function of lncRNA MIR31HG in breast cancer and the underlying mechanisms. Stable expression cell lines were constructed by using lentivirus particles. MTT assay was used to determine cell viability. Wound healing and Transwell assay were used to determine cell migration and invasion, respectively. The changes in biomarkers were determined by using qPR-PCT and Western blotting, respectively. BALB/c nude mice were used to generate a xenograft mouse model. MIR31HG regulated cell proliferation, migration and invasion in MCF7 cells. Besides, MIR31HG regulated N-Cadherin, Vimentin, and E-Cadherin. MIR31HG positively regulated receptor-interacting serine-threonine kinase 4 (RIPK4), as supported by the fact that knockdown of MIR31HG suppressed RIPK4, and the knockdown of RIPK4 did not affect MIR31HG. Additionally, we found that RIPK4 regulated cell proliferation, migration and invasion in MCF7 cells. The changes in RIPK4 regulated N-Cadherin, Vimentin, and E-Cadherin. Consistently, in vivo studies showed that the knockdown of MIR31HG or RIPK4 reduced tumor size in xenograft animal models. The roles of lncRNA MIR31HG in breast cancer were associated with its regulatory effects against RIPK4.