Role of mitochondria in pathogenesis and therapy of renal fibrosis.

Renal fibrosis, specifically tubulointerstitial fibrosis, represents the predominant pathological consequence observed in the context of progressive chronic kidney conditions. The pathogenesis of renal fibrosis encompasses a multifaceted interplay of mechanisms, including but not limited to interstitial fibroblast proliferation, activation, augmented production of extracellular matrix (ECM) components, and impaired ECM degradation. Notably, mitochondria, the intracellular organelles responsible for orchestrating biological oxidation processes in mammalian cells, assume a pivotal role within this intricate milieu. Mitochondrial dysfunction, when manifest, can incite a cascade of events, including inflammatory responses, perturbed mitochondrial autophagy, and associated processes, ultimately culminating in the genesis of renal fibrosis. This comprehensive review endeavors to furnish an exegesis of mitochondrial pathophysiology and biogenesis, elucidating the precise mechanisms through which mitochondrial aberrations contribute to the onset and progression of renal fibrosis. We explored how mitochondrial dysfunction, mitochondrial cytopathy and mitochondrial autophagy mediate ECM deposition and renal fibrosis from a multicellular perspective of mesangial cells, endothelial cells, podocytes, macrophages and fibroblasts. Furthermore, it succinctly encapsulates the most recent advancements in the realm of mitochondrial-targeted therapeutic strategies aimed at mitigating renal fibrosis.

Advances of Wnt/ß-catenin Signaling Pathway in Lung Cancer: A review.

Lung cancer is currently the leading cause of cancer mortality and morbidity worldwide and greatly burdens humanity. Therefore, the prevention and treatment of lung cancer remains a serious global problem. The Wnt/ß-catenin signaling pathway also regulates tumor cell growth and invasion through epithelial-mesenchymal transition and tumor stem cells. In this review, we first summarise the role of the Wnt/ß-catenin signaling pathway in lung cancer, focusing on the reported links in the Wnt/ß-catenin signaling pathway that are relevant to lung cancer cell line growth, cell survival, and patient prognosis. Then describe the advances in the Wnt/ß-catenin signaling pathway in lung cancer therapy, the precise regulation of the Wnt/ß-catenin signaling pathway, that precise regulation of the Wnt/ß-catenin signaling pathway should be used to balance anti-tumor effects and adverse events.

Peroxisome proliferator-activated receptors: A key link between lipid metabolism and cancer progression.

Lipids represent the essential components of membranes, serve as fuels for high-energy processes, and play crucial roles in signaling and cellular function. One of the key hallmarks of cancer is the reprogramming of metabolic pathways, especially abnormal lipid metabolism. Alterations in lipid uptake, lipid desaturation, de novo lipogenesis, lipid droplets, and fatty acid oxidation in cancer cells all contribute to cell survival in a changing microenvironment by regulating feedforward oncogenic signals, key oncogenic functions, oxidative and other stresses, immune responses, or intercellular communication. Peroxisome proliferator-activated receptors (PPARs) are transcription factors activated by fatty acids and act as core lipid sensors involved in the regulation of lipid homeostasis and cell fate. In addition to regulating whole-body energy homeostasis in physiological states, PPARs play a key role in lipid metabolism in cancer, which is receiving increasing research attention, especially the fundamental molecular mechanisms and cancer therapies targeting PPARs. In this review, we discuss how cancer cells alter metabolic patterns and regulate lipid metabolism to promote their own survival and progression through PPARs. Finally, we discuss potential therapeutic strategies for targeting PPARs in cancer based on recent studies from the last five years.

Prognostic Value of Pre-Treatment Neutrophil-To-Lymphocyte Ratio and Platelet-To-Lymphocyte Ratio in Patients With Brain Metastasis From Lung Cancer: A systematic Review and Meta-Analysis.

In modern clinical medicine, lung cancer is one of the most common types of cancer, and the brain is a routine organ of metastasis. Recently, researchers have evaluated hematologic indicators, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and confirmed that they are valid indices for predicting the outcome of patients with lung cancer. However, their prognostic significance for patients with lung cancer who have progressed to brain metastasis (BM) has not been clarified. Our study performed and reported a meta-analysis focusing on the association of pre-treatment NLR, PLR, and overall survival (OS) in lung cancer patients with BM. We searched the PubMed, Embase, and China National Knowledge Infrastructure databases using the PRISMA strategy. Meta-analyses of OS were performed using random-effects models because of the significant heterogeneity. We included 11 articles to evaluate NLR and PLR in 1,977 eligible patients. The NLR group consisted of 11 studies whose meta-analysis showed that OS was significantly shorter in patients with high NLR than in those with low NLR (pooled HR=1.84 (95% CI: 1.47-2.31). Five studies were included in the PLR group, and the results suggested that OS was significantly shorter in patients with high PLR than in those with low PLR (pooled HR=1.53 (95% CI: 1.07-2.20). Our meta-analysis showed a statistically significant association between NLR, PLR, and OS. Lower pre-treatment NLR and PLR predicted a better OS.

Role of extracellular vesicles in pathogenesis and therapy of renal ischemia-reperfusion injury.

Renal ischemia-reperfusion injury (RIRI) is a complex disorder characterized by both intrinsic damage to renal tubular epithelial cells and extrinsic inflammation mediated by cytokines and immune cells. Unfortunately, there is no cure for this devastating condition. Extracellular vesicles (EVs) are nanosized membrane-bound vesicles secreted by various cell types that can transfer bioactive molecules to target cells and modulate their function. EVs have emerged as promising candidates for cell-free therapy of RIRI, owing to their ability to cross biological barriers and deliver protective signals to injured renal cells. In this review, we provide an overview of EVs, focusing on their functional role in RIRI and the signaling messengers responsible for EV-mediated crosstalk between various cell types in renal tissue. We also discuss the renoprotective role of EVs and their use as therapeutic agents for RIRI, highlighting the advantages and challenges encountered in the therapeutic application of EVs in renal disease.

The risk of intracranial hemorrhage in glioma patients receiving anticoagulant treatment for venous thromboembolism: a bayesian network meta-analysis.

PURPOSE: We aimed to perform a Bayesian network meta-analysis to assess the risk of intracranial hemorrhage (ICH) in patients with glioma receiving anticoagulant treatment for venous thromboembolism. METHODS: The PubMed, Embase and Web of Science databases were searched for relevant publications until September 2022. All studies evaluating the risk of ICH in patients with glioma receiving anticoagulant treatment were included. Bayesian network meta-analysis and pairwise meta-analysis were performed to compare the ICH risk between the anticoagulant treatments. The Cochrane's Risk of Bias Tool and the Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of studies. RESULTS: A total of 11 studies with 1301 patients were included. Pairwise comparisons showed no significant differences excepted with LMWH vs. DOACs (OR: 7.28, 95% CI: 2.11-25.17) and LMWH vs. Placebo (OR: 3.66, 95% CI: 2.15-6.24). For network meta-analysis, significant difference was found between patients treated with LMWH vs. Placebo (OR: 4.16, 95% CI: 2.00-10.14) and LMWH vs. DOACs (OR: 10.13, 95% CI: 2.70-70.19). CONCLUSIONS: It seems that LMWH has the highest risk of ICH in glioma patients, while no evidence indicates that DOACs increase the risk of ICH. The use of DOACs may perhaps be a better choice. Further larger studies focusing on the benefit-to-risk ratio are warranted.

Key events in cancer: Dysregulation of SREBPs.

Lipid metabolism reprogramming is an important hallmark of tumor progression. Cancer cells require high levels of lipid synthesis and uptake not only to support their continued replication, invasion, metastasis, and survival but also to participate in the formation of biological membranes and signaling molecules. Sterol regulatory element binding proteins (SREBPs) are core transcription factors that control lipid metabolism and the expression of important genes for lipid synthesis and uptake. A growing number of studies have shown that SREBPs are significantly upregulated in human cancers and serve as intermediaries providing a mechanistic link between lipid metabolism reprogramming and malignancy. Different subcellular localizations, including endoplasmic reticulum, Golgi, and nucleus, play an indispensable role in regulating the cleavage maturation and activity of SREBPs. In this review, we focus on the relationship between aberrant regulation of SREBPs activity in three organelles and tumor progression. Because blocking the regulation of lipid synthesis by SREBPs has gradually become an important part of tumor therapy, this review also summarizes and analyzes several current mainstream strategies.