Explore the vast range of titles available.

Gastric cancer is one of the top causes of cancer-related death globally. Although novel treatment strategies have been developed, attempts to eradicate gastric cancer have been proven insufficient. Oxidative stress is continually produced and continually present in the human body. Increasing evidences show that oxidative stress contributes significantly to the development of gastric cancer, either through initiation, promotion, and progression of cancer cells or causing cell death. As a result, the purpose of this article is to review the role of oxidative stress response and the subsequent signaling pathways as well as potential oxidative stress-related therapeutic targets in gastric cancer. Understanding the pathophysiology of gastric cancer and developing new therapies for gastric cancer depends on more researches focusing on the potential contributors to oxidative stress and gastric carcinogenesis.

The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, responsible for a wide range of vital functions, including the modification, folding, and trafficking of proteins, as well as the biosynthesis of lipids and the maintenance of intracellular calcium homeostasis. A variety of factors can disrupt the function of the ER, leading to the aggregation of unfolded and misfolded proteins within its confines and the induction of ER stress. A conserved cascade of signaling events known as the unfolded protein response (UPR) has evolved to relieve the burden within the ER and restore ER homeostasis. However, these processes can culminate in cell death while ER stress is sustained over an extended period and at elevated levels. This review summarizes the potential role of ER stress and the UPR in determining cell fate and function in various diseases, including cardiovascular diseases, neurodegenerative diseases, metabolic diseases, autoimmune diseases, fibrotic diseases, viral infections, and cancer. It also puts forward that the manipulation of this intricate signaling pathway may represent a novel target for drug discovery and innovative therapeutic strategies in the context of human diseases. The endoplasmic reticulum (ER) serves as a vital organelle in eukaryotic cells, performing essential roles such as protein folding, modification, and trafficking, lipid biosynthesis, and calcium regulation. Various conditions may disrupt ER function, potentially leading to the accumulation of unfolded and misfolded proteins, and triggering ER stress. This prompts the unfolded protein response (UPR), a conserved signaling cascade, to mitigate the stress by regulating gene expression and protein synthesis, aiming to restore ER equilibrium. However, prolonged or severe ER stress can lead to cell death. As our understanding of the molecular mechanisms linking ER stress to human diseases improves, ER stress and UPR activation are increasingly recognized as significant contributors to various diseases. The balancing of ER stress and the UPR is crucial for the pathogenesis of diseases, such as cardiovascular diseases, neurodegenerative diseases, metabolic diseases, autoimmune diseases, fibrotic diseases, viral infections, and cancer. It also considers how manipulation of this complex signaling pathway may provide a new target for drug discovery and innovative therapeutic strategies in human disease.

ObjectiveThis study is to explore the exact roles of extracellular vesicle (EVs) miRNAs from brain microvascular pericytes in the pathogenesis of hypertension.ResultsForty-eight significantly differentially expressed miRNAs were identified, of which 17 were found to be upregulated and 31 were found to be downregulated in brain microvascular pericytes of spontaneous hypertensive rats, compared with that of normotension Wistar Kyoto rats. The GO enrichment analysis verified that the target genes were enriched in signaling pathways and molecular functions, such as metal ion binding, nucleotide binding and ATP binding. The KEGG analysis indicated that the target genes were enriched in Linoleic acid, alpha-linolenic acid and sphingolipid metabolism pathways.ConclusionsSeveral EV derived miRNAs, such as miR-21-5p, let-7c-5p and let-7a-5p, were found to be abnormally expressed in brain microvascular pericytes obtained from spontaneous hypertensive rats, compared with that of normotension Wistar Kyoto rats. The results of our research provide more insights into the functional link between brain microvascular pericytes and the pathogenesis of hypertension.

Metabolic Associated Fatty Liver Disease (MAFLD), previously known as Non-Alcoholic Fatty Liver Disease, is a growing global health issue associated with obesity, type 2 diabetes, and metabolic syndrome. This study investigates the potential of metformin, a common anti-diabetic drug, to slow the progression of MAFLD using a multi-omics approach. Male Wistar rats were fed a choline-deficient diet to induce MAFLD and treated with metformin through their drinking water for 48 weeks. We conducted a comprehensive analysis including liver histology, untargeted metabolomics, lipidomics, and gut microbiome profiling to assess the effects of metformin on liver and gut metabolic patterns. Metformin administration led to significant changes in gut microbiome diversity and the abundance of specific microbial species in MAFLD rats. Histological analysis showed that metformin-treated rats had reduced lipid accumulation and fibrosis in the liver compared to untreated MAFLD rats. Metabolomic and lipidomic analyses revealed that metformin corrected abnormal lipid metabolism patterns, reduced hepatic fat deposition, and influenced key metabolic pathways associated with MAFLD progression. Our findings suggest that metformin has a protective role against MAFLD by modulating gut microbiota and liver metabolism, thereby slowing the progression of hepatic fibrosis. This study provides insights into the therapeutic potential of metformin for MAFLD by addressing metabolic pattern disorders and abnormal changes in gut microbial diversity, highlighting its impact on lipid metabolism and gut-liver axis interactions.

Endothelial cells, which regulate arterial stiffness via endothelial-derived substances, are independently and strongly associated with hypertension. However, the exact roles of exosome miRNAs from brain endothelial cells in the development of hypertension are still not fully explored. Here, we investigated the miRNA functions systematically by examining both exosomal small RNA and mRNA of endothelial cells in Wistar Kyoto (WKY) rats versus spontaneously hypertensive rats (SHRs). Our findings revealed that miRNAs, representing ~60–70%, account for the majority of small RNAs. Moreover, we found 159 novel miRNAs in total from the unannotated reads across the diverse samples. Afterwards, 76 differentially expressed miRNAs (37 upregulated, 39 downregulated) and 1709 differentially expressed mRNAs (775 upregulated, 934 downregulated) were identified between SHRs and WKY rats, respectively. Finally, 647 genes targeted by 36 miRNAs came to our attention via identification of the target genes of those abnormal miRNAs. The differentially expressed target genes induced by miRNA changes were mapped to a number of genes involved in various gene functions and pathways. These changes lead to dysregulation of angiogenesis, axonogenesis, neuron-to-neuron synapses, focal adhesion, axon guidance, cell adhesion molecules (CAMs), adherens junction, and ECM-receptor interaction pathways. Together, our study revealed that the miRNAs are changed and contribute to the dysregulated functions and pathways of their target genes and provided more insights into their regulation mechanisms during mammalian hypertension development.

The limited stability of L. reuteri in liquid formulations during storage, transport, and gastrointestinal transit presents a major challenge for its application as a probiotic. To address this, our study developed two distinct microcapsulation models for L. reuteri A-1, tailored for specific release profiles: slow-release and quick-release model. Utilizing single-factor experiments and response surface methodology, we optimized the encapsulation process, achieving a maximum embedding efficiency of 88.64% for the slow-release model. The quick-release model demonstrated a high cumulative release rate of 83.3%. Structural characterization revealed microcapsules with dense, smooth surfaces and internal porous structures. Storage stability tests confirmed that low temperature (4 °C) best preserved viability. In the DSS-induced murine colitis model, the quick-release model significantly alleviated disease symptoms, including weight loss, colon shortening, inflammatory cytokine imbalance, and mucosal damage. 16S rRNA analysis further showed that the quick-release system helped restore the gut microbiota of colitis mice to a state closer to that of healthy controls. This work establishes a novel technological platform for the controlled release and targeted delivery of probiotics, holding significant promise for the development of live biotherapeutic products.

Objective Brain functional connectivity alterations have been observed in cardiovascular diseases (CVDs), but the causality between brain resting-state functional connectivity networks and CVDs remains undetermined. We aimed to investigate the bidirectional causality between brain network connectivity and CVDs using Mendelian randomization (MR) analysis. Methods Using genome-wide association study (GWAS) data from the UK Biobank ( n  = 34,691), we conducted bidirectional two-sample MR analyses between 191 resting-state functional MRI phenotypes and four major CVDs: hypertension, atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD). Sensitivity analyses, including MR-Egger regression and weighted median methods, were conducted to ensure the robustness of causal estimates and to test for potential pleiotropy. Results For hypertension, four networks showed negative causal associations (ORs 0.882–0.904), primarily involving motor, subcortical-cerebellar, default mode, and visual networks. In AF, we observed both increased connectivity in salience and default mode networks (ORs 1.157–1.288) and decreased connectivity in visual-motor networks (OR 0.790). For HF, three networks showed significant associations: decreased connectivity in visual and temporal networks (ORs 0.791–0.804) and increased connectivity in motor networks (OR 1.352). CAD was associated with increased connectivity in both default mode and central executive networks (ORs 1.145–1.147). These relationships remained robust after multiple sensitivity analyses. Conclusion Our findings reveal novel bidirectional causal relationships between specific brain functional networks and CVDs, with distinct patterns of network involvement for different CVDs suggesting disease-specific mechanisms in the cardio-cerebral axis. These findings identify potential neuroimaging biomarkers for early detection and monitoring of cardiovascular diseases.

ChatGPT, an advanced AI language model, presents a transformative opportunity in several fields including the medical education. This article examines the integration of ChatGPT into healthcare learning environments, exploring its potential to revolutionize knowledge acquisition, personalize education, support curriculum development, and enhance clinical reasoning. The AI’s ability to swiftly access and synthesize medical information across various specialties offers significant value to students and professionals alike. It provides rapid answers to queries on medical theories, treatment guidelines, and diagnostic methods, potentially accelerating the learning curve. The paper emphasizes the necessity of verifying ChatGPT’s outputs against authoritative medical sources. A key advantage highlighted is the AI’s capacity to tailor learning experiences by assessing individual needs, accommodating diverse learning styles, and offering personalized feedback. The article also considers ChatGPT’s role in shaping curricula and assessment techniques, suggesting that educators may need to adapt their methods to incorporate AI-driven learning tools. Additionally, it explores how ChatGPT could bolster clinical problem-solving through AI-powered simulations, fostering critical thinking and diagnostic acumen among students. While recognizing ChatGPT’s transformative potential in medical education, the article stresses the importance of thoughtful implementation, continuous validation, and the establishment of protocols to ensure its responsible and effective application in healthcare education settings.

To investigate the effect of salvianolic acid A (SA) on the permeability of blood-brain barrier (BBB) and brain microvascular pericyte apoptosis in spontaneously hypertensive rats (SHR). Evans Blue was used to determine the BBB permeability in control rats and SHR. Western blotting was used to evaluate the expression levels of relevant proteins in the pericytes isolated from the differentially treated animals. An in vitro model of hypertension was established by stimulating pericytes with angiopoietin-2 (Ang2). MTT assay was used to assess cell viability, and apoptosis and cell cycle distribution were analyzed by flow cytometry. SA attenuated BBB permeability in SHR in a dose-dependent manner. It downregulated pro-apoptotic proteins including p53, p21, Fas, FasL, cleaved-caspase 3/caspase 3 and Bax in the pericytes of SHR and upregulated CDK6, cyclin D1, CDK2, cyclin E and Bcl2. In addition, SA activated the Ras/Raf/MEK/ERK pathway in a dose-dependent manner by increasing the levels of Ras, Raf, p-MEK1, p-MEK2, p-ERK1 and p-ERK2. Finally, SA reduced Ang2-induced apoptosis of cerebral microvessels pericytes and decreased the proportion of cells in the G0/G1 phase of the cell cycle by inhibiting the p53 pathway and activating the Ras/Raf/MEK/ERK pathway. SA reduced BBB permeability in spontaneously hypertensive rats, possibly by inhibiting Ang2-induced apoptosis of pericytes by activating the Ras/Raf/MEK/ERK pathway.

Polyhydroxybutyrate (PHB) is a class of biodegradable polymers generally used by prokaryotes as carbon sources and for energy storage. This study explored the feasibility of repurposing used soybean oil (USO) as a cost-effective carbon substrate for the production of PHB by the strain Gordonia terrae S-LD, marking the first report on PHB biosynthesis by this rare actinomycete species. This strain can grow under a broad range of temperatures (25–40 ℃), initial pH values (4–10), and salt concentrations (0–7%). The findings indicate that this strain can synthesize PHB at a level of 2.63 ± 0.6 g/L in a waste-containing medium containing 3% NaCl within a 3 L triangular flask, accounting for 66.97% of the cell dry weight. Furthermore, 1 H NMR, 13 C NMR, and GC–MS results confirmed that the polymer was PHB. The thermal properties of PHB, including its melting (T m ) and crystallization (T c ) temperatures of 176.34 °C and 56.12 °C respectively, were determined via differential scanning calorimetry analysis. The produced PHB was characterized by a weight-average molecular weight (M w ) of 5.43 × 10 5  g/mol, a number-average molecular weight (M n ) of 4.00 × 10 5  g/mol, and a polydispersity index (PDI) of 1.36. In addition, the whole genome was sequenced, and the PHB biosynthetic pathway and quantitative expression of key genes were delineated in the novel isolated strain. In conclusion, this research introduces the first instance of polyhydroxyalkanoate (PHA) production by Gordonia terrae using used soybean oil as the exclusive carbon source, which will enrich strain resources for future PHB biosynthesis.