Pathways

OBJECTIVES: Dopamine and related receptors are evidenced in pancreatic endocrine tissue, but the impact on islet β-cell stimulus-secretion as well as (patho)physiological role are unclear. METHODS: The present study has evaluated islet cell signalling pathways and biological effects of dopamine, as well as alterations of islet dopamine in rodent models of diabetes of different aetiology. KEY FINDINGS: The dopamine precursor L-DOPA partially impaired glucose tolerance in mice and attenuated glucose-, exendin-4, and alanine-induced insulin secretion...

Mesenchymal stem cells (MSCs) have demonstrated potent immunomodulatory properties that have shown promise in the treatment of autoimmune diseases, including rheumatoid arthritis (RA). However, the inherent heterogeneity of MSCs triggered conflicting therapeutic outcomes, raising safety concerns and limiting their clinical application. This study aimed to investigate the potential of extracellular vesicles derived from human gingival mesenchymal stem cells (GMSC-EVs) as a therapeutic strategy for RA. Through in vivo experiments using an experimental RA model, our results demonstrated that GMSC-EVs selectively homed to inflamed joints and recovered Treg and Th17 cells balance, resulting in the reduction of arthritis progression...

PURPOSE OF REVIEW: Gastrointestinal mucositis (GIM) is a significant complication of cancer therapy. Whilst inflammation is a central feature of GIM, studies attempting to mitigate mucosal damage via this mechanism are scarce. This review describes the relation between GIM, local and systemic inflammation, and the microbiome and its metabolites, and explores recent research on therapeutics that target this relationship. RECENT FINDINGS: Recent literature underscores the pivotal role of inflammation in GIM, elucidating its bidirectional relation with disturbance of the gut microbiota composition and intestinal permeability...

Cystic fibrosis (CF), an inherited genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, results in sticky and thick mucosal fluids. This environment facilitates the colonization of various microorganisms, some of which can cause acute and chronic lung infections, while others may positively impact the disease. Rothia mucilaginosa , an oral commensal, is relatively abundant in the lungs of CF patients. Recent studies have unveiled its anti-inflammatory properties using in vitro three-dimensional lung epithelial cell cultures and in vivo mouse models relevant to chronic lung diseases...

Intervertebral disc degeneration is characterized by deterioration in structural support that is potentially followed by stimulated neuronal ingrowth, and dysfunction of cellular physiology in the disc. Discogenic low back pain originates from nociceptors within the intervertebral disc or the cartilage endplate. This narrative review examines the mechanisms of disc degeneration, the association between degeneration and pain, and the current diagnosis and treatment of discogenic low back pain. Mechanisms of disc degeneration include dysregulated homeostasis of the extracellular matrix of the disc, altered spine mechanics, DNA damage, oxidative stress, perturbed cell signaling pathways, and cellular senescence...

To investigate the impact of Poa alpigena Lindm on rhizosphere and bulk soil microorganisms in Haixin Mountain, Qinghai Lake, this study employed metagenomics technology to analyze the microbial communities of the samples. Results showed that 65 phyla, 139 classes, 278 orders, 596 families, 2376 genera, and 5545 species of soil microorganisms were identified from rhizosphere and bulk soil samples. Additionally, a microbial gene library specific to Poa alpigena Lindm was established for Qinghai Lake. Through α-diversity analysis, the richness and diversity of bulk microorganisms both significantly had a higher value than that in rhizosphere soil...

PURPOSE OF REVIEW: This review aims to provide a theoretical basis and insights for quercetin's clinical application in the prevention and treatment of osteoporosis (OP), analyzing its roles in bone formation promotion, bone resorption inhibition, anti-inflammation, antioxidant effects, and potential mechanisms. RECENT FINDINGS: OP, a prevalent bone disorder, is marked by reduced bone mineral density and impaired bone architecture, elevating the risk of fractures in patients...

The effect of Ryanodine receptor2 (RyR2) and its stabilizer on cardiac hypertrophy is not well known. C57/BL6 mice underwent transverse aortic contraction (TAC) or sham surgery were administered dantrolene, the RyR2 stabilizer, or control drug. Dantrolene significantly alleviated TAC-induced cardiac hypertrophy in mice, and RNA sequencing was performed implying calcineurin/NFAT3 and TNF-α/NF-κB/NLRP3 as critical signaling pathways. Further expression analysis and Western blot with heart tissue as well as neonatal rat cardiomyocyte (NRCM) model confirmed dantrolene decreases the activation of calcineurin/NFAT3 signaling pathway and TNF-α/NF-κB/NLRP3 signaling pathway, which was similar to FK506 and might be attenuated by calcineurin overexpression...

Ferroptosis is a form of intracellular iron-dependent cell death that differs from necrosis, autophagy and apoptosis. Intracellular iron mediates Fenton reaction resulting in lipid peroxidation production, which in turn promotes cell death. Although cancer cell exhibit's ability to escape ferroptosis by multiple pathways such as SLC7A11, GPX4, induction of ferroptosis could inhibit cancer cell proliferation, migration and invasion. In tumor microenvironment, ferroptosis could affect immune cell (T cells, macrophages etc...

PURPOSE: A strong immunosuppressive tumor microenvironment (TME) represents the major barrier responsible for the failure of current immunotherapy approaches in treating Glioblastoma Multiforme (GBM). Within the TME, the regulatory T cells (Tregs) exert immunosuppressive effects on CD8+ T cell - mediated anti-cancer immune killing. Consequently, targeting and inhibiting their immunosuppressive function emerges as an effective therapeutic strategy for GBM. The present study aimed to investigate the mechanisms and effects of Suberanilohydroxamic Acid (SAHA), a histone deacetylase inhibitor, on immunosuppressive Tregs...

Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO...

PURPOSE: Identifying the molecular mechanisms behind SARS-CoV-2 disparities and similarities will help find new treatments. The present study determines networks' shared and non-shared (specific) crucial elements in response to HCoV-229E and SARS-CoV-2 viruses to recommend candidate medications. METHODS: We retrieved the omics data on respiratory cells infected with HCoV-229E and SARS-CoV-2, constructed PPIN and GRN, and detected clusters and motifs. Using a drug-gene interaction network, we determined the similarities and disparities of mechanisms behind their host response and drug-repurposed...

Dry eye disease (DED) can arise from a variety of factors, including inflammation, meibomian gland dysfunction (MGD), and neurosensory abnormalities. Individuals with DED may exhibit a range of clinical signs, including tear instability, reduced tear production, and epithelial disruption, that are driven by different pathophysiological contributors. Those affected often report a spectrum of pain and visual symptoms that can impact physical and mental aspects of health, placing an overall burden on an individual's well-being...

Epilepsy is one of the most common neurological disorders in the world. Common epileptic drugs generally affect ion channels or neurotransmitters and prevent the emergence of seizures. However, up to a third of the patients suffer from drug-resistant epilepsy, and there is an urgent need to develop new therapeutic strategies that go beyond acute antiepileptic (antiseizure) therapies towards therapeutics that also might have effects on chronic epilepsy comorbidities such as cognitive decline and depression. The mitochondrial calcium uniporter (MCU) mediates rapid mitochondrial Ca2+ transport through the inner mitochondrial membrane...

BACKGROUND: Breast cancer is a heterogeneous and complex etiological disease. Understanding perturbations of circulating metabolites could improve prognosis. METHODS: We recruited breast cancer patients from Kaohsiung Medical University (KMU) to perform untargeted (case-control design) and targeted (patient cohort) metabolomics analyses in the discovery and validation phases to evaluate interaction effects between clinical factors and plasma metabolites using multivariable Cox proportional hazards model...

Drug repositioning or repurposing has gained worldwide attention as a plausible way to search for novel molecules for the treatment of particular diseases or disorders. Drug repurposing essentially refers to uncovering approved or failed compounds for use in various diseases. Cancer is a deadly disease and leading cause of mortality. The search for approved non-oncologic drugs for cancer treatment involved in silico modeling, databases, and literature searches. In this review, we provide a concise account of the existing non-oncologic drug molecules and their therapeutic potential in chemotherapy...

Chronic inflammatory and immune responses play key roles in the development and progression of chronic obstructive pulmonary disease (COPD). PANoptosis, as a unique inflammatory cell death modality, is involved in the pathogenesis of many inflammatory diseases. We aim to identify critical PANoptosis-related biomarkers and explore their potential effects on respiratory tract diseases and immune infiltration landscapes in COPD. Total microarray data consisting of peripheral blood and lung tissue datasets associated with COPD were obtained from the GEO database...

We identify three SDEs that inhibiting host defence from Candidatus Liberibacter asiaticus psy62, which is an important supplement to the pathogenesis of HLB. Candidatus Liberibacter asiaticus (CLas) is the main pathogen of citrus Huanglongbing (HLB). 38 new possible sec-dependent effectors (SDEs) of CLas psy62 were predicted by updated predictor SignalP 5.0, which 12 new SDEs were found using alkaline phosphate assay. Among them, SDE4310, SDE4435 and SDE4955 inhibited hypersensitivity reactions (HR) in Arabidopsis thaliana (Arabidopsis, At) and Nicotiana benthamiana leaves induced by pathogens, which lead to a decrease in cell death and reactive oxygen species (ROS) accumulation...

The acetylation of α-tubulin on lysine 40 is a well-studied post-translational modification which has been associated with the presence of long-lived stable microtubules that are more resistant to mechanical breakdown. The discovery of α-tubulin acetyltransferase 1 (ATAT1), the enzyme responsible for lysine 40 acetylation on α-tubulin in a wide range of species, including protists, nematodes, and mammals, dates to about a decade ago. However, the role of ATAT1 in different cellular activities and molecular pathways has been only recently disclosed...

We have identified and analyzed 28 SUMO-pathway proteins from pigeonpea. Enhanced transcripts of pathway genes and increased SUMO conjugation under drought signifies the role of SUMO in regulating stress. Being a protein-rich and nutrient-dense legume crop, pigeonpea (Cajanus cajan) holds a vital position in a vegetarian meal. It is a resilient crop capable of striving in harsh climates and provides a means of subsistence to small-holding farmers. Nevertheless, extremes of water scarcity and drought conditions, especially during seedling and reproductive stages, remains a major issue severely impacting the growth and overall productivity of pigeonpea...