Metabolic modulation

The interaction network and pathway map uncover the potential crosstalk between sugar and hormone metabolisms as a possible reason for leaf senescence in P. ternata. Pinellia ternata, an environmentally sensitive medicinal plant, undergoes leaf senescence twice a year, affecting its development and yield. Understanding the potential mechanism that delays leaf senescence could theoretically decrease yield losses. In this study, a typical senescent population model was constructed, and an integrated analysis of transcriptomic and metabolomic profiles of P...

This study explores the molecular underpinnings of neuropathic pain (NPP) and neuroinflammation, focusing on the role of TRIM28 in the regulation of autophagy and microglia ferroptosis. Leveraging transcriptomic data associated with NPP, we identified TRIM28 as a critical regulator of ferroptosis. Through comprehensive analysis, including Gene Ontology enrichment and protein-protein interaction network assessments, we unveiled GSK3B as a downstream target of TRIM28. Experimental validation confirmed the capacity of TRIM28 to suppress GSK3B expression and attenuate autophagic processes in microglia...

In view of the safety concerns of probiotics, more and more attention is paid to the beneficial effects of dead probiotics cells. Herein, we investigated and compared the alleviation effects of viable Bifidobacterium longum subsp. infantis B8762 ( B. infantis B8762) and its heat-killed cells on dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) rats. Four groups of rats ( n = 12 per group) were included: normal control, DSS-induced colitis rats without bacterial administration (DSS), DSS-induced colitis rats with viable B...

UNLABELLED: Numerous studies have supported that nonalcoholic fatty liver disease (NAFLD) is highly associated with gut microbiota dysbiosis. Ling-Gui-Zhu-Gan decoction (LG) has been clinically used to treat NAFLD, but the underlying mechanism remains unknown. This study investigated the therapeutic effect and mechanisms of LG in mice with NAFLD induced by a high-fat diet (HD). An HD-induced NAFLD mice model was established to evaluate the efficacy of LG followed by biochemical and histopathological analysis...

Proteases are enzymes that induce irreversible post-translational modifications by hydrolyzing amide bonds in proteins. One of these proteases is matrix metalloproteinase-2 (MMP-2), which has been shown to modulate extracellular matrix remodeling and intracellular proteolysis during myocardial injury. However, the substrates of MMP-2 in heart tissue are limited, and lesser known are the cleavage sites. Here, we used degradomics to investigate the substrates of intracellular MMP-2 in rat ventricular extracts...

Absorption, distribution, metabolism, excretion and toxicity (ADMET) properties play a crucial role in drug discovery and chemical safety assessment. Built on the achievements of admetSAR and its successor, admetSAR2.0, this paper introduced the new version of the series, admetSAR3.0, as a comprehensive platform for chemical ADMET assessment, including search, prediction and optimization modules. In the search module, admetSAR3.0 hosted over 370 000 high-quality experimental ADMET data for 104 652 unique compounds, and supplemented chemical structure similarity search function to facilitate read-across...

PURPOSE: Benzalkonium chloride (BAK) is a common preservative in ophthalmic formulations that causes cytotoxic damage to the corneal epithelial cells. This study aims to explore the role of mesenchymal stem cell (MSC)-derived conditioned medium in modulating the BAK-induced cytotoxic effects in cultured human corneal epithelial cells (HCECs) as a cell-free therapeutic agent. METHODS: The in vitro cultured HCECs derived from a HCE cell line were treated with BAK (0...

The problem of soil barrier caused by excessive accumulation of nitrogen is common in continuous cropping soil of facility agriculture. To investigate the modulating effects of biochar amendment on soil nitrogen transformation in greenhouse continuous cropping systems, we conducted a pot experiment with two treatments, no biochar addition (CK) and 5% biochar addition (mass ratio). We analyzed the effects of biochar addition on soil microbial community structure, abundances of genes functioning in nitrogen cycling, root growth and nitrogen metabolism-related genes expressions of cucumber seedlings...

Bioelectronic medicine are an emerging class of treatments aiming to modulate body nervous activity to correct pathological conditions and restore health. Recently, it was shown that the high frequency electrical neuromodulation of the carotid sinus nerve (CSN), a small branch of the glossopharyngeal nerve that connects the carotid body (CB) to the brain, restores metabolic function in type 2 diabetes (T2D) animal models highlighting its potential as a new therapeutic modality to treat metabolic diseases in humans...

The morphology is the consequence of evolution and adaptation. Escherichia coli is rod-shaped bacillus with regular dimension of about 1.5 μm long and 0.5 μm wide. Many shape-related genes have been identified and used in morphology engineering of this bacteria. However, little is known about if specific metabolism and metal irons could modulate bacteria morphology. Here in this study, we discovered filamentous shape change of E. coli cells overexpressing pigeon MagR, a putative magnetoreceptor and extremely conserved iron-sulfur protein...

INTRODUCTION: Amidst the challenging environmental conditions characterized by low oxygen levels and cold temperatures on the plateau, alterations in nutrient supply emerge as pivotal factors influencing the survival and reproduction of yaks. Intensive feeding stands out as a substantial mechanism for nutrient provision, initiating discernible changes in the host's rumen flora. Within the extreme natural conditions prevailing in the plateau area of northwest Yunnan, China, there exists a con-strained comprehension of the variations in rumen microflora, fermentation parameters, and growth responses exhibited by yaks subjected to intensive feeding...

Sucrose content is one of the important factors to determine longan fruit flavor quality. To gain deep insight of molecular mechanism on sucrose accumulation in longan, we conducted comparative transcriptomic analysis between low sucrose content longan cultivar 'Qingkebaoyuan' and high sucrose content cultivar 'Songfengben'. A total of 12,350 unique differentially expressed genes (DEGs) were detected across various development stages and different varieties, including hexokinase (HK) and sucrose-phosphate synthase (SPS), which are intricately linked to soluble sugar accumulation and metabolism...

Isoproterenol (ISO), a chemically synthesized catecholamine, belongs to β-adrenoceptor agonist used to treat bradycardia. The β-adrenergic agonist is an essential regulator of myocardial metabolism and contractility; however, excessive exposure to ISO can initiate oxidative stress and inflammation. This study aims to investigate the molecular mechanisms underlying ISO-induced cardiac remodeling, the protective efficacy of resveratrol (RSVR), and its liposomal formulation (L-RSVR) against such cardiac change...

Alcohol use disorders (AUDs) impose an enormous societal and financial burden, and world-wide, alcohol misuse is the 7th leading cause of premature death1. Despite this, there are currently only 3 FDA approved pharmacological treatments for the treatment of AUDs in the United States. The neurotensin (Nts) system has long been implicated in modulating behaviors associated with alcohol misuse. Recently, a novel compound, SBI-553, that biases the action of Nts receptor 1 (NTSR1) activation, has shown promise in preclinical models of psychostimulant misuse...

Interleukin-6 (IL-6) is a major pro-inflammatory cytokine for which the levels in plasma demonstrate a robust correlation with age and body mass index (BMI) as part of the senescence-associated secretory phenotype. IL-6 cytokines also play a crucial role in metabolic homeostasis and regenerative processes, primarily via the canonical STAT3 pathway. Thus, selective modulation of IL-6 signaling may offer a unique opportunity for therapeutic interventions. Recently, we discovered that a non-canonical signaling pathway downstream of tyrosine (Y) 814 within the intracellular domain of gp130, the IL-6 co-receptor, is responsible for the recruitment and activation of SRC family of kinases (SFK)...

The plasticity and diversity of cell types with specialized functions likely defines the capacity of multicellular organisms to adapt to physiologic stressors. The kidney collecting ducts contribute to water, electrolyte, and pH homeostasis and are composed of mature intermingled epithelial cell types that are susceptible to transdifferentiate. The conversion of kidney collecting duct principal cells to intercalated cells is actively inhibited by Notch signaling to ensure urine concentrating capability. Here we identify Hes1, a target of Notch signaling, allows for maintenance of functionally distinct epithelial cell types within the same microenvironment by regulating mechanistic target of rapamycin complex 1 (mTORC1) activity...

Diabetes mellitus is one of the biggest challenges for the scientific community in the 21st century. With the increasing number of cases of diabetes and drug-resistant diabetes, there is an urgent need to develop new potent molecules capable of combating this cruel disease. Medicinal chemistry concerns the discovery, development, identification, and interpretation of the mode of action of biologically active compounds at the molecular level. Oxadiazole-based derivatives have come up as a potential option for antidiabetic drug research...

Protein-encoding genes only constitute less than 2% of total human genomic sequences, and 98% of genetic information was previously referred to as "junk DNA". Meanwhile, non-coding RNAs (ncRNAs) consist of approximately 60% of the transcriptional output of human cells. Thousands of ncRNAs have been identified in recent decades, and their essential roles in the regulation of gene expression in diverse cellular pathways associated with fundamental cell processes, including proliferation, differentiation, apoptosis, and metabolism, have been extensively investigated...

Sepsis, a severe systemic inflammatory response to infection, remains a leading cause of morbidity and mortality worldwide. Exosomes, as mediators of intercellular communication, play a pivotal role in the pathogenesis of sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, and organ dysfunction. This review highlights the emerging significance of exosomes in these processes. Initially, it provides an in-depth insight into exosome biogenesis and characterization, laying the groundwork for understanding their diverse and intricate functions...

Intervertebral Disc (IVD) degeneration has been associated with a chronic inflammatory response, but knowledge on the contribution of distinct IVD cells, namely CD44, to the progression of IVD degeneration remains elusive. Here, bovine nucleus pulposus (NP) CD44 cells were sorted and compared by gene expression and proteomics with the negative counterpart. NP cells were then stimulated with IL-1b (10 ng/ml) and dynamics of CD44 gene and protein expression was analyzed upon pro-inflammatory treatment. The results emphasize that CD44 has a multidimensional functional role in IVD metabolism, ECM synthesis and production of neuropermissive factors...