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Frontiers in Endocrinology 2023Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, and nonalcoholic...
Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, and nonalcoholic fatty liver disease, and provides the basis for a common understanding of these chronic diseases. In this study, we provide a systematic review of the causes, mechanisms, and treatments of IR. The pathogenesis of IR depends on genetics, obesity, age, disease, and drug effects. Mechanistically, any factor leading to abnormalities in the insulin signaling pathway leads to the development of IR in the host, including insulin receptor abnormalities, disturbances in the internal environment (regarding inflammation, hypoxia, lipotoxicity, and immunity), metabolic function of the liver and organelles, and other abnormalities. The available therapeutic strategies for IR are mainly exercise and dietary habit improvement, and chemotherapy based on biguanides and glucagon-like peptide-1, and traditional Chinese medicine treatments (e.g., herbs and acupuncture) can also be helpful. Based on the current understanding of IR mechanisms, there are still some vacancies to follow up and consider, and there is also a need to define more precise biomarkers for different chronic diseases and lifestyle interventions, and to explore natural or synthetic drugs targeting IR treatment. This could enable the treatment of patients with multiple combined metabolic diseases, with the aim of treating the disease holistically to reduce healthcare expenditures and to improve the quality of life of patients to some extent.
Topics: Insulin Resistance; Humans; Chronic Disease; Signal Transduction; Metabolic Diseases; Receptor, Insulin
PubMed: 37056675
DOI: 10.3389/fendo.2023.1149239 -
Toxins Apr 2020Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of...
Centipedes are among the oldest venomous arthropods that use their venom to subdue the prey. The major components of centipede venom are a variety of low-molecular-weight peptide toxins that have evolved to target voltage-gated ion channels to interfere with the central system of prey and produce pain or paralysis for efficient hunting. Peptide toxins usually contain several intramolecular disulfide bonds, which confer chemical, thermal and biological stability. In addition, centipede peptides generally have novel structures and high potency and specificity and therefore hold great promise both as diagnostic tools and in the treatment of human disease. Here, we review the centipede peptide toxins with reported effects on ion channels, including Nav, Kv, Cav and the nonselective cation channel polymodal transient receptor potential vanilloid 1 (TRPV1).
Topics: Animals; Arthropod Proteins; Arthropod Venoms; Bites and Stings; Chilopoda; Drug Discovery; Humans; Ion Channels; Membrane Transport Modulators; Protein Conformation; Signal Transduction; Structure-Activity Relationship
PubMed: 32260499
DOI: 10.3390/toxins12040230 -
Molecules (Basel, Switzerland) Nov 2021Peptides are characterized by their wide range of biological activity: they regulate functions of the endocrine, nervous, and immune systems. The mechanism of such...
Peptides are characterized by their wide range of biological activity: they regulate functions of the endocrine, nervous, and immune systems. The mechanism of such action of peptides involves their ability to regulate gene expression and protein synthesis in plants, microorganisms, insects, birds, rodents, primates, and humans. Short peptides, consisting of 2-7 amino acid residues, can penetrate into the nuclei and nucleoli of cells and interact with the nucleosome, the histone proteins, and both single- and double-stranded DNA. DNA-peptide interactions, including sequence recognition in gene promoters, are important for template-directed synthetic reactions, replication, transcription, and reparation. Peptides can regulate the status of DNA methylation, which is an epigenetic mechanism for the activation or repression of genes in both the normal condition, as well as in cases of pathology and senescence. In this context, one can assume that short peptides were evolutionarily among the first signaling molecules that regulated the reactions of template-directed syntheses. This situation enhances the prospects of developing effective and safe immunoregulatory, neuroprotective, antimicrobial, antiviral, and other drugs based on short peptides.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Histones; Humans; Peptides; Signal Transduction
PubMed: 34834147
DOI: 10.3390/molecules26227053 -
NeuroImage. Clinical 2024Changes in eating behaviour including reductions in appetite and food intake, and healthier food cue reactivity, reward, hedonics and potentially also preference,... (Review)
Review
Changes in eating behaviour including reductions in appetite and food intake, and healthier food cue reactivity, reward, hedonics and potentially also preference, contribute to weight loss and its health benefits after obesity surgery. Functional magnetic resonance imaging (fMRI) has been increasingly used to interrogate the neural correlates of eating behaviour in obesity, including brain reward-cognitive systems, changes after obesity surgery, and links with alterations in the gut-hormone-brain axis. Neural responses to food cues can be measured by changes in blood oxygen level dependent (BOLD) signal in brain regions involved in reward processing, including caudate, putamen, nucleus accumbens, insula, amygdala, orbitofrontal cortex, and top-down inhibitory control, including dorsolateral prefrontal cortex (dlPFC). This systematic review aimed to examine: (i) results of human fMRI studies involving obesity surgery, (ii) important methodological differences in study design across studies, and (iii) correlations and associations of fMRI findings with clinical outcomes, other eating behaviour measures and mechanistic measures. Of 741 articles identified, 23 were eligible for inclusion: 16 (69.6%) longitudinal, two (8.7%) predictive, and five (21.7%) cross-sectional studies. Seventeen studies (77.3%) included patients having Roux-en-Y gastric bypass (RYGB) surgery, six (26.1%) vertical sleeve gastrectomy (VSG), and five (21.7%) laparoscopic adjustable gastric banding (LAGB). The majority of studies (86.0%) were identified as having a very low risk of bias, though only six (27.3%) were controlled interventional studies, with none including randomisation to surgical and control interventions. The remaining studies (14.0%) had a low risk of bias driven by their control groups not having an active treatment. After RYGB surgery, food cue reactivity often decreased or was unchanged in brain reward systems, and there were inconsistent findings as to whether reductions in food cue reactivity was greater for high-energy than low-energy foods. There was minimal evidence from studies of VSG and LAGB surgeries for changes in food cue reactivity in brain reward systems, though effects of VSG surgery on food cue reactivity in the dlPFC were more consistently found. There was consistent evidence for post-operative increases in satiety gut hormones glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) mediating reduced food cue reactivity after RYGB surgery, including two interventional studies. Methodological heterogeneity across studies, including nutritional state, nature of food cues, post-operative timing, lack of control groups for order effects and weight loss or dietary/psychological advice, and often small sample sizes, limited the conclusions that could be drawn, especially for correlational analyses with clinical outcomes, other eating behaviour measures and potential mediators. This systematic review provides a detailed data resource for those performing or analysing fMRI studies of obesity surgery and makes suggestions to help improve reporting and design of such studies, as well as future directions.
Topics: Humans; Cross-Sectional Studies; Obesity; Feeding Behavior; Magnetic Resonance Imaging; Weight Loss
PubMed: 38237270
DOI: 10.1016/j.nicl.2024.103563 -
Frontiers in Medicine 2023Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). In the present study, the...
Treatment of liver fibrosis in hepatolenticular degeneration with traditional Chinese medicine: systematic review of meta-analysis, network pharmacology and molecular dynamics simulation.
BACKGROUND
Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). In the present study, the curative effect was assessed using meta-analysis. The possible mechanism of TCM against LF in HLD was investigated using network pharmacology and molecular dynamics simulation.
METHODS
For literature collection, we searched several databases, including PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP) and Wan Fang database until February 2023, and the Review Manager 5.3 was used to analyze the data. Network pharmacology and molecular dynamics simulation were used to explore the mechanism of TCM in treating LF in HLD.
RESULTS
The results of the meta-analysis revealed that the addition of Chinese herbal medicine (CHM) in treating HLD resulted in a higher total clinical effective rate than western medicine alone [RR 1.25, 95% CI (1.09, 1.44), = 0.002]. It not only has a better effect on liver protection [Alanine aminotransferase: SMD = -1.20, 95% CI (-1.70, -0.70), < 0.00001; Aspartate aminotransferase: SMD = -1.41, 95% CI (-2.34, -0.49), = 0.003; Total bilirubin: SMD = -1.70, 95% CI (-3.36, -0.03), = 0.05] but also had an excellent therapeutic effect on LF through four indexes [Hyaluronic acid: SMD = -1.15, 95% CI (-1.76, -0.53), = 0.0003; Procollagen peptide III: SMD = -0.72, 95% CI (-1.29, -0.15), = 0.01; Collagen IV: SMD = -0.69, 95% CI (-1.21, -0.18), = 0.008; Laminin: SMD = -0.47, 95% CI (-0.95, 0.01), = 0.06]. Concurrently, the liver stiffness measurement decreased significantly [SMD = -1.06, 95% CI (-1.77, -0.36), = 0.003]. The results of network pharmacological experiments and molecular dynamics simulation indicate that the three high-frequency TCMs (Rhei Radix Et Rhizoma-Coptidis Rhizoma-Curcumae Longae Rhizoma, DH-HL-JH) primarily act on the core targets (AKT1, SRC, and JUN) via the core components (rhein, quercetin, stigmasterol, and curcumin), regulate the signal pathway (PI3K-Akt, MAPK, EGFR, and VEGF signaling pathways), and play a role of anti-LF.
CONCLUSION
Meta-analysis indicates that TCM is beneficial in treating HLD patients and improving LF. The present study successfully predicts the effective components and potential targets and pathways involved in treating LF for the three high-frequency CHMs of DH-HL-JH. The findings of the present study are hoped to provide some evidence support for clinical treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022302374.
PubMed: 37250630
DOI: 10.3389/fmed.2023.1193132 -
Pharmacological Research Jun 2020Since the discovery of Nesfatin-1 in 2006, intensive research was finalized to further and deeper investigate the precise physiological functions of the peptide at both...
Since the discovery of Nesfatin-1 in 2006, intensive research was finalized to further and deeper investigate the precise physiological functions of the peptide at both central and peripheral levels, rapidly enriching the knowledge regarding this intriguing molecule. Nesfatin-1 is a hypothalamic peptide generated via the post-translational processing of its precursor Nucleobindin 2, a protein supposed to play a role in many biological processes thanks to its ability to bind calcium and to interact with different intracellular proteins. Nesfatin-1 is mainly known for its anorexic properties, but it also controls water intake and glucose homeostasis. Recent experimental evidences describe the peptide as a possible direct/indirect orchestrator of central and peripheral cardiovascular control. A specific Nesfatin-1 receptor still remains to be identified although numerous studies suggest that the peptide activates extra- and intracellular regulatory pathways by involving several putative binding sites. The present paper was designed to systematically review the latest findings about Nesfatin-1, focusing on its cardiovascular regulatory properties under normal and physiopathological conditions. The hope is to provide the conceptual basis to consider Nesfatin-1 not only as a pleiotropic neuroendocrine molecule, but also as a homeostatic modulator of the cardiovascular function and with a crucial role in cardiovascular diseases.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Cardiovascular System; Hemodynamics; Humans; Nucleobindins; Prognosis; Signal Transduction; Translational Research, Biomedical
PubMed: 32201244
DOI: 10.1016/j.phrs.2020.104766 -
Journal of Molecular Medicine (Berlin,... Sep 2021As in other cardiomyopathies, extracellular matrix (ECM) remodeling plays an important role in anthracycline-induced cardiomyopathy. To understand the pattern and timing... (Meta-Analysis)
Meta-Analysis
As in other cardiomyopathies, extracellular matrix (ECM) remodeling plays an important role in anthracycline-induced cardiomyopathy. To understand the pattern and timing of ECM remodeling pathways, we conducted a systematic review in which we describe protein and mRNA markers for ECM remodeling that are differentially expressed in the hearts of animals with anthracycline-induced cardiomyopathy. We included 68 studies in mice, rats, rabbits, and pigs with follow-up of 0.1-8.2 human equivalent years after anthracycline administration. Using meta-analysis, we found 29 proteins and 11 mRNAs that were differentially expressed in anthracycline-induced cardiomyopathy compared to controls. Collagens, matrix metalloproteinases (MMPs), inflammation markers, transforming growth factor ß signaling markers, and markers for cardiac hypertrophy were upregulated, whereas the protein kinase B (AKT) pro-survival pathway was downregulated. Their expression patterns over time from single time point studies were studied with meta-regression using human equivalent years as the time scale. Connective tissue growth factor showed an early peak in expression but remained upregulated at all studied time points. Brain natriuretic peptide (BNP) and MMP9 protein levels increased in studies with longer follow-up. Significant associations were found for higher atrial natriuretic peptide with interstitial fibrosis and for higher BNP and MMP2 protein levels with left ventricular systolic function.
Topics: Animals; Anthracyclines; Apoptosis; Cardiomyopathies; Disease Models, Animal; Extracellular Matrix; Extracellular Matrix Proteins; Fibrosis; Gene Expression Regulation; Myocardium; RNA, Messenger; Signal Transduction; Time Factors; Ventricular Function, Left; Ventricular Remodeling
PubMed: 34052857
DOI: 10.1007/s00109-021-02098-8 -
Biomeditsinskaia Khimiia May 2020The C-peptide is a fragment of proinsulin, the cleavage of which forms active insulin. In recent years, new information has appeared on the physiological effects of the...
The C-peptide is a fragment of proinsulin, the cleavage of which forms active insulin. In recent years, new information has appeared on the physiological effects of the C-peptide, indicating its positive effect on many organs and tissues, including the kidneys, nervous system, heart, vascular endothelium and blood microcirculation. Studies on experimental models of diabetes mellitus in animals, as well as clinical trials in patients with diabetes, have shown that the C-peptide has an important regulatory effect on the early stages of functional and structural disorders caused by this disease. The C-peptide exhibits its effects through binding to a specific receptor on the cell membrane and activation of downstream signaling pathways. Intracellular signaling involves G-proteins and Ca2+-dependent pathways, resulting in activation and increased expression of endothelial nitric oxide synthase, Na+/K+-ATPase and important transcription factors involved in apoptosis, anti-inflammatory and other intracellular defense mechanisms. This review gives an idea of the C-peptide as a bioactive endogenous peptide that has its own biological activity and therapeutic potential.
Topics: Animals; Anti-Inflammatory Agents; C-Peptide; Diabetes Mellitus, Type 1; Humans; Insulin; Signal Transduction
PubMed: 32588825
DOI: 10.18097/PBMC20206603196 -
Biomedicine & Pharmacotherapy =... Jul 2020The vascular endothelium plays a vital role in regulating normal vascular function. Endothelial lining maintains the balance of thrombolytic and fibrinolytic...
The vascular endothelium plays a vital role in regulating normal vascular function. Endothelial lining maintains the balance of thrombolytic and fibrinolytic microenvironment in the vasculature. Alterations of vascular endothelium referred to as endothelial dysfunction, caused the pathological changes in vessel wall such activation of proinflammatory and procoagulatory that initiate atherosclerosis. The concept that endothelial dysfunction plays a critical role in the initiation of atherosclerosis due to vascular inflammation gained tremendous attention. Diabetes mellitus is a metabolic-related disease that caused high mortality and morbidity, leading to its cardiovascular complication over the past decade. Atherosclerosis is the leading cardiovascular complication in diabetes mellitus. Despite metabolic and glycemic control, atherosclerotic plaque progression remains an enormous problem in diabetes mellitus complications. Thus, new inroads therapeutic approach in preventing complications that induced inflammation in endothelial cells could help prevent the disease progression. Signal peptide-CUB-EGF like domain-containing protein 2 (SCUBE2) expressed in vascular endothelium and reported to involve in inflammation. A recent study reported an increased SCUBE2 expression in diabetes mellitus and correlated with high expression of endothelin-1 (ET-1), a proinflammatory endothelial cell-derived peptide. Moreover, this gene showed to increase during atherosclerosis development. The present systematic review will summarize the involvement of SCUBE2 in vascular endothelium function changes and vascular complication, particularly in diabetes mellitus and atherosclerosis.
Topics: Adaptor Proteins, Signal Transducing; Atherosclerosis; Blood-Brain Barrier; Calcium-Binding Proteins; Diabetic Angiopathies; Endothelium, Vascular; Hedgehog Proteins; Humans
PubMed: 32278240
DOI: 10.1016/j.biopha.2020.110129 -
Neuroscience and Biobehavioral Reviews Dec 2021The relaxin-3/RXFP3 system is one of several neuropeptidergic systems putatively implicated in regulating the behavioural alterations that characterise clinical... (Review)
Review
The relaxin-3/RXFP3 system is one of several neuropeptidergic systems putatively implicated in regulating the behavioural alterations that characterise clinical depression and anxiety, making it a potential target for clinical translation. Accordingly, this systematic review identified published reports on the role of relaxin-3/RXFP3 signalling in these neuropsychiatric disorders and their behavioural endophenotypes, evaluating evidence from animal and human studies to ascertain any relationship. We searched PubMed, EMBASE, PsycINFO and Google Scholar databases up to February 2021, finding 609 relevant records. After stringent screening, 51 of these studies were included in the final synthesis. There was considerable heterogeneity in study designs and some inconsistency across study outcomes. However, experimental evidence is consistent with an ability of relaxin-3/RXFP3 signalling to promote arousal and suppress depressive- and anxiety-like behaviour. Moreover, meta-analyses of six to eight articles investigating food intake revealed that acute RXFP3 activation had strong orexigenic effects in rats. This appraisal also identified the lack of high-quality clinical studies pertinent to the relaxin-3/RXFP3 system, a gap that future research should attempt to bridge.
Topics: Animals; Anxiety; Depression; Humans; Rats; Receptors, G-Protein-Coupled; Receptors, Peptide; Relaxin; Signal Transduction
PubMed: 34537263
DOI: 10.1016/j.neubiorev.2021.09.028