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Biomolecules Nov 2023Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular... (Review)
Review
Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular control. There are over 1000 known proteins that either reside within the mitochondria or are transiently associated with it. These mitochondrial proteins represent a functional subcellular protein network (mtProteome) that is encoded by mitochondrial and nuclear genomes and significantly varies between cell types and conditions. In neurons, the high metabolic demand and differential energy requirements at the synapses are met by specific modifications to the mtProteome, resulting in alterations in the expression and functional properties of the proteins involved in energy production and quality control, including fission and fusion. The composition of mtProteomes also impacts the localization of mitochondria in axons and dendrites with a growing number of neurodegenerative diseases associated with changes in mitochondrial proteins. This review summarizes the findings on the composition and properties of mtProteomes important for mitochondrial energy production, calcium and lipid signaling, and quality control in neural cells. We highlight strategies in mass spectrometry (MS) proteomic analysis of mtProteomes from cultured cells and tissue. The research into mtProteome composition and function provides opportunities in biomarker discovery and drug development for the treatment of metabolic and neurodegenerative disease.
Topics: Humans; Proteome; Neurodegenerative Diseases; Proteomics; Mitochondria; Neurons; Mitochondrial Proteins
PubMed: 38002320
DOI: 10.3390/biom13111638 -
Frontiers in Endocrinology 2023Diabetic retinopathy (DR) is a common complication of diabetes. The adipocytokines are closely associated with the occurrence and development of diabetes and its related... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic retinopathy (DR) is a common complication of diabetes. The adipocytokines are closely associated with the occurrence and development of diabetes and its related complications. Literature confirms that the level of adiponectin in patients with DR is significantly higher; however, the relationship between other adipocytokines (leptin, chemerin, apelin, and omentin-1) and DR remains unclear.
AIM
This study aimed to systematically evaluate the association between adipocytokines (leptin, chemerin, apelin, and omentin-1) and DR.
METHODS
The PubMed, Web of Science, Embase, EBSCO and Willy databases were used to search for potential studies with keywords such as "diabetic retinopathy" or "DR" in combination with the terms "leptin," "chemerin", "apelin" or "omentin-1" in the search titles or abstracts. Standardized mean differences (SMD) with corresponding 95% confidence intervals (CIs) were determined as the results of the meta-analysis.
RESULTS
After screening, 18 articles were included in the meta-analysis including 750 DR cases and 993 controls. Leptin and chemerin levels in patients with DR were significantly higher than those in the control group (SMD: 0.68, 95% CI [0.1, 1.26]; SMD: 0.79, 95% CI [0.35, 1.23]). The omentin-1 levels in patients with DR were significantly lower than those in the controls (SMD: -0.85, 95% CI [-1.08, -0.62]).
CONCLUSIONS
To the best of our knowledge, this is the first meta-analysis to evaluate the leptin, chemerin, apelin, and omentin-1 levels in patients with DR. Further high-quality studies are warranted to support the association between these adipocytokines and DR.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=443770, identifier CRD42023443770.
Topics: Humans; Adipokines; Diabetic Retinopathy; Leptin; Apelin; Adiponectin; Diabetes Mellitus
PubMed: 37867518
DOI: 10.3389/fendo.2023.1271027 -
Journal of Sport and Health Science Mar 2024One of the pathological hallmarks distinguishing Alzheimer's disease from other dementias is the accumulation of amyloid beta (Aβ). Higher physical activity is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
One of the pathological hallmarks distinguishing Alzheimer's disease from other dementias is the accumulation of amyloid beta (Aβ). Higher physical activity is associated with decreased dementia risk, and one potential path could be through Aβ levels modulation. We aimed to explore the relationship between physical activity and Aβ in middle-aged and older adults.
METHODS
A systematic search of PubMed, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, and SPORTDiscus was performed from inception to April 28, 2022. Studies were eligible if they included physical activity and Aβ data in adults aged 45 years or older. Multi-level meta-analyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβ levels.
RESULTS
In total, 37 articles were included (8 randomized controlled trials, 3 non-randomized controlled trials, 4 prospective longitudinal studies, and 22 cross-sectional studies). The overall effect size of physical activity interventions on changes in blood Aβ was medium (pooled standardized mean difference = -0.69, 95% confidence interval (95%CI): -1.41 to 0.03; I = 74.6%). However, these results were not statistically significant, and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid (CSF) and brain Aβ. Data from observational studies were examined based on measurements of Aβ in the brain using positron emission tomography scans, CSF, and blood. Higher physical activity was positively associated with Aβ only in the CSF (Estimate r = 0.12; 95%CI: 0.05-0.18; I = 38.00%).
CONCLUSION
Physical activity might moderately reduce blood Aβ in middle-aged and older adults. However, results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies. In observational studies, higher levels of physical activity were positively associated with Aβ only in CSF. Therefore, further research is needed to understand the modulating role of physical activity in the brain, CSF, and blood Aβ, as well as its implication for cognitive health.
Topics: Middle Aged; Humans; Aged; Amyloid beta-Peptides; Prospective Studies; Cross-Sectional Studies; Alzheimer Disease; Brain
PubMed: 37558161
DOI: 10.1016/j.jshs.2023.08.001 -
Molecular Psychiatry Dec 2023The γ-aminobutyric acid (GABA)ergic system is the primary inhibitory neurotransmission system in the mammalian brain. Its dysregulation has been shown in multiple brain... (Meta-Analysis)
Meta-Analysis
The γ-aminobutyric acid (GABA)ergic system is the primary inhibitory neurotransmission system in the mammalian brain. Its dysregulation has been shown in multiple brain conditions, but in Alzheimer's disease (AD) studies have provided contradictory results. Here, we conducted a systematic review with meta-analysis to investigate whether the GABAergic system is altered in AD patients compared to healthy controls (HC), following the PRISMA 2020 Statement. We searched PubMed and Web of Science from database inception to March 18, 2023 for studies reporting GABA, glutamate decarboxylase (GAD) 65/67, GABA, GABA and GABA receptors, GABA transporters (GAT) 1-3 and vesicular GAT in the brain, and GABA levels in the cerebrospinal fluid (CSF) and blood. Heterogeneity was estimated using the I index, and the risk of bias was assessed with an adapted questionnaire from the Joanna Briggs Institute Critical Appraisal Tools. The search identified 3631 articles, and 48 met the final inclusion criteria (518 HC, mean age 72.2, and 603 AD patients, mean age 75.6). Random-effects meta-analysis [standardized mean difference (SMD)] revealed that AD patients presented lower GABA levels in the brain (SMD = -0.48 [95% CI = -0.7, -0.27], adjusted p value (adj. p) < 0.001) and in the CSF (-0.41 [-0.72, -0.09], adj. p = 0.042), but not in the blood (-0.63 [-1.35, 0.1], adj. p = 0.176). In addition, GAD65/67 (-0.67 [-1.15, -0.2], adj. p = 0.006), GABA receptor (-0.51 [-0.7, -0.33], adj. p < 0.001), and GABA transporters (-0.51 [-0.92, -0.09], adj. p = 0.016) were lower in the AD brain. Here, we showed a global reduction of GABAergic system components in the brain and lower GABA levels in the CSF of AD patients. Our findings suggest the GABAergic system is vulnerable to AD pathology and should be considered a potential target for developing pharmacological strategies and novel AD biomarkers.
Topics: Alzheimer Disease; Humans; gamma-Aminobutyric Acid; Glutamate Decarboxylase; Brain; Aged; Receptors, GABA; GABA Plasma Membrane Transport Proteins; Female; Male
PubMed: 37419974
DOI: 10.1038/s41380-023-02140-w -
Biomedicine & Pharmacotherapy =... Dec 2023Deep Brain Stimulation (DBS) and Spinal Cord Stimulation (SCS) represent burgeoning treatments for diverse neurological disorders. This systematic review aims to... (Review)
Review
INTRODUCTION
Deep Brain Stimulation (DBS) and Spinal Cord Stimulation (SCS) represent burgeoning treatments for diverse neurological disorders. This systematic review aims to consolidate findings on the immunological and endocrine effects of DBS and SCS, shedding light on the intricate mechanisms of neuromodulation.
MATERIALS AND METHODS
This systematic review, aligned with PRISMA protocols, synthesizes findings from 33 references-20 on DBS and 13 on SCS-to unravel the immunological and endocrine impacts of neuromodulation.
RESULTS
DBS interventions exhibited divergent effects on cytokines, with an increase in hepcidin levels and a variable impact on the IL-6/IL-10 ratio. While some studies reported elevated IL-6, animal studies consistently demonstrated a reduction in IL-1β and IL-6, with no significant changes in TNF-α and an increase in IL-10. Noteworthy hormonal changes included decreased corticosterone and ACTH concentrations and increased oxytocin levels following DBS of the hypothalamus. SCS mirrored similar effects on interleukins, indicating a reduction in IL-6 and IL-1β and an increase in IL-10 levels. Additionally, SCS led to reduced VEGF levels and elevated expression of neurotrophic factors such as BDNF and GDNF, particularly under burst stimulation.
CONCLUSIONS
Both DBS and SCS exert anti-inflammatory effects, manifesting as a decrease in pro-inflammatory cytokines alongside the stimulation of anti-inflammatory cytokine synthesis. These findings, observed in both animal and human models, imply that neurostimulation may modify the trajectory of neurological diseases by modulating local immune responses in an immunomodulatory and endocrine manner. This comprehensive exploration sets the stage for future research endeavors in this evolving domain.
Topics: Animals; Humans; Interleukin-10; Spinal Cord Stimulation; Deep Brain Stimulation; Interleukin-6; Vascular Endothelial Growth Factor A; Cytokines; Immunity; Anti-Inflammatory Agents; Spinal Cord
PubMed: 37862972
DOI: 10.1016/j.biopha.2023.115732 -
Thorax Oct 2023Obesity is associated with more severe asthma, however, the mechanisms responsible are poorly understood. Obesity is also associated with low-grade systemic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obesity is associated with more severe asthma, however, the mechanisms responsible are poorly understood. Obesity is also associated with low-grade systemic inflammation; it is possible that this inflammation extends to the airways of adults with asthma, contributing to worse asthma outcomes. Accordingly, the aim of this review was to examine whether obesity is associated with increased airway and systemic inflammation and adipokines, in adults with asthma.
METHODS
Medline, Embase, CINAHL, Scopus and Current Contents were searched till 11 August 2021. Studies reporting measures of airway inflammation, systemic inflammation and/or adipokines in obese versus non-obese adults with asthma were assessed. We conducted random effects meta-analyses. We assessed heterogeneity using the I statistic and publication bias using funnel plots.
RESULTS
We included 40 studies in the meta-analysis. Sputum neutrophils were 5% higher in obese versus non-obese asthmatics (mean difference (MD)=5.0%, 95% CI: 1.2 to 8.9, n=2297, p=0.01, I=42%). Blood neutrophil count was also higher in obesity. There was no difference in sputum %eosinophils; however, bronchial submucosal eosinophil count (standardised mean difference (SMD)=0.58, 95% CI=0.25 to 0.91, p<0.001, n=181, I=0%) and sputum interleukin 5 (IL-5) (SMD=0.46, 95% CI=0.17 to 0.75, p<0.002, n=198, I=0%) were higher in obesity. Conversely, fractional exhaled nitric oxide was 4.5 ppb lower in obesity (MD=-4.5 ppb, 95% CI=-7.1 ppb to -1.8 ppb, p<0.001, n=2601, I=40%). Blood C reactive protein, IL-6 and leptin were also higher in obesity.
CONCLUSIONS
Obese asthmatics have a different pattern of inflammation to non-obese asthmatics. Mechanistic studies examining the pattern of inflammation in obese asthmatics are warranted. Studies should also investigate the clinical relevance of this altered inflammatory response.
PROSPERO REGISTERATION NUMBER
CRD42021254525.
Topics: Adult; Humans; Asthma; Inflammation; Eosinophils; Obesity; Leukocyte Count; Sputum
PubMed: 36948588
DOI: 10.1136/thorax-2022-219268 -
Cytokine Sep 2023Biliary tract cancer (BTC) is a highly malignant tumor that originates from bile duct epithelium and is categorized into intrahepatic cholangiocarcinoma (iCCA),... (Review)
Review
Biliary tract cancer (BTC) is a highly malignant tumor that originates from bile duct epithelium and is categorized into intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA), distal cholangiocarcinoma (dCCA) and gallbladder cancer (GBC) according to the anatomic location. Inflammatory cytokines generated by chronic infection led to an inflammatory microenvironment which influences the carcinogenesis of BTC. Interleukin-6 (IL-6), a multifunctional cytokine secreted by kupffer cells, tumor-associated macrophages, cancer-associated fibroblasts (CAFs) and cancer cells, plays a central role in tumorigenesis, angiogenesis, proliferation, and metastasis in BTC. Besides, IL-6 serves as a clinical biomarker for diagnosis, prognosis, and monitoring for BTC. Moreover, preclinical evidence indicates that IL-6 antibodies could sensitize tumor immune checkpoint inhibitors (ICIs) by altering the number of infiltrating immune cells and regulating the expression of immune checkpoints in the tumor microenvironment (TME). Recently, IL-6 has been shown to induce programmed death ligand 1 (PD-L1) expression through the mTOR pathway in iCCA. However, the evidence is insufficient to conclude that IL-6 antibodies could boost the immune responses and potentially overcome the resistance to ICIs for BTC. Here, we systematically review the central role of IL-6 in BTC and summarize the potential mechanisms underlying the improved efficacy of treatments combining IL-6 antibodies with ICIs in tumors. Given this, a future direction is proposed for BTC to increase ICIs sensitivity by blocking IL-6 pathways.
Topics: Humans; Interleukin-6; Biliary Tract Neoplasms; Cholangiocarcinoma; Cytokines; Antibodies; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Tumor Microenvironment
PubMed: 37331095
DOI: 10.1016/j.cyto.2023.156271 -
The American Journal of Clinical... Aug 2023Serving whey protein before a meal in order to lower postprandial blood glucose concentrations is known as a premeal. The underlying mechanisms are only partly... (Meta-Analysis)
Meta-Analysis
Whey Protein Premeal Lowers Postprandial Glucose Concentrations in Adults Compared with Water-The Effect of Timing, Dose, and Metabolic Status: a Systematic Review and Meta-analysis.
BACKGROUND
Serving whey protein before a meal in order to lower postprandial blood glucose concentrations is known as a premeal. The underlying mechanisms are only partly understood but may involve stimulation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and insulin secretion together with a slower gastric emptying rate.
OBJECTIVES
The objective of this systematic review and meta-analysis was to review all randomized clinical trials investigating premeals with whey protein in comparison with a nonactive comparator (control) that evaluated plasma glucose, GLP-1, GIP, insulin, and/or gastric emptying rate. Secondary aims included subgroup analyses on the timing and dose of the premeal together with the metabolic state of the participants [lean, obese, and type 2 diabetes mellitus (T2DM)].
METHODS
We searched EMBASE, CENTRAL, PUBMED, and clinicaltrials.gov and found 16 randomized crossover trials with a total of 244 individuals. The last search was performed on 9 August, 2022.
RESULTS
Whey protein premeals lowered peak glucose concentration by -1.4 mmol/L [-1.9 mmol/L; -0.9 mmol/L], and the area under the curve for glucose was -0.9 standard deviation (SD) [-1.2 SD; -0.6 SD] compared with controls (high certainty). In association with these findings, whey protein premeals elevated GLP-1 (low certainty) and peak insulin (high certainty) concentrations and slowed gastric emptying rate (high certainty) compared with controls. Subgroup analyses showed a more pronounced and prolonged glucose-lowering effect in individuals with T2DM compared with participants without T2DM. The available evidence did not elucidate the role of GIP. The protein dose used varied between 4 and 55 g, and meta-regression analysis showed that the protein dose correlated with the glucose-lowering effects.
CONCLUSIONS
In conclusion, whey protein premeals lower postprandial blood glucose, reduce gastric emptying rate, and increase peak insulin. In addition, whey protein premeals may elevate plasma concentrations of GLP-1. Whey protein premeals may possess clinical potential, but the long-term effects await future clinical trials.
Topics: Humans; Adult; Whey Proteins; Glucagon; Blood Glucose; Diabetes Mellitus, Type 2; Water; Insulin; Glucagon-Like Peptide 1; Gastric Inhibitory Polypeptide; Glucose; Gastric Emptying; Postprandial Period
PubMed: 37536867
DOI: 10.1016/j.ajcnut.2023.05.012 -
Virology Aug 2023Senecavirus A (SVA) is an emerging virus, causing vesicular disease in swine. SVA is a single-stranded, positive-sense RNA virus, which is the only member of the genus... (Review)
Review
Senecavirus A (SVA) is an emerging virus, causing vesicular disease in swine. SVA is a single-stranded, positive-sense RNA virus, which is the only member of the genus Senecavirus in the family Picornaviridae. SVA genome encodes 12 proteins: L, VP4, VP2, VP3, VP1, 2A, 2B, 2C, 3A, 3B, 3C and 3D. The VP1 to VP4 are structural proteins, and the others are nonstructural proteins. The replication of SVA in host cells is a complex process coordinated by an elaborate interplay between the structural and nonstructural proteins. Structural proteins are primarily involved in the invasion and assembly of virions. Nonstructural proteins modulate viral RNA translation and replication, and also take part in antagonizing the antiviral host response and in disrupting some cellular processes to allow virus replication. Here, we systematically reviewed the molecular functions of SVA structural and nonstructural proteins by reference to literatures of SVA itself and other picornaviruses.
Topics: Animals; Swine; Picornaviridae; Viral Proteins; RNA, Viral
PubMed: 37348144
DOI: 10.1016/j.virol.2023.06.004 -
Journal of Ethnopharmacology Sep 2023Functional dyspepsia (FD), a chronic upper gastrointestinal syndrome, seriously affects the quality of life of patients and poses a significant economic burden. Since... (Meta-Analysis)
Meta-Analysis Review
ETHNOPHARMACOLOGICAL RELEVANCE
Functional dyspepsia (FD), a chronic upper gastrointestinal syndrome, seriously affects the quality of life of patients and poses a significant economic burden. Since the pathological mechanisms of FD have not been fully elucidated, conventional therapies such as prokinetics, proton pump inhibitors, and antidepressants have some limitations. Siho-sogan-san (SHS) is commonly used as a therapeutic alternative in traditional medicine; however, scientific and clinical evidence supporting its application in FD remains insufficient.
AIM OF THE STUDY
This review aimed to assess the safety and effectiveness of SHS and in combined with Western medicine (WM) for the treatment of FD.
METHODS
Eleven databases, including EMBASE, Medline, and Cochrane Library, were searched for randomized controlled trials (RCTs) on FD published before December 31, 2022. After two independent reveiwers sceened and selected studies according to the inclusion and exclusion criteria, clinical data was pooled and synthesized via Review Manager software. The outcome parameters included total clinical effectiveness rate (TCE), time for symptom improvement, levels of motilin and corticotropin-releasing hormone (CRH), and adverse events. Cochrane's risk of bias tool was used for quality assessment.
RESULTS
A total of 12 studies that included 867 participants comparing WM with SHS or combination therapy (SHS plus WM) were identified. Through a meta-analysis of five studies including 363 patients, SHS compared with WM showed a positive result in safely increasing TCE [risk ratio = 1.36, 95% confidence interval (CI) 1.22 to 1.51, P < 0.00001]. The time for symptom improvement, including abdominal pain, belching, nausea, vomiting, and abdominal distension, was significantly more shortened in the combination therapy than WM group. Furthermore, combination therapy resulted in greater secretion of motilin than WM alone [mean difference = 67.95, 95% CI 39.52 to 96.39, P < 0.00001]. No remarkable difference was observed in CRH levels between the combination therapy and WM groups. For a subgroup analysis, the administration of SHS based on the type of pattern identification (PI) showed larger effect size than in the group that do not consider PI.
CONCLUSIONS
These results suggest that SHS and combination therapy can be considered effective and safe options for the treatment of FD. However, owing to the low quality of the included studies, more well-designed investigational studies and RCTs with longer treatment and follow-up period are needed.
Topics: Humans; Dyspepsia; Motilin; Drugs, Chinese Herbal; Phytotherapy; Plants, Medicinal; Medicine, Traditional
PubMed: 37127143
DOI: 10.1016/j.jep.2023.116518