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Arthroscopy : the Journal of... May 2024To assess the current scientific literature on the microbiome's relationship with knee osteoarthritis (OA), with specific focuses on the gut microbiome-joint axis and... (Review)
Review
PURPOSE
To assess the current scientific literature on the microbiome's relationship with knee osteoarthritis (OA), with specific focuses on the gut microbiome-joint axis and joint microbiome-joint axis.
METHODS
A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, searching PubMed, Embase, and Cochrane databases for relevant English-language clinical studies on the gut and/or joint microbiomes' association with knee OA in humans. Bias was evaluated using the methodological index for non-randomized studies score.
RESULTS
Thirty-five thousand bacterial species comprise the gut microbiome; approximately 90% are members of the phyla Bacteroides and Firmicutes. Symbiosis between the gut microbiome and host under normal physiological conditions positively affects host growth, development, immunity, and longevity. Gut microbiome imbalance can negatively influence various physiological processes, including immune response, inflammation, metabolism, and joint health including development of knee OA. In addition, next generation gene sequencing suggests the presence of microorganisms in the synovial fluid of osteoarthritic knees, and distinct microbiome profiles detected are presumed to play a role in the development of OA. With regard to the gut microbiome, consistent alterations in microbial composition between OA patients and controls are noted, in addition to several associations between certain gut bacteria with OA-related knee pain, patient-reported outcome measure performance, imaging findings, and changes in metabolic and inflammatory pathways. Regarding the joint microbiome, studies revealed increased levels of lipopolysaccharide (LPS) and LPS-binding protein in synovial fluid are associated with activated macrophages, and correlated with worsened osteophyte severity, joint space narrowing, and pain scores in knee OA patients. In addition, studies demonstrated various microbial composition differences in OA patients compared to control, with certain joint microbes directly associated with OA pathogenesis, inflammation, and metabolic dysregulation.
CONCLUSIONS
The gut microbiome-joint axis and joint microbiome shows alterations in microbial composition between osteoarthritic patients and controls. These alterations are associated with perturbations of metabolic and inflammatory pathways, imaging findings, osteoarthritis-related pain, and patient reported outcome measure performance.
LEVEL OF EVIDENCE
Systematic Review; Level III.
PubMed: 38797504
DOI: 10.1016/j.arthro.2024.05.010 -
BMJ Mental Health May 2024Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of... (Meta-Analysis)
Meta-Analysis Review
QUESTION
Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of dementia in people with schizophrenia compared with the general population. This may reflect a higher risk of developing neurodegenerative diseases such as vascular dementia or Alzheimer's disease (AD). Alternatively, this may reflect non-pathological, age-related cognitive decline in a population with low cognitive reserve.
STUDY SELECTION AND ANALYSIS
We reviewed papers that compared postmortem findings, hippocampal MRI volume or cerebrospinal fluid (CSF) markers of AD, between patients with schizophrenia with evidence of cognitive impairment (age ≥45 years) with controls. We subsequently performed a meta-analysis of postmortem studies that compared amyloid-β plaques (APs) or neurofibrillary tangles (NFTs) in cognitively impaired patients with schizophrenia to normal controls or an AD group.
FINDINGS
No studies found a significant increase of APs or NFTs in cognitively impaired patients with schizophrenia compared with controls. All postmortem studies that compared APs or NFTs in patients with schizophrenia to an AD group found significantly more APs or NFTs in AD. No studies found a significant differences in CSF total tau or phosphorylated tau between patients with schizophrenia and controls. The two studies which compared CSF Aβ42 between patients with schizophrenia and controls found significantly decreased CSF Aβ42 in schizophrenia compared with controls. Hippocampal volume findings were mixed.
CONCLUSIONS
Studies have not found higher rates of AD-related pathology in cognitively impaired individuals with schizophrenia compared with controls. Higher rates of dementia identified in population studies may reflect a lack of specificity in clinical diagnostic tools used to diagnose dementia.
Topics: Humans; Schizophrenia; Biomarkers; Neurodegenerative Diseases; Alzheimer Disease; Amyloid beta-Peptides; Neurofibrillary Tangles; Plaque, Amyloid
PubMed: 38796179
DOI: 10.1136/bmjment-2024-301017 -
Biomedicine & Pharmacotherapy =... Jul 2024Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising... (Review)
Review
Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aβ, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.
Topics: Activating Transcription Factor 4; Humans; Central Nervous System Diseases; Animals; Phytochemicals; Neuroprotective Agents
PubMed: 38795641
DOI: 10.1016/j.biopha.2024.116811 -
Nutrients May 2024Hypoalbuminemia associates with poor acute ischemic stroke (AIS) outcomes. We hypothesised a non-linear relationship and aimed to systematically assess this association... (Meta-Analysis)
Meta-Analysis
Hypoalbuminemia associates with poor acute ischemic stroke (AIS) outcomes. We hypothesised a non-linear relationship and aimed to systematically assess this association using prospective stroke data from the Norfolk and Norwich Stroke and TIA Register. Consecutive AIS patients aged ≥40 years admitted December 2003-December 2016 were included. Outcomes: In-hospital mortality, poor discharge, functional outcome (modified Rankin score 3-6), prolonged length of stay (PLoS) > 4 days, and long-term mortality. Restricted cubic spline regressions investigated the albumin-outcome relationship. We updated a systematic review (PubMed, Scopus, and Embase databases, January 2020-June 2023) and undertook a meta-analysis. A total of 9979 patients were included; mean age (standard deviation) = 78.3 (11.2) years; mean serum albumin 36.69 g/L (5.38). Compared to the cohort median, albumin < 37 g/L associated with up to two-fold higher long-term mortality (HR; 95% CI = 2.01; 1.61-2.49) and in-hospital mortality (RR; 95% CI = 1.48; 1.21-1.80). Albumin > 44 g/L associated with up to 12% higher long-term mortality (HR1.12; 1.06-1.19). Nine studies met our inclusion criteria totalling 23,597 patients. Low albumin associated with increased risk of long-term mortality (two studies; relative risk 1.57 (95% CI 1.11-2.22; = 81.28)), as did low-normal albumin (RR 1.10 (95% CI 1.01-1.20; = 0.00)). Strong evidence indicates increased long-term mortality in AIS patients with low or low-normal albumin on admission.
Topics: Humans; Registries; Hospital Mortality; Aged; Serum Albumin; Female; Male; United Kingdom; Stroke; Aged, 80 and over; Length of Stay; Hypoalbuminemia; Ischemic Stroke; Middle Aged
PubMed: 38794724
DOI: 10.3390/nu16101486 -
Nutrients May 2024This review aimed to synthesise existing literature on the efficacy of personalised or precision nutrition (PPN) interventions, including medical nutrition therapy... (Review)
Review
Do Precision and Personalised Nutrition Interventions Improve Risk Factors in Adults with Prediabetes or Metabolic Syndrome? A Systematic Review of Randomised Controlled Trials.
This review aimed to synthesise existing literature on the efficacy of personalised or precision nutrition (PPN) interventions, including medical nutrition therapy (MNT), in improving outcomes related to glycaemic control (HbA1c, post-prandial glucose [PPG], and fasting blood glucose), anthropometry (weight, BMI, and waist circumference [WC]), blood lipids, blood pressure (BP), and dietary intake among adults with prediabetes or metabolic syndrome (MetS). Six databases were systematically searched (Scopus, Medline, Embase, CINAHL, PsycINFO, and Cochrane) for randomised controlled trials (RCTs) published from January 2000 to 16 April 2023. The Academy of Nutrition and Dietetics Quality Criteria were used to assess the risk of bias. Seven RCTs ( = 873), comprising five PPN and two MNT interventions, lasting 3-24 months were included. Consistent and significant improvements favouring PPN and MNT interventions were reported across studies that examined outcomes like HbA1c, PPG, and waist circumference. Results for other measures, including fasting blood glucose, HOMA-IR, blood lipids, BP, and diet, were inconsistent. Longer, more frequent interventions yielded greater improvements, especially for HbA1c and WC. However, more research in studies with larger sample sizes and standardised PPN definitions is needed. Future studies should also investigate combining MNT with contemporary PPN factors, including genetic, epigenetic, metabolomic, and metagenomic data.
Topics: Adult; Female; Humans; Male; Middle Aged; Blood Glucose; Glycated Hemoglobin; Lipids; Metabolic Syndrome; Nutrition Therapy; Precision Medicine; Prediabetic State; Randomized Controlled Trials as Topic; Risk Factors; Waist Circumference; Young Adult; Aged
PubMed: 38794717
DOI: 10.3390/nu16101479 -
Nutrients May 2024Previous studies have shown encouraging results regarding the efficacy and safety of nutraceuticals, such as "red yeast rice (RYR) extract", on reducing... (Meta-Analysis)
Meta-Analysis Review
Safety and Efficacy of the Consumption of the Nutraceutical "Red Yeast Rice Extract" for the Reduction of Hypercholesterolemia in Humans: A Systematic Review and Meta-Analysis.
Previous studies have shown encouraging results regarding the efficacy and safety of nutraceuticals, such as "red yeast rice (RYR) extract", on reducing hypercholesterolemia in humans. A systematic review and meta-analysis was conducted from January 2012 to May 2022. The search was strictly focused on clinical trials that examined the association between RYR extract consumption and parameters of the lipid profile in humans. Fourteen double-blinded clinical trials were identified. The interventions lasted 4-24 weeks. In most studies, there was one intervention group and one control group. RYR extract consumption statistically significantly reduced total cholesterol (mean absolute reduction: 37.43 mg/dL; 95% confidence interval [CI]: -47.08, -27.79) and low-density lipoprotein cholesterol (LDL-C; mean absolute reduction: 35.82 mg/dL; 95% CI: -43.36, -28.29), but not high-density lipoprotein cholesterol, triglycerides and apolipoproteins A-I and B. As regards the safety, RYR extract was considered a safe choice with neither threatening nor frequent side effects. The consumption of RYR extract by people with hypercholesterolemia was associated with statistically significant reduction in total cholesterol and LDL-C, whereas it was not associated with an increase in life-threatening side effects. Further research on specific subpopulations and outcomes could establish a consensus on determining the clinical benefits and potential risks, if any, of this nutraceutical.
Topics: Adult; Humans; Middle Aged; Anticholesteremic Agents; Biological Products; Cholesterol; Cholesterol, LDL; Dietary Supplements; Hypercholesterolemia; Treatment Outcome; Young Adult; Aged; Aged, 80 and over
PubMed: 38794691
DOI: 10.3390/nu16101453 -
Medicina (Kaunas, Lithuania) May 2024Heart failure (HF) remains a major medical and social problem. The NT-pro-brain natriuretic peptide (NT-proBNP) and its active form, brain-type natriuretic peptide... (Review)
Review
Heart failure (HF) remains a major medical and social problem. The NT-pro-brain natriuretic peptide (NT-proBNP) and its active form, brain-type natriuretic peptide (BNP), in a simple blood test are the gold-standard biomarkers for HF diagnosis. However, even good biomarkers such as natriuretic peptides fail to predict all the risks associated with HF due to the diversity of the mechanisms involved. The pathophysiology of HF is determined by numerous factors, including oxidative stress, inflammation, neuroendocrine activation, pathological angiogenesis, changes in apoptotic pathways, fibrosis and vascular remodeling. High readmission and mortality rates prompt a search for new markers for the diagnosis, prognosis and treatment of HF. Oxidative-stress-mediated inflammation plays a crucial role in the development of subsequent changes in the failing heart and provides a new insight into this complex mechanism. Oxidative stress and inflammatory biomarkers appear to be a promising diagnostic and prognostic tool in patients with HF. This systematic review provides an overview of the current knowledge about oxidative stress and inflammation parameters as markers of HF.
Topics: Humans; Oxidative Stress; Heart Failure; Inflammation; Biomarkers; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis
PubMed: 38792942
DOI: 10.3390/medicina60050760 -
International Journal of Molecular... May 2024Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets... (Review)
Review
Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets is more necessary than ever to tackle this pathology. Heat-Shock Protein 90 (HSP90), a chaperone protein, is implicated in breast cancer pathogenesis, rendering it an appealing target. Looking for alternative approach such as Plant-based compounds and natural HSP90 inhibitors offer promising prospects for innovative therapeutic strategies. This study aims to identify plant-based compounds with anticancer effects on breast cancer models and elucidate their mechanism of action in inhibiting the HSP90 protein. A systematic review was conducted and completed in January 2024 and included in vitro, in vivo, and in silico studies that investigated the effectiveness of plant-based HSP90 inhibitors tested on breast cancer models. Eleven studies were included in the review. Six plants and 24 compounds from six different classes were identified and proved to be effective against HSP90 in breast cancer models. The studied plant extracts showed a dose- and time-dependent decrease in cell viability. Variable IC50 values showed antiproliferative effects, with the plant demonstrating the lowest value. Withanolides was the most studied class. Fennel, , and extracts were shown to inhibit tumor growth and angiogenesis and modulate HSP90 expression as well as its cochaperone interactions in breast cancer mouse models. The identified plant extracts and compounds were proven effective against HSP90 in breast cancer models, and this inhibition showed promising effects on breast cancer biology. Collectively, these results urge the need of further studies to better understand the mechanism of action of HSP90 inhibitors using comparable methods for preclinical observations.
Topics: Animals; Female; Humans; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; HSP90 Heat-Shock Proteins; Plant Extracts; Neoplasms, Experimental
PubMed: 38791506
DOI: 10.3390/ijms25105468 -
International Journal of Molecular... May 2024Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as... (Meta-Analysis)
Meta-Analysis Review
Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets.
Topics: Humans; Colorectal Neoplasms; Prognosis; Biomarkers, Tumor; Chemokines; Receptors, CXCR4; Disease-Free Survival
PubMed: 38791414
DOI: 10.3390/ijms25105374 -
International Journal of Molecular... May 2024Numerous challenges remain within conventional cell-based therapy despite the growing trend of stem cells used to treat various life-debilitating diseases. These... (Review)
Review
Numerous challenges remain within conventional cell-based therapy despite the growing trend of stem cells used to treat various life-debilitating diseases. These limitations include batch-to-batch heterogeneity, induced alloreactivity, cell survival and integration, poor scalability, and high cost of treatment, thus hindering successful translation from lab to bedside. However, recent pioneering technology has enabled the isolation and enrichment of small extracellular vesicles (EVs), canonically known as exosomes. EVs are described as a membrane-enclosed cargo of functional biomolecules not limited to lipids, nucleic acid, and proteins. Interestingly, studies have correlated the biological role of MSC-EVs to the paracrine activity of MSCs. This key evidence has led to rigorous studies on MSC-EVs as an acellular alternative. Using EVs as a therapy was proposed as a model leading to improvements through increased safety; enhanced bioavailability due to size and permeability; reduced heterogeneity by selective and quantifiable properties; and prolonged shelf-life via long-term freezing or lyophilization. Yet, the identity and potency of EVs are still relatively unknown due to various methods of preparation and to qualify the final product. This is reflected by the absence of regulatory strategies overseeing manufacturing, quality control, clinical implementation, and product registration. In this review, the authors review the various production processes and the proteomic profile of MSC-EVs.
Topics: Humans; Mesenchymal Stem Cells; Extracellular Vesicles; Proteomics; Umbilical Cord; Exosomes; Proteome
PubMed: 38791378
DOI: 10.3390/ijms25105340