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Stem Cell Research & Therapy Jun 2024Mesenchymal stem cells (MSCs) have emerged as living biodrugs for myocardial repair and regeneration. Recent randomized controlled trials (RCTs) have reported that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mesenchymal stem cells (MSCs) have emerged as living biodrugs for myocardial repair and regeneration. Recent randomized controlled trials (RCTs) have reported that MSC-based therapy is safe and effective in heart failure patients; however, its dose-response relationship has yet to be established. We aimed to determine the optimal MSC dose for treating HF patients with reduced ejection fraction (EF) (HFrEF).
METHODS
The preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Cochrane Handbook guidelines were followed. Four databases and registries, i.e., PubMed, EBSCO, clinicaltrials.gov, ICTRP, and other websites, were searched for RCTs. Eleven RCTs with 1098 participants (treatment group, n = 606; control group, n = 492) were selected based on our inclusion/exclusion criteria. Two independent assessors extracted the data and performed quality assessments. The data from all eligible studies were plotted for death, major adverse cardiac events (MACE), left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and 6-minute walk distance (6-MWD) as safety, efficacy, and performance parameters. For dose-escalation assessment, studies were categorized as low-dose (< 100 million cells) or high-dose (≥ 100 million cells).
RESULTS
MSC-based treatment is safe across low and high doses, with nonsignificant effects. However, low-dose treatment had a more significant protective effect than high-dose treatment. Subgroup analysis revealed the superiority of low-dose treatment in improving LVEF by 3.01% (95% CI; 0.65-5.38%) compared with high-dose treatment (-0.48%; 95% CI; -2.14-1.18). MSC treatment significantly improved the 6-MWD by 26.74 m (95% CI; 3.74-49.74 m) in the low-dose treatment group and by 36.73 m (95% CI; 6.74-66.72 m) in the high-dose treatment group. The exclusion of studies using ADRCs resulted in better safety and a significant improvement in LVEF from low- and high-dose MSC treatment.
CONCLUSION
Low-dose MSC treatment was safe and superior to high-dose treatment in restoring efficacy and functional outcomes in heart failure patients, and further analysis in a larger patient group is warranted.
Topics: Humans; Heart Failure; Randomized Controlled Trials as Topic; Mesenchymal Stem Cell Transplantation; Stroke Volume; Mesenchymal Stem Cells; Ventricular Function, Left
PubMed: 38867306
DOI: 10.1186/s13287-024-03713-4 -
Food & Function Jul 2024The most significant contributor to global mortality are cardiovascular diseases. Dietary factors significantly impact the risk, advancement, and treatment of...
The most significant contributor to global mortality are cardiovascular diseases. Dietary factors significantly impact the risk, advancement, and treatment of cardiometabolic conditions. Chocolate, known for its adaptability and capacity to stimulate pleasure centers, emerges as a promising vehicle for integrating different bioactive elements. This systematic review analyzed 10 randomized controlled trials investigating the health effects of consuming enriched, fortified, or supplemented chocolate. These trials varied in chocolate intake amounts (ranging from 5 to 101 g day), incorporated bioactive components (co-crystalized astaxanthin, lycopene, wood-based phytosterol-phytostanol mixture, canola sterol esters, .), and duration (from 2 weeks to 1 year). Some enriched chocolates were found to reduce total and LDL cholesterol and influence markers of oxidative damage, inflammation, immune function, and skin parameters. However, certain trials showed a minimal impact on health outcomes. Therefore, while enriched chocolate holds promise as a carrier for beneficial bioactive compounds, rigorous scientific inquiry and methodological rigor are crucial to fully substantiate these claims. Comprehensive evaluations covering cardiovascular health, metabolic function, immune response, and other aspects are needed to understand its potential benefits and limitations. Advancing robust research initiatives could help realize the full potential of enriched chocolate in promoting human health and well-being.
Topics: Humans; Cardiovascular Diseases; Chocolate; Dietary Supplements; Food, Fortified; Functional Food; Randomized Controlled Trials as Topic
PubMed: 38864465
DOI: 10.1039/d4fo01574f -
Hypertension (Dallas, Tex. : 1979) Jun 2024Alcohol consumption has been associated with higher blood pressure and an increased risk of hypertension. However, the possible exposure thresholds and effect-modifiers... (Review)
Review
BACKGROUND
Alcohol consumption has been associated with higher blood pressure and an increased risk of hypertension. However, the possible exposure thresholds and effect-modifiers are uncertain.
METHODS
We assessed the dose-response relationship between usual alcohol intake and hypertension incidence in nonexperimental cohort studies. After performing a systematic literature search through February 20, 2024, we retrieved 23 eligible studies. We computed risk ratios and 95% CI of hypertension incidence using a nonlinear meta-analytic model based on restricted cubic splines, to assess the dose-response association with alcohol consumption.
RESULTS
We observed a positive and almost linear association between alcohol intake and hypertension risk with risk ratios of 0.89 (0.84-0.94), 1.11 (1.07-1.15), 1.22 (1.14-1.30), and 1.33 (1.18-1.49) for 0, 24, 36 and 48 g/d, respectively, using 12 g alcohol/d as the reference value. In sex-specific analyses, the association was almost linear in men over the entire range of exposure but only observed above 12 g/d in women, although with a steeper association at high levels of consumption compared with men. The increased risk of hypertension above 12 to 24 g alcohol/d was similar in Western and Asian populations and considerably greater in Whites than in Blacks, mainly due to the positive association in women at moderate-to-high intake.
CONCLUSIONS
Overall, our results lend support to a causal association between alcohol consumption and risk of hypertension, especially above an alcohol intake of 12 g/d, and are consistent with recommendations to avoid or limit alcohol intake. Sex and ethnicity appear to be major effect-modifiers of such association.
PubMed: 38864208
DOI: 10.1161/HYPERTENSIONAHA.124.22703 -
Frontiers in Microbiology 2024Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Mounting evidence suggests microbiota dysbiosis augment autoimmune response. This study aims to...
INTRODUCTION
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Mounting evidence suggests microbiota dysbiosis augment autoimmune response. This study aims to provide a systematic overview of this research field in SLE through a bibliometric analysis.
METHODS
We conducted a comprehensive search and retrieval of literature related to microbial researches in SLE from the Web of Science Core Collection (WOSCC) database. The retrieved articles were subjected to bibliometric analysis using VOSviewer and Bibliometricx to explore annual publication output, collaborative patterns, research hotspots, current research status, and emerging trends.
RESULTS
In this study, we conducted a comprehensive analysis of 218 research articles and 118 review articles. The quantity of publications rises annually, notably surging in 2015 and 2018. The United States and China emerged as the leading contributors in microbial research of SLE. Mashhad University of Medical Sciences had the highest publication outputs among the institutions. Frontiers in Immunology published the most papers. Luo XM and Margolles A were the most prolific and highly cited contributors among individual authors. Microbial research in SLE primarily focused on changes in microbial composition, particularly gut microbiota, as well as the mechanisms and practical applications in SLE. Recent trends emphasize "metabolites," "metabolomics," "fatty acids," "T cells," "," and "dietary supplementation," indicating a growing emphasis on microbial metabolism and interventions in SLE.
CONCLUSION
This study provides a thorough analysis of the research landscape concerning microbiota in SLE. The microbial research in SLE mainly focused on three aspects: microbial dysbiosis, mechanism studies and translational studies (microbiota-based therapeutics). It identifies current research trends and focal points, offering valuable guidance for scholars in the field.
PubMed: 38863759
DOI: 10.3389/fmicb.2024.1319654 -
The ISME Journal Jan 2024Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing... (Review)
Review
Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing microbial ecology. Since their first application for aerobic gammaproteobacterial methane oxidizers less than a decade ago, GEMs have substantially increased our understanding of the metabolism of methanotrophs, a microbial guild of high relevance for the natural and biotechnological mitigation of methane efflux to the atmosphere. Particularly, GEMs helped to elucidate critical metabolic and regulatory pathways of several methanotrophic strains, predicted microbial responses to environmental perturbations, and were used to model metabolic interactions in cocultures. Here, we conducted a systematic review of GEMs exploring aerobic methanotrophy, summarizing recent advances, pointing out weaknesses, and drawing out probable future uses of GEMs to improve our understanding of the ecology of methane oxidizers. We also focus on their potential to unravel causes and consequences when studying interactions of methane-oxidizing bacteria with other methanotrophs or members of microbial communities in general. This review aims to bridge the gap between applied sciences and microbial ecology research on methane oxidizers as model organisms and to provide an outlook for future studies.
Topics: Methane; Oxidation-Reduction; Aerobiosis; Metabolic Networks and Pathways; Models, Biological
PubMed: 38861460
DOI: 10.1093/ismejo/wrae102 -
Frontiers in Immunology 2024Immunotherapeutic approaches, including immune checkpoint inhibitor (ICI) therapy, are increasingly recognized for their potential. Despite notable successes, patient... (Meta-Analysis)
Meta-Analysis
Myeloid-derived suppressor cells in peripheral blood as predictive biomarkers in patients with solid tumors undergoing immune checkpoint therapy: systematic review and meta-analysis.
BACKGROUND
Immunotherapeutic approaches, including immune checkpoint inhibitor (ICI) therapy, are increasingly recognized for their potential. Despite notable successes, patient responses to these treatments vary significantly. The absence of reliable predictive and prognostic biomarkers hampers the ability to foresee outcomes. This meta-analysis aims to evaluate the predictive significance of circulating myeloid-derived suppressor cells (MDSC) in patients with solid tumors undergoing ICI therapy, focusing on progression-free survival (PFS) and overall survival (OS).
METHODS
A comprehensive literature search was performed across PubMed and EMBASE from January 2007 to November 2023, utilizing keywords related to MDSC and ICI. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) directly from the publications or calculated them based on the reported data. A hazard ratio greater than 1 indicated a beneficial effect of low MDSC levels. We assessed heterogeneity and effect size through subgroup analyses.
RESULTS
Our search yielded 4,023 articles, of which 17 studies involving 1,035 patients were included. The analysis revealed that patients with lower levels of circulating MDSC experienced significantly improved OS (HR=2.13 [95% CI 1.51-2.99]) and PFS (HR=1.87 [95% CI 1.29-2.72]) in response to ICI therapy. Notably, heterogeneity across these outcomes was primarily attributed to differences in polymorphonuclear MDSC (PMN-MDSC) subpopulations and varying cutoff methodologies used in the studies. The monocytic MDSC (M-MDSC) subpopulation emerged as a consistent and significant prognostic marker across various subgroup analyses, including ethnicity, tumor type, ICI target, sample size, and cutoff methodology.
CONCLUSIONS
Our findings suggest that standardized assessment of MDSC, particularly M-MDSC, should be integral to ICI therapy strategies. These cells hold the promise of identifying patients at risk of poor response to ICI therapy, enabling tailored treatment approaches. Further research focusing on the standardization of markers and validation of cutoff methods is crucial for integrating MDSC into clinical practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023420095, identifier CRD42023420095.
Topics: Humans; Myeloid-Derived Suppressor Cells; Neoplasms; Immune Checkpoint Inhibitors; Biomarkers, Tumor; Prognosis
PubMed: 38855104
DOI: 10.3389/fimmu.2024.1403771 -
Renal Failure Dec 2024To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by... (Meta-Analysis)
Meta-Analysis
Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.
OBJECTIVE
To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis.
METHODS
PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software.
RESULTS
A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (β-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or β-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias.
CONCLUSIONS
The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.
Topics: Humans; Diabetic Nephropathies; Angiotensin-Converting Enzyme Inhibitors; Renin-Angiotensin System; Drug Therapy, Combination; Angiotensin Receptor Antagonists; Astragalus Plant; Randomized Controlled Trials as Topic; Drugs, Chinese Herbal; Treatment Outcome; Creatinine; Glycated Hemoglobin; Proteinuria
PubMed: 38836372
DOI: 10.1080/0886022X.2024.2359033 -
The Pan African Medical Journal 2024Chronic kidney disease (CKD) is commonly complicated by anemia. Treating dialysis-dependent patients with anemia, including daprodustat and other inhibitors of prolyl... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Chronic kidney disease (CKD) is commonly complicated by anemia. Treating dialysis-dependent patients with anemia, including daprodustat and other inhibitors of prolyl hydroxylase of hypoxia-inducible factor, recombinant human erythropoietin (rhEPO), and iron supplements. We conducted this study to test our postulation; daprodustat is superior to rhEPO and other conventional treatments respecting efficacy and safety parameters. We made systematic search through PubMed, Web of Science, Scopus, and Cochrane. Seven unique trials were eventually included for systematic review; six of them with a sample size of 759 patients entered our network meta-analysis (NMA). Daprodustat 25-30 mg was associated with the greatest change in serum hemoglobin (MD=1.86, 95%CI= [1.20; 2.52]), ferritin (MD= -180.84, 95%CI= [-264.47; -97.20]), and total iron binding capacity (TIBC) (MD=11.03, 95%CI= [3.15; 18.92]) from baseline values. Dialysis-dependent patients with anemia had a significant increment in serum Hemoglobin and TIBC and a reduction in serum ferritin, in a dose-dependent manner, when administered daprodustat.
Topics: Humans; Anemia; Renal Dialysis; Hemoglobins; Renal Insufficiency, Chronic; Glycine; Ferritins; Barbiturates; Network Meta-Analysis; Erythropoietin; Recombinant Proteins; Dose-Response Relationship, Drug; Iron
PubMed: 38828426
DOI: 10.11604/pamj.2024.47.114.37278 -
Advances and prospects in deuterium metabolic imaging (DMI): a systematic review of in vivo studies.European Radiology Experimental Jun 2024Deuterium metabolic imaging (DMI) has emerged as a promising non-invasive technique for studying metabolism in vivo. This review aims to summarize the current... (Review)
Review
BACKGROUND
Deuterium metabolic imaging (DMI) has emerged as a promising non-invasive technique for studying metabolism in vivo. This review aims to summarize the current developments and discuss the futures in DMI technique in vivo.
METHODS
A systematic literature review was conducted based on the PRISMA 2020 statement by two authors. Specific technical details and potential applications of DMI in vivo were summarized, including strategies of deuterated metabolites detection, deuterium-labeled tracers and corresponding metabolic pathways in vivo, potential clinical applications, routes of tracer administration, quantitative evaluations of metabolisms, and spatial resolution.
RESULTS
Of the 2,248 articles initially retrieved, 34 were finally included, highlighting 2 strategies for detecting deuterated metabolites: direct and indirect DMI. Various deuterated tracers (e.g., [6,6'-H2]glucose, [2,2,2'-H3]acetate) were utilized in DMI to detect and quantify different metabolic pathways such as glycolysis, tricarboxylic acid cycle, and fatty acid oxidation. The quantifications (e.g., lactate level, lactate/glutamine and glutamate ratio) hold promise for diagnosing malignancies and assessing early anti-tumor treatment responses. Tracers can be administered orally, intravenously, or intraperitoneally, either through bolus administration or continuous infusion. For metabolic quantification, both serial time point methods (including kinetic analysis and calculation of area under the curves) and single time point quantifications are viable. However, insufficient spatial resolution remains a major challenge in DMI (e.g., 3.3-mL spatial resolution with 10-min acquisition at 3 T).
CONCLUSIONS
Enhancing spatial resolution can facilitate the clinical translation of DMI. Furthermore, optimizing tracer synthesis, administration protocols, and quantification methodologies will further enhance their clinical applicability.
RELEVANCE STATEMENT
Deuterium metabolic imaging, a promising non-invasive technique, is systematically discussed in this review for its current progression, limitations, and future directions in studying in vivo energetic metabolism, displaying a relevant clinical potential.
KEY POINTS
• Deuterium metabolic imaging (DMI) shows promise for studying in vivo energetic metabolism. • This review explores DMI's current state, limits, and future research directions comprehensively. • The clinical translation of DMI is mainly impeded by limitations in spatial resolution.
Topics: Humans; Deuterium; Animals
PubMed: 38825658
DOI: 10.1186/s41747-024-00464-y -
Phytomedicine : International Journal... Jul 2024Sulforaphane (SFN) is a dietary isothiocyanate, derived from glucoraphanin, present in cruciferous vegetables belonging to the Brassica genus. It is a biologically... (Review)
Review
BACKGROUND
Sulforaphane (SFN) is a dietary isothiocyanate, derived from glucoraphanin, present in cruciferous vegetables belonging to the Brassica genus. It is a biologically active phytochemical that acts as a nuclear factor erythroid 2-related factor 2 (Nrf2) inducer. Thus, it has been reported to have multiple protective functions including anticancer responses and protection against a toxic agent's action.
PURPOSE
The present work systematically reviewed and synthesised the protective properties of sulforaphane against a toxic agent. This review reveals the mechanism of the action of SFN in each organ or system.
METHODS
The PRISMA guideline was followed in this sequence: researched literature, organised retrieved documents, abstracted relevant information, assessed study quality and bias, synthesised data, and prepared a comprehensive report. Searches were conducted on Science Direct and PubMed using the keywords "Sulforaphane" AND ("protective effects" OR "protection against").
RESULTS
Reports showed that liver and the nervous system are the target organs on which attention was focused, and this might be due to the key role of oxidative stress in liver and neurodegenerative diseases. However, protective activities have also been demonstrated in the lungs, heart, immune system, kidneys, and endocrine system. SFN exerts its protective effects by activating the Nrf2 pathway, which enhances antioxidant defenses and reduces oxidative stress. It also suppresses inflammation by decreasing interleukin production. Moreover, SFN inhibits apoptosis by preventing caspase 3 cleavage and increasing Bcl2 levels. Overall, SFN demonstrates multifaceted mechanisms to counteract the adverse effects of toxic agents.
CONCLUSION
SFN has potential clinical applications as a chemoprotective agent. Nevertheless, more studies are necessary to set the safe doses of SFN in humans.
Topics: Isothiocyanates; Sulfoxides; Humans; Animals; Brassica; Oxidative Stress; NF-E2-Related Factor 2; Protective Agents
PubMed: 38824824
DOI: 10.1016/j.phymed.2024.155731