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Chest Jul 2020Despite the wide-ranging benefits of pulmonary rehabilitation, conflicting results remain regarding whether people with COPD can improve their peak oxygen uptake (V˙O... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the wide-ranging benefits of pulmonary rehabilitation, conflicting results remain regarding whether people with COPD can improve their peak oxygen uptake (V˙O with aerobic training.
RESEARCH QUESTION
The goal of this study was to investigate the effect of aerobic training and exercise prescription on V˙O in COPD.
STUDY DESIGN AND METHODS
A systematic review was performed by using MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases for all studies measuring V˙O prior to and following supervised lower-limb aerobic training in COPD. A random effects meta-analysis limited to randomized controlled trials comparing aerobic training vs usual care was conducted. Other study designs were included in a secondary meta-analysis and meta-regression to investigate the influence of program and patient factors on outcome.
RESULTS
A total of 112 studies were included (participants, N = 3,484): 21 controlled trials (n = 489), of which 13 were randomized (n = 288) and 91 were uncontrolled (n = 2,995) studies. Meta-analysis found a moderate positive change in V˙O (standardized mean difference, 0.52; 95% CI, 0.34-0.69) with the intervention. The change in V˙O was positively associated with target duration of exercise session (P = .01) and, when studies > 1 year duration were excluded, greater total volume of exercise training (P = .01). Similarly, the change in V˙O was greater for programs > 12 weeks compared with those 6 to 12 weeks when adjusted for age and sex. However, reported prescribed exercise intensity (P = .77), training modality (P > .35), and mode (P = .29) did not affect V˙O. Cohorts with more severe airflow obstruction exhibited smaller improvements in V˙O (P < .001).
INTERPRETATION
Overall, people with COPD achieved moderate improvements in V˙O through supervised aerobic training. There is sufficient evidence to show that programs with greater total exercise volume, including duration of exercise session and program duration, are more effective. Reduced effects in severe disease suggest alternative aerobic training methods may be needed in this population.
CLINICAL TRIAL REGISTRATION
PROSPERO; No.: CRD42018099300; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Exercise; Exercise Therapy; Humans; Oxygen Consumption; Pulmonary Disease, Chronic Obstructive
PubMed: 32173489
DOI: 10.1016/j.chest.2020.01.053 -
Phytomedicine : International Journal... May 2023Sepsis and septic shock are the main causes of mortality and complications in intensive care units all over the world. Luteolin is thought to have a significant role as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sepsis and septic shock are the main causes of mortality and complications in intensive care units all over the world. Luteolin is thought to have a significant role as a free radical scavenger, an anti-inflammatory agent, and an immune system modulator. The object of this review is to conduct a systematic review of the effects of luteolin and its mechanisms of action in the treatment of sepsis and its complications.
METHOD
The investigation was carried out in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines (PROSPERO: CRD42022321023). We searched Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases up to January 2023 by using the relevant keywords.
RESULTS
Out of 1,395 records screened, 33 articles met the study criteria. In the collected papers, the main reported findings are that luteolin can affect inflammation-initiating pathways such as toll-like receptors and high mobility group box-1 and reduces the expression of genes that produce inflammatory cytokines, such as the Nod receptor protein-3, and nuclear factor kappa-light chain-enhancer of activated B cells. Luteolin also reduces the overactivity of macrophages, neutrophil extracellular traps and lymphocytes by regulating the immune response.
CONCLUSION
Most studies revealed luteolin's positive benefits on sepsis through several pathways. Luteolin showed the capacity to reduce inflammation and oxidative stress, control immunological response, and prevent organ damage (in vivo studies) during sepsis. Large-scale in vivo experiments are necessary to elucidate its potential impacts on sepsis.
Topics: Humans; Luteolin; Sepsis; Shock, Septic; Oxidative Stress; Inflammation
PubMed: 36898254
DOI: 10.1016/j.phymed.2023.154734 -
Journal of Psychosomatic Research Jan 2017Despite that burnout presents a serious burden for modern society, there are no diagnostic criteria. Additional difficulty is the differential diagnosis with depression.... (Review)
Review
Despite that burnout presents a serious burden for modern society, there are no diagnostic criteria. Additional difficulty is the differential diagnosis with depression. Consequently, there is a need to dispose of a burnout biomarker. Epigenetic studies suggest that DNA methylation is a possible mediator linking individual response to stress and psychopathology and could be considered as a potential biomarker of stress-related mental disorders. Thus, the aim of this review is to provide an overview of DNA methylation mechanisms in stress, burnout and depression. In addition to state-of-the-art overview, the goal of this review is to provide a scientific base for burnout biomarker research. We performed a systematic literature search and identified 25 pertinent articles. Among these, 15 focused on depression, 7 on chronic stress and only 3 on work stress/burnout. Three epigenome-wide studies were identified and the majority of studies used the candidate-gene approach, assessing 12 different genes. The glucocorticoid receptor gene (NR3C1) displayed different methylation patterns in chronic stress and depression. The serotonin transporter gene (SLC6A4) methylation was similarly affected in stress, depression and burnout. Work-related stress and depressive symptoms were associated with different methylation patterns of the brain derived neurotrophic factor gene (BDNF) in the same human sample. The tyrosine hydroxylase (TH) methylation was correlated with work stress in a single study. Additional, thoroughly designed longitudinal studies are necessary for revealing the cause-effect relationship of work stress, epigenetics and burnout, including its overlap with depression.
Topics: Animals; Burnout, Professional; DNA Methylation; Depression; Humans; Stress, Psychological
PubMed: 27998510
DOI: 10.1016/j.jpsychores.2016.11.005 -
Frontiers in Immunology 2022CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense... (Meta-Analysis)
Meta-Analysis
CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). Of these, 6.4% experienced complete response, 10.4% partial response, and 26.1% stable disease for a 16.7% objective response rate (ORR), 42.8% disease control rate, and 4.8-month median duration of response. ORR was significantly higher for hematologic cancers (25.3%) than solid cancers (9.1%, p=0.042). Comparing by mechanism, seven CD47 monoclonal antibodies (mAbs) and six selective SIRPα blockers were given alone or combined with checkpoint inhibitors, targeted therapy, and/or chemotherapy. In solid cancers, selective SIRPα blockade showed a higher ORR (16.2%) than anti-CD47 mAbs (2.8%, p=0.079), which was significant for combination therapies (ORR 28.3% vs 3.0%, respectively, p=0.010). Responses were seen in head and neck, colorectal, endometrial, ovarian, hepatocellular, non-small cell lung, and HER2+gastroesophageal cancers. Dose-limiting toxicity (DLT) was seen in 3.3% of patients (5.4% anti-CD47 mAbs, 1.4% selective SIRPα blockers; p=0.01). The frequency of treatment-related adverse events (TRAEs) ≥grade 3 was 18.0%, similar between the two groups (p=0.082), and mostly laboratory abnormalities. For anti-CD47 mAbs, the most common toxicities included grade 1-2 fatigue (27.2%), headache (21.0%), and anemia (20.5%). For selective SIRPα blockers, these included grade 1-2 infusion reaction (23.1%) and fatigue (15.8%). Anti-CD47 mAbs were significantly more likely than selective SIRPα blockers to cause grade 1-2 fever, chills, nausea/vomiting, headache, and anemia. In conclusion, combination therapies using selective SIRPα blockade had higher response rates in solid tumors than anti-CD47 mAb combinations. Hematologic changes were the main TRAEs, and selective SIRPα blockers seemed to have a better grade 1-2 toxicity profile. Treatment was well-tolerated with minimal DLTs.
Topics: Humans; Protein Binding; Antibodies, Monoclonal; Fatigue; Headache; Neoplasms; CD47 Antigen
PubMed: 36439116
DOI: 10.3389/fimmu.2022.1027235 -
Frontiers in Immunology 2022Metabolic reprogramming in immune cells is diverse and distinctive in terms of complexity and flexibility in response to heterogeneous pathogenic stimuli. We studied the...
INTRODUCTION
Metabolic reprogramming in immune cells is diverse and distinctive in terms of complexity and flexibility in response to heterogeneous pathogenic stimuli. We studied the carbohydrate metabolic changes in immune cells in different types of infectious diseases. This could help build reasonable strategies when understanding the diagnostics, prognostics, and biological relevance of immune cells under alternative metabolic burdens.
METHODS
Search and analysis were conducted on published peer-reviewed papers on immune cell metabolism of a single pathogen infection from the four known types (bacteria, fungi, parasites, and viruses). Out of the 131 selected papers based on the PIC algorithm (pathogen type/immune cell/carbohydrate metabolism), 30 explored immune cell metabolic changes in well-studied bacterial infections, 17 were on fungal infections of known medical importance, and 12 and 57 were on parasitic and viral infections, respectively.
RESULTS AND DISCUSSION
While carbohydrate metabolism in immune cells is signaled by glycolytic shift during a bacterial or viral infection, it is widely evident that effector surface proteins are expressed on the surface of parasites and fungi to modulate metabolism in these cells.
CONCLUSIONS
Carbohydrate metabolism in immune cells can be categorized according to the pathogen or the disease type. Accordingly, this classification can be used to adopt new strategies in disease diagnosis and treatment.
Topics: Animals; Bacteria; Carbohydrates; Fungi; Parasites; Virus Diseases; Viruses
PubMed: 35983037
DOI: 10.3389/fimmu.2022.912899 -
International Journal of Medical... 2023The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5,... (Review)
Review
The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5, 6, 7) and δ (TMED 10), with a total of nine members, which are important regulators of intracellular protein transport and are involved in normal embryonic development, as well as in the pathogenic processes of many human diseases. Here we systematically review the composition, structure and function of TMED family members, and describe the progress of TMED family in human diseases, including malignancies (head and neck tumors, lung cancer, breast cancer, ovarian cancer, endometrial cancer, gastrointestinal tumors, urological tumors, osteosarcomas, etc.), immune responses, diabetes, neurodegenerative diseases, and nonalcoholic fatty liver disease, dilated cardiomyopathy, mucin 1 nephropathy (MKD), and desiccation syndrome (SS). Finally, we discuss and prospect the potential of TMED for disease prognosis prediction and therapeutic targeting, with a view to laying the foundation for therapeutic research based on TMED family causative genes.
Topics: Pregnancy; Female; Humans; Membrane Proteins; Protein Transport; Non-alcoholic Fatty Liver Disease; Vesicular Transport Proteins
PubMed: 37928880
DOI: 10.7150/ijms.87272 -
Sports Medicine (Auckland, N.Z.) Dec 2020The alteration of individual sets during resistance training (RT) is often used to allow for greater velocity and power outputs, reduce metabolite accumulation such as... (Meta-Analysis)
Meta-Analysis
Acute Effects of Cluster and Rest Redistribution Set Structures on Mechanical, Metabolic, and Perceptual Fatigue During and After Resistance Training: A Systematic Review and Meta-analysis.
BACKGROUND
The alteration of individual sets during resistance training (RT) is often used to allow for greater velocity and power outputs, reduce metabolite accumulation such as lactate and also reduce perceived exertion which can ultimately affect the resultant training adaptations. However, there are inconsistencies in the current body of evidence regarding the magnitude of the effects of alternative set structures (i.e., cluster sets and rest redistribution) on these acute mechanical, metabolic, and perceptual responses during and after RT.
OBJECTIVE
This study aimed to systematically review and meta-analyse current evidence on the differences between traditional and alternative (cluster and rest redistribution) set structures on acute mechanical, metabolic, and perceptual responses during and after RT, and to discuss potential reasons for the disparities noted in the literature.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and five databases were searched until June 2019. Studies were included when they were written in English and compared at least one acute mechanical, metabolic, or perceptual response between traditional, cluster or traditional and rest redistribution set structures in healthy adults. Random-effects meta-analyses and meta-regressions were performed where possible.
RESULTS
Thirty-two studies were included. Pooled results revealed that alternative set structures allowed for greater absolute mean [standardized mean difference (SMD) = 0.60] and peak velocity (SMD = 0.41), and mean (SMD = 0.33) and peak power (SMD = 0.38) during RT. In addition, alternative set structures were also highly effective at mitigating a decline in velocity and power variables during (SMD = 0.83-1.97) and after RT (SMD = 0.58) as well as reducing lactate accumulation (SMD = 1.61) and perceived exertion (SMD = 0.81). These effects of alternative set structures on velocity and power decline and maintenance during RT were considerably larger than for absolute velocity and power variables. Sub-group analyses controlling for each alternative set structure independently showed that cluster sets were generally more effective than rest redistribution in alleviating mechanical, metabolic, and perceptual markers of fatigue.
CONCLUSION
Alternative set structures can reduce mechanical fatigue, perceptual exertion, and metabolic stress during and after RT. However, fundamental differences in the amount of total rest time results in cluster sets generally being more effective than rest redistribution in alleviating fatigue-induced changes during RT, which highlights the importance of classifying them independently in research and in practice. Additionally, absolute values (i.e., mean session velocity or power), as well as decline and maintenance of the mechanical outcomes during RT, and residual mechanical fatigue after RT, are all affected differently by alternative set structures, suggesting that these variables may provide distinct information that can inform future training decisions.
PROTOCOL REGISTRATION
The original protocol was prospectively registered (CRD42019138954) with the PROSPERO (International Prospective Register of Systematic Reviews).
Topics: Adult; Fatigue; Humans; Lactic Acid; Physical Exertion; Resistance Training; Rest
PubMed: 32901442
DOI: 10.1007/s40279-020-01344-2 -
PM & R : the Journal of Injury,... Sep 2022To assess the effects of different prosthetic feet on energy costs associated with walking and running in people with transtibial amputation. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the effects of different prosthetic feet on energy costs associated with walking and running in people with transtibial amputation.
LITERATURE SURVEY
The Pubmed, CINAHL, and Web-of-Science bibliographic databases were searched for original research published through June 30, 2018. References from identified articles were also reviewed.
METHODOLOGY
Two reviewers screened titles, abstracts, and articles for pertinent studies. Details were extracted with a standardized template. Risk of bias was assessed using domain-based methods. Prosthetic feet were grouped into categories and compared according to energy costs associated with walking or running over various terrain conditions. Meta-analyses were conducted when data quantity and homogeneity permitted. Evidence statements were formed when results were consistent or undisputed.
SYNTHESIS
Fifteen studies were included. Participants (n = 141) were predominantly male (87.9%), had unilateral amputation (95.7%) from non-dysvascular causes (87.9%), and were classified as unlimited community ambulators or active adults (56.0%). Participants were often young but varied in age (mean age 24.8-66.6 years). Available evidence indicates that feet with powered dorsiflexion reduce energy costs relative to dynamic response feet in unlimited community ambulators or active adults when walking on level or declined surfaces. Dynamic response feet do not significantly reduce energy costs compared to energy storing, flexible keel, or solid ankle feet when walking on level terrain. Running feet do not reduce energy costs relative to dynamic response in active adults when running. Select feet may reduce energy costs under specific conditions, but additional research is needed to confirm preliminary results.
CONCLUSIONS
The overall body of evidence is based on small samples, comprised mostly of participants who may not well represent the population of prosthesis users and test conditions that may not well reflect how prostheses are used in daily life. However, evidence suggests energy costs are affected by prosthetic foot type only under select conditions.
Topics: Adult; Aged; Amputation, Surgical; Amputees; Artificial Limbs; Biomechanical Phenomena; Energy Metabolism; Female; Foot; Gait; Humans; Male; Middle Aged; Prosthesis Design; Walking; Young Adult
PubMed: 34390623
DOI: 10.1002/pmrj.12693 -
BMC Medical Genomics Sep 2017PD is a progressive neurodegenerative disorder commonly treated by levodopa. The findings from genetic studies on adverse effects (ADRs) and levodopa efficacy are mostly... (Meta-Analysis)
Meta-Analysis
BACKGROUND
PD is a progressive neurodegenerative disorder commonly treated by levodopa. The findings from genetic studies on adverse effects (ADRs) and levodopa efficacy are mostly inconclusive. Here, we aim to identify predictive genetic biomarkers for levodopa response (LR) and determine common molecular link with disease susceptibility. A systematic review for LR was conducted for ADR, and drug efficacy, independently. All included articles were assessed for methodological quality on 14 parameters. GWAS of PD were also reviewed. Protein-protein interaction (PPI) analysis using STRING and functional enrichment using WebGestalt was performed to explore the common link between LR and PD.
RESULTS
From 37 candidate studies on levodopa toxicity, 18 genes were found associated, of which, CA STR 13, 14 (DRD2) was most significantly associated with dyskinesia, followed by rs1801133 (MTHFR) with hyper-homocysteinemia, and rs474559 (HOMER1) with hallucination. Similarly, 8 studies on efficacy resulted in 4 genes in which rs28363170, rs3836790 (SLC6A3) and rs4680 (COMT), were significant. To establish the molecular connection between LR with PD, we identified 35 genes significantly associated with PD. With 19 proteins associated with LR and 35 with PD, two independent PPI networks were constructed. Among the 67 nodes (263 edges) in LR, and 62 nodes (190 edges) in PD pathophysiology, UBC, SNCA, FYN, SRC, CAMK2A, and SLC6A3 were identified as common potential candidates.
CONCLUSION
Our study revealed the genetically significant polymorphism concerning the ADRs and levodopa efficacy. The six common genes may be used as predictive markers for therapy optimization and as putative drug target candidates.
Topics: Genetic Predisposition to Disease; Humans; Levodopa; Parkinson Disease; Protein Interaction Maps
PubMed: 28927418
DOI: 10.1186/s12920-017-0291-0 -
Cancer Treatment Reviews Mar 2017It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the treatment of haematological malignancies. Based on encouraging preclinical results, demethylating agents may also be effective in solid tumours. This systematic review summarizes the evidence of the effect of demethylating agents on clinical response, methylation and the immune system in solid tumours.
METHODS
We conducted a systematic literature search from 1949 to December 2016, according to the PRISMA guidelines. Studies which evaluated treatment with azacitidine, decitabine, guadecitabine, hydralazine, procaine, MG98 and/or zebularine in patients with solid tumours were included. Data on clinical response, effects on methylation and immune response were extracted.
RESULTS
Fifty-eight studies were included: in 13 studies complete responses (CR) were observed, 35 studies showed partial responses (PR), 47 studies stable disease (SD) and all studies except two showed progressive disease (PD). Effects on global methylation were observed in 11/15 studies and demethylation/re-expression of tumour specific genes was seen in 15/17 studies. No clear correlation between (de)methylation and clinical response was observed. In 14 studies immune-related responses were reported, such as re-expression of cancer-testis antigens and upregulation of interferon genes.
CONCLUSION
Demethylating agents are able to improve clinical outcome and alter methylation status in patients with solid tumours. Although beneficial effect has been shown in individual patients, overall response is limited. Further research on biomarker predicting therapy efficacy is indicated, particularly in earlier stage and highly methylated tumours.
Topics: Antimetabolites, Antineoplastic; Azacitidine; Cytidine; DNA Methylation; Decitabine; Humans; Hydralazine; Immune System; Methylation; Neoplasms; Procaine; Treatment Outcome
PubMed: 28189913
DOI: 10.1016/j.ctrv.2017.01.004