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Frontiers in Bioscience (Landmark... Nov 2023Obesity is a significant health problem with an increasing incidence, causing a low-grade systemic inflammatory state and being implicated in various chronic diseases.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obesity is a significant health problem with an increasing incidence, causing a low-grade systemic inflammatory state and being implicated in various chronic diseases. Moreover, obesity has been shown to cause mitochondrial dysfunction through oxidative stress and inflammation, eventually affecting energy metabolism. However, high-intensity interval training (HIIT) can improve mitochondrial efficiency through exercise-induced mitochondrial adaptations. This systematic review and meta-analysis aims to examine the potential effects of HIIT on mitochondrial-associated indices in obese and overweight adults.
METHODS
PubMed, Scopus, and Web of Science databases were searched.
RESULTS
Twenty-eight eligible studies were included, involving 530 participants. HIIT was found to significantly improve the activity of citrate synthase (CS), cytochrome C (COX-IV), beta-hydroxyacyl CoA-dehydrogenase (β-HAD), Complexes I-V as well as VO2max in overweight and obese individuals, whereas no significant changes were shown in PGC-1α and SIRT1. Interestingly, subgroup analyses revealed that CS, COX-IV, β-HAD, and Complexes I-V activity exhibited a significant improvement only in the healthy subgroup.
CONCLUSIONS
Overall, HIIT can be utilized to enhance mitochondrial-associated indices in overweight and obese individuals. However, this improvement may be health status dependent.
Topics: Adult; Humans; Overweight; High-Intensity Interval Training; Oxygen Consumption; Obesity; Mitochondria
PubMed: 38062841
DOI: 10.31083/j.fbl2811281 -
International Journal of Molecular... Dec 2023Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and... (Review)
Review
Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relationship exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms". Bibliographic references to relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.
Topics: Humans; Atrial Fibrillation; Cardiac Conduction System Disease; Heart Diseases; Mitochondrial Diseases; Oxidative Stress
PubMed: 38203704
DOI: 10.3390/ijms25010535 -
Journal of Clinical Medicine Oct 2023Exercise therapy as part of the clinical management of patients with neuromuscular diseases (NMDs) is complicated by the limited insights into its efficacy. There is an... (Review)
Review
Exercise therapy as part of the clinical management of patients with neuromuscular diseases (NMDs) is complicated by the limited insights into its efficacy. There is an urgent need for sensitive and non-invasive quantitative muscle biomarkers to monitor the effects of exercise training. Therefore, the objective of this systematic review was to critically appraise and summarize the current evidence for the sensitivity of quantitative, non-invasive biomarkers, based on imaging and electrophysiological techniques, for measuring the effects of physical exercise training. We identified a wide variety of biomarkers, including imaging techniques, i.e., magnetic resonance imaging (MRI) and ultrasound, surface electromyography (sEMG), magnetic resonance spectroscopy (MRS), and near-infrared spectroscopy (NIRS). Imaging biomarkers, such as muscle maximum area and muscle thickness, and EMG biomarkers, such as compound muscle action potential (CMAP) amplitude, detected significant changes in muscle morphology and neural adaptations following resistance training. MRS and NIRS biomarkers, such as initial phosphocreatine recovery rate (V), mitochondrial capacity (Q), adenosine phosphate recovery half-time (ADP t), and micromolar changes in deoxygenated hemoglobin and myoglobin concentrations (Δ[deoxy(Hb + Mb)]), detected significant adaptations in oxidative metabolism after endurance training. We also identified biomarkers whose clinical relevance has not yet been assessed due to lack of sufficient study.
PubMed: 37959299
DOI: 10.3390/jcm12216834 -
PloS One 2024Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually... (Meta-Analysis)
Meta-Analysis
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually patient mortality. In recent years, neuromodulation techniques have emerged as promising potential therapeutic approaches to slow disease progression and improve the quality of life of ALS patients. A systematic review was conducted until August 8, 2023, to evaluate the neuromodulation methods used and their potential in the treatment of ALS. The search strategy was applied in the Cochrane Central database, incorporating results from other databases such as PubMed, Embase, CTgov, CINAHL, and ICTRP. Following the exclusion of papers that did not fulfil the inclusion criteria, a total of 2090 records were found, leaving a total of 10 studies. R software was used to conduct meta-analyses based on the effect sizes between the experimental and control groups. This revealed differences in muscle stretch measures with manual muscle testing (p = 0.012) and resting motor threshold (p = 0.0457), but not with voluntary isometric contraction (p = 0.1883). The functionality of ALS was also different (p = 0.007), but not the quality of life. Although intracortical facilitation was not seen in motor cortex 1 (M1) (p = 0.1338), short-interval intracortical inhibition of M1 was significant (p = 0.0001). BDNF showed no differences that were statistically significant (p = 0.2297). Neuromodulation-based treatments are proposed as a promising therapeutic approach for ALS that can produce effects on muscle function, spasticity, and intracortical connections through electrical, magnetic, and photonic stimulation. Photobiomodulation stands out as an innovative approach that uses specific wavelengths to influence mitochondria, with the aim of improving mitochondrial function and reducing excitotoxicity. The lack of reliable placebo controls and the variation in stimulation frequency are some of the drawbacks of neuromodulation.
Topics: Humans; Amyotrophic Lateral Sclerosis; Quality of Life; Neurodegenerative Diseases; Exercise Therapy; Muscle Spasticity
PubMed: 38551974
DOI: 10.1371/journal.pone.0300671 -
Cerebellum (London, England) Jun 2024Although a large array of biomarkers have been investigated in Friedreich's ataxia (FRDA) trials, the optimal biomarker for assessing disease progression or therapeutic... (Meta-Analysis)
Meta-Analysis Review
Although a large array of biomarkers have been investigated in Friedreich's ataxia (FRDA) trials, the optimal biomarker for assessing disease progression or therapeutic benefit has yet to be identified. We searched PubMed, MEDLINE, and EMBASE databases up to June 2023 for any original study (with ≥ 5 participants and ≥ 2 months' follow-up) reporting the effect of therapeutic interventions on any clinical, cardiac, biochemical, patient-reported outcome measures, imaging, or neurophysiologic biomarker. We also explored the biomarkers' ability to detect subtle disease progression in untreated patients. The pooled standardized mean difference (SMD) was calculated using a random-effects model. The study's protocol was registered in PROSPERO (CRD42022319196). In total, 43 studies with 1409 FRDA patients were included in the qualitative synthesis. A statistically significant improvement was observed in Friedreich Ataxia Rating Scale scores [combining Friedreich Ataxia Rating Scale (FARS) and modified FARS (mFARS): SMD = - 0.32 (- 0.62 to - 0.02)] following drugs that augment mitochondrial function in a sensitivity analysis. Left ventricular mass index (LVMI) was improved significantly [SMD = - 0.34 (- 0.5 to - 0.18)] after 28.5 months of treatment with drugs that augment mitochondrial function. However, LVMI remained stable [SMD = 0.05 (- 0.3 to 0.41)] in untreated patients after 6-month follow-up. None of the remaining biomarkers changed significantly following any treatment intervention nor during the natural disease progression. Nevertheless, clinical implications of these results should be interpreted with caution because of low to very low quality of evidence. Further randomized controlled trials of at least 24 months' duration using a biomarker toolbox rather than a single biomarker are warranted.
Topics: Friedreich Ataxia; Humans; Biomarkers
PubMed: 37889470
DOI: 10.1007/s12311-023-01621-6 -
Antioxidants (Basel, Switzerland) Mar 2024The aging of the global population has increased the prevalence of neurodegenerative conditions. (BM), an herb with active compounds, such as bacosides A and B,... (Review)
Review
Investigating the Neuroprotective and Cognitive-Enhancing Effects of : A Systematic Review Focused on Inflammation, Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis.
The aging of the global population has increased the prevalence of neurodegenerative conditions. (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.
PubMed: 38671841
DOI: 10.3390/antiox13040393 -
Biomedicines Jan 2024Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with... (Review)
Review
Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO's reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
PubMed: 38255313
DOI: 10.3390/biomedicines12010208 -
Problemy Endokrinologii Nov 2023Recent studies show that Alzheimer's disease (AD) has many common links with conditions associated with insulin resistance, including neuroinflammation, impaired insulin...
Recent studies show that Alzheimer's disease (AD) has many common links with conditions associated with insulin resistance, including neuroinflammation, impaired insulin signaling, oxidative stress, mitochondrial dysfunction and metabolic syndrome. The authors conducted an electronic search for publications in the PubMed/MEDLINE and Google Scholar databases using the keywords "amyloid beta", "Alzheimer type-3-diabetes", "intranasal insulin", "metformin", "type 2 diabetes mellitus", "incretins" and "PPARy agonists». A systematic literature search was conducted among studies published between 2005 and 2022. The authors used the following inclusion criteria: 1) Subjects who received therapy for AD and/or DM2, if the expected result concerned the risk of cognitive decline or the development of dementia; 2) The age of the study participants is > 50 years; 3) The type of studies included in this review were randomized clinical trials, population-based observational studies or case-control studies, prospective cohort studies, as well as reviews and meta-analyses; 4) The included articles were written in English. In recent years, there has been considerable interest in identifying the mechanisms of action of antidiabetic drugs and their potential use in AD. Human studies involving patients with mild cognitive impairment and Alzheimer's disease have shown that the administration of certain antidiabetic drugs, such as intranasal insulin, metformin, incretins and thiazolidinediones, can improve cognitive function and memory. The purpose of this study is to evaluate the effectiveness of antidiabetic drugs in the treatment of AD. According to the results of the study, metformin, intranasal insulin, thiazolidinediones and incretins showed a positive effect both in humans and in animal models. Recent studies show that thiazolidinediones can activate pathways in the brain that are regulated by IGF-1; however, rosiglitazone may pose a significant risk of side effects. The results of clinical studies on the use of metformin in AD are limited and contradictory.
Topics: Animals; Humans; Middle Aged; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Alzheimer Disease; Incretins; Prospective Studies; Metformin; Insulin; Thiazolidinediones; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 37968954
DOI: 10.14341/probl13183 -
Orphanet Journal of Rare Diseases Oct 2023Mitochondrial disease is a degenerative, progressive, heterogeneous group of genetic disorders affecting children and adults. Mitochondrial disease is associated with... (Review)
Review
The burden of mitochondrial disease with associated seizures: systematic literature reviews of health-related quality of life, utilities, costs and healthcare resource use data.
BACKGROUND
Mitochondrial disease is a degenerative, progressive, heterogeneous group of genetic disorders affecting children and adults. Mitochondrial disease is associated with morbidity and mortality, with predominantly neurological and neuromuscular symptoms including dystonia, weakness, encephalopathy, developmental delay and seizures. Seizures are one of the most common and severe manifestations of mitochondrial disease. These seizures are typically refractory to common anti-seizure therapies. There are no approved disease-modifying treatments for mitochondrial disease. Our objective was to conduct two systematic literature reviews to identify health-related quality of life (HRQoL), utilities, costs and healthcare resource use data in mitochondrial disease with associated seizures.
METHODS
A range of databases and information sources were searched up to July 2022 to identify eligible studies. Search strategies included a range of variant terms for mitochondrial disease and HRQoL, utilities, cost and healthcare resource use outcomes. Two reviewers independently assessed articles against the eligibility criteria; studies were extracted by one reviewer and checked by a second. Risk of bias was assessed for studies reporting HRQoL data. Results were narratively assessed.
RESULTS
Seven studies were eligible for the HRQoL and utilities review. The studies used different tools to report data, and despite the variability in methods, HRQoL scores across the studies showed moderate/severe disease in patients with mitochondrial disease with associated seizures. Parents of patients with mitochondrial disease with associated seizures were characterised by high total parenting stress. No studies reported utilities data. Two case reports and one retrospective review of medical records of children who died in hospital were eligible for the costs and resource use review. These provided limited information on the duration of hospital stay, in an intensive care unit (ICU), on mechanical ventilation. No studies reported costs data.
CONCLUSION
These reviews highlight the limited HRQoL, utilities, costs and resource use data and the variability of instruments used in mitochondrial disease with associated seizures. However, the data available indicate that mitochondrial disease with associated seizures affects patients' and caregivers' HRQoL alike. No robust conclusion can be drawn on the impact of mitochondrial disease with associated seizures on hospital or ICU length of stay. Trial registration PROSPERO: CRD42022345005.
Topics: Child; Adult; Humans; Quality of Life; Mitochondrial Diseases; Delivery of Health Care
PubMed: 37821990
DOI: 10.1186/s13023-023-02945-6 -
Heliyon Sep 2023Geniposide, as a pharmacologically bioactive component, is derived from a classic and common Chinese herb, Ellis. Geniposide has been shown to be effective for treating...
Protective effect and possible mechanisms of geniposide for ischemia-reperfusion injury: A systematic review with meta-analysis and network pharmacology of preclinical evidence.
BACKGROUND
Geniposide, as a pharmacologically bioactive component, is derived from a classic and common Chinese herb, Ellis. Geniposide has been shown to be effective for treating I/R injury in recent studies. Current effectively pharmaceutical treatments are scarce, and treatment based on geniposide may become a novel option. As far as we know, this research is the initial systematic evaluation of the protective effects of geniposide in I/R injury.
AIM OF THE STUDY
This study is engrossed in evaluating the mechanism of action of geniposide in I/R injury through a preclinical systematic review with meta-analysis and network pharmacology.
MATERIALS AND METHODS
We built a systematic review which provided a view of effect and mechanism of geniposide for I/R injury. Based on seven databases, an open-ended search from their inception to August 31st, 2022, was conducted. Animal studies on the effects of geniposide in I/R injury were considered. The data was analyzed using Review Manager 5.3, and bias was assessed using the CAMARADES 10-item scale. 13 articles including 279 animals were selected finally. And network pharmacology was joined to elucidate the mechanism.
RESULTS
According to the meta-analysis, in I/R injury, geniposide can attenuate cardiomyocytes viability and the size of MI, decrease the volume of cerebral infraction and neurological score, decrease serum ALT and AST activity, and downregulated serum Cr and BUN. The review found that geniposide protects against I/R injury by inhibiting apoptosis, oxidation, inflammation and improvement of autophagy and mitochondrial respiration, which is consistent with the results of the network pharmacology screening.
CONCLUSION
This preclinical systematic review including meta-analysis and network pharmacology, which was the first one summarizing the relationship between geniposide and ischemia diseases, shows a novel therapy for I/R injury and appears an enticing implication of geniposide in I/R injury, and further research is looked forward. Given the restricted quantity of included researches and the unclear risk of bias of the studies, we should interpret the results with caution.
PubMed: 37809705
DOI: 10.1016/j.heliyon.2023.e20114