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Pharmacological Reports : PR Oct 2020Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular childhood disorder that causes progressive muscle weakness and degeneration and results in...
BACKGROUND
Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular childhood disorder that causes progressive muscle weakness and degeneration and results in functional decline, loss of ambulation and early death of young men due to cardiac or respiratory failure. Although the major cause of the disease has been known for many years-namely mutation in the DMD gene encoding dystrophin, one of the largest human genes-DMD is still incurable, and its treatment is challenging.
METHODS
A comprehensive and systematic review of literature on the gene, cell, and pharmacological experimental therapies aimed at restoring functional dystrophin or to counteract the associated processes contributing to disease progression like inflammation, fibrosis, calcium signaling or angiogenesis was carried out.
RESULTS
Although some therapies lead to satisfying effects in skeletal muscle, they are highly ineffective in the heart; therefore, targeting defective cardiac and respiratory systems is vital in DMD patients. Unfortunately, most of the pharmacological compounds treat only the symptoms of the disease. Some drugs addressing the underlying cause, like eteplirsen, golodirsen, and ataluren, have recently been conditionally approved; however, they can correct only specific mutations in the DMD gene and are therefore suitable for small sub-populations of affected individuals.
CONCLUSION
In this review, we summarize the possible therapeutic options and describe the current status of various, still imperfect, strategies used for attenuating the disease progression.
Topics: Animals; Dystrophin; Heart; Humans; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Mutation
PubMed: 32691346
DOI: 10.1007/s43440-020-00134-x -
Journal of Clinical Medicine Dec 2022Fatty acid translocase/cluster of differentiation 36 (FAT/CD36) is a multifunctional membrane protein activated by a high-fat diet, physical exercise, fatty acids (FAs),... (Review)
Review
Fatty acid translocase/cluster of differentiation 36 (FAT/CD36) is a multifunctional membrane protein activated by a high-fat diet, physical exercise, fatty acids (FAs), leptin, and insulin. The principal function of FAT/CD36 is to facilitate the transport of long-chain fatty acids through cell membranes such as myocytes, adipocytes, heart, and liver. Under high-energy expenditure, the different isoforms of FAT/CD36 in the plasma membrane and mitochondria bind to the mobilization and oxidation of FAs. Furthermore, FAT/CD36 is released in its soluble form and becomes a marker of metabolic dysfunction. Studies with healthy animals and humans show that physical exercise and a high-lipid diet increase FAT/CD36 expression and caloric expenditure. However, several aspects such as obesity, diabetes, Single Nucleotide polymorphisms (SNPs), and oxidative stress affect the normal FAs metabolism and function of FAT/CD36, inducing metabolic disease. Through a comprehensive systematic review of primary studies, this work aimed to document molecular mechanisms related to FAT/CD36 in FAs oxidation and trafficking in skeletal muscle under basal conditions, physical exercise, and diet in healthy individuals.
PubMed: 36615118
DOI: 10.3390/jcm12010318 -
Reviews in Medical Virology Nov 2021Infectious diseases occur worldwide with great frequency in both adults and children, causing 350,000 deaths in 2017, according to the latest World Health Organization... (Review)
Review
Infectious diseases occur worldwide with great frequency in both adults and children, causing 350,000 deaths in 2017, according to the latest World Health Organization reports. Both infections and their treatments trigger mitochondrial interactions at multiple levels: (i) incorporation of damaged or mutated proteins into the complexes of the electron transport chain; (ii) impact on mitochondrial genome (depletion, deletions and point mutations) and mitochondrial dynamics (fusion and fission); (iii) membrane potential impairment; (iv) apoptotic regulation; and (v) generation of reactive oxygen species, among others. Such alterations may result in serious adverse clinical events with considerable impact on the quality of life of the children and could even cause death. Herein, we use a systematic review to explore the association between mitochondrial alterations in paediatric infections including human immunodeficiency virus, cytomegalovirus, herpes viruses, various forms of hepatitis, adenovirus, T-cell lymphotropic virus and influenza. We analyse how these paediatric viral infectious processes may cause mitochondrial deterioration in this especially vulnerable population, with consideration for the principal aspects of research and diagnosis leading to improved disease understanding, management and surveillance.
Topics: Antiviral Agents; Child; Communicable Diseases; DNA, Mitochondrial; Humans; Mitochondria; Pediatrics; Virus Diseases
PubMed: 33792105
DOI: 10.1002/rmv.2232 -
Cancers Jul 2019Preoperative physical exercise protocols prior to cancer surgery increased in popularity over recent years; however, the beneficial effect of such protocols is not well... (Review)
Review
Preoperative physical exercise protocols prior to cancer surgery increased in popularity over recent years; however, the beneficial effect of such protocols is not well established, with conflicting results reported. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effects of different modalities or combinations of preoperative exercise interventions and/or prehabilitation multicomponent training in patients with non-small-cell lung cancer (NSCLC) after surgery on the outcomes related to functional capacity, mental wellness and medical care. We searched in OVID Embase, Pubmed, Cochrane Library, CINAHL, Scopus, and Web of Science. Characteristics of studies and program results and outcome data were extracted. Changes between the intervention and control groups, from baseline to follow-up (standardized mean difference (SMD) or relative risk (RR) with 95% confidence interval (CI) for each intervention was pooled using weighted random-effects models). A total of 676 participants from 10 RCTs were included in the final analysis (aerobic training + inspiratory muscle training, = 5; aerobic training + strength training + inspiratory muscle training, = 2; aerobic training + strength training, = 1; multicomponent training, = 1; aerobic training alone, = 1). The results showed intervention-induced improvement in walking endurance (SMD = 0.27; 95% CI, 0.11 to 0.44; = 0.0%), peak exercise capacity (SMD = 0.78; 95% CI, 0.35 to 1.21; = 76.7%), dyspnoea (SMD = -0.30; 95% CI, -0.51 to -0.10; = 0.0%), risk of hospitalization (SMD = -0.58; 95% CI, -0.97 to -0.20; = 70.7%), and postoperative pulmonary complications (relative risk (RR) = 0.50; 95% CI, 0.39 to 0.66; = 0.0%). For the functional capacity and medical care parameters, preoperative combined aerobic, resistance, and inspiratory muscle training was shown to be effective if comprising one to four weeks, performing 1-3 sessions per week, with moderate intensity (50% for endurance capacity). Further studies with larger samples and higher methodological quality are needed to clarify the potential benefits of preoperative exercise training for patients with NSCLC.
PubMed: 31284372
DOI: 10.3390/cancers11070944 -
Medicina Oral, Patologia Oral Y Cirugia... Nov 2022Rhabdomyosarcoma (RMS) is a soft tissue malignant tumor of mesenchymal cell origin, which usually shows variable differentiation of muscle cells. It is the most common...
BACKGROUND
Rhabdomyosarcoma (RMS) is a soft tissue malignant tumor of mesenchymal cell origin, which usually shows variable differentiation of muscle cells. It is the most common solid sarcoma in children. The most usual site of occurrence are the head and neck regions. RMS presents a variety of histologic features, and so differential diagnosis with other small round cell tumors is needed. Hence, it has been very useful to the field to undertake additional immunohistochemical studies to determine the diagnosis and, on occasions, to assign subtype tumors.
MATERIAL AND METHODS
A systematic review of three databases (Medline, Biological Science Collection and Health & Medical Collection) was carried out with the purpose of analyzing rhabdomyosarcoma cases reported in the literature, specifically with localization in the head and neck regions in children. This strategy allowed us to identify the main anatomical site of appearance, the subtype of RMS, average age, histologic characteristics and immunohistochemistry markers used in a usual and any additional way.
RESULTS
According to the selection criteria in this systematic review, twelve articles, and fourteen cases were identified that highlight that the histological diagnosis usually presents cellular heterogeneity. Therefore, immunohistochemistry is needed to confirm the diagnosis.
CONCLUSIONS
Histologic characterization is not always sufficient for a conclusive diagnosis of RMS. Therefore, immunohistochemistry is helpful to determine the subtype and consequently, sometimes the behavior, treatment and prognosis. Additional markers may vary according to the institution and the need of particular cases.
Topics: Child; Humans; Rhabdomyosarcoma; Immunohistochemistry; Prognosis; Diagnosis, Differential
PubMed: 36173721
DOI: 10.4317/medoral.25508 -
International Journal of Molecular... Feb 2023Among the most common muscular dystrophies in adults is Myotonic Dystrophy type 1 (DM1), an autosomal dominant disorder characterized by myotonia, muscle wasting and... (Review)
Review
Among the most common muscular dystrophies in adults is Myotonic Dystrophy type 1 (DM1), an autosomal dominant disorder characterized by myotonia, muscle wasting and weakness, and multisystemic dysfunctions. This disorder is caused by an abnormal expansion of the CTG triplet at the gene that, when transcribed to expanded mRNA, can lead to RNA toxic gain of function, alternative splicing impairments, and dysfunction of different signaling pathways, many regulated by protein phosphorylation. In order to deeply characterize the protein phosphorylation alterations in DM1, a systematic review was conducted through PubMed and Web of Science databases. From a total of 962 articles screened, 41 were included for qualitative analysis, where we retrieved information about total and phosphorylated levels of protein kinases, protein phosphatases, and phosphoproteins in DM1 human samples and animal and cell models. Twenty-nine kinases, 3 phosphatases, and 17 phosphoproteins were reported altered in DM1. Signaling pathways that regulate cell functions such as glucose metabolism, cell cycle, myogenesis, and apoptosis were impaired, as seen by significant alterations to pathways such as AKT/mTOR, MEK/ERK, PKC/CUGBP1, AMPK, and others in DM1 samples. This explains the complexity of DM1 and its different manifestations and symptoms, such as increased insulin resistance and cancer risk. Further studies can be done to complement and explore in detail specific pathways and how their regulation is altered in DM1, to find what key phosphorylation alterations are responsible for these manifestations, and ultimately to find therapeutic targets for future treatments.
Topics: Animals; Adult; Humans; Myotonic Dystrophy; Phosphorylation; Alternative Splicing; RNA, Messenger; Muscular Atrophy; Muscle, Skeletal
PubMed: 36834509
DOI: 10.3390/ijms24043091 -
Oral Surgery, Oral Medicine, Oral... Jun 2022Oral squamous cell carcinoma involving the maxilla (MSCC) is a rare malignancy. The aim was to perform a systematic review and meta-analysis of available literature on... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Oral squamous cell carcinoma involving the maxilla (MSCC) is a rare malignancy. The aim was to perform a systematic review and meta-analysis of available literature on local recurrence (LR), overall survival (OS), and associated risk factors of MSCC.
STUDY DESIGN
The Cochrane, PubMed, and EMBASE databases were searched with related keywords and synonyms. The pooled proportions of both LR and OS were subsequently calculated with 95% confidence intervals.
RESULTS
In total, 2638 articles were screened on title and abstract, 131 articles were screened on full text, and 20 were included. The pooled 5-year LR rate was 19.3%, and the 5-year OS rate was 53.7%. The subgroup analysis between surgery only and surgery with (neo)adjuvant treatment resulted in an odds ratio (OR) of .76 (95% confidence interval [CI]; .41-1.40).
CONCLUSIONS
Postoperative (chemo)radiotherapy or preoperative intra-arterial chemoradiotherapy improves survival when adverse tumor characteristics are present. Posterior tumor extension into the soft palate, pterygoid muscle, pterygoid process, and infratemporal fossa was significantly associated with decreased OS in multiple studies. More research into the risk-reduction of local recurrence is warranted.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Maxilla; Mouth Neoplasms; Neoplasm Recurrence, Local; Squamous Cell Carcinoma of Head and Neck
PubMed: 35165055
DOI: 10.1016/j.oooo.2021.10.003 -
Nutrients May 2023Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a...
Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a potential environmental factor in asthma pathogenesis, due to its immunomodulatory effects. This systematic review aimed to evaluate the effect of vitamin D supplementation in order to prevent airway remodeling in asthmatic patients. Four electronic databases, namely PubMed, Embase, Clinical trails.gov, and CINAHL, were thoroughly searched to conduct a comprehensive literature review. The International Prospective Register of Systematic Reviews (CRD42023413798) contains a record of the registered protocol. We identified 9447 studies during the initial search; 9 studies (0.1%) met the inclusion criteria and were included in the systematic review. All included studies were experimental studies that investigated the impact of vitamin D supplementation on airway remodeling in asthma. The studies included in this review suggest that vitamin D inhibits airway smooth muscle cell contraction and remodeling, reduces inflammation, regulates collagen synthesis in the airways, and modulates the action of bronchial fibroblasts. However, one study suggests that TGF-β1 can impair vitamin D-induced and constitutive airway epithelial host defense mechanisms. Overall, vitamin D appears to have a potential role in the prevention and management of asthma.
Topics: Humans; Airway Remodeling; Asthma; Bronchi; Dietary Supplements; Vitamin D; Vitamins
PubMed: 37299440
DOI: 10.3390/nu15112477 -
Journal of Cardiothoracic Surgery Aug 2022Pulmonary arterial hypertension (PAH) is a progressive disease. Although great progress has been made in its diagnosis and treatment in recent years, its mortality rate... (Review)
Review
Pulmonary arterial hypertension (PAH) is a progressive disease. Although great progress has been made in its diagnosis and treatment in recent years, its mortality rate is still very significant. The pathophysiology and pathogenesis of PAH are complex and involve endothelial dysfunction, chronic inflammation, smooth muscle cell proliferation, pulmonary arteriole occlusion, antiapoptosis and pulmonary vascular remodeling. These factors will accelerate the progression of the disease, leading to poor prognosis. Therefore, accurate etiological diagnosis, treatment and prognosis judgment are particularly important. Here, we systematically review the pathophysiology, diagnosis, genetics, prognosis and treatment of PAH.
Topics: Animals; Cell Proliferation; Disease Models, Animal; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Muscle, Smooth, Vascular; Pulmonary Arterial Hypertension; Pulmonary Artery
PubMed: 36038916
DOI: 10.1186/s13019-022-01947-y -
International Journal of Environmental... Jan 2022This study looks at the effects of exercise programs on physical factors and safety in adult patients with cancer and hematopoietic stem cell transplantation (HSCT) or... (Review)
Review
This study looks at the effects of exercise programs on physical factors and safety in adult patients with cancer and hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT). A systematic search was performed in the PubMed and Web of Science databases (from inception to 26 August 2021). A review was carried out following the Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) checklist. The methodological quality of the included studies was assessed with the Physiotherapy Evidence Database (PEDro) scale, based, in turn, on the Delphi list. A total of 25 randomized controlled trials studies were included, comprising 1434 patients. The most significant result of this systematic review is that exercise program interventions are safe and produce positive changes in cardiorespiratory fitness, muscle strength, and the functional mobility-state in adult patients with cancer and HSCT or BMT. Only 3 patients from the 711 participants in the exercise interventions (i.e., 0.42%) reported adverse events related to exercise interventions. Moreover, exercise training programs may have a cardiological and muscular protective effect, as well as a healthy effect on the prevention and control of transplant complications, improving health outcomes.
Topics: Exercise; Exercise Therapy; Hematopoietic Stem Cell Transplantation; Humans; Muscle Strength; Neoplasms; Quality of Life
PubMed: 35162312
DOI: 10.3390/ijerph19031288