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BMC Cancer Dec 2023Cardiac Myxoma is a primary tumor of heart. Its origins, rarity of the occurrence of primary cardiac tumors and how it may be related to limited cardiac regenerative...
BACKGROUND
Cardiac Myxoma is a primary tumor of heart. Its origins, rarity of the occurrence of primary cardiac tumors and how it may be related to limited cardiac regenerative potential, are not yet entirely known. This study investigates the key cardiac genes/ transcription factors (TFs) and signaling pathways to understand these important questions.
METHODS
Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving cardiac myxoma, cardiac genes/TFs/signaling pathways and their roles in cardiogenesis, proliferation, differentiation, key interactions and tumorigenesis, with focus on cardiomyocytes.
RESULTS
The cardiac genetic landscape is governed by a very tight control between proliferation and differentiation-related genes/TFs/pathways. Cardiac myxoma originates possibly as a consequence of dysregulations in the gene expression of differentiation regulators including Tbx5, GATA4, HAND1/2, MYOCD, HOPX, BMPs. Such dysregulations switch the expression of cardiomyocytes into progenitor-like state in cardiac myxoma development by dysregulating Isl1, Baf60 complex, Wnt, FGF, Notch, Mef2c and others. The Nkx2-5 and MSX2 contribute predominantly to both proliferation and differentiation of Cardiac Progenitor Cells (CPCs), may possibly serve roles based on the microenvironment and the direction of cell circuitry in cardiac tumorigenesis. The Nkx2-5 in cardiac myxoma may serve to limit progression of tumorigenesis as it has massive control over the proliferation of CPCs. The cardiac cell type-specific genetic programming plays governing role in controlling the tumorigenesis and regenerative potential.
CONCLUSION
The cardiomyocytes have very limited proliferative and regenerative potential. They survive for long periods of time and tightly maintain the gene expression of differentiation genes such as Tbx5, GATA4 that interact with tumor suppressors (TS) and exert TS like effect. The total effect such gene expression exerts is responsible for the rare occurrence and benign nature of primary cardiac tumors. This prevents the progression of tumorigenesis. But this also limits the regenerative and proliferative potential of cardiomyocytes. Cardiac Myxoma develops as a consequence of dysregulations in these key genes which revert the cells towards progenitor-like state, hallmark of CM. The CM development in carney complex also signifies the role of TS in cardiac cells.
Topics: Humans; Transcription Factors; Myocytes, Cardiac; Cell Differentiation; Heart Neoplasms; Myxoma; Carcinogenesis; Tumor Microenvironment
PubMed: 38110859
DOI: 10.1186/s12885-023-11723-3 -
Muscle & Nerve Feb 2024Many small-sized, single-center preclinical studies have investigated the benefits of introducing stem cells into the interior of nerve conduit. The aims of this... (Meta-Analysis)
Meta-Analysis
INTRODUCTION/AIMS
Many small-sized, single-center preclinical studies have investigated the benefits of introducing stem cells into the interior of nerve conduit. The aims of this meta-analysis are to review and contrast the effects of various types of stem cells in in vivo models used to reconstruct peripheral nerve injuries (PNIs) and to assess the reliability and stability of the available evidence.
METHODS
A systematic search was conducted using Cochrane Library, Embase, PubMed, and Web of Science to identify studies conducted from January 1, 2000, to September 21, 2022, and investigate stem cell therapy in peripheral nerve reconstruction animal models. Studies that met the relevant criteria were deemed eligible for this meta-analysis.
RESULTS
Fifty-five preclinical studies with a total of 1234 animals were incorporated. Stem cells demonstrated a positive impact on peripheral nerve regeneration at different follow-up times in the forest plots of five outcome indicators: compound muscle action potential (CMAP) amplitude, latency, muscle mass ratio, nerve conduction velocity, and sciatic functional index (SFI). In most comparisons, stem cell groups showed substantial differences compared with the control groups. The superior performance of adipose-derived stem cells (ADSCs) in terms of SFI, CMAP amplitude, and latency (p < .001) was identified.
DISCUSSION
The findings consistently demonstrated a favorable outcome in the reconstruction process when utilizing different groups of stem cells, as opposed to control groups where stem cells were not employed.
Topics: Animals; Nerve Regeneration; Peripheral Nerve Injuries; Reproducibility of Results; Stem Cells
PubMed: 38063327
DOI: 10.1002/mus.28018 -
Evaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review.American Journal of Physiology.... Apr 2024Nicotinamide adenine dinucleotide (NAD) is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including... (Review)
Review
Nicotinamide adenine dinucleotide (NAD) is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including oxidative phosphorylation and production of adenosine triphosphate, DNA repair, calcium-dependent secondary messenger and gene expression. The purpose of this systematic review is to examine whether the coenzyme formulae NAD and NADH are safe and effective when acting as a supplement to humans. This systematic review of randomized clinical trials performed a search in six electronic databases: PubMed, MEDLINE (), Embase, Cochrane CENTRAL (clinical trials), Web of Science, and Scopus. Secondary search included the databases (e.g., Clinical trials.gov, Rebec, Google Scholar - advance). Two reviewers assessed and extracted the studies independently. The risk of bias in studies was performed using version 2 of the Cochrane risk of bias tool for randomized trials. This review includes 10 studies, with a total of 489 participants. The studies included different clinical conditions, such as chronic fatigue syndrome (CFS), older adults, Parkinson's disease, overweight, postmenopausal prediabetes, and Alzheimer's disease. Based on studies, the supplementation with NADH and precursors was well tolerated and observed clinical results such as, a decrease in anxiety conditions and maximum heart rate was observed after a stress test, increased muscle insulin sensitivity, insulin signaling. Quality of life, fatigue intensity, and sleep quality among others were evaluated on patients with CFS. All studies showed some side effects, thus, the most common associated with NADs use are muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches. All adverse events cataloged by the studies did not present a serious risk to the health of the participants. Overall, these findings support that the oral administration of NADH can be associated to an increase in general quality of life and improvement on health parameters (e.g., a decrease in anxiety, maximum heart rate, inflammatory cytokines in serum, and cerebrospinal fluid). NADH supplementation is safe and has a low incidence of side effects. Future investigations are needed to evidence the clinical benefits regarding specific diseases and doses administered.
Topics: Humans; Aged; Quality of Life; Fatigue Syndrome, Chronic; NAD; Dietary Supplements
PubMed: 37971292
DOI: 10.1152/ajpendo.00242.2023 -
International Journal of Molecular... Oct 2023Ageing is an irreversible and inevitable biological process and a significant risk factor for the development of various diseases, also affecting the musculoskeletal... (Review)
Review
Ageing is an irreversible and inevitable biological process and a significant risk factor for the development of various diseases, also affecting the musculoskeletal system, resulting from the accumulation of cell senescence. The aim of this systematic review was to collect the in vitro studies conducted over the past decade in which cell senescence was induced through various methods, with the purpose of evaluating the molecular and cellular mechanisms underlying senescence and to identify treatments capable of delaying senescence. Through three electronic databases, 22 in vitro studies were identified and included in this systematic review. Disc, cartilage, or muscle cells or tissues and mesenchymal stem cells were employed to set-up in vitro models of senescence. The most common technique used to induce cell senescence was the addition to the culture medium of tumor necrosis factor (TNF)α and/or interleukin (IL)1β, followed by irradiation, compression, hydrogen peroxide (HO), microgravity, in vitro expansion up to passage 10, and cells harvested from damaged areas of explants. Few studies evaluated possible treatments to anti-senescence effects. The included studies used in vitro models of senescence in musculoskeletal tissues, providing powerful tools to evaluate age-related changes and pathologies, also contributing to the development of new therapeutic approaches.
Topics: Cells, Cultured; Cellular Senescence; Hydrogen Peroxide
PubMed: 37958603
DOI: 10.3390/ijms242115617 -
Stem Cell Reviews and Reports Jan 2024Duchenne Muscular Dystrophy (DMD) is an inherited genetic disorder characterized by progressive degeneration of muscle tissue, leading to functional disability and... (Review)
Review
Duchenne Muscular Dystrophy (DMD) is an inherited genetic disorder characterized by progressive degeneration of muscle tissue, leading to functional disability and premature death. Despite extensive research efforts, the discovery of a cure for DMD continues to be elusive, emphasizing the need to investigate novel treatment approaches. Cellular therapies have emerged as prospective approaches to address the underlying pathophysiology of DMD. This review provides an examination of the present situation regarding cell-based therapies, including CD133 + cells, muscle precursor cells, mesoangioblasts, bone marrow-derived mononuclear cells, mesenchymal stem cells, cardiosphere-derived cells, and dystrophin-expressing chimeric cells. A total of 12 studies were found eligible to be included as they were completed cell therapy clinical trials, clinical applications, or case reports with quantitative results. The evaluation encompassed an examination of limitations and potential advancements in this particular area of research, along with an assessment of the safety and effectiveness of cell-based therapies in the context of DMD. In general, the available data indicates that diverse cell therapy approaches may present a new, safe, and efficacious treatment modality for patients diagnosed with DMD. However, further studies are required to comprehensively understand the most advantageous treatment approach and therapeutic capacity.
Topics: Humans; Muscular Dystrophy, Duchenne; Muscle, Skeletal; Mesenchymal Stem Cells; Treatment Outcome; Cell- and Tissue-Based Therapy
PubMed: 37955832
DOI: 10.1007/s12015-023-10653-8 -
Frontiers in Neuroscience 2023Intracranial aneurysms (IA) are the most common cerebral vascular pathologies. Their rupture leads to the most dangerous subtype of stroke-aneurysmal subarachnoid... (Review)
Review
Intracranial aneurysms (IA) are the most common cerebral vascular pathologies. Their rupture leads to the most dangerous subtype of stroke-aneurysmal subarachnoid hemorrhage (aSAH), which may be followed by cerebral vasospasm and ischemic sequelae. Recently, an imbalance within the intestinal microbiota, referred to as dysbiosis, was suggested to play a role in the formation, progression, and rupture of IA. As no systematic review on this topic exists, considering the significance of this matter and a lack of effective prophylaxis against IA or cerebral vasospasm, we aim to sum up the current knowledge regarding their associations with intestinal microbiome, identify the gaps, and determine future prospects. Scientific databases were systematically and independently searched by two authors from inception to 1st May 2023 for original articles regarding the role of intestinal microbiota in intracranial aneurysmal growth, aSAH occurrence, as well as in cerebral vasospasm following aSAH. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist was followed in an abstraction process. The STROBE tool was applied to assess the risk of bias. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 302 records, four studies were included that fully met eligibility criteria. Studies reported (1) that the relative abundance of is a protective factor against aneurysm growth and rupture, resulting from the reduced inflammation and extracellular matrix remodeling in the cerebral arterial wall and from reduced metalloproteinase-mediated degradation of smooth muscle cells in cerebral vessels. (2) Relative abundance of is associated with aSAH. (3) No article has evaluated microbiota in relation to cerebral vasospasm following aSAH although there is an ongoing study. We concluded that intestinal microbiota might be a potential target for diagnostic and therapeutic tools to improve the management of cerebral aneurysms. However, more studies of prospective design are needed.
PubMed: 37928732
DOI: 10.3389/fnins.2023.1247151 -
Nutrients Oct 2023Vitamin D deficiency, prevalent worldwide, is linked to muscle weakness, sarcopenia, and falls. Muscle regeneration is a vital process that allows for skeletal muscle... (Review)
Review
Vitamin D deficiency, prevalent worldwide, is linked to muscle weakness, sarcopenia, and falls. Muscle regeneration is a vital process that allows for skeletal muscle tissue maintenance and repair after injury. PubMed and Web of Science were used to search for studies published prior to May 2023. We assessed eligible studies that discussed the relationship between vitamin D, muscle regeneration in this review. Overall, the literature reports strong associations between vitamin D and skeletal myocyte size, and muscle regeneration. In vitro studies in skeletal muscle cells derived from mice and humans showed vitamin D played a role in regulating myoblast growth, size, and gene expression. Animal studies, primarily in mice, demonstrate vitamin D's positive effects on skeletal muscle function, such as improved grip strength and endurance. These studies encompass vitamin D diet research, genetically modified models, and disease-related mouse models. Relatively few studies looked at muscle function after injury, but these also support a role for vitamin D in muscle recovery. The human studies have also reported that vitamin D deficiency decreases muscle grip strength and gait speed, especially in the elderly population. Finally, human studies reported the benefits of vitamin D supplementation and achieving optimal serum vitamin D levels in muscle recovery after eccentric exercise and surgery. However, there were no benefits in rotator cuff injury studies, suggesting that repair mechanisms for muscle/ligament tears may be less reliant on vitamin D. In summary, vitamin D plays a crucial role in skeletal muscle function, structural integrity, and regeneration, potentially offering therapeutic benefits to patients with musculoskeletal diseases and in post-operative recovery.
Topics: Aged; Humans; Animals; Mice; Vitamin D; Muscle, Skeletal; Vitamins; Vitamin D Deficiency; Muscular Diseases; Models, Animal; Regeneration
PubMed: 37892452
DOI: 10.3390/nu15204377 -
Orthopaedics & Traumatology, Surgery &... Feb 2024Muscle fatty degeneration following rotator cuff tears has been unequivocally associated with poorer functional outcomes and increased risk for retear following rotator... (Review)
Review
BACKGROUND
Muscle fatty degeneration following rotator cuff tears has been unequivocally associated with poorer functional outcomes and increased risk for retear following rotator cuff repair. Promising results have emerged from animal studies, with the implementation of various interventions for biologic inhibition of this fatty muscle degeneration. The lack of high quality randomized human evidence on this topic, increases the impact of pooled results from animal literature. The aim of the present study was to systematically review the available published literature for animal studies evaluating the ability of several interventions used to mitigate muscle fatty degeneration following the repair of massive rotator cuff tears.
PATIENTS AND METHODS
A comprehensive search was conducted on Pubmed, Scopus and Google Scholar, covering the period from conception until 16th April 2022. Datasets were stratified based on the type of intervention performed. SYRCLE risk of bias instrument was implemented for quality assessment of the included studies.
RESULTS
Rotator cuff repair augmentation with Adipose derived stem cells (ADSC's), Mesenchymal stem cells (MSC's) and Nandrolone was effective against fatty infiltration, but less effective against muscle atrophy. More beneficial effect was shown by the utilization of Beige adipose tissue - Fibroadipogenic progenitors (BAT-FAP) stimulation, using either Amibregon or BAT-FAPs transplantation. Both provided good results in mitigating muscle atrophy, fatty infiltration and fibrosis.
DISCUSSION
ADSC's, MSC's, Nandrolone and BAT-FAP stimulation may have a role in mitigating muscle fatty degeneration following rotator cuff tears. Large scale human studies are required to further elucidate their role in the clinical setting.
LEVEL OF EVIDENCE
V; systematic review of pre-clinical studies.
Topics: Animals; Adipose Tissue; Muscular Atrophy; Nandrolone; Rotator Cuff; Rotator Cuff Injuries
PubMed: 37879533
DOI: 10.1016/j.otsr.2023.103723 -
Endocrine Pathology Dec 2023Anaplastic thyroid carcinoma (ATC) demonstrates a wide variety of morphologies and is characteristically associated with a differentiated thyroid carcinoma component.... (Meta-Analysis)
Meta-Analysis
Glomangiosarcoma-like Anaplastic Transformation in Papillary Thyroid Carcinoma: A Novel Form of Heterologous Differentiation and a Systematic Review of Heterologous Element Prevalence.
Anaplastic thyroid carcinoma (ATC) demonstrates a wide variety of morphologies and is characteristically associated with a differentiated thyroid carcinoma component. Heterologous differentiation is a rare, potentially challenging phenomenon in ATC, mostly observed as osteosarcomatous or chondrosarcomatous differentiation. We now describe a novel 'glomangiosarcoma-like' differentiation, review our archival experience from two institutions (UPMC, CC), and perform a systematic review for the prevalence of heterologous elements in ATC. The patient is a 57-year-old female who presented with 4.5 cm left thyroid, and 3.4 cm neck masses. Histologically, the thyroid demonstrated a differentiated high grade papillary thyroid carcinoma, tall cell and hobnail/micropapillary subtypes transitioning into an anaplastic component with spindled to ovoid cells with hemangiopericytoma-like vasculature showing CD34 positivity, variable muscle marker expression and pericellular lace-like type IV collagen deposition. The neck mass consisted solely of the latter morphology. Targeted next-generation sequencing was performed on high grade DTC and adjacent ATC from the thyroid as well as ATC from the neck metastasis. All three components shared BRAF, TERT promoter, and PIK3CA mutations confirming a clonal origin. Archival (UPMC: n = 150, CC: n = 74) and literature review showed no prior examples. Systematic review and meta-analysis of prevalence showed a baseline pooled prevalence (generalized linear mixed model) of heterologous elements of any type to be 1.6% (95% confidence interval: 1.0-2.6%) for studies where this was specifically addressed. ATC with glomangiosarcoma-like heterologous differentiation is a rarity among an already rare morphologic category with unique diagnostic pitfalls.
Topics: Female; Humans; Middle Aged; Thyroid Cancer, Papillary; Prevalence; Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Cell Differentiation; Adenocarcinoma; Sarcoma; Proto-Oncogene Proteins B-raf
PubMed: 37792156
DOI: 10.1007/s12022-023-09787-9 -
Open Access Emergency Medicine : OAEM 2023Heatstroke (HS) is a severe form of heat-related illness (HRI) associated with high morbidity and mortality, representing a condition that includes long-term multiorgan...
INTRODUCTION
Heatstroke (HS) is a severe form of heat-related illness (HRI) associated with high morbidity and mortality, representing a condition that includes long-term multiorgan dysfunction and susceptibility to further heat illness.
METHODS
In a systematic review searching Medline PubMed from the studies conducted between 2009 and 2020, 16 papers were identified.
RESULTS
A hallmark symptom of heat stroke is CNS dysfunction (a hallmark sign of HS) which manifests as mental status changes, including agitation, delirium, epilepsy, or coma at the time of the collapse. Acute kidney injury (AKI), gut ischemia, blood clots in the stomach and small intestine, cytoplasmic protein clumps in the spleen, and injury of skeletal muscle (rhabdomyolysis) are all characteristics of peripheral tissue damage. Severe heat stroke tends to be complicated by rhabdomyolysis, especially in patients with exertional heat stroke. Rhabdomyolysis may lead to systemic effects, including the local occurrence of compartment syndrome, hyperkalemic cardiac arrest, and/or lethal disseminated intravascular coagulopathy. Untreated heat stroke might exacerbate psychosis, lactic acidosis, consumptive coagulopathy, hematuria, pulmonary edema, renal failure, and other metabolic abnormalities. Core body temperature and level of consciousness are the most significant indicators to diagnose the severity of heat stroke and prevent unfavorable consequences. Heatstroke is a life-threatening illness if not promptly recognized and effectively treated.
DISCUSSION
This review highlighted that core body temperature and white blood cell count are significant contributing factors affecting heat stroke outcomes. Other factors contributing to the poor outcome include old age, low GCS, and prolonged hospital stay. The prevalence of both classic and exertional heatstroke can be reduced by certain simple preventive measures, such as avoiding strenuous activity in hot environments and reducing exposure to heat stress.
PubMed: 37771523
DOI: 10.2147/OAEM.S419028