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Frontiers in Endocrinology 2024Various stem cell-loaded scaffolds have demonstrated promising endometrial regeneration and fertility restoration. This study aimed to evaluate the efficacy of stem... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Various stem cell-loaded scaffolds have demonstrated promising endometrial regeneration and fertility restoration. This study aimed to evaluate the efficacy of stem cell-loaded scaffolds in treating uterine injury in animal models.
METHODS
The PubMed, Embase, Scopus, and Web of Science databases were systematically searched. Data were extracted and analyzed using Review Manager version 5.4. Improvements in endometrial thickness, endometrial glands, fibrotic area, and number of gestational sacs/implanted embryos were compared after transplantation in the stem cell-loaded scaffolds and scaffold-only group. The standardized mean difference (SMD) and confidence interval (CI) were calculated using forest plots.
RESULTS
Thirteen studies qualified for meta-analysis. Overall, compared to the scaffold groups, stem cell-loaded scaffolds significantly increased endometrial thickness (SMD = 1.99, 95% CI: 1.54 to 2.44, P < 0.00001; I² = 16%) and the number of endometrial glands (SMD = 1.93, 95% CI: 1.45 to 2.41, P < 0.00001; I² = 0). Moreover, stem cell-loaded scaffolds present a prominent effect on improving fibrosis area (SMD = -2.50, 95% CI: -3.07 to -1.93, P < 0.00001; I² = 36%) and fertility (SMD = 3.34, 95% CI: 1.58 to 5.09, P = 0.0002; I² = 83%). Significant heterogeneity among studies was observed, and further subgroup and sensitivity analyses identified the source of heterogeneity. Moreover, stem cell-loaded scaffolds exhibited lower inflammation levels and higher angiogenesis, and cell proliferation after transplantation.
CONCLUSION
The evidence indicates that stem cell-loaded scaffolds were more effective in promoting endometrial repair and restoring fertility than the scaffold-only groups. The limitations of the small sample sizes should be considered when interpreting the results. Thus, larger animal studies and clinical trials are needed for further investigation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024493132.
Topics: Female; Endometrium; Regeneration; Tissue Scaffolds; Animals; Humans; Fertility; Stem Cells; Infertility, Female; Stem Cell Transplantation
PubMed: 38846497
DOI: 10.3389/fendo.2024.1397783 -
Anatomy & Cell Biology Jun 2024In the last decade, melatonin has gained recognition as a potent scavenger and an effective antioxidant capable of neutralizing free radicals, including reactive oxygen... (Review)
Review
In the last decade, melatonin has gained recognition as a potent scavenger and an effective antioxidant capable of neutralizing free radicals, including reactive oxygen species. Additionally, it exhibits anti-apoptotic properties. In this review, we will examine a compilation of articles that explore the cellular signaling function of melatonin on spermatogonial stem cells (SSCs) and adjacent cells such as Sertoli and Leydig cells. These cells play a crucial role in the proliferation of SSCs both and . In this review, we analyze the function of melatonin in the proliferation of SSCs from other aspects. For this purpose, we examine the articles based on the presence of melatonin on SSCs in four groups: As a supplement in SSCs medium culture, SSCs three-dimensional culture system, SSCs freezing medium, and as a therapeutic factor . Mechanisms of growth and proliferation of SSCs were considered. The purpose of this study is to investigate the potential effects of melatonin as a powerful antioxidant or growth stimulant for SSCs, both and .
PubMed: 38590095
DOI: 10.5115/acb.23.256 -
Cureus Mar 2024A large portion of the world's population is affected by acne vulgaris (AV), with many of these individuals being adolescents. The underlying mechanism of AV is... (Review)
Review
A large portion of the world's population is affected by acne vulgaris (AV), with many of these individuals being adolescents. The underlying mechanism of AV is hyperkeratinization and infection of the pilosebaceous follicle secondary to excessive stimulation of sebaceous glands by androgens. Metformin is a biguanide medication primarily used in efforts to lower patients' sugar levels in the management of type 2 diabetes. It has been proven to reduce levels of circulating androgens in patients with insulin resistance, indicating its potential for treating AV. A search strategy was developed and performed using the databases Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Controlled Register of Trials (CENTRAL), and Web of Science. The keywords "metformin" and "acne" were searched, along with related Medical Subject Headings (MeSH) and other subject headings. Studies that met the inclusion criteria were controlled trials, published after 2010, and in the English language. Participants with and without comorbidities such as polycystic ovary syndrome (PCOS) were considered. Two independent reviewers screened studies based on predefined criteria and extracted data from each study, which were quantitatively combined. A total of 15 studies were included in this systematic review. Across the 15 studies, there were 1,046 participants, with 13 studies looking exclusively at women with PCOS. Of the remaining two studies, one examined males with altered metabolic profiles, while the other included men and women with moderate AV. Notable risks of bias included studies that did not exclusively state the blindness of the study. Of the studies that were examined, 13 showed that metformin reduces AV, with seven studies showing statistical significance. Acne vulgaris is an inflammatory condition that has plagued patients for years due to the limited treatment options available. The hyperglycemic medication metformin, used in the management of type 2 diabetes, is being explored as a novel therapeutic that can possibly be repurposed for the treatment of AV. The use of metformin in AV is hypothesized to disrupt the proposed linkage between insulin resistance and AV proliferation. This proposed research could offer physicians a new option for the treatment of AV as well as render an alternative AV treatment for patients.
PubMed: 38623111
DOI: 10.7759/cureus.56246 -
Frontiers in Cardiovascular Medicine 2024Neural crest cells (NCCs) are multipotent and are attributed to the combination of complex multimodal gene regulatory mechanisms. Cardiac neural crest (CNC) cells,...
INTRODUCTION
Neural crest cells (NCCs) are multipotent and are attributed to the combination of complex multimodal gene regulatory mechanisms. Cardiac neural crest (CNC) cells, originating from the dorsal neural tube, are pivotal architects of the cardio-neuro-vascular domain, which orchestrates the embryogenesis of critical cardiac and vascular structures. Remarkably, while the scientific community compiled a comprehensive inventory of neural crest derivatives by the early 1980s, our understanding of the CNC's role in various cardiovascular disease processes still needs to be explored. This review delves into the differentiation of NCC, specifically the CNC cells, and explores the diverse facets of non-syndromic cardiovascular neurocristopathies.
METHODS
A systematic review was conducted as per the PRISMA Statement. Three prominent databases, PubMed, Scopus, and Embase, were searched, which yielded 1,840 studies. We excluded 1,796 studies, and the final selection of 44 studies formed the basis of this comprehensive review.
RESULTS
Neurocristopathies are a group of genetic disorders that affect the development of cells derived from the NC. Cardiovascular neurocristopathy, i.e., cardiopathy and vasculopathy, associated with the NCC could occur in the form of (1) cardiac septation disorders, mainly the aortico-pulmonary septum; (2) great vessels and vascular disorders; (3) myocardial dysfunction; and (4) a combination of all three phenotypes. This could result from abnormalities in NCC migration, differentiation, or proliferation leading to structural abnormalities and are attributed to genetic, familial, sporadic or acquired causes.
DISCUSSION
Phenotypic characteristics of cardiovascular neurocristopathies, such as bicuspid aortic valve and thoracic aortic aneurysm, share a common embryonic origin and are surprisingly prevalent in the general population, necessitating further research to identify the underlying pathogenic and genetic factors responsible for these cardiac anomalies. Such discoveries are essential for enhancing diagnostic screening and refining therapeutic interventions, ultimately improving the lives of individuals affected by these conditions.
PubMed: 38660479
DOI: 10.3389/fcvm.2024.1333265 -
Neural Regeneration Research Jan 2024Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases, and although most studies focus on its effects on neuronal... (Review)
Review
Repetitive transcranial magnetic stimulation has been increasingly studied in different neurological diseases, and although most studies focus on its effects on neuronal cells, the contribution of non-neuronal cells to the improvement triggered by repetitive transcranial magnetic stimulation in these diseases has been increasingly suggested. To systematically review the effects of repetitive magnetic stimulation on non-neuronal cells two online databases, Web of Science and PubMed were searched for the effects of high-frequency-repetitive transcranial magnetic stimulation, low-frequency-repetitive transcranial magnetic stimulation, intermittent theta-burst stimulation, continuous theta-burst stimulation, or repetitive magnetic stimulation on non-neuronal cells in models of disease and in unlesioned animals or cells. A total of 52 studies were included. The protocol more frequently used was high-frequency-repetitive magnetic stimulation, and in models of disease, most studies report that high-frequency-repetitive magnetic stimulation led to a decrease in astrocyte and microglial reactivity, a decrease in the release of pro-inflammatory cytokines, and an increase of oligodendrocyte proliferation. The trend towards decreased microglial and astrocyte reactivity as well as increased oligodendrocyte proliferation occurred with intermittent theta-burst stimulation and continuous theta-burst stimulation. Few papers analyzed the low-frequency-repetitive transcranial magnetic stimulation protocol, and the parameters evaluated were restricted to the study of astrocyte reactivity and release of pro-inflammatory cytokines, reporting the absence of effects on these parameters. In what concerns the use of magnetic stimulation in unlesioned animals or cells, most articles on all four types of stimulation reported a lack of effects. It is also important to point out that the studies were developed mostly in male rodents, not evaluating possible differential effects of repetitive transcranial magnetic stimulation between sexes. This systematic review supports that through modulation of glial cells repetitive magnetic stimulation contributes to the neuroprotection or repair in various neurological disease models. However, it should be noted that there are still few articles focusing on the impact of repetitive magnetic stimulation on non-neuronal cells and most studies did not perform in-depth analyses of the effects, emphasizing the need for more studies in this field.
PubMed: 37488852
DOI: 10.4103/1673-5374.374140 -
Journal of Hepatology May 2024Idiosyncratic drug-induced liver injury (DILI) is a complex and unpredictable event caused by drugs, and herbal or dietary supplements. Early identification of human...
BACKGROUND & AIMS
Idiosyncratic drug-induced liver injury (DILI) is a complex and unpredictable event caused by drugs, and herbal or dietary supplements. Early identification of human hepatotoxicity at preclinical stages remains a major challenge, in which the selection of validated in vitro systems and test drugs has a significant impact. In this systematic review, we analyzed the compounds used in hepatotoxicity assays and established a list of DILI-positive and -negative control drugs for validation of in vitro models of DILI, supported by literature and clinical evidence and endorsed by an expert committee from the COST Action ProEuroDILI Network (CA17112).
METHODS
Following 2020 PRISMA guidelines, original research articles focusing on DILI which used in vitro human models and performed at least one hepatotoxicity assay with positive and negative control compounds, were included. Bias of the studies was assessed by a modified 'Toxicological Data Reliability Assessment Tool'.
RESULTS
A total of 51 studies (out of 2,936) met the inclusion criteria, with 30 categorized as reliable without restrictions. Although there was a broad consensus on positive compounds, the selection of negative compounds lacked clarity. 2D monoculture, short exposure times and cytotoxicity endpoints were the most tested, although there was no consensus on drug concentrations.
CONCLUSIONS
Extensive analysis highlighted the lack of agreement on control compounds for in vitro DILI assessment. Following comprehensive in vitro and clinical data analysis together with input from the expert committee, an evidence-based consensus-driven list of 10 positive and negative control drugs for validation of in vitro models of DILI is proposed.
IMPACT AND IMPLICATIONS
Prediction of human toxicity early in the drug development process remains a major challenge, necessitating the development of more physiologically relevant liver models and careful selection of drug-induced liver injury (DILI)-positive and -negative control drugs to better predict the risk of DILI associated with new drug candidates. Thus, this systematic study has crucial implications for standardizing the validation of new in vitro models of DILI. By establishing a consensus-driven list of positive and negative control drugs, the study provides a scientifically justified framework for enhancing the consistency of preclinical testing, thereby addressing a significant challenge in early hepatotoxicity identification. Practically, these findings can guide researchers in evaluating safety profiles of new drugs, refining in vitro models, and informing regulatory agencies on potential improvements to regulatory guidelines, ensuring a more systematic and efficient approach to drug safety assessment.
PubMed: 38703829
DOI: 10.1016/j.jhep.2024.04.026 -
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 -
Annals of Joint 2024Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to mitigate pain and inflammation associated with musculoskeletal conditions; however, there is... (Review)
Review
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to mitigate pain and inflammation associated with musculoskeletal conditions; however, there is conflicting data on the adverse effects of these drugs on tissue and bone healing. The objective of this study was to investigate the effect of NSAIDs on the healing of knee, soft tissue, and bone.
METHODS
A systematic literature search was conducted across PubMed/MEDLINE, Excerpta Medical Database (Embase)/Ovid, and the Cochrane Central Register of Controlled Trials databases. Clinical, animal, and studies on the effect of NSAIDs on knee healing were included. Risk of bias assessment was performed using the Cochrane bias assessment tool and Methodological Index for Non-Randomized Studies scoring system for included clinical studies, and the Systematic Review Center for Laboratory Animal Experimentation assessment tool for all included animal studies. General study population characteristics, interventions used, NSAIDs utilized, outcome measures, and study results were analyzed using descriptive statistics.
RESULTS
Fifteen articles met the inclusion criteria. Of the 15 studies, there were three clinical, ten animal, and two studies. In clinical studies, nonselective cyclooxygenase (COX) inhibitors and selective COX-2 inhibitors did not cause a significant increase in failure of anterior cruciate ligament (ACL) reconstructions or meniscal repairs with NSAID administration pre-, peri-, or post-operatively in comparison to placebo or no NSAID administration. Among animal studies assessing COX-2 inhibitor effects on soft tissue, healing was impaired (2/4), delayed but unaffected (1/4), or unaffected (1/4). In animal studies assessing COX-1 inhibitors, ligament healing was either increased (1/4), unaffected (2/4), or impaired (1/4). Meanwhile, administration of non-selective COX inhibitors in animals did not affect soft tissue (3/3) and cartilage (1/1) healing. Two studies identified a negative outcome on patellar tendon and ACL cell proliferation or viability after non-selective COX inhibition and variable results after selective COX-2 inhibition.
CONCLUSIONS
Animal studies on postoperative NSAID use after knee surgery suggest that administration of selective and nonselective COX-2 inhibitors may impair healing of soft tissue, bone and tendon-to-bone; however, further clinical studies are needed to better characterize dose and duration dependent risks of NSAIDs.
PubMed: 38529297
DOI: 10.21037/aoj-23-58 -
Frontiers in Endocrinology 2024Thin endometrium (TE) is defined as a mid-luteal endometrial thickness ≤7mm. TE can affect endometrial tolerance, leading to lower embryo implantation rates and...
Thin endometrium (TE) is defined as a mid-luteal endometrial thickness ≤7mm. TE can affect endometrial tolerance, leading to lower embryo implantation rates and clinical pregnancy rates, and is also associated with impaired outcomes from assisted reproductive treatment. Herein, we systematically review TE causes, mechanisms, and treatments. TE pathogenesis has multiple causes, with the endometrium becoming thinner with age under hormonal influence. In addition, uterine cavity factors are important, as the inflammatory environment may affect expressions of certain genes thereby inhibiting endometrial stromal cell proliferation and promoting apoptosis. Long-term oral contraceptive use or the use of ovulation-promoting drugs are also definite factors contributing to endometrial thinning. Other patients have primary factors, for which the clinical etiology remains unknown. The main therapeutic strategies available for TE are pharmacological (including hormonal and vasoactive drugs), regenerative medicine, intrauterine infusion of growth factor-granulocyte colony-stimulating factor, autologous platelet-rich plasma, and complementary alternative therapies (including traditional Chinese herbal medicine and acupuncture). However, the associated mechanisms of action are currently unclear. Clinical scholars have proposed various approaches to improve treatment outcomes in patients with TE, and are exploring the principles of efficacy, offering potentials for novel treatments. It is hoped that this will improve TE tolerance, increase embryo implantation rates, and help more couples with infertility with effective treatments.
Topics: Female; Humans; Pregnancy; Embryo Implantation; Endometrium; Infertility, Female
PubMed: 38745960
DOI: 10.3389/fendo.2024.1269382 -
Breast (Edinburgh, Scotland) Oct 2023Adenosquamous proliferation (ASP) is known to occur in the central nidus of radial sclerosing lesions (RSL) of the breast. However, their significance is debated and...
Adenosquamous proliferation (ASP) is known to occur in the central nidus of radial sclerosing lesions (RSL) of the breast. However, their significance is debated and remains largely unknown. In addition, there is a histologic overlap between ASP and low-grade adenosquamous carcinomas (LGASC). We conducted a large retrospective review of 247 RSLs to evaluate the prevalence of ASP and quantitatively analyze associated histologic features of RSLs including size, stromal cellularity, and presence of chronic inflammation. The central nidus of RSLs were classified as hyalinized in 121 cases (49%), cellular in 37 cases (15%), and equally mixed hyalinized and cellular in 89 (36%). ASP occurred in 92 of 247 RSLs (37.2%). Cases with ASP were significantly associated with a cellular stroma; 78.4% of RSLS with cellular stroma had ASP versus just 11.6% of hyalinized RSLs. In our large cohort, inflammation is commonly found in RSLs with ASP (p= <0.001). In conclusion, we confirm that ASP is statistically more likely to be found in RSLs with a cellular stroma. In addition, ASP is commonly associated with chronic inflammation. The finding challenges the notion that prominent lymphocytes are a diagnostic clue to LGASC on limited biopsy material.
Topics: Female; Humans; Breast Neoplasms; Breast; Fibrocystic Breast Disease; Carcinoma, Adenosquamous; Inflammation; Cell Proliferation
PubMed: 37566996
DOI: 10.1016/j.breast.2023.08.002