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F1000Research 2022Retinoic acid plays an essential role in testicular development and functions, especially spermatogenesis. We have reviewed the role of retinoic acid from basic...
Retinoic acid plays an essential role in testicular development and functions, especially spermatogenesis. We have reviewed the role of retinoic acid from basic (molecular) to clinical application. A search was conducted in the online database including PubMed, Google Scholar, and Scopus for English studies published in the last eight years about this issue. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in assessing the studies we are going to investigate. Studies indicated that retinoic acid plays an essential role during pluripotent stem cell migration and lineage commitment, cell differentiation, apoptosis, stem cell number regulation, and maturation arrest in spermatogenic cells. Retinoic acid can also affect related protein expression and signaling pathways at different stages of spermatogenesis. Four studies have applied retinoic acid to humans, all of them in the single-arm observational study. The results look promising but need further research with more controlled study methods, randomization, and large samples. This current systematic review emphasizes a novel retinoic acid mechanism that has not been well described in the literature previously on its functions during the first seven days of spermatogenesis, leading to new directions or explanations of male infertility cause and treatments as a part of reproductive health care.
Topics: Germ Cells; Humans; Infertility, Male; Male; Observational Studies as Topic; Spermatogenesis; Spermatozoa; Tretinoin
PubMed: 35967975
DOI: 10.12688/f1000research.110510.2 -
Alimentary Pharmacology & Therapeutics Aug 2012Over the past 30 years, nanotechnology has evolved dramatically. It has captured the interest of variety of fields from computing and electronics to biology and... (Review)
Review
BACKGROUND
Over the past 30 years, nanotechnology has evolved dramatically. It has captured the interest of variety of fields from computing and electronics to biology and medicine. Recent discoveries have made invaluable changes to future prospects in nanomedicine; and introduced the concept of theranostics. This term offers a patient specific 'two in one' modality that comprises of diagnostic and therapeutic tools. Not only nanotechnology has shown great impact on improvements in drug delivery and imaging techniques, but also there have been several ground-breaking discoveries in regenerative medicine.
AIM
Gastroenterology invites multidisciplinary approach owing to high complexity of gastrointestinal (GI) system; it includes physicians, surgeons, radiologists, pharmacologists and many more. In this article, we concentrate on current developments in nano-gastroenterology.
METHODS
Literature search was performed using Web of Science and Pubmed search engines with terms--nanotechnology, nanomedicine and gastroenterology. Article search was concentrated on developments since 2005.
RESULTS
We have described original and innovative approaches in gastrointestinal drug delivery, inflammatory disease and cancer-target treatments. Here, we have reviewed advances in GI imaging using nanoparticles as fluorescent contrast, and their potential for site-specific targeting. This review has also depicted various approaches and novel discoveries in GI regenerative medicine using nanomaterials for scaffold designs and induced pluripotent stem cells as cell source.
CONCLUSIONS
Developments in nanotechnology have opened new range of possibilities to help our patients. This includes novel drug delivery vehicles, diagnostic tools for early and targeted disease detection and nanocomposite materials for tissue constructs to overcome cosmetic or physical disabilities.
Topics: Diagnostic Imaging; Drug Delivery Systems; Gastroenterology; Humans; Nanoparticles; Nanotechnology; Regenerative Medicine
PubMed: 22686286
DOI: 10.1111/j.1365-2036.2012.05179.x -
The Cochrane Database of Systematic... May 2022Crohn's disease (CD) is an inflammatory bowel disease that causes inflammation and stricture, of any part of the mucosa and the gut wall. It forms skip lesions, sparing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Crohn's disease (CD) is an inflammatory bowel disease that causes inflammation and stricture, of any part of the mucosa and the gut wall. It forms skip lesions, sparing the areas in between the affected parts of the gastrointestinal tract. Crohn's disease could have one of three complications; fistula, intestinal obstruction due to stricture, or gastrointestinal inflammation presenting as severe diarrhoea. Stem cell therapy (SCT) is an innovative treatment that has been recently used in CD. The exact role of SCT in CD is still unclear. Stem cells modify the immunity of the patients or act as a "reset tool" for the immune system as in the case of systemically-injected stem cells, or regenerate the affected area of necrotic and inflammatory tissue as in the case of local injection into the lesion. Stem cells are a wide variety of cells including pluripotent stem cells or differentiated stem cells. The hazards range from rejection to symptomatic manifestations as fever or increase infection. OBJECTIVES: The objective of this Cochrane systematic review is to assess the effects of stem cell transplantation compared to standard of care alone or with placebo on efficacy and safety outcomes in patients with refractory CD.
SEARCH METHODS
We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and clinical trial registries (Clinicaltrials.gov, World Health Organization-International Clinical Trials Registry Platform WHO ICTRP) from inception to 19 March 2021, without any language, publication year, or publication status restrictions. In addition, we searched references of included studies and review articles for further references. An update of the published studies was done during the writing of the review.
SELECTION CRITERIA
We included only randomised controlled trials (RCTs) that assessed the effectiveness and safety of SCT in refractory CD versus standard care alone (control) or with placebo.
DATA COLLECTION AND ANALYSIS
Two review authors (SEN and SFA) independently screened the studies retrieved from the search results for inclusion, extracted data and assessed the risk of bias. Any disagreement was resolved through a consensus between the authors. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We conducted our search on 19 March 2021 and identified 639 records. We added two records by a manual search of the published reviews on the topic to a total of 641 records. The Covidence program removed 125 duplicates making a total of 516 reports. Two review authors (SEN and SFA) screened titles and abstracts and excluded 451 records with the remaining 65 for full-text records screened independently by the two authors; only 18 studies were considered for inclusion. We included seven RCTs with a total of 442 participants for the meta-analysis. The intervention group included 234 patients, and the control group included 208 patients. Nine trials are ongoing and, two abstracts are awaiting classification. All patients in the control and intervention groups received the standard therapy for CD. Only three studies used blinding methods for the control group in the form of a placebo, with one study of the three stated that the blinding method was inefficient. The patients and personnel were aware of the intervention in the rest of the four studies as they were open-label trials. However, the effect of unblinding was balanced by the low risk of detection bias in five of the included studies. The evidence is uncertain about the effect of SCT on achieving clinical remission as compared to control/placebo (risk ratio (RR) 1.88, 95% Confidence Interval (CI) 0.80 to 4.41; 3 studies; low-certainty evidence). The evidence is very uncertain about the effect of SCT on achieving Crohn's Disease Activity Index (CDAI) <150 at 24 weeks compared to control (RR1.02 95% CI 0.67 to 1.56; 4 studies; very-low certainty evidence). SCT is likely to achieve fistula closure as compared to the control/placebo both in the short term (RR 1.48, 95% CI 1.12 to 1.96); low-certainty evidence) and in the long term (RR 1.42, 95% CI 1.09 to 1.87; 4 studies; low-certainty evidence) follow-up. The evidence is very uncertain about the effect of SCT to cause no difference in the number of total adverse events as compared to the control/placebo (RR 0.99, 95% CI [0.88 to 1.13); 4 studies; very-low-certainty evidence). However, SCT is likely to increase the number of serious adverse events as compared to the control/placebo (RR 1.22, 95% CI 0.88 to 1.67; 7 studies; low-certainty evidence). The evidence is very uncertain about the effect of SCT to decrease the withdrawal due to adverse events as compared to the control/placebo (RR 0.78, 95% CI 0.32 to 1.89; 3 studies; very-low certainty evidence). Funding by pharmaceutical companies was found in three studies, with one including more than 50% of our studied population.
AUTHORS' CONCLUSIONS
SCT shows an uncertain effect on clinical remission with low certainty of evidence. SCT shows an uncertain effect on CDAI score to reach <150 after 24 weeks of treatment, with very low certainty evidence. SCT shows beneficial effects on fistula-closure during short and long-term follow-up with low-certainty evidence in both outcomes. There was no change in the total number of adverse events with SCT as compared to control, with very low certainty evidence. While there was a moderate effect on increasing the number of serious adverse events in the SCT group, as compared to the control with low-certainty evidence. Withdrawal due to adverse events was slightly higher in the control group with very low certainty evidence. All the participants were refractory to standard medical treatment, but the number of participants was small, this may limit the generalizability of the results. Further research is needed for validation. More objective outcomes are needed in the assessment of stem cell effectiveness in the treatment of Crohn's disease, especially the intestinal CD subtype; with standardization of the dose, methods of stem cell preparation, route of administration, and inclusion criteria to the studies to achieve clear results.
Topics: Constriction, Pathologic; Crohn Disease; Hematopoietic Stem Cell Transplantation; Humans; Inflammation; Remission Induction
PubMed: 35556242
DOI: 10.1002/14651858.CD013070.pub2 -
International Journal of Molecular... Apr 2023The extracellular matrix (ECM) of the brain is a dynamic structure made up of a vast network of bioactive macromolecules that modulate cellular events. Structural,... (Review)
Review
The extracellular matrix (ECM) of the brain is a dynamic structure made up of a vast network of bioactive macromolecules that modulate cellular events. Structural, organizational, and functional changes in these macromolecules due to genetic variation or environmental stressors are thought to affect cellular functions and may result in disease. However, most mechanistic studies to date usually focus on the cellular aspects of diseases and pay less attention to the relevance of the processes governing the dynamic nature of the extracellular matrix in disease pathogenesis. Thus, due to the ECM's diversified biological roles, increasing interest in its involvement in disease, and the lack of sufficient compiled evidence regarding its relationship with Parkinson's disease (PD) pathology, we aimed to compile the existing evidence to boost the current knowledge on the area and provide refined guidance for the future research. Here, in this review, we gathered postmortem brain tissue and induced pluripotent stem cell (iPSC)-related studies from PubMed and Google Scholar to identify, summarize and describe common macromolecular alterations in the expression of brain ECM components in Parkinson's disease (PD). A literature search was conducted up until 10 February 2023. The overall hits from the database and manual search for proteomic and transcriptome studies were 1243 and 1041 articles, respectively. Following a full-text review, 10 articles from proteomic and 24 from transcriptomic studies were found to be eligible for inclusion. According to proteomic studies, proteins such as collagens, fibronectin, annexins, and tenascins were recognized to be differentially expressed in Parkinson's disease. Transcriptomic studies displayed dysregulated pathways including ECM-receptor interaction, focal adhesion, and cell adhesion molecules in Parkinson's disease. A limited number of relevant studies were accessed from our search, indicating that much work remains to be carried out to better understand the roles of the ECM in neurodegeneration and Parkinson's disease. However, we believe that our review will elicit focused primary studies and thus support the ongoing efforts of the discovery and development of diagnostic biomarkers as well as therapeutic agents for Parkinson's disease.
Topics: Humans; Parkinson Disease; Proteomics; Brain; Extracellular Matrix; Tenascin
PubMed: 37108598
DOI: 10.3390/ijms24087435 -
Acta Orthopaedica Feb 2016The value of core decrompression for treatment of osteonecrosis of the femoral head (ONFH) is unclear. We investigated by a literature review whether implantation of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
The value of core decrompression for treatment of osteonecrosis of the femoral head (ONFH) is unclear. We investigated by a literature review whether implantation of autologous bone marrow aspirate, containing high concentrations of pluripotent mesenchymal stem cells, into the core decompression track would improve the clinical and radiological results compared with the classical method of core decompression alone. The primary outcomes of interest were structural failure (collapse) of the femoral head and conversion to total hip replacement (THR).
PATIENTS AND METHODS
All randomized and non-randomized control trials comparing simple core decompression with autologous bone marrow cell implantation into the femoral head for the treatment of ONFH were considered eligible for inclusion. The methodological quality of the studies included was assessed independently by 2 reviewers using the Cochrane Collaboration tool for assessing risk of bias in randomized studies. Of 496 relevant citations identified, 7 studies formed the basis of this review.
RESULTS
The pooled estimate of effect size for structural failure of the femoral head favored the cell therapy group, as, in this treatment group, the odds of progression of the femoral head to the collapse stage were reduced by a factor of 5 compared to the CD group (odds ratio (OR) = 0.2, 95% CI: 0.08-0.6; p = 0.02). The respective summarized estimate of effect size yielded halved odds for conversion to THR in the cell therapy group compared to CD group (OR = 0.6, 95% CI: 0.3-1.02; p = 0.06).
INTERPRETATION
Our findings suggest that implantation of autologous mesenchymal stem cells (MSCs) into the core decompression track, particularly when employed at early (pre-collapse) stages of ONFH, would improve the survivorship of femoral heads and reduce the need for hip arthroplasty.
Topics: Arthroplasty, Replacement, Hip; Cell- and Tissue-Based Therapy; Controlled Clinical Trials as Topic; Female; Femur Head Necrosis; Humans; Incidence; Male; Mesenchymal Stem Cell Transplantation; Prognosis; Radiography; Randomized Controlled Trials as Topic; Risk Assessment; Role; Severity of Illness Index; Transplantation, Autologous; Treatment Outcome
PubMed: 26220203
DOI: 10.3109/17453674.2015.1077418 -
Odontology Jan 2023The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in the regeneration of periodontal bone defects in animal models. A systematic review... (Meta-Analysis)
Meta-Analysis
The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in the regeneration of periodontal bone defects in animal models. A systematic review and meta-analysis were conducted following the PRISMA guidelines, and the study was recorded in PROSPERO under reference number CDR42021247462. The PICO question was: is periodontal regeneration (cementum, periodontal ligament and alveolar bone) with MSCs more effective than other techniques? Three groups were considered: Group 1: MSCs alone or mixed with regenerative materials. Group 2: only regenerative materials. Group 3: no regenerative material nor MSCs. The search was conducted using MeSH with a total of 18 articles for qualitative analysis and 5 for quantitative analysis. For the meta-analysis, a modification of the effect size algorithm was developed, which considered a comparison of means between treatments using the Student's t sample distribution. When comparing the effect size between Group 1 and Group 2, the effect size for the new cementum was 2.83 mm with an estimated confidence interval of 95% (CI 95%) between 0.48 and 5.17 mm. When considering the fit to a random-effects model, the combined variance (τ) was 6.1573 mm, with a standard deviation (SD) of 5.6008 mm and a percentage of total heterogeneity I of 92.33% (p < 0.0001). For new bone, the effect size was 0.88 mm, CI 95% - 0.25 to 2.01 mm, τ = 1.3108 mm (SD = 1.2021 mm) and I = 80.46%, p = 0.0004). With regard to the new periodontal ligament, it was not possible for the meta-analysis to be performed. MSCs have a greater capacity for tissue regeneration in root cementum than in alveolar bone compared to other regenerative materials.
Topics: Animals; Alveolar Bone Loss; Bone Regeneration; Guided Tissue Regeneration, Periodontal; Models, Animal; Periodontal Ligament; Mesenchymal Stem Cells
PubMed: 35788845
DOI: 10.1007/s10266-022-00725-5 -
European Review For Medical and... Aug 2023This systematic review focuses on which sources of mesenchymal stem cells (MSCs) are more beneficial for cartilage repair, specifically comparing umbilical cord...
The clinical outcomes of intra-articular injection of human umbilical cord blood-derived mesenchymal stem cells vs. bone marrow aspirate concentrate in cartilage regeneration: a systematic review.
OBJECTIVE
This systematic review focuses on which sources of mesenchymal stem cells (MSCs) are more beneficial for cartilage repair, specifically comparing umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and bone marrow aspirate concentrate (BMAC) in patients treated via a high tibial osteotomy (HTO) plus mesenchymal stem cells augmentation.
MATERIALS AND METHODS
PubMed, Scopus, Embase, Cochrane, and Web of Science were searched for literature published in English that compared the effects of hUCB-MSC amplification and BMAC transplantation in articular cartilage lesions of the human knee with at least 1 year of follow-up after surgery. The risk of bias in the included retrospective studies was assessed via the Coleman Methodology Score. The clinical prognosis was assessed based on the total clinical score, pain, function, and degree of cartilage repair.
RESULTS
The risk of bias in the included retrospective cohort studies was evaluated as fair. A formal meta-analysis of outcomes was not possible as the low evidence level and the nature of pooled retrospective studies introduced considerable heterogeneity. At an average of 1 year after surgery, two included studies reported that the ratio of normal and nearly normal cartilage repair assessed by International Cartilage Repair Society grading system (ICRS) grading in the second arthroscopy was higher in the hUCB-MSC group (Lee: 71.2% and 81.3%; Yang: 77.3%) than in the BMAC group (Lee: 45% and 40.5%; Yang: 56.8%). Ryu et al reported no significant difference between groups in the ICRS grade at 1-year post-operation (p = 0.655). Overall clinical outcome, pain and function were significantly improved at the last follow-up in both the BMAC group and the hUCB-MSC group, and there were no significant differences in these measures between groups.
CONCLUSIONS
This systematic review presents evidence that compared with BMAC injection, intra-articular hUCB-MSCs can induce significantly better tissue repair at 1 year after surgery, as assessed by the ICRS grade. Although there is only short-term follow-up evidence and a lack of histochemical evidence, our systematic review supports the recommendation to use hUCB-MSCs as the source of pluripotent stem cells for treating ICRS III cartilage lesions.
Topics: Humans; Bone Marrow; Cartilage, Articular; Fetal Blood; Injections, Intra-Articular; Mesenchymal Stem Cells; Pain; Retrospective Studies
PubMed: 37667930
DOI: 10.26355/eurrev_202308_33405 -
Stem Cells (Dayton, Ohio) Oct 2022The TP53 gene is unarguably one of the most studied human genes. Its encoded protein, p53, is a tumor suppressor and is often called the "guardian of the genome" due to...
The TP53 gene is unarguably one of the most studied human genes. Its encoded protein, p53, is a tumor suppressor and is often called the "guardian of the genome" due to its pivotal role in maintaining genome stability. Historically, most studies of p53 have focused on its roles in somatic cells and tissues, but in the last 2 decades, its functions in embryonic stem cells (ESCs) and induced pluripotent stem cells have attracted increasing attention. Recent studies have identified p53 as a critical regulator of pluripotency, self-renewal, differentiation, proliferation, and genome stability in mouse and human embryonic stem cells. In this article, we systematically review the studies on the functions of p53 in ESCs, provide an updated overview, attempt to reconcile controversial results described in the literature, and discuss the relevance of these cellular functions of p53 to its roles in tumor suppression.
Topics: Animals; Humans; Mice; Cell Differentiation; Embryonic Stem Cells; Genes, p53; Genomic Instability; Tumor Suppressor Protein p53
PubMed: 35904997
DOI: 10.1093/stmcls/sxac051 -
Cureus May 2022Somatic () mutations are the most common mutations in various hematological malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).... (Review)
Review
A Systematic Review of the Role of Runt-Related Transcription Factor 1 (RUNX1) in the Pathogenesis of Hematological Malignancies in Patients With Inherited Bone Marrow Failure Syndromes.
Somatic () mutations are the most common mutations in various hematological malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Mono-allelic mutations in germline cells may cause familial platelet disorder (FPD), an inherited bone marrow failure syndrome (IBMFS) associated with an increased lifetime risk of AML. It is suspected that additional mutations may play a role in the pathogenesis of hematological malignancies in IBMFS. This review aims to study the role of mutations in the pathogenesis of hematological malignancies in patients with IBMFS. A PubMed database search was conducted using the following medical subject heading (MeSH) terms: "inherited bone marrow failure syndromes," "hematological neoplasms," "gene expression regulation, leukemic," "RUNX1 protein, human," "RUNX1 protein, mouse," and "Neutropenia, Severe Congenital, Autosomal recessive." Three studies published in 2020 were identified as meeting our inclusion and exclusion criteria. Leukemic progression in severe congenital neutropenia was used as a disease model to evaluate the clinical, molecular, and mechanistic basis of mutations identified in hematological malignancies. Studies in mice and genetically reprogrammed or induced pluripotent stem cells (iPSCs) have shown that isolated mutations are weakly leukemogenic and only initiate hyperproduction of immature hematopoietic cells when in combination with () mutations. Despite this, whole-exome sequencing (WES) performed on leukemogenic transformed cells revealed that all AML cells had an additional mutation in the () gene that caused hyperproduction of the ten-eleven translocation (TET2) protein. This protein causes inflammation in cells with mutations. This process is thought to be critical for clonal myeloid malignant transformation (CMMT) of leukemogenic cells. In conclusion, the combinations of and mutations have a prominent effect on myeloid differentiation resulting in the hyperproduction of myeloblasts. In other studies, it has been noted that the mutations in and genes are not sufficient for the full transformation of leukemogenic cells to AML, and an additional clonal mutation in the gene is essential for full transformation to occur. These data have implicitly demonstrated that mutations are critical in the pathogenesis of various hematological malignancies, and further investigations into the role of are paramount for the development of new cancer treatments.
PubMed: 35765406
DOI: 10.7759/cureus.25372 -
World Journal of Gastroenterology Apr 2019Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also...
Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also highly heterogeneous among individuals. At present, research on liver diseases is conducted mainly through cell culture, animal models, pathological specimens, . However, these methods cannot fully reveal the pathogenic mechanism and therapeutic characteristics of individualized liver diseases. Recent advances in three-dimensional cell culture technology (organoid culture techniques) include pluripotent stem cells and adult stem cells that are cultured to form self-organizing properties, making it possible to achieve individualized liver disease research. This review provides a comprehensive overview of the development of liver organoids, the existing and potential applications of liver regenerative medicine, the pathogenesis of liver disease heterogeneity, and drug screening.
Topics: Animals; Cell Culture Techniques; Disease Models, Animal; Drug Evaluation, Preclinical; Humans; Liver; Liver Diseases; Organoids; Regenerative Medicine; Translational Research, Biomedical
PubMed: 31086460
DOI: 10.3748/wjg.v25.i16.1913