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Asian Pacific Journal of Cancer... May 2024To systematically review the existing scientific literature in providing a comprehensive, quantitative analysis on the prognostic ability of Cancer Associated... (Meta-Analysis)
Meta-Analysis
AIM
To systematically review the existing scientific literature in providing a comprehensive, quantitative analysis on the prognostic ability of Cancer Associated Fibroblasts (CAFs) in Oral Squamous Cell Carcinoma (OSCC) a novel meta-analysis.
METHODS
Review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and registered in PROSPERO - CRD CRD42023467899. Electronic databases were searched for studies having data on effect of CAFs on overall survival rate and disease prognosis in patients with OSCC, oral epithelial dysplasia (OED) compared to normal healthy controls. Quality assessment of included was evaluated through Newcastle Ottawa scale (NOS) for included studies through its domains. The hazard ratio (HR) and risk ratio (RR) was used as summary statistic measure with random effect model and p value <0.05 as statistically significant.
RESULTS
Twenty studies fulfilled the eligibility criteria and were included in qualitative synthesis and eighteen studies for meta -analysis. Included studies had moderate to low risk of bias. It was observed through the pooled estimate that overall survival rate - (HR) =2.30 (1.71 - 3.10) was lesser in group with high CAFs compared to low CAFs while pooled estimate through RR =1.53 (0.73 - 3.19) and RR = 5.72 (2.40 - 13.59) signified that overall survival rate was lower n OSCC patients with high CAF compared to patients with OED and healthy controls. Publication bias through the funnel plot showed asymmetric distribution with presence of systematic heterogeneity indicating presence of publication bias.
CONCLUSION
Abundance of CAFs in tumor stroma of OSCC patients is associated with overall poor survival rate and poor disease prognosis. CAFs acts as a good prognostic and therapeutic marker in disease progression and advancements and should be assessed early to reduce patient's mortality and morbidity.
Topics: Humans; Mouth Neoplasms; Prognosis; Myofibroblasts; Carcinoma, Squamous Cell; Survival Rate; Biomarkers, Tumor
PubMed: 38809619
DOI: 10.31557/APJCP.2024.25.5.1477 -
The Archives of Bone and Joint Surgery 2024Brachial plexus injuries (BPI), although rare, often results in significant morbidity. Stem cell was thought to be one of BPI treatment modalities because of their... (Review)
Review
OBJECTIVES
Brachial plexus injuries (BPI), although rare, often results in significant morbidity. Stem cell was thought to be one of BPI treatment modalities because of their nerve-forming regeneration potential. Although there is a possibility for the use of mesenchymal stem cells as one of BPI treatment, it is still limited on animal studies. Therefore, this systematic review aimed to analyze the role of mesenchymal stem cells in nerve regeneration in animal models of brachial plexus injury.
METHOD
This study is a systematic review with PROSPERO registration number CRD4202128321. Literature searching was conducted using keywords experimental, animal, brachial plexus injury, mesenchymal stem cell implantation, clinical outcomes, electrophysiological outcomes, and histologic outcomes. Searches were performed in the PubMed, Scopus, and ScienceDirect databases. The risk of bias was assessed using SYRCLE's risk of bias tool for animal studies. The data obtained were described and in-depth analysis was performed.
RESULT
Four studies were included in this study involving 183 animals from different species those are rats and rabbits. There was an increase in muscle weight and shortened initial onset time of muscle contraction in the group treated with stem cells. Electrophysiological results showed that mesenchymal stem cells exhibited higher (Compound muscle action potential) CMAP amplitude and shorter CMAP latency than control but not better than autograft. Histological outcomes showed an increase in axon density, axon number, and the formation of connections between nerve cells and target muscles.
CONCLUSION
Mesenchymal stem cell implantation to animals with brachial plexus injury showed its ability to regenerate nerve cells as evidenced by clinical, electrophysiological, and histopathological results. However, this systematic study involved experimental animals from various species so that the results cannot be uniformed, and conclusion should be drawn cautiously.
PubMed: 38577510
DOI: 10.22038/ABJS.2024.68053.3224 -
European Journal of Medical Research Mar 2024Enterocystoplasty is the most commonly used treatment for bladder reconstruction. However, it has some major complications. In this study, we systematically reviewed the... (Review)
Review
Enterocystoplasty is the most commonly used treatment for bladder reconstruction. However, it has some major complications. In this study, we systematically reviewed the alternative techniques for enterocystoplasty using different scaffolds. A comprehensive search was conducted in PubMed, Embase, and Cochrane Library, and a total of 10 studies were included in this study. Five different scaffolds were evaluated, including small intestinal submucosa (SIS), biodegradable scaffolds seeded with autologous bladder muscle and urothelial cells, dura mater, human cadaveric bladder acellular matrix graft, and bovine pericardium. The overall results revealed that bladder reconstruction using regenerative medicine is an excellent alternative method to enterocystoplasty regarding the improvement of bladder capacity, bladder compliance, and maximum detrusor pressure; however, more large-scale studies are required.
Topics: Humans; Animals; Cattle; Regenerative Medicine; Urinary Bladder; Urologic Surgical Procedures; Muscles; Plastic Surgery Procedures
PubMed: 38475865
DOI: 10.1186/s40001-024-01757-z -
International Journal of Molecular... Jun 2024Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context,... (Review)
Review
Gap injuries to the peripheral nervous system result in pain and loss of function, without any particularly effective therapeutic options. Within this context, mesenchymal stem cell (MSC)-derived exosomes have emerged as a potential therapeutic option. Thus, the focus of this study was to review currently available data on MSC-derived exosome-mounted scaffolds in peripheral nerve regeneration in order to identify the most promising scaffolds and exosome sources currently in the field of peripheral nerve regeneration. We conducted a systematic review following PRISMA 2020 guidelines. Exosome origins varied (adipose-derived MSCs, bone marrow MSCs, gingival MSC, induced pluripotent stem cells and a purified exosome product) similarly to the materials (Matrigel, alginate and silicone, acellular nerve graft [ANG], chitosan, chitin, hydrogel and fibrin glue). The compound muscle action potential (CMAP), sciatic functional index (SFI), gastrocnemius wet weight and histological analyses were used as main outcome measures. Overall, exosome-mounted scaffolds showed better regeneration than scaffolds alone. Functionally, both exosome-enriched chitin and ANG showed a significant improvement over time in the sciatica functional index, CMAP and wet weight. The best histological outcomes were found in the exosome-enriched ANG scaffold with a high increase in the axonal diameter and muscle cross-section area. Further studies are needed to confirm the efficacy of exosome-mounted scaffolds in peripheral nerve regeneration.
Topics: Exosomes; Nerve Regeneration; Mesenchymal Stem Cells; Humans; Animals; Tissue Scaffolds; Peripheral Nerve Injuries; Mesenchymal Stem Cell Transplantation
PubMed: 38928194
DOI: 10.3390/ijms25126489 -
Journal of Clinical Medicine Feb 2024Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result...
Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli-Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review.
Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor () gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient's gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli-Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient's karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations-a pathogenic frameshift deletion in the gene (c.77delT) and a likely pathogenic missense variant in the gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads ( = 225; age: 4-84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases ( = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2-49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.
PubMed: 38398243
DOI: 10.3390/jcm13040929 -
Archives of Gynecology and Obstetrics Jan 2024The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This... (Review)
Review
PURPOSE
The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This systematic literature review aims at giving an overview of the existing concepts on how endogenous progesterone influences the female immune system along the menstrual cycle.
METHODS
The inclusion criteria were healthy female subjects in their reproductive age with a regular menstrual cycle. The exclusion criteria were exogenous progesterone, animal models, nonhealthy study populations and pregnancy. This led to 18 papers covered in this review. The search was performed using the databases EMBASE, Ovid MEDLINE and Epub, and the last search was conducted on September 18, 2020. Our findings were analyzed in four categories: cellular immune defense, humoral immune defense, objective and subjective clinical parameters.
RESULTS
We demonstrated that progesterone acts in an immunosuppressive way, favoring a Th-2-like cytokine profile. Further, we showed that progesterone inhibits mast cell degranulation and relaxes smooth muscle cells. Furthermore, we found supporting evidence for a so-called window of vulnerability after ovulation, where immune functions are lowered and mediated through progesterone.
CONCLUSION
The clinical relevance of these findings is not completely understood yet. As the sample sizes of included studies were rather small and the content of them was broad, further investigations are needed to define to which extent the described changes actually clinically meaningful, whether they are capable of influencing the female health and how these findings can be used to increase well-being.
Topics: Female; Humans; Immune System; Menstrual Cycle; Ovulation; Progesterone; Reproduction
PubMed: 36933040
DOI: 10.1007/s00404-023-06996-9 -
Acta Biomaterialia Apr 2024While most of current models investigating bone remodelling are based on matrix deformation, intramedullary pressure also plays a role. Bone remodelling is orchestrated... (Review)
Review
While most of current models investigating bone remodelling are based on matrix deformation, intramedullary pressure also plays a role. Bone remodelling is orchestrated by the Lacuno-Canalicular Network (LCN) fluid-flow. The aim of this review was hence to assess the influence of intramedullary pressure on the fluid circulation within the LCN. Three databases (Science Direct, Web of Science, and PubMed) were used. The first phase of the search returned 731 articles, of which 9 respected the inclusion/exclusion criteria and were included. These studies confirm the association between intramedullary pressure and fluid dynamics in the LCN. Among the included studies, 7 experimental studies using animal models and 2 numerical models were found. The studies were then ranked according to the nature of the applied loading, either axial compression or direct cyclic intramedullary pressure. The current review revealed that there is an influence of intramedullary pressure on LCN fluid dynamics and that this influence depends on the magnitude and the frequency of the applied pressure. Two studies confirmed that the influence was effective even without bone matrix deformation. While intramedullary pressure is closely associated with LCN fluid, there is a severe lack of studies on this topic. STATEMENT OF SIGNIFICANCE: Since the 1990's, numerical models developed to investigate fluid flow in bone submicrometric porous network are based on the flow induced by matrix deformation. Bone fluid flow is known to be involved in cells stimulation and hence directly influences bone remodeling. Different studies have shown that intramedullary pressure is also associated with bone mechanosensitive adaptation. This pressure is developed in bone due to blood circulation and is increased during loading or muscle stimulation. The current article reviews the studies investigating the influence of this pressure on bone porous fluid flow. They show that fluid flow is involved by this pressure even without bone matrix deformation. The current review article highlights the severe lack of studies about this mechanism.
Topics: Animals; Bone and Bones; Bone Matrix; Bone Remodeling; Hydrodynamics; Models, Animal; Osteocytes
PubMed: 38484832
DOI: 10.1016/j.actbio.2024.03.003 -
Skin Research and Technology : Official... May 2024Notalgia paresthetica (NP) is a rare condition characterized by localized pain and pruritus of the upper back, associated with a distinct area of hyperpigmentation....
BACKGROUND
Notalgia paresthetica (NP) is a rare condition characterized by localized pain and pruritus of the upper back, associated with a distinct area of hyperpigmentation. Given the lack of standardized treatment and the uncertain efficacy of available options, applying procedural methods is of growing interest in treating NP.
AIMS
We sought to comprehensively evaluate the role of procedural treatments for NP.
METHODS
We systematically searched PubMed/Medline, Ovid Embase, and Web of Science until November 14th, 2023. We also performed a citation search to detect all relevant studies. Original clinical studies published in the English language were included.
RESULTS
Out of 243 articles, sixteen studies have reported various procedural modalities, with or without pharmacological components, in treating NP. Pharmacological procedures, including injections of botulinum toxin, lidocaine, and corticosteroids, led to a level of improvement in case reports and case series. However, botulinum toxin did not show acceptable results in a clinical trial. Moreover, non-pharmacological procedures were as follows: physical therapy, exercise therapy, kinesiotherapy, acupuncture and dry needling, electrical muscle stimulation, surgical decompression, and phototherapy. These treatments result in significant symptom control in refractory cases. Physical therapy can be considered a first-line choice or an alternative in refractory cases.
CONCLUSION
Procedural modalities are critical in the multidisciplinary approach to NP, especially for patients who are refractory to topical and oral treatments. Procedural modalities include a spectrum of options that can be applied based on the disease's symptoms and severity.
Topics: Humans; Pruritus; Lidocaine; Paresthesia; Hyperpigmentation; Physical Therapy Modalities; Acupuncture Therapy; Botulinum Toxins; Anesthetics, Local; Exercise Therapy; Adrenal Cortex Hormones; Dry Needling
PubMed: 38696233
DOI: 10.1111/srt.13723 -
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 -
Genome Research Apr 2024Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a...
Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and cell types is unclear. In our systematic review, we sought to identify the biochemical threshold of mtDNA variants in relation to VAF by human tissue/cell type. We used controlled vocabulary terms to identify articles measuring oxidative phosphorylation (OXPHOS) complex activities in relation to VAF. We identified 76 eligible publications, describing 69, 12, 16, and 49 cases for complexes I, III, IV, and V, respectively. Few studies evaluated OXPHOS activities in diverse tissue types, likely reflective of clinical access. A number of cases with similar VAFs for the same pathogenic variant had varying degrees of residual activity of the affected complex, alluding to the presence of modifying variants. Tissues and cells with VAFs <60% associated with low complex activities were described, suggesting the possibility of a biochemical threshold of <60%. Using Kendall rank correlation tests, the VAF of the m.8993T > G variant correlated with complex V activity in skeletal muscle (τ = -0.58, = 0.01, n = 13); however, no correlation was observed in fibroblasts ( = 0.7, n = 9). Our systematic review highlights the need to investigate the biochemical threshold over a wider range of VAFs in disease-relevant cell types to better define the biochemical threshold for specific mtDNA variants.
Topics: Humans; DNA, Mitochondrial; Gene Frequency; Genetic Variation; Mitochondria; Mitochondrial Diseases; Oxidative Phosphorylation
PubMed: 38627095
DOI: 10.1101/gr.278200.123