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The Journal of Clinical Endocrinology... Feb 2024Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome usually caused by oversecretion of fibroblast growth factor 23 (FGF23) from a phosphaturic mesenchymal...
CONTEXT
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome usually caused by oversecretion of fibroblast growth factor 23 (FGF23) from a phosphaturic mesenchymal tumor (PMT). PMTs are usually benign neoplasms but some of them show malignant characteristics.
OBJECTIVE
The aim of this study was to compare the clinical characteristics of benign and malignant PMTs inducing TIO.
METHODS
On March 31, 2023, we performed a systematic review of individual patient data analysis in Medline, Google Scholar, Google book, and Cochrane Library using the terms "tumor induced osteomalacia," "oncogenic osteomalacia," "hypophosphatemia," with no language restrictions and according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria.
RESULTS
Overall, we collected data from 837 patients with TIO in which the diagnosis of benign and malignant PMT was specified. Of them, 89 were affected by malignant PMT and 748 by benign PMT. Patients with malignant PMTs were younger and presented bone pain, functional impairment, and bone deformities more frequently. Malignant PMTs showed higher values of intact FGF23 and a higher mortality rate.
CONCLUSION
The study results identify the clinical characteristics of patients with malignant TIO, permitting the early identification of patients with PMT at increased risk of malignancy. This may significantly improve the diagnostic approach to disease. Further experimental studies are mandatory to clarify the role of FGF23 in the pathogenesis of malignancy in PMTs.
Topics: Humans; Osteomalacia; Neoplasms, Connective Tissue; Fibroblast Growth Factors; Paraneoplastic Syndromes; Soft Tissue Neoplasms; Mesenchymoma
PubMed: 38006315
DOI: 10.1210/clinem/dgad690 -
International Immunopharmacology Nov 2023Allergic rhinitis (AR) is a worldwide problem that affects people of all ages, impairing patients' physical and mental health and causing great social expenditure.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Allergic rhinitis (AR) is a worldwide problem that affects people of all ages, impairing patients' physical and mental health and causing great social expenditure. Animal studies have suggested the potential efficacy of mesenchymal stem cell (MSC) therapy in treating AR. Our meta-analysis was performed to evaluate the effect of MSC therapy in animal models of AR by pooling animal studies.
METHODS
The search was executed in PubMed, Embase, Web of Science, OVID, and the Cochrane Library for relevant studies up to February 2023. The applicable data were extracted from the eligible studies, and the risk of bias was assessed for each study. The meta-analysis was conducted using Review Manager (version 5.4.1) and Stata (version 15.1).
RESULTS
A total of 12 studies were included in the final analysis. Compared to the model control group, the MSC therapy group presented lower frequency of sneezing [(Standardized mean difference (SMD) -1.87, 95% CI -2.30 to -1.43)], nasal scratching (SMD -1.41, 95% CI -1.83 to -0.99), and overall nasal symptoms (SMD -1.88, 95% CI -3.22 to -0.54). There were also remarkable reductions after transplantation with MSCs in the levels of total immunoglobulin E (IgE) (SMD -1.25, 95% CI -1.72 to -0.79), allergen-specific IgE (SMD -1.79, 95% CI -2.25 to -1.32), and allergen-specific immunoglobulin G1 (SMD -1.29, 95% CI -2.03) in serum, as well as the count of eosinophils (EOS) in nasal mucosa (SMD -3.48, 95% CI -4.48 to -2.49). In terms of cytokines, MSC therapy significantly decreased both protein and mRNA levels of T helper cell 2 (Th2)-related cytokines, including interleukin (IL)-4, IL-5, IL-10, and IL-13.
CONCLUSION
MSC therapy has the potential to be an effective clinical treatment for AR patients by attenuating Th2 immune responses, reducing secretion of IgE and nasal infiltration of EOS, and consequently alleviating nasal symptoms.
Topics: Animals; Humans; Mesenchymal Stem Cell Transplantation; Rhinitis, Allergic; Nasal Mucosa; Cytokines; Disease Models, Animal; Immunoglobulin E; Allergens; Mesenchymal Stem Cells
PubMed: 37806104
DOI: 10.1016/j.intimp.2023.111003 -
Vascular Oct 2023Few studies have reported on the safety and durability of adipose-derived stem cells (ADSCs) to support healing in patients with venous leg ulcers (VLU). To establish if... (Review)
Review
OBJECTIVES
Few studies have reported on the safety and durability of adipose-derived stem cells (ADSCs) to support healing in patients with venous leg ulcers (VLU). To establish if there is any evidence to support ADSC use in VLU patients, a systematic review was conducted.
METHODS
A systematic review was conducted following the PRISMA guidelines. PubMed and Embase databases were searched for relevant papers. References from retrieved papers were reviewed to identify any extra eligible studies.
RESULTS
After duplicate removal, 950 papers were screened for eligibility of which 932 were excluded based on title and abstract. Four papers were included in the final analysis (one randomised study and three non-randomised studies). 66 patients in total received ADSCs for VLU treatment. The only randomised paper reported 6-month healing rates of 75% with ADSCs compared to 50% in controls. 100% healing was achieved in one study. The remaining 2 studies reported 25% and 58% healing; however, they included patients with relatively large VLUs. Pain scores decreased after ADSCs application where reported. No serious procedure related complications were reported.
CONCLUSION
ADSCs may enhance ulcer healing in patients with chronic VLU and appears safe based on initial reports. Large, randomised trials are needed to definitively establish the technique's role in VLU patients.
Topics: Humans; Varicose Ulcer; Ulcer; Wound Healing; Stem Cells
PubMed: 35491989
DOI: 10.1177/17085381221098279 -
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 -
Journal of Crohn's & Colitis Apr 2024Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD.
METHODS
MEDLINE, Embase, and CENTRAL were searched on May 26, 2022, for randomized controlled trials [RCTs] of pharmacological therapy in adults with fistulizing CD. The primary outcome was induction and maintenance of fistula response. Pooled risk ratios [RRs] and 95% confidence intervals [CIs] were calculated. GRADE was used to assess the certainty of evidence.
RESULTS
Thirty-eight RCTs were included. Nineteen trials [50%] exclusively involved perianal fistula. The remaining studies included some participants with non-perianal fistula. Pooled RRs for anti-tumour necrosis factor [TNF] agents were not statistically significant for induction [RR 1.36, 95% CI 0.97-1.91] or maintenance of fistula response [RR 1.48, 95% CI 0.97-2.27]. However, in a sensitivity analysis of studies with fistula response as the primary outcome, anti-TNFs were superior to placebo for induction [RR 1.94, 95% CI 1.10-3.41] and maintenance [RR 1.88, 95% CI 1.23-2.88] of fistula response. Oral small molecules [RR 2.56, 95% CI 1.18-5.53] and mesenchymal stem cell [MSC] therapy [RR 1.26, 95% CI 1.01-1.57] were effective for induction of fistula response. Ustekinumab was associated with maintenance of fistula response [RR 1.80, 95% CI 1.04-3.11]. Vedolizumab was not superior to placebo. The certainty of evidence ranged from very low to moderate.
CONCLUSION
Very low- to moderate-certainty evidence suggests that anti-TNF therapy, oral small molecules, ustekinumab, and MSCs are effective for perianal fistulizing CD. Dedicated fistula studies evaluating biologics and small molecules are needed.
Topics: Humans; Crohn Disease; Rectal Fistula; Gastrointestinal Agents; Intestinal Fistula; Randomized Controlled Trials as Topic
PubMed: 37933849
DOI: 10.1093/ecco-jcc/jjad185 -
Gene Feb 2024Colorectal cancer (CRC) is ranked as the second leading cause of mortality worldwide, mainly due to metastasis. Epithelial to mesenchymal transition (EMT) is a complex... (Review)
Review
Insights into the molecular mechanisms and signalling pathways of epithelial to mesenchymal transition (EMT) in colorectal cancer: A systematic review and bioinformatic analysis of gene expression.
Colorectal cancer (CRC) is ranked as the second leading cause of mortality worldwide, mainly due to metastasis. Epithelial to mesenchymal transition (EMT) is a complex cellular process that drives CRC metastasis, regulated by changes in EMT-associated gene expression. However, while numerous genes have been identified as EMT regulators through various in vivo and in vitro studies, little is known about the genes that are differentially expressed in CRC tumour tissue and their signalling pathway in regulating EMT. Using an integration of systematic search and bioinformatic analysis, gene expression profiles of CRC tumour tissues were compared to non-tumour adjacent tissues to identify differentially expressed genes (DEGs), followed by performing systematic review on common identified DEGs. Fifty-eight common DEGs were identified from the analysis of 82 tumour tissue samples obtained from four gene expression datasets (NCBI GEO). These DEGS were then systematically searched for their roles in modulating EMT in CRC based on previously published studies. Following this, 10 common DEGs (CXCL1, CXCL8, MMP1, MMP3, MMP7, TACSTD2, VIP, HPGD, ABCG2, CLCA4) were included in this study and subsequently subjected to further bioinformatic analysis. Their roles and functions in modulating EMT in CRC were discussed in this review. This study enhances our understanding of the molecular mechanisms underlying EMT and uncovers potential candidate genes and pathways that could be targeted in CRC.
Topics: Humans; Epithelial-Mesenchymal Transition; Colorectal Neoplasms; Signal Transduction; Gene Expression; Computational Biology; Gene Expression Regulation, Neoplastic; Cell Line, Tumor
PubMed: 38043836
DOI: 10.1016/j.gene.2023.148057 -
Journal of Cancer 2023Cathepsin B (CTSB), a lysosomal cysteine protease, plays an important role in human physiology and pathology. CTSB is associated with various human diseases, and its... (Review)
Review
Cathepsin B (CTSB), a lysosomal cysteine protease, plays an important role in human physiology and pathology. CTSB is associated with various human diseases, and its expression level and activity are closely related to disease progression and severity. Physiologically, CTSB is integrated into almost all lysosome-related processes, including protein turnover, degradation, and lysosome-mediated cell death. CTSB can lead to the development of various pathological processes through degradation and remodeling of the extracellular matrix. During tumor development and progression, CTSB has two opposing effects. Its pro-apoptotic properties reduce malignancy, while its proteolytic enzymatic activity promotes invasion and metastasis, thereby inducing malignancy. Here, we discuss the roles of CTSB in tumor and non-tumor disease pathophysiologies. We conclude that targeting the activity or expression of CTSB may be important for treating tumor and non-tumor diseases.
PubMed: 37576397
DOI: 10.7150/jca.86531 -
Head and Neck Pathology Dec 2023The BRAF p.V600E genetic variant facilitates the pathogenesis of various tumors by triggering tumor proliferation and progression. The aim of this study was to analyze... (Review)
Review
BACKGROUND
The BRAF p.V600E genetic variant facilitates the pathogenesis of various tumors by triggering tumor proliferation and progression. The aim of this study was to analyze the prevalence of BRAF p.V600E in benign mixed epithelial and mesenchymal and malignant odontogenic tumors. In addition, we discussed the different detection methods used to assess for aberrant BRAF.
METHODS
This systematic review followed the PRISMA guidelines and was registered in Prospero (CRD42023445689). A comprehensive search of the PubMed/MEDLINE, Scopus, Web of Science, and Embase electronic databases was performed to answer the question "What is the prevalence of the BRAF p.V600E mutation in benign mixed and malignant odontogenic tumors?" The methodological quality of the selected studies was assessed using the JBI's Critical Appraisal Tool.
RESULTS
Initially, 387 records were identified, but only 11 articles met the inclusion criteria. A total of 70 patients with benign mixed epithelial and mesenchymal odontogenic tumors and 63 with malignant odontogenic tumors were included in the analysis. We found that the BRAF p.V600E mutation had a prevalence of 31.42% in mixed tumors and 26.98% in malignant odontogenic tumors. Moreover, immunohistochemistry showed high concordance with DNA-based molecular methods.
CONCLUSION
In general, the BRAF p.V600E variant exhibited a prominent prevalence in mixed and malignant odontogenic tumors. However, most of the findings are based on small cohorts of patients and further studies with larger cohorts are needed.
Topics: Humans; Mutation; Proto-Oncogene Proteins B-raf; Prevalence; Odontogenic Tumors; Mouth Neoplasms
PubMed: 38057461
DOI: 10.1007/s12105-023-01601-6 -
Cancers Jan 2024Given the heterogeneity of different malignant processes, planning cancer treatment is challenging. According to recent studies, natural products are likely to be... (Review)
Review
Given the heterogeneity of different malignant processes, planning cancer treatment is challenging. According to recent studies, natural products are likely to be effective in cancer prevention and treatment. Among bioactive flavonoids found in fruits and vegetables, kaempferol (KMP) is known for its anti-inflammatory, antioxidant, and anticancer properties. This systematic review aims to highlight the potential therapeutic effects of KMP on different types of solid malignant tumors. This review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Science Direct, Scopus, and Google Scholar. After the application of study criteria, 64 studies were included. In vitro experiments demonstrated that KMP exerts antitumor effects by controlling tumor cell cycle progression, proliferation, apoptosis, migration, and invasion, as well as by inhibiting angiogenesis. KMP was also able to inhibit important markers that regulate epithelial-mesenchymal transition and enhanced the sensitivity of cancer cells to traditional drugs used in chemotherapy, including cisplatin and 5-fluorouracil. This flavonoid is a promising therapeutic compound and its combination with current anticancer agents, including targeted drugs, may potentially produce more effective and predictable results.
PubMed: 38339336
DOI: 10.3390/cancers16030585 -
European Journal of Obstetrics,... May 2024The rate of caesarean section (CS) is increasing worldwide. Defects in uterine healing have a major gynaecological and obstetric impact (uterine rupture, caesarean scar...
The rate of caesarean section (CS) is increasing worldwide. Defects in uterine healing have a major gynaecological and obstetric impact (uterine rupture, caesarean scar defect, caesarean scar pregnancy, placenta accreta spectrum). The complex process of cellular uterine healing after surgery, and specifically after CS, remains poorly understood in contrast to skin wound healing. This literature review on uterine wound healing was mainly based on histological observations, particularly after CS. The primary objective of the review was to examine the effects of CS on uterine tissue at the cellular level, based on histological observations. The secondary objectives were to describe the biomechanical characteristics and the therapies used to improve scar tissue after CS. This review was performed using PRISMA criteria, and PubMed was the data source. The study included all clinical and animal model studies with CS and histological analysis of the uterine scar area (macroscopic, microscopic, immunohistochemical and biomechanical). Twenty studies were included: 10 human and 10 animal models. In total, 533 female humans and 511 female animals were included. Review articles, meeting abstracts, case series, case reports, and abstracts without access to full-text were excluded. The search was limited to studies published in English. No correlation was found between cutaneous and uterine healing. The histology of uterine scars is characterized by disorganized smooth muscle, fibrosis with collagen fibres and fewer endometrial glands. As for skin healing, the initial inflammation phase and mediation of some growth factors (particularly connective tissue growth factor, vascular endothelial growth factor, platelet-derived growth factor, tumour necrosis factor α and tumour necrosis factor β) seem to be essential. This initial phase has an impact on the subsequent phases of proliferation and maturation. Collagen appears to play a key role in the initial granulation tissue to replace the loss of substance. Subsequent maturation of the scar tissue is essential, with a decrease in collagen and smooth muscle restoration. Unlike skin, the glandular structure of uterine tissue could be responsible for the relatively high incidence of healing defects. Uterine scar defects after CS are characterized by an atrophic disorganized endometrium with atypia and a fibroblastic highly collagenic stromal reaction. Concerning immunohistochemistry, one study found a decrease in tumour necrosis factor β in uterine scar defects. No correlation was found between biomechanical characteristics (particularly uterine strength) and the presence of a collagenous scar after CS. Based on the findings of this review, an illustration of current understanding about uterine healing is provided. There is currently no validated prevention of caesarean scar defects. Various treatments to improve uterine healing after CS have been tested, and appeared to have good efficacy in animal studies: alpha lipoic acid, growth factors, collagen scaffolds and mesenchymal stem cells. Further prospective studies are needed.
Topics: Animals; Female; Humans; Pregnancy; Cesarean Section; Cicatrix; Collagen; Lymphotoxin-alpha; Uterine Diseases; Vascular Endothelial Growth Factor A; Wound Healing
PubMed: 38417279
DOI: 10.1016/j.ejogrb.2024.02.045