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Nutrients Mar 2024The evidence suggests that diet can modulate endogenous microRNA (miRNA) expression. Changes in miRNA expression may affect metabolic processes and consequently be... (Review)
Review
The evidence suggests that diet can modulate endogenous microRNA (miRNA) expression. Changes in miRNA expression may affect metabolic processes and consequently be involved in health status and disease development. The aim of this systematic review was to summarize the evidence of the role of diet and specific food components in the regulation of miRNA expression and discuss its implications for human health and disease development. The PubMed, Embase and Web of Science databases were searched in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for relevant studies. A total of 32 interventional and 5 observational studies performed in adults and evaluating dietary modulation of miRNA expression were included. Energy- and fat-controlled diets along with plant-based foods show substantial evidence of modulating endogenous miRNA levels. Plasma, serum and peripheral blood mononuclear cells (PBMCs) are the main sources used to measure miRNAs. A total of 108 miRNAs modulated by diet were identified. We confirmed that dietary habits are closely associated with the modulation of endogenous miRNAs. Particularly, energy content and fat intake appeared to be key factors influencing miRNA levels. Furthermore, since miRNAs are involved in the regulation of several biological processes, this modulatory process may affect health status and lead to metabolic disorders.
Topics: Adult; Humans; MicroRNAs; Leukocytes, Mononuclear; Diet
PubMed: 38542682
DOI: 10.3390/nu16060770 -
International Journal of Molecular... Mar 2024Breast cancer is a growing disease, with a high worldwide incidence and mortality rate among women. Among the various types, the treatment of triple-negative breast...
Breast cancer is a growing disease, with a high worldwide incidence and mortality rate among women. Among the various types, the treatment of triple-negative breast cancer (TNBC) remains a challenge. Considering the recent advances in cold atmospheric plasma (CAP) cancer research, our goal was to evaluate efficacy data from studies based on chemotherapy and CAP in TNBC cell lines and animal models. A search of the literature was carried out in the PubMed, Web of Science, Cochrane Library, and Embase databases. Of the 10,999 studies, there were fifty-four in vitro studies, three in vivo studies, and two in vitro and in vivo studies included. MDA-MB-231 cells were the most used. MTT, MTS, SRB, annexin-V/propidium iodide, trypan blue, and clonogenic assay were performed to assess efficacy in vitro, increasing the reliability and comprehensiveness of the data. There was found to be a decrease in cell proliferation after both chemotherapy and CAP; however, different protocol settings, including an extensive range of drug doses and CAP exposure times, were reported. For both therapies, a considerable reduction in tumor volume was observed in vivo compared with that of the untreated group. The treatment of TNBC cell lines with CAP proved successful, with apoptosis emerging as the predominant type of cellular death. This systematic review presents a comprehensive overview of the treatment landscape in chemotherapy and CAP regarding their efficacy in TNBC cell lines.
Topics: Animals; Female; Humans; Apoptosis; Cell Line, Tumor; Cell Proliferation; Reproducibility of Results; Triple Negative Breast Neoplasms
PubMed: 38542225
DOI: 10.3390/ijms25063254 -
Medicina (Kaunas, Lithuania) Mar 2024: An extracellular vesicle is part of a class of submicron particles derived from cells, mediating cellular crosstalk through microRNA (miRNA). MiRNA is a group of RNA...
: An extracellular vesicle is part of a class of submicron particles derived from cells, mediating cellular crosstalk through microRNA (miRNA). MiRNA is a group of RNA molecules, each of which consists of 15-22 nucleotides and post-transcriptionally modulates gene expression. The complementary mRNAs-onto which the miRNAs hybridize-are involved in processes such as implantation, tumor suppression, proliferation, angiogenesis, and metastasis that define the entire tumor microenvironment. The endometrial biopsy is a standard technique used to recognize cellular atypia, but other non-invasive markers may reduce patient discomfort during the use of invasive methods. The present study aims to examine the distribution and the regulation of the differentially expressed miRNAs (DEMs) and EV-derived substances in women with endometrial cancer. : We systematically searched the PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect databases in April 2023, adopted the string "Endometrial Neoplasms AND Exosomes", and followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We selected all the studies that included patients with endometrial cancer and that described the regulation of miRNA molecules in that context. The differences in molecule expression between patients and controls were evaluated as significant when the proteins had a fold change of ±1.5. : Seventeen records fulfilled the inclusion criteria: a total of 371 patients and 273 controls were analyzed. The upregulated molecules that had the widest delta between endometrial cancer patients and controls-relative expression ≥ 1 > 3 log2(ratio)-were miR-20b-5p, miR-204-5p, miR-15a-5p, and miR-320a. In particular, miR-20b-5p and miR-204-5p were extracted from both serum and endometrial specimens, whereas miR-15a-5p was only isolated from plasma, and miR-320a was only extracted from the endometrial specimens. In parallel, the most downregulated miRNA in the endometrial cancer patients compared to the healthy subjects was miR-320a, which was found in the endometrial specimens. : Although their epigenetic regulation remains unknown, these upregulated molecules derived from EVs are feasible markers for the early detection of endometrial cancer. The modulation of these miRNA molecules should be assessed during different treatments or if recurrence develops in response to a targeted treatment modality.
Topics: Female; Humans; Embryo Implantation; Endometrial Neoplasms; Endometrium; Epigenesis, Genetic; MicroRNAs; Tumor Microenvironment
PubMed: 38541212
DOI: 10.3390/medicina60030486 -
Alzheimer's Research & Therapy Mar 2024Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid...
BACKGROUND
Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.
METHODS
Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.
RESULTS
We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.
CONCLUSIONS
These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
Topics: Male; Humans; Female; Progranulins; Frontotemporal Dementia; Intercellular Signaling Peptides and Proteins; Virulence; Mutation; Membrane Proteins; Nerve Tissue Proteins
PubMed: 38539243
DOI: 10.1186/s13195-024-01420-z -
Pharmacological Research May 2024There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed... (Meta-Analysis)
Meta-Analysis
There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed this systematic review and meta-analysis to gain an overview of what a role immunotherapy plays in the treatment of T1D. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to December 2023. We included clinical trials of immunotherapy conducted in patients with T1D that reported the incidence of hypoglycemia or changes from baseline in at least one of following outcomes: 2 h and 4 h mixed-meal-stimulated C-peptide area under the curve (AUC), fasting C-peptide, daily insulin dosage, glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The results were computed as the weighted mean differences (WMDs) or odds ratios (ORs) and 95% confidence intervals (CIs) in random-effect model. In all, 34 clinical trials were included. When compared with control groups, 2 h C-peptide AUC was marginally higher in patient treated with nonantigen-based immunotherapies (WMD, 0.04nmol/L, 95% CI, 0.00-0.09 nmol/L, P=0.05), which was mainly driven by the effects of T cell-targeted therapy. A greater preservation in 4 h C-peptide AUC was observed in patients with nonantigen-based immunotherapies (WMD, 0.10nmol/L, 95% CI, 0.04-0.16 nmol/L, P=0.0007), which was mainly driven by the effects of tumor necrosis factor α (TNF-α) inhibitor and T cell-targeted therapy. After excluding small-sample trials, less daily insulin dosage was observed in patient treated with nonantigen-based immunotherapies when compared with control groups (WMD, -0.07units/kg/day, 95% CI, -0.11 to -0.03units/kg/day, P=0.0004). The use of antigen-based immunotherapies was also associated with a lower daily insulin dosage versus control groups (WMD, -0.11units/kg/day, 95% CI, -0.23 to -0.00units/kg/day, P=0.05). However, changes of HbA1c or FPG were comparable between nonantigen-based immunotherapies or antigen-based immunotherapies and control groups. The risk of hypoglycemia was not increased in patients treated with nonantigen-based immunotherapies or patients treated with antigen-based immunotherapies when compared with control groups. In conclusion, nonantigen-based immunotherapies were associated with a preservation of 2 h and 4 h C-peptide AUC in patients with T1D when compared with the controls, which was mainly driven by the effects of TNF-a inhibitor and T cell-targeted therapy. Both nonantigen-based immunotherapies and antigen-based immunotherapies tended to reduce the daily insulin dosage in patients with T1D when compared with the controls. However, they did not contribute to a substantial improvement in HbA1c or FPG. Both nonantigen-based immunotherapies and antigen-based immunotherapies were well tolerated with not increased risk of hypoglycemia in patients with T1D.
Topics: Diabetes Mellitus, Type 1; Humans; Immunotherapy; Hypoglycemic Agents; Blood Glucose; Insulin; Glycated Hemoglobin
PubMed: 38531504
DOI: 10.1016/j.phrs.2024.107157 -
World Journal of Emergency Surgery :... Mar 2024Tourniquets (TQ) have been increasingly adopted in pre-hospital settings recently. This study examined the effectiveness and safety of applying TQ in the pre-hospital... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tourniquets (TQ) have been increasingly adopted in pre-hospital settings recently. This study examined the effectiveness and safety of applying TQ in the pre-hospital settings for civilian patients with traumatic vascular injuries to the extremities.
MATERIALS AND METHODS
We systematically searched the Ovid Embase, PubMed, and Cochrane Central Register of Controlled Trials databases from their inception to June 2023. We compared pre-hospital TQ (PH-TQ) use to no PH-TQ, defined as a TQ applied after hospital arrival or no TQ use at all, for civilian vascular extremity trauma patients. The primary outcome was overall mortality rate, and the secondary outcomes were blood product use and hospital stay. We analyzed TQ-related complications as safety outcomes. We tried to include randomized controlled trials (RCTs) and non-randomized studies (including non-RCTs, interrupted time series, controlled before-and-after studies, cohort studies, and case-control studies), if available. Pooled odds ratios (ORs) were calculated and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.
RESULTS
Seven studies involving 4,095 patients were included. In the primary outcome, pre-hospital TQ (PH-TQ) use significantly decrease mortality rate in patients with extremity trauma (odds ratio [OR], 0.48, 95% confidence interval [CI] 0.27-0.86, I = 47%). Moreover, the use of PH-TQ showed the decreasing trend of utilization of blood products, such as packed red blood cells (mean difference [MD]: -2.1 [unit], 95% CI: -5.0 to 0.8, I = 99%) or fresh frozen plasma (MD: -1.0 [unit], 95% CI: -4.0 to 2.0, I = 98%); however, both are not statistically significant. No significant differences were observed in the lengths of hospital and intensive care unit stays. For the safety outcomes, PH-TQ use did not significantly increase risk of amputation (OR: 0.85, 95% CI: 0.43 to 1.68, I = 60%) or compartment syndrome (OR: 0.94, 95% CI: 0.37 to 2.35, I = 0%). The certainty of the evidence was very low across all outcomes.
CONCLUSION
The current data suggest that, in the pre-hospital settings, PH-TQ use for civilian patients with vascular traumatic injury of the extremities decreased mortality and tended to decrease blood transfusions. This did not increase the risk of amputation or compartment syndrome significantly.
Topics: Humans; Vascular System Injuries; Hemorrhage; Tourniquets; Hospitals; Extremities; Compartment Syndromes
PubMed: 38504263
DOI: 10.1186/s13017-024-00536-9 -
Medicine and Science in Sports and... May 2024Platelet-rich plasma (PRP) has been used for arthroscopic rotator cuff repairs (aRCR), but no studies have addressed the impact of platelet concentration. The primary... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Platelet-rich plasma (PRP) has been used for arthroscopic rotator cuff repairs (aRCR), but no studies have addressed the impact of platelet concentration. The primary aim was to evaluate whether the PRP cell concentration has an effect on tendon healing after aRCR compared with surgery alone. The secondary aim was to assess the functional and pain outcomes.
MATERIALS AND METHODS
A systematic review was performed with searches in the MEDLINE (PubMed), Scopus, Web of Science, and Cochrane (Central) databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Metanalytic procedures were performed for randomized controlled trials (RCTs), and a subgroup analysis was used for studies with target (approximately 10 6 cells·μL -1 ) or below-target PRP cellular concentrations (app. 5 × 10 5 cells·μL -1 ) regarding the primary outcome of tendon healing.
RESULTS
This review included 10 studies (8 RCTs) with 342 patients in the aRCR + PRP group and 344 patients with isolated aRCR. The risk of bias was low to intermediate (6/4, respectively). Meta-analysis of the RCT revealed that the aRCR + high-concentration PRP group had an approximately 3.9-fold higher chance of healing than the non-PRP group (odds ratio, 3.89; 95% confidence interval, 1.78-8.44; P = 0.0007). No significant difference in healing was found between the aRCR + low-concentration PRP and non-PRP groups (odds ratio, 2.21; 95% confidence interval, 0.66-7.45; P = 0.2). The Constant-Murley score and University of California Los Angeles scores were significantly improved in the aRCR + PRP groups with more than 12 months of follow-up, and no significant differences were found consistently for the American Shoulder and Elbow Society and visual analog scale scores.
CONCLUSIONS
This study highlights that a PRP cell concentration close to the target (10 6 cells·μL -1 ) of patients with aRCR may improve their healing and functional outcomes and that dosing may be potentially useful in therapy.
Topics: Humans; Rotator Cuff Injuries; Rotator Cuff; Treatment Outcome; Wound Healing; Platelet-Rich Plasma; Arthroscopy
PubMed: 38480490
DOI: 10.1249/MSS.0000000000003361 -
International Journal of Molecular... Mar 2024Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful... (Review)
Review
Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful tissue repair hinges on controlled inflammation, angiogenesis, and remodeling facilitated by the exchange of cytokines and growth factors. Comorbid conditions can disrupt this process, leading to significant morbidity and mortality. Stem cell therapy has emerged as a promising strategy for enhancing wound healing, utilizing cells from diverse sources such as endothelial progenitor cells, bone marrow, adipose tissue, dermal, and inducible pluripotent stem cells. In this systematic review, we comprehensively investigated stem cell therapies in chronic wounds, summarizing the clinical, translational, and primary literature. A systematic search across PubMed, Embase, Web of Science, Google Scholar, and Cochrane Library yielded 22,454 articles, reduced to 44 studies after rigorous screening. Notably, adipose tissue-derived mesenchymal stem cells (AD-MSCs) emerged as an optimal choice due to their abundant supply, easy isolation, ex vivo proliferative capacities, and pro-angiogenic factor secretion. AD-MSCs have shown efficacy in various conditions, including peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and post-Mohs micrographic surgery wounds. Delivery methods varied, encompassing topical application, scaffold incorporation, combination with plasma-rich proteins, and atelocollagen administration. Integration with local wound care practices resulted in reduced pain, shorter healing times, and improved cosmesis. Stem cell transplantation represents a potential therapeutic avenue, as transplanted stem cells not only differentiate into diverse skin cell types but also release essential cytokines and growth factors, fostering increased angiogenesis. This approach holds promise for intractable wounds, particularly chronic lower-leg wounds, and as a post-Mohs micrographic surgery intervention for healing defects through secondary intention. The potential reduction in healthcare costs and enhancement of patient quality of life further underscore the attractiveness of stem cell applications in wound care. This systematic review explores the clinical utilization of stem cells and stem cell products, providing valuable insights into their role as ancillary methods in treating chronic wounds.
Topics: Humans; Endothelial Cells; Quality of Life; Wound Healing; Pluripotent Stem Cells; Intercellular Signaling Peptides and Proteins; Cytokines; Mesenchymal Stem Cell Transplantation
PubMed: 38474251
DOI: 10.3390/ijms25053006 -
Journal of the American Veterinary... Jun 2024Platelet-rich plasma (PRP) and mesenchymal stromal or stem cells (MSCs) have been investigated as treatments for equine tendon and ligament injuries, but little... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Platelet-rich plasma (PRP) and mesenchymal stromal or stem cells (MSCs) have been investigated as treatments for equine tendon and ligament injuries, but little consensus exists on the efficacy of these treatments. The study sought to evaluate the efficacy of PRP and MSC treatments by systematic review and meta-analysis.
METHODS
A systematic review was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Inclusion criteria required an original, peer-reviewed study where horses were administered MSCs or PRP (or both), and a comparator group was described. Studies were assessed for risk of bias and study quality. Random effects meta-analysis with inverse variance weighting was used to calculate pooled estimates of the ORs for the primary outcomes of return to performance and reinjury.
RESULTS
The search criteria identified 764 unique studies, and 21 studies met the inclusion criteria for the systematic review. Seventeen studies were further assessed for the primary outcomes of return to performance and reinjury rate within a meta-analysis. Meta-analyses revealed no increase in the likelihood of a return to performance with any of the biologic treatments. However, MSCs and MSCs administered concurrently with PRP provide a reduced risk of reinjury.
CLINICAL RELEVANCE
The current study identified a decrease in reinjury rate in horses administered MSCs or a combination of MSCs and PRP for tendinopathy and desmopathy. However, results should be interpreted with consideration of the heterogeneity of findings, poor study quality, and high risk of bias in the majority of studies.
Topics: Animals; Horses; Platelet-Rich Plasma; Tendon Injuries; Ligaments; Horse Diseases; Mesenchymal Stem Cell Transplantation
PubMed: 38471305
DOI: 10.2460/javma.23.12.0723 -
PloS One 2024Mesenchymal stem cells (MSCs) hold promise for osteoarthritis (OA) treatment, potentially enhanced by combining them with platelet-rich plasma (PRP) and hyaluronic acid... (Meta-Analysis)
Meta-Analysis
Modified Mesenchymal stem cell, platelet-rich plasma, and hyaluronic acid intervention in early stage osteoarthritis: A systematic review, meta-analysis, and meta-regression of arthroscopic-guided intra-articular approaches.
BACKGROUND
Mesenchymal stem cells (MSCs) hold promise for osteoarthritis (OA) treatment, potentially enhanced by combining them with platelet-rich plasma (PRP) and hyaluronic acid (HA). This study aimed to assess the synergy of MSCs, PRP, and varying HA doses, and determine optimal MSC sources to treat early-stage OA in the perspective of Lysholm score, VAS Score, KSS score, and WOMAC score.
METHOD
Original articles from 2013 to 2023 were screened from four databases, focusing on clinical trials and randomized controlled trials. The Risk of Bias in Non-randomized Studies-of Interventions (ROB-2) tool evaluated bias, and a PICOS criteria table guided result construction. Revman 5.4 analyzed outcomes such as Lysholm score, VAS score, KSS, WOMAC score, cartilage volume, and defect size using MRI. This systematic review adhered to PRISMA guidelines.
RESULT
Nine studies met the final inclusion criteria. Meta-analysis revealed a significant improvement in Lysholm score (MD: 17.89; 95% CI: 16.01, 19.77; I2 = 0%, P = 0.56), a notable reduction in VAS score (MD: -2.62; 95% CI: -2.83, -2.41; I2 = 99%, P < 0.00001), elevated KSS (MD: 29.59; 95% CI: 27.66, 31.52; I2 = 95%, P < 0.0001), and reduced WOMAC score (MD: -12.38; 95% CI: -13.75, -11.01; I2 = 99%, P < 0.0001).
CONCLUSIONS
Arthroscopic guided high-dose subchondral application of primary cultured synovial MSCs in popliteal PRP media with HA effectively regenerates cartilage defects and improves clinical outcomes in early-stage osteoarthritis. Clarification of MSC sources and quantities enhances the understanding of this promising treatment modality.
Topics: Humans; Hyaluronic Acid; Viscosupplements; Osteoarthritis, Knee; Injections, Intra-Articular; Platelet-Rich Plasma; Treatment Outcome
PubMed: 38457479
DOI: 10.1371/journal.pone.0295876