-
International Journal of Molecular... Nov 2022We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle... (Meta-Analysis)
Meta-Analysis Review
We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studies on plasma HC and 22 on MTHFR genotypes. Due to age-related HC differences, adult and paediatric SCD were separated: 879 adult SCD and 834 controls (CTR) yielded a neutral effect size; 427 paediatric SCD and 625 CTR favoured SCD (p = 0.001) with wide heterogeneity (I2 = 95.5%) and were sub-grouped by country: six studies (Dutch Antilles n = 1, USA n = 5) yielded a neutral effect size, four (India n = 1, Arab countries n = 3) favoured SCD (p < 0.0001). Moreover, 249 SCD in VOC and 419 out of VOC yielded a neutral effect size. The pooled prevalence of the MTHFR TT genotype in 267 SCD equalled that of 1199 CTR (4.26% vs. 2.86%, p = 0.45), and in 84 SCD with IS equalled that of 86 without IS (5.9% vs. 3.7%, p = 0.47); removal of one paediatric study yielded a significant effect size (p = 0.006). Plasma HC in paediatric SCD from Middle East and India was higher, possibly due to vitamin deficiencies. Despite its low prevalence in SCD, the MTHFR TT genotype relates to adult IS.
Topics: Adult; Child; Humans; Anemia, Sickle Cell; Genotype; Homocysteine; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic
PubMed: 36498990
DOI: 10.3390/ijms232314641 -
International Journal of Molecular... Sep 2022Over the past decade, we witnessed a promising application of cold atmospheric plasma (CAP) in cancer therapy. The aim of this systematic review was to provide an... (Review)
Review
Over the past decade, we witnessed a promising application of cold atmospheric plasma (CAP) in cancer therapy. The aim of this systematic review was to provide an exhaustive state of the art of CAP employed for the treatment of head and neck cancer (HNC), a tumor whose late diagnosis, local recurrence, distant metastases, and treatment failure are the main causes of patients' death. Specifically, the characteristics and settings of the CAP devices and the in vitro and in vivo treatment protocols were summarized to meet the urgent need for standardization. Its molecular mechanisms of action, as well as the successes and pitfalls of current CAP applications in HNC, were discussed. Finally, the interesting emerging preclinical hypotheses that warrant further clinical investigation have risen. A total of 24 studies were included. Most studies used a plasma jet device (54.2%). Argon resulted as the mostly employed working gas (33.32%). Direct and indirect plasma application was reported in 87.5% and 20.8% of studies, respectively. In vitro investigations were 79.17%, most of them concerned with direct treatment (78.94%). Only eight (33.32%) in vivo studies were found; three were conducted in mice, and five on human beings. CAP showed pro-apoptotic effects more efficiently in tumor cells than in normal cells by altering redox balance in a way that oxidative distress leads to cell death. In preclinical studies, it exhibited efficacy and tolerability. Results from this systematic review pointed out the current limitations of translational application of CAP in the urge of standardization of the current protocols while highlighting promising effects as supporting treatment in HNC.
Topics: Animals; Argon; Head and Neck Neoplasms; Humans; Mice; Plasma Gases
PubMed: 36142145
DOI: 10.3390/ijms231810238 -
Annals of Medicine Dec 2024Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.
METHODS
The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software.
RESULTS
Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, < 0.001).
CONCLUSION
Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.
Topics: Humans; Multiple Myeloma; Plasma Cells; Prognosis; Biomarkers; Proportional Hazards Models
PubMed: 38599340
DOI: 10.1080/07853890.2024.2338604 -
The Physician and Sportsmedicine 2016Knee osteoarthritis (OA) is a debilitating condition that may ultimately require total knee arthroplasty (TKA). Non-operative treatments are bracing, oral analgesics,... (Review)
Review
OBJECTIVES
Knee osteoarthritis (OA) is a debilitating condition that may ultimately require total knee arthroplasty (TKA). Non-operative treatments are bracing, oral analgesics, physical therapy, and intra-articular knee injection (IAKI). The objective of this paper is to provide a systematic literature review regarding intra-articular treatment of knee OA and insight into promising new products of regenerative medicine that may eventually have a substantial effect on treatment.
METHODS
A literature search was executed using Medline, Cochrane, and Embase with keywords "knee osteoarthritis" and "injection." Specifically, 45 articles that discussed intra-articular knee injection using corticosteroids, hyaluronic acid, analgesics, local anesthetics, and newer products of regenerative medicine, such as platelet-rich plasma (PRP) and mesenchymal stem cells (MSC), were analyzed. Of these, eleven were level 1, three were level 2, twelve were level 3, two were level 4, and seventeen were level 5 evidence. Papers included animal models.
RESULTS
Local anesthetics have potential side effects and may only be effective for a few hours. Morphine and ketorolac may provide significant pain relief for 24 hours. Corticosteroids may give patients weeks to months of effective analgesia, but complications may occur, such as systemic hyperglycemia, septic arthritis, and joint degradation . Hyaluronic acid is a natural component of synovial fluid, but efficacy with respect to analgesia is controversial. Platelet-rich plasma formulations, autologous conditioned serum, autologous protein solution, and mesenchymal stem cell injections contain anti-inflammatory molecules and have been proposed to attenuate joint destruction or potentially remodel the joint.
CONCLUSIONS
Currently, knee OA treatment does not address the progressively inflammatory environment of the joint. More investigation is needed regarding products of regenerative medicine, but they may ultimately have profound implications in the way knee OA is managed.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Arthroplasty, Replacement, Knee; Braces; Humans; Hyaluronic Acid; Injections, Intra-Articular; Mesenchymal Stem Cell Transplantation; Osteoarthritis, Knee; Pain; Platelet-Rich Plasma; Viscosupplements
PubMed: 26985986
DOI: 10.1080/00913847.2016.1168272 -
Cancers Dec 2023Urogenital cancers, which include prostate, bladder, and kidney malignancies, exert a substantial impact on global cancer-related morbidity and mortality. Proteomic... (Review)
Review
Urogenital cancers, which include prostate, bladder, and kidney malignancies, exert a substantial impact on global cancer-related morbidity and mortality. Proteomic biomarkers, emerging as valuable tools, aim to enhance early detection, prognostic accuracy, and the development of personalized therapeutic strategies. This study undertook a comprehensive systematic review and meta-analysis of the existing literature investigating the role and potential of proteomic biomarkers in plasma, tissue, and urine samples in urogenital cancers. Our extensive search across several databases identified 1879 differentially expressed proteins from 37 studies, signifying their potential as unique biomarkers for these cancers. A meta-analysis of the significantly differentially expressed proteins was executed, accentuating the findings through visually intuitive volcano plots. A functional enrichment analysis unveiled their significant involvement in diverse biological processes, including signal transduction, immune response, cell communication, and cell growth. A pathway analysis highlighted the participation of key pathways such as the nectin adhesion pathway, TRAIL signaling pathway, and integrin signaling pathways. These findings not only pave the way for future investigations into early detection and targeted therapeutic approaches but also underscore the fundamental role of proteomics in advancing our understanding of the molecular mechanisms underpinning urogenital cancer pathogenesis. Ultimately, these findings hold remarkable potential to significantly enhance patient care and improve clinical outcomes.
PubMed: 38201450
DOI: 10.3390/cancers16010022 -
Oncotarget Nov 2017Selected circulating microRNAs (miRNAs) have been suggested for non-invasive screening of non-small cell lung cancer (NSCLC), however the numerous proposed miRNA... (Review)
Review
Selected circulating microRNAs (miRNAs) have been suggested for non-invasive screening of non-small cell lung cancer (NSCLC), however the numerous proposed miRNA signatures are inconsistent. Aiming to identify miRNAs suitable specifically for stage I-II NSCLC screening in serum/plasma samples, we searched the databases "Pubmed", "Medline", "Scopus", "Embase" and "WOS" and systematically reviewed the publications reporting quantitative data on the efficacy [sensitivity, specificity and/or area under the curve (AUC)] of circulating miRNAs as biomarkers of NSCLC stage I and/or II. The 20 studies fulfilling the search criteria included 1110 NSCLC patients and 1009 controls, and were of medium quality according to Quality Assessment of Diagnostic Accuracy Studies checklist. In these studies, the patient cohorts as well as the control groups were heterogeneous for demographics and clinicopathological characteristics; moreover, numerous pre-analytical and analytical variables likely influenced miRNA determinations, and potential bias of hemolysis was often underestimated. We identified four circulating miRNAs scarcely influenced by hemolysis, each featuring high sensitivity (> 80%) and AUC (> 0.80) as biomarkers of stage I-II NSCLC: miR-223, miR-20a, miR-448 and miR-145; four other miRNAs showed high specificity (> 90%): miR-628-3p, miR-29c, miR-210 and miR-1244. In a model of two-step screening for stage I-II NSCLC using first the above panel of serum miRNAs with high sensitivity and high AUC, and subsequently the panel with high specificity, the estimated overall sensitivity is 91.6% and overall specificity is 93.4%. These and other circulating miRNAs suggested for stage I-II NSCLC screening require validation in multiple independent studies before they can be proposed for clinical application.
PubMed: 29212284
DOI: 10.18632/oncotarget.21739 -
Aging and Disease Feb 2020Diabetes mellitus (DM) is a chronic metabolic disease with high morbidity and mortality. Recently, stem cell-based therapy for DM has shown considerable promise. Here,... (Review)
Review
Diabetes mellitus (DM) is a chronic metabolic disease with high morbidity and mortality. Recently, stem cell-based therapy for DM has shown considerable promise. Here, we undertook a systematic review and meta-analysis of published clinical studies to evaluate the efficacy and safety of stem cell therapy for both type 1 DM (T1DM) and type 2 DM (T2DM). The PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and ClinicalTrials.gov databases were searched up to November 2018. We employed a fixed-effect model using 95% confidence intervals (CIs) when no statistically significant heterogeneity existed. Otherwise, a random-effects statistical model was used. Twenty-one studies met our inclusion criteria: ten T1DM studies including 226 patients and eleven T2DM studies including 386 patients. Stem cell therapy improved C-peptide levels (mean difference (MD), 0.41; 95% CI, 0.06 to 0.76) and glycosylated hemoglobin (HbA1c; MD, -3.46; 95% CI, -6.01 to -0.91) for T1DM patients. For T2DM patients, stem cell therapy improved C-peptide levels (MD, 0.33; 95% CI, 0.07 to 0.59), HbA1c (MD, -0.87; 95% CI, -1.37 to -0.37) and insulin requirements (MD, -35.76; 95% CI, -40.47 to -31.04). However, there was no significant change in fasting plasma glucose levels (MD, -0.52; 95% CI, -1.38 to 0.34). Subgroup analyses showed significant HbA1c and C-peptide improvements in patients with T1DM treated with bone marrow hematopoietic stem cells (BM-HSCs), while there was no significant change in the mesenchymal stem cell (MSC) group. In T2DM, HbA1c and insulin requirements decreased significantly after MSC transplantation, and insulin requirements and C-peptide levels were significantly improved after bone marrow mononuclear cell (BM-MNC) treatment. Stem cell therapy is a relatively safe and effective method for selected individuals with DM. The data showed that BM-HSCs are superior to MSCs in the treatment of T1DM. In T2DM, MSC and BM-MNC transplantation showed favorable therapeutic effects.
PubMed: 32010488
DOI: 10.14336/AD.2019.0421 -
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 -
Clinical Rheumatology Sep 2021Rheumatoid arthritis (RA) is a chronic inflammatory disease that carries high social and economic costs and can lead to permanent disability. RA pathogenesis has not... (Review)
Review
Rheumatoid arthritis (RA) is a chronic inflammatory disease that carries high social and economic costs and can lead to permanent disability. RA pathogenesis has not been completely elucidated yet. Extracellular vesicles (EVs) are membrane-contained vesicles released by cells playing a role in cell-to-cell communication and they could be involved in different diseases. Evidence on the involvement of EVs in RA is currently inconclusive. Therefore, a systematic review on the role of EVs in RA was performed in order to explore this relationship. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research was conducted on PubMed, Scopus, and Embase up to March 5, 2020: 41 studies were analyzed out of 674 screened. The total plasmatic and synovial fluid (SF) EV number seems increased in RA as compared with healthy controls. Both RA plasma and SF contained EVs subpopulations of heterogenous origin, especially derived from platelets and immune system cells. No univocal evidence emerged on miRNA expression and EV content profile within RA patients. EVs showed to enhance pro-inflammatory pathways, such as cytokines and chemokine release and TNF blockade seemed to revert this effect. Our work highlights the requirement to standardize study methodologies in order to make results comparable and draw conclusions that remain, at present, unclear.
Topics: Arthritis, Rheumatoid; Blood Platelets; Extracellular Vesicles; Humans; MicroRNAs; Synovial Fluid
PubMed: 33544235
DOI: 10.1007/s10067-021-05614-w -
The Cochrane Database of Systematic... Apr 2017Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration.... (Review)
Review
BACKGROUND
Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration. Vaso-occlusive crises are common painful events responsible for a variety of clinical complications; overall mortality is increased and life expectancy decreased compared to the general population. Experimental studies suggest that intravenous magnesium has proven to be well-tolerated in individuals hospitalised for the immediate relief of acute (sudden onset) painful crisis and has the potential to decrease the length of hospital stay. Some in vitro studies and open studies of long-term oral magnesium showed promising effect on pain relief but failed to show its efficacy. The studies show that oral magnesium therapy may prevent sickle red blood cell dehydration and prevent recurrent painful episodes. There is a need to access evidence for the impact of oral and intravenous magnesium effect on frequency of pain, length of hospital stay and quality of life.
OBJECTIVES
To evaluate the effects of short-term intravenous magnesium on the length of hospital stay and quality of life in children and adults with sickle cell disease. To determine the effects of long-term oral magnesium therapy on the frequency of painful crises and the quality of life in children and adults with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 01 December 2016.Date of last search of other resources (clinical trials registries): 29 March 2017.
SELECTION CRITERIA
We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium.
DATA COLLECTION AND ANALYSIS
Authors independently assessed the study quality and extracted the data using standard Cochrane methodologies.
MAIN RESULTS
We included five randomized placebo-controlled studies with a total of 386 participants (aged three to 53 years). Two shorter parallel studies (n = 306) compared intravenous magnesium sulphate to placebo (normal saline) for admission to hospital due to a vaso-occlusive crisis, for which we were able to analyse data. The quality of evidence was moderate for studies presenting this comparison mainly due to limitations due to risk of bias and imprecision. Two of the three longer-term studies comparing oral magnesium pidolate to placebo had a cross-over design. The third was a parallel factorial study which compared hydroxyurea and oral magnesium to each other and to placebo over a longer period of time; we only present the comparison of oral magnesium to placebo from this study. The quality of evidence was very low with uncertainty of the estimation.The eight-hourly dose levels in the two studies of intravenous magnesium were different; one used 100 mg/kg while the second used 40 mg/kg. Only one of these studies (n = 104) reported the mean daily pain score while hospitalised (a non-significant difference between groups, moderate quality evidence). The second study (n = 202) reported a number of child- and parent-reported quality of life scores. None of the scores showed any difference between treatment groups (low quality evidence). Data from one study (n = 106) showed no difference in length of stay in hospital between groups (low quality evidence). Both studies reported on adverse events, but not defined by severity as we had planned. One study showed significantly more participants receiving intravenous magnesium experienced warmth at infusion site compared to placebo; there were no differences between groups for other adverse events (low quality evidence).Three studies (n = 80) compared oral magnesium pidolate to placebo. None of them reported data which we were able to analyse. One study (n = 24) reported on the number of painful days and stated there was no difference between two groups (low quality evidence). None of the studies reported on quality of life or length of hospital stay. Two studies (n = 68) reported there were no differences in levels of magnesium in either plasma or red blood cells (moderate quality evidence). Two studies (n = 56) reported adverse events. One reported episodes of mild diarrhoea and headache, all of which resolved without stopping treatment. The second study reported adverse events as gastrointestinal disorders, headache or migraine, upper respiratory infections and rash; which were all evenly distributed across treatment groups (moderate quality evidence).
AUTHORS' CONCLUSIONS
Moderate to low quality evidence showed neither intravenous magnesium and oral magnesium therapy has an effect on reducing painful crisis, length of hospital stay and changing quality of life in treating sickle cell disease. Therefore, no definitive conclusions can be made regarding its clinical benefit. Further randomized controlled studies, perhaps multicentre, are necessary to establish whether intravenous and oral magnesium therapies have any effect on improving the health of people with sickle cell disease.
Topics: Administration, Oral; Adolescent; Adult; Anemia, Sickle Cell; Antisickling Agents; Child; Child, Preschool; Humans; Hydroxyurea; Injections, Intravenous; Magnesium; Magnesium Sulfate; Middle Aged; Pain Measurement; Parents; Pyrrolidonecarboxylic Acid; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 28409830
DOI: 10.1002/14651858.CD011358.pub2