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International Journal of Molecular... Jul 2023Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and... (Review)
Review
Recovery from a traumatic spinal cord injury (TSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. Cell therapy, particularly with mesenchymal stem cells (MSCs), holds significant promise for TSCI treatment. This systematic review aims to analyze the efficacy, safety, and therapeutic potential of MSC-based cell therapies in TSCI. A comprehensive search of PUBMED and COCHRANE databases until February 2023 was conducted, combining terms such as "spinal cord injury," "stem cells," "stem cell therapy," "mesenchymal stem cells," and "traumatic spinal cord injury". Among the 53 studies initially identified, 22 (21 clinical trials and 1 case series) were included. Findings from these studies consistently demonstrate improvements in AIS (ASIA Impairment Scale) grades, sensory scores, and, to a lesser extent, motor scores. Meta-analyses further support these positive outcomes. MSC-based therapies have shown short- and medium-term safety, as indicated by the absence of significant adverse events within the studied timeframe. However, caution is required when drawing generalized recommendations due to the limited scientific evidence available. Further research is needed to elucidate the long-term safety and clinical implications of these advancements. Although significant progress has been made, particularly with MSC-based therapies, additional studies exploring other potential future therapies such as gene therapies, neurostimulation techniques, and tissue engineering approaches are essential for a comprehensive understanding of the evolving TSCI treatment landscape.
Topics: Humans; Mesenchymal Stem Cell Transplantation; Spinal Cord Injuries; Cell- and Tissue-Based Therapy; Myelin Sheath; Mesenchymal Stem Cells; Spinal Cord
PubMed: 37511478
DOI: 10.3390/ijms241411719 -
Psychopharmacology Bulletin Oct 2020This evidence-based systematic review will focus on the use of dexmedetomidine and its role as adjuvant anesthetics in regional blocks to help better guide physicians in... (Review)
Review
PURPOSE OF REVIEW
This evidence-based systematic review will focus on the use of dexmedetomidine and its role as adjuvant anesthetics in regional blocks to help better guide physicians in their practice. This review will cover background and mechanism of dexmedetomidine as well as the use in various regional blocks.
RECENT FINDINGS
Local anesthetics are preferred for nerve blocks over opioids; however, both due come with its own side effects. Local anesthetics may be toxic as they disrupt cell membrane and proteins, but by using adjuvants such as dexmedetomidine, that can prolong sensory and motor blocks can reduce total amount of local anesthetics needed. Dexmedetomidine is an alpha-2-adrenergic agonist used as additive for regional nerve block. It has a relatively low side effect profile and have been researched in various regional blocks (intrathecal, paravertebral, axillary, infraclavicular brachial plexus, interscalene). Dexmedetomidine shows promising results as adjuvant anesthetics in most regional blocks.
SUMMARY
Many studies have been done and many show promising results for the use of dexmedetomidine in regional blocks. It may significantly increase in duration of sensory and motor blocks that correlates with lower pain scores and less need of morphine in various regional blocks.
Topics: Adrenergic alpha-2 Receptor Agonists; Anesthesia, Conduction; Anesthetics, Local; Brachial Plexus Block; Dexmedetomidine
PubMed: 33633422
DOI: No ID Found -
The Cochrane Database of Systematic... Feb 2023Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains... (Review)
Review
BACKGROUND
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow, leading to haemolytic anaemia. The life-long management of the general health effects of thalassaemia is highly challenging, and failure to deal with dental and orthodontic complications exacerbates the public health, financial and personal burden of the condition. There is a lack of evidence-based guidelines to help care seekers and providers manage such dental and orthodontic complications. This review aimed to evaluate the available evidence on methods for treating dental and orthodontic complications in people with thalassaemia to inform future recommendations. This is an update of a Cochrane Review first published in 2019.
OBJECTIVES
To assess different methods for treating dental and orthodontic complications in people with thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register in September 2022, and we searched nine online databases and trials registries in January 2022. We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organisations, pharmaceutical companies and researchers working in this field.
SELECTION CRITERIA
We searched for published or unpublished randomised controlled trials (RCTs) that evaluated treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, sex and ethnic origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the 37,242 titles retrieved by the search. After deduplication, we identified two potentially relevant RCTs. On assessing their eligibility against our inclusion and exclusion criteria, we excluded one and included the other.
MAIN RESULTS
We included one parallel-design RCT conducted in Saudi Arabia and involving 29 participants (19 males, 10 females) with thalassaemia. It aimed to assess the effectiveness of photodynamic therapy as an adjuvant to conventional full-mouth ultrasonic scaling for the treatment of gingivitis. The average age of participants was around 23 years. There is very low-certainty evidence from this trial that full-mouth ultrasonic scaling plus photodynamic therapy compared to full-mouth ultrasonic scaling alone may improve gingival index score and bleeding on probing after 12 weeks in people with thalassaemia. We found no studies that assessed other interventions for the various dental or orthodontic complications of thalassaemia.
AUTHORS' CONCLUSIONS
Although the included study showed greater reduction in gingivitis in the group treated with full-mouth ultrasonic scaling plus photodynamic therapy, the evidence is of very low certainty. The study had unclear risk of bias, a short follow-up period and no data on safety or adverse effects. We cannot make definitive recommendations for clinical practice based on the limited evidence of a single trial. Future studies will very likely affect the conclusions of this review. This review highlights the need for high-quality RCTs that investigate the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. It is crucial that future trials assess adverse effects of interventions.
Topics: Male; Female; Humans; Thalassemia; Gingivitis
PubMed: 36732291
DOI: 10.1002/14651858.CD012969.pub3 -
Molecular & Cellular Proteomics : MCP Aug 2023Osteoarthritis (OA) is the most prevalent rheumatic pathology. However, OA is not simply a process of wear and tear affecting articular cartilage but rather a disease of...
Osteoarthritis (OA) is the most prevalent rheumatic pathology. However, OA is not simply a process of wear and tear affecting articular cartilage but rather a disease of the entire joint. One of the most common locations of OA is the knee. Knee tissues have been studied using molecular strategies, generating a large amount of complex data. As one of the goals of the Rheumatic and Autoimmune Diseases initiative of the Human Proteome Project, we applied a text-mining strategy to publicly available literature to collect relevant information and generate a systematically organized overview of the proteins most closely related to the different knee components. To this end, the PubPular literature-mining software was employed to identify protein-topic relationships and extract the most frequently cited proteins associated with the different knee joint components and OA. The text-mining approach searched over eight million articles in PubMed up to November 2022. Proteins associated with the six most representative knee components (articular cartilage, subchondral bone, synovial membrane, synovial fluid, meniscus, and cruciate ligament) were retrieved and ranked by their relevance to the tissue and OA. Gene ontology analyses showed the biological functions of these proteins. This study provided a systematic and prioritized description of knee-component proteins most frequently cited as associated with OA. The study also explored the relationship of these proteins to OA and identified the processes most relevant to proper knee function and OA pathophysiology.
Topics: Humans; Cartilage, Articular; Knee Joint; Osteoarthritis, Knee
PubMed: 37356495
DOI: 10.1016/j.mcpro.2023.100606 -
Targeted Oncology Nov 2023Delta-like ligand 3 (DLL3), a member of the Notch pathway, has been identified as a potential therapeutic target as it is highly expressed in small cell lung cancer...
BACKGROUND
Delta-like ligand 3 (DLL3), a member of the Notch pathway, has been identified as a potential therapeutic target as it is highly expressed in small cell lung cancer (SCLC), a subtype accounting for 15% of lung cancer cases.
OBJECTIVE
A systematic literature review (SLR) was conducted to understand the prevalence and prognostic impact of DLL3 expression on survival of patients with SCLC and treatment response.
PATIENTS AND METHODS
Systematic literature searches were conducted across multiple databases to capture studies of any SCLC population that evaluated DLL3 expression. Specific outcomes of interest included prevalence of DLL3 expression, method of expression analysis, and impact on outcome, including treatment response and survival (overall, progression-free, disease-free) according to varying levels of DLL3 expression/positivity. Standard risk of bias tools were used to evaluate study quality.
RESULTS
Among the 30 included studies, the most common DLL3 testing method was immunohistochemistry (N = 26, 86.7%). For comparability, results focused on the 13 (22.3%) studies that used the Ventana DLL3 (SP347) immunohistochemistry assay. The prevalence of DLL3 positivity ranged from 80.0-93.5% for studies using a threshold of ≥ 1% of tumor cells (N = 4) and 58.3-91.1% for studies with a ≥ 25% threshold (N = 4). DLL3 expression was generally categorized as high using cutoffs of ≥ 50% (prevalence range: 45.8-79.5%; N = 6) or ≥ 75% (prevalence range: 47.3-75.6%; N = 5) of cells with positivity. Two studies used an H-score of ≥ 150 to define high DLL3 expression with prevalence ranging from 33.3-53.1%. No consistent associations were seen between DLL3 expression level and patient age, sex, smoking history, or disease stage. Two studies reported change in DLL3 expression category (high versus low) before and after chemotherapy. No statistically significant differences were reported between DLL3 expression groups and survival (overall, progression-free, or disease-free) or treatment response.
CONCLUSIONS
There is a high prevalence of DLL3 expression in SCLC. Further research and analytical methods may help to characterize different populations of patients with SCLC based on DLL3 expression. While no significant prognostic factor in the included studies was identified, additional cohort studies using standardized methodology, with longer follow-up, are needed to better characterize any potential differences in patient survival or response by DLL3 expression level in SCLC.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Prognosis; Ligands; Prevalence; Membrane Proteins; Intracellular Signaling Peptides and Proteins
PubMed: 37930513
DOI: 10.1007/s11523-023-01008-x -
Journal of Nippon Medical School =... 2018Epigenetic inactivation of tumor suppressor genes is an important molecular mechanism in the formation and development of human tumors. The purpose of our study was to... (Review)
Review
BACKGROUND/AIM
Epigenetic inactivation of tumor suppressor genes is an important molecular mechanism in the formation and development of human tumors. The purpose of our study was to evaluate the correlation between the methylation level of the secreted frizzled-related protein 1 (SFRP1) gene and the risk of renal cell carcinoma (RCC).
METHODS
The relevant literature was searched in detail in several electronic databases. The methodological heterogeneity was analyzed by meta-regression and subgroup analyses. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to summarize the dichotomous outcomes of our meta-analysis.
RESULTS
The ten included articles contained 535 RCC samples and 475 normal controls. The results demonstrated that the methylation level of the SFRP1 promoter region was significantly correlated with an increased incidence of RCC (OR=13.72; 95% CI: 6.01-31.28; P=0.000). Furthermore, the eligible studies that had sufficient clinical data about the RCC cases were included in the analysis, and the results indicated that the frequency of SFRP1 promoter methylation was associated with a higher histological grade (P=0.000), tumor stage (P=0.033), tumor size (≥5 cm; P=0.029), and distant metastasis (P=0.047).
CONCLUSION
Our results indicate that the methylation level of the SFRP1 promoter region is increased in patients with RCC compared to normal controls and might be involved in the occurrence and development of RCC. Additional well-designed studies are needed to further verify our conclusions.
Topics: Carcinoma, Renal Cell; Confidence Intervals; Humans; Incidence; Intercellular Signaling Peptides and Proteins; Kidney Neoplasms; Membrane Proteins; Meta-Analysis as Topic; Methylation; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Promoter Regions, Genetic; Risk
PubMed: 29731501
DOI: 10.1272/jnms.2018_85-13 -
Acta Histochemica Jan 2023Epithelial membrane protein 2 (EMP2) is a cell surface protein composed of approximately 160 amino acids and encoded by the growth arrest-specific 3 (GAS3)/peripheral... (Review)
Review
OBJECTIVES
Epithelial membrane protein 2 (EMP2) is a cell surface protein composed of approximately 160 amino acids and encoded by the growth arrest-specific 3 (GAS3)/peripheral myelin protein 22 kDa (PMP22) gene family. Although EMP2 expression has been investigated in several diseases, much remains unknown regarding its mechanism of action and the extent of its role in pathogenesis. Our aim was to perform a systematic review on the involvement of EMP2 in disease processes and the current usage of anti-EMP2 therapies.
METHODS
A Boolean search of the English-language medical literature was performed. PubMed, Scopus, Cochrane, and Web of Science were used to identify relevant citations. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
52 studies met the inclusion criteria for qualitative analysis. Of those, 28 (53.8%) were human-only studies, 11 (21.2%) were animal-only studies, and 13 (25%) studies included both human and animal models. Furthermore, 34 (65.4%) studies focused on EMP2's role in neoplasms, while the remaining 18 (34.6%) articles evaluated its role in other pathologies.
CONCLUSION
Overall, the evidence suggests the mechanisms of action of EMP2 are context dependent. Promising results have been produced by utilizing EMP2 as a biomarker and therapeutic target. More studies are warranted to better understand the mechanism and comprehend the role of EMP2 in the pathogenesis of diseases.
Topics: Animals; Humans; Membrane Glycoproteins; Membrane Proteins
PubMed: 36455339
DOI: 10.1016/j.acthis.2022.151976 -
Oxidative Medicine and Cellular... 2018Mitochondria are metabolically active organelles that produce significant reactive oxygen species, linked with aging and degenerative diseases. In recent years,... (Meta-Analysis)
Meta-Analysis Review
Mitochondria are metabolically active organelles that produce significant reactive oxygen species, linked with aging and degenerative diseases. In recent years, particular focus has been put on mitochondria-targeted antioxidants, to decrease the concentration of reactive oxygen species and help alleviate the accumulation of oxidative damage and associated aging. MitoQ is a mitochondria-targeted antioxidant of which is reported to support healthy aging. The aim of this systematic review is to investigate the effects of MitoQ on oxidative outcomes related to the aging process. A predeveloped search strategy was run against MEDLINE (Ovid), EMBASE (Ovid), and CINAHL databases, which identified 10,255 articles of interest, with 27 of these finalised for use after screening. Three outcomes had sufficient data to meta-analyse nitrotyrosine concentration (190 animals, SMD -0.67, 95% CI (-1.30, -0.05), = 0.04), membrane potential (63 animals, MD 11.44, 95% CI (1.28-21.60), = 0.03), and protein carbonyl concentration (182 animals, SMD -0.13, 95% CI (-0.44, 0.18), = 0.41). MitoQ intervention produced a statistically significant reduction in nitrotyrosine concentration and increased membrane potential. MitoQ may be of some benefit in alleviating oxidative stress related to aging.
Topics: Aging; Biomarkers; Humans; Mitochondria; Organophosphorus Compounds; Ubiquinone
PubMed: 30116495
DOI: 10.1155/2018/8575263 -
International Journal of Molecular... Mar 2023Seminal plasma contains numerous extracellular vesicles (sEVs). Since sEVs are apparently involved in male (in)fertility, this systematic review focused on studies... (Review)
Review
Seminal plasma contains numerous extracellular vesicles (sEVs). Since sEVs are apparently involved in male (in)fertility, this systematic review focused on studies specifically investigating such relationship. Embase, PubMed, and Scopus databases were searched up to 31 December 2022, primarily identifying a total of 1440 articles. After processing for screening and eligibility, 305 studies were selected as they focused on sEVs, and 42 of them were considered eligible because they included the word fertility or a related word such as infertility, subfertility, fertilization, and recurrent pregnancy loss in the title, objective(s), and/or keywords. Only nine of them met the inclusion criteria, namely (a) conducting experiments aimed at associating sEVs with fertility concerns and (b) isolating and adequately characterizing sEVs. Six studies were conducted on humans, two on laboratory animals, and one on livestock. The studies highlighted some sEV molecules, specifically proteins and small non-coding RNAs, that showed differences between fertile and subfertile or infertile males. The content of sEVs was also related to sperm fertilizing capacity, embryo development, and implantation. Bioinformatic analysis revealed that several of the highlighted sEV fertility-related proteins would be cross-linked to each other and involved in biological pathways related to (i) EV release and loading and (ii) plasma membrane organization.
Topics: Pregnancy; Animals; Female; Male; Humans; Semen; Fertility; Infertility, Male; Spermatozoa; Extracellular Vesicles
PubMed: 36902244
DOI: 10.3390/ijms24054818 -
Biomedicines Aug 2022Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated... (Review)
Review
Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated by the epidermal growth factor. Intravenous and subcutaneous administration of trastuzumab have comparable clinical and pharmacological characteristics, but trastuzumab biosimilars are currently only available in intravenous form. Trastuzumab biosimilars are ultimately preferred by a proportion of patients, especially in cases where co-administration of other chemotherapeutic agents, such as trastuzumab and tucatinib, a small molecule of tyrosine kinase inhibitor, is required in patients with HER-positive metastatic breast cancer. Oncologists should be well-aware of the advantages of intravenously administered trastuzumab biosimilars over subcutaneous administration, certainly also taking into account the patient's preferences. Further cost-effectiveness analyses will be very important, along with expectations regarding successful concomitant subcutaneous administration of trastuzumab with other anticancer drugs, such as pertuzumab. This systematic review describes and analyzes the so-far published studies concerning the use of the available trastuzumab biosimilars in HER-positive early and metastatic breast cancer in terms of efficacy, safety, and cost-benefit ratio. An attempt was also made to draw some conclusions and to comment on future needs and perspectives.
PubMed: 36009592
DOI: 10.3390/biomedicines10082045