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Foot and Ankle Surgery : Official... Mar 2017Today, autogenous bone graft (ABG) is still considered as the gold standard for joint fusion. Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) which is of... (Comparative Study)
Comparative Study Meta-Analysis Review
Today, autogenous bone graft (ABG) is still considered as the gold standard for joint fusion. Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) which is of chemotactic and mitogenic to mesenchymal stem cells and possesses outstanding osteogenetic potentials has been used for ankle and foot fusion in recent years. The goal of this article is to evaluate the safety and efficacy of rhPDGF-BB versus ABG in foot and ankle fusion. The PubMed MEDLINE, EMBASE, Web of Science, and Cochrane Library were systematic searched. Finally, three randomized controlled trials (RCTs) with 634 patients were enrolled in this study. Results of radiologic effectiveness which included CT and radiographic union rates revealed that there was no significant difference between rhPDGF-BB approach and ABG approach. Analysis of clinical results held the same outcomes expect that ABG group was superior in long-term Short Form-12 physical component scores. The pooled results also demonstrated that rhPDGF-BB was as safe as ABG in foot and ankle surgery. However, autograft harvesting procedure has some drawbacks such as donor-site pain and morbidity, additional operation time, blood loss, and scarring, which can be overcome by rhPDGF-BB. Thus, rhPDGF-BB is a viable alternative to autograft in foot and ankle fusion surgery. Yet, more high-quality RCTs with long-term follow-up are still required to make the final conclusion.
Topics: Angiogenesis Inducing Agents; Ankle Joint; Arthrodesis; Becaplermin; Bone Transplantation; Humans; Joint Diseases; Proto-Oncogene Proteins c-sis; Transplantation, Autologous
PubMed: 28159040
DOI: 10.1016/j.fas.2016.02.001 -
Cureus Jul 2023Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early... (Review)
Review
Protective Effects of Long-Term Usage of Cyclo-Oxygenase-2 Inhibitors on Colorectal Cancer in Genetically Predisposed Individuals and Their Overall Effect on Prognosis: A Systematic Review.
Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early detection and treatment modalities, the prevention of CRC remains a critical goal. Cyclo-oxygenase-2 (COX-2) is an inducible enzyme involved in the production of pro-inflammatory prostaglandins, which play a crucial role in various cellular processes, including inflammation, cell proliferation, apoptosis, and angiogenesis. Elevated COX-2 expression has been consistently observed in colorectal tumors, indicating their role in the pathogenesis of cancer. COX-2 inhibitors, such as celecoxib and rofecoxib, have been studied as potentially effective treatment modalities due to their ability to decrease prostaglandin levels, which are generally higher in cancer patients. Aberrant prostaglandin production is linked to the adenoma-carcinoma sequence, during which adenomas turn dysplastic and accumulate enough damage to become malignant. COX-2 inhibitors have also been shown to modulate various signaling pathways involved in CRC development, such as wingless-related integration site/β-catenin (Wnt/β-catenin), mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathways. This systematic review aimed to evaluate the protective effects of long-term usage of COX-2 inhibitors on CRC in genetically predisposed individuals and their overall effect on the prognosis of the disease. The researchers conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and collected data from several databases, including PubMed, PubMed Central, Cochrane Library, and Web of Science. The search strategy combined keywords related to CRC, COX-2 inhibitors, protective effects, and prognosis. They identified 1189 articles and shortlisted 26 full-text articles that met the eligibility criteria. Quality assessment tools, such as the Assessment of Multiple Systematic Review (AMSTAR) for systematic reviews, the Cochrane bias assessment tool for randomized control trials, the scale for the assessment of narrative review articles (SANRA) checklist for narrative reviews, and the Joanna Briggs Institute (JBI) tool for cross-sectional studies and case reports, are used. This review's conclusions will assist in determining the effectiveness of COX-2 inhibitors to prevent CRC. This review may also contribute to developing guidelines for clinicians to manage genetically predisposed individuals with CRC. Furthermore, the results of this review will shed light on the potential of COX-2 inhibitors as a preventive measure against CRC in genetically predisposed individuals.
PubMed: 37588311
DOI: 10.7759/cureus.41939 -
Journal of Strength and Conditioning... Mar 2023Lee, CJ and Nicoll, JX. Time course evaluation of mitogen-activated protein kinase phosphorylation to resistance exercise: a systematic review. J Strength Cond Res...
Lee, CJ and Nicoll, JX. Time course evaluation of mitogen-activated protein kinase phosphorylation to resistance exercise: a systematic review. J Strength Cond Res 37(3): 710-725, 2023-Resistance exercise (RE) can increase the signaling activities of mitogen-activated protein kinases (MAPKs), specifically extracellular signal-regulated kinases 1/2 (ERK1/2), p90 ribosomal S6 kinases (p90RSK), c-Jun NH2-terminal kinases (JNK), and p38-MAPK. These RE-induced responses contribute to various intracellular processes modulating growth and development in skeletal muscles, playing an essential role in resistance training adaptations. The time course of MAPK phosphorylation to different RE conditions, such as training experience and varying loads, remains ambiguous. A systematic review was conducted to determine the effects of different post-RE recovery time points on the MAPK signaling cascade. In addition, the effects of loading and training statuses on MAPK responses were also investigated. The review was performed according to the preferred reporting items for systematic reviews and meta-analyses guidelines with a literature search incorporating 3 electronic databases. A modified version of the Downs and Black checklist was used to evaluate the methodological quality of the studies. The signaling responses were measured within a time range between immediately post-RE and >6 hours post-RE. Forty-four studies met the inclusion criteria, and all were classified as good-to-moderate methodological quality. Mitogen-activated protein kinase phosphorylation increased to different levels after RE, with the highest near the cessation of exercise. Although overall signaling was attenuated among trained individuals likely because of training adaptations, greater MAPK responses can be attributed to moderate loads of 65-85% 1RM regardless of the training experience. However, specific training-induced responses remain equivocal, and further investigations are required to determine the ideal training parameters to optimize anabolic intramuscular signaling, which may likely optimize resistance training adaptations.
Topics: Humans; Mitogen-Activated Protein Kinases; Phosphorylation; Resistance Training; Mitogen-Activated Protein Kinase 1; MAP Kinase Signaling System
PubMed: 36727997
DOI: 10.1519/JSC.0000000000004409 -
Bioorganic Chemistry Jan 2023Discoidin domain receptors (DDRs) are one of the less explored targets for the treatment of cancer which belong to receptor tyrosine kinases family. Discoidin domain... (Review)
Review
Discoidin domain receptor inhibitors as anticancer agents: A systematic review on recent development of DDRs inhibitors, their resistance and structure activity relationship.
Discoidin domain receptors (DDRs) are one of the less explored targets for the treatment of cancer which belong to receptor tyrosine kinases family. Discoidin domain receptors (DDRs) are a collagen-activated receptor tyrosine kinase and essential for controlling cellular functions like proliferation, morphogenesis, adhesion, differentiation, invasion, matrix remodeling, and migration. Although there are many targets and their inhibitors are reported which treat cancer. But most of drugs were amalgamated with moderate to severe side effects. This results in untreated cancerous cells. One of the reasons that cancer is considered challenging to treat because the targets were mutating rapidly and the inhibitor become less potent. The target identification is a tedious task for the researchers from the early 1990 s till date. When it comes to cancer, there has not been any magical stick to treat it undisputedly. Therefore, need for discovery of new receptor may helpful to overcome these difficulties. The development of DDR inhibitors has received a lot of attention ever since the target was discovered. In this review we have reported the development of most promising DDR1 and DDR2 small molecule inhibitors from the perspective of medicinal chemistry. We have also discussed about the clinical trials, recent patents, selectivity biological activity, and structure-activity relationship (SAR) of DDR1 and DDR2 inhibitors.
Topics: Humans; Antineoplastic Agents; Discoidin Domain Receptors; Neoplasms; Receptor Protein-Tyrosine Kinases; Receptors, Mitogen; Structure-Activity Relationship
PubMed: 36384067
DOI: 10.1016/j.bioorg.2022.106215 -
Archives of Cardiovascular Diseases 2020The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK)... (Meta-Analysis)
Meta-Analysis
Cardiovascular safety of rapidly accelerated fibrosarcoma B-type and/or mitogen-activated extracellular signal-regulated kinase inhibitors: A mixed approach combining a meta-analysis and a pharmacovigilance disproportionality analysis.
BACKGROUND
The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is not fully characterized.
AIM
To evaluate the cardiovascular adverse events risks related to BRAF and/or MEK inhibitors in randomized placebo-controlled clinical trials and in the real-life setting.
METHODS
We used two approaches. First, we conducted a systematic review and meta-analysis of randomized placebo-controlled clinical trials reporting the incidence of cardiovascular adverse events for BRAF and/or MEK inhibitors in cancer patients. Second, we performed a disproportionality analysis, using age- and sex-adjusted reporting odds ratios (arORs) and their 95% confidence intervals (CIs) from the World Health Organization's pharmacovigilance database (VigiBase®) of anticancer drug-associated reports, to investigate real-life data.
RESULTS
MEK inhibitors increased the risk of ejection fraction decrease (odds ratio [OR] 3.35, 95% CI 1.58-7.07), peripheral oedema (OR 2.87 95% CI 1.93-4.27) and syncope (OR 6.71, 95% CI 3.00-14.99) compared with placebo in randomized placebo-controlled clinical trials. BRAF and MEK inhibitor combination therapy further increased the risk of ejection fraction decrease. In the disproportionality analysis, we found over-reporting of ejection fraction decrease (arOR 8.42, 95% CI 7.03-10.09), peripheral oedema (arOR 1.39, 95% CI 1.17-1.66), syncope (arOR 1.56, 95% CI 1.22-1.99), torsade de pointes/QT prolongation (arOR 6.13, 95% CI 5.04-7.47) and supraventricular arrhythmias (arOR 1.50, 95% CI 1.21-1.85) for BRAF and MEK inhibitors. BRAF and MEK inhibitors were not associated with hypertension in either approach.
CONCLUSIONS
In conclusion, MEK inhibitors increase the risk of ejection fraction decrease, peripheral oedema and syncope in randomized placebo-controlled clinical trials. Real-life data confirm these findings, and suggested additional risks of torsade de pointes/QT prolongation and supraventricular arrhythmias with BRAF/MEK inhibitors.
Topics: Adverse Drug Reaction Reporting Systems; Aged; Antineoplastic Agents; Cardiovascular Diseases; Databases, Factual; Female; Fibrosarcoma; Humans; Male; Middle Aged; Mitogen-Activated Protein Kinase Kinases; Patient Safety; Pharmacovigilance; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32418884
DOI: 10.1016/j.acvd.2020.03.014 -
International Journal of Molecular... Dec 2016The physiological and pathophysiological roles of sex hormones have been well documented and the modulation of their effects is applicable in many current treatments. On... (Review)
Review
Overlapping molecular pathways between cannabinoid receptors type 1 and 2 and estrogens/androgens on the periphery and their involvement in the pathogenesis of common diseases (Review).
The physiological and pathophysiological roles of sex hormones have been well documented and the modulation of their effects is applicable in many current treatments. On the other hand, the physiological role of endocannabinoids is not yet clearly understood and the endocannabinoid system is considered a relatively new therapeutic target. The physiological association between sex hormones and cannabinoids has been investigated in several studies; however, its involvement in the pathophysiology of common human diseases has been studied separately. Herein, we present the first systematic review of molecular pathways that are influenced by both the cannabinoids and sex hormones, including adenylate cyclase and protein kinase A, epidermal growth factor receptor, cyclic adenosine monophosphate response element-binding protein, vascular endothelial growth factor, proto-oncogene serine/threonine-protein kinase, mitogen-activated protein kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, C-Jun N-terminal kinase and extracellular-signal-regulated kinases 1/2. Most of these influence cell proliferative activity. Better insight into this association may prove to be beneficial for the development of novel pharmacological treatment strategies for many common diseases, including breast cancer, endometrial cancer, prostate cancer, osteoporosis and atherosclerosis. The associations between cannabinoids, estrogens and androgens under these conditions are also presented and the molecular interactions are highlighted.
Topics: Androgens; Animals; Cannabinoids; Disease Susceptibility; Estrogens; Humans; Proto-Oncogene Mas; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Signal Transduction
PubMed: 27779654
DOI: 10.3892/ijmm.2016.2779 -
Reproductive Biology and Endocrinology... Aug 2023To systematically identify and narratively synthesize the evidence surrounding liposomal delivery of gene therapy and the outcome for ovarian cancer. (Review)
Review
OBJECTIVE
To systematically identify and narratively synthesize the evidence surrounding liposomal delivery of gene therapy and the outcome for ovarian cancer.
METHODS
An electronic database search of the Embase, MEDLINE and Web of Science from inception until July 7, 2023, was conducted to identify primary studies that investigated the effect of liposomal delivery of gene therapy on ovarian cancer outcomes. Retrieved studies were assessed against the eligibility criteria for inclusion.
RESULTS
The search yielded 564 studies, of which 75 met the inclusion criteria. Four major types of liposomes were identified: cationic, neutral, polymer-coated, and ligand-targeted liposomes. The liposome with the most evidence involved cationic liposomes which are characterized by their positively charged phospholipids (n = 37, 49.3%). Similarly, those with neutrally charged phospholipids, such as 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine, were highly researched as well (n = 25, 33.3%). Eight areas of gene therapy research were identified, evaluating either target proteins/transcripts or molecular pathways: microRNAs, ephrin type-A receptor 2 (EphA2), interleukins, mitogen-activated protein kinase (MAPK), human-telomerase reverse transcriptase/E1A (hTERT/EA1), suicide gene, p53, and multidrug resistance mutation 1 (MDR1).
CONCLUSION
Liposomal delivery of gene therapy for ovarian cancer shows promise in many in vivo studies. Emerging polymer-coated and ligand-targeted liposomes have been gaining interest as they have been shown to have more stability and specificity. We found that gene therapy involving microRNAs was the most frequently studied. Overall, liposomal genetic therapy has been shown to reduce tumor size and weight and improve survivability. More research involving the delivery and targets of gene therapy for ovarian cancer may be a promising avenue to improve patient outcomes.
Topics: Humans; Female; Liposomes; Ligands; MicroRNAs; Phospholipids; Genetic Therapy; Ovarian Neoplasms
PubMed: 37612696
DOI: 10.1186/s12958-023-01125-2 -
Medicine Dec 2016The receptor for advanced glycosylation end products (RAGE) has been widely linked to diabetic atherosclerosis, but its effects on coronary artery disease (CAD) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The receptor for advanced glycosylation end products (RAGE) has been widely linked to diabetic atherosclerosis, but its effects on coronary artery disease (CAD) and ischemic stroke (IS) remain controversial. The Gly82Ser polymorphism is located in the ligand-binding V domain of RAGE, suggesting a possible influence of this variant on RAGE function. The aim of the present study is to clarify the association between the RAGE Gly82Ser polymorphism and susceptibility to CAD and IS.
METHODS
Eligible studies were identified through a comprehensive literature search. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association of Gly82Ser polymorphism with CAD and IS risk. Fixed- or random-effects model was used depending on the heterogeneity between studies. A funnel plot and Egger linear regression test were applied to assess publication bias. We also performed subgroup analyses to investigate potential sources of heterogeneity.
RESULTS
A total of 16 eligible articles containing 18 studies were analyzed. The pooled analysis indicated that the Gly82Ser polymorphism significantly increased CAD risk in recessive and homozygous genetic models (SS vs GS + GG: OR = 1.34, 95% CI = 1.09-1.64; SS vs GG: OR = 1.38, 95% CI = 1.12-1.71). A significant association between the Gly82Ser polymorphism and IS risk was observed in all tested models except the heterozygous genetic model (GS + SS vs GG: OR = 1.20, 95% CI = 1.04-1.38; SS vs GS + GG: OR = 2.20, 95% CI = 1.74-2.78; SS vs GG: OR = 2.23, 95% CI = 1.72-2.91; S vs G: OR = 1.32, 95% CI = 1.05-1.65). Subgroup analysis suggested an association between CAD and IS risk and the Gly82Ser polymorphism in the Chinese population, but not in the non-Chinese population.
CONCLUSIONS
The current meta-analysis suggests that the RAGE Gly82Ser polymorphism is associated with an increased risk of CAD and IS, especially in the Chinese population. However, better-designed studies with larger sample sizes are needed to validate the results.
Topics: Antigens, Neoplasm; Brain Ischemia; Coronary Artery Disease; Female; Genetic Predisposition to Disease; Humans; Incidence; Male; Mitogen-Activated Protein Kinases; Polymorphism, Genetic; Risk Assessment; Sensitivity and Specificity; Stroke
PubMed: 27930580
DOI: 10.1097/MD.0000000000005593 -
Seminars in Oncology 2023Available evidence suggests that in patients with advanced BRAF V600-mutant melanoma treated with the combination of BRAF and MEK inhibitors, gender could be associated... (Meta-Analysis)
Meta-Analysis Review
Available evidence suggests that in patients with advanced BRAF V600-mutant melanoma treated with the combination of BRAF and MEK inhibitors, gender could be associated with survival outcome. We performed a systematic review and meta-analysis of all randomized clinical trials (RCTs) testing the combination of BRAF and MEK inhibitors, to assess the interaction between treatment effect and patients' gender. We searched PubMed, MEDLINE, Embase, and Scopus, for phase II and III RCTs up to January 30, 2022. We included all RCTs that enrolled patients with BRAF V600-mutant advanced cutaneous melanoma and assessed combinations of BRAF and MEK inhibitors versus BRAF inhibitor monotherapy. Our aim was to assess differences if any in treatment efficacy between men and women, measured in terms of the differences in progression-free survival (PFS) and overall survival (OS) log-hazard ratios (log-HRs). We calculated the pooled PFS- and OS-HRs with 95% confidence intervals (CIs) in men and women using a random-effects model and assessed the heterogeneity between the estimates using an interaction test. Five RCTs that enrolled a total of 2,113 patients were included in the analysis. In women, the combination of BRAF and MEK inhibitors halved the risk of progression or death as compared with BRAF inhibitor monotherapy with a pooled PFS-HR of 0.50 (95%CI 0.41-0.61). In men, the benefit obtained with BRAF and MEK inhibitors was smaller with a pooled PFS-HR of 0.63 (95%CI 0.54-0.74), P-heterogeneity = .05. A similar trend was observed for OS where the pooled OS-HR was 0.62 (95%CI 0.48-0.80) in women and only 0.78, (95%CI 0.67-0.92) in men, P-heterogeneity = 0.11. These results support meaningful gender-based heterogeneity of response to combination of BRAF and MEK inhibitors targeted therapy in patients with advanced BRAF-mutant melanoma, that should be considered in future research to improve treatment effectiveness.
Topics: Male; Female; Humans; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Melanoma; Skin Neoplasms; Protein Kinase Inhibitors; Mitogen-Activated Protein Kinase Kinases; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36967333
DOI: 10.1053/j.seminoncol.2023.03.003 -
European Psychiatry : the Journal of... Nov 2021Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients' quality of life. We hypothesized the comorbidity of depression,...
BACKGROUND
Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients' quality of life. We hypothesized the comorbidity of depression, anxiety syndromes, or symptoms as attributable to biological mechanisms that the combined diseases share.
METHODS
We conducted a systematic review based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement searching into PubMed, PsycInfo, and Scopus databases. We examined the literature regarding the comorbidity of psoriasis (Ps), atopic dermatitis (AD), or hidradenitis suppurativa with depression and/or anxiety in adults ≥18 years and the hypothetical shared underlying biological mechanisms.
RESULTS
Sixteen studies were analyzed, mostly regarding Ps and AD. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling and nuclear factor kappa-light-chain-enhancer of activated B cells/p38 mitogen-activated protein kinase pathways arose as shared mechanisms in Ps animal models with depression- and/or anxiety-like behaviors. Activated microglia and neuroinflammatory responses emerged in AD depressive models. As to genetic studies, atopic-dermatitis patients with comorbid anxiety traits carried the short variant of serotonin transporter and a polymorphism of the human translocator protein gene. A GA genotype of catechol-O-methyltransferase gene was instead associated with Ps. Reduced natural killer cell activity, IL-4, serotonin serum levels, and increased plasma cortisol and IgE levels were hypothesized in comorbid depressive AD patients. In Ps patients with comorbid depression, high serum concentrations of IL-6 and IL-18, as well as IL-17A, were presumed to act as shared inflammatory mechanisms.
CONCLUSIONS
Further studies should investigate mental disorders and chronic skin diseases concurrently across patients' life course and identify their temporal relation and biological correlates. Future research should also identify biological characteristics of individuals at high risk of the comorbid disorders and associated complications.
Topics: Animals; Anxiety; Catechol O-Methyltransferase; Comorbidity; Depression; Dermatitis, Atopic; Hidradenitis Suppurativa; Humans; Psoriasis; Quality of Life
PubMed: 34819201
DOI: 10.1192/j.eurpsy.2021.2249