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Biomedicine & Pharmacotherapy =... Nov 2023Humans rely on vision as their most important sense. This is accomplished by photoreceptors (PRs) in the retina that detect light but cannot function without the support... (Review)
Review
Humans rely on vision as their most important sense. This is accomplished by photoreceptors (PRs) in the retina that detect light but cannot function without the support and maintenance of the retinal pigment epithelium (RPE). In subretinal hemorrhage (SRH), blood accumulates between the neurosensory retina and the RPE or between the RPE and the choroid. Blood breakdown products subsequently damage PRs and the RPE and lead to poor vision and blindness. Hence, there is a high need for options to preserve the retina and visual functions. We conducted a systematic review of the literature in accordance with the PRISMA guidelines to identify the cell death mechanisms in RPE and PRs after SRH to deepen our understanding of the pathways involved. After screening 736 publications published until November 8, 2022, we identified 19 records that assessed cell death in PRs and/or RPE in experimental models of SRH. Among the different cell death mechanisms, apoptosis was the most widely investigated mechanism (11 records), followed by ferroptosis (4), whereas necroptosis, pyroptosis, and lysosome-dependent cell death were only assessed in one study each. We discuss different therapeutic options that were assessed in these studies, including the removal of the hematoma/iron chelation, cytoprotection, anti-inflammatory agents, and antioxidants. Further systematic investigations will be necessary to determine the exact cell death mechanisms after SRH with respect to different blood breakdown components, cell types, and time courses. This will form the basis for the development of novel treatment options for SRH.
Topics: Humans; Retinal Pigment Epithelium; Retina; Cell Death; Photoreceptor Cells; Hemorrhage
PubMed: 37742603
DOI: 10.1016/j.biopha.2023.115572 -
Medicine Jul 2018BCL-2 Associated X (BAX) is an important modulator of apoptosis. The associations between BAX gene polymorphism and cancer susceptibility and prognosis in different... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
BCL-2 Associated X (BAX) is an important modulator of apoptosis. The associations between BAX gene polymorphism and cancer susceptibility and prognosis in different ethnic groups and types of cancer have yielded controversial results. To reconcile the results, a systematic review followed by meta-analysis was performed to assess the associations.
METHODS
A systematic search of Medline database (PubMed), EMBASE, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang databases for publications on BAX polymorphisms, and susceptibility and prognosis was carried out until July 2017. Retrieved 14 articles met the inclusions. Summary odds ratios (ORs) and hazard ratios (HRs) with their 95% confidence intervals (CIs) were harnessed to determine the strength of correlation between BAX polymorphisms and cancer susceptibility and prognosis, which were combined using fixed- or random-effects models as appropriate.
RESULTS
A total of 12 trials involving 3321 cases and 3209 controls were included in our pooled analysis regarding the polymorphisms and the susceptibility of cancers. Overall, results of the present meta-analysis demonstrated that there was no significant association between BAX polymorphisms and susceptibility of cancers (OR = 1.052, 95% CI: 0.827-1.339, P = .679, A vs G). Even in a stratified analysis by ethnicity and the sources of control groups, the results were consistent. Four retrospective studies of 549 cases qualified for meta-analysis were identified to set forth the associations of the polymorphisms with cancer prognosis. Our results suggested that BAX gene polymorphisms were significantly associated with unfavorable prognosis (HR = 1.735, 95% CI: 1.368-2.202, P = .000, GG vs GA/AA).
CONCLUSION
There is no significant association between BAX gene polymorphism and cancer susceptibility, but it probably contributes to increased adverse prognosis to cancer.
Topics: Genetic Predisposition to Disease; Humans; Neoplasms; Polymorphism, Genetic; Prognosis; bcl-2-Associated X Protein
PubMed: 30024563
DOI: 10.1097/MD.0000000000011591 -
Progres En Urologie : Journal de... Feb 2014A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the... (Review)
Review
INTRODUCTION
A controversy animates the literature on the potential role of the renin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the involvement of this pathway in cancer, and more specifically in urological cancers.
MATERIAL AND METHOD
We made a systematic review of articles referenced in Pubmed, using the following keywords alone or combined: cancer, renin, angiotensin, VEGF, AT1R, antagonists of angiotensin-2 receptors, inhibitors of angiotensinogen converting.
RESULTS
Many types of cancers overexpress AT1-R in their tumoral tissues (breast, stomach, bladder, astrocytoma, glioblastoma, ovary, uterus, pancreas, kidney, prostate, adrenal gland). Ang-II can induce VEGF-A expression and promote neoangiogenesis, but also can trigger different molecular pathways involved in cell proliferation or inhibit apoptosis. Several xenograft murin models demonstrated anti-tumoral efficacy of RAS blockers, alone or using combined therapies, targeting angiogenesis and slowing down tumor growth. Retrospective studies in patients have also revealed a better progression-free survival and a better response to therapies in those treated with RAS blockers.
CONCLUSION
Many data seem to demonstrate the involvement of the RAS in carcinogenesis, as well as anti-tumoral effect of RAS blockers in addition to anti-cancer treatments. Clinical data are now expected to confirm these experimental findings.
Topics: Humans; Renin-Angiotensin System; Urologic Neoplasms
PubMed: 24485075
DOI: 10.1016/j.purol.2013.09.010 -
Frontiers in Pharmacology 2022Cancers are a potential cause of death worldwide and represent a massive burden for healthcare systems. Treating cancers requires substantial resources, including...
Cancers are a potential cause of death worldwide and represent a massive burden for healthcare systems. Treating cancers requires substantial resources, including skilled personnel, medications, instruments, and funds. Thus, developing cancer prevention and treatment measures is necessary for healthcare personnel and patients alike. (Polygonaceae family) is a plant used as a culinary ingredient. It exhibits several pharmacological activities, such as antibacterial, antifungal, antioxidant, anti-inflammatory, and anticancer. Several classes of phytochemical constituents of have been reported. The important ones might be polyphenol and flavonoid derivatives. In this systematic review, the activities of against cancerous cells were determined and summarized. Data were obtained through a systematic search of electronic databases (EMBASE, PubMed, Scopus, Thai Thesis Database, Science Direct and Clinical Key). Eight studies met the eligibility criteria. The cancerous cell lines used in the studies were lymphoma, leukemia, oral, lung, breast, colon, and liver cancer cells. Based on this review, extracts significantly affected Epstein-Barr virus (EBV) genome-carrying human lymphoblastoid (Raji), mouse lymphocytic leukemia (P388), human acute lymphocytic leukemia (Jurkat), breast adenocarcinoma (MCF-7), human colon adenocarcinoma (HT-29), human T lymphoblast (MOLT-4), human promyelocytic leukemia cell line (HL-60), human hepatocellular carcinoma (HepG2), and oral squamous cell carcinoma (SAS, SCC-9, HSC-3) through induction of cell apoptosis, arrest of the cell cycle, inhibition of cell proliferation, migration, and colonization. The molecular mechanism of against cancers was reported to involve suppressing essential proteins required for cell proliferation, colonization, migration, apoptosis, and angiogenesis. They were survivin, cyclin-D, cyclooxygenase 2 (COX-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGF-A). The extract of was also involved in the protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway by inhibiting the expression of Akt, phosphorylated Akt, mTOR, and phosphorylated mTOR. From the key results of this review, is a promising chemotherapy and chemopreventive agent. Further investigation of its pharmacological activity and mechanism of action should be conducted using standardized extracts. experiments and clinical trials are required to confirm the anticancer activity.
PubMed: 35571080
DOI: 10.3389/fphar.2022.875016 -
Frontiers in Pharmacology 2023Cancer is a disease with a high fatality rate representing a serious threat to human health. Researchers have tried to identify effective anticancer drugs. Licorice is a...
Cancer is a disease with a high fatality rate representing a serious threat to human health. Researchers have tried to identify effective anticancer drugs. Licorice is a widely used traditional Chinese medicine with various pharmacological properties, and licorice-derived flavonoids include licochalcones like licochalcone A, licochalcone B, licochalcone C, licochalcone D, licochalcone E, and licochalcone H. By regulating the expression in multiple signaling pathways such as the EGFR/ERK, PI3K/Akt/mTOR, p38/JNK, JAK2/STAT3, MEK/ERK, Wnt/β-catenin, and MKK4/JNK pathways, and their downstream proteins, licochalcones can activate the mitochondrial apoptosis pathway and death receptor pathway, promote autophagy-related protein expression, inhibit the expression of cell cycle proteins and angiogenesis factors, regulate autophagy and apoptosis, and inhibit the proliferation, migration, and invasion of cancer cells. Among the licochalcones, the largest number of studies examined licochalcone A, far more than other licochalcones. Licochalcone A not only has prominent anticancer effects but also can be used to inhibit the efflux of antineoplastic drugs from cancer cells. Moreover, derivatives of licochalcone A exhibit strong antitumor effects. Currently, most results of the anticancer effects of licochalcones are derived from cell experiments. Thus, more clinical studies are needed to confirm the antineoplastic effects of licochalcones.
PubMed: 36755942
DOI: 10.3389/fphar.2023.1074506 -
Plants (Basel, Switzerland) Dec 2021The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant focusing on compounds harboring activities... (Review)
Review
The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant focusing on compounds harboring activities against cancer models detailed in depth herein at both in vitro and in vivo preclinical levels. The review was conducted through Pubmed and Google Scholar. Nineteen out of the forty-two secondary metabolites isolated to date from displayed interesting in vitro and/or in vivo antitumor activities. They belonged to alkaloid (Erysodine), triterpenes (Erythrodiol, maniladiol, oleanolic acid), prenylated isoflavonoids (senegalensin, erysenegalensein E, erysenegalensein M, alpinumisoflavone, derrone, warangalone), flavonoids (erythrisenegalone, senegalensein, lupinifolin, carpachromene) and pterocarpans (erybraedine A, erybraedine C, phaseollin). Among the isoflavonoids called "erysenegalensein", only erysenealenseins E and M have been tested for their anticancerous properties and turned out to be cytotoxic. Although the stem bark is the most frequently used part of the plant, all pterocarpans were isolated from roots and all alkaloids from seeds. The mechanisms of action of its metabolites include apoptosis, pyroptosis, autophagy and mitophagy via the modulation of cytoplasmic proteins, miRNA and enzymes involved in critical pathways deregulated in cancer. Alpinumisoflavone and oleanolic acid were studied in a broad spectrum of cancer models both in vitro and in preclinical models in vivo with promising results. Other metabolites, including carpachromen, phaseollin, erybraedin A, erysenegalensein M and maniladiol need to be further investigated, as they display potent in vitro effects.
PubMed: 35009024
DOI: 10.3390/plants11010019 -
Frontiers in Immunology 2023Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even... (Review)
Review
Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even endanger life. Acupuncture is widely accepted and applied in the treatment of sepsis, and breakthroughs have been made regarding its mechanism of action in recent years. In this review, we systematically discuss the current clinical applications of acupuncture in the treatment of sepsis and focus on the mechanisms of acupuncture in animal models of systemic inflammation. In clinical research, acupuncture can not only effectively inhibit excessive inflammatory reactions but also improve the immunosuppressive state of patients with sepsis, thus maintaining immune homeostasis. Mechanistically, a change in the acupoint microenvironment is the initial response link for acupuncture to take effect, whereas PROKR2 neurons, high-threshold thin nerve fibres, cannabinoid CB2 receptor (CB2R) activation, and Ca influx are the key material bases. The cholinergic anti-inflammatory pathway of the vagus nervous system, the adrenal dopamine anti-inflammatory pathway, and the sympathetic nervous system are key to the transmission of acupuncture information and the inhibition of systemic inflammation. In MODS, acupuncture protects against septic organ damage by inhibiting excessive inflammatory reactions, resisting oxidative stress, protecting mitochondrial function, and reducing apoptosis and tissue or organ damage.
Topics: Animals; Humans; Sepsis; Acupuncture Therapy; Inflammation; Vagus Nerve
PubMed: 37753078
DOI: 10.3389/fimmu.2023.1242640 -
International Journal of Medical... 2021Neutrophil extracellular traps (NETs) have been implicated in host immune responses. Attempts have been made to examine how NETs affect the pathogenesis of...
Neutrophil extracellular traps (NETs) have been implicated in host immune responses. Attempts have been made to examine how NETs affect the pathogenesis of complications such as autoimmune and vascular disorders. This study aimed to explore the relationship between NETs and vasculitis. The current study entailed the searching of PsycINFO, PubMed, Web of Science, and CINAHL for articles related to the research topic. The search terms and phrases included "vasculitis," "NETs," "neutrophil extracellular traps," "NETosis," and "pathogenesis." The search was limited to articles published between 2009 and 2019. Researchers have shown that NETs contribute to the pathogenesis of vasculitis through different mechanisms and processes, including renal failure and vascular damage. The protective effects of NETs have also been highlighted. Overall, some scholars have shown the effectiveness of using DNase I and the PAD4 inhibitor Cl-amidine to treat vasculitis by restricting NET formation. However, observations have been noted in only animal experimental models. Neutrophil hyperactivity and its role in vasculitis are not yet fully understood. More studies aiming to determine the accurate function of NETs in vasculitis pathogenesis, particularly in humans, should be undertaken. Intensive research on NETs and vasculitis can increase the knowledge of medical practitioners and contribute to the development of new treatment methods to enhance patient outcomes in the future.
Topics: Animals; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Apoptosis; Deoxyribonuclease I; Disease Models, Animal; Extracellular Traps; Giant Cell Arteritis; Humans; Neutrophils; Ornithine; Protein-Arginine Deiminase Type 4; Regulated Cell Death; Takayasu Arteritis
PubMed: 33746569
DOI: 10.7150/ijms.53728 -
Frontiers in Pediatrics 2022The links of sedentary behavior and physical activity with health outcomes in children and adolescents is well known. However, the molecular mechanisms involved are...
BACKGROUND
The links of sedentary behavior and physical activity with health outcomes in children and adolescents is well known. However, the molecular mechanisms involved are poorly understood. We aimed to synthesize the current knowledge of the association of sedentary behavior and physical activity (acute and chronic effects) with gene expression and epigenetic modifications in children and adolescents.
METHODS
PubMed, Web of Science, and Scopus databases were systematically searched until April 2022. A total of 15 articles were eligible for this review. The risk of bias assessment was performed using the Joanna Briggs Institute Critical Appraisal Tool for Systematic Reviews and/or a modified version of the Downs and Black checklist.
RESULTS
Thirteen studies used candidate gene approach, while only 2 studies performed high-throughput analyses. The candidate genes significantly linked to sedentary behavior or physical activity were: , , -α, , , , and . Non-coding Ribonucleic acids (RNAs) regulated by sedentary behavior or physical activity were: miRNA-222, miRNA-146, miRNA-16, miRNA-126, miR-320, and long non-coding RNA MALAT1. These molecules are involved in inflammation, immune function, angiogenic process, and cardiovascular disease. Transcriptomics analyses detected thousands of genes that were altered following an acute bout of physical activity and are linked to gene pathways related to immune function, apoptosis, and metabolic diseases.
CONCLUSION
The evidence found to date is rather limited. Multidisciplinary studies are essential to characterize the molecular mechanisms in response to sedentary behavior and physical activity in the pediatric population. Larger cohorts and randomized controlled trials, in combination with multi-omics analyses, may provide the necessary data to bring the field forward.
SYSTEMATIC REVIEW REGISTRATION
[www.ClinicalTrials.gov], identifier [CRD42021235431].
PubMed: 35813370
DOI: 10.3389/fped.2022.917152 -
The Cochrane Database of Systematic... Jan 2008Ischaemic preconditioning is a mechanism for reducing organ ischaemia reperfusion injury by a brief period of organ ischaemia. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ischaemic preconditioning is a mechanism for reducing organ ischaemia reperfusion injury by a brief period of organ ischaemia.
OBJECTIVES
To assess the advantages and disadvantages of ischaemic preconditioning during donor hepatectomy for liver transplant recipients.
SEARCH STRATEGY
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until March 2007.
SELECTION CRITERIA
We included only randomised clinical trials comparing ischaemic preconditioning versus no ischaemic preconditioning during donor liver retrievals performed in humans in this review (irrespective of language or publication status).
DATA COLLECTION AND ANALYSIS
We collected the data on the characteristics of the trial, methodological quality of the trials, mortality, initial poor function, primary graft non-function, re-transplantation, liver function tests, markers of neutrophil activation, apoptosis, and intensive therapy unit stay. We analysed the data with both the fixed-effect and the random-effects models. For each binary outcome we calculated the odds ratio (OR) with 95% confidence intervals (CI) based on intention-to-treat analysis. For continuous outcomes, we calculated the weighted mean difference (WMD) with 95% CI.
MAIN RESULTS
In three trials, 162 cadaveric liver donor retrievals were randomised; 78 to ischaemic preconditioning and 84 to no ischaemic preconditioning. In one trial, 15 living donor liver retrievals were randomised; 10 to ischaemic preconditioning and 5 to no ischaemic preconditioning. Three of the four trials were of low-risk bias. There was no statistically significant difference in mortality, initial poor function, primary graft non-function, or re-transplant. There was no statistically significant difference in the transaminase activity, bilirubin level, prothrombin activity, median myeloperoxidase activity, median cluster of differentiation eight (CD8) expression, median inducible nitrogen oxide synthetase, or apoptosis. There was also no significant difference in the median intensive therapy unit stay of the recipients.
AUTHORS' CONCLUSIONS
There is currently no evidence to support or refute the use of ischaemic preconditioning in donor liver retrievals. Further studies are necessary to identify the optimal ischaemic preconditioning stimulus. Further randomised clinical trials are necessary to evaluate the role of ischaemic preconditioning in donor liver retrievals involving a period of warm reperfusion, following ischaemic preconditioning during donor liver retrieval.
Topics: Humans; Ischemic Preconditioning; Liver; Liver Transplantation; Randomized Controlled Trials as Topic; Reperfusion Injury
PubMed: 18254099
DOI: 10.1002/14651858.CD006315.pub2