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Cell Stress Sep 2019The supply of oxygen and nutrients to the brain is vital for its function and requires a complex vascular network that, when disturbed, results in profound neurological... (Review)
Review
The supply of oxygen and nutrients to the brain is vital for its function and requires a complex vascular network that, when disturbed, results in profound neurological dysfunction. As part of the pathology in stroke, endothelial cells die. As endothelial cell death affects the surrounding cellular environment and is a potential target for the treatment and prevention of neurological disorders, we have systematically reviewed important aspects of endothelial cell death with a particular focus on stroke. After screening 2876 publications published between January 1, 2010 and August 7, 2019, we identified 154 records to be included. We found that endothelial cell death occurs rapidly as well as later after the onset of stroke conditions. Among the different cell death mechanisms, apoptosis was the most widely investigated (92 records), followed by autophagy (20 records), while other, more recently defined mechanisms received less attention, such as lysosome-dependent cell death (2 records) and necroptosis (2 records). We also discuss the differential vulnerability of brain cells to injury after stroke and the role of endothelial cell death in the no-reflow phenomenon with a special focus on the microvasculature. Further investigation of the different cell death mechanisms using novel tools and biomarkers will greatly enhance our understanding of endothelial cell death. For this task, at least two markers/criteria are desirable to determine cell death subroutines according to the recommendations of the Nomenclature Committee on Cell Death.
PubMed: 31799500
DOI: 10.15698/cst2019.11.203 -
Neural Regeneration Research Jun 2023Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding... (Review)
Review
Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding and aggregation due to aging, intrinsic mutations, or autophagy dysregulation. This systematic review summarizes the effects of trehalose on its underlying mechanisms in animal models of selected neurodegenerative disorders (tau pathology, synucleinopathy, polyglutamine tract, and motor neuron diseases). All animal studies on neurodegenerative diseases treated with trehalose published in Medline (accessed via EBSCOhost) and Scopus were considered. Of the 2259 studies screened, 29 met the eligibility criteria. According to the SYstematic Review Center for Laboratory Animal Experiment (SYRCLE) risk of bias tool, we reported 22 out of 29 studies with a high risk of bias. The present findings support the purported role of trehalose in autophagic flux and protein refolding. This review identified several other lesser-known pathways, including modifying amyloid precursor protein processing, inhibition of reactive gliosis, the integrity of the blood-brain barrier, activation of growth factors, upregulation of the downstream antioxidant signaling pathway, and protection against mitochondrial defects. The absence of adverse events and improvements in the outcome parameters were observed in some studies, which supports the transition to human clinical trials. It is possible to conclude that trehalose exerts its neuroprotective effects through both direct and indirect pathways. However, heterogeneous methodologies and outcome measures across the studies rendered it impossible to derive a definitive conclusion. Translational studies on trehalose would need to clarify three important questions: 1) bioavailability with oral administration, 2) optimal time window to confer neuroprotective benefits, and 3) optimal dosage to confer neuroprotection.
PubMed: 36453391
DOI: 10.4103/1673-5374.360164 -
BMC Medicine Jun 2022The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well studied. There is a lack of a comprehensive study to elucidate the role of genetic factors in the survival of ALS.
METHODS
The published studies were systematically searched and obtained from PubMed, EMBASE, and the Cochrane Library without any language restrictions from inception to Oct 27, 2021. A network meta-analysis for ALS causative/risk genes and a systematic review and pairwise meta-analysis for other genetic modifiers were conducted. The PROSPERO registration number: CRD42022311646.
RESULTS
A total of 29,764 potentially relevant references were identified, and 71 papers were eligible for analysis based on pre-decided criteria, including 35 articles in network meta-analysis for 9 ALS causative/risk genes, 17 articles in pairwise meta-analysis for four genetic modifiers, and 19 articles described in the systematic review. Variants in three genes, including ATXN2 (HR: 3.6), C9orf72 (HR: 1.6), and FUS (HR:1.8), were associated with short survival of ALS, but such association was not identified in SOD1, TARDBP, TBK1, NEK1, UBQLN2, and CCNF. In addition, UNC13A rs12608932 CC genotype and ZNF521B rs2275294 C allele also caused a shorter survival of ALS; however, APOE ε4 allele and KIFAP3 rs1541160 did not be found to have any effect on the survival of ALS.
CONCLUSIONS
Our study summarized and contrasted evidence for prognostic genetic factors in ALS and would help to understand ALS pathogenesis and guide clinical trials and drug development.
Topics: Adaptor Proteins, Signal Transducing; Alleles; Amyotrophic Lateral Sclerosis; Autophagy-Related Proteins; Genotype; Humans; Network Meta-Analysis
PubMed: 35754054
DOI: 10.1186/s12916-022-02411-3 -
Nutrients Mar 2024Periodontitis is an inflammatory condition initiated by oral bacteria and is associated with several systemic diseases. Quercetin is an anti-inflammatory and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periodontitis is an inflammatory condition initiated by oral bacteria and is associated with several systemic diseases. Quercetin is an anti-inflammatory and anti-bacterial poly-phenol present in various foods. The aim of this meta-analysis was the evaluation of the effects of quercetin administration in animal models of experimental periodontitis.
METHODS
A systematic search was performed in electronic databases using the following search terms: "periodontitis" or "periodontal disease" or "gingivitis" and "quercetin" or "cyanidanol" or "sophoretin" or "pentahydroxyflavone". In vivo preclinical animal models of experimental periodontal disease with a measurement of alveolar bone loss were included in the analysis. The risk of bias of the included studies was assessed using the SYRCLE tool.
RESULTS
The systematic search yielded 335 results. Five studies were included, four of them qualified for a meta-analysis. The meta-analysis showed that quercetin administration decreased alveolar bone loss (τ = 0.31, 1.88 mm 95%CI: 1.09, 2.67) in experimental periodontal disease animal models. However, the risk of bias assessment indicated that four SYRCLE domains had a high risk of bias.
CONCLUSIONS
Quercetin diminishes periodontal bone loss and prevents disease progression in animal models of experimental periodontal disease. Quercetin might facilitate periodontal tissue hemostasis by reducing senescent cells, decreasing oxidative stress via SIRT1-induced autophagy, limiting inflammation, and fostering an oral bacterial microenvironment of symbiotic microbiota associated with oral health. Future research will show whether and how the promising preclinical results can be translated into the clinical treatment of periodontal disease.
Topics: Animals; Quercetin; Alveolar Bone Loss; Periodontal Diseases; Periodontitis; Gingivitis
PubMed: 38474862
DOI: 10.3390/nu16050735 -
Nutrients May 2024Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate,... (Review)
Review
Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.
Topics: Humans; Biological Products; Liver Neoplasms; Apoptosis; Signal Transduction; Antineoplastic Agents; Animals; Antineoplastic Agents, Phytogenic; Autophagy
PubMed: 38892575
DOI: 10.3390/nu16111642 -
Cell Cycle (Georgetown, Tex.) Nov 2020Autophagy, an evolutionarily conserved mechanism that promotes cell survival by recycling nutrients and degrading long-lived proteins and dysfunctional organelles, is an...
Autophagy, an evolutionarily conserved mechanism that promotes cell survival by recycling nutrients and degrading long-lived proteins and dysfunctional organelles, is an important defense mechanism, and its attenuation has been well documented in senescence and aging-related diseases. Abdominal aortic aneurysm (AAA), a well-known aging-related disease, has been defined as a chronic degenerative process in the abdominal aortic wall; however, the complete mechanism is unknown, and a clinical treatment is lacking. Accumulating evidence has recently revealed that numerous drugs that can induce autophagy are effective in the treatment of AAA. The purpose of this systematic review was to focus on the cross-talk between autophagy and high-risk factors and the potential pathogenesis of AAA to understand not only the host defense and pathogenesis but also potential treatments.
Topics: Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Autophagy; Humans
PubMed: 32960711
DOI: 10.1080/15384101.2020.1823731 -
International Journal of Molecular... Aug 2020Melanoma is the fourth most common type of cancer diagnosed in Australians after breast, prostate, and colorectal cancers. While there has been substantial progress in...
Melanoma is the fourth most common type of cancer diagnosed in Australians after breast, prostate, and colorectal cancers. While there has been substantial progress in the treatment of cancer in general, malignant melanoma, in particular, is resistant to existing medical therapies requiring an urgent need to develop effective treatments with lesser side effects. Several studies have shown that "cannabinoids", the major compounds of the plant, can reduce cell proliferation and induce apoptosis in melanoma cells. Despite prohibited use of in most parts of the world, in recent years there have been renewed interests in exploiting the beneficial health effects of the plant-derived compounds. Therefore, the aim of this study was in the first instance to review the evidence from in vivo studies on the effects of cannabinoids on melanoma. Systematic searches were carried out in PubMed, Embase, Scopus, and ProQuest Central databases for relevant articles published from inception. From a total of 622 potential studies, six in vivo studies assessing the use of cannabinoids for treatment of melanoma were deemed eligible for the final analysis. The findings revealed cannabinoids, individually or combined, reduced tumor growth and promoted apoptosis and autophagy in melanoma cells. Further preclinical and animal studies are required to determine the underlying mechanisms of cannabinoids-mediated inhibition of cancer-signaling pathways. Well-structured, randomized clinical studies on cannabinoid use in melanoma patients would also be required prior to cannabinoids becoming a viable and recognized therapeutic option for melanoma treatment in patients.
Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cannabinoids; Cell Proliferation; Clinical Trials as Topic; Disease Models, Animal; Humans; Melanocytes; Melanoma; Mice; Skin Neoplasms; Survival Analysis; Tumor Burden; Tumor Cells, Cultured; Melanoma, Cutaneous Malignant
PubMed: 32839414
DOI: 10.3390/ijms21176040 -
Frontiers in Neurology 2021Subarachnoid hemorrhage (SAH) is a severe disease characterized by sudden headache, loss of consciousness, or focal neurological deficits. Melatonin has been reported...
Subarachnoid hemorrhage (SAH) is a severe disease characterized by sudden headache, loss of consciousness, or focal neurological deficits. Melatonin has been reported as a potential neuroprotective agent of SAH. It provides protective effects through the anti-inflammatory effects or the autophagy pathway. Our systematic review aims to evaluate the efficacy of melatonin administration on experimental SAH animals and offer support for the future clinical trial design of the melatonin treatment following SAH. The following online databases were searched for experimentally controlled studies of the effect of melatonin on SAH models: PubMed, Web of Knowledge, Embase, and China National Knowledge Infrastructure (all until March 2021). The melatonin effect on the brain water content (BWC) and neurological score (NS) were compared between the treatment and control groups using the standardized mean difference (SMD). Our literature identified 160 possible articles, and most of them were excluded due to duplication ( = 69) and failure to meet the inclusion criteria ( = 56). After screening the remaining 35 articles in detail, we excluded half of them because of no relevant outcome measures ( = 16), no relevant interventions ( = 3), review articles ( = 1), duplicated publications ( = 1), and studies on humans or cells ( = 2). Finally, this systematic review contained 12 studies between 2008 and 2018. All studies were written in English except for one study in Chinese, and all of them showed the effect of melatonin on BWC and NS in SAH models. Our research shows that melatonin can significantly improve the behavior and pathological results of SAH animal models. However, due to the small number of studies included in this meta-analysis, the experimental design and experimental method limitations should be considered when interpreting the results. Significant clinical and animal studies are still required to evaluate whether melatonin can be used in the adjuvant treatment of clinical SAH patients.
PubMed: 34539547
DOI: 10.3389/fneur.2021.685731 -
International Wound Journal Aug 2023Ferroptosis is a newly discovered cell death type which is different from apoptosis, autophagy, pyroptosis as well as necrosis in the following aspects: morphology,...
Ferroptosis is a newly discovered cell death type which is different from apoptosis, autophagy, pyroptosis as well as necrosis in the following aspects: morphology, biochemistry, gene and regulatory mechanisms. Ferroptosis is regulated by multiples of mechanisms such as system Xc mechanism, glutathione peroxidase 4 (GPX4) mechanism, iron metabolism and lipid metabolism. Currently, ferroptosis has been revealed to be significant in wound healing such as diabetic wound, irradiated wound and ultraviolet (UV)-driven wound. Hence, how to intervene in the pathogenesis as well as the development of wounds and promote the wound healing by the regulation of ferroptosis have become a research hotspot. This review systematically summarises the latest scientific advances of ferroptosis and wound healing fields, with hoping to propose a new insight and advance in the wound treatment.
Topics: Humans; Ferroptosis; Wound Healing
PubMed: 36788729
DOI: 10.1111/iwj.14102 -
Frontiers in Physiology 2021Renal ischemia-reperfusion (I/R) injury is one of the major causes related to acute kidney damage. Melatonin has been shown as a powerful antioxidant, with many animal...
Renal ischemia-reperfusion (I/R) injury is one of the major causes related to acute kidney damage. Melatonin has been shown as a powerful antioxidant, with many animal experiments have been designed to evaluate the therapeutic effect of it to renal I/R injury. This systematic review aimed to assess the therapeutic effect of melatonin for renal I/R injury in animal models. The PubMed, Web of Science, Embase, and Science Direct were searched for animal experiments applying melatonin to treat renal I/R injury to February 2021. Thirty-one studies were included. The pooled analysis showed a greater reduction of blood urea nitrogen (BUN) (21 studies, weighted mean difference (WMD) = -30.00 [-42.09 to -17.91], < 0.00001), and serum creatinine (SCr) (20 studies, WMD = -0.91 [-1.17 to -0.66], < 0.00001) treated with melatonin. Subgroup analysis suggested that multiple administration could reduce the BUN compared with control. Malondialdehyde and myeloperoxidase were significantly reduced, meanwhile, melatonin significantly improved the activity of glutathione, as well as superoxide dismutase. The possible mechanism for melatonin to treat renal I/R injury is inhibiting endoplasmic reticulum stress, apoptosis, inflammation, autophagy, and fibrillation in AKI to chronic kidney disease. From the available data of small animal studies, this systematic review demonstrated that melatonin could improve renal function and antioxidative effects to cure renal I/R injury through, then multiple administration of melatonin might be more appropriate. Nonetheless, extensive basic experiments are need to study the mechanism of melatonin, then well-designed randomized controlled trials to explore the protective effect of melatonin.
PubMed: 35095558
DOI: 10.3389/fphys.2021.791036