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Frontiers in Pharmacology 2022Methamphetamine, commonly referred to as METH, is a highly addictive psychostimulant and one of the most commonly misused drugs on the planet. Using METH continuously...
Methamphetamine, commonly referred to as METH, is a highly addictive psychostimulant and one of the most commonly misused drugs on the planet. Using METH continuously can increase your risk for drug addiction, along with other health complications like attention deficit disorder, memory loss, and cognitive decline. Neurotoxicity caused by METH is thought to play a significant role in the onset of these neurological complications. The molecular mechanisms responsible for METH-caused neuronal damage are discussed in this review. According to our analysis, METH is closely associated with programmed cell death (PCD) in the process that causes neuronal impairment, such as apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. In reviewing this article, some insights are gained into how METH addiction is accompanied by cell death and may help to identify potential therapeutic targets for the neurological impairment caused by METH abuse.
PubMed: 36059947
DOI: 10.3389/fphar.2022.980340 -
Clinical and Translational Science Nov 2021Frailty is a condition of global impairment due to depletion of physiological reserves. However, the underlying biological mechanisms are poorly understood. The aims of... (Meta-Analysis)
Meta-Analysis
Frailty is a condition of global impairment due to depletion of physiological reserves. However, the underlying biological mechanisms are poorly understood. The aims of the current study were to identify the differences in mitochondrial function and iron metabolism between frail and nonfrail populations, and to investigate the contribution of different methodological approaches to the results. Searches were performed, using five online databases up to November 2019. Studies reporting measurements of mitochondrial function or iron metabolism in frail and nonfrail subjects or subjects with and without sarcopenia, were included. Pooled effect estimates were expressed as Standardized Mean Differences. Heterogeneity, expressed as I , was explored using regression analyses. In total, 107 studies, reporting 75 measures of mitochondrial function or iron metabolism, using six different experimental approaches, in three species were identified. Significant decreases in measures of oxygen consumption were observed for frail humans but not in animal models. Conversely, no differences between frail and nonfrail humans were observed for apoptosis and autophagy, in contrast to animal models. The most significant effect of the type of frailty assessment was observed for respiratory chain complexes where only subjects categorized as frail by the Fried Frailty Index showed a significant decrease in activity. We identified iron metabolism in frailty as an important knowledge gap, highlighted the need of consistent frailty diagnostic tools, and pointed out the limited translational potential of animal models. Inconsistency between studies evaluating the molecular mechanisms underlying frailty may present a barrier to the development of effective therapies.
Topics: Frailty; Humans; Iron; Mitochondria
PubMed: 34240568
DOI: 10.1111/cts.13101 -
Frontiers in Physiology 2022Exercise is one of the most effective interventions for preventing and treating skeletal muscle aging. Exercise-induced autophagy is widely acknowledged to regulate...
Exercise is one of the most effective interventions for preventing and treating skeletal muscle aging. Exercise-induced autophagy is widely acknowledged to regulate skeletal muscle mass and delay skeletal muscle aging. However, the mechanisms underlying of the effect of different exercises on autophagy in aging skeletal muscle remain unclear. A systematic review was performed following an electronic search of SCOPUS, PubMed, Web of Science, ScienceDirect, and Google Scholar and two Chinese electronic databases, CNKI and Wan Fang. All articles published in English and Chinese between January 2010 and January 2022 that quantified autophagy-related proteins in aging skeletal muscle models. The primary outcome was autophagy assessment, indicated by changes in the levels of any autophagy-associated proteins. A total of fifteen studies were included in the final review. Chronic exercise modes mainly comprise aerobic exercise and resistance exercise, and the intervention types include treadmill training, voluntary wheel running, and ladder training. LC3, Atg5-Atg7/9/12, mTOR, Beclin1, Bcl-2, p62, PGC-1α, and other protein levels were quantified, and the results showed that long-term aerobic exercise and resistance exercise could increase the expression of autophagy-related proteins in aging skeletal muscle ( < 0.05). However, there was no significant difference in short term or high-intensity chronic exercise, and different types and intensities of exercise yielded different levels of significance for autophagy-related protein expression. Existing evidence reveals that high-intensity exercise may induce excessive autophagy, while low-intensity exercise for a short period (Intervention duration <12 weeks, frequency <3 times/week) may not reach the threshold for exercise-induced autophagy. Precise control of the exercise dose is essential in the long term to maximize the benefits of exercise. Further investigation is warranted to explore the relationship between chronic exercise and different exercise duration and types to substantiate the delaying of skeletal muscle aging by exercise.
PubMed: 35910582
DOI: 10.3389/fphys.2022.930185 -
Frontiers in Immunology 2022Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that...
Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that renal inflammatory injury as a result of the cell-crystal reaction plays a crucial role in the development of calcium oxalate kidney stones. An increasing amount of research have confirmed that inflammation mediated by the cell-crystal reaction can lead to inflammatory injury of renal cells, promote the intracellular expression of NADPH oxidase, induce extensive production of reactive oxygen species, activate NLRP3 inflammasome, discharge a great number of inflammatory factors, trigger inflammatory cascading reactions, promote the aggregation, nucleation and growth process of calcium salt crystals, and ultimately lead to the development of intrarenal crystals and even stones. The renal tubular epithelial cells (RTECs)-crystal reaction, macrophage-crystal reaction, calcifying nanoparticles, endoplasmic reticulum stress, autophagy activation, and other regulatory factors and mechanisms are involved in this process.
Topics: Endoplasmic Reticulum Stress; Epithelial Cells; Humans; Inflammasomes; Inflammation; NLR Family, Pyrin Domain-Containing 3 Protein; Nephrolithiasis; Reactive Oxygen Species
PubMed: 35154136
DOI: 10.3389/fimmu.2022.818625 -
Nutrients Apr 2023Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of... (Review)
Review
BACKGROUND
Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of endoplasmic reticulum stress (ERS) and subsequent unfolded protein response (UPR) as the underlying molecular mechanisms for the anticancer properties of tocotrienol.
METHOD
A comprehensive literature search was performed in March 2023 using the PubMed, Scopus, Web of Science, and EMBASE databases. In vitro, in vivo, and human studies were considered.
RESULT
A total of 840 articles were retrieved during the initial search, and 11 articles that fit the selection criteria were included for qualitative analysis. The current mechanistic findings are based solely on in vitro studies. Tocotrienol induces cancer cell growth arrest, autophagy, and cell death primarily through apoptosis but also through paraptosis-like cell death. Tocotrienol-rich fractions, including α-, γ- and δ-tocotrienols, induce ERS, as evidenced by upregulation of UPR markers and/or ERS-related apoptosis markers. Early endoplasmic reticulum calcium ion release, increased ceramide level, proteasomal inhibition, and upregulation of microRNA-190b were suggested to be essential in modulating tocotrienol-mediated ERS/UPR transduction. Nevertheless, the upstream molecular mechanism of tocotrienol-induced ERS is largely unknown.
CONCLUSION
ERS and UPR are essential in modulating tocotrienol-mediated anti-cancer effects. Further investigation is needed to elucidate the upstream molecular mechanism of tocotrienol-mediated ERS.
Topics: Humans; Tocotrienols; Endoplasmic Reticulum Stress; Unfolded Protein Response; Apoptosis; Cell Death
PubMed: 37111076
DOI: 10.3390/nu15081854 -
Frontiers in Immunology 2023Extracellular vesicles (EVs) carrying functional cargoes are emerging as biomarkers and treatment strategies in multiple liver diseases. Nevertheless, the potential of...
INTRODUCTION
Extracellular vesicles (EVs) carrying functional cargoes are emerging as biomarkers and treatment strategies in multiple liver diseases. Nevertheless, the potential of EVs in liver failure remains indistinct. In this systematic review, we comprehensively analyzed the potential of EVs as biomarkers of liver failure and the therapeutic effects and possible mechanisms of EVs for liver failure.
METHODS
We conducted a systematic review by comprehensively searching the following electronic databases: PubMed, Web of Science, Embase and Cochrane Central Register of Controlled Trials from inception to March 2022. The used text words (synonyms and word variations) and database-specific subject headings included "Extracellular Vesicles", "Exosomes", "Liver Failure", "Liver Injury", etc.
RESULTS
A total of 1479 studies were identified. After removing 680 duplicate studies and 742 irrelevant studies, 57 studies were finally retained and analyzed. Fourteen studies revealed EVs with functional cargoes could be used to make the diagnosis of liver failure and provide clues for early warning and prognostic assessment of patients with liver failure. Forty-three studies confirmed the administration of EVs from different sources alleviated hepatic damage and improved survival through inhibiting inflammatory response, oxidative stress as well as apoptosis or promoting hepatocyte regeneration and autophagy.
CONCLUSIONS
EVs and their cargoes can be used not only as superior biomarkers of early warning, early diagnosis and prognostic assessments for liver failure, but also as potentially effective treatment options for liver failure. In the future, large-scale studies are urgently needed to verify the diagnostic, predictive and therapeutic value of EVs for liver failure.
Topics: Humans; Biomarkers; Extracellular Vesicles; Liver Failure; Liver Diseases
PubMed: 36911706
DOI: 10.3389/fimmu.2023.1116518 -
OncoTargets and Therapy 2021Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play a vital role in the chemoresistance of gastric cancer (GC). The present systematic review... (Review)
Review
PURPOSE
Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play a vital role in the chemoresistance of gastric cancer (GC). The present systematic review summarises the emerging role, potential targets or pathways and regulatory mechanisms of lncRNAs involved in chemoresistance and proposes a number of clinical implications of lncRNAs as novel therapeutic targets for GC.
METHODS
Studies on lncRNAs involved in the chemoresistance of GC published until July 2020 in the PubMed and Web of Science databases were systematically reviewed and the expression form, role in chemoresistance, targets or pathways, corresponding drugs and potential mechanisms of relevant lncRNAs were summarised in detail.
RESULTS
A total of 48 studies were included in this systematic review. Amongst these studies, 32 involved single drug resistance and 16 involved in multidrug resistance (MDR). The 48 studies collected described 38 lncRNAs in the drug-resistant cells of GC, including 33 upregulated and 5 downregulated lncRNAs. Cisplatin (DDP) was the most studied drug and lncRNA MALAT1 was the most studied lncRNA related to the chemoresistance of GC. The potential mechanisms of chemoresistance for lncRNAs in GC mainly included, amongst others, reduction of apoptosis, induction of autophagy, repair of DNA damage, promotion of epithelial-mesenchymal transition (EMT) and regulation of the related signalling pathways.
CONCLUSION
LncRNAs play a vital role in the chemoresistance of GC and are novel therapeutic targets for the disease. Detailed chemoresistance mechanisms, translational studies and clinical trials on lncRNAs in GC are urgently needed.
PubMed: 33500626
DOI: 10.2147/OTT.S294378 -
Frontiers in Neurology 2024Traumatic brain injury (TBI), a leading cause of high morbidity and mortality, represents a significant global public health challenge. Currently, no effective treatment...
BACKGROUND AND AIM
Traumatic brain injury (TBI), a leading cause of high morbidity and mortality, represents a significant global public health challenge. Currently, no effective treatment for TBI exists. Curcumin, an active compound extracted from the root of , has demonstrated neuroprotective properties both and . Notably, it has shown potential in reducing oxidative stress and inflammation and enhancing redox balance. This paper conducts a systematic review and meta-analysis to explore curcumin's role in TBI animal models extensively. The findings offer valuable insights for future human clinical trials evaluating curcumin as a therapeutic supplement or nutraceutical in TBI management.
METHODS
Comprehensive literature searches were conducted across MEDLINE, Embase, Cochrane, Web of Science, and Google Scholar databases. These searches aimed to identify relevant manuscripts in all languages, utilizing the keywords "curcumin" and "traumatic brain injury."
RESULTS
The final quantitative analysis included 18 eligible articles corresponding to animal studies. The analysis revealed that curcumin significantly reduced inflammatory cytokines, including IL-1β ( = 0.000), IL-6 ( = 0.002), and TNF-α ( = 0.000), across various concentrations, time points, and administration routes. Additionally, curcumin markedly enhanced the activity of oxidative stress markers such as SOD ( = 0.000), Sir2 ( = 0.000), GPx ( = 0.000), and Nrf2 ( = 0.000), while reducing MDA ( = 0.000), 4-HNE ( = 0.001), and oxyprotein levels ( = 0.024). Furthermore, curcumin improved cerebral edema ( = 0.000) and upregulated neuroprotective factors like synapsin I ( = 0.019), BDNF ( = 0.000), and CREB ( = 0.000), without reducing mNSS ( = 0.144). About autophagy and apoptosis, curcumin increased the activity of Beclin-1 ( = 0.000) and Bcl-2 ( = 0.000), while decreasing caspase-3 ( = 0.000), the apoptosis index ( = 0.000), and P62 ( = 0.002).
CONCLUSION
Curcumin supplementation positively affects traumatic brain injury (TBI) by alleviating oxidative stress and inflammatory responses and promoting neuroprotection. It holds potential as a therapeutic agent for human TBI. However, this conclusion necessitates further substantiation through high-quality literature and additional randomized controlled trials (RCTs).
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/. The registration number of PROSPERO: CRD42023452685.
PubMed: 38798711
DOI: 10.3389/fneur.2024.1380353 -
Frontiers in Pharmacology 2023Recently, multiple preclinical studies have reported the beneficial effect of berberine in the treatment of Alzheimer's disease (AD). Nevertheless, the neuroprotective...
Recently, multiple preclinical studies have reported the beneficial effect of berberine in the treatment of Alzheimer's disease (AD). Nevertheless, the neuroprotective effects and possible mechanisms of berberine against AD are not universally recognized. This study aimed to conduct a systematic review and meta-analysis by integrating relevant animal studies to assess the neuroprotective effects and potential mechanisms of berberine on AD. We systematically searched PubMed, Embase, Scopus and Web of Science databases that reported the effects of berberine on AD models up to 1 February 2023. The escape latency, times of crossing platform, time spent in the target quadrant and pro-oligomerized amyloid beta 42 (Aβ) were included as primary outcomes. The secondary outcomes were the Tau-ps 204, Tau-ps 404, β-site of APP cleaving enzyme (BACE1), amyloid precursor protein (APP), acetylcholine esterase (AChE), tumor necrosis factor ⍺ (TNF-α), interleukin 1β (IL-1β), IL-6, nitric oxide (NO), glial fibrillary acidic protein (GFAP), malonaldehyde (MDA), glutathione S-transferase (GST), glutathione (GSH), glutathione peroxidase (GPx), Beclin-1 and neuronal apoptosis cells. This meta-analysis was conducted using RevMan 5.4 and STATA 15.1. The SYRCLE's risk of bias tool was used to assess the methodological quality. Twenty-two studies and 453 animals were included in the analysis. The overall results showed that berberine significantly shortened the escape latency ( < 0.00001), increased times of crossing platform ( < 0.00001) and time spent in the target quadrant ( < 0.00001), decreased Aβ deposition ( < 0.00001), Tau-ps 202 ( < 0.00001) and Tau-ps 404 ( = 0.002), and improved BACE1, APP, AChE, Beclin-1, neuronal apoptosis cells, oxidative stress and inflammation levels. Berberine may be a promising drug for the treatment of AD based on preclinical evidence (especially when the dose was 5-260 mg/kg). The potential mechanisms for these protective effects may be closely related to anti-neuroinflammation, anti-oxidative stress, modulation of autophagy, inhibition of neuronal apoptosis and protection of cholinergic system. However, these results may be limited by the quality of existing research. Larger and methodologically more rigorous preclinical research are needed to provide more convincing evidence.
PubMed: 38259291
DOI: 10.3389/fphar.2023.1287750 -
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