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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 -
Frontiers in Physiology 2022Autophagy is a highly conserved process that is indispensable for cell survival, embryonic development, and tissue homeostasis. Activation of autophagy protects cells...
Autophagy is a highly conserved process that is indispensable for cell survival, embryonic development, and tissue homeostasis. Activation of autophagy protects cells against oxidative stress and is a major adaptive response to injury. When autophagy is dysregulated by factors such as smoking, environmental insults and aging, it can lead to enhanced formation of aggressors and production of reactive oxygen species (ROS), resulting in oxidative stress and oxidative damage to cells. ROS activates autophagy, which in turn promotes cell adaptation and reduces oxidative damage by degrading and circulating damaged macromolecules and dysfunctional cell organelles. The cellular response triggered by oxidative stress includes changes in signaling pathways that ultimately regulate autophagy. Chronic obstructive pulmonary disease (COPD) is the most common lung disease among the elderly worldwide, with a high mortality rate. As an induced response to oxidative stress, autophagy plays an important role in the pathogenesis of COPD. This review discusses the regulation of oxidative stress and autophagy in COPD, and aims to provide new avenues for future research on target-specific treatments for COPD.
PubMed: 36225291
DOI: 10.3389/fphys.2022.1004275 -
Frontiers in Physiology 2022Calcium oxalate kidney stone is one of the common diseases in the urinary system and has a high recurrence rate. Currently, the pathogenesis of kidney stone and the...
Calcium oxalate kidney stone is one of the common diseases in the urinary system and has a high recurrence rate. Currently, the pathogenesis of kidney stone and the methods to prevent recurrence are still being investigated. Autophagy, as an event of cellular self-repair, has received attention in the field of kidney stone in recent years. In some current studies, autophagy has shown destructiveness and protectiveness in the pathogenesis of kidney stone. The inhibition or promotion of autophagy may be a key target for future kidney stone therapy. This systematic literature review discusses the function of autophagy in kidney stone pathogenesis in the context of current research and synthesizes the evidence analysis to provide a basis for new future therapies. We systematically reviewed the literature during September 2021 according to the Preferred Reporting Items for Systematic Evaluation and Meta-Analysis (PRISMA) guidelines. Articles on studying the role of autophagy in the pathogenesis of calcium oxalate kidney stone were extracted from PubMed, MEDLINE, Embase and Scopus, including versus experiments. The study topic, language and publication date were not restricted. Two authors (Li and Zhou) searched and screened the literature. We screened 18 articles from the 33 collected articles, of which 6 conducted cellular studies, four conducted animal studies, eight conducted cellular studies with animal studies, and five studied human specimens. In early studies, the literature generally concluded that autophagy is deleterious in the development of kidney stone. In 2020, the idea of the protectiveness of autophagy associated with kidney stone was first proposed and focused on targeting transcription factor EB. In addition, the interaction of autophagy with other cellular events and the regulation of signaling molecules are focused on in this paper. This systematic review provides advances in research on the role of autophagy in renal calculi. The current studies suggest that both upregulation and downregulation of autophagy may ameliorate injury in kidney stone models. The authors prefer the upregulation of autophagy as a future research direction for kidney stone treatment.
PubMed: 36213233
DOI: 10.3389/fphys.2022.1008264 -
Life Sciences Nov 2022We conducted a meta-analysis to investigate whether diabetes induced by a high-fat diet (HFD) has the potential to alter the process of autophagy in the murine liver. (Meta-Analysis)
Meta-Analysis Review
AIMS
We conducted a meta-analysis to investigate whether diabetes induced by a high-fat diet (HFD) has the potential to alter the process of autophagy in the murine liver.
METHODS
A systematic literature search was performed with electronic databases (PubMed, EMBASE, Web of Science). Study design, population, intervention, outcome, and risk of bias were analyzed. Given the availability of studies, a quantitative meta-analysis including 23 studies was performed.
KEY FINDINGS
The search found 5754 articles, with 48 matching the eligibility criteria, comprising of 1033 animals. The meta-analysis showed that diabetic murines fed with HFD presented an absence of p62 degradation (SMD 4.63, 95 % CI 2.02 to 7.24, p = 0.0005; I = 77 %), higher expression of p-mTOR/mTOR (SMD 5.20, 95 % CI 1.00 to 9.39, p = 0.01; I = 78 %), and a decreased p-AMPK/AMPK ratio (SMD -2.02, 95 % CI -3.96 to -0.09, p = 0.04; I = 85 %) when compared to nondiabetic murines. When associated with streptozotocin, the animals presented decreased ATG-7 and LC3-II. The meta-regression results showed a decrease in autophagy responses due to increased glycemic levels, fat content, and long-term exposure to HFD, and advanced animal age. The common and species-specific protein responses were also consistent with the inhibition of autophagy.
SIGNIFICANCE
The normal process of autophagy mechanisms in the liver is less competent after HFD consumption. The destabilization of (auto)phagolysosomes contributes to the perpetuation of diabetes, metabolic dysfunction-associated fatty liver disease, and cell death.
Topics: Mice; Animals; Diet, High-Fat; AMP-Activated Protein Kinases; Streptozocin; Liver; Autophagy; TOR Serine-Threonine Kinases; Diabetes Mellitus; Mice, Inbred C57BL
PubMed: 36179817
DOI: 10.1016/j.lfs.2022.121012 -
Biomolecules Sep 2022Prostate cancer is one of the leading causes of death for men worldwide. The development of resistance, toxicity, and side effects of conventional therapies have made... (Review)
Review
Prostate cancer is one of the leading causes of death for men worldwide. The development of resistance, toxicity, and side effects of conventional therapies have made prostate cancer treatment become more intensive and aggressive. Many phytochemicals isolated from plants have shown to be tumor cytotoxic. In vitro laboratory studies have revealed that natural compounds can affect cancer cell proliferation by modulating many crucial cellular signaling pathways frequently dysregulated in prostate cancer. A multitude of natural compounds have been found to induce cell cycle arrest, promote apoptosis, inhibit cancer cell growth, and suppress angiogenesis. In addition, combinatorial use of natural compounds with hormone and/or chemotherapeutic drugs seems to be a promising strategy to enhance the therapeutic effect in a less toxic manner, as suggested by pre-clinical studies. In this context, we systematically reviewed the currently available literature of naturally occurring compounds isolated from vegetables, fruits, teas, and herbs, with their relevant mechanisms of action in prostate cancer. As there is increasing data on how phytochemicals interfere with diverse molecular pathways in prostate cancer, this review discusses and emphasizes the implicated molecular pathways of cell proliferation, cell cycle control, apoptosis, and autophagy as important processes that control tumor angiogenesis, invasion, and metastasis. In conclusion, the elucidation of the natural compounds' chemical structure-based anti-cancer mechanisms will facilitate drug development and the optimization of drug combinations. Phytochemicals, as anti-cancer agents in the treatment of prostate cancer, can have significant health benefits for humans.
Topics: Antineoplastic Agents; Apoptosis; Hormones; Humans; Male; Neovascularization, Pathologic; Phytochemicals; Prostatic Neoplasms
PubMed: 36139145
DOI: 10.3390/biom12091306 -
Nutrients Aug 2022The therapeutic effects of food rich in ellagitannins have been established to stem from its microbial metabolite, urolithin. Over the past decade, there has been a... (Review)
Review
UNLABELLED
The therapeutic effects of food rich in ellagitannins have been established to stem from its microbial metabolite, urolithin. Over the past decade, there has been a growing trend in urolithin research pertaining to its pharmacological properties. The purpose of this systematic review is to collate and synthesise all available data on urolithin's therapeutic ability, to highlight its potential as a pharmaceutical agent, and prospective direction on future research.
METHODS
This systematic review was written based on the PRISMA guideline and was conducted across Ovid via Embase, Ovid MEDLINE, Cochrane Central Register for Controlled Trials, and Web of Science Core Collection.
RESULTS
A total of 41 animal studies were included in this systematic review based on the appropriate keyword. The included studies highlighted the neuroprotective, anti-metabolic disorder activity, nephroprotective, myocardial protective, anti-inflammatory, and musculoskeletal protection of urolithin A, B, and its synthetic analogue methylated urolithin A. The Sirt1, AMPK, and PI3K/AKT/mTOR signalling pathways were reported to be involved in the initiation of autophagy and mitochondrial biogenesis by urolithin A.
CONCLUSIONS
This review methodically discusses the therapeutic prospects of urolithins and provides scientific justification for the potential development of urolithin A as a potent natural mitophagy inducer for anti-ageing purposes.
Topics: Animals; Coumarins; Hydrolyzable Tannins; Phosphatidylinositol 3-Kinases; Prospective Studies
PubMed: 36079752
DOI: 10.3390/nu14173494 -
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 -
Neurotoxicology Sep 2022Investigation of the toxicity triggered by chemicals on the human brain has traditionally relied on approaches using rodent in vivo models and in vitro cell models... (Review)
Review
Investigation of the toxicity triggered by chemicals on the human brain has traditionally relied on approaches using rodent in vivo models and in vitro cell models including primary neuronal cultures and cell lines from rodents. The issues of species differences between humans and rodents, the animal ethical concerns and the time and cost required for neurotoxicity studies on in vivo animal models, do limit the use of animal-based models in neurotoxicology. In this context, human cell models appear relevant in elucidating cellular and molecular impacts of neurotoxicants and facilitating prioritization of in vivo testing. The SH-SY5Y human neuroblastoma cell line (ATCC® CRL-2266™) is one of the most used cell lines in neurosciences, either undifferentiated or differentiated into neuron-like cells. This review presents the characteristics of the SH-SY5Y cell line and proposes the results of a systematic review of literature on the use of this in vitro cell model for neurotoxicity research by focusing on organic environmental pollutants including pesticides, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), flame retardants, PFASs, parabens, bisphenols, phthalates, and PAHs. Organic environmental pollutants are widely present in the environment and increasingly known to cause clinical neurotoxic effects during fetal & child development and adulthood. Their effects on cultured SH-SY5Y cells include autophagy, cell death (apoptosis, pyroptosis, necroptosis, or necrosis), increased oxidative stress, mitochondrial dysfunction, disruption of neurotransmitter homeostasis, and alteration of neuritic length. Finally, the inherent advantages and limitations of the SH-SY5Y cell model are discussed in the context of chemical testing.
Topics: Adult; Animals; Cell Line, Tumor; Cell Survival; Child; Environmental Pollutants; Flame Retardants; Fluorocarbons; Humans; Neuroblastoma; Neurotoxicity Syndromes; Parabens; Pesticides; Polychlorinated Dibenzodioxins
PubMed: 35914637
DOI: 10.1016/j.neuro.2022.07.008 -
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 -
CNS Neuroscience & Therapeutics Oct 2022To systematically review studies using remote ischemia postconditioning (RIPostC) for ischemic stroke in experimental models and obtain factors that significantly... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To systematically review studies using remote ischemia postconditioning (RIPostC) for ischemic stroke in experimental models and obtain factors that significantly influence treatment outcomes.
MATERIALS AND METHODS
Peer-reviewed studies were identified and selected based on the eligibility criteria, followed by extraction of data on potentially influential factors related to model preparation, postconditioning, and measure time based on outcome measures including infarct size, neurological scales, and cell tests with autophagy, apoptosis, normal-neuron, and damaged-neuron counting. Then, all data were preprocessed, grouped, and meta-analyzed with the indicator of the standardized mean difference.
RESULTS
Fifty-seven studies with 224 experiments (91 for infarct size, 92 for neurological scales, and 41 for cell-level tests) were included. There was little statistical difference between different model preparations, treated body parts, number of treatments, and sides. And treatment effect was generally a positive correlation with the duration of conditioning time to stroke onset with exceptions at some time points. Based on infarct size, the number of cycles per treatment, duration of occlusion, and release per cycle showed significant differences. Combined with the effect sizes by other measures, the occlusion/release duration of 8-10 min per cycle is better than 5 min, and three cycles per treatment were most frequently used with good effects. Effect also varied when measuring at different times, showing statistical differences in infarct size and most neurological scales. RIPostC is confirmed as an effective therapeutic intervention for ischemic stroke, while the RIPostC-mediated autophagy level being activated or inhibited remained conflicting.
CONCLUSIONS
Conditioning time, number of cycles per treatment, duration of occlusion, and release per cycle were found to influence the treatment effects of RIPostC significantly. More studies on the relevant influential factors and autophagy mechanisms are warranted.
Topics: Autophagy; Humans; Infarction; Ischemic Postconditioning; Ischemic Stroke; Stroke
PubMed: 35896511
DOI: 10.1111/cns.13925