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International Journal of Molecular... Sep 2021The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells,...
The ocular surface is a gateway that contacts the outside and receives stimulation from the outside. The corneal innate immune system is composed of many types of cells, including epithelial cells, fibroblasts, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, basophils, eosinophils, mucin, and lysozyme. Neutrophil infiltration and degranulation occur on the ocular surface. Degranulation, neutrophil extracellular traps formation, called NETosis, and autophagy in neutrophils are involved in the pathogenesis of ocular surface diseases. It is necessary to understand the role of neutrophils on the ocular surface. Furthermore, there is a need for research on therapeutic agents targeting neutrophils and neutrophil extracellular trap formation for ocular surface diseases.
Topics: Cell Degranulation; Cornea; Extracellular Traps; Eye Diseases; Humans; Neutrophil Infiltration; Neutrophils
PubMed: 34638724
DOI: 10.3390/ijms221910386 -
Life (Basel, Switzerland) Nov 2022Spinal cord injury (SCI) possesses a complicated etiology. There is no FDA-approved treatment for SCI, and the majority of current interventions focus on reducing... (Review)
Review
Spinal cord injury (SCI) possesses a complicated etiology. There is no FDA-approved treatment for SCI, and the majority of current interventions focus on reducing symptoms. During SCI, inflammation, oxidative stress, apoptosis, and autophagy are behind the secondary phase of SCI and cause serious consequences. It urges the need for providing multi-targeting agents, that possess lower side effects and higher efficacy. The plant secondary metabolites are multi-targeting agents and seem to provide new roads in combating diseases. Flavonoids are phytochemicals of continual interest to scientists in combating neurodegenerative diseases (NDDs). Flavonoids are being studied for their biological and pharmacological effects, particularly as antioxidants, anti-inflammatory agents, anti-apoptotic, and autophagy regulators. Quercetin is one of the most well-known flavonols known for its preventative and therapeutic properties. It is a naturally occurring bioactive flavonoid that has recently received a lot of attention for its beneficial effects on NDDs. Several preclinical evidence demonstrated its neuroprotective effects. In this systematic review, we aimed at providing the biological activities of quercetin and related derivatives against SCI. Detailed neuroprotective mechanisms of quercetin derivatives are also highlighted in combating SCI.
PubMed: 36556325
DOI: 10.3390/life12121960 -
Frontiers in Endocrinology 2023Diabetic kidney disease (DKD) is the main cause of end-stage renal disease worldwide, and there is a lack of effective treatment strategies. Autophagy is a highly... (Review)
Review
Diabetic kidney disease (DKD) is the main cause of end-stage renal disease worldwide, and there is a lack of effective treatment strategies. Autophagy is a highly conserved lysosomal degradation process that maintains homeostasis and energy balance by removing protein aggregates and damaged organelles. Increasing evidence suggests that dysregulated autophagy may contribute to glomerular and tubulointerstitial lesions in the kidney under diabetic conditions. Emerging studies have shown that Chinese herbal medicine and its active compounds may ameliorate diabetic kidney injury by regulating autophagy. In this review, we summarize that dysregulation or insufficiency of autophagy in renal cells, including podocytes, glomerular mesangial cells, and proximal tubular epithelial cells, is a key mechanism for the development of DKD, and focus on the protective effects of Chinese herbal medicine and its active compounds. Moreover, we systematically reviewed the mechanism of autophagy in DKD regulated by Chinese herb compound preparations, single herb and active compounds, so as to provide new drug candidates for clinical treatment of DKD. Finally, we also reviewed the candidate targets of Chinese herbal medicine regulating autophagy for DKD. Therefore, further research on Chinese herbal medicine with autophagy regulation and their targets is of great significance for the realization of new targeted therapies for DKD.
Topics: Humans; Diabetic Nephropathies; Drugs, Chinese Herbal; Kidney; Podocytes; Autophagy; Diabetes Mellitus
PubMed: 36942026
DOI: 10.3389/fendo.2023.1142805 -
Frontiers in Genetics 2022Heparan sulfate modified proteins or proteoglycans (HSPGs) are an abundant class of cell surface and extracellular matrix molecules. They serve important co-receptor...
Heparan sulfate modified proteins or proteoglycans (HSPGs) are an abundant class of cell surface and extracellular matrix molecules. They serve important co-receptor functions in the regulation of signaling as well as membrane trafficking. Many of these activities directly affect processes associated with neurodegeneration including uptake and export of Tau protein, disposition of Amyloid Precursor Protein-derived peptides, and regulation of autophagy. In this review we focus on the impact of HSPGs on autophagy, membrane trafficking, mitochondrial quality control and biogenesis, and lipid metabolism. Disruption of these processes are a hallmark of Alzheimer's disease (AD) and there is evidence that altering heparan sulfate structure and function could counter AD-associated pathological processes. Compromising presenilin function in several systems has provided instructive models for understanding the molecular and cellular underpinnings of AD. Disrupting presenilin function produces a constellation of cellular deficits including accumulation of lipid, disruption of autophagosome to lysosome traffic and reduction in mitochondrial size and number. Inhibition of heparan sulfate biosynthesis has opposing effects on all these cellular phenotypes, increasing mitochondrial size, stimulating autophagy flux to lysosomes, and reducing the level of intracellular lipid. These findings suggest a potential mechanism for countering pathology found in AD and related disorders by altering heparan sulfate structure and influencing cellular processes disrupted broadly in neurodegenerative disease. Vertebrate and invertebrate model systems, where the cellular machinery of autophagy and lipid metabolism are conserved, continue to provide important translational guideposts for designing interventions that address the root cause of neurodegenerative pathology.
PubMed: 36699460
DOI: 10.3389/fgene.2022.1012706 -
BioMed Research International 2021Probiotics are living microorganisms increasingly used to treat or modulate different diseases or disorders because of their benefits and also low adverse reaction, and...
Probiotics are living microorganisms increasingly used to treat or modulate different diseases or disorders because of their benefits and also low adverse reaction, and their positive and protective effects on various cells and tissues have been reported. The mechanisms by which probiotics exert their beneficial effects in different cells and tissues were investigated, and autophagy is one of the main mechanisms to induce their positive effects. Autophagy is a conserved process that occurs in all eukaryotic cells and plays an essential role in homeostasis and cell survival by degrading damaged and dysfunctional intracellular organelles. On the other hand, the role of autophagy is diverse in different tissues and situations, and cell death derived from autophagy has been observed in some cells. This search was done in PubMed, WOS, and Scopus using the keywords probiotic, microbiota, and autophagy. The search strategy was focused on the in vitro and animal model studies, and the included filters were English language publications and full-text articles (by June 2020). Studies that investigated other underlying mechanisms except autophagy were excluded. Among more than 105 papers, 24 studies were considered eligible for more evaluation. The obtained results indicated that most studies were performed on intestinal cell lines or tissue compared with other types of cell lines and tissue. This review article discusses our current understanding of the probiotic effects through autophagy in different cell lines and tissues that would be a useful guide to daily and clinical usage of these living microorganisms, but despite promising results of this systematic review, further studies need to assess this issue. This systematic review has demonstrated that autophagy is an effective mechanism in inducing beneficial effects of probiotics in different tissues.
Topics: Animals; Autophagy; Homeostasis; Humans; Microbiota; Probiotics
PubMed: 34901266
DOI: 10.1155/2021/2931580 -
Frontiers in Neuroscience 2023Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant...
Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant activities, is finding its new application in the field of SCI. Here, we performed a systematic review to assess the neurological roles of AST in rats following SCI, and assessed the potential for clinical translation. Searches were conducted on PubMed, Embase, Cochrane Library, the Web of Science, China National Knowledge Infrastructure, WanFang data, Vip Journal Integration Platform, and SinoMed databases. Animal studies that evaluated the neurobiological roles of AST in a rat model of SCI were included. A total of 10 articles were included; most of them had moderate-to-high methodological quality, while the overall quality of evidence was not high. Generally, the meta-analyses revealed that rats treated with AST exhibited an increased Basso, Beattie, and Bresnahan (BBB) score compared with the controls, and the weighted mean differences (WMDs) between those two groups showed a gradual upward trend from days 7 (six studies, n = 88, WMD = 2.85, 95% CI = 1.83 to 3.87, < 0.00001) to days 28 (five studies, n = 76, WMD = 6.42, 95% CI = 4.29 to 8.55, < 0.00001) after treatment. AST treatment was associated with improved outcomes in spared white matter area, motor neuron survival, and SOD and MDA levels. Subgroup analyses indicated there were differences in the improvement of BBB scores between distinct injury types. The trial sequential analysis then firmly proved that AST could facilitate the locomotor recovery of rats following SCI. In addition, this review suggested that AST could modulate oxidative stress, neuroinflammation, neuron loss, and autophagy multiple signaling pathways for treating SCI. Collectively, with a protective effect, good safety, and a systematic action mechanism, AST is a promising candidate for future clinical trials of SCI. Nonetheless, in light of the limitations of the included studies, larger and high-quality studies are needed for verification.
PubMed: 37881327
DOI: 10.3389/fnins.2023.1255755 -
International Journal of Molecular... Nov 2020Autophagy is a highly conserved catabolic homeostatic process, crucial for cell survival. It has been shown that autophagy can modulate different cardiovascular... (Review)
Review
BACKGROUND
Autophagy is a highly conserved catabolic homeostatic process, crucial for cell survival. It has been shown that autophagy can modulate different cardiovascular pathologies, including vascular calcification (VCN).
OBJECTIVE
To assess how modulation of autophagy, either through induction or inhibition, affects vascular and valvular calcification and to determine the therapeutic applicability of inducing autophagy.
DATA SOURCES
A systematic review of English language articles using MEDLINE/PubMed, Web of Science (WoS) and the Cochrane library. The search terms included autophagy, autolysosome, mitophagy, endoplasmic reticulum (ER)-phagy, lysosomal, calcification and calcinosis. Study characteristics: Thirty-seven articles were selected based on pre-defined eligibility criteria. Thirty-three studies (89%) studied vascular smooth muscle cell (VSMC) calcification of which 27 (82%) studies investigated autophagy and six (18%) studies lysosomal function in VCN. Four studies (11%) studied aortic valve calcification (AVCN). Thirty-four studies were published in the time period 2015-2020 (92%).
CONCLUSION
There is compelling evidence that both autophagy and lysosomal function are critical regulators of VCN, which opens new perspectives for treatment strategies. However, there are still challenges to overcome, such as the development of more selective pharmacological agents and standardization of methods to measure autophagic flux.
Topics: Aortic Valve; Aortic Valve Stenosis; Autophagy; Calcinosis; Cell Survival; Endoplasmic Reticulum; Humans; Lysosomes; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Vascular Calcification
PubMed: 33255685
DOI: 10.3390/ijms21238933 -
Frontiers in Pharmacology 2023is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years.... (Review)
Review
is a core Chinese herbal medicine for the treatment of diabetes and diabetic nephropathy (DN). It has been used for the treatment of diabetes for over 1,000 years. Catalpol is the main active compound in Rehmannia roots. Current evidence suggests that catalpol exhibits significant anti-diabetic bioactivity, and thus it has attracted increasing research attention for its potential use in treating DN. However, no studies have systematically evaluated these effects, and its mechanism of action remains unclear. This study aimed to evaluate the effects of catalpol on DN, as well as to summarize its possible mechanisms of action, in DN animal models. We included all DN-related animal studies with catalpol intervention. These studies were retrieved by searching eight databases from their dates of inception to July 2022. In addition, we evaluated the methodological quality of the included studies using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool. Furthermore, we calculated the weighted standard mean difference (SMD) with 95% confidence interval (CI) using the Review Manager 5.3 software and evaluated publication bias using the Stata (12.0) software. A total of 100 studies were retrieved, of which 12 that included 231 animals were finally included in this review. As compared to the control treatment, treatment with catalpol significantly improved renal function in DN animal models by restoring serum creatinine (Scr) ( = 0.0009) and blood urea nitrogen (BUN) ( < 0.00001) levels, reducing proteinuria ( < 0.00001) and fasting blood glucose (FBG) ( < 0.0001), improving kidney indices ( < 0.0001), and alleviating renal pathological changes in the animal models. In addition, it may elicit its effects by reducing inflammation and oxidative stress, improving podocyte apoptosis, regulating lipid metabolism, delaying renal fibrosis, and enhancing autophagy. The preliminary findings of this preclinical systematic review suggest that catalpol elicits significant protective effects against hyperglycemia-induced kidney injury. However, more high-quality studies need to be carried out in the future to overcome the methodological shortcomings identified in this review.
PubMed: 37621314
DOI: 10.3389/fphar.2023.1192694 -
Chinese Medicine Aug 2023Pulmonary fibrosis is a chronic progressive interstitial lung disease caused by a variety of etiologies. The disease can eventually lead to irreversible damage to the... (Review)
Review
Pulmonary fibrosis is a chronic progressive interstitial lung disease caused by a variety of etiologies. The disease can eventually lead to irreversible damage to the lung tissue structure, severely affecting respiratory function and posing a serious threat to human health. Currently, glucocorticoids and immunosuppressants are the main drugs used in the clinical treatment of pulmonary fibrosis, but their efficacy is limited and they can cause serious adverse effects. Traditional Chinese medicines have important research value and potential for clinical application in anti-pulmonary fibrosis. In recent years, more and more scientific researches have been conducted on the use of traditional Chinese medicine to improve or reduce pulmonary fibrosis, and some important breakthroughs have been made. This review paper systematically summarized the research progress of pharmacological mechanism of traditional Chinese medicines and their active compounds in improving or reducing pulmonary fibrosis. We conducted a systematic search in several main scientific databases, including PubMed, Web of Science, and Google Scholar, using keywords such as idiopathic pulmonary fibrosis, pulmonary fibrosis, interstitial pneumonia, natural products, herbal medicine, and therapeutic methods. Ultimately, 252 articles were included and systematically evaluated in this analysis. The anti-fibrotic mechanisms of these traditional Chinese medicine studies can be roughly categorized into 5 main aspects, including inhibition of epithelial-mesenchymal transition, anti-inflammatory and antioxidant effects, improvement of extracellular matrix deposition, mediation of apoptosis and autophagy, and inhibition of endoplasmic reticulum stress. The purpose of this article is to provide pharmaceutical researchers with information on the progress of scientific research on improving or reducing Pulmonary fibrosis with traditional Chinese medicine, and to provide reference for further pharmacological research.
PubMed: 37537605
DOI: 10.1186/s13020-023-00797-7 -
Evidence-based Complementary and... 2020At present, the relationship between autophagosomes and the prognosis of various cancers has become a subject of active investigation. A series of studies have... (Review)
Review
OBJECTIVE
At present, the relationship between autophagosomes and the prognosis of various cancers has become a subject of active investigation. A series of studies have demonstrated the correlation between autophagy microtubule-associated protein light chain 3 (LC-3), Beclin-1, and colorectal cancer (CRC). Since autophagy has dual regulatory roles in tumors, the results of this correlation are also uncertain. Hence, we summarized the relationship between Beclin-1, LC-3, and CRC using systematic reviews and meta-analysis to clarify their prognostic significance in it.
METHODS
PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched online up to April 1, 2019. The quality of the involving studies was assessed against the Newcastle-Ottawa Scale (NOS). Pooled hazard ratio (HR) and 95% confidence interval (CI) in a fixed or random effects model were used to assess the strength of correlation between Beclin-1, LC-3, and CRC.
RESULTS
A total of 9 articles were collected, involving 2,297 patients. Most literatures scored more than 6 points, suggesting that the quality of our including research was acceptable. Our finding suggested that the expression of Beclin-1 was not associated with overall survival (HR = 0.68, 95% CI (0.31-1.52), =0.351). Nonetheless, LC-3 expression exerted significant impact on OS (HR = 0.51, 95% CI (0.35-0.74), < 0.05). Subgroup analysis exhibited that Beclin-1 expression was associated with OS at TNM stage III (HR = 0.04, 95% CI = 0.02-0.08, < 0.05), surgical treatment (HR = 1.53, 95% CI (1.15-2.02), =0.003), and comprehensive treatment (HR = 0.27 95% CI (0.08-0.92), =0.036), respectively. Similarly, the results showed the increased LC-3 expression in CRC was related to OS in multivariate analyses (HR = 0.44, 95% CI (0.34-0.57), < 0.05), stages (HR = 0.51, 95% CI (0.35-0.74), < 0.05), and comprehensive treatment (HR = 0.44, 95% CI (0.34-0.57), < 0.05).
CONCLUSIONS
Autophagy-related proteins of LC-3 might be an important marker of CRC progression. However, since the number of the original studies was limited, more well-designed, large-scale, high-quality studies are warranted to provide more convincing and reliable information.
PubMed: 32280357
DOI: 10.1155/2020/8475840