TiO2 nanoparticles (NPs) are extensively used in various applications, highlighting the importance of ongoing research into their effects. This work belongs among rare whole-body inhalation studies investigating the effects of TiO2 NPs on mice. Unlike previous studies, the concentration of TiO2 NPs in the inhalation chamber (130.8 μg/m3) was significantly lower. This 11-week study on mice confirmed in vivo the presence of TiO2 NPs in lung macrophages and type II pneumocytes including their intracellular localization by using the electron microscopy and the state-of-the-art methods detecting NPs' chemical identity/crystal structure, such as the energy-dispersed X-ray spectroscopy (EDX), cathodoluminescence (CL), and detailed diffraction pattern analysis using powder nanobeam diffraction (PNBD). For the first time in inhalation study in vivo, the alterations in erythrocyte morphology with evidence of echinocytes and stomatocytes, accompanied by iron accumulation in spleen, liver, and kidney, are reported following NP's exposure. Together with the histopathological evidence of hyperaemia in the spleen and kidney, and haemosiderin presence in the spleen, the finding of NPs containing iron might suggest the increased decomposition of damaged erythrocytes. The detection of TiO2 NPs on erythrocytes through CL analysis confirmed their potential systemic availability. On the contrary, TiO2 NPs were not confirmed in other organs (spleen, liver, and kidney); Ti was detected only in the kidney near the detection limit.

Cardiovascular diseases (CVDs) pose a serious threat to human health and represent one of the leading causes of death worldwide. Cellular autophagy, an essential intracellular self-degradation and homeostasis maintenance mechanism, plays a pivotal role in the pathogenesis of cardiovascular diseases. Traditional Chinese Medicine (TCM), with its unique theoretical framework and therapeutic principles, has demonstrated remarkable efficacy in CVDs management, garnering increasing scientific attention. In recent years, growing research attention has focused on TCM's autophagy regulation for CVDs treatment. However, most studies remain limited to cellular and animal models, with insufficient clinical data and unclear specific metabolic pathways and targets. Therefore, it is imperative to (1) investigate autophagy mechanisms in depth (2), explore methods for autophagy balance, and (3) clarify drug interactions to establish a foundation for clinical applications. This article comprehensively summarizes relevant research findings, provides an in-depth discussion of TCM's mechanisms in autophagy regulation for CVDs treatment, reviews current research status, and outlines future development trends, aiming to offer valuable theoretical foundations and therapeutic strategies for clinical CVDs management.

Myocardial ischemia-reperfusion injury (MIRI) is fatal to patients, leading to cardiomyocyte death and myocardial remodeling. Reactive oxygen species (ROS) and oxidative stress play important roles in MIRI. There is a complex crosstalk between ROS and regulatory cell deaths (RCD) in cardiomyocytes, such as apoptosis, pyroptosis, autophagy, and ferroptosis. ROS is a double-edged sword. A reasonable level of ROS maintains the normal physiological activity of myocardial cells. However, during myocardial ischemia-reperfusion, excessive ROS generation accelerates myocardial damage through a variety of biological pathways. ROS regulates cardiomyocyte RCD through various molecular mechanisms. Targeting the removal of excess ROS has been considered an effective way to reverse myocardial damage. Many studies have applied antioxidant drugs or new advanced materials to reduce ROS levels to alleviate MIRI. Although the road from laboratory to clinic has been difficult, many scholars still persevere. This article reviews the molecular mechanisms of ROS inhibition to regulate cardiomyocyte RCD, with a view to providing new insights into prevention and treatment strategies for MIRI.

HBV has a small genome and thrives in the infected hepatocytes by hijacking the cellular machinery and cellular pathways. HBV induces incomplete autophagy for its replication and survival. This study showed that HBV replication induces Reactive oxygen species (ROS) production, which in turn augments the formation of autophagosomes. Augmenter of liver regeneration (ALR) is a sufhydryl oxidase and has an anti-oxidative property. We sought to determine the interplay between HBV and antioxidant protein ALR. We showed that HBV downregulated ALR expression in hepatic cells. There was increased ROS production in HBV-infected cells while ALR downregulated ROS levels and expression of NADPH oxidase NOX4. N-acetyl cysteine, a ROS scavenger, downregulated ROS level and autophagosome formation in HBV-expressing cells. ALR overexpression in HBV-expressing cells downregulated the expression of autophagy marker proteins while upregulated the expression of p-MTOR. ALR overexpression decreased the expression of HBx, HBsAg, and total HBV load. This study showed that HBx relieved ALR-mediated inhibition by upregulating the miR-181a expression in HBV-infected cells, which in turn downregulated ALR expression.

Pseudomonas aeruginosa (PA) is an opportunistic gram-negative pathogen that can infect the cornea, leading to permanent vision loss. Autophagy is a cannibalistic process that drives cytoplasmic components to the lysosome for degradation and/or recycling. Autophagy has been shown to play a key role in the removal of intracellular pathogens and, as such, is an important component of the innate immune response. Autophagy is intimately linked to mitochondria, organelles that mediate energy homeostasis, immune signaling, and cell death. Using a combination of biochemical and imaging approaches, we investigated the effects of PA on autophagy and host cell mitochondria in relation to pro-inflammatory cytokine expression. Using a standard invasive test strain of PA, we show that PA infection triggers dephosphorylation of the mechanistic target of rapamycin in corneal epithelial cells, leading to the induction of autophagy through ULK1/2. This was associated with robust mitochondrial depolarization, changes in mitochondrial ultrastructure, and an increase in IL-6 and IL-8 secretion. PA infection was also associated with an increase in purine metabolism by host cells. Treatment with the ULK1/2 inhibitor, MRT68921, which blocks phagophore formation, attenuated levels of intracellular PA in corneal epithelial cells. Unexpectedly, treatment of cells with MRT68921 blocked PA-induced mitochondrial depolarization and downregulated purine and pyrimidine metabolism. While MRT68921 attenuated the PA-induced increase in IL-6, it further increased IL-8 and neutrophil chemotaxis. This was associated with the nuclear internalization of NFκB. Taken together, these findings highlight a novel mechanism whereby the inhibition of ULK1/2 activity confers mitoprotection during PA infection in corneal epithelial cells.IMPORTANCEPseudomonas aeruginosa (PA) is a common pathogen that can cause severe disease in man. In the eye, PA infection can lead to blindness. In this study, we show that PA induces autophagy, a mechanism whereby cells recycle damaged proteins and organelles. PA infection further depolarizes mitochondria, leading to the release of pro-inflammatory mediators. Unexpectedly, the inhibition of ULK1/2, an enzyme involved in the early stages of autophagy, not only inhibits autophagy but enhances mitochondrial polarization. This leads to a reduction in intracellular levels of PA and changes in the inflammatory milieu. Together, these data suggest that the inhibition of ULK1/2 may be mitoprotective in corneal epithelial cells during PA infection.

Neurodegenerative diseases are mainly a consequence of degenerated proteins in neurons. Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by Lewy body deposition. Autophagy is known as one of the cell maintenance mechanisms. Autophagy targets are damaged or degenerated macromolecules and organelles for lysosomal degradation. The role of disrupted autophagy in PD was established earlier. In this regard, the current study aimed to evaluate the frequency and status of the autophagy gene polymorphisms in PD by a systematic review approach.

In the current study, electronic databases including Scopus, PubMed, and Science Direct were used for the search. The search was performed by using Parkinson's disease, autophagy, autophagy-related gene, ATG, Single-nucleotide polymorphisms, variant, Sequence variants, and with a date limitation of 2010 to 2023. All original research papers in the English language that evaluate the ATG polymorphisms in PD were included in the study.

The conducted search leads to 2626 primary studies screened based on the inclusion criteria. After the screening stage, 8 studies were included. ATG7 rs1375206 and ATG5 rs510432, rs573775 and rs17587319 were associated with PD. However, some other polymorphisms in ATGs that were not associated with PD were listed.

In conclusion, regardless of the critical role of autophagy in PD pathogenesis, it seems that ATG16 and ATG7 polymorphisms are not associated with PD; however, ATG7 rs1375206 needs more evaluation for a clearer conclusion in future studies. ATG5 and ATG12 polymorphisms seem to be more important in PD. More comprehensive studies about all ATG5, 7, 12, and 16 seem to be urgently required for a conclusive judgment about their role in PD or even other neurodegenerative disorders.

Autophagy, a cellular process essential for maintaining homeostasis, plays a fundamental role in recycling damaged components and in adapting to stress. The dysregulation of autophagy is implicated in numerous human diseases, including cancer, where it exhibits a dual role as both a suppressor and a promoter, depending on the context and the stage of tumor development. The significant sex differences observed in autophagic processes are determined by biological factors, such as genetic makeup and sex hormones. Estrogens, through their interaction with specific receptors, modulate autophagy and influence tumor progression, therapy resistance, and the immune response to tumors. In females, the escape from X inactivation and estrogen signaling may be responsible for the advantages, in terms of lower incidence and longer survival, observed in oncology. Women often show better responses to traditional chemotherapy, while men respond better to immunotherapy. The action of sex hormones on the immune system could contribute to these differences. However, women experience more severe adverse reactions to anticancer drugs. The estrogen/autophagy crosstalk-involved in multiple aspects of the tumor, i.e., development, progression and the response to therapy-deserves an in-depth study, as it could highlight sex-specific mechanisms useful for designing innovative and gender-tailored treatments from the perspective of precision medicine.

We previously demonstrated that hyperosmotic stress, which acts as mechanical stress, induces autophagy of tubular epithelial cells. This study aims to elucidate the molecular mechanisms of hyperosmolarity-induced autophagy. The research question addresses how hyperosmotic stress activates autophagy through transcription factor EB (TFEB) and Ca2+ signaling pathways, contributing to understanding cellular responses to mechanical stress.

NRK-52E normal rat kidney cells were subjected to hyperosmotic stress using mannitol-containing medium. Fluorescence microscopy was utilized to observe TFEB nuclear translocation, a crucial event in autophagy regulation. An intracellular Ca2+ chelator, BAPTA-AM, and a calcineurin inhibitor were used to dissect the Ca2+ signaling pathway involved in TFEB translocation. The phosphorylation of p70S6K, a substrate of the mammalian target of rapamycin complex 1 kinase, was analyzed to explore its role in TFEB localization. Additionally, the function of transient receptor potential mucolipin 1 (TRPML1), an intracellular Ca2+ channel, was assessed using pharmacological inhibition to determine its impact on TFEB translocation and autophagy marker LC3-II levels.

Mannitol-induced hyperosmotic stress promoted the nuclear translocation of TFEB, which was completely abolished by treatment with BAPTA-AM. Inhibition of calcineurin suppressed TFEB nuclear translocation under hyperosmolarity, indicating that a signaling pathway governed by intracellular Ca2+ is involved in TFEB's nuclear translocation. In contrast, hyperosmotic stress did not significantly alter p70S6K phosphorylation. Pharmacological inhibition of TRPML1 attenuated both TFEB nuclear translocation and LC3-II upregulation in response to hyperosmotic stress.

Hyperosmotic stress promotes TFEB nuclear localization, and TRPML1-induced activation of calcineurin is involved in the mechanism of hyperosmolarity-induced autophagy.

The online version contains supplementary material available at 10.1007/s12195-024-00839-6.

Cerebral ischemia-reperfusion injury (CIRI) is a common and serious complication of reperfusion therapy in patients with ischemic stroke (IS). The regulation of microglia-mediated neuroinflammation to control CIRI has garnered considerable attention. The balance of iron metabolism is key to maintaining the physiological functions of microglia. Nuclear Receptor Coactivator 4 (NCOA4)-mediated ferritinophagy, an important pathway in regulating iron metabolism, is a promising intervention target. However, studies on the impacts of ferritinophagy on microglia-mediated neuroinflammation are lacking. This study aimed to identify potential treatments for CIRI-induced neuroinflammation by focusing on ferritinophagy and the specific mechanisms whereby iron metabolism regulates microglia-mediated neuroinflammation. CIRI induced the activation of ferritinophagy in microglia, characterized by the upregulation of NCOA4, downregulation of Ferritin Heavy Chain 1 (FTH1), and increased intracellular iron levels. This activation contributes to increased ferroptosis, oxidative stress, and the release of inflammatory factors. Silencing NCOA4 or application of the ferroptosis-specific inhibitor Ferrostatin-1 (Fer-1) effectively suppressed the CIRI-induced damage in vivo and in vitro. While Fer-1 addition did not inhibit the CIRI-activated ferritinophagy, it did partially reverse the alleviation of NCOA4 depletion-induced neuroinflammation, suggesting that ferroptosis is an essential intermediate step in ferritinophagy-induced neuroinflammatory damage. Furthermore, using IS-related transcriptomic data, the cGAS-STING pathway was identified as a crucial mechanism connecting ferritinophagy and ferroptosis. Specific inhibition of the cGAS-STING pathway reduced ferritinophagy-induced ferroptosis and neuroinflammation. In summary, our results indicated that ferritinophagy activates the cGAS-STING signaling pathway, which promotes the inflammatory response and oxidative stress in microglia in a ferroptosis-dependent manner, thereby exacerbating CIRI-induced neuroinflammation. These findings provide theoretical support for the clinical treatment of CIRI.

This study aimed to elucidate the potential causal relationship between 4,907 plasma proteins and the risk of gastric cancer using a two-sample Mendelian randomization approach. We utilized genome-wide association study (GWAS) data to perform two-sample Mendelian randomization analyses, treating the 4,907 plasma proteins as exposure factors and gastric cancer as the outcome. Instrumental variables for plasma proteins were selected based on strongly correlated SNPs identified through data processing and screening of the GWAS data provided by the deCode database. We employed a set of statistical methods centered on inverse variance weighting (IVW) for Mendelian randomization analysis to estimate the odds ratios (ORs) for the effects of these plasma proteins on gastric cancer susceptibility. According to the IVW method, 14 plasma proteins were associated with gastric cancer (p < 0.005). Specifically, CHST15 (OR = 0.7553, 95% CI = 0.6346 - 0.8988), L1CAM (OR = 0.7230, 95% CI = 0.5876 - 0.8896), FTMT (OR = 0.8246, 95% CI = 0.7241 - 0.9391), and PMM2 (OR = 0.5767, 95% CI = 0.3943 - 0.8433) were negatively correlated with GASTRIC CANCER, whereas ABO (OR = 1.1868, 95% CI = 1.0638 - 1.3240), FAM3D (OR = 1.2109, 95% CI = 1.0850 - 1.3515), FAM3B (OR = 1.2988, 95% CI = 1.0953 - 1.5402), ADH7 (OR = 1.3568, 95% CI = 1.1044 - 1.6670), MAP1LC3A (OR = 1.3704, 95% CI = 1.1194 - 1.6778), PGLYRP1 (OR = 1.4071, 95% CI = 1.1235 - 1.7623), PDE5A (OR = 1.7446, 95% CI = 1.2693 - 2.3978), GLUL (OR = 3.1203, 95% CI = 1.5017 - 6.4839), NFE2L1 (OR = 3.1759, 95% CI = 1.6163 - 6.2402), and MAFG (OR = 3.1945, 95% CI = 1.5329 - 6.6575) were positively correlated. Convergent results from Weighted Median and MR-Egger analyses confirmed these associations. Reverse Mendelian randomization analysis indicated that gastric cancer does not significantly alter the levels of these 14 plasma proteins (p > 0.05). Sensitivity analyses, including assessments of heterogeneity and horizontal pleiotropy, confirmed the robustness and reliability of our findings without significant bias. Pathway enrichment analysis of gene expression associated with these 14 plasma proteins, using GO and KEGG pathways, revealed that CHST15, L1CAM, FTMT, and PMM2 may serve as protective factors against gastric cancer, while ABO, FAM3D, FAM3B, ADH7, MAP1LC3A, PGLYRP1, PDE5A, GLUL, NFE2L1, and MAFG may contribute to gastric cancer pathogenesis. These results highlight the complex biological interactions between plasma proteins and tumorigenesis, providing valuable insights for preventive and therapeutic strategies in gastric malignancy management.

The glomerular podocyte endoplasmic reticulum is a critical component in renal function, yet its research landscape is not fully understood. This study aims to map the existing research on podocyte endoplasmic reticulum by analyzing publications in the Web of Science Core Collection (WOSCC) from the past 19 years.

We conducted a bibliometric analysis using Citespace, VOSviewer, the Metrology Literature Online platform, and the Bibliometrix software package to visualize and interpret the data from WOSCC. The analysis focused on publication volume, authorship, institutional contributions, and research trends.

The analysis revealed a significant growth in publications, indicating a surge in interest in podocyte endoplasmic reticulum research. Cybulsky, Andrey V, and Papillon, Joan emerge as the most prolific authors, and the Journal of the American Society of Nephrology is the leading journal in this field. China is the top contributor in terms of publications, with McGill University being the most productive institution. The research primarily focuses on endoplasmic reticulum stress, diabetic nephropathy, and apoptosis, with emerging trends in "foot cell apoptosis," "cell signaling pathways," and "autophagy."

The findings highlight the expanding scope of podocyte endoplasmic reticulum research, with a particular emphasis on the mechanisms of endoplasmic reticulum stress and podocyte apoptosis. Future research directions may include the identification of specific therapeutic targets, detailed exploration of podocyte signaling pathways, and the role of autophagy. This study provides a comprehensive overview of the major research areas, frontiers, and trends in podocyte endoplasmic reticulum research, which are pivotal for guiding future investigations.

Acute lymphoblastic leukemia (ALL) is a malignant disorder in both humans and animals. L-asparaginase (L-ASNase) has limitations as a chemotherapy agent due to adverse effects and low serum stability. In a previous study, L-ASNase was chemically modified with carboxymethyl dextran to enhance its properties.

This study aimed to validate the potential of these modifications using the NALM-6 cell line.

NALM-6 cells were cultured and treated with various concentrations, including 0 IU/ml as negative control, 0.5, 1, 1.5, and 2 IU/ml of modified L-ASNase and L-ASNase. The optimal concentration was determined at specific intervals, and viability and metabolic activity were assessed through Trypan blue and MTT tests. Flow cytometry, using Annexin V/PI staining, was employed to evaluate apoptosis. Real-time RT-PCR techniques were used to determine changes in the expression of the ATG2B and LC3-II genes (important genes in autophagy), with data analysis conducted using PRISM software.

The modified L-ASNase reduced the viability of NALM-6 cells and induced higher levels of apoptosis (P=0.001). Interestingly, the modified enzyme had a lesser impact on autophagy, which is important for avoiding treatment resistance.

The modified L-ASNase showed enhanced effectiveness in reducing the viability of NALM-6 cells and induced higher levels of apoptosis. Interestingly, the modified enzyme had a lesser effect on autophagy, which is important as excessive autophagy can lead to treatment resistance. These findings suggest that the modified L-ASNase may have the potential to be a more effective chemotherapeutic agent for ALL treatments.

Endoplasmic reticulum (ER) stress is extensively studied as a pivotal role in the pathological processes associated with intestinal microecology. In antineoplastic drug treatments, ER stress is implicated in altering the permeability of the mechanical barrier, depleting the chemical barrier, causing dysbiosis, exacerbating immune responses and inflammation in the immune barrier. Enteric dysbiosis and intestinal dysfunction significantly affect the circulatory system in various heart disorders. In antineoplastic drug-related cardiovascular (CV) toxicity, ER stress constitutes a web of relationships in the host-microbiome symbiotic regulatory loop. Therefore, understanding the holobiont perspective will help de-escalate spatial and temporal restrictions. This review investigates the role of ER stress-mediated gut microecological alterations in antineoplastic treatment-induced CV toxicity.

Atorvastatin (ATV) is a representative for hypolipidemic pharmaceuticals and is widely detectable in aquatic environments around the world. However, there are limited studies on the potential effects of ATV on aquatic non-target organisms, especially on aquatic invertebrates. In the present study, the model organism, Daphnia magna was used to investigate the responses of antioxidant system, autophagy process and energy metabolism under the acute exposure of ATV (24 h-96 h), and the changes of physiological parameters of D. magna in response to chronic ATV exposure (21 d) was addressed as well. The results showed that ATV caused oxidative stress in D. magna and elevated activities of antioxidant enzymes (SOD, GST, GPx, and TrxR) at 48 h. However, the progressively increasing oxidative pressure eventually suppressed antioxidant capacities and triggered the transcriptional autophagy process in organism under the regulation of Sestrin as well as its regulated genes (P62, LC3, ATG1, and ATG4B). ATV also altered the expression of DNA methylation related genes. Unlike the clinical response, we found acute ATV exposure led to lipid accumulation in D. magna, affecting energy metabolism. Chronic exposure of higher concentration of ATV (50, 500 μg L-1) adversely affected growth and reproduction parameters of D. magna, caused delayed molting, reduced body length, and decreased number and delayed time of neonates production. Lethal effects were observed in the 5000 μg L-1 of ATV. The present study investigated the toxic effects and mechanisms of acute and chronic ATV exposure on D. magna to provide a scientific basis for evaluating the potential ecological risks of statins on aquatic invertebrates.

Osteoporosis is a major degenerative metabolic bone disease that threatens the life and health of postmenopausal women. Owing to limitations in detection methods and prevention strategy awareness, the purpose of osteoporosis treatment is more to delay further deterioration rather than to fundamentally correct bone mass. We aimed to clarify the pathogenesis of postmenopausal osteoporosis and optimize treatment plans. Our experiments were based on previous findings that oxidative stress mediates bone metabolism imbalance after oestrogen deficiency. Through energy metabolism-targeted metabolomics, we revealed that purine metabolism disorder is the main mechanism involved in inducing oxidative damage in bone tissue, which was verified via the use of machine-learning data from human databases. Xanthine and xanthine oxidase were used to treat osteoblasts to construct a purine metabolism disorder model. The activity and differentiation ability of osteoblasts decreased after X/XO treatment. Transcriptomic sequencing indicated that autophagic flux damage was involved in purine metabolism-induced oxidative stress in osteoblasts. Additionally, we performed serum metabolomics combined with network pharmacology to determine the pharmacological mechanism of metformin in the treatment of postmenopausal osteoporosis. HPRT1 was the potential target filtered from the hub genes, and FoxO1 signalling was the key pathway mediating the effect of metformin in osteoblasts. We also revealed that SIRT3-mediated deacetylation promoted the nuclear localization of FoxO1 to increase the expression of HPRT1. HPRT1 upregulation promoted purine anabolism and prevented the accumulation of ROS caused by purine catabolism to reverse oxidative damage in osteoblasts. We propose that purine metabolism disorder-induced oxidative stress is important for the pathogenesis of postmenopausal osteoporosis. The therapeutic mechanism of metformin should be confirmed through subsequent drug optimization and development studies to improve bone health in postmenopausal women.

GLP-1 (Glucagon-like peptide 1) serves as both a peptide hormone and a growth factor, is released upon nutrient intake and contributes to insulin secretion stimulated by glucose levels. Also, GLP-1 is synthesized within several brain areas and plays a vital function in providing neuroprotection and reducing inflammation through the activation of the GLP-1 receptor. Parkinson's Disease (PD) is a neurodegenerative illness that worsens with time and is defined by considerable morbidity. Presently, there are few pharmaceutical choices available, and none of the existing therapies are capable of modifying the course of the disease. There is a suggestion that type 2 diabetes mellitus (T2DM) could increase the risk of PD, and the presence of both conditions concurrently might exacerbate PD symptoms and hasten neurodegeneration. GLP-1 receptor (GLP-1R) agonists exhibit numerous implications like enhancement of glucose-dependent insulin release and biosynthesis, suppression of glucagon secretion and gastric emptying. Also, some GLP-1R agonists have received clinical approval for the management of T2DM. Moreover, the use of GLP-1R agonists has demonstrated counter-inflammatory, neurotrophic, and neuroprotective actions in various preclinical models of neurodegenerative disorders. Considering the significant amount of evidence backing the potential of GLP-1R agonists to protect the nervous system across different research settings, this article delves into examining the hopeful prospect of GLP-1R agonists as a treatment option for PD. This review sheds light on combined neuroprotective benefits of GLP-1R agonists and the possible mechanisms driving the protective effects on the PD brain, through the collection of data from various preclinical and clinical investigations.

Lung disease development involves multiple cellular processes, including inflammation, cell death, and proliferation. Research increasingly indicates that autophagy and its regulatory proteins can influence inflammation, programmed cell death, cell proliferation, and innate immune responses. Autophagy plays a vital role in the maintenance of homeostasis and the adaptation of eukaryotic cells to stress by enabling the chelation, transport, and degradation of subcellular components, including proteins and organelles. This process is essential for sustaining cellular balance and ensuring the health of the mitochondrial population. Recent studies have begun to explore the connection between autophagy and the development of different lung diseases. This article reviews the latest findings on the molecular regulatory mechanisms of autophagy in lung diseases, with an emphasis on potential targeted therapies for autophagy.

Background/Objectives: This review aims to provide a detailed understanding of the current evidence on Alpinia officinarum Hance (A. officinarum) and its potential therapeutic role in central nervous system (CNS) disorders. CNS disorders encompass a wide range of disorders affecting the brain and spinal cord, leading to various neurological, cognitive and psychiatric impairments. In recent years, natural products have emerged as potential neuroprotective agents for the treatment of CNS disorders due to their outstanding bioactivity and favourable safety profile. One such plant is A. officinarum, also known as lesser galangal, a perennial herb from the Zingiberaceae family. Its phytochemical compounds such as flavonoids and phenols have been documented to have a powerful antioxidants effect, capable of scavenging free radicals and preventing oxidative damage. Methods: In this review, we critically evaluate the in vitro and in vivo studies and examine the mechanisms by which A. officinarum exerts its neuroprotective effect. Results: Several studies have confirmed that A. officinarum exerts its neuroprotective effects by reducing oxidative stress and cell apoptosis, promoting neurite outgrowth, and modulating neurotransmitter levels and signalling pathways. Conclusions: Although previous studies have shown promising results in various models of neurological disorders, the underlying mechanisms of A. officinarum in Alzheimer's (AD) and Parkinson's disease (PD) are still poorly understood. Further studies on brain tissue and cognitive and motor functions in animal models of AD and PD are needed to validate the results observed in in vitro studies. In addition, further clinical studies are needed to confirm the safety and efficacy of A. officinarum in CNS disorders.

Autophagy is a cellular homeostatic mechanism characterized by cyclic degradation. It plays an essential role in maintaining cellular quality and survival by eliminating dysfunctional cellular components. This process is pivotal in various pathophysiological processes. Benign prostatic hyperplasia (BPH) is a common urological disorder in middle-aged and elderly men. It frequently presents as lower urinary tract symptoms due to an increase in epithelial and stromal cells surrounding the prostatic urethra. The precise pathogenesis of BPH is complex. In recent years, research on autophagy in BPH has gained significant momentum, with accumulating evidence indicating its crucial role in the onset and progression of the disease. This review aims to outline the various roles of autophagy in BPH and elucidate potential therapeutic strategies targeting autophagy for managing BPH.

Cancer is a collection of illnesses characterized by aberrant cellular proliferation that can infiltrate or metastasize to distant anatomical sites, posing a notable threat to human well-being due to its substantial morbidity and death rates worldwide. The potential of plant-derived natural compounds as anticancer medicines has been assessed owing to their favorable attributes of few side effects and significant antitumor activity. Mangrove plants and their derived compounds have been scientifically shown to exhibit many significant beneficial biological activities, such as anti-inflammatory, immunomodulatory, antioxidant, neuroprotective, cardioprotective, and hepatoprotective properties. This study summarized mangrove plants and their derived compounds as potential anticancer agents, with an emphasis on the underlying molecular mechanisms. To explore this, we gathered data on the preclinical (in vivo and in vitro) anticancer effects of mangrove plants and their derived compounds from reputable literature spanning 2000 to 2023. We conducted thorough searches in various academic databases, including PubMed, ScienceDirect, Wiley Online, SpringerLink, Google Scholar, Scopus, and the Web of Science. The results demonstrated that mangrove plants and their derived compounds have promising anticancer properties in preclinical pharmacological test systems through various molecular mechanisms, including induction of oxidative stress and mitochondrial dysfunction, cytotoxicity, genotoxicity, cell cycle arrest, apoptosis, autophagy, antiproliferative, antimetastatic, and other miscellaneous actions. Upon thorough observation of the pertinent information, it is suggested that mangrove plants and their derived chemicals may serve as a potential lead in the development of novel drugs for cancer therapy.

Macroautophagy/autophagy is primarily accountable for the degradation of damaged organelles and toxic macromolecules in the cells. Regarding the essential function of autophagy for preserving cellular homeostasis, changes in, or dysfunction of, autophagy flux can lead to disease development. In the current paper, the complicated function of autophagy in aging-associated pathologies and cancer is evaluated, highlighting the underlying molecular mechanisms that can affect longevity and disease pathogenesis. As a natural biological process, a reduction in autophagy is observed with aging, resulting in an accumulation of cell damage and the development of different diseases, including neurological disorders, cardiovascular diseases, and cancer. The MTOR, AMPK, and ATG proteins demonstrate changes during aging, and they are promising therapeutic targets. Insulin/IGF1, TOR, PKA, AKT/PKB, caloric restriction and mitochondrial respiration are vital for lifespan regulation and can modulate or have an interaction with autophagy. The specific types of autophagy, such as mitophagy that degrades mitochondria, can regulate aging by affecting these organelles and eliminating those mitochondria with genomic mutations. Autophagy and its specific types contribute to the regulation of carcinogenesis and they are able to dually enhance or decrease cancer progression. Cancer hallmarks, including proliferation, metastasis, therapy resistance and immune reactions, are tightly regulated by autophagy, supporting the conclusion that autophagy is a promising target in cancer therapy.

The evolutionarily conserved ATG4 cysteine proteases regulate macroautophagy/autophagy through the priming and deconjugation of the Atg8-family proteins. In mammals there are four ATG4 family members (ATG4A, ATG4B, ATG4C, ATG4D) but ATG4D has been relatively understudied. Heightened interest in ATG4D has been stimulated by recent links to human disease. Notably, genetic variations in human ATG4D were implicated in a heritable neurodevelopmental disorder. Genetic analyses in dogs, along with loss-of-function zebrafish and mouse models, further support a neuroprotective role for ATG4D. Here we discuss the evidence connecting ATG4D to neurological diseases and other pathologies and summarize its roles in both autophagy-dependent and autophagy-independent cellular processes.Abbrevation: ATG: autophagy related; BafA1: bafilomycin A1; BCL2: BCL2 apoptosis regulator; BH3: BCL2 homology region 3; CASP3: caspase 3; EV: extracellular vesicle; GABA: gamma aminobutyric acid; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor associated protein like 1; GABARAPL2: GABA type A receptor associated protein like 2; GFP: green fluorescent protein; LIR: LC3-interacting region; MAP1LC3: microtubule associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; MYC: MYC proto-oncogene, bHLH transcription factor; PE: phosphatidylethanolamine; PS: phosphatidylserine; QKO: quadruple knockout; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel; SQSTM1: sequestosome 1.

Intestinal inflammation and compromised barrier function are critical factors in the pathogenesis of gastrointestinal disorders. This study aimed to investigate the role of miR-192-5p in modulating intestinal epithelial barrier (IEB) integrity and its association with autophagy. A DSS-induced colitis model was used to assess the effects of miR-192-5p on intestinal inflammation. In vitro experiments involved cell culture and transient transfection techniques. Various assays, including dual-luciferase reporter gene assays, quantitative real-time PCR, Western blotting, and measurements of transepithelial electrical resistance, were performed to evaluate changes in miR-192-5p expression, Rictor levels, and autophagy flux. Immunofluorescence staining, H&E staining, TEER measurements, and FITC-dextran analysis were also used. Our findings revealed a reduced expression of miR-192-5p in inflamed intestinal tissues, correlating with impaired IEB function. Overexpression of miR-192-5p alleviated TNF-induced IEB dysfunction by targeting Rictor, resulting in enhanced autophagy flux in enterocytes (ECs). Moreover, the therapeutic potential of miR-192-5p was substantiated in colitis mice, wherein increased miR-192-5p expression ameliorated intestinal inflammatory injury by enhancing autophagy flux in ECs through the modulation of Rictor. Our study highlights the therapeutic potential of miR-192-5p in enteritis by demonstrating its role in regulating autophagy and preserving IEB function. Targeting the miR-192-5p/Rictor axis is a promising approach for mitigating gut inflammatory injury and improving barrier integrity in patients with enteritis.NEW & NOTEWORTHY We uncover the pivotal role of miR-192-5p in fortifying intestinal barriers amidst inflammation. Reduced miR-192-5p levels correlated with compromised gut integrity during inflammation. Notably, boosting miR-192-5p reversed gut damage by enhancing autophagy via suppressing Rictor, offering a potential therapeutic strategy for fortifying the intestinal barrier and alleviating inflammation in patients with enteritis.

Oxidative stress (OS) and apoptosis are critical factors in placental development and function. Their interplay influences trophoblast proliferation, differentiation, and invasion, as well as vascular development. An imbalance between these processes can lead to pregnancy-related disorders such as preeclampsia, intrauterine growth restriction, and even spontaneous abortion. Our study seeks to elucidate the associations between preventive antioxidant/protective OS response factors-glutathione (GSH), MutT Homolog 1 (MTH1), and apoptotic regulation modulators-tumor protein p53 and B-cell lymphoma (Bcl-2) transcripts, in the context of spontaneous abortion (30 samples) versus elective termination of pregnancy (20 samples), using immunohistochemistry (IHC) to determine their proteomic expression in chorionic villi within abortive fetal placenta tissue samples. Herein, comparative statistical analyses revealed that both OS response factors, GSH and MTH1, were significantly under-expressed in spontaneous abortion cases as compared to elective. Conversely, for apoptotic regulators, p53 expression was significantly higher in spontaneous abortion cases, whereas Bcl-2 expression was significantly lower in spontaneous abortion cases. These findings suggest that a strong pro-apoptotic signal is prevalent within spontaneous abortion samples, alongside reduced anti-apoptotic protection, depleted antioxidant defenses and compromised oxidative DNA damage prevention/repair, as compared to elective abortion controls. Herein, our hypothesis that OS and apoptosis are closely linked processes contributing to placental dysfunction and spontaneous abortion was thus seemingly corroborated. Our results further highlight the importance of maintaining redox homeostasis and apoptotic regulation for a successful pregnancy. Understanding the mechanisms underlying this interplay is essential for developing potential therapies to manage OS, promote placentation, and avoid unwanted apoptosis, ultimately improving pregnancy outcomes. Antioxidant supplementation, modulation of p53 activity, and the enhancement of DNA repair mechanisms may represent potential approaches to mitigate OS and apoptosis in the placenta. Further research is needed to explore these strategies and their efficacy in preventing spontaneous abortion.

Acquired chemoresistance remains a significant challenge in the clinics as most of the treated cancers eventually emerge as hard-to-treat phenotypes. Therefore, identifying chemoresistance targets is highly warranted to manage the disease better. In this study, we employed a label-free LC-MS/MS-based quantitative proteomics analysis to identify potential targets and signaling pathways underlying acquired chemoresistance in a sub-cell line (A549DR) derived from the parental lung adenocarcinoma cells (A549) treated with gradually increasing doses of doxorubicin (DOX). Our proteomics analysis identified 146 upregulated and 129 downregulated targets in A549DR cells. The KEGG pathway and Gene ontology (GO) analysis of differentially expressed upregulated and downregulated proteins showed that most abundant upregulated pathways were related to metabolic pathways, cellular senescence, cell cycle, and p53 signaling. Meanwhile, the downregulated pathways were related to spliceosome, nucleotide metabolism, DNA replication, nucleotide excision repair, and nuclear-cytoplasmic transport. Further, STRING analysis of upregulated biological processes showed a protein-protein interaction (PPI) between CDK1, AKT2, SRC, STAT1, HDAC1, FDXR, FDX1, NPC1, ALDH2, GPx1, CDK4, and B2M, proteins. The identified proteins in this study might be the potential therapeutic targets for mitigating DOX resistance.

Diabetes leads to a significantly accelerated incidence of various related macrovascular complications, including peripheral vascular disease and cardiovascular disease (the most common cause of mortality in diabetes), as well as microvascular complications such as kidney disease and retinopathy. Endothelial dysfunction is the main pathogenic event of diabetes-related vascular disease at the earliest stage of vascular injury. Understanding the molecular processes involved in the development of diabetes and its debilitating vascular complications might bring up more effective and specific clinical therapies. Long-acting glucagon-like peptide (GLP)-1 analogs are currently available in treating diabetes with widely established safety and extensively evaluated efficacy. In recent years, autophagy, as a critical lysosome-dependent self-degradative process to maintain homeostasis, has been shown to be involved in the vascular endothelium damage in diabetes. In this review, the GLP-1/GLP-1R system implicated in diabetic endothelial dysfunction and related autophagy mechanism underlying the pathogenesis of diabetic vascular complications are briefly presented. This review also highlights a possible crosstalk between autophagy and the GLP-1/GLP-1R axis in the treatment of diabetic angiopathy.

Psoriasis (PsO) is a prevalent chronic inflammatory skin disease. It is a complex condition that is affected by environmental and hereditary variables. Numerous pathogens, including viruses, bacteria, and even fungi, have been linked to PsO. One of the mechanisms that clears infections is autophagy. The mechanism by which a cell feeds itself is called autophagy by reusing cytoplasmic components in the lysosome. The autophagy-related (ATG) proteins are essential components of the system that control the strictly regulated process of autophagy. Among these 41 proteins, ATG5 is one that is required in order for autophagic vesicles to develop. This research aimed to compare ATG5 levels in serum among those suffering from psoriasis vulgaris and healthy controls. This cross-sectional research was carried out on 45 individuals with vulgaris psoriasis and 45 healthy, sex and age-matched control subjects. All participants underwent a clinical examination, a laboratory investigation, and a history taking, including lipid profiles and serum ATG5. The mean age of the control and PsO were 40.6 ± 9.6, and 43.7 ± 9.3 years respectively. The mean total PASI score was 13.9 ± 8.9, with a median of 11.7 (8.8). According to the PASI score, about 38% (n = 17) had mild disease (PASI < 10), and about 62% (n = 28) had moderate/severe disease (PASI ≥ 10). There was a significantly higher median (IQR) (25th-75th) ATG5 level in PsO 206 (97) (145-242) ng/ml than in the control 147 (98) (111-209) ng/ml (p = 0.002). An insignificant higher median level (IQR) was observed in PsO with mild disease 207(95) compared with those with moderate/severe disease 183(98.5) (p = 0.057). Dissimilarly, the median (IQR) ATG5 level was significantly lower in PsO individuals with metabolic syndrome 170(72) compared with those without 207(104) (p = 0.044). Four predictors were identified following sex and age adjustments, in the final linear regression model: PASI score, triglyceride, High-Density Lipoprotein, and presence of metabolic syndrome. There can be a connection between autophagy as measured by ATG5 and psoriasis vulgaris. ATG5 was elevated in the serum of individuals with psoriasis vulgaris. However, it decreased in patients with metabolic syndrome. No relation was found between serum ATG5 and PASI score. Psoriasis vulgaris patients may benefit from using an autophagy enhancer as a potential treatment target.

T cells, as a major lymphocyte population involved in the adaptive immune response, play an important immunomodulatory role in the early stages of autoimmune diseases. Autophagy is a cellular catabolism mediated by lysosomes. Autophagy maintains cell homeostasis by recycling degraded cytoplasmic components and damaged organelles. Autophagy has a protective effect on cells and plays an important role in regulating T cell development, activation, proliferation and differentiation. Autophagy mediates the participation of T cells in the acquired immune response and plays a key role in antigen processing as well as in the maintenance of T cell homeostasis. In autoimmune diseases, dysregulated autophagy of T cells largely influences the pathological changes. Therefore, it is of great significance to study how T cells play a role in the immune mechanism of autoimmune diseases through autophagy pathway to guide the clinical treatment of diseases.

Amyotrophic lateral sclerosis (ALS) is the most prevalent and lethal class of severe motor neuron diseases (MND) with no efficacious treatment. The pathogenic mechanisms underlying ALS remain unclear. Nearly 90% of patients exhibit sporadic onset (sALS). Therefore, elucidating the pathophysiology of ALS is imperative. Long non-coding RNA (lncRNA) is a large class of non-coding RNAs that regulate transcription, translation, and post-translational processes. LncRNAs contribute to the pathogenesis of diverse neurodegenerative disorders and hold promise as targets for interference in the realm of neurodegeneration. However, the mechanisms of which lncRNAs are involved in ALS have not been thoroughly investigated. We identified and validated a downregulated lncRNA, lnc-HIBADH-4, in ALS which correlated with disease severity and overall survival. Lnc-HIBADH-4 acted as a "molecular sponge" regulating lysosomal function through the lnc-HIBADH-4/miR-326/CTSD pathway, thereby impacting autophagy-lysosome dynamics and the levels of cell proliferation and apoptosis. Therefore, this study discovered and revealed the role of lnc-HIBADH-4 in the pathogenesis of ALS. With further research, lnc-HIBADH-4 is expected to provide a new biomarker in the diagnosis and treatment of ALS.

Intestinal barrier dysfunction is a significant complication induced by sepsis, yet therapeutic strategies targeting such dysfunction remain inadequate. This study investigates the protective effects of Gypenoside XLIX (Gyp XLIX) against intestinal damage induced by sepsis. Septic intestinal injury in mice was induced by cecum ligation and puncture (CLP) surgery. The biological activity and potential mechanisms of Gyp XLIX were explored through intraperitoneal injection of Gyp XLIX (40 mg/kg). The study demonstrates that Gyp XLIX improves the pathological structural damage of the intestine and increases tight junction protein expression as well as the number of cup cells. Through activation of the nuclear factor erythroid 2-related factor 2 - Kelch-like ECH-associated protein 1 (Nrf2-Keap1) pathway, Gyp XLIX enhances antioxidant enzyme levels while reducing the excessive accumulation of reactive oxygen species (ROS). In addition, Gyp XLIX effectively alleviates sepsis-induced intestinal inflammation by inhibiting the nuclear factor kappa B (NF-κB) pathway and activation of the NLRP3 inflammasome. Moreover, Gyp XLIX inhibits cell death through modifying phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, further enhancing its ability to shield the intestinal barrier. The combined action of these molecular mechanisms promotes the restoration of immune balance and reduces excessive autophagy activity induced under septic conditions. In summary, Gyp XLIX exhibits a significant preventive action against intestinal damage brought on by sepsis, with its mechanisms involving the improvement of intestinal barrier function, antioxidative stress, inhibition of inflammatory response, and cell apoptosis. This research offers a potential strategy for addressing intestinal barrier impairment brought on by sepsis.

Diabetic cardiomyopathy (DCM) represents a distinct myocardial disorder elicited by diabetes mellitus, characterized by aberrations in myocardial function and structural integrity. This pathological condition predominantly manifests in individuals with diabetes who do not have concurrent coronary artery disease or hypertension. An escalating body of scientific evidence substantiates the pivotal role of programmed cell death (PCD)-encompassing apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis-in the pathogenic progression of DCM, thereby emerging as a prospective therapeutic target. Additionally, numerous non-coding RNAs (ncRNAs) have been empirically verified to modulate the biological processes underlying programmed cell death, consequently influencing the evolution of DCM. This review systematically encapsulates prevalent types of PCD manifest in DCM as well as nascent discoveries regarding the regulatory influence of ncRNAs on programmed cell death in the pathogenesis of DCM, with the aim of furnishing novel insights for the furtherance of research in PCD-associated disorders relevant to DCM.

Chlamydia trachomatis (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and cervical and fallopian tube inflammation, and poses a threat to human health. Rosmarinic acid (RosA) is an active ingredient of natural products with anti-inflammatory and immunomodulatory effects. This study aimed to investigate the role of RosA in inhibiting autophagy-regulated immune cells-CD8+ T cells via the Ras/Raf/MEK/ERK signaling pathway in a CT-infected mouse model. Mice were inoculated with CT infection solution vaginally, and the mechanistic basis of RosA treatment was established using H&E staining, flow cytometry, immunofluorescence, transmission electron microscopy, and western blot. The key factors involved in RosA treatment were further validated using the MEK inhibitor cobimetinib. Experimental results showed that both RosA and the reference drug azithromycin could attenuate the pathological damage to the endometrium caused by CT infection; flow cytometry showed that peripheral blood CD8+ T cells increased after CT infection and decreased after treatment with RosA and the positive drug azithromycin (positive control); immunofluorescence showed that endometrial CD8 and LC3 increased after CT infection and decreased after RosA and positive drug treatment; the results of transmission electron microscopy showed that RosA and the positive drug azithromycin inhibited the accumulation of autophagosomes; western bolt experiments confirmed the activation of autophagy proteins LC3Ⅱ/Ⅰ, ATG5, Beclin-1, and p62 after CT infection, as well as the inhibition of Ras/Raf/MEK/ERK signaling. RosA and azithromycin inhibition of autophagy proteins activates Ras/Raf/MEK/ERK signaling. In addition, the MEK inhibitor cobimetinib attenuated RosA's protective effect on endometrium by further activating CD8+ T cells on a CT-induced basis, while transmission electron microscopy, immunofluorescence, and western blots showed that cobimetinib blocked ERK signals activation and further induced phagocytosis on a CT-induced basis. These data indicated that RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and RosA could also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice.

Autophagy is a cytoplasmic defense mechanism that cells use to break and reprocess their intracellular components. This utilization of autophagy is regarded as a savior in nutrient-deficient and other stressful conditions. Hence, autophagy keeps contact with and responds to miscellaneous cellular tensions and diverse pathways of signal transductions, such as growth signaling and cellular death. Importantly, autophagy is regarded as an effective tumor suppressor because regular autophagic breakdown is essential for cellular maintenance and minimizing cellular damage. However, paradoxically, autophagy has also been observed to promote the events of malignancies. This review discussed the dual role of autophagy in cancer, emphasizing its influence on tumor survival and progression. Possessing such a dual contribution to the malignant establishment, the prevention of autophagy can potentially advocate for the advancement of malignant transformation. In contrast, for the context of the instituted tumor, the agents of preventing autophagy potently inhibit the advancement of the tumor. Key regulators, including calpain 1, mTORC1, and AMPK, modulate autophagy in response to nutritional conditions and stress. Oncogenic mutations like RAS and B-RAF underscore autophagy's pivotal role in cancer development. The review also delves into autophagy's context-dependent roles in tumorigenesis, metastasis, and the tumor microenvironment (TME). It also discusses the therapeutic effectiveness of autophagy for several cancers. The recent implication of autophagy in the control of both innate and antibody-mediated immune systems made it a center of attention to evaluating its role concerning tumor antigens and treatments of cancer.

Abiotic stresses pose a major increasing problem for the cultivation of maize. Autophagy plays a vital role in recycling and re-utilizing nutrients and adapting to stress. However, the role of autophagy in the response to abiotic stress in maize has not yet been investigated. Here, ZmATG3, which is essential for ATG8-PE conjugation, was isolated from the maize inbred line B73. The ATG3 sequence was conserved, including the C-terminal domains with HPC and FLKF motifs and the catalytic domain in different species. The promoter of the ZmATG3 gene contained a number of elements involved in responses to environmental stresses or hormones. Heterologous expression of ZmATG3 in yeast promoted the growth of strain under salt, mannitol, and low-nitrogen stress. The expression of ZmATG3 could be altered by various types of abiotic stress (200 mM NaCl, 200 mM mannitol, low N) and exogenous hormones (500 µM ABA). GUS staining analysis of ZmATG3-GUS transgenic Arabidopsis revealed that GUS gene activity increased after abiotic treatment. ZmATG3-overexpressing Arabidopsis plants had higher osmotic and salinity stress tolerance than wild-type plants. Overexpression of ZmATG3 up-regulated the expression of other AtATGs (AtATG3, AtATG5, and AtATG8b) under NaCl, mannitol and LN stress. These findings demonstrate that overexpression of ZmATG3 can improve tolerance to multiple abiotic stresses.

Sciatic nerve injury leads to molecular events that cause muscular dysfunction advancement in atrophic conditions. Nerve damage renders muscles permanently relaxed which elevates intracellular resting Ca2+ levels. Increased Ca2+ levels are associated with several cellular signaling pathways including AMPK, cGMP, PLC-β, CERB, and calcineurin. Also, multiple enzymes involved in the tricarboxylic acid cycle and oxidative phosphorylation are activated by Ca2+ influx into mitochondria during muscle contraction, to meet increased ATP demand. Nerve damage induces mitophagy and skeletal muscle atrophy through increased sensitivity to Ca2+-induced opening of the permeability transition pore (PTP) in mitochondria attributed to Ca2+, ROS, and AMPK overload in muscle. Activated AMPK interacts negatively with Akt/mTOR is a highly prevalent and well-described central pathway for anabolic processes. Over the decade several reports indicate abnormal behavior of signaling machinery involved in denervation-induced muscle loss but end up with some controversial outcomes. Therefore, understanding how the synthesis and inhibitory stimuli interact with cellular signaling to control muscle mass and morphology may lead to new pharmacological insights toward understanding the underlying mechanism of muscle loss after sciatic nerve damage. Hence, the present review summarizes the existing literature on denervation-induced muscle atrophy to evaluate the regulation and expression of differential regulators during sciatic damage.

Acute respiratory distress syndrome (ARDS) is a serious lung condition that often leads to hospitalization in intensive care units and a high mortality rate. Sevoflurane is a volatile anesthetic with growing interest for sedation in ventilated patients with ARDS. It has been shown to have potential lung-protective effects, such as reduced inflammation and lung edema, or improved arterial oxygenation. In this study, we investigated the effects of sevoflurane on lung injury in cultured human carcinoma-derived lung alveolar epithelial (A549) cells. We found that sevoflurane was associated with improved wound healing after exposure to inflammatory cytokines, with preserved cell proliferation but no effect on cell migration properties. Sevoflurane exposure was also associated with enhanced cell viability and active autophagy in A549 cells exposed to cytokines. These findings suggest that sevoflurane may have beneficial effects on lung epithelial injury by promoting alveolar epithelial wound healing and by influencing the survival and proliferation of A549 epithelial cells in vitro. Further research is needed to confirm these findings and to investigate the key cellular mechanisms explaining sevoflurane's potential effects on lung epithelial injury.

The presence of respiratory diseases demonstrates a positive correlation with atmospheric fine particulate matter (PM2.5) exposure. The respiratory system is the main target organ affected by PM2.5, and exposure to PM2.5 elevates the likelihood of developing pulmonary fibrosis (PF). In this study, lung epithelial cell (BEAS-2B) and fibroblast (NIH-3T3) were used as in vitro exposure models to explore the mechanisms of PF. PM2.5 exposure caused mitochondrial damage in BEAS-2B cells and increased a fibrotic phenotype in NIH-3T3 cells. Epithelial cells and fibroblasts have different fates after PM2.5 exposure due to their different sensitivities to trigger autophagy. Exposure to PM2.5 inhibits mitophagy in BEAS-2B cells, which hinders the removal of damaged mitochondria and triggers cell death. In this process, the nuclear retention of the mitophagy-related protein Parkin prevents it from being recruited to mitochondria, resulting in mitophagy inhibition. In contrast, fibroblasts exhibit increased levels of autophagy, which may isolate PM2.5 and cause abnormal fibroblast proliferation and migration. Fibrotic phenotypes such as collagen deposition and increased α-actin also appear in fibroblasts. Our results identify PM2.5 as a trigger of PF and delineate the molecular mechanism of autophagy in PM2.5 induced PF, which provides new insights into the pulmonary injury.

Reactive oxidative species (ROS) is a crucial factor in the regulation of cellular biological activity and function, and aberrant levels of ROS can contribute to the development of a variety of diseases, particularly cancer. Numerous discoveries have affirmed that this process is strongly associated with "programmed cell death (PCD)," which refers to the suicide protection mechanism initiated by cells in response to external stimuli, such as apoptosis, autophagy, ferroptosis, etc. Research has demonstrated that ROS-induced PCD is crucial for the development of hepatocellular carcinoma (HCC). These activities serve a dual function in both facilitating and inhibiting cancer, suggesting the existence of a delicate balance within healthy cells that can be disrupted by the abnormal generation of reactive oxygen species (ROS), thereby influencing the eventual advancement or regression of a tumor. In this review, we summarize how ROS regulates PCD to influence the tumorigenesis and progression of HCC. Studying how ROS-induced PCD affects the progression of HCC at a molecular level can help develop better prevention and treatment methods and facilitate the design of more effective preventative and therapeutic strategies.

Oral health is of fundamental importance to maintain systemic health in humans. Stem cell-based oral tissue regeneration is a promising strategy to achieve the recovery of impaired oral tissue. As a highly conserved process of lysosomal degradation, autophagy induction regulates stem cell function physiologically and pathologically. Autophagy activation can serve as a cytoprotective mechanism in stressful environments, while insufficient or over-activation may also lead to cell function dysregulation and cell death.

This review focuses on the effects of autophagy on stem cell function and oral tissue regeneration, with particular emphasis on diverse roles of autophagy in different oral tissues, including periodontal tissue, bone tissue, dentin pulp tissue, oral mucosa, salivary gland, maxillofacial muscle, temporomandibular joint, etc. Additionally, this review introduces the molecular mechanisms involved in autophagy during the regeneration of different parts of oral tissue, and how autophagy can be regulated by small molecule drugs, biomaterials, exosomes/RNAs or other specific treatments. Finally, this review discusses new perspectives for autophagy manipulation and oral tissue regeneration.

Overall, this review emphasizes the contribution of autophagy to oral tissue regeneration and highlights the possible approaches for regulating autophagy to promote the regeneration of human oral tissue.