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Octreotide ameliorates Bisphenol A-induced testicular toxicity via autophagy-inflammation pathway modulation.

IntroductionTesticular toxicity commonly manifests as impaired spermatogenesis and testicular atrophy. Bisphenol A (BPA), a commonly used or … ficantly impaired spermatogenesis, reduced serum testosterone and TAC, and increased MDA, TNFα, and autophagy-related markers, along with histopathological damage of testis. Co-treatment with OCT mitigated these effects by improving sperm parameters, hormone levels, oxidative stress markers, inflammatory cytokines, and testicular histology.DiscussionThe fin …

TBBPA-BDBPE induces ferroptosis in trophoblasts through chaperone-mediated autophagy of GPX4.

Tetrabromobisphenol A-bis (2,3-dibromopropyl ether) (TBBPA-BDBPE), a novel brominated flame retardant, is increasingly utilized across vario … AMP-2a, which facilitates their interaction with GPX4. This interaction triggers chaperone-mediated autophagy (CMA) of GPX4, ultimately leading to ferroptosis in trophoblasts. Importantly, our study showed that inhibiting ferroptosis effectively rescues trophoblast function, with cordycepin emerging as a promising therapeutic agent to mitigate TBBPA-BDBPE-i …

Maladaptive autophagy mediates renal fibrosis under caloric restriction in aristolochic acid nephropathy.

BACKGROUND: Caloric restriction (CR) is widely promoted for systemic health benefits, yet its impact on toxin-induced nephropathy remains uncertain. We investigated whether CR modifies injury and repair in aristolochic acid (AA) nephropathy and delineated the underlying mechanism. METHODS: Male C57BL/6J mice were subjected to AA-induced nephropathy and assigned to ad libitum (AL) or CR diets initiated after injury. Renal function, histology and fibrosis markers were quantified. CAG-RFP-GFP-LC3 reporter mice were used for in vivo autophagy flux imaging. Rapamycin (mTORC1 inhibition) and 3-MA (…

Kangshujiangu granules improve NAFLD via cross-organ autophagy activation shared with osteoporosis.

BACKGROUND: Osteoporosis (OP), an age-related skeletal disorder characterized by reduced bone mass and deteriorated microarchitecture, and n … trol, NAFLD-OP model, low/medium/high-dose KSJG, and Icariin (ICA) groups. Metabolic indicators and autophagy related proteins were evaluated. In vitro: FFA-induced hepatocytes were treated with Compound C, KSJG, or FF. Cells were divided into six groups: BSA control, FFA model, FFA + Compound C, FFA + KSJG, FFA + FF, and FFA + KSJG + Compound C. Lipid accu …

YY1-VDR axis-mediated autophagy slows the progression of intervertebral disc degeneration.

BACKGROUND: Aging is accompanied by degeneration of the intervertebral discs (IVDD), which leads to a poor quality of life and a significant … cted to IVDD modeling, and NP cells were treated with H2O2 and lentivirus. The oxidative stress and autophagy were assessed in mice and H2O2-treated NP cells. Genes closely associated with YY1 expression were predicted, and ChIP and dual-luciferase experiments were conducted to authenticate their binding relationship. Autophagy agonist rapamycin rescue expe …

Transcriptomic profiles of single-cell autophagy-related genes (ATGs) in lung diseases.

Autophagy related genes (ATGs) play essential roles in maintaining cellular functions, although biological and pathological alterations of ATG phenotypes remain poorly understood. To address this knowledge gap, we utilized the single-cell sequencing technology to elucidate the transcriptomic atlas of ATGs in lung diseases, with a focus on lung epithelium and lymphocytes. This study conducted a comprehensive investigation into RNA profiles of ATGs in the lung tissues obtained from healthy subjects and patients with different lung diseases through single-cell RNA sequencing (scRNA-seq), includin…

HIF1A overexpression promotes osteoblast differentiation through activation of autophagy to alleviate osteoporosis.

Objective Osteoporosis (OP) is a systemic skeletal disease that increases the risk of fractures by weaking bone. Hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in osteogenesis and osteoblastic differentiation. The purpose of this study is to examine the underlying mechanism of HIF-1α overexpression and its impact on osteoblast development. Methods First, we used the autophagy inhibitor 3-MA in conjunction with either a control lentivirus or an HIF-1α overexpression lentivirus to transfect rat osteoblasts in osteogenic induction media for 3, 7, 14, and 21 days. The effects of HIF-1α …

Piezo1 induces mitochondrial autophagy dysfunction leading to cartilage injury in knee osteoarthritis.

BACKGROUND: External mechanical stress plays a pivotal role in the pathogenesis of knee osteoarthritis. Piezo1 can sense mechanical stress c … is of the extracellular matrix in chondrocytes, potentially through the inhibition of mitochondrial autophagy levels, leading to increased mitochondrial dysfunction and the induction of pro-apoptotic proteins and pro-inflammatory cytokines. CONCLUSIONS: Mechanical stress induces extracellular matrix degradation and promotes KOA progression through Piezo1-m …

Autophagy-Induced Microglial Death Contributes to Neuroinflammation in Acute Optic Nerve Injury.

PURPOSE: Optic neuropathy is a leading cause of blindness. Autophagy activation has been reported following optic nerve injury, but its precise role remains unclear. We investigated the involvement of autophagy in the early stages of optic nerve injury and explored potential therapeutic strategies. METHODS: A mouse optic nerve crush (ONC) model was established. Autophagy levels were assessed at different time points using electron microscopy and markers LC3 and Beclin-1. The relationship between autophagy and cell death was examined by Beclin-1 co-localization combined with TUNEL. Receptor-in…

Effect of autophagy-related (Atg) protein 5 on mouse epididymal sperm maturation.

PURPOSE: Sperm mature as they transit through the epididymis, during which they gain progressive motility and the capability to fertilize oocytes. Autophagy plays a significant role in the regulation of testicular spermiogenesis. Autophagy-related gene 5 (Atg5) is recognized as a crucial regulator of autophagy progression. However, the role of Atg5 in regulating epididymal sperm maturation has yet to be elucidated. METHODS: To investigate the function of Atg5 in regulating epididymal sperm maturation, Atg5 conditional knockout mice were generated using Cre/LoxP technology, and sperm quality a…

PLEKHM1 Overexpression Impairs Autophagy and Exacerbates Neurodegeneration in rAAV-α-Synuclein Mice.

The aggregation of α-synuclein (αSyn) is a central feature of Parkinson's disease (PD) and other synucleinopathies. The efficient clearance of αSyn depends largely on the autophagy-lysosomal pathway. Emerging genetic evidence highlights the role of pleckstrin homology and RUN domain-containing M1 protein (PLEKHM1), a critical regulator of autophagosome-lysosome fusion, in the pathogenesis of multiple neurodegenerative diseases. This study investigates the possible effects of increased PLEKHM1 expression on αSyn pathology and neurodegeneration in mice. We utilized a mouse model of PD that is ba…

Celastrol Targets FANCD2 to Induce Autophagy-Dependent Ferroptosis in Hepatocellular Carcinoma Cells.

BACKGROUND: Celastrol has been shown to inhibit hepatocellular carcinoma (HCC) progression, but the underlying mechanism is unknown. Fanconi … lines (SNU-423 and SNU-387) were overexpressed or silenced with FANCD2 and treated with Celastrol. Autophagy and ferroptosis were evaluated by measuring oxidative stress and related markers, and cell function experiments were performed. RESULTS: High expression of FANCD2 was correlated with poor survival in HCC patients. Celastrol targeted FANCD2, reducin …

Beclin-1-dependent autophagy protects perivascular adipose tissue function from hyperaldosteronism effects.

Hyperaldosteronism (HA), characterized by excessive production of aldosterone (Aldo), contributes to cardiovascular damage and perivascular adipose tissue (PVAT) dysfunction. Previous studies have shown that Aldo can impair autophagy in various tissues. However, it remains unclear whether this impairment occurs specifically in PVAT and whether it involves disruption of autophagic flux through Beclin-1 (BCN1), a key regulator of autophagosome formation and maturation. We hypothesize that BCN1-dependent autophagy plays a protective role in PVAT by limiting inflammation and preserving its anticon…

Динамическое регулирование автофагии во время заражения вирусом Семлики в организме клеток нейробластомы.

Автофагия может защитить от инфекции, доставляя вирусы лизосомам для разложения. Вирус Semliki Forest (SFV) — одиночковый вирус, который широко используется в качестве модели для арбовирусной инфекции и нейронного энцефалита. Здесь мы показываем, что автофагию подавляют в ранние часы заражения СФВ нейронами. Мы также показываем, что переход от автоматического подавления к регулированию между ранними и поздними стадиями проходил через модуляцию млекопитающей цели рэпамицин (mTOR) во время инфекции. На более поздних стадиях инфекции автофагосомы солокации с неструктурными белками SFV предлагают

Совпадение в аннотации оригинала
Autophagy can defend against infection by delivering viruses to lysosomes for degradation. Semliki Forest virus (SFV) is a positive-sense, single-stranded RNA virus of the alphavirus genus which has been used extensively as a model for arbovirus infection and neuronal encephalitis. Here, we show that autophagy is suppressed during the early hours of SFV infe…

Pomalidomide promotes macrophage control of Mycobacterium tuberculosis via enhancing HDAC6-mediated autophagy.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a critical global health challenge. The development of new anti-tuber … pomalidomide, an immunomodulatory drug, enhanced HDAC6 expression under Mtb infection and promoted autophagy and acidification of Mtb-containing phagosomes, thus reducing Mtb survival within macrophages. Importantly, pomalidomide enhanced autophagy in a manner dependent on HDAC6. Additionally, pomalidomide inhibited the production of pro-inflammatory cytok …

Autophagy in mycobacterial infections: molecular mechanisms, host-pathogen interactions, and therapeutic opportunities.

Mycobacteria pose significant global health burdens, with Mycobacterium tuberculosis complex causing tuberculosis-a leading infectious killer claiming over 1.25 million lives annually-and NTM driving pulmonary and ulcerative infections, particularly in immunocompromised populations. Autophagy, a conserved cellular degradation pathway, serves as a critical mechanism of host defense against mycobacteria by delivering bacteria to the lysosome. As a response, mycobacteria have evolved intricate strategies to subvert or exploit autophagy for survival. Consequently, autophagy exhibits a dichotomous …

STAT1-IFITM3 promotes autophagy in epithelial cells to control Cryptosporidium parvum infection.

Cryptosporidium parvum infects intestinal epithelial cells, causing cryptosporidiosis in humans and neonatal livestock. Autophagy is an important component of the defense against C. parvum infection. IFITM3 is an IFN-stimulated gene that regulates viral infection through autophagy; however, its role in C. parvum infection is unknown. Herein, IFITM3 levels increased significantly after C. parvum infection and promoted autophagy. IFITM3 overexpression up-regulated LC3B II/LC3B I, Beclin-1, ATG7, and ATG5, but down-regulated p62 during infection. In C. parvum-infected HCT-8 cells, IFITM3 interact…

Rapamycin mitigates organ damage by autophagy-mediated NLRP3 inflammasome inactivation in sepsis.

Autophagy activation can alleviate sepsis-induced organ injuries. Rapamycin (Rap) has emerged as an autophagy regulator in multiple forms of organ injuries. This study aimed to assess whether Rap protects rats from cecal ligation and puncture (CLP)-induced sepsis through autophagy-mediated inactivation of the NLRP3 inflammasome. Rats were allocated to the sham, CLP, Rap (10 mg/kg), or 3-Methyladenine (3-MA) (15 mg/kg) groups. A rat CLP model was established. The survival of rats and lung wet-to-dry weight ratio in each group was assessed. Blood biochemical indexes and oxidative stress-related …

Diabetic Macrophage Exosomal miR-381-3p Inhibits Epithelial Cell Autophagy Via NR5A2.

PURPOSE: To explore the mechanism underlying autophagy disruption in gingival epithelial cells (GECs) in diabetic individuals. METHODS AND MATERIALS: Bone marrow-derived macrophages (BMDMs) and GECs were extracted from C57/bl and db/db mice, the exosomes (Exo) were isolated from BMDMs. qRT‒PCR and Western blotting were performed to analyse gene expression. The AnimalTFDB database was used to identify relevant transcription factors, and miRNA sequencing was utilised to identify relevant miRNAs with the aid of the TargetScan/miRDB/miRWalk databases. A dual-luciferase assay was conducted to veri…

Copper Chelation Therapy Attenuates Periodontitis Inflammation through the Cuproptosis/Autophagy/Lysosome Axis.

Periodontitis development arises from the intricate interplay between bacterial biofilms and the host's immune response, where macrophages s … hagosome expression and mitophagy-related gene expression, countering the LPS-induced inhibition of autophagy flux. TTM also attenuates the LPS-induced fusion of autophagosomes and lysosomes, the degradation of lysosomal acidic environments, lysosomal membrane permeability increase, and cathepsin B secretion. In mice with periodontitis, TTM reduces cupropto …