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1.
Reprod Domest Anim ; 59(4): e14565, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38646981

ABSTRACT

Mangiferin (MGN) is primarily found in the fruits, leaves, and bark of plants of the Anacardiaceae family, including mangoes. MGN exhibits various pharmacological effects, such as protection of the liver and gallbladder, anti-lipid peroxidation, and cancer prevention. This study aimed to investigate the effects of MGN supplementation during in vitro culture (IVC) on the antioxidant capacity of early porcine embryos and the underlying mechanisms involved. Porcine parthenotes in the IVC medium were exposed to different concentrations of MGN (0, 0.01, 0.1, and 1 µM). The addition of 0.1 µM MGN significantly increased the blastocyst formation rate of porcine embryos while reducing the apoptotic index and autophagy. Furthermore, the expression of antioxidation-related (SOD2, GPX1, NRF2, UCHL1), cell pluripotency (SOX2, NANOG), and mitochondria-related (TFAM, PGC1α) genes was upregulated. In contrast, the expression of apoptosis-related (CAS3, BAX) and autophagy-related (LC3B, ATG5) genes decreased after MGN supplementation. These findings suggest that MGN improves early porcine embryonic development by reducing oxidative stress-related genes.


Subject(s)
Embryo Culture Techniques , Embryonic Development , Oxidative Stress , Xanthones , Animals , Oxidative Stress/drug effects , Embryonic Development/drug effects , Xanthones/pharmacology , Embryo Culture Techniques/veterinary , Apoptosis/drug effects , Antioxidants/pharmacology , Autophagy/drug effects , Swine , Blastocyst/drug effects , Female , Gene Expression Regulation, Developmental/drug effects , Parthenogenesis
2.
Kidney Int ; 103(6): 1093-1104, 2023 06.
Article in English | MEDLINE | ID: mdl-36921719

ABSTRACT

Transcriptional profiling studies have identified several protective genes upregulated in tubular epithelial cells during acute kidney injury (AKI). Identifying upstream transcriptional regulators could lead to the development of therapeutic strategies augmenting the repair processes. SOX9 is a transcription factor controlling cell-fate during embryonic development and adult tissue homeostasis in multiple organs including the kidneys. SOX9 expression is low in adult kidneys; however, stress conditions can trigger its transcriptional upregulation in tubular epithelial cells. SOX9 plays a protective role during the early phase of AKI and facilitates repair during the recovery phase. To identify the upstream transcriptional regulators that drive SOX9 upregulation in tubular epithelial cells, we used an unbiased transcription factor screening approach. Preliminary screening and validation studies show that zinc finger protein 24 (ZFP24) governs SOX9 upregulation in tubular epithelial cells. ZFP24, a Cys2-His2 (C2H2) zinc finger protein, is essential for oligodendrocyte maturation and myelination; however, its role in the kidneys or in SOX9 regulation remains unknown. Here, we found that tubular epithelial ZFP24 gene ablation exacerbated ischemia, rhabdomyolysis, and cisplatin-associated AKI. Importantly, ZFP24 gene deletion resulted in suppression of SOX9 upregulation in injured tubular epithelial cells. Chromatin immunoprecipitation and promoter luciferase assays confirmed that ZFP24 bound to a specific site in both murine and human SOX9 promoters. Importantly, CRISPR/Cas9-mediated mutation in the ZFP24 binding site in the SOX9 promoter in vivo led to suppression of SOX9 upregulation during AKI. Thus, our findings identify ZFP24 as a critical stress-responsive transcription factor protecting tubular epithelial cells through SOX9 upregulation.


Subject(s)
Acute Kidney Injury , SOX9 Transcription Factor , Animals , Humans , Mice , Acute Kidney Injury/prevention & control , Epithelial Cells/metabolism , Kidney/metabolism , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Up-Regulation , Zinc Fingers
3.
Connect Tissue Res ; 63(6): 650-662, 2022 11.
Article in English | MEDLINE | ID: mdl-35491814

ABSTRACT

BACKGROUND: Low back pain is a common symptom of intervertebral disc degeneration (IDD), which seriously affects the quality of life of patients. The abnormal apoptosis and senescence of nucleus pulposus (NP) cells play important roles in the pathogenesis of IDD. Proanthocyanidins (PACs) are polyphenolic compounds with anti-apoptosis and anti-aging effects. However, their functions in NP cells are not yet clear. Therefore, this study was performed to explore the effects of PACs on NP cell apoptosis and aging and the underlying mechanisms of action. METHODS: Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. The apoptosis rate was determined TUNEL assays. Levels of apoptosis-associated molecules (Bcl-2, Bax, C-caspase-3 and Caspase-9) were evaluated via western blot. The senescence was observed through SA-ß-gal staining and western blotting analysis was performed to observe the expression of senescence-related molecules (p-P53, P53, P21 and P16). RESULTS: Pretreatment with PACs exhibited protective effects against IL-1ß-induced NP cell apoptosis including apoptosis rate, expressions of proapoptosis and antiapoptosis related genes and protein. PACs could also alleviate the increase of p-p53, P21, and P16 in IL-1ß-treated NP cells. SA-ß-gal staining showed that IL-1ß-induced senescence of NP cells was prevented by PACs pertreatment. In addition, PACs activated PI3K/Akt pathway in IL-1ß-stimulated NP cells. However, these protected effects were inhibited after LY294002 treatment. CONCLUSION: The results of the present study showed that PACs inhibit IL-1ß-induced apoptosis and aging of NP cells by activating the PI3K/Akt pathway, and suggested that PACs have therapeutic potential for IDD.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Nucleus Pulposus , Proanthocyanidins , Aging , Caspase 3/metabolism , Caspase 9/metabolism , Caspase 9/pharmacology , Cells, Cultured , Humans , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/pathology , Nucleus Pulposus/pathology , Phosphatidylinositol 3-Kinases/metabolism , Proanthocyanidins/metabolism , Proanthocyanidins/pharmacology , Proanthocyanidins/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Quality of Life , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/pharmacology , Tumor Suppressor Protein p53/therapeutic use , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/pharmacology
4.
Mediators Inflamm ; 2022: 2579003, 2022.
Article in English | MEDLINE | ID: mdl-35966334

ABSTRACT

Spinal cord injury (SCI) is a highly disabling disorder for which few effective treatments are available. Grape seed proanthocyanidins (GSPs) are polyphenolic compounds with various biological activities. In our preliminary experiment, GSP promoted functional recovery in rats with SCI, but the mechanism remains unclear. Therefore, we explored the protective effects of GSP on SCI and its possible underlying mechanisms. We found that GSP promoted locomotor recovery, reduced neuronal apoptosis, increased neuronal preservation, and regulated microglial polarisation in vivo. We also performed in vitro studies to verify the effects of GSP on neuronal protection and microglial polarisation and their potential mechanisms. We found that GSP regulated microglial polarisation and inhibited apoptosis in PC12 cells induced by M1-BV2 cells through the Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/AKT) signaling pathways. This suggests that GSP regulates microglial polarisation and prevents neuronal apoptosis, possibly by the TLR4-mediated NF-κB and PI3K/AKT signaling pathways.


Subject(s)
Neuroprotective Agents , Spinal Cord Injuries , Animals , Grape Seed Extract , Microglia/metabolism , NF-kappa B/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Phosphatidylinositol 3-Kinases/metabolism , Proanthocyanidins , Proto-Oncogene Proteins c-akt/metabolism , Rats , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/metabolism , Toll-Like Receptor 4/metabolism
5.
J Cell Mol Med ; 25(17): 8174-8186, 2021 09.
Article in English | MEDLINE | ID: mdl-34309216

ABSTRACT

The involvement of long non-coding RNAs (lncRNAs), differentially expressed genes and signals in prostate cancer (PCa) continues to be a subject of investigation. This study determined effects of LOC100996425 on human PCa by targeting hepatocyte nuclear factor 4A (HNF4A) via the AMPK/mTOR pathway. PCa and adjacent normal tissues were obtained to characterize expression pattern of LOC100996425, HNF4A and the AMPK/mTOR pathway-related genes. Then, the target gene of LOC100996425 was determined with lncRNA target prediction website and further verification was obtained through luciferase assay and ribonucleoprotein immunoprecipitation. After that, PCa cells were introduced with LOC100996425, HNF4A, siLOC100996425 or siHNF4A to explore the specific significance of LOC100996425 and HNF4A in PCa. The mechanism associated with AMPK/mTOR pathway was investigated using AMPK inhibitor or activator. LOC100996425 was up-regulated, while HNF4A was down-regulated in the PCa tissues. HNF4A was a target gene of LOC100996425. PCa cells transfected with either siLOC100996425 or HNF4A displayed reduced rates of PCa cell proliferation and migration while elevating cell apoptosis. HNF4A overexpression reversed the promotive effect of LOC100996425 overexpression on PCa. The activation of AMPK pathway involved in the cancer progression mediated by LOC100996425. Down-regulation of LOC100996425 retards progression of PCa through HNF4A-mediated AMPK/mTOR pathway.


Subject(s)
Hepatocyte Nuclear Factor 4/metabolism , Prostatic Neoplasms/metabolism , RNA, Long Noncoding/physiology , TOR Serine-Threonine Kinases/metabolism , Adult , Aged , Cell Line, Tumor , Cell Proliferation , Disease Progression , Humans , Male , Middle Aged
6.
Prostaglandins Other Lipid Mediat ; 156: 106584, 2021 10.
Article in English | MEDLINE | ID: mdl-34352381

ABSTRACT

Systemic lupus erythematosus (SLE) is a highly prevalent autoimmune disease characterized by the malfunction of the immune system and the persistent presence of an inflammatory environment. Multiple organs can be affected during SLE, leading to heterogeneous manifestations, which eventually result in the death of patients. Due to the lack of understanding regarding the pathogenesis of SLE, the currently available treatments remain suboptimal. Sphingosine-1-phosphate (S1P) is a central bioactive lipid of sphingolipid metabolism, which serves a pivotal role in regulating numerous physiological and pathological processes. As a well-recognized regulator of lymphocyte trafficking, S1P has been shown to be closely associated with autoimmune diseases, including SLE. Importantly, S1P levels have been found to be elevated in patients with SLE. In murine models of lupus, the increased levels of S1P also contribute to disease activity and organ impairment. Moreover, data from several studies also support the hypothesis that S1P receptors and its producer-sphingosine kinases (SPHK) may serve as the potential targets for the treatment of SLE and its co-morbidities. Given the significant success that intervening with S1P signaling has achieved in treating multiple sclerosis, further exploration of its role in SLE is necessary. Therefore, the aim of the present review is to summarize the recent advances in understanding the potential mechanism by which S1P influences SLE, with a primary focus on its role in immune regulation and inflammatory responses.


Subject(s)
Lysophospholipids , Sphingosine/analogs & derivatives
7.
J Chem Ecol ; 44(10): 905-914, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30097768

ABSTRACT

Female-released chemical signals are crucial clues for mate-searching males to locate and gain sexual receptivity of conspecific females. Abundant behavioral evidence indicates that female spiders release sex pheromones to guide mate-searching behavior of conspecific mature males. However, the chemical nature of spider pheromones is poorly understood. Females of the funnel-web spider, Allagelena difficilis, employ sit-and-wait tactics for mating. Field observations indicate that males leave their retreats to search for potential mates during the breeding season. Therefore, we investigated whether virgin females release a sex attractant to conspecific males and then explored the chemical nature of the female pheromone. Four fatty acids extracted from the female bodies (palmitic acid, linoleic acid, cis-vaccenic acid and stearic acid) constitute a multiple-component sex attractant to conspecific males in A. difficilis. Unexpectedly, mated females also produce the same fatty acids, but at trace levels. Two-choice experiments showed that males were significantly attracted by the blend of the four fatty acids in appropriate concentrations while avoiding the blend consisting of the same acids at very low concentrations, suggesting that mate-searching males are able to discriminate virgin females from mated females by the quantities of female-specific fatty acids in the funnel-web spider A. difficilis.


Subject(s)
Odorants/analysis , Sex Attractants/pharmacology , Sexual Behavior, Animal/drug effects , Spiders/drug effects , Animals , Female , Male , Sex Attractants/chemistry , Sex Attractants/metabolism , Spiders/metabolism , Volatilization
8.
J Minim Access Surg ; 14(1): 74-75, 2018.
Article in English | MEDLINE | ID: mdl-28695884

ABSTRACT

Extrahepatic spread of hepatocellular carcinoma (HCC) is uncommon; and, pelvic metastasis, in particular, is extremely rare. A 71-year-old woman was admitted for evaluation of pelvic solitary solid mass. She had undergone a left lobectomy 28 years previously. Magnetic resonance imaging of the abdomen and pelvis demonstrated a heterogeneous mass in the right pelvic cavity, whereas no space-occupying lesions or ascites were detected in the liver. CA 125 levels were within normal limits; however, serum alpha-fetoprotein levels were markedly elevated. She underwent laparoscopic pelvic mass excision, total hysterectomy, and bilateral salpingo-oophorectomy. Histopathologic findings and immunochemical staining results indicated metastatic HCC. Herein, we report an unusual case of a patient with solitary recurrence in the pelvic cavity 28 years after initial diagnosis and treatment.

9.
Angew Chem Int Ed Engl ; 57(51): 16888-16892, 2018 Dec 17.
Article in English | MEDLINE | ID: mdl-30417592

ABSTRACT

A one-step procedure for the self-switchable block copolymerization of monomer mixtures of epoxides, cyclic anhydrides, and lactide (LA) was developed by using simple organocatalysts without an external stimulus. This multicomponent polymerization bridges two catalytic cycles involving ring-opening alternating copolymerization of epoxides with anhydrides and ring-opening polymerization (ROP) of LA, in which the presence/absence of anhydrides in mixed feedstocks switched the ROP of LA off/on. The self-switchable terpolymerization showed distinct noncoordinating and living nature, as well as perfect chemoselectivity. Different combinations of epoxides, anhydrides, and initiators enabled the generation of a variety of new block polyester polyols.

10.
Eur Radiol ; 24(9): 2227-35, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24895040

ABSTRACT

OBJECTIVES: The aim of our study was to evaluate the tumour volume doubling time (TVDT) of molecular breast cancer subtypes by serial ultrasound (US). METHODS: Sixty-six patients (mean age, 50 years; range, 29-78 years) with invasive breast cancer underwent initial and follow-up breast US examinations (at least three months apart) with no intervention. TVDT was determined using the tumours' greatest dimensions in two orthogonal planes. The results were compared with clinical, imaging, and tumour variables and molecular subtypes (oestrogen receptor [ER]-positive, human epidermal growth factor receptor 2 [HER2]-positive, and triple negative) using a multiple linear regression analysis. RESULTS: TVDT exhibited a wide range (46-825 days; median, 141 days) with an overall mean of 193 ± 141 days and mean values of 241 ± 166 days for ER-positive tumours (n = 37), 162 ± 60 days for HER2-positive tumours (n = 12), and 103 ± 43 days for triple-negative tumours (n = 17) (P < 0.0001). In a multivariate regression analysis, compared to other features, only the different molecular breast cancer subtypes showed significant difference in TVDT (P < 0.0001). CONCLUSIONS: TVDT differed significantly among the three molecular breast cancer subtypes, with the triple-negative tumours showing the fastest growth. KEY POINTS: Knowledge of tumour volume doubling time provides clues for improving screening. TVDT assessed by serial US differed significantly between breast cancer subtypes. Triple-negative tumours had 2.4-fold shorter TVDT compared to ER-positive tumours. Tumours classified as BI-RADS 3 had shorter TVDT than BI-RADS 4.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnostic imaging , Tumor Burden , Ultrasonography, Mammary/methods , Adult , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/surgery , Disease Progression , Female , Follow-Up Studies , Humans , Immunohistochemistry , Mastectomy , Middle Aged , Multivariate Analysis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Retrospective Studies , Time Factors
11.
ACS Nano ; 18(28): 18548-18559, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38968387

ABSTRACT

Polymer fibers that combine high toughness and heat resistance are hard to achieve, which, however, hold tremendous promise in demanding applications such as aerospace and military. This prohibitive design task exists due to the opposing property dependencies on chain dynamics because traditional heat-resistant materials with rigid molecular structures typically lack the mechanism of energy dissipation. Aramid nanofibers have received great attention as high-performance nanoscale building units due to their intriguing mechanical and thermal properties, but their distinct structural features are yet to be fully captured. We show that aramid nanofibers form nanoscale crimps during the removal of water, which primarily resides at the defect planes of pleated sheets, where the folding can occur. The precise control of such a structural relaxation can be realized by exerting axial loadings on hydrogel fibers, which allows the emergence of aramid fibers with varying angles of crimps. These crimped fibers integrate high toughness with heat resistance, thanks to the extensible nature of nanoscale crimps with rigid molecular structures of poly(p-phenylene terephthalamide), promising as a template for stable stretchable electronics. The tensile strength/modulus (392-944 MPa/11-29 GPa), stretchability (25-163%), and toughness (154-445 MJ/cm3) are achieved according to the degree of crimping. Intriguingly, a toughness of around 430 MJ/m3 can be maintained after calcination below the relaxation temperature (259 °C) for 50 h. Even after calcination at 300 °C for 10 h, a toughness of 310 MJ/m3 is kept, outperforming existing polymer materials. Our multiscale design strategy based on water-bearing aramid nanofibers provides a potent pathway for tackling the challenge for achieving conflicting property combinations.

12.
Sci Total Environ ; 949: 174961, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39067584

ABSTRACT

The potential ecological risk of per- and polyfluorinated alkyl substances (PFASs) in phytoremediation has raised social concerns, promoting a need to better understand their distribution and risks in the recovery process of aquatic plants. Herein, we aim to fill this knowledge gap by investigating the distribution and ecotoxicological effects of PFASs on the structure and function of water-macrophyte-sediment microcosm systems. Among the entire system, 63.0 %-73.1 % PFOA was found in sediments and submerged plants, however, 52.5 %-53.0 % of PFPeA and 47.0 %-47.5 % of PFBS remained in the water under different treatments. PFOA was more bioavailable than the other substances, as demonstrated by the bioaccumulation factors (BAF) with ranges exposed to PFPeA and PFBS. Bioaccumulation PFASs induced plant oxidative stress which generates enzymes to suppress superoxide, and disturbed the processes of lysine biosynthesis, in which allysine, meso-2,6-diaminoheptanedioate, and Nsuccinyl-2-amino-6-ketopimelate were downregulated. PFASs were detected in the propagator (turions) of an ecological restoration species, where short-chain PFASs (70.1 % and 45.7 % for 2 or 20 µg/L PFAS exposure, respectively) were found to spread further into new individuals and profoundly influence ecological processes shaping populations. PFASs significantly enhanced the number of microbial species in the sediment, but the degree of differentiation in the microbial community structure was not significantly different. This study enhances our understanding of the ecological mechanisms of PFASs in the water-macrophyte-sediment systems and potential threats to the recovery process of macrophytes.


Subject(s)
Biodegradation, Environmental , Water Pollutants, Chemical , Water Pollutants, Chemical/analysis , Fluorocarbons/metabolism , Plants/metabolism , Plants/drug effects , Hydrocarbons, Fluorinated/metabolism , Geologic Sediments/chemistry
13.
J Hazard Mater ; 476: 135146, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38991643

ABSTRACT

The pathway for pollutant degradation involving reactive oxygen species (ROS) in the rhizosphere is poorly understood. Herein, a rootchip system was developed to pinpoint the ROS hotspot along the root tip of Iris tectorum. Through mass balance analysis and quenching experiment, we revealed that ROS contributed significantly to rhizodegradation for beta-blockers, ranging from 22.18 % for betaxolol to 83.83 % for atenolol. The identification of degradation products implicated ROS as an important agent to degrade atenolol into less toxic transformation products during phytoremediation. Moreover, an active production of ROS in rhizosphere was identified by mesocosm experiment. Across three root-associated regions aquatic plants inhabiting the rhizosphere accumulated the highest •OH of ∼1200 nM after 3 consecutive days, followed by rhizoplane (∼230 nM) and bulk environment (∼60 nM). ROS production patterns were driven by rhizosphere chemistry (Fe and humic substances) and microbiome variations in different rhizocompartments. These findings not only deepen understanding of ROS production in aquatic plants rhizosphere but also shed light on advancing phytoremediation strategies.


Subject(s)
Adrenergic beta-Antagonists , Biodegradation, Environmental , Reactive Oxygen Species , Rhizosphere , Water Pollutants, Chemical , Reactive Oxygen Species/metabolism , Adrenergic beta-Antagonists/metabolism , Water Pollutants, Chemical/metabolism , Iris Plant/metabolism , Plant Roots/metabolism , Microbiota
14.
Antioxidants (Basel) ; 13(1)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38275647

ABSTRACT

Our previous study established that chrysoeriol (CHE) can reduce reactive oxygen species (ROS) accumulation, apoptosis, and autophagy in vitro culture (IVC) of porcine embryos. However, the role of CHE in oocyte maturation and lipid homeostasis is unclear. Herein, we aimed to elucidate the effect of CHE on porcine oocyte competence in vitro maturation (IVM) and subsequent embryo development. The study chooses parthenogenetic activated porcine oocytes as the research model. The study revealed that the cumulus expansion index and related gene expressions are significantly elevated after supplementing 1 µM CHE. Although there were no significant differences in nuclear maturation and cleavage rates, the blastocyst formation rate and total cell numbers were significantly increased in the 1 µM CHE group. In addition, CHE improved the expression of genes related to oocyte and embryo development. ROS was significantly downregulated in all CHE treatment groups, and intracellular GSH (glutathione) was significantly upregulated in 0.01, 0.1, and 1 µM CHE groups. The immunofluorescence results indicated that mitochondrial membrane potential (MMP) and lipid droplet (LD), fatty acid (FA), ATP, and functional mitochondria contents significantly increased with 1 µM CHE compared to the control. Furthermore, CHE increased the expression of genes related to lipid metabolism, mitochondrial biogenesis, and ß-oxidation.

15.
Sci Total Environ ; 887: 164007, 2023 Aug 20.
Article in English | MEDLINE | ID: mdl-37172857

ABSTRACT

Knowledge of the long-term flooding response to climatic changes is critical for probing the flooding future in an oncoming warmer world. In this paper, three well-dated wetland sedimentary cores with high-resolution grain-size records were employed to reconstruct the historical flooding regime along the Ussuri River during the past 7000 years. The results show that five flooding-prone intervals marked by increased mean rates of sand-fraction accumulation occurred at 6.4-5.9 ka BP, 5.5-5.1 ka BP, 4.6-3.1 ka BP, 2.3-1.8 ka BP, and 0.5-0 ka BP, respectively. These intervals are generally consistent with the higher mean annual precipitation controlled by the strengthened East Asian summer monsoon which has been widely documented in geological records across the monsoonal regions of East Asia. Considering the prevalent monsoonal climate along the modern Ussuri River, we suggest that the regional flooding evolution during the Holocene Epoch should be generally controlled by the East Asian summer monsoon circulation which was initially linked to the ENSO activities in the tropical Pacific Ocean. While for the last interval spanning 0.5-0 ka BP, human influence, compared with the long-serving climatic controls, has played a more critical role in driving the regional flooding regime.

16.
Dis Markers ; 2023: 3350685, 2023.
Article in English | MEDLINE | ID: mdl-36776921

ABSTRACT

Muscle diseases are closely related to autophagy disorders. Studies of autophagy inhibition indicated the importance of autophagy in muscle regeneration, while activation of autophagy can restore muscle function in some myopathies. Previous studies have revealed that mutations in the MYOT gene may lead to several kinds of hereditary myopathies. However, whether the autophagy played a crucial role in hereditary myopathy caused by MYOT mutations was still not clear. In this study, we established the MYOT knockdown human skeletal muscle cell models (HSkMCs) by small interfering RNA. Real-time PCR and Western blot studies found that the expression of p62 and LC3B-II was decreased dramatically, which suggested that silencing MYOT expression may regulate the autophagy in HSkMCs. Further immunofluorescence study on Ad-mCherry-GFP-LC3B adenovirus transfection and monodansylcadaverine (MDC) staining revealed that knocking down the expression of MYOT may inhibit the autophagy. Next, we used the autophagy inducer Earle's balanced salt solution (EBSS) and late-autophagy inhibitor bafilomycin A1 (BAF A1) to treat the HSkMCs, respectively, and found that silencing MYOT expression can inhibit the activation of autophagy by EBSS and aggravate the inhibition of autophagy by BAF A1. Finally, we also found that silencing MYOT expression can downregulate the expression of ATG7 and ATG5, two important autophagy regulatory molecules. Hence, our study may first reveal that knocking down the expression of MYOT may inhibit the autophagy. Hereditary myopathies caused by MYOT mutations may partly result from the inhibition of autophagy in HSkMCs.


Subject(s)
Autophagy , Microfilament Proteins , Muscle, Skeletal , Humans , Autophagy/genetics , RNA, Small Interfering/genetics , Transfection , Microfilament Proteins/genetics
17.
Neuroscience ; 517: 18-25, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36893983

ABSTRACT

N-acetylserotonin (NAS) is a chemical intermediate in melatonin biosynthesis. NAS and its derivative N-(2-(5-hydroxy-1H-indol-3-yl) ethyl)-2-oxopiperidine-3-carboxamide (HIOC) are potential therapeutic agents for traumatic brain injury, autoimmune encephalomyelitis, hypoxic-ischemic encephalopathy, and other diseases. Evidence shows that NAS and its derivative HIOC have neuroprotective properties, and can exert neuroprotective effects by inhibiting oxidative stress, anti-apoptosis, regulating autophagy dysfunction, and anti-inflammatory. In this review, we discussed the neuroprotective effects and related mechanisms of NAS and its derivative HIOC to provide a reference for follow-up research and applications.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Melatonin , Neuroprotective Agents , Animals , Humans , Neuroprotective Agents/pharmacology , Serotonin/pharmacology , Neuroprotection , Melatonin/pharmacology
18.
Vet Sci ; 10(2)2023 Feb 10.
Article in English | MEDLINE | ID: mdl-36851447

ABSTRACT

Chrysoeriol (CHE) is a flavonoid substance that exists in many plants. It has various physiological and pharmacological effects, including anti-inflammatory, antioxidant, anti-tumor, and protective activity, especially for the cardiovascular system and liver. Among common livestock embryos, porcine embryos are often considered high-quality objects for studying the antioxidant mechanisms of oocytes. Because porcine embryos contain high levels of lipids, they are more vulnerable to external stimuli, which affect development. Our study explored the influence of CHE supplementation on oxidative stress in porcine oocytes and its possible mechanisms. Different concentrations of CHE (0, 0.1, 1, and 3 µM) were supplemented in the in vitro culture medium of the porcine oocytes. The results showed that supplementation with 1 µM CHE significantly increased the blastocyst rate and total cell number of embryos in vitro. After finding the beneficial effects of CHE, we measured reactive oxygen species (ROS), glutathione (GSH), and mitochondrial membrane potential (MMP) when the oocytes reached the 4-cell stage of development and determined the levels of apoptosis, cell proliferation, and autophagy at the blastocyst stage of development. The expression levels of some related genes were preliminarily detected by qRT-PCR. The results showed that the apoptosis of blastocysts in the CHE-treated culture also decreased compared with the untreated culture. Furthermore, CHE downregulated intracellular ROS and increased GSH in the embryos. CHE was also shown to improve the activity of mitochondria and inhibit the occurrence of autophagy. In addition, antioxidant-related genes (SOD1, SOD2, and CAT) and cell pluripotency-related genes (SOX2, OCT4, and NANOG) were upregulated. At the same time, apoptosis-related (Caspase 3) and autophagy-related (LC3B) genes showed a downward trend after supplementation with CHE. These results indicate that CHE improved the development of porcine embryos in vitro by reducing oxidative stress and autophagy levels.

19.
Sheng Li Xue Bao ; 64(1): 27-32, 2012 Feb 25.
Article in Zh | MEDLINE | ID: mdl-22348957

ABSTRACT

The present study aimed to investigate the protective effect and mechanism of hydrogen sulfide donor NaHS administration against gastric mucosal injury induced by gastric ischemia-reperfusion (GI-R) in rats. GI-R injury was induced by clamping the celiac artery of adult male SD rats for 30 min and followed by reperfusion for 1 h. The rats were randomly divided into sham group, GI-R group, NaHS group, glibenclamide group and pinacidil group. Gastric mucosal damage was analyzed with macroscopic injured area, deep damage was assessed with histopathology scores, and the hydrogen sulfide concentration in plasma was determined by colorimetric method. The results showed that pretreatment of NaHS significantly reduced the injured area and deep damage of the gastric mucosa induced by GI-R. However, NaHS did not significantly alter the levels of hydrogen sulfide in plasma 14 d after NaHS administration. The gastric protective effect of NaHS during reperfusion could be attenuated by glibenclamide, an ATP-sensitive potassium channel (K(ATP)) blocker. However, K(ATP) opener pinacidil inhibited the GI-R-induced injury. These results suggest that exogenous hydrogen sulfide plays a protective role against GI-R injury in rats possibly through modulation of K(ATP) channel opening.


Subject(s)
Hydrogen Sulfide/metabolism , Ischemic Preconditioning/methods , KATP Channels/physiology , Reperfusion Injury/prevention & control , Stomach/blood supply , Animals , Gastric Mucosa/pathology , KATP Channels/metabolism , Male , Rats , Rats, Sprague-Dawley , Sulfides/pharmacology
20.
Res Sports Med ; 20(2): 75-85, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22458825

ABSTRACT

The objective of this study is to compare plantar loads during running on different overground surfaces. Fifteen heel-to-toe runners participated in the study. Plantar load data were collected and analyzed using an insole sensor system during running on concrete, synthetic rubber, and grass surfaces at a running speed of 3.8 m/s. Compared with running on concrete surface, running on natural grass showed a lower magnitude of maximum plantar pressure at the total foot (451.8 kPa vs. 401.7 kPa, p = 0.016), lateral midfoot (175.3 kPa vs. 148.0 kPa, p = 0.004), central forefoot (366.3 kPa vs. 336.8 kPa, p = 0.003), and lateral forefoot (290.2 kPa vs. 257.9 kPa, p = 0.004). Moreover, running on natural grass showed a longer relative contact time compared with running on a concrete surface at the central forefoot (81.9% vs. 78.8%, p = 0.017) and lateral forefoot (75.2% vs. 73.1%, p = 0.007). No significant difference was observed in other multiple comparisons. Different surfaces affected the plantar loads while running. The differences may help us to understand potential injury mechanisms.


Subject(s)
Athletic Injuries/etiology , Foot/physiology , Posture/physiology , Running/physiology , Weight-Bearing/physiology , Analysis of Variance , Athletic Injuries/epidemiology , Biomechanical Phenomena , Confidence Intervals , Humans , Male , Poaceae , Rubber , Running/injuries , Statistics as Topic , Young Adult
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