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Clinics (Sao Paulo, Brazil) May 2024To investigate the influence of aerobic exercise on myocardial injury, NF-B expression, glucolipid metabolism and inflammatory factors in rats with Coronary Heart...
OBJECTIVE
To investigate the influence of aerobic exercise on myocardial injury, NF-B expression, glucolipid metabolism and inflammatory factors in rats with Coronary Heart Disease (CHD) and explore the possible causative role.
METHODS
45 Sprague Dawley® rats were randomized into model, control and experimental groups. A high-fat diet was adopted for generating a rat CHD model, and the experimental group was given a 4-week aerobic exercise intervention. ECG was utilized to evaluate the cardiac function of the rats; HE staining to evaluate the damage of myocardial tissue; TUNEL staining to evaluate cardiomyocyte apoptosis level; ELISA to assay the contents of inflammatory factors and glucolipid metabolism in cardiomyocytes; qPCR to assay IB- and NF-B mRNA expression; Western-blot to assay the apoptosis-related proteins and NF-B signaling pathway-related proteins expressions in myocardial tissue.
RESULTS
In contrast to the model group, aerobic exercise strongly improved the rat's cardiac function and glucolipid metabolism (p < 0.01), enhanced IL-10 content, Bcl-2/Bax level as well as IB- protein and mRNA expression (p < 0.01), and reduced myocardial injury and cardiomyocyte apoptosis, the contents of IL-6, IL-1 and TNF-, Caspase 3 level, NF-B mRNA and protein expression and p-p38 and p-STAT3 expressions (p < 0.01).
CONCLUSION
Aerobic exercise can not only effectively reduce myocardial injury, the release of inflammatory factors and NF-B expression in CHD rats, but also improve cardiac function and glucolipid metabolism. Its mechanism is likely to be related to the inhibition of the NF-B signaling pathway.
PubMed: 38815541
DOI: 10.1016/j.clinsp.2024.100386 -
PloS One 2024Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and oxidative stress plays a crucial role in its development. Juglone, a naturally...
Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and oxidative stress plays a crucial role in its development. Juglone, a naturally occurring naphthoquinone in J. mandshurica, exhibits significant cytotoxic activity against various cancer cell lines. However, whether the anticancer activity of juglone is associated with oxidative stress remains unexplored. In this study, mouse Lewis lung cancer (LLC) and human non-small cell lung cancer A549 cells were used to explore the anticancer mechanisms of juglone. Juglone inhibited LLC and A549 cells viability, with IC50 values of 10.78 μM and 9.47 μM, respectively, for 24 h, and substantially suppressed the migration and invasion of these two lung cancer cells. Additionally, juglone arrested the cell cycle, induced apoptosis, increased the cleavage of caspase 3 and the protein expression of Bax and Cyt c, and decreased the protein expression of Bcl-2 and caspase-3. Furthermore, juglone treatment considerably increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, but suppressed glutathione peroxidase 4 (GPX4) and superoxide dismutase (SOD) activities. It also inhibited the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, which was attenuated by 1,3-diCQA (an activator of PI3K/Akt). Moreover, N-acetylcysteine (a ROS scavenger) partially reversed the positive effects of juglone in terms of migration, invasion, ROS production, apoptosis, and PI3K/Akt pathway-associated protein expression. Finally, in tumor-bearing nude mouse models, juglone inhibited tumor growth without any apparent toxicity and significantly induced apoptosis in NSCLC cells. Collectively, our findings suggest that juglone triggers apoptosis via the ROS-mediated PI3K/Akt pathway. Therefore, juglone may serve as a potential therapeutic agent for the treatment of NSCLC.
Topics: Naphthoquinones; Carcinoma, Non-Small-Cell Lung; Reactive Oxygen Species; Humans; Animals; Apoptosis; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Lung Neoplasms; Mice; Signal Transduction; A549 Cells; Cell Movement; Carcinoma, Lewis Lung; Cell Line, Tumor
PubMed: 38814975
DOI: 10.1371/journal.pone.0299921 -
Turkish Journal of Medical Sciences 2023Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are...
Protective effects of swimming exercises and metformin on cardiac and aortic damage caused by a high-fat diet in obese rats with type 2 diabetes, by regulating the Bcl2/Bax signaling pathway.
BACKGROUND/AIM
Due to the increasing mortality and morbidity rates in diabetes mellitus (DM), which is one of the biggest health problems of our age, many treatment modalities are still being tried. The positive effects of metformin (MET) and physical exercise (EXE) on the pathophysiology of diabetes are well known. In this study, it was aimed to detail these positive effects of MET and EXE in combination on the basis of inflammation, apoptosis mechanisms, and endogen nesfatin-1 (NES-1) synthesis.
MATERIALS AND METHODS
Twenty-seven type 2 DM (DM-2) male Wistar Albino rats were divided into 4 groups, as the high-fat diet (HFD), MET, EXE, and MET+EXE groups. The total duration of the study was 3 months. At the end of the experiment, blood glucose and lipid profiles were measured. Histopathological evaluation was performed on the cardiac and aortic tissues and apoptotic markers were evaluated immunohistochemically. Inflammatory markers and NES-1 levels were analyzed by enzyme-linked immunosorbent assay.
RESULTS
The plasma glucose, homeostatic model evaluation-insulin resistance (HOMA-IR), low-density lipoprotein (LDL) levels increased, and high-density lipoprotein (HDL) levels decreased significantly in the HFD group. In the treatment groups, the glucose, HOMA-IR, LDL, NES-1 levels in the plasma, as well as tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, caspase-3 (Cas-3), Bcl-2-associated X protein (Bax), and histopathological findings of inflammation in tissues were decreased. Additionally, there was an increase in plasma insulin, HDL, and tissue B-cell lymphoma-2 and levels.
CONCLUSION
It was observed that the MET and EXE treatments in the DM-2 model reduced cellular damage mechanisms such as inflammation and apoptosis. The decrease in NES-1 levels was thought to be secondary to this antiinflammatory effect. In conclusion, the results demonstrated the effectiveness of EXE in reducing DM-2 and the NES-1 levels. Further studies are needed to evaluate the effect in different EXE models and treatment durations.
Topics: Animals; Metformin; Diet, High-Fat; Diabetes Mellitus, Type 2; Rats, Wistar; Male; Rats; Signal Transduction; Proto-Oncogene Proteins c-bcl-2; Swimming; bcl-2-Associated X Protein; Obesity; Physical Conditioning, Animal; Hypoglycemic Agents; Apoptosis; Aorta; Nucleobindins; Diabetes Mellitus, Experimental
PubMed: 38813486
DOI: 10.55730/1300-0144.5727 -
Heliyon May 2024APAP (Acetaminophen)-induced hepatic injury is a major public health threat that requires continuous searching for new effective therapeutics. KSG...
APAP (Acetaminophen)-induced hepatic injury is a major public health threat that requires continuous searching for new effective therapeutics. KSG (Kaempferol-3-sophoroside-7-glucoside) is a kaempferol derivative that was separated from plant species belonging to different genera. This study explored the protective effects of KSG on ALI (acute liver injury) caused by APAP overdose in mice and elucidated its possible mechanisms. The results showed that KSG pretreatment alleviated APAP-induced hepatic damage as it reduced hepatic pathological lesions as well as the serum parameters of liver injury. Moreover, KSG opposed APAP-associated oxidative stress and augmented hepatic antioxidants. KSG suppressed the inflammatory response as it decreased the genetic and protein expression as well as the levels of inflammatory cytokines. Meanwhile, KSG enhanced the mRNA expression and level of anti-inflammatory cytokine, IL-10 (interleukin-10). KSG repressed the activation of NF-κB (nuclear-factor kappa-B), besides it promoted the activation of Nrf2 signaling. Additionally, KSG markedly hindered the elevation of ASK-1 (apoptosis-signal regulating-kinase-1) and JNK (c-Jun-N-terminal kinase). Furthermore, KSG suppressed APAP-induced apoptosis as it decreased the level and expression of Bax (BCL2-associated X-protein), and caspase-3 concurrent with an enhancement of anti-apoptotic protein, Bcl2 in the liver. More thoroughly, Computational studies reveal indispensable binding affinities between KSG and Keap1 (Kelch-like ECH-associated protein-1), ASK1 (apoptosis signal-regulating kinase-1), and JNK1 (c-Jun N-terminal protein kinase-1) with distinctive tendencies for selective inhibition. Taken together, our data showed the hepatoprotective capacity of KSG against APAP-produced ALI via modulation of Nrf2/NF-κB and JNK/ASK-1/caspase-3 signaling. Henceforth, KSG could be a promising hepatoprotective candidate for ALI.
PubMed: 38813141
DOI: 10.1016/j.heliyon.2024.e31448 -
Brazilian Journal of Medical and... 2024Osteoarthritis (OA) is a highly prevalent joint disorder characterized by progressive degeneration of articular cartilage, subchondral bone remodeling, osteophyte...
Osteoarthritis (OA) is a highly prevalent joint disorder characterized by progressive degeneration of articular cartilage, subchondral bone remodeling, osteophyte formation, synovial inflammation, and meniscal damage. Although the etiology of OA is multifactorial, pro-inflammatory processes appear to play a key role in disease pathogenesis. Previous studies indicate that electroacupuncture (EA) exerts chondroprotective, anti-inflammatory, and analgesic effects in preclinical models of OA, but the mechanisms underlying these potential therapeutic benefits remain incompletely defined. This study aimed to investigate the effects of EA on OA development in a rat model, as well as to explore associated molecular mechanisms modulated by EA treatment. Forty rats were divided into OA, EA, antagomiR-214, and control groups. Following intra-articular injection of monosodium iodoacetate to induce OA, EA and antagomiR-214 groups received daily EA stimulation at acupoints around the knee joint for 21 days. Functional pain behaviors and chondrocyte apoptosis were assessed as outcome measures. The expression of microRNA-214 (miR-214) and its downstream targets involved in apoptosis and nociception, BAX and TRPV4, were examined. Results demonstrated that EA treatment upregulated miR-214 expression in OA knee cartilage. By suppressing pro-apoptotic BAX and pro-nociceptive TRPV4, this EA-induced miR-214 upregulation ameliorated articular pain and prevented chondrocyte apoptosis. These findings suggested that miR-214 plays a key role mediating EA's therapeutic effects in OA pathophysiology, and represents a promising OA treatment target for modulation by acupuncture.
Topics: Animals; TRPV Cation Channels; MicroRNAs; Electroacupuncture; Apoptosis; Male; Osteoarthritis; Chondrocytes; Disease Models, Animal; bcl-2-Associated X Protein; Rats, Sprague-Dawley; Rats
PubMed: 38808885
DOI: 10.1590/1414-431X2024e13238 -
Oncology Letters Jul 2024Artesunate (ART), an antimalarial drug, has a broad spectrum of antitumour effects in cancer types such as esophageal and gastric cancer. However, evidence demonstrating...
Artesunate (ART), an antimalarial drug, has a broad spectrum of antitumour effects in cancer types such as esophageal and gastric cancer. However, evidence demonstrating the role of ART in cervical cancer cells is limited. In the present study, the inhibitory effect of ART on the growth of cervical cancer cells through the modulation of the cell cycle and apoptosis was investigated. The growth-inhibitory effect of ART on a cervical cancer cell line (SiHa) was detected using a Cell Counting Kit-8 assay after treatment with ART for 24 h, after which the half-maximal inhibitory concentration (IC) was calculated. Using flow cytometry assays, apoptosis, the cell cycle, the levels of reactive oxygen species (ROS) and calcium (Ca) ions, as well as the mitochondrial membrane potential were evaluated in SiHa cells following treatment with ART for 24 and 48 h. The mRNA expression levels of Bcl2, Bcl-xl, (myeloid cell leukaemia 1) Mcl-1, Bcl2-like protein 11 (BIM), (Bcl2-related ovarian killer protein) Bok, Bax and (Bcl2 homologous antagonist/killer) Bak in SiHa cells were detected using reverse transcription-quantitative PCR. ART inhibited the growth of SiHa cells in a dose-dependent manner. The IC of ART in SiHa cells was 26.32 µg/ml. According to the IC value, 15, 30 and 100 µg/ml ART were selected for further experiments, and normal saline (0 µg/ml ART) was used as the control group. The results indicated that treatment with 15, 30 and 100 µg/ml ART for 24 and 48 h induced apoptosis, increased the levels of ROS, the levels of Ca and the mRNA expression levels of BIM, Bok, Bax and Bak, but decreased the cell proliferation indices, the mitochondrial membrane potential and the mRNA expression levels of Bcl2, Bcl-xl and Mcl-1 in a dose- and time-dependent manner. In conclusion, ART inhibited the growth of SiHa cells and induced apoptosis via a mechanism associated with the regulation of Bcl2 family member expression, which was associated with the increase of the levels of ROS and Ca and the reduction of the mitochondrial membrane potential.
PubMed: 38807670
DOI: 10.3892/ol.2024.14447 -
Journal of Translational Medicine May 2024Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and...
BACKGROUND
Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and apoptosis in retinal tissues of negative lens-induced myopic (LIM) guinea pigs by targeting BTG2.
METHODS
Biometric measurements of ocular parameters, flash electroretinogram (FERG), and retinal thickness (RT) were performed after miR-92b-3p intravitreal injection in LIM guinea pigs. The apoptotic rate was detected by Annexin V-FITC/PI double staining, and the change in mitochondrial membrane potential was measured by JC-1 staining. Retinal apoptosis and expression of p53, BTG2, and CDK2 were explored by TdT-mediated dUTP-biotin nick labeling (TUNEL) and immunofluorescence staining assays, respectively. BTG2 and its upstream and downstream molecules at gene and protein levels in retinal tissues were measured by real-time quantitative PCR (qPCR) and Western blotting.
RESULTS
Compared with normal controls (NC), the ocular axial length of LIM guinea pig significantly increased, whereas refraction decreased. Meanwhile, dMax-a and -b wave amplitudes of ERG declined, retinal thickness was decreased, the number of apoptotic cells and apoptotic rate in LIM eyes was exaggerated, and the mitochondrial membrane potential significantly decreased. In addition, results of qPCR and Western blot assays showed that the expression levels of p53, BTG2, CDK2, and BAX in LIM guinea pigs were higher than the levels of the NC group, whereas the BCL-2 expression level was decreased. By contrast, the miR-92b-3p intravitreal injection in LIM guinea pigs could significantly inhibit axial elongation, alleviate DNA damage and apoptosis, and thus protect guinea pigs against myopia.
CONCLUSION
In conclusion, p53 and BTG2 were activated in the retinal tissue of myopic guinea pigs, and the activated BTG2 could elevate the expression of CDK2 and BAX, and attenuate the expression of BCL-2, which in turn promote apoptosis and eventually lead to retinal thinning and impaired visual function in myopic guinea pigs. The miR-92b-3p intravitreal injection can attenuate the elongation of ocular length and retinal thickness, and inhibit the CDK2, BAX, and p53 expression by targeting BTG2, thereby ameliorating DNA damage and apoptosis in LIM guinea pigs and protecting ocular tissues.
Topics: Animals; Guinea Pigs; Apoptosis; MicroRNAs; Retina; DNA Damage; Myopia; Membrane Potential, Mitochondrial; Base Sequence; Immediate-Early Proteins; Tumor Suppressor Proteins; Tumor Suppressor Protein p53; Electroretinography; Disease Models, Animal
PubMed: 38807184
DOI: 10.1186/s12967-024-05288-3 -
Experimental and Therapeutic Medicine Jul 2024In the development of diabetic nephropathy, pathological damage such as interstitial fibrosis and cell apoptosis often occur in renal tubules. In the present study,...
Therapeutic potential of vitamin D3 in mitigating high glucose‑induced renal damage: Mechanistic insights into oxidative stress inhibition and TXNIP/NLRP3 signaling pathway blockade.
In the development of diabetic nephropathy, pathological damage such as interstitial fibrosis and cell apoptosis often occur in renal tubules. In the present study, diabetic and control group mice were randomly treated with vitamin D3 or vehicle for 6 months. In addition, human renal tubular epithelial (HK-2) cells were cultured in high-glucose medium and treated with vitamin D3 or the oxidative inhibitor NAC. Immunohistochemistry, western blotting, quantitative PCR), and ELISA showed that vitamin D3 decreased the expression of α-smooth muscle actin and E-cadherin in renal tubular epithelial cells, improving interstitial fibrosis. It also downregulated the ratio of Bax/Bcl2 protein, alleviating apoptosis in renal tubular epithelial cells. Furthermore, vitamin D3 significantly inhibited oxidative stress response in renal tubular epithelial cells and blocked the (Thioredoxin Interacting Protein) TXNIP/NLRP3 inflammatory pathway. Therefore, vitamin D3 can protect renal tubular epithelial cells from fibrosis and apoptosis by inhibiting oxidative stress response and blocking the TXNIP/NLRP3 inflammatory pathway in diabetic nephropathy.
PubMed: 38800040
DOI: 10.3892/etm.2024.12565 -
Iranian Journal of Basic Medical... 2024Cervical cancer (CC) is the most common gynecological malignant tumor and the fourth leading cause of cancer-related death in women. The progression of CC is...
OBJECTIVES
Cervical cancer (CC) is the most common gynecological malignant tumor and the fourth leading cause of cancer-related death in women. The progression of CC is significantly affected by autophagy. Our objective was to use bioinformatics analysis to explore the expression, prognostic significance, and immune infiltration of autophagy-related genes in CC.
MATERIALS AND METHODS
We identified a set of autophagy-related differentially expressed genes (ARDEGs) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ARDEGs were further validated by The Human Protein Atlas (HPA), GSE52903, and GSE39001 dataset. Hub genes were found by the STRING network and Cytoscape. We performed Gene Set Enrichment Analysis (GSEA), Gene ontology analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and immune infiltration analysis to further understand the functions of the hub genes. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) were used to check the hub genes.
RESULTS
A total of 10 up-regulated (CXCR4, BAX, SPHK1, EIF2AK2, TBK1, TNFSF10, ITGB4, CDKN2A, IL24, and BIRC5) and 19 down-regulated (PINK1, ATG16L2, ATG4D, IKBKE, MLST8, MAPK3, ERBB2, ULK3, TP53INP2, MTMR14, BNIP3, FOS, CCL2, FAS, CAPNS1, HSPB8, PTK6, FKBP1B , and DNAJB1) ARDEGs were identified. The ARDEGs were enriched in cell growth, apoptosis, human papillomavirus infection, and cytokine-mediated. Then, we found that low expression of MAPK3 was associated with poor prognosis in CC patients and was significantly enriched in immune pathways. In addition, the expression of MAPK3 was significantly positively correlated with the infiltration levels of macrophages, B cells, mast cell activation, and cancer-associated fibroblasts. Furthermore, MAPK3 was positively correlated with LGALS9, and negatively correlated with CTLA4 and CD40.
CONCLUSION
Our results show that MAPK3 can be used as a new prognostic biomarker to predict the prognosis of patients with CC.
PubMed: 38800011
DOI: 10.22038/IJBMS.2024.74431.16168 -
Frontiers in Public Health 2024Nanoplastics, an emerging form of pollution, are easily consumed by organisms and pose a significant threat to biological functions due to their size, expansive surface...
BACKGROUND
Nanoplastics, an emerging form of pollution, are easily consumed by organisms and pose a significant threat to biological functions due to their size, expansive surface area, and potent ability to penetrate biological systems. Recent findings indicate an increasing presence of airborne nanoplastics in atmospheric samples, such as polystyrene (PS), raising concerns about potential risks to the human respiratory system.
METHODS
This study investigates the impact of 800 nm diameter-PS nanoparticles (PS-NPs) on A549, a human lung adenocarcinoma cell line, examining cell viability, redox balance, senescence, apoptosis, and internalization. We also analyzed the expression of hallmark genes of these processes.
RESULTS
We demonstrated that PS-NPs of 800 nm in diameter significantly affected cell viability, inducing oxidative stress, cellular senescence, and apoptosis. PS-NPs also penetrated the cytoplasm of A549 cells. These nanoparticles triggered the transcription of genes comprised in the antioxidant network [SOD1 (protein name: superoxide dismutase 1, soluble), SOD2 (protein name: superoxide dismutase 2, mitochondrial), CAT (protein name: catalase), Gpx1 (protein name: glutathione peroxidase 1), and HMOX1 (protein name: heme oxygenase 1)], senescence-associated secretory phenotype [Cdkn1a (protein name: cyclin-dependent kinase inhibitor 1A), IL1A (protein name: interleukin 1 alpha), IL1B (protein name: interleukin 1 beta), IL6 (protein name: interleukin 6), and CXCL8 (protein name: C-X-C motif chemokine ligand 8)], and others involved in the apoptosis modulation [BAX (protein name: Bcl2 associated X, apoptosis regulator), CASP3 (protein name: caspase 3), and BCL2 (protein name: Bcl2, apoptosis regulator)].
CONCLUSION
Collectively, this investigation underscores the importance of concentration (dose-dependent effect) and exposure duration as pivotal factors in assessing the toxic effects of PS-NPs on alveolar epithelial cells. Greater attention needs to be directed toward comprehending the risks of cancer development associated with air pollution and the ensuing environmental toxicological impacts on humans and other terrestrial mammals.
Topics: Humans; Oxidative Stress; Apoptosis; Polystyrenes; Cellular Senescence; A549 Cells; Nanoparticles; Alveolar Epithelial Cells; Cell Survival; Microplastics
PubMed: 38799687
DOI: 10.3389/fpubh.2024.1385387