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Molecular analysis of breast cancer cells by niosomal encapsulated Withania somnifera (WS) extract is the focus of this investigation. Characterization of ASH-loaded niosomes produced by a thin film technique showed that they have an appropriate zeta potential, small particle size, and low polydispersity index. The concentration-dependent suppression of cell proliferation was seen in MCF-7 breast cancer cells treated with ASH-NIO, with an IC50 of 24.13 µM, and olaparib at values of 10.45 µM. Molecular investigation showed that ASH-NIO treated cells had lower levels of B-cell lymphoma 2 (Bcl2) mRNA expression compared to untreated cells, and upregulated levels of Tumor protein 53 (P53), Bcl-2-associated X protein (Bax), caspase-9, and caspase-3. These results provide more evidence that ASH-NIO has potential anti-cancer effects and may be useful as an adjunctive treatment for breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of (+)-borneol on neuroinflammation and microglia phenotype polarization in epileptogenesis and its possible mechanism. Methods: Based on mouse models of status epilepticus (SE) induced by pilocarpine, and treated with 15 mg/kg (+)-borneol, western-blot was used to detect the expressions of NeuN, Iba-1, TLR4, p65 and p-p65 in the hippocampus. Immunofluorescence was used to detect the expression of apoptosis-related proteins Bax and Bcl-2. To explore the effect of (+)-borneol on microglia in vitro , we used the kainic acid-induced microglia model and the concentration of (+)-borneol was 25 μM according to CCK-8 results. The levels of tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in the supernatant of each group was detected by ELISA. The nitric oxide (NO) content in the supernatant was detected by Griess method. The expressions of Iba-1 and TLR4-NFκB signaling pathway-related proteins (TLR4, p65, p-p65) were detected by Western-Blot. Immunofluorescence was used to detect microglia's M1 and M2 phenotype polarization and the expression of Iba-1 and TLR4. Results: (+)-borneol reduced hippocampal neuronal injury, apoptosis, and microglia activation by inhibiting the TLR-NFκB signaling pathway in SE mice. TLR4 agonist LPS partially reversed the neuroprotective effect of (+)-borneol. In the KA-induced microglia model, (+)-borneol inhibited microglia activation, M1 phenotype polarization, and secretion of pro-inflammatory cytokines through the TLR4-NFκB signaling pathway. LPS treatment inhibited the therapeutic effects of (+)-borneol. Conclusion: (+)-borneol inhibits microglial neuroinflammation and M1 phenotype polarization through TLR4-NFκB signaling pathway and reduces neuronal damage and apoptosis in SE mice. Therefore, (+)-borneol may be a potential drug for epilepsy modification therapy. [ABSTRACT FROM AUTHOR]

2H‐pyran compound 1 synthesized from 6‐methylpyridine‐2,4‐diol and citral, has been used for Cu‐catalyzed N‐arylation with a range of arylboric acids to obtain arylated pyranopyridine core structure derivatives (yield up to 77 %). Among them, compound 3 h exhibited a much better inhibitory effect on HepG2 liver cancer cells compared to citral, and the IC50 value was 5.3 μM following exposure with the newly synthesized derivatives (herein named 3 h for short in this paper), which was lower than that of the cisplatin (6.5 μM). Meanwhile, the cell‐cycle arrest of HepG2 cells occurred in the S phase, and the apoptosis of HepG2 cells was significantly increased with increasing drug concentration. In addition, real‐time fluorescence quantification PCR and Western blotting experiments showed that the expression of apoptotic protein BAX was increased, while the expression of anti‐apoptotic protein BCL2 was inhibited in a dose‐dependent fashion. The results of these experiments indicated that apoptosis was promoted in HepG2 cells via apoptotic signaling pathway activated by 3 h. Furthermore, 3 h effectively decreased the phosphorylation levels of PI3 K, ATK and ERK, resulting in the inhibitions of MAPK/ERK and PI3 K/ATK signaling pathways. Briefly, 3 h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells and may be used as anti‐cancer drug in the future. [ABSTRACT FROM AUTHOR]

Introduction: Interleukin-41 (IL-41), also known as Metrnl, is a multifunctional adipokine recognized for its neurotrophic and anti-inflammatory properties that play a significant role in diseases such as sepsis and chronic obstructive pulmonary disease. Despite its crucial biological functions, the mechanisms by which IL-41 mitigates lipopolysaccharide (LPS)-induced acute lung injury (ALI) are not well understood. This study aimed to elucidate the protective effects of IL-41 against LPS-induced inflammation and apoptosis in a murine model and in vitro using bronchial epithelial cells (Beas-2b). Methods: We administered recombinant IL-41 to mice subjected to LPS-induced ALI and observed changes in lung histopathology, inflammation, and apoptosis. Concurrently, Beas-2b cells were transfected with IL-41 constructs, and the role of the AMPK/SIRT1 pathway was investigated using specific inhibitors and agonists. Results: Our results demonstrated that LPS-induced ALI is characterized by increased inflammatory cell chemotaxis in lung lavage fluid, enhanced phosphorylation of NFκB p65, and elevated Bax protein expression, coupled with a decrease in IL-41 protein levels. Treatment with recombinant IL-41 effectively mitigated these pathological changes by upregulating AMPK phosphorylation and SIRT1 expression and inhibiting IκB/NFκB p65 phosphorylation. In cellular assays, overexpression of IL-41 reversed LPS-induced oxidative stress, apoptosis, and the secretion of inflammatory cytokines, whereas suppression of IL-41 or inhibition of AMPK reversed these protective effects. Conclusions: In conclusion, IL-41 exerts significant protective effects against ALI by activating the AMPK/SIRT1 signaling pathway and reducing excessive inflammation and apoptosis. These findings suggest that IL-41 holds promise as a therapeutic target for ALI, potentially allowing for personalized treatments based on serum IL-41 levels. [ABSTRACT FROM AUTHOR]

Fusarium sacchari is a significant pathogenic fungus that causes sugarcane Pokkah Boeng. Proteins secreted by pathogenic fungi can be delivered into hosts to suppress plant immunity and establish infection. However, there is still much to be discovered regarding F. sacchari's secreted effectors in overcoming plant immunity. In this paper, we characterize a novel effector called FsMEP1, which is essential for the virulence of F. sacchari. FsMEP1 contains a conserved zinc-binding motif sequence, HEXXH, and is highly expressed during host infection. Using the Agrobacterium tumefaciens-mediated transient expression system, it was confirmed that FsMEP1 could suppress Bcl-2-associated X protein (BAX)-triggered cell death, callose deposition, and ROS explosion in Nicotiana benthamiana. Furthermore, the deletion of FsMEP1 demonstrated its requirement for contributing to the pathogenicity of F. sacchari in sugarcane. Further analysis revealed that FsMEP1 could interact with the sugarcane thiamine thiazole synthase ScTHI2 and disrupt its normal localization, thereby inhibiting the synthesis of thiamine and the defense responses mediated by ScTHI2. Based on these findings, we propose that ScTHI2 represents a potential molecular target for improving sugarcane resistance to Pokkah Boeng disease. [ABSTRACT FROM AUTHOR]

In this study, water-soluble polysaccharides purified from burdock root were used to intervene in carbon tetrachloride (CCl4)-induced acute liver injury (ALI) of BRL3A hepatocytes and rats. Our results indicated that CCl4 significantly inhibited hepatocyte viability and upregulated the expression of reactive oxygen species (ROS), malondialdehyde (MDA), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and the pro-apoptotic protein Bax. However, Arctium lappa L. root polysaccharides (ALP) could effectively ameliorate liver function and histopathology, oxidative stress, and inflammatory markers. In addition, ALP reduced the expression of apoptotic markers and promoted the proliferation of damaged hepatocytes. In conclusion, ALP possesses a hepatoprotective effect mediated by attenuating oxidative damage, inflammation and apoptosis in ALI. [ABSTRACT FROM AUTHOR]

Vincamine, a monoterpenoid indole alkaloid with vasodilatory properties, is extracted from the leaves of Vinca minor. The present study aimed to determine the potential anticancer effects of vincamine loaded in silver nanoparticles (VCN-AgNPs) in mice with Ehrlich solid carcinoma (ESC). After tumor transplantation, the mice were divided into five groups: ESC, ESC+Cisplatin (CPN; 5 mg/kg), ESC+VCN (40 mg/kg), ESC+AgNPs (6 mg/kg), and ESC+VCN-AgNPs (20 mg/kg). The administration of VCN-AgNPs to ESC-bearing mice improved their survival rate and reduced their body weight, tumor size, and tumor weight compared to the ESC group. Furthermore, VCN-AgNPs intensified oxidative stress in tumor tissues, as evidenced by elevated levels of lipid peroxidation (LPO) and nitric oxide (NO), along with a reduction in the levels of the antioxidants investigated (GSH, GPx, GR, SOD, CAT, and TAC). Furthermore, VCN-AgNPs increased the apoptotic proteins Bax and caspase-3, decreased the anti-apoptotic protein (Bcl-2), increased the inflammatory markers TNF-α and IL-1β, and inhibited angiogenesis by lowering VEGF levels in tumor tissues, all of which led to apoptosis. Furthermore, histopathological studies showed that VCN-AgNPs suppressed the progression of Ehrlich carcinoma and induced the formation of clusters of necrotic and fragmented tumor cells. VCN-AgNPs possess cytotoxic and genotoxic effects against ESC because of their pro-oxidant, pro-apoptotic, pro-inflammatory, and antiangiogenic effects. Additionally, the combination of VCN-AgNPs was more effective and safer than chemically synthesized AgNPs, as indicated by an increase in the lifespan of animals and the total tumor inhibition index. [ABSTRACT FROM AUTHOR]

Venetoclax is a BH3 mimetic that was recently approved for the treatment of acute myeloid leukemia (AML) treatment. However, the effect of venetoclax on AML remains limited, and a novel strategy is required. Here, we demonstrate for the first time that the cytotoxic effect of venetoclax drastically increased when by combined with the naturally occurring flavonoid quercetin. Combined treatment with venetoclax and quercetin caused most of AML KG-1 cells to exhibit a condensed morphology. Cell cycle analysis revealed that the combination strongly induced cell death. Caspase inhibitor blocked this cell death, and the combination induced poly (ADP-ribose) polymerase (PARP) cleavage, indicating that apoptosis was the primary mechanism. These effects were also observed in another AML cell line Kasumi-1 but not in chronic myeloid leukemia (CML) K562 cells. Public data analysis demonstrated that B-cell/CLL lymphoma 2 (Bcl-2) expression is increased in AML cells compared to other malignant tumors, and the survival and the growth of AML cell line depends on Bcl-2. We found that quercetin increased Bcl-2-associated X protein (Bax) expression in KG-1. Our study provides a novel function for quercetin and presents a promising strategy for AML treatment using venetoclax. [ABSTRACT FROM AUTHOR]

Objective: Previously, we have successfully purified and synthesized viscolin, an agent derived from Viscum coloratum extract, which has shown significant potential in the treatment of stroke. Our study aimed to evaluate the neuroprotective effects of viscolin. Methods: We first assessed the cytotoxicity of viscolin on primary neuronal cultures and determined its antioxidant and radical scavenging properties. Subsequently, we identified the optimal dose-response of viscolin in protecting against glutamate-induced neurotoxicity. Results: Our results demonstrated that viscolin at a concentration of 10 μM effectively reduced neuronal cell death up to 6 hours after glutamate-induced neurotoxicity. Additionally, we investigated the therapeutic window of opportunity and the potential of viscolin in preventing necrotic and apoptotic damage in cultured neurons exposed to oxygen glucose deprivation-induced neurotoxicity. Our findings showed that viscolin treatment significantly reduced DNA breakage, prevented the release of cytochrome c from mitochondria to cytosol, increased the expression of anti-apoptotic protein Bcl-2, decreased the expression of pro-apoptotic protein Bax, and reduced the number of TUNEL-positive cells. Additionally, our in vivo investigation demonstrated a reduction in brain infarction following middle cerebral artery occlusion. Conclusion: Viscolin has potential utility as a therapeutic agent in the treatment of stroke. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether the damage to male offspring induced by cadmium (Cd) exposure during embryonic period leads to the apoptosis of ovarian granulosa cells (OGCs) in the next generation of female offspring, and whether this apoptosis in the offspring was due to paternal genetic effects. Pregnant Sprague–Dawley (SD) rats were exposed to CdCl2 (0, 0.5, 2.0, or 8.0 mg/kg) by gavage daily for 20 days to produce the filial 1 (F1) generation. F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was generated in the same way. No apoptotic bodies were observed in the OGCs of either the F2 or F3 generation as shown by electron microscopy, and a reduced OGC apoptosis rate (detected by flow cytometry) was observed in F2 OGCs from the Cd‐exposed group. Moreover, the mRNA (qRT‐PCR) levels of Bax and Bcl‐2 and the protein (western blotting) level of pro‐caspase‐8 increased in the F2 generation (p < 0.05). The expression of apoptosis‐related miRNAs (qRT‐PCR) and methylation of apoptosis‐related genes (determined via bisulfite‐sequencing PCR) in OGCs were further determined. Compared with those of the controls, the expression patterns of microRNAs (miRNAs) in the F2 offspring were different in the Cd‐exposed group. The miR‐92a‐2‐5p expression levels were decreased in both the F2 and F3 generations (p < 0.05), while the average methylation level of apoptosis‐related genes did not change significantly (except for individual loci). In summary, this study showed that the paternal genetic intergenerational effect of male Cd exposure during embryonic period induced apoptosis of OGCs in the offspring was weakened, and the transgenerational effect disappeared; nevertheless, intergenerational and transgenerational changes in apoptosis‐related genes, epigenetic modifications, DNA methylation, and miRNAs were observed, and may be important for understanding the homeostatic mechanisms of the body to alleviate the intergenerational transmission of Cd‐induced damage. [ABSTRACT FROM AUTHOR]

The most common mutation in southern Chinese individuals with late-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD; a fatty acid metabolism disorder) is c.250G > A (p.Ala84Thr) in the electron transfer flavoprotein dehydrogenase gene (ETFDH). Various phenotypes, including episodic weakness or rhabdomyolysis, exercise intolerance, and peripheral neuropathy, have been reported in both muscular and neuronal contexts. Our cellular models of MADD exhibit neurite growth defects and excessive apoptosis. Given that axonal degeneration and neuronal apoptosis may be regulated by B-cell lymphoma (BCL)-2 family proteins and mitochondrial outer membrane permeabilization through the activation of proapoptotic molecules, we measured the expression levels of proapoptotic BCL-2 family proteins (e.g., BCL-2-associated X protein and p53-upregulated modulator of apoptosis), cytochrome c, caspase-3, and caspase-9 in NSC-34 cells carrying the most common ETFDH mutation. The levels of these proteins were higher in the mutant cells than in the wide-type cells. Subsequent treatment of the mutant cells with coenzyme Q10 downregulated activated protein expression and mitigated neurite growth defects. These results suggest that the activation of the BCL-2/mitochondrial outer membrane permeabilization/apoptosis pathway promotes apoptosis in cellular models of MADD and that coenzyme Q10 can reverse this effect. Our findings aid the development of novel therapeutic strategies for reducing axonal degeneration and neuronal apoptosis in MADD. [ABSTRACT FROM AUTHOR]

Introduction: Pituitary adenomas (PAs) are benign tumors with high prevalence and, occasionally, aggressive course. The tumorigenesis of these lesions is not completely understood at the molecular level. BAK1 and BAX proteins play fundamental roles in apoptosis and seem to interact with VDAC proteins, whose expressions have been markedly altered in cancer, impacting their prognosis. Objective: to evaluate the gene expression of VDAC1, VDAC2, BAK1 and BAX and their association with clinical and imaging characteristics in PA. Methods: Clinical-epidemiological data were collected from 117 tumor samples from patients affected by PA. Invasiveness was assessed by the Knosp scale. Gene expression was examined by real-time PCR. Relative expression analysis was performed by 2^(-DDCt) method. Results: The sample was mainly composed of women (69/117 -- 57.2%). Tumor subtypes observed were Non-Functioning (NF) (73/117 -- 62.4%), Acromegaly (24/117 -- 20.5%) and Cushing's Disease (CD) (20/117 -- 17.1%). Compared to normal tissue, there was a significant reduction in VDAC1 expression in the Acromegaly (p=0.029) and NF (p=0.002) groups. BAX expression was lower in all groups (p <0.001; p=0.007; P =0.005). No difference was found in VDAC2 and BAK1 expression, compared to normal pituitary. Overexpression of VDAC2 occurred in PAs with post-surgical regrowth (p=0.042). A strongly negative correlation was observed in BAX and BAK1 expression in CD. Conclusion: The results indicated that downregulations of VDAC1 and BAX may be related to resistance to apoptosis. In contrast, overexpression of VDAC2 in regrowing PAs suggests an antiapoptotic role for this gene. In summary, the genes evaluated might be involved in the biopathology of PAs. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of sodium glucose cotransporter 2 inhibitor (SGLT-2i) regulating the TLRs/MyD88 pathway on high glucose induced autophagy and apoptosis in human aortic endothelial cells (HAECs). Methods: Using HAECs, the cells were divided into NG group (5.5 mmol/L glucose), HG group (30 mmol/L glucose), and SGLT-2i+HG group (30 mmol/L glucose+50) μ Mol/L of SGLT-2 inhibitor. Detect the growth vitality; the level of cell apoptosis; the expression levels of TLRs and MyD88 mRNA; the levels of TLRs, MyD88, Bax, Bcl-2, Beclin 1, and LC3II in each group of cells. Results: Compared with the NG group, the cell proliferation rate of the HG group was significantly reduced (P<0.05); Compared with the HG group, the SGLT-2i+HG group showed a significant increase in cell proliferation rate (P<0.05). At 12 hours and 24 hours, compared with the NG group, the apoptosis rate of cells in the HG group was significantly increased (P<0.05); Compared with the HG group, the apoptosis rate of SGLT-2i+HG group was significantly reduced (P<0.05). Compared with the NG group, the expression levels of apoptosis related proteins Bax and Bcl-2 in the HG group increased (P<0.05); Compared with the HG group, the expression levels of Bax and Bcl-2 in cells of the SGLT-2i+HG group decreased (P<0.05). Compared with the NG group, the levels of autophagy related proteins Beclin 1 and LC3II in the HG group increased (P<0.05); Compared with the HG group, the levels of Beclin 1 and LC3II in cells of the SGLT-2i+HG group decreased (P<0.05). Compared with the NG group, the expression levels of TLRs and MyD88 proteins in the HG group increased (P<0.05); Compared with the HG group, the expression levels of TLRs and MyD88 in the SGLT-2i+HG group decreased (P<0.05). Conclusion: SGLT-2 inhibits high glucose induced autophagy and apoptosis in human aortic endothelial cells by regulating the TLRsMyD88 pathway. [ABSTRACT FROM AUTHOR]

Difenoconazole (DIF) is a fungicide used to control various fungi. It is absorbed on the surface of different plants and contributes significantly to increased crop production. However, DIF is reported to exhibit toxicity to fungi and to aquatic plants, fish, and mammals, including humans, causing adverse effects. However, research on the impact of DIF on the mammary epithelial cells of herbivorous bovines is limited. DIF-induced damage and accumulation in the mammary glands can have direct and indirect effects on humans. Therefore, we investigated the effects and mechanisms of DIF toxicity in MAC-T cells. The current study revealed that DIF reduces cell viability and proliferation while triggering apoptotic cell death through the upregulation of pro-apoptotic proteins, including cleaved caspase 3 and Bcl-2-associated X protein (BAX), and the downregulation of leukemia type 2 (BCL-2). DIF also induced endoplasmic reticulum (ER) stress by increasing the expression of genes or proteins of Bip/GRP78, protein disulfide isomerase (PDI), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and endoplasmic reticulum oxidoreductase 1 Alpha (ERO1-Lα). We demonstrated that DIF induces mitochondria-mediated apoptosis in MAC-T cells by activating ER stress pathways. This cellular damage resulted in a significant increase in the expression of inflammatory response genes and proteins, including cyclooxygenase 2 (COX2), transforming growth factor beta 3 (TGFB3), CCAAT enhancer binding protein delta (CEBPD), and iNOS, in DIF-treated groups. In addition, spheroid formation by MAC-T cells was suppressed by DIF treatment. Our findings suggest that DIF exposure in dairy cows may harm mammary gland function and health and may indirectly affect human consumption of milk. [ABSTRACT FROM AUTHOR]

Microgravity can induce alterations in liver morphology, structure, and function, with mitochondria playing an important role in these changes. Tail suspension (TS) is a well-established model for simulating the effects of microgravity on muscles and bones, but its impact on liver function remains unclear. In the current study, we explored the regulatory mechanisms of apoptosis, autophagy, fission, and fusion in maintaining liver mitochondrial homeostasis in mice subjected to TS for 2 or 4 weeks (TS2 and TS4). The results showed the following: (1) No significant differences were observed in nuclear ultrastructure or DNA fragmentation between the control and TS-treated groups. (2) No significant differences were detected in the mitochondrial area ratio among the three groups. (3) Cysteine aspartic acid-specific protease 3 (Caspase3) activity and the Bcl-2-associated X protein (bax)/B-cell lymphoma-2 (bcl2) ratio were not higher in the TS2 and TS4 groups compared to the control group. (4) dynamin-related protein 1 (DRP1) protein expression was increased, while mitochondrial fission factor (MFF) protein levels were decreased in the TS2 and TS4 groups compared to the control, suggesting stable mitochondrial fission. (5) No significant differences were observed in the optic atrophy 1 (OPA1), mitofusin 1 and 2 (MFN1 and MFN2) protein expression levels across the three groups. (6) Mitochondrial autophagy vesicles were present in the TS2 and TS4 groups, with a significant increase in Parkin phosphorylation corresponding to the duration of the TS treatment. (7) ATP synthase and citrate synthase activities were significantly elevated in the TS2 group compared to the control group but were significantly reduced in the TS4 group compared to the TS2 group. In summary, the coordinated regulation of apoptosis, mitochondrial fission and fusion, and particularly mitochondrial autophagy preserved mitochondrial morphology and contributed to the restoration of the activities of these two key mitochondrial enzymes, thereby maintaining liver mitochondrial homeostasis in mice under TS conditions. [ABSTRACT FROM AUTHOR]

5-Demethylnobiletin is the active ingredient in citrus polymethoxyflavones that could inhibit the proliferation of several tumor cells. However, the anti-tumor effect of 5-Demethylnobiletin on glioblastoma and the underlying molecular mechanisms are remains unknown. In our study, 5-Demethylnobiletin markedly inhibited the viability, migration and invasion of glioblastoma U87-MG, A172 and U251 cells. Further research revealed that 5-Demethylnobiletin induces cell cycle arrest at the G0/G1 phase in glioblastoma cells by downregulating Cyclin D1 and CDK6 expression levels. Furthermore, 5-Demethylnobiletin significantly induced glioblastoma cells apoptosis by upregulating the protein levels of Bax and downregulating the protein level of Bcl-2, subsequently increasing the expression of cleaved caspase-3 and cleaved caspase-9. Mechanically, 5-Demethylnobiletin trigged G0/G1 phase arrest and apoptosis by inhibiting the ERK1/2, AKT and STAT3 signaling pathway. Furthermore, 5-Demethylnobiletin inhibition of U87-MG cell growth was reproducible in vivo model. Therefore, 5-Demethylnobiletin is a promising bioactive agent that might be used as glioblastoma treatment drug. [ABSTRACT FROM AUTHOR]

Objective To analyze the effects of agatroban combined with mitochondrial transplantation on endothelial function and hemorheology in mice with cerebral ischemia-reperfusion injury. Methods 50 SPF grade Kunming mice, with 10 as the normal group, 38 mices were successfully modeled and divided into a model group of 9, a mitochondrial transplantation group of 9, an Agatroban group of 10, and a combination group of 10. The mitochondrial transplantation group was given exogenous mitochondrial extract, the agatroban group was given agatroban, the combined group was given agatroban combined with mitochondrial transplantation, and the blank group and model group were injected with normal saline. Observation of changes in cerebral infarction volume, pathological morphology of brain tissue, endothelial function, hemorheology, and relative expression of apoptosis related proteins in mice after 7 days of intervention. Results Compared with normal group, cerebral infarction volume ratio, ET-1, whole blood viscosity, plasma viscosity, Caspase-3 and Bax protein expression levels were increased in model group, mitochondrial transplantation group, agatroban group and combined group, while NO level and Bcl-2 protein expression levels were decreased (P < 0.05). Compared with the model group, the cerebral infarction volume ratio, ET-1, whole blood viscosity, plasma viscosity, Caspase-3 and Bax protein expressions in the mitochondrial transplantation group, agatroban group and combined group were decreased, and the combined group was lower than the mitochondrial transplantation group and agatroban group, and the NO level and Bcl-2 protein expression were increased. The combined group was higher than that of mitochondrial transplantation group and agatriban group (P < 0.05). Conclusion In mice with cerebral ischemia-reperfusion injury, endothelial function injury was improved, hemorheology was regulated, and brain injury was alleviated after agatroban combined with mitochondrial transplantation. [ABSTRACT FROM AUTHOR]

Lung ischemia-reperfusion injury (LIRI) causes oxidative stress, inflammation, and immune system activation. The Nrf2/Keap1/HO-1 pathway is important in cellular defense against these effects. Quercetin, a flavonoid with antioxidant, anti-inflammatory, and anti-cancer properties, has been investigated. Our aim in this study was to investigate the effect of quercetin on preventing lung ischemia-reperfusion injury and the role of the Nrf2/Keap1/HO-1 pathway. Sixty-four male Wistar rats were divided into four distinct groups(n = 16). Sham, lung ischemia-reperfusion (LIR), Saline + LIR, Quercetin + LIR (30 mg/kg i.p for a week before LIR). LIR groups were subjected to 60 min of ischemia (left pulmonary artery, vein, and bronchus) and 120 min of reperfusion. Our assessment encompassed a comprehensive analysis of various factors, including the evaluation of expression Nrf2, Keap1, and Heme Oxygenase-1 (HO-1) levels and NF-κB protein. Furthermore, we examined markers related to inflammation (interleukin-1β and tumor necrosis factor alpha), oxidative stress (malondialdehyde, total oxidant status, superoxide dismutase, glutathione peroxidase, total antioxidant capacity), lung edema (Wet/dry lung weight ratio and total protein concentration), apoptosis (Bax and Bcl2 protein), and histopathological alterations (intra-alveolar edema, alveolar hemorrhage, and neutrophil infiltration). Our results show that ischemia-reperfusion results in heightened inflammation, oxidative stress, apoptosis, lung edema, and histopathological damage. Quercetin showed preventive effects by reducing these markers, acting through modulation of the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway. This anti-inflammatory effect, complementary to the antioxidant effects of quercetin, provides a multifaceted approach to cell protection that is important for developing therapeutic strategies against ischemia-reperfusion injury and could be helpful in preventive strategies against ischemia-reperfusion. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effect of protein kinase C （PKC）-mammalian target of rapamycin （mTOR） pathway on the apoptosis of gastric smooth muscle cells in diabetic rats, and to explore the related mechanism. METHODS: Male and female 4-week-old specific pathogen-free Sprague-Dawley rats were randomly allocated to control, diabetes, diabetes+0. 1 μmol/L phorbol 12, 13-myristate acetate （PMA）, diabetes+0. 2 μmol/L PMA, diabetes+0. 5 μmol/L PMA, diabetes+2 μmol/L bisindolylmaleimide I （GF109203X）, diabetes+5 μmol/L GF109203X, and diabetes+ 10 μmol/L GF109203X groups （n=9）. Primary rat gastric smooth muscle cells cultured in a high-glucose environment in vitro were treated with 0. 1 μmol/L PMA, 0. 2 μmol/L PMA, 0. 5 μmol/L PMA, 2 μmol/L GF109203X, 5 μmol/L GF109203X, 10 μmol/L GF109203X, or vehicle. The isolated muscle technique was used to evaluate the spontaneous contraction of gastric antral smooth muscle. The pathologic changes and apoptosis of rat gastric smooth muscle were identified using HE staining and flow cytometry, respectively. The expression levels of stem cell factor （SCF）, c-Kit, mTOR, phosphorylated （p）-mTOR, p70 ribosomal protein S6 kinase（ p70S6K）, p-p70S6K, eIF4E-binding protein 1（ 4E-BP1）, p-4E-BP1, caspase-3, B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax） in gastric smooth muscle were measured by Western blot. RESULTS: The contractility of the gastric antral smooth muscle was lower （P<0. 05）, gastric smooth muscle atrophy and the apoptosis rate was higher （P<0. 01）, and the expression of SCF, c-Kit, and p-mTOR was lower（ P<0. 05 or P<0. 01） in the diabetes group than in the control group. There was no significant difference in the spontaneous contraction of the gastric antral smooth muscle between the diabetes and diabetes+0. 1 μmol/L PMA groups, but it was significantly greater in the diabetes+0. 2 μmol/L PMA and diabetes+0. 5 μmol/L PMA groups （P<0. 05 or P<0. 01）. The phosphorylation levels of mTOR, p70S6K （T421/S424）, and p70S6K （T389） were also higher in the diabetes + 0. 2 μmol/L PMA and diabetes+0. 5 μmol/L PMA groups than in diabetes group （P<0. 01）. Furthermore, the phosphorylation of 4E-BP1 was higher（ P<0. 05） in the diabetes+0. 5 μmol/L PMA group than in the diabetes group（ P<0. 01）. There was no significant difference in the spontaneous contraction of the gastric antral smooth muscle between the diabetes and diabetes+2 μmol/L GF109203X groups, but it was significantly lower in the diabetes+5 μmol/L GF109203X and diabetes+10 μmol/L GF109203X groups （P<0. 05 or P<0. 01）. The phosphorylation levels of mTOR and p70S6K （T389） were lower in the diabetes+5 μmol/L GF109203X and diabetes+10 μmol/L GF109203X groups （P<0. 05）, the phosphorylation of p70S6K（ T421/S424） was lower in the diabetes+10 μmol/L GF109203X group（ P<0. 05）, and the phosphorylation of 4EBP1 was lower in the diabetes+GF109203X （2, 5 and 10 μmol/L） groups （P<0. 05） than in the diabetes group. Compared with the CK group, the apoptosis rate was high in the GF109203X-treated（ 2, 5 and 10 μmol/L） groups（ P<0. 01）, the expression of Bax and caspase-3 was low （P<0. 05）, and the expression of Bcl-2 was high in the PMA-treated （0. 1, 0. 2 and 0. 5 μmol/L） groups（ P<0. 05）. CONCLUSION: The downregulation of the PKC-mTOR pathway in the gastric smooth muscle of diabetic rats leads to apoptosis of gastric smooth muscle cells through Bax/Bcl-2 and caspase-3 and the downregulation of SCF and c-Kit, which may play an important role in the gastric dysmotility that characterizes diabetes. [ABSTRACT FROM AUTHOR]

Background: Poekilocerus pictus (Fabricius 1771), a painted grasshopper, sequesters cardenolides from its food plant, the Apple of Sodom or Aak, Calotropis procera (Aiton) W.T. Aiton (Family-Asclepiadaceae). In our present investigation, we were able to isolate Pseudomonas aeruginosa KRK6 from the intestine of Poekilocerus pictus responsible for the biotransformation of cardenolides. Methods: Pseudomonas aeruginosa KRK6 was grown in methanolic extracts of Calotropis procera and the modified cardenolides were detected by Liquid Chromatography-Mass Spectrometry (LCMS) and also used to induce apoptosis in cancer cells (MCF-7 cells and T-47 D). Result: The modified cardenolides CPMEP6 was found to induce apoptosis in human breast adenocarcinoma cells (MCF cells-IC50= 6.31±0.4 µg/mL, T-47D cells-IC50= 10.1±1.02 µg/mL). Phosphatidylserine exposure and DNA fragmentation suggested apoptosis in treated cancer cells. CPMEP6 induced apoptosis in cancer cells via the mitochondrial pathway by down-regulating BCL-2 protein expression and up-regulating BAX protein expression. [ABSTRACT FROM AUTHOR]

In the present study, we utilized db/db mice to investigate the mechanisms of apoptosis in brain and retinal neurons. A total of 30 male db/db mice aged 8–9 weeks were randomly assigned to the model group, Dihuangyinzi decoction (DHYZ) group (30.03 g/kg), and metformin (MET) group (0.58 g/kg), with 10 mice in each group. The control group comprised 10 db/m mice of the same background and age. Paired-associate learning (PAL) tests were conducted to evaluate the learning and memory functions of the mice. Histological assessments, including Hematoxylin-Eosin (H&E) and Nissl staining, were employed to observe changes in nerve cells in the hippocampus and retina. Immunohistochemistry and real-time fluorescence quantitative PCR were employed to detect the positive expression of anti-apoptotic factor Bcl-2 and pro-apoptotic factor Bax at the protein and mRNA levels in the hippocampus and retina. Western blotting analysis was adopted to assess protein expression levels of JNK, p-JNK, p38 MAPK, and p-p38 MAPK. Results revealed a significant decline in the correct rate of PAL test results in the model group (P < 0.001), accompanied by increased reaction and delay times (P < 0.001) and higher blood glucose levels (P < 0.001). H&E and Nissl staining indicated a reduction in the number of nerve cells in the CA1 area of the hippocampus in the model group, with scattered arrangement and decreased Nissl corpuscles. Positive expression and mRNA expression of Bax in the hippocampus and retina increased significantly (P < 0.001), while positive expression and mRNA expression of Bcl-2 decreased (P < 0.001). Protein expression levels of p-JNK/JNK and p-p38 MAPK/p38 MAPK showed a significant increase (P < 0.001). The DHYZ and MET groups exhibited enhanced accuracy in PAL experiments (P < 0.05), decreased reaction time and delay time (P < 0.05), and reduced blood glucose levels (P < 0.05). The number of neurons in the CA1 region of the hippocampus increased, morphological structure improved, and the arrangement of the hippocampal structure became more orderly. Additionally, no obvious vacuolization was observed in the neuronal cell layer. The number of Nissl bodies increased, and the layers of the retina were closely arranged, with an increase in the number of Nissl bodies. Positive expressions of Bax in the hippocampus and retina, both at the protein and mRNA levels, decreased significantly (P < 0.001), while positive expressions of Bcl-2 and its mRNA increased (P < 0.01, P < 0.001). Furthermore, the protein expressions of p-JNK/JNK and p-p38 MAPK/p38 MAPK decreased significantly (P < 0.01). This study suggested that DHYZ decoction could inhibit the JNK/p38 MAPK signaling pathway, thereby increasing the anti-apoptotic factor Bcl-2 and reducing the expression of the pro-apoptotic factor Bax, consequently inhibiting apoptosis in the hippocampal CA1 region and retinal neurons of db/db mice. [ABSTRACT FROM AUTHOR]

The pathological and physiological process of spinal cord injury is complex, and there is currently no effective treatment method. Magnetic stimulation is an emerging electromagnetic therapy method in recent years, and studies have shown its potential to reduce cell apoptosis. This study used an improved Allen's method to replicate an incomplete spinal cord injury rat model, and repetitive magnetic stimulation (rMS) intervention was performed on the rats for 21 days. The research plan consists of two parts. The first part aims to observe the effects of rMS on motor function and neuronal cell apoptosis in rats. The Basso-Beattie-Bresnahan (BBB) score results indicate that rMS promotes the recovery of motor function in rats; H&E staining showed that rMS improved spinal cord structural damage and inflammatory infiltration; TUNEL and NeuN staining suggest that rMS can reduce cell apoptosis and promote neuronal cell survival. The second part aims to explore the mechanism of action of rMS. Immunofluorescence staining showed that after rMS intervention, the positive counts of PI3K and Akt increased, whereas the positive counts of caspase-3 decreased. Western blot showed that after rMS intervention, the expression of phospho-phosphatidylinositol-3 kinase (p-PI3K)/PI3K, phospho (p)-Akt/Akt, and Bcl-2 increased, whereas the expression of Bcl-2-associated X protein (Bax) and caspase-3 decreased. In summary, rMS can significantly reduce cell apoptosis in the damaged spinal cord and promote neuronal cell survival. Its mechanism of action may be related to promoting the expression of PI3K/Akt pathway proteins, upregulating the antiapoptotic protein Bcl-2, downregulating the proapoptotic protein Bax, and thereby inhibiting the expression of apoptotic protein caspase-3. NEW & NOTEWORTHY: Spinal cord injury is a serious disabling central nervous system disease. Recently, research on magnetic stimulation therapy for spinal cord injury has been increasing, and its potential has gradually attracted the attention of experts. This study found that repetitive magnetic stimulation (rMS) can improve motor function and reduce neuronal apoptosis in spinal cord injury rats. The mechanism may be related to increasing the expression of phosphatidylinositol-3 kinase (PI3K)/Akt protein, thereby inhibiting cell apoptosis and promoting neuronal survival. [ABSTRACT FROM AUTHOR]

This study investigated the neuroprotective effect of chlorogenic acid (CGA) on pentylenetetrazole (PTZ)-induced acute epileptic seizures in mice. Epileptic animals received CGA (200 mg/kg) or sodium valproate (standard antiepileptic agent, 200 mg/kg) for four weeks. Results revealed that pre-administration of CGA significantly reversed the behavioral changes following pentylenetetrazole (PTZ) injection. Further, CGA pre-treatment caused significant increases in acetylcholinesterase (AChE) activity and brain-derived neurotrophic factor (BDNF) levels, along with marked increases in dopamine, norepinephrine, and serotonin levels. Additionally, the increased antioxidant enzymes activities, along with higher glutathione (GSH) contents and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression, were indicative of a notable improvement in the cellular antioxidant defense in mice treated with CGA. These results were associated with lowered malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, epileptic mice that received CGA showed significant declines in the content of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa-B (NF-κB), besides downregulating inducible nitric oxide synthase (iNOS) expression. Remarkably, CGA counteracted hippocampal apoptosis by lessening the levels of pro-apoptotic biomarkers [Bcl-2-associated X protein (Bax) and caspase-3] and increasing the anti-apoptogenic marker level of B-cell lymphoma 2 (Bcl-2). The hippocampal histopathological findings corroborated the abovementioned changes. In sum, these findings suggest that CGA could mediate the neuroprotective effect against PTZ-induced epilepsy via modulation of neurotransmitters, oxidative damage, neuroinflammation, and apoptosis. CGA, therefore, could be considered a valuable antiepileptic therapeutic supplement. [ABSTRACT FROM AUTHOR]

Objective: To explore the impacts and possible mechanism of donepezil combined with Madopar on neuronal apoptosis and cognitive function in Parkinson's disease (PD) rats. Methods: The PD rats with successful modeling were grouped into model group (normal saline), Madopar group (11.0 mg/kg Madopar), donepezil group (0.6 mg/kg donepezil hydrochloride), and donepezil+ Madopar group (11.0 mg/kg Medopa+0.6 mg/kg donepezil hydrochloride), another 12 rats were taken as the sham operation group (normal saline). The motor function and cognitive function of the rats in each group were evaluated; the positive expression of tyrosine hydroxylase (TH) was detected by immunohistochemistry; Western blot was used to detect the expression levels of TH protein, apoptosis related proteins (cleaved caspase-3, Bax, Bcl-2) and PI3K/AKT pathway related proteins; TUNEL staining was used to detect the apoptosis rate; commercial kits were applied to detect the levels of oxidative stress indicators (MDA, SOD, GSH-Px) and inflammatory factors (IL-6, IL-18, TNF-α). Results: Compared with the sham operation group, the number of rotations in model group was increased, the fall latency was shortened, the spontaneous alternation behavior (SAB) correct rate was reduced, the escape latency was prolonged, and the number of crossing the original platform was reduced, the positive expression of TH in the substantia nigra, the expression levels of TH and Bcl-2 proteins, the activities of SOD and GSH-Px, p-PI3K/PI3K and p-AKT/AKT were decreased, the apoptosis rate of substantia nigra neurons, the expression levels of cleaved caspase-3 and Bax proteins, the content of MDA, the levels of IL-6, IL-18 and TNF- α were increased (P<0.05); the Madopar, donepezil and donepezil+Madopar could reduce the number of rotations, prolong the fall latency, increase the SAB correct rate, shorten the escape latency, and increase the number of crossing the original platform in PD rats, increased the positive expression of TH in the substantia nigra, the expression levels of TH and Bcl-2 proteins, the activities of SOD and GSH-Px, p-PI3K/PI3K and p-AKT/AKT, decreased the apoptosis rate of substantia nigra neurons, the expression levels of cleaved caspase-3 and Bax proteins, the content of MDA, and the levels of IL-6, IL-18 and TNF-α (P<0.05), and the effect of donepezil+Madopar group were significantly better than that of Madopar group and donepezil group (P<0.05). Conclusion: Donepezil combined with Madopar can reduce oxidative stress and inflammatory reaction in PD rats, and improve cognitive function, which may be achieved by activating PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Background: Glioma stands as the most prevalent primary brain tumor found within the central nervous system, characterized by high invasiveness and treatment resistance. Although immunotherapy has shown potential in various tumors, it still faces challenges in gliomas. This study seeks to develop and validate a prognostic model for glioma based on immune-related genes, to provide new tools for precision medicine. Methods: Glioma samples were obtained from a database that includes the ImmPort database. Additionally, we incorporated ten machine learning algorithms to assess the model's performance using evaluation metrics like the Harrell concordance index (C-index). The model genes were further studied using GSCA, TISCH2, and HPA databases to understand their role in glioma pathology at the genomic, molecular, and single-cell levels, and validate the biological function of IKBKE in vitro experiments. Results: In this study, a total of 199 genes associated with prognosis were identified using univariate Cox analysis. Subsequently, a consensus prognostic model was developed through the application of machine learning algorithms. In which the Lasso + plsRcox algorithm demonstrated the best predictive performance. The model showed a good ability to distinguish two groups in both the training and test sets. Additionally, the model genes were closely related to immunity (oligodendrocytes and macrophages), and mutation burden. The results of in vitro experiments showed that the expression level of the IKBKE gene had a significant effect on the apoptosis and migration of GL261 glioma cells. Western blot analysis showed that down-regulation of IKBKE resulted in increased expression of pro-apoptotic protein Bax and decreased expression of anti-apoptotic protein Bcl-2, which was consistent with increased apoptosis rate. On the contrary, IKBKE overexpression caused a decrease in Bax expression an increase in Bcl-2 expression, and a decrease in apoptosis rate. Tunel results further confirmed that down-regulation of IKBKE promoted apoptosis, while overexpression of IKBKE reduced apoptosis. In addition, cells with down-regulated IKBKE had reduced migration in scratch experiments, while cells with overexpression of IKBKE had increased migration. Conclusion: This study successfully constructed a glioma prognosis model based on immune-related genes. These findings provide new perspectives for glioma prognosis assessment and immunotherapy. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionThis study examines the therapeutic potential of monotropein (Mon) in a rat model of acute pulmonary embolism (APE), aiming to elucidate its mechanistic role and provide new insights for APE treatment.Thirty Sprague Dawley (SD) rats were randomly assigned to five groups (n = 6 per group): sham, Mon (40 mg/kg), APE, APE + 20 mg/kg Mon, and APE + 40 mg/kg Mon. APE was induced via autologous thrombus infusion in all groups except sham and Mon-only groups. We assessed blood gas parameters, lung wet/dry weight (W/D) ratio, and oxidative stress markers. Additionally, excised lung tissues underwent evaluation for serum inflammatory factors via ELISA, apoptotic cells via TUNEL assay, and protein expression via Western blot.Compared to the sham group, APE-induced rats exhibited significantly elevated blood oxygen levels and increased pro-inflammatory factors, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8. Mon treatment effectively mitigated these APE-induced changes, reducing blood oxygen concentration and downregulating IL-1β and TNF-α levels. Furthermore, Mon demonstrated anti-apoptotic effects by decreasing cleaved caspase-3 and Bax protein levels while upregulating Bcl-2 expression. Mon also suppressed nuclear factor-κB (NF-κB) activation by inhibiting the phosphorylation levels of p65/RelA and IκBα proteins, while the total protein level of IκBα was increased with Mon treatment.Mon effectively ameliorated lung tissue injury in APE rats by inhibiting apoptosis, attenuating inflammatory responses, and alleviating oxidative stress. These beneficial effects appear to be mediated through modulation of the NF-κB pathway, suggesting Mon as a promising therapeutic candidate for APE treatment. [ABSTRACT FROM AUTHOR]

Stroke is recognized as a leading cause of disability and mortality worldwide, posing a significant challenge, particularly in developing countries. The current study aimed to evaluate the neuroprotective effect of Ganoderic acid (GA) against focal ischemic stroke in rats. Material and methods.: Swiss Wistar rats were used for the current study. The rats were subjected to middle cerebral artery occlusion (MCAO) to simulate transient focal ischemia, followed by reperfusion. Various neurological parameters, including infarct size, neurological deficit score, brain water content, Evans blue leakage, nitric oxide (NO), inducible nitric oxide synthase (iNOS), lactate dehydrogenase (LDH), antioxidant levels, inflammatory cytokines, apoptosis markers, inflammatory parameters, and matrix metalloproteinases (MMP) levels, were estimated. Additionally, mRNA expressions were evaluated in the brain tissue. Results.: Dose dependently treatment of GA significantly (P < 0.001) suppressed the infarct size, neurological deflects score, brain water, evans blue leakage, NO, iNOS, LDH, C-X-C chemokine receptor type 4 (CXCR-4), monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein B (S-100β) and K+-Cl− cotransporter 1 (KCC1) positive cells. GA altered the level of oxidative stress parameters like Total antioxidant capacity (T-AOC), 8-hydroxy-2'-deoxyguanosine (8-OhdG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), malonaldehyde (MDA); cytokines viz., tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-1β, IL-6, IL-9, IL-10; inflammatory parameters such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin (PGE2), Nuclear factor kappa B (NF-κB); apoptosis parameters like B-cell leukemia/lymphoma 2 protein (Bcl-2), Bcl-2-associated protein x (Bax), Caspase-3; matrix metallopeptidase (MMP) parameters like MMP-2, MMP-3, and MMP-9, respectively. GA remarkably suppressed the mRNA expression of TRL-4, Syndecan-1, CSF, Aquaporin-1, OCT3, and RFX1. Conclusion.: Ganoderic acid exhibited the protection against the cerebral ischemia reperfusion via multiple mechanism. [ABSTRACT FROM AUTHOR]

Background Neonicotinoid insecticides are used worldwide for crop protection. They act as agonists at postsynaptic nicotinic acetylcholine receptors (nAChRs), disrupting normal neurotransmission in target insects. Human exposure is high due to the widespread use of neonicotinoids and their residues in food. This study aimed to evaluate the in vitro neurotoxicity of three neonicotinoid commercial formulations Much 600 FS® (imidacloprid 600 g L−1), Evidence 700 WG® (imidacloprid 700 g kg−1), and Actara 250 WG® (thiamethoxam 250 g kg−1) in differentiated human neuroblastoma SH-SY5Y cell line. Methods Cells were incubated with the pesticides for 96 h, and the cytotoxicity was evaluated through the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium·bromide (MTT) reduction and neutral red (NR) uptake assays. Toxicological pathways such as reactive oxygen (ROS) and nitrogen species (RNS) production, mitochondrial membrane potential, cell death mode, and the expression of the pro-apoptotic protein Bax were also evaluated. Results EC50 values of 266.4, 4,175, and 653.2 mg L−1 were found for Much®, Evidence® and Actara®, respectively. Significant increases in ROS and RNS generation were observed for all pesticides, while mitochondrial membrane potential and Bax protein expression showed no significant changes. Analysis of cell death mode revealed an increase in early apoptotic cells. Conclusion Therefore, neonicotinoid insecticides are potentially neurotoxic, reinforcing concerns about human exposure to these commercial formulations. [ABSTRACT FROM AUTHOR]

Parthenolide (PTL) is a sesquiterpene lactone that occurs naturally. It demonstrates a variety of beneficial effects, such as antioxidant, anti-inflammatory, and antiapoptotic properties. The study investigated the potential protective impact of PTL on indomethacin (INDO) induced stomach ulcers in rats. The rats were classified into 5 distinct categories. Group 1 served as the "control" group. Rats in the second group received a single oral dosage of INDO (50 mg kg−1). Rats in Groups three and four received 20 and 40 mg kg−1 oral PTL 1 h before INDO. Omeprazole (30 mg kg−1) was given orally to Group 5 rats 1 h before INDO. Pretreatment with PTL increased stomach pH and decreased gastric volume as well as reduced the morphological and histological changes induced by INDO. Analysis of probable pathways showed that pre-treatment with PTL successfully reduced oxidative, inflammatory, and apoptotic consequences caused by INDO. The ingestion of PTL leads to a notable increase in the levels of glutathione reduced (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT). Furthermore, PTL decreased the concentration of malondialdehyde (MDA). In contrast, it was shown that PTL increased both cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2). PTL shows a significant decrease in the expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB). PTL therapy resulted in a decrease in Bcl-2-associated X protein (Bax) levels and an increase in B-cell lymphoma 2 (Bcl2) levels. In conclusion, PTL offers gastroprotection by its antioxidant, anti-inflammatory, and anti-apoptotic qualities. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chondrocyte apoptosis is an important factor in the development of osteoarthritis, and Complanatoside A has a flavonoid effect, which can inhibit apoptosis of various cells, but its effect on chondrocyte apoptosis and the mechanism of action are not clear. OBJECTIVE: To investigate the intrinsic association and mechanism of Complanatoside A in chondrocyte apoptosis based on the Wnt/β-catenin signaling pathway. METHODS: (1) The cartilage tissues of the femur and tibia transected during knee arthroplasty were collected, and chondrocytes were isolated, cultured in vitro, and identified. (2) Cell counting kit-8 was used to detect the optimal intervention concentration of Complanatoside A in the concentration range of 0- 160 μmol/L. (3) Chondrocytes were divided into blank group, sodium nitroprusside (1.5 mmol/L)-induced group, and sodium nitroprusside (1.5 mmol/L)+ Complanatoside A (5 μmol/L) group. The viability and apoptosis rate of the cells in each group were detected by cell counting kit-8 and flow cytometry. The expression of type II collagen and SOX9 was detected by immunofluorescence staining. The expression of apoptosis-related proteins and Wnt/β-catenin pathway proteins was detected by western blot assay. RESULTS AND CONCLUSION: The cells extracted in vitro were cultured and stained, and were clearly identified as chondrocytes. Complanatoside A had no obvious cytotoxicity to chondrocytes in the concentration range of 0-80 μmol/L, and significantly improved the chondrocyte viability in the concentration range of 2.5-10 μmol/L, especially when the concentration was 5 μmol/L. The apoptotic rate of chondrocytes was higher in the sodium nitroprusside-induced group than the blank control group, while the apoptotic rate was lower in the sodium nitroprusside+Complanatoside A group than the sodium nitroprusside-induced group. The fluorescence intensity of type II collagen and SOX9 in chondrocytes was weaker in the sodium nitroprusside-induced group than the blank control group, while the fluorescence intensity of type II collagen and SOX9 in the sodium nitroprusside+Complanatoside A group was higher than that of the sodium nitroprusside-induced group. In the sodium nitroprusside-induced group, the protein expression of Bax, Caspase-3, matrix metalloproteinase 13, Wnt3a, Wnt5a and β-catenin was higher than that of the blank control group, while the protein expression of Bcl-2 was lower than that of the blank control group. In the sodium nitroprusside+Complanatoside A group, except for the protein expression of Bcl-2 which was higher than that of the sodium nitroprusside-induced group, the expression of the other aforementioned proteins was lower than that of the sodium nitroprusside-induced group. To conclude, Complanatoside A has a certain inhibitory effect on chondrocyte apoptosis, which could regulate apoptosis-related proteins and promote the expression of chondrocyte regulatory factors, and presumably might play a role through inhibiting the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the direct effects of α-Linolenic acid (ALA) on the in vitro production of testosterone and the expression of key enzymes and proteins related to steroidogenesis in Leydig cells of roosters. Purified primary Leydig cells isolated from 65-week-old roosters were purified and treated with different concentrations of ALA treatments: (0 μm/L [control], solvent control group (DMSO), 20 μM/L, 40 μM/L, and 80 μM/L) and cell counting-8 (CCK-8) for cell viability assay, Enzyme-linked immunosorbent assay (ELISA) kit for the determination of testosterone in cell supernatants, quantitative (real-time) PCR, and analysis of activities of antioxidants catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA), evaluation of mitochondrial membrane potential, pro- and anti-apoptotic proteins/genes Bcl-2, Bcl-2-associated X protein (Bax), apoptosis-inducing factor (AIF) were done respectively. Our results showed that ALA significantly increased testosterone secretion in primary rooster Leydig cells (P < 0.05), and 40 μM/L is the optimal dose. Leydig cells supplemented with ALA (20, 40, 80 μM) increased the expression of key enzymes and proteins 3β-hydroxysteroid dehydrogenase (3β-HSD), steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc) concerning steroidogenesis, enhanced antioxidant capability, improved mitochondrial biogenesis, and markedly improved the mitochondrial membrane potential (P < 0.05). Furthermore, the expression of the apoptosis-suppressive gene Bcl-2 was significantly increased, but Bax and AIF expression was decreased in the ALA group compared to that in the control group (P < 0.05). ALA promoted testosterone production, enhanced steroidogenic enzyme expression, improved mitochondrial function, and antioxidant capacity, and reduced apoptosis in primary rooster Leydig cells, with 40 μM/L identified as the optimal concentration. [ABSTRACT FROM AUTHOR]

Background: Oral mucositis (OM) is an acute debilitating side effects of chemoradiotherapy (CRT) in head and neck cancer (HNC) patients. Salivary biomarkers are noninvasive and aid in early diagnosis and disease prevention. Objective: This study analyzed Bcl-2, Mcl-1, and Bax as potential biomarkers in CRT-induced OM in HNC patients. Methods: Forty-six HNC patients receiving CRT with OM were evaluated using WHO grading. Two time points were observed for saliva sample collection: Day 0 (prior to CRT) and Day 30 (CRT with OM) and from 46 healthy volunteers. Using an enzyme-linked immunosorbent assay (ELISA), levels of Bcl-2, Mcl-1, and Bax were measured. Oral mucositis progression was analyzed using Friedman’s test, and statistical significance between means of different salivary marker was determined using the ANOVA test. Results: From Day 0 to Day 30, grades of OM were statistically significant (P < 0.05). Apoptotic biomarkers showed statistically significant higher expression of proapoptotic regulator Bax and lower expressions of antiapoptotic markers Bcl-2 and Mcl-1 on Day 30 (severe OM) compared to Day 0 and healthy controls (P < 0.0001). Conclusion: Our research showcased Bax, Bcl-2, and Mcl-1 as early predictive indicators of OM, and targeted drugs should be developed against these to prevent onset and severity of oral mucositis that improves patients quality of life.

Background: Ovarian granulosa cells (GCs) play crucial roles in follicular growth and development. Their normal function is influenced by various factors, including oxidative stress, which is a significant factor. Afamin protein is a vitamin E-specific binding protein that acts as a vitamin E carrier in follicular fluid. Although the mechanism of the protective effect of afamin on human ovarian GCs is still unclear, there is evidence it has an antioxidant effect in neuronal cells. Methods: In this study, we investigated the protective effects of afamin proteins on testosterone propionate (TP)-induced ovarian GCs using a human ovarian tumor granulosa cell line (KGN). Results: The results showed that afamin reduced TP-induced oxidative stress in KGN cells by decreasing the levels of oxidative damage markers, enhancing the activity of antioxidant enzymes, and exerting a protective effect on GCs. Supplementation with afamin repaired mitochondrial dysfunction by improving mitochondrial membrane potential damage and ATP levels. It counteracted TP-induced apoptosis by decreasing the activity of Caspase-3 and upregulating the expression of the anti-apoptotic gene (BCL-2) while downregulating the expression of the pro-apoptotic gene BCL-2-associated X protein (BAX). In addition, afamin regulated the expression of genes related to ovarian steroid hormone synthesis, ameliorating the endocrine dysfunction observed in TP-induced KGN cells. Conclusion: Therefore, Afamin proteins may serve as important complementary factors that protect GCs from other types of damage, such as oxidative stress, and may help improve ovarian follicle quality and female reproductive function. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of puerarin (GGS) on lipopolysaccharide (LPS) -induced inflammatory response in human gingival fibroblasts (HGFs) by regulating nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Methods: HGFs cells were cultured in vitro, HGFs cells were divided into blank control (CK) group (0.9% sodium chloride), LPS group (100 nM LPS), LPS+GGS low dose (LPS+GGS-L) group (100 nM LPS+50 μΜ GGS), LPS+GGS high dose (LPS+GGS-H) group (100 nM LPS+100 μΜ GGS), LPS+GGS-H+ML385 (Nrf2/HO-1 signaling pathway inhibitor) group (100 nM LPS+100 μΜ GGS+10 μΜ ML385). The cell proliferation ability was detected by cell counting kit-8 (CCK-8). The levels of interleukin (IL) -6, lactate dehydrogenase (LDH), IL-10 and IL-1ẞ were detected by enzyme-linked immunosorbent assay (ELISA). The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected by kits. The apoptosis rate of HGFs was detected by flow cytometry. The formation of cell membrane pores was detected by propidium iodide (PI) staining. The expressions of B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-2 associated X protein (Bax), NOD-like receptor protein 3 (NLRP3), Nrf2 and HO-1 were detected by Western blot. Results: Compared with CK group, the OD450 (24 and 48 h) value, IL-10 level, GSH-Px and SOD activity, Bcl-2, Nrf2 and HO-1 protein expression of HGFs cells in LPS group were significantly decreased, and the levels of IL-6, LDH, IL-1B, MDA content, apoptosis rate, positive rate of PI staining, Bax and NLRP3 protein expression were significantly increased (P<0.05). Compared with LPS group, the OD450 (24 and 48 h) value, IL-10 level, GSH-Px and SOD activity, Bcl-2, Nrf2 and HO-1 protein expression of HGFs cells in LPS+GGS-L group and LPS+GGS-H group were significantly increased, and the levels of IL-6, LDH, IL-1B, MDA content, apoptosis rate, positive rate of PI staining, Bax and NLRP3 protein expression were significantly decreased (P<0.05). ML385 could reduce the improvement of GGS on LPS-induced inflammatory injury in HGFs cells(P<0.05). Conclusion: GGS may alleviate LPS-induced inflammation and oxidative stress in HGFs cells by activating Nrf2/HO-1 signaling pathway, and reduce cell apoptosis. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of Alzheimer's disease (AD) is significantly gender-differentiated, with the number of female AD patients far exceeding that of males, accounting for two-thirds of the total prevalence. Although postmenopausal AD mice have been shown to have more prominent pathologic features and memory impairments than normal AD mice, the relevant molecular mechanisms leading to these outcomes have not been well elucidated. In the present study, we used the disturbance of excitation-inhibition balance in the postmenopausal brain as an entry point to explore the link between estrogen deficiency, disorders of the glutamatergic-GABAergic nervous system, and memory impairment. Methods: Wild-type (WT) mice and APP/PS1/tau (3 x Tg-AD) mice (10 months old) were randomly divided into four groups: WT+Sham group, WT+OVX group, 3 x Tg-AD+Sham group and 3 x Tg-AD+OVX group. Ovariectomy (OVX) was performed in the WT+OVX group and the 3 x Tg-AD+OVX group, and sham surgery was performed in the WT+Sham group and the 3 x Tg-AD+Sham group. The learning and memory ability and the anxiety and depression-like behavior changes of mice were evaluated by behavioral experiments, and the association between estrogen-estrogen receptors pathway and glutamatergic/GABAergic nervous system and female AD was evaluated by neurochemical experiments. Results: In WT and 3 x Tg-AD mice, OVX resulted in impaired learning and memory abilities and anxiety and depression-like behaviors; reduced estrogen levels and downregulated the expression of estrogen receptors; upregulated the expression of amyloid-b, amyloid precursor protein, presenilin 1, and p-tau; upregulated the expression of Bcl-2-associated X protein and downregulated the expression of B-cell lymphoma-2, promoting cell apoptosis; reduced the number of neuronal dendrites and downregulated the expression of postsynaptic density protein-95; more importantly, OVX increased brain glutamate levels but downregulated the expression of N-methyl-Daspartate receptor-2B, excitatory amino acid transporter 1, excitatory amino acid transporter 2, g-aminobutyric acid receptor-A and g-aminobutyric acid receptor-B. Conclusion: Our results suggested that OVX-induced estrogen-estrogen receptors pathway disruption caused learning and memory impairment and anxiety and depression-like behaviors, upregulated the expression of AD pathological markers, promoted apoptosis, destroyed neuronal structure, and most importantly, caused glutamatergic/GABAergic nervous system disorders. [ABSTRACT FROM AUTHOR]

Objective: To discuss the effects of 5-aza-2'-deoxycytidine (5-Aza-CdR) on autophagy and apoptosis of the TPC-1 cells in subcutaneous xenograft tumor tissue of the nude mice, and to clarify its mechanism. Methods: Sixteen female BALB/c nude mice were inoculated with human papillary thyroid carcinoma (PTC) TPC-1 cells in the right axilla to establish the xenograft tumor model. After tumor formation, the mice were randomly divided into control group and experiment group (n=8). The nude mice in control group were given an intraperitoneal injection of saline, while the nude mice in experiment group were given the intraperitoneal injection of 5-Aza-CdR, administered once every other day for four weeks. The growth status of xenograft tumor of the mice in both groups was observed, and the mice were sacrificed after the final administration and the tumor weights of the nude mice in two groups were detected. HE staining was used to observe the pathomorphology of xenograft tumor tissue of the nude mice in both groups; immunohistochemistry was used to detect the expression levels of microtubule-associated protein light chain 3 (LC3), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) in xenograft tumor tissue of the nude mice in two groups; real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting methods were used to detect the expression levels of LC3, Beclin-1, Bcl-2, Bax, mitogenactivated protein kinase kinase (MEK), extracellular signal-regulated kinase 1 (ERK1), extracellular signal-regulated kinase 2 (ERK2), phosphorylated EPK1 (p-ERK1), and phosphorylated EPK2 (p-ERK2) mRNA and proteins in xenograft tumor tissue of the nude mice in two groups. Results: Compared with control group, the tumor volume and weight of the nude mice in experiment group were significantly decreased (P<0. 01). The number of cancer cells of the nude mice in control group was high, and the cells were densely arranged, with irregular shapes, clear nuclear staining, large overlapping nuclei, and lobulation, showing significant pathological mitotic figures consistent with PTC pathological characteristics. The number of cancer cells of the nude mice in experiment group showed a significant decresing trend, and the cells were sparse arrangement, nuclear shrinkage, and less distinct nuclei, with a significant increase in connective tissue. Compared with control group, the expression levels of LC3B and Beclin-1 mRNA and proteins in xenograft tumor tissue of the nude mice in experiment group were significantly increased (P<0. 05) and the ratio of and Bax/Bcl-2 was increased (P<0. 05 or P<0. 01), while the expression levels of MEK, ERK1/2, and p-ERK1/2 mRNA and proteins were significantly decreased (P<0. 05 or P<0. 01). Conclusion: 5-Aza-CdR can inhibit the growth of TPC-1 cells in subcutaneous xenograft tumor tissue of the nude mice, induce the autophagy, and promote the apoptosis of the tumor cells. The mechanism may be related to the inhibition of the mitogen-activated protein kinase (MAPK) /MEK/ extracellular signal-regulated kinase (ERK) signaling pathways. [ABSTRACT FROM AUTHOR]

Objective: To discuss the effect of curcumin on ameliorating doxorubicin (DOX) -induced cytotoxicity in the H9c2 cardiomyocytes, and to clarify its mechanism. Methods: The H9c2 cardiomyocytes were treated with DOX to establish the cardiotoxicity model. The H9c2 cells were divided into normal group, DOX group, DOX+curcumin group, and DOX+curcumin+silent information regulator 3 (SIRT3) inhibitor-3 (3-TYP) group. After 24 h, the morphology of the cells in various groups were observed; CCK-8 method was used to detect the viabilities of the cells in various groups; TUNEL staining was used to detect the apoptotic rates of the cells in various groups; enzyme-linked immunosorbent assay (ELISA) method was used to detect the activities of catalase (CAT) and superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) in the cells in various groups; 2, 7-dichlorofluorescein diacetate (DCFH-DA) staining was used to detect the levels of reactive oxygen species (ROS) in the cells in various groups; Western blotting method was used to detect the expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), NADPH oxidase 4 (NOX4), SIRT3, acetylated superoxide dismutase 2 (Ac-SOD2), and superoxide dismutase 2 (SOD2) proteins in the cells in various groups. Results: Compared with normal group, the H9c2 cells in DOX group exhibited swelling, the activity of the cells was decreased (P< 0. 05), the CAT and SOD activities were decreased (P<0. 05), the MDA and ROS levels were increased (P<0. 05), the expression levels of NOX2, and NOX4 proteins were increased (P< 0. 05), the ratio of Bcl-2/Bax and the expression level of SIRT3 protein were decreased (P<0. 05), and the expression levels of SOD2 and Ac-SOD2 proteins were increased (P<0. 05). Compared with DOX group, the H9c2 cells in DOX+curcumin group showed improved morphology, the activity of the cells was increased (P<0. 05), the CAT and SOD activities were increased (P<0. 05), the MDA and ROS levels were decreased (P<0. 05), the expression levels of NOX2, and NOX4 proteins were decreased (P< 0. 05), the ratio of Bcl-2/Bax and the expression level of SIRT3 protein were increased (P<0. 05), and the expression levels of SOD2 and Ac-SOD2 proteins were decreased (P<0. 05). Compared with DOX+ curcumin group, the cells in DOX+curcumin+3-TYP group exhibited swelling, the activity of the cells was decreased (P<0. 05), the apoptotic rate of the cells was significantly increased (P<0. 05), the CAT and SOD activities were decreased (P<0. 05), the MDA and ROS levels were significantly increased (P<0. 05), the expression levels of NOX2 and NOX4 proteins were increased (P<0. 05), the ratio of Bcl-2/Bax and the expression level of SIRT3 protein were decreased (P<0. 05), and the expression levels of SOD2 and Ac-SOD2 proteins were increased (P<0. 05). Conclusion: Curcumin suppresses the oxidative stress and apoptosis by activating the SIRT3/SOD2 signaling pathway, improving the cell activity and alleviating the DOX-induced cytotoxicity in the H9c2 cells. [ABSTRACT FROM AUTHOR]

[Objectives] The paper aimed to investigate the effects of heat stress in late gestation on differentiation, development and apoptosis of piglet skeletal muscle. [Methods] Twelve sows (Dabai × Changbai) with similar due dates were selected, in the late gestation (84 days of gestation), the sows were randomly divided into heat stress group (HS, 28-32 ℃) and control group (CON, 18-22 ℃) . After farrowing, longissimus dorsi (LD) was collected from one weaning piglet per litter. Western blot was used to detect the expression of related proteins in the samples. [Results]Heat stress of sows during late gestation significantly increased the contents of INF-γ and COR in colostrum (P<0.05); heat stress in late gestation of sows significantly decreased MyoD protein expression level of LD (P<0.05), and increased Myogenin protein expression level of LD (P<0.05); and heat stress in late pregnancy of sows, the protein expression level of MyHCⅡb in LD of weaning piglets significantly increased (P<0.05), but MyHCⅡx protein expression level had no significant changes (P>0.05); the glucose metabolism-related protein expression showed that heat stress in late gestation of sows significantly reduced PCK1 and GLUT4 expression levels in LD of weaning piglets (P<0.05); the expression levels of apoptosis-related proteins Bax and Bcl-2 in LD of weaning piglets significantly increased by heat stress during late gestation (P<0.05) . [Conclusions] Heat stress in sows during late gestation could significantly reduce the body weight and LD weight of weaning piglets, it might be related to the decreased expression level of MyoD and glucose metabolism in LD of weaning piglets. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis is a progressive and age‐related disease that results from impaired lung repair following injury. Targeting senescent myofibroblasts with senolytic drugs attenuates pulmonary fibrosis, revealing a detrimental role of these cells in pulmonary fibrosis. The mechanisms underlying the occurrence and persistence of senescent myofibroblasts in fibrotic lung tissue require further clarification. In this study, we demonstrated that senescent myofibroblasts are resistant to apoptosis by upregulating the proapoptotic protein BAX and antiapoptotic protein BCL‐2 and BCL‐XL, leading to BAX inactivation. We further showed that high levels of inactive BAX‐mediated minority mitochondrial outer membrane permeabilization (minority MOMP) promoted DNA damage and myofibroblasts senescence after insult by a sublethal stimulus. Intervention of minority MOMP via the inhibition of caspase activity by quinolyl‐valyl‐O‐methylaspartyl‐[2,6‐difluorophenoxy]‐methyl ketone (QVD‐OPH) or BAX knockdown significantly reduced DNA damage and ultimately delayed the progression of senescence. Moreover, the BAX activator BTSA1 selectively promoted the apoptosis of senescent myofibroblasts, as BTSA1‐activated BAX converted minority MOMP to complete MOMP while not injuring other cells with low levels of BAX. Furthermore, therapeutic activation of BAX with BTSA1 effectively reduced the number of senescent myofibroblasts in the lung tissue and alleviated both reversible and irreversible pulmonary fibrosis. These findings advance the understanding of apoptosis resistance and cellular senescence mechanisms in senescent myofibroblasts in pulmonary fibrosis and demonstrate a novel senolytic drug for pulmonary fibrosis treatment. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the therapeutic effects and related mechanisms of Tanshinone IIA and Tetramethylpyrazine O/W composite nanoemulsions on Alzheimer's disease (AD) rats. Methods: The therapeutic effect of TSN/TMP O/W NEs on AD rats was evaluated by behavioral tests, H&E, Nissl, and Immunohistochemistry staining. ELISA and Western blot were used to analyze the mechanism. Key findings: The results showed that TSN/TMP O/W NEs could down-regulate the expression of Bax and Caspase-3 proteins, decrease the level of MDA, increase the expression of SOD and GSH-Px, and alleviate cognitive impairment in AD rats. Conclusions: TSN/TMP O/W NEs can inhibit MAPK/ERK/CREB signaling pathway and effectively alleviate cognitive impairment, oxidative stress injury, and neuronal apoptosis in AD rats. [ABSTRACT FROM AUTHOR]

The response to endoplasmic reticulum (ER) stress has been noted in both human depression cases and depression models in rodents. Wuling powder, derived from the mycelium of the esteemed fungus Xylaria Nigripes (Kl.) Sacc, has demonstrated efficacy in alleviating depressive symptoms. The purpose of this research was to explore the antidepressant properties of Wuling powder and its basic molecular effects, particularly regarding alterations in ER stress. A model of social defeat stress was created by introducing a mouse to the cage of an unfamiliar, hostile mouse for intervals of 5-10 min daily over a span of 10 d. Subsequently, the mice received oral doses of Wuling powder for 2 weeks. The social approach-avoidance assay was employed to evaluate signs of depression-like behaviors. Moreover, protein and gene expressions linked to ER stress triggered by social defeat were analyzed through Western blotting analysis and quantitative real-time PCR. The behavioral tests indicated that Wuling powder ameliorated behaviors associated with depression due to social defeat stress. Treatment with Wuling powder markedly reduced the increased levels of the 78-kDa glucose-regulated protein and protein disulfide isomerase caused by social defeat stress. It also diminished the expression of inositol-requiring enzyme 1α (IRE1α) and spliced X box-binding protein-1 (sXBP1) at the protein and mRNA levels. Furthermore, Wuling treatment notably decreased the levels of phosphorylated eukaryotic initiation factor 2 alpha kinase (P-eIF2α), activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), simultaneously enhancing the ratio of B-cell lymphoma 2 (Bcl-2) to Bcl-2-associated X protein (Bax). These results suggested that Wuling powder could alleviate ER stress and inhibit cell apoptosis in the hippocampus by inhibiting protein translation and synthesis, thereby attenuating depressive-like behavior. [ABSTRACT FROM AUTHOR]

AIM: To investigate the mechanism of chronic stress-induced myocardial injury in atherosclerotic (AS) mice. METHODS: Eight-week-old SPF-grade male ApoE~'~ mice and C57BL/6J mice used in this study. The mice received dietary intervention for 10 weeks followed by pathological examination to test the successful AS modeling. After AS establishment, the mice were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks and then divided into five groups: control, CUMS, AS-regular diet (AS-r)+CUMS, AS-high-fat diet (AS-h), and AS-h+CUMS. During CUMS, open-field test and sucrose preference test were performed on mice in all groups. Blood lipids were characterized using an automatic biochemical analyzer. Hematoxylin-eosin (HE) and oil red O staining were performed to evaluate pathological changes in the aortic root. Cardiac function was assessed using echocardiography. The serum concentration of myocardial injury markers and ATP content was detected by ELISA. Transmission electron microscopy was employed to observe the ul-trastructure of myocardial mitochondria. Myocardial mitochondrial oxygen consumption rate was determined using the Oxy-graph-2k high-resolution respiratory energy metabolism analyzer. Western blot was conducted to quantify the expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3. RESULTS: compared with the Control group, the total distance traveled, the number of entries into the central area, and the sucrose preference rate were significantly decreased in all CUMS groups (P<0. 05). All AS groups exhibited varying levels of lipid deposition and endothelial damage in the aortic root, along with a significant reduction in cardiac function (P<0. 05) and varying degrees of myocardial injury (P<0. 05). In the AS-h+CUMS and AS-r+CUMS groups, myocardial mitochondrial structure was significantly disrupted. ATP content was significantly reduced (P<0. 05), and the rates of oxygen consumption associated with mitochondrial respiratory chain complex I, mitochondrial respiratory chain complexes I+II, and the maximum respiratory capacity of the electron transport system were all significantly decreased (P<0. 05). Moreover, the protein levels of Bax and cleaved caspase-3 were significantly incr eased (P<0. 05), while that of Bcl-2 protein was significantly decreased (P< 0. 05). CONCLUSION: Chronic stress triggers mitochondrial non-steady-state load by disrupting myocardial structure and energy metabolism in AS mice, promoting myocardial cell apoptosis and myocardial injury. [ABSTRACT FROM AUTHOR]

Chronic immunosuppressive therapy is currently the only effective method to prevent acute rejection of a transplanted organ. Unfortunately, the expected effect of treatment brings a number of grave side effects, one of the most serious being cardiovascular complications. In our study, we wanted to investigate how treatment with commonly used immunosuppressive drugs affects the occurrence of programmed cardiac cell death. For this purpose, five groups of rats were treated with different triple immunosuppressive regimens. Cardiac tissue fragments were subjected to the TUNEL assay to visualize apoptotic cells. The expression of Bcl-2 protein, Bax protein, caspase 3 and caspase 9 was also assessed. This study indicates that all immunosuppressive protocols used chronically at therapeutic doses result in an increased percentage of cells undergoing apoptosis in rat heart tissue. The greatest changes were recorded in the TMG (rats treated with tacrolimus, mycophenolate mofetil and glucocorticosteroids) and CMG (rats treated with cyclosporin A, mycophenolate mofetil and glucocorticosteroids) groups. The TRG (rats treated with rapamycin, tacrolimus and glucocorticosteroids) group showed the lowest percentage of apoptotic cells. The internal apoptosis pathway was confirmed only in the TMG group; in the remaining groups, the results indicate programmed cell death via the receptor pathway. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the inhibitory effect of edaravone (EDR) lotion on chemotherapy-induced alopecia (CIA) to improve the quality of life for patients with cancer. Methods: Wistar rats were intraperitoneally injected with cyclophosphamide (CPA, 75 mg/kg) to induce CIA and divided into six groups: (1) Control; (2) EDR 0%; (3) EDR 0.3%; (4) EDR 3%. The TUNEL-positive area was examined histologically, and mRNA expression levels of the apoptosis-related factors, such as B-cell/CLL lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax), were determined. Results: In the three CPA-treated groups, a decrease in the coverage score (percentage of hairs covered) was observed from days 16 to 18. In addition, coverage scores on day 21, the last day of observation, showed a tendency for the suppression of hair loss to increase, though hair loss was observed in all groups. The coverage scores of the EDR 0.3% and 3% groups after day 17 were significantly higher than those of the EDR 0% group. The TUNEL-positive area of skin tissue on day 16 was extensive in the EDR 0% group and decreased in the EDR 0.3% and 3% groups. The mRNA expression ratio of Bcl-2/Bax on day 21 was maintained at the same level as that of the control group only in the EDR 3% group. Conclusion: This study confirmed the use of EDR lotion to inhibit hair loss, indicating that the clinical application of EDR lotion may improve the quality of life for patients with cancer and their willingness to undergo treatment. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that perioperative anesthesia could have direct impacts on cancer cell biology. The present study investigated the effects of ropivacaine administration on lung adenocarcinoma cells. Methods: Ropivacaine was administered to A549 cells at concentrations of 0.1, 1, and 6 mM for 2 h. Angiotensin-converting enzyme 2 (ACE2) small interfering RNA (siRNA) transfection was performed 6 h prior to ropivacaine administration. Cell proliferation and migration were assessed with cell counting kit 8 (CCK-8) and a wound healing assay at 0 and 24 h after anesthesia exposure. PCR arrays were performed, followed by PCR validation. Results: Ropivacaine administration inhibited A549 cell proliferation and migration in a concentration-dependent manner, with ACE2 upregulation and HIF1α (hypoxia-inducible factor 1α) downregulation. The anticancer effect of ropivacaine was canceled out via ACE2 siRNA transfection. PCR arrays showed specific gene change patterns in the ropivacaine and respective ACE2-knockdown groups. EGFR (epidermal growth factor receptor), BAX (Bcl-2-associated X protein) and BCL2 (B-cell/CLL lymphoma 2) were suppressed with ropivacaine administration; these effects were reversed via ACE2 siRNA induction. Conclusion: Ropivacaine administration inhibited A549 cell biology in conjunction with ACE2 upregulation via the inhibition of the Wnt1 (wingless/Integrated 1) pathway. [ABSTRACT FROM AUTHOR]

The cell signaling pathways involved in the antiproliferative activities of T. rosea inner bark remain unexplored. This study evaluated the apoptotic effects of two iridoids from the inner bark of T. rosea and apicidin on THP-1 cells. The cytotoxic effects of the extract and the pure compounds on THP-1 and Jurkat cells were also evaluated using the MTT assay. The apoptotic effect was determined by measuring the mitochondrial membrane potential. The expression of mRNA and MAPK kinase, Bax, and Bcl-2 proteins was detected by Western blotting and RT–qPCR, respectively. The extract and the compounds evaluated increased the percentage of apoptotic cells. Depolarization of the mitochondrial membrane was observed, and the number of cells in the G0/G1 phase increased. Catalposide and specioside significantly increased p38 protein expression, mostly in cells pretreated with apicidin. The p38 MAPK signaling pathway is at least one of the pathways by which the n-butanol extract obtained from Tabebuia rosea, catalposide, and specioside exerts its apoptotic effect on THP-1 cells, and this effect generates a response in the G0/G1 phase and subsequent cell death. In addition, there was depolarization of the mitochondrial membrane, an effect that was related to the participation of the proapoptotic protein Bax. [ABSTRACT FROM AUTHOR]

Levamisole is an anti-helminthic drug developed and introduced in veterinary medicine, and it has been used more frequently after the inclusion of its usage in human medicine regarding disorders with immunomodulatory properties. In recent years, it has started to attract attention since it has beneficial effects on the treatment of COVID-19 due to its immunomodulatory properties. To investigate the effects of levamisole on sexual behavior and the reproductive system in male rats, two groups were formed the vehicle (n = 10) and levamisole (n = 10) groups. The vehicle group was given purified water whereas the levamisole group was administered with levamisole (2 mg/kg) by oral gavage daily for 4 weeks. Levamisole treatment significantly increased the mount latency (ML, P < 0.001) as well as the intromission latency (IL, P < 0.01). It also significantly prolonged postejaculatory interval (PEI, P < 0.01), decreased copulatory rate (CR, P < 0.05), and sexual activity index (SAI, P < 0.05). It significantly decreased serum monoamine oxidase A (MAO-A) levels (P < 0.05). Additionally, levamisole induced disorganizations of germinal epithelial cells of seminiferous tubules, congestion, edema in the interstitial area, and metaphase arrest in some spermatocytes (P < 0.001), and it significantly increased the immunohistochemical expressions of apoptotic Bax and cytochrome c, which is crucial proapoptotic protein, in the testis (P < 0.001). Also, levamisole significantly upregulated the mRNA levels of the apoptosis-related key regulatory genes, including Bax (Bcl-2-associated X protein, P = 0.05) and Bax/Bcl-2 ratio (P < 0.01) in testis. The current research is the first to show that levamisole may decrease sexual performance, potency, sexual motivation, and libido and induce apoptosis in the testis. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Chinese Institute of Food Science & Technology / Zhongguo Shipin Xuebao is the property of Journal of Chinese Institute of Food Science & Technology Periodical Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) is one of the most commonly employed Lactobacillus in the food industry. Exopolysaccharides (EPS) of Lactobacillus, which are known to exhibit probiotic properties, are secondary metabolites produced during the growth of Lactobacillus. This study identified the structure of the EPS produced by L. bulgaricus 1.0207 and investigated the mitigation of L. bulgaricus 1.0207 EPS on H2O2-induced oxidative stress in IPEC-J2 cells. L. bulgaricus 1.0207 EPS consisted of glucose and galactose and possessed a molecular weight of 4.06 × 104 Da. L. bulgaricus 1.0207 EPS exhibited notable scavenging capacity against DPPH, hydroxyl radicals, superoxide anions, and ABTS radicals. Additionally, L. bulgaricus 1.0207 EPS enhanced cell proliferation, reduced intracellular reactive oxygen species (ROS) accumulation, increased activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC) elevated the relative expression of CAT, SOD, HO-1, NQO1, ZO-1, and Occludin genes. Moreover, L. bulgaricus 1.0207 EPS improved the expression of Nrf2, pNrf2, pNrf2/Nrf2, and Bcl-2 proteins, while decreasing the expression of Keap1, Caspase3, and Bax proteins, with the best effect at a concentration of 100 μg/mL. L. bulgaricus 1.0207 EPS mitigated H2O2-induced oxidative stress injury in IPEC-J2 cells by activating the Keap1/Nrf2 pathway. Meanwhile, L. bulgaricus 1.0207 EPS exhibited the potential to decrease apoptosis and restore the integrity of the gut barrier. The findings establish a theoretical foundation for the development and application of L.bulgaricus 1.0207 and its EPS. [ABSTRACT FROM AUTHOR]