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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]

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]

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]

AbstractObjectiveMethods:Results:Conclusion:This 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]

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: 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]

[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 Chinese Institute of Food Science & Technology 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.)

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.)

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]

AbstractBackgroundMethodsResultsConclusionBreast cancer (BC) is characterized by an increasing incidence and mortality rate. Juzaowan inhibits various malignant processes, although its mechanism in BC remains unclear.To evaluate the impact of Juzaowan on biological functions of BC cells, cellular assays were done to assess proliferation, migration, invasion, and apoptosis. Bioinformatics was used to identify signaling pathways affected by active ingredients of Juzaowan. BC cells were treated with Juzaowan. Western blot assayed lactate production, glucose consumption, and expression of proteins related to glycolytic pathway and STAT3/C-Myc axis.Juzaowan suppressed BC cell proliferation and increased apoptosis. It downregulated anti-apoptotic protein BCL2 while upregulating pro-apoptotic proteins Bax and cleaved caspase 3. Juzaowan significantly inhibited BC cell migration and invasion. Significant upregulation of E-cadherin and significant downregulation of E-cadherin-binding protein ZEB1, N-cadherin, and vimentin were observed. Bioinformatics analysis and cellular experiments confirmed inhibition of Juzaowan on BC cell glucose uptake and glycolytic pathways-related key metabolic enzymes (GLUT1, PKM2, LDH) expressions. Western blot revealed that Juzaowan induced metabolic alterations in BC cells by impeding STAT3/C-Myc axis.This study elucidated molecular mechanisms of Juzaowan inhibiting BC cell glycolysis by repressing STAT3/C-Myc axis, thus suppressing malignant progression. These findings supported clinical applications of Juzaowan. [ABSTRACT FROM AUTHOR]

Simple Summary: Hexavalent chromium (Cr(VI)) poses a considerable threat to aquatic ecosystems and aquatic organisms due to pollution. This study explored the toxic effects of Cr(VI) on the primary hepatocytes of the Reeves' turtles (Mauremys reevesii) by isolating the hepatocytes. The results showed that Cr(VI)-treated cells exhibited increased antioxidant enzyme activity and reactive oxygen species levels. ATP levels decreased, and related mitochondrial dynamics genes underwent changes. Ultimately, this led to apoptosis and autophagy in the cells. These findings indicate that Cr(VI) pollution is a critical health issue, offering fresh perspectives and guiding principles for the protection of turtles. Hexavalent chromium (Cr(VI)), a pervasive industrial contaminant, is highly toxic to both humans and animals. However, its effects on turtles are largely unexplored. Our study aimed to investigate the toxic effects of Cr(VI) on the Reeves' turtles (Mauremys reevesii) primary hepatocytes. We exposed hepatocytes to two concentrations (25 μM and 50 μM) of Cr(VI) for 24 h. The results showed that compared to controls, Cr(VI)-treated cells showed elevated antioxidant enzyme activity (catalase (CAT) and superoxide dismutase (SOD)) and increased reactive oxygen species (ROS) levels. Adenosine triphosphatae (ATP) levels decreased, indicating mitochondrial dysfunction. Additionally, we found significant changes in mitochondrial dynamics related genes, with downregulation of mitofusin 2 (Mfn2) and silent information regulator 1 (SIRT1) and a decrease in sirtuin 3 (SIRT3) and tumor protein 53 (p53) mRNA levels. Annexin V-FITC fluorescence staining-positive cells increased with higher Cr(VI) concentrations, marked by elevated bcl-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase (Caspase3) mRNA levels and reduced B-cell lymphoma-2 (Bcl2) expression. Autophagy-related genes were also affected, with increased microtubule-associated protein 1 light chain 3 (LC3-I), microtubule-associated protein light chain 3II (LC3-II), unc-51-like autophagy-activating kinase 1 (ULK1), and sequestosome 1 (p62/SQSTM1) mRNA levels and decreased mammalian target of rapamycin (mTOR) and Beclin1 expression. Taken together, Cr(VI) promotes cell apoptosis and autophagy in turtle hepatocytes by inducing oxidative stress and disrupting mitochondrial function. These findings highlight the serious health risks posed by Cr(VI) pollution and emphasize the need for protecting wild turtle populations. [ABSTRACT FROM AUTHOR]

Objective: To investigate impacts of usnic acid （UA） on malignant behavior of gastric cancer cells by regulating the chemokine （C-C motif） ligand 2 （CCL2）-CCL2 receptor （CCR2） signal axis. Methods: SGC-7901 cells, a well growing human gastric cancer cell line, were treated with different concentrations of UA, which were grouped into low concentration （UA-L） group （62.5 μmol/L UA）, medium concentration （UA-M） group （125 μmol/L UA） and high concentration （UA-H） group （250 μmol/L UA）; meantime, the cells were transfected with CCL2 overexpression vector （pc DNA3.1 CCL2）, empty vector （pc DNA3.1）, silenced CCL2 （si CCL2） and negative control （si control）, and SGC-7901 cells were treated with 250 μmol/L UA, labeled as UA-H+pc DNA3.1 CCL2 group, UA-H+pc DNA3.1 group, UA-H+si control group and UA-H+si CCL2 group, another untreated SGC-7901 cells were taken as the control group. Flow cytometry, MTT and qRT-PCR were applied to detect cell apoptosis, proliferation, and expression levels of CCL2 and CCR2 mRNA; Western blot was applied to detect expression levels of PD-L1, apoptotic protein（ Bax）, proliferative protein （CyclinD1, CCL2, CCR2） and immune escape related protein （B7H1）; after co-culturing with CD8+T cells isolated and cultured in vitro, ELISA was applied to detect levels of IL-4, IFN-γ and IL-10 in the supernatant. Gastric cancer cells in each group were co-cultured with activated peripheral blood mononuclear cell （PBMC） 1∶1 for 72 hours, and the sensitivity of gastric cancer cells in each group to T-cell-mediated killing was compared. Results: Compared with control group, cell proliferation rate, IL-10 level, CyclinD1, PD-L1, CCL2, CCR2 and B7H1 protein and mRNA expressions, cell counts after co-culturing with activated PBMC 1∶1 for 72 hours in UA-L group, UA-M group and UA-H group were obviously reduced, while apoptosis rate, IL-4 and IFN-γ levels, Bax protein expression were obviously increased （P<0.05）; compared with UA-H+pc DNA3.1 group, cell proliferation rate, IL-10 level, CyclinD1, PD-L1, CCL2, CCR2 protein and mRNA expressions, cell counts after co-culturing with activated PBMC 1∶1 for 72 hours in UA-H+pc DNA3.1 CCL2 group were obviously increased, while apoptosis rate, IL-4 and IFN-γ levels, and Bax protein expression were obviously reduced （P<0.05）; compared with UA-H+si control group, cell proliferation rate, IL-10 level, CyclinD1, PD-L1, CCL2, CCR2 and B7H1 protein and mRNA expressions, cell counts after co-culturing with activated PBMC 1∶1 for 72 hours in UA-H+si CCL2 group were obviously reduced, while apoptosis rate, IL-4 and IFN-γ levels and Bax protein expression were obviously increased（ P<0.05）. Conclusion: UA can inhibit gastric cancer cells proliferation, immune escape, and induce apoptosis, which may be related to the inhibition of the CCL2-CCR2 signaling axis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impacts of hirudin （HRD） on neuronal apoptosis and inflammatory response in rats with cerebral infarction by regulating Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil-forming protein kinase （ROCK） signaling pathway. Methods: SD rats were grouped into Ct group, Model group, low-dose HRD group （HRD-L group, 13.33 mg/kg）, high-dose HRD group （HRD-H group, 26.66 mg/kg）, positive control Nimodipine group （NMDP group, 40 mg/kg）, U-46619 （RhoA agonist, 0.03 mg/kg） group and HRD-H+U-46619 group （26.66 mg/kg+0.03 mg/kg）, with 24 rats per group. Except for the Ct group, rats in other groups constructed the rat model of cerebral infarction by the modified suture method. The rats in the Ct group only exposed the blood vessels without incision and suture insertion. After 1 hour of successful modeling, drug treatment was carried out, once a day for 4 weeks. Zea-Longa method was applied to evaluate the neurological function of rats; dry and wet weight method was applied to detect the water content of rat brain tissue; 2, 3, 5-triphenyltetrazolium chloride（ TTC） staining was applied to determine the volume of cerebral infarction in rats; TUNEL staining was applied to detect the apoptosis of neurons in the CA1 region of the hippocampus of rats. The levels of TNF-α, IL-1β and IL-6 in rat hippocampus were detected by ELISA; the protein expressions of cleaved-Caspase-3 Cleaved-Caspase-3, Bcl-2-associated X protein （Bax）, RhoA, ROCK1 and ROCK2 in rat hippocampus were dedotected by Western blot. Results: Compared with Ct group, the neurological function scores, brain tissue water content, cerebral infarction volume percentage, neuron apoptosis rate, levels of TNF-α, IL-1β, IL-6, the protein expressions of Cleaved-Caspase-3, Bax, RhoA, ROCK1 and ROCK2 increased in the Model group （P<0.05）. Compared with Model group, the neurological function scores, brain tissue water content, cerebral infarction volume percentage, neuron apoptosis rate, levels of TNF-α, IL-1β, IL-6, the protein expressions of Cleaved-Caspase-3, Bax, RhoA, ROCK1 and ROCK2 decreased in HRD-L group, HRD-H group, NMDP group, however, the corresponding index changes in the U-46619 group showed an opposite trend （P<0.05）. Compared with HRD-H group, the neurological function scores, brain tissue water content, cerebral infarction volume percentage, neuron apoptosis rate, levels of TNF-α, IL-1β, IL-6, the protein expressions of Cleaved-Caspase-3, Bax, RhoA, ROCK1 and ROCK2 were increased in the HRD-H+U-46619 group（ P<0.05）. Conclusion: HRD may inhibit neuronal apoptosis and inflammatory response in rats with cerebral infarction by inhibiting RhoA/ROCK signaling pathway. [ABSTRACT FROM AUTHOR]

Lycium ruthenicum Murray (LR) is a medicine and edible plant in Northwest China, and L. ruthenicum Murray anthocyanins (LRA) are green antioxidants with various pharmacological activities, such as antioxidant and anti‐inflammatory activities. However, the protective effect and mechanism of LRA against retinal damage induced by blue light exposure are poorly understood. This study explored the protective effects and potential mechanisms of LRA on retinal damage induced by blue light exposure in vitro and in vivo. The results showed that LRA could ameliorate oxidative stress injury by activating the antioxidant stress nuclear factor‐related factor 2 pathway, promoting the expression of phase II detoxification enzymes (HO‐1, NQO1) and endogenous antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), and reducing reactive oxygen species and malondialdehyde levels. Additionally, LRA could inhibit inflammatory response by decreasing the expression of blue light exposure‐induced nuclear factor‐κB (NF‐κB) pathway‐related proteins (NF‐κB and p‐IκBα), as well as interleukin (IL)‐6, tumor necrosis factor‐α, IL‐1β pro‐inflammatory factors and pro‐inflammatory chemokine VEGF, and increasing the expression of anti‐inflammatory factor IL‐10. Furthermore, LRA could ameliorate oxidative stress‐induced apoptosis by upregulating Bcl‐2 and downregulating Bax and Caspase‐3 protein expression. All these results indicate that LRA can be used as an antioxidant dietary supplement for the treatment or prevention of retinal diseases. [ABSTRACT FROM AUTHOR]

Cardiovascular dysfunctions complicate 10–20% of pregnancies, increasing the risk for postpartum mortality. Various gestational insults, including preeclampsia are reported to be associated with adverse maternal cardiovascular outcomes. One such insult, gestational hyperandrogenism increases the risk for preeclampsia and other gestational morbidities but its impact on postpartum maternal health is not well known. We hypothesize that gestational hyperandrogenism such as testosterone (T) excess will adversely impact the maternal heart in the postpartum period. Pregnant ewes were injected with T propionate from day 30 to day 90 of gestation (term 147 days). Three months postpartum, echocardiograms, plasma cytokine profiles, cardiac morphometric, and molecular analysis were conducted [control (C) n = 6, T-treated (T) n = 7 number of animals]. Data were analyzed by two-tailed Student's t test and Cohen's effect size (d) analysis. There was a nonsignificant large magnitude decrease in cardiac output (7.64 ± 1.27 L/min vs. 10.19 ± 1.40, P = 0.22, d = 0.81) and fractional shortening in the T ewes compared with C (35.83 ± 2.33% vs. 41.50 ± 2.84, P = 0.15, d = 0.89). T treatment significantly increased 1) left ventricle (LV) weight-to-body weight ratio (2.82 ± 0.14 g/kg vs. 2.46 ± 0.08) and LV thickness (14.56 ± 0.52 mm vs. 12.50 ± 0.75), 2) proinflammatory marker [tumor necrosis factor-alpha (TNF-α)] in LV (1.66 ± 0.35 vs. 1.06 ± 0.18), 3) LV collagen (Masson's Trichrome stain: 3.38 ± 0.35 vs. 1.49 ± 0.15 and Picrosirius red stain: 5.50 ± 0.32 vs. 3.01 ± 0.23), 4) markers of LV apoptosis, including TUNEL (8.3 ± 1.1 vs. 0.9 ± 0.18), bcl-2-associated X protein (Bax)+-to-b-cell lymphoma 2 (Bcl2)+ ratio (0.68 ± 0.30 vs. 0.13 ± 0.02), and cleaved caspase 3 (15.4 ± 1.7 vs. 4.4 ± 0.38). These findings suggest that gestational testosterone excess adversely programs the maternal LV, leading to adverse structural and functional consequences in the postpartum period. NEW & NOTEWORTHY: Using a sheep model of human translational relevance, this study provides evidence that excess gestational testosterone exposure such as that seen in hyperandrogenic disorders adversely impacts postpartum maternal hearts. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science 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.)

The ischemia–reperfusion process of a donor heart during heart transplantation leads to severe mitochondrial dysfunction, which may be the main cause of donor heart dysfunction after heart transplantation. Pyruvate carboxylase (PC), an enzyme found in mitochondria, is said to play a role in the control of oxidative stress and the function of mitochondria. This research examined the function of PC and discovered the signaling pathways controlled by PC in myocardial IRI. We induced IRI using a murine heterotopic heart transplantation model in vivo and a hypoxia–reoxygenation cell model in vitro and evaluated inflammatory responses, oxidative stress levels, mitochondrial function, and cardiomyocyte apoptosis. In both in vivo and in vitro settings, we observed a significant decrease in PC expression during myocardial IRI. PC knockdown aggravated IRI by increasing MDA content, LDH activity, TUNEL-positive cells, serum cTnI level, Bax protein expression, and the level of inflammatory cytokines and decreasing SOD activity, GPX activity, and Bcl-2 protein expression. PC overexpression yielded the opposite findings. Additional research indicated that reducing PC levels could block the Wnt/β-catenin pathway and glutamine metabolism by hindering the movement of β-catenin to the nucleus and reducing the activity of complex I and complex II, as well as ATP levels, while elevating the ratios of NADP+/NADPH and GSSG/GSH. Overall, the findings indicated that PC therapy can shield the heart from IRI during heart transplantation by regulating glutamine metabolism through the Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Aim This study is primarily designed to investigate the potential neuroprotective effects of polyphenol against 6-OHDAcaused neurotoxicity on SH-SY5Y cells. Materials and Methods Cytotoxic effect of 6-OHDA and valuable role of quercetin, myricetin and kaempferol on SH-SY5Y cells were analyzed by MTT assay. Generation of 6-OHDA-stimulated reactive oxygen species (ROS) was measured using DCFDA fluorescence dye. Alteration of 6-OHDA-caused mitochondrial membrane potential and nuclear condensation was investigated with the help of rhodamine-123 and hoechest stain. Immunoblotting was performed to detect the expression level of 6-OHDA-caused alpha-synuclein (á-syn), Bcl-2 associated protein X (BAX), caspase 3, cleaved Poly ADP – ribose polymerase (PARP) and Bcell lymphoma 2 proteins (Bcl-2). Result Through MTT assay, quercetin was selected over myricetin and kaempferol to counter 6-OHDA-caused cell death. The research delves into unraveling the intricate mechanisms underlying 6-OHDA-induced neurotoxicity, encompassing alterations in cellular morphology, escalation of oxidative stress, perturbation in mitochondrial membrane potential, and nuclear condensation. Exposure to 6-OHDA is implicated in the upregulation of á-syn protein, contributing to the aggravation of neurotoxicity. Concurrently, 6-OHDA orchestrates the apoptotic pathway by upregulating the expression of proapoptotic proteins such as BAX, caspase 3, and PARP, while down regulating the expression of the Bcl-2, affirming its role in apoptosis induction. Quercetin demonstrated ability to attenuate the expression of á-syn in the presence of 6-OHDA-caused injury in SH-SY5Y cells. Conclusion Taken together, these findings collectively underscore the therapeutic potential of quercetin as a promising agent against neurotoxicity caused by 6-OHDA. [ABSTRACT FROM AUTHOR]

This study aims to investigate the curative effects of Morin, a flavonoid, against arsenic toxicity in 3T3 embryonic fibroblast cells and its effect on the molecular mechanisms of cells. The cytotoxicity and viability of the cells were measured by MTT and LDH tests. Arsenic (0.74 μM) was used to trigger toxicity and Morin (50 μM) was used for treatment. The levels of oxidative stress biomarkers and the activities of antioxidant enzymes were measured by spectrophotometric method, and inflammatory markers were measured by ELISA method. While mRNA expression levels of Bax, Bcl-2 levels, and Caspase-3 activity were measured by qRT-PCR technique, TUNEL staining was performed to detect DNA breaks and DAPI staining to visualize nuclear changes. Protein structures were retrieved from the protein data bank. OpenBabel and Autodock programs were used for the molecular docking study. Morin rescued the 3T3 embryonic fibroblast cells exposed to arsenic. However, Arsenic decreased the activities of antioxidant enzymes in cells and significantly increased oxidative stress, inflammation, and apoptosis. Morin treatment reduced oxidative damage and TNF-α and IL-1β levels. Arsenic-induced Caspase-3 mRNA expression level and Bax protein mRNA expression level were significantly increased, while Bcl-2 mRNA expression level was significantly decreased. While Caspase-3 mRNA expression level and Bax protein mRNA expression level decreased with morin treatment, Bcl-2 mRNA expression level increased significantly. Molecular docking study results showed good binding affinity of morin in SOD, GSH-Px, Bax, Bcl-2, Caspase-3, TNF-α, and IL-1β structures. Morin showed antioxidant, anti-inflammatory, and anti-apoptotic effects against Arsenic-induced cellular toxicity. [ABSTRACT FROM AUTHOR]

Oxidized light-density lipoprotein (ox-LDL) causes endothelial dysfunction, which is an important determinant of atherogenesis, and subsequently leads to apoptosis. Atherosclerosis is one of the most significant cardiovascular diseases (CVDs) threatening human health and causes death worldwide. Recently, long noncoding RNAs (lncRNAs) have been suggested to involved in vascular biology. Ox-LDL activates nuclear factor kappa-B (NF-κB), and NF-κB interacting lncRNA (NKILA) inhibits NF-κB signaling. In this study, the hypothesis is that NKILA may regulate endothelial cell (EC) apoptosis and, therefore, play a role in the pathogenesis of atherosclerosis. This hypothesis is based on the knowledge that EC apoptosis contributes to atherosclerosis development and that NKILA has become a prominent lncRNA in CVDs. The expression of Bcl-2-associated X protein (BAX), caspase 9 (CASP9), cytochrome c (Cyt c, CYCS), apoptotic protease activating factor 1 (APAF1), and B-cell lymphoma 2 (BCL-2) genes in human umbilical vein endothelial cells (HUVEC) treated with ox-LDL and transfected with NKILA siRNA was analyzed using quantitative reverse transcription polymerase chain reaction (RT-qPCR). BAX, CASP9, CYCS, APAF1, and BCL-2 gene expression was downregulated in ox-LDL and NKILA siRNA-treated HUVEC. In addition, when threshold/quantification cycle (Cq) values of NKILA gene expression increased, Cq values of BAX, CASP9, APAF1, and BCL-2 gene expression increased statistics significantly. The expression detection of all these genes, resulting from NKILA gene silencing, may provide guidance for epigenetic studies on EC apoptosis in atherosclerosis. [ABSTRACT FROM AUTHOR]

To explore the feasibility of stellate ganglion block (SGB) for the treatment of brain injury and the inhibitory effect of neuronal apoptosis. SD rats were randomly divided into control group, model group (LPS 0.6 mg/kg), and SGB group (LPS 0.6 mg/kg + lidocaine 0.2 mL). The rats were sacrificed after SGB block for 2 h to separate the hippocampus. The pathological changes of hippocampal tissue were observed by HE staining, the apoptosis of hippocampal neurons was observed by TUNEL staining, the positive expression of B-cell lymphoma-2-Associated X (Bax) in hippocampal tissue was detected by immunohistochemistry, and the expression of Bax mRNA in hippocampal tissue was detected by qRT-PCR method. Results: Compared with the control group, the hippocampal tissue of the model group was severely damaged, and the apoptosis rate of hippocampal neurons, the positive rate of Bax protein, the expression of Bax mRNA, and the protein expressions of Baxwere significantly increased, the protein expression of Bcl-2 was significantly decreased (P < 0.05).Compared with the model group, the hippocampal tissue damage of the SGB group was significantly reduced, and the hippocampal neuron apoptosis rate, Bax protein positive rate, Bax mRNA expression and Bax protein expressions were significantly decreased, and the expression of Bcl-2 protein was significantly increased (P < 0.05). Conclusion: SGB can reduce the apoptosis of neurons in rats and improve brain injury by inhibiting the expression of Bax gene. [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.

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]

Glucocorticoids (GCs) are known to stimulate pancreatic beta (β)-cell apoptosis via several mechanisms, including oxidative stress. Our previous study suggested an increase in dexamethasone-induced pancreatic β-cell apoptosis via a reduction of glutathione S-transferase P1 (GSTP1), which is an antioxidant enzyme. Imatinib, which is a tyrosine kinase inhibitor, also exerts antioxidant effect. This study aims to test our hypothesis that imatinib would prevent pancreatic β-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress. Our results revealed that dexamethasone significantly increased apoptosis in INS-1 cells when compared to the control, and that imatinib significantly decreased INS-1 cell apoptosis induced by dexamethasone. Moreover, dexamethasone significantly increased superoxide production in INS-1 cells when compared to the control; however, imatinib, when combined with dexamethasone, significantly reduced superoxide production in INS-1 cells. Dexamethasone significantly decreased GSTP1, p-ERK1/2, and BCL2 protein expression, but significantly increased p-JNK, p-p38, and BAX protein expression in INS-1 cells—all compared to control. Importantly, imatinib significantly ameliorated the effect of dexamethasone on the expression of GSTP1, p-ERK1/2, p-JNK, p-p38 MAPK, BAX, and BCL2. Furthermore—6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX), which is a GSTP1 inhibitor, neutralized the protective effect of imatinib against pancreatic β-cell apoptosis induced by dexamethasone. In conclusion, imatinib decreases pancreatic β-cell apoptosis induced by dexamethasone via increased GSTP1 expression and reduced oxidative stress. [ABSTRACT FROM AUTHOR]

Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with poor social interaction, communication issues, aberrant motor movements, and limited repetitive interests and behaviour. Spirulina platensis (SP) contains several multi-nutrients and has a wide range of neuroprotective properties.Aim: The target of the current experiment is to detect the protective effects of S. platensis on valproic-induced autism in adult female albino rats’ siblings for the first time.Materials and Methods: Twelve Pregnant rats were separated into four main groups; Group I (control); Group II (S. platensis); Group III (autistic group); and Group IV (autistic SP-treated group). Fifteen offspring pups from each group were sacrificed, brain was divided for biochemical analysis as superoxide dismutase and malondialdehyde were evaluated spectrophotometrically while interleukin-6, interleukin-12, Bcl-2-associated X protein, B-cell lymphoma-2, Beclin-1, brain-derived neurotrophic factor were assessed by ELISA, other division of brain were used for gene expression of PI3k, Akt and mTOR pathway, last division of brain were stained using (H&E) and Giemsa stains. Tumour necrosis factor alpha (TNF-$\alpha \rpar$α) and Synaptophysin (SYN) markers were used for immunohistochemical staining.Results: Autistic Group (III) showed an increment in levels of MDA, IL-6, IL12 and BAX while showing a decrement in SOD, Bcl-2 and Beclin-1 as well as increased PI3k, Akt and mTOR gene expression. Autistic Group (III) also exhibited hypocellularity and disorganization of hippocampal and prefrontal cortex cells. The autistic SP-treated group (IV) showed improvement in these biochemical markers and pathological changes. Our findings suggest that Spirulina platensis will be significant in managing autism. [ABSTRACT FROM AUTHOR]

Background: Among bone diseases, osteoporosis-like skeleton, such as trabecular thinning, fracture and so on, is the main pathological change of cadmium-induced osteoporosis(Cd-OP), accompanied by brittle bone and increased fracture rate. However, the mechanism underlying cadmiuminduced osteoporosis has remained elusive. Compound Lurong Jiangu Capsule (CLJC) is an experienced formula for the treatment of bone diseases, which has the effect of tonifying kidney and strengthening bones, promoting blood circulation and relieving pain. Objective: Network pharmacology and molecular docking technology combined with experiments were used to investigate the potential mechanism of CLJC in treating Cd-OP. Method: The active compounds and corresponding targets of each herb in CLJC were searched in the TCMSP and BATMAN-TCM databases. The DisGeNet, OMIM, and GeneCards databases searched for Cd-OP targets. The relationship between both of them was visualized by establishing an herbcompound- target network using Cytoscape 3.9.1 software. Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed after determining the intersection of the targets from CLJC and Cd-OP. What's more, molecular docking was performed to validate the results. All of them were aim to obtain hud signaling pathways for further study. Finally, BAX, BCL-2, and CASPASE-3 were screened and selected for further experiments, which included bone imaging and reconstruction analysis (Micro-CT), hematoxylin-eosin Staining (HE), and western blot (WB). Results: 106 common targets from CLJC and Cd-OP targets were identified. KEGG pathway analysis suggested that multiple signaling pathways, such as the pathways in cancer, may play roles in treatment. Verification of the molecular docking was successful. Here we showed that Cd-OP displayed Tb.Th and Tb.N significantly reduced and even broke, irregular proliferation of bone cortex, uneven and loose trabecular bone arrangement, changed in apoptosis-related proteins, such as significant upregulation of CASPASE-3, BAX protein and significant downregulation of BCL-2 protein in vivo, while CLJC rescued these phenotypes. Conclusion: This study revealed that CLJC can reduce the expression of apoptosis-related proteins, and multiple components and multiple targets inhibit Cd-OP through apoptosis signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this article was to investigate the exerting protective effect of smilagenin on MPP+-induced apoptosis in SH-SY5Y cells. Methods: In the experiment, PD cell model was constructed using MPP+ treated human neuroblastoma SH-SY5Y cells. SH-SY5Y cells in logarithmic growth phase were taken and divided into four groups: the Control group (Control), the MPP+ group (model group), the smilagenin group (10 μM), and the MPP++ smilagenin group (3 mm,10 μM). The cell proliferation assay (CCK-8) was firstly used to detect the optimal concentration of smilagenin action and the effect on SH-SY5Y cell viability. The effect of smilagenin on the apoptosis rate of SH-SY5Y cells was detected by AnnexinV-FITC/PI double staining assay, and the protein expression of apoptosis-related proteins Bax, Bcl-2 was detected by protein immunoblotting assay. Results: The cell viability assay determined 10 μM/mL of smilagenin as the added concentration for the subsequent experiments. Compared with the control group, the MPP+ group showed significantly lower cell viability (P＜0.001), higher apoptosis rate(P＜0.001), and significantly higher expression of apoptosis-related protein Bax/Bcl-2(P＜0.01). Compared with the MPP+ group, cell viability was significantly higher in the MPP++ smilagenin group (P<0.001), apoptosis rate was significantly lower(P<0.01), apoptosis-related protein Bax/Bcl-2 expression was significantly lower (P<0.01). Conclusion: Smilagenin can inhibit MPP+-induced apoptosis in SH-SY5Y cells, which may be related to its regulation of protein expression of apoptosis-related proteins Bax and Bcl-2. [ABSTRACT FROM AUTHOR]

BACKGROUND: Mesenchymal stem cell-derived exosomes may play a crucial role in tissue damage repair, and miRNA is an important component of exosomes for therapeutic effects. Among them, miR-29b-3p has the effect of reducing cell apoptosis, promoting axonal regeneration, and angiogenesis. OBJECTIVE: To study the protective effect of adipose-derived mesenchymal stem cell-derived exosome via miR-29b-3p on a neural cell injury model simulated by H2O2-treated PC12 cells, and explore the relevant mechanisms. METHODS: (1) First, the collagenase digestion method was used to extract rat adipose-derived mesenchymal stem cells. Adipose-derived mesenchymal stem cells were transfected with miR-29b-3p mimics and inhibitors. Exosomes were extracted from the culture supernatant by ultracentrifugation and identified so as to construct adipose-derived mesenchymal stem cell-derived exosomes with high expression and knockdown miR-29b-3p. (2) By constructing a neural cell injury model simulated by PC12 cells treated with H2O2, the relevant mechanisms of the protective effect of adipose-derived mesenchymal stem cell-derived exosome via miR-29b-3p on the simulated neuronal cell injury model were studied. RESULTS AND CONCLUSION: (1) Adipose-derived mesenchymal stem cell-derived exosome had a typical cup-shaped shape and a diameter distribution in the range of 50-140 nm, expressed membrane proteins Alix, CD63, and TSG101, which were specific markers on the surface of exosomes, and could be successfully ingested by PC12 cells. (2) Adipose-derived mesenchymal stem cell-derived exosome pretreatment could reduce cell apoptosis induced by H2O2 treatment in PC12 cells, and this protective effect was enhanced with the increase of miR-29b-3p expression in the exosomes and weakened with the decrease of miR-29b-3p expression in the exosomes. The mechanism of its effect was related to adipose-derived mesenchymal stem cell-derived exosome via miR-29b-3p promoting the expression of anti-apoptotic protein Bcl-2 and inhibiting the expression of apoptotic protein Bax. [ABSTRACT FROM AUTHOR]

Cataract, a common eye disease among middle-aged and elderly individuals, can lead to retinopathy and subsequent retinal tissue hypoxia, increasing the risk of blindness due to large capillary occlusions. In this study, we synthesized a novel Co(II)-bearing coordination polymer (CP), [Co(L)2(MeOH)]n, by reacting Co(NO3)2·6H2O with the HL ligand in a DMF and MeOH mixed solvent. HL, a dual-functional organic ligand, features both pyridine and carboxylic groups. Molecular docking simulations revealed that the carbonyl and carboxyl functional groups on the Co(II) complex contribute to its biological activity. Fluorescence spectroscopy tests confirmed the fluorescence properties of the CP samples and their selective sensing for Fe3+ ions. Uncoordinated O- or N-donor sites in CP enhanced bioactivity via hydrogen-bond interactions. Encapsulation of CP in biocompatible hydrogels like hyaluronic acid (HA) and chitosan (CMCS) improved stability and enabled controlled release, making it a promising option for targeted drug delivery. Aminoguanidine was used as a drug model, and a HA/CMCS-CP 1@Aminoguanidine delivery system was developed. The system significantly upregulated the expression of anti-apoptotic protein BCL-2 and downregulated the expression of pro-apoptotic protein BAX, suggesting its potential for regulating apoptosis in lens epithelial cells and as a treatment for age-related cataracts. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effects of Cong Rong San (CRS) on neuronal injury and endoplasmic reticulum stess (ERS) in rat models of Alzheimer disease. METHODS: Sixty male Sprague-Dawley rats (2 months old) were randomly divided into control (CON), model (MOD), low-dose CRS (CRSD), medium-dose CRS (CRSZ), high-dose CRS (CRSG), and memantine hydrochloride (MJG) groups. Morris water maze experiments were used to assess learning and memory in the rats. The morphology of neurons in the CA1 region of the hippocampus was examined using HE and Nissl staining, and the morphology of the endoplasmic reticulum in hippocampal cells was observed by transmission electron microscopy. Neuronal apoptosis in the CA1 region of the hippocampus was evaluated by TUNEL staining, while Western blot was used to assess the protein expression of glucose-regulated protein 78 (GRP78), B-cell lymphoma-2 (Bcl-2, Bcl-2-associated X protein (Bax), caspase-3, protein kinase R-like endoplasmic reticulum kinase (PERK), p-PERK, activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) in rat hippocampal tissues. RESULTS : Compared with those in the MOD group, rats in the CRSZ and CRSG groups showed improved learning and memory, together with reduced hippocampal neuronal loss, PERK-ATF4-CHOP activity, and the expression of the pro-apoptotic proteins Bax and caspase-3, while the expression of the anti-apoptotic protein Bcl-2 was increased. CONCLUSION: Treatment with Cong Rong San was found to mitigate cognitive impairment, as well as damage and apoptosis in hippocampal neurons, in rat models of Alzheimer disease, possibly by inhibition of endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

Background: Despite the important clinical issue of cognitive impairment after moderate traumatic brain injury (TBI), there is currently no suitable treatment. Here, we used in vitro and in vivo models to investigate the effect of Donepezil—an acetylcholinesterase (AChE) inhibitor—on cognitive impairment in the acute period following injury, while focusing on neuroinflammation and autophagy- and mitophagy-related markers. Methods: The purpose of the in vitro study was to investigate potential neuroprotective effects in TBI-induced cells after donepezil treatment, and the in vivo study, the purpose was to investigate therapeutic effects on cognitive impairment in the acute period after injury by analyzing neuroinflammation and autophagy- and mitophagy-related markers. The in vitro TBI model involved injuring SH-SY5Y cells using a cell-injury controller and then investigating the effect of donepezil at a concentration of 80 μM. The in vivo TBI model was made using a stereotaxic impactor for male C57BL/6J mice. Immuno-histochemical markers and cognitive functions were compared after 7 days of donepezil treatment (1 mg/kg/day). Mice were divided into four groups: sham operation with saline treatment, sham operation with donepezil treatment, TBI with saline treatment, and TBI with donepezil treatment (18 mice in each group). Donepezil treatment was administered within 4 h post-TBI. Results: In vitro, donepezil was found to lead to increased cell viability and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1), along with decreased reactive oxygen species (ROS), lactate-dehydrogenase (LDH), 2′-7′-dichlorodihydrofluorescein diacetate (DCFH-DA)-positive cells, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. The mRNA and protein expressions of neuroinflammation (Cyclooxygenase-2, COX-2; NOD-like receptor protein 3, NLRP3; Caspase-1; and Interleukin-1 beta, IL-1β), as well as autophagy- and mitophagy-related markers (death-associated protein kinase 1, DAPK1; PTEN-induced kinase 1, PINK1; BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like, BNIP3L; Beclin-1, BECN1; BCL2-associated X protein, BAX; microtubule-associated protein 1A/1B-light chain 3B (LC3B); Sequestosome-1; and p62) were all found to decrease after donepezil treatment. The in vivo study also showed that donepezil treatment resulted in decreased levels of cortical tissue losses and brain swelling in TBI compared to the TBI group without donepezil treatment. Donepezil treatment was also shown to decrease the mRNA and Western blotting expressions of all markers, and especially COX-2 and BNIP3L, which showed the most significant decreases. Moreover, TBI mice showed an decreased escape latency, increased alteration rate, and improved preference index, altogether pointing to better cognitive performance after donepezil treatment. Conclusions: Donepezil treatment may be beneficial in improving cognitive impairment in the early phase of moderate traumatic brain injury by ameliorating neuroinflammation, as well as autophagy and mitophagy. [ABSTRACT FROM AUTHOR]

Escherichia coli (E. coli) is commonly utilized as a vehicle for anti-tumor therapy due to its unique tumor-targeting capabilities and ease of engineering modification. To further explore the role of E. coli in tumor treatment, we consider that E. coli outer membrane vesicles (E. coli-OMVs) play a crucial role in the therapeutic process. Firstly, E. coli-OMVs were isolated and partially purified by filtration and ultracentrifugation, and were characterized using techniques such as nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western Blot (WB). The obtained extracellular nanoparticles, containing OMVs, were found to inhibited the growth of CT26 tumor in mice, while the expression of Bax protein was increased and the expression of Bcl-2 protein decreased. In vitro experiments showed that E. coli-OMVs entered CT26 cells and inhibited cell proliferation, invasion and migration. In addition, in the presence of E. coli-OMVs, we observed an increase in apoptosis rate and a decrease in the ratio of Bcl-2/Bax. These data indicate that E. coli-OMVs inhibits the growth of CT26 colon cancer by inducing apoptosis of CT26 cells. These findings propose E. coli-OMVs as a promising therapeutic drug for colorectal cancer (CRC), providing robust support for further research in related fields. [ABSTRACT FROM AUTHOR]

Haskap berry (Lonicera caerulea L.) is a rich dietary source of anthocyanins with potent anti-inflammatory properties. In this study, isolated haskap berry anthocyanins were encapsulated in maltodextrin and inulin (3:1) by freeze-drying to improve stability and bioavailability. The structural properties of microcapsules, encapsulation yield, efficiency, recovery, and powder retention were evaluated. The microcapsules that exhibited the highest encapsulation efficiency (60%) and anthocyanin recovery (89%) were used in the dextran sulfate sodium (DSS)-induced acute colitis in mice. Thirty-five BALB/c male mice of seven weeks old were divided into seven dietary supplementation groups (n = 5) to receive either free anthocyanins, encapsulated anthocyanins (6.2 mg/day), or probiotics (1 × 109 CFU/day) alone or as combinations of anthocyanin and probiotics. As observed by clinical data, free anthocyanin and probiotic supplementation significantly reduced the severity of colitis. The supplementary diets suppressed the DSS-induced elevation of serum inflammatory (interleukin (IL)-6 and tumor necrosis factor) and apoptosis markers (B-cell lymphoma 2 and Bcl-2-associated X protein) in mice colon tissues. The free anthocyanins and probiotics significantly reduced the serum IL-6 levels. In conclusion, the dietary supplementation of haskap berry anthocyanins and probiotics protects against DSS-induced colitis possibly by attenuating mucosal inflammation, and this combination has the potential as a health-promoting dietary supplement and nutraceutical. [ABSTRACT FROM AUTHOR]

Objective To investigate the protective effect of target temperature management based different durations with delayed hypothermia for traumatic brain injury(TBI) in rats. Methods 36 healthy adult male SD rats were randomly divided into NT group, HT4h group, HT24h group and HT48h group. The TBI model of rats was prepared with an electronic controllable cortical injury device. NT group was treated with normal temperature (37 ) 4 h after TBI, and the experimental groups were treated with low temperature (33.0 ± 1.0 ) 4 h after TBI for 4 h, 24 h, and 48 h. Three days after TBI, the motor function of the rats in each group was evaluated by beam walking test and inclined-grid climbing test, EB staining was used to measure the blood-brain barrier permeability, the change of hippocampal neurons was observed by Nissl staining, the expression of DCX and GFAP was detected by immunofluorescence, and the expression of Bcl-2 and Bax was measured by Western blot and immunohistochemistry. Results Compared with NT group, the experimental groups could significantly improve the motor function of TBI rats, reduce the permeability of blood-brain barrier,protect hippocampal neurons, promote DCX expression, inhibit GFAP expression, up-regulate the expression of Bcl-2 protein, and down-regulate the expression of Bax protein. However, the protective effect was more apparent in HT48h group than other experimental groups (P < 0.05). Conclusion Long-term delayed target temperature management has a significant brain protective effect. [ABSTRACT FROM AUTHOR]