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BCL-w is a BCL-2 family protein that promotes cell survival in tissue- and disease-specific contexts. The canonical anti-apoptotic functionality of BCL-w is mediated by a surface groove that traps the BCL-2 homology 3 (BH3) α-helices of pro-apoptotic members, blocking cell death. A distinct N-terminal portion of BCL-w, termed the BCL-2 homology 4 (BH4) domain, selectively protects axons from paclitaxel-induced degeneration by modulating IP3 receptors, a noncanonical BCL-2 family target. Given the potential of BCL-w BH4 mimetics to prevent or mitigate chemotherapy-induced peripheral neuropathy, we sought to characterize the interaction between BCL-w BH4 and the IP3 receptor, combining "staple" and alanine scanning approaches with molecular dynamics simulations. We generated and identified stapled BCL-w BH4 peptides with optimized IP3 receptor binding and neuroprotective activities. Point mutagenesis further revealed the sequence determinants for BCL-w BH4 specificity, providing a blueprint for therapeutic targeting of IP3 receptors to achieve neuroprotection. [Display omitted] • Hydrocarbon staple scanning yielded optimal BCL-w BH4 domain binders of IP3R1 • Molecular dynamics simulations identified a BH4-binding site in ARM2 of IP3R1 • Point mutagenesis revealed the binding determinants for BH4 interaction • A lead stapled BCL-w BH4 peptide protects axons from chemo-induced degeneration Tang et al. report that staple and alanine scanning of the BCL-w BH4 domain revealed binding determinants for targeting IP3R1 by interaction with a surface groove on ARM2, as predicted by molecule dynamics simulations. A lead construct protected axons from paclitaxel-induced degeneration, with point mutagenesis impairing IP3R1 interaction and neuroprotection. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disorder that commonly affects the skin, kidneys, joints, and various other systemic tissues, with its development intricately linked to the process of immunosenescence. Quercetin (QC), a phytochemical that occurs naturally, demonstrates many different biological capabilities, such as antibacterial, antioxidant, and anti-inflammatory activities. Our investigation found that QC effectively reduced kidney damage and relieved mesenteric lymph nodes (mLNs) swelling in MRL/lpr lupus mice. Moreover, QC has been found to decrease the number of senescent follicular helper T (Tfh) cells, a pivotal kind of T cells that contribute to the progression of SLE. In vitro, QC exhibited the capacity to modulate mRNA expression levels, with the downregulation of IL-6, IL21-AS1, IL-27, BCL6, and BCL2L12, and the upregulation of FOXP1 and BIM. This modulation resulted in the suppression of Tfh cells differentiation and the enhancement of apoptosis in senescent CD4+ T cells. In addition, the HuProtTM Human Proteome Microarray revealed that QC can directly bind to BCL-2 protein and therefore promote the apoptosis of senescent CD4+ T cell. As a result, our investigative elucidate the potent inhibitory action of QC on the ontogeny of Tfh cells, along with its capacity to abrogate the immunosenescent phenotype. This positions QC as a promising therapeutic strategy for treating SLE. [ABSTRACT FROM AUTHOR]

Background: Various medicinal plants and their bioactive compounds exhibited promising anticancer activities by inducing apoptosis, inhibiting angiogenesis, and modulating several signaling pathways in cancer cells. This study aims to assess whether two medicinal plant extracts have anticancer properties, Suaeda Palaestina and Zygophyllum album. Methods: This study used Ehrlich solid tumor mice as its in vivo model. We divided male mice into five groups (n = 5 per group). Group I was used as a control for Ehrlich ascites carcinoma (EAC). Groups 2 and 3 were given Z. album extract 180 mg/kg and 360 mg/kg body weight intraperitoneally. Groups 4 and 5 were given the same dose of S. palaestina and treated three times a week for 2 weeks, starting on day 10 after EAC implantation. After 3 weeks, we collected blood samples and thigh skeletal muscle, homogenized them, and processed them for analysis. The results showed that Ehrlich solid rats (EST) treated with low-dose dichloromethane extracts from Z. album and S. palaestina had significantly smaller tumor sizes than the control group. Protein expression levels of p53, caspase 3, and Bcl-2 were quantified by western blotting. Results: The extracts from both plants induced the hunger mechanism, leading to increased expression of p53 and caspase 3 and decreased expression of Bcl-2 at the protein level in EST mice treated with Z. album and S. palaestina. In addition, the comet assay indicated that these plants have a genotoxic potential for solid tumor cells. The T3 and T4 levels in EST blood samples revealed that both plants had significantly reduced the concentration of T3 and significantly increased T4 compared to the EST mice untreated group. Furthermore, these results showed that Z. album and S. palaestina had antiproliferative effects in EST mice through apoptosis-mediated genotoxicity. Conclusions: These findings indicated that S. palaestina and Z. album could be considered potential natural sources of anticancer agents. [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]

Apoptosis is an evolutionarily conserved cell death pathway that plays a crucial role in maintaining tissue homeostasis, orchestrating organismal development, and eliminating damaged cells. Dysregulation of apoptosis can contribute to the pathogenesis of malignant tumors and neurodegenerative diseases. Anticancer drugs typically possess the capacity to induce apoptosis in tumor cells. The Bcl-2 protein family, consisting of 27 members in humans, serves as the key regulator of mitochondrial function. This family can be divided into two functional groups: anti-apoptotic proteins (e.g., Bcl-2, Bcl-xl, Mcl-1) and pro-apoptotic proteins (e.g., Bad, Bax). Mcl-1 exerts its function by binding pro-apoptotic Bcl-2 proteins thereby preventing apoptosis induction. Overexpression of Mcl-1 not only correlates closely with tumorigenesis but also associates significantly with resistance towards targeted therapy and conventional chemotherapy. Effective induction of apoptosis can be achieved through inhibition or interference with Mcl-1. Thus, this mini review discusses existing Mcl-1 inhibitors. [ABSTRACT FROM AUTHOR]

Breast cancer is the predominant form of cancer among women and ranks as the second most prevalent cancer globally, affecting both developed and less developed countries. Presently, accessible cancer treatment methods either employ recently created, secure, and efficient chemotherapeutic medications or directly target innovative pathways that cause apoptosis. One of the indirect strategies for treating this fatal illness has mostly depended on its essential role in cell cycle arrest and apoptosis induction, as well as the antagonistic interaction between the Bcl-2 and Mcl-1 proteins, in order to avert major health repercussions. We reported that newly synthesized fused chromenopyrimidines (3a and 4a) showed potential cell cycle arrest and dual Bcl-2 and Mcl-1 inhibitory characteristics. Bcl-2 and Mcl-1 were the targets of a molecular docking procedure. The previous docking results are in line with the biological data and suggest that 3a may have promising anti-cancer activity. [ABSTRACT FROM AUTHOR]

Despite significant advances in prenatal medicine, spontaneous miscarriage remains one of the most common and serious pregnancy complications, affecting an increasing number of women. Since many aspects of the pathogenesis of spontaneous miscarriage remain unexplained, the aim of this study has been to assess the involvement of the NLRP3 inflammasome as a potential causative factor. The concentrations of NLRP3, IL-1β, IL-18, and cytochrome C in the serum of patients after miscarriage were measured by means of the immunoenzymatic method. In the placental tissue, the expression of NLRP3, IL-1β, IL-18, and Caspase-1 as well as that of the classical apoptosis biomarkers Fas, FasL, Bcl-2, and Ca was evaluated by means of immunohistochemistry techniques. Additionally, in whole blood, the concentrations of elements crucial for pregnancy progression, such as Ca, K, Mg, and Na, were examined by means of the ICP-OES method. Significantly higher concentrations of NLRP3 and IL-18 were demonstrated in the serum of patients with miscarriage as compared to the control group. In the placental tissue samples, a higher expression of IL-1β, IL-18, and Caspase-1 proteins was noted in women who had experienced miscarriage as compared to the control group. At the same time, a significantly lower expression of FasL and Bcl-2 proteins as well as Ca deposits was observed in women after miscarriage as compared to those with a normal pregnancy outcome. Significantly lower concentrations of Ca and K were recorded in the blood of patients with spontaneous miscarriage as compared to pregnant women. The analysis of the results x indicated a greater involvement of the inflammasome in women with spontaneous miscarriage associated with oxidative–antioxidative imbalance than in the case of miscarriage related to NET formation. Our research has provided evidence for the involvement of the inflammasome in the process of spontaneous miscarriage and identifies a new direction for diagnostics that includes NLRP3 as a preventive element in prenatal care, particularly in light of the steadily declining number of pregnancies and the increasing number of reproductive failures. [ABSTRACT FROM AUTHOR]

Mitochondria-targeting agents, known as mitocans, are emerging as potent cancer therapeutics due to pronounced metabolic and apoptotic adaptations in the mitochondria of cancer cells. ONC212, an imipridone-family compound initially identified as a ClpP agonist, is currently under investigation as a potential mitocan with demonstrated preclinical efficacy against multiple malignancies. Despite this efficacy, the molecular mechanism underlying the cell death induced by ONC212 remains unclear. This study systematically investigates the mitochondrial involvement and signaling cascades associated with ONC212-induced cell death, utilizing HeLa and A549 cancer cells. Treated cancer cells exhibited characteristic apoptotic features, such as annexin-V positivity and caspase-3 activation; however, these occurred independently of typical mitochondrial events like membrane potential loss (ΔΨm) and cytochrome c release, as well as caspase-8 activation associated with the extrinsic pathway. Additionally, ONC212 treatment increased the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, which impeded apoptosis, as the overexpression of Bcl-2-GFP and Bcl-xL-GFP significantly reduced ONC212-mediated cell death. Furthermore, combining a sub-lethal dose of the Bcl-2/Bcl-xL inhibitor Navitoclax with ONC212 markedly augmented caspase-3 activation and cell death, still without any notable ΔΨm loss or cytochrome c release. Moreover, inhibition of caspase-9 activity unexpectedly augmented, rather than attenuated, caspase-3 activation and the subsequent cell death. Collectively, our research identifies ONC212 as an atypical mitochondrial-independent, yet Bcl-2/Bcl-xL-inhibitable, caspase-3-mediated apoptotic cell death inducer, highlighting its potential for combination therapies in tumors with defective mitochondrial apoptotic signaling. [ABSTRACT FROM AUTHOR]

Minocycline (Min), as an antibiotic, possesses various beneficial properties such as anti-inflammatory, antioxidant, and anti-apoptotic effects. Despite these known qualities, the precise cardioprotective effect and mechanism of Min in protecting against sepsis-induced cardiotoxicity (SIC) remain unspecified. To address this, our study sought to assess the protective effects of Min on the heart. Lipopolysaccharide (LPS) was utilized to establish a cardiotoxicity model both in vivo and in vitro. Min was pretreated in the models. In the in vivo setting, evaluation of heart tissue histopathological injury was performed using hematoxylin and eosin (H&E) staining and TUNEL. Immunohistochemistry (IHC) was employed to evaluate the expression levels of NLRP3 and Caspase-1 in the heart tissue of mice. During in vitro experiments, the viability of H9c2 cells was gauged utilizing the CCK8 assay kit. Intracellular ROS levels in H9c2 cells were quantified using a ROS assay kit. Both in vitro and in vivo settings were subjected to measurement of oxidative stress indexes, encompassing glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. Additionglly, myocardial injury markers like lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB) activity were quantified using appropriate assay kits. Western blotting (WB) analysis was conducted to detect the expression levels of NOD-like receptor protein-3 (NLRP3), caspase-1, IL-18, and IL-1β, alongside apoptosis-related proteins such as Bcl-2 and Bax, and antioxidant proteins including superoxide dismutase-1 (SOD-1) and antioxidant proteins including superoxide dismutase-1 (SOD-2), both in H9c2 cells and mouse heart tissues. In vivo, Min was effective in reducing LPS-induced inflammation in cardiac tissue, preventing cell damage and apoptosis in cardiomyocytes. The levels of LDH and CK-MB were significantly reduced with Min treatment. In vitro studies showed that Min improved the viability of H9C2 cells, reduced apoptosis, and decreased ROS levels in these cells. Further analysis indicated that Min decreased the protein levels of NLRP3, Caspase-1, IL-18, and IL-1β, while increasing the levels of SOD-1 and SOD-2 both in vivo and in vitro. Min alleviates LPS-induced SIC by suppressing the NLRP3/Caspase-1 signalling pathway in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Background: Breast cancer, with its high morbidity and mortality rates, is a significant global health burden. Traditional treatments—surgery, chemotherapy, and radiotherapy—are widely used but come with drawbacks such as recurrence, metastasis, and significant side effects, including damage to healthy tissues. To address these limitations, new therapeutic strategies are being developed. Peroxidases (POD) can catalyze excess H2O2 in the tumor microenvironment to generate reactive oxygen species (ROS), which induce cancer cell apoptosis by disrupting redox homeostasis and modulating apoptosis-related proteins. However, natural enzymes face challenges like poor stability, high cost, and sensitivity to environmental conditions, limiting their application in breast cancer treatment. Nanozymes, nanomaterials with enzyme-like activity, offer a promising alternative by overcoming these limitations. Methods: In this study, we successfully prepared Au@Pd nanozymes with peroxidase activity by depositing metallic Pd on Au nanoparticles (Au NPs) synthesized using a trisodium citrate reduction method and ascorbic acid reduction. The in vitro validation was conducted through a series of experiments, including ROS detection, flow cytometry, CCK-8 assay, DNA damage assessment, live/dead cell staining, Western blot (WB), and qPCR. Tumor treatment was performed via tail vein injection of the drug, followed by HE staining of the treated tissues and biochemical analysis of the blood. Results: Au@Pd nanozymes can effectively accumulate at the tumor site through the EPR effect and exert peroxidase-like activity, catalyzing the excess H2O2 in the tumor microenvironment to produce ROS. This triggers apoptosis pathways and DNA damage, leading to the downregulation of the anti-apoptotic protein Bcl-2, upregulation of the pro-apoptotic protein Bax, and induction of apoptosis-related genes, demonstrating strong anti-tumor effects. Conclusions: This study developed an efficient nanozyme-mediated catalytic therapy strategy targeting the tumor microenvironment for the treatment of breast cancer cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Endothelial cells play a critical role in maintaining vascular function and kinetic homeostasis, but excessive accumulation of palmitic acid (PA) may lead to endoplasmic reticulum stress and trigger endothelial cell dysfunction. Baicalin (BCL), a natural plant extract, has received widespread attention for its biological activities in anti-inflammation and anti-oxidative stress. However, the mechanism of BCL on PA-induced endothelial cell dysfunction is unclear. Therefore, the aim of this study was to investigate whether BCL could inhibit PA-induced endoplasmic reticulum stress and thus attenuate endothelial cell dysfunction. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into Control, PA, PA + BCL-10 μM, PA + BCL-20 μM, and PA + BCL-50 μM groups. The PA group was treated with PA (200 μM), while the PA + BCL groups were co-treated with different concentrations of BCL (10 μM, 20 μM, 50 μM) for 24 hours. Cell viability was detected by MTT. Cell migration ability was determined by Transwell assay, apoptosis level by flow cytometry, and tube formation ability by tube formation assay. Finally, the levels of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and angiogenesis-related proteins (VEGFA and FGF2) were detected by western blot, MMP-9, as well as the protein levels of endoplasmic reticulum stress biomarkers (GRP78, CHOP, PERK, and ATF4). RESULTS: The results at the cellular level showed that cell viability, migration ability and tube formation ability of PA-induced HUVECs were significantly reduced, while apoptosis level was significantly increased. However, administration of different concentrations of BCL significantly enhanced PA-induced cell viability, migration ability and tube formation ability of HUVECs while inhibiting apoptosis. The results of protein levels showed that the protein levels of Bax and cleaved caspase-3 were observably up-regulated in the cells of the PA group, while the protein level of Bcl-2 was significantly down-regulated; compared with the PA group, the protein levels of Bax and cleaved caspase-3 were much lower and the Bcl-2 protein level was much higher in the PA + BCL group. Additionally, the protein levels of VEGFA, FGF2 and MMP-9 were raised and those of GRP78, CHOP, PERK and ATF4 were lowered in the PA + BCL group of cells in a concentration-dependent manner. CONCLUSION: BCL significantly attenuates PA-induced endothelial cell dysfunction by inhibiting endoplasmic reticulum stress. [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]

Terminalia catappa is a plant with potential for application in various antioxidant, anti-inflammatory, antimetastatic and antitumor treatments. Therefore, this study aimed to investigate anticancer properties of methanol extract derived from T. catappa leaves, using both in vitro and in silico methods. The results showed that methanol extract had inhibition of HeLa and DU145 cell lines, with respective IC50 values of 352.50 and 954.99 μg/mL. LC-MS/MS analysis identified several active compounds within the extract, including catechin, quercetin, rutin, hirsutrin, loliolide, sesquiterpene, kaempferol, apigenin, cirsiliol, cirsimaritin and demethoxycurcumin, all of which had promising anticancer potential. These compounds performed well in the in silico test. According to computational predictions, rutin (-9.1 kcal/mol), catechin (-8.0 kcal/mol) and sesquiterpene (-8.2 kcal/mol) had higher binding affinity values than cisplatin and paclitaxel (-7.5 kcal/mol). Considering these results, the compounds were potentially anticancer agents through the inhibition of the Bcl-2 protein. Finally, T. catappa active compounds can be used as alternative candidates as a chemopreventive agent. [ABSTRACT FROM AUTHOR]

Background: Improved technologies for chromatin accessibility sequencing such as ATAC-seq have increased our understanding of gene regulation mechanisms, particularly in disease conditions such as cancer. Methods: This study introduces a computational tool that quantifies and establishes connections between chromatin accessibility, transcription factor binding, transcription factor mutations, and gene expression using publicly available colorectal cancer data. The tool has been packaged using a workflow management system to allow biologists and researchers to reproduce the results of this study. Results: We present compelling evidence linking chromatin accessibility to gene expression, with particular emphasis on SNP mutations and the accessibility of transcription factor genes. Furthermore, we have identified significant upregulation of key transcription factor interactions in colon cancer patients, including the apoptotic regulation facilitated by E2F1, MYC, and MYCN, as well as activation of the BCL-2 protein family facilitated by TP73. Conclusion: This study demonstrates the effectiveness of the computational tool in linking chromatin accessibility to gene expression and highlights significant transcription factor interactions in colorectal cancer. The code for this project is openly available on GitHub. [ABSTRACT FROM AUTHOR]

This review presents current knowledge related to the voltage-dependent anion channel-1 (VDAC1) as a multi-functional mitochondrial protein that acts in regulating both cell life and death. The location of VDAC1 at the outer mitochondrial membrane (OMM) allows control of metabolic cross-talk between the mitochondria and the rest of the cell, and also enables its interaction with proteins that are involved in metabolic, cell death, and survival pathways. VDAC1′s interactions with over 150 proteins can mediate and regulate the integration of mitochondrial functions with cellular activities. To target these protein–protein interactions, VDAC1-derived peptides have been developed. This review focuses specifically on cell-penetrating VDAC1-based peptides that were developed and used as a "decoy" to compete with VDAC1 for its VDAC1-interacting proteins. These peptides interfere with VDAC1 interactions, for example, with metabolism-associated proteins such as hexokinase (HK), or with anti-apoptotic proteins such as Bcl-2 and Bcl-xL. These and other VDAC1-interacting proteins are highly expressed in many cancers. The VDAC1-based peptides in cells in culture selectively affect cancerous, but not non-cancerous cells, inducing cell death in a variety of cancers, regardless of the cancer origin or genetics. They inhibit cell energy production, eliminate cancer stem cells, and act very rapidly and at low micro-molar concentrations. The activity of these peptides has been validated in several mouse cancer models of glioblastoma, lung, and breast cancers. Their anti-cancer activity involves a multi-pronged attack targeting the hallmarks of cancer. They were also found to be effective in treating non-alcoholic fatty liver disease and diabetes mellitus. Thus, VDAC1-based peptides, by targeting VDAC1-interacting proteins, offer an affordable and innovative new conceptual therapeutic paradigm that can potentially overcome heterogeneity, chemoresistance, and invasive metastatic formation. [ABSTRACT FROM AUTHOR]

Acetamiprid (ACMP) is a neonicotinoid insecticide that poses a significant threat to the environment and mankind. Oxidative stress and mitochondrial dysfunction are considered prime contributors to ACMP-induced toxic effects. Meanwhile, berberine (BBR) a natural plant alkaloid, is a topic of interest because of its therapeutic and prophylactic actions. Therefore, this study evaluated the effects of BBR on ACMP-mediated alterations in mitochondrial functions and apoptosis in rat liver tissue. Male Wistar rats were divided into four groups: (I) control, (II) BBR-treated, (III) ACMP-exposed, and (IV) BBR+ACMP co-treated groups. The doses of BBR (150 mg/kg b.wt) and ACMP (1/10 of LD50, i.e., 21.7 mg/kg b.wt) were given intragastrically for 21 consecutive days. The results showed that the administration of ACMP diminished mitochondrial complex activity, downregulated complex I (ND1 and ND2) and complex IV (COX1 and COX4) subunit mRNA expression, depleted the antioxidant defense system, and induced apoptosis in rat liver. BBR pre-treatment significantly attenuated ACMP-induced mitochondrial dysfunction by maintaining mitochondrial complex activity and upregulating ND1, ND2, COX1, and COX4 mRNA expression. BBR reversed ACMP-mediated apoptosis by diminishing Bax and caspase-3 and increasing the Bcl-2 protein level. BBR also improved the mitochondrial antioxidant defense system by upregulating mRNA expression of PGC-1α, MnSOD, and UCP-2 in rat liver tissue. This study is the first to evaluate the protective potential of BBR against pesticide-induced mitochondrial dysfunction in liver tissue. In conclusion, BBR offers protection against ACMP-induced impairment in mitochondrial functions by maintaining the antioxidant level and modulating the apoptotic cascade. [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]

Hesperidin (Hes) functions as a strong antioxidant and anti-inflammatory to guard against damage to the heart, liver, and kidneys. Nevertheless, due to its restricted solubility and bioavailability, a delivery method is required for it to reach a specific organ. In this study, ion gelation was used to synthesize a chitosan/hesperidin nanoformulation. Numerous characterization techniques, such as zeta potential, particle size, XRD, TEM, SEM, and FTIR analyses, were used to corroborate the synthesis of hesperidin nanoparticles (Hes-NPs). Male albino mice were given a pretreatment dose of 100 mg/kg, PO, of Hes or Hes-NPs, which was administered daily for 14 days before the induction of doxorubicin nephrotoxicity on the 12th day. Kidney function (urea and creatinine levels) was measured. Lipid peroxidation (MDA) and antioxidant enzyme (CAT and SOD) activities were estimated. TNF-α, IL-1β, and VEGF content; histopathological examination of kidney tissue; and immunohistochemical staining of NF-κB, Caspase-3, BAX, Bcl-2, and TGF-β1 were evaluated. The gene expressions of Sirt-1, Bcl-2, VEGF, HIF1-α, and Kim-1 were also considered. The results showed that pretreatment with Hes or Hes-NPs reduced doxorubicin's nephrotoxic effects, with Hes-NPs showing the greatest reduction. Kidney enzyme and MDA content were lowered in response to the Hes or Hes-NP pretreatment, whereas antioxidant enzyme activities were increased. Hes or Hes-NP pretreatment suppressed the levels of TNF-α, IL-1β, VEGF, NF-κB, Caspase-3, BAX, and TGF-β1; however, pretreatment increased Bcl-2 protein levels. Furthermore, the gene expressions of Sirt-1, Bcl-2, VEGF, HIF1-α, and Kim-1 were considerably higher with Hes-NP than with Hes treatment. These results suggest that Hes-NP treatment might reduce DOX-induced nephrotoxicity in mice via modulating Sirt-1/HIF1-α/VEGF/NF-κB signaling to provide antioxidant, anti-inflammatory, and anti-apoptotic effects. [ABSTRACT FROM AUTHOR]

This study investigates the underlying mechanism through which dietary supplementation of pyrroloquinoline quinone disodium (PQQ) alleviates intestinal inflammation and cell apoptosis in piglets challenged with lipopolysaccharide (LPS). Seventy-two barrows were divided into three groups: control (CTRL), LPS challenged (LPS), and LPS challenged with PQQ supplementation (PQQ + LPS). On d 7, 11, and 14, piglets received intraperitoneal injections of LPS or 0.9% of NaCl (80 μg/kg). After a 4 h interval following the final LPS injection on d 14, blood samples were obtained, and all piglets were euthanized for harvesting jejunal samples. The results showed that dietary supplementation of PQQ improved the damage of intestinal morphology, increased the down-regulated tight junction proteins, and reduced the increase of serum diamine oxidase activity, the intestinal fatty acid binding protein, and TNF-α levels in piglets challenged with LPS (p < 0.05). The proteomics analysis revealed a total of 141 differentially expressed proteins (DEPs), consisting of 64 up-regulated DEPs and 77 down-regulated DEPs in the PQQ + LPS group compared to the LPS group. The KEGG pathway analysis indicated enrichment of the tight junction pathway and the apoptosis pathway (p < 0.05). Compared to the LPS group, the piglets in the PQQ + LPS group had increased levels of Bcl-2 protein, reduced positive apoptosis signals, and a decrease in the abundance of MKK 3/6 and p-p38 proteins (p < 0.05). In conclusion, dietary supplementation of PQQ could alleviate jejunal inflammatory damage and cell apoptosis in piglets challenged with LPS through the MKK3/6-p38 signaling 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]

In this study, we established SH-SY5Y human neuroblastoma cells as an in vitro model to investigate whether oxidative stress and the nuclear erythroid-2 related factor 2 (Nrf2) signaling pathway are associated with 1-bromopropane (1-BP) -induced nerve cell injury. We identified that 1-BP exhibited neurotoxicity mainly through oxidant-based processes in SH-SY5Y cells, as reactive oxygen species, malondialdehyde levels, and 8-hydroxy-2' -deoxyguanosine significantly increased, while superoxide dismutase activity decreased. Furthermore, Nrf2 translocation from the cytosol to the nucleus was inhibited, as was downstream protein expression of the Nrf2-regulated genes HO-1 and Bcl-2. Activation of caspase-9 and −3 increased, and apoptosis was observed. Vitamin C alleviated 1-BP-induced apoptosis by decreasing oxidative stress and activating the Nrf2 signaling pathway. Knockdown of Nrf2 in SH-SY5Y cells increased 1-BP-induced reactive oxygen species production and cell apoptosis, and inhibited HO-1 and Bcl-2 protein expression, while overexpression of Nrf2 alleviated these processes. These findings suggest that 1-BP-induced oxidative stress and apoptosis in SH-SY5Y cells are associated with Nrf2 function inhibition. [ABSTRACT FROM AUTHOR]

The aim of this research was to explore the potential of treadmill exercise in preventing brain aging and neurodegenerative diseases caused by oxidative stress, by studying its effects on d-galactose-induced mice and the mechanisms involved. The results showed that C57BL/6 mice induced with d-gal exhibited cognitive impairment and oxidative stress damage, which was ameliorated by treadmill exercise. The Morris water maze also showed that exercise improved cognitive performance in aging mice and alleviated hippocampal and mitochondrial damage. The study also found that treadmill exercise increased the expression of nuclear factor Nrf2, p-GSK3β, HO-1, NQO1, BDNF, and Bcl-2 proteins while decreasing the expression of Bax. Furthermore, there was a substantial increase in the levels of CAT, GSH-PX and SOD in the serum, along with a decrease in MDA levels. The outcomes propose that aerobic exercise has the potential to hinder oxidative stress and cell death in mitochondria through the modulation of the Nrf2/GSK3β signaling pathway, thus improving cognitive impairment observed in the aging model induced by d-galactose. It appears that treadmill exercise could potentially serve as an effective therapeutic approach to mitigating brain aging and neurodegenerative diseases triggered by oxidative stress. [ABSTRACT FROM AUTHOR]

To investigate the effects of resveratrol (Res) on human fetal scleral fibroblasts (HFSFs) and its potential mechanism. HFSFs were randomly divided into the Res-treated group and the control group. Following, HFSFs were treated with or without a concentration of 10 μM Res for 48 h. To detect the expression of related genes, reverse transcription quantitative PCR (RT-qPCR) and western blotting were used. The apoptosis rate of different groups was determined using flow cytometry. The mRNA expression of matrix metalloproteinase 2 (MMP-2), Collagen, Type I, Alpha 1 (COL1A1), Janus Kinase 2 (JAK2), and Signal Transducer and Activator of Transcription 3 (STAT3)" was downregulated in the Res-treatment group compared to the control group, according to RT-qPCR. Western blotting revealed that Res therapy reduced the expression of MMP-2, JAK2, P-JAK2, STAT3, P-STAT3, and Bcl-2 associated protein X (Bax) while increasing the expression of COL1A1 and B-cell lymphoma-2 (Bcl-2). Flow cytometry showed that the cell apoptosis rate was significantly lower in HFSFs treated with Res. In conclusion, these findings suggest that Res increases COL1A1 expression while inhibiting MMP-2 and cell apoptosis in HFSFs, possibly through modulation of the JAK2/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • Provides a detailed process optimisation of a formula of fermented finger millet. • The formula exhibits anti-proliferative and anti-migratory effects in HCT116 and MDA-MB-231. • Shows increased expression of Bak and decrease in full-length Bcl2 expression. The objective of this study was to optimise the millet formulation using Levilactobacillus brevis and to evaluate its anticarcinogenic potential in vitro. The formula was developed in the course of the fermentation of finger millet (Eleusine coracana) using L. brevis MTTC 4460 and optimised by response surface methodology and validation by artificial neural networking (ANN). The optimised millet formulation could be obtained using 2 % of bacterial inoculum, 2 % of glucose, and a fermentation duration of 3.3 days with a yield of 5.98 mg/mL lactic acid and 3.38 log 10 (CFU/mL) viable L. brevis with overall desirability value of 1. The fermented millet formulation exhibited antiproliferative and antimigratory effects on MDA-MB-231 and HCT116 cancer cell lines. In addition, the outcomes observed in western blot analysis revealed that the formulation elicited apoptotic responses mediated by the Bcl-2 family of proteins in MDA-MB-231 and HCT116 cell lines while demonstrating no discernible impact on HEK293 normal cells. [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.)

Cardiolipin (CL), a critical phospholipid situated within the mitochondrial membrane, plays a significant role in modulating intramitochondrial processes, especially in the context of certain cardiac pathologies; however, the exact effects of alterations in cardiolipin on septic cardiomyopathy (SCM) are still debated and the underlying mechanisms remain incompletely understood. This study highlights a notable increase in the expressions of ALCAT1 and PLSCR3 during the advanced stage of lipopolysaccharide (LPS)-induced SCM. This up-regulation potential contribution to mitochondrial dysfunction and cellular apoptosis—as indicated by the augmented oxidative stress and cytochrome c (Cytc) release—coupled with reduced mitophagy, decreased levels of the antiapoptotic protein B-cell lymphoma-2 (Bcl-2) and lowered cell viability. Additionally, the timing of LPS-induced apoptosis coincides with the decline in both autophagy and mitophagy at the late stages, implying that these processes may serve as protective factors against LPS-induced SCM in HL-1 cells. Together, these findings reveal the mechanism of LPS-induced CL changes in the center of SCM, with a particular emphasis on the importance of pathological remodeling and translocation of CL to mitochondrial function and apoptosis. Additionally, it highlights the protective effect of mitophagy in the early stage of SCM. This study complements previous research on the mechanism of CL changes in mediating SCM. These findings enhance our understanding of the role of CL in cardiac pathology and provide a new direction for future research. [ABSTRACT FROM AUTHOR]

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]

BACKGROUND: The intestine is a barrier resisting various stress responses. Intrauterine growth restriction (IUGR) can cause damage to the intestinal barrier via destroying the balance of intestinal epithelial cells' proliferation and apoptosis. Bacillus subtilis has been reported to regulate intestinal epithelial cells' proliferation and apoptosis. Thus, the purpose of this study was to determine if B. subtilis could regulate intestinal epithelial cells' proliferation and apoptosis in intrauterine growth restriction suckling piglets. RESULTS: Compared with the normal birth weight group, the IUGR group showed greater mean optical density values of Ki‐67‐positive cells in the ileal crypt (P < 0.05). IUGR resulted in higher ability of proliferation and apoptosis of intestinal epithelial cells, by upregulation of the messenger RNA (mRNA) or proteins expression of leucine rich repeat containing G protein coupled receptor 5, Caspase‐3, Caspase‐7, β‐catenin, cyclinD1, B‐cell lymphoma‐2 associated agonist of cell death, and BCL2 associated X (P < 0.05), and downregulation of the mRNA or protein expression of B‐cell lymphoma‐2 and B‐cell lymphoma‐2‐like 1 (P < 0.05). However, B. subtilis supplementation decreased the mRNA or proteins expression of leucine rich repeat containing G protein coupled receptor 5, SPARC related modular calcium binding 2, tumor necrosis factor receptor superfamily member 19, cyclinD1, Caspase‐7, β‐catenin, B‐cell lymphoma‐2 associated agonist of cell death, and Caspase‐3 (P < 0.05), and increased the mRNA expression of B‐cell lymphoma‐2 (P < 0.05). CONCLUSION: IUGR led to excessive apoptosis of intestinal epithelial cells, which induced compensatory proliferation. However, B. subtilis treatment prevented intestinal epithelial cells of IUGR suckling piglets from excessive apoptosis. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Over the last decade, automatic chemical design frameworks for discovering molecules with drug-like properties have significantly progressed. Among them, the variational autoencoder (VAE) is a cutting-edge approach that models the tractable latent space of the molecular space. In particular, the usage of a VAE along with a property estimator has attracted considerable interest because it enables gradient-based optimization of a given molecule. However, although successful results have been achieved experimentally, the theoretical background and prerequisites for the correct operation of this method have not yet been clarified. In view of the above, we theoretically analyze and rigorously reconstruct the entire framework. From the perspective of parameterized distribution and the information theory, we first describe how the previous model overcomes the limitations of the beta VAE in discovering molecules with the desired properties. Furthermore, we describe the prerequisites for training the above model. Next, from the log-likelihood perspective of each term, we reformulate the objectives for exploring latent space to generate drug-like molecules. The distributional constraints are defined in this study, which will break away from the invalid molecular search. We demonstrated that our model could discover a novel chemical compound for targeting BCL-2 family proteins in de novo approach. Through the theoretical analysis and practical implementation, the importance of the aforementioned prerequisites and constraints to operate the model was verified. [ABSTRACT FROM AUTHOR]

BCL‐2, a member of the BCL‐2 protein family, is an antiapoptotic factor that regulates the intrinsic pathway of apoptosis. Due to its aberrant activity, it is frequently implicated in haematopoietic cancers and represents an attractive target for the development of therapeutics that antagonize its activity. A selective BCL‐2 inhibitor, venetoclax, was approved for treating chronic lymphocytic leukaemia, acute myeloid leukemia, and other haematologic malignancies, validating BCL‐2 as an anticancer target. Since then, alternative therapeutic approaches to modulate the activity of BCL‐2 have been explored, such as antibody‐drug conjugates and proteolysis‐targeting chimeras. Despite numerous research groups focusing on developing degraders of BCL‐2 family member proteins, selective BCL‐2 PROTACs remain elusive, as disclosed compounds only show dual BCL‐xL/BCL‐2 degradation. Herein, we report our efforts to develop BCL‐2 degraders by incorporating two BCL‐2 binding moieties into chimeric compounds that aim to hijack one of three E3 ligases: CRBN, VHL, and IAPs. Even though our project did not result in obtaining a potent and selective BCL‐2 PROTAC, our research will aid in understanding the narrow chemical space of BCL‐2 degraders. [ABSTRACT FROM AUTHOR]

Although clinical outcomes in chronic lymphocytic leukemia (CLL) have greatly improved with several approved small molecular inhibitors, acquired resistance does occur, leading to disease progression and eventual death. Thus, the effort to explore novel inhibitors and combination therapeutic regimens is needed. The inhibition of MDM2-p53 interaction to restore p53 function has been regarded as a potential strategy for treating different cancers. We investigated the effects of novel MDM2 inhibitor APG-115 in CLL. We found that APG-115 treatment upregulated the expression of p53, MDM2, and p21 at the mRNA and protein level. APG-115 inhibited cell proliferation, induced apoptosis, and arrested the cell cycle at G0/G1 stage. Moreover, APG-115 inhibited the expression of BCL-2, BCLxL, and MCL-1, and suppressed the activation of AKT and ERK signaling pathways. APG-115 combined with the BCL2 inhibitor, ABT-199 (venetoclax), led to further inhibition of the expression of BCL-2 family anti-apoptotic proteins and consequently enhanced cell death. Collectively, this study demonstrates that APG-115 activates p53 and thus inhibits multiple pro-survival mechanisms, which provides a rational explanation for APG-115 efficiency in inducing cell apoptosis in CLL. The synergistic effect of APG-115 with ABT-199 suggested a potential combination application in CLL therapy. [ABSTRACT FROM AUTHOR]

Anal cancer is uncommon, comprising 2.2% of gastrointestinal cancers. Squamous cell carcinoma (SCC) is the most common; while perianal basal cell carcinoma (BCC) is rare, representing only 0.2% of anorectal malignancies. BCC, associated with sun exposure and immunosuppression, often resembles benign conditions and manifests as perianal ulcers or masses. Histologically, BCC exhibits basaloid tumor cells with distinct patterns. Despite its rarity, accurate diagnosis is crucial. We expose a case study of a 59-year-old male, previously healthy, that presented with hematochezia and perianal pain, leading to a diagnosis of lower gastrointestinal bleeding. Colonoscopy was needed, and a biopsy revealed an ulcerated, indurated lesion involving the left lateral hemorrhoidal bundle, diagnosed as pigmented basaloid carcinoma. Microscopic examination showed malignant nests of cells with peripheral nuclear palisading, melanocytes, and melanin pigment. Immunohistochemistry confirmed positivity for p63, CK5/6, and BCL2. Respect the treatment, due to the involvement of the anal sphincteric muscle, radiotherapy was chosen. [ABSTRACT FROM AUTHOR]

Using plant extracts as photosensitizers in photodynamic therapy (PDT) represents a significant green approach toward sustainability. This study investigates beetroot juice (BRJ), betanin, and their liposomal formulations (Lip-BRJ, Lip-Bet) as photosensitizers in cancer PDT. BRJ was prepared, and its betanin content was quantified via HPLC. The p-nitrosodimethylaniline (RNO)/imidazole technique monitored the singlet oxygen formation. BRJ and betanin decreased the RNO absorbance at 440 nm by 12% and 9% after 45 min of irradiation, respectively. Furthermore, betanin interaction with Bcl-2 proteins was examined using binding free energy analysis and molecular dynamic simulation. The results revealed favorable interactions with ΔG values of −40.94 kcal/mol. Then, BRJ, betanin, Lip-BRJ, and Lip-Bet were tested as photosensitizers on normal (HEK 293) and human lung cancer (A549) cell lines. Irradiation significantly enhanced the cytotoxicity of Lip-Bet on HEK 293 cells (20% cell viability at 2000 µg/mL) and A549 cells (13% cell viability at 1000 µg/mL). For Lip-BRJ, irradiation significantly enhanced the cytotoxicity on HEK 293 cells at lower concentrations and on A549 cells at all tested concentrations. These results proved the positive effect of light and liposomal encapsulation on the anticancer activity of betanin and BRJ, suggesting the efficiency of liposomal beetroot pigments as green photosensitizers. [ABSTRACT FROM AUTHOR]

T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic heterogeneous disease. This study explored the mechanism of specificity protein 1/3 (Sp1/3) in T-ALL cells through β-catenin by acting as targets of miR-495-3p. Expression levels of miR-495-3p, Sp1, Sp3, and β-catenin in the serum from T-ALL children patients, healthy controls, and the T-ALL cell lines were measured. The cell proliferation ability and apoptosis rate were detected. Levels of proliferation-related proteins proliferating cell nuclear antigen (PCNA)/cyclinD1 and apoptosis-related proteins B-cell lymphoma-2 associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) were determined. The binding of Sp1/3 and β-catenin promoter and the targeted relationship between miR-495-3p with Sp1/3 were analyzed. Sp1/3 were upregulated in CD4+ T-cells in T-ALL and were linked with leukocyte count and risk classification. Sp1/3 interference prevented proliferation and promoted apoptosis in T-ALL cells. Sp1/3 transcription factors activated β-catenin expression. Sp1/3 enhanced T-ALL cell proliferation by facilitating β-catenin expression. miR-495-3p targeted and repressed Sp1/3 expressions. miR-495-3p overexpression inhibited T-ALL cell proliferation and promoted apoptosis. Conjointly, Sp1/3, as targets of miR-495-3p limit apoptosis and promote proliferation in T-ALL cells by promoting β-catenin expression. [ABSTRACT FROM AUTHOR]

Protocatechuic acid (PCA) is a water-soluble polyphenol compound that is extracted from certain fruits and plants or obtained from glucose fermentation. Several in vivo and in vitro studies have determined that PCA has protective effects against the toxicity of natural and chemical toxicants. We searched these articles in PubMed, Google Scholar, and Scopus with appropriate keywords from inception up to August 2023. Forty-nine studies were found about protective effects of PCA against drug toxicity, metal toxicity, toxins, chemical toxicants, and some other miscellaneous toxicants. PCA indicates these protective effects by suppression of oxidative stress, inflammation, and apoptosis. PCA reduces reactive oxygen/nitrogen species (RONS) and enhances the level of antioxidant parameters mainly through the activation of the Nrf-2 signaling pathway. PCA also decreases the levels of inflammatory mediators via downregulating the TLR‐4‐mediated IKBKB/NF‐κB and MAPK/Erk signaling pathways. In addition, PCA inhibits apoptosis by lowering the expression of Bax, caspase-3, and caspase-9 along with enhancing the level of the antiapoptotic protein Bcl-2. Further evaluation, especially in humans, is necessary to confirm PCA as a potential therapeutic approach to intervene in such toxicities. [ABSTRACT FROM AUTHOR]

Recent global scientific attention has been directed towards eco-friendly synthesis and versatile applications of silver nanoparticles (AgNPs) due to their effectiveness against specific cells and tissues. This study aimed to develop a green synthesis method for AgNPs using ethanolic extract from Salvia sclarea aerial parts, and to assess their protective efficacy against streptozotocin (STZ)-induced diabetic nephropathy in rats. Additionally, antioxidant, anti-inflammatory, and apoptosis studies were conducted to understand their mode of action. Characterization via ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR) spectroscopy, and X-ray diffraction (XRD) confirmed the formation of ethanol extract of Salvia sclarea silver nanoparticles (EESS AgNPs), with a distinctive absorption peak at 400 nm. Scanning electron microscopy (SEM) analysis revealed predominantly spherical and quasi-spherical shapes of the synthesized nanoparticles. The treatment procedure spanned for a period of 12 weeks in diabetic rats and were evaluated for inflammatory markers (tumor necrosis factor-α, antioxidant markers (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) and apoptosis markers (Bcl-2, Bax, cleaved-caspase-3). Results demonstrated that treatment with EESS AgNPs significantly reduced blood glucose levels compared to the diabetic group. Additionally, EESS AgNPs treatment led to a significant decrease in levels of pro-inflammatory cytokines TNF-α, IL-1β, and PKC-β in renal cells. Furthermore, EESS AgNPs effectively modulated antioxidant enzyme concentrations, including GSH, SOD, GPx, and CAT, bringing them to acceptable levels. Administration of EESS AgNPs also resulted in a significant decrease in protein levels of Bax and activated caspase-3, while increasing expression of the anti-apoptotic protein Bcl-2 in renal cells of STZ-induced diabetic rats. In conclusion, EESS AgNPs demonstrate potent anti-hyperglycemic effects, potentially mitigating diabetic nephropathy by suppressing hyperglycemia-induced oxidative stress, apoptosis, and inflammation in renal cells of diabetic rats. [ABSTRACT FROM AUTHOR]

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]

Acute pancreatitis (AP) is a sudden-onset disease of the digestive system caused by abnormal activation of pancreatic enzymes. Dual oxidase 2 (DUOX2) has been found to be elevated in the progression of a variety of inflammatory diseases. Therefore, we analyzed the specific roles of DUOX2 in AP development. Blood samples were collected from of AP patients and healthy people, and the caerulein- stimulated human pancreatic duct cells (H6C7) were utilized to establish an AP cell model. Cell growth and apoptosis were measured using an MTT assay and TUNEL staining. Additionally, RT-qPCR and western blot assays were conducted to assess the RNA and protein expressions of the cells. ELISA kits were used to determine TNF-α, IL-6, IL-8, and IL-1β levels. The interaction between DUOX2 and miR-605-3p was predicted using the Targetscan database and confirmed by dual-luciferase report assay. We found that DUOX2 increased while miR-605-3p decreased in the blood of AP patients and caerulein-stimulated H6C7 cells. DUOX2 was targeted by miR-605-3p. Furthermore, DUOX2 knockdown or miR-605-3p overexpression promoted cell viability, decreased the TNF-α, IL-6, IL-8, and IL-1β levels, and inhibited apoptosis rate in caerulein-stimulated H6C7 cells. DUOX2 knockdown or miR-605-3p overexpression also increased the Bcl-2 protein levels and down-regulated Bax, cleaved-caspase-1, NLRP3 and p-p65. Interestingly, DUOX2 overexpression reversed the miR-605-3p mimic function in the caerulein-treated H6C7 cells. In conclusion, our research demonstrated that DUOX2 knockdown relieved the injury and inflammation in caerulein-stimulated H6C7 cells. [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]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial 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.)

To investigate the protective mechanisms of hydrogen sulfide (H 2 S) in sepsis-induced acute kidney injury (SAKI), we conducted an in vivo study using a SAKI mouse model induced by intraperitoneal lipopolysaccharide (LPS) injection. Following 6 h of LPS injection, levels of tumor necrosis factor-alpha (TNF-α) and blood urea nitrogen (Bun) were significantly elevated in mouse plasma. In the kidneys of SAKI mice, expression of H 2 S-generating enzymes cysteinyl-tRNA synthetase (CARS), cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) was markedly downregulated, while glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R-like endoplasmic reticulum kinase/protein kinase R-like endoplasmic reticulum kinase (p-PERK/PERK), and B-cell lymphoma-2 recombinant protein X/B-cell lymphoma-2 (Bax/Bcl2) expression was significantly upregulated. H 2 S improved renal function and attenuated renal histopathological changes in SAKI mice, thereby alleviating LPS-induced endoplasmic reticulum stress (ERS). Additionally, it inhibited the expression of p-PERK/PERK and Bax/Bcl2. After inhibiting CSE activity with dl -propargylglycine (PPG i. p.), the renal tissue pathology in LPS-induced AKI mice was further exacerbated, leading to enhanced activation of the PERK/Bax-Bcl2 pathway. Our findings suggest that endogenous H 2 S influences the pathogenesis of SAKI, while exogenous H 2 S protects against LPS-induced AKI by inhibiting the PERK/Bax-Bcl2 pathway involved in ERS. • The lack of endogenous hydrogen sulfide generation is the cause of SAKI in sepsis. • Exogenous hydrogen sulfide treatment inhibits ER stress and improves SAKI. • Exogenous hydrogen sulfide improves SAKI by suppressing ER stress through inhibition of the PERK/Bax-Bcl2 pathway. [ABSTRACT FROM AUTHOR]

This review provides a comprehensive analysis of apoptotic signaling pathways in the context of bone metastatic lung cancer, emphasizing the intricate molecular mechanisms and microenvironmental influences. Beginning with an overview of apoptosis in cancer, the paper explores the specific molecular characteristics of bone metastatic lung cancer, highlighting alterations in apoptotic pathways. Focused discussions delve into key apoptotic signaling pathways, including the intrinsic and extrinsic pathways, and the roles of critical molecular players such as Bcl-2 family proteins and caspases. Microenvironmental factors, such as the tumor microenvironment, extracellular matrix interactions, and immune cell involvement, are examined in depth. The review also addresses experimental approaches and techniques employed in studying apoptotic signaling, paving the way for a discussion on current therapeutic strategies, their limitations, and future prospects. This synthesis contributes a holistic understanding of apoptosis in bone metastatic lung cancer, offering insights for potential therapeutic advancements. [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]

BACKGROUND: Studies have shown that imbalance of bone metabolism during glucocorticoid-induced osteonecrosis of the femoral head necrosis is closely related to oxidative stress. OBJECTIVE: To investigate the pathological mechanism by which oxidative stress-induced ferroptosis promote apoptosis in osteoblasts involved in steroidinduced osteonecrosis of the femoral head. METHODS: General data and serum specimens were collected from 47 patients with steroid-induced osteonecrosis of the femoral head. In addition, six femoral head specimens were collected from these patients. According to the Association Research Circulation Osseous (ARCO) staging system, serum specimens were grouped into ARCO II, III, and IV, while femoral head specimens were classified into ARCO III and IV. Serum levels of malondialdehyde and superoxide dismutase 1 were measured. The protein expression of superoxide dismutase 1, glutathione peroxidase 4, Bcl-2 in the femoral head was detected and verified by Data independent acquisition (DIA) for quantitative sequencing, western blot and alkaline phosphate detection. RESULTS AND CONCLUSION: The ARCO stage of patients with steroid-induced osteonecrosis of the femoral head was independent of age, sex and necrotic side. The serum levels of malondialdehyde and superoxide dismutase 1 were higher in patients with ARCO stage III compared with those with ARCO stage II and IV. The results of DIA protein quantification showed that the function of differential proteins was mainly related to redox. The levels of superoxide dismutase 1, glutathione peroxidase 4, and Bcl-2 in the necrotic region were lower than in the normal region, as well as lower in ARCO stage IV than in ARCO stage III. Western blot verified the results of DIA protein quantification. The alkaline phosphatase activity was lower in the necrotic region than in the normal region, as well as lower in ARCO stage IV than in ARCO stage III. In the necrotic and sclerotic regions, the function of differential proteins was also related to redox, and superoxide dismutase 1, glutathione peroxidase 4, Bcl-2 protein expression and alkaline phosphatase activity were lower in the necrotic area than in the sclerotic region, as well as lower in ARCO stage IV than in ARCO stage III. To conclude, glucocorticoids can influence the progression of steroid-induced osteonecrosis of the femoral head by upregulating oxidative stress levels, inducing osteoblast ferroptosis, and inhibiting osteogenic function. [ABSTRACT FROM AUTHOR]

Programmed cell death via the both intrinsic and extrinsic pathways is regulated by interactions of the Bcl-2 family protein members that determine whether the cell commits to apoptosis via mitochondrial outer membrane permeabilization (MOMP). Recently the conserved C-terminal sequences (CTSs) that mediate localization of Bcl-2 family proteins to intracellular membranes, have been shown to have additional protein-protein binding functions that contribute to the functions of these proteins in regulating MOMP. Here we review the pivotal role of CTSs in Bcl-2 family interactions including: (1) homotypic interactions between the pro-apoptotic executioner proteins that cause MOMP, (2) heterotypic interactions between pro-apoptotic and anti-apoptotic proteins that prevent MOMP, and (3) heterotypic interactions between the pro-apoptotic executioner proteins and the proapoptotic direct activator proteins that promote MOMP. [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]

Objective: To investigate the mechanism by cryptotanshinone regulates the signaling pathway of stromal cell derived factor 1 (SDF-1)/C-X-C chemokine receptor 4 (CXCR4) and inhibits hydrogen peroxide induced cell apoptosis of human bone marrow mesenchymal stem cells (BMSCs). Methods: Cultivated human bone marrow mesenchymal stem cells (HBMSCs) in vitro and established an oxidative stress model by H2O2. Divided HBMSC cells into control group (without oxidative stress induction) and model group (500 μmol/L H2O2 induction for 24 hours), low-dose group of cryptotanshinone(10 μmol/L), medium dose group of cryptotanshinone (20 μmol/L), high-dose group of cryptotanshinone(40 μmol/L). Cell activity was detected by Cell Count Kit (CCK-8). Cell apoptosis was detected by flow cytometry detection. Cellular glucose uptake and lactate levels was detected by enzyme linked immunosorbent assay(Elisa) testing. The content of glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in cells were detected by micro method. Cysteine aspartate protease 3(caspase-3), B-lymphoblastoma-2 associated X protein (Bax), B-lymphoblastoma-2 (Bcl-2), expression of SDF-1 and CXCR4 proteins was detected by western blot detection (Western blot). Results: Compared with the control group, the glucose uptake and lactate levels, GSH, SOD activity, Bcl-2 protein expression, and SDF-1/CXCR4 signaling pathway protein expression of HBMSC cells in the model group decreased, while the cell apoptosis rate, expression of apoptotic protein caspase-3, Bax, and MDA content increased(P<0.05). Compared with the model group, the low, medium, and high dose groups of cryptotanshinone showed an increase in glucose uptake and lactate levels, GSH, SOD activity, Bcl-2 protein expression, and SDF-1/CXCR4 signaling pathway protein expression in HBMSC cells, while the cell apoptosis rate, expression of apoptotic proteins caspase-3, Bax, and MDA content decreased (P<0.05). The differences in various indicators among the low, medium, and high dose groups of cryptotanshinone were statistically significant(P<0.05). Conclusion: Cryptotanshinone may inhibit oxidative stress damage and apoptosis of BMSC induced by hydrogen peroxide by promoting SDF-1/CXCR4 signaling pathway transduction, with high-dose cryptotanshinone having the best effect. [ABSTRACT FROM AUTHOR]

Objective: To investigate the protective effect of cinnamic acid on H2O2-induced H9c2 cell injury and its relationship with PI3K/Akt signaling pathway. Methods: Predicting the mechanism of chronic heart failure with the help of bioinformatics, using H2O2 (100 μmol/L) induced cardiomyocyte H9c2 to construct an oxidative stress injury model. The CCK-8 method was used to detect cinnamic acid (1, 2, 4μmol/L) on H2-induced H9c2 cell viability, Hochest33342/PI double staining and flow cytometry were used to detect apoptosis. Flow cytometry was used to detect the level of ROS in cells. Colorimetric assay was used to detect the levels of oxidative stress markers SOD, MDA, LDH, GSH, and CAT. The mRNA levels of PI3K, Akt, caspase-9, caspase-3, Bax and Bcl-2 were detected by Rt-qPCR. Western blot was used to detect the protein expressions of PI3K, p-PI3K, Akt, p-Akt and caspase-3. After adding LY294002 (PI3K inhibitor), the apoptosis rate, ROS, SOD, MDA, LDH, GSH, CAT levels, and the protein expression of PI3K, p-PI3K, Akt, p-Akt and caspase-3 were detected. Results: Bioinformatics analysis showed that the occurrence and development of chronic heart failure were mainly related to the PI3K/Akt signaling pathway. In vitro experiments showed that cinnamic acid could significantly increase the viability of cardiomyocytes after H2 induction (P<0.01), reduce the apoptosis rate and the levels of ROS, MDA and LDH (P<0.01), increased the levels of SOD, GSH, CAT (P<0.01), down-regulated the mRNA levels of caspase-9, caspase-3, Bax and the expression of caspase-3 protein (P<0.05), the mRNA levels of PI3K, Akt and Bcl-2 and the protein expressions of p-PI3K and p-Akt were up-regulated (P< 0.05). After adding LY294002, the above effect of cinnamic acid on cardiomyocyte H9c2 was reversed (P<0.05). Conclusion: Cinnamic acid can protect cardiomyocytes by regulating the PI3K/Akt signaling pathway by inhibiting H2-induced H9c2 oxidative stress damage and apoptosis of cardiomyocytes. [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]