Search

The current investigation explores the mechanisms of ammonia and arsenic toxicity, along with high-temperature stress, which other researchers rarely addressed. Pangasianodon hypophthalmus was exposed to low doses of ammonia and arsenic (1/10th of LC50, 2.0 and 2.68 mg L−1, respectively) and high temperature (34 °C) for 105 days. The following treatments were applied: control (unexposed), arsenic (As), ammonia (NH3), ammonia + arsenic (NH3 + As), ammonia + temperature (NH3 + T), and NH3 + As + T. Cortisol levels significantly increased with exposure to ammonia (NH3), arsenic (As), and high temperature (34 °C) compared to the unexposed group. Heat shock protein (HSP 70), inducible nitric oxide synthase (iNOS), and metallothionein (MT) gene expressions were notably upregulated by 122–210%, 98–122%, and 64–238%, respectively, compared to the control. Neurotransmitter enzymes (acetylcholine esterase, AChE) were significantly inhibited by NH3 + As + T, followed by other stressor groups. The apoptotic (caspase, Cas 3a and 3b) and detoxifying (cytochrome P450, CYP P450) pathways were substantially affected by the NH3 + As + T group. Immune (total immunoglobulin, Ig; tumor necrosis factor TNFα; and interleukin IL) and growth-related genes (growth hormone, GH; growth hormone regulator, GHR1 and GHRβ; myostatin, MYST and somatostatin, SMT) were noticeably upregulated by NH3 + As + T, followed by other stress groups, compared to the control group. Weight gain %, protein efficiency ratio, feed efficiency ratio, specific growth rate, and other growth attributes were significantly affected by low doses of ammonia, arsenic, and high-temperature stress. Albumin, total protein, globulin, A:G ratio, and myeloperoxidase (MPO) were highly affected by the As + NH3 + T group. Blood profiling, including red blood cells (RBC), white blood count (WBC), and hemoglobin (Hb), were also impacted by stressor groups compared to the control group. Genotoxicity, as DNA damage, was significantly higher in groups exposed to NH3 + As + T (89%), NH3 + T (78%), NH3 (73), NH3 + As (71), and As (68%). The bioaccumulation of arsenic was substantially higher in liver and kidney tissues. The present study contributes to understanding the toxicity mechanisms of ammonia and arsenic, as well as high-temperature stress, through different gene expressions, biochemical attributes, genotoxicity, immunological status, and growth performance of P. hypophthalmus. [ABSTRACT FROM AUTHOR]

Ustiloxins are vital cyclopeptide mycotoxins originally isolated from rice false smut balls that form in rice spikelets infected by the fungal pathogen Ustilaginoidea virens. The toxicity of the water extract of rice false smut balls (RBWE) remains to be investigated. Studies have shown that RBWE may be toxic to animals, but toxicological evidence is still lacking. In this study, we found that the IC50 values of RBWE to BNL CL.2 cells at 24 and 48 h were 40.02 and 30.11 μg/mL, respectively, with positive correlations with dose toxicity and time toxicity. After treatment with RBWE, the number of BNL CL.2 cells decreased significantly, and the morphology of BNL CL.2 cells showed atrophy and wall detachment. RBWE induced DNA presynthesis phase arrest of BNL CL.2 cells, increased the proportion of apoptotic cells and inhibited cell proliferation. RBWE up-regulated reactive oxygen species (ROS) levels and lowered mitochondrial membrane potentials. Additionally, Western blot and qRT-PCR results suggested that RBWE exerted the above effects by promoting the Nrf2/HO-1 and caspase-induced apoptosis pathways in vitro and in vivo. The contents of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bile acids in the serum of mice from Institute of Cancer were significantly up-regulated by RBWE. At the same time, RBWE can lead to increases in ROS and malondialdehyde contents, decreases in contents of oxidized glutathione, glutathione and reduced glutathione, as well as decrease in catalase and superoxide dismutase activities in mouse liver tissues, demonstrating that oxidative stress occurred in mice. Moreover, liver damage was further detected by haematoxylin-eosin staining and electron microscopy to verify the damage to the mice caused by RBWE. In general, RBWE may cause hepatotoxicity in vivo and in vitro via the apoptosis pathway, which provides a reference for hepatotoxicity and its mechanism of action.

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family includes CMTM1–8 and CKLF, and they play key roles in the hematopoietic, immune, cardiovascular, and male reproductive systems, participating in the physiological functions, cancer, and other diseases associated with these systems. CMTM family members activate and chemoattract immune cells to affect the proliferation and invasion of tumor cells through a similar mechanism, the structural characteristics typical of chemokines and transmembrane 4 superfamily (TM4SF). In this review, we discuss each CMTM family member’s chromosomal location, involved signaling pathways, expression patterns, and potential roles, and mechanisms of action in pancreatic, breast, gastric and liver cancers. Furthermore, we discuss several clinically applied tumor therapies targeted at the CMTM family, indicating that CMTM family members could be novel immune checkpoints and potential targets effective in tumor treatment.

Background: Osteoporosis is a disease of the bone system that causes a decrease in skeletal density and degrades skeletal tissue. Decreased bone quality, so that bones are easily broken, damaged and fractured, is an important public health problem. Previous studies have shown that the maintenance of adult bone mass is not only due to changes in bone marrow and bone cells. By regulating apoptosis, they change the lifespan of each individual. This study influences understanding of the function of apoptosis in the pathogenesis of osteoporosis and the importance of controlling the mechanisms of osteoporosis. Methods: On the National Institute of Biotechnology Information website, Gene Expression Omnibus (GEO) microarray data and GSE551495 GEO profiles were collected. The gene set enrichment analysis tool was used to confirm the enrichment of genetic sets in relation to the gene set. The collection of C2 gene sets is compiled from the KEGG (https://www.gsea-msigdb.org/gsea/msigdb/human/search.jsp and https://www.kegg.jp/kegg/) online database and REACTOME (https://www.gsea-msigdb.org/gsea/msigdb/human/search.jsp and https://reactome.org/) pathway analysis. The Search Tool for the Retrieval of Interaction Genes (STRING) website was used to construct and select proteins and genes. The comparative toxicological genomic database (CTD) tools can be used to predict the relationship between apoptosis, osteoporosis‐related genes and interactions between central genes and osteoporosis. Results: These results generally expand our understanding of the path of apoptosis in osteoporosis. We have discovered genes CASP9, CASP8, CASP3, BAX and TP53 associated with osteoporosis. In activation of KEGG apoptosis and REACTOME, caspase activation through the extrinsic apoptotic signaling pathway is characterized by the identification of a subcollection of C2. Other STRINGs show the formation of protein networks and central gene selection, and CTD can accurately predict the relationship between these apoptosis pathways and central genes. Conclusions: Our research has highlighted the importance of the osteoporosis pathway associated with osteoporosis apoptosis with several analytical approaches. These results have broadened our understanding of the pathways of osteoporosis apoptosis. It is particularly possible to predict the sensitivity and vulnerability to osteoporosis. [ABSTRACT FROM AUTHOR]

Ustiloxins are vital cyclopeptide mycotoxins originally isolated from rice false smut balls that form in rice spikelets infected by the fungal pathogen Ustilaginoidea virens. The toxicity of the water extract of rice false smut balls (RBWE) remains to be investigated. Studies have shown that RBWE may be toxic to animals, but toxicological evidence is still lacking. In this study, we found that the IC 50 values of RBWE to BNL CL.2 cells at 24 and 48 h were 40.02 and 30.11 μg/mL, respectively, with positive correlations with dose toxicity and time toxicity. After treatment with RBWE, the number of BNL CL.2 cells decreased significantly, and the morphology of BNL CL.2 cells showed atrophy and wall detachment. RBWE induced DNA presynthesis phase arrest of BNL CL.2 cells, increased the proportion of apoptotic cells and inhibited cell proliferation. RBWE up-regulated reactive oxygen species (ROS) levels and lowered mitochondrial membrane potentials. Additionally, Western blot and qRT-PCR results suggested that RBWE exerted the above effects by promoting the Nrf2/HO-1 and caspase-induced apoptosis pathways in vitro and in vivo. The contents of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bile acids in the serum of mice from Institute of Cancer were significantly up-regulated by RBWE. At the same time, RBWE can lead to increases in ROS and malondialdehyde contents, decreases in contents of oxidized glutathione, glutathione and reduced glutathione, as well as decrease in catalase and superoxide dismutase activities in mouse liver tissues, demonstrating that oxidative stress occurred in mice. Moreover, liver damage was further detected by haematoxylin-eosin staining and electron microscopy to verify the damage to the mice caused by RBWE. In general, RBWE may cause hepatotoxicity in vivo and in vitro via the apoptosis pathway, which provides a reference for hepatotoxicity and its mechanism of action. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The most common histopathological subtype of lung cancer is adenocarcinoma. MicroRNAs are a class of non-coding RNAs that play roles in the regulation of gene expression. MicroRNAs affecting apoptosis may have different roles in lung adenocarcinoma development, progression, and differentiation. The objective of this study is to profile all known microRNAs linked to apoptosis in normal and lung cancer tissue using real-time polymerase chain reaction. MATERIAL AND METHODS: Tissues with adenocarcinoma and healthy tissues were taken from the same lung. The degree of differentiation of all tumors was determined. Expressions of 84 apoptosis-associated microRNAs in both tissues were analyzed by real-time polymerase chain reaction array. RESULTS: Eleven patients and 22 samples were included in the study. In the comparison of expression levels of apoptosis-associated microRNAs in normal and adenocarcinoma tissue, miR-134, miR-183-5p, miR-192-5p, miR-193b-3, miR-194-5p, miR-200c-3, miR-212-3p, miR-25-3p, miR-449a, and miR-9-5p showed significant difference in downregulation. Receiver operating characteristic curve analysis of 10 identified microRNAs was performed, and cut-off values, sensitivity, and specificity were determined. No significant difference was found between microRNA expression levels in adenocarcinoma tissues classified as moderate-well to poorly differentiated. CONCLUSION: Differently, downregulated expressed apoptosis-associated microRNAs were detected in lung adenocarcinoma tissues. MicroRNAs can be used as biomarkers in the diagnosis in lung adenocarcinoma. The expression of microRNAs linked to apoptosis should be investigated in different lung cancer histological subtypes in order to identify potential biomarkers. [ABSTRACT FROM AUTHOR]

Background: B.serrata is commonly known as Indian olibanum, it is mainly used in the production of Indian frankincense. B.serrata is used for many other purposes including asthma diabetes. The medicinal plant Boswelliaserrata has great potential for treating cancer. Since many cancer therapies have their origins in natural ingredients, this study aims to explore the anti-tumorigenic effect of B.serrata using KB cell line. Materials and methods: Seed of B.serrata was collected and extraction was done. Then the extract was added to the culture and the oral cancer cells were obtained from Pune. The cultured oral cells were incubated in a CO2 incubator. Treated oral cancer cell sample was done MTT assay and gene expression analysis. Result: The collected data from MTT assay and gene expression analysis tabulated using SPSS software. MTT assay results showed gradual decrease in cell viability with increase in concentration of Boswelliaserrata and the gene expression showed up regulation of caspase 3 and 9 expression. Conclusion: From the study, Boswelliaserrata has a significant effect on anti-tumorigenic activity; this might be due to the active bio components present in Boswelliaserrata extract. [ABSTRACT FROM AUTHOR]

The bovine viral diarrhea virus 1 (BVDV-1), belonging to the Pestivirus genus, is characterized by the presence of two biotypes, cytopathogenic (cp) or non-cytopathogenic (ncp). For a better understanding of the host pathogen interactions, we set out to identify transcriptomic signatures of bovine lung primary cells (BPCs) infected with a cp or a ncp strain. For this, we used both a targeted approach by reverse transcription droplet digital PCR and whole genome approach using RNAseq. Data analysis showed 3571 differentially expressed transcripts over time (Fold Change >2) and revealed that the most deregulated pathways for cp strain are signaling pathways involved in responses to viral infection such as inflammatory response or apoptosis pathways. Interestingly, our data analysis revealed a deregulation of Wnt signaling pathway, a pathway described in embryogenesis, that was specifically seen with the BVDV-1 cp but not the ncp suggesting a role of this pathway in viral replication. • RNAseq study to compare cytopathogenic and non cytopathogenic BVDV-1 infection. • BVDV-1 biotype dependent cell response on primary cells. • Mitochondrial apoptosis pathway highlighted in infected primary cells. • Involvement of Wnt signalling pathway only in cytopathogenic strain. [ABSTRACT FROM AUTHOR]

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

Hypoxia‐induced cardiomyocyte apoptosis is one of the leading causes of heart failure. Nuclear respiratory factor 1 (NRF‐1) was suggested as a protector against cell apoptosis; However, the mechanism is not clear. Therefore, the aim of this study was to elucidate the role of NRF‐1 in hypoxia‐induced H9C2 cardiomyocyte apoptosis and to explore its effect on regulating the death receptor pathway and mitochondrial pathway. NRF‐1 was overexpressed or knocked down in H9C2 cells, which were then exposed to a hypoxia condition for 0, 3, 6, 12, and 24 h. Changes in cell proliferation, cell viability, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) were investigated. The activities of caspase‐3, ‐8, and ‐9, apoptosis rate, and the gene and protein expression levels of the death receptor pathway and mitochondrial pathway were analyzed. Under hypoxia exposure, NRF‐1 overexpression improved the proliferation and viability of H9C2 cells and decreased ROS generation, MMP loss, caspase activities, and the apoptosis rate. However, the NRF‐1 knockdown group showed the opposite results. Additionally, NRF‐1 upregulated the expression of antiapoptotic molecules involved in the death receptor and mitochondrial pathways, such as CASP8 and FADD‐like apoptosis regulator, B‐cell lymphoma 2, B‐cell lymphoma‐extra‐large, and cytochrome C. Conversely, the expression of proapoptotic molecules, such as caspase‐8, BH3‐interacting domain death agonist, Bcl‐2‐associated X protein, caspase‐9, and caspase‐3 was downregulated by NRF‐1 overexpression in hypoxia‐induced H9C2 cells. These results suggest that NRF‐1 functions as an antiapoptotic factor in the death receptor and mitochondrial pathways to mitigate hypoxia‐induced apoptosis in H9C2 cardiomyocytes. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies 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.)

Tauopathies belong to a heterogeneous class of neuronal diseases resulting in the metabolic disturbance. A disulfide natural compound of Alpha-Lipoic acid (ALA) has shown numerous pharmacologic, antioxidant, and neuroprotective activities under neuropathological conditions. The aim of this study was to investigate the neuroprotective effects of ALA on the tauopathy-induced oxidative disturbance and behavioral deficits. The transgenic Drosophila model of tauopathy induced by human tauR406W using GAL4/UAS system and effects of ALA (0.001, 0.005, and 0.025 % w/w of diet) on the neuropathology of tau in younger (20 days) and older (30 days) adults were investigated via biochemical, molecular, behavioral and in-situ tissue analyses. Expression of apoptosis-related proteins involving Drosophila Cyt-c-d (trigger of intrinsic apoptosis) and DrICE (effector caspase) were upregulated in both ages (20 and 30 days) and DIAP1 (caspase inhibitor) has reduced only in older model flies compared to the controls. Remarkably, all doses of ALA increased DIAP1 and glutathione (GSH) as well as reducing Cyt-c-d and lipid peroxidation (LPO) in the younger flies compared to the model flies. Moreover, the higher doses of ALA were able to decrease thiol concentrations, to increase total antioxidant capacity, and to improve the behavioral deficits (locomotor function, olfactory memory, and ethanol sensitivity) in the younger flies. On the other hand, only a higher dose of ALA was able to decrease DrICE, Cyt-c-d, LPO, and thiol as well as increasing antioxidant capacity and decreasing ethanol sensitivity (ST50, RT50) in the older flies. TUNEL assay showed that all doses of ALA could potentially increase the DIAP1/DrICE ratio and exert anti-apoptotic effects on younger, but not on the older adults. Furthermore, data obtained from the in-situ ROS assay confirmed that only a higher dose of ALA significantly decreased the ROS level at both ages. Our data showed that an effective neuroprotective dose of ALA and its mechanism of action on this model of tauopathy could potentially be influenced by longevity. Moreover, it was shown that ALA prevents apoptosis and decreases the redox homeostasis, and this partially explains the mechanism by which ALA diminishes behavioral deficits. [ABSTRACT FROM AUTHOR]

The crisis of male infertility is an issue of human reproductive health worldwide. The Wuzi Yanzong pill (WZYZP) is a traditional Chinese medicine prescription that shows efficacy in kidney reinforcement and essence benefit to ameliorate male reproductive dysfunctions. However, the pharmacological mechanisms of the WZYZP on male infertility have not been investigated and clarified clearly. This study was designed to investigate the effects of the WZYZP on spermatogenesis disorder and explore its underlying pharmacological mechanisms. First, based on a network pharmacology study, 39 bioactive compounds and 40 targets of the WZYZP associated with spermatogenesis disorder were obtained, forming a tight compound-target network. Molecular docking tests showed tight docking of these compounds with predicted targeted proteins. The protein–protein interaction (PPI) network identified TP53, TNF, AKT1, Bcl-XL, Bcl-2, and IκBA as hub targets. The Kyoto Encyclopedia of Genes and Genomes pathway network and pathway-target-compound network revealed that the apoptosis pathway was enriched by multiple signaling pathways and multiple targets, including the hub targets. Subsequently, the chemical characterization of WZYZP was analyzed using liquid chromatography to quadrupole/time-of-flight mass spectrometry, and 40 compounds in positive ion mode and 41 compounds in negative ion mode in the WZYZP were identified. Furthermore, based on the prediction of a network pharmacology study, a rat model of spermatogenesis disorder was established to evaluate the curative role and underlying mechanisms of the WZYZP. The results showed that WZYZP treatment improved rat sperm quality and attenuated serum hormone levels, reversed histopathological damage of the testis, reduced cell apoptosis in testis tissues, and ameliorated the expression of the predicted hub targets (TP53, TNF-α, AKT1, NFκB, and IκBA) and the apoptosis related proteins (Bcl-XL, Bcl-2, Bax, Caspase 3, and Caspase 9). These results indicated that the WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy.

β-lactoglobulin is important fraction in bovine milk. Selenium is an essential nutrient element. The apoptosis and autophagy induction of Se-β-Lg combined selenic acid in β-lactoglobulin on Hep G2 and Hep 3B cells were investigated in this study. MTT assay showed Se-β-Lg inhibited cells viability. Annexin V-FITC/PI and PI staining indicated Se-β-Lg triggered cells apoptosis and cell cycle arrest. Western blot of caspase-cascade suggested Hep G2 and Hep 3B cells occurred irreversible extrinsic apoptosis. TEM and protein expression of LC3 indicated Se-β-Lg induced cells autophagy. Further explore found Se-β-Lg induced up-regulation of p53 and Fas/FasL in Hep G2 cells. Simultaneously, N-acetyl-L-cysteine, pifithrin-α, Z-VAD-FMK and 3-MA were used. These results further demonstrated Se-β-Lg triggered autophagy and receptor-related apoptosis via p53-mediated Fas/FasL pathway in Hep G2 cells and induced autophagy and p53/Fas-independent caspase activation in Hep 3B cells. Our research revealed that Se-β-Lg had potential to act as chemopreventive compounds in HCC therapy.

Our aim is to evaluate the effects of high-fat diet and strength training on ventral prostate health through investigations of rat prostate histology, endocrine modulation, and the expression of proliferative and apoptotic marker, including androgen receptors (AR), glucocorticoid receptors (GR), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (BAX), Fas cell surface death receptor (Fas/CD95/Apo-1), and Nuclear Factor Kappa-B (NF-κB). Eighty Wistar rats were into one of four subgroups: control (CT), strength training (ST), high-fat diet consumption (HF), and high-fat diet consumption with strength training (HFT). Animals then underwent strength training and/or high-fat diet consumption for 8 or 12 weeks, after which animals were euthanized and markers of prostatic health were evaluated histologically and through immunolabeling. Our results indicate that physical strength training reduced the expression of the prostate cell proliferation marker Bcl-2 while increasing expression of the pro-apoptotic marker BAX, as well as increasing expression of AR and GR relevant in the Bcl-2 pathway. We conclude that a high-fat diet can alter hormone receptor levels and cell-cycle protein expression, thereby modifying prostatic homeostasis, and that strength training was able to reduce prostate damage induced by high-fat diet consumption. [ABSTRACT FROM AUTHOR]

Soybean protein‐derived peptides (SBP) are a rich source of various bioactive peptides with multiple health benefits. However, the prospective effects of SBP on human cells are still unclear. Therefore, this article investigated the effects of small molecular weight SBP on MG132‐induced apoptosis in RAW264.7 cells. SBP inhibited MG132‐induced apoptosis of RAW264.7 cells in a dose‐dependent manner by flow cytometry. To further study its molecular mechanisms, Western blot analysis demonstrated that SBP could activate the PI3K‐AKT pathway by increasing the phosphorylation of PI3K and AKT and inhibiting apoptosis pathway by downregulating the expressions of pro‐apoptotic proteins of Bim, Bax, Fas, and Fasl and promoting the expressions of anti‐apoptotic proteins of Bcl‐xL and Bcl‐2. These results indicated the protective effect of SBP on MG132‐induced apoptosis in RAW264.7 cells. [ABSTRACT FROM AUTHOR]

Background: Exposure to airborne fine particulate matter (PM2.5) has been reported to be harmful to the human kidney. However, whether the activation of oxidative stress and cell apoptosis plays key roles in the nephrotoxicity caused by PM2.5 exposure is still poorly understood. The aim of this study was to explore the mechanism of cytotoxicity after PM2.5 exposure in human proximal tubule epithelial cells (HK-2 cells). Results: PM2.5 exposure resulted in a significant decrease in cell viability, with an increase in LDH release and the early kidney damage marker kidney injury molecule-1 (KIM-1) expression in a dose-dependent manner and time-dependent manner. PM2.5 exposure induced reactive oxygen species (ROS) generation and markedly elevated apoptosis in HK-2 cells. In addition, PM2.5 exposure resulted in the activation of antioxidant pathway, as evidenced by the increased expressions of Nrf2, HO-1 and NQO1 and decreased expression of Keap1. Moreover, PM2.5 exposure also induced the activation of apoptotic pathway, as evidenced by the increased expressions of pro-apoptotic proteins Bax, caspase-3 and caspase-8 and decreased expression of antiapoptotic protein Bcl-2. Conclusions: Our results demonstrated that both antioxidant pathway and apoptotic pathway played critical roles in the damage mediated by PM2.5 in HK-2 cells. This study would give us a strategy to prevent the impairment of renal function by PM2.5 induced through repression of oxidative stress and apoptosis. [ABSTRACT FROM AUTHOR]

Background: Cisplatin could result in a wide range of kidney injuries. During the pathogenetic process, the excessive generation of reactive oxygen species (ROS) induced by cisplatin has been regarded as the initial and critical role, by which DNA damage and cell death could subsequently come up. Therefore the elimination of ROS has long been considered as effective mean to prevent cisplatin-induced kidney injury. Myricitrin is a newfound natural polyphenol hydroxy flavonoid glycoside compound, whose forceful anti-oxidative properties had been confirmed. Thus, we aim to investigate if myricitrin could protect against cisplatin-induced kidney injury. Methods: A cisplatin-induced kidney injury model was established in mice by intraperitoneal injection of cisplatin. The protective effect of myricitrin on kidney injury was evaluated by serum BUN and Cre level. The Kidney pathology was observed with H&E and TUNEL staining. Then cell viability and apoptosis rate were measured using MMT assay and flow cytometry to assess if myricitrin could protect KH-2 cells against cisplatin-induced injury. The intracellular ROS was detected by ROS fluorogenic probe and quantitatively analyzed by flow cytometry. Finally, the expression of Bcl-2 and Bax was investigated by western blotting to indicate the influence in apoptosis pathway. Results: Myricitrin could significantly remit kidney injury induced by cisplatin and inhibit apoptosis of KH-2 cells. In mechanism, myricitrin could eliminate ROS and subsequently block activation of apoptosis pathway. Conclusion: Myricitrin protects against cisplatin-induced kidney injury by eliminating excessive ROS. [ABSTRACT FROM AUTHOR]

Apoptosis is a typical programmed death mode with complex molecular regulation mechanisms. Developing advanced strategies to monitor apoptosis progression is conducive to disease treatment related with apoptosis. Herein, we developed a regulator-carrying dual-responsive integrated AuNP composite fluorescence probe for in situ real time monitoring apoptosis progression. The nanoprobe is constructed by modifying specially designed double-stranded DNA (dsDNA) and caspase 3-specific cleavable peptides (pep) to the surface of AuNP. After uptake by cells, the nanoprobe recognizes miRNA 21 and triggers fluorescence recovery, enabling silencing and imaging of the upstream signaling molecule miRNA 21. Once miRNA 21 is silenced, the downstream signaling molecule caspase 3 is activated and cleaves the substrate peptides, and fluorescence is restored for in situ imaging of caspase 3. The apoptosis induced by silencing miRNA 21 has been successfully implemented in HeLa and A549 cells. The expression level of miRNA 21 and corresponding changes of caspase 3 have also been effectively monitored. These results suggested this nanoprobe will be a potential tool for apoptosis-related biomedical research and clinical application. [Display omitted] • A regulator-carrying dual-responsive integrated nanoprobe was proposed. • In situ imaging and silence of miRNA 21 could be achieved by this method. • The monitoring of activated caspase 3 could be achieved by this method. • The method could be used to monitor apoptosis progression. [ABSTRACT FROM AUTHOR]

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family includes CMTM1-8 and CKLF, and they play key roles in the hematopoietic, immune, cardiovascular, and male reproductive systems, participating in the physiological functions, cancer, and other diseases associated with these systems. CMTM family members activate and chemoattract immune cells to affect the proliferation and invasion of tumor cells through a similar mechanism, the structural characteristics typical of chemokines and transmembrane 4 superfamily (TM4SF). In this review, we discuss each CMTM family member's chromosomal location, involved signaling pathways, expression patterns, and potential roles, and mechanisms of action in pancreatic, breast, gastric and liver cancers. Furthermore, we discuss several clinically applied tumor therapies targeted at the CMTM family, indicating that CMTM family members could be novel immune checkpoints and potential targets effective in tumor treatment., Competing Interests: The authors declare that they have no competing interests., (© 2024 Duan et al.)

Abstract One obstacle in de novo protein design is the vast sequence space that needs to be searched through to obtain functional proteins. We developed a new method using structural profiles created from evolutionarily related proteins to constrain the simulation search process, with functions specified by atomic-level ligand–protein binding interactions. The approach was applied to redesigning the BIR3 domain of the X-linked inhibitor of apoptosis protein (XIAP), whose primary function is to suppress the cell death by inhibiting caspase-9 activity; however, the function of the wild-type XIAP can be eliminated by the binding of Smac peptides. Isothermal calorimetry and luminescence assay reveal that the designed XIAP domains can bind strongly with the Smac peptides but do not significantly inhibit the caspase-9 proteolytic activity in vitro compared with the wild-type XIAP protein. Detailed mutation assay experiments suggest that the binding specificity in the designs is essentially determined by the interplay of structural profile and physical interactions, which demonstrates the potential to modify apoptosis pathways through computational design. Graphical abstract Unlabelled Image Highlights • Potential to modify apoptosis pathways through computational protein design • New protein design algorithm built on evolutionary profiles • Design functional XIAP BIR3 domain using evolutionary profiles • Design binding specificity by combining profile and physical interactions • Testify protein design by hybrid structure prediction and biochemistry experiments [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to investigate whether bone marrow stem cells (MSCs) derived exosomes in rats could promote osteoblast proliferation and improve osteoporosis via inhibiting cell apoptosis. MATERIALS AND METHODS: MSCs in rats were isolated and cultured, followed by the identification of surface antigens via flow cytometry. The differentiation of MSCs was detected by alizarin red staining and oil red staining. After extraction from MSCs by ultracentrifugation, the size distribution of exosomes was detected by tunable resistive pulse sensing (TRPS). Specific antigens in MSCs-derived exosomes were determined by flow cytometry. Furthermore, the proliferation and viability of hFOB1.19 cells treated with MSCs-derived exosomes were detected by cell count kit-8 (CCK-8) assay. The effect of MSCs-derived exosomes on cell apoptosis was evaluated by flow cytometry. Protein expression levels of apoptosis-related genes in hFOB1.19 cells were detected by Western blot. RESULTS: MSCs differentiated into osteoblasts and lipoblasts under different treatments. Meanwhile, MSCs-derived exosomes exhibited typical elongated morphology after isolation and culture for 1 and 3 days, respectively. Functionally, MSCs-derived exosomes could promote the viability of hFOB1.19 cells, and significantly increase the expression level of GLUT3. In addition, MSCs-derived exosomes remarkably downregulated apoptosis-related genes and decreased apoptosis in hFOB1.19 cells. CONCLUSIONS: MSCs-derived exosomes could promote osteoblast proliferation via inhibiting cell apoptosis, eventually improving osteoporosis. [ABSTRACT FROM AUTHOR]

Abstract Mitochondria are ideal anti-tumor target due to mitochondria's central regulation role in cell apoptosis and tumor resistance to apoptosis. There are several challenges for mitochondrial targeting drug delivery, including complex multistep preparations, low drug- loading and systemic toxicity from the carriers. To address these issues, we firstly constructed mitochondria-targeting nanodrugs self-assembled from 9-O-octadecyl substituted berberine derivative (BD) using simple nano-precipitation approach. BD-based nanodrugs were modified by DSPE-PEG2000 (distearylphosphatidylethanolamine- methoxypolyethylene glycol 2000) to increase stability. Negatively charged hyaluronic acid (HA) was further coated to conceal positive charges and achieve tumor targeting. PEG and HA dually modified BD NDs (HA/PEG/BD NDs) were prepared with surface charge of −25.8 mV and high drug loading >70%. The degradation of HA by hyaluronidase (HAase) at tumor tissue allowed the exposure of the positively charged PEG/BD NDs to the cells, which is beneficial for cell uptake and further lysosome escape and mitochondrial targeting. Then, HA/PEG/BD NDs were investigated to induce apoptosis through dissipating mitochondria membrane potential, releasing cytochrome C, increasing the activities of caspase 9/3, activating the pro-apoptotic Bax, suppressing the anti-apoptotic Bcl-2 and upregulating ROS levels. In the A549 xenografted tumor model, HA/PEG/BD NDs exhibited obvious tumor cell mitochondrial targeting and significant anti-tumor efficacy. Overall, comparing to conventional nanoparticles, mitochondrial targeting HA/PEG/BD NDs provide a new strategy for cancer treatment with enhanced drug-loading, relatively simplified preparation processes and reduced carrier toxicities. Graphical abstract Unlabelled Image Highlights • 9-O-octadecyl berberine in nanodrugs was used as both drug and mitochondrial targeting ligand. • Nanodrugs characterized high drug loading (>70%) and mitochondira targeting via mitochondria apoptosis pathway. • Nanodrugs demonstrated significant anti-tumor efficacy in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a highly malignant and rapidly advancing astrocytic brain tumor in adults. Current therapy possibilities are chemotherapy, surgical resection, and radiation. The complexity of drug release through the blood-brain barrier, tumor reaction to chemotherapy, and the inherent resistance of tumor cells present challenges. New therapies are needed for individual use or combination with conventional methods for more effective treatment and improved survival for patients. GBM is difficult to treat because it grows quickly, spreads finger-shaped tentacles, and creates an irregular margin of normal tissue surrounding the tumor. Non-thermal biocompatible plasma (NBP) has recently been shown to selectively target cancer cells with minimal effects on regular cells, acting by generating reactive oxygen species (ROS) and reactive nitrogen species (RNS). We applied a soft jet plasma device with a syringe shape to U87 MG cells and astrocytes. Our results show that NBP-J significantly inhibits cell proliferation and changes morphology, induces cell cycle arrest, inhibits the survival pathway, and induces apoptosis. Our results indicate that NBP-J may be an efficient and safe clinical device for brain cancer therapy.

• Bap exposure translocates McNrf2 to the nucleus thereafter activates it. • McNrf2 antagonizes Bap-induced oxidative stress through mitochondrial pathways. • McNrf2 antagonizes Bap-induced oxidative stress through apoptosis pathways. Benzopyrene (Bap) is a major constituent of petroleum pollutants commonly found in aquatic environments, and its mutagenic and carcinogenic properties have adverse effects on aquatic organisms' development, growth, and reproduction. The antioxidant defense system element, NF-E2-related factor 2 (Nrf2), has been linked to the oxidative stress response in marine invertebrates exposed to toxic substances. In a previous study, a novel Nrf2 homologue, Mc Nrf2, was identified in mussel Mytilus coruscus , a significant model marine molluscs in ecotoxicology studies. Mc Nrf2 showed the potential to trigger an antioxidant defense against oxidative stress induced by Bap. Here, we employed an Nrf2 overexpression and inhibition model using SFN and ML385 as Nrf2 inducer and inhibitor, respectively. Next, immunofluorescence technique was used to evaluate the nuclear activation of Nrf2 induced by Bap-mediated oxidative stress. Transmission electron microscopy revealed that overexpression of Nrf2 could maintain the quantity and structural integrity of mitochondria, while flow cytometry analysis showed that Nrf2 could alleviate Bap-induced cellular apoptosis. These findings suggest that Nrf2 can protect molluscs from Bap-induced oxidative stress through the mitochondria and apoptosis pathways, providing a novel perspective on Nrf2′s antioxidant function. [ABSTRACT FROM AUTHOR]

Geopropolis is produced by some stingless bee species, such as Melipona fasciculata Smith, a native species from Brazil. This study aims to investigate the antioxidant and anti-inflammatory activities and cytotoxicity effects of geopropolis hydroethanolic extracts against lung (H460 and A549) and ovarian (A2780 and ES2) cancer cell lines and non-tumor (HUVEC) cell lines using chemical identification by LC/MS/MS analysis and in silico assays to determine which compounds are associated with bioactivity. The antioxidant activity of extracts and inhibitory activity against COX enzymes were assessed by in vitro assays; cytotoxicity effect was evaluated by the MTT assay; cell cycle was assessed by flow cytometry and apoptosis by Western blotting. The geopropolis extracts showed great radical scavenging potential, preferential inhibition of COX-2, decreased cancer cell viability, non-cytotoxic effects against the non-tumoral cell line, besides modulating the cell cycle and inducing cancer cell apoptosis through the activation of caspase-3 and PARP protein cleavage. The in silico study suggests that corilagin, typhaneoside, taraxerone and marsformosanone, identified by LC/MS/MS, can be associated with anti-inflammatory activity and cytotoxic effects. Thus, the current study suggests the potential of geopropolis concerning the research field of new pharmacological alternatives regarding cancer therapy.

Six separated compounds were identified from Artemisia capillaris Thunb., and they were 7-methoxycoumarin (1), 6,7-dimethoxycoumarin (2), 7-hydroxy-6-methoxycoumarin (3), quercetin (4), chlorogenic acid (5) and caffeic acid (6). Among them, 6,7-dimethoxycoumarin, as known as scoparone, was the most effective on scavenging ABTS free radicals (IC 50 = 0.97 μΜ) and was then tested by cytotoxic activity and pro-apoptotic activity against HepG2 cells. Scoparone dose-dependently and time-dependently inhibited the cell proliferation. Furthermore, scoparone induced the expression of Bax, concurrently suppressing the expression of Bcl-2, resulting in a noteworthy elevation in the Bax/Bcl-2 ratio to up-regulate Caspase-3 activity, thus inducing cell apoptosis via the intracellular pathway. Meanwhile, scoparone promoted the expression of Fas, FasL, FADD, Caspase-8 and Caspase-3, indicating that scoparone also triggered apoptosis via the extracellular pathway. In a word, scoparone demonstrated remarkable antitumor capability to induce apoptosis of HepG2 cells through both intracellular and extracellular pathways.

Leukemia is a hematologic malignancy with poor prognosis in humans and chemotherapy is the main strategy for treating leukemia patients. Novel drugs with better selectivity and lower toxicity are required for the treatment of patients. A novel 3’,5’-diprenylated chalcone, (E)-1-(2-hydroxy-4-methoxy-3,5-diprenyl) phenyl-3-(3- pyridinyl)-propene-1-one ( C10 ) is a potential new anti-leukemia agent. In this study, we investigated the molecular mechanisms of the anti-leukemia effects of C10 on different leukemia cells in vitro . C10 showed strong inhibition of proliferation of the human erythroleukemia cell line HEL and human myeloid leukemia cell line K562, and several cell and flow cytometer assays showed that inhibition by C10 was due to the regulation of gene expression or phosphorylation in the apoptosis and autophagy pathways. The results showed that C10 regulated the expression of Bax, c-Myc, Bcl-2, P38/AMPK and ERK 1/2, activated the expression of Caspase-3, -8, and PARP at the protein level in the apoptosis pathway of the two leukemia cell types, and inhibited the expression of erythroleukemia carcinogene Fli-1 in the human erythroleukemia cell line HEL. Additionally,treatment with the compound induced a time-dependent increase in expression of LC 3A/B via inhibiting the AKT-mTOR pathway, which is associated with cell autophagy. Taken together, the above results suggest that the novel synthesized 3’,5’-diprenylated chalcone can prevent the growth of leukemia cells by inducing apoptosis and autophagy. [ABSTRACT FROM AUTHOR]

In the CNS, including the optic nerve, oligodendrocytes play a critical role in the myelination of axons. Oligodendrocytes are exceptionally sensitive to insults to the CNS, such as injury, ischemia, or inflammation, which result in the loss of oligodendrocytes and myelin and eventually secondary axon degeneration. Oligodendrocytes are sensitive to excitotoxic insults mediated by overactivation of their AMPA ionotropic glutamate receptors. Phenolic compounds, which are widely distributed in fruits and vegetables, received the great attention of scientists due to their antioxidant activities and free radical scavenging abilities. Chlorogenic acid (CGA) has been demonstrated to possess potent neuroprotective activities against oxidative stress in various cellular models and pathological conditions. Hence, CGA protect against oxidative stress and excitotoxic insults mediated by AMPA receptors and that the protective mechanisms involve free radical scavenging, Ca2+ handling in the cytosol, and modulating antioxidant enzyme system. CGA was associated with the protein kinase A (PKC) signaling pathways transduction. Caspases and calpains have been studied as apoptotic mediators and cell death in this model of AMPA toxicity. Inhibitors of caspases initiators, caspases 1, 8, and 9, the upstream of caspase 3 effectors, have totally abrogated the protective activity of CGA. Inhibitors of calpains also totally abrogated the protective activity of CGA. In addition, a potential role for the CGA in inhibiting Bax in oligodendrocyte cell model undergoing AMPA is inducing excitotoxic death. Our results indicate that CGA exhibits a protective potential via antioxidant and apoptosis caspases and calpains dependent against AMPA-mediated excitotoxicity, and these finding indicate that CGA is able to be a good candidate for preventive approach for neurodegenerative disorders associated with loss and damage in oligodendrocytes and AMPA-mediated excitotoxicity. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Se-β-Lg is a novel and effective chemopreventive compounds in HCC treatment. • Se-β-Lg induced autophagy and ROS-dependently p53-mediated apoptosis in Hep G2 cells. • Se-β-Lg induced autophagy and p53/Fas-independent caspase activation in Hep3B cells. Abstract β-lactoglobulin is important fraction in bovine milk. Selenium is an essential nutrient element. The apoptosis and autophagy induction of Se-β-Lg combined selenic acid in β-lactoglobulin on Hep G2 and Hep 3B cells were investigated in this study. MTT assay showed Se-β-Lg inhibited cells viability. Annexin V-FITC/PI and PI staining indicated Se-β-Lg triggered cells apoptosis and cell cycle arrest. Western blot of caspase-cascade suggested Hep G2 and Hep 3B cells occurred irreversible extrinsic apoptosis. TEM and protein expression of LC3 indicated Se-β-Lg induced cells autophagy. Further explore found Se-β-Lg induced up-regulation of p53 and Fas/FasL in Hep G2 cells. Simultaneously, N-acetyl-L-cysteine, pifithrin-α, Z-VAD-FMK and 3-MA were used. These results further demonstrated Se-β-Lg triggered autophagy and receptor-related apoptosis via p53-mediated Fas/FasL pathway in Hep G2 cells and induced autophagy and p53/Fas-independent caspase activation in Hep 3B cells. Our research revealed that Se-β-Lg had potential to act as chemopreventive compounds in HCC therapy. [ABSTRACT FROM AUTHOR]

Activating transcription factor 6 (ATF6), one of three sensor proteins in the endoplasmic reticulum (ER), is an important regulatory factor in the ER stress‑induced apoptosis pathway. Although recent studies have made some progress in elucidating the regulation mechanism of ATF6, the specific regulatory mechanism of ER stress‑induced vascular endothelial cell (VEC) apoptosis is still unclear. The present study was designed to investigate the role of ATF6 in VECs under thapsigargin (TG)‑induced ER stress. ATF6 (1‑366aa; ATF6 high‑expressed plasmid) and ATF6 (151‑366aa; plasmid without transcriptional activity) were transfected into VECs to yield an ATF6 high‑expression model and a positive control model, respectively. High expression of ATF6 decreased viability and aggravated ER stress‑induced apoptosis in VECs. Increased expression of apoptosis‑related genes, including those encoding caspase‑3, caspase‑9, C/EBP homologous protein (CHOP), cytochrome c and B‑cell lymphoma‑associated protein X (Bax)/B‑cell lymphoma (Bcl‑)2, was detected by polymerase chain reaction and western blotting in the ATF6 (1‑366aa) + TG group. No significant effect of TG treatment and high ATF6 expression was indicated on the expression of death receptor‑related genes, including those encoding caspase‑8 and Fas. The results demonstrated that high expression of activated ATF6 aggravates ER stress‑induced VEC apoptosis through the mitochondrial apoptotic pathway. Furthermore, in response to ER stress, ATF6 upregulates the expression of caspase‑3, caspase‑9, CHOP, cytochrome c and Bax/Bcl‑2. [ABSTRACT FROM AUTHOR]

A new series of ligustrazine-cinnamon acid derivatives had been designed and synthesized as potential neuro-protective agents. Among the derivatives, 3a exhibited the promising neuroprotective activity (EC 50  = 3.68 μM). Moreover, with the deep research of the drug pathway, it (the further mechanism researches) suggested compound 3a could inhibit the apoptosis of injured PC12 cells via blocking the mitochondria apoptosis pathway including up-regulation the ratio of Bcl-2/Bax, down-regulation the expression of cytochrome- c (Cyt- c ) and inhibition of the activity of caspase-9 and -3. In addition, the structure-activity relationships (SARs) of novel compounds were also discussed. [ABSTRACT FROM AUTHOR]

Background: Cell fate regulation directly affects tissue homeostasis and human health. Research on cell fate decision sheds light on key regulators, facilitates understanding the mechanisms, and suggests novel strategies to treat human diseases that are related to abnormal cell development. Results: In this study, we proposed a polynomial based model to predict cell fate. This model was derived from Taylor series. As a case study, gene expression data of pancreatic cells were adopted to test and verify the model. As numerous features (genes) are available, we employed two kinds of feature selection methods, i.e. correlation based and apoptosis pathway based. Then polynomials of different degrees were used to refine the cell fate prediction function. 10-fold cross-validation was carried out to evaluate the performance of our model. In addition, we analyzed the stability of the resultant cell fate prediction model by evaluating the ranges of the parameters, as well as assessing the variances of the predicted values at randomly selected points. Results show that, within both the two considered gene selection methods, the prediction accuracies of polynomials of different degrees show little differences. Interestingly, the linear polynomial (degree 1 polynomial) is more stable than others. When comparing the linear polynomials based on the two gene selection methods, it shows that although the accuracy of the linear polynomial that uses correlation analysis outcomes is a little higher (achieves 86.62%), the one within genes of the apoptosis pathway is much more stable. Conclusions: Considering both the prediction accuracy and the stability of polynomial models of different degrees, the linear model is a preferred choice for cell fate prediction with gene expression data of pancreatic cells. The presented cell fate prediction model can be extended to other cells, which may be important for basic research as well as clinical study of cell development related diseases. [ABSTRACT FROM AUTHOR]

The chemical composition, antibacterial activity and mechanism of essential oil from Cyperus rotundus rhizomes against Staphylococcus aureus were investigated in this study. Results showed that α-cyperone, cyperene and α-selinene were the major components of the essential oil. The essential oil exhibited strong antibacterial activity against S. aureus with the minimum inhibitory concentration (MIC) and minimum bactericide concentration (MBC) were 10 and 20 mg/mL respectively, and the antibacterial effects increased with increasing essential oil concentrations and treatment time. The electric conductivity, cell membrane integrity, NPN uptake, and membrane potential assays demonstrated that essential oil disrupted the membrane integrity of S. aureus . Electron microscope observations further confirmed that essential oil destroyed cell membrane. Moreover, we found that essential oil could induce cells death of S. aureus through apoptosis pathway based on apoptosis analysis. These findings suggested that essential oil mainly exerted antibacterial activity by damaging cell membrane and membrane-mediated apoptosis pathway. [ABSTRACT FROM AUTHOR]

Objective: In this study, a series of experiments were conducted to research the mechanism of anticancer and preliminary molecular effects of PAMs on the HEPG-2 cancer cells. Methods: Morphological observation and MTT assay were used to explore the inhibition and killing effect of PAMs acting on HEPG-2. AO/EB staining and Annexin V-FITC/PI staining were employed to observe the apoptosis of HEPG-2 treated with PAMs. The expression level o^ bcl-2 and others genes in HEPG-2 cells were detected by using qRT-PCR and western blot. Wound healing and transwell experiments determined ifPAMs can inhibit the migration of HEPG-2. Results: PAMs can inhibit and kill HEPG-2 cells in time and dose-dependent manners, and the cytotoxic effects were closely related to the cell apoptosis. The mRNA expression of foxml,bcl-2 and surviving gene were remarkably decreased in HEPG-2 cells after the treatment of PAMs. PAMs decreased the FoXM1 protein expression in HEPG-2 cells, while up-regulating the protein expression. ，and it could also inhibit the migration of cancer cells. Conclusions: The possible molecular mechanism for the killing of HEPG-2 cancer cells by PAMs was proposed. By down-regulating the expression of/oxml and up-regulating the expression of p53, the transcriptional expression of their downstream target genes survivin and bcl-2 was inhibited or reduced, hence enhancing the cancer cell apoptosis. This study provides an important foundation for the development of anti-cancer Chinese folk medicine based on PAMs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The incidence of gastric cancer is very high all over the world, but the mechanism of the occurrence and development of gastric cancer is unclear. Secretory leukocyte protease inhibitor (SLPI) is overexpressed in gastric, lung and ovarian cancers, which accelerates the metastasis of cancer cells. In this research, we mainly explored the expression level and possible mechanism of SLPI in gastric cancer. PATIENTS AND METHODS: The expression and clinical significance of SLPI in 68 cases of gastric cancer tissues and adjacent tissues were detected by qRT-PCR. Cell Counting Kit-8 (CCK8) assay was used to detect the proliferation ability of gastric cancer cell lines. In addition, we used Western blot to clarify the relationship between SLPI and metastasis. RESULTS: Compared with the adjacent tissues, we found that SLPI was highly expressed in gastric cancer tissues. We also found that the expression of SLPI was in significant correlation with the survival time, clinical classification and size of the tumor. What's more, SLPI could promote the proliferation and metastasis of gastric cancer by regulating P53, Bcl-2 and Caspase-8 expression through apoptosis signaling pathway. CONCLUSIONS: We concluded that SLPI was closely related with to invasion and metastasis of gastric cancer. Perhaps we can hopefully find new targets for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Nervous necrosis virus (NNV), the causative agent of viral nervous necrosis (VNN) disease, has caused mass mortality of cultured marine and freshwater fish worldwide, resulting in enormous economic losses in the aquaculture industry. However, the molecular mechanisms underlying the pathogenicity of NNV are still poorly understood. In this study, the transcriptomic profiles of striped snakehead fish ( Channa striatus ) cells (SSN-1) infected with red-spotted grouper NNV (RGNNV) were investigated using deep RNA sequencing technique. From 254,955,234 raw reads, a total of 253,338,544 clean reads were obtained and they were assembled into 93,372 unigenes. Differentially expressed genes (DEGs) were identified from RGNNV-infected or mock-infected SSN-1 cells, including 1184 up-regulated and 1456 down-regulated genes at 3 h (h) post of infection (poi), and 1138 up-regulated and 2073 down-regulated genes at 24 h poi, respectively. These DEGs were involved in many pathways related to viral pathogenesis, including retinoic acid-inducible gene I (RIG-I) like receptors pathway, apoptosis pathway, oxidative phosphorylation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Subsequent analysis focusing on the apoptosis pathway showed that the expression of Endonuclease G (EndoG) was up-regulated upon RGNNV infection at both 3 and 24 h poi. Therefore, EndoG gene was cloned and its function was further characterized. The results showed that over-expression of EndoG could also induce cellular apoptosis in SSN-1 cells, indicating that RGNNV infection might induce apoptosis of SSN-1 cells via EndoG-associated mitochondrial pathway. These results will shed a new light on the pathogenesis of NNV. [ABSTRACT FROM AUTHOR]

In order to discover more effective and less toxic drugs in the field of anti-tumor, the backbone structure of 17 β -estradiol was modified, and 11 target compounds were synthesized. Compounds 5 and 10 , which exhibited better anti-tumor activity and higher selectivity (more than 10-fold), were chosen for further biological investigation. Flow cytometry results indicated that 5 and 10 could arrest MCF-7 cells in the G2 phase and induce apoptosis. Immunohistochemical analysis revealed that 5 and 10 could bind to the estradiol receptor alpha in MCF-7 cells. Western blotting and real-time PCR assays were performed to detect the effects of compounds on apoptosis-related targets at the protein and gene levels. These results showed that both 5 and 10 could dosed-dependently increase the expression of Apaf-1, Bax, caspase-3,8,9 and reduce the expression levels of the anti-apoptotic factors Bcl-2 and Bcl-xL. Besides, the Human apoptosis array assay demonstrated the expression level of death receptor Trail R2/DR5 was upregulated obviously while the expression of TNF R1, IAPs and Hsp27/60/70 were downregulated. On the whole, 5 induced MCF-7 cell death through the endogenous pathway in mitochondria and the exogenous pathway with death receptor Trail R2/DR5. • Eleven 17 β -estradiol derivatives from modification were synthesized. • 5 and 10 possessed much better antiproliferative activities and higher selectivity than 17 β -estradiol. • 5 and 10 could arrest cell cycle at the G2 phase in MCF-7 cells and partly bind with the estradiol receptor alpha. • 5 induced MCF-7 cells death through both endogenous and exogenous pathways. [ABSTRACT FROM AUTHOR]