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Mass production of vermicompost using suitable species of earthworms and selecting target organic waste materials has appeared to be a great development in the realm of biotechnological research for the sustainable eco-management. Although, for the bioconversion of organic wastes to vermicompost, suitable earthworm species play major roles, a hoard of bacterial assemblages by virtue of production of different enzymes facilitate the process of vermicomposting. The present study has documented the roles of vermicompost associated bacteria in combating, preventing, and controlling of cancer so as to open a new vista not only in the field of vermitechnology but also on biomedical research. Earthworms’ associated bacterial metabolic products having their unique physicochemical excellence have gained importance due to their roles as a facilitator of apoptosis (programed cell death in a MCF-7 cell line). The antioxidant and anticancer activities of ethyl acetate extracts’ of vermicompost associated bacterium Bacillus anthracis were undertaken by antioxidant assay which revealed maximum DPPH radical scavenging effect (75.79 ± 5.41%) of the extracts’ at 9 00 μg ml-1. Furthermore, the crude extracts obtained from the same bacteria were found to decrease the activity of SOD (superoxide dismutase) with the increase in doses. MTT assay showed potent cytotoxic activity against human breast adenocarcinoma cells (MCF-7) with the IC50 value of 46.64 ± 0.79 μg ml-1. It was further confirmed through Hoechst 33258 staining of nuclear fragmentation assay and DNA fragmentation analysis. Western blotting test has confirmed a downregulation of Akt upon application of crude extracts. Increase of SOD activity along with decrease of Akt level reflects that the mode of action is entirely PI-3K dependent. This study tends to indicate that B. anthracis isolated from vermicompost could be potentially explored for the development of new therapeutic agents, especially against cancer. [ABSTRACT FROM AUTHOR]

In recent years, people's living standards are getting higher and higher, and life pressure is also increasing, and there are also many problems in eating habits. This is also the direct cause of colon cancer. The aim of this paper was to investigate whether anesthetic drugs could positively affect the proliferation and apoptosis of colon cancer cells. In this paper, the significance of anesthetic drugs is proposed, and an artificial neural network algorithm based on artificial intelligence is proposed. It is well known that artificial neural networks play an important role in medicine. The experimental results of this paper show that the incidence of colon cancer in 2020 will be in the range of 5%-35%, and the incidence of colon cancer in 2021 will be in the range of 7%-30%. While colon cancer rates in 2021 do not appear to be as high as colon cancer rates in 2020, they are generally much higher than colon cancer rates in 2020. It can be seen that as the population ages, the number of colon cancer patients is increasing due to the lack of emphasis on health. This also means that the incidence of colon cancer is getting higher and higher, and traditional drug chemotherapy has been unable to play a good role in inhibiting the proliferation of colon cancer cells. Therefore, this paper investigated the effects of anesthetic drugs on the proliferation and apoptosis of human colon cancer cells. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which causes membrane injury. Under the catalysis of iron ions, cells deficient in glutathione peroxidase (GPX4) cannot preserve the balance in lipid oxidative metabolism, and the buildup of reactive oxygen species on the membrane lipids leads to cell death. An increasing body of evidence suggests that ferroptosis plays a significant role in the development and occurrence of cardiovascular diseases. In this paper, we mainly elaborated on the molecular mechanisms regulating ferroptosis and its impact on cardiovascular disease to lay the groundwork for future studies on the prophylaxis and treatment of this patient population. [ABSTRACT FROM AUTHOR]

Breast cancer is a highly harmful malignant tumor, which poses a great threat to women's body and mind, and the mortality rate ranks second among all women's diseases. The incidence rate accounts for 7-10% of various malignant tumors in the whole body, second only to uterine cancer in women, and has become the main cause of threatening women's health. Advanced breast cancer is often considered an incurable disease. The family of heterogeneous nuclear ribonucleoprotein complexes is composed of about 20 hnRNP proteins with molecular weights ranging from 32 to 120 kDa, and they are named according to their molecular weights. Among them, hnRNPA2 and hnRNPB1 are the two most important members of the hnRNP family, both derived from the same gene on chromosome 7p15. Therefore, research to understand the molecular mechanism and process of breast cancer progression has an important role in promoting the current medical research on breast cancer treatment methods. Therefore, studying the mechanism of tumorigenesis is the key to tumor prevention and treatment. Therefore, this paper proposes that A2/B1 promotes the stability of NRF2 mRNA and inhibits ferroptosis and cell proliferation in breast cancer cells. The article mainly introduces the disease diagnosis method based on artificial neural network and its neural network algorithm. In the experimental part, the activity of hnRNP A2/B1 on cancer cells is deeply studied. The results show that the absorbance of the MTT method increases continuously with the extension of the culture time, and the maximum reaches 1.2. This fully shows that its absorption capacity is very strong, especially after 24 hours, the absorption rate rises from 0.6 to 0.9, which shows that 24 hours is the best absorption time. And it can also be found that hnRNPA2/B1 has a significant inhibitory effect on breast cancer cells; it can reduce the effect on breast cancer cell cycle and apoptosis. [ABSTRACT FROM AUTHOR]

The majority of Parkinson's disease (PD) is sporadic in elderly and is characterized by α-synuclein (αS) aggregation and other alterations involving mitochondria, ubiquitin-proteasome, and autophagy. The remaining are familial PD associated with gene mutations of either autosomal dominant or recessive inheritances. However, the former ones are similar to sporadic PD, and the latter ones are accompanied by impaired mitophagy during the reproductive stage. Since no radical therapies are available for PD, the objective of this paper is to discuss a mechanistic role for amyloidogenic evolvability, a putative physiological function of αS, among PD subtypes, and the potential relevance to therapy. Presumably, αS evolvability might benefit familial PD due to autosomal dominant genes and also sporadic PD during reproduction, which may manifest as neurodegenerative diseases through antagonistic pleiotropy mechanism in aging. Indeed, there are some reports describing that αS prevents apoptosis and mitochondrial alteration under the oxidative stress conditions, notwithstanding myriads of papers on the neuropathology of αS. Importantly, β-synuclein (βS), the nonamyloidogenic homologue of αS, might buffer against evolvability of αS protofibrils associated with neurotoxicity. Finally, it is intriguing to predict that increased αS evolvability through suppression of βS expression might protect against autosomal recessive PD. Collectively, further studies are warranted to better understand αS evolvability in PD pathogenesis, leading to rational therapy development. [ABSTRACT FROM AUTHOR]

Vision loss is primarily caused by age-related macular degeneration (AMD) due to oxidative retinal pigment epithelial (RPE) cell injury. Carotenoid utilization is deemed a possible strategy for treating AMD. Cordyceps militaris has advantages like immunomodulatory, anti-inflammatory, and antioxidative characteristics. This paper assessed the possible protective influence of carotenoids obtained by isolating and purifying the Cordyceps militaris (CMCT) into human RPE cells (ARPE-19) damaged by hydrogen peroxide (H2O2). The findings demonstrated that CMCT safeguarded the ARPE-19 cells against the damage and apoptosis caused by H2O2 and oxidative stress via Bcl-2 protein upregulation, as well as the expression of Bax and cleaved caspase-3 protein. In addition, CMCT treatment increased cell survival and restricted the generation of H2O2-induced reactive oxygen species (ROS) and the protein expression of NADPH oxidase-1 (NOX1). Additionally, the CMCT treatment of H2O2-induced ARPE-19 cells ameliorated high malondialdehyde (MDA) levels in oxidative stress-induced cells. The catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH) returned to standard levels, which were governed by the higher expression of nuclear Nrf2 protein in the ARPE-19 cells. Moreover, this study showed that CMCT safeguarded the ARPE-19 cells against the damage caused by oxidative stress via its antioxidant activity and antiapoptotic functionality, suggesting the potential therapeutic role of CMCT in AMD prevention and mitigation. [ABSTRACT FROM AUTHOR]

Objectıve. Ankaferd hemostat (ABS; Ankaferd Blood Stopper®) contains standardized plant extracts comprising Alpinia officinarum, Glycyrrhiza glabra, Thymus vulgaris, Urtica dioica, and Vitis vinifera. ABS especially was recognized for its hemostatic effect; however, antineoplastic role of ABS was identified during the last decade. The aim of this paper is to review the molecular basis and associated clinical implications of the ABS as a topical antineoplastic agent. Materials and Methods. Up to June 2022, literature searches were performed using the internet search engines Medline, Google Scholar, and Embase: Ankaferd. PRISMA flow diagram described the Ankaferd search. Results. ABS have important effects in several cellular processes, like control of the cell cycle, apoptosis, angiogenesis, signal transduction, inflammation, immunologic, and metabolic mechanisms. The molecular basis of antineoplastic roles of ABS depends on its proteomics, metabolomics, and transcriptomics features. ABS has antineoplastic effects on solid tumors like colon, bladder, breast, and osteosarcoma cancer cells. Also, ABS effects renal tubular apoptosis and has antitumoral roles on malign melanoma cells. ABS inhibits hematological tumors like myeloma and lymphoid cells. ABS induces apoptosis in retinal cells and has inhibitory effects on mesenchymal stem cells. It has an antiproliferative role on gastrointestinal tumors like hepatocellular carcinoma cells. Moreover, ABS has a treatment supportive role in cancer since it can prevent oxidative DNA damage and decrease the intestinal damage in necrotizing enterocolitis. Furthermore, it has chemopreventive and hepatoprotective features and can be used for prophylaxis and treatment of oral mucositis. Conclusion. ABS alters cell metabolism and cell cycle. ABS has antineoplastic role on cancer cells. The expanding context of ABS compromises anti-infective, antineoplastic, and wound healing features. ABS may also be used for the palliative, adjuvant, neoadjuvant, or supportive use by interventional radiology procedures for the treatment of solid tumors. Future controlled studies are necessary to clarify the pleiotropic role of ABS like antineoplastic, antithrombotic, anti-inflammatory, anti-infective, antifungal, and antioxidative effects. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a hepatobiliary carcinoma characterized by the differentiation of bile duct cells, and the patients with CCA often have a poor prognosis. Eukaryotic translation initiation factor 5A (eIF5A) is reported to have multiple biological activities. Targeted activation of ferroptosis may be a therapeutic strategy for cancer. Nevertheless, the effects of eIF5A and ferroptosis on CCA are still elucidated. Our study explored the effects of eIF5A in CCA, and the mechanisms also are studied. In this paper, TCGA database analysis suggested that eIF5A was upregulated in CCA, and high expression of eIF5A might predict a poor prognosis. Moreover, FANCD2, SLC7A11, and HSPB1 were significantly overexpressed in CCA. The results indicated that eIF5A was overexpressed in CCA tissues and cells. Further experiments demonstrated that eIF5A silencing decreased CCA cell activity and enhanced ferroptosis and mitochondrial apoptosis. In addition, upregulation of eIF5A showed the opposite effect on CCA cells compared with downregulation of eIF5A. Finally, the silencing of eIF5A could restrain the growth of xenografted tumors and promote ferroptosis. Overall, eIF5A enlarged CCA cell activity and attenuated ferroptosis and mitochondrial apoptosis. The results suggested that assessment of eIF5A might provide help for the diagnosis and treatment of CCA. [ABSTRACT FROM AUTHOR]

A large number of facts have shown that epigenetic modification and metabolic reprogramming represented by noncoding RNA play an important role in the invasion and metastasis of breast cancer, but the mechanism is not clear. The purpose of our study is to find a new biomarker of breast cancer and to provide a new perspective for regulating glucose metabolism and aerobic glycolysis of BC. In this paper, by downregulating C-myc protein, our team found that the expression of long-chain noncoding RNATSPAR-AS2 was significantly downregulated. However, the expression of long-chain noncoding RNASPAR-AS2 in BC is relatively high, and the prognosis is poor. TSPEAR-AS2 can promote the malignant phenotype of BC cells, including proliferation, apoptosis, invasion and metastasis, and glycolysis. At the same time, TSPEAR-AS2 can also upregulate the expression of GLUT1, an important regulator of glycolysis, thus promoting the metabolic reprogramming of BC. Molecular mechanism experiments show that TSPEAR-AS2 may promote the expression of GLUT1 by participating in IGF2BP2 modified by the GLUT1 gene. Our results suggest that the C-myc/TSPEAR-AS2/GLUT1 axis promotes the invasion and metastasis of BC by inducing glucose metabolism reprogramming. However, more phenotypic and molecular mechanism results need to be further verified. [ABSTRACT FROM AUTHOR]

Background. Pyroptosis is a form of programmed cell death, playing a significant role in cancer. Glioblastoma multiforme (GBM) is the most common malignant brain tumor. The poor prognosis in GBM due to temozolomide (TMZ) resistance has been widely discussed. Such being the case, the correlation between TMZ resistance and pyroptosis is seldom investigated. On this basis, this paper aims to explore the potential prognostic value of genes related to TMZ resistance and pyroptosis as well as their relationship to the immune microenvironment in GBM. Methods. A total of 103 patients from TCGA were assigned to a training cohort; 190 from CGGA were assigned to a validation cohort. The prognostic risk model reflecting pyroptosis and TMZ resistance was built from the training cohort using multivariate Cox regression and performed validation. RT-qPCR was used to examine the expression of 4 genes from the risk signature. FOXP3 was selected for overexpression and verified using the western blot. The TMZ IC50 of FOXP3-overexpressed cell lines was determined by CCK8. Results. A four genes-based risk signature was established and validated, separating GBM patients into high- and low-risk groups. Compared with the low-risk group, the high-risk group presented worse clinical survival outcomes. Its differential expressed genes were enriched in immune-related pathways and closely related to the immune microenvironment. Moreover, RT-qPCR results suggested that FOXP3, IRF3, and CD274 were significantly upregulated in TMZ-resistant strains, while TP63 was downregulated. FOXP3-overexpressed GBM cell lines had higher TMZ IC50, implying an increased resistance of TMZ. Conclusion. A novel gene signature relevant to pyroptosis and TMZ resistance was constructed and could be used for the prognosis of GBM. The four genes from the risk model might play a potential role in antitumor immunity and serve as therapeutic targets for GBM. [ABSTRACT FROM AUTHOR]

Background. Osteoarthritis (OA) is a clinical joint degenerative disease, the pathogenic factors of which include age, obesity, and mechanical injury. Its main pathological features include cartilage loss, narrowing of joint space, and osteophyte formation. At present, there are a variety of treatment methods for OA. Natural products, which are gradually being applied in the treatment of OA, are advantageous as they present with low toxicity and low costs and act on multiple targets. Methods. The terms "natural products," "osteoarthritis," and "chondrocytes" were searched in PubMed to screen the related literature in the recent 10 years. Results. We comprehensively introduced 62 published papers on 48 natural products involving 6, 3, 5, 12, 4, and 5 kinds of terpenoids, polysaccharides, polyphenols, flavonoids, alkaloids, and saponins, respectively (and others). Conclusion. The mechanisms of their anti-OA action mainly involve reducing the production of inflammatory factors, reducing oxidative stress, regulating the metabolism of chondrocytes, promoting the proliferation of chondrocytes, or inhibiting chondrocyte apoptosis. This article summarizes the anti-OA activity of natural products in the last 10 years and provides candidate monomers for further study for use in OA treatment. [ABSTRACT FROM AUTHOR]

Isodon lophanthoides var. gerardianus (Benth.) H. Hara, a native medicinal plant produced chiefly across Southern China, is one of the mainstream varieties of Xihuangcao, which has long been applied in preventing and treating some common liver or gall diseases. Water-soluble total flavonoids (WSTF) extracted from folk herbal medicine have many pharmacological effects. The objective of the paper is to investigate the synergy of WSTF with 5-fluorouracil (5-FU) on HCC and the related mechanisms. Cells were exposed to WSTF alone or combination treatment with 5-FU. Then, in this study, we conducted cell viability test, cell cycle and clone forming test, apoptosis assay, reactive oxygen species (ROS), Western blotting, immunohistochemistry, and a xenograft tumor growth model for investigating the role of WSTF in HCC in vivo and in vitro. It was discovered that WSTF caused cell cycle arrest at the G0/G1 phase while increasing the ROS contents. The generation of ROS levels could cause cell apoptosis and inhibit colony formation. WSTF decreased the Bcl-2 level but promoted the Bax level. These showed the mitochondrial dependence of WSTF-mediated apoptosis. WSTF combined with 5-FU have a synergistic effect to significantly inhibit carcinogenicity in vivo and in vitro. The reduced ROS changed the synergy of WSTF with 5-FU. At last, WSTF inhibit the growth of HCC and promote the HCC sensitivity to 5-FU through ROS accumulation. WSTF-increased ROS levels may partially or completely contribute to enhanced toxicity. WSTF combined with 5-FU in HCC can play a synergistic effect when applied in the clinical setting. [ABSTRACT FROM AUTHOR]

Transplantation of bone marrow mesenchymal stem cells has attracted more and more attention as a regenerative therapy for the treatment of liver diseases. A large number of studies have shown that this kind of cells can inhibit the activation of hepatic stellate cells and regulate tissue homeostasis and immune system via a variety of ways. Meanwhile, bone marrow mesenchymal stem cells can inhibit apoptosis of hepatocyte, improve liver function, and reduce inflammation through multiple pathways. These cells have a broad prospect in the treatment of liver cirrhosis. At present, there are many studies on the specific mechanism of bone marrow mesenchymal stem cells transplantation in the treatment of liver cirrhosis. This paper reviews the pathogenesis of liver cirrhosis and the mechanism of bone marrow mesenchymal stem cells transplantation in the treatment of liver cirrhosis, discusses the effectiveness of traditional Chinese medicine method in enhancing the efficacy of bone marrow mesenchymal stem cells transplantation, and looks forward to its application prospect in the future. [ABSTRACT FROM AUTHOR]

To investigate trends in long-noncoding (lnc) RNA research systematically, we compared the contribution of publications among different regions, institutions, and authors. Publications on lncRNA were retrieved from Web of Science (WoS) from 1975 to 2017. A total of 3879 papers were identified, and together they were cited 62967 times. The literature on lncRNA had been continuously growing since 2006, and the expansion might continue at a rapid pace until around 2021. China contributed the greatest proportion (63.47%) of lncRNA publications, and the USA ranked second in the number of publications (944 articles), while it had the highest citation frequency (43168 times) and H-index (97). The journal Oncotarget has the greatest number of publications on lncRNA research, with 305 papers. The keywords could be stratified into two clusters: cluster 1 (application) and cluster 2 (characteristics). Correspondingly, the “TNM stage,” “epithelial mesenchymal transition (EMT),” “cell apoptosis,” and “overall survival” are research hotspots since 2015. Thus, research on lncRNA showed a swiftly expanding trend, with China making the largest contribution. The focus on lncRNA is gradually shifting from “characteristics” to “application.” [ABSTRACT FROM AUTHOR]

The traditional Mongolian medicine (TMM) RuXian-I is an empirical formula specifically used for treating the hyperplasia of mammary gland (HMG) in clinic based on the principles of traditional Mongolian medicine, but the treatment mechanism is not completely clear. In this paper, we elaborated the mechanism of RuXian-I in the treatment of HMG induced by estrogen and progestogen from its toxicity and activity. Firstly, RuXian-I exhibited no toxic effect on HMG rats through no changes of body weight and food intake measurement and no pathologic changes of the organs (heart, liver, spleen, lung, and kidney) detected. Secondly, RuXian-I could decrease the increased nipple height and diameter and remarkably relieve the pathologic changes of HMG rats and also alleviate serum sex hormone levels (estradiol (E2), luteinizing hormone (LH), progesterone (P), and testosterone (T)) of HMG rats. Finally, RuXian-I could obviously inhibit the upregulation level of antiapoptotic protein CRYAB of HMG rats and promote mammary gland cell apoptosis of HMG rats via increases of promoting apoptosis protein caspases-3, 8, and 9 and Bax and tumor suppressor protein p53, decreases of antiapoptosis protein Bcl-2, and release of cytochrome c. These results suggested that RuXian-I has protective and therapeutic effects on HMG rats induced by estrogen and progestogen possibly via promoting apoptotic pathway regulated by CRYAB and is a promising agent for treating HMG. [ABSTRACT FROM AUTHOR]

Gastric precancerous lesions (GPLs) are an essential precursor in the occurrence and development of gastric cancer, known to be one of the most common and lethal cancers worldwide. Traditional Chinese medicine (TCM) has a positive prospect for the prevention and therapy of GPL owing to several advantages including a definite curative effect, fewer side effects compared to other treatments, multiple components, and holistic regulation. Despite these characteristic advantages, the mechanisms of TCM in treating GPL have not been fully elucidated. In this review, we summarize the current knowledge with respect to herbal formulations and the therapeutic mechanisms of TCM active ingredients for GPL. This paper elaborates on the mechanisms of TCM underlying the prevention and treatment of GPL, specifically those that are linked to anti-H. pylori, anti-inflammation, antiproliferation, proapoptotic, antioxidation, antiglycolytic, and antiangiogenesis effects. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the quality of surface contouring of chondromalacic cartilage by bipolar radio frequency energy using different treatment patterns in an animal model, as well as examining the impact of the treatment onto chondrocyte viability by two different methods. Our experiments were conducted on 36 fresh osteochondral sections from the tibia plateau of slaughtered 6-month-old pigs, where the thickness of the cartilage is similar to that of human wrist cartilage. An area of 1 cm2 was first treated with emery paper to simulate the chondromalacic cartilage. Then, the treatment with RFE followed in 6 different patterns. The osteochondral sections were assessed for cellular viability (live/dead assay, caspase (cell apoptosis marker) staining, and quantitative analysed images obtained by fluorescent microscopy). For a quantitative characterization of none or treated cartilage surfaces, various roughness parameters were measured using confocal laser scanning microscopy (Olympus LEXT OLS 4000 3D). To describe the roughness, the Root-Mean-Square parameter (Sq) was calculated. A smoothing effect of the cartilage surface was detectable upon each pattern of RFE treatment. The Sq for native cartilage was Sq = 3.8 ± 1.1 μ m. The best smoothing pattern was seen for two RFE passes and a 2-second pulsed mode (B2p2) with an Sq = 27.3 ± 4.9 μ m. However, with increased smoothing, an augmentation in chondrocyte death up to 95% was detected. Using bipolar RFE treatment in arthroscopy for small joints like the wrist or MCP joints should be used with caution. In the case of chondroplasty, there is a high chance to destroy the joint cartilage. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) with large aspect ratios and excellent electrical properties can enhance the killing effect of nanosecond pulsed electric fields (nsPEFs) on tumor cells, which can improve the electrical safety of nsPEF during tumor treatment. To study the mechanism of the CNT-enhanced killing effect of a nsPEF on tumor cells, a spherical, single-cell, five-layer dielectric model containing randomly distributed CNTs was established using COMSOL and MATLAB, and then, the effects of the addition of CNTs on the electric field and the electroporation effect on the inner and outer membranes were analyzed. The results showed that CNTs can enhance the local electric field strength due to a lightning rod effect, and the closer the CNT tip was to the cell, the greater the electric field strength was around the cell. This increase in the local electric field strength near the cells enhanced the electroporation effects, including pore density, pore area, and pore flux. The simulation results presented in this paper provide theoretical guidance for subsequent development of nsPEF combined with CNTs for use in both cell and tissue experiments. [ABSTRACT FROM AUTHOR]

The dysfunction and decreased number of islet β cells are central to the main pathogenesis of diabetes. Improving islet β cell function and increasing the number of β cells are effective approaches to treat diabetes and constitute the main direction of diabetes drug development. The role of Chinese medicine in the treatment of diabetes began to be recognized. In recent years, Chinese medicine monomers have been found to increase insulin synthesis and secretion, reduce β cell-apoptosis, and protect the function of β cells. The results of in vivo animal experiments and in vitro studies on insulinoma cells also suggested TCMs could promote the proliferation of pancreatic islet β cells and induce other cells differentiation or transdifferentiation to islet β cells. Thereby, they may play a role in the treatment of diabetes. In this paper, we will review islet β cell protection with TCMs and the related mechanisms found in recent studies. An in-depth explanation of the role of TCM in islet β cell protection can provide a theoretical basis and research ideas for the development of TCM-based diabetes treatment drugs. [ABSTRACT FROM AUTHOR]

Currently, the age of the population is increasing as a result of increased life expectancy. Ageing is defined as the progressive loss of physiological integrity, which can be characterized by functional impairment and high vulnerability to various types of diseases, such as diabetes, hypertension, Alzheimer's disease (AD), Parkinson's disease (PD), and atherosclerosis. Numerous studies have reported that the presence of oxidative stress and inflammation contributes to the development of these diseases. In general, oxidative stress could induce proinflammatory cytokines and reduce cellular antioxidant capacity. Increased oxidative stress levels beyond the production of antioxidant agents cause oxidative damage to biological molecules, including DNA, protein, and carbohydrates, which affects normal cell signalling, cell growth, differentiation, and apoptosis and leads to disease pathogenesis. Since oxidative stress and inflammation contribute to these diseases, ginger (Zingiber officinale Roscoe) is one of the potential herbs that can be used to reduce the level of oxidative stress and inflammation. Ginger consists of two major active components, 6-gingerol and 6-shogaol, which are essential for preventing oxidative stress and inflammation. Thus, this paper will review the effects of ginger on ageing and degenerative diseases, including AD, PD, type 2 diabetes mellitus (DM), hypertension, and osteoarthritis. [ABSTRACT FROM AUTHOR]

Cancer is a complex disease residing in various tissues of human body, accompanied with many abnormalities and mutations in genomes, transcriptome, and epigenome. Early detection plays a crucial role in extending survival time of all major cancer types. Recent advances in microarray and sequencing techniques have given more support to identifying effective biomarkers for early detection of cancer. MicroRNAs (miRNAs) are more and more frequently used as candidates for biomarkers in cancer related studies due to their regulation of target gene expression. In this paper, the comparative analysis is used to discover miRNA expression patterns in cancer versus normal samples on early stage of eight prevalent cancer types. Our work focuses on the specific miRNAs biomarkers identification and function analysis. Several identified miRNA biomarkers in this paper are matched well with those reported in existing researches, and most of them could serve as potential candidate indicators for clinical early diagnosis applications. [ABSTRACT FROM AUTHOR]

Cuphea aequipetala (C. aequipetala) has been used in Mexican traditional medicine since prehispanic times to treat tumors. In this paper, we evaluated the antiproliferative and apoptotic effect of the methanolic and aqueous extracts of C. aequipetala on several cancer cell lines including the B16F10 cell line of murine melanoma and carried a murine model assay. In vitro assay analyzed the effect in the cellular cycle and several indicators of apoptosis, such as the caspase-3 activity, DNA fragmentation, phosphatidylserine exposure (Annexin-V), and induction of cell membrane permeabilization (propidium iodide) in the B16F10 cells. In vivo, groups of C57BL/6 female mice were subcutaneously injected with 5x105 B16F10 cells and treated with 25 mg/mL of C. aequipetala extracts via oral. Aqueous and methanolic extracts showed a cytotoxic effect in MCF-7, HepG2, and B16F10 cell lines. The methanolic extract showed more antiproliferative effect with less concentration, and for this reason, the in vitro experiments were only continued with it. This extract was able to induce accumulation of cells on G1 phase of the cell cycle; moreover, it was able to induce DNA fragmentation and increase the activity of caspase-3 in B16F10 cells. On the other hand, in the murine model of melanoma, the aqueous extract showed a greater reduction of tumor size in comparison with the methanolic extract, showing an 80% reduction versus one of around 31%, both compared with the untreated control, indicating a better antitumor effect of C. aequipetala aqueous extract via oral administration. In conclusion, the in vitro data showed that both C. aequipetala extracts were able to induce cytotoxicity through the apoptosis pathway in B16F10 cells, and in vivo, the oral administration of aqueous extract reduces the melanoma tumoral mass, suggesting an important antitumoral effect and the perspective to search for effector molecules involved in it. [ABSTRACT FROM AUTHOR]

Purpose. Multidrug resistance (MDR) is a major obstacle in chemotherapy of leukemia treatments. In this paper, we investigated Usnea Acid (UA) as MDR reversal agent on hematologic K562/ADR cells via ROS dependent apoptosis. Methods. CCK8 assay was used to measure cell viability rate of K562/ADR. Intracellular reactive oxygen species (ROS) generation, cell cycle distribution, cell apoptosis were measured with flow cytometry, respectively. Proteins related to apoptosis were measured by Western blot. Intracellular Adriamycin accumulation was observed by confocal microscopy and measured by flow cytometry. Results. In vitro study showed intracellular Adriamycin accumulation was remarkably increased by UA. Cell viability treated with Adr (4 μM) was decreased from 89.8%  ± 4.7 to 32%  ± 8.9 by combined with UA (4 μM). Adr-induced apoptosis and G1/G0 phase cell cycle arrest were remarkably increased by UA, as well as, intracellular ROS level. However, MDR reversing activity of UA was inhibited by N-acetyl cysteine (NAC), a ROS scavenger. Conclusion. These data provide compelling evidence that UA is a promising agent against MDR in leukemia cell line and suggest a promising therapeutic approach for leukemia. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is one of the most serious complications of diabetes. Lipotoxicity in glomerular mesangial cells is associated with the progression of diabetic nephropathy. Paper mulberry, Broussonetia kazinoki Siebold (BK), has been used in oriental medicine for human health problems. However, to date, the beneficial effect of BK fruit has not been studied. In this study, we investigated the protective effect of an ethanolic extract of BK fruit (BKFE) against palmitate- (PA-) induced toxicity in mesangial cells. BKFE significantly increased the viability of PA-treated SV40 MES13 cells. BKFE significantly inhibited PA-induced apoptosis and decreased the expression of apoptotic genes, cleaved caspase-3, and cleaved PARP. Moreover, BKFE inhibited the expression of endoplasmic reticulum (ER) stress-related genes, such as BiP, phosphorylated eIF2α, cleaved ATF6, and spliced XBP-1, in PA-treated SV40 MES13 cells. BKFE decreased PA-induced ROS production. In addition, BKFE activated the transcription factor Nrf2 and increased the expression of antioxidant enzymes. However, knockdown of Nrf2 using siRNA suppressed this BKFE-induced increase in antioxidant enzyme expression. Furthermore, the protective effect of BKFE on PA-induced apoptosis was significantly reduced by Nrf2 knockdown. In conclusion, BKFE induced the expression of antioxidant enzymes via activation of Nrf2 and protected against PA-induced lipotoxicity in mesangial cells. [ABSTRACT FROM AUTHOR]

Sitagliptin is a member of a class of drugs that inhibit dipeptidyl peptidase (DPP-4). It increases the levels of the active form of incretins such as GLP-1 (glucagon-like peptide-1) or GIP (gastric inhibitory polypeptide) and by their means positively affects glucose metabolism. It is successfully applied in the treatment of diabetes mellitus type 2. The most recent scientific reports suggest beneficial effect of sitagliptin on diseases in which neuron damage occurs. Result of experimental studies may indicate a reducing influence of sitagliptin on inflammatory response within encephalon area. Sitagliptin decreased the levels of proinflammatory factors: TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), IL-17 (interleukin-17), and CD-163 (cluster of differentiation 163), and contributed to an increase in levels of anti-inflammatory factors: IL-10 (interleukin-10) and TGF-β (transforming growth factor β). Moreover, sitagliptin demonstrated antioxidative and antiapoptotic properties by modifying glutamate and glutathione levels within the region of hippocampus in mice. It has been observed that sitagliptin decreases accumulation of β-amyloid within encephalon structures in experimental models of Alzheimer’s dementia. This effect may be connected with SDF-1α (stromal cell-derived factor 1α) concentration. Administration of sitagliptin caused a significant improvement in MMSE (Mini–Mental State Examination) tests used for assessment of dementias. The paper presents potential mechanisms of sitagliptin activity in conditions connected with neuroinflammation with special emphasis on Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

The objective of this study was to perform a systematic review of published literature on differentially expressed genes (DEGs) in human epicardial adipose tissue (EAT) to identify molecules associated with CVDs. A systematic literature search was conducted in PubMed, SCOPUS, and ISI Web of Science literature databases for papers published before October 2014 that addressed EAT genes and cardiovascular diseases (CVDs). We included original papers that had performed gene expressions in EAT of patients undergoing open-heart surgery. The Reporting Recommendations for Tumor Marker Prognostic Studies (PRIMARK) assessment tool was also used for methodological quality assessment. From the 180 papers identified by our initial search strategy, 40 studies met the inclusion criteria and presented DEGs in EAT samples from patients with and without CVDs. The included studies reported 42 DEGs identified through comparison of EAT-specific gene expression in patients with and without CVDs. Among the 42 DEGs, genes involved in regulating apoptosis had higher enrichment scores. Notably, interleukin-6 (IL-6) and tumor protein p53 (TP53) were the main hub genes in the network. The results suggest that regulation of apoptosis in EAT is critical for CVD development. Moreover, IL-6 and TP53 as hub genes could serve as biomarkers and therapeutic targets for CVDs. [ABSTRACT FROM AUTHOR]

What is known and objective To review the pharmacology, efficacy, safety, formulary and economic considerations of pembrolizumab, a novel, first-in-class, anti- PD-1 monoclonal antibody for treatment of advanced melanoma. Methods A literature search was conducted using PubMed (July 2013-December 2014) with search terms: pembrolizumab, MK-3475 and lambrolizumab. Additional sources were identified through a subsequent review of all relevant papers, clinicaltrials.gov, product labelling and media releases. All English-language studies conducted in humans with clinical data were included. Review papers were excluded from analysis. Results and discussion Patients with advanced melanoma have limited options available. Immune therapies have shown promise in treating advanced melanoma, but can have significant toxicities. Identification of the role of PD-1 in tumour immune evasion and the subsequent development of pembrolizumab, a novel agent that inhibits PD-1, has led to the availability of an additional treatment option for patients who have progressive disease despite treatment with currently approved agents. Phase I cohort studies have demonstrated promising overall response rates and an estimated progression-free survival of approximately 5·5 months. Minimal toxicity has been observed in patients receiving pembrolizumab, although significant severe immune-mediated reactions have been reported. What is new and conclusion Pembrolizumab is a novel anti- PD-1 monoclonal antibody that is an effective option for advanced melanoma previously treated with agents such as ipilimumab and BRAF inhibitors. Additional studies will provide the necessary data for determining its true place in therapy for advanced melanoma and exploring its efficacy in additional malignant indications. [ABSTRACT FROM AUTHOR]

This paper aims to study the dynamics of immune suppressors/checkpoints, immune system, and BCG in the treatment of superficial bladder cancer. Programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), and transforming growth factor-beta (TGF-β) are some of the examples of immune suppressors/checkpoints. They are responsible for deactivating the immune system and enhancing immunological tolerance. Moreover, they categorically downregulate and suppress the immune system by preventing and blocking the activation of T-cells, which in turn decreases autoimmunity and enhances self-tolerance. In cancer immunotherapy, the immune checkpoints/suppressors prevent and block the immune cells from attacking, spreading, and killing the cancer cells, which leads to cancer growth and development. We formulate a mathematical model that studies three possible dynamics of the treatment and establish the effects of the immune checkpoints on the immune system and the treatment at large. Although the effect cannot be seen explicitly in the analysis of the model, we show it by numerical simulations. [ABSTRACT FROM AUTHOR]

Cancer treatment has developed over the years; however not all patients respond to this treatment, and therefore further research is needed. In this paper, we employ mathematical modeling to understand the behavior of cancer and its interaction with therapy. We study a drug delivery and drug-cell interaction model along with cell proliferation. Due to the fact that cancer cells grow when there are enough nutrients and oxygen, proliferation can be a barrier against a response to therapy. To understand the effect of this factor, we perform numerical simulations of the model for different values of the parameters with a continuous delivery of the drug. The numerical results showed that cancer dies after short apoptotic cycles if the cancer is highly vascularized or if the penetration of the drug is high. This suggests promoting angiogenesis or perfusion of the drug. This result is similar to the situation where proliferation is not considered since the constant release of drug overcomes the growth of the cells and thus the effect of proliferation can be neglected. [ABSTRACT FROM AUTHOR]

Apoptosis proteins play an important role in the mechanism of programmed cell death. Predicting subcellular localization of apoptosis proteins is an essential step to understand their functions and identify drugs target. Many computational prediction methods have been developed for apoptosis protein subcellular localization. However, these existing works only focus on the proteins that have one location; proteins with multiple locations are either not considered or assumed as not existing when constructing prediction models, so that they cannot completely predict all the locations of the apoptosis proteins with multiple locations. To address this problem, this paper proposes a novel multilabel predictor named MultiP-Apo, which can predict not only apoptosis proteins with single subcellular location but also those with multiple subcellular locations. Specifically, given a query protein, GO-based feature extraction method is used to extract its feature vector. Subsequently, the GO feature vector is classified by a new multilabel classifier based on the label-specific features. It is the first multilabel predictor ever established for identifying subcellular locations of multilocation apoptosis proteins. As an initial study, MultiP-Apo achieves an overall accuracy of 58.49% by jackknife test, which indicates that our proposed predictor may become a very useful high-throughput tool in this area. [ABSTRACT FROM AUTHOR]

ROCK (Rho kinase) signaling regulates a wide spectrum of fundamental cellular events and is involved in a variety of pathological conditions. It has therefore attracted research interest as a potential therapeutic target for combating various diseases. We showed that inhibition of ROCK enhances cell proliferation, promotes cell adhesion onto a substrate, and suppresses apoptosis of corneal endothelial cells (CECs). In addition, we reported that a ROCK inhibitor enhances wound healing in the corneal endothelium in animal models and in pilot clinical research. We also demonstrated the usefulness of a ROCK inhibitor as an adjunct drug in tissue engineering therapy as it enhances the engraftment of CECs onto recipient corneas. In 2013, we initiated a clinical trial to test the effectiveness of injection of cultured human CECs into the anterior chamber of patients with corneal endothelial decompensation. This paper reviews the accumulating evidence supporting the potency of ROCK inhibitors in clinical use, both as eye drops and as adjunct drugs in cell-based therapies, for the treatment of corneal endothelial decompensation. [ABSTRACT FROM AUTHOR]

Glossostemon bruguieri (moghat) is used as a nutritive and demulcent drink. This study was performed to investigate the antiproliferative effects of moghat root extract (MRE) and its apoptotic mechanism in hepatocellular carcinoma (HCC) cells, HepG2 and Hep3B. MTT assay, morphological changes, apoptosis enzyme linked immunosorbent assay, caspase and apoptotic activation, flow cytometry, and immunoblot analysis were employed. The IC50 of MRE for HepG2 (910±6 μg/ml) and for Hep3B (1510±5 μg/ml) induced significant growth-inhibitory effects against HCC cells, with no cytotoxic effect on normal hepatocytes. MRE treatment induced apoptotic effects to HepG2 cells in a caspase-dependent manner and via upregulating p53/p21 and PCNA. The upregulation of p21 was controlled by p53 expression in HepG2 but not in Hep3B despite upregulation of Bax protein in both cell lines. Interestingly, p21 may be a remarkable switch to G1 arrest in HepG2 cells, but not in Hep3B cells. In addition, Fas- and mitochondria-mediated pathways were found to be involved in MRE-induced apoptosis in Hep3B cells. The GC-MS analysis of MRE revealed two major constituents of pharmaceutical importance: the flavonoid apigenin (17.04%) and the terpenoid squalene (11.32%). The data presented in this paper introduces G. bruguieri as a promising nontoxic herb with therapeutic potential for HCC. To the authors’ knowledge, the present study provides the first report on the anticancer activity of MRE on HCC cells. [ABSTRACT FROM AUTHOR]

One of the often reported artefacts during cell preparation to scanning electron microscopy (SEM) is the shrinkage of cellular objects, that mostly occurs at a certain time-dependent stage of cell drying. Various methods of drying for SEM, such as critical point drying, freeze-drying, as well as hexamethyldisilazane (HMDS)-drying, were usually used. The latter becomes popular since it is a low cost and fast method. However, the correlation of drying duration and real shrinkage of objects was not investigated yet. In this paper, cell shrinkage at each stage of preparation for SEM was studied. We introduce a shrinkage coefficient using correlative light microscopy (LM) and SEM of the same human mesenchymal stem cells (hMSCs). The influence of HMDS-drying duration on the cell shrinkage is shown: the longer drying duration, the more shrinkage is observed. Furthermore, it was demonstrated that cell shrinkage is inversely proportional to cultivation time: the longer cultivation time, the more cell spreading area and the less cell shrinkage. Our results can be applicable for an exact SEM quantification of cell size and determination of cell spreading area in engineering of artificial cellular environments using biomaterials. SCANNING 38:625-633, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

This paper investigates the protective effect of interleukin-1 receptor antagonist (IL-1Ra) released from hyaluronic acid chitosan (HA-CS) microspheres in a controlled manner on IL-1β-induced inflammation and apoptosis in chondrocytes. The IL-1Ra release kinetics was characterized by an initial burst release, which was reduced to a linear release over eight days. Chondrocytes were stimulated with 10 ng/ml IL-1β and subsequently incubated with HA-CS-IL-1Ra microspheres. The cell viability was decreased by IL-1β, which was attenuated by HA-CS-IL-1Ra microspheres as indicated by an MTT assay. ELISA showed that HA-CS-IL-1Ra microspheres inhibited IL-1β-induced inflammation by attenuating increases in NO2- and prostaglandin E2 levels as well as increase in glycosaminoglycan release. A terminal deoxyribonucleotide transferase deoxyuridine triphosphate nick-end labeling assay revealed that the IL-1β-induced chondrocyte apoptosis was decreased by HA-CS-IL-1Ra microspheres. Moreover, HA-CS-IL-1Ra microspheres blocked IL-1β-induced chondrocyte apoptosis by increasing B-cell lymphoma 2 (Bcl-2) and decreasing Bcl-2-associated X protein and caspase-3 expressions at mRNA and protein levels, as indicated by reverse-transcription quantitative polymerase chain reaction and western blot analysis, respectively. The results of the present study indicated that HA-CS-IL-1Ra microspheres as a controlled release system of IL-1Ra possess potential anti-inflammatory and antiapoptotic properties in rat chondrocytes due to their ability to regulate inflammatory factors and apoptosis associated genes. [ABSTRACT FROM AUTHOR]

ER stress has been implicated in pathophysiological development of many diseases. Persistent overwhelming stimuli trigger ER stress to initiate apoptosis, autophagy, and cell death. IRE1-JNK and eIF2α-CHOP signaling pathways are the two important players of ER stress, which is also modulated by ROS production, calcium disturbance, and inflammatory factors. ER stress has been developed as a novel strategy for diseases management. Recently, a vast of research focuses on the natural occurring compounds targeting ER stress, which results in medical benefits to human diseases. These small reported molecules mainly include polyphenols, alkaloids, and saponins. Many of them have been developed for use in clinical applications. To better understand the pharmacological mechanism of these molecules in ER stress in diseases, efforts have been made to discover and deliver medical merits. In this paper, we will summarize the natural occurring compounds targeting ER stress. [ABSTRACT FROM AUTHOR]

The risk of influenza A virus (IAV) is more likely caused by secondary bacterial infections. During the past decades, a great amount of studies have been conducted on increased morbidity from secondary bacterial infections following influenza and provide an increasing number of explanations for the mechanisms underlying the infections. In this paper, we first review the recent research progress that IAV infection increased susceptibility to bacterial infection. We then propose an assumption that autophagy and apoptosis manipulation are beneficial to antagonize post-IAV bacterial infection and discuss the clinical significance. [ABSTRACT FROM AUTHOR]

Apoptosis proteins play a key role in maintaining the stability of organism; the functions of apoptosis proteins are related to their subcellular locations which are used to understand the mechanism of programmed cell death. In this paper, we utilize GO annotation information of apoptosis proteins and their homologous proteins retrieved from GOA database to formulate feature vectors and then combine the distance weighted KNN classification algorithm with them to solve the data imbalance problem existing in CL317 data set to predict subcellular locations of apoptosis proteins. It is found that the number of homologous proteins can affect the overall prediction accuracy. Under the optimal number of homologous proteins, the overall prediction accuracy of our method on CL317 data set reaches 96.8% by Jackknife test. Compared with other existing methods, it shows that our proposed method is very effective and better than others for predicting subcellular localization of apoptosis proteins. [ABSTRACT FROM AUTHOR]

Although apoptosis plays an important role in the development of Diabetic Encephalopathy (DE), the underlying molecular mechanisms remain unclear. With respect to this, the present work aims to study the variation in chloride/proton exchanger ClC-3 expression and its association with HT22 hippocampal neuronal apoptosis under hyperglycemic condition in vitro. The cells were stimulated with added 0, 5, or 25 mM glucose or mannitol for up to 72 hours before assessing the rate of ClC-3 expression, cell viability, and apoptosis. In a consecutive experiment, cells received chloride channel blocker in addition to glucose. The rate of cellular death/apoptosis and viability was measured using Flow Cytometry and MTT assay, respectively. Changes in ClC-3 expression were assessed using immunofluorescence staining and western blot analysis. The results revealed a significant increase in cellular apoptosis and reduction in viability, associated with increased ClC-3 expression in high glucose group. Osmolarity had no role to play. Addition of chloride channel blocker completely abolished this effect. Thus we conclude that, with its increased expression, ClC-3 plays a major role in hyperglycemia induced hippocampal neuronal apoptosis. To strengthen our understanding of this aforesaid association, we conducted an extensive literature search which is presented in this paper. [ABSTRACT FROM AUTHOR]

Although apoptosis plays an important role in the development of Diabetic Encephalopathy (DE), the underlying molecular mechanisms remain unclear. With respect to this, the present work aims to study the variation in chloride/proton exchanger ClC-3 expression and its association with HT22 hippocampal neuronal apoptosis under hyperglycemic condition in vitro. The cells were stimulated with added 0, 5, or 25 mM glucose or mannitol for up to 72 hours before assessing the rate of ClC-3 expression, cell viability, and apoptosis. In a consecutive experiment, cells received chloride channel blocker in addition to glucose. The rate of cellular death/apoptosis and viability was measured using Flow Cytometry and MTT assay, respectively. Changes in ClC-3 expression were assessed using immunofluorescence staining and western blot analysis. The results revealed a significant increase in cellular apoptosis and reduction in viability, associated with increased ClC-3 expression in high glucose group. Osmolarity had no role to play. Addition of chloride channel blocker completely abolished this effect. Thus we conclude that, with its increased expression, ClC-3 plays a major role in hyperglycemia induced hippocampal neuronal apoptosis. To strengthen our understanding of this aforesaid association, we conducted an extensive literature search which is presented in this paper. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) affects millions of people worldwide. MI causes massive cardiac cell death and heart function decrease. However, heart tissue cannot effectively regenerate by itself. While stem cell therapy has been considered an effective approach for regeneration, the efficacy of cardiac stem cell therapy remains low due to inferior cell engraftment in the infarcted region. This is mainly a result of low cell retention in the tissue and poor cell survival under ischemic, immune rejection and inflammatory conditions. Various approaches have been explored to improve cell engraftment: increase of cell retention using biomaterials as cell carriers; augmentation of cell survival under ischemic conditions by preconditioning cells, genetic modification of cells, and controlled release of growth factors and oxygen; and enhancement of cell survival by protecting cells from excessive inflammation and immune surveillance. In this paper, we review current progress, advantages, disadvantages, and potential solutions of these approaches. [ABSTRACT FROM AUTHOR]

Apoptosis has been reported to induce changes in the remodelling of membrane lipids; after death receptor engagement, specific changes of lipid composition occur not only at the plasma membrane, but also in intracellular membranes. This paper focuses on one important aspect of apoptotic changes in cellular lipids, namely, the redistribution of the mitochondria-specific phospholipid, cardiolipin (CL). CL predominantly resides in the inner mitochondrial membrane, even if the rapid remodelling of its acyl chains and the subsequent degradation occur in other membrane organelles. After death receptor stimulation, CL appears to concentrate into mitochondrial "raft-like" microdomains at contact sites between inner and outer mitochondrial membranes, leading to local oligomerization of proapoptotic proteins, including Bid. Clustering of Bid in CL-enriched contacts sites is interconnected with pathways of CL remodelling that intersect membrane traffic routes dependent upon actin. In addition, CL association with cytoskeleton protein vimentin was observed. Such novel association also indicated that CL molecules may be expressed at the cell surface following apoptotic stimuli. This observation adds a novel implication of biomedical relevance. The association of CL with vimentin at the cell surface may represent a "new" target antigen in the context of the apoptotic origin of anti-vimentin/CL autoantibodies in Antiphospholipid Syndrome. [ABSTRACT FROM AUTHOR]

Indirubin is the active component of Danggui Longhui Wan, a traditional Chinese medicine formulation. The encouraging clinical results from the 1980s obtained in chronic myelocytic leukemia patients treated with indirubin stimulated numerous studies on this compound. These investigations explored the use of indirubin in different types of cancer and reported the synthesis of novel derivatives with improved chemical and pharmacokinetic properties. In this paper, we review the impressive progress that has been made in elucidating the mechanistic understanding of how indirubin and its derivatives affect physiological and pathophysiological processes, mainly by inhibition of cell proliferation and induction of cell death. Furthermore, we survey the therapeutic use of these compounds in combating proliferative diseases such as cancer, restenosis, and psoriasis. [ABSTRACT FROM AUTHOR]

Hepatic encephalopathy (HE), characterized by impaired cerebellar functions during chronic liver failure (CLF), involves N-methyl-D-aspartate receptor (NMDAR) overactivation in the brain cells. Bacopa monnieri (BM) extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B) and its downstream mediators in cerebellum of rats with chronic liver failure (CLF), induced by administration of 50 mg/kg bw thioacetamide (TAA) i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS-) apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE. [ABSTRACT FROM AUTHOR]

Previous studies indicated that bone marrow mesenchymal stem cells (BM-MSCs) from patients with systemic lupus erythematosus (SLE) exhibited the phenomenon of apoptosis. In this study, we aimed to investigate whether apoptosis of BM-MSCs from SLE patients were dysregulated. In this paper, endoplasmic reticulum stress (ERS) was evidenced by increased expression of phosphorylated protein kinase RNA-like ER kinase (PERK) and inositol-requiring protein-1 (IRE-1). We also found the activation of downstream target eukaryotic translation initiator factor 2α (eIF 2α) and CCAAT/enhancer-binding protein- (C/EBP-) homologous protein (CHOP) in BM-MSCs from SLE patients. Interestingly, we discovered that 4-phenylbutyric acid (4-PBA), a selective inhibitor of ERS, blocked the apoptosis of BM-MSCs from SLE patients and alleviated the level of Jun N-terminal kinase1/2 (JNK1/2) and CHOP. Furthermore, blockage of PERK signaling expression by siRNA not only significantly reduced the expression of CHOP, but also activated the anti-apoptotic regulator B-cell lymphoma-2 (Bcl-2). Blockage of IRE-1 or JNK1/2 by siRNA resulted in the decreased expression of JNK1/2 and proapoptosis protein Bcl-2 associated protein X (BAX). These results implicated that ERS-mediated apoptosis was a critical determinant of BM-MSCs from SLE patients. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major healthcare problem with increasing prevalence in the population. CKD leads to end stage renal disease and increases the risk of cardiovascular disease. As such, it is important to study the mechanisms underlying CKD progression. To this end, an animal model was developed to allow the testing of new treatment strategies or molecular targets for CKD prevention. Many underlying risk factors result in CKD but the disease itself has common features, including renal interstitial fibrosis, tubular epithelial cell loss through apoptosis, glomerular damage, and renal inflammation. Further, CKD shows differences in prevalence between the genders with premenopausal women being relatively resistant to CKD. We sought to develop and characterize an animal model with these common features of human CKD in the C57BL/6 mouse. Mice of this genetic background have been used to produce transgenic strains that are commercially available. Thus, a CKD model in this strain would allow the testing of the effects of numerous genes on the severity or progression of CKD with minimal cost. This paper describes such a mouse model of CKD utilizing angiotensin II and deoxycorticosterone acetate as inducers. [ABSTRACT FROM AUTHOR]

In this paper, a novel small-molecular apoptotic PET imaging probe, 18F-ML-8 with a malonate motif structure, is presented and discussed. After study, the small tracer that belongs to a member of ApoSense family is proved to be capable of imaging merely apoptotic regions in the CTX treated tumor-bearing mice. The experimental result is further confirmed by in vitro cell binding assays and TUNEL staining assay. As a result, 18F-ML-8 could be used for noninvasive visualization of apoptosis induced by antitumor chemotherapy. [ABSTRACT FROM AUTHOR]

Obesity is considered a major health problem. However, mechanisms involved and its comorbidities are not elucidated. Recent theories concerning the causes of obesity have focused on a limit to the functional capacity of adipose tissue, comparing it with other vital organs. This assumption has been the central point of interest in our laboratory. We proposed that the failure of adipose tissue is initiated by the difficulty of this tissue to increase its cellularity due to excess in fat contribution, owing to genetic or environmental factors. Nevertheless, why the adipose tissue reduces its capacity to make new adipocytes via mesenchymal cells of the stroma has not yet been elucidated. Thus, we suggest that this tissue ceases fulfilling its main function, the storage of excess fat, thereby affecting some of the key factors involved in lipogenesis, some of which are reviewed in this paper (PPARγ, ROR1, FASN, SCD1, Rab18, BrCa1, ZAG, and FABP4). On the other hand, mechanisms involved in adipose tissue expandability are also impaired, predominating hypertrophy via an increase in apoptosis and a decrease in adipogenesis and angiogenesis. However, adipose tissue failure is only part of this great orchestra, only a chapter of this nightmare. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to explore the change of NF-κB signaling pathway in intestinal epithelial cell induced by fission neutron irradiation and the influence of the PI3K/Akt pathway inhibitor LY294002. Three groups of IEC-6 cell lines were given: control group, neutron irradiation of 4Gy group, and neutron irradiation of 4Gy with LY294002 treatment group. Except the control group, the other groups were irradiated by neutron of 4Gy. LY294002 was given before 24 hours of neutron irradiation. At 6 h and 24 h after neutron irradiation, the morphologic changes, proliferation ability, apoptosis, and necrosis rates of the IEC-6 cell lines were assayed and the changes of NF-κB and PI3K/Akt pathway were detected. At 6 h and 24 h after neutron irradiation of 4Gy, the proliferation ability of the IEC-6 cells decreased and lots of apoptotic and necrotic cells were found. The injuries in LY294002 treatment and neutron irradiation group were more serious than those in control and neutron irradiation groups. The results suggest that IEC-6 cells were obviously damaged and induced serious apoptosis and necrosis by neutron irradiation of 4Gy; the NF-κB signaling pathway in IEC-6 was activated by neutron irradiation which could protect IEC-6 against injury by neutron irradiation; LY294002 could inhibit the activity of IEC-6 cells. [ABSTRACT FROM AUTHOR]

Nf‐E2‐related transcription factor 2 (Nrf2) helps cells fight oxidative stress events in vivo and in vitro by promoting the expression of antioxidants and detoxification enzymes. The necessary factors regulating Nrf2 activity and stability during analgesic nephropathy are not fully understood. Our results suggest that acetaminophen produces nephrotoxicity in HK‐2 cells by inhibiting keap1 degradation. APAP subsided Nrf2 nuclear accumulation by inhibition of keap1 degradation, thereby reducing the binding of Nrf2 to ARE, leading to the loss of expression of antioxidant proteins such as HO‐1, inducing a series of oxidative stress and apoptosis events. Therefore, Nrf2/keap1/HO‐1 signal transduction pathway has a poor prognosis during analgesic nephrotoxicity. Sika deer antler protein (SDAPR) significantly prevented APAP‐induced HK‐2 cell damage by constitutively stabilized Nrf2 nuclear retention. Excess APAP leads to a decrease in Nrf2 nuclear translocation, leading to severe oxidative stress, increasing the levels of GSH and MDA in HK‐2 cells, and reducing the enzyme activities of SOD and CAT in HK‐2 cells. Increased biomarker levels of acute kidney injury (AKI) in HK‐2 cells, including kidney injury molecule‐1, neutrophil gelatinase‐associated lipocalin and cystatin C, decrease the mitochondrial membrane potential in HK‐2 cells, and cause mitochondrial dysfunction, it also reduced the ratio of mitochondria‐associated apoptotic protein Bax/Bcl‐2, leading to cell apoptosis. SDAPR dose dependently accorded protection against acetaminophen‐induced nephrotoxicity, oxidative damage, and cell apoptosis by its molecular intervention with Nrf2/keap1/HO‐1 pathway via keap1 degradation. Practical applications: In this paper, we investigated the protective effect of SDAPR on APAP‐induced AKI in HK‐2 cells, and briefly explained its possible mechanism of action, providing a basis for future clinical trials and the development of anti‐APAP AKI drugs. [ABSTRACT FROM AUTHOR]