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Biomedicine & pharmacotherapy
Masson Pub. USA, Inc.
Biomedicine & pharmacotherapy

Masson Pub. USA, Inc.

0753-3322

Biomedicine & pharmacotherapy/Journal Biomedicine & pharmacotherapySCIISTP
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    Biomarkers related to immune checkpoint inhibitors therapy

    Na LiXin HouShaogang HuangRisheng Tai...
    1页
    查看更多>>摘要：Immune checkpoint inhibitors (ICIs) therapy is an emerging cancer treatment. During treatment it is necessary to monitor the patient at all times and respond to any adverse reactions that may occur, such as immune-related adverse events and unconventional reactions. Biomarkers, the biochemical indicators that mark changes in the structure or function of systems, organs, tissues, and cells, may be used to predict and design treatment for such reactions. Anti-tumor immunotherapy biomarkers can be derived from the tumors themselves (e.g. negative regulatory molecules and dynamic changes in genome sequence) or from the immune system (e.g. peripheral blood cell population counts, various cytokines, tumor-infiltrating lymphocytes, and intestinal microbes). The development of biomarkers is important for monitoring the effect of treatment, assessing the patient's response to ICIs, determining adverse reactions, and predicting the direction of disease development. In addition, organ toxicity and systemic events also have an impact on the therapeutic effect of ICIs.
      原文链接:
    • NSTL

    Virtual screening and in vitro experimental verification of LuxS inhibitors from natural products for Lactobacillus reuteri

    Fanying MengFan ZhangQiuding ChenMin Yang...
    1页
    查看更多>>摘要：The rapid proliferation and colonization of probiotics in the intestines are essential for human health. Quorum sensing (QS) is a communication mechanism among bacteria, which can regulate various bacterial crowd behavior. This study aimed to enhance the viability of Lactobacillus reuteri 1-12 by regulating QS. Herein, we built a database containing 72 natural products (previously reported) that can improve intestinal flora. Virtual screening (VS) was subsequently conducted to screen four potential active compounds. After that, molecular docking was conducted to analyze the binding mode of the four natural products to S-Ribosylhomocysteinase (LuxS). The results showed that norathyriol, mangiferin, baicalein, and kaempferol had good binding ability to LuxS. The validation experiment showed that norathyriol, mangiferin, baicalein, and kaempferol could inhibit the production of autoinducer-2 (AI-2). Moreover, mangiferin significantly increased L. reuteri 1-12 biomass and promoted L. reuteri 1-12 biofilm formation and structure. Besides, only mangiferin inhibited luxS expression, thus increasing L. reuteri 1-12 biomass. This research indicated that mangiferin may be a potential inhibitor of LuxS, promoting the probiotic properties of L. reuteri and human health.
      原文链接:
    • NSTL

    HDAC inhibitor cowanin extracted from G. fusca induces apoptosis and autophagy via inhibition of the PI3K/Akt/mTOR pathways in Jurkat cells

    Sakdiphong PunpaiAudchara SaenkhamFaongchat JarintananSuchada Jongrungruangchok...
    1页
    查看更多>>摘要：Cowanin, a xanthone derivative extracted from the Garcinia fusca plant, has been recognized for various biological activities including, antimicrobial, anti-inflammatory, and anticancer activities. However, the mechanism to induce cancer cell death in cancer cells remains to be fully elucidated. Our previous report showed that other xanthones from these plants could act as histone deacetylase inhibitors (HDACi), so we deeply analyzed the role of cowanin, a major compound of G.fusca, and investigated through the mode of cell death both apoptosis and autophagy that have never been reported. As a result, it was demonstrated that cowanin indicated the role of HDACi as other xanthones. The molecular docking analysis showed that cowanin could interact within the catalytic pocket region of HDAC class I (HDAC2, 8) and II (HDAC4, 7) proteins and inhibit their activity. Also, the level of protein expression of HDAC2, 4, 7, and 8 was distinctly decreased, and the level of histone H3 and H4 acetylation increased in cowanin treated cells. For the mode of cell death, cowanin demonstrated both apoptosis and autophagy activation in Jurkat cells. Besides, cowanin significantly suppressed phosphorylation of PI3K, Akt, and mTOR signaling. Therefore, these findings revealed that cowanin represents a new promising candidate for development as an anticancer agent by inducing apoptosis and autophagy via PI3K/AKT/mTOR pathway and effectively inhibiting HDAC activity.
      原文链接:
    • NSTL

    Cell-derived artificial nanovesicle as a drug delivery system for malignant melanoma treatment

    Ying-Yi LinChung-Yi ChenDik-Lung MaChung-Hang Leung...
    1页
    查看更多>>摘要：Extracellular vehicles have a natural targeting ability and immune tolerance of being usually applied in drug delivery systems; however, the purification of EVs is complicated and the production yield was quite low. We developed an artificial cellular mimetic nanovesicle (NV) with melanoma fragment membrane for the transportation with curcumin to achieve the anticancer purpose. B16F10 derived NVs were manufactured by the breakdown of cells using a series of extrusions through cut-off size filters (10 and 5 μm), and the whole procedure was easy and time-saving. To terminate the suspicion of cancer metastatic issue, B16F10 cells were treated by 30-min sonication and 1-min UVB exposure to remove genetic materials before the extrusion. B16F10 derived NV loaded with curcumin was called NV(S30U1/Cur), and the anticancer effect was evaluated by cell-based viability, immune, migration, and invasion. The results showed that NVs were manufactured by passing through 10 and 5 μm filters having an enviable production yield, and the mRNA amounts were declined within NVs produced by B16F10 cells treated with UVB in a comparison to the control group. NV(S30U1/Cur) were effectively decreased B1610 cell viability, and migratory and invasive abilities were also reduced significantly. Besides, CD8~+ expression of murine primary lymphocytes was activated with CD4~+ reduction by NV(S30U1/Cur) to stimulate the inherent tumor suppressive capacity in the immune system. Taken together, we established bioengineered NVs serving as novel cell mimetic nanocarriers to deliver natural compound for malignant melanoma potential immune chemotherapy. Data Availability Statement: The data used to support the findings of this study are available from the corresponding author upon requests.
      原文链接:
    • NSTL

    Prednisolone induces sleep disorders via inhibition of melatonin secretion by the circadian rhythm in zebrafish

    Yu JiangNan GenPeisong WangNinghang Feng...
    1页
    查看更多>>摘要：Prednisolone (PN) is a glucocorticoid (GC) analog that is clinically used to treat allergic inflammation and autoimmune diseases. However, the long-term use of GC-like drugs results in many side effects, among which sleep disorders caused by PN have attracted much attention. Many studies have showed that GCs indirectly cause sleep disorders by disrupting the circadian rhythm of the peripheral biological clock. However, the detailed mechanism of this effect in zebrafish remains unclear. In the present study, we aimed to study the pharmacology and toxicology of PN by analyzing the sleep phenotype and internal circadian oscillation of zebrafish. Exposure of zebrafish to PN resulted in decreased melatonin secretion and shortened sleep time. Additionally, analysis of the internal circadian rhythm of the zebrafish revealed that the expression of per and cry was significantly upregulated, resulting in a significant delay in the phase of the zebrafish behavioral rhythm. A dual-luciferase reporter assay further revealed that PN repressed per2 and cry1aa expression via the GC receptor (GR), which inhibited aanat2 expression. This caused a decrease in melatonin secretion and led to sleep disorders. The findings of this study highlight the mechanisms underlying the effects of GCs on sleep.
      原文链接:
    • NSTL

    Peristrophe bicalyculata (Retz) Nees contains principles that are cytotoxic to cancer cells and induce caspase-mediated, intrinsic apoptotic death through oxidative stress, mitochondrial depolarisation and DNA damage

    Hiba A. JasimMusa BashirKehinde RossAmos A. Fatokun...
    1页
    查看更多>>摘要：The plant Peristrophe bicalyculata (Retz) Nees is used for the treatment of cancer. While its leaf extracts have been shown to inhibit the growth of some cancer cells, there is little information supporting the constituents' anti-tumour potential. This study, therefore, investigated the effects of the plant's leaf extracts on cancer cells and the associated cellular/molecular mechanisms. Extracts were prepared using hexane (PBH), chloroform (PBC), ethyl acetate (PBE) and methanol (PBM) and constituents were identified by Liquid Chromatography-Mass Spectrometry (LC-MS). Their cytotoxic effects on human cervical (HeLa) and lung cancer (MRC5-SV2) cells were assessed using the MTT and LDH release assays. Reactive oxygen species (ROS) production was assessed using 2',7'-dichlorofluorescein diacetate (DCFDA) and mitochondrial membrane potential by staining with JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide). Caspase activation was determined using a Caspase-Glo-3/7 assay, and DNA damage by the Comet assay. Changes to mRNA expression were assessed using Quantitative Real-Time PCR. PBC, PBE and PBM reduced cell viability and induced LDH release, with IC50 values (48 h, MTT, in μg/ml), respectively, of 6.21 ± 0.70, 23.39 ± 3.92, and 22.43 ± 3.58 (HeLa); and 1.98 ± 0.33, 8.57 ± 1.91 and 28.24 ± 5.57 (MRC5-SV2). PBC induced ROS, while PBC, PBE and PBM impaired mitochondrial membrane potential and induced caspase 3/7 activation. PBC and PBE induced DNA damage, and PBE induced caspase-3 mRNA expression. Constituents of the extracts included derivatives of gallic acid, di-peptides, diterpenoids and flavones. We conclude that P. bicalyculata contains cytotoxic principles that could be potential leads for developing novel anti-cancer agents.
      原文链接:
    • NSTL

    Protective effect of Yangxue Jiedu Soup against psoriasis-like lesions by regulating TLR4/NF-κB signaling pathway mediated by secretion of exosome HSP70

    Jingjing LvYan WangJingna XuTao Zhou...
    1页
    查看更多>>摘要：Psoriasis is a common chronic inflammatory hypertrophic skin disease characterized by abnormal proliferation and differentiation of keratinocyte and immune T cell. The pathogenesis of psoriasis has not been fully elucidated and there is no effective therapy in clinic. As a traditional Chinese medicine formula, Yangxue Jiedu Soup (YJS) has been used to treat inflammatory diseases caused by Yin Deficiency and Blood Dryness. The purpose of present study was to investigate the therapeutic effect and molecular mechanism of YJS on psoriasis model mice. Results showed that YJS effectively inhibited the hypertrophy, erythema and scales of psoriasis-like lesions to alleviate the pathological changes of skin lesions, and further decreased the production of TNF-α, IL-6, IL-1β, IFN-γ, IL-17 and IL-23. Meanwhile, YJS also significantly reduced keratinocyte proliferation and maintained immune system balance by inhibiting the expression of PCNA, Ki-67, CD4 + and CD8 + in psoriasis mice. Moreover, the results further indicated that YJS could inhibit TLR4 activation and NF-κB p65 nuclear transfer by suppressing HSP70 secretion to attenuate the inflammatory response in IMQ-induced mice, which provided a theoretical basis for the clinical use of YJS in the treatment of psoriasis.
      原文链接:
    • NSTL

    Targeting chronic COVID-19 lung injury; Tofacitinib can be used against tissue-resident memory T cells

    Sepideh Zununi VahedSeyed Mahdi Hosseiniyan KhatibiElham AhmadianMohammadreza Ardalan...
    1页
    查看更多>>摘要：Post-Covid pulmonary fibrosis is evident following severe COVID-19. There is an urgent need to identify the cellular and pathophysiological characteristics of chronic lung squeals of Covid-19 for the development of future preventive and/or therapeutic interventions. Tissue-resident memory T (Trm) cells can mediate local immune protection against infections and cancer. Less beneficially, lung Trm cells cause chronic airway inflammation and fibrosis by stimulating pathologic inflammation. The effects of Janus kinase (JAK), an inducer pathway of cytokine storm, inhibition on acute Covid-19 cases have been previously evaluated. Here, we propose that Tofacitinib by targeting the CD8~+ Trm cells could be a potential candidate for the treatment of chronic lung diseases induced by acute SARS-CoV-2 infection.
      原文链接:
    • NSTL

    Self-developed NF-κB inhibitor 270 protects against LPS-induced acute kidney injury and lung injury through improving inflammation

    Yan-yan YuXiang-qian LiWen-peng HuShi-chao Cu...
    1页
    查看更多>>摘要：Sepsis-induced acute kidney injury (AKI) and acute lung injury (ALI) have high morbidity and mortality, with no effective clinically available drugs. Anti-inflammation is effective strategy in the therapy of AKI and ALI. NF-κB is a target for the development of anti-inflammatory agents. The purpose of the study is to evaluate the effect of 270, self-developed NF-κB inhibitor, in LPS-induced AKI and ALI. LPS-induced macrophages were used to examine the anti-inflammation activity of 270 in vitro. Sepsis-induced AKI and ALI mice models were established by intraperitoneal injection of LPS (10 mg/kg) for 24 h. Oral administration 270 for 14 days before LPS stimulation. Plasma, kidney and lung tissues were collected and used for histopathology, biochemical assay, ELISA, RT-PCR, and western blot analyses. In vitro, we showed that 270 suppressed the inflammation response in LPS-induced RAW 264.7 macrophages and bone marrow derived macrophages. In vivo, we found that 270 ameliorated LPS-induced AKI and ALI, as evidenced by improving various pathological changes, reducing the expression of pro-inflammation genes, blocking the activation of NF-κB and JNK pathways, attenuating the elevated myeloperoxidase (MPO) activity and malondialdehyde (MDA) content, ameliorating the activated ER stress, reversing the inhibition effect on autophagy in kidney and lung tissues, and alleviating the enhanced plasma level of creatinine (Crea), blood urea nitrogen (BUN) and pro-inflammation cytokines. Our investigations provides evidence that NF-κB inhibitor 270 is a potential drug that against LPS-induced AKI and ALI in the future.
      原文链接:
    • NSTL

    Role, molecular mechanism and the potential target of breast cancer stem cells in breast cancer development

    Tianshu ZhangHuimin ZhouKexin WangXiaowei Wang...
    1页
    查看更多>>摘要：Breast cancer (BC) is one of the most common malignant tumors in women globally, and its occurrence has surpassed lung cancer and become the biggest threat for women. At present, breast cancer treatment includes surgical resection or postoperative chemotherapy and radiotherapy. However, tumor relapse and metastasis usually lead to current therapy failure thanks to breast cancer stem cells (BCSCs)-mediated tumorigenicity and drug resistance. Drug resistance is mainly due to the long-term quiescent G0 phase, strong DNA repairability, and high expression of ABC transporter, and the tumorigenicity is reflected in the activation of various proliferation pathways related to BCSCs. Therefore, understanding the characteristics of BCSCs and their intracellular and extracellular molecular mechanisms is crucial for the development of targeted drugs for BCSCs. To this end, we discussed the latest developments in BCSCs research, focusing on the analysis of specific markers, critical signaling pathways that maintain the stemness of BCSCs , such as NOTCH, Wnt/β-catenin, STAT3, Hedgehog, and Hippo-YAP signaling, immunomicroenviroment and summarizes targeting therapy strategies for stemness maintenance and differentiation, which provides a theoretical basis for further exploration of treating breast cancer and preventing relapse derived from BCSCs.
      原文链接:
    • NSTL