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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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    Dopamine, a co-regulatory component, bridges the central nervous system and the immune system

    Mingan LiLin ZhouXiaohui SunYunqi Yang...
    1页
    查看更多>>摘要：Dopamine (DA) is a crucial neurotransmitter that plays an important role in maintaining physiological function in human body. In the past, most studies focused on the relationship between the dopaminergic system and neurological-related diseases. However, it has been found recently that DA is an immunomodulatory mediator and many immune cells express dopamine receptors (DRs). Some immune cells can synthesize and secrete DA and then participate in regulating immune function. DRs agonists or antagonists can improve the dysfunction of immune system through classical G protein signaling pathways or other non-receptor-dependent pathways. This article will discuss the relationship between the dopaminergic system and the immune system. It will also review the use of DRs agonists or antagonists to treat chronic and acute inflammatory diseases and corresponding immunomodulatory mechanisms.
      原文链接:
    • NSTL

    Beneficial effects of PCSK9 inhibition with alirocumab in familial hypercholesterolemia involve modulation of new immune players

    Patrice MarquesElena DomingoArantxa RubioSergio Martinez-Hervas...
    1页
    查看更多>>摘要：Familial hypercholesterolemia (FH) is associated with low-grade systemic inflammation, a key driver of premature atherosclerosis. We investigated the effects of inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) function on inflammatory state, endothelial dysfunction and cardiovascular outcomes in patients with FH. Fourteen patients with FH were evaluated before and 8 weeks after administration of a PCSK9 blocking monoclonal antibody (alirocumab, 150mg/subcutaneous/14 days). In vivo and ex vivo analysis revealed that alirocumab blunted the attachment of leukocytes to TNFα-stimulated human umbilical arterial endothelial cells (HUAEC) and suppressed the activation of platelets and most leukocyte subsets, which was accompanied by the diminished expression of CX3CR1, CXCR6 and CCR2 on several leukocyte subpopulations. By contrast, T-regu-latory cell activation was enhanced by alirocumab treatment, which also elevated anti-inflammatory IL-10 plasma levels and lowered circulating pro-inflammatory cytokines. Plasma levels of IFNγ positively correlated with levels of total and LDL-cholesterol, whereas circulating IL-10 levels negatively correlated with these key lipid parameters. In vitro analysis revealed that TNFα stimulation of HUAEC increased the expression of PCSK9, whereas endothelial PCSK9 silencing reduced TNFα-induced mononuclear cell adhesion mediated by Nox5 up-regulation and p38-MAPK/NFκB activation, concomitant with reduced SREBP2 expression. PCSK9 silencing also decreased endothelial CX3CL1 and CXCL16 expression and chemokine generation. In conclusion, PCSK9 inhibition impairs systemic inflammation and endothelial dysfunction by constraining leukocyte-endothelium interactions. PCSK9 blockade may constitute a new therapeutic approach to control the inflammatory state associated with FH, preventing further cardiovascular events in this cardiometabolic disorder.
      原文链接:
    • NSTL

    Polymethoxyflavones from Kaempferia parviflora ameliorate skin aging in primary human dermal fibroblasts and ex vivo human skin

    Phattharachanok KhumkhrongMattaka KhongkowKatawut NamdeeSurapun Tepaamorndech...
    1页
    查看更多>>摘要：Skin aging is accompanied by an increase in the number of senescent cells, resulting in various pathological outcomes. These include inflammation, impaired barrier function, and susceptibility to skin disorders such as cancer. Kaempferia parviflora (Thai black ginger), a medicinal plant native to Thailand, has been shown to counteract inflammation, cancer, and senescence. This study demonstrates that polymethoxyflavones (5,7-dimethoxyflavone, 5,7,4'-trimethoxyflavone, and 3,5,7,3',4'-pentamethoxyflavone) purified from K. parviflora rhizomes suppressed cellular senescence, reactive oxygen species, and the senescence-associated secretory phenotype in primary human dermal fibroblasts. In addition, they increased tropocollagen synthesis and alleviated free radical-induced cellular and mitochondrial damage. Moreover, the compounds mitigated chronological aging in a human ex vivo skin model by attenuating senescence and restoring expression of essential components of the extracellular matrix, including collagen type I, fibrillin-1, and hyaluronic acid. Finally, we report that polymethoxyflavones enhanced epidermal thickness and epidermal-dermal stability, while blocking age-related inflammation in skin explants. Our findings support the use of polymethoxyflavones from K. parviflora as natural anti-aging agents, highlighting their potential as active ingredients in cosmeceutical and nutraceutical products.
      原文链接:
    • NSTL

    Methyl ferulic acid ameliorates alcohol-induced hepatic insulin resistance via miR-378b-mediated activation of PI3K-AKT pathway

    Yan ZhangJun LuYu-juan ZhongCheng-fang Yang...
    1页
    查看更多>>摘要：A previous study indicated that microRNA-378b (miR-378b) plays a critical role in controlling hepatic insulin resistance by targeting insulin receptor (IR) and p110α in alcoholic liver disease (ALD). Methyl ferulic acid (MFA), a bioactive ingredient in Securidaca inappendiculata Hassk rhizomes, exhibits multiple pharmacological activities. It has been reported that MFA ameliorates insulin resistance in ALD, whereas the underlying molecular mechanism remains unclear. The objective of study was to evaluate the influence of MFA on insulin sensitivity in ethanol-induced L-02 cells as well as alcohol-fed mice and illuminate the function of miR-378b-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway in system. MFA was found to remarkably down-regulate miR-378b level and increase IR and p110α expressions. Furthermore, the effect of MFA on modulating miR-378b/PI3K-AKT pathway to enhance insulin sensitivity was corroborated by overexpressing and inhibiting miR-378b. Taken together, MFA exhibited a positive effect against ALD by attenuating the inhibition of miR-378b on IR/p110α and partly activating the insulin signaling to alleviate alcohol-induced hepatic insulin
      原文链接:
    • NSTL

    Current status on the therapeutic strategies for heart failure and diabetic cardiomyopathy

    Amy Hyein KimJung Eun JangJin Han
    1页
    查看更多>>摘要：Heart failure (HF) is a leading cause of disease and death from cardiovascular diseases, with cardiovascular diseases accounting for the highest cases of deaths worldwide. The reality is that the quality-of-life survival for those suffering HF remains poor with 45-60% reported deaths within five years. Furthermore, cardiovascular disease is the foremost cause of mortality and disability in people with type 2 diabetes mellitus (T2DM), with T2DM patients having a two-fold greater risk of developing heart failure. The number of T2DM affected persons only continues to surge as there are more than 400 million adults affected by diabetes and an estimated 64.3 million affected by heart failure globally (1). In order to cater to the demands of modern society, the medical field has continuously improved upon the standards for clinical management and its therapeutic approaches. For this purpose, in this review, we aim to provide an overview of the current updates regarding heart failure, to include both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) and their respective treatments, while also diving further into heart failure and its correlation with diabetes and diabetic cardiomyopathy and their respective therapeutic approaches.
      原文链接:
    • NSTL

    Photodynamic therapy with the dual-mode association of IR780 to PEG-PLA nanocapsules and the effects on human breast cancer cells

    Marina Guimaraes Carvalho MachadoMaria Alice de OliveiraElisa Gomes LannaRaoni Pais Siqueira...
    1页
    查看更多>>摘要：IR780 is a near-infrared fluorescent dye, which can be applied as a photosensitizer in photodynamic (PDT) and photo thermal (PTT) therapies and as a biodistribution tracer in imaging techniques. We investigated the growth and migration inhibition and mechanism of death of breast tumor cells, MCF-7 and MDA-MB-231, exposed to polymeric nanocapsules (NC) comprising IR780 covalently linked to the biodegradable polymer PLA (IR-PLA) and IR780 physically encapsulated (IR780-NC) in vitro. Both types of NC had mean diameters around 120 nm and zeta potentials around -40 mV. IR-PLA-NC was less cytotoxic than IR780 NC to a non-tumorigenic mammary epithelial cell line, MCF-10A, which is an important aspect of selectivity. Free-IR780 was more cytotoxic than IR-PLA-NC for MCF-7 and MDA-MB-231 cells after illumination with a 808 nm laser. IR-PLA NC was effective to inhibit colony formation (50%) and migration (30-40%) for both cancer cell lines. MDA-MB-231 cells were less sensitive to all IR780 formulations compared to MCF-7 cells. Cell uptake was higher with IR-PLA-NC than with IR780-NC and free-IR780 in both cancer cell lines (p < 0.05). NC uptake was higher in MCF-7 than in MDA-MB-231 cells. IR-PLA-NC induced a higher percentage of apoptosis upon illumination in MDA-MB-231 than in MCF-7 cells. The necrosis mechanism of death predominated in treatments with free-IR780 and with encapsulated IR780 NC, suggestive of damages at the plasma membrane. IR780 conjugated with PLA increased the apoptotic pathway and demonstrated potential as a multifunctional theranostic agent for breast cancer treatment with increased cellular uptake, photodynamic activity and more reliable tracking in cell-image studies.
      原文链接:
    • NSTL

    Metformin action over gut microbiota is related to weight and glycemic control in gestational diabetes mellitus: A randomized trial

    María Molina-VegaMaría J. Picon-CesarCarolina Gutierrez-RepisoAndrea Fernez-Valero...
    1页
    查看更多>>摘要：Background: Metformin, which is known to produce profound changes in gut microbiota, is being increasingly used in gestational diabetes mellitus (GDM). The aim of this study was to elucidate the differences in gut microbiota composition and function in women with GDM treated with metformin compared to those treated with insulin. Methods: From May to December 2018, 58 women with GDM were randomized to receive insulin (INS; n = 28) or metformin (MET; n = 30) at the University Hospital Virgen de la Victoria, Malaga, Spain. Basal visits, with at least 1 follow-up visit and prepartum visit, were performed. At the basal and prepartum visits, blood and stool samples were collected. The gut microbiota profile was determined through 16S rRNA analysis. Results: Compared to INS, women on MET presented a lower mean postprandial glycemia and a lower increase in weight and body mass index (BMI). Firmicutes and Peptostreptococcaceae abundance declined, while Proteobacteria and Enterobacteriaceae abundance increased in the MET group. We found inverse correlations between changes in the abundance of Proteobacteria and mean postprandial glycemia (p = 0.023), as well as between Enterobacteriaceae and a rise in BMI and weight gain (p = 0.031 and p = 0.036, respectively). Regarding the metabolic profile of gut microbiota, predicted metabolic pathways related to propionate degradation and ubiquinol biosynthesis predominated in the MET group. Conclusion: Metformin in GDM affects the composition and metabolic profile of gut microbiota. These changes could mediate, at least in part, its clinical effects. Studies designed to assess how these changes influence metabolic control during and after pregnancy are necessary.
      原文链接:
    • NSTL

    Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen

    Yung-Yi ChengElise T. TuzoJeffrey W. DalleyTung-Hu Tsai...
    1页
    查看更多>>摘要：Tamoxifen, a widely prescribed medication in premenopausal women diagnosed with hormone-dependent breast cancer, is potentially co-prescribed with Hedyotis diffusa (H. diffusa), particularly in Taiwan. However, no related report has investigated the drug-herb interaction of H. diffusa on the pharmacokinetics of tamoxifen and its metabolites. In the present study, male Sprague-Dawley rats were administered different doses of H. diffusa extract for 5 consecutive days prior to the administration of tamoxifen (10 mg/kg). A validated ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) system was developed to monitor tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and endoxifen in rat plasma. Pharmacokinetic results demonstrated that the area under curves (AUCs) of tamoxifen and the relative bioavailability (%) of tamoxifen were dose-dependently decreased (31-68%) by pre-treatment with H. diffusa extract (3 g/kg and 6 g/kg). In addition, the conversion ratio of 4-hydroxytamoxifen was downregulated (0.5-fold change) and the N-desmethyltamoxifen conversion ratio was upregulated (2-fold change) by high-dose H. diffusa extract. As a result, the relative bioavailability and biotransformation changes affect the clinical efficacy of tamoxifen treatment. These pre-clinical findings reveal a hitherto unreported interaction between tamoxifen and H. diffusa extract that has implications for their therapeutic efficacy in treating breast cancer.
      原文链接:
    • NSTL

    Synthesis compound XCR-7a ameliorates LPS-induced inflammatory response by inhibiting the phosphorylation of c-Fos

    Haimei TangPrasanta RoyQianqian DiXingyu Ma...
    1页
    查看更多>>摘要：Inflammation is a biological process closely related to different kinds of diseases, such as cancer and metabolic diseases. Therefore, effective control of the occurrence and development of inflammation is of great significance for disease prevention and control. Recently, 2-substituted indoles have gradually become a research hotspot because of their stability and pharmacological activity. Here we synthesized a series of compound containing 2-substituted indoles and investigated XCR-7a's role in inflammatory response. Our data show that XCR-7a can inhibit the production of inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and inflammatory mediator cyclooxygenase-2 (COX-2) induced by lipopolysaccharide (LPS) in mouse peritoneal macrophages. Also, XCR-7a has a protective effect on LPS-induced inflammatory response in mice. Mechanically, we found that XCR-7a could inhibit the phosphorylation of c-Fos induced by LPS, which suggested that the protective effect of XCR-7a on inflammation was related to its negative regulation to phosphorylation of c-Fos. Briefly, our results demonstrated that XCR-7a could be expected to be a potential drug for controlling inflammation.
      原文链接:
    • NSTL

    Repurposing an atherosclerosis targeting peptide for tumor imaging

    Luciana KovacsRyan A. DavisTanushree GangulyRoger Chammas...
    1页
    查看更多>>摘要：Cancer and atherosclerosis are chronic diseases that share common characteristics at both early and advanced stages and can arise from multiple factors. Both diseases are characterized by uncontrolled cell proliferation, inflammation, angiogenesis and apoptosis. Herein we investigated the ability of a peptide (CTHRSSVVC), that was previously reported to bind atherosclerotic lesions to home in the tumor microenvironment. The CTHRSSVVC peptide was synthesized on solid phase and N-terminally labeled with a sulfo-Cy5 dye. The specific binding to macrophage was evaluated in vitro with flow cytometry and immunofluorescence and in vivo for tumor targeting in BALB/c mice bearing a 4T1 tumor using optical imaging. The sulfo-Cy5-CTHRSSVVC peptide was synthesized in greater than 99% purity. No selective binding of the sulfo-Cy5-CTHRSSVVC peptide to macro-phages in vitro was observed, however in vivo the sulfo-Cy5-CTHRSSVVC peptide accumulated in the 4T1 tumor, with a tumor-to-normal tissue ratio of 7.21 ± 1.44 at 2 h post injection. Ex vivo analysis of tumor tissue by confocal microscopy suggested that the sulfo-Cy5-CTHRSSVVC peptide had accumulated in the stroma of the tumor specifically, in regions of spindle shaped cells. In conclusion, although the target for the sulfo-Cy5-CTHRSSVVC peptide remains to be identified, the Cy5-CTHRSSVVC peptide warrants further investigation as a tumor imaging agent.
      原文链接:
    • NSTL