首页期刊导航|Biomedicine & pharmacotherapy
期刊信息/Journal information
Biomedicine & pharmacotherapy
Masson Pub. USA, Inc.
Biomedicine & pharmacotherapy

Masson Pub. USA, Inc.

0753-3322

Biomedicine & pharmacotherapy/Journal Biomedicine & pharmacotherapySCIISTP
正式出版
收录年代

    Oryeongsan (Wulingsan) ameliorates impaired ANP secretion of atria from spontaneously hypertensive rats

    Dae Gill KangHo Sub LeeKyung Woo ChoHye Yoom Kim...
    1页
    查看更多>>摘要：Oryeongsan (ORS), a herbal medicine formula, has long been used for the treatment of impaired body water balance in Asian countries. Recently, it was shown that ORS administration modulates the renin-angiotensin system (RAS). Purpose of the present study was to determine characteristics of atrial ANP secretion and effects of ORS on the secretion in the atria from spontaneously hypertensive rats (SHR). Normotensive WKY groups (WKY-V, WKY-ORS, WKY-LOS) and hypertensive SHR groups (SHR-V, SHR-ORS, SHR-LOS) treated with vehicle, ORS, and losartan as a positive control group, respectively, were used. Experiments were performed in perfused beating atria (1.3 Hz) allowing atrial distension, acetylcholine (ACh) stimulation, and serial collection of atrial perfusates. The secreted ANP concentration was measured using radioimmunoassay. Interstitial fluid (ISF) translocation was measured using [~3H]inulin clearance. Stepwise increase in atrial distension by 1.1, 2.0, and 2.7 cmH_2O above basal distension further increased ANP secretion proportionally in the atria from WKY-V, but the response was significantly suppressed in the atria from SHR-V. Cardiomyocyte ANP release, the first step of atrial ANP secretion, was suppressed in the atria from SHR-V compared to those from WKY-V (—8.02 ±2.86, -15.86 ±2.27, and -20.09 ± 3.62%; n = 8, for SHR-V vs. 8.59 ±2.81, 15.65 ±7.14, and 38.12 ± 8.28%; n = 8, for WKY-V; p < 0.001 for all stepwise distension, respectively). Chronic treatment with ORS reversed the suppressed ANP release in atria from SHR-ORS group (6.76 ± 3.92, 9.12 ± 2.85, and 28.79 ±1.79% for SHR-ORS; n = 5 vs. SHR-V; n = 8; p = 0.01, p< 0.001, p < 0.001, respectively). The effects of ORS were comparable to those of losartan. Trans-endocardial translocation of ISF, the second step of atrial ANP secretion was similar in the atria from the hypertensive SHR-V and normotensive WKY-V. ACh-induced ANP secretion and cardiomyocyte ANP release were also suppressed in the atria from SHR-V compared to WKY-V and ORS reversed the suppression. These findings were accompanied with accentuation of the AT_1 receptor expression and suppression of the AT_2/Mas receptor, M_2 mACh receptor and GIRK4, a molecular component of K_ACh channel, expression in the atria from SHR-V. Further, treatment with ORS or losartan reversed the expressions in the groups of SHR-ORS and SHR-LOS. These results show that ANP secretion is suppressed in the atria from SHR in association with accentuation of AT_1 receptor and suppression of AT_2/Mas receptor and K_ACh channel expression. Treatment with ORS ameliorates impaired ANP secretion through improving cardiomyocyte ANP release with modulation of the cardiac RAS and muscarinic signaling. These findings provide experimental evidence which supports the effect of ORS on the regulation of atrial ANP secretion in the atria from SHR.
      原文链接:
    • NSTL

    Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms

    Ali H. EidGheyath NasrallahAbdullah ShaitoHasan Slika...
    1页
    查看更多>>摘要：Cancer is a leading cause of morbidity and mortality around the globe. Reactive oxygen species (ROS) play contradicting roles in cancer incidence and progression. Antioxidants have attracted attention as emerging therapeutic agents. Among these are flavonoids, which are natural polyphenols with established anticancer and antioxidant capacities. Increasing evidence shows that flavonoids can inhibit carcinogenesis via suppressing ROS levels. Surprisingly, flavonoids can also trigger excessive oxidative stress, but this can also induce death of malignant cells. In this review, we explore the inherent characteristics that contribute to the antioxidant capacity of flavonoids, and we dissect the scenarios in which they play the contrasting role as pro-oxidants. Furthermore, we elaborate on the pathways that link flavonoid-mediated modulation of ROS to the prevention and treatment of cancer. Special attention is given to the ROS-mediated anticancer functions that (-)-epigallocatechin gallate (EGCG), hesperetin, naringenin, quercetin, luteolin, and apigenin evoke in various cancers. We also delve into the structure-function relations that make flavonoids potent antioxidants. This review provides a detailed perspective that can be utilized in future experiments or trials that aim at utilizing flavonoids or verifying their efficacy for developing new pharmacologic agents. We support the argument that flavonoids are attractive candidates for cancer therapy.
      原文链接:
    • NSTL

    Curcumin modulates multiple cell death, matrix metalloproteinase activation and cardiac protein release in susceptible and resistant Plasmodium berghei-infected mice

    John O. OlanlokunWisdom Oshireku AbiodunOluwakemi EbenezerNeil A. Koorbanally...
    1页
    查看更多>>摘要：Pro-inflammatory signaling, cell death, and metalloproteinases activation are events in Plasmodium infection. However, it is not known if treatment with mefloquine (MF), and curcumin (CM) supplementation, will modulate these conditions. Malaria was induced in two different studies using susceptible (NK 65, study 1) and resistant (ANKA, study 2) strains of mouse malaria parasites (Plasmodium berghei) in thirty male Swiss mice (n = 5) in each study. Following confirmation of parasitemia, mice received 10 mL/kg distilled water (infected control), MF (10 mg/kg), MF and CM (25 mg/kg), MF and CM (50 mg/kg), CM (25 mg/kg) and CM (50 mg/kg). Five mice (not infected) were used as control. After treatment, the animals were sacrificed, serum obtained and liver mitochondria were isolated. Serum Tumour Necrosis Factor alpha (TNF-α), C-reactive protein (CRP), Interleukins-1 beta (IL-1β) and Interleukins-6 (IL-6) as well as caspases-3, 9 (C3 and C9), p53, serum troponin I (TI) and cre-atine kinase (CK), were assayed using ELISA techniques. Mitochondrial membrane permeability transition (mPT) pore opening, mitochondrial F_0F_1 ATPase activity, and lipid peroxidation (mLPO) were determined spectro-photometrically. Matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) expressions were determined using electrophoresis. CM supplementation (25 mg/kg) significantly decreased serum p53, TNF-α, CRP and IL-6 compared with MF. In the resistant model, CM prevented mPT pore opening, significantly decreased F_0F_1 ATPase activity and mLPO. MF activated caspase-3 while supplementation with CM significantly decreased this effect. Furthermore, MMP-2 and MMP-9 were selectively expressed in the susceptible model. Malarial treatment with mefloquine elicits different cell death responses while supplementation with curcumin decreased TI level and CK activities.
      原文链接:
    • NSTL

    Discovery of a novel cyclin-dependent kinase 8 inhibitor with an oxindole core for anti-inflammatory treatment

    Tony Eight LinChia-Ron YangChing-Hsuan ChouJui-Yi Hsu...
    1页
    查看更多>>摘要：Chronic inflammation is an underlying cause in a number of diseases. Cyclin-dependent kinase 8 (CDK8) has been implicated as an inflammatory mediator, indicating its potential as an anti-inflammatory target. Herein, we performed structure-based virtual screening (SBVS) to identify novel CDK8 inhibitors. The pharmacological interactions for CDK8 were identified and incorporated into a SBVS protocol. Selected compounds were tested in enzymatic assays, and one compound was confirmed to be a CDK8 inhibitor with a 50% inhibitory concentration (IC_50) value of 1684.4 nM. Comparing structural analogs identified a compound, F059-1017, with greater potency (IC_50 558.1 nM). When tested in cell lines, the compounds displayed low cytotoxicity. Cellular assays revealed that the identified CDK8 inhibitors can reduce phosphorylation and expression of signaling mediators associated with inflammation. In addition, results of kinase profiling showed that compound F059-1017 is selective towards CDK8. These findings suggest that the new inhibitors have great potential as lead compounds for developing novel anti-inflammatory therapeutics.
      原文链接:
    • NSTL

    Lipoic acid (LA) dose-dependently protects bone losses in the mandible of rats during the development of osteopenia by inhibiting oxidative stress and promoting bone formation

    Marek BienkoRadoslaw Piotr RadzkiDariusz WolskiTomasz Oniszczuk...
    1页
    查看更多>>摘要：Our study was carried out to evaluate the effect of lipoic acid (LA) on the densitometric properties, structure and mechanical strength of the mandible of Wistar rats with developing osteopenia. The study used 42 sham-operated (SHO) and ovariectomized (OVX) rats. The OVX rats were randomly divided (n = 6) onto two controls treated subcutaneously with physiological saline (OVX-PhS) and 17β-estradiol (OVX-E2), respectively, and onto four experimental OVX groups that received LA in the doses of 12.5, 25, 50 and 100 mg/kg/day for 28 days. The results demonstrated that the lack of estrogen brought about osteopenic bone changes, especially in the trabecular compartment. In addition, while the usage of LA in the doses of 12.5 and 25 LA had no effect in OVX rats, the dose of 100 effectively inhibited osteopenic changes of the mandible. This dose maintained structural, densitometric and mechanical parameters at levels like that in the SHO and OVX-E2 groups by inhibiting the destructive influence of oxidative stress. Dose 50, however, was revealed to be the most effective. It not only inhibited atrophic changes and the influence of oxidative stress, but also stimulated the formation of mandibular bone tissue. Our results suggest that the administration of LA is effective in preventing atrophic changes in the mandibular bone tissue in conditions of ovarian hormone deficiency and suggest its potential in the therapy of osteoporosis.
      原文链接:
    • NSTL

    Mortality risk and antibiotic use for COVID-19 in hospitalized patients over 80

    Andreea RoscaThibaut BalcaenJean-Philippe LanoixAudrey Michaud...
    1页
    查看更多>>摘要：Introduction: Patients over 80 years of age are more prone to develop severe symptoms and die from COVID-19. Antibiotics were massively prescribed in the first days of the pandemic without evidence of super infection. Antibiotics may increase the risk of mortality in cases of viral pneumonia. With age and antibiotic use, the microbiota becomes altered and less protective effect against lethal viral pneumonia. Thus we assessed whether it is safe to prescribe antibiotics for COVID-19 pneumonia to patients over 80 years of age. Method: We conducted a retrospective monocentric study in a 1240-bed university hospital. Our inclusion criteria were patients aged ≥ 80 years, hospitalized in a COVID-19 unit, with either a positive SARS-CoV-2 RT-PCR from a nasopharyngeal swab or a CT scan within 72 h after or prior to hospitalization in the unit suggestive of infection. Results: We included 101 patients who received antibiotics and 48 who did not. The demographics in the two groups were similar. Overall mortality was higher for the group that received antibiotics than for the other group (36.6% vs 14.6%,). According to univariate COX analysis, the risk of mortality was higher (HR = 1.98 [0.926; 4.23]) but non-significantly for the antibiotic group. In multivariate analysis, independent risk factors of mortality were an increased leukocyte count and decreased oxygen saturation (HR = 1.097 [1.022; 1.178] and HR = 0.927 [0.891; 0.964], respectively). Conclusion: This study raises questions about the interest of antibiotic therapy, its efficacy, and its effect on COVID-19 and encourages further research.
      原文链接:
    • NSTL

    Involvement of the adenosine A_1 receptor in the hypnotic effect of rosmarinic acid

    Katrina Joy BormateRaly James Perez CustodioJae Hoon CheongBo Kyung Lee...
    1页
    查看更多>>摘要：Insomnia, the most common sleep disorder, is characterized by a longer sleep latency, greater sleep fragmentation, and consequent excessive daytime fatigue. Due to the various side effects of prescribed hypnotics, demand for new drugs is still high. Recent studies have suggested the adenosine receptor (AR) as a potential therapeutic target for insomnia, however, clinically useful hypnotics targeting AR are not yet available. In the present study, we evaluated the hypnotic effect of rosmarinic acid, a phenolic compound widely found in medicinal plants, through pentobarbital-induced sleep test, electroencephalography/electromyography (EEG/EMG), and immu-nohistochemistry in mice. The underlying mechanisms were assessed by pharmacological approach using 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and SCH5826, antagonists for A_1R and A_2AR, respectively. Receptor-binding assay and functional agonism were also performed. Our study provides a new evidence that rosmarinic acid has a direct binding activity (Ki = 14.21 ± 0.3μM) and agonistic activity for A_1R. We also found that rosmarinic acid significantly decreased sleep fragmentation and onset latency to NREM sleep, and these effects were abolished by DPCPX. The results from c-Fos immunostaining showed that rosmarinic acid decreased the neuronal activity in wake-promoting brain regions, such as the basal forebrain and the lateral hypothalamus, while increasing the neuronal activity in the ventrolateral preoptic nucleus, a sleep-promoting region; all these effects were significantly inhibited by DPCPX. Taken together, this study suggests that rosmarinic acid possesses novel activity as an A1R agonist and thereby exerts a hypnotic effect, and thus it may serve as a potential therapeutic agent for insomnia through targeting
      原文链接:
    • NSTL

    Intermittent antibiotic treatment accelerated the development of colitis in IL-10 knockout mice

    Shiyu LiYusong JinWenyi FuAbigail D. Cox...
    1页
    查看更多>>摘要：Background and aims: Many epidemiological studies suggest an association between antibiotic exposure and the development of inflammatory bowel disease [IBD]. However, the majority of these studies are observational and still the question remains, "Does the specific antibiotic administration regimen play a role in the development of colitis?" This study aimed to compare the possible effects of continuous and intermittent antibiotic exposure on the development of colitis using a colitis-susceptible IL-10 knockout [IL-10~-/-] mouse model. Methods: IL-10-/- mice [C57BL/6] were randomly assigned to a non-antibiotic group, continuous antibiotic group and intermittent antibiotic group, and observed for 30 weeks. The antibiotic cocktail was given via the drinking water. The differential response to antibiotics was assessed. Results: Intermittent antibiotic treatment resulted in severe colitis with early disease onset in IL-10-/- mice. Higher unit colon weight and spleen weight were observed in intermittent antibiotic-treated mice but not in the continuous antibiotic group. Moreover, intermittent antibiotic treatment aggravated epithelial damage and colonic inflammation, mucosal barrier dysfunction and colonic allergic sensitization in IL-10-/- mice, whereas continuous antibiotic treatment ameliorated these symptoms. Male IL-10-/- mice with intermittent antibiotic exposure were more susceptible to colonic inflammation and allergic response than females. Conclusions: In summary, intermittent antibiotic exposure accelerated the development of severe colitis more than continuous antibiotic exposure in IL-10-/- male mice. In addition to the colonic damage and impaired barrier function, stimulation of allergic response may play a role in accelerating the development of colitis in genetically susceptible mice.
      原文链接:
    • NSTL

    Periplocin ameliorates mouse age-related meibomian gland dysfunction through up-regulation of Na/K-ATPase via SRC pathway

    Huifeng WangZongzheng ZouLuqin WanJunfa Xue...
    1页
    查看更多>>摘要：Age-related meibomian gland dysfunction (MGD) is the main cause of evaporative dry eye disease in an aging population. Decreased meibocyte cell renewal and lipid synthesis are associated with age-related MGD. Here, we found an obvious decline of Ki67, ΔNp63, and Na~+/K~+ ATPase expression in aged meibomian glands. Potential Na~+/K~+ ATPase agonist periplocin, a naturally occurring compound extracted from the traditional herbal medicine cortex periplocae, could promote the proliferation and stem cell activity of meibocyte cells in vitro. Moreover, we observed that periplocin treatment effectively increased the expression of Na~+ /K~+ ATPase, accompanied with the enhanced expression of Ki67 and ΔNp63 in aged meibomian glands, indicating that periplocin may accelerate meibocyte cell renewal in aged mice. LipidTox staining showed increased lipid accumulation after periplocin treatment in cultured meibomian gland cells and aged meibomian glands. Furthermore, we demonstrated that the SRC pathway was inhibited in aged meibomian glands; however, it was activated by periplocin. Accordingly, the inhibition of the SRC signaling pathway by saracatinib blocked periplocin-induced proliferation and lipid accumulation in meibomian gland cells. In sum, we suggest periplocin-ameliorated meibocyte cell renewal and lipid synthesis in aged meibomian glands via the SRC pathway, which could be a promising candidate for age-related MGD.
      原文链接:
    • NSTL

    Current advances in prognostic and diagnostic biomarkers for solid cancers: Detection techniques and future challenges

    Mintu PalThingreila MuinaoHari Prasanna Deka BoruahNeeraj Mahindroo...
    1页
    查看更多>>摘要：Solid cancers are one of the leading causes of cancer related deaths, characterized by rapid growth of tumour, and local and distant metastases. Current advances on multimodality care have substantially improved local control and metastasis-free survival of patients by resection of primary tumour. The major concern in disease prognosis is the timely detection of resectable or metastatic tumour, thus reinforcing the need for identification of biomarkers for premalignant lesions of solid cancer. This ultimately improves the outcome for the patients. Therefore, the purpose of this review is to update the recent advancements on prognostic and diagnostic biomarkers to enhance early detection of common solid cancers including, breast, lung, colorectal, prostate and stomach cancer. We also provide an insight into Food and Drug Administration (FDA)-approved solid cancers biomarkers; various conventional techniques used for detection of prognostic and diagnostic biomarkers and discuss approaches to turn challenges in this field into opportunities.
      原文链接:
    • NSTL