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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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    Evaluating the effects of a standardized polyphenol mixture extracted from poplar-type propolis on healthy and diseased human gut microbiota

    Emanuele Ugo GarzarellaBeatriz Navajas-PorrasSergio Perez-BurilloHammad Ullah...
    1页
    查看更多>>摘要：Introduction: A large body of evidence suggests that propolis exerts antioxidant, anti-inflammatory, and antimicrobial activities, mostly ascribed to its polyphenol content. Growing evidence suggests that propolis could modulate gut microbiota exerting a positive impact on several pathological conditions. The aim of this study was to determine the in vitro impact of a poplar-type propolis extract with a standardized polyphenol content, on the composition and functionality of gut microbiota obtained from fecal material of five different donors (healthy adults, and healthy, obese, celiac, and food allergic children). Methods: The standardized polyphenol mixture was submitted to a simulated in vitro digestion-fermentation process, designed to mimic natural digestion in the human oral, gastric, and intestinal chambers. The antioxidant profile of propolis before and after the digestion-fermentation process was determined. 16 S rRNA amplicon next-generation sequencing (NGS) was used to test the effects on the gut microbiota of propolis extract. The profile of the short-chain fatty acids (SCFA) produced by the microbiota was also investigated through a chro-matographic method coupled with UV detection. Results: In vitro digestion and fermentation induced a decrease in the antioxidant profile of propolis (i.e., decrease of total polyphenol content, antiradical and reducing activities). Propolis fermentation exhibited a modulatory effect on gut microbiota composition and functionality of healthy and diseased subjects increasing the concentration of SCFA. Conclusions: Overall, these data suggest that propolis might contribute to gut health and could be a candidate for further studies in view of its use as a prebiotic ingredient.
      原文链接:
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    Angioregulatory role of miRNAs and exosomal miRNAs in glioblastoma pathogenesis

    Behnaz BouzariShabahang MohammadiDmitry Olegovich BokovIvan Ivanovich Krasnyuk...
    1页
    查看更多>>摘要：Glioblastoma (GB) is a highly aggressive cancer of the central nervous system, occurring in the brain or spinal cord. Many factors such as angiogenesis are associated with GB development. Angiogenesis is a procedure by which the pre-existing blood vessels create new vessels that play an essential role in health and disease, including tumors. Also, angiogenesis is one of the significant factors thought to be responsible for treatment resistance in many tumors, including GB. Hence, an improved understanding of the molecular processes underlying GB angiogenesis will pave the way for developing potential new treatments. Recently, it has been found that microRNAs (miRNAs) and exosomal miRNAs have a crucial role in inducing or inhibiting the angiogenesis process in GB development. A better knowledge of the miRNA's regulation pathway in the angiogenesis process in cancer offers unique mechanistic insight into the mechanism of tumor-associated neovascularization. Because of advancements in miRNA characterization and delivery methods, miRNAs can also be employed in clinical settings as potential biomarkers for anti-angiogenic treatment response as well as therapies targeting tumor angiogenesis. The recent finding and insights about miRNAs' angioregulatory role and exosomal miRNAs in GB are provided throughout the review. Also, we discuss the new concept of miRNAs-based therapies for GB in the future.
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    Trypanocidal effect of alcoholic extract of Castanedia santamartensis (Asteraceae) leaves is based on altered mitochondrial function

    Ruben Veas-AlbornozIleana CarrilloFabiola Gonzalez-HerreraMichel Lapier...
    1页
    查看更多>>摘要：The deficit of effective treatments for Chagas disease has led to searching for new substances with therapeutic potential. Natural products possess a wide variety of chemical structural motifs and are thus a valuable source of diverse lead compounds for the development of new drugs. Castanedia santamartensis is endemic to Colombia, and local indigenous communities often use it to treat skin sores from leishmaniasis; however, its mechanism of action against the infective form of Trypanosoma cruzi has not been determined. Thus, we performed chemical and biological studies of two alcoholic leaf extracts of C. santamartensis to identify their active fractions and relate them to a trypanocidal effect and evaluate their mechanism of action. Alcoholic extracts were obtained through cold maceration at room temperature and fractionated using classical column chromatography. Both ethanolic and methanolic extracts displayed activity against T. cruzi. Chemical studies revealed that kaurenoic acid was the major component of one fraction of the methanolic extract and two fractions of the ethanolic extract of C. santamartensis leaves. Moreover, caryophyllene oxide, kaurenol, taraxasterol acetate, pentadecanone, and methyl and ethyl esters of palmitate, as well as a group of phenolic compounds, including ferulic acid, caffeic acid, chlorogenic acid, myricetin, quercitrin, and cryptochlorogenic acid were identified in the most active fractions. Kaurenoic acid and the most active fractions CS400 and CS402 collapsed the mitochondrial membrane potential in trypomastigotes, demonstrating for the first time the likely mechanism against T. cruzi, probably due to interactions with other components of the fractions.
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    KDM1A/LSD1 as a promising target in various diseases treatment by regulating autophagy network

    Hongmin LiuTing MaAnqi LiYueyang Guo...
    1页
    查看更多>>摘要：Epigenetics refers to alterations in gene expressions that are reversible and stable, but do not involve changes in DNA sequences. In recent years, an increasing number of studies have shown that epigenetics plays a critical role in autophagy, which can be schematized as a biological process comprising of the following steps: autophagy signal activation, autophagic vesicle elongation, autophagosome maturation and autophagosome-lysosome fusion. As previously reported, autophagy can maintain intracellular homeostasis and autophagy dysfunction will lead to various diseases. For instance, the abnormal expression of genes involved in autophagy can result in the occurrence of many cancers and atherosclerosis. It is also well known that epigenetic modifications can affect autophagy related genes expressions and modulate other signaling molecular involved in autophagy. As an important epigenetic enzyme, LSD1 (lysine specific demethylase 1) plays an essential role in modulating autophagy. On one hand, LSD1 directly regulates autophagy-related genes expressions, including ATGs, Beclin-1, LC3 and SQSTM1/p62. On the other hand, inhibition of LSD1 can activate autophagy through regulating the activities of some other proteins such as p53, SESN2, mTORC1 and PTEN. Since autophagy activation is tightly related to the occurrence of various diseases and can be induced by LSD1 inhibition, development of LSD1 inhibitors will provide a new direction to treat such diseases. In this review, we described the mechanisms by which LSD1 regulates autophagy in different manners and how autophagic dysfunction leads to diseases occurrence. In addition, some LSD1 inhibitors used to treat diseases through modulating autophagy are also summarized in our review.
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    Eugenitol ameliorates memory impairments in 5XFAD mice by reducing Aβ plaques and neuroinflammation

    Eunbi ChoKumju YounJieun JeonWan-Seob Cho...
    1页
    查看更多>>摘要：Alzheimer's disease (AD) is caused by various pathological mechanisms; therefore, it is necessary to develop drugs that simultaneously act on multiple targets. In this study, we investigated the effects of eugenitol, which has anti-amyloid β (Aβ) and anti-neuroinflammatory effects, in an AD mouse model. We found that eugenitol potently inhibited Aβ plaque and oligomer formation. Moreover, eugenitol dissociated the preformed Aβ plaques and reduced Aβ-induced nero2a cell death. An in silico docking simulation study showed that eugenitol may interact with Aβ_1_42 monomers and fibrils. Eugenitol showed radical scavenging effects and potently reduced the release of proinflammatory cytokines from lipopolysaccharide-treated BV2 cells. Systemic administration of eugenitol blocked Aβ aggregate-induced memory impairment in the Morris water maze test in a dose-dependent manner. In 5XFAD mice, prolonged administration of eugenitol ameliorated memory and hippocampal long-term potentiation impairment. Moreover, eugenitol significantly reduced Aβ deposits and neuroinflammation in the hippocampus of 5XFAD mice. These results suggest that eugenitol, which has anti-Aβ aggregation, Aβ fibril dissociation, and anti-inflammatory effects, potently modulates AD-like pathologies in 5XFAD mice, and could be a promising candidate for AD therapy.
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    Corrigendum to "G-quadruplex stabilization via small-molecules as a potential anti-cancer strategy" [Biomed. Pharmacother. 139 (2021) 111550]

    Xudong MaYanling WuWen ZhangAnnoor Awadasseid...
    1页
    查看更多>>摘要：The authors would like to modify sections of the published article as below, following concern of a reader. 1. The following text: "About 50% of human genes are predicted to produce G4 s in the vicinity of their promoter regions, which are more generally located near oncogene promoters or regulatory genes than near household genes Should be replaced with: "It has been estimated that nearly 50% of human genes contain G4 s near their promotor regions, and they are more frequently found near the promoters of oncogenes or regulatory genes than near housekeeping genes."2. The following text: "The genes related to cell proliferation and cancer are predominantly located in telomeric regions, promoters, and 5'-untranslated regions (5'-UTRs)". Should be replaced with: "They have been found to be mainly concentrated in telomeric regions and the promoters and UTRs of genes associated with cell proliferation and cancer." The authors would like to apologize for any inconvenience caused.
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    Glutamine restores testicular glutathione-dependent antioxidant defense and upregulates NO/cGMP signaling in sleep deprivation-induced reproductive dysfunction in rats

    M.A. AdewoleO.O. AboyejiH.O. YisauG.O. Tajudeen...
    1页
    查看更多>>摘要：Oxidative stress has been linked with sleep deprivation (SD)-induced pathological conditions and reproductive dysfunction. On the other hand, glutamine has been established to have antioxidant property. However, the impact of SD, with or without glutamine, on male reproductive function is yet to be elucidated. Thus, this study was designed to investigate the role of SD, with or without glutamine, on male reproductive function and possible associated mechanisms. Ten-week old male Wistar rats weighing 175.6 g± 0.42 were randomly assigned into vehicle that received per os (p.o.) distilled water, glutamine (1 g/kg; po), SD, and SD + glutamine that received treatments as glutamine and SD. Treatment/exposure lasted for 72 h. The results showed that SD led to reduced body weight, seminiferous luminal and epididymal sperm density, low sperm quality, increased testicular and epididymal malondialdehyde, uric acid, DNA fragmentation, and testicular injury markers. In addition, SD caused a reduction in reduced glutathione level and activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione-S-transferase. Also, SD increased tumor necrotic factor-α, interleukin-1β, and nuclear factor-kappa B levels. Furthermore SD led to impaired libido and erectile dysfunction, and suppression of circulatory nitric oxide, gonadotropins and testosterone, and penile cGMP. However, glutamine attenuated the effects induced by SD. Taken together, the findings of this study demonstrate that SD induces reproductive dysfunction via glutathione-dependent defense depletion and down-regulation of NO/cGMP signaling, which was abolished by glutamine supplementation.
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    Antiophidic potential of chlorogenic acid and rosmarinic acid against Bothrops leucurus snake venom

    Diana Pontes da SilvaSarah de Sousa FerreiraManoela Torres-RegoAllanny Alves Furtado...
    1页
    查看更多>>摘要：Bothrops leucurus is responsible for most cases of snakebite in Northeast Brazil; however, this species is not included in the pool of venoms used in antivenom production in Brazil. The serotherapy has logistical and effectiveness limitations, which stimulates the search for therapeutic alternatives. Chlorogenic acid and rosmarinic acid present several biological activities, but their antiophidic potential has been poorly explored. Thus, the aim of this approach was to evaluate the potential inhibitory effects of these compounds on B. leucurus venom. Initially, the enzymatic inhibition of toxins was evaluated in vitro. Then, anti-hemorrhagic, anti-myo-toxic, and anti-edematogenic assays were performed in vivo, as well analysis of several biochemical markers and hemostatic parameters. In addition, the interaction of inhibitors with SVMP and PLA2 was investigated by docking analysis. Results revealed that compounds inhibited in vitro the enzymatic activities and venom-induced edema, with a decrease in both myeloperoxidase and interleukin quantification. The inhibitors also attenuated the hemorrhagic and myotoxic actions and mitigated changes in serum biochemical and hemostatic markers, as well as decreased lipid peroxidation in liver and kidney tissues. Docking analysis revealed attractive interactions of both inhibitors with the zinc-binding site of SVMP and, in the case of PLA_2, chlorogenic acid showed a similar inhibition mechanism to that described for rosmarinic acid. The results evidenced the antiophidic potential of both compounds, which showed higher efficiency than antivenom serum. Thus, both inhibitors are promising candidates for future adjuvants to be used to complement antivenom serotherapy.
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    The potential role of resveratrol as supportive antiviral in treating conditions such as COVID-19 - A formulator's perspective

    Roy van BrummelenAnna C. van Brummelen
    1页
    查看更多>>摘要：With an increased transmissibility but milder form of disease of the omicron variant of COVID-19 and the newer antivirals often still out of reach of many populations, a refocus of the current treatment regimens is required. Safe, affordable, and available adjuvant treatments should also be considered and known drugs and substances need to be repurposed and tested. Resveratrol, a well-known antioxidant of natural origin, shown to act as an antiviral as well as playing a role in immune stimulation, down regulation of the pro-inflammatory cytokine release and reducing lung injury by reducing oxidative stress, is such an option. New initiatives and collaborations will however need to be found to unleash resveratrol's full potential in the pharmaceutical market.
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    PD-1/PD-L1 inhibitor ameliorates silica-induced pulmonary fibrosis by maintaining systemic immune homeostasis

    Changfu HaoMeng LiYaqian QuYonghua Guo...
    1页
    查看更多>>摘要：Pulmonary fibrosis induced by silica particles is defined as silicosis, which is an incurable disease. The patho-genesis of silicosis is not completely clear, but it's certain that immune system dysfunction is closely related to it. Immune checkpoint inhibitors (ICIs) are emerging immunotherapeutic agents that mainly target adaptive immune cells, and there is abundant evidence that ICIs are of great value in cancer treatment. However, whether these attractive agents can be implemented in silicosis treatment is unclear. In this study, we explored the efficacy of small molecule inhibitors targeted PD-1/PD-L1 and CTLA-4 on silica-induced pulmonary fibrosis in mice. ICIs were injected intraperitoneally into mice that received silica instillation twice a week. The mice were sacrificed 7 and 28 days after the injection. The lungs, spleen, hilar lymph nodes, thymus, and peripheral blood of mice were collected and subjected to histological examination, flow cytometry analysis, and mRNA and protein quantification. Our results demonstrated that silica exposure caused damage to multiple immune organs in mice, leading to an imbalance in systemic immune homeostasis. Specifically, proportions and subtypes of T and B cells were significantly altered, and the expressions of PD-1, PD-L1 and CTLA-4 were abnormal on these cells. Both PD-1/PD-L1 and CTLA-4 inhibitor administration modulated silica-induced immune system disruption, however, only PD-1/PD-L1 signaling inhibition showed significant amelioration of silicosis. Our findings confirmed for the first time the potential value of ICIs for the treatment of silica-induced pulmonary fibrosis, and this may provide new ideas for the treatment of other fibrosis-related diseases.
      原文链接:
    • NSTL