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Can ‘toxic’ bilirubin treat a variety of illnesses?
Generations of medical and biology students have been instilled with a dim view of bilirubin. Spawned when the body trashes old red blood cells, the molecule is harmful refuse and a sign of illness. High blood levels cause jaundice, which turns the eyes and skin yellow and can signal liver trouble. Newborns can’t process the compound, and although high levels normally subside, a persistent surplus can cause brain damage. Yet later this year up to 40 healthy Australian volunteers may begin receiving infusions of the supposedly good-for-nothing molecule. They will be participating in a phase 1 safety trial, sponsored ...
Source: ScienceNOW - June 8, 2023 Category: Science Source Type: news

Cholestyramine resin administration alleviated cerebral ischemic injury in obese mice by improving gut dysbiosis and modulating the bile acid profile
In conclusion, Obesity induces gut dysbiosis, worsens stroke outcomes, and perturbs the BA profile. The dysbiotic microbiome is an important linkage between obesity and stroke. CR confers metabolic benefits and neuroprotective effects in obesity, perhaps by modulating gut microbial composition and BA metabolism.PMID:36179877 | DOI:10.1016/j.expneurol.2022.114234
Source: Experimental Neurology - September 30, 2022 Category: Neurology Authors: Jianhai Liang Mingsi Zhang Huidi Wang Yueran Ren Qiheng Wu Ranshi Huang Jiahui Xie Jia Yin Jiajia Zhu Source Type: research

Akebia saponin D ameliorates metabolic syndrome (MetS) via remodeling gut microbiota and attenuating intestinal barrier injury
Biomed Pharmacother. 2021 Feb 27;138:111441. doi: 10.1016/j.biopha.2021.111441. Online ahead of print.ABSTRACTMetabolic syndrome (MetS) is a complex, multifactorial disease which lead to an increased risk of cardiovascular disease, type 2 diabetes, and stroke. However, selective, and potent drugs for the treatment of MetS are still lacking. Previous studies have found that Akebia saponin D (ASD) has beneficial effects on metabolic diseases such as obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Therefore, our study was designed to determine the effect and mechanism of action of ASD against MetS in ...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - March 2, 2021 Category: Drugs & Pharmacology Authors: Song Yang Ting Hu He Liu Ya-Li Lv Wen Zhang Han Li Lingling Xuan Li-Li Gong Li-Hong Liu Source Type: research

Challenge to the Intestinal Mucosa During Sepsis
Conclusion The impact of sepsis on the gut is manifold, e.g., sepsis mediated alteration of the gut-blood barrier and increase in the intestinal permeability, which may correlate with the phenomena of bacterial translocation and lymphatic activation (“toxic-lymph”). Systemic consequences of sepsis are widespread and concern to the coagulative system, the microbiome as well as enzymes, such as pancreatic proteases, MMPs and IAPs. Nevertheless, the therapeutic approaches for modulating the mucosal immune system are still rarely effective in daily routine. Recent published studies showing that treatment with ...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

6-Bromoindirubin-3 ′-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver
In this study, we aimed to investigate the anti-aging effect, and molecular mechanism, of the novel anti-aging drug 6BIO on naturally aged mouse liver. Rapamycin, a well-known promising anti-aging drug that delays aging through mTOR-dependent autophagy (Zhou and Ye, 2018), was used as the positive control in the study. To our knowledge, this is the first study to demonstrate the effects of 6BIO treatment in models of natural aging. Our results indicated that 6BIO ameliorates the decline of liver function with age, including lipid metabolism disorder, and attenuates hepatocyte senescence in aged mice, as revealed by altera...
Source: Frontiers in Pharmacology - April 9, 2019 Category: Drugs & Pharmacology Source Type: research

Cell-Based Therapies for Stroke: Promising Solution or Dead End? Mesenchymal Stem Cells and Comorbidities in Preclinical Stroke Research
Conclusion The high prevalence of comorbidities in patients with stroke indicates the need for therapies in preclinical studies that take into account these comorbidities in order to avoid failures in translation to the patient. Preclinical studies are beginning to evaluate the efficacy of MSC treatment in stroke associated with comorbidities, especially hypertension, for ischemic and hemorrhagic stroke. Regarding aging and diabetes, only ischemic stroke studies have been performed. For the moment, few studies have been performed and contradictory results are being reported. These contradictory results may be due to the u...
Source: Frontiers in Neurology - April 8, 2019 Category: Neurology Source Type: research

Attenuation of Myeloid Specific TGF β Signaling Induces Inflammatory Cerebrovascular Disease and Stroke.
Conclusions: Our studies show that TGFβ signaling in myeloid cells is required for maintenance of vascular health, and provide insight into inflammation-mediated cerebrovascular disease and stroke. PMID: 29051340 [PubMed - as supplied by publisher]
Source: Circulation Research - October 19, 2017 Category: Cardiology Authors: Hollander MC, Latour LL, Yang D, Ishii H, Xiao Z, Min Y, Ray-Choudhury A, Munasinghe J, Merchant AS, Lin PC, Hallenbeck J, Boehm M, Yang L Tags: Circ Res Source Type: research

Macrophage-Specific Expression of IL-37 in Hyperlipidemic Mice Attenuates Atherosclerosis.
This study was undertaken to elucidate the role of macrophage-expressed IL-37 in reducing the production and effects of proinflammatory cytokines, preventing foam cell formation, and reducing the development of atherosclerosis. Expression of human IL-37 was achieved with a macrophage-specific overexpression system, using the CD68 promoter in mouse primary bone marrow-derived macrophages via retroviral transduction. Macrophage IL-37 expression in vitro resulted in decreased mRNA (e.g., IL-1B, IL-6, and IL-12) and secreted protein production (e.g., IL-6, M-CSF, and ICAM-1) of key inflammatory mediators. IL-37 expression also...
Source: Journal of Immunology - October 13, 2017 Category: Allergy & Immunology Authors: McCurdy S, Baumer Y, Toulmin E, Lee BH, Boisvert WA Tags: J Immunol Source Type: research