- Neochlorogenic acid inhibits against LPS-activated inflammatory responses through up-regulation of Nrf2/HO-1 and involving AMPK pathway. [Journal Article]
- ETEnviron Toxicol Pharmacol 2018 Jun 08; 62:1-10
- Acute and chronic inflammatory diseases are associated with excessive inflammation due to the accumulation of pro-inflammatory mediators and cytokines produced by macrophages. In the present study, w...
Acute and chronic inflammatory diseases are associated with excessive inflammation due to the accumulation of pro-inflammatory mediators and cytokines produced by macrophages. In the present study, we investigated the anti-inflammatory properties of neochlorogenic acid (nCGA) from Lonicera japonica on lipopolysaccharide (LPS)-activated inflammation in macrophages and participation of the AMPK/Nrf2 pathway. nCGA pretreatment significantly reduced the production of nitric oxide, prostaglandin E2, TNF-α, reactive oxygen species, IL-1β, and IL-6 by LPS-activated macrophages. Moreover, both transcript and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 were reduced by nCGA in LPS-activated macrophages. nCGA inhibited NF-κB activation by attenuating IKKα/β and IκBα phosphorylation in LPS-stimulated macrophages. Moreover, nCGA attenuated LPS-elevated JAK-1, STAT-1, and MAPK phosphorylation. We further evaluated the possible role of nCGA in the induction of AMPK/Nrf2 signal pathways required for the protein expression of HO-1 and NQO-1. nCGA induced AMPK activation via phosphorylation of LKB1 and CaMKII and by the inhibitory phosphorylation of GSK3β. It stimulated the overexpression of Nrf2/ARE-regulated downstream proteins, such as NQO-1 and HO-1. Furthermore, the anti-inflammatory effects of nCGA were attenuated in macrophages subjected to siRNAs specific for HO-1, NQO-1, Nrf2, and AMPK. Accordingly, these results indicate that nCGA, as an AMPK/Nrf2 signal activator, prevents excessive macrophage-mediated responses associated with acute and chronic inflammatory disorders.
- The protective effect of α-lipoic acid against bisphenol A-induced neurobehavioral toxicity. [Journal Article]
- NINeurochem Int 2018 Jun 13
- Bisphenol A (BPA), a well-known xenoestrogen, is ubiquitously utilized in manufacturing of polycarbonated plastics. Convincing evidence suggests that BPA induces neurotoxicity and certain behavioral ...
Bisphenol A (BPA), a well-known xenoestrogen, is ubiquitously utilized in manufacturing of polycarbonated plastics. Convincing evidence suggests that BPA induces neurotoxicity and certain behavioral deficits. α-Lipoic acid (ALA) supplementation has shown protective effect against heart and liver diseases, diabetes, and neurological debility associated with aging. We studied the neuromodulatory effect of ALA against neurotoxicity of BPA in vitro in C8-D1A mouse astrocyte cell line and in vivo in C57BL/6J male mice. In vitro ALA (100 μM) protected cells from BPA (30 μM)-induced reactive oxygen species generation and increased activity of glial fibrillary acidic protein. ALA showed reduction in cell death in astrocytes treated with BPA. In vivo ALA (50 mg/kg) increased the neurospecific acetylcholinesterase activity and decreased the monoamine oxidase activity altered by BPA exposure (10 mg/kg, per os x 30 days). In addition to neuroprotective effects, ALA also showed protective effects against BPA-induced oxidative stress. We observed that ALA significantly replenished the declined neurobehavioral and cognitive performances, decreased muscle coordination and alerted short-term recognition memory in mice exposed to BPA. Our results suggest that ALA has a promising role in modulating BPA-induced neurotoxicity in C8-D1A mouse astrocyte cells as well as neurochemical and neurobehavioral deficits in C57BL/6J male mice and its antioxidant and free radical scavenging activities may in part be responsible for such an effect.
- Low body mass index is a risk factor for hyperkalaemia associated with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers treatments. [Journal Article]
- JCJ Clin Pharm Ther 2018 Jun 16
- CONCLUSIONS: The study included 2987 patients aged 70.1 ± 12.9 years, 61.0% were men, and BMI was 23.8 ± 4.4 kg/m2 . The incidence of hyperkalaemia was 7.8%. Multivariable logistic regression analysis revealed that age >65 years, low BMI, diabetes, history of treatment for hyperkalaemia, serum sodium <135 meq/L, eGFR <30 mL/min/1.73m2 and the concomitant use of hyperkalaemia-inducing medications were independent risk factors for hyperkalaemia associated with ACEI and ARB.This study demonstrated that BMI provides useful information for the identification of potential risk for hyperkalaemia associated with ACEI and ARB treatments.
- Designed Macrocyclic Peptides as Nanomolar Amyloid Inhibitors Based on Minimal Recognition Elements. [Journal Article]
- ACAngew Chem Int Ed Engl 2018 Jun 16
- Amyloid self-assembly is linked to the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes (T2D), but so far none of the anti-amyloid molecules has reached the clinic. Macrocyclic peptides b...
Amyloid self-assembly is linked to the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes (T2D), but so far none of the anti-amyloid molecules has reached the clinic. Macrocyclic peptides belong to the most attractive drug candidates. Here we present macrocyclic peptides (MCIPs) designed using minimal IAPP-derived recognition elements as a novel class of nanomolar amyloid inhibitors of both Abeta40(42) and IAPP or Abeta40(42) alone and show that chirality controls inhibitor selectivity. Sequence optimization led to the discovery of an Abeta40(42)-selective MCIP exhibiting high proteolytic stability in human plasma and human blood-brain-barrier (BBB) crossing ability in a cell model, two highly desirable properties for anti-amyloid drugs in AD. Based on their favorable properties, MCIPs are leads for macrocyclic peptide-based anti-amyloid drugs and scaffolds for designing small-molecule peptidomimetics for targeting amyloidogenesis in AD or in both AD and T2D.
- Body mass index and the risk of mortality among Chinese adults with Type 2 diabetes. [Journal Article]
- DMDiabet Med 2018 Jun 16
- CONCLUSIONS: The increased all-cause mortality in men with low BMI and in women with either low or high BMI indicate the importance of keeping BMI in a normal range for Chinese adults with Type 2 diabetes. This article is protected by copyright. All rights reserved.
- The role of Sigma-1 receptor in sex-specific heat shock response in an experimental rat model of renal ischemia/reperfusion injury. [Journal Article]
- TITranspl Int 2018 Jun 16
- We previously showed that female rats are more protected against renal ischemia/reperfusion (I/R) injury than males, which is partly attributed to their more pronounced heat shock response. We recent...
We previously showed that female rats are more protected against renal ischemia/reperfusion (I/R) injury than males, which is partly attributed to their more pronounced heat shock response. We recently described that Sigma-1 receptor (S1R) activation improves postischemic survival and renal function. 17β-estradiol activates S1R, thus here we investigated the role of sex-specific S1R activation and heat shock response in severe renal I/R injury. Proximal tubular cells were treated with 17β-estradiol, which caused direct S1R activation and subsequent induction of heat shock response. Uninephrectomized female, male, and ovariectomized female (Ovx) Wistar rats were subjected to 50 min renal ischemia followed by 2 (T2) and 24 (T24) hours of reperfusion. At T24 renal functional impairment was less severe and structural damage was less prominent in females vs. males or Ovx. Postischemic increase in S1R, pAkt, HSF-1, HSP72 levels were detected as early as at T2, while pHSP27 was elevated later at T24. Abundance of HSPs was higher in healthy female rats and remained higher at T2 and T24 (female vs. male or Ovx; resp.). We propose a S1R-dependent mechanism, which contributes to the relative renoprotection of females after I/R injury by enhancing the heat shock response. This article is protected by copyright. All rights reserved.
- Ultrasound detection of insulin-induced lipohypertrophy in Type 1 and Type 2 diabetes. [Journal Article]
- DMDiabet Med 2018 Jun 16
- CONCLUSIONS: The ultrasound detection of lipohypertrophy is consistent with clinical examination and is reproducible using a defined echo signature. This article is protected by copyright. All rights reserved.
- Diabetes associated with immune checkpoint inhibition: presentation and management challenges. [Case Reports]
- DMDiabet Med 2018 Jun 16
- CONCLUSIONS: Onset of diabetes occurred within 12 weeks of commencing therapy. Anti- GAD antibodies were present in six people. Retrospective testing of islet antibodies in pre-treatment samples was possible in two people and this revealed anti-GAD seroconversion in the first and high anti-GAD titres pre and post-treatment in the second person. Six people had high risk HLA haplotypes. Clinical and genetic factors are described and compared with previously published cases. This article is protected by copyright. All rights reserved.
- Prediabetes and diabetes are both risk factors for adverse outcomes in infective endocarditis. [Journal Article]
- DMDiabet Med 2018 Jun 16
- CONCLUSIONS: In addition to diabetes, prediabetes was also associated with a higher risk of in-hospital and long-term mortality among people with infective endocarditis. Therefore, attention should be paid to this population. This article is protected by copyright. All rights reserved.
New Search Next
- A Randomized Controlled Feasibility Trial in Behavioral Weight Management for Underserved Postpartum African American Women: The RENEW Study. [Journal Article]
- PCPrev Chronic Dis 2018 Jun 14; 15:E77
- We aimed to test the feasibility of an in-person behavioral weight-loss intervention for underserved postpartum African American women with overweight or obesity in an urban hospital setting. Partici...
We aimed to test the feasibility of an in-person behavioral weight-loss intervention for underserved postpartum African American women with overweight or obesity in an urban hospital setting. Participants were randomized to an intervention of a culturally tailored adaptation of the Diabetes Prevention Program or usual care. The primary outcome was program satisfaction. Women who completed the intervention reported higher levels of satisfaction with the program, despite low attendance rates at group meetings. The intervention was not feasible because of these low rates of attendance and high rates of attrition after randomization. Offering the program electronically and off-site for convenience and more psychosocial support for postpartum women with obesity may improve feasibility.