Objective: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has been proposed to be a downstream mediator of neuroinflammation in individuals with Parkinson’s disease (PD). However, its involvement across disease stages and related synucleinopathies, such as multiple system atrophy (MSA), remains unclear. We aimed to analyze the peripheral mRNA expression of NLRP3-related genes and cytokines across individuals with isolated REM sleep behavior disorder (iRBD), early-stage PD, late-stage PD, and MSA. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 151 participants: 35 healthy controls (HCs), 31 patients with iRBD, 41 patients with early-stage PD, 21 patients with late-stage PD, and 23 patients with MSA. mRNA expression was measured using quantitative real-time polymerase chain reaction. Statistical comparisons were performed using analysis of variance (ANOVA) or Welch’s ANOVA, and associations with clinical variables were analyzed through stepwise multiple linear regression. Results: NLRP3 expression was significantly lower in patients with iRBD (p=0.0263) and patients with early-stage PD (p= 0.0101) than in HCs. NIMA-related kinase 7 (NEK7) expression progressively decreased across the disease spectrum (HCs vs. patients with early-stage PD, p=0.0008; vs. patients with late-stage PD, p<0.0001). In contrast, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 were elevated in patients with PD, especially those in the late stages. Levels of patients with MSA resembled those of HCs but differed from those of patients with PD. Interleukin (IL)-1β and IL-18 levels were not significantly different. In patients with early-stage PD, NLRP3 expression was negatively correlated with disease duration, the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part II score, and the cognitive score. Conclusion Our findings challenge the prevailing hypothesis that NLRP3 inflammasome activation directly contributes to PD pathogenesis. Instead, the observed increase in ASC and caspase-1 expression suggests the potential involvement of alternative inflammasome pathways during disease progression.

Objective: The purpose of this survey was to estimate the prevalence of viral load (VL) suppression and emergence of HIV drug resistance (HIVDR) among individuals receiving antiretroviral therapy (ART) for 36 months or longer in Viet Nam using a nationally representative sampling method. Methods: The survey was conducted between May and August 2014 using a two-stage cluster design. Sixteen ART clinics were selected using probability proportional to proxy size sampling, and patients receiving ART for at least 36 months were consecutively enrolled. Epidemiological information and blood specimens were collected for HIV-1 VL and HIVDR testing; HIVDR was defined by the Stanford University HIVDR algorithm. Results: Overall, 365 eligible individuals were recruited with a mean age of 38.2 years; 68.4% were men. The mean time on ART was 75.5 months (95% confidence interval [CI]: 69.0–81.9 months), and 93.7% of the patients were receiving non-nucleoside reverse transcriptase inhibitor-based regimens. Of the 365 individuals, 345 (94.7%, 95% CI: 64.1–99.4%) had VL below 1000 copies/mL and 19 (4.6%, 95% CI: 2.8-–7.5) had HIVDR mutations. Discussion Our nationally representative survey found a high level of VL suppression and a low prevalence of HIVDR among individuals who received ART for at least 36 months in Viet Nam. Continued surveillance for HIVDR is important for evaluating and improving HIV programs.

In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, an extract of the dried whole plants of Euphorbia supina Rafin was found to significantly inhibit sEH activity in vitro. Phytochemical investigation of E. supina resulted in isolation of 17 compounds (1 - 17), including triterpenes (1 - 4), phenolic compounds (5 - 8), and flavonoid derivatives (9 - 17). The structures of the isolated compounds were established mainly by extensive analysis of the 1D and 2D NMR, and MS data. All of the isolated compounds were evaluated for their sEH inhibitory activity. Among the isolated phenolic compounds, 8 was identified as a significant inhibitor of sEH, with an IC50 value of 15.4 +/- 1.3 microM. Additionally, a kinetic analysis of isolated compounds (2, 5, 8 - 11, 13, and 17) indicated that the inhibitory effects of flavonoid derivatives 10 and 11 were of mixed-type, with inhibitory constants (Ki) ranging from 3.6 +/- 0.8 to 21.8 +/- 1.0 microM, whereas compounds 2, 5, 8, 9, 13, and 17 were non-competitive inhibitors with inhibition Ki values ranging from 3.3 +/- 0.2 to 39.5 +/- 0.0 microM.
Euphorbia* ; Euphorbiaceae ; Inhibitory Concentration 50 ; Phenol ; Triterpenes

Phytochemical investigation of Kandelia candel resulted in the isolation of six triterpenes (1 - 5) and two glyceryl glycosides (6 and 7) and their structures were determined by comparing the spectroscopic data with those of reported values. In present study, we described the inhibitory effects of fractions and isolated compounds from K. candel on pro-inflammatory cytokines (IL-12 p40, IL-6, and TNF-alpha) production in lipopolysaccharide (LPS) stimulated bone marrow-derived dendritic cells (BMDCs). Results indicated that compounds 3, 6, and 7 showed potent inhibition on IL-6 production (IC50 values at less than 0.5 microM, respectively). Meanwhile, compounds 6 and 7 exhibited strong inhibitory effects on the production of TNF-alpha (IC50 values of 1.7 +/- 0.1 and 5.5 +/- 0.2 microM). Compounds 1 and 3 were also showed the inhibitory effects on IL-12 p40 production (IC50 values of 8.9 +/- 0.4 and 3.3 +/- 0.1 microM, respectively).
Cytokines ; Dendritic Cells ; Glycosides* ; Interleukin-12 ; Interleukin-6 ; Rhizophoraceae* ; Triterpenes* ; Tumor Necrosis Factor-alpha