A microbiome-directed therapeutic food for children recovering from severe acute malnutrition.

Severe acute malnutrition (SAM), defined anthropometrically as a weight-for-length z-score more than 3 standard deviations below the mean (WLZ<-3), affects 19 million children under 5-years-old worldwide. Complete anthropometric recovery after standard inventions is rare with children often left with moderate acute malnutrition (MAM; WLZ -2 to -3). Here we conduct a randomized controlled trial (RCT), involving 12-18-month-old Bangladeshi children from urban and rural sites, who after hospital-based treatment for SAM received a 3-month intervention with a microbiota-directed complementary food (MDCF-2) or a ready-to-use supplementary food (RUSF) as they transitioned to MAM. The rate of WLZ improvement was significantly greater with MDCF-2 than the more calorically-dense RUSF, as we observed in a previous RCT of Bangladeshi children with MAM without antecedent SAM. A correlated meta-analysis of aptamer-based measurements of 4,520 plasma proteins in this and the prior RCT revealed 215 proteins positively-associated with WLZ (prominently those involved in musculoskeletal and CNS development) and 44 negatively-associated proteins (related to immune activation), with a significant enrichment in levels of the positively WLZ-associated proteins in the MDCF-2 arm. Characterizing changes in 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome, its transition as each child achieves a state of MAM, and how specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and the rescue of growth faltering. These results provide a rationale for further testing the generalizability of the efficacy of MDCF and identify biomarkers for defining treatment responses.

Using heat shock protein (HSP) inducers as an approach to increase the viability of sterlet (Pisces; Acipenseridae; Acipenser ruthenus) cells against environmental diazinon toxicity.

Diazinon (DZN) is an organophosphate pesticide frequently used in agriculture and released into aquatic environments. In this study, sterlet sturgeon cells were exposed to DZN to investigate possible defense mechanisms via HSP induction (HSPi). Liver, kidney, and gill cells of Acipenser ruthenus were isolated and cultured and then treated with HSPi (Pro-Tex®, amygdalin, and a novel pirano-piranazole-based synthesized compound: SZ) in the presence and absence of DZN. MTT assays were used to evaluate the effects of different HSPis and their combinations with DZN. Western blotting analysis was conducted to evaluate HSP27, HSP70, and HSP90 expression patterns in each group. The highest rates of caspase-3 and caspase-8 activities were found in the DZN group, whereas HSPi treatment resulted in the lowest rates. The combination of HSPi+DZN resulted in increased HSP levels and antioxidant parameters but decreased cortisol, immune parameters, and metabolic enzymes. Many of the studied parameters (caspases, acetylcholinesterase, antioxidant, immune, and metabolic parameters) showed significant correlations with HSP expression, indicating that HSPs may be associated with markers of sterlet cell health. The results of this study demonstrate that using HSP inducers may be a powerful and reliable way to increase A. ruthenus resistance prior to exposure to DZN.

The Impact of STAT3 rs1053005 Variation on Type 1 Diabetes Mellitus Susceptibility: Association Study and in Silico Analysis.

AIMS: Type 1 diabetes (T1DM) is an autoimmune disorder with multiple genetic and environmental risk factors that are still poorly understood. The signal transducer and activator of transcription (STAT) proteins play a pivotal role in immune-cell genesis and regulation. This study aimed to determine the effect of rs1053005 single nucleotide polymorphism (SNP) in 3'-UTR of STAT3 mRNA on the susceptibility to T1DM in an Iranian population. METHODS: PCR-RFLP was conducted on 250 T1DM patients and 250 control cases to assess STAT3 rs1053005 polymorphism. Moreover, several bioinformatics tools were employed to identify the candidate miRNAs targeting the STAT3 mRNA region under study as well as the effect of rs1053005 on their binding site. RESULTS: Significant variations in the distribution of genotypes and alleles were seen between cases and controls. The comparison results of the frequency of AA, AG, and GG genotypes between T1DM patients and control groups were 49.2% versus 64.8%, 39.2 versus 30%, and 11.6 versus 5.2%, respectively. Individuals who carried GG genotype were at 2.93-fold increased risk of developing T1DM and the G allele was associated with 1.79-fold higher T1DM risk. Bioinformatics analysis demonstrated that due to rs1053005, the interaction of 3 miRNAs were broken, 3 were weakened, 2 were reinforced, and 4 binding sites were created. CONCLUSION: The result of this study indicates an association between STAT3 rs1053005 and T1DM susceptibility which may be due to interference of the SNP with native-binding site of some predicted miRNAs.