Rumen microbiota responses to the enzymatic hydrolyzed cottonseed peptide supplement under high-concentrate diet feeding process.

In current dairy production, dietary energy is always excessively provided with a high-concentrate diet feeding to improve milk production. However, this feeding practice disturbed the rumen microbial ecosystem and the balance between ruminal energy and nitrogen, resulting in decreased nutrient fermentability, which in turn declined the milk yield of dairy cows. Therefore, supplementation of dietary degradable nitrogen may be helpful for high dairy production. In this study, we evaluated the regulatory effects of easily utilized enzymatic hydrolyzed cottonseed peptide (EHP) supplements on rumen microbiota communities and rumen nutrient fermentability under high-concentrate feeding. For this purpose, a gradient concentrate of EHP (from 0.2 to 1.0%) was added to the high-concentrate basal substrates for an in vitro experiment. Each treatment contained three replicates, with three bottles in each replicate. Rumen fermentable parameters included microbial protein content, volatile fatty acids, and ammonia-N; the rumen nutrient degradability of dry matter, crude protein, neutral detergent fiber, acid detergent fiber, ether extracts, calcium, and phosphorus were further investigated after in vitro fermentation for 72 h. Then, rumen microbiota communities and their correlation with ruminal fermentation parameters and rumen nutritional degradability were analyzed to understand the regulatory mechanism of the EHP supplements on rumen fermentability. Results indicate that treatment with 0.6% of EHP supplements had the highest content of acetate, butyrate, and neutral detergent fiber degradability among all treatments. Furthermore, EHP supplements significantly increased the relative abundance of rumen cellulose and starch-degrading bacteria such as Ruminococcus, Bifidobacterium, and Acetitomaculum, and the high nitrogen utilizing bacteria Butyrivibrio and Pseudobutyrivibrio, which may further promote the rumen carbohydrate and nitrogen metabolism. In summary, supplementation of easily degraded small peptides helps reestablish rumen energy and nitrogen balance to promote the rumen fermentable functions and nutritional degradability under high-concentrate diet feeding circumstances. These findings may further promote dairy production.

Gut microbiota and differential genes-maintained homeostasis is key to maintaining health of individuals with Yang-deficiency constitution.

OBJECTIVE: Yang-deficiency constitution (YADC) is a common unbalanced constitution that predisposes individuals to certain diseases. However, not all people with YADC manifest develop diseases. This calls for delineation of the underlying molecular mechanisms. Previous studies suggested that the gut microbiota and gene differential expression should be considered. METHODS: In the present study, we compared profiles of gut microbiota between four healthy YADC individuals and those of five healthy balanced constitution (BC) counterparts, based on 16S rRNA gene sequence analysis. Furthermore, YADC relevant genes identified by comparing 62 healthy YADC and 58 healthy BC individuals in total to perform intersection analysis, functional clustering and pathway enrichment analyses. RESULTS: The levels of harmful gut microbiota (Prevotellaceae, LDA score > 4.0, P = 0.0141) and beneficial gut microbiota (Ruminococcaceae, LDA score > 4.0, P = 0.0025, Faecalibacterium, LDA score > 4.0, P = 0.0484) were both elevated in healthy YADC individuals. Also, we found that the specific metabolic pathway with 2, 6-Dichloro-p-hydroquinone 1, 2-Dioxygenase (PcpA) as the core in gut microbiota and the glutathione transferase activity has been enriched by YADC relevant genes in healthy YADC individuals were both responsible for the detoxification of halogenated aromatic hydrocarbon substances. CONCLUSIONS: Both beneficial and harmful factors had been detected in healthy YADC individuals, functionally, they may have triggered homeostasis to maintain the health of individuals with YADC. The homeostasis may be maintained by beneficial and harmful factors from gut flora and genes. Future studies are expected to focus on halogenated aromatic hydrocarbons and their detoxification processes.

Isoforskolin, an adenylyl cyclase activator, attenuates cigarette smoke-induced COPD in rats.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by limited airflow due to pulmonary and alveolar abnormalities from exposure to cigarette smoke (CS). Current therapeutic drugs are limited and the development of novel treatments to prevent disease progression is challenging. Isoforskolin (ISOF) from the plant Coleus forskohlii is an effective activator of adenylyl cyclase (AC) isoforms. Previously we found ISOF could attenuate acute lung injury in animal models, while the effect of ISOF on COPD has not been elucidated. PURPOSE: In this study, we aimed to evaluate the efficacy of ISOF on COPD and reveal its potential mechanisms. METHODS: A rat model of COPD was established by long-term exposure to CS, then the rats were orally administered with ISOF (0.5, 1 and 2 mg/kg). The pulmonary function, lung morphology, inflammatory cells and cytokines in serum or bronchoalveolar lavage fluid (BALF) were evaluated. Transcriptomics, proteomics and network pharmacology analysis were utilized to identify potential mechanisms of ISOF. Droplet digital PCR was used to detect the mRNA expression of AC1-10 in donor lung tissues. AC activation was determined in recombinant human embryonic kidney 293 (HEK293) cells stably expressing human AC isoforms. In addition, ISOF caused trachea relaxation ex vivo were assessed in isolated trachea rings from guinea pigs. RESULTS: ISOF significantly ameliorated pathological damage of lung tissue and improved pulmonary function in COPD rats. ISOF treatment decreased the number of inflammatory cells in peripheral blood, and also the levels of pro-inflammatory cytokines in serum and BALF. Consistent with omics-based analyses, ISOF markedly downregulated the mTOR level in lung tissue. Flow cytometry analysis revealed that ISOF treatment reduced the ratio of Th17/Treg cells in peripheral blood. Furthermore, the expression levels of AC1 and AC2 are relatively higher than other AC isoforms in normal lung tissues, and ISOF could potently activate AC1 and AC2 in vitro and significantly relax isolated guinea pig trachea. CONCLUSION: Collectively, our studies suggest that ISOF exerts its anti-COPD effect by improving lung function, anti-inflammation and trachea relaxation, which may be related to AC activation, mTOR signaling and Th17/Treg balance.

Aconiti lateralis Radix Praeparata inhibits Alzheimer's disease by regulating the complex regulation network with the core of GRIN1 and MAPK1.

CONTEXT: Current medicine for Alzheimer's disease (AD) cannot effectively reverse or block nerve injury. Traditional Chinese Medicine practice and research imply Aconiti lateralis Radix Praeparata (Fuzi) may meet this goal. OBJECTIVE: Analysing the anti-AD effect of Fuzi and its potential molecular mechanism. MATERIALS AND METHODS: AD model cells were treated with Fuzi in 0-300 mg/mL for 24 h in 37 °C. The cell viability (CV) and length of cell projections (LCP) for each group were observed, analysed, and standardised using control as a baseline (CVs and LCPs). The Fuzi and AD relevant genes were identified basing on databases, and the molecular mechanism of Fuzi anti-AD was predicted by network analysis. RESULTS: Experiment results showed that Fuzi in 0.4 mg/mL boosted LCP (LCPs = 1.2533, p ≤ 0.05), and in 1.6-100 mg/mL increased CV (CVs from 1.1673 to 1.3321, p ≤ 0.05). Bioinformatics analysis found 17 Fuzi target genes (relevant scores ≥ 20), showing strong AD relevant signals (RMS_p ≤ 0.05, related scores ≥ 5), enriched in the pathways regulating axon growth, synaptic plasticity, cell survival, proliferation, apoptosis, and death (p ≤ 0.05). Especially, GRIN1 and MAPK1 interacted with APP protein and located in the key point of the "Alzheimer's disease" pathway. DISCUSSION AND CONCLUSIONS: These results suggest that Fuzi may have therapeutic and prevention potential in AD, and GRIN1 and MAPK1 may be the core of the pathways of the Fuzi anti-AD process. Fuzi should be studied more extensively, especially for the prevention of AD.