Purinergic P2X3 receptors in the carotid body as new therapeutic targets for controlling heart failure.

Heart failure is associated with multiple mechanisms, including sympatho-excitation, and is one of the leading causes of death worldwide. Enhanced carotid body chemoreflex function is strongly related to excessive sympathetic nerve activity and sleep-disordered breathing in heart failure. How to reduce the excitability of the carotid body is still scientifically challenging. Both clinical and experimental evidence have suggested that targeting purinergic receptors is of great potential to combat heart failure. In a recent study, Lataro et al. (Lataro et al. in Nat Commun 14:1725, 5) demonstrated that targeting purinergic P2X3 receptors in the carotid body attenuates the progression of heart failure. Using a series of molecular, biochemical, and functional assays, the authors observed that the carotid body generates spontaneous, episodic burst discharges coincident with the onset of disordered breathing in male rats with heart failure, which was generated by ligating the left anterior descending coronary artery. Moreover, P2X3 receptor expression was found to be upregulated in the petrosal ganglion chemoreceptive neurons of rats with heart failure. Of particular note, treatment with a P2X3 antagonist rescued pathological breathing disturbances, abolished episodic discharges, reinstated autonomic balance, attenuated cardiac dysfunction, and reduced the immune cell response and plasma cytokine levels in those rats.

P2X7 receptor involved in antitumor activity of atractylenolide I in human cervical cancer cells.

Atractylenolide I (Atr-I) was found to sensitize a variety of human cancer cells in previous studies. Purinergic P2X7R plays important role in different cancers. However, whether Atr-I could generate antitumor activity in human cervical cancer cells and P2X7R get involved in this effect remain unclear. In this study, Hela (HPV 18 +) and SiHa (HPV 16 +) cells were treated with different doses of Atr-I. The results indicated that agonist and antagonist of P2X7 receptors, BzATP and JNJ-47965567 (JNJ), could suppress the proliferation of Hela and SiHa cells. Atr-I demonstrated a considerable antitumor effect in both human cervical cancer cells in vitro. Atr-I combined with P2X7R agonist, BzATP, restored Atr-I-induced growth inhibition in Hela cells but not in SiHa cells. However, the combinatorial treatment of P2X7R antagonist JNJ and Atr-I has an additive effect on cell growth inhibition in SiHa cells rather than in Hela cells. It implied that P2X7R would get involved in the anti-human cervical cancer cells effect of Atr-I.

Compound enzyme preparation supplementation improves the production performance of goats by regulating rumen microbiota.

Enzyme preparation is one of the widely used additives in ruminant production. However, a suitable method of adding compound enzyme preparation (CEP) to the feeds is still lacking. This study investigated the effect of adding CEP on the diet of goats. Twenty 4-month-old Boer goats were randomly assigned to four groups. The dietary treatments contained different CEPs (Saccharomyces cerevisiae cells, cellulase, xylanase, ß-glucanase amylase, and protease) at the concentrations of 0, 0.25, 0.50, and 0.75 g/kg of feed provided for a period of 56 days. Adding CEP in goat feed significantly increased average daily gain (ADG) during the entire test period. The oxidative indices, hormones, and immune cells did not differ significantly among the different groups. CEP significantly increased the content of total volatile fatty acids measured at the end of the experiment on day 56 of the final normal feeding phase. 16S rDNA sequencing revealed that CEP increased the abundance of Ruminococcaceae in the rumen and g__norank_f__Eubacterium_coprostanoligenes_group, Oscillibacter g__unclassified_f__Ruminococcaceae, and g__unclassified_o__Oscillospirales in fecal matter collected on day 56 of the final normal feeding phase. However, CEP decreased the abundance of unclassified_f__Lachnospiraceae, norank_f__UCG-010, Butyrivibrio, and Saccharofermentans in the rumen. The abundance of Ruminococcaceae in the rumen and propionic acid was positively correlated with ADG. Function prediction showed that carbon fixation, carbohydrate digestion and absorption pathways were significantly enriched in rumen microbiota in the treatment group. The findings indicated that supplementation with 0.5 g CEP/kg of feed for 56 days significantly improves the production performance of goats without adverse health effects. KEY POINTS: • Feeding with compound enzyme preparation for 56 days significantly improved the productive performance but did not affect the antioxidative capacity and immunity of goats. • Supplementing compound enzyme preparation in diet could increase the relative abundance of Ruminococcus to increase the levels of short-chain fatty acids produced. • The most appropriate supplemental amount of compound enzyme preparation per kilogram of the diet was 0.5 g.

Multi-omics revealed the mechanism of feed efficiency in sheep by the combined action of the host and rumen microbiota.

This study was conducted to investigate potential regulatory mechanisms of feed efficiency (FE) in sheep by linking rumen microbiota with its host by the multi-omics analysis. One hundred and ninety-eight hybrid female sheep (initial body weight = 30.88 ± 4.57 kg; 4-month-old) were selected as candidate sheep. Each test sheep was fed in an individual pen for 60 days, and the residual feed intake (RFI) was calculated. The ten candidate sheep with the highest RFI were divided into the Low-FE group, and the ten with the lowest RFI were divided into the High-FE group, all selected for sample collection. The RFI, average daily gain and average daily feed intake were highly significantly different between the two experimental groups (P < 0.05). Compared with Low-FE group, the insulin-like growth factor-1 and very low-density lipoprotein in serum and the propionate in rumen significantly increased in High-FE group (P < 0.01), but the acetate:propionate ratio in rumen significantly decreased in High-FE group (P = 0.034). Metagenomics revealed Selenomonas ruminantium, Selenomonas sp. and Faecalibacterium prausnitzi i were key bacteria, and increased abundance of the genes encoding the enzymes for cellulose degradation and production of propionate in High-FE group. The results of proteomics and section showed the rumen papilla length (P < 0.001) and expression of carbonic anhydrase and Na+/K+-ATPase were significantly higher in High-FE group (P < 0.05). On the other hand, the acetyl-CoA content significantly increased in the liver of High-FE group (P = 0.002). The relative expression levels of insulin-like growth factor-1 and apolipoprotein A4 genes were significantly up-regulated in the liver of High-FE group (P < 0.01), but relative expression level of monoacylglycerol O-acyltransferase 3 gene was significantly down-regulated (P = 0.037). These findings provide the mechanism by which the collaborative interaction between rumen microbiota fermentation and host uptake and metabolism of fermentation products impacts feed efficiency traits in sheep.

Acupuncture methods for insomnia disorder in the elderly: protocol for a systematic review and network meta-analysis.

BACKGROUND: Insomnia disorder remains one of the most common sleep disorders in the elderly, with high prevalence and substantial consequences for patients' general health. Despite that increasing clinical trials have indicated that acupuncture seems to be effective for insomnia disorder in the elderly, comparative efficacy and safety of different acupuncture methods for elderly individuals with insomnia disorder has been unclear. Therefore, this protocol outlined a plan to evaluate and rank the efficacy and safety of various acupuncture approaches for insomnia disorder in the elderly. METHODS: A systematic search of 8 bibliographic databases will be conducted from their inception to 18 June 2023, including Cochrane Library, MEDLINE (via PubMed), Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and Chinese Biomedical Literature Database (CBM). Randomized controlled trials investigating acupuncture methods for insomnia disorder in the elderly, published in English or Chinese will be included. The primary outcome is sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). Two reviewers will independently perform study selection, data extraction and risk assessment of bias. The quality of included literatures will be appraised using Cochrane risk-of-bias tool (ROB 2.0). ADDIS (Aggregate Data Drug Information System) V.1.16.8 will be used to conduct Bayesian network meta-analysis. The quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation System (GRADE). DISCUSSION: In this study, the results will provide credible evidence to assess the efficacy and safety of acupuncture therapies for elderly patients with insomnia disorder, assisting patients, physicians and clinical research investigators to select the most appropriate acupuncture method. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered at OSF ( https://osf.io/3kjpq/ ) with a registration number https://doi.org/10.17605/OSF.IO/3KJPQ .

Extracellular polymeric substance profiling and biophysical analysis reveal influence factors of spontaneous flocculation in rich lipid alga Heveochlorella sp. Yu.

Microalgae harvest and lipid accumulation were important factors influencing commercialized development of microalgae biodiesel. Spontaneous flocculation was an ideal method in microalgae harvest, but few rich lipid microalgae could be harvested by spontaneous flocculation. Rich lipid alga Heveochlorella sp. Yu has a characteristic of spontaneous flocculation to be harvested. Heveochlorella sp. Yu has high lipid productivity (105.24 mg L-1 d-1) and fine spontaneous flocculation efficiency (82.93 %, 2 h) on early stationary phase (day 9). The polysaccharides consisting of glucose, mannose, galactose, rhamnose and fructose (8.67:4.90:3.27:2.16:1) in loose-bound extracellular polymeric substance (LB-EPS) might make great contribution in microalgae flocculation. Meanwhile, the zeta potential close to zero was also beneficial to microalgae flocculation. Besides, the adhesion free energy related with cells adhesion was detected by thermomechanical analysis. Afterward, Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory was utilized to quantitatively evaluate short-range interactions involved in the spontaneous aggregation among cells. Collectively, biophysical analyses indicated that content and composition of EPS, Zeta potential, thermodynamic parameter and total interaction based on XDLVO theory were closely connected with spontaneous flocculation in microalga Yu. Our study provided a harvest-simplified process of rich microalgae, which proposes a new idea for commercial development of microalgae biodiesel.