Positive effects of dietary supplementation of three probiotics on milk yield, milk composition and intestinal flora in Sannan dairy goats varied in kind of probiotics.

In this study, we investigated the effects of Saccharomyces cerevisiae (SC), Bacillus subtilis (BS) and Enterococcus faecalis (EF), singly and in combination, on the dry matter intake (DMI), milk production and composition, and faecal microflora of Saanen dairy goats. Fifty goats were randomly divided into five groups: (a) basal diet (control); (b) basal diet + SC; (c) basal diet + BS; (d) basal diet + EF; and (e) basal diet + mixed probiotics. Each treated animal received 5 g/d of probiotics for a total administration of 5 × 1,011 CFU/goat per day. The inclusion of B. subtilis and E. faecalis in the diet of lactating Saanen goats increased DMI (p < .05). Enhanced milk yield was observed with BS and EF. Milk fat percentage was significantly increased by feeding mixed probiotics compared with the control (p < .05); supplying SC, BS and mixed probiotics enhanced the protein percentage (p < .05). The milk lactose percentage in the SC and BS groups was higher than in the control (p < .05). The amount of milk total solids was higher after feeding EF or mixed probiotics than in the control group (p < .05). Non-fat solids showed no notable differences among groups (p > .05). There was no significant influence on gut bacterial abundance and diversity from adding these three probiotics, singly or in combination. Bacteroidales, Escherichia-Shigella and Christensenellaceae abundances were decreased by supplying these probiotics but Succinivibrionaceae increased. In conclusion, there were positive influences of probiotic feed supplementation on intake, milk performance and intestinal microecology.

The Worsening Renal Perfusion Index Predicts the Prognoses of Heart Failure Patients Treated with Sacubitril/Valsartan.

INTRODUCTION: Sacubitril/valsartan (S/V) reduces all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF), but it may decline their estimated glomerular filtration rates (eGFR). In addition to eGFR, this clinical study aimed to develop a blood urea nitrogen (BUN)-based index to evaluate the status of renal perfusion and then identify predictors of all-cause death or heart transplant in patients with HFrEF receiving S/V. METHODS: From the recruited 291 patients with HFrEF who were prescribed S/V from March 2017 to March 2019, we collected demographic, drug history, laboratory, echocardiographic, and clinical data from 1 year before S/V initiation until December 2020. Regression analysis was conducted by fitting Cox's models with time-dependent covariates for the survival time and applying the modern stepwise variable selection procedure. The smoothing spline method was used to detect nonlinearity in effect and yield optimal cut-off values for continuous covariates. RESULTS: In the Cox's model, decreased hemoglobin level, decreased mean left ventricular ejection fraction, declined daily dose of S/V, decreased eGFR within 3 months, and increased BUN levels within 1 month and 9 months over time were significantly associated with an increased risk of all-cause death or heart transplant in patients with HFrEF. CONCLUSIONS: Adequate maintenance of renal perfusion is crucial for the continuous use of S/V and to avoid worsening renal function in patients with HFrEF. We defined the maximum increase in BUN levels within a specified period as the Worsening Renal Perfusion Index (WRPSV Index) to capture the prognostic effect of renal hypoperfusion in patients with HFrEF.

Cyclooxygenase-2 expression is up-regulated by 2-aminobiphenyl in a ROS and MAPK-dependent signaling pathway in a bladder cancer cell line.

Overexposure to biphenyl amine compounds, which are found in smoke and azo-dyes, is linked to the occurrence of bladder cancer. However, the molecular mechanisms of biphenyl amine compound-induced bladder cancer are still unclear. Many studies have demonstrated that overexpression of cyclooxygenase-2 (COX-2) in neoplastic lesions is associated with carcinogenesis. In this study, we have demonstrated that 2-aminobiphenyl (2-ABP) up-regulated the expression of COX-2 in a dose- and time-dependent manner in TSGH-8301 bladder cancer cells. This 2-ABP-induced COX-2 expression was attenuated by ROS scavenger NAC and NADPH oxidase inhibitors apocynin and DPI. The p22phox subunit of NADPH oxidase, but not p67, and Nox2 was up-regulated by 2-ABP. Knocking down p22phox by siRNA significantly reduced 2-ABP-induced COX-2 expression. Furthermore, 2-ABP also activated the ERK/JNK-AP1 pathways, and this effect was also abolished by NADPH oxidase inhibitors. Blocking the ERK/JNK-AP1 signaling pathways by pharmacological inhibitors attenuated 2-ABP-induced COX-2 expression. Overexpression of the upstream ERK activator MEK1 significantly and consistently increased 2-ABP-mediated COX-2 expression. Transfection of a dominant negative c-Jun mutant, TAM-67, blocked 2-ABP-mediated COX-2 expression, demonstrating that c-Jun was responsible for the transcriptional activation. Taken together, these results demonstrate that 2-ABP induces the carcinogenic factor COX-2 and that this induction is mediated through NADPH oxidase-derived ROS-dependent JNK/ERK-AP-1 pathways.

Anemia warrants treatment to improve survival in patients with heart failure receiving sacubitril-valsartan.

Angiotensin inhibition remains a cornerstone for pharmacologic management of heart failure (HF), despite being associated with decreased hemoglobin (Hb) levels. To investigate the effect of anemia and its treatment on patients with HF treated with sacubitril-valsartan (S/V), we conducted a retrospective study involving patients with recorded left ventricular ejection fractions (LVEFs) of < 40% between January 2017 and December 2019. We identified 677 patients, 37.7% of whom received S/V. The median follow-up period was 868 days. Anemia was associated with significantly decreased survival, increased mortality rates, and higher all-cause hospitalizations in S/V-using patients. We further analyzed 236 patients with HF who had recorded renal function, LVEF, and Hb at the initiation of S/V therapy to identify Hb patterns after S/V therapy. Of these patients, 35.6% exhibited decreasing Hb 12 months after S/V initiation, which was associated with a lower survival rate. Among the patients who were not prescribed anemia medications, Hb of ≥ 12 (vs. < 12 g/dL) was associated with a higher survival rate; this association was absent among the patients undergoing anemia treatment. These results emphasize that consistent screening and treatment for anemia should be implemented to reduce the morbidity and mortality of patients with HF receiving S/V.