Effects of Fermentation Temperature and Time on the Physicochemical and Sensory Characteristics of Douchi

In this paper studies were made to generate data on the physicochemical and sensory characteristics of douchi prepared by fermentation at different temperatures for variable time prior to mechanical drying. Fermentation was carried out at 20, 30 and 40 °C for 12, 24, 48 and 72 h prior to drying at 50 °C. Physiochemical and sensory characteristics were monitored. The results show that fermentation conditions of 30 °C for 24 h and 30 °C for 48 h bring about more acidic douchi with superior sensory characteristics

Inhibition of STAT3 activation mediated by toll-like receptor 4 attenuates angiotensin II-induced renal fibrosis and dysfunction

Background and Purpose: Hypertension adversely affects the kidney and is the second leading cause of kidney failure. Overproduction of angiotensin II greatly contributes to the progression of hypertensive kidney disease. Angiotensin II has recently been shown to activate STAT3 in cardiovascular cells. However, the underlying mechanisms of STAT3 activation by angiotensin II and downstream functional consequences in the kidneys are not fully understood. Experimental Approach: C57BL/6 mice were treated with angiotensin II by subcutaneous infusion for 1 month to develop nephropathy. Mice were treated with either adeno-associated virus expressing STAT3 shRNA or STAT3 inhibitor, S3I-201. Human archival kidney samples from five patients with hypertension and five individuals without hypertension were also examined. In vitro, STAT3 was blocked using siRNA or STAT3 inhibitor S3I-201 in the renal proximal tubular cell line, NRK52E, after exposure to angiotensin II. Key Results: Angiotensin II activated STAT3 in kidney epithelial cells through engaging toll-like receptor 4 (TLR4) and JAK2, which was independent of IL-6/gp130 and angiotensin AT1 receptors. Angiotensin II-mediated STAT3 activation increased fibrotic proteins and resulted in renal dysfunction. Both STAT3 inhibition by the low MW compound S3I-201 and TLR4 deficiency normalized renal fibrosis and dysfunction caused by Ang II in mice, without affecting hypertension. Conclusions and Implications: Our study reveals a novel mechanism of STAT3 activation, induced by angiotensin II, in kidney tissues and highlights a translational significance of a STAT3 inhibitor as potential therapeutic agent for hypertensive kidney disease

Elucidating the mechanism by which synthetic helper peptides sensitize Pseudomonas aeruginosa to multiple antibiotics

The emergence and rapid spread of multi-drug resistant (MDR) bacteria pose a serious threat to global healthcare. There is an urgent need for new antibacterial substances or new treatment strategies to deal with the infections by MDR bacterial pathogens, especially the Gram-negative pathogens. In this study, we show that a number of synthetic cationic peptides display strong synergistic antimicrobial effects with multiple antibiotics against the Gram-negative pathogen Pseudomonas aeruginosa. We found that an all-D amino acid containing peptide called D-11 increases membrane permeability by attaching to LPS and membrane phospholipids, thereby facilitating the uptake of antibiotics. Subsequently, the peptide can dissipate the proton motive force (PMF) (reduce ATP production and inhibit the activity of efflux pumps), impairs the respiration chain, promote the production of reactive oxygen species (ROS) in bacterial cells and induce intracellular antibiotics accumulation, ultimately resulting in cell death. By using a P. aeruginosa abscess infection model, we demonstrate enhanced therapeutic efficacies of the combination of D-11 with various antibiotics. In addition, we found that the combination of D-11 and azithromycin enhanced the inhibition of biofilm formation and elimination of established biofilms. Our study provides a realistic treatment option for combining close-to-nature synthetic peptide adjuvants with existing antibiotics to combat infections caused by P. aeruginosa

Effects of Fermentation Temperature and Time on the Physicochemical and Sensory Characteristics of Douchi

In this paper studies were made to generate data on the physicochemical and sensory characteristics of douchi prepared by fermentation at different temperatures for variable time prior to mechanical drying. Fermentation was carried out at 20, 30 and 40 °C for 12, 24, 48 and 72 h prior to drying at 50 °C. Physiochemical and sensory characteristics were monitored. The results show that fermentation conditions of 30 °C for 24 h and 30 °C for 48 h bring about more acidic douchi with superior sensory characteristics

Enhanced production of dimethyl phthalate-degrading strain Bacillus sp. QD14 by optimizing fermentation medium

Background: Integrated statistical experimental designs were applied to optimize the medium constituents for the production of a dimethyl phthalate (DMP)-degrading strain Bacillus sp. QD14 in shake-flask cultures. A Plackett\u2013Burman design (PBD) was applied to screen for significant factors, followed by the Steepest Ascent Method (SAM) to find the nearest region of maximum response. A Box\u2013Behnken design (BBD) of the Response Surface Methodology (RSM) was conducted to optimize the final levels of the medium components. Results: After the regression equation and response surface contour plots were analyzed, the concentrations of glucose, corn meal and NaCl were found to significantly influence the biomass of DMP-degrading bacteria. A combination of 22.88 g/L of glucose, 11.74 g/L of corn meal, and 10.34 g/L of NaCl was optimum for maximum biomass production of Bacillus sp. QD14. A 57.11% enhancement of the biomass production was gained after optimization in shake-flask cultivation. The biomass production of Bacillus sp. QD14 reached 9.13 \ub1 0.29 7 108 CFU/mL, which was an excellent match for the predicted value, and the mean value of the match degree was as high as 99.30%. Conclusion: In this work, the key factors affected by the fermentation of DMP-degrading strain Bacillus sp. QD14 were optimized by PBD, SAM and BBD (RSM); the yield was increased by 57,11% in the conditions in our study. We propose that the conditions optimized in the study can be applied to the fermentation for commercialization production

Xin-Li-Fang efficacy and safety for patients with chronic heart failure: A study protocol for a randomized, double-blind, and placebo-controlled trial

IntroductionXin-Li-Fang (XLF), a representative Chinese patent medicine, was derived from years of clinical experience by academician Chen Keji, and is widely used to treat chronic heart failure (CHF). However, there remains a lack of high-quality evidence to support clinical decision-making. Therefore, we designed a randomized controlled trial (RCT) to evaluate the efficacy and safety of XLF for CHF.Methods and designThis multicenter, double-blinded RCT will be conducted in China. 300 eligible participants will be randomly assigned to either an XLF group or a control group at a 1:1 ratio. Participants in the XLF group will receive XLF granules plus routine care, while those in the control group will receive placebo granules plus routine care. The study period is 26 weeks, including a 2-week run-in period, a 12-week treatment period, and a 12-week follow-up. The primary outcome is the proportion of patients whose serum NT-proBNP decreased by more than 30%. The secondary outcomes include quality of life, the NYHA classification evaluation, 6-min walking test, TCM symptom evaluations, echocardiography parameters, and clinical events (including hospitalization for worsening heart failure, all-cause death, and other major cardiovascular events).DiscussionThe results of the study are expected to provide evidence of high methodological and reporting quality on the efficacy and safety of XLF for CHF.Clinical trial registrationChinese Clinical Trial Registration Center (www.chictr.org.cn). The trial was registered on 13 April 2022 (ChiCTR2200058649)

Factors related to the length of stay for major depressive disorder patients in China: A real-world retrospective study

BackgroundAs numerous patients with depression have to be hospitalized because of various reasons, the demand far exceeds the limited bed count in the psychiatry department. Controlling the length of stay (LOS) of the patient is gradually being considered an effective method to alleviate this problem. Given the lack of statistical evidence of the LOS of patients with major depressive disorder (MDD) in China and the strain on the limited psychiatric resources, the purpose of our study was to investigate the LOS of patients with MDD among in-patient samples and to analyze related factors of the LOS in China by building a regression model.MethodThe data were exported from the electronic medical record system. A total of three categories of independent variables were enrolled in our study, namely, demographic, clinical, and biochemical. Univariate analysis and binominal regression analysis were applied comprehensively to find the factors related to the LOS among MDD samples. The discrimination accuracy of the model was evaluated by the receiver operating characteristic (ROC) analysis. ROC analysis indicated that the discrimination accuracy of our model was acceptable (AUC = 0.790, 95% CI = 0.714–0.865, P < 0.001).ResultA total of 254 patients were finally brought into analysis after filtering. Regression analysis indicated that abnormal LDL was the only risk factor of long LOS (OR = 3.352, 95% CI = 1.087–10.337, P = 0.035) among all the kinds of variables. Notably, in the statistically irrelevant factors of the LOS, the category of anti-depressant drugs [serotonin–norepinephrine reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI)] prescribed to patients with MDD was not associated statistically with the LOS, which was against our initial hypothesis that the LOS of patients with MDD treated with SNRI would vary from that of the patients treated with SSRI.ConclusionUp to our knowledge, our research is the first study to show the potential factors related to the LOS from various domains, especially biochemical indexes, and the effect of drugs, among clinical patients with MDD in China. Our results could provide a theoretical reference for efficient psychiatry hospitalization management and prioritization of allocating medical resources. Future studies are required for updating independent variables which are potentially related to the LOS and verifying existing results in a larger sample

Endoribonuclease YbeY Is Essential for RNA Processing and Virulence in Pseudomonas aeruginosa

Posttranscriptional regulation plays an essential role in the quick adaptation of pathogenic bacteria to host environments, and RNases play key roles in this process by modifying small RNAs and mRNAs. We find that the Pseudomonas aeruginosa endonuclease YbeY is required for rRNA processing and the bacterial virulence in a murine acute pneumonia model. Transcriptomic analyses reveal that knocking out the ybeY gene results in downregulation of oxidative stress response genes, including the catalase genes katA and katB Consistently, the ybeY mutant is more susceptible to H2O2 and neutrophil-mediated killing. Overexpression of katA restores the bacterial tolerance to H2O2 and neutrophil killing as well as virulence. We further find that the downregulation of the oxidative stress response genes is due to defective expression of the stationary-phase sigma factor RpoS. We demonstrate an autoregulatory mechanism of RpoS and find that ybeY mutation increases the level of a small RNA, ReaL, which directly represses the translation of rpoS through the 5' UTR of its mRNA and subsequently reduces the expression of the oxidative stress response genes. In vitro assays demonstrate direct degradation of ReaL by YbeY. Deletion of reaL or overexpression of rpoS in the ybeY mutant restores the bacterial tolerance to oxidative stress and the virulence. We also demonstrate that YbeZ binds to YbeY and is involved in the 16S rRNA processing and regulation of reaL and rpoS as well as the bacterial virulence. Overall, our results reveal pleiotropic roles of YbeY and the YbeY-mediated regulation of rpoS through ReaL.IMPORTANCE The increasing bacterial antibiotic resistance imposes a severe threat to human health. For the development of effective treatment and prevention strategies, it is critical to understand the mechanisms employed by bacteria to grow in the human body. Posttranscriptional regulation plays an important role in bacterial adaptation to environmental changes. RNases and small RNAs are key players in this regulation. In this study, we demonstrate critical roles of the RNase YbeY in the virulence of the pathogenic bacterium Pseudomonas aeruginosa We further identify the small RNA ReaL as the direct target of YbeY and elucidate the YbeY-regulated pathway on the expression of bacterial virulence factors. Our results shed light on the complex regulatory network of P. aeruginosa and indicate that inference with the YbeY-mediated regulatory pathway might be a valid strategy for the development of a novel treatment strategy.</p

The mechanisms of Yu Ping Feng San in tracking the cisplatin-resistance by regulating ATP-binding cassette transporter and glutathione S-transferase in lung cancer cells

Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs