Integrating network pharmacology and experimental models to investigate the mechanisms of XCHD and YCSLS in preventing HUA progression via TLR4/MYD88/NF-κB signaling.

With the alterations in dietary structure and the augmentation of the human living standard, hyperuricemia (HUA) has emerged as a significant factor impacting contemporary human health. It has also been scientifically validated as an independent risk determinant for the progression of renal disease. Existing literature indicates that XCHD (Xiao Chai Hu Decoction) and YCSLS (Yinchen Siling San) possess a capability to ameliorate UA levels and fortify renal function, yet a comprehensive understanding of their mechanisms of action remains elusive. This investigation is designed to elucidate the therapeutic efficacy and mechanistic underpinnings of XCHD/YCSLS on the renal tissues of HUA-afflicted rats, with the objective of fortifying the evidence base to advocate its clinical application. Our preliminary findings substantiated that XCHD and YCSLS impede HUA progression through the inhibition of inflammatory and oxidative stress pathways. Further, we synthesized data from publicly accessible repositories to forecast interactions between XCHD, YCSLS, and their prospective targets in HUA, including the associated signaling pathways. This approach facilitated the identification of shared targets of XCHD/YCSLS, and HUA, and the subsequent correlation analysis of these targets employing KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) methodologies. The findings indicate that the TLR4/MYD88/NF-κB signaling constitutes one of the potential crucial conduits engaged in XCHD and YCSLS-induced HUA mitigation. In conclusion, the analysis of WB and IHC from HUA rat models corroborated that XCHD and YCSLS do indeed attenuate the expression of TLR4/MYD88/NF-κB, reinforcing the hypothesized pivotal role of the its signaling cascade in HUA. This warrants subsequent scholarly exploration.

A fluorescent probe based on cyclochalcone for detecting peroxynitrite.

A novel cyclic chalcone fluorescent probe C-PN was synthesized to detect ONOO-. After reaction with peroxynitrite, the double bond of C-PN in the cyclic chalcone structure was disconnected, which caused the change of intramolecular charge transfer (ICT) effect, emitting blue fluorescence and quenching orange red fluorescence. Visible to the naked eye, the color of the probe solution changed. The probe showed low sensitivity (detection limit = 20.2 nm), short response time (less than 60 s) at low concentration of ONOO-, good visibility, and good selectivity and stability for ONOO-.

Molecular Insights to the Structure-Interaction Relationships of Human Proton-Coupled Oligopeptide Transporters (PepTs).

Human proton-coupled oligopeptide transporters (PepTs) are important membrane influx transporters that facilitate the cellular uptake of many drugs including ACE inhibitors and antibiotics. PepTs mediate the absorption of di- and tri-peptides from dietary proteins or gastrointestinal secretions, facilitate the reabsorption of peptide-bound amino acids in the kidney, and regulate neuropeptide homeostasis in extracellular fluids. PepT1 and PepT2 have been the most intensively investigated of all PepT isoforms. Modulating the interactions of PepTs and their drug substrates could influence treatment outcomes and adverse effects with certain therapies. In recent studies, topology models and protein structures of PepTs have been developed. The aim of this review was to summarise the current knowledge regarding structure-interaction relationships (SIRs) of PepTs and their substrates as well as the potential applications of this information in therapeutic optimisation and drug development. Such information may provide insights into the efficacy of PepT drug substrates in patients, mechanisms of drug-drug/food interactions and the potential role of PepTs targeting in drug design and development strategies.

Accurate Detection of Salmonella Based on Microfluidic Chip to Avoid Aerosol Contamination.

Salmonella is a type of common foodborne pathogen of global concern, seriously endangering human health. In molecular biological detection of Salmonella, the method of amplifying DNA often faces the problem of aerosol pollution. In this study, a microfluidic chip was developed to integrate loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system to detect Salmonella. The LAMP reaction solution was initially injected into the chamber to amplify at 65 °C for 20 min; the CRISPR/Cas12a reaction solution was subsequently injected to mix with the amplicons for fluorescent signal production at 43 °C for 30 min. Then, the results can be confirmed by naked eyes under 495 nm light or by a fluorescence immunochromatographic reader. The detection limit of this method for Salmonella DNA was 118 pg/µL. The sensitivity and specificity of this method was 100%. Furthermore, this method was used to detect Salmonella after enrichment for 4 h in salmon and chicken samples spiked with 30 CFU/25 g, and was verified to have a stable detection capability in real samples. The microfluidic chip integrated with the LAMP and CRISPR/Cas12a system not only provides a possibility of highly sensitive endpoint fluorescent visual detection of a foodborne pathogen, but also greatly eliminates the risk of aerosol contamination.

Efficacy and safety of Wenxin Keli combined with metoprolol tartrate in the treatment of premature ventricular contractions: A systematic review and meta-analysis.

Background: Wenxin Keli (WXKL) has good clinical value in the treatment of premature ventricular contractions, but there is insufficient evidence to support it. This study evaluates the efficacy and safety of WXKL combined with metoprolol tartrate in the treatment of ventricular premature beats (VPCs). Methods: We searched seven databases to identify randomized controlled trials (RCTs) for this study. Two reviewers independently screened and extracted the data. The Cochrane Manual criteria were used for methodological quality assessment. Meta-analyses were performed using Review Manager 5.4.1 software. Risk ratios (RR) were used for effect sizes for dichotomous data, demonstrated in effect sizes and 95% confidence intervals (CIs). Results: A total of 11 RCTs of WXKL combined with metoprolol tartrate in the treatment of premature ventricular contractions were included in this study. Meta-analysis showed that WXKL combined with metoprolol tartrate (treatment group) was more effective than metoprolol tartrate (control group) in improving premature ventricular contractions (RR = 1.32, 95% CI: [1.24, 1.40], P < 0.00001); significantly improved the rate of premature ventricular contractions (RR = 1.32, 95% CI: [1.23, 1.41], P < 0.00001); there was no difference in adverse drug reactions compared with the control group (RR = 0.61, 95% CI: [0.35, 0.1.05], P = 0.08), but the number of adverse reactions (n = 18) was less than that of the control group (n = 32), and the severity was lower than that of the control group. The included studies only mentioned randomization and did not describe the generation of random sequences in detail. Conclusion: This study found that Wenxin Keli combined with metoprolol tartrate in the treatment of premature ventricular contractions increased the efficacy of the drug, reduced the occurrence of adverse reactions, and reduced the severity of adverse reactions. Due to the quality limitations of the included studies, more high-quality RCTs are needed in the future to provide more evidence for longer-term analyses.

The potential applications of traditional Chinese medicine in Parkinson's disease: A new opportunity.

Parkinson's disease (PD) presents a common challenge for people all over the world and has become a major research hotspot due to the large population affected by the illness and the difficulty of clinical treatment. The prevalence of PD is increasing every year, the pathogenesis is complex, and the current treatment is ineffective. Therefore, it has become imperative to find effective drugs for PD. With the advantages of low cost, high safety and high biological activity, Chinese medicine has great advantages in the prevention and treatment of PD. This review systematically summarizes the potential of Chinese medicine for the treatment of PD, showing that Chinese medicine can exert anti-PD effects through various pathways, such as anti-inflammatory and antioxidant pathways, reducing mitochondrial dysfunction, inhibiting endoplasmic reticulum stress and iron death, and regulating intestinal flora. These mainly involve HMGB1/TLR4, PI3K/Akt, NLRP3/ caspase-1/IL-1ß, Nrf2/HO-1, SIRT1/Akt1, PINK1/parkin, Bcl-2/Bax, BDNF-TrkB and other signaling pathways. In sum, based on modern phytochemistry, pharmacology and genomic proteomics, Chinese medicine is likely to be a potential candidate for PD treatment, which requires more clinical trials to further elucidate its importance in the treatment of PD.

Multiple dehydrogenation of fluorene cation and neutral fluorene using the statistical molecular fragmentation model.

The statistical molecular fragmentation (SMF) model was used to analyze the 306 fragmentation channels (containing 611 different species) that result from the fluorene (C13H10+) cation losing up to three hydrogen atoms (neutral radicals and/or a proton). Breakdown curves from such analysis permit one to extract experimentally inaccessible information about the fragmentation of the fluorene cation, such as the locations of the lost hydrogen atoms (or proton), yields of the neutral fragments, electronic states of the residues, and quantification of very low probability channels that would be difficult to detect. Charge localization during the fragmentation pathways was studied to provide a qualitative understanding of the fragmentation process. Breakdown curves for both the fluorene cation and neutral fluorene were compared. The SMF results match the rise and fall of the one hydrogen loss yield experimentally measured by imaging photoelectron-photoion coincidence spectroscopy using a VUV synchrotron.

MiR-145-5p inhibits proliferation and inflammatory responses of RMC through regulating AKT/GSK pathway by targeting CXCL16.

The main pathological characteristics of chronic glomerulonephritis (CGN) are diffuse mesangial cells proliferation and inflammatory responses. Our previous studies have confirmed that miR-145-5p was abnormally elevated in CGN rats, but its mechanism remains unclear. Therefore, this study aimed to elucidate the mechanism of miR-145-5p in regulation of renal mesangial cells proliferation and inflammatory responses. In vivo study, the cationic bovine serum albumin (C-BSA)-induced CGN rat model was established, and the content of miR-145-5p in renal was examined by qRT-PCR, meanwhile, we also determined the renal function and inflammatory infiltrate. In vitro, the cell proliferation rate, cell cycle and inflammatory changes of rat mesangial cells (RMCs) were measured. Our results suggested that miR-145-5p extended the G0-G1 phase, shortened S phase, inhibited cell proliferation and suppressed inflammatory responses in RMCs. Moreover, miR-145-5p inhibited CXCL16 protein expression through binding the 3'-UTR of CXCL16, suppressed AKT/GSK signaling pathway, and decreased expression of inflammation related mRNAs, such as IL-1α, IL-2, IL-6, and TNF-α mRNAs. Further, locking CXCL16 alleviated inflammatory reactions and down-regulated AKT/GSK pathway in RMCs. Above all, we concluded that miR-145-5p inhibited proliferation and inflammatory responses of RMCs through regulation of AKT/GSK pathway by targeting CXCL16.

Statistical virtual eye model based on wavefront aberration.

Wavefront aberration affects the quality of retinal image directly. This paper reviews the representation and reconstruction of wavefront aberration, as well as the construction of virtual eye model based on Zernike polynomial coefficients. In addition, the promising prospect of virtual eye model is emphasized.