Up-regulation on cytochromes P450 in rat mediated by total alkaloid extract from Corydalis yanhusuo

BACKGROUND: Yanhusuo (Corydalis yanhusuo W.T. Wang; YHS), is a well-known traditional Chinese herbal medicine, has been used in China for treating pain including chest pain, epigastric pain, and dysmenorrhea. Its alkaloid ingredients including tetrahydropalmatine are reported to inhibit cytochromes P450 (CYPs) activity in vitro. The present study is aimed to assess the potential of total alkaloid extract (TAE) from YHS to effect the activity and mRNA levels of five cytochromes P450 (CYPs) in rat. METHODS: Rats were administered TAE from YHS (0, 6, 30, and 150 mg/kg, daily) for 14 days, alanine aminotransferase (ALT) levels in serum were assayed, and hematoxylin and eosin-stained sections of the liver were prepared for light microscopy. The effects of TAE on five CYPs activity and mRNA levels were quantitated by cocktail probe drugs using a rapid chromatography/tandem mass spectrometry (LC-MS/MS) method and reverse transcription-polymerase chain reaction (RT-PCR), respectively. RESULTS: In general, serum ALT levels showed no significant changes, and the histopathology appeared largely normal compared with that in the control rats. At 30 and 150 mg/kg TAE dosages, an increase in liver CYP2E1 and CYP3A1 enzyme activity were observed. Moreover, the mRNA levels of CYP2E1 and CYP3A1 in the rat liver, lung, and intestine were significantly up-regulated with TAE from 6 and 30 mg/kg, respectively. Furthermore, treatment with TAE (150 mg/kg) enhanced the activities and the mRNA levels of CYP1A2 and CYP2C11 in rats. However, the activity or mRNA level of CYP2D1 remained unchanged. CONCLUSIONS: These results suggest that TAE-induced CYPs activity in the rat liver results from the elevated mRNA levels of CYPs. Co-administration of prescriptions containing YHS should consider a potential herb (drug)–drug interaction mediated by the induction of CYP2E1 and CYP3A1 enzymes

A Time-Varying Mixture Integer-Valued Threshold Autoregressive Process Driven by Explanatory Variables

In this paper, a time-varying first-order mixture integer-valued threshold autoregressive process driven by explanatory variables is introduced. The basic probabilistic and statistical properties of this model are studied in depth. We proceed to derive estimators using the conditional least squares (CLS) and conditional maximum likelihood (CML) methods, while also establishing the asymptotic properties of the CLS estimator. Furthermore, we employed the CLS and CML score functions to infer the threshold parameter. Additionally, three test statistics to detect the existence of the piecewise structure and explanatory variables were utilized. To support our findings, we conducted simulation studies and applied our model to two applications concerning the daily stock trading volumes of VOW

Bioactive electrospun nanoyarn-constructed textile dressing patches delivering Chinese herbal compound for accelerated diabetic wound healing

The treatment of tenacious diabetic wounds still remains an enormous challenge in clinics, originated from the complicated pathological microenvironment of wound sites. Therefore, it's urgently required to develop one type of innovative dressing patch with appropriate microstructure and multifunctions to regulate the pathological microenvironment and promote the regeneration of diabetic wounds. In this study, novel gelatin (Gel)/poly (L-lactic acid) (PLLA) nanofibrous yarns loading with or without Salvia miltiorrhiza Bunge-Radix Puerariae herbal compound (SRHC) are fabricated by using our modified electrospinning strategy, which are further interlaced into nanofibrous woven fabrics respectively, serving as biofunctional dressing patches for potential diabetic wound treatment application. The actual photographs and SEM images confirm that all the different nanofibrous textiles with or without SRHC exhibit a uniform interwoven structure of warp and weft, and the internal nanofibers present bead-free morphology and uniaxially oriented structure along the longitudinal axis of nanofibrous yarns. Moreover, all the different nanofibrous woven fabrics are demonstrated to possess strong mechanical properties and great surface wettability. The in vitro cell characterization shows that the addition of SRHC can significantly promote the attachment and proliferation of human dermal fibroblasts (HDFs), and also dramatically inhibit the secretion levels of proinflammatory factors of M1 macrophages. The in vivo diabetic mouse full-thickness skin model experiments reveal that the as-developed SRHC-loaded Gel/PLLA nanofibrous textile shows the best performances referring to shorten wound healing time (100 % wound closure after 18 days of treatment) and high-quality regeneration (i.e., enhance collagen deposition, improve re-epithelialization and neovascularization, and increase hair follicles), which assuredly finds great interests serving as an innovative dressing patch for the treatment of hard-to-heal diabetic wounds

Potential Mechanisms of Yanghe Decoction in the Treatment of Soft Tissue Sarcoma and Arteriosclerosis Obliterans Based on Network Pharmacology

Objective The objective of this study was to investigate potential mechanisms of Yanghe Decoction ( , YHD) in treating soft tissue sarcoma (STS) and arteriosclerosis obliterans (ASO) based on the use of network pharmacology

Effect of physical properties of Cu-Ni-graphite composites on tribological characteristics by grey correlation analysis

Cu-Ni-graphite composites are intended for using as switch slide baseplates materials in high-speed railways industrials. The tribological characteristics of Cu-Ni-graphite composites with different graphite content were affected by physical properties and were generated variation correspondingly. It is difficult to study the correlation degree between tribological characteristics and physical properties by the means of experiments. However, grey correlation analysis (GCA) is a suitable mathematic method for researching the correlation with each factor. In this study, Cu-Ni-graphite composites were prepared by powder metallurgy and the correlation degree between tribological characteristics (Cu-Ni-graphite composites slid against U75V steel) and physical properties were calculated by GCA method. The results showed that through the calculating by GCA method, compared with physical properties of Cu-Ni-graphite composites, the most effective way to reduce the friction coefficient is to improve the relative density as well as the increasing of hardness can also bring down the friction coefficient usefully. The best way to reduce wear rate is the increasing of work of rupture and flexural strength, when these two properties have a small amount of ascension, the wear rate would be rapidly decreasing. The GCA results could help to improve materials’ performance and give reasonable advices to the following studies. Keywords: Switch slide baseplates, Gray correlation analysis, Cu-Ni-graphite composite

Progress of the effect of hydroxyacyl- coenzyme A dehydrogenase in cancer development and its mechanism

A close relationship between fatty acid metabolism and cancer development is well-established. The hydroxyacyl-coenzyme a dehydrogenase (HADH), a key enzyme in fatty acid beta-oxidation, has recently been identified as an anti-oncogenic factor in various cancers and an oncogenic factor in conditions like acute myeloid leukemia. In cancer cells, HADH not only directly catalyzes fatty acid beta-oxidation but also indirectly influences multiple signaling pathways such as PPAR, TNF-α, JAK-STAT3, PI3K/Akt, IFN-γ, MAPK, and non-canonical Wnt signaling pathways, affecting cancer cell proliferation and migration. HADH shows promise as a potential tumor biomarker for diagnosis, treatment, and prognosis in different cancer types, holding significant clinical value

Pressure Prediction of Electronic, Anisotropic Elastic, Optical, and Thermal Properties of Quaternary (M2/3Ti1/3)3AlC2 (M = Cr, Mo, and Ti)

The electronic, mechanical, anisotropic elastic, optical, and thermal properties of quaternary (M2/3Ti1/3)3AlC2 (M = Cr, Mo, and Ti) under different pressure are systematically investigated by first-principles calculations. The bonding characteristics of these compounds are the mixture of metallic and covalent bonds. With an increase of pressure, the heights of total density of states (TDOS) for these compounds decrease at Fermi level. The highest volume compressibility among three compounds is Mo2TiAlC2 for its smallest relative volume decline. The relative bond lengths are decreasing when the pressure increases. The bulk and shear modulus of the one doped with Cr or Mo are larger than those of Ti3AlC2 with pressure increasing. With an increase of pressure, the anisotropy of these compounds also increases. Moreover, Mo2TiAlC2 has the biggest anisotropy among the three compounds. The results of optical functions indicate that the reflectivity of the three compounds is high in visible-ultraviolet region up to ~10.5 eV under ambient pressure and increasing constantly when under pressure. Mo2TiAlC2 has the highest loss function. The calculated sound velocity and Debye temperature show that they all increase with pressure. CV of the three compounds is also calculated

Elevated B Cell Activation is Associated with Type 2 Diabetes Development in Obese Subjects

Background/Aims: Despite strong association between obesity and the pathogenesis of type 2 diabetes (T2D), only a subset of obese individuals eventually develops T2D. We sought to determine the immunological factors behind this heterogeneity. Methods: Peripheral blood of obese non-diabetic subjects and obese diabetic subjects were collected and the B cell responses in these subjects were analyzed. Results: We found that the B cells from obese diabetic subjects had similar B cell subtype composition and secreted similar levels of low-grade pro-inflammatory cytokines to obese non-diabetic subjects, characteristic to the background chronic immune activation frequently observed in obese subjects. When examining adaptive B cell antibody responses, however, obese diabetic subjects presented much higher levels of polyclonal activation and antibody secretion, with impaired ability to response to new antigens such as seasonal influenza vaccination. Conclusions: These data demonstrated that in obese diabetic subjects, B cell adaptive response is impaired and potentially contribute to overall higher inflammation

Effects of glyphosate-based herbicide on gut microbes and hepatopancreatic metabolism in Pomacea canaliculata

Roundup®, a prominent glyphosate-based herbicide (GBH), holds a significant position in the global market. However, studies of its effects on aquatic invertebrates, including molluscs are limited. Pomacea canaliculata, a large freshwater snail naturally thrives in agricultural environments where GBH is extensively employed. Our investigation involved assessing the impact of two concentrations of GBH (at concentrations of 19.98 mg/L and 59.94 mg/L, corresponding to 6 mg/L and 18 mg/L glyphosate) during a 96 h exposure experiment on the intestinal bacterial composition and metabolites of P. canaliculata. Analysis of the 16 S rRNA gene demonstrated a notable reduction in the alpha diversity of intestinal bacteria due to GBH exposure. Higher GBH concentration caused a significant shift in the relative abundance of dominant bacteria, such as Bacteroides and Paludibacter. We employed widely-targeted metabolomics analysis to analyze alterations in the hepatopancreatic metabolic profile as a consequence of GBH exposure. The shifts in metabolites primarily affected lipid, amino acid, and glucose metabolism, resulting in compromised immune and adaptive capacities in P. canaliculata. These results suggested that exposure to varying GBH concentrations perpetuates adverse effects on intestinal and hepatopancreatic health of P. canaliculata. This study provides an understanding of the negative effects of GBH on P. canaliculata and may sheds light on its potential implications for other molluscs