The protective mechanism of Tao Hong Si Wu decoction against breast cancer through regulation of EGFR/ERK1/2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Tao Hong Si Wu Decoction (THSWD), a traditional Chinese herbal medicine, is widely utilized in clinical settings, either alone or in combination with other medications, for the treatment of breast cancer. AIM OF THE STUDY: The specific targeting molecule(s) of THSWD and its associated molecular mechanisms remain unclear. This research aims to elucidate the underlying molecular mechanisms of THSWD in the treatment of breast cancer. MATERIALS AND METHODS: The pharmacological properties of THSWD were investigated in breast cancer cells and tumor tissues using a range of methods including Acridine Orange/Ethidium Bromide (AO/EB) staining, Transwell assay, flow cytometry, immunofluorescence assay, and breast cancer mice models. RESULTS: Our findings demonstrate that THSWD induces necrosis and/or apoptosis in breast cancer cells, while significantly inhibiting cell migration. Target proteins of THSWD in anticancer activity include EGFR, RAS, and others. THSWD treatment for breast cancer is associated with the EGFR/ERK1/2 signaling pathway. CONCLUSION: Our findings offer initial insights into the primary mechanism of action of THSWD in breast cancer treatment, indicating its potential as a complementary therapy deserving further investigation.

Sodium cholate ameliorates nonalcoholic steatohepatitis by activation of FXR signaling.

Non-alcoholic steatohepatitis (NASH) has become a major cause of liver transplantation and liver-associated death. The gut-liver axis is a potential therapy for NASH. Sodium cholate (SC) is a choleretic drug whose main component is bile acids and has anti-inflammatory, antifibrotic, and hepatoprotective effects. This study aimed to investigate whether SC exerts anti-NASH effects by the gut-liver axis. Mice were fed with an high-fat and high-cholesterol (HFHC) diet for 20 weeks to induce NASH. Mice were daily intragastric administrated with SC since the 11th week after initiation of HFHC feeding. The toxic effects of SC on normal hepatocytes were determined by CCK8 assay. The lipid accumulation in hepatocytes was virtualized by Oil Red O staining. The mRNA levels of genes were determined by real-time quantitative PCR assay. SC alleviated hepatic injury, abnormal cholesterol synthesis, and hepatic steatosis and improved serum lipid profile in NASH mice. In addition, SC decreased HFHC-induced hepatic inflammatory cell infiltration and collagen deposition. The target protein-protein interaction network was established through Cytoscape software, and NR1H4 [farnesoid x receptor (FXR)] was identified as a potential target gene for SC treatment in NASH mice. SC-activated hepatic FXR and inhibited CYP7A1 expression to reduce the levels of bile acid. In addition, high-dose SC attenuated the abnormal expression of cancer markers in NASH mouse liver. Finally, SC significantly increased the expression of FXR and FGF15 in NASH mouse intestine. Taken together, SC ameliorates steatosis, inflammation, and fibrosis in NASH mice by activating hepatic and intestinal FXR signaling so as to suppress the levels of bile acid in NASH mouse liver and intestine.

The Association of Sarcopenia and Visceral Obesity with Lean Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus.

Background: Few studies have specifically observed the relationship of sarcopenia, visceral obesity, or their joint effects with lean NAFLD in patients with diabetes. We aimed to investigate the associations of lean NAFLD with sarcopenia, visceral obesity, and sarcopenic visceral obesity (SV) in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: Altogether, 1,112 T2DM patients with BMI <25 kg/m2 were enrolled, and 33.18% of them were diagnosed with lean NAFLD by abdominal ultrasonography. Body composition markers were measured by bioelectrical impedance (BIA). Skeletal muscle mass index (SMI) was calculated as appendicular skeletal muscle mass (ASM) divided by weight, and sarcopenia was defined as SMI < 1 standard deviation (SD) below the sex-specific average for a young reference population. Visceral obesity was defined as visceral fat area (VFA) ≥ 100 cm2. Participants were categorized into one of the four body composition groups: nonsarcopenia/nonvisceral obesity (NN), nonsarcopenia/visceral obesity (NV), sarcopenia/nonvisceral obesity (SN), and SV. Results: Compared to those in the NN group, patients in the NV and SN groups had a higher risk of lean NAFLD after full adjustments (NV: OR = 1.74; 95% CI: 1.09, 2.78; SN: OR =2.07; 95% CI: 1.23, 3.46). Of note, patients in the SV group had the highest odds of lean NAFLD (OR = 3.29; 95% CI: 2.10, 5.17). There were no significant interaction effects between sarcopenia and metabolic risk factors on prevalent lean NAFLD. Conclusions: The current study demonstrated that SV was more closely associated with higher prevalent lean NAFLD than sarcopenia or visceral obesity alone in Chinese patients with T2DM. Besides, the harmful effect of sarcopenia on lean NAFLD was not influenced by visceral obesity or other metabolic risk factors. We hypothesize that increasing skeletal muscle mass more than just reducing visceral fat might be more optimal for the prevention and management of lean NAFLD, which needs further investigation in future studies.

Inverse Association of Fruit and Vegetable Consumption with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus.

We aimed to investigate the association of fruit and vegetable consumption with nonalcoholic fatty liver disease (NAFLD) in Chinese patients with type 2 diabetes mellitus (T2DM). This cross-sectional study included 2667 Chinese patients with T2DM aged 18 to 76 years from March 2017 to October 2021. Dietary intake was assessed using a food frequency questionnaire, and prevalent NAFLD was diagnosed with abdominal ultrasonography. High fruit−vegetable consumption was determined using ≥500 g/day consumption of both fruit and vegetable, and both fruit and vegetable consumption were divided into three categories of <200 g/day (low), 200−400 g/day (median) and >400 g (high). The primary outcome measurement was multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the prevalence of NAFLD in relation to the highest fruit and (or) vegetable intake compared with the lowest. Secondary analyses were conducted to assess the effects of either fruit or vegetable intake on the fatty liver index (FLI) using multivariable linear regressions. There were 1694 men and 973 women in this study, and 1445 (54.06%) participants had prevalent NAFLD. Patients with high fruit−vegetable intake had a lower prevalence of NAFLD than those with low fruit−vegetable intake (52.04% vs. 56.48%), but this difference was not statistically significant (p = 0.065). Vegetable intake had a significantly inverse association with NAFLD (OR: 0.68, 95% CI: 0.52−0.90), but this association was not pronounced with fruit intake (OR: 1.23, 95% CI: 0.89−1.69) or fruit−vegetable intake (OR: 0.90, 95% CI: 0.73−1.10). Additional analyses showed that an increase in vegetable intake was linearly associated with a significant reduction in FLI (ß: −1.028, 95% CI: −1.836, −0.219). In conclusion, higher vegetable consumption was associated with lower odds of NAFLD in Chinese patients with T2DM, which suggested that increased vegetable intake might protect patients with diabetes against NAFLD.

Fufang Zhenzhu Tiaozhi Capsule Prevents Intestinal Inflammation and Barrier Disruption in Mice With Non-Alcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) has become a major cause of liver transplantation and liver-associated death. Targeting the gut-liver axis is a potential therapy for NASH. The Fufang Zhenzhu Tiaozhi (FTZ) capsule, a traditional Chinese medicine commonly used in clinical practice, has recently emerged as a promising drug candidate for metabolic diseases such as NASH. The present study aimed to investigate whether FTZ exerts an anti-NASH effect by targeting the gut-liver axis. Mice were fed with a high-fat diet (HFD) for 20 weeks to induce NASH. HFD-fed mice were daily intragastrically administrated with FTZ at 10 weeks after tbe initiation of HFD feeding. The mRNA levels of genes associated with the intestinal tight junction, lipid metabolism, and inflammation were determined by the q-PCR assay. Hepatic pathology was evaluated by H&E staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. FTZ attenuated HFD-induced obesity, insulin resistance, and hepatic steatosis in mice. FTZ treatment decreased the elevated levels of serum aminotransferases and liver triglyceride in NASH mice. Furthermore, FTZ treatment reduced hepatic inflammatory cell infiltration and fibrosis in mice. In addition, FTZ attenuated the intestinal inflammatory response and improved intestinal barrier function. Mechanistically, FTZ-treated mice showed a different gut microbiota composition compared with that in HFD-fed mice. Finally, we identified eight differential metabolites that may contribute to the improvement of NASH with FTZ treatment. In summary, FTZ ameliorates NASH by inhibiting gut inflammation, improving intestinal barrier function, and modulating intestinal microbiota composition.

Analytical Lifecycle Management (ALM) and Analytical Quality by Design (AQbD) for analytical procedure development of related substances in tenofovir alafenamide fumarate tablets.

Analytical procedure development for quantifying 10 impurities in Tenofovir Alafenamide Fumarate (TAF) tablets was a challenge for analytical and formulation researchers. The aim of this paper was to develop a robust, regulatory-flexible, application-specific Ultra Performance Liquid Chromatography (UPLC) analytical procedure using the Analytical Lifecycle Management (ALM) and the Analytical Quality by Design (AQbD) for the estimation of the TAF tablets. In this work, the Analytical Target Profile (ATP) for the analytical procedure and the Critical Analytical Attributes (CAAs) were identified. Through the risk assessment studies, the high-risk analytical conditions were found, and they were screened and optimized by the Design of Experiment (DoE) to obtain the Design Space (DS) and identify the working point. The prediction intervals were used to examine the robustness of the analytical procedure. And the procedure performance qualification and the continued procedure performance verification were used to ensure routine application of analytical procedure. Finally, the 10 impurities were separated within 20 min by UPLC. The success of this study demonstrates the usefulness of using ALM and AQbD for analytical procedure development and provides a reference for the analytical procedure development for other drugs.

Neck-to-height ratio is positively associated with diabetic kidney disease in Chinese patients with type 2 diabetes mellitus.

Introduction: The aim of this study was to investigate the associations of neck circumference (NC) and neck-to-height (NHR) with diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM). Materials and methods: A total of 2,615 patients with prevalent T2DM were enrolled. NHR was calculated through NC (cm) divided by height (cm), and prevalent DKD was defined as the urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g or the estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 in the absence of other primary kidney diseases. Results: The levels of NC and NHR were higher in DKD patients compared with non-DKD patients (38.22 vs. 37.71, P = 0.003; 0.232 vs. 0.227, P < 0.001, respectively). After full adjustments, individuals at the highest tertile of NHR had higher odds of DKD than those at the lowest tertile (multivariate-adjusted OR = 1.63, 95% CI: 1.22, 2.18), but this association was not pronounced with NC (multivariate-adjusted OR = 1.24, 95% CI: 0.87, 1.76). Individuals at the highest tertile of NHR had lower eGFR (ß = -4.64, 95% CI: -6.55, -2.74) and higher UACR levels (ß = 0.27, 95% CI: 0.10, 0.45) than those at the lowest tertile. The adverse association between NHR and prevalent DKD remained statistically significant among most of the subgroups analyzed and no interaction effects were observed. Conclusion: The increase in NHR was adversely and independently associated with DKD in this Chinese T2DM population.

Nitrogen-Doped Carbon Vesicles with Dual Iron-Based Sites for Efficient Oxygen Reduction.

A nitrogen-doped vesicle-like porous carbon with well-integrated dual iron-based catalytic sites was developed through direct pyrolysis of inexpensive and abundant precursors. Benefiting from the mesoporous structures with synchronous construction of Fe-Nx and Fe/Fe3 C@NC sites, the optimized catalyst exhibited outstanding performance for the oxygen reduction reaction (ORR) in alkaline media, even superior to the commercial Pt/C catalyst. Detailed characterizations revealed that Fe/Fe3 C@NC sites can make major catalytic contributions in basic media, whereas the Fe-Nx sites were found to play an indispensable role for ORR in acidic media.

One-pot hydrothermal synthesis of CuBi co-doped mesoporous zeolite Beta for the removal of NOx by selective catalytic reduction with ammonia.

A series of CuBi co-doped mesoporous zeolite Beta (CuxBiy-mBeta) were prepared by a facile one-pot hydrothermal treatment approach and were characterized by XRD, N2 adsorption-desorption, TEM/SEM, XPS, H2-TPR, NH3-TPD and in situ DRIFTS. The catalysts CuxBiy-mBeta were applied to the removal of NOx by selective catalytic reduction with ammonia (NH3-SCR), especially the optimized Cu1Bi1-mBeta achieved the high efficiency for the removal of NOx and N2 selectivity, superior water and sulfur resistance as well as good durability. The excellent catalytic performance could be attributed to the acid sites of the support and the synergistic effect between copper and bismuth species. Moreover, in situ DRIFTS results showed that amides NH2 and NH4(+) generated from NH3 adsorption could be responsible for the high selective catalytic reduction of NOx to N2. In addition, a possible catalytic reaction mechanism on Cu1Bi1-mBeta for the removal of NOx by NH3-SCR was proposed for explaining this catalytic process.