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This study compares two diets, Dietary Approaches to Stop Hypertension (DASH) and a Low-Calorie Diet on Trimethylamine N-oxide (TMAO) levels and gut microbiota. 120 obese adults were randomly allocated to these three groups: a low-calorie DASH diet, a Low-Calorie diet, or a control group for 12 weeks. Outcomes included plasma TMAO, lipopolysaccharides (LPS), and gut microbiota profiles. After the intervention, the low-calorie DASH diet group demonstrated a greater decrease in TMAO levels (-20 ± 8.1 vs. −10.63 ± 4.6 μM) and a significant decrease in LPS concentration (-19.76 ± 4.2 vs. −5.68 ± 2.3) compared to the low-calorie diet group. Furthermore, the low-calorie DASH diet showed a higher decrease in the Firmicutes and Bactericides (F/B) ratio, which influenced TMAO levels, compared to the Low-Calorie diet (p = 0.028). The current study found the low-calorie DASH diet improves TMAO and LPS in comparison to a Low-Calorie diet. [ABSTRACT FROM AUTHOR]

[Display omitted] • The possibility of anti-arthritic effects was determined by the protein denaturation methods. • The in vitro antioxidant potential was analyzed through a reducing power assay. • Silver nanoparticles markedly decreased the levels of rheumatoid parameters. • Silver nanoparticles markedly enhanced the modified hematological factors. • Silver nanoparticles had a beneficial effect on both histopathological and radiographic changes. Rheumatoid arthritis is a persistent inflammatory disorder that typically impacts individuals aged 20 to 40. It is characterized by inflammation of the synovial membrane, degradation of cartilage, and joint pain among its various symptoms. Researchers have recently developed, analyzed, and altered biomarkers and nanomaterials that are frequently employed to improve the diagnostic and therapeutic approaches for rheumatoid arthritis. Here, we have created and formulated a novel therapeutic agent that incorporates silver nanoparticles@ Allium sativum L. leaves to treat arthritis. The characterization of silver nanoparticles (AgNPs) was performed utilizing various techniques. The FE-SEM and TEM images demonstrated that the majority of these nanoparticles exhibited a spherical shape (10 to 50 nm). Additionally, a notable peak at a wavelength of 403 nm in the UV–Vis spectrum confirmed the successful formulation of the Ag NPs. The antioxidant assay revealed that the IC 50 values for the silver nanoparticles@ Allium sativum L. and BHT in relation to DPPH were 21 and 44 µg/mL, respectively. In vivo assessments were performed utilizing models involving formaldehyde, CFA, and turpentine oil at various dosage levels. Silver nanoparticles@ Allium sativum L. exhibited anti-arthritic properties with the most significant potential observed at 1 mg/kg. Data from the CFA model revealed a more substantial protective effect on arthritic lesions and alterations in body weight. The recent results indicates the recovery of rheumatoid arthritis criteria including synovial cavity swelling and edema inhibition percentage in turpentine test, paw diameter in CFA test and paw edema in formaldehyde test. In conclusion, these data support the administration of silver nanoparticles as potent therapeutic agents for rheumatoid arthritis treatment in humans. [ABSTRACT FROM AUTHOR]

To characterise the dose-dependent pharmacokinetics of midazolam and evaluate the intestinal and hepatic first-pass effects on midazolam in Sprague-Dawley rats, the concentrations and area under the concentration-time curve (AUC) of midazolam in the portal and systemic plasma were simultaneously determined with a double cannulation method. It was found that about 75% of the dose was left in the portal blood with different oral administration doses, while the bioavailability in the liver was 37.86% at 20 mg/kg, significantly higher than 9.16% at 2 mg/kg. The disproportional increase in AUC of midazolam and significant decrease in exposure of metabolites were observed in systemic plasma after hepatic portal vein administration. And in the in vitro study, the formation rate of the metabolites of midazolam significantly decreased when midazolam was at 300 μM compared with 100 μM. These results indicated that not only the saturation of first-pass metabolism but also the inhibition of hepatic metabolism is responsible for the nonlinear PK of midazolam. Thus, a rational dose should be chosen when midazolam is used as a probe in the drug-drug interaction study, particularly for orally administered drugs that undergo hepatic first-pass metabolism. [ABSTRACT FROM AUTHOR]

Qing-Zhi-Tiao-Gan-Tang or Qing-Zhi-Tiao-Gan Decoction (QZTGT) is based on the compatibility theory of traditional Chinese medicine (TCM), that is a combination of three classical formulae for the treatment of nonalcoholic fatty liver disease (NAFLD). Its pharmacodynamic material basis is made up of quinones, flavanones, and terpenoids. This study aimed to look for a promising recipe for treating nonalcoholic steatohepatitis (NASH), a more advanced form of NAFLD, and to use a transcriptome-based multi-scale network pharmacological platform (TMNP) to find its therapy targets. A classical dietary model of NASH was established using MCD (Methionine- and choline-deficient) diet-fed mice. Liver coefficients like ALT, AST, serum TC, and TG levels were tested following QZTGT administration. A transcriptome-based multi-scale network pharmacological platform (TMNP) was used to further analyze the liver gene expression profile. The composition of QZTGT was analyzed by HPLC-Q-TOF/MS, a total of 89 compounds were separated and detected and 31 of them were found in rat plasma. QZTGT improved liver morphology, inflammation and fibrosis in a classical NASH model. Transcriptomic analysis of liver samples from NASH animal model revealed that QZTGT was able to correct gene expression. We used transcriptome-based multi-scale network pharmacological platform (TMNP) to predicted molecular pathways regulated by QZTGT to improve NASH. Further validation indicated that "fatty acid degradation", "bile secretion" and "steroid biosynthesis" pathways were involved in the improvement of NASH phenotype by QZTGT. Using HPLC-Q-TOF/MS, the compound composition of QZTGT, a Traditional Chinese prescription, was separated, analyzed and identified systematically. QZTGT mitigated NASH symptoms in a classical dietary model of NASH. Transcriptomic and network pharmacology analysis predicted the potential QZTGT regulated pathways. These pathways could be used as therapeutic targets for NASH. [Display omitted] • Identification of more than 89 compounds in QZTGT and more than 30 components were found in rat serum. • By using TNMP, 3 pathways have been found closely related to the efficacy of QZTGT. • QZTGT had advantage of elevating therapeutic effects in MCD-induced NASH mouse model. [ABSTRACT FROM AUTHOR]

The blueschist-bearing Aksu Group and the associated rocks in the Aksu–Wushi area play a crucial role in understanding Neoproterozoic tectonic evolution of the Tarim Craton. However, the age and tectonic setting of the Aksu Group, and its relationship with the Qiaoenbrak Formation, remain controversial. Previous studies were mainly focused on the well-known Aksu Group from the Aksu area, but little attention has been paid to the equivalent rocks from the Wushi area. In this paper, we present the first detrital zircon LA-ICP-MS U–Pb ages for the Aksu Group metasedimentary rocks from the Wushi area, and we also measure U–Pb ages for detrital zircons from the Qiaoenbrak Formation to figure out its affinity to the Aksu Group. Our data show that the protolith of the metasedimentary rocks of the Aksu Group from the Wushi area was deposited between ca. 790 and 761 Ma, which was earlier than that from the Aksu area (>ca. 750 Ma). The Qiaoenbrak Formation was deposited between ca. 780 and 744 Ma, probably contemporaneous with or earlier than the metasedimentary rocks of the Aksu Group. Geochemical data for the metasedimentary rocks of the Aksu Group from the Wushi area suggest that they were deposited in an arc-related setting. Combining the detrital zircon age spectra and geochemistry analyses, we propose that the sedimentary rocks of the Aksu Group and the Qiaoenbrak Formation were probably deposited in a similar tectonic setting related to an active continental margin in the northern margin of the Tarim Craton. The Aksu blueschists and the associated Neoproterozoic arc were probably related to the circum-Rodinia subduction system, rather than assembly of the Rodinia or Gondwana in the interior of the supercontinents. [ABSTRACT FROM AUTHOR]