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The efficient three‐component cascade coupling reaction of 3‐haloisoquinolines, haloalkanes, and sp3‐carbon nucleophiles (acetophenone or nitromethane) led to a series of structurally novel 1,2‐disubstituted‐3‐isoquinolinones through the formation of C(sp3)−C(sp2), C−N, and C=O bonds. The NaOAc‐promoted reaction described in this work is simple to operate, environment friendly, and highly selective. [ABSTRACT FROM AUTHOR]

A one‐pot protocol for constructing 1,4‐difunctionalized quinoline/pyridine derivatives via the reaction of N‐heteroaromatics, alkyl halides, and active methylene/methyl compounds was developed. The transformation involves dearomative functionalization of an in situ‐activated N‐heteroaromatic to construct new C−N and C=C bonds. This reaction has a broad substrate scope and functional group tolerance. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the role of scoparone (SCO) in hepatic fibrosis. For this, we conducted in vivo and in vitro experiments. In vivo rats that were divided into six groups, control, carbon tetrachloride, and colchicine, as well as SCO groups, SCO50, SCO100, and SCO200 treated with 50, 100, and 200 mg/kg SCO doses, respectively. Furthermore, SCO was shown to inhibit Toll‐like receptor‐4 (TLR‐4)/nuclear factor kappa‐B (NF‐κB; TLR‐4/NF‐κB) signals by inhibiting TLR‐4, which in turn downregulates the expression of MyD88, promotes NF‐κB inhibitor‐α, NF‐κB inhibitor‐β, and NF‐κB inhibitor‐ε activation, while inhibiting NF‐κB inhibitor‐ζ. Subsequently, the decrease of phosphorylation of nuclear factor‐κB levels leads to the downregulation of the downstream inflammatory factors' tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and IL‐1 beta, thus weakening hepatic fibrosis. Notably, the SCO200 treated group presented the most significant improvement. Hence, we conclude that SCO alleviates hepatic fibrosis by inhibiting TLR‐4/NF‐κB signals. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer, shows higher metastases and relapse rates than other subtypes. The metastasis of TNBC is the main reason for the death of TNBC patients. Increasing evidence has shown that inhibiting the metastasis of TNBC is a good method for TNBC treatment. Here, VSP-17 was designed and synthesized as an agonist of PPARγ, evidenced by upregulating the expression of CD36 and increasing the activity of PPARγ reporter gene. VSP-17 obviously inhibited the migration and invasion process of MDA-MB-231 cells but showed little effect on the viability of MDA-MB-231 cells. Notably, VSP-17 could selectively promote the expression of E-cadherin without affecting the expression of BRMS1, CXCL12, MMP9, Orai1, Stim1, TGF-β, and VEGF. In addition, VSP-17 significantly suppressed the metastasis of liver and promoted the expression of E-cadherin in MDA-MB-231 xenograft model. In conclusion, VSP-17 inhibited the metastasis process of TNBC via upregulating the expression of E-cadherin. [ABSTRACT FROM AUTHOR]

During the studies on the intramolecular cyclization of 4-arylamino-2(5H)-furanones via the Pd-catalyzed C-H activation, a kind of difunctionalization reaction caused by the designed oxidant PhI(OAc)2[(diacetoxyiodo)benzene, DIB] was accidentally discovered. When 1.5 eq. DIB is used as a difunctionalizable transfer reagent in the 40 h reaction at 60°C and CH3CN as solvent, 4-diarylamino-3-iodo-2(5H)-furanones can be obtained with the yields of 57–91% (usually more than 73%). The simultaneousα-iodination andNβ-arylation reaction without metal catalyst is efficient and convenient. This novel utilization with a greater atom economy provides a simple and practical conversion route for the synthesis of the potential biological 2(5H)-furanone compounds containing multifunctional groups. [ABSTRACT FROM AUTHOR]

The article presents chemical equations related to Synthesis of 4-Diarylamino-3-iodo-2(5H)-furanones by an Efficient Difunctionalizable Transfer Reagent PhI(OAc)2. by P. Peng, J. SHI and others, published in the periodical "Synthetic Communications" in 2014.

Background: Results from both clinical trials and real-world observational studies suggest that lamivudine plus dolutegravir (3TC + DTG) dual therapy has excellent virological efficacy and safety in HIV-1-infected patients. However, there is still no relevant study related to this dual therapy reported in China., Methods: In this multicenter, retrospective, observational study that included HIV-1-infected patients in China, baseline and follow-up data were collected to analyze the virological suppression rate, immune restoration, and adverse events during follow-up in HIV-1-infected patients who switched to the 3TC + DTG dual therapy., Results: This study recruited 112 HIV-1-infected patients, including 101 men (90.2%), with a median age of 44.0 years (IQR: 33.00-57.75) and median CD4+ T-cell count of 432.13 cells/μL (IQR: 237.75-578.50). The overall virological suppression rate was 94.5% at the 24-week follow-up. However, the virological suppression rates of men who have sex with men patients and patients with CD4+ T-cell count of <350 cells/μL were higher than the baseline value (P < 0.05) at week 24. The results of Cox regression analysis showed that the baseline CD4+ T-cell count was an independent determinant of immune restoration in patients, and patients with baseline CD4+ T-cell count of 350-500 cells/μL outperformed patients with baseline CD4+ T-cell count of <350 cells/μL in immune restoration (hazard ratio: 4.469, 95% confidence interval: 1.801 to 11.091, P = 0.001). Adverse events were reported in 5 patients (incidence rate of 4.5%); among them, 3 patients developed neuropsychiatric symptoms. Results from the laboratory data analysis showed that patients with grade 1 and 2 adverse events had elevated levels of low-density lipoprotein cholesterol and total bilirubin. Furthermore, grade 3 and 4 adverse events were associated with the elevation of blood glucose level in 4 patients., Conclusions: Thus, the 3TC + DTG dual therapy displayed an excellent virological efficacy against HIV-1 infections and had an acceptable safety profile, with predominantly mild adverse events in HIV-1-infected patients in China., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Marchantia polymorpha L. (MPL), a common type of liverwort, has been used as herbal medicine to improve liver function in China for many years. Although modern studies revealed that MPL contains various polyphenols, terpenoids, and bis[bibenzyls], its biological effects on liver function have never been systemically studied in any animal model. In this study, flavonoids were extracted from MPL and the components in the MPL flavonoids as well as the antioxidant capacity of MPL flavonoids were analysed. A rat model of liver injury was induced by intraperitoneal injection of 10% carbon tetrachloride (CCl4). MPL flavonoids were administered daily at a dose of 50, 100, and 200 mg/kg body weight to the rats for 2 weeks prior to injection of CC14. Treatment with MPL flavonoids, especially at a dose of 200 mg/kg, attenuated CCl4-induced increases in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, nitric oxide, malondialdehyde, tumour necrosis factor-α, interleukin-1β, and interleukin-6, as well as reductions in superoxide dismutase and glutathione peroxidase. Microarray analyses showed that co-treatment with MPL flavonoids and CCl4 up-regulated many antioxidant and anti-apoptotic genes, but down-regulated several pro-inflammatory genes, compared to treatment with CCl4 alone. PCR and western blot assays further identified that MPL flavonoids increased GPX1, TMX1, TXN, and XIAP expression, but decreased IL-1 and IL1RAP expression and inhibited Jak/stat3 signalling. In conclusion, MPL flavonoids exerted hepatoprotective effects via antioxidant and gene regulatory mechanisms. (Altern Ther Health Med.