Malus toringoides (Rehd.) Hughes decoction alleviates ISO-induced cardiac fibrosis by inhibiting cardiomyocyte inflammation and pyroptosis via the HK1/NLRP3-signaling pathway.

Malus toringoides (Rehd.) Hughes leave, called "Eseye (Ese)", is a traditional medicinal plant from the Tibet province of China that has efficiency of anti-inflammatory, antioxidant and anti-apoptosis to treat cardiac conditions. We herein explored the underlying protective mechanisms of Ese decoction in isoproterenol (ISO)-induced cardiac fibrosis (CF). And treatment with an Ese decoction attenuated tissue injury and decreased the release of IL-1ß, IL-18, TNF-α, and caspase-3 and elevated the Bax/Bcl-2 ratio in CF mice. Damage to the mitochondrial ultrastructure of myocardium was alleviated, and the level of ROS was markedly diminished with Ese treatment. Ese inhibited the expression of proteins associated with pyroptosis by the HK1/NLRP3-signaling pathway, and also improved CF. Based on anti-inflammatory, antioxidative and anti-apoptosis activities effects of Ese decoction, we found that Ese protected against ISO-induced CF, which attributed to its inhibition of inflammation and pyroptosis as mediated by the HK1/NLRP3-signaling pathway.

Recent Advances of N-2,2,2-Trifluoroethylisatin Ketimines in Organic Synthesis.

The special properties of fluorine atoms and fluorine-containing groups have led to an increasing number of applications for fluorine-containing organic compounds, which are also extremely widely used in the field of new drug development. Unfortunately, naturally fluorinated organics are rare in nature, so the selective introduction of fluorine atoms or fluorine-containing groups into organic molecules is very important for pharmaceutical/synthetic chemists. N-2,2,2-trifluoroethylisatin ketimines have received the attention of many chemists since they were first developed as fluorine-containing synthons in 2015. This paper reviews the organic synthesis reactions in which trifluoroethyl isatin ketimine has been involved in recent years, focusing on the types of reactions and the stereoselectivity of products, and also provides a prospect of its application in this field.

A Retrospective Study of 105 Patients with Elastolytic Giant Cell Granuloma and a Proposal for a New Clinical Classification.

Elastolytic giant cell granuloma, an idiopathic granulomatous dermatosis, is characterized by annular plaques on sun-exposed areas, and has been termed actinic granuloma or annular elastolytic giant cell granuloma. Many atypical clinical manifestations and lesions involving sun-protected areas have been reported. The aims of this retrospective study of 105 patients were to summarize the clinical and histological features of patients with this condition; to provide evidence for the viewpoint that elastolytic giant cell granuloma is a better term to include all clinical morphological types presenting with elastolysis, elastophagocytosis, and an infiltrate of multinucleated giant cells histologically; and to establish a new clinical classification. The varying clinical manifestations were further categorized into annular, papular, giant, mixed and generalized forms. The pathological manifestations were classified into giant cell, necrobiotic, histiocytic, sarcoidal and mixed patterns. Diabetes mellitus or impaired glucose tolerance were the most commonly identified comorbidities. Oral low-dose corticosteroid may be an effective treatment.

Liquiritigenin protects against myocardial ischemic by inhibiting oxidative stress, apoptosis, and L-type Ca2+ channels.

Liquiritigenin (Lq) offers cytoprotective effects against various cardiac injuries, but its beneficial effects on myocardial ischemic (MI) injury and the related mechanisms remain unclear. In the in vivo study, an animal model of MI was induced by intraperitoneal injection of isoproterenol (Iso, 85 mg/kg). ECG, heart rate, serum levels of CK and CK-MB, histopathological changes, and reactive oxygen species (ROS) levels were all measured. In vitro, H9c2 cells were divided into four groups and treated for 24 hr with liquiritigenin (30 µmol/L and 100 µmol/L) followed with CoCl2 (800 µmol/L) for another 24 hr. Cell viability, apoptosis, mitochondrial membrane potential, and intracellular Ca2+ concentration ([Ca2+ ]i ) were then assessed. The L-type Ca2+ current (ICa-L ) was detected using a patch clamp technique on isolated rat ventricular myocytes. The myocyte contraction and Ca2+ transients were measured using an IonOptix detection system. The remarkable cardiac injury and generation of intracellular ROS induced by Iso were alleviated via treatment with Lq. CoCl2 administration induced cell apoptosis, mitochondrial dysfunction, and Ca2+ overload in H9c2; Lq reduces these deleterious effects of CoCl2 . Meanwhile, Lq blocked ICa-L in a dose-dependent manner. The half-maximal inhibitory concentration of Lq was 110.87 µmol/L. Lq reversibly reduced the amplitude of cell contraction as well as the Ca2+ transients. The results show that Lq protects against MI injury by antioxidation, antiapoptosis, counteraction mitochondrial dysfunction, and inhibition of ICa-L , thus damping intracellular Ca2+ .

Structural modification and antihypertensive activity study of formononetin derivatives.

A series of formononetin derivatives with substituted benzyloxy groups on the 4' position of isoflavone were designed and synthesized. Their vasodilative activities were evaluated by wire myograph system on isolated rat mesenteric arterial ring. The preliminary SAR of target compounds was thus discussed. Compounds 3d and 3e exhibited potent vasodilative activities against the rat mesenteric arterial rings induced contraction with K+. Compounds 3d and 3e also showed antihypertensive effects in SHRs by oral administration.

Design, synthesis and antibacterial activity evaluation of pleuromutilin derivatives according to twin drug theory.

A series of novel pleuromutilin derivatives were designed and synthesized based on the twin drugs theory. Piperazinyl and thioether were used as the linkage to connect the pleuromutilin nuclear and sulfonamide to improve the biological activity and water solubility of derivatives. The in vitro antibacterial activities against drug-sensitive and drug-resistance bacteria were evaluated by agar dilution method. Most of the 25 compounds displayed excellent antibacterial activities against drug-sensitive bacteria, particularly, five compounds (9, 10, 11, 14a and 14b) exerted the excellent antibacterial activities against drug-resistance bacteria.

Swertia mussotii prevents high-fat diet-induced non-alcoholic fatty liver disease in rats by inhibiting expression the TLR4/MyD88 and the phosphorylation of NF-κB.

CONTEXT: Swertia mussotii Franch. (Gentianaceae) is a source of the traditional Tibetan medicine, ZangYinChen, and is used to treat chronic hepatitis and many types of jaundice. OBJECTIVE: This study explored the therapeutic effects and mechanism of S. mussotii on non-alcoholic fatty liver disease in diet-induced hypercholesterolaemia. MATERIALS AND METHODS: After a week of adaptive feeding, 32 Sprague-Dawley rats were divided into four groups: (1) Control, (2) Control-S, (3) Model, and (4) Model-S. During the 12 experimental weeks, we established the Model using a high-fat diet. Control-S and Model-S were given 1.0 g/kg S. mussotii water extract via gavage starting in the fifth week until the end of experiment. RESULTS: When compared with Model rats, the S. mussotii water extract led to a reduction in high-density lipoproteins (43.9%) and albumin (13.9%) and a decrease in total cholesterol (54.0%), triglyceride (45.6%), low-density lipoproteins (8.6%), aspartate aminotransferase (11.0%), alanine aminotransferase (15.5%), alkaline phosphatase (19.1%), total protein (6.4%), and glucose (20.8%) in serum. A reduction in three cytokines (IL-1ß, IL-6, and TNFα) was detected. Histopathological examination showed that liver steatosis was significantly relieved in S. mussotii-treated high-fat diet rats. S. mussotii also caused a downregulation in the expression of TLR4 (43.2%), MyD88 (33.3%), and a decrease in phosphorylation of NF-κB. DISCUSSION AND CONCLUSIONS: Our findings indicate that S. mussotii may act as a potential anti-inflammation drug via inhibition of the TLR4/MyD88/NF-κB pathway. Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.

Association Between Peripheral Eosinophilia and Clinical Characteristics of Adult-onset Still's Disease with Persistent Eruption: A Retrospective Study.

Persistent eruption occurs in a subset of patients with adult-onset Still's disease. In our experience, a considerable proportion of these patients present with peripheral eosinophilia. The aims of this study were to summarize the clinical and histological features of patients with adult-onset Still's disease with persistent eruption in the current study cohort, and to assess the association between peripheral eosinophil levels and disease characteristics. A total of 21 patients with adult-onset Still's disease with persistent eruption were included in this retrospective study. Koebner signs, an important diagnostic clue, were found in 85.7% of patients. The proportion of patients presenting with eosinophilia within the disease course was 57.1%. Skin histology revealed infiltration of eosinophils in 90.5% of patients. Peripheral eosinophil levels were positively associated with involved body surface area. Patients with normal peripheral eosinophil counts were more likely to achieve complete remission than those with abnormal peripheral eosinophil counts. Eosinophils may be involved in the pathogenesis of skin eruption. Abnormal peripheral eosinophil counts in these patients may indicate a more refractory disease course.

Two novel SASH1 mutations in Chinese families with dyschromatosis universalis hereditaria.

BACKGROUND: Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by hyper- and hypo-pigmented macules on the face, trunk, and extremities. The condition causes severe cosmetic problem which can lead to significant psychological distress to the patients and bear a negative impact on society. DUH is a condition with genetic heterogeneity. The SASH1 gene was recently identified as pathogenic genes in DUH patients. METHODS: Two families clinically diagnosed with dyschromatosis universalis hereditaria were enrolled. Whole-exome sequencing combined with Sanger sequencing and bioinformatics analysis was performed in the probands. MutationTaster, CADD, SIFT, PolyPhen-2, and LRT software, and The American College of Medical Genetics and Genomics Standards and Guidelines were employed to assess the pathogenicity of detected missense mutations. One hundred healthy unrelated Chinese individuals were used as controls. All participants signed an informed consent form. RESULTS: Genetic screening revealed a heterozygous SASH1 c.1547G>A (p.Ser516Asn) mutation for patients in family 1, and SASH1 c.1547G>T (p.Ser516Ile) for family 2. Both such de novo mutations are located in a highly conserved SLY domain in SASH1, have not been previously reported in any publication, and were not detected in any control databases. CONCLUSIONS: The novel heterozygous mutations, SASH1 c.1547G>A and c.1547G>T, are likely responsible for the DUH phenotype in these two families. Our study expands the mutation spectrum of DUH. Whole-exome sequencing showed its efficiency in the diagnostic of hereditary skin disorders.

Design, synthesis and antibacterial activities of pleuromutilin derivatives.

We described the design, synthesis and antimicrobial activities of novel pleuromutilin derivatives with substituted piperazine substrate. Minimum inhibitory concentration (MIC) was used to evaluate the activity of the derivatives against six bacteria in vitro, and compound 8 was potent against Staphylococcus aureus and Staphylococcus epidermidis with the MIC value of 0.0625 µg/ml. 10a and 10 b showed similar activity to positive control drugs (tiamulin, erythromycin) against S. aureus with the MIC value of 0.125 µg/ml. The binding mode of compound 8 and tiamulin to the ribosome pocket showed the correlation between binding parameters and the antibacterial activity, and more bonds and stronger combination could effectively enhance the activity of compounds.[Formula: see text].

Visible-light-mediated copper photocatalysis for organic syntheses.

Photoredox catalysis has been applied to renewable energy and green chemistry for many years. Ruthenium and iridium, which can be used as photoredox catalysts, are expensive and scarce in nature. Thus, the further development of catalysts based on these transition metals is discouraged. Alternative photocatalysts based on copper complexes are widely investigated, because they are abundant and less expensive. This review discusses the scope and application of photoinduced copper-based catalysis along with recent progress in this field. The special features and mechanisms of copper photocatalysis and highlights of the applications of the copper complexes to photocatalysis are reported. Copper-photocatalyzed reactions, including alkene and alkyne functionalization, organic halide functionalization, and alkyl C-H functionalization that have been reported over the past 5 years, are included.

Images in clinical medicine: Segmental neurofibromatosis.

A 4-year-old girl presented for evaluation of cutaneous nodules that had been present on the left side of her trunk since birth. Physical examination revealed numerous soft, nontender papules and nodules across the left upper abdomen and wrapping around to the back.