Radix Tetrastigma Hemsleyani Flavone represses cutaneous squamous cell carcinoma via Janus kinase/signal transducer and activator of transcription 3 pathway inactivation.

Cutaneous squamous cell carcinoma (CSCC) is the second most common malignant skin tumor and significantly affects patients' quality of life and health. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway activation is involved in CSCC development. Radix Tetrastigma hemsleyani flavone (RTHF) is an active Radix Tetrastigma extract (RTE), which was recently reported to have promising inhibitory effects on CSCC. However, the underlying functional mechanisms of this inhibition remain unknown. In the present study, A431 cells or SCL-1 cells were incubated with 1, 5, and 10 mg/mL RTHF for 48 h, respectively. A significantly increased wound closure rate, decreased number of migrated and invaded cells, decreased colony number, and elevated apoptotic rate were observed after treatment with 1, 5, and 10 mg/mL RTHF. Furthermore, after incubation with RTHF, p-JAK1/JAK1, p-JAK2/JAK2, and p-STAT3/STAT3 levels were drastically reduced. An A431 xenograft model was constructed, followed by oral administration of 15, 30, or 60 mg/kg RTHF for 21 consecutive days. A significantly lower increase in tumor volume and reduced tumor weight were observed in all RTHF-treated groups. In addition, JAK/STAT3 signaling was drastically repressed in tumor tissues. Collectively, RTHF inhibited CSCC progression, which may be associated with JAK/STAT3 pathway inactivation.

The predictive efficacy of programmed cell death in immunotherapy of melanoma: A comprehensive analysis of gene expression data for programmed cell death biomarker and therapeutic target discovery.

In this study, genes linked to prognosis in skin cutaneous melanoma (SKCM) involved in programmed cell death (PCD) were identified and confirmed and prognostic models based on these genes were constructed. Acquisition and analysis of clinical data and RNA sequencing information from The Cancer Genome Atlas-SKCM (TCGA-SKCM) and Sangerbox databases, gene expression data for 477 tumor samples and 2 normal samples were successfully gathered. The patients were separated into two clusters based on consensus clustering of PCD-related genes, with Cluster A having greater tumor purity, ESTIMATE score, immune score, and matrix score, and Cluster B having a significantly distinct pattern of immune cell infiltration. The use of gene set enrichment analysis and weighted correlation network analysis showed significant associations between certain genes and factors such as tumor mutation burden, age, stage, grade, and tumor subtype. Finally, based on the 12 genes selected by Least Absolute Shrinkage and Selection Operator regression analysis (STAT3, IRF2, SLC7A11, ZEB1, LIPT1, PML, GCH1, GYS1, ABCC1, XBP1, TFAP2C, NOX4), a prognostic model of PGD-related genes was constructed. The effectiveness of the model's prognostic value was confirmed through survival analysis, time-dependent receiver operating characteristic curve, single-factor Cox regression analysis, and nomogram. We also verified the relationship between the GCH1 and MKI67 expression by wet experiment. This model has high prediction accuracy in SKCM patients and can provide a reference for clinical treatment.

The role of PKP1 in tumor progression in melanoma: Analysis of a cell adhesion-related model.

The incidence rate of melanoma varies across regions, with Europe, the United States, and Australia having 10-25, 20-30, and 50-60 cases per 1 00 000 people. In China, patients with melanoma exhibit different clinical manifestations, pathogenesis, and outcomes. Current treatments include surgery, adjuvant therapy, and immune checkpoint inhibitors. Nonetheless, complications may arise during treatment. Melanoma development is heavily reliant on cell adhesion molecules (CAMs), and studying these molecules could provide new research directions for metastasis and progression. CAMs include the integrin, immunoglobulin, selectin, and cadherin families, and they affect multiple processes, such as maintenance, morphogenesis, and migration of adherens junction. In this study, a cell adhesion-related risk prognostic signature was constructed using bioinformatics methods, and survival analysis was performed. Plakophilin 1 (PKP1) was observed to be crucial to the immune microenvironment and has significant effects on melanoma cell proliferation, migration, invasion, and the cell cycle. This signature demonstrates high reliability and has potential for clinical applications.

Asymmetric Aminalization via Cation-Binding Catalysis.

Asymmetric cation-binding catalysis, in principle, can generate "chiral" anionic nucleophiles, where the counter cations are coordinated within chiral environments. Nitrogen nucleophiles are intrinsically basic, therefore, its use as nucleophiles is often challenging and limiting the scope of the reaction. Particularly, a formation of configurationally labile aminal centers with alkyl substituents has been a formidable challenge due to the enamine/imine equilibrium of electrophilic substrates. Herein, we report enantioselective nucleophilic addition reactions of potassium phthalimides to Boc-protected alkyl- and aryl-substituted α-amido sulfones. In situ generated imines smoothly reacted with the nitrogen nucleophiles to corresponding aminals with good to excellent enantioselectivitiy under mild reaction conditions. In addition, transformation of aminal products gave biologically relevant pyrrolidinone-fused hexahydropyrimidine scaffold with excellent stereoselectivity and good yield.

Case report: Lower eyelid Reconstruction with the rotation flap pedicled by orbicularis oculi muscle.

Background: Loss of eyelid tissue can be caused by trauma, congenital defects or tumors. Eyelid reconstruction is complicated and challengingly difficult because of the complex anatomy of the eyelid. Several types of surgical procedures for the reconstruction of eyelid defects are available. Objective: To describe reconstruction of lower-eyelid defects using a rotation flap pedicled by the orbicularis oculi. Methods: Fourteen patients (mean age = 67 years old; ages range of 53-86 years old) who suffered from tumor excision from the lower eyelid were treated by the method. Results: The mean duration of follow-up was 14 (range, 12-16) months. Ectropion, abnormal eyelid position and donor-site morbidity were not observed during follow-up. Conclusion: A rotation flap pedicled by the orbicularis oculi can be a good choice for single-stage reconstruction of lower-eyelid defects.

Extraction condition optimization and effects of drying methods on physicochemical properties and antioxidant activities of polysaccharides from Astragalus cicer L.

Response surface methodology (RSM) including three variables was performed to optimize the extraction parameters of Astragalus cicer L. polysaccharides (ACPs). The influence of different drying techniques on the physicochemical properties and antioxidant abilities of ACPs were evaluated. The ACPs were dried with hot air (HD), vacuum (VD) and freeze drying (FD) methods. The optimal conditions for ACPs extraction were as follows: water to raw material ratio of 25 mL/g, extraction time of 61 min and temperature of 75 °C. Under these parameters, an ACPs yield of 10.97% was obtained. HPLC analysis showed that the monosaccharide compositions of the three ACPs dried with HD, VD or FD techniques were identical. The three ACPs exhibited antioxidant abilities in a concentration-dependent manner. ACPs dried with the FD method (FD-ACPs) had the best antioxidant activities, which might be related to their smaller molecular weight and higher uronic acid content. At the determined concentration of 1 mg/mL, the ferric reducing power, and DPPH and ABTS free radical scavenging capacities of FD-ACPs were 0.762, 75.30% and 99.21%, respectively. Therefore, FD was a good choice for the drying of Astragalus cicer L. polysaccharides.

Extraction condition optimization and effects of drying methods on physicochemical properties and antioxidant activities of polysaccharides from comfrey (Symphytum officinale L.) root.

This study was designed to investigate the extraction conditions of polysaccharides from comfrey (Symphytum officinale L.) root (CRPs) using response surface methodology (RSM). The effects of three variables including liquid-solid ratio, extraction time and extraction temperature on the extraction yield of CRPs were taken into consideration. Moreover, the effects of drying methods including hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the physicochemical properties and antioxidant activities of CRPs were evaluated. The optimal conditions to extract the polysaccharides were as follows: liquid-solid ratio (15mL/g), extraction time (74min), and extraction temperature (95°C), allowed a maximum polysaccharides yield of 22.87%. Different drying methods had significant effects on the physicochemical properties of CRPs such as the chemical composition (contents of total polysaccharides and uronic acid), relative viscosity, solubility and molecular weight. CRPs drying with FD method showed stronger reducing power and radical scavenging capacities against DPPH and ABTS radicals compared with CRPs drying with HD and VD methods. Therefore, freeze drying served as a good method for keeping the antioxidant activities of polysaccharides from comfrey root.

Physicochemical properties and activities of comfrey polysaccharides extracted by different techniques.

The effects of extraction techniques on the physicochemical properties, antioxidant activity and antihyperglycemic activity of comfrey polysaccharides (CPs) were evaluated. Four techniques were used to extract CPs: hot water extraction (HW), ultrasonic-assisted extraction (UA), enzyme-assisted extraction (EA) and enzyme-ultrasonic-assisted extraction (EUA). Experimental results indicated that CPs extracted by the UA (UA-CPs) and EUA methods (EUA-CPs) had higher extraction yields. The four CPs showed the same monosaccharide composition but a significant difference in monosaccharide content. CPs showed antioxidant activities and antihyperglycemic activities in a concentration-dependent manner. UA-CPs exhibited better antioxidant capacity, which might have been related to its smaller molecular weight and higher uronic acid content. In addition, UA-CPs showed notable α-glucosidase inhibition activity. These results suggested that ultrasonic-assisted extraction technology was more beneficial to enhance the extraction yields of the polysaccharides, and obtain higher bioactive polysaccharides from comfrey.

Thermal inactivation kinetics and effects of drying methods on the phenolic profile and antioxidant activities of chicory (Cichorium intybus L.) leaves.

The thermal inactivation kinetics of enzymes, including polyphenol oxidase (PPO) and peroxidase (POD), in chicory (Cichorium intybus L.) leaves were evaluated. In addition, the influences of different drying techniques (shade drying, hot air drying and freeze drying) on the phenolic profiles and antioxidant activities of chicory leaves were determined. The antioxidant activities of chicory leaves were evaluated on the basis of their 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, reducing power, and 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity. The results showed that the activation energy for PPO and POD inactivation were 123.00 kJ/mol and 78.99 kJ/mol, respectively. Preliminary treatment with hot water for 3 min at 90 °C was beneficial for preserving the phenolics present in fresh leaves. Hot air drying was better for the phenolics preservation. The hot air-dried and freeze-dried leaves possessed good antioxidant activities. The leaves with higher phenolics contents had better antioxidant activities, which indicated that the preservation of the phenolics was important for maintaining the antioxidant activity of chicory leaves.

Extraction optimization and influences of drying methods on antioxidant activities of polysaccharide from cup plant (Silphium perfoliatum L.).

Response surface methodology (RSM) was used to investigate the extraction condition of polysaccharide from cup plant (Silphium perfoliatum L.) (named CPP). Water to raw material ratio (10-30 mL/g), extraction time (40-80 min) and extraction temperature (60-100°C) were set as the 3 independent variables, and their effects on the extraction yield of CPP were measured. In addition, the effects of drying methods including hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the antioxidant activities of CPP were evaluated. The results showed that the optimal condition to extract CPP was: water to raw material ratio (15 mL/g), extraction time (61 min), and extraction temperature (97°C), a maximum CPP yield of 6.49% was obtained under this condition. CPP drying with FD method showed stronger reducing power (0.943 at 6 mg/mL) and radical scavenging capacities against DPPH radical (75.71% at 1.2 mg/mL) and ABTS radical (98.06 at 1.6 mg/mL) than CPP drying with HD and VD methods. Therefore, freeze drying served as a good method for keeping the antioxidant activities of polysaccharide from cup plant. The polysaccharide from cup plant has potential to use as a natural antioxidant.

Asymmetric Synthesis of Trisubstituted Tetrahydrothiophenes via in Situ Generated Chiral Fluoride-Catalyzed Cascade Sulfa-Michael/Aldol Reaction of 1,4-Dithiane-2,5-diol and α,ß-Unsaturated Ketones.

A chiral fluoride-catalyzed asymmetric cascade sulfa-Michael/aldol condensation reaction of 1,4-dithiane-2,5-diol and a series of α,ß-unsaturated ketones is described to access chiral trisubstituted tetrahydrothiophene derivatives. The target products, including the spiro tetrahydrothiophene derivatives bearing a five-, six-, and seven-membered ring, were highly functionalized and showed high ee value. This established protocol realized a highly enantioselective reaction with a catalytic amount of KF and Song's chiral oligoEG via in situ generated chiral fluoride to construct useful heterocyclic skeletons with great complexity.