Topical Application of Chinese Formula Yeliangen Promotes Wound Healing in Streptozotocin-Induced Diabetic Rats.

Diabetic wound is one of the most severe complications of diabetes mellitus (DM). Despite the associated risks of wound healing impairment in diabetes, treatment strategies remain limited. Yeliangen (YLG) is a Chinese formulation mainly composed of the rhizome of Coptis chinensis, the root of Isatis tinctoria, and the leaf of Isatis indigotica. We investigated the wound healing effects of YLG in type 2 diabetic (T2DM) rats, which were induced by intraperitoneal administration of streptozotocin after a high-fat diet for four weeks. 3 × 3 cm2 full-thickness excisional wounds were created on the dorsal surface of rats and then divided to control (DC), negative (DPJ), positive (DPC), and YLG-treated (DYLG) groups. Rat's wounds were treated twice daily for 21 days. Wound area and wound contraction were detected on days 0, 3, 7, 14, and 21. Histopathological examinations were performed by H&E staining and immunohistochemistry (IHC). The biochemical parameters, mRNAs, and protein expressions were analyzed through enzyme-linked immunoassays (ELISA), qPCR, and western blot, respectively. Compared with other groups, the histological changes of wound tissue in the DYLG group were improved, and the expressions of CD31, eNOS, and PCNA were significantly upregulated. Besides, YLG significantly reduced the inflammatory factors' expressions of TNF-α, NF-κB, MMP-9, and IL-1B on days 7, 14, and 21 postwounding. Moreover, YLG induced angiogenesis and neovascularization by significantly increasing the levels of VEGF, TGF-ß1, EGF, PDGF, and SDF-1α on days 3, 7, and 14. In conclusion, YLG improved wound healing by reducing inflammation and increasing angiogenesis which may provide an alternative and effective approach for diabetic wound therapy.

Quantitative Proteomics Based on iTRAQ Reveal that Nitidine Chloride Induces Apoptosis by Activating JNK/c-Jun Signaling in Hepatocellular Carcinoma Cells.

The aim of the present study was to investigate the cytotoxic effects and underlying molecular mechanisms of nitidine chloride (NC) in hepatocellular carcinoma cells via quantitative proteomics. MTT assays were used to detect the inhibitory effects of NC in Bel-7402 liver cancer cells, and the number of apoptotic cells was measured by flow cytometry. Quantitative proteomics technology based on iTRAQ was used to discover differential expressed proteins after NC treatment, and bioinformatic techniques were further used to screen potential targets of NC. Molecular docking was applied to evaluate the docking activity of NC with possible upstream proteins, and their expression was detected at the mRNA and protein levels by quantitative reverse transcription PCR and western blotting. NC inhibited the proliferation of Bel-7402 cells after 24 h of treatment and stimulated apoptosis in vitro. The proteomics experiment showed that NC triggers mitochondrial damage in HCC cells and transcription factor AP-1 (c-Jun) may be a potential target of NC (fold change = 4.36 ± 0.23). Molecular docking results revealed the highest docking score of NC with c-Jun N-terminal kinase (JNK), one of the upstream proteins of c-Jun. Moreover, the mRNA and protein expression of c-Jun and JNK were significantly increased after NC treatment (p < 0.05). These findings indicate that NC significantly induced mitochondrial damage in HCC cells, and induced apoptosis by activating JNK/c-Jun signaling.

The fabrication, characterization, and application of chitosan-NaOH modified casein nanoparticles and their stabilized long-term stable high internal phase Pickering emulsions.

The demand for facile delivery systems from natural biopolymers with long-term storage stability to deliver liposoluble nutraceuticals such as ß-carotene (BC) is increasing. In this work, a facile and reliable emulsifier of chitosan (CS)-NaOH-modified casein (CA) nanoparticles (NPs) was fabricated for the stabilization of high internal phase Pickering emulsions (HIPPEs) with versatile stability. Dynamic light scattering, TEM, FTIR, and interface tension results indicated that CS-CA NPs exhibited nanoscale (109-373 nm), positive charge (22-38 mV), pH-response, spherical in shape, assembled spontaneously by non-covalent interactions, and high surface activity. Optical microscopy, confocal laser scanning microscopy (CLSM), and rheometer results demonstrated that HIPPEs were emulsified by a dense and compact 3D network between the continuous phase and the interfacial region. Hence, the CS-CA NP-stabilized HIPPEs showed long-term storage stability (over 18 months at ambient temperature) and thermostabilization (1 month at 80 °C). The robust and compact CS-CA NPs dramatically declined the contents of primary and secondary oxidation production in HIPPEs than that by corn oil. Moreover, CS-CA NPs stabilized HIPPEs appreciably enhanced the bioaccessibility (2.56 times) and chemical stability (thermal, UV-light, and storage) of BC. This research evidenced that CS-protein or polysaccharide-CA-based systems could be an encouraging formulation to commercially construct tunable HIPPEs with adorable stability for liposoluble nutraceuticals with enhanced attributes.

Identification of key genes in osteosarcoma - before and after CDK7 treatment.

BACKGROUND: Osteosarcoma is one of the most common bone tumors, with a high degree of malignancy and a poor prognosis. Recent studies have shown that THZ2, a cyclin-dependent kinase 7 inhibitor, can exhibit strong antibone tumor effects in vivo and in vitro by inhibiting transcriptional activity. In this study, by screening the differentially expressed genes (DEGs) of osteosarcoma cells before and after THZ2 treatment, it provides new possible targets for the future targeted therapy of osteosarcoma. METHODS: Download the gene expression profile of GSE134603 from the Gene Expression Omnibus database, and use the R software package "limma Geoquery" to screen DEGs. DAVID database was used for gene ontology analysis of DEGs. Use search tool for the retrieval of interacting genes online database and Cytoscape software to construct protein-protein interaction network. Use the "MCODE" plugin in Cytoscape to analyze key molecular complexes (module) of DEGs, and use the "Cluego" plugin to perform Kyoto Encyclopedia of Genes and Genomes enrichment analysis on module genes. The Hub gene is selected from the genes in DEGs that coexist in the top 30 Degree and the Kyoto Encyclopedia of Genes and Genomes pathway. RESULTS: A total of 1033 DEGs were screened, including 800 up-regulated genes and 233 down-regulated genes. Gene ontology analysis showed that cell component is the main enrichment area of DEGs, mainly in the nucleus, cytoplasm, and nucleoplasm. In addition, in molecular function analysis, DEGs are mainly enriched in the process of protein binding. In biological process analysis, changes in DEGs can also be observed in transcription and regulation using DNA as a template. Twenty-nine module genes are enriched in the Ribosome biogenesis in eukaryotes pathway. Finally, 4 key genes are drawn: essential for mitotic growth 1, U3 SnoRNP protein 3 homolog, U3 small nucleolar RNA-associated protein 15 homolog, and WD repeat domain 3. CONCLUSION: This study found that the 4 genes essential for mitotic growth 1, U3 SnoRNP protein 3 homolog, U3 small nucleolar RNA-associated protein 15 homolog, WD repeat domain 3, and the ribosome biogenesis in eukaryotes pathway play a very important role in the occurrence and development of osteosarcoma, and can become a new target for molecular targeted therapy of osteosarcoma in the future.

Efficacy and safety of interferon α-2b spray for herpangina in children: A randomized, controlled trial.

OBJECTIVES: The treatment of acute herpangina is inconsistent. We aim to evaluate the effectiveness and safety of interferon α-2b spray versus Ribavirin for this disease. METHODS: A randomized, controlled trial was conducted in eight hospitals in China between 2016 and 2018. 668 patients (1-7 years old) were randomized into an experimental group (treated with Interferon α-2b spray) or control group (received Ribavirin Aerosol). Body temperature returning to normal within 72 h and remaining so for 24 h was the primary outcome; release of oral herpes and adverse events were the secondary outcomes. RESULTS: (1) The average age of onset was 2.5 years old. (2) After 72 h treatment, body temperature of 98.5% patients in experimental group and 94.3% in control group returned to normal and remained so for 24 h (P = 0.004). The differences were greater at 48 h treatment (95.2% vs. 85.9%, P < 0.001) and at 24 h (77.5% vs. 66.5%, P = 0.001). (3) The rate of improved oral herpes in the experimental group was higher than that in control group (46.7% vs.37.1%, P = 0.011). No adverse reaction occurred. CONCLUSIONS: Local application of recombinant interferon α-2b spray showed better efficacy for acute herpangina in children. It was safe for use.

Advances in the treatment of novel coronavirus disease (COVID-19) with Western medicine and traditional Chinese medicine: a narrative review.

In December 2019, the coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered. Since its emergence, COVID-19 has been outbreaking rapidly worldwide, where the virus has so far caused the death of hundreds of thousands and infected more than a million, what has been called a pandemic by the World Health Organization (WHO). According to the WHO-Coronavirus disease 2019 Situation Report-142, by June 10, 2020, there are 7,145,539 confirmed cases and 408,025 deaths. There is an urgent need to develop a suitable specific medicine against this novel coronavirus; therefore, scientists and researchers around the world are making great efforts endeavoring to discover an efficient specific medication for COVID-19 treatment. Given the similarity of the novel coronavirus with previous epidemic viruses, namely, the acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), previously tested drugs could potentially work against the novel coronavirus. In this narrative review, we aim to summarize and discuss the effectiveness of current Western medicine and traditional Chinese medicine options for COVID-19 treatment based on the overview of the scientific literature. Some Western medicines including remdesivir, chloroquine, hydroxychloroquine, favipiravir, lopinavir/ritonavir, and arbidol, as well as some traditional Chinese medicine (TCM) such as Qingfei Paidu decoction, Yupingfeng, Lianhua Qingwen, and TCM injections have revealed a relative activity against SARS-CoV-2 in vitro, in observational studies, and in clinical trials. However, further extensive studies and clinical trials including double-blind and randomized clinical trials, with a higher number of patients, are necessary to confirm the activity of these medicines. There are several ongoing trials conducted on the drugs of COVID-19, and the results are urgently needed to make a suitable treatment recommendation.

Evaluation of ergosterol composition and esterification rate in fungi isolated from mangrove soil, long-term storage of broken spores, and two soils.

Ergosterol is an important fungal-specific biomarker, but its use for fungal biomass estimation is still varied. It is important to distinguish between free and esterified ergosterols, which are mainly located on the plasma membrane and the cytosolic lipid particles, respectively. The present study analyzes free and esterified ergosterol contents in: (1) the fifty-nine strains of culturable fungi isolated from mangrove soil, (2) the broken spores of the fungus Ganoderma lucidum stored in capsule for more than 12 years, and (3) the mangrove soil and nearby campus wood soil samples by high performance liquid chromatography (HPLC). The results show that the contents of free and esterified ergosterols varied greatly in fifty-nine strains of fungi after 5 days of growth, indicating the diversity of ergosterol composition in fungi. The average contents of free and total ergosterols from the fifty-nine strains of fungi are 4.4 ± 1.5 mg/g and 6.1 ± 1.9 mg/g dry mycelia, respectively, with an average ergosterol esterification rate of 27.4%. The present study suggests that the fungi might be divided into two classes, one is fungi with high esterification rates (e.g., more than 27%) such as Nectria spp. and Fusarium spp., and the other is fungi with low esterification rates (e.g., less than 27%) such as Penicillium spp. and Trichoderma spp. Moreover, the ergosterol esterification rate in the spores of G. lucidum is 91.4% with a very small amount of free ergosterol (0.015 mg/g), compared with 41.9% with a higher level of free ergosterol (0.499 mg/g) reported in our previous study in 2007, indicating that free ergosterol degrades more rapidly than esterified ergosterol. In addition, the ergosterol esterification rates in mangrove soil and nearby campus wood soil samples range from 0 to 39.0%, compared with 80% in an old soil organic matter reported in a previous study, indicating the potential relationship between aging degree of fungi or soil and esterification rate. The present study proposes that both free and esterified ergosterols should be analyzed for fungal biomass estimation. When the ergosterol esterification rates in soils are higher, free ergosterol might be a better marker for fungal biomass. It is speculated that the ergosterol esterification rate in soils might contain some important information, such as the age of old-growth forests over time scales of centuries to millennia, besides the senescence degree of fungal mycelia in soils. KEY POINTS: • Fungi might be divided into two classes depending on ergosterol esterification rates. • Ergosterol esterification rate of broken spores stored for long time raised evidently. • Both free and esterified ergosterols should be analyzed for fungal biomass estimate. • Free ergosterol is a better marker for fungal biomass with a high esterification rate.

Shrinkage methods enhanced the accuracy of parameter estimation using Cox models with small number of events.

OBJECTIVE: When the number of events is small during Cox regression analysis, it is unclear what alternative analytical strategies can be used and when this type of alternative approach is needed. This study explores several analytical strategies in this situation. STUDY DESIGN AND SETTING: Simulations and sensitivity analyses were performed on data with numbers of events per predictive variable (EPVs) below 10 using a Cox model with a partial likelihood (PL), Firth's penalized likelihood, or the Bayesian approach. RESULTS: For scenarios involving binary predictors with an EPV of six or less, the simulations showed that the Firth and Bayesian approaches were more accurate than was PL. The performances of various approaches were similar when the EPV was greater than six in the binary predictor. Furthermore, the performances involving continuous predictors were similar, regardless of the EPV. The bias and precision of the parameter estimates using Bayesian analysis depended on the selection of priors. CONCLUSIONS: When the EPV is six or less, the results for categorical predictors tend to be too conservative. Firth's estimator may be a good alternative in this situation. Appropriate choices of priors when using Bayesian analysis should increase the accuracy of the parameter estimates, although this requires expertise.