Effect of garlic essential oil in 97 patients hospitalized with covid-19: A multi-center experience.

To observe the synergistic effect of garlic essential oil in patients with novel coronavirus disease (COVID-19), in addition to the routine treatment, we used garlic essential oil in COVID-19 patients with mild to moderate symptoms and compared their results to those of patients who did not receive the essential oil. We conducted a quasi-experimental study with COVID-19 patients from 3 hospitals. In the experimental group, 97 patients received garlic essential oil combined with conventional treatment. In the control group, 100 patients received only the conventional treatment for COVID-19. The effectiveness and safety of the garlic essential oil were assessed. Compared to the control group, the group receiving garlic essential oil showed a shorter duration of symptoms, shorter time to negative nucleic acid testing (NAT) results and shorter time to improvement on the computed tomography (CT). In the same period, the experimental group showed an increase in the rate of the disappearance of symptoms and the improvement rates of NAT and CT. Due to its effectiveness and safety in patients with COVID-19, garlic essential oil is recommended as a preventive measure or a supportive therapy during the COVID-19 pandemic.

Microencapsulation of blueberry anthocyanins by spray drying with soy protein isolates/high methyl pectin combination: Physicochemical properties, release behavior in vitro and storage stability.

Eleven anthocyanins in the blueberry anthocyanins powders (BAP) were identified and quantified by HPLC-DAD-ESI-MS. BAP microcapsules (MBAP) were produced by spray drying using high methyl pectin (HMP) combined with whey protein isolates (WPI) or soy protein isolates (SPI) in different proportions as wall materials. Generally, SPI/HMP combination was more efficient in increasing the encapsulation efficiency and Tg, and in decreasing the particle size and hygroscopicity of the microcapsules than WPI or HMP or WPI/HMP combination. Microcapsules created with 4% SPI + 2% HMP combination (MBAPc), possessed superior anthocyanin release behavior and antioxidant stability to those produced with 4% SPI alone (MBAPs). Both MBAPc and MBAPs had continuous release of anthocyanins throughout the simulated gastrointestinal digestion, and exhibited two first-order kinetics, but MBAPc exhibited higher stability than MBAPs and BAP, because it showed the longest half-life and the lowest anthocyanin degradation rate at 25 °C and 35 °C during 6-months' storage.

miRNA and miRNA target genes in intervention effect of Zhuyu pill on cholestatic rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhuyu pill (ZYP), an effective prescription of traditional Chinese medicine, is composed of Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley and has shown potential anticholestatic effects. However, its mechanism of action in treating cholestasis remains unclear. Since post-transcriptional control of mRNA by micro-RNAs (miRNAs) represents an important mechanism of gene regulation, it is promising to explore this in relation to ZYP and cholestasis. AIM OF THE STUDY: To confirm the anticholestatic effect of ZYP and to explore its potential biological mechanism. MATERIALS AND METHODS: In this study, a cholestasis rat model was induced by α-naphthyl-isothiocyanate (ANIT, 50 mg/kg) and treated with ZYP (low dose: 0.6 g/kg, high dose: 1.2 g/kg). Serum biochemistry indices and liver histopathology were used to evaluate the model and efficacy, and miRNA sequencing was used to measure differences in miRNA expression in the liver between the control, model, low-dose ZYP, and high-dose ZYP groups. To verify the accuracy of sequencing results and explore the potential anti-cholestasis mechanism of ZYP, RT-PCR was used to identify differentially expressed miRNAs and their target genes. RESULTS: Both high- and low-dose ZYP exhibited significant anticholestatic effects, with the high-dose showing better effects than low-dose ZYP. Additionally, four differentially expressed miRNAs, rno-miR-147, rno-miR-20b-5p, rno-miR-29b-3p, and rno-miR-3586-3p, were found to be upregulated in cholestasis and downregulated after ZYP intervention. Eight target genes of the above miRNAs, including ABCG8, CLOCK, PLEC, SLC4A2, NEB, ADAMTS12, TTN and FAM174B were inhibited in cholestatic rats, exhibiting up-regulated expression tendencies after ZYP intervention, and the expression tendencies were significant negatively correlated with serum biochemical indices. CONCLUSIONS: ZYP can significantly reduce liver biochemical indices and improve liver tissue damage in cholestasis rats through the regulation of miRNA expression in the liver, producing a positive regulatory effect on bile excretion-related genes.

Two new taraxerane-type triterpenes from Ledum palustre L.

Two new compounds, namely 6α-hydroxy-14-taraxerene-3,16,21-trione and 6α,26-dihydroxy-14-taraxerene-3,16,21-trione were isolated from the Ledum palustre L. Their chemical structures were confirmed after a combined analysis of IR, HR-ESI-TOFMS, 1D-NMR, and 2D-NMR. The compounds were evaluated for cell growth inhibitory activity against two cancer cell lines.

Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism.

Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression.

Synergistic effect of vitamin D and low concentration of transforming growth factor beta 1, a potential role in dermal wound healing.

Dermal wound healing, in which transforming growth factor beta 1 (TGFß1) plays an important role, is a complex process. Previous studies suggest that vitamin D has a potential regulatory role in TGFß1 induced activation in bone formation, and there is cross-talk between their signaling pathways, but research on their effects in other types of wound healing is limited. The authors therefore wanted to explore the role of vitamin D and its interaction with low concentration of TGFß1 in dermal fibroblast-mediated wound healing through an in vitro study. Human dermal fibroblasts were treated with vitamin D, TGFß1, both, or vehicle, and then the wound healing functions of dermal fibroblasts were measured. To further explore possible mechanisms explaining the synergistic effect of vitamin D and TGFß1, targeted gene silencing of the vitamin D receptor was performed. Compared to either factor alone, treatment of fibroblasts with both vitamin D and low concentration of TGFß1 increased gene expression of TGFß1, connective tissue growth factor, and fibronectin 1, and enhanced fibroblast migration, myofibroblast formation, and collagen production. Vitamin D receptor gene silencing blocked this synergistic effect of vitamin D and TGFß1 on both collagen production and myofibroblast differentiation. Thus a synergistic effect of vitamin D and low TGFß1 concentration was found in dermal fibroblast-mediated wound healing in vitro. This study suggests that supplementation of vitamin D may be an important step to improve wound healing and regeneration in patients with a vitamin D deficiency.

[Impacts on neutrophil to lymphocyte ratio in patients of chronic stable angina pectoris treated with acupuncture at Neiguan (PC 6)].

OBJECTIVE: To observe the clinical efficacy on chronic stable angina pectoris treated with acupuncture at Neiguan (PC 6) and explore the impacts of acupuncture on peripheral blood neutrophil to lymphocyte ratio (NLR) in the patients of stable angina pectoris. METHODS: Thirty patients of chronic stable angina pectoris met the inclusive criteria were randomized into an acupuncture group (15 cases) and a medication group (15 cases), and a healthy control group (15 cases of the same ages) was set up separately. In the acupuncture group, at the same time of the basic medication, acupuncture was applied to bilateral Neiguan (PC 6), once every two days, 3 days a week, totally for 4 weeks. In the medication group, the basic medication was applied, without acupuncture intervention. In the healthy control group, no any intervention was applied. The attack frequency of angina pectoris, dose of nitrogly-cerin, the evaluation of visual analogue scale (VAS), Seattle angina questionnaire (SAQ), the six-minute walking test (6MWT), the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were observed before and after treatment in the subjects. Additionally, the peripheral blood cells were detected to analyze specifically the changes in NLR before and after treatment and observe the relationship between NLR and clinical efficacy. RESULTS: Compared with the medication group, the attack frequency of angina pectoris was reduced within 30 days (P<0.01); the dose of nitroglycerin was reduced (P<0.01); VAS was reduced (P<0.01) and SAQ was increased (P<0.05) in the acupuncture group. The differences in 6 MWT, SAS and SDS were not significant between the two groups after treatment (all P>0.05). Additionally, compared with the medication group, in 30 days of acupuncture, NLR was reduced apparently in the acupuncture group (P<0.05). CONCLUSION: Acupuncture relieves the clinical symptoms of chronic stable angina pectoris, but has not apparent effects on motor ability and psychological health. Corresponding to that before treatment, the decreased NRL in the patients of acupuncture group suggests the potential good prognosis on coronary heart disease after acupuncture.

A protocol of histone modification-based mechanistic study of acupuncture in patients with stable angina pectoris.

BACKGROUND: Angina pectoris (Angina) is a medical condition related to myocardial ischemia. Although acupuncture has been widely accepted as a clinical approach for angina, there is no sufficient evidence of its effectiveness against this syndrome, and its mechanisms have not yet been well elucidated. We develop this protocol to confirm the clinical efficacy of electro-acupuncture on stable angina pectoris by needling on acupoint Neiguan (PC6). Furthermore, we employ high-throughput sequencing technology to investigate the gene expression profiling and determine involvement of histone modifications in the regulation of genes after electro-acupuncture treatment. METHODS/DESIGN: A randomized, controlled, double-blinded (assessor and patients) trial will be carried out. Sixty participants will be randomly assigned to two acupuncture treatment groups and one control group in a 1:1:1 ratio. Participants in acupuncture groups will receive 12 sessions of electro-acupuncture treatment across 4 weeks, followed by a 12-week randomization period. The acupuncture groups are divided into Neiguan (PC6) on Pericardium Meridian of Hand-jueyin or a non-acupoint. The primary clinical measure of effect is the frequency of angina attacks between these groups for four weeks after randomization. RNAs are extracted from peripheral neutrophils collected from all participants on day 0, day 30, and week 16, and are processed to RNA-Seq. We then investigate profiles of histone modifications by ChIP-Seq, for H3 Lysine 4 (H3K4me) and acetylation of H3 Lysine 27 (H3K27ac), in the presence or absence of acupuncture treatment. DISCUSSION: This study determines the efficacy and mechanisms of electro-acupuncture on stable angina pectoris. We focus on effectiveness of acupuncture on alleviating symptoms of myocardial ischemia and the gene regulation and the chromatin remodeling marks, including H3K4me1, H3K4me2, and H3K27ac, which could be key factors for regulating gene expressions caused by electro-acupuncture treatment at Neiguan. This is the first genome-wide study of electro-acupuncture treatment in angina patients, and will provide valuable information for future studies in the fields of acupuncture and its underlying mechanisms. Fourteen patients have been recruited since recruitment opened in November of 2012. This study is scheduled to end in November of 2014. TRIALS REGISTRATION: ChiCTR-TRC-12002668.

[Effect of Crop Rotation and Biological Manure on Quality and Yield of "Chuju" Chrysanthemum morifolium and Continuous Cropping Soil Enzyme Activities].

OBJECTIVE: To investigate the effects of chrysanthemum-wheat rotation system and biological manure on continuous cropping soil enzyme activities and quality and yield of Chrysanthemum morifolium. METHODS: Field experiments were conducted at the research base of Anhui Jutai Chuju Chrysanthemum morifolium Herbal Technology Co. , Ltd. ,in Shiji Town, Nanqiao Country, Anhui Province. Samples were collected from treatments under chrysanthemum-wheat rotation system receiving bio-organic manure application of 200 kg/667 m2, conventional chrysanthemum-wheat rotation system and chrysanthemum continuous cropping system. RESULTS: Chrysanthemum-wheat rotation system and biological manure obviously influenced the quality and yield of Chrysanthemum morifolium and continuous cropping soil enzyme activities. Compared with chrysanthemum continuous cropping system, total flavonoids, chlorogenic acid, soluble sugar and free amino acid contents, quantitative of ray floret, inflorescence diameter, diameter of tubular floret, number of branch, number of flower and yield of Chrysanthemum morifolium and the activities of urease, acid phosphatase, invertase and protease in soil were increased to 42.59 mg/g, 2.52 mg/g, 4.04 mg/g, 73.33 mg/100 g, 179.56, 5.57 cm, 1.43 cm, 36.10, 330.00 and 400.09 kg/667 m2, respectively, while hydrogen peroxidase of soil under chrysanthemum-wheat rotation system was decreased. CONCLUSION: Bio-organic manure application of 200 kg/667 m2 is benefit to soil environment establishment of chrysanthemum-wheat rotation system and enhancement of quality and yield of Chrysanthemum morifolium while reducing the obstacles of continuous cropping.

Optimized protein kinase Cθ (PKCθ) inhibitors reveal only modest anti-inflammatory efficacy in a rodent model of arthritis.

We previously demonstrated that selective inhibition of protein kinase Cθ (PKCθ) with triazinone 1 resulted in dose-dependent reduction of paw swelling in a mouse model of arthritis.1,2 However, a high concentration was required for efficacy, thus providing only a minimal safety window. Herein we describe a strategy to deliver safer compounds based on the hypothesis that optimization of potency in concert with good oral pharmacokinetic (PK) properties would enable in vivo efficacy at reduced exposures, resulting in an improved safety window. Ultimately, transformation of 1 yielded analogues that demonstrated excellent potency and PK properties and fully inhibited IL-2 production in an acute model. In spite of good exposure, twice-a-day treatment with 17l in the glucose-6-phosphate isomerase chronic in vivo mouse model of arthritis yielded only moderate efficacy. On the basis of the exposure achieved, we conclude that PKCθ inhibition alone is insufficient for complete efficacy in this rodent arthritis model.

Discovery of selective and orally bioavailable protein kinase Cθ (PKCθ) inhibitors from a fragment hit.

Protein kinase Cθ (PKCθ) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKCθ inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.

Current status of animal welfare and animal rights in China.

In the past few years, new social passions have sparked on the Chinese mainland. At the centre of these burgeoning passions is a focus on animal welfare, animal treatment, and even animal rights, by the public and academic sectors. With China's rapid economic changes and greater access to information from around the world, societal awareness of animal issues is rising very fast. Hastening this paradigm shift were several highly public incidents involving animal cruelty, including exposés on bear bile harvesting for traditional Chinese medicine, the thousands of dogs rescued from China's meat trade, and the call to boycott shark fin soup and bird nest soup. This article outlines the current status of campaigning by animal advocates in China (specifically the animal rights movement) from three interlinked perspectives: wildlife conservation, companion animal protection, and laboratory animal protection. By reviewing this campaigning, we attempt to present not only the political and social impact of the concept of animal rights, but also the perceptions of, and challenges to, animal rights activities in China.

[Effect of water and nitrogen fertilizer coupling on yield and growth of genuine medicinal materials Chuzhou Chrysanthemum morifolium].

OBJECTIVE: To discuss the suitable water and nitrogen management mode in artificial cultivation of Chuzhou Chrysanthemum morifolium. METHODS: According to two factors quadratic regression rotation design experience, pot experiment was conducted. RESULTS: There were remarkable effects of water and nitrogen coupling on inflorescence number, yield and overground part biomass of Chuzhou Chrysanthemum morifolium, and there were significant positive interaction between water and nitrogen. Effects of water on early-term inflorescence yield and overground part biomass of Chuzhou Chrysanthemum morifolium were higher than that of nitrogen fertilizer, but the effect on total inflorescence yield was opposite. CONCLUSION: Considering for the fresh inflorescence yield, the suitable water and nitrogen management mode is to keep 93% of the water holding capacity and nitrogen fertilizer (N) 0.34 g/kg of Chuzhou Chrysanthemum morifolium in pot experiment, and as for the dry inflorescence yield, the suitable water and nitrogen management mode is to keep 75% of the water holding capacity and nitrogen fertilizer (N) 0.2 g/kg.

[Roles of organic acid metabolism in plant adaptation to nutrient deficiency and aluminum toxicity stress].

Organic acids not only act as the intermediates in carbon metabolism, but also exert key roles in the plant adaptation to nutrient deficiency and metal stress and in the plant-microbe interactions at root-soil interface. From the viewpoint of plant nutrition, this paper reviewed the research progress on the formation and physiology of organic acids in plant, and their functions in nitrogen metabolism, phosphorus and iron uptake, aluminum tolerance, and soil ecology. New findings in the membrane transport of organic acids and the biotechnological manipulation of organic acids in transgenic model were also discussed. This novel perspectives of organic acid metabolism and its potential manipulation might present a possibility to understand the fundamental aspects of plant physiology, and lead to the new strategies to obtain crop varieties better adapted to environmental and metal stress.

[Study on optimizing extraction process of root of Polygonum multiflorum].

OBJECTIVE: To optimize the extraction process of root of Polygoni multflori and validate the interrelation between antioxdative capacity and the content of 2,3,4,5-tetrahydroxystilbene-2-O-beta-D-glucoside in root of P. multiflori. METHOD: The optimum extraction was abserved with the orthogonal design; 2,3,4,5-tetrahydroxystilbene-2-O-beta-D-glucoside was determined by HPLC and the antioxidative capacity by using photochemiluminescence detection method with the Photochem supplied by Analytik Jena AG; the concentration of ethanol, amount of ethanol, extraction time and extraction times were the four factors in the extraction. RESULT: The concentration of ethanol and extraction times had significant effect on the content of 2,3,4,5-tetrahydroxystilbene-2-O-beta-D-glucoside and the antioxidative capacity of the crude extract. CONCLUSION: The best extraction process is to extract three times by using 10 fold EtOH(60%), refluxing at 85 degrees C and to extract one and half hours each time.