Shexiang Baoxin Pill treats acute myocardial infarction by promoting angiogenesis via GDF15-TRPV4 signaling.

Angiogenesis has been considered a pivotal strategy for treating ischemic heart disease. One possible approach, the Shexiang Baoxin Pill (MUSKARDIA), has been noted to promote angiogenesis, but its underlying mechanism is still largely unknown. We aimed to determine the effects of MUSKARDIA on acute myocardial infarction (AMI), as well as the underlying mechanistic bases. AMI was induced in rats, using left anterior descending coronary arterial occlusion, and either 6 (low) or 12 (high-dose) mg/kg/day of MUSKARDIA was administered for 56 days. We found that MUSKARDIA improved cardiac function and counteracted against adverse remodeling among AMI rats, which most likely is due to it promoting angiogenesis. Transcriptome analysis by RNA-sequencing found that MUSKARDIA up-regulated cardiac pro-angiogenic genes, particularly growth differentiation factor 15 (GDF15), which was confirmed by RT-qPCR. This up-regulation was also correlated with elevated serum GDF15 levels. In vitro analyses with human umbilical vein endothelial cells found that increased GDF15, stimulated by MUSKARDIA, resulted in enhanced cell migration, proliferation, and tubular formation, all of which were reversed after GDF15 knockdown using a lentiviral vector. Gene Ontology, as well as Kyoto Genes and Genomes enrichment analyses identified calcium signaling pathway as a major contributor to these outcomes, which was verified by Western blot and Cal-590 AM loading showing that transient receptor potential cation channel subfamily V member 4 protein (TRPV4) and intracellular Ca2+ levels increased in accordance with MUSKARDIA-induced GDF15 up-regulation, and decreased with GDF15 knock-down. Therefore, MUSKARDIA may exert its cardioprotective effects via stimulating the GDF15/TRPV4/calcium signaling/angiogenesis axis.

Optimal postoperative surveillance strategies for cancer survivors with gastric neuroendocrine carcinoma based on individual risk: a multicenter real-world cohort study.

BACKGROUND: The best follow-up strategy for cancer survivors after treatment should balance the effectiveness and cost of disease detection while detecting recurrence as early as possible. Due to the low incidence of gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma [G-(MA)NEC], high-level evidence-based follow-up strategies is limited. Currently, there is a lack of consensus among clinical practice guidelines regarding the appropriate follow-up strategies for patients with resectable G-(MA)NEC. MATERIALS AND METHODS: The study included patients diagnosed with G-(MA)NEC from 21 centers in China. The random forest survival model simulated the monthly probability of recurrence to establish an optimal surveillance schedule maximizing the power of detecting recurrence at each follow-up. The power and cost-effectiveness were compared with the National Comprehensive Cancer Network, European Neuroendocrine Tumor Society, and European Society for Medical Oncology Guidelines. RESULTS: A total of 801 patients with G-(MA)NEC were included. The patients were stratified into four distinct risk groups utilizing the modified TNM staging system. The study cohort comprised 106 (13.2%), 120 (15.0%), 379 (47.3%), and 196 cases (24.5%) for modified groups IIA, IIB, IIIA, and IIIB, respectively. Based on the monthly probability of disease recurrence, the authors established four distinct follow-up strategies for each risk group. The total number of follow-ups 5 years after surgery in the four groups was 12, 12, 13, and 13 times, respectively. The risk-based follow-up strategies demonstrated improved detection efficiency compared to existing clinical guidelines. Further Markov decision-analytic models verified that the risk-based follow-up strategies were better and more cost-effective than the control strategy recommended by the guidelines. CONCLUSIONS: This study developed four different monitoring strategies based on individualized risks for patients with G-(MA)NEC, which may improve the detection power at each visit and were more economical, effective. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending follow-up strategies for G-(MA)NEC.

[Effects of Polystyrene Nanoplastics (PS-NPs) on the Physiology of Allium sativum L.]

The pollution of micro/nanoplastics in the natural environment is becoming increasingly serious, but the potential effects of nanoplastics on crops remain unclear. In the present study, the effects of polystyrene nanoplastics (PS-NPs) with a particle size of 80 nm on the chlorophyll content, antioxidant enzyme activity, and nutritional quality of Allium sativum L. were explored via hydroponic culture. The results showed that the chlorophyll contents in leaves of A. sativum treated with PS-NPs were significantly lower than those in the control, indicating that the synthesis of chlorophyll was inhibited. The superoxide dismutase (SOD), ascorbate peroxidase (APX) activities, and proline contents in leaves of A. sativum initially increased but then decreased with the increase in ρ(PS-NPs). The activity of guaiacol peroxidase (POD) increased with the increase in ρ(PS-NPs) for 10 days of treatment; however, it was inhibited for 20 days of treatment. The malondialdehyde (MDA) content increased with the rise in ρ(PS-NPs). When ρ(PS-NPs) increased to 100 mg·L-1, the MDA content in leaves of A. sativum increased by 43.24% and 89.70% for 10 and 20-day treatments, respectively, compared with those in the control. Meanwhile, the contents of soluble protein, soluble sugar, and vitamin C were higher than those in the control for 10-day treatments; however, the vitamin C content decreased by 26.53% after 20 days of treatment. These results indicated that PS-NPs had a significant oxidative stress on A. sativum, and a high concentration of PS-NPs stress would have deleterious effects on the nutritional quality of A. sativum.

[Research progress of Gan-Yu-Hua-Huo syndrome based on emotional stress-induced latent herpes simplex virus-1 reactivation].

Gan-Yu-Hua-Huo syndrome(Live qi stagnation transforming into fire pattern) is one of the core contents of the theory of emotional diseases in traditional Chinese medicine(TCM). It is the key link of the pathogenesis change of emotion-related diseases and widely exists in the pathological process of various related diseases. However, due to the lack of animal models in line with the characteristics of TCM syndromes, the research on biomedical basis of Gan-Yu-Hua-Huo syndrome and study of Chinese medicines for soothing liver and purging fire have been restricted seriously. This study found that the pathological process of facial fire-heat symptoms of Gan-Yu-Hua-Huo syndrome was similar to the facial symptoms due to the emotional stress-induced latent herpes simplex virus-1(HSV-1) reactivation. Therefore, this study proposed that the emotional stress-induced latent HSV-1 activation be used to establish the animal model of Gan-Yu-Hua-Huo syndrome. In this study, the state-of-art literature in the field of Gan-Yu-Hua-Huo syndrome was summarized, and the experimental animal model of Gan-Yu-Hua-Huo syndrome was established from the perspective of emotional stress-induced latent HSV-1 reactivation to reveal the active substances, potential targets and pathways related to the pathological mechanism of the syndrome. This study was expected to provide reference and basis for the pharmacodynamic characterization of commonly used Chinese medicine for Gan-Yu-Hua-Huo syndrome in clinical practice.

Celastrol ameliorates Propionibacterium acnes/LPS-induced liver damage and MSU-induced gouty arthritis via inhibiting K63 deubiquitination of NLRP3.

BACKGROUND: Celastrol, a pentacyclic triterpenoid quinonemethide isolated from several spp. of Celastraceae family, exhibits anti-inflammatory activities in a variety of diseases including arthritis. PURPOSE: This study aims to investigate whether the inhibition of NLRP3 inflammasome is engaged in the anti-inflammatory activities of celastrol and delineate the underlying mechanism. METHODS: The influence of celastrol on NLRP3 inflammasome activation was firstly studied in lipopolysaccharide (LPS)-primed mouse bone marrow-derived macrophages (BMDMs) and phorbol 12-myristate 13-acetate (PMA)-primed THP-1 cells treated with nigericin. Reconstituted inflammasome was also established by co-transfecting NLRP3, ASC, pro-caspase-1 and pro-IL-1ß in HEK293T cells. The changes of inflammasome components including NLRP3, ASC, pro-caspase-1/caspase-1 and pro-IL-1ß/IL-1ß were examined by enzyme-linked immunosorbent assay (ELISA), western blotting and immunofluorescence. Furthermore, Propionibacterium acnes (P. acnes)/LPS-induced liver injury and monosodium urate (MSU)-induced gouty arthritis in mice were employed in vivo to validate the inhibitory effect of celastrol on NLRP3 inflammasome. RESULTS: Celastrol significantly suppressed the cleavage of pro-caspase-1 and pro-IL-1ß, while not affecting the protein expressions of NLRP3, ASC, pro-caspase-1 and pro-IL-1ß in THP-1 cells, BMDMs and HEK293T cells. Celastrol suppressed NLRP3 inflammasome activation and alleviated P. acnes/LPS-induced liver damage and MSU-induced gouty arthritis. Mechanism study revealed that celastrol could interdict K63 deubiquitination of NLRP3, which may concern interaction of celastrol and BRCA1/BRCA2-containing complex subunit 3 (BRCC3), and thereby prohibited the formation of NLRP3, ASC and pro-caspase-1 complex to block the generation of mature IL-1ß. CONCLUSION: Celastrol suppresses NLRP3 inflammasome activation in P. acnes/LPS-induced liver damage and MSU-induced gouty arthritis via inhibiting K63 deubiquitination of NLRP3, which presents a novel insight into inhibition of celastrol on NLRP3 inflammasome and provides more evidences for its application in the therapy of inflammation-related diseases.

Research Progress on Molecular Mechanism of Lipid-lowering and Anti-inflammatory Effect of Zexietang / 中国实验方剂学杂志

Zexietang is a Chinese herbal compound prescription with a long history， which consists of Rhizoma alismatis and Atractylodes macrocephala. Zexietang comes from "Synopsis of Golden Chamber"， as "there is a drink under the heart， and its people are bitter and dizzy". Zexietang has the effect of removing water from drinking water and invigorating spleen for diuresis. Modern pharmacological studies have shown that its lipid-lowering and anti-inflammatory effects are very significant. It can be used to treat hyperlipidemia， anti-atherosclerosis and non-alcoholic fatty liver disease. With the continuous development of molecular biology， the research on the pharmacological effects of Zexietang， extracts and their monomers has deepened to the molecular level gradually， and the relevant mechanism of action has also been continuously elucidated. In terms of lipid-lowering effect of Zexietang， the levels of cytokines or receptors such as 3-hydroxy-3-methyl glutaryl coenzyme A reductase （HMGCR）， cholesterol 7α-hydroxylase （CYP7A1）， and liver X receptors （LXR） are affected. It is widely involved in adenosine 5'-monophosphate-activated protein kinase （AMPK） and peroxisome proliferators-activated receptors （PPAR） pathways， while Zexietang's anti-inflammatory effect mainly affects inflammatory factors such as interleukins （IL） and tumor necrosis factors （TNF）， and simultaneously nuclear factor κB （NF-κB）， toll-like receptors （TLR） and other cytokines or receptor-related pathways. In order to promote the further research and clinical application of Zexietang and contribute to the development of modernization of traditional Chinese medicine， the studies of the past 15 years on molecular mechanism of the lipid-lowering and anti-inflammatory effect of Zexietang， Alisma and Atractylodes extract as well as their monomer components were reviewed.

[Research progress on chemical composition and pharmacological effects of Periplocae Cortex and predictive analysis on Q-marker].

Periplocae Cortex is a traditional Chinese medicine in China, which is mainly produced in northeast China, north China, northwest China, southwest China. In recent years, the increasing in-depth research resulted in the discovery of anti-tumor and cardiac pharmacological activities of Periplocae Cortex, which has broad application prospects. On the basis of summarizing chemical components and pharmacological effects, combined with the theoretical system of Q-marker, the quality control components of Periplocae Cortex were predicted from the aspects of the correlation between chemical composition and traditional medicinal properties, traditional efficacy, and new clinical use, plasma composition, measurable composition, storage time by analyzing literature. Among the components, periplocoside, periplocin, periplogenin, 4-methoxy salicylaldehyde showed significant activity, which provides a scientific basis for quality evaluation of Periplocae Cortex.

Influence of nutrient mitigation measures on the fractional export of watershed inputs in an urban watershed.

Enhanced nutrient inputs due to human activities have been noted as a significant driving force for riverine nutrient exports which are responsible for the eutrophication issues in freshwaters. Current studies are mostly focused on the relationship between anthropogenic inputs and riverine exports, and little has been done to assess the role of nutrient mitigation measures in the fractional export of watershed nutrient inputs in urban regions. A highly urbanized watershed in Yun-Gui plateau of China, Lake Dianchi basin was studied as a case to assess the impact of nutrient mitigation measures on riverine nutrient exports. Based on net anthropogenic nitrogen and phosphorus inputs (NANI and NAPI, respectively) models, nutrient inputs from human activities in the basin from 1980 to 2015 were calculated, and the impact of nutrient mitigation measures were identified using a statistical model incorporating land use, precipitation, and temperature. Nutrient inputs from human action in the basin has increased rapidly, mainly from fertilizer application and food and feed imports. Enhanced riverine nutrient exports were found at the same time, and significantly correlated to nutrient inputs. The construction of water transfer projects and wastewater treatment plants in the basin has changed the controlling factors and processes of the fractional export of watershed nutrient inputs, which is weak in explanatory ability and eliminated the role of the land use. A modified model was established by incorporating the effect of water transfer projects and wastewater treatment plants, which showed a significant increase in model performance. The results from the modified model reveal that urban land percentage has become a positively driving force for the fractional export of watershed N and P inputs, and temperature a positive driving force for the fractional export of watershed N inputs while precipitation a negative driving force for the fractional export of watershed P inputs.

Disturbed Yin-Yang balance: stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1.

Herpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, is able to establish a lifelong latent infection in the human host. Following primary replication in mucosal epithelial cells, the virus can enter sensory neurons innervating peripheral tissues via nerve termini. The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny, and thus latency is established in the cell. Yin-Yang balance is an essential concept in traditional Chinese medicine (TCM) theory. Yin represents stable and inhibitory factors, and Yang represents the active and aggressive factors. When the organism is exposed to stress, especially psychological stress caused by emotional stimulation, the Yin-Yang balance is disturbed and the virus can re-engage in productive replication, resulting in recurrent diseases. Therefore, a better understanding of the stress-induced susceptibility to HSV-1 primary infection and reactivation is needed and will provide helpful insights into the effective control and treatment of HSV-1. Here we reviewed the recent advances in the studies of HSV-1 susceptibility, latency and reactivation. We included mechanisms involved in primary infection and the regulation of latency and described how stress-induced changes increase the susceptibility to primary and recurrent infections.

Animal study of the anti-diarrhea effect and microbial diversity of dark tea produced by the Yao population of Guangxi.

Chinese dark teas (CDTs) are a special type of tea traditionally consumed by ethnic minorities around the border regions of China. Dark tea produced by the Yao population of Guangxi could help prevent diarrhea following the heavy consumption of food. However, the underlying mechanisms behind this effect are not clear. This study aimed to investigate the function and underlying mechanisms of dark tea by examining the effects of different doses of dark tea on diarrhea in mice caused by Folium Sennae. It was found that dark tea could significantly improve the rate of loose stools and diarrhea index, and had an inhibitory effect on intestine peristalsis in high- and moderate-dose groups. Compared with green tea, significantly decreased levels of water extract, tea polyphenol and amino acid were found in dark tea, whereas the content of both caffeine and gallocatechin was increased. The result of dilution plating showed that Aspergillus niger and Byssochlamys fulva were consistent with microbial diversity as assessed by high-throughput sequencing technology. A total of 12 metabolites related to an anti-diarrhea effect were identified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). These findings provide a physiological basis for developing dark tea produced by the Yao population of Guangxi as a drink that can regulate and improve the intestinal flora in humans.

Study on the mechanism of intense pulsed light therapy for evaporative dry eye disease / 国际眼科杂志(Guoji Yanke Zazhi)

@#Dry eye disease(DED)is closely related to inflammatory diseases of the skin near the eyelids, such as ocular rosacea, <i>etc</i>. At present, intense pulsed light(IPL)is one of the main treatments for rosacea. Recent studies have found that patients with meibomian gland dysfunction(MGD)have alleviated the symptoms and signs of dry eyes during IPL treatment, but its specific mechanism is not clear. The purpose of this paper is to review the possible mechanisms of IPL treatment of dry eye and to discuss its rationality.

Traditional Chinese Medicine as a Potential Source for HSV-1 Therapy by Acting on Virus or the Susceptibility of Host.

Herpes simplex virus type 1 (HSV-1) is the most common virus, with an estimated infection rate of 60⁻95% among the adult population. Once infected, HSV-1 can remain latent in the host for a lifetime and be reactivated in patients with a compromised immune system. Reactivation of latent HSV-1 can also be achieved by other stimuli. Though acyclovir (ACV) is a classic drug for HSV-1 infection, ACV-resistant strains have been found in immune-compromised patients and drug toxicity has also been commonly reported. Therefore, there is an urge to search for new anti-HSV-1 agents. Natural products with potential anti-HSV-1 activity have the advantages of minimal side effects, reduced toxicity, and they exert their effect by various mechanisms. This paper will not only provide a reference for the safe dose of these agents if they are to be used in humans, referring to the interrelated data obtained from in vitro experiments, but also introduce the main pharmacodynamic mechanisms of traditional Chinese medicine (TCM) against HSV-1. Taken together, TCM functions as a potential source for HSV-1 therapy by direct (blocking viral attachment/absorption/penetration/replication) or indirect (reducing the susceptibility to HSV-1 or regulating autophagy) antiviral activities. The potential of these active components in the development of anti-HSV-1 drugs will also be described.

Resveratrol significantly improves the fertilisation capacity of bovine sex-sorted semen by inhibiting apoptosis and lipid peroxidation.

The aim of this study was to test the effects of five different concentrations (0, 10-3, 10-4, 10-5, and 10-6 M) of resveratrol (Res) supplementation in bull sperm washing and fertilisation medium on levels of reactive oxygen species (ROS), phosphatidylserine (PS) externalisation, mitochondrial membrane potential (Δψm), ATP and malondialdehyde (MDA), acrosomal integrity, blastocyst rate, and blastocyst quality after in vitro fertilisation (IVF). The results for sex-sorted sperm from three bulls showed: (1) ROS and MDA levels in 10-3 M and 10-4 M Res groups were significantly lower than those of controls (P < 0.05); (2) the percentage of viable sperm, percentage of sperm with high Δψm, and the ATP content in 10-3 M and 10-4 M Res groups were significantly higher than those of controls (P < 0.05); (3) the percentage of viable sperm with acrosomal integrity, and the blastocyst percentage and quality of the 10-4 M Res group were significantly higher than those of controls (P < 0.05). In conclusion, 10-4 M Res supplementation in washing and fertilisation medium of sex-sorted bull sperm significantly decreased ROS, PS externalisation, and MDA, and protected mitochondrial function and acrosomal integrity, thereby increasing blastocyst percentage and quality following IVF.

Fostering efficacy and toxicity evaluation of traditional Chinese medicine and natural products: Chick embryo as a high throughput model bridging in vitro and in vivo studies.

Efficacy and safety assessments are essential thresholds for drug candidates from preclinical to clinical research. Conventional mammalian in vivo models cannot offer rapid pharmacological and toxicological screening, whereas cell-based or cell-free in vitro systems often lead to inaccurate results because of the lack of physiological environment. Within the avian species, gallus gallus is the first bird to have its genome sequencing. Meantime, chick embryo is an easily operating, relatively transparent and extensively accessible model, whose physiological and pathological alterations can be visualized by egg candler, staining and image technologies. These features facilitate chick embryo as a high-throughput screening platform bridging in vivo and in vitro gaps in the pharmaceutical research. Due to the complicated ingredients and multiple-targets natures of traditional Chinese medicine (TCM), testing the efficacy and safety of TCM by in vitro methods are laborious and inaccurate, while testing in mammalian models consume massive cost and time. As such, the productive living organism chick embryo serves as an ideal biological system for pharmacodynamics studies of TCM. Herein, we comprehensively update recent progresses on the specialty of chick embryo in evaluation of efficacy and toxicity of drugs, with special concerns of TCM.

pH-triggered charge-reversible of glycol chitosan conjugated carboxyl graphene for enhancing photothermal ablation of focal infection.

Subcutaneous abscesses infected by multidrug-resistant bacteria are becoming an increasing challenge to human health. To address this challenge, a surface-adaptive and biocompatible glycol chitosan conjugated carboxyl graphene (GCS-CG) is developed, which exhibits unique self-adaptive target to the acidic microenvironment of abscess (∼pH 6.3) and no damage to the healthy tissue (pH 7.4) around the abscess. Originally, following conjugated with GCS, the absorbance of CG obviously increases in the near-infrared (NIR) region, enabling GCS-CG to generate an increment amount of heat. GCS-CG shows fast pH-responsive surface charge transition from negative to positive, which presents strong adherence to negatively charged bacteria surface in abscess, while exhibits poor affinity to host cells in healthy tissues. The local temperature of NIR-irradiated GCS-CG is estimated to be higher than their ambient temperature, ensuring targeted heating and eradicating the bacteria to reduce the damage to tissue; hence, wound healing is accelerated. Moreover, the in vitro and in vivo biosafety results demonstrate that GCS-CG presents greatly biocompatible even at a high concentration of 1 mg·mL-1. Given the above advantages as well as the simple preparation, graphene developed here may provide a new potential application as a useful antibacterial agent in the areas of healthcare. STATEMENT OF SIGNIFICANCE: A surface-adaptive nanomaterial, glycol chitosan conjugated carboxyl graphene (GCS-CG) is developed, which realizes the acidity-triggered bacteria targeting. GCS-CG can result in direct thermal ablation of bacteria and enhancement of the infected wound healing, but exhibit no damage to healthy tissues. The pH-responsive GCS-CG described here, containing no antibiotics, has great potentials in treating bacterial infection and even multidrug-resistant bacteria.

Melatonin improves the fertilization capacity and developmental ability of bovine oocytes by regulating cytoplasmic maturation events.

Melatonin is a well-characterized antioxidant that has been successfully used to protect oocytes from reactive oxygen species during in vitro maturation (IVM), resulting in improved fertilization capacity and development ability. However, the mechanism via which melatonin improves oocyte fertilization capacity and development ability remains to be determined. Here, we studied the effects of melatonin on cytoplasmic maturation of bovine oocytes. In the present study, bovine oocytes were cultured in IVM medium supplemented with 0, 10-7 , 10-9 , and 10-11  mol/L melatonin, and the cytoplasmic maturation parameters of MII oocytes after IVM were investigated, including redistribution of organelles (mitochondria, cortical granules [CGs], and endoplasmic reticulum [ER]), intracellular glutathione (GSH) and ATP levels, expression of endogenous antioxidant genes (Cat, Sod1, and GPx), and fertilization-related events (IP3R1 distribution and expression of CD9 and Juno). Our results showed that melatonin significantly improved the cytoplasmic maturation of bovine oocytes by improving the normal distribution of organelles, increasing intracellular GSH and ATP levels, enhancing antioxidant gene expression levels, and modulating fertilization-related events, all of which resulted in increased fertilization capacity and developmental ability. Meanwhile, melatonin also increased the mRNA and protein expression levels of the Tet1 gene and decreased the Dnmt1 gene mRNA and protein levels in bovine oocytes, indicating that melatonin regulates the expression of the detected genes via demethylation. These findings shed insights into the potential mechanisms by which melatonin improves oocyte quality during IVM.

Calcium ion regulation by BAPTA-AM and ruthenium red improved the fertilisation capacity and developmental ability of vitrified bovine oocytes.

Vitrification reduces the fertilisation capacity and developmental ability of mammalian oocytes; this effect is closely associated with an abnormal increase of cytoplasmic free calcium ions ([Ca2+]i). However, little information about the mechanism by which vitrification increases [Ca2+]i levels or a procedure to regulate [Ca2+]i levels in these oocytes is available. Vitrified bovine oocytes were used to analyse the effect of vitrification on [Ca2+]i, endoplasmic reticulum Ca2+ (ER Ca2+), and mitochondrial Ca2+ (mCa2+) levels. Our results showed that vitrification, especially with dimethyl sulfoxide (DMSO), can induce ER Ca2+ release into the cytoplasm, consequently increasing the [Ca2+]i and mCa2+ levels. Supplementing the cells with 10 µM 1,2-bis (o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM or BAPTA) significantly decreased the [Ca2+]i level and maintained the normal distribution of cortical granules in the vitrified bovine oocytes, increasing their fertilisation ability and cleavage rate after in vitro fertilisation (IVF). Treating vitrified bovine oocytes with 1 µM ruthenium red (RR) significantly inhibited the Ca2+ flux from the cytoplasm into mitochondria; maintained normal mCa2+ levels, mitochondrial membrane potential, and ATP content; and inhibited apoptosis. Treating vitrified oocytes with a combination of BAPTA and RR significantly improved embryo development and quality after IVF.

New insights into the effects and mechanism of a classic traditional Chinese medicinal formula on influenza prevention.

BACKGROUND: KangBingDu (KBD) is a classic traditional Chinese medicinal formula widely used to treat influenza. However, little information is available from controlled studies regarding the anti-influenza pharmacological activities of KBD and its underlying mechanisms, at least partly due to the lack of appropriate study models. PURPOSE: We hypothesized that KBD might provide a protection against influenza infection by reducing the host's susceptibility to viruses. To prove it, mouse restraint stress model was employed. METHODS: Mice were restricted and infected with influenza virus. KBD (13 and 26mg/kg/d) was orally administrated to mice from the first day of restraint stress and lasted for 7 days (twice a day). Mice were monitored daily for morbidity, symptom severity, and mortality for 21 days. The histopathologic changes were examined. For the study of mechanisms of action, we investigated whether KBD could promote mitochondria antiviral signaling protein (MAVS)-mediated antiviral signal and inhibit nuclear factor-kappa B (NF-κB)-mediated inflammation response. RESULTS: KBD significantly decreased the susceptibility of restraint mice to influenza virus, as evidenced by lowered mortality, attenuated inflammation and reduced viral replications in lungs. Further results revealed that KBD elevated the protein expression of MAVS, which subsequently increased the IFN-ß and IFITM3 protein levels, thereby helping to fight viral infections. Finally, we identified that (R,S)-goitrin, mangiferin, forsythin and forsythoside A were effective components in KBD against influenza viral infections. CONCLUSION: KBD can reduce the susceptibility to influenza virus via mitochondrial antiviral signaling.

Synthesis and anti-hepatocellular carcinoma activity of novel O2-vinyl diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid.

Considering that high levels of nitric oxide (NO) exert anti-cancer effect and the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity, new O2-vinyl diazeniumdiolate-based NO releasing derivatives (5a-l, 11a-l) of OA were designed, synthesized, and biologically evaluated in the present study. These derivatives could release different amounts of NO in liver cells. Among them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and displayed stronger proliferative inhibition against SMMC-7721 and HepG2 cells than OA and other tested compounds. The most active compound 5j showed almost 20-fold better solubility than OA in aqueous solution, released larger amounts of NO in liver cancer cells than that in normal ones, and exhibited potent anti-hepatocellular carcinoma activity but little effect on the normal liver cells. The inhibitory activity against the cancer cells was significantly diminished upon addition of an NO scavenger, suggesting that NO may contribute, at least in part, to the activity of 5j.

[Distributions of Arsenic Species in Different Eutrophic Waters of Lake Taihu and Their Relations to Environmental Factors].

A detailed field survey of arsenic species and water quality parameters was conducted in different eutrophicated regions of Lake Taihu (Zhushan Bay, Meiliang Bay, Gonghu Bay and Southern Taihu) in summer and winter. Furthermore, spatial and seasonal distributions of arsenic species and their relations to water quality parameters were investigated with multivariate analysis techniques. Higher average contents of total arsenic (TAs), arsenate[As(Ⅴ)], arsenite[ As(Ⅲ)] and methylarsenicals [sum of monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA)] were observed in northern regions (including Zhushan Bay, Meiliang Bay, and Gonghu Bay) (TAs:2.58-3.34 µg·L-1, As(Ⅴ):1.37-2.34 µg·L-1, As(Ⅲ):0.53-0.64 µg·L-1, methylarsenicals:0.16-0.36 µg·L-1), compared to those in Southern Taihu (1.73, 1.10, 0.31, 0.10 µg·L-1). The results exhibited obvious spatial characteristics of arsenic species in the surface water of Lake Taihu. Besides, average values of TAs, As(Ⅴ), As(Ⅲ) and methylarsenicals in summer were 3.40, 2.06, 0.73 and 0.25 µg·L-1, respectively, higher than those in winter (1.78, 1.10, 0.30, 0.17 µg·L-1), reflecting significant seasonal characteristics of arsenic distribution. Factor analysis revealed the significant relationships of TAs and As(Ⅴ) with several water quality parameters, which suggested that spatial and seasonal distributions of TAs and As(Ⅴ) in Lake Taihu were affected by external pollution and internal arsenic release from sediments. Redundancy analysis further indicated significant effects of total phosphorus (TP) and total iron (TFe) on the distributions of TAs and As(Ⅴ). At the mean time, the above statistical analyses exhibited that As(Ⅲ) and methylarsenicals were positively correlated with chlorophyll-a (Chl-a). A large amount of microalgae could accumulate As(Ⅴ) and transform it more strongly to As(Ⅲ) and methylarsenicals in eutrophic regions when compared to mesotrophic region,especially in summer, reflecting the regulation of microalgae on arsenic biotransformation.