Effect of moxibustion combined with intraperitoneal injection of benazepril on endoplasmic reticulum stress-related protein phosphorylation in rats with chronic heart failure. / è‰¾ç¸è”åˆè´é‚£æ™®åˆ©å¯¹æ ¢æ€§å¿ƒåŠ›è¡°ç«­å¤§é¼ å¿ƒè‚Œå† è´¨ç½‘åº”æ¿€ç›¸å ³è›‹ç™½ç£·é ¸åŒ–è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effect of moxibustion at "Xinshu"(BL15) and "Feishu"(BL13) combined with intraperitoneal injection of benazepril on cardiac function and phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor 2α (elF2α) proteins in myocardium of rats with chronic heart failure (CHF), so as to explore its potential mechanism underlying improvement of CHF. METHODS: A total of 42 male SD rats were randomly assigned to blank control (n=10), CHF model (n=7), medication (benazepril, n=8), moxibustion (n=8) and moxibustion+benazepril (n=9) groups, after cardiac ultrasound model identification and elimination of the dead. The CHF model was established by intraperitoneal injection of doxorubicin hydrochloride (DOX), once every week for 6 weeks. Mild moxibustion was applied to bilateral BL15 and BL13 regions for 20 min, once daily for 3 weeks. The rats of the medication group and moxibustion+benazepril group (benazepril was given first, followed by moxibustion) received intraperitoneal injection of benazepril (0.86 mg/kg) solution once daily for 3 weeks . The cardiac ejection fraction (EF) and left ventricular fractional shortening (FS) were measured using echocardiography. Histopathological changes of the cardiac muscle tissue were observed under light microscope after hematoxylin-eosin (H.E.) staining. Serum contents of B-type brain natriuretic peptide (BNP) and angiotensin Ⅱ (AngⅡ) were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of phospho-PERK (p-PERK) and phospho-elF2α (p-elF2α) in the myocardium were detected by Western blot. RESULTS: Compared with the blank control group, the EF and FS of the left cardiac ventricle were significantly decreased (P<0.01), while the contents of serum BNP and AngⅡ, and expression levels of p-PERK and p-eIF2α significantly increased in the model group (P<0.01). In comparison with the model group, both the decreased EF and FS and the increased BNP and AngⅡ contents as well as p-PERK and p-elF2α expression levels were reversed by moxibustion, medication and moxibustion+benazepril (P<0.01). The effects of moxibustion+benazepril were markedly superior to those of simple moxibustion and simple medication in raising the levels of EF and FS rate and in down-regulating the contents of BNP, Ang Ⅱ, levels of p-PERK and p-elF2α (P<0.01, P<0.05). Outcomes of H.E. staining showed irregular arrangement of cardiomyocytes, cell swelling, vacuole and inflammatory infiltration in the model group, which was relatively milder in the 3 treatment groups. The effects of moxibustion+benazepril were superior to those of moxibustion or benazepril. CONCLUSIONS: Moxibustion combined with Benazepril can improve the cardiac function in CHF rats, which may be related to its functions in down-regulating the expression levels of myocardial p-PERK and p-elF2α to inhibit endoplasmic reticulum stress response.

High-fat diet promotes liver tumorigenesis via palmitoylation and activation of AKT.

OBJECTIVE: Whether and how the PI3K-AKT pathway, a central node of metabolic homeostasis, is responsible for high-fat-induced non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain a mystery. Characterisation of AKT regulation in this setting will provide new strategies to combat HCC. DESIGN: Metabolite library screening disclosed that palmitic acid (PA) could activate AKT. In vivo and in vitro palmitoylation assay were employed to detect AKT palmitoylation. Diverse cell and mouse models, including generation of AKT1C77S and AKT1C224S knock-in cells, Zdhhc17 and Zdhhc24 knockout mice and Akt1C224S knock-in mice were employed. Human liver tissues from patients with NASH and HCC, hydrodynamic transfection mouse model, high-fat/high-cholesterol diet (HFHCD)-induced NASH/HCC mouse model and high-fat and methionine/choline-deficient diet (HFMCD)-induced NASH mouse model were also further explored for our mechanism studies. RESULTS: By screening a metabolite library, PA has been defined to activate AKT by promoting its palmitoyl modification, an essential step for growth factor-induced AKT activation. Biologically, a high-fat diet could promote AKT kinase activity, thereby promoting NASH and liver cancer. Mechanistically, palmitoyl binding anchors AKT to the cell membrane in a PIP3-independent manner, in part by preventing AKT from assembling into an inactive polymer. The palmitoyltransferases ZDHHC17/24 were characterised to palmitoylate AKT to exert oncogenic effects. Interestingly, the anti-obesity drug orlistat or specific penetrating peptides can effectively attenuate AKT palmitoylation and activation by restricting PA synthesis or repressing AKT modification, respectively, thereby antagonising liver tumorigenesis. CONCLUSIONS: Our findings elucidate a novel fine-tuned regulation of AKT by PA-ZDHHC17/24-mediated palmitoylation, and highlight tumour therapeutic strategies by taking PA-restricted diets, limiting PA synthesis, or directly targeting AKT palmitoylation.

Cymbaria daurica L.: A Mongolian herbal medicine for treating eczema via natural killer cell-mediated cytotoxicity pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbaria daurica L. (C. daurica) is a perennial herb known commonly as "Xinba" (Chinese) and "Kanba-Arong" (Mongolian). In Mongolia, it is used as a traditional medicine to treat eczema and other skin diseases due to its anti-swelling, anti-inflammatory, anti-hemorrhagic, and anti-itching properties. However, the potential mechanism of action for eczema treatment has not been reported. AIM OF THE STUDY: To investigate the effect of C. daurica on 1-chloro-2,4-dinitrobenzene (DNCB)-induced eczema in rats and the associated action mechanism. MATERIALS AND METHODS: Qualitative analysis of C. daurica was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on information obtained from compound identification and relevant literature, the possible targets of C. daurica against eczema were analyzed using network pharmacology and molecular docking methods. The DNCB-induced eczema rat models were treated with different dosages of C. daurica extract (10, 50, and 250 mg/mL per day), and the therapeutic effects subsequently evaluated based on the degree of skin inflammation, spleen index, and hematoxylin and eosin staining (H&E staining). Enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative polymerase chain reaction (RT-qPCR), and western blotting were used to analyze the relevant target effects. The C. daurica mechanism of action on eczema was verified by animal experiments. High-performance liquid chromatography (HPLC) was carried out to determine the content of active ingredients in C. daurica. In addition, the physicochemical properties of the extract were evaluated. RESULTS: Our analysis of the 173 targets included in the protein-protein interaction (PPI) network identified tumor necrosis factor (TNF) and interleukin 2 (IL-2) as key targets involved in the treatment of eczema with C. daurica extract. Furthermore, the 173 targets were associated with the natural killer cell-mediated cytotoxicity pathway. Our results showed that C. daurica significantly reduced IL-2 and TNF-α serum levels in eczema rat models (P < 0.0001); thus, playing an important role in the anti-inflammatory response. Furthermore, according to the p-value, RT-qPCR and western blotting showed that the expression of Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), Vav guanine nucleotide exchange factor (Vav), and growth factor receptor-bound protein 2 (Grb2) changed in the skin of the eczema model rats after treatment with the C. daurica extract. CONCLUSION: Our study confirms that C. daurica can inhibit SHP-1, Vav, and Grb2 expression; thereby, inhibiting the natural killer cell-mediated cytotoxicity pathway. These results provide insight into the mechanism of C. daurica in treating eczema.

Moxibustion alleviates chronic heart failure by regulating mitochondrial dynamics and inhibiting autophagy.

Moxibustion (MOX) is a traditional Chinese medicine preparation, which has been clinically used to treat cardiac diseases in recent years. The present study aimed to examine the protective effects and possible mechanisms of MOX on doxorubicin (DOX)-induced chronic heart failure (CHF) in rats. The animals were divided into five groups, including the Control (normal saline), DOX (doxorubicin 15 mg/kg), MOX (doxorubicin 15 mg/kg + moxibustion), BEN (doxorubicin 15 mg/kg + benazepril 0.86 mg/kg) and MOX + BEN (doxorubicin 15 mg/kg + moxibustion + benazepril 0.86 mg/kg) groups. After three weeks, echocardiography was performed to assess cardiac function and structure, including left ventricular internal diameter in systole, ejection fraction and fractional shortening (FS). Serum brain natriuretic peptide levels and adenosine triphosphate (ATP) levels were measured by enzyme-linked immunosorbent assay and ATP assay. Cardiac pathology was assessed by hematoxylin and eosin and Masson's trichrome staining. Cardiac ultrastructure and the number of autophagosomes formed were visualized by transmission electron microscopy. Western blotting was performed to assess mitochondrial dynamics, autophagy proteins and mitochondrial autophagy-related pathway proteins. The expression levels of these genes were assessed by reverse transcription-quantitative PCR. The results indicated MOX could improve cardiac function, increased cardiac ATP levels and reduced myocardial fibrosis. Western blotting indicated that MOX treatment elevated the expression of optic atrophy 1 protein (OPA1), while decreasing the expression of dynamin-related protein 1 and mitochondrial fission 1 protein. In addition, MOX inhibited autophagy, as evidenced by decreased number of autophagosomes, reduced LC3II/LC3I ratio and increased p62 expression. Furthermore, MOX downregulated DOX-induced FUNDC1 signaling pathway. In summary, MOX has protective effects on DOX-induced CHF in rats, promoting mitochondrial fusion while inhibiting mitochondrial fission and mitophagy. The underlying mechanisms may be related to the inhibition of the FUNDC1 signaling pathway.

[Effect of moxibustion combined with benazepril on expression of IL-18 and phosphorylated protein kinase B in myocardial tissue of rats with chronic heart failure].

OBJECTIVE: To observe the effect of moxibustion combined with benazepril on cardiac function and expression levels of myocardial interleukin-18(IL-18), phosphorylated protein kinase B(p-Akt) in rats with chronic heart failure (CHF), so as to explore its underlying mechanisms in improvement of CHF. METHODS: Fifty male rats were randomly divided into normal, model, moxibustion, benazepril and moxibustion+benazepril groups (n=10 rats per group). The CHF model was established by intraperitoneal injection of doxorubicin hydrochloride solution (DOX, 2.5 mg/kg) twice a week for 4 weeks. After successful modeling, the rats in the normal and model groups were fed with normal diet, and fixed on a rat plate for 20 min each time without any treatment. Mild moxibustion was applied to bilateral "Feishu" (BL13) and "Xinshu" (BL15) for 20 min each time, for 3 weeks in the moxibustion and moxibustion+benazepril groups. Rats of the benazepril and moxibustion+benazepril groups received gavage of benazepril (2 mg/kg) once daily for 3 weeks. The general behaviors of rats were observed. The ejection fraction (EF), left ventricular diameter shortening (FS), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), heart rate (HR) and ventricular septal thickness (IVS) were examined by echocardiography. The content of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) was detected by enzyme-linked immunosorbent assay, and expression levels of myocardial IL-18, p-Akt were detected by Western blot. RESULTS: Compared with the normal group, the EF, FS, IVS, and myocardial p-Akt expression level were significantly reduced (P<0.01), and the LVIDd, LVIDs, HR, and serum NT-proBNP content and myocardial IL-18 expression level were significantly increased in the model group (P<0.01). In comparison with the model group, the EF, FS, IVS, and myocardial p-Akt were remarkably up-regulated (P<0.05, P<0.01), and the LVIDd, LVIDs, HR, serum NT-proBNP content, and myocardial IL-18 expression level were significantly down-regulated (P<0.05, P<0.01) in the moxibustion, benazepril, and moxibustion+benazepril groups. Compared with the moxibustion+benazepr group, the levels of LVIDs, HR, serum NT-proBNP and myocardial IL-18 expression were obviously higher (P<0.05, P<0.01), while the levels of EF, FS, IVS and p-Akt were significantly lower in the moxibustion and benazepril groups (P<0.01). CONCLUSION: Moxibustion combined with benazepril improves cardiac function in CHF rats, and is superior to simple moxibustion and simple benazepril in reducing IL-18 expression and increasing p-Akt expression in myocardial tissue.

[Exploration on the diagnosis and treatment of generalized myasthenia gravis with acupuncture and moxibustion based on the study of ancient medical works].

Through collecting the relevant provisions and medical cases of wei syndrome treated with acupuncture and moxibustion from ancient medical works, the diagnosis and acupoint selection in treatment of generalized myasthenia gravis (gMC) with acupuncture and moxibustion were analyzed systematically from 3 aspects, i.e. meridian differentiation, disease differentiation and syndrome differentiation. In treatment based on meridian differentiation, the acupoints are selected in the light of the running course of meridian and characteristics of meridian disorders. In treatment based on disease differentiation, the acupoints are selected in accordance with etiology, pathogenesis and transmission stages of wei syndrome. Concerning to syndrome differentiation in treatment, the acupoints are selected on the basis of therapeutic principles determined by different syndromes/patterns of wei syndrome. In modern clinical practice, the treatment for gMC should be rooted at ancient literature, thus a standardized regimen can be developed for diagnosis and treatment with acupuncture and moxibustion.

Growing phosphorus dilemma: The opportunity from aquatic systems' secondary phosphorus retention capacity.

The essential cause of phosphorus scarcity and phosphorus-induced risks, i.e. phosphorus dilemma, mainly lies in current low phosphorus flow efficiency (PFE) in agricultural systems. Improving PFE largely depends on secondary phosphorus retention along the phosphorus flow chain from phosphate mining to terrestrial agricultural systems, to aquatic systems, and ultimately to seabed deposition. Our review found that aquatic systems will have the opportunity and growing capacity to retain seaward secondary phosphorus carried by the runoff, due to its location between land and water systems, its ability of converting secondary phosphorus from both land and aquatic systems into aquatic products, and its rapid expansion with low PFE. However, a knowledge gap exists in secondary phosphorus retention in aquatic systems compared to in terrestrial systems. Although the phosphorus retention literature continues to grow in environmental and agricultural & biological sciences, only 8.8% of the documents are related to aquatic systems with few quantification studies. Based on the literature with phosphorus retention quantification since 1979, we divided the reported phosphorus interceptors into abiotic and biotic groups, further into 7 categories and more subcategories. By 2020, eight categories of interceptors had been reported, increased from only one interceptor in 1979. However, most of them focused on wetlands, only a few studies on aquatic organisms which concentrated in 8 countries before 2000. Thus, it is urgent to emphasize aquatic systems' secondary phosphorus retention capacity and its systemic benefits for a sustainable phosphorus use.

A Network Pharmacology Study to Uncover the Multiple Molecular Mechanism of the Chinese Patent Medicine Toujiequwen Granules in the Treatment of Corona Virus Disease 2019 (COVID-19).

Since the outbreak of the novel corona virus disease 2019 (COVID-19) at the end of 2019, specific antiviral drugs have been lacking. A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COVID-19. The present study was designed to reveal the molecular mechanism of Toujiequwen granules against COVID-19. A network pharmacological method was applied to screen the main active ingredients of Toujiequwen granules. Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredient interacting with many drug targets is quercetin. Drug targets most affected by the active ingredients were PTGS2, PTGS1, and DPP4. Drug target disease enrichment analysis showed drug targets were significantly enriched in cardiovascular diseases and digestive tract diseases. An "active ingredient-target-disease" network showed that 57 active ingredients from Toujiequwen granules interacted with 15 key targets of COVID-19. There were 53 ingredients that could act on DPP4, suggesting that DPP4 may become a potential new key target for the treatment of COVID-19. GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide, cytokine activity and other functions. KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors and endocrine resistance pathway. The evidence suggests that Toujiequwen granules might play an effective role by improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against multiple signaling pathways related to the pathogenesis of COVID-19.

Moxibustion Improves Chronic Heart Failure by Inhibiting Autophagy and Inflammation via Upregulation of mTOR Expression.

How moxibustion improves chronic heart failure is extremely complex and still unclear. This study aimed to explore whether moxibustion inhibits autophagy and reduces inflammation by regulating mTOR expression to induce myocardial protective effects and alleviate symptoms associated with chronic heart failure. Echocardiography was used to detect cardiac function and cardiac structure of rats, including heart rate (HR), left atrium diameter (LA), left ventricular diameter (LV), left ventricular posterior wall (LVPW), interventricular septum (IVS), ejection fraction (EF), and fractional shortening (FS). BNP and NT-pro BNP levels were measured by enzyme-linked immunosorbent assay (ELISA). Autophagy-associated protein (ATG) genes and mTOR were detected by PCR. The expression of mTOR and phosphorylated-mTOR was detected through western blotting of proteins from myocardial tissue samples. The left ventricular inflammatory response was detected by immunohistochemistry and included ICAM-1, VCAM-1, MMP-2, and MMP-9 expression. The relationship between autophagy and inflammation was analyzed by correlation analysis. The results from echocardiography and ELISA showed that moxibustion could significantly improve heart function and structure. Western blot and PCR results showed that moxibustion treatment elevated mTOR expression. Further, moxibustion could inhibit autophagy and regulate the expression of key autophagy-related genes, including Vps34, ATG3, ATG5, ATG7, ATG12, and ATG13. By contrast, rapamycin could partially reduce the effects of moxibustion. Immunohistochemistry results indicated that moxibustion could reduce myocardial inflammation. Moreover, there was a positive correlation between autophagy and inflammation. Moxibustion can protect cardiac function in rats with heart failure, possibly inhibiting excessive autophagy of cardiomyocytes and reducing inflammatory reactions through the elevation of mTOR expression.

[Analysis of the divergent meridians of twelve meridians].

This paper analyzes the problems existing in the current theory of divergent meridian ("Jingbie"), such as the unclear route of divergent meridian, the controversy in the "li-he-chu-ru" and the lack of in-depth research on the theory of "liuhe", clarifies the source and privides insights. The author analyzed the word "Jingbie" by means of the four proofreading methods combined with philology method to explore the origin of "Jingbie ". The divergent meridians is the remnant of the original meridians system in the bamboo and silk documents, which was put into the meridians system after being sorted out by doctors. The twelve meridians are combined in two, forming the "liuhe" point, which is located in the neck, and has a great influence on the blood circulation of the head and neck. "liuhe" point and theory can guide the differentiation of acupuncture and moxibustion, and has an important guiding significance for the treatment of empirical, emergency and head and face diseases.

Effect of Alpina oxyphylla extract on streptozotocin-induced kidney injure via regulating TGF-ß1 and MyD88.

BACKGROUND: Abnormal renal metabolism is closely related to the development of chronic kidney disease. It is well known that renal inflammation plays an important role in the occurrence and development of tubulointerstitial damage in the renal tubules. The purpose of the experiment was to observe the bioactivity of Alpina oxyphylla extract (AOE) on renal injury in diabetic nephropathy (DN) rats induced by streptozotocin (STZ). METHODS: Thirty male Wistar rats were randomly divided into five group (n = 6): (1) intact control (non-diabetic, ND); (2) intact diabetic (STZ), (3) diabetic rats treated with gliclazide 5 mg/kg (STZ-gli), (4) diabetic rats treated with AOE 400 mg/kg (AOE 400), (5) diabetic rats treated with AOE 800 mg/kg (AOE 800). The diabetic nephropathy rat model was established by single intraperitoneal injected 50 mg/kg STZ. Fasting blood glucose (FBG) and body weight was observed at 1、3、6 weeks. After 6 weeks, the renal function parameters of five groups and 24 h urinary protein were detected. Expression of transforming growth factor-beta1 (TGF-ß1) and myeloid differentiation factor 88 (MyD88) were assessed by Western Blot. RESULTS: The STZ group showed hyperglycemia, proteinuria, renal function damage, and the levels of 24 h urinary protein, fasting blood glucose (FBG), blood urea nitrogen (BUN), serum creatinine (Scr), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and interleukin-6 (IL-6) in the STZ group increased significantly compared with the ND group. The expression of TGF-ß1 in STZ group was increase (p < 0.01), and the expression of MyD88 was significantly lower than in ND group (p < 0.05). The treatment of DN rats with AOE attenuated DN-associated in the serum biochemical index and the expression of TGF-ß1. CONCLUSIONS: AOE can effectively protect kidney tissues of diabetic nephropathy, and probably through regulating level of TGF-ß1/MyD88.

A Theoretical Analysis of the Effects of Tumor-Treating Electric Fields on Single Cells.

Tumor-treating fields (TTFields) are low-intensity and intermediate-frequency alternating electric fields that have been found to inhibit tumor cell growth. While effective, the mechanism by which TTFields affect cell growth is not yet clearly understood. Although numerous mathematical studies on the effects of electromagnetic fields on single cells exist, the effect of TTFields on single cells have been analyzed less frequently. The goal of this study is to explore through a mathematical analysis the effects of TTFields on single cells, with particular emphasis on the thermal effect. We examine herein two single-cell models, a simplified spheroidal model and a simulation of a U-87 MG glioblastoma cell model obtained from microscopic images. A finite element method is used to analyze the electric field distribution, electromagnetic loss, and thermal field distribution. The results further prove that the electric field in the cytoplasm is too weak and its thermal damage can be excluded as a mechanism for cell death in TTFields. Bioelectromagnetics. 2020;41:438-446. © 2020 Bioelectromagnetics Society.

Comprehensive Environmental Assessment of Potato as Staple Food Policy in China.

The Chinese government projected 30% of total consumed potatoes as a staple food (PSF) by 2020. We comprehensively assessed the potential impacts of PSF on rice and flour consumption, rice and wheat planting, energy and nutrient supply, irrigation-water, chemical nitrogen (N), phosphorus pentoxide (P2O5) and potassium oxide (K2O) fertilizer inputs and total greenhouse gases (GHG) emission for potatoes, rice and wheat, by assuming different proportions of potato substitutes for rice and flour. The results showed that per capita, 2.9 ± 0.3 and 4.7 ± 0.5 kg more potatoes per year would enter the Chinese staple-food diet, under the government's target. PSF consumed are expected to reach 5.2 ± 0.7 Tg yr-1, equivalent to substituting potatoes for 4.2 ± 0.8-8.5 ± 0.8 Tg yr-1 wheat and 5.1 ± 0.9-10.1 ± 1.8 Tg yr-1 rice under different scenarios. While this substitution can increase the nutrient supply index by 63% towards nutrient reference values, it may induce no significant effect on staple-food energy supply with lower chemical fertilizer (except for K2O) and irrigation-water inputs and GHG emissions in different substitution scenarios than the business as usual scenario. The reduction in rice and wheat demands lead to wheat in the North China Plain and early rice decrease by 6.1-11.4% and 12.1-24.1%, respectively. The total GHG reduction is equal to 1.1-9.0% of CO2 equivalent associated with CH4 and N2O emitted from the Chinese agroecosystem in 2005. The saved irrigation water for three crops compared to 2012 reaches the total water use of 17.9 ± 4.9-21.8 ± 5.9 million people in 2015. More N fertilizer, irrigation-water, and GHG can be reduced, if the PSF ratio is increased to 50% together with potato yield improves to the optimal level. Our results implied that the PSF policy is worth doing not only because of the healthier diets, but also to mitigate resource inputs and GHG emissions and it also supports agricultural structure adjustments in the areas of irrigated wheat on the North China Plain and early rice across China, designed to increase the adaptability to climate change.

[Study on characteristics and data mining of 464 cases of lung diseases in Xin'an Wang's medicine].

The purpose of this paper is to study the use rules of drugs for lung diseases in internal medicine department of Xin'an Wang's family, discuss the compatibility of common drugs for lung diseases, guide clinical application, and inherit Xin'an medicine. By retrospective study on lung diseases cases in Wang's internal medicine works, the lung diseases and use frequency of common drugs treated by Wang's medicine were counted, and the systematic clustering and association rule analysis of common drugs were conducted by using SPSS Statistic 20 and SPSS Modeler 18.0, respectively. The results showed that asthma, cold and cough were the main lung diseases treated by Wang's medicine, and the commonly used medicines included antitussive and antiasthmatic drugs, spleen-invigorating and dampness-removing drugs, and expectorants. The medicine taste was mainly bitter, pungent and sweet, with cold and warm properties in a balanced way, without severely cold or hot herbs, mainly attributing to the lung and stomach meridians. In clustering analysis, 10 drug combinations were obtained; association analysis showed that two, three, four association rules respectively had 11, 21, and 10 groups, and each drug group had 11, 16, and 5 items. Core combinations: Poria, Armeniacae Semen Amarum, Asteris Radix et Rhizome, Coicis Semen, Farfarae Flos, Dendrobii Caulis, Perilla Frutescens, Stemonae Radix, Citri Reticulatae Pericarpium, Cynanchi Stauntonii Rhizome et Radix, Meretricis Concha Cyclinae Concha, Belamcandae Rhizoma, and Pinelliae Rhizome. Xin'an Wang's medicine paid attention to the lung nature when treating lung diseases. Lung is a delicate organ, not resistant to coldness or heat, so severely cold or hot herbs shall not be used, and the clear and light drugs with functions of dispersing lung Qi, clearing phlegm evil, strengthening spleen, eliminating phlegm, and relieving cough and asthma are often used. Lung deficiency is a kind of deficiency of Qi and Yin, so both Qi and Yin shall be regulated. Deficiency of Yin would burn the lung and make the lung collaterals blocked. In this case, the lung collaterals shall be dredged for hemostasis. Long time of lung deficiency would hinder the distribution of body fluid, and lung shall be regulated to dissipate phlegm.

Computer-Assisted Drug Virtual Screening Based on the Natural Product Databases.

BACKGROUND: Computer-assisted drug virtual screening models the process of drug screening through computer simulation technology, by docking small molecules in some of the databases to a certain protein target. There are many kinds of small molecules databases available for drug screening, including natural product databases. METHODS: Plants have been used as a source of medication for millennia. About 80% of drugs were either natural products or related analogues by 1990, and many natural products are biologically active and have favorable absorption, distribution, metabolization, excretion, and toxicology. RESULTS: In this paper, we review the natural product databases' contributions to drug discovery based on virtual screening, focusing particularly on the introductions of plant natural products, microorganism natural product, Traditional Chinese medicine databases, as well as natural product toxicity prediction databases. CONCLUSION: We highlight the applications of these databases in many fields of virtual screening, and attempt to forecast the importance of the natural product database in next-generation drug discovery.

[Regularity of prescription medication of Xin'an Wang's internal medicine in treating stomach cramps based on data mining].

The study analyzes the medication rules of Xin'an Wang's internal medicine for treating stomach cramps by data mining technology,in order to provide reference for clinical medication. Through the summarization of the medical cases of stomach cramps treated by Xin'an Wang's doctors( Wang Ren-zhi,Wang Zhong-qi,Wang Le-tao),statistics was made for the frequency of symptoms,signs,syndromes and drugs in Office 2010. Apriori algorithm in IBM SPSS Modeler 14. 1,and SPSS Statistics 22. 0 were used for association rule analysis and cluster analysis. The results showed that the 310 prescriptions collected involved totally 322 syndromes( including symptoms and signs) and 336 drugs,with the cumulative dose of 4 072 times; the symptoms were correlated to the spleen and stomach,liver and gallbladder,and the heart system; syndrome differentiation was mainly based on liver-Qi invasion of the stomach,diet impairment to the stomach,deficiency of spleen and stomach and cold syndrome; commonly used drugs were Qi regulating drugs,phlegm eliminating drugs and blood circulation promoting and stasis removing drugs; high-frequency drug complex network diagram showed that Pinelliae Rhizoma,Aurantii Fructus,Trichosanthis Fructus,Allii Macrostemonis Bulbus were closely related; the analysis showed 12,20,and 17 two,three,and four association rules; cluster analysis showed 10 pairs of Trichosanthis Fructus-Allii Macrostemonis Bulbus,Pinelliae Rhizoma-Aurantii Fructus,and Aspongopus-Toosendan Fructus drug combinations. According to Xin' an Wang's doctors,stomach cramps are closely related to liver and spleen,Qi stagnation,phlegm and blood stasis are the standard.Xin'an Wang's doctors give the first priority on " deoppilation",focus on soothing the liver and spleen,activating Qi and eliminating phlegm,and promoting blood circulation,and refer to use modified Xiaoxianxiong Decoction and modified Gualou Xiebai Banxia Decoction based on symptoms.

Advanced glycation end products induce neural tube defects through elevating oxidative stress in mice.

Our previous study showed an association between advanced glycation end products (AGEs) and neural tube defects (NTDs). To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with commercial food containing 3% advanced glycation end product bovine serum albumin (AGE-BSA) or 3% bovine serum albumin (BSA) as a control. After mating mice, oxidative stress markers including malondialdehyde and H2O2 were measured at embryonic day 7.5 (E7.5) of gestation, and the level of intracellular reactive oxygen species (ROS) in embryonic cells was determined at E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-(carboxymethyl) lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at E10.5 in embryos of mice fed with AGE-BSA (no hyperglycemia) compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-(carboxymethyl) lysine and N(ε)-(carboxyethyl) lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.

Physiological and biochemical responses of Ulva prolifera and Ulva linza to cadmium stress.

Responses of Ulva prolifera and Ulva linza to Cd(2+) stress were studied. We found that the relative growth rate (RGR), Fv/Fm, and actual photochemical efficiency of PSII (Yield) of two Ulvaspecies were decreased under Cd(2+) treatments, and these reductions were greater in U. prolifera than in U. linza. U. prolifera accumulated more cadmium than U. linza under Cd(2+) stress. While U. linza showed positive osmotic adjustment ability (OAA) at a wider Cd(2+) range than U. prolifera. U. linza had greater contents of N, P, Na(+), K(+), and amino acids than U. prolifera. A range of parameters (concentrations of cadmium, Ca(2+), N, P, K(+), Cl(-), free amino acids (FAAs), proline, organic acids and soluble protein, Fv/Fm, Yield, OAA, and K(+)/Na(+)) could be used to evaluate cadmium resistance in Ulva by correlation analysis. In accordance with the order of the absolute values of correlation coefficient, contents of Cd(2+) and K(+), Yield, proline content, Fv/Fm, FAA content, and OAA value of Ulva were more highly related to their adaptation to Cd(2+) than the other eight indices. Thus, U. linza has a better adaptation to Cd(2+) than U. prolifera, which was due mainly to higher nutrient content and stronger OAA and photosynthesis in U. linza.

Folic acid-conjugated silica-modified gold nanorods for X-ray/CT imaging-guided dual-mode radiation and photo-thermal therapy.

Multifunctional nanoprobes are designed to own various functions such as tumor targeting, imaging and selective therapy, which offer great promise for the future of cancer prevention, diagnosis, imaging and treatment. Herein, silica was applied to replace cetyltrimethylammonium bromide (CTAB) molecules on the surface of gold nanorods (GNRs) by the classic Stöber method, thus eliminating their cytotoxicity and improving their biocompatibility. Folic acid molecule was covalently anchored on the surface of GNRs with silane coupling agent. The resultant folic acid-conjugated silica-modified GNRs show highly selective targeting, enhanced radiation therapy (RT) and photo-thermal therapy (PTT) effects on MGC803 gastric cancer cells, and also exhibited strong X-ray attenuation for in vivo X-ray and computed tomography (CT) imaging. In conclusion, the as-prepared nanoprobe is a good candidate with excellent imaging and targeting ability for X-ray/CT imaging-guided targeting dual-mode enhanced RT and PTT.

Protonated arginine and protonated lysine: hydration and its effect on the stability of salt-bridge structures.

Using a mass spectrometer equipped with a drift cell, water binding energies of protonated arginine (ArgH+) and protonated lysine (LysH+) were determined in equilibrium experiments and supplementary calculations at the B3LYP/6-311++G** level of theory. The binding energy of the first water molecule was measured to be 10.3 and 10.9 kcal/mol for ArgH+ and LysH+, respectively. Water binding energies decrease with increasing degree of hydration reaching values of 6-7 kcal/mol for the fourth and fifth water molecule. Theory reproduces this trend of decreasing binding energies correctly and theoretical water binding energies agree with experiment quantitatively within 2 kcal/mol. Lowest-energy theoretical structures of ArgH+ and LysH+ are characterized by protonated side chains and neutral alpha-amino and carboxyl groups which form intramolecular hydrogen bonds to the ionic group (charge solvation or CS structures). The salt bridge (SB) structures with two cationic groups (side chain and alpha-amine) and one anionic group (carboxyl) are 13.1 and 9.3 kcal/mol higher in energy for ArgH+ and LysH+, respectively. Theory indicated that the first water molecule binds to the ionic group of the CS structures of ArgH+ and LysH+. With increasing degree of hydration intramolecular interactions are replaced one by one with water bridges with water inserted into the intramolecular hydrogen bonds. Whereas the global minima of ArgH+.(H2O)n and LysH+.(H2O)n, n<7, were calculated to represent CS structures, 7-fold hydrated CS and SB structures, ArgH+.(H2O)7 and LysH+.(H2O)7, are nearly isoenergetic (within <1 kcal/mol).