Chemical detection and analysis of Astragalus-Cassia twig drug pair using UHPLC-Q-TOF-MS and HPLC-UV methods.

The classic Astragalus-Cassia twig drug pair has a long history of proven efficacy. However, a fewer studies on material basis of the Astragalus and Cassia twig decoction (ACD) was researched at present. The method of UPLC-Q-TOF-MS for classifying and identifying the main chemical components of ACD was established and the differences in composition between single decoction and co-decoction were compared by using HPLC-UV. The therapeutic role of ACD on type 2 diabetes (T2D) rats was investigated. Thirty-five compounds were resolved from the ACD. Fifteen compounds were deduced from the decoction of Astragalus, whereas nine compounds were identified from Cassia twig. Pairing of herbs make a significant effect on the chemical composition of herbal decoction. ACD can play a more obvious role in alleviating the symptoms of T2D rats, compared to the application of single herb.

Advancements in Antiviral Drug Development: Comprehensive Insights into Design Strategies and Mechanisms Targeting Key Viral Proteins.

Viral infectious diseases have always been a threat to human survival and quality of life, impeding the stability and progress of human society. As such, researchers have persistently focused on developing highly efficient, low-toxicity antiviral drugs, whether for acute or chronic infectious diseases. This article presents a comprehensive review of the design concepts behind virus-targeted drugs, examined through the lens of antiviral drug mechanisms. The intention is to provide a reference for the development of new, virus-targeted antiviral drugs and guide their clinical usage.

Optimized new Shengmai powder inhibits myocardial fibrosis in heart failure by regulating the rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway.

OBJECTIVE: Exploring the effect of Optimized New Shengmai powder (, ONSMP) on myocardial fibrosis in heart failure (HF) based on rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinases (ERK) signaling pathway. METHODS: Randomized 70 Sprague-Dawley rats into sham (n = 10) and operation (n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low (L), medium (M), and high (H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat's body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen (COL) I and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the mRNA levels of COL I, COL Ⅲ, α-smooth muscle actin (α-SMA), and c-Fos proto-oncogene (c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor (p-ELK1), p-c-Fos, α-SMA, COL I, and COL Ⅲ by Western blot. RESULTS: ONSMP can effectively improve HF rat's cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL I/Ⅲ content, down-regulate the mRNA of COL I/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/ 2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA. CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.

Anti-aging Effect of Rutin in Caenorhabditis elegans and D-Gal-Induced Aging Mouse Model.

Caenorhabditis elegans and D-Gal-induced aging mouse model were used to investigate the anti-aging effect of rutin. The effects of different concentrations of rutin (0, 12.5, 25, and 50 µg/mL) on locomotor behavior, reproductive rate, and lifespan of C. elegans were determined. For establishing the aging mouse model, D-Gal (200 mg/kg) was subcutaneously injected into the back of mice, and mice were treated with rutin (200 mg/kg). At the end of treatment, memory and motor function was assessed by nest building test, open field test, and Y-maze. Serum and brain tissue were collected from each mouse to examine the ROS, lipofuscin, MDA, GSH-Px, and SOD levels. The results showed that rutin prolonged the lifespan of C. elegans, and increased the number of eggs of C. elegans (p < 0.05). In addition, rutin significantly improved the exercise capacity in mice (p < 0.05) and significantly reduced brain tissue ROS (p < 0.05) and MDA (p < 0.01) levels. Meanwhile, rutin could enhance the activity of SOD (p < 0.05) and GSH-Px (p < 0.01) significantly in the serum and brain. In summary, rutin exhibits anti-senescence capabilities which could be ascribed to its antioxidant activities.

Effect of biochar from peanut shell on speciation and availability of lead and zinc in an acidic paddy soil.

Biochar has been used to reduce the mobility and availability of heavy metals in contaminated paddy soils. A pot experiment was carried out to analyze the effects of peanut shell biochar (PBC) on the speciation and phytoavailability of Pb and Zn in contaminated acidic paddy soil using rice (Oryza sativa L.) as an indicator plant. Peanut shell biochar was applied to an acidic paddy soil contaminated with Pb and Zn at four rates (0%, 1%, 2%, and 5% w/w), and rice plants were grown in this soil. The soil pH, cation exchange capacity (CEC), water-soluble SO42-, dissolved organic carbon (DOC), CaCl2-extractable heavy metals, and speciation of heavy metals were determined. Additionally, biomass and concentrations of heavy metals in rice tissues were determined. The application of PBC significantly increased the pH, CEC, water-soluble SO42-, and DOC in the paddy soil, but decreased the content of CaCl2-extractable Pb and Zn. The CaCl2-extractable Pb and Zn showed significant negative correlations with the pH, CEC, water-soluble SO42-, and DOC (p < 0.05). Following the application of biochar to the contaminated paddy soil, the Pb and Zn concentrations in the CaCl2 extracts were reduced by 41.04-98.66% and 17.78-96.87% (p < 0.05), respectively. Sequential chemical extractions showed a reduction in the acid-soluble Pb and Zn fraction and an increase in the reducible fraction following the addition of biochars. PBC obviously inhibited the uptake and accumulation of Pb and Zn in the rice plants. The Pb concentrations in the rice grain were significantly reduced by 60.32%, with the addition of 5% PBC. Neither of the biochars significantly changed the Zn concentrations in the rice grain. The influence of biochar on Pb and Zn phytoavailability varied not only with the application rate of biochar, but also with the kind of metals. Overall, the use of peanut shell biochar at a high application rate is more effective in immobilizing Pb and Zn in the acidic paddy soil contaminated with heavy metals, especially in reducing the phytoavailability of Pb to the rice plants.

Synchronous model-based approach for wavefront sensorless adaptive optics system.

In this paper, an aberration correction algorithm for wavefront sensorless adaptive optics system is presented, which is based on the approximately linear relation between the mean square of the aberration gradients and the second moment of far-field intensity distribution. To demonstrate algorithm's performance, an experiment system of aberration corrections for Fresnel zone plates imaging is set up. The correction results show the excellent performance of this method in correction speed, and correction capability. Comparing with conventional stochastic parallel gradient descent (SPGD) algorithm, the correction speed with this method is improved about four times for the similar correction effect.

A three-season field study on the in-situ remediation of Cd-contaminated paddy soil using lime, two industrial by-products, and a low-Cd-accumulation rice cultivar.

To mitigate the serious problem of Cd-contaminated paddy soil, we investigated the remediation potential of combining in-situ immobilization with a low-Cd-accumulation rice cultivar. A three-season field experiment compared the soil pH, available Cd and absorption of Cd by three rice cultivars with different Cd accumulation abilities grown in Cd-contaminated paddy soil amended with lime (L), slag (S), and bagasse (B) alone or in combination. The three amendments applied alone and in combination significantly increased soil pH, reduced available Cd and absorption of Cd by rice with no effect on grain yield. Among these, the LS and LSB treatments reduced the brown rice Cd content by 38.3-69.1% and 58.3-70.9%, respectively, during the three seasons. Combined with planting of a low-Cd-accumulation rice cultivar (Xiang Zaoxian 32) resulted in a Cd content in brown rice that met the contaminant limit (≤0.2mgkg-1). However, the grain yield of the low-Cd-accumulation rice cultivar was approximately 30% lower than the other two rice cultivars. Applying LS or LSB as amendments combined with planting a low-Cd-accumulation rice cultivar is recommended for the remediation of Cd-contaminated paddy soil. The selection and breeding of low-Cd-accumulation rice cultivars with high grain production requires further research.

Syringe test screening of microbial gas production activity: Cases denitrification and biogas formation.

Mass produced plastic syringes may be applied as vessels for cheap, simple and large scale batch culture testing. As illustrated for the cases of denitrification and of biogas formation, metabolic activity was monitored by direct reading of the piston movement due to the gas volume formed. Pressure buildup due to friction was shown to be moderate. A piston pull and slide back routine can be applied before recording gas volume to minimize experimental errors due to friction. Inoculum handling and activity may be conveniently standardized as illustrated by applying biofilm carriers. A robust set of positive as well as negative controls ("blanks") should be included to ensure quality of the actual testing. The denitrification test showed saturation response at increasing amounts of inoculum in the form of adapted moving bed biofilm reactor (MBBR) carriers, with well correlated nitrate consumption vs. gas volume formed. As shown, the denitrification test efficiently screened different inocula at standardized substrates. Also, different substrates were successfully screened and compared at standardized inocula. The biogas potential test showed efficient screening of different substrates with effects of relative amounts of carbohydrate, protein, fat. A second case with CO2 capture reclaimer waste as substrate demonstrated successful use of co-feeding to support waste treatment and how temperature effects on kinetics and stoichiometry can be observed. In total, syringe test screening of microbial gas production seems highly efficient at a low cost when properly applied.

Species classification and bioactive ingredients accumulation of BaiJiangCao based on characteristic inorganic elements analysis by inductively coupled plasma-mass spectrometry and multivariate analysis.

BACKGROUND: Patrinia scabiosaefolia Fisch and Patrinia villosa (Thunb.) Juss., two species herbs with the same Chinese name "BaiJiangCao", are important ancient herbal medicines widely used for more than 2000 years. The clinical application of two species herb is confused due to the difficult identification. OBJECTIVE: The objective was to authenticate the species of BaiJiangCao and analyze the accumulation of bioactive ingredients based on characteristic inorganic elements analysis. MATERIALS AND METHODS: Content of 32 inorganic elements in BaiJiangCao from different habitats were determined by inductively coupled plasma-mass spectrometry (ICP-MS), and the characteristic inorganic elements were picked to distinguish the species of the herb by principal component analysis and cluster analysis. Contents of two bioactive ingredients, luteoloside, and oleanolic acid, in the samples, were also analyzed by high-performance liquid chromatography method. Relationship between accumulation of bioactive ingredients and content of macroelements in BaiJiangCao was established by statistics. RESULTS: A 4 macroelements (Na, Mg, K, Fe) in 32 determined inorganic elements were picked for characteristic inorganic elements. Content of Na, Mg, K and Fe showed positive correlations with that of luteoloside, content of Na, Mg showed positive correlations with that of oleanolic acid, but content of K and Fe showed negative correlations with that of oleanolic acid. CONCLUSION: It is for the first time to utilize the characteristic inorganic elements as an index to classify the herb species by the method of ICP-MS and multivariate analysis. And it is also the first report to investigate the influence of inorganic elements in herb on the accumulation of bioactive components which could affect the pharmacological efficacy of the herb medicine. And this method could also be utilized in research of corresponding aspects.

Study on the in vivo toxic mechanism of xixin based on trace elements determination by inductively coupled plasma-mass spectrometry.

BACKGROUND: Xixin has been widely used as a traditional Chinese medicine for headache, toothache and inflammatory diseases. Clinical investigation indicated that adverse drug reactions occurred with an overdose of xixin, but the toxic mechanism of xixin in vivo based on trace elements has not been researched yet. OBJECTIVE: To explore the in vivo toxic mechanism of xixin induced by trace elements. MATERIALS AND METHODS: The contents of trace elements in the serum and liver of mice were determined by inductively coupled plasma-mass spectrometry (ICP-MS) after obtaining xixin extracts. Principal component analysis (PCA) and cluster analysis (CA) were performed between the trace elements' content and dosage using the software GeneSpring 12.1 to analyze the main toxic elements in vivo. RESULTS: Trace elements' contents were obviously raised after xixin extracts were taken as a dosage of 150 mg/mL and 50 mg/mL, respectively. Na, Ca, Cu and Cd in serum and Ca and Zn in liver were the main trace elements inducing the toxic reaction of xixin. CONCLUSION: Xixin possesses the potential function of indirectly upregulating trace elements in vivo. This study, for the first time, elucidated the in vivo toxic mechanism of xixin based on trace elements. This method could also be utilized in the research of corresponding aspects.

Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in gastric ulcer and intervention effects of Corydalis yanhusuo alkaloid.

Metabolomics, the systematic analysis of potential metabolites in a biological specimen, has been increasingly applied to discovering biomarkers, identifying perturbed pathways, measuring therapeutic targets, and discovering new drugs. By analyzing and verifying the significant difference in metabolic profiles and changes of metabolite biomarkers, metabolomics enables us to better understand substance metabolic pathways which can clarify the mechanism of Traditional Chinese Medicines (TCM). Corydalis yanhusuo alkaloid (CA) is a major component of Qizhiweitong (QZWT) prescription which has been used for treating gastric ulcer for centuries and its mechanism remains unclear completely. Metabolite profiling was performed by high-performance liquid chromatography combined with time-of-flight mass spectrometry (HPLC/ESI-TOF-MS) and in conjunction with multivariate data analysis and pathway analysis. The statistic software Mass Profiller Prossional (MPP) and statistic method including ANOVA and principal component analysis (PCA) were used for discovering novel potential biomarkers to clarify mechanism of CA in treating acid injected rats with gastric ulcer. The changes in metabolic profiling were restored to their base-line values after CA treatment according to the PCA score plots. Ten different potential biomarkers and seven key metabolic pathways contributing to the treatment of gastric ulcer were discovered and identified. Among the pathways, sphingophospholipid metabolism and fatty acid metabolism related network were acutely perturbed. Quantitative real time polymerase chain reaction (RT-PCR) analysis were performed to evaluate the expression of genes related to the two pathways for verifying the above results. The results show that changed biomarkers and pathways may provide evidence to insight into drug action mechanisms and enable us to increase research productivity toward metabolomics drug discovery.

The magnitude of dengue virus NS1 protein secretion is strain dependent and does not correlate with severe pathologies in the mouse infection model.

There are conflicting data on the relationship between the level of secreted NS1 (sNS1), viremia, and disease severity upon dengue virus (DENV) infection in the clinical setting, and therefore, we examined this relationship in the widely accepted AG129 mouse model. Because of the failure of a routinely used NS1 detection kit to detect sNS1 of the mouse-adapted DENV2 strain, we screened 15 previously undescribed NS1 monoclonal antibodies and developed a robust capture enzyme-linked immunosorbent assay (ELISA) with detection sensitivity at the low nanogram level (0.2 ng/ml) using recombinant baculovirus-expressed sNS1 as well as sNS1 that was immunoaffinity purified from the various DENV2 strains employed in this study. Using this test, we demonstrated that increased viremia paralleled severe pathologies; however, sNS1 level did not correlate with viremia or severity. Furthermore, among the DENV2 strains that were tested, the level of NS1 secretion did not correspond to virus replication rate in vitro, at the cellular level. Together, our data indicate that the magnitude of NS1 secretion appears to be strain dependent and does not correlate with viral virulence in the AG129 mouse model.

Cutting edge: granulocyte-macrophage colony-stimulating factor is the major CD8+ T cell-derived licensing factor for dendritic cell activation.

During priming, CD8(+) T lymphocytes can induce robust maturation of dendritic cells (DCs) in a CD40-independent manner by secreting licensing factor(s). In this study, we isolate this so-far elusive licensing factor and identify it, surprisingly, as GM-CSF. This provides a new face for an old factor with a well-known supporting role in DC development and recruitment. Signaling through the GM-CSFR in ex vivo-purified DCs upregulated the expression of costimulatory molecules more efficiently than did any tested TLR agonist and provided a positive feedback loop in the stimulation of CD8(+) T cell proliferation. Combined with a variety of microbial stimuli, GM-CSF supports the formation of potent "effector" DCs capable of secreting a variety of proinflammatory cytokines that guide the differentiation of T cells during the immune response.