Renzhu Ointment Regulates L-Type Voltage-Dependent Calcium Channel in Mice Model of Senna-Induced Diarrhea by Transdermal Administration.

Purpose: In China, herbal preparation is commonly administered transdermally for treating pediatric diarrhea. However, few studies have probed into their antidiarrheal mechanisms. This study was designed to investigate the antidiarrheal effect of Renzhu ointment (Renzhuqigao, RZQG) and its underlying mechanisms via transdermal administration. Methods: The main components of RZQG were confirmed by gas chromatography-mass spectrometry (GC-MS). The effect of RZQG on L-type voltage-dependent calcium channel (L-VDCC) was evaluated by CaCl2- and ACh-induced contraction in isolated colon. The antidiarrheal efficacy of RZQG was further investigated by the senna-induced diarrhea mice based on the frequency of loose stools, diarrhea rate and index, fecal moisture content, and the basal tension of the colon. Additionally, the protein expression of CACNA1C, CACNA1D, cAMP, and PKA were detected with Western blot and immunohistochemistry (IHC). Results: GC-MS analysis determined 14 components in RZQG. In vitro, RZQG relaxed the CaCl2- and ACh-induced tension, while nifedipine (a L-VDCC inhibitor) and H-89 (a PKA inhibitor) decreased the relaxation. In vivo, animal model showed that transdermal administration of RZQG exhibited a significant reduction in the frequency of loose stools, diarrhea rate and index, fecal moisture content and the basal tension. Compared to the model group, the colon of mice treated with RZQG showed lower expression of CACNA1C, CACNA1D, cAMP, and PKA. IHC results showed that cAMP was downregulated in colonic smooth muscle after RZQG treatment. Conclusion: RZQG improved diarrhea symptoms and down-regulated the expression of CACNA1C and CACNA1D via transdermal administration, which is closely associated with the cAMP/PKA signaling pathway in colonic smooth muscle.

Recent progress in performance optimization of Cu-SSZ-13 catalyst for selective catalytic reduction of NO x.

Nitrogen oxides (NO x ), which are the major gaseous pollutants emitted by mobile sources, especially diesel engines, contribute to many environmental issues and harm human health. Selective catalytic reduction of NO x with NH3 (NH3-SCR) is proved to be one of the most efficient techniques for reducing NO x emission. Recently, Cu-SSZ-13 catalyst has been recognized as a promising candidate for NH3-SCR catalyst for reducing diesel engine NO x emissions due to its wide active temperature window and excellent hydrothermal stability. Despite being commercialized as an advanced selective catalytic reduction catalyst, Cu-SSZ-13 catalyst still confronts the challenges of low-temperature activity and hydrothermal aging to meet the increasing demands on catalytic performance and lifetime. Therefore, numerous studies have been dedicated to the improvement of NH3-SCR performance for Cu-SSZ-13 catalyst. In this review, the recent progress in NH3-SCR performance optimization of Cu-SSZ-13 catalysts is summarized following three aspects: 1) modifying the Cu active sites; 2) introducing the heteroatoms or metal oxides; 3) regulating the morphology. Meanwhile, future perspectives and opportunities of Cu-SSZ-13 catalysts in reducing diesel engine NO x emissions are discussed.

Sub-chronic and developmental toxicity of transdermal delivery of Renzhu ointment in young SD rats.

Purpose: Renzhu ointment (Renzhuqigao, RZQG) is a patented herbal drug derived from Chinese traditional medicine formula and modern clinical experience for the transdermal treatment of non-infectious infantile diarrhoea. The safety of RZQG in preclinical studies has not been reported.Materials and methods: In this study, the pups of parent rats were examined for sub-chronic toxicity and developmental toxicity. After 21 days of birth, they were exposed to RZQG through their abdominal skin at doses of 0.1, 0.3, and 0.9 g/kg/day for 4 weeks and then were observed for another four weeks during their recovery period.Results: During the administration period, RZQG had no significant toxicological effect on body weight, food consumption, external eye examination, urinalysis, bone marrow examination, histopathology, central nervous system, reproductive system, or skeletal development. However, in the 0.9 g/kg/day group, the skin of some rats became dry and cracked, red and swollen, forming a white scab, while the white blood cells (WBC) count in female rats was lower and cholesterol (CHOL), triglycerides (TG), and glutamyl-transferase (GGT) were higher (p < 0.05).Conclusions: Rats receiving 0.9 g/kg/day exhibited skin irritation and were suspected to have a mild liver injury. There was no evidence of delayed toxicity four weeks after withdrawal. Therefore, the no-observed adverse effect level of RZQG was 0.3 g/kg/day (30 times the clinical dose planned and 4.92 times the human equivalent dose).

Kangbainian Lotion Ameliorates Vulvovaginal Candidiasis in Mice by Inhibiting the Growth of Fluconazole-Resistant Candida albicans and the Dectin-1 Signaling Pathway Activation.

Vulvovaginal candidiasis (VVC) is an infectious disease caused by Candida species, which affects millions of women worldwide every year. The resistance to available antifungal drugs for clinical treatment is a growing problem. The treatment of refractory VVC caused by azole-resistant Candida is still facing challenges. However, research on new antifungal drugs is progressing slowly. Although a lot of reports on new antifungal drugs, only three new antifungal drugs (Isavuconazole, ibrexafungerp, and rezafungin) and two new formulations of posaconazole were marketed over the last decade. Chinese botanical medicine has advantages in the treatment of drug-resistant VVC, such as outstanding curative effects and low adverse reactions, which can improve patients' comfort and adherence to therapy. Kangbainian lotion (KBN), a Chinese botanical formulation, has achieved very good clinical effects in the treatment of VVC. In this study, we investigated the antifungal and anti-inflammatory effects of KBN at different doses in fluconazole-resistant (FLC-resistant) VVC model mice. We further studied the antifungal mechanism of KBN against FLC-resistant Candida albicans (C. albicans) and the anti-inflammatory mechanism correlated with the Dectin-1 signaling pathway. In vivo and in vitro results showed that KBN had strong antifungal and anti-inflammatory effects in FLC-resistant VVC, such as inhibiting the growth of C. albicans and vaginal inflammation. Further studies showed that KBN inhibited the biofilm and hypha formation, reduced adhesion, inhibited ergosterol synthesis and the expression of ergosterol synthesis-related genes ERG11, and reduced the expression of drug-resistant efflux pump genes MDR1 and CDR2 of FLC-resistant C. albicans in vitro. In addition, in vivo results showed that KBN reduced the expression of inflammatory factor proteins TNF-α, IL-1ß, and IL-6 in vaginal tissues, and inhibited the expression of proteins related to the Dectin-1 signaling pathway. In conclusion, our study revealed that KBN could ameliorate vaginal inflammation in VVC mice caused by FLC-resistance C. albicans. This effect may be related to inhibiting the growth of FLC-resistance C. albicans and Dectin-1 signaling pathway activation.

High-throughput sequencing of the microbial diversity of roasted-sesame-like flavored Daqu with different characteristics.

The purpose of this experiment was to analyze the microbial community diversity in three Daqu samples displaying different characteristics in the same Daqu fermentation chamber. A high throughput sequencing technique was used to detect the microbial abundance and diversity in these Daqu samples. Of the three samples, the microbial diversity in the Black sample (sample B) was significantly higher than in the other two. At the genus level, Saccharopolyspora, Bacillus, Lentibacillus, Staphylococcus, Kroppenstedtia, and Thermoactinomyces were the primary bacterial groups in the sesame-flavored liquor, while Thermomyces, Thermoascus, and Aspergillus represented the main fungal groups. In sample B, the dominant bacteria were Thermoactinomyces, Saccharopolyspora, and Pseudomonas. In the White sample (sample W), Thermoactinomyces was the most abundant, followed by Saccharopolyspora and Lentibacillus. Staphylococcus dominated in the Yellow sample (sample Y), followed by Bacillus and Kroppenstedtia. Regarding the fungi in the three samples, Thermomyces accounted for 93.70% in sample B, and Aspergillus dominated in sample W, while the Thermoascus and Aspergillus content were similar in the sample Y. This study examined the microbial diversity in liquor Daqu with different sesame flavors, providing a foundation for microbial regulation, while investigating the relationship between flavored liquor compounds and microorganisms.

An endophytic strain of the genus Bacillus isolated from the seeds of maize (Zea mays L.) has antagonistic activity against maize pathogenic strains.

Plant endophytes are microbes that colonize plant internal tissues and are ubiquitously associated with plants. In this study, seven endophytic bacterial strains, 665L2, 725L2, 725R2, 92R2, 728R3, 728R4 and 2416T3, were isolated from seeds of five healthy maize varieties (Zea mays L.) and all identified as Bacillus velezensis by polyphasic taxonomy based on 16S rRNA and gyrA gene phylogenetic analysis. In addition, according to the genotyping results from random amplified polymorphic DNA (RAPD), 665L2, 725L2, 725R2 and 92R2 belonged to the same strain, while 728R3 and 2416T3 belonged to another strain. Pathogenic fungal strains 4, 5 and 6 were isolated from three diseased maize varieties (Zea mays L.), and they were identified as Talaromyces funiculosus, Penicillium oxalicum and Fusarium verticillioides, respectively, by polyphasic taxonomy based on morphological identification, ITS rDNA and bio-control gene phylogenetic analyses. Seven endophytic bacterial Bacillus velezensis strains had favourable antagonistic activity, and antagonistic testing was carried out against the three pathogenic strains, Talaromyces funiculosus 4, Penicillium oxalicum 5 and Fusarium verticillioides 6. Biological control lipopeptide antibiotic genes (bioA, bmyB, ituC, fenD, srfAA, srfAB, yngG and yndJ) were amplified using specific primers, and they were found in the seven endophytic bacterial Bacillus velezensis strains. This study provides a scientific basis for future research on the use of resistant endophytic bacterial resources to enhance crop production.

Analyzing nanoparticle-induced neurotoxicity: A bibliometric analysis.

BACKGROUND: In recent years, nanoparticles have been widely used in many fields, ranging from cosmetics, agriculture, environment, and biomedical areas. The increasing use of nanoproducts induces a potential increasing exposure to human body, and then, unknown pathological consequences could increase. METHODS: The database was searched from 2008 to 2018 by the Web of Science Core Collection. The bibliometric methods, CiteSpace and HistCite, were used for analysis and visualization of the data. RESULTS: The 2932 publications were analyzed and the annual publications grew from 78 to 512 in a decade. The United States and China mainly contribute to this research area, which accounted for 29.5% and 22.9%, respectively. PLoS One, Scientific Reports, and Nanoscale were the three journals that published the most articles. Keyword analysis indicated that the major research direction was the mechanisms of nanoneurotoxicity, which included oxidative stress, inflammation, astrocyte activation, and the fibrillation of amyloid ß protein. CONCLUSION: This bibliometric study revealed that nanoneurotoxicity was still a research hot topic and could be a promising area of research in the next few years. Nanoparticles play a role in neurodegenerative diseases by inducing reactive oxygen species production, inflammation, alterations of gene expression, and signal pathways.

Investigating the endophytic bacterial diversity and community structures in seeds of genetically related maize (Zea mays L.) genotypes.

This research aimed to investigate the composition and diversity of endophytic bacterial community in seeds of four hybrid maize and their parental lines, which was used to reveal the potential relationship and association of endophytic bacteria between maize genotypes and their genetic relevance. High-throughput sequencing (HTS) technology showed that a total of 1419 OTUs (46.6%) were parental lines unique and 1052 OTUs (34.5%) were hybrid varieties unique, with only 575 core OTUs revealed in all the samples. Most OTUs belonged to Proteobacteria. Enterobacter (23.2%), Shigella (21.2%), Pseudomonas (15.8%) and Achromobacter (10.1%) were the major genera; the bacterial community composition and diversity of endophytic bacteria were inconsistent among different seed genotypes. Based on principal component analysis (PCA), the results referred that the endophytic composition of hybrid sample showed obvious correlation with their female parental lines, and in 'Jingke968' and 'MC738' with the same female line the endophytic community was more similar than other hybrid samples. This was the first ever use of HTS technology for investigating the endophytic bacterial diversity and community structures in seeds of genetically related maize genotypes, it was shown that, there were core microbes shared among all genotypes of seed samples, and the female parental line was more significant to impact on the composition of their hybrid seeds than male parental line. This study would provide scientific clues for the future research on the vertical transmission of endophytes among maize generations.

Complete genome sequence of Bacillus ciccensis 5L6T, a new species isolated from maize (Zea mays L.) seeds with anti-fungal activity.

Maize is a crop grown worldwide. Bacillus ciccensis 5L6T was isolated from maize (Zea mays L., Jingke968) seeds and was a new species of Bacillus with potential anti-fungal activity. The complete genome of 5L6T was sequenced and assembled with a length of 5,207,802 bp and a GC content of 37.42%. The proteins responsible for anti-fungal activity and the potential beneficial interaction with maize of 5L6Twere annotated and reported here. The complete genome sequence of the new species B. ciccensis 5L6T will promote its biological application.

CaMKKß is involved in AMP-activated protein kinase activation by baicalin in LKB1 deficient cell lines.

AMP-activated protein kinase (AMPK) plays an important role in mediating energy metabolism and is controlled mainly by two upstream kinases, LKB1 or Ca(2+)/calmodulin-dependent protein kinase kinase-ß (CaMKKß). Previously, we found that baicalin, one of the major flavonoids in a traditional Chinese herb medicine, Scutellaria baicalensis, protects against the development of hepatic steatosis in rats feeding with a high-fat diet by the activation of AMPK, but, the underlying mechanism for AMPK activation is unknown. Here we show that in two LKB1-deficient cells, HeLa and A549 cells, baicalin activates AMPK by α Thr-172 phosphorylation and subsequent phosphorylation of its downstream target, acetyl CoA carboxylase, at Ser-79, to a similar degree as does in HepG2 cells (that express LKB1). Pharmacologic inhibition of CaMKKß by its selective inhibitor STO-609 markedly inhibits baicalin-induced AMPK activation in both HeLa and HepG2 cells, indicating that CaMKKß is the responsible AMPK kinase. We also show that treatment of baicalin causes a larger increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), although the maximal level of [Ca(2+)](i) is lower in HepG2 cells compared to HeLa cells. Chelation of intracellular free Ca(2+) by EDTA and EGTA, or depletion of intracellular Ca(2+) stores by the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin abrogates baicalin-induced activation of AMPK in HeLa cells. Neither cellular ATP nor the production of reactive oxygen species is altered by baicalin. Finally, in HeLa cells, baicalin treatment no longer decreases intracellular lipid accumulation caused by oleic acid after inhibition of CaMKKß by STO-609. These results demonstrate that a potential Ca(2+)/CaMKKß dependent pathway is involved in the activation of AMPK by baicalin and suggest that CaMKKß likely acts as an upstream kinase of AMPK in response to baicalin.