Intracellular Zn2+ promotes extracellular matrix remodeling in dexamethasone-treated trabecular meshwork.

Given the widespread application of glucocorticoids in ophthalmology, the associated elevation of intraocular pressure (IOP) has long been a vexing concern for clinicians, yet the underlying mechanisms remain inconclusive. Much of the discussion focuses on the extracellular matrix (ECM) of trabecular meshwork (TM). It is widely agreed that glucocorticoids impact the expression of matrix metalloproteinases (MMPs), leading to ECM deposition. Since Zn2+ is vital for MMPs, we explored its role in ECM alterations induced by dexamethasone (DEX). Our study revealed that in human TM cells treated with DEX, the level of intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. This correlated with changes in several Zrt-, Irt-related proteins (ZIPs) and metallothionein. ZIP8 knockdown impaired extracellular Zn2+ uptake, but Zn2+ chelation did not affect ZIP8 expression. Resembling DEX's effects, chelation of Zn2+ decreased MMP2 expression, increased the deposition of ECM proteins, and induced structural disarray of ECM. Conversely, supplementation of exogenous Zn2+ in DEX-treated cells ameliorated these outcomes. Notably, dietary zinc supplementation in mice significantly reduced DEX-induced IOP elevation and collagen content in TM, thereby rescuing the visual function of the mice. These findings underscore zinc's pivotal role in ECM regulation, providing a novel perspective on the pathogenesis of glaucoma.NEW & NOTEWORTHY Our study explores zinc's pivotal role in mitigating extracellular matrix dysregulation in the trabecular meshwork and glucocorticoid-induced ocular hypertension. We found that in human trabecular meshwork cells treated with dexamethasone, intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. Zinc supplementation rescues visual function by modulating extracellular matrix proteins and lowering intraocular pressure, offering a direction for further exploration in glaucoma management.

Fractionation and antioxidation activities of polysaccharides from Zanthoxylum bungeanum Maxim.

Zanthoxylum bungeanum has a lengthy history of widespread use as a food ingredient in China. However, the composition of Zanthoxylum bungeanum polysaccharide remains ambiguous, and the antioxidant effect has received limited attention. This study aimed to extract water-soluble polysaccharide from the dried pericarp of Zanthoxylum bungeanum, referred to as WZBP, which was fractionated into a neutral component (WZBP-N) and three pectic components (WZBP-A-I, WZBP-A-II, WZBP-A-III). The findings indicated that WZBP-A-III is a pectic polysaccharide "smooth region" without many side chains. All components of WZBP exhibited a notable capacity for scavenging free radicals, with WZBP-A-III demonstrating the most potent antioxidation activity, and WZBP-A-III also observed to effectively extend the lifespan of Drosophila melanogaster and enhanced the activity of antioxidant enzymes. These results provide valuable insight and direction for future research on Zanthoxylum bungeanum polysaccharide as an antioxidant agent.

Myrothins A-F from Endophytic Fungus Myrothecium sp. BS-31 Harbored in Panax notoginseng.

Endophytic fungi play important roles for host's stress tolerance including invasion by pathogenic microbes. Small molecules are common weapons in the microbe-microbe interactions. Panax notoginseng is a widely used traditional Chinese medicinal plant and harbors many endophytes, some exert functions against pathogens. Here, we report six new compounds named myrothins A-F (1-6) produced by Myrothecium sp. BS-31, an endophyte isolated from P. notoginseng, and their antifungal activities against pathogenic fungi causing host root-rot disease. Their structures were elucidated with analysis of spectroscopic data including 1D and 2D NMR, HR-ESI-MS. Myrothins B (2) and E (5) showed the weak activity against Fusarium oxysporum and Phoma herbarum, and myrothins F (6) showed weak activity against F. oxysporum.

Enzyme stoichiometry indicates the variation of microbial nutrient requirements at different soil depths in subtropical forests.

Soil extracellular enzyme activities and associated enzymatic stoichiometry are considered sensitive indicators of nutrient availability and microbial substrate limitation. However, many of previous studies have been focusing on uppermost soil layer with a single enzyme as representative of the whole nutrient acquisition, leading to critical uncertainties in understanding soil nutrient availability and its relationship with microbial activities in deeper soils. In the current study, we investigated C-, N- and P-acquiring enzyme activities across a range of soil layers (0-10, 10-20, 20-40 and 40-60 cm), and examined the microbial C, N and P limitation in natural secondary forests (NSF) and Chinese fir (Cunninghamia lanceolata) plantation forests (CPF) in subtropical China. The results showed that microbial C and P co-limitation was detected in the two typical subtropical forests at all soil depths, rather than microbial N limitation. Microbial C and P limitation fluctuated along soil depth, but higher N was demanded by microbes in soil under 20 cm in both forests. The present results highlight the asymmetrical patterns of microbial nutrient limitation along the whole soil profile, and provide essential information in understanding nutrient limitations in deeper soils. These vertical and asymmetrical nutrient limitation patterns should be incorporated into future research studies priority.

Nocardia panacis sp. nov., a novel actinomycete with antiphytopathogen activity isolated from the rhizosphere of Panax notoginseng.

Strain YIM PH21724T was isolated from the rhizosphere of Panax notoginseng. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strain exhibits close phylogenetic relatedness to Nocardia kroppenstedtii N1286T (97.70%), Nocardia farcinica NCTC 11134T (97.67%) and Nocardia puris DSM 44599T (97.40%). The menaquinones were identified as MK-9 (H4), MK-8 (H4, ω-cyclo) and MK-8 (H4), and the major fatty acids (> 10%) were identified as C16:0, C18:1 ω9c and C18:0 10-methyl. The polar lipids were found to be composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides and an unidentified lipid. The G + C content of the genomic DNA was determined to be 67.01 mol%. The phenotypic, chemotaxonomic, phylogenetic and genomic results clearly show strain YIM PH21724T should be classified in the genus Nocardia and represents a novel species, for which the name Nocardia panacis sp. nov. is proposed. The type strain is YIM PH21724T (= DSM 105904T = KCTC 49030T = CCTCC AA 2017043T).

Effects of Danshen tablets on pharmacokinetics of amlodipine in rats.

CONTEXT: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with amlodipine (ALDP) for treating coronary heart disease. OBJECTIVE: This study investigated the effects of DST on the pharmacokinetics of ALDP and the potential mechanism. MATERIALS AND METHODS: The pharmacokinetics of ALDP (1 mg/kg) in male Sprague-Dawley rats (n = 6), with or without pretreatment of DST (100 mg/kg for 7 d), were investigated using LC-MS/MS. The effects of DST on the metabolic stability of ALDP were also investigated using rat liver microsomes (RLM). RESULTS: The results indicated that Cmax (16.25 ± 2.65 vs. 22.79 ± 2.35 ng/ml), AUC(0-t) (222.87 ± 59.95 vs. 468.32 ± 69.87 n gh/ml), and t1/2 (10.60 ± 1.05 vs. 14.15 ± 1.59 h) decreased significantly when DST and ALDP were co-administered, which suggested that DST might influence the pharmacokinetic behaviour of ALDP when they are co-administered. The metabolic stability of ALDP was also decreased (23.6 ± 4.7 vs. 38.9 ± 5.2) with the pretreatment of DST. DISCUSSION AND CONCLUSIONS: This study indicated that DST could accelerate the metabolism of ALDP in RLM and change the pharmacokinetic behaviours of ALDP. Accordingly, these results showed that the herb-drug interaction between DST and ALDP might occur when they were co-administered. Therefore, the clinical dose of ALDP should be increased when DST and ALDP are co-administered.

Dauricine negatively regulates lipopolysaccharide- or cecal ligation and puncture-induced inflammatory response via NF-κB inactivation.

Acute lung injury (ALI) is a challenging clinical problem worldwide characterized by severe pulmonary inflammation. Dauricine, extracted from the root of traditional Chinese medicine Menispermum dauricum DC, is employed as anti-inflammatory herbs. In this study, we explored the inhibitory effects of dauricine on lipopolysaccharide (LPS)-induced inflammation in macrophages and LPS- or cecal ligation and puncture (CLP)-induced ALI in C57BL/6 mice. Our in vitro study identified that pretreatment of dauricine dose-dependently inhibited pro-inflammatory cytokines including nitric oxide (NO), interleukin-1ß (IL1ß), IL6, tumor necrosis factor-α (TNFα), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) in LPS-stimulated macrophages. Moreover, dauricine could suppress LPS-mediated nuclear translocation and transcriptional activity of nuclear factor-kappaB (NF-κB) by suppressing the phosphorylation of NF-κB inhibitors (IκB). In vivo studies, administration of dauricine, especially high-dose dauricine, potently improved the survival rate, reduced the production of pro-inflammatory cytokines in serum, and ameliorated ALI induced by LPS or CLP via blockage of NF-κB activation. Collectively, the present study discovers a new biological effect of dauricine in prevention of inflammation, indicating that dauricine can be served as a potential therapeutic agent to treat inflammatory diseases.

Dibasic Ammonium Phosphate Application Enhances Aromatic Compound Concentration in Bog Bilberry Syrup Wine.

A nitrogen deficiency always causes bog bilberry syrup wine to have a poor sensory feature. This study investigated the effect of nitrogen source addition on volatile compounds during bog bilberry syrup wine fermentation. The syrup was supplemented with 60, 90, 120 or 150 mg/L dibasic ammonium phosphate (DAP) before fermentation. Results showed that an increase of DAP amounts accelerated fermentation rate, increased alcohol content, and decreased sugar level. Total phenol and total flavonoid content were also enhanced with the increase of DAP amounts. A total of 91 volatile compounds were detected in the wine and their concentrations were significantly enhanced with the increase of DAP. Ethyl acetate, isoamyl acetate, phenethyl acetate, ethyl butanoate, ethyl hexanoate, ethyl octanoate, ethyl decanoate, isobutanol, isoamyl alcohol, levo-2,3-butanediol, 2-phenylethanol, meso-2,3-butanediol, isobutyric acid, hexanoic acid, and octanoic acid exhibited a significant increase of their odor activity value (OAV) with the increase of DAP amounts. Bog bilberry syrup wine possessed fruity, fatty, and caramel flavors as its major aroma, whereas a balsamic note was the least present. The increase of DAP amounts significantly improved the global aroma attributes, thereby indicating that DAP supplementation could promote wine fermentation performance and enhance the sensory quality of bog bilberry syrup wine.

Deep vein thrombosis: related to anemophilous pollen?

The etiology of deep vein thrombosis (DVT) is still not elucidated nowadays. Based on the accordance between DVT incidence and the anemophilous pollen concentration in the air, we proposed the hypothesis that allergic reaction induced by anemophilous pollen may cause "idiopathic" DVT, and proinflammatory factors may play an important role in the thrombosis process.

[Immuno-regulatory effect of 3'-meisoindigo in mice of various germlines].

OBJECTIVE: To investigate the effect of 3'-meisoindigo on the proliferation and the biological function of the splenocyte and thymocyte of mouse, which were 8 weeks old masculinity BALB/c, C57BL/6 and F1 hybridization mouse. METHODS: Cells of thymus and spleen were harvested and prepared as the unicell suspension, then treated with 5, 10, 15, 20, 25 micromol/L 3'-meisoindigo. The cell proliferation was by MTT method, concentration of IL-12 was dectected by ELISA method, the mRNA levels of Bcl-2 and CDK2 were decected by RT-PCR. The cell cycle, apoptosis ratio, death ratio and intracellular ROS concentration were detected by FCM method. The protein level of Bcl-2, CDK2 and Bax were detected by immumofluorescence method. RESULTS: 15, 20, 25 micromol/L 3'-meisoindigo can inhibit the proliferation of thymocyte and splenocyte (P < 0.05). It had dose-dependent and time-dependent manner. 3'-meisoindigo inhibit the secretion of IL-12, even at 5 micromol/L concentration. 15 micromol/L 3'-meisoindigo decrease the mRNA level of Bcl-2 and CDK2, induced apoptosis and G2 arrestting of the thymocyte and splenocyte. (P < 0.05). The intracellular ROS level increased after treated by 3'-meisoindigo at 15 micromol/L for 24 h (P < 0.05). There were no difference among three germ line mouse. CONCLUSION: Above 15 micromol/L, 3'-meisoindigo can inhibit the proliferation and externalization function of thymocyte and splenocyte from different germ line mouse, meanwhile the mRNA and protein level of Bcl-2 and CDK2 decrease, the Bax protein expressed increased, the intracellular ROS level increase too.

Protective effect of bilberry (Vaccinium myrtillus L.) extracts on cultured human corneal limbal epithelial cells (HCLEC).

The use of bilberry (Vaccinium myrtillus L.) as a food and medicine for improving human vision has a long history all over the world. However, there is lack of convincing evidence from rigorous clinical trials or scientific research. This study investigated the effects of different concentrations of bilberry extracts on the cell viability, cell cycle and the expression of hyaluronic acid and glycosaminoglycans of cultured human corneal limbal epithelial cells. The data showed that bilberry extracts had no cytotoxicity to the corneal limbal epithelial cells at a wide range of concentrations (10(-9)-10(-4) M, equalized to the content of cyanidin-3-O-glucoside). Bilberry extract (10(-6), 10(-5) and 10(-4) M) increased cell viability after 48 h incubation. The number of cells decreased in G(0)/G(1) phase and increased prominently in S and G(2)/M phases after treatment with bilberry extracts at a high concentration (10(-4) M). The expression of glycosaminoglycans increased prominently after incubation with bilberry extracts (10(-7) and 10(-4) M) for 48 h while no significant changes were observed for the expression of hyaluronic acid. The results indicated that bilberry extract may be beneficial for the physiological renewal and homeostasis of corneal epithelial cells.