Cationic regulation of specificity and activity of defective MCo2O4 nanozyme (M=Fe, Co, Ni, Cu) for colorimetric detection of caffeic acid.

Spinel oxide has great promise in constructing highly active nanozymes due to its tunable crystal structure. However, it still faces the problems of poor specificity and insufficient enzyme activity, which limits its application in the field of analysis. Herein, a series of transition metal spinel oxides were synthesized by cation regulation strategy, and their enzymatic activity and catalytic mechanism were analyzed. Interestingly, FeCo2O4, Co3O4 and NiCo2O4 had oxidase-like activity and peroxidase-like activity, while CuCo2O4 had specific and high oxidase-like activity. Their oxidase-like activities follow the order of FeCo2O4 < Co3O4 < NiCo2O4 < CuCo2O4, which is consistent with their cation radius. The smaller the cation radius of tetrahedral site, the more beneficial it is to increase the oxidase-like activity. The high oxidase-like activity of CuCo2O4 may be attributed to the production of 1O2, •O2- and •OH. EPR results showed the presence of abundant oxygen vacancies in CuCo2O4. Upon the introduction of EDTA, TMB color reaction fades because of oxygen vacancies elimination by EDTA, indicating that oxygen vacancies played an important role in the reaction. Based on the inhibition effect of caffeic acid on the high oxidase-like activity of CuCo2O4, a simple and sensitive caffeic acid colorimetric sensing platform was developed. The linear range for the detection of caffeic acid is 0.02-15 µM, with a detection limit as low as 13 nM. The constructed sensor enables the detection of caffeic acid in caffeic acid tablets and actual water samples, providing a new strategy for the detection of caffeic acid and drug quality control.

Sex-related differences in safety profiles, pharmacokinetics and tissue distribution of sinomenine hydrochloride in rats.

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum (Thunb.) Rehd. et Wils which exhibits significant analgesic, anti-inflammatory, and immunosuppressive effects. Sinomenine hydrochloride (SH) preparations, classified as natural disease-modifying antirheumatic drugs, are currently available for the treatment of rheumatoid arthritis and other rheumatic diseases. Our toxicity evaluation demonstrated that the median lethal dose of SH in female Sprague-Dawley (SD) rats was over 11 times greater than that in male SD rats, revealing striking sex-linked differences in the safety profile of SH. The present study was designed to investigate differences in the pharmacokinetics (PKs) and tissue distribution of SH between male and female SD rats after a single oral dose of 25 mg/kg. PK and tissue distribution studies were performed using a validated UPLC-MS/MS method. The results showed that SH-treated SD female rats displayed markedly greater drug exposure, and SH exhibited a longer half-life and slower clearance rate than comparable studies in male rats. Moreover, the tissue distribution study confirmed that the sinomenine concentration in female rats was considerably greater in the internal organs than in male rats. Our study demonstrates, for the first time, significant sex-related differences in the safety profile and PKs of SH, which may be associated with a distinct sex-dependent metabolic mechanism of sinomenine.

Microsomal prostaglandin E2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance.

Inflammation is closely linked to the abnormal phospholipid metabolism chain of cyclooxygenase-2/microsomal prostaglandin E2 synthase-1/prostaglandin E2 (COX-2/mPGES-1/PGE2). In clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) as upstream COX-2 enzyme activity inhibitors are widely used to block COX-2 cascade to relieve inflammatory response. However, NSAIDs could also cause cardiovascular and gastrointestinal side effects due to its inhibition on other prostaglandins generation. To avoid this, targeting downstream mPGES-1 instead of upstream COX is preferable to selectively block overexpressed PGE2 in inflammatory diseases. Some mPGES-1 inhibitor candidates including synthetic compounds, natural products and existing anti-inflammatory drugs have been proved to be effective in in vitro experiments. After 20 years of in-depth research on mPGES-1 and its inhibitors, ISC 27864 have completed phase II clinical trial. In this review, we intend to summarize mPGES-1 inhibitors focused on their inhibitory specificity with perspectives for future drug development.

Curcumin inhibits calcification of human aortic valve interstitial cells by interfering NF-κB, AKT, and ERK pathways.

The osteogenic differentiation of human aortic valve interstitial cells (hVICs) is the key cellular mechanism of calcified aortic valve disease (CAVD). This study aimed to explore how curcumin (CCM) inhibits the osteogenic differentiation of hVICs and elucidate the molecular mechanisms involved. In this study, CCM inhibited the osteogenic differentiation of hVICs under osteogenic medium (OM) conditions by reversing the OM-induced increase in calcified nodule formation and osteogenesis-specific markers (ALP and Runx2). RNA sequencing identified 475 common differentially expressed genes with Venn diagrams of the different groups. Kyoto Encyclopedia of Genes and Genomes enrichment revealed that the CCM inhibition of hVIC osteogenic differentiation was enriched in the NF-κB, PI3K-AKT, TNF, Jak-STAT, and MAPK signaling pathways. In addition, CCM suppressed the phosphorylation of ERK, IκBα, AKT, and interfered with the translocation of P65 into the cell nucleus in hVICs under OM culture conditions. In conclusion, CCM inhibited the osteogenic differentiation of hVICs via interfering with the activation of NF-κB/AKT/ERK signaling pathways. Our findings provide novel insights into a critical role for CCM in CAVD progression and shed new light on CCM-directed therapeutics for CAVD.

Nobiletin exhibits potent inhibition on tumor necrosis factor alpha-induced calcification of human aortic valve interstitial cells via targeting ABCG2 and AKR1B1.

Inflammation is considered to be one of the initial critical factors in the occurrence of calcific heart valve disease. This study was to prove Nobiletin (NBT) inhibits inflammation-caused calcification of human valve interstitial cells (hVICs) and to elucidate the involved molecular mechanisms. Tumor necrosis factor-alpha (TNF-α)-induced hVICs were treated with or without NBT. Cell growth and calcification of hVICs were assessed. RNA sequencing was utilized to investigate the gene expression changes. Molecular target prediction and docking assay were further performed. NBT interfered with hVIC growth under TNF-α condition in a dose-dependent manner also presented a gradual decrease of positive Alizarin Red S staining, down-regulation of BMP2, and RUNX2 gene expression. Based on the global gene expression cluster, control and TNF-α plus NBT group showed a high similarity versus TNF-α only group. After Venn interaction of differential expression genes (DEGs), 2,236 common DEGs were identified to display different biological functions and signaling pathways. ABCG2 and AKR1B1 were further selected as prediction targets of NBT involved in RELA, TNF, BMP2, RUNX2, etc. interactions in mediating hVIC calcification. The results show that NBT is a natural product to prevent the occurrence of heart valve calcification.

Unconventional application of gold nanoclusters/Zn-MOF composite for fluorescence turn-on sensitive detection of zinc ion.

Contrary to organic solvent-induced aggregation of Au nanoclusters (AuNCs), herein, we reported aggregation induced emission enhancement (AIEE) of AuNCs in an aqueous media through confinement of AuNCs by in situ formed Zn-MOF for detecting Zn2+. Glutathione capped AuNCs (GSH-AuNCs) was synthesized through reduction of Au3+ by glutathione. Zn2+ could significantly enhance the fluorescence of GSH-AuNCs upon addition of 2-methylimidazole, which was attributed to the formation of Zn-MOF. XRD and TEM were used to characterize the in situ formed Zn-MOF. Zn2+ induced aggregation was demonstrated by dynamic light scattering and TEM. The quantum yields (QYs) of AuNCs after aggregation induced by in situ formed Zn-MOF attained to 36.6%, which was nearly 9 times that of the sole AuNCs. On this basis, a fluorogenic sensor was reported for Zn2+ detection with a linear range from 12.3 nM to 24.6 µM and a detection limit of 6 nM (S/N = 3). The proposed sensor was successfully applied to assay the content of zinc in human serum, milk, water, and zinc sulfate syrup oral solution samples. The novel strategy proposed in this work may open a new window of interest in an unconventional application of gold nanoclusters/MOF nanoscale platform for metal ion detection and nutritional assessment of food.

2-thio-6-azauridine inhibits Vpu mediated BST-2 degradation.

BACKGROUD: BST-2 is an interferon-induced host restriction factor that inhibits the release of diverse mammalian enveloped viruses from infected cells by physically trapping the newly formed virions onto the host cell surface. Human Immunodeficiency Virus-1 (HIV-1) encodes an accessory protein Vpu that antagonizes BST-2 by down-regulating BST-2 from the cell surface. RESULTS: Using a cell-based ELISA screening system, we have discovered a lead compound, 2-thio-6-azauridine, that restores cell surface BST-2 level in the presence of Vpu. This compound has no effect on the expression of BST-2 and Vpu, but inhibits Vpu-mediated BST-2 down-regulation and exerts no effect on Vpu-induced down-regulation of CD4 or KSHV K5 protein induced BST-2 down-regulation. 2-thio-6-azauridine suppresses HIV-1 production in a BST-2-dependent manner. Further results indicate that 2-thio-6-azauridine does not interrupt the interaction of BST-2 with Vpu and ß-TrCP2, but decreases BST-2 ubiquitination. CONCLUSION: Our study demonstrates the feasibility of using small molecules to target Vpu function and sensitize wild type HIV-1 to BST-2-mediated host restriction.

[Effect of the subsurface constructed wetland evolution into free surface flow constructed wetland on the removal of organic matter, nitrogen, and phosphor in wastewater].

Many previous studies demonstrated that the performance of the subsurface constructed wetlands (SSCW) for wastewater treatment was superior to that of the free flow surface constructed wetlands (FFSCW). However, our results indicated that the performance of FFSCW derived from the evolution of SSCW due to clogging for COD, TOC, total nitrogen (TN), and total phosphor (TP) removal was higher than those of SSCW with the same substrate and plant. The laboratory culture experiments were adopted to evaluate the effect of the constructed wetland evolution on the organic matter mineralization, nitrification/denitrification as well as removal of nitrogen and phosphor. It was shown that, after evolution of SSCW into FFSCW, the mineralization rate for organic matter (as TOC) was 1.82 mg x h(-1), and it was 1.49 mg x h(-1) for SSCW. The removal efficiency for NO3(-) was 96.8%, and it was 58.1% for SSCW. The abiotic denitrification removal efficiency was 40%, and it was 28.2% for SSCW. In addition, the maximum equilibrium adsorption capacity of the substrate after evolution for phosphor (as P) was 160 mg x kg(-1), and it was 140 mg x kg(-1) for SSCW substrate. The organic coverage of the substrate was found to be beneficial to phosphor removal. The nitrification ability decreased after evolution. These results suggest the important effect of constructed wetland evolution on its performance.

[Experimental study on effect of Suifukang in promoting repairing and regeneration of nerve fibers in spinal cord].

OBJECTIVE: To study the change in expressions of nerve growth related protein (GAP-43) and neurofilament (NF) after experimental injury of spinal cord, and the regulatory effect of Chinese medicine Suifukang (SFK) on them. METHODS: Forty-eight from the 54 selected adult SD rats were established into spinal cord injury model by making hemitransection at the T12 level, and randomly divided into two groups, the SFK group feed with SKF contained liquor and the model group feeding with equal volume of saline. The another 6 rats were untreated and taken as the normal group. All rats were sacrificed in batches at different time points of day 3, 7, 15 and 30 after modeling. The spinal cord was obtained for determining the optic density (OD) of positive expression of GAP-43 and NF with immunohistochemical stain by microscopic and semi-quantitative image analysis. RESULTS: (1) OD of NF in the model group was obviously decreased on day 7, showing significant difference to that in the normal group and that in the SFK group (P < 0.05), and it maintained at low level after then, while the OD of NF in the SFK group was obviously higher than that in the model group (P < 0.05), it arrived the peak on day 15 and then dropped near the level in the normal group on day 30; (2) OD and of GAP-43 in the model group obviously decreased on day 3 (P < 0.05), showing significant difference to that in the normal group (P < 0.05), then it returned to approach to the level in the normal group on day 7. It was higher in the SFK group than in the model group on day 3, and maintained the high level to day 7, at that time, it was still higher than that in the model group and also higher than that in the normal group (P < 0.05). CONCLUSION: SFK can promote the repair and regeneration of injured nerve fibers in spinal cord by up-regulating the expression of GAP-43 and NF.

[Synthesis and anti-inflammatory analgesic activities of sinomenine derivatives].

AIM: To provide basic data for the synthesis of new sinomenine derivatives. METHODS: The C ring in sinomenine was modified. RESULTS: Seven compounds were prepared and screened for anti-inflammatory and analgesic activities. Compounds 2 and 5 showed better activities. CONCLUSION: Modification of the C ring in sinomenine should be worthy to be studied further.

Initial contaminant removal performance factors in horizontal flow reed beds used for treating urban wastewater.

This study evaluates the effect of hydraulic loading rate (HLR), aspect ratio, granular medium size and water depth on the removal of selected contaminants during the start up of horizontal subsurface flow reed beds (HFRBs). Experiments were carried out in a pilot-scale HFRB system comprising four pairs of lined beds of almost equal surface area (54-56 m(2) each bed), with the following aspect ratios: 1:1, 1.5:1, 2:1 and 2.5:1. The size of the granular medium of each pair varied from coarse granitic gravel ( D(60) = 10mm, C(u) = 1.6) to small granitic gravel (D(60) = 3.5 mm, C(u) = 1.7). The beds of the pair with longest aspect ratio were made shallower (0.27 m) than the rest (0.5m) The system was sampled weekly from May 2001 to January 2002. The results indicate that HLR and water depth are determining factors in the performance of the HFRBs. Beds with a water depth of 0.27 m removed more COD (70-80%), BOD(5) (70-85%), ammonia (40-50%) and dissolved reactive phosphorus (DRP) (10-22%) than beds with a depth of 0.5m (60-65% for COD, 50-60% for BOD(5), 25-30% for ammonia, and 2-10% for DRP). The higher efficiency observed shallower beds was related to their less reducing conditions (average redox potential (E) ranging from -351 to -338 mV) than beds with a depth of 0.5m (-390 to -358 mV). The difference in E status between two bed types seems to lead to differences in the biochemical processes. In fact, denitrification was estimated to be a significant reaction in shallower beds.