Activation of peroxydisulfate by zero valent iron-carbon composites prepared by carbothermal reduction: Enhanced non-radical and radical synergies.

Since its application in environmental remediation, nano zero-valent iron (nZVI) has gained wide attention for its environmental friendliness, strong reducing ability, and wide range of raw materials. However, its high preparation cost and difficulty in preservation remain the bottlenecks for their application. Carbothermal reduction is a promising method for the industrial preparation of nZVI. Micronized zero-valent iron/carbon materials (Fe0/CB) were produced in one step by co-pyrolysis of carbon and iron. The performance of the Fe0/CB is comparable to that of nZVI. In addition, Fe0/CB overcomed the disadvantages of agglomeration and oxidative deactivation of nZVI. Experiments on the Fenton-like reaction of its activated PDS showed that metronidazole (MNZ) was efficiently removed through the synergistic action of radicals and non-radicals, which were mainly superoxide radicals (·O2-), monoclinic oxygen (1O2), and high-valent iron (FeIVO). Moreover, the degradation process showed better generalization, making it suitable for a wide range of applications in the degradation of antibiotics.

Evolutionary trajectory of TRPM2 channel activation by adenosine diphosphate ribose and calcium.

Ion channel activation upon ligand gating triggers a myriad of biological events and, therefore, evolution of ligand gating mechanism is of fundamental importance. TRPM2, a typical ancient ion channel, is activated by adenosine diphosphate ribose (ADPR) and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates, but the evolutionary process is still unknown. Molecular evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that, the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation, while the N-terminal MHR domain maintains a conserved ligand binding site. Calcium gating pattern has also evolved, from one Ca2+-binding site as in sea anemones to three sites as in human. Importantly, we identified a new group represented by olTRPM2, which has a novel gating mode and fills the missing link of the channel gating evolution. We conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and coordinated. Such findings benefit the evolutionary investigations of other channels and proteins.

Single VHH-directed BCMA CAR-NK cells for multiple myeloma.

Natural killer (NK) cells are promising alternatives for the production of "off-the-shelf" CAR products, posing a lower risk of cytokine release syndrome (CRS) than CAR-T cells. We synthesized four single VHH-directed anti-BCMA CARs, incorporating various intracellular regions (2B4 versus CD28) and hinge domains (CD28 versus IgG1) and ectopically producing IL-15. NK cells derived from peripheral blood (PB) were expanded ex vivo by K562-mbIL21 feeder cells. Stable CAR transduction was obtained through lentiviral transduction with the BaEV-Rless pseudotyped lentiviral vector. BCMA-CD28-IL15 CAR-NK cells with ectopic expression of IL-15 exhibited superior cytotoxicity were compared to BCMA-CD28 CAR-NK cells lacking IL-15 and BCMA-hIgG1-IL15 CAR-NK cells with an IgG1 hinge domain. We further assessed the cytotoxic capabilities of BCMA-2B4-IL15 CAR-NK cells with 2B4 intracellular domain. The BCMA-CD28-IL15 CAR-NK cells revealed stronger cytotoxicity and higher cytokine secretion against BCMA+ tumor cells than BCMA-2B4-IL15 CAR-NK cells in vitro. In the MM.1S-Luc mouse model, BCMA-CD28-IL15 CAR-NK inhibited the growth of tumor cells and prolonged mouse survival. These results show that the single VHH-directed BCMA CAR-NK cells exhibited remarkable specific killing ability, making them a potential candidate for immunotherapy in multiple myeloma treatment.

Comparison and subsets analysis of peripheral CD4+T cells in patients with psoriasis and psoriatic arthritis.

Psoriatic arthritis (PsA) is a disease that transformed from psoriasis (PsO), and its underlying mechanisms are still not fully understood. Overactivation of the immune system is a key factor driving inflammatory diseases. Our goal is to define the unbalanced subsets of peripheral blood CD4 +T cells between PsO and PsA patients. Blood samples from 43 patients (23 PsA and 20 PsO) and 36 healthy donors (HD) were studied. Peripheral blood mononuclear cells (PBMC) were separated from blood and underwent fluorescent staining to assess CD4+T cell subsets by flow cytometry. We found that frequencies of various CD4+T cells including Th1, Th2, Th17, and Tfh were higher in the patients with PsO or PsA than those of healthy donors, indicating the general expansion of CD4+T cells in inflammatory conditions. More importantly, we observed the significant imbalance of Th1/Th2 between patients with PsO and PsA. Pearson correlation analysis showed that Th1/Th2 ratio was positively correlated with disease activity in psoriatic arthritis (DAPSA), Tfh/Tfr ratio was positively correlated with DAPSA score and visual analogue scale (VAS) score in PsA patients. Together, our results highlight the CD4+T cell changes in the transition from PsO to PsA, may contribute to early assessment and intervention.

Association between miR-365 polymorphism and ischemic stroke in a Chinese population.

Background: Ischemic stroke (IS) represents a major cause of morbidity and mortality across the globe. The aberrant expression of miR-365 has been found to be implicated in a wide array of human diseases, including atherosclerosis and cancer. Studies on single-nucleotide polymorphisms (SNPs) in miRNA genes can help gain insight into the susceptibility to the condition. This study aimed to examine the relationship between miR-365 SNPs and the risk of IS. Methods: The study recruited 215 IS patients and 220 controls. The SNPscans genotyping was employed to genotype three polymorphic loci (rs121224, rs30230, and rs178553) of miR-365. The relative expression of miR-365 in peripheral blood mononuclear cells of the patients and controls was determined by using real-time quantitative PCR. Results: The miR-365 rs30230 polymorphism exhibited a significant association with the risk of developing IS (TC vs. CC: adjusted OR = 0.55, 95% CI: 0.33-0.92, P = 0.022; TT vs. CC: adjusted OR = 0.34, 95% CI: 0.14-0.85, P = 0.021; TC +TT vs. CC: adjusted OR = 0.51, 95% CI: 0.31-0.83, P = 0.007; T vs. C: adjusted OR = 0.57, 95% CI: 0.39-0.83, P = 0.004). Haplotype analysis revealed that the C-T-G haplotype was associated with a decreased risk of IS (OR = 0.68, 95% CI: 0.46-1.00, P = 0.047). Furthermore, miR-365 expression was significantly higher in IS patients than in controls (P < 0.001). Interestingly, patients with rs30230 TC or TT genotypes had lower miR-365 levels compared to their counterparts with CC genotypes (P < 0.001). Conclusions: The miR-365 rs30230 polymorphism might bear an association with IS susceptibility in the Chinese population, and the rs30230 TC/TT genotype might be a protective factor against IS.

CX-4945 inhibits fibroblast-like synoviocytes functions through the CK2-p53 axis to reduce rheumatoid arthritis disease severity.

Fibroblast-like synoviocytes (FLS) mediate many pathological processes in rheumatoid arthritis (RA), including pannus formation, bone erosion, and inflammation. RA FLS have unique aggressive phenotypes and exhibit several tumor cell-like characteristics, including hyperproliferation, excessive migration and invasion. Casein kinase 2 (CK2) is reportedly overexpressed in numerous tumor types, and targeted inhibition of CK2 has therapeutic benefits for tumors. However, the expression level of CK2 and its functions in RA FLS remain unclear. Herein, we aimed to elucidate whether CK2 is responsible for the aggressive phenotypes of RA FLS and whether targeted therapy can alleviate the severity of RA. We found that CK2 subunits were elevated in RA FLS compared with osteoarthritis FLS, and the activity of CK2 also markedly increased in RA FLS. Targeted inhibition of CK2 using CX-4945 suppressed RA FLS proliferation through cell cycle arrest. Cell migration and invasion were also inhibited by CX-4945 treatment. Moreover, CX-4945 reduced Interleukin-6 (IL-6), CC motif chemokine ligand 2 (CCL2) and Matrix metalloproteinase-3 (MMP-3) secretion in RA FLS. Further proteomic investigation revealed that p53 signaling pathway significantly changes after CX-4945 treatment in RA FLS. The siRNA-mediated p53 knockdown partly abolished the anti-proliferation and reduced IL-6, MMP-3 secretion effects of CX-4945. Furthermore, CX-4945 administration alleviates arthritis severity in CIA mice. Collectively, our results demonstrated the abnormal elevation of CK2 and its positive association with abnormal phenotypes in RA FLS. Our novel findings suggest the possible therapeutic potential of CX-4945 for RA.

CD151 and prostate cancer progression: A review of current literature.

Prostate cancer morbidity and mortality are increasing globally and in China, and the rate of metastasis is also rising, limiting the therapeutic effect and clinical prognosis of prostate cancer. CD151 is considered to be the first promoter of tumor metastasis in the tetraspanin superfamily. Previous research has linked CD151 to the progression of a number of malignancies, including prostate cancer. However, a recent study found that CD151 can inhibit the progression of prostate cancer. As a result, this paper examines existing research on CD151 and prostate cancer progression in order to clarify the relationship and provide a possible reference for future studies.

Antimicrobial effect of methylene blue in microbiologic culture to diagnose periprosthetic joint infection: an in vitro study.

BACKGROUND: As one of the major diagnostic criteria in Musculoskeletal Infection Society, the microbiological diagnosis of periprosthetic joint infection (PJI) performed by analyzing periprosthetic tissue culture is recommended. The goal of this study was to determine if methylene blue (MB) has antibacterial effects that might interfere with microbial culture in vitro. METHODS: Eight isolates of reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus pyogenes, and Candida albicans were incubated appropriately on blood agar, China blue agar, or Sabouraud's agar plates at 35 â„ƒ. (Streptococci were cultured in a CO2-rich atmosphere.) Each bacterial suspension was formed by 50-fold dilution before the test MB was added. For each strain, bacterial suspension was divided into 3 groups (5 samples each) exposed either MB 0.1%, MB 0.05% or sterile non-bacteriostatic 0.45% saline. The antimicrobial property of MB was determined by measuring the bacterial density on agar plates incubated for 24 h and comparing it with controls unexposed to MB. RESULTS: Exposure to MB 0.1% or MB 0.05% negatively affected microbial viability in vitro. Of the diluted form of MB exposure, reference strains of S. hominis and A. baumannii resulted in fewer colony-forming units compared with the sterile saline control. MB concentration was significantly negatively correlated with CFU counts of S. hominis and A. baumannii strains. The antibacterial property of MB 0.1% or MB 0.05% appears to affect the ability to culture the organism in in vitro assays. CONCLUSION: MB 0.1% or MB 0.05% has strong antimicrobial activities against some commonly encountered bacterial strains in PJI in vitro. To further evaluate its potential antibacterial usefulness in clinical applications, the next studies are needed to assess the ability of MB to affect the ability to culture the pathogens in vivo, especially in periprosthetic tissue.

Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-ß1 signaling in vitro and in vivo.

Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo, and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 µg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro. Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-ß1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC50 = 25.29 and 42.94 µg/ml than albendazole with IC50 = 3.71 and 21.22 µg/ml in vitro, and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-ß1 signaling.

Potential Biochemical Pesticide-Synthesis of Neofuranocoumarin and Inhibition the Proliferation of Spodoptera frugiperda Cells through Activating the Mitochondrial Pathway.

Furanocoumarins, the secondary metabolites of plants, are considered to be natural insecticides and fungicides because they prevent the invasion of plant pathogenic microorganisms and the predation of herbivorous insects. In this study, novel 2-arylfuranocoumarin derivatives were designed to synthesize by condensation, esterification, bromination, and Wittig reaction. The results showed an excellent photosensitive activity of 2-thiophenylfuranocoumarin (I34). Cell Counting Kit-8 detected that I34 could inhibit the proliferation of Spodoptera frugiperda (Sf9) cells in a time- and concentration-dependent manner under ultraviolet A (UV-A) light for 3 min. The inverted microscope revealed that cells treated with I34 swelled, the membrane was ruptured, and apoptotic bodies appeared. The flow cytometry detected that I34 could induce apoptosis of Sf9 cells, increase the level of intracellular reactive oxygen species (ROS), decrease the mitochondrial membrane potential, and block cell cycle arrest in the G2/M phase. Transmission electron microscopy detected cell mitochondrial cristae damage, matrix degradation, and mitochondrial vacuolation. Further enzyme activity detection revealed that the enzyme activities of apoptosis-related proteins caspase-3 and caspase-9 increased significantly (p < 0.05). Finally, Western blotting analysis detected that the phosphorylation level of Akt and Bad and the expression of the apoptosis inhibitor protein Bcl-XL were inhibited, cleaved-PARP and P53 were increased, and cytochrome C was released from the mitochondria into the cytoplasm. Moreover, under UV-A irradiation, I34 promoted the increase in ROS in Sf9 cells, activated the mitochondrial apoptotic signal transduction pathway, and finally, inhibited cell proliferation. Thus, novel furanocoumarins exhibit a potential application prospect as a biochemical pesticide.

Intratumoral IL-28B Gene Delivery Elicits Antitumor Effects by Remodeling of the Tumor Microenvironment in H22-Bearing Mice.

IL-28B, belonging to type III interferons (IFN-λs), exhibits a potent antitumor activity with reduced regulated T cells (Tregs) population, yet the effect of IL-28B on the tumor microenvironment (TME) and if IL-28B can downregulate Tregs directly in vitro are still unknown. In this study, we investigated the effects of IL-28B on Tregs in the spleen and TME in H22 tumor-bearing mice and verified the downregulation of IL-28B on Tregs in vitro. We found that rAd-mIL-28B significantly inhibited tumor growth and reduced the frequency of splenic CD4+Foxp3+ T cells. The levels of CXCL13, ICAM-1, MCP-5, and IL-7 in the serum, and the levels of IL-15 and sFasL in the tumor tissue decreased significantly after rAd-mIL-28B treatment relative to rAd-EGFP. Furthermore, the percentage of CD8+ cells in the TME was significantly increased in the rAd-mIL-28B group compared with the untreated group. In vitro, splenocytes were stimulated with anti-CD3/CD28 and IL-2 in the presence of TGF-ß with or without IL-28B for three days and followed by flow cytometric, RT-PCR, and IL-10 production analysis. The results showed that IL-28B significantly reduced the proportion of induced Foxp3+ cells. It demonstrated that IL-28B may be used as a promising immunotherapy strategy against cancer.

Potential Chemoprevention of Paeoniflorin in Colitis-Associated Colorectal Cancer by Network Pharmacology, Molecular Docking, and In Vivo Experiment.

Chronic inflammation plays a positive role in the development and progression of colitis-associated colorectal cancer (CAC). Medicinal plants and their extracts with anti-inflammatory and immunoregulatory properties may be an effective treatment and prevention strategy for CAC. This research aimed to explore the potential chemoprevention of paeoniflorin (PF) for CAC by network pharmacology, molecular docking technology, and in vivo experiments. The results showed that interleukin-6 (IL-6) is a key target of PF against CAC. In the CAC mouse model, PF increased the survival rate of mice and decreased the number and size of colon tumors. Moreover, reduced histological score of colitis and expression of Ki-67 and PCNA were observed in PF-treated mice. In addition, the chemoprevention mechanisms of PF in CAC may be associated with suppression of the IL-6/STAT3 signaling pathway and the IL-17 level. This research provides experimental evidence of potential chemoprevention strategies for CAC treatment.

Antitumor Effect of Pseudolaric Acid B Involving Regulation of Notch1/Akt Signaling Response in Human Hepatoma Cell In Vitro.

Background: Liver cancer, particularly hepatocellular carcinoma (HCC), is the fourth leading cause of cancer-related death worldwide. Sorafenib is a crucial drug for the treatment of advanced HCC, but it is difficult to meet the challenge of increasing clinical demands due to its severe side effects and drug resistance. Hence, development of novel antitumor drugs is urged. Previous studies showed that pseudolaric acid B (PAB) could reduce the expression of protein kinase B (PKB/Akt), a downstream effector of Notch signaling, facilitating cell apoptosis in HCC. The disruption of Notch signaling was verified to exacerbate malignant progression and drug resistance, however, the antitumor effect of PAB on Notch signaling in HCC remains unclear. Thus, this study aims to investigate the anti-HCC effect of PAB in association with the regulation of Notch1/Akt signaling. Methods: CCK-8 assay and transwell assay were used to examine the cell proliferation and invasion in Huh7 cells after treatment with PAB and a Notch inhibitor DAPT. Moreover, the cell cycle of Huh7 cells after treatment with PAB was analyzed using flow cytometry. Finally, the changes of Notch1, Jagged1, Hes1, and Akt expression at the protein and mRNA level in Notch1/Akt signaling in Huh7 cells after treatment with PAB and DAPT were analyzed using immunofluorescence assay and real-time qPCR. Results: The proliferation rate of Huh7 cells exposed to PAB of 0.5, 1, 2, 4, 8, 10, 20, 40, 80, 100, and 200 µmol/L revealed a time-and dose-dependent decrease in vitro, showing cell cycle arrest at G2/M phase (P < 0.05). Furthermore, compared with the untreated group, at the concentration of 40 µmol/L, the proliferation rate and invasion rate of Huh7 cells in PAB, DAPT, and PAB-DAPT combination (PAB + DAPT) group were significantly decreased (P < 0.05), but the PAB + DAPT showed no synergistic antiproliferation and anti-invasion effect in comparison with PAB treatment alone (P > 0.05). In addition, compared with the untreated group, PAB and DAPT alone significantly downregulated the expression of Notch1, Jagged1, Hes1, Akt mRNA, or/and protein in Huh7 cells (P < 0.05), but there was no significant difference in synergistic downregulated effect between the PAB + DAPT group and the PAB group (P > 0.05). Conclusion: PAB can suppress proliferation and invasion of HCC cells through downregulating the expression of Notch1/Akt signaling protein and mRNA, and may be a potential novel antitumor drug candidate for the clinical treatment of HCC in the future.

Structural basis of ALMT1-mediated aluminum resistance in Arabidopsis.

The plant aluminum (Al)-activated malate transporter ALMT1 mediates the efflux of malate to chelate the Al in acidic soils and underlies the plant Al resistance. Here we present cryo-electron microscopy (cryo-EM) structures of Arabidopsis thaliana ALMT1 (AtALMT1) in the apo, malate-bound, and Al-bound states at neutral and/or acidic pH at up to 3.0 Å resolution. The AtALMT1 dimer assembles an anion channel and each subunit contains six transmembrane helices (TMs) and six cytosolic α-helices. Two pairs of Arg residues are located in the center of the channel pore and contribute to malate recognition. Al binds at the extracellular side of AtALMT1 and induces conformational changes of the TM1-2 loop and the TM5-6 loop, resulting in the opening of the extracellular gate. These structures, along with electrophysiological measurements, molecular dynamic simulations, and mutagenesis study in Arabidopsis, elucidate the structural basis for Al-activated malate transport by ALMT1.

Synergism therapeutic and immunoregulatory effects of Albendazole + rAd-mIL-28B against Echinococcosis in experiment-infected mice with protoscoleces.

The metacestode stage of Echinococcus granulosus can cause cystic echinococcosis (CE), which still widely occurs around the world. Since the early 1970s, benzimidazoles have been shown to inhibit the growth of cysts and used to treat CE. However, benzimidazoles are still ineffective in 20%-40% of cases. In order to explore the new agents against CE, we have investigated the therapeutic effect of the recombinant adenoviral vector expressing mouse IL-28B (rAd-mIL-28B) on protoscoleces-infected mice. In our study, we successfully established the model mice which infected with protoscoleces intraperitoneally. At 18 weeks post-infection, the mice received rAd-mIL-28B (1×107 PFU) weekly by intramuscular injection for 6 weeks. Compared with the untreated control (13.1 ± 2.2 g), there was a significant reduction in cysts wet weight in rAd-mIL-28B group (8.3 ± 3.5 g) (P < 0.05), especially in Albendazole (ABZ) + rAd-mIL-28B group (5.8 ± 1.4 g) (P < 0.01). We also observed the severe damage of the germinal layer and the laminated layer of cysts after treatment. rAd-mIL-28B group showed a prominent increase in the level of Th1 type cytokines (such as IFN-γ, IL-2 and TNF-α). Meanwhile, the frequency of Foxp3+ T cells was decreased in the rAd-mIL-28B group (4.83 ± 0.81%) and ABZ + rAd-mIL-28B group (4.60 ± 0.51%), comparing with the untreated group (8.13 ± 2.60%) (P < 0.05). In addition, compared with the untreated control (122.14 ± 81.09 pg/ml), the level of IFN-γ significantly increased in peritoneal fluid in the rAd-mIL-28B group (628.87 ± 467.16 pg/ml) (P < 0.05) and ABZ + rAd-mIL-28B group (999.76 ± 587.60 pg/ml) (P < 0.001). Taken together, it suggested that ABZ + IL-28B may be a potential therapeutic agent against CE.

60Co-γ Radiation Alters Developmental Stages of Zeugodacus cucurbitae (Diptera: Tephritidae) Through Apoptosis Pathways Gene Expression.

Radiation is considered as a promising insect pest control strategy for minimizing postharvest yield losses. Among various techniques, irradiation is a method of choice as it induces lethal biochemical or molecular changes that cause a downstream cascade of abrupt physiological abnormalities at the cellular level. In this study, we evaluated the effect of 60Co-γ radiation on various developmental stages of Zeugodacus cucurbitae Coquillett and subsequent carry-over effects on the progeny. For this purpose, we treated eggs with 30- and 50-Gy radiation doses of 60Co-γ. We found that radiation significantly affected cellular antioxidants, insect morphology, and gene expression profiles. Our results indicate that in response to various doses of irradiation reactive oxygen species, catalase, peroxidase, and superoxide dismutase activities were increased along with a significant increase in the malondialdehyde (MDA) content. We observed higher mortality rates during the pupal stage of the insects that hatched from irradiated eggs (50 Gy). Furthermore, the life span of the adults was reduced in response to 50 Gy radiation. The negative effects carried over to the next generation were marked by significantly lower fecundity in the F1 generation of the irradiation groups as compared to control. The radiation induced morphological abnormalities at the pupal, as well as the adult, stages. Furthermore, variations in the gene expression following irradiation are discussed. Taken together, our results signify the utility of 60Co-γ radiation for fruit fly postharvest management.

Comparison of Antioxidant and Antibacterial Activities of Camellia Oil From Hainan With Camellia Oil From Guangxi, Olive Oil, and Peanut Oil.

Background/Aim: Camellia oil from Hainan (SY) is a unique vegetable oil in Hainan, China, due to the geographical environment and oil extraction only through simple physical treatments. To compare SY with camellia oil from Guangxi (SC), olive oil (GL), and peanut oil (HS), this study analyzed the antioxidant and antibacterial activity of four vegetable oils. Methods: Using Gallic acid, BHT as the control, Saccharomyces cerevisiae as the model organism, the antioxidant activities of vegetable oils were measured in vitro and in vivo, and the antibacterial activity was measured with the minimum inhibitory concentration (MIC) method. Results: The major contents of SY, SC, and HS were oleic Acid; the major content of GL was squalene. The highest total flavonoids content of SY was 39.50 ± 0.41 mg RE/g DW; and the highest total phenolic content of SC was 47.05 ± 0.72 mg GAE/g DW. SY exhibited the strongest scavenging activity of hydroxyl radical (HO·) and superoxide anions ( O 2 - · ), the IC50 value were 2.06 mg/mL, 0.62 mg/mL, respectively; and SC showed the strongest DPPH· and ABTS· scavenging activity and the reducing abilities. SY showed excellent effect on survival rate, protection rate, flavonoids uptake of S. cerevisiae cells, decreased MDA content and ROS level, inhibited CAT, POD, and GR enzyme activity. The absorption of SC total phenols was the highest by cells. The activity showed GL had a broad-spectrum antibacterial activity. Conclusion: Thus, SY shows potential antioxidant activity and provides an important reference value for people to choose edible vegetable oils.

Anti-echinococcal effect of verapamil involving the regulation of the calcium/calmodulin-dependent protein kinase II response in vitro and in a murine infection model.

BACKGROUND: Echinococcosis, which is caused by the larvae of cestodes of the genus Echinococcus, is a parasitic zoonosis that poses a serious threat to the health of humans and animals globally. Albendazole is the drug of choice for the treatment of echinococcosis, but it is difficult to meet clinical goals with this chemotherapy due to its low cure rate and associated side effects after its long-term use. Hence, novel anti-parasitic targets and effective treatment alternatives are urgently needed. A previous study showed that verapamil (Vepm) can suppress the growth of Echinococcus granulosus larvae; however, the mechanism of this effect remains unclear. The aim of the present study was to gain insight into the anti-echinococcal effect of Vepm on Echinococcus with a particular focus on the regulatory effect of Vepm on calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-CaMKII) in infected mice. METHODS: The anti-echinococcal effects of Vepm on Echinococcus granulosus protoscoleces (PSC) in vitro and Echinococcus multilocularis metacestodes in infected mice were assessed. The morphological alterations in Echinococcus spp. induced by Vepm were observed by scanning electron microscopy (SEM), and the changes in calcium content in both the parasite and mouse serum and liver were measured by SEM-energy dispersive spectrometry, inductively coupled plasma mass spectrometry and alizarin red staining. Additionally, the changes in the protein and mRNA levels of CaM and CaMKII in infected mice, and in the mRNA levels of CaMKII in E. granulosus PSC, were evaluated after treatment with Vepm by immunohistochemistry and/or real-time quantitative polymerase chain reaction. RESULTS: In vitro, E. granulosus PSC could be killed by Vepm at a concentration of 0.5 µg/ml or higher within 8 days. Under these conditions, the ultrastructure of PSC was damaged, and this damage was accompanied by obvious calcium loss and downregulation of CaMKII mRNA expression. In vivo, the weight and the calcium content of E. multilocularis metacestodes from mice were reduced after treatment with 40 mg/kg Vepm, and an elevation of the calcium content in the sera and livers of infected mice was observed. In addition, downregulation of CaM and CaMKII protein and mRNA expression in the livers of mice infected with E. multilocularis metacestodes was found after treatment with Vepm. CONCLUSIONS: Vepm exerted a parasiticidal effect against Echinococcus both in vitro and in vivo through downregulating the expression of Ca2+/CaM-CaMKII, which was over-activated by parasitic infection. The results suggest that Ca2+/CaM-CaMKII may be a novel drug target, and that Vepm is a potential anti-echinococcal drug for the future control of echinococcosis.

Synthesis and Photoactivated Toxicity of 2-Thiophenylfuranocoumarin Induce Midgut Damage and Apoptosis in Aedes aegypti Larvae.

Furanocoumarins are photoactive compounds derived from secondary plant metabolites. They possess many bioactivities, including antioxidative, anticancer, insecticidal, and bactericidal activities. Here, we designed a new scheme for synthesizing 2-arylfuranocoumarin derivatives by condensation, esterification, bromination, and Wittig reaction. We found that 2-thiophenylfuranocoumarin (Iy) had excellent photosensitive activity. Three Iy concentrations (LC25, LC50, and LC75) were used to treat the fourth instar larvae of Aedes aegypti (A. aegypti). The photoactivated toxicity, sublethal dose, mitochondrial dysfunction, oxidative stress level, intestinal barrier dysfunction, and apoptosis were studied. The results showed that Iy induced reactive oxygen species (ROS) production in midgut cells under ultraviolet light. Ultrastructural analysis demonstrated that mitochondria were damaged, and the activities of related enzymes were inhibited. Ultimately, Iy exposure led to excessive ROS production followed by the inhibition of antioxidant enzymes, including SOD, CAT, GPx, and GR, which diminished ROS elimination and escalated oxidative stress in midgut cells, aggravating the degree of oxidative damage in these cells. Histopathological changes were observed in the midgut, which led to intestinal barrier dysfunction. When the elimination of ROS was blocked and it accumulated in cells, apoptosis-related genes, including AeDronc, AeCaspase7, and AeCaspase8, were induced and activated. In addition, Iy affected the growth and development of A. aegypti at sublethal concentrations, and there was an obvious post-lethal effect. Thus, we found that Iy caused midgut damage and apoptosis in A. aegypti larvae under ultraviolet light, which preliminarily revealed the mode of action of Iy in A. aegypti.

Investigation and control of an outbreak of urinary tract infections caused by Burkholderia cepacian-contaminated anesthetic gel.

BACKGROUND: This report describes an outbreak of 71 patients developed B. cepacia urinary tract infection (UTI) by contaminated single-use anesthetic gel. METHODS: Epidemiological investigation of patients with B. cepacia-positive urine or blood samples between March 19, 2018 and Novemeber 15, 2018 was conducted to identify the source of infection. Microbiological samples from hospital surfaces, endoscopes, disposable items, and the hands of staff were tested for B. cepacia contamination. Pulsed-field gel electrophoresis (PFGE) was used to compare homology in B. cepacia isolates. RESULTS: During the outbreak, nosocomial B. cepacia UTI was confirmed in 71 patients. Epidemiological investigation showed that 66 patients underwent invasive urological diagnosis and treatment, while the remaining five patients underwent bedside indwelling catheterization, with all patients exposed to single-use anesthetic gel. All batches of anesthetic gel were recalled and the outbreak abated. Overall, 155 samples were collected from environmental surfaces and disposable items, and B. cepacia contamination was confirmed in samples from one used cystoscope and three anesthetic gels from the same batch. PFGE showed homology between 17 out of 20 B. cepacia isolates from patients and three isolates from the contaminated anesthetic gel. All patients achieved cure. CONCLUSION: Contaminated single-use anesthetic gel was confirmed as the source of the B. cepacia outbreak, with infection occurring during invasive urological diagnostic and treatments. Thus, investigations of nosocomial outbreaks of B. cepacia infection should consider contamination of diagnostic and treatment items used in infected patients.