This study describes a virtual screening performed for two series of selenides (28 compounds), derived from N-phenylacetamides chlorides and 7-chloro-quinoline, to determine their potential for leishmanicidal activity against Leishmania amazonensis and Leishmania donovani. Seven compounds were predicted as potential leishmanicides; therefore, they were synthesized from elemental selenium, as a precursor for the production of NaHSe, and subsequent reactions with 4,7-dichloro-quinoline and N-phenylacetamides chlorides were performed. The compounds were characterized by infrared (IR), 1H and 13C nuclear magnetic resonance (NMR), and sent for in vitro cytotoxicity tests against L. amazonensis and were found to be active and selective, and two compounds presented half-maximal inhibitory concentrations (IC50) of 5.67 and 10.81 µg mL-1. They also presented good interaction energies in the docking study, suggesting that may exert their effects by inhibiting the N-myristoyltransferase and O-acetylserine sulfhydrylase enzymes in parasites.

RESUMO Infecção com o vírus Hepatite E (HEV) é uma importante questão de saúde pública global. Infecções HEV são reconhecidas como doença zoológica. Acredita-se que suínos são o principal reservatório de HEV. Recentemente iaques, vacas, e gado amarelo foram reportados como novos reservatórios do HEV. Porém, não se sabe se outras espécies de gado e búfalo são sensíveis a infecção HEV. Para investigar a prevalência de infecção HEV em búfalos, foram realizados prova de imunoabsorção enzimática e polimerização em cadeia inversa ancorada em transcrição. Apenas um búfalo foi positivo para o anticorpo anti-HEV IgM (1/106, 0,94%), e nenhum foi positivo para o anticorpo anti-HEV IgG. Para nossa surpresa cinco (5/106, 4,72%) e três amostras de leite (3/40, 7,50%) de búfalos foram positivos para HEV RNA. Todas as estirpes de HEV isoladas de búfalos pertencem ao genótipo 4. Resultados indicam que búfalos podem ser um reservatório de HEV.

ABSTRACT Hepatitis E virus (HEV) infection is an important global public health issue. HEV infections are recognized as a zoonotic disease. Swine are believed to be the main reservoir of HEV. Recently, yaks, cows, and yellow cattle have been reported as new reservoirs of HEV. However, whether other species of cattle and buffaloes are sensitive to HEV infection is unknown. To investigate the prevalence of HEV infection in buffaloes, enzyme-linked immunosorbent assay (ELISA) and reverse transcription-nested polymerase chain reaction (RT-nPCR) were performed. Only one buffalo was positive to anti-HEV IgM antibody (1/106, 0.94%), and none were positive for anti-HEV IgG antibody. To our surprise, five serum (5/106, 4.72%) and three milk samples (3/40, 7.50%) from buffaloes were positive to HEV RNA. All strains of HEV isolated from buffaloes belong to genotype 4. Results indicate that buffaloes may be a new reservoir of HEV.

New diesters derived from phthaloylglycine (7a-7i) were synthesized and their structures characterized by infrared, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. The compounds were evaluated in an in silico study, which demonstrated positive features indicating a possible drug candidate. The diesters showed antifungal activity ranging from moderate to strong against strains of Candida. Compounds 7a, 7b, 7c, 7e and 7i had a moderate minimum inhibitory concentration (MIC) of 1024 µg mL−1 against all fungal strains, while 7h showed a very good MIC of 256 µg mL−1 against Candida albicans, Candida parapsilosis and Candida krusei and 64 µg mL−1 against Candida tropicalis. However, only 7h and 7i were able to inhibit bacterial growth of strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia coli with an MIC of 1024 µg mL−1.

ABSTRACT Chromoblastomycosis is a chronic fungal infection. Itraconazole and terbinafine are the most recommended antifungal drugs for chromoblastomycosis, while amphotericin B is not usually recommended. A patient with chromoblastomycosis in our hospital showed poor clinical responses to itraconazole and terbinafine. The fungus isolated from the lesions of this patient was identified as Fonsecaea nubica and numbered zssy0803. In vitro antifungal susceptibilities of F. nubica zssy0803 to terbinafine, amphotericin B, itraconazole, voriconazole and caspofungin were evaluated, as well as the combinations of terbinafine with the other four antifungals. The combined effect of terbinafine and amphotericin B on other 20 clinical F. nubica strains was also evaluated. The minimal inhibitory concentrations of terbinafine, amphotericin B, itraconazole, voriconazole and caspofungin on F. nubica zssy0803 were 0.25 μg/mL, 2 μg/mL, 1 μg/mL, 4 μg/mL and 8 μg/mL, respectively. The combination of terbinafine and amphotericin B showed the lowest fractional inhibitory concentration index of 0.28 to F. nubica zssy0803 in comparison with combinations of terbinafine and the other four antifungal drugs. The combination of terbinafine and amphotericin B was also synergistic for all the other 20 F. nubica strains. Then, the combination of oral terbinafine (500 mg/day) and intralesional injections of amphotericin B (1 mg/mL) was used to treat this patient. After this combined therapy for 25 weeks and terbinafine monotherapy for additional 12 weeks, the patient was cured. These findings indicate for the first time that terbinafine and amphotericin B are synergistic in killing F. nubica both in vitro and in vivo.

Myocardial ischemia is a major cause of death and remains a disease with extremely deficient clinical therapies and a major problem worldwide. Cold inducible RNA-binding protein (CIRBP) is reported to be involved in multiple pathological processes, including myocardial ischemia. However, the molecular mechanisms of myocardial ischemia remain elusive. Here, we first overexpressed CIRBP by transfection of pc-CIRBP (pcDNA3.1 containing coding sequenced for CIRBP) and silenced CIRBP by transfection of small interfering RNA targeting CIRBP (siCIRBP). pcDNA3.1 and the negative control of siCIRBP (siNC) were transfected into H9C2 cells to act as controls. We then constructed a cell model of myocardial ischemia through culturing cells in serum-free medium with hypoxia in H9C2 cells. Subsequently, AlamarBlue assay, flow cytometry and western blot analysis were used, respectively, to assess cell viability, reactive oxygen species (ROS) level and apoptosis, and expression levels of IκBα, p65 and Bcl-3. We demonstrated that CIRBP overexpression promoted cell proliferation (P<0.001), inhibited cell apoptosis (P<0.05), reduced ROS level (P<0.001), down-regulated phosphorylated levels of IκBα and p65 (P<0.01 or P<0.001), and up-regulated expression of Bcl-3 (P<0.001) in H9C2 cells with myocardial ischemia. The influence of CIRBP knockdown yielded opposite results. Our study revealed that CIRBP could protect H9C2 cells against myocardial ischemia through inhibition of NF-κB pathway.

We aimed to evaluate the effectiveness and safety of bismuth-containing quadruple therapy plus postural change after dosing for Helicobacter pylori eradication in gastrectomized patients. We compared 76 gastric stump patients with H. pylori infection (GS group) with 50 non-gastrectomized H. pylori-positive patients who met the treatment indication (controls). The GS group was divided into GS group 1 and GS group 2. All groups were administered bismuth potassium citrate (220 mg), esomeprazole (20 mg), amoxicillin (1.0 g), and furazolidone (100 mg) twice daily for 14 days. GS group 1 maintained a left lateral horizontal position for 30 min after dosing. H. pylori was detected using rapid urease testing and histologic examination of gastric mucosa before and 3 months after therapy. Mucosal histologic manifestations were evaluated using visual analog scales of the updated Sydney System. GS group 1 had a higher prevalence of eradication than the GS group 2 (intention-to-treat [ITT]: P=0.025; per-protocol [PP]: P=0.030), and the control group had a similar prevalence. GS group 2 had a lower prevalence of eradication than controls (ITT: P=0.006; PP: P=0.626). Scores for chronic inflammation and activity declined significantly (P<0.001) 3 months after treatment, whereas those for atrophy and intestinal metaplasia showed no significant change. Prevalence of adverse reactions was similar among groups during therapy (P=0.939). A bismuth-containing quadruple therapy regimen plus postural change after dosing appears to be a relatively safe, effective, economical, and practical method for H. pylori eradication in gastrectomized patients.

Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment of type 2 diabetes (T2D). Emerging evidence indicates that GLP-1 has anti-inflammatory activity. Chronic inflammation in the adipose tissue of obese individuals is a cause of insulin resistance and T2D. We hypothesized that GLP-1 analogue therapy in patients with T2D could suppress the inflammatory response of macrophages, and therefore inhibit insulin resistance. Our results showed that GLP-1 agonist (exendin-4) not only attenuated macrophage infiltration, but also inhibited the macrophage secretion of inflammatory cytokines including TNF-β, IL-6, and IL-1β. Furthermore, we observed that lipopolysaccharide (LPS)-induced macrophage conditioned media could impair insulin-stimulated glucose uptake. This effect was compensated by treatment with the conditioned media from macrophages treated with the combination of LPS and exendin-4. It was also observed that exendin-4 directly inhibited the activation of NF-κB in macrophages. In conclusion, our results indicated that GLP-1 improved inflammatory macrophage-derived insulin resistance by inhibiting NF-κB pathway and secretion of inflammatory cytokines in macrophages. Furthermore, our observations suggested that the anti-inflammatory effect of GLP-1 on macrophages can contribute to GLP-1 analogue therapy of T2D.

This study aims to explore the effect of microRNA-21 (miR-21) on the proliferation of human degenerated nucleus pulposus (NP) by targeting programmed cell death 4 (PDCD4) tumor suppressor. NP tissues were collected from 20 intervertebral disc degeneration (IDD) patients, and from 5 patients with traumatic spine fracture. MiR-21 expressions were tested. NP cells from IDD patients were collected and divided into blank control group, negative control group (transfected with miR-21 negative sequences), miR-21 inhibitor group (transfected with miR-21 inhibitors), miR-21 mimics group (transfected with miR-21 mimics) and PDCD4 siRNA group (transfected with PDCD4 siRNAs). Cell growth was estimated by Cell Counting Kit-8; PDCD4, MMP-2,MMP-9 mRNA expressions were evaluated by qRT-PCR; PDCD4, c-Jun and p-c-Jun expressions were tested using western blot. In IDD patients, the expressions of miR-21 and PDCD4 mRNA were respectively elevated and decreased (both P<0.05). The miR-21 expressions were positively correlated with Pfirrmann grades, but negatively correlated with PDCD4 mRNA (both P<0.001). In miR-21 inhibitor group, cell growth, MMP-2 and MMP-9 mRNA expressions, and p-c-Jun protein expressions were significantly lower, while PDCD4 mRNA and protein expressions were higher than the other groups (all P<0.05). These expressions in the PDCD4 siRNA and miR-21 mimics groups was inverted compared to that in the miR-21 inhibitor group (all P<0.05). MiR-21 could promote the proliferation of human degenerated NP cells by targeting PDCD4, increasing phosphorylation of c-Jun protein, and activating AP-1-dependent transcription of MMPs, indicating that miR-21 may be a crucial biomarker in the pathogenesis of IDD.

<p>Cerâmicas à base de alumina exibem combinações de propriedades as quais favorecem seu uso como biomaterial, com destaque para estruturas de prótese dentária. Entre as mais importantes propriedades para uso como biomaterial estão a dureza elevada, a estabilidade química e a biocompatibilidade. Normalmente, Al₂O₃é sinterizada no estado sólido em temperaturas superiores a 1600 ^oC; porem, devido às suas características difusionais, há grande dificuldade em eliminar completamente a porosidade. O objetivo deste trabalho foi o desenvolvimento e a caracterização de cerâmicas de Al₂O₃densificadas com uma fase liquida formada por um vidro bioativo do sistema 3CaO.P₂O₅-SiO₂-MgO. Misturas de pó com 90% em peso de Al₂O₃ e 10% em peso de vidro foram preparadas, compactadas e sinterizadas entre 1200^oC e 1450 ^oC. Comparativamente, amostras de Al₂O₃ monolíticas foram sinterizadas a 1600 ^oC/120 min. As amostras foram caracterizadas por densidade relativa, fases cristalinas, microestrutura e propriedades mecânicas. Os resultados indicaram que as amostras sinterizadas a 1450 ^oC/120 min apresentaram as melhores propriedades, com densidade relativa de 95% além de dureza de 9 GPa e tenacidade a fratura de 6,2 MPa.m^1/2. Análises de difração de raios X indicaram alumina (α-Al₂O₃), whitlockita (3CaO.P₂O₅) e diopsita [3(Ca,Mg)O.P₂O₅], como fases cristalinas após sinterização. Comparativamente, as amostras de Al₂O₃ apresentaram 92% de densidade relativa com 17,4 GPa e 3,8 MPa.m^1/2 de dureza e tenacidade a fratura, respectivamente.</p>

<p>Alumina-based ceramics, Al₂O₃, exhibit a combination of properties which favor its use as biomaterial, specifically as structural dental prosthesis. Its most important properties as biomaterial are its elevated hardness, chemical stability and biocompatibility. Usually, Al₂O₃ is processed by solid-state sintering at a temperature of about 1600 ^oC, but it is very difficult to eliminate the porosity due to its diffusional characteristics. The objective of this work was the development and characterization of sintered Al₂O₃ ceramics, densified with a transient liquid phase formed by a bioactive 3CaO.P₂O₅-SiO₂-MgO glass. Powder mixtures of 90 wt.% Al₂O₃ and 10 wt.% bioglass were milled, compacted and sintered at 1200 ^oC to 1450 ^oC. Comparatively, monolithic Al₂O₃ samples were sintered at 1600 ^oC/120 min. The sintered specimens were characterized by relative density, crystalline phases, microstructure and mechanical properties. The results indicate that the specimen sintered at 1450 ^oC/120 min present the best properties. Under this sintering condition, a relative density of 95% was reached, besides hardness higher than 9 GPa and fracture toughness of 6.2 MPa.m^1/2. XRD analysis indicate alumina (αAl₂O₃), whitlockite (3CaO.P₂O₅) and diopsite [3(Ca,Mg)O.P₂O₅], as crystalline phases. Comparatively, monolithic sintered Al₂O₃ samples presented 92% of relative density with 17.4 GPa and 3.8 MPa.m^1/2 of hardness and fracture toughness respectively.</p>

The effects of ultra-high pressure (UHP) treatment on the chemical properties, colour and sensory quality of young red wine were studied. UHP did not significantly affect the alcohol content, and the methanol content was higher than that of the control, with the latter first increasing and then decreasing with the increase in the pressure or period of treatment. The glycerol content was also markedly changed by UHP, although without a regular pattern. The pH value was not markedly changed by the treatments, and the contents of total acids and volatile acids were scarcely affected. The fructose and glucose contents were clearly changed according to the different treatment conditions. The tartaric acid, citric acid and lactic acid levels showed evident changes, whereas the malic acid level was not changed by UHP treatment. The trend of these changes was similar to what occurs during natural ageing. As the pressure of the treatment was increased to 200 MPa, the chroma value increased, followed by a decline upon higher pressure treatments. The hue of the wine was significantly changed by treatment at different pressures, reaching the highest value after treatment at 400 MPa and then decreasing with increasing pressure. The chroma and hue values of the wine were changed significantly according to the duration of the UHP. After UHP, the appearance, aroma and taste of the wine was improved, with the score for appearance obviously increased. When the wine was treated at 500 MPa for 30 min, its sensory quality received the highest score.

This study proposes a block-edge-based perceptual zero-tree coding (PZTC) method, which is implemented with efficient optimization on the embedded platform. PZTC combines two novel compression concepts for coding efficiency and quality: block-edge detection (BED) and the low-complexity and low-memory entropy coder (LLEC). The proposed PZTC was implemented as a fixed-point version and optimized on the DSP-based platform based on both the presented platform-independent and platform-dependent optimization technologies. For platform-dependent optimization, this study examines the fixed-point PZTC and analyzes the complexity to optimize PZTC toward achieving an optimal coding efficiency. Furthermore, hardware-based platform-dependent optimizations are presented to reduce the memory size. The performance, such as compression quality and efficiency, is validated by experimental results.

Recent evidence shows that moxifloxacin could exert an antimicrobial effect against Helicobacter pylori in both in vitroand in vivo models. To systematically evaluate whether moxifloxacin-containing triple therapy could improve eradication rates and reduce side effects in first-line or second-line anti-H. pyloritreatment, eligible articles were identified by searches of electronic databases. We included all randomized trials comparing moxifloxacin-based triple therapy with standard triple or quadruple therapy during H. pylori eradication treatment. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis/sensitivity analysis was also performed. We identified seven randomized trials (n=1263). Pooled H. pylori eradication rates were 79.03% (95%CI: 75.73-82.07) and 68.33% (95%CI: 64.44-72.04) for patients with moxifloxacin-based triple therapy or with standard triple or quadruple therapy, respectively (intention-to-treat analysis). The odds ratio (OR) was 1.82 (95%CI: 1.17-2.81), the occurrence of total side effects was 15.23% (95%CI: 12.58-18.20) and 27.17% (95%CI: 23.64-30.92) for groups with or without moxifloxacin, and the summary OR was 0.45 (95%CI: 0.26-0.77). In subgroup analyses, we noted that the second-line eradication rate in the moxifloxacin group was significantly higher than that in the quadruple therapy group (73.33 vs 60.17%, OR: 1.78, 95%CI: 1.16-2.73, P<0.001). However, there was no difference in first-line eradication treatment. Findings from this meta-analysis suggest that moxifloxacin-based triple therapy is more effective and better tolerated than standard triple or quadruple therapy. Therefore, a moxifloxacin-based triple regimen should be used in the second-line treatment of H. pylori infection.

Distribution behavior of ketoprofen enantiomers was examined in a two-phase system containing R, R-di-tartarates or S, S-di-tartarates. The influences of different alkyl chain of R, R-di-tartarates or S, S-di-tartarates, concentrations of R, R-di-tartarate, organic solvent and content of methanol on partition coefficient and separation factor were investigated, respectively. The experimental results show that R, R-di-tartarates studied all form more stable diastereomeric complexes with ketoprofen S-enantiomer than with R-enantiomer. The partition coefficients and enantioselectivity generally increase with the addition of length of alkyl chain of alcohol. The concentration of chiral selector and methanol also have bigger influences on enantioselectivity.