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Curcumin analogue AI-44 relieves MSU-induced gouty rheumatoid arthritis in rats by means of inhibiting cathepsin B-mediated NLRP3 inflammasome activation.
The experiments using our proposed system were conducted at a large dairy farm in Oita Prefecture in Japan. Experimental results show that the proposed method has promise in practical applications. In particular, we found that the high frequency of posture changes has played a central role in accurately predicting the time of calving.Two families of glasses in the Li2O-Al2O3-B2O3-TiO2-P2O5 system were prepared via two different synthesis routes melt-quenching and ball-milling. Subsequently, they were submitted to crystallization and yielded the Li1.3Al0.3Ti1.7(PO4)3 (LATP)-based glass-ceramics. Glasses and corresponding glass-ceramics were studied by complementary X-ray diffraction (XRD) and 27Al, 31P, 7Li, 11B magic-angle spinning nuclear magnetic resonance (MAS NMR) methods in order to compare their structure and phase composition and elucidate the impact of boron additive on their glass-forming properties and crystallization process. XRD studies show that the addition of B2O3 improves the glass-forming properties of glasses prepared by either method and inhibits the precipitation of unwanted phases during heat treatment. MAS NMR studies allowed us to distinguish two LATP phases of slightly different chemical composition suggesting that LATP grains might not be homogeneous. In conclusion, the crystallization of boron-incorporated LATP glasses can is an effective way of obtaining LATP-based solid state electrolytes for the next generation of lithium-ion batteries provided the proper heat-treatment conditions are chosen.Biocides are commonly used as spray- or trigger-type formulations, thus dermal and respiratory exposure to biocide aerosol is unavoidable. However, little is known about the impact of aerosolization on the local toxicity of biocides on the skin or the airway. We compared the local toxicity of biocides after direct or aerosol exposure on reconstructed human skin epidermis and upper airway models. Three biocides, 1,2-benzisothiazol-3(2H)-one (BIT), 2-phenoxyethanol (PE), and 2-phenylphenol (OPP), most widely used in the market were selected. When the biocide was treated in aerosols, toxicity to the skin epidermis and upper airway tissue became significantly attenuated compared with the direct application as determined by the higher tissue viabilities. This was further confirmed in histological examination, wherein the tissue damages were less pronounced. LC-MS/MS and GC/MS analysis revealed that concentrations of biocides decreased during aerosolization. Importantly, the toxicity of biocides treated in 3 μm (median mass aerodynamic diameter (MMAD)) aerosols was stronger than that of 5 μm aerosol, suggesting that the aerosol particle size may affect biocide toxicity. Collectively, we demonstrated that aerosolization could affect the local toxicity of biocides on the skin epidermis and the upper airway.Coumarins possesses immeasurable antitumor potential with minimum side effects depending on the substitutions on the basic nucleus, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, a series of coumarin sulfonamides and amides derivatives were designed and synthetized. The majority of these derivatives showed good cytotoxic activity against MDA-MB-231 and KB cell lines, among which compound 9c was the most potent against MDA-MB-231 cells, with IC50 value of 9.33 μM, comparable to 5-fluorouracil. Further investigation revealed that compound 9c had versatile properties against tumors, including inhibition of cell migration and invasion as well as inducing apoptosis. Reactive oxygen species (ROS) assay and western blotting analysis suggested that compound 9c promoted cancer cell apoptosis by increasing ROS levels and upregulating the expression of caspase-3 in MDA-MB-231 cells. These results indicated that compound 9c could be promising lead compound for further antitumor drug research.Endometrial cancer is the most common gynecological cancer in developed countries. The disease is diagnosed with increasing frequency in younger women, commonly also in their reproductive age. The standard treatment of endometrial cancer is surgical in the form of hysterectomy and bilateral salpingo-oophorectomy, and this precludes future fertility in younger women. The current challenge is to identify the group of women with endometrial cancer and low-risk features that would benefit from more conservative treatment options. More focus in management needs to be aimed towards the preservation of quality of life, without jeopardizing oncological outcomes. In this review, we analyze the current approaches to identification of women for conservative management and evaluate the success of different medical options for treatment and surgical techniques that are fertility sparing. We also elaborate on the future perspectives, focusing on the incorporation of molecular characterization of endometrial cancer to fertility preservation algorithms. Future studies should focus specifically on identifying reliable clinical and molecular predictive markers in this group of young women. With improved knowledge and better risk assessment, the precision medicine is the path towards improved understanding of the disease and possibly widening the group of women that could benefit from treatment methods preserving their fertility.Knowledge of the diverse DNA binding specificities of transcription factors is important for understanding their specific regulatory functions in animal development and evolution. We have examined the genome-wide binding properties of the mouse HOXB1 protein in embryonic stem cells differentiated into neural fates. Unexpectedly, only a small number of HOXB1 bound regions (7%) correlate with binding of the known HOX cofactors PBX and MEIS. In contrast, 22% of the HOXB1 binding peaks display co-occupancy with the transcriptional repressor REST. Analyses revealed that co-binding of HOXB1 with PBX correlates with active histone marks and high levels of expression, while co-occupancy with REST correlates with repressive histone marks and repression of the target genes. Analysis of HOXB1 bound regions uncovered enrichment of a novel 15 base pair HOXB1 binding motif HB1RE (HOXB1 response element). In vitro template binding assays showed that HOXB1, PBX1, and MEIS can bind to this motif. In vivo, this motif is sufficient for direct expression of a reporter gene and over-expression of HOXB1 selectively represses this activity. Our analyses suggest that HOXB1 has evolved an association with REST in gene regulation and the novel HB1RE motif contributes to HOXB1 function in part through a repressive role in gene expression.A flexible ankle joint is suggested to be a contributing factor for vertical squat jump (SQJ) performance. The purpose of the study was to investigate the effect of the active (ACT) and passive (PAS) ankle joint range of motion (ROM) on SQJ performed by adolescent female volleyball players. ACT and PAS ankle ROM at knee extension angles of 90, 140, and 180 degrees (180 degrees full extension) were measured with a video analysis method for 35 female post-pubertal volleyball players (16.3 ± 1.1 yrs, 1.80 ± 0.04 m, 68.8 ± 6.8 kg). Additionally, the players fulfilling previously recommended criteria were assigned to the flexible (n = 10) and inflexible (n = 8) groups and executed SQJ with and without an arm swing on a force-plate. Results of the 2 × 2 × 3 MANOVA revealed a significant (p less then 0.05) flexibility type and knee angle effect, as ankle ROM was larger in PAS compared to ACT and as the knee joint progressed from 90 to 180 degrees extension. The 2 × 2 ANOVA revealed a significant (p less then 0.05) group effect, as flexible players jumped higher in the arm swing SQJ, along with a significant arm swing effect on key SQJ kinetic parameters. In conclusion, a more flexible ankle joint result in improved SQJ performance. Therefore, ankle flexibility training should be implemented in youth volleyball players.Melanoma is one of the most aggressive forms of skin cancer, with few possibilities for therapeutic approaches, due to its multi-drug resistance and, consequently, low survival rate for patients. Conventional therapies for treatment melanoma include radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which have various side effects. For this reason, in recent years, pharmaceutical and biomedical research has focused on new sito-specific alternative therapeutic strategies. In this regard, nanotechnology offers numerous benefits which could improve the life expectancy of melanoma patients with very low adverse effects. This review aims to examine the latest advances in nanotechnology as an innovative strategy for treating melanoma. In particular, the use of different types of nanoparticles, such as vesicles, polymers, metal-based, carbon nanotubes, dendrimers, solid lipid, microneedles, and their combination with immunotherapies and vaccines will be discussed.Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine's effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine's effects on energy balance.Dhaiphul (Woodfordia fruticosa) is a frequently demanded plant in South-East Asian regions for its diverse medicinal values. This study was proposed to examine antioxidant, antidiabetic, and antidepressant potentials of methanol extract of W. fruticosa leaves (MEWF) and its derived n-hexane (NHFMEWF) and ethyl acetate (EAFMEWF) fractions through in vitro, in vivo, and computational models. Among test samples, MEWF and EAFMEWF contained the highest phenolic content and showed maximal antioxidant activity in DPPH radical scavenging and ferric reducing power assays. In comparison, NHFMEWF possessed maximum flavonoid content and a significantly potent α-amylase inhibitory profile comparable with positive control acarbose. In animal models of depression (forced swimming and tail suspension test), EAFMEWF and NHFMEWF demonstrated a dose-dependent antidepressant-like effect; explicitly, the depressive-like behaviors significantly declined in EAFMEWF-treated dosing groups in contrast to the control group. In the computational analysis, previously isolated flavonoid compounds from Dhaiphul leaves manifested potent binding affinity against several key therapeutic target proteins of diabetes and depressive disorders including α-amylase, serotonin transporter, dopamine transporter, and neuronal nitric oxide synthase with varying pharmacokinetics and toxicity profiles.
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