Optically Anisotropic Mixed-Metal Fluoroiodate Ba2[GaF5(IO3F)] with a Wide Optical Transparent Window and a Moderate Birefringence.

An optically anisotropic alkali-earth-metal gallium fluoroiodate, Ba2[GaF5(IO3F)] (1), was ingeniously obtained by integrating fluoride and fluoroiodate functional units under moderate hydrothermal conditions. It features a three-dimensional (3D) structure constructed by the highly polarizable fluoroiodate unit [IO3F] and the fluoride groups [GaOF5] and [BaO3Fx] (x = 6, 7). The compound is stable at temperatures up to 500 °C. With the synergistic interaction between [IO3F] and the fluoride groups, the mixed-metal fluoroiodate induces a short ultraviolet cutoff edge at about 230 nm, a medium measured birefringence of 0.068 @ 550 nm, and a wide optical transparent window (0.34-11.9 µm), indicating that 1 has potential applications as a birefringent material from near-UV to mid-infrared. Theoretical calculations prove that the optical characteristics of the compound are mainly attributed to [IO3F] and the fluoride functional groups. This work demonstrates that the presence of various specific functional groups in compounds will help to develop promising inorganic functional materials possessing good optical performance.

Ketogenic diet in women with polycystic ovary syndrome and liver dysfunction who are obese: A randomized, open-label, parallel-group, controlled pilot trial.

AIM: To evaluate the effect of a ketogenic diet (KD) in women with polycystic ovary syndrome (PCOS) and liver dysfunction who were obese. METHODS: Women with PCOS and liver dysfunction who were obese were enrolled in this prospective, open-label, parallel-group, controlled pilot trial, and randomly received KD (KD group) or conventional pharmacological treatment (Essentiale plus Yasmin, control group) in a 1:1 ratio for 12 weeks. The primary endpoint was the liver function markers. Secondary endpoints included the menstrual cycle, anthropometric characteristics, body composition, hormonal levels, and metabolic biomarkers. RESULTS: Of the 20 eligible participants enrolled, 18 participants completed the study. The KD group reported a significant reduction in anthropometric characteristics and body composition from baseline to week 12 (all p < 0.05). In addition, there were significant reductions in menstrual cycle, plasma estradiol, and progesterone levels in two groups (all p < 0.05), but no significant between-group difference was observed. KD significantly reduced the liver function markers compared with control group (p < 0.05). The signs of fatty liver disappeared in six out of seven fatty liver participants in KD group after 12 weeks of intervention, while only one of 10 fatty liver participants in control group disappeared. CONCLUSIONS: In addition to improving the menstrual cycle, KD had the additional benefits of reducing blood glucose and body weight, improving liver function, and treating fatty liver compared to traditional pharmacological treatment in women with PCOS and liver dysfunction who were obese.

Anti-Programmed Cell Death (PD)-1 Immunotherapy for Malignant Tumor: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated anti-programmed cell death (PD)-1 immunotherapy (nivolumab or pembrolizumab) for overall efficacy, safety, and effective dose relative to standard chemotherapy or other conventional drugs in the treatment of malignant tumors. We searched the following databases, PubMed, Medline, Embase, Cochrane, Wangfang Data, Weipu, and China National Knowledge Infrastructure, and the reference lists of the selected articles for randomized controlled trials (RCTs) of anti-PD-1 therapies in humans. The outcome measures were overall survival, treatment response, and adverse events. Only four randomized controlled trials met our inclusion criteria. Three of these evaluated responses to nivolumab, whereas one tested pembrolizumab. The result of our analysis suggested that nivolumab may improve the overall response rate in treating melanoma relative to chemotherapy and has few associated adverse events. Similarly, in metastatic melanoma patients, nivolumab had a significant advantage over dacarbazine in terms of 1-year survival, progression-free survival, and objective response rate. Regarding dose levels of nivolumab for patients with metastatic renal cell carcinoma, the outcomes in response to 2 and 10 mg/kg were similar, but both had significant advantages over 0.3 mg/kg. In addition, pembrolizumab showed similar outcomes in response to 2- and 10-mg/kg treatment. Anti-PD-1 immunotherapy appears to be safe and effective for patients with melanoma or metastatic renal cell carcinoma. Our meta-analysis is limited, but additional clinical trials are warranted to verify this preliminary evidence of positive outcomes and before anti-PD-1 therapy can be recommended for routine clinical use.

Pharmacological characterization and therapeutic potential for the treatment of opioid abuse with ATPM-ET, an N-ethyl substituted aminothiazolomorphinan with κ agonist and µ agonist/antagonist activity.

We previously reported that the κ agonists with mixed µ activity could attenuate heroin self-administration with less potential to develop tolerance. The present study further investigated the effects of (-)-3-N-Ethylamino-thiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride (ATPM-ET), a κ agonist and µ agonist/antagonist, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP), heroin self-administration and heroin-primed reinstatement of drug-seeking behavior. We found that ATPM-ET produced a longer duration of potent antinociceptive effects with less side effect of sedation. More importantly, ATPM-ET attenuated the acquisition of morphine-induced CPP, without affecting the reinstatement of morphine CPP. Furthermore, ATPM-ET significantly inhibited heroin self-administration and the reinstatement of heroin primed drug-seeking behavior. Taken together, ATPM-ET, a novel κ agonist and µ agonist/antagonist may have utility for the treatment of drug dependence.

Effects of ATPM-ET, a novel κ agonist with partial µ activity, on physical dependence and behavior sensitization in mice.

AIM: to investigate the effects of ATPM-ET [(-)-3-N-Ethylaminothiazolo [5,4-b]-N-cyclopropylmethylmorphinan hydrochloride] on physical dependence and behavioral sensitization to morphine in mice. METHODS: the pharmacological profile of ATPM-ET was characterized using competitive binding and GTPγS binding assays. We then examined the antinociceptive effects of ATPM-ET in the hot plate test. Morphine dependence assay and behavioral sensitization assay were used to determine the effect of ATPM-ET on physical dependence and behavior sensitization to morphine in mice. RESULTS: the binding assay indicated that ATPM-ET ATPM-ET exhibited a high affinity to both κ- and µ-opioid receptors with K(i) values of 0.15 nmol/L and 4.7 nmol/L, respectively, indicating it was a full κ-opioid receptor agonist and a partial µ-opioid receptor agonist. In the hot plate test, ATPM-ET produced a dose-dependent antinociceptive effect, with an ED(50) value of 2.68 (2.34-3.07) mg/kg. Administration of ATPM-ET (1 and 2 mg/kg, sc) prior to naloxone (3.0 mg/kg, sc) injection significantly inhibited withdrawal jumping of mice. In addition, ATPM-ET (1 and 2 mg/kg, sc) also showed a trend toward decreasing morphine withdrawal-induced weight loss. ATPM-ET (1.5 and 3 mg/kg, sc) 15 min before the morphine challenge significantly inhibited the morphine-induced behavior sensitization (P<0.05). CONCLUSION: ATPM-ET may have potential as a therapeutic agent for the treatment of drug abuse.

Pharmacological characterization of ATPM [(-)-3-aminothiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride], a novel mixed kappa-agonist and mu-agonist/-antagonist that attenuates morphine antinociceptive tolerance and heroin self-administration behavior.

ATPM [(-)-3-amino-thiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride] was found to have mixed kappa- and mu-opioid activity and identified to act as a full kappa-agonist and a partial mu-agonist by in vitro binding assays. The present study was undertaken to characterize its in vivo effects on morphine antinociceptive tolerance in mice and heroin self-administration in rats. ATPM was demonstrated to yield more potent antinociceptive effects than (-)U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide). It was further found that the antinociceptive effects of ATPM were mediated by kappa- and mu-, but not delta-opioid, receptors. In addition to its agonist profile on the mu-receptor, ATPM also acted as a mu-antagonist, as measured by its inhibition of morphine-induced antinociception. It is more important that ATPM had a greater ratio of the ED(50) value of sedation to that of antinociception than (-)U50,488 (11.8 versus 3.7), indicative of a less sedative effect than (-)U50,488H. In addition, ATPM showed less potential to develop antinociceptive tolerance relative to (-)U50,488H and morphine. Moreover, it dose-dependently inhibited morphine-induced antinociceptive tolerance. Furthermore, it was found that chronic treatment of rats for 8 consecutive days with ATPM (0.5 mg/kg s.c.) produced sustained decreases in heroin self-administration. (-)U50,488H (2 mg/kg s.c.) also produced similar inhibitory effect. Taken together, our findings demonstrated that ATPM, a novel mixed kappa-agonist and mu-agonist/-antagonist, could inhibit morphine-induced antinociceptive tolerance, with less potential to develop tolerance and reduce heroin self-administration with less sedative effect. kappa-Agonists with some mu-activity appear to offer some advantages over selective kappa-agonists for the treatment of heroin abuse.

[Efficacy of HSV-tk/GCV system on human laryngeal squamous cell cancer in vitro].

OBJECTIVE: Efficacy of HSV-tk/GCV system antitumor effects was assessed on human laryngeal cancer cell line Hep-2 in vitro. To assess the HSV-tk/CGV system whether has an antitumour effect on human laryngeal squamous cell cancer Hep-2 in vitro. The mechanisms of cytotoxity were also assessed. METHODS: Hep-2 cells were transfected with HSV-tk gene by lipofection. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the HSV-tk gene expression. MTT was utilized to test for the cytotoxicity of this system. The cell-circle arrest and apoptosis were analyzed by flowcytometry assay. RESULTS: HSV-tk gene transfected cells demonstrated obvious cytoreductivity followed by ganciclovir (GCV) administration and this cytoreductivity showed partial GCV dose-independent. HSV-tk gene transfected cells demonstrated obvious s-phase arrest, no apoptosis and necrosis occurred. CONCLUSIONS: The HSV-tk/GCV system can inhabit the growth of Hep-2 cells effectively. S-phase arrest perhaps is the main reason that leads to the cell inhibition in our study. HSV-tk/GCV system has potential antitumor effects for the future clinical practice.

[Effect of icariin on hypoxia induced vascular endothelial cells injury].

OBJECTIVE: To study the effect of icariin on vascular endothelial cells (VECs) injury induced by hypoxia. METHODS: The hypoxia-ischemia model was established. The effect of icariin on injury of VECs activity induced by hypoxia was determined by MTT assay. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and lactate dehydrogenase (LDH) activity in cell homogenate were measured with corresponding kit. Effect of icariin on cells apoptosis induced by hypoxia was determined by Hoechst 33342 fluorescent staining, cell ultrastructure observation under transmission electron microscopy and analysis on gene fragmentation by flow cytometry and DNA gel electrophoresis. RESULTS: ICA could inhibit the hypoxia induced VECs reduction, suppress LDH activity, reduce the MDA production, and enhance SOD activity under hypoxia. Hypoxia could induce VECs apoptosis, revealed chromation condensed in nuclei with the fragments arranged along the nuclear membrane. DNA gel electrophoresis showed typical ladder strands of DNA. Cells displayed a typical sub-diploid peak in flow cytometry. ICA could significantly inhibit the hypoxia induced apoptosis of VECs. CONCLUSION: ICA has the protective effect on hypoxia injured VECs, which may be related to its effect of anti-apoptosis, anti-lipid peroxidation and SOD activity enhancing.