Stevensonirwin9043

Therapist-guided ICBT was more effective than self-directed ICBT. ICBT lasting for ≤12weeks could relieve anxiety and depressive symptoms of cancer patients. S-Adenosyl-L-homocysteine datasheet ICBT with number of modules ≥5 had a small effect on anxiety and depression relief while ICBT with number of modules <5 was found to be ineffective.

ICBT lasting for ≤12weeks, especially therapist-directed, helps relieve the anxiety and depressive symptoms of cancer patients. The ideal number of modules for ICBT and its long-term efficacy need to be validated by more studies of higher-quality.

ICBT lasting for ≤12 weeks, especially therapist-directed, helps relieve the anxiety and depressive symptoms of cancer patients. The ideal number of modules for ICBT and its long-term efficacy need to be validated by more studies of higher-quality.

Targets of intervention in cognitive behavioral stress management (CBSM), such as benefit finding (BF) and perceived stress management skills (PSMS), may counteract stress-related changes that impact the immune system. This study tested whether BF, PSMS, and optimism influence the effects of CBSM on immune status in men with prostate cancer.

Men with prostate cancer were randomized to receive CBSM or a psychoeducation (PE) control comparison (NCT05486754). Life Orientation Test-Revised assessed baseline optimism. The Benefit Finding Scale and Measure of Current Status measured BF and PSMS after CBSM. T-cells and T-helper cells captured immune status change at baseline and 6-months post-CBSM. MPlus and SPSS (PROCESS) tested condition effects and moderated mediation, controlling for covariates.

256 primarily middle-aged, White Non-Hispanic or Hispanic men enrolled. PSMS mediated CBSM effects on T-cell and T-helper cell percentage, such that T-cell and T-helper cell percentages were reduced in men in CBSM versus PE via PSMS. Optimism moderated this mediation with the mediating effect of PSMS only observed among men with average optimism versus those with low or high optimism.

Baseline psychological characteristics, as well as limited specificity of immune measurement, could explain the conditional effects in this sample.

NCT05486754.

NCT05486754.

The present study aimed to systematically analyze the risk factors for RBD.

A systematic review and meta-analysis of case-control studies, cohort studies, and cross-sectional studies derived from the articles published in eight electronic databases before December 1, 2021. The primary outcome was the odds ratio (OR) and 95% confidence interval (95% CI), and heterogeneity was quantified using I

. Subgroup analyses and meta-regression were used to explore sources of heterogeneity. Egger's test and sensitivity analysis were performed. The PROSPERO ID number of the present study is CRD42021293942.

We identified 26 studies (44,230 subjects) among 2022 citations, and 13 factors were considered. Male sex (OR=1.36, 95% CI=1.13-1.64), smoking (OR=1.37, 95% CI 1.26-1.50), depression (OR=2.06, 95% CI=1.66-2.56), antidepressant use (OR=2.36, 95% CI=1.98-2.82), duration of neuropsychiatric disorders(OR=1.43, 95% CI=1.13-1.73), levodopa equivalent daily dose (LEDD, OR=60.15, 95% CI=23.95-96.35) and observable motor dysfunction (OR=2.43, 95% CI=0.65-4.22) were associated with a higher risk of RBD. Tertiary education and above (OR=0.58, 95% CI=0.35-0.96) was associated with a lower RBD risk. Men (OR=1.40, 95% CI 1.10-1.78, I

=0%, P=0.005) and older individual (OR=2.73, 95% CI 1.03-4.43, I

=60%, P=0.002) were more likely to have iRBD.

Six modifiable risk factors and one protective factor were associated with RBD. Further research is required to understand the mechanisms and to develop preventative strategies.

Six modifiable risk factors and one protective factor were associated with RBD. Further research is required to understand the mechanisms and to develop preventative strategies.Malaria is among the tropical diseases that cause the most deaths in Africa. Around 500,000 malaria deaths are reported yearly among African children under the age of five. Chloroquine (CQ) is a low-cost antimalarial used worldwide for the treatment of Plasmodium vivax malaria. Due to resistance mechanisms, CQ is no longer effective against most malaria cases caused by P. falciparum. The World Health Organization recommends artemisinin combination therapies for P. falciparum malaria, but resistance is emerging in Southeast Asia and some parts of Africa. Therefore, new medicines for treating malaria are urgently needed. Previously, our group identified the 4-aminoquinoline DAQ, a CQ analog containing an acetylenic bond in its side chain, which overcomes CQ resistance in K1 P. falciparum strains. In this work, the antiplasmodial profile, drug-like properties, and pharmacokinetics of DAQ were further investigated. DAQ showed no cross-resistance against standard CQ-resistant strains (e.g., Dd2, IPC 4912, RF12) nor against P. falciparum and P. vivax isolates from patients in the Brazilian Amazon. Using drug pressure assays, DAQ showed a low propensity to generate resistance. DAQ showed considerable solubility but low metabolic stability. The main metabolite was identified as a mono N-deethylated derivative (DAQM), which also showed significant inhibitory activity against CQ-resistant P. falciparum strains. Our findings indicated that the presence of a triple bond in CQ-analogues may represent a low-cost opportunity to overcome known mechanisms of resistance in the malaria parasite.Malaria is among the most devastating and widespread tropical parasitic diseases in developing countries. To prevent a potential public health emergency, there is an urgent need for new antimalarial drugs, with single-dose cures, broad therapeutic potential, and novel mechanism of action. We synthesized HCl salt of SKM13 (SKM13-2HCl) based on the modification of SKM13 to improve solubility in water. The anti-malarial activity of the synthesized drug was evaluated in both in vitro and in vivo models. The selective index indicated that SKM13-2HCl showed the same effectiveness with SKM13 in Plasmodium falciparum in in-vitro. Even though, in vivo mouse study demonstrated that SKM13 (20 mg/kg) at single dose could not completely inhibit P. berghei growth in blood. The survival rate increased from 33 to 90% at 15 days after infection. However, SKM13-2HCl (20 mg/kg) at a single dose increased the survival rate up to 100% at the same duration. Ultra-High-Performance Liquid Chromatography (UHPLC) showed that solubility in water of SKM13 and SKM13-2HCL was 0.389 mg/mL and 417 mg/mL, respectively. Pharmacokinetics (PK) analysis corresponded to the increased solubility of SKM13-2HCl over SKM13. Haematological parameters [red blood cell (RBC) count, haemoglobin level, and haematocrit level] supported the comparable efficacy of SKM13 and SKM13-2HCl in a 4-day suppression test. One mode of these drugs was found to be activating phosphorylation of eIF2α, hallmark of ER-stress, to kill parasite. Novel salt derivative of SKM13 (SKM13-2HCl) have enhanced anti-malarial activity against P. falciparum with endoplasmic reticulum (ER)-stress and salt form of SKM13 is an excellent direction to develop anti-malarial drug candidate in mice model.Here in, we report the design, synthesis and in vitro anticancer activity of a novel series of 24 quinoline analogues of substituted amide and sulphonamide derivatives. The anticancer activity of the synthesised compounds was evaluated against the HCC827, H1975 (L858R/T790 M), A549 (WT EGFR), A-549 and BEAS-2B cell lines. The majority of quinoline compounds demonstrated a significant cytotoxic effect. Compound 21 was found to be the most potent, with IC50 values of 0.010 μM, 0.21 μM, 0.99 μM and 2.99 μM as compared to Osimertinib with IC50 values with of 0.0042 μM, 0.04 μM, 0.92 μM and 2.67 μM. Compound 21 exhibited promising inhibitory enzymatic activity against the EGFR L858R/T790 M with IC50 value of 138 nM, comparable to Osimertinib's 110 nM. Employing a Western blot assay on the phosphorylation of EGFR and the signalling pathways transmission in HCC827 cells, the anticancer activity of the synthesised compounds 18 and 21 was evaluated in terms of its mechanism of action. All the compounds were subjected to a comparative molecular docking study against various EGFR enzyme types, including the wild-type (PDB 4I23) and T790 M mutant (PDB 2JIV) enzymes. Furthermore, compounds were examined at the allosteric binding site of the EGFR enzyme with the L858R/T790 M/C797S mutation (PDB ID 5D41). The MD simulation study was also performed for EGFR-compound 21 complex which indicates the stability compound 21 in both ATP and allosteric site of enzyme. Further, in silico ADME prediction studies of all derivatives were found promising, signifying the drug like properties.Farnesoid X receptor (FXR) is an attractive target for drug discovery against non-alcoholic fatty liver disease (NAFLD). We previously reported an orally active, new-chemotype FXR agonist XJ034 by ensemble learning-driven drug discovery. However, its FXR agonistic activity and the efficacy in vivo remain to be improved. In this study, we designed and synthesized 52 derivatives, and preliminarily evaluated their FXR transactivation activity in HEK293T cells at the concentration of 10 μM. 12 FXR agonists were superior or comparable to compound XJ034, two of which showed over 9-fold activity of compound XJ034, and were as potent as OCA. The molecular docking and molecular dynamics simulations implied an additional hydrogen bond with TYR383 is involved in FXR transactivation for both compounds. According to EC50 determined by the confirmatory transactivation assay, we selected adamantan-1-yl(4-(2-amino-5-chlorophenyl)piperazin-1-yl)methanone (10a, EC50 1.05 μM) as our lead compound. Interestingly, compound 10a had no agonistic effect on TGR5 or PPAR, and no cytotoxicity to HepG2 cells. In vivo bioassays with high-fat-diet induced C57BL/6J obese (DIO) mice have shown that compound 10a (100 mg/kg) is more effective than compound XJ034 (200 mg/kg) in improving hyperlipidemia, hepatic steatosis and insulin resistance. We also observed that compound 10a down-regulated the expression of genes involved in liver inflammation in vivo, implying its potential to treat hepatic inflammation. In summary, the present data have proved that our strategy for structural optimization is effective, and compound 10a is a promising lead compound with improved efficacy for NAFLD.Despite great advances in the development of modern anticancer drugs, it is still challenging to find safer and more effective ones due to a new spectrum of diseases and emerging drug resistance. Natural quinazolinones exist widely in natural plants, microorganisms and animals and possess a variety of biological activities. Over the past three to four decades, there has been a growing volume of literature concerning the effects of natural quinazolinones and their derivatives upon a variety of cancers. In this paper, 58 natural quinazolinones with anticancer activities were reviewed in term of their anticancer effects, cellular and molecular mechanisms, ability to overcome cancer drug resistance, and structure-activity relationship of anticancer quinazolinone representatives as well. This paper will offer new clues for discovering new and better lead compounds against malignant tumor and cancer drug resistance from natural quinazolinones.