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Evaluation of Antimalarial Action associated with 80% Methanolic Actual Draw out involving Dorstenia barnimiana Towards Plasmodium berghei-Infected Rodents.
This study aimed to investigate the efficacy and safety of mirabegron for Parkinsonism patients with overactive bladder (OAB) symptoms in a randomized, placebo-controlled, multicenter study.

Inclusion criteria are Parkinsonism with OAB symptoms for 4 weeks or more, OAB symptom score (OABSS) questionnaire scores greater than 2, and OABSS urgency question scores greater than 1. After a 2-week wash-out period, the patients were randomized into placebo and mirabegron groups at visit 2. Visit 3 was performed after 4 weeks of medication. Mirabegron was prescribed to the two groups for the rest of the study period at visit 4.

The mean age was 68.1 ± 8.1 years and 72 males and 64 females were included. A total of 136 patients were screened, 117 patients were randomized, and 25 patients dropped out. The OABSS scores were significantly different between the two groups at Weeks 4 and 8. The OABSS scores became the same in the two groups at Week 12 (visit 5). The postvoid residual urine volume showed a mild increase to 64 ml in the mirabegron group compared to the placebo group at visit 4. Adverse events occurred in 27 patients (23.1%). The degree was mild in 26 cases (78.8%), moderate in five (15.2%), and severe in two (6.1%). Only 13 cases (39.4%) showed medication-related adverse events. Acute urinary retention occurred in a single case. The treatment satisfaction questionnaires showed no significant differences between the two groups.

Mirabegron was effective in treating OAB symptoms in patients with Parkinsonism with acceptable adverse events.
Mirabegron was effective in treating OAB symptoms in patients with Parkinsonism with acceptable adverse events.Polyene polyketides amphotericin B (AMB) and nystatin (NYS) are important antifungal drugs. Thioesterases (TEs), located at the last module of PKS, control the release of polyketides by cyclization or hydrolysis. Intrigued by the tiny structural difference between AMB and NYS, as well as the high sequence identity between AMB TE and NYS TE, we constructed four systems to study the structural characteristics, catalytic mechanism, and product release of AMB TE and NYS TE with combined MD simulations and quantum mechanics/molecular mechanics calculations. The results indicated that compared with AMB TE, NYS TE shows higher specificity on its natural substrate and R26 as well as D186 were proposed to a key role in substrate recognition. The energy barrier of macrocyclization in AMB-TE-Amb and AMB-TE-Nys systems were calculated to be 14.0 and 22.7 kcal/mol, while in NYS-TE-Nys and NYS-TE-Amb systems, their energy barriers were 17.5 and 25.7 kcal/mol, suggesting the cyclization with their natural substrates were more favorable than that with exchanged substrates. Pixantrone in vitro At last, the binding free energy obtained with the MM-PBSA.py program suggested that it was easier for natural products to leave TE enzymes after cyclization. And key residues to the departure of polyketide product from the active site were highlighted. We provided a catalytic overview of AMB TE and NYS TE including substrate recognition, catalytic mechanism and product release. These will improve the comprehension of polyene polyketide TEs and benefit for broadening the substrate flexibility of polyketide TEs.Excess heavy metals affect plant physiology by inducing stress symptoms, however several species have evolved the ability to hyperaccumulate metals in above-ground tissues without phytotoxic effects. In this study we assume that at subcellular level, different strategies were adopted by hyperaccumulator versus the non-accumulator plant species to face the excess of heavy metals. At this purpose the comet assay was used to investigate the nucleoid structure modifications occurring in response to Zn and Cd treatments in the I16 and PL22 populations of the hyperaccumulator Arabidopsis halleri versus the nonaccumulator species Arabidopsis thaliana. Methy-sens comet assay and RT-qPCR were also performed to associate metal induced variations in nucleoids with possible epigenetic modifications. The comet assay showed that Zn induced a mild but non significant reduction in the tail moment in A. thaliana and in both I16 and PL22. Cd treatment induced an increase in DNA migration in nuclei of A. thaliana, whereas no differences in DNA migration was observed for I16, and a significant increase in nucleoid condensation was found in PL22 Cd treated samples. This last population showed higher CpG DNA methylation upon Cd treatment than in control conditions, and an up-regulation of genes involved in symmetric methylation and histone deacetylation. Our data support the hypothesis of a possible role of epigenetic modifications in the hyperaccumulation trait to cope with the high Cd shoot concentrations. In addition, the differences observed between PL22 and I16 could reinforce previous suggestions of divergent strategies for metals detoxification developing in the two metallicolous populations.There is no consensus on the true meaning of clinical regenerative endodontics, and there is confusion over the concept and the term. Commonly used terms include revitalization and revascularization. The clinical methods for endodontic revitalization procedures and the tissue engineering concept differ depending on whether there is exogenous delivery of cells - called cell therapy, or not. Here, in this review, the difference is clarified by emphasizing the correct terminology cell-free versus cell-based regenerative endodontic therapy (CF-RET versus CB-RET). The revitalization procedures practised clinically do not fit into the modern tissue engineering concepts of pulp regeneration but can be categorized as CF-RET. The modern tissue engineering concept in pulp regeneration is a CB-RET, which so far is at the clinical trial stage. However, histological examination of teeth following regenerative endodontic treatments reveals healing with repair derived from stem cells that originate from the periodontal, bone and other tissues. The aim of regenerative endodontics is regeneration of the pulp-dentine complex. This review discusses why CF-RET is unlikely to regenerate a pulp-dentine complex with current protocols. The American Association of Endodontists and the European Society of Endodontology have not yet recommended autologous stem cell transplantation (CB-RERT) which aspires for regeneration. Therefore, an understanding of the concept, term, difficulties and differences in current protocols is important for the clinician. However, rather than being discouraged that ideal regeneration has not been achieved to date, repair can be an acceptable outcome in clinical regenerative endodontics as it has also been accepted in medicine. Repair should also be considered in the context that resolution of the clinical signs/symptoms of pulp necrosis/apical periodontitis is generally reliably obtained in clinical regenerative endodontics.
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