Clinical assessment of levamlodipine besylate combination therapy for essential hypertension: A protocol for systematic review and meta-analysis.

BACKGROUND: Essential hypertension has been regarded a significant risk factor for cardiovascular disease across the globe, and a significant escapable causation of early death as well as morbidity in the U.S. When angiotensin II receptor blockers and calcium channel blockers are used to treat essential hypertension, most patients will have inadequate blood pressure management. As a result, including a diuretic in the regimen is necessary. The current study's aim is to investigate the effectiveness as well as safety of levamlodipine besylate combination therapy in treating essential hypertension at varying degrees of severity. METHODS: In establishing the effectiveness and safety of the mix of levamlodipine besylate and dihydropyridine for essential hypertension, the authors will conduct a systematic review and, where applicable, a meta-analysis of randomized controlled clinical trials. A total of 8 electronic databases will be used in the search, including 4 English databases (PubMed, Web of Science, EMBASE, and Cochrane Library) and 4 Chinese databases (China National Knowledge Infrastructure, Chinese BioMedical Literature database, Chinese Scientific Journal database, and WanFang database). All articles published in the databases will be considered between their inception and January 18, 2022. Only articles published in English or Mandarin Chinese will be picked. A group of writers will independently evaluate each reference to see if it is eligible and whether there are any duplicates. The same authors will do data extraction for all eligible studies and use the Cochrane risk of bias tool to evaluate the risk of bias in the trials chosen for inclusion. RESULTS: The analysis will evaluate the efficiency and level of safeness of levamlodipine besylate combined treatment for essential hypertension. CONCLUSIONS: Our systematic review will offer evidence for judging whether levamlodipine besylate combination therapy can be considered an effective intercession for essential hypertension. ETHICS AND DISSEMINATION: Ethical approval will not be required as no original data will be collected as part of this review. REGISTRATION NUMBER: DOI 10.17605/OSF.IO/H8ZR2.

Rhodium(III)-Catalyzed Oxidative Annulation of 4-Aminoquinolines and Acrylate through Two Consecutive C(sp2)-H Activations.

The C-H annulation of the five-position of quinolines and acrylates to afford heterocycles is an active field of research in organic synthesis. Herein the annulation of 4-aminoquinolines with acrylates through two consecutive C-H activations catalyzed by Rh(III) is described. The reaction proceeds with high atom efficiency under mild reaction conditions, and this protocol will provide appealing strategies for the synthesis of fused quinoline heterocycles.

Combined pharmacophore modeling, 3D-QSAR and docking studies to identify novel HDAC inhibitors using drug repurposing.

Histone deacetylases (HDACs), a critical family of epigenetic enzymes, has emerged as a promising target for antitumor drugs. Here, we describe our protocol of virtual screening in identification of novel potential HDAC inhibitors through pharmacophore modeling, 3D-QSAR, molecular docking and molecular dynamics (MD) simulation. Considering the limitation of current virtual screening works, drug repurposing strategy was applied to discover druggable HDAC inhibitor. The ligand-based pharmacophore and 3D-QSAR models were established, and their reliability was validated by different methods. Then, the DrugBank database was screened, followed by molecular docking. MD simulation (100 ns) was performed to further study the stability of ligand binding modes. Finally, results indicated the hit DB03889 with high in silico inhibitory potency was suitable for further experimental analysis.Communicated by Ramaswamy H. Sarma.

Discovery of novel serine/threonine protein phosphatase 1 inhibitors from traditional Chinese medicine through virtual screening and biological assays.

Protein phosphatase 1 (PP1) is a critical regulator of several processes, such as muscle contraction, neuronal signaling, glycogen synthesis, and cell proliferation. Dysregulation of PP1 has recently been found to be implicated in cardiac dysfunctions, which indicates that PP1 could be an attractive therapeutic target. However, discovery of PP1 inhibitors with satisfied safety and efficiency is still a challenge. Here, in order to discover potential PP1 inhibitors, compounds extracted from traditional Chinese medicine (TCM) were screened by a novel integrated virtual screening protocol including pharmacophore modeling and docking approaches. Combined with protein phosphatase inhibition assay, ZINC43060554 showed strongly inhibitory activity with IC50 values of 26.78 µM. Furthermore, molecular dynamics simulation and Molecular Mechanics/Generalized Born Surface Area binding free-energy analysis were performed to examine the stability of ligand binding modes. These novel scaffolds discovered in the present study can be used for rational design of PP1 inhibitors with high affinity.Communicated by Ramaswamy H. Sarma.

Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold.

Both histone deacetylase (HDAC) and fibroblast growth factor receptor (FGFR) are important targets for cancer therapy. Although combining dual HDAC pharmacophore with tyrosine kinase inhibitors (TKIs) had achieved a successful progress, dual HDAC/FGFR1 inhibitors haven't been reported yet. Herein, we designed a series of hybrids bearing 1H-indazol-3-amine and benzohydroxamic acids scaffold with scaffold hopping and molecular hybridization strategies. Among them, compound 7j showed the most potent inhibitory activity against HDAC6 with IC50 of 34 nM and exhibited the great inhibitory activities against a human breast cancer cell line MCF-7 with IC50 of 9 µM in vitro. Meanwhile, the compound also exhibited moderate FGFR1 inhibitory activities. This study provides new tool compounds for further exploration of dual HDAC/FGFR1 inhibition.

Low enhancement on multiphase contrast-enhanced CT images: an independent predictor of the presence of high tumor grade of clear cell renal cell carcinoma.

OBJECTIVE: The purpose of this study was to assess the relation between tumor enhancement on multiphase contrast-enhanced CT images and Fuhrman grade of clear cell renal cell carcinoma. MATERIALS AND METHODS: A single-institution retrospective review was conducted on the records of 255 patients who underwent radical or partial nephrectomy and received a histologic diagnosis of clear cell renal cell carcinoma. Two radiologists recorded the radiographic features of each patient, including the attenuation value of the lesion, lesion size, calcification within the lesion, cystic versus solid appearance, and margin regularity. Parameters representing the extent of tumor enhancement were defined and calculated. The association between tumor enhancement and Fuhrman grade was analyzed, and multivariate analysis was performed to find independent predictors of high tumor grade. RESULTS: Significant differences existed in tumor enhancement among different Fuhrman grades (p < 0.001). High-grade tumors had significantly lower enhancement (p < 0.001). The enhancement parameter had a sensitivity of 0.84 and specificity of 0.93 in prediction of high tumor grade. In the multivariate analysis, more advanced age, irregular margin, and low tumor enhancement were the three independent predictors of high tumor grade. CONCLUSION: Tumor enhancement of clear cell renal cell carcinoma on multiphase contrast-enhanced CT images is associated with Fuhrman grade. Low tumor enhancement in the corticomedullary phase is an independent predictor of high tumor grade. This system may be helpful in clinical decision making about the care of patients treated by nonsurgical approaches.

Competitive adsorption of Pb(II), Cu(II) and Zn(II) onto xanthate-modified magnetic chitosan.

The competitive adsorption of Pb(II), Cu(II) and Zn(II) onto a novel xanthate-modified magnetic chitosan (XMCS) was systematically investigated in single and ternary metal systems. In single system, equilibrium studies showed that the adsorption of Pb(II), Cu(II) and Zn(II) followed the Langmuir model and the maximum adsorption capacities were found to be 76.9, 34.5 and 20.8mg/g, respectively. In ternary system, the combined action of the metals was found to be antagonistic and the metal sorption followed the order of Pb(II)>Cu(II)>Zn(II); the Langmuir isotherm fitted the data of Pb(II) and Cu(II) well while the isotherm data of Zn(II) correlated well with the Freundlich model. The Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectra (XPS) studies showed that the thiol and amino group participated in the adsorption of Pb(II), Cu(II) and Zn(II).

[Serum ferritin in donors with regular plateletpheresis].

This study was aimed to evaluate the impact of regular donating platelets on serum ferritin (SF) of donors. A total of 93 male blood donors including 24 initial plateletpheresis donors and 69 regular plateletpheresis donors were selected randomly. Their SF level was measured by ELISA. The results showed that the SF level of initial plateletpheresis donors and regular plateletpheresis donors were 91.08 ± 23.38 µg/L and 57.16 ± 35.48 µg/L respectively, and all were in normal levels, but there was significant difference between the 2 groups (p < 0.05). The SF level decreased when the donation frequency increased, there were no significant differences between the groups with different donation frequency. Correlation with lifetime donations of platelets was not found. It is concluded that regular plateletpheresis donors may have lower SF level.