Background: Flavonoid glycosides are known to possess diverse bioactivities including antitumor and anti-inflammatory properties. Hesperetin is abundant in nature and can be used to synthesize bioactive flavonoids. This has the advantages of low cost, short synthetic steps, simple operation, and good yields.
View Article and Find Full Text PDFThe selective inhibition of RET kinase as a treatment for relevant cancer types including lung adenocarcinoma has garnered considerable interest in recent years and prompted a variety of efforts toward the discovery of small-molecule therapeutics. Hits uncovered via the analysis of archival kinase data ultimately led to the identification of a promising pyrrolo[2,3-]pyrimidine scaffold. The optimization of this pyrrolo[2,3-]pyrimidine core resulted in compound , which demonstrated potent RET kinase inhibition and robust efficacy in RET-driven tumor xenografts upon multiday dosing in mice.
View Article and Find Full Text PDFThe aim of this study was to investigate the incidence of erectile dysfunction (ED) in nonmuscle-invasive bladder cancer (NMIBC) patients before and after transurethral resection (TUR) in China. Clinical data from 165 male patients with NMIBC who received adjuvant intravesical chemotherapy after TUR in Neijiang First People's Hospital (Neijiang, China) between January 2010 and June 2019 were retrospectively reviewed. The sexual function of these patients was evaluated before and 1.
View Article and Find Full Text PDFFive previously undescribed lanostane-type triterpenoids, including two triterpenoids with a rearranged side chain (applanoic acids E and F), one C21 nortriterpenoid (16,17-dehydroapplanone E), as well as two highly oxygenated lanostane triterpenoids (methyl applaniate B and applanoic acid G), were isolated from the fruiting bodies of Ganoderma applanatum (Pers.) Pat. Their structures were elucidated on the basis of spectroscopic analysis, X-ray crystallography and ECD data.
View Article and Find Full Text PDFRET (REarranged during Transfection) kinase gain-of-function aberrancies have been identified as potential oncogenic drivers in lung adenocarcinoma, along with several other cancer types, prompting the discovery and assessment of selective inhibitors. Internal mining and analysis of relevant kinase data informed the decision to investigate a pyrazolo[1,5-]pyrimidine scaffold, where subsequent optimization led to the identification of compound WF-47-JS03 (), a potent RET kinase inhibitor with >500-fold selectivity against KDR (Kinase insert Domain Receptor) in cellular assays. In subsequent mouse studies, compound demonstrated effective brain penetration and was found to induce strong regression of RET-driven tumor xenografts at a well-tolerated dose (10 mg/kg, po, qd).
View Article and Find Full Text PDFSteroid hormones released from manure agricultural application are a matter of global concern. The residual levels of steroid hormones were studied in a typical intensive vegetable cultivation area in northeast China, with a long history of heavy manure application. Seven steroids (estrone, 17α-estradiol, 17β-estradiol, estriol, testosterone, androstendione and progesterone) were analyzed from soil sampled from vegetable greenhouses, from sediments and water from the adjacent drainage ditch and from the groundwater.
View Article and Find Full Text PDFOne of the largest vegetable cultivation field sites in Northeast China was selected to investigate the occurrence and distribution pattern of fluoroquinolones (FQs) in the soil-vegetable system. A total of 100 surface soil samples and 68 vegetable samples were collected from this study area. The antibiotic concentration was analyzed using high-performance liquid chromatography tandem mass spectrometry.
View Article and Find Full Text PDFAntibiotic residues in surface soils can lead to serious health risks and ecological hazards. Spatial mean concentration of antibiotic residues in the soil is the most important indicator of a region's environmental risk to antibiotic residues. Considerable estimation error would lead to an inefficient strategy of pollution control that happens when sample size is small and the estimation model does not match the spatial features of the object to be surveyed.
View Article and Find Full Text PDFObjective: To explore the lower urinary tract symptoms (LUTS), especially those in the urinary storage phase, following transurethral resection of the prostate (TURP), and to improve the postoperative management and patients' quality of life after TURP.
Methods: A total of 86 patients with benign prostate hyperplasia (BPH) underwent TURP, and were interviewed on urinary symptoms at 1, 3, 7, 15 and 30 days after removal of the catheter. The patients were divided into two groups according to whether they had preoperative detrusor instability and/or compliance of the bladder (Group A) or not (Group B), and observed for the changes in IPSS scores and urinary storage symptoms after removal of the catheter.
A hit-to-lead optimization process was carried out on the high throughput screening hit compound 1 resulting in the identification of several potent and selective CCR1 receptor antagonists. Compound 37 shows the best overall profile with IC(50) values of <100 nM in binding and functional assays.
View Article and Find Full Text PDFShanghai Kou Qiang Yi Xue
October 2007
Purpose: To evaluate the impact of Yishenqinghuo recipe on alveolar bone reconstruction of rats with experimental periodontitis.
Methods: 12-months old Spague-Dawley rats were selected for the study. All rats were randomly divided into 4 groups.
Shanghai Kou Qiang Yi Xue
December 2006
Purpose: To investigate and analyze the state of periodontal health of 400 adults at their post and risk factors in Shanghai.
Methods: 400 subjects (249 male, 151 female), aged from 25 to 59, were requested to fill a questionnaire. The probing depth (PD), clinical attachment level (CAL), tooth mobility (TM) and bleeding on probing(BOP) on 6 sites of each indicated tooth were measured and recorded.
Design and synthesis of a series of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl)-2-oxoethoxy)phenylamino)cyclobutenedione derivatives as novel CCR1 antagonists are described. Structure-activity relationship studies led to the identification of compound 22, which demonstrated potent binding activity, functional antagonism of CCR1 as well as good species cross-reactivity. In addition, compound 22 also showed desirable pharmacokinetic profiles and was selected for in vivo studies in the mouse collagen-induced arthritis model.
View Article and Find Full Text PDFWe have previously shown that 3-phenylpyrazolo[1,5-a]pyrimidines exemplified by 8 were potent antagonists of the human corticotropin-releasing factor-1 receptor. A series of 3-pyridylpyrazolo[1,5-a]pyrimidines 15, 25-30, 34, and 35 containing a weakly basic pyridine ring at the 3-position of the bicyclic nucleus was designed to reduce lipophilicity from the initial leads such as 7. Here, we showed that these 3-pyridyl compounds exhibited potent antagonists at the human CRF(1) receptor.
View Article and Find Full Text PDFShanghai Kou Qiang Yi Xue
October 2003
Objective: The purpose of this study was to compare the difference of sexual hormone receptors' expression and distribution in the gingival tissues between periodontitis patients and normal females and to provide the theoretical facts for the clarification of periodontitis's pathogenesis.
Methods: The test group was 34 samples and normal control group was 30 samples. The test group and the normal control group were divided into 3 subgroups separately according to age.
A series of 4-substituted 8-aryl-2-methylquinolines 4 was designed and synthesized as highly potent antagonists for the human CRF(1) receptor. This series of compounds displayed parallel SAR to other bicyclic systems such as pyrazolo[1,5-a]pyrimidines, with several compounds possessing low nanomolar binding affinity. In addition to the high potency, the basicity of this 4-aminoquinoline core may offer CRF(1) antagonists with lower lipophilicity.
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