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1.
BMC Surg ; 19(1): 128, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488117

RESUMO

BACKGROUND: The aim of the study was to develop a scoring system for the prediction of postoperative complications of open hepatectomy. METHOD: All consecutive patients receiving open hepatectomy from 2015 to 2017 were included in the study. Univariate and multivariate analyses were used to confirm the risk factors for postoperative complications. Afterwards, a novel scoring system was developed to predict the postoperative complications. RESULTS: The study included a total of 207 patients. For the test dataset, multivariate analysis indicated that diabetes, scale of surgery, serum potassium, and blood loss versus body weight were independent risk factors of the postoperative complications. The area under the curve (AUC) of the novel scoring system we proposed for prediction of postoperative complications of hepatectomy was 0.803, which is comparable with the AUCs of previous scoring systems. Furthermore, in the validation dataset, the corresponding AUC of the new scoring system was 0.717. CONCLUSION: This novel and simplified scoring system can effectively predict the postoperative complications of open hepatectomy and could help identify patients who are at high risk of postoperative complications.

2.
J Natl Compr Canc Netw ; 17(9): 1026-1030, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31487676

RESUMO

Immune checkpoint inhibitors represent a newly established standard of care in patients with refractory metastatic colorectal cancer with mismatch repair deficiency and microsatellite instability. However, the use of immunotherapy is unclear in recipients of liver transplants with or without concurrent liver function abnormalities. Clinical trials investigating immunotherapy have mostly excluded liver transplant recipients and patients with abnormal liver function. This report presents the first case, to our knowledge, of a liver transplant patient with mismatch repair-deficient colon adenocarcinoma with liver metastases and concurrent abnormal liver function who safely responded to immunotherapy. We also review the literature on checkpoint inhibitor use in patients with other metastatic solid tumors after liver transplant and those with baseline liver function abnormalities. An increasing body of evidence supports the safety of checkpoint inhibition in patients with cancer and solid organ transplants, but further prospective studies are warranted. Use of immunotherapy in liver transplant recipients who have metastatic colorectal cancer with microsatellite instability is feasible but should be performed in a multidisciplinary team setting.

4.
Medicine (Baltimore) ; 98(34): e16922, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441876

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have displayed dysregulated expression in several types of cancer. Nevertheless, their function and underlying mechanisms in cervical cancer remains largely unknown. This study aimed to describe the regulatory mechanisms in cervical cancer. METHODS: We downloaded the circRNAs expression profiles from Gene Expression Omnibus database, and RNAs expression profiles from The Cancer Genome Atlas database. We established a circRNA-miRNA-mRNA and circRNA-miRNA-hubgene network. The interactions between proteins were analyzed using the STRING database and hubgenes were identified using MCODE plugin. Then, we conducted a circRNA-miRNA-hubgenes regulatory module. Functional and pathway enrichment analyses were conducted using R packages "Clusterprofile". RESULTS: Six circRNAs, 15 miRNAs, and 158 mRNAs were identified to construct the ceRNA network of cervical cancer. PPI (protein-protein interaction) network and module analysis identified 7 hubgenes. Then, a circRNA-miRNA-hubgene subnetwork was constructed based on the 1 DEcircRNAs, 3 DEmiRNAs, and 3 DEmRNAs. The KEGG pathway analysis indicated DEmRNAs are involved in progesterone-mediated oocyte maturation, cell cycle, and oocyte meiosis. CONCLUSION: These ceRNAs are critical in the pathogenesis of cervical and may serve as future therapeutic biomarkers.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , RNA/genética , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/genética , Feminino , Humanos , Mapas de Interação de Proteínas , RNA/metabolismo
5.
Chem Commun (Camb) ; 55(72): 10768-10771, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31432821

RESUMO

By covalent combination of a chiral amino acid, lipid, and achiral phenothiazine derivative, a reaction-based chiroptical probe, PTZ-D, was obtained. PTZ-D could self-assemble into a chiral organogel realizing the chirality transformation from a chiral amino acid to a self-assembled system and displaying unprecedented chiroptical monitoring of ClO- with switchable CPL signals.


Assuntos
Aminoácidos/química , Ácido Hipocloroso/análise , Luminescência , Imagem Óptica , Géis/síntese química , Géis/química , Estrutura Molecular , Tamanho da Partícula
6.
J Laparoendosc Adv Surg Tech A ; 29(9): 1116-1121, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31329021

RESUMO

Objective: This study was aimed to evaluate the correlation between clinically significant portal hypertension (CSPH) and postoperative complications and risk predictors of postoperative complications. Methods: The retrospective study was conducted to identify the effect. The cirrhotic patients were divided into two groups, those with or without CSPH. The intraoperative and postoperative conditions were evaluated. Multivariate logistic regression analysis was performed to identify potential risk predictors for postoperative complications in cirrhotic patients with CSPH. Results: The cirrhotic patients with CSPH who underwent laparoscopic cholecystectomy (LC) had postoperative hospitalization than the patients without CSPH. However, the incidence of postoperative complications between two groups showed no significant difference. The results of multivariate analysis showed that male, gallbladder wall >3 mm, size of stones ≥1 cm, scores of Model for end-stage liver disease (MELD) ≥10, and operation time >60 minutes were the potential risk predictors for postoperative complications. Conclusions: CSPH did not increase the incidence of postoperative complications in cirrhotic patients who underwent LC, but increased conversion rate and prolonged postoperative hospitalization. Furthermore, our study showed that gender, sizes of gallbladder wall and stones, scores of MELD, and operation time were the important postoperative risk predictors for cirrhotic patients with CSPH.

7.
Hepatol Int ; 13(5): 631-640, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31342250

RESUMO

PURPOSE: The diagnostic potential of hepatic stellate cells (HSCs) and γδT cells for patients with hepatocellular carcinoma (HCC) and their synergistic contributions to the prognosis of these patients have not yet been investigated. The aim of this study was to elucidate the prognostic value of these cells in HCC. METHODS: The prognostic significance of the ratio of HSCs to γδT cells (SGR) was assessed in a total of 339 HCC patients undergoing resection. The correlation between the circulating tumor cell (CTC) level and SGR in 71 HCC patients was determined using the CellSearch system. In vitro experiments were performed to validate the synergistic effects of HSCs and γδT cells on hepatoma cells. RESULTS: Peritumoral SGR was closely associated with overall survival (OS) and recurrence-free survival (RFS) of HCC patients after resection. In the testing cohort, two nomograms incorporating the SGR were constructed for the prediction of OS and RFS. The predictive accuracy of the two nomograms was verified by the validation cohort. CTC levels were positively correlated with SGR (r = 0.479, p < 0.001). Among the patients with CTCs > 2/7.5 ml, those with a high SGR exhibited higher early recurrence rates than those with a low SGR. In vitro experiments revealed that the secretion of INF-γ, IL-17, and TNF-α from γδT cells was increased after culture with HSC-conditioned medium. In addition, γδT cells cultured with HSC-conditioned medium decreased the proliferative and invasive abilities of hepatoma cells. CONCLUSIONS: The peritumoral SGR is related to aggressive tumor behavior and has a powerful predictive value in HCC. Early recurrence in patients with a high peritumoral SGR might be associated with high CTC levels.

8.
Nat Commun ; 10(1): 3368, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358761

RESUMO

For seeking high enantiopurity, the previously reported thermal asymmetric catalysis is usually carried out at low temperature sometimes with limited yield, that is, the high enantiomeric excess (ee) usually at the cost of high yield. Thus, the achieving both high stereoselectivity and yield is an enormous challenge. We report herein two metal nanoparticle (M NP)-loaded and porphyrin-containing homochiral covalent organic framework (CCOF)-based composite catalysts, and their application in the thermally-driven asymmetric one-pot Henry and A3-coupling reactions. All the reactions are conducted at elevated temperatures with both excellent stereoselectivity and yield which resulted from the synergy of CCOF confinement effect and M NP catalytic activation. Notably, the needed thermal energy for the asymmetric reactions herein is derived from the photothermal conversion via porphyrin-based CCOF upon irradiation with visible light. Remarkably, the CCOF confinement effect can be effectively maintained up to 100 °C for the asymmetric one-pot Henry and A3-coupling reactions herein.

9.
Nature ; 572(7767): 56-61, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31316207

RESUMO

The radiation-based sterile insect technique (SIT) has successfully suppressed field populations of several insect pest species, but its effect on mosquito vector control has been limited. The related incompatible insect technique (IIT)-which uses sterilization caused by the maternally inherited endosymbiotic bacteria Wolbachia-is a promising alternative, but can be undermined by accidental release of females infected with the same Wolbachia strain as the released males. Here we show that combining incompatible and sterile insect techniques (IIT-SIT) enables near elimination of field populations of the world's most invasive mosquito species, Aedes albopictus. Millions of factory-reared adult males with an artificial triple-Wolbachia infection were released, with prior pupal irradiation of the released mosquitoes to prevent unintentionally released triply infected females from successfully reproducing in the field. This successful field trial demonstrates the feasibility of area-wide application of combined IIT-SIT for mosquito vector control.

10.
J Ovarian Res ; 12(1): 51, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151469

RESUMO

INTRODUCTION: Prognostic biomarkers are highly needed to properly manage patients with cancer and improve their clinical courses. The relationship between lymphocyte-to-monocyte ratio (LMR) at diagnosis and ovarian cancer prognosis has been extensively studied, but little consensus has been reached regarding its utility as a biomarker of poor outcome. Thus, this study aimed to investigate the potential prognostic value of pretreatment LMR in such patients to shed light on this issue. METHODS: We searched the scientific databases of MEDLINE, Embase, Cochrane Library, and WangFang for relevant studies about the inflammatory prognostic factor LMR in ovarian cancer, based on specific inclusion and exclusion criteria. The following parameters were analyzed among others: LMR values and respective cut-offs, patient's overall survival (OS) and progression-free survival (PFS), and clinicopathological features. RESULTS: Eight studies, including 2259 patients, were eligible for inclusion in this meta-analysis. We found that low LMR was associated with both poor OS [Hazard ratio (HR): 1.92; 95% confidence interval (CI): 1.58-2.34; p < 0.001] and PFS (HR: 1.70; 95% CI: 1.54-1.88; p < 0.001). Moreover, our findings revealed that low LMR was correlated with high G2/G3 histological grade (OR: 1.67; 95% CI: 1.26-2.20; p < 0.001) and late III-IV FIGO stage tumors (OR: 3.55; 95% CI: 2.68-4.70; p < 0.001), high serum CA-125 level (OR: 2.18; 95% CI: 1.71-2.77; p < 0.001), and presence of malignant ascites (OR: 1.87; 95% CI: 1.11-3.14; p = 0.02) and lymph node metastases (OR: 1.70; 95% CI: 1.13-2.54; p = 0.01). CONCLUSION: Pretreatment LMR is a potential prognostic marker of poor outcome in ovarian cancer patients and may thus be important in clinical care and disease control.

11.
BMC Cancer ; 19(1): 548, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174493

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF), tyrosine kinase (TK) and mechanistic target of rapamycin kinase (mTOR) inhibitors are common first-line (1 L) treatments for metastatic renal cell carcinoma (mRCC). Despite treatment availability, the 5-year survival rate in patients diagnosed at the metastatic stage is only ≈ 10%. To gain contemporary insights into RCC treatment trends that may inform clinical, scientific and payer considerations, treatment patterns and adverse events (AEs) associated with 1 L therapy were examined in a retrospective, longitudinal, population-based, observational study of patients with mRCC. METHODS: US administrative claims data (Truven Health MarketScan Commercial Databases) were used to assess trends in 1 L treatment initiation in mRCC (2006-2015) and characterize patterns of individual 1 L treatments, baseline characteristics, comorbidities and treatment-related AEs from 2011 through 2015. Outcomes were evaluated by drug class and route of administration. RESULTS: Ten-year trend analysis (n = 4270) showed that TK/VEGF-directed therapy rapidly became more common than mTOR-directed therapy, and oral treatments were favored over intravenous (IV) treatments. Overall, 1992 eligible patients initiated 1 L treatment for mRCC from 2011 through 2015: 1752 (88%) received TK/VEGF-directed agents and 233 (12%) received mTOR-directed agents; 1674 (84%) received oral treatments, and 318 (16%) received IV treatments. The most common 1 L treatment was sunitinib (n = 849), followed by pazopanib (n = 631), temsirolimus (n = 157) and bevacizumab (n = 154). Patient characteristics and comorbidities, including age, diabetes and congestive heart failure, were independent predictors of 1 L mRCC treatment choice. The three most common potentially 1 L treatment-related AEs were nausea/vomiting (128.2 per 100 patient-years [PY]), hypertension (69 per 100 PY) and renal insufficiency (44.6 per 100 PY). A wide variety of agents were used as second-line (2 L) therapy. Substantial latency of onset was observed for several potentially treatment-related toxicities in patients treated with TK/VEGF- or mTOR-directed agents. CONCLUSIONS: In the US, 1 L TK/VEGF inhibitor uptake in recent years appears largely in line with national approvals and guidelines, with varied 2 L agent use. Although retrospective evaluation of claims data cannot assess underlying causality, insights from these real-world RCC treatment and AE patterns will be useful in informing medical and payer decisions.

12.
Biochem Pharmacol ; 166: 231-241, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158339

RESUMO

Protein glycation in the body can lead to malfunction of intracellular and extracellular proteins. Reactive carbonyl species (RCS) have been identified to be key intermediates in the reactions. The reaction products, generally termed as advanced glycation end products (AGEs), have been implicated in the development of diabetic complications. In this study, the activity of apigenin (API), a natural flavone in scavenging RCS and the molecular mechanism involved in its protective effect against AGEs-induced oxidative stress and inflammation were examined in vitro. Results showed that API could directly trap methylglyoxal (MGO) to form API-MGO adducts, thus inhibiting AGEs formation. API and di-apigenin adduct (DMA) were found to inhibit AGEs-induced oxidative stress and inflammation in human umbilical vein endothelial cells (HUVECs) by significantly suppressing reactive oxygen species (ROS) production (30% relative to control) and decreasing the protein expression of pro-inflammatory cytokines and adhesion molecules by 30-70%. Further mechanistic investigation revealed that the protective effect was likely mediated via suppression of the extracellular-signal-regulated kinase 1/2 (ERK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway initiated by AGEs-RAGE (receptor for AGEs) interaction and induction of ERK/nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway with subsequent up-regulation of antioxidant defense molecules. In summary, our results suggest that API possesses great potential to protect against AGEs-associated health disorders by modulating cellular inflammatory and antioxidant defense signaling pathways.

13.
Inorg Chem ; 58(14): 9253-9259, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31247830

RESUMO

A new homochiral BINAPDA-Zr-MOF was prepared by a new chiral organic linker of (R)-4,4'-(6,6'-dichloro-2,2'-diethoxyl-[1,1'-binaphthalene]-4,4'-diyl)dibenzoic acid (R-L) and ZrCl4 under solvothermal conditions. Its structure was determined by Pawley refinement on the basis of the measured PXRD pattern determined for BINAPDA-Zr-MOF, and it showed that the obtained chiral MOF crystallized in the F23 space group with the same topological structure as that of UiO-66. The obtained BINAPDA-Zr-MOF can be a very active catalyst to catalyze aldehyde cyanosilylation. In addition, the chiral BINAPDA-Zr-MOF was a typical solid catalyst, which was proved by a hot leaching test; moreover, it could be reused at least five times without loss of its catalytic activity and enantioselectivity.

14.
J Insect Physiol ; 116: 125-133, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31128084

RESUMO

Wolbachia are intracellular bacteria carried by thousands of arthropod species. The success of Wolbachia is due to efficient vertical transmission by the host maternal germline. Wolbachia's behavior during host oogenesis is well characterized, although their behavior during embryogenesis is unclear. Vertical transmission of Wolbachia wStri in the small brown planthopper, Laodelphax striatellus is extraordinarily efficient. To understand why, we investigated its localization and dynamics in L. striatellus embryos. Microscopic observations indicated that the Wolbachia were mainly localized at the anterior region of the embryo during early embryogenesis. The distribution of Wolbachia within the anterior region was established during oogenesis, and according to a phylogenetic analysis, may be due to intrinsic factors in Wolbachia. We observed that wStri migrated to the posterior part cells during late embryogenesis, in the region where gonads were formed. An expression profile of Wolbachia-infected host embryonic development genes revealed Ddx1 mRNAs, which is required for host viability and in the germ line, accumulated in the posterior region of 3-day-old embryos, while other development genes mRNAs were significantly more abundant in the posterior region of 6-day-old embryos. These genes thus appear to be associated with the localization of Wolbachia wStri in the anterior region, although their functions remain unclear. These results can explain Wolbachia wStri high prevalence in L. striatellus.

15.
Target Oncol ; 14(3): 269-283, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31069647

RESUMO

Developments in systemic therapies beyond traditional cytotoxic chemotherapy have resulted in an unparalleled number of US Food and Drug Administration approvals in the past 5 years for ovarian, endometrial, and cervical cancer. In this review, we highlight registration trials leading to recent Food and Drug Administration approvals for targeted systemic therapies in advanced gynecologic malignancies, encompassing three classes of agents: the antiangiogenic anti-vascular endothelial growth factor antibody bevacizumab in ovarian and cervical cancer, poly (ADP-ribose) polymerase inhibitors in ovarian cancer, and the immune checkpoint inhibitor pembrolizumab in cervical and endometrial cancer. The addition of bevacizumab to chemotherapy has been approved in frontline and relapsed advanced ovarian cancer, in both platinum-resistant and platinum-sensitive settings. Three poly (ADP-ribose) polymerase inhibitors are approved for women with ovarian cancer. Olaparib and rucaparib are utilized in recurrent germline or somatic BRCA mutated ovarian cancer. Along with a third poly (ADP-ribose) polymerase inhibitor, niraparib, they are also Food and Drug Administration approved as maintenance therapy regardless of BRCA mutation status for patients with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy. More recently, olaparib was approved as maintenance therapy for BRCA mutated ovarian cancer following first-line platinum-based chemotherapy. Pembrolizumab has been approved for relapsed cervical cancer with programmed death ligand 1 positivity and relapsed solid tumors with mismatch repair deficiency, which applies to 30% of endometrial cancers. Together, these therapies represent the advent of personalized medicine in gynecologic malignancies. Additional information is required to determine cost-effective strategies for incorporating these therapies and rational means of sequencing these agents.

16.
J Cell Physiol ; 234(12): 22331-22342, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31140597

RESUMO

Ovarian cancer characterizes as the fourth leading consequence of death associated with cancer for women. Accumulating evidence underscores the vital roles of microRNAs (miRNAs) in preventing ovarian cancer development. Besides, induction of the phosphatidylinositol-3 kinase/serine/threonine kinase (PI3K/Akt) pathway associated with the ovarian cancer cell migration and invasion. The study aims to examine the effects of miR-15b on the proliferation, apoptosis, and senescence of human ovarian cancer cells by binding to lysophosphatidic acid receptor 3 (LPAR3) with the involvement of the PI3K/Akt pathway. The positive expression of LPAR3 protein was detected by immunohistochemistry. Then the interaction between miR-15b and LPAR3 was examined. The possible role of miR-15b in ovarian cancer was explored using gain- and loss-of-function experiments. Subsequently, the functions of miR-15b on PI3K/Akt pathway, proliferation, migration, invasion, senescence and apoptosis of ovarian cancer cells were assessed. Furthermore, in vivo tumorigenicity assay in nude mice was performed. LPAR3 was overexpressed, whereas miR-15b was poorly expressed in ovarian cancer tissues. LPAR3 is a direct target of miR-15b. Restored miR-15b promoted Bax expression, apoptosis, and senescence, inhibited expression of LPAR3 and Bcl-2, the extent of PI3K and Akt phosphorylation, as well as ovarian cancer cell proliferation, migration, and invasion. Further, tumor growth was observed to be prevented by miR-15b overexpression. Collectively, our study demonstrates that miR-15b represses the proliferation and drives the senescence and apoptosis of ovarian cancer cells through the suppression of LPAR3 and the PI3K/Akt pathway, highlighting an antitumorigenic role of miR-15b.

17.
Food Chem Toxicol ; 129: 291-300, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059746

RESUMO

Methylglyoxal (MGO), a cytotoxic factor, reacts irreversibly with the side chains of lysine, cysteine, and arginine residues in proteins to form advanced glycation end products (AGEs) which might be a major pathological factor associated with diabetic complications. Thus, it is necessary to prevent or alleviate such diseases through inhibiting the formation of AGEs or lowering these AGEs-induced cellular damages. Based on our previous work, it was known that phloretin, an apple polyphenol, can inhibit the formation of AGEs under simulated physiological conditions. In this study, we found that phloretin prevented the formation of AGEs through trapping MGO in human umbilical endothelial cells (HUVECs). The phloretin-MGO adducts were analyzed in PBS and HUVECs. Surprisingly, only 1 MGO-phloretin adduct was detected in HUVECs, which was formed within 0.5 h and metabolized eventually within 24 h. The specific phloretin-MGO adduct was synthesized and identified by MS and NMR analysis. Its anti-inflammatory effect against AGEs was further investigated together with the parent compound, phloretin, which was proved to be through RAGE/p38 MAPK/NF-κB signaling pathway. Taken together, our data indicated the positive role of phloretin-MGO adduct on phloretin's protective effects, which might offer a new insight into the action mechanism of polyphenols against AGEs-induced damages.


Assuntos
Endotélio Vascular/efeitos dos fármacos , Produtos Finais de Glicação Avançada/metabolismo , Inflamação/metabolismo , Floretina/farmacologia , Aldeído Pirúvico/farmacologia , Sistema Livre de Células , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , NF-kappa B/metabolismo , Floretina/química , Polifenóis/farmacologia , Aldeído Pirúvico/química , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Org Biomol Chem ; 17(25): 6069-6098, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31090773

RESUMO

Palladium pincer complexes, containing a monoanionic terdentate ligand composed of an anionic aryl carbon atom and two mutually compatible donor sites, have aroused considerable interest since their first reports in the late 1970s. The high stability of the Pd pincer complexes and particularly their high modularity make these species ideal candidates for catalysis. Furthermore, the nature of the meridional coordination of the pincer ligands, and along with this their ability to enforce a stereo-specific environment around the Pd center, provide a good opportunity for developing chiral Pd pincer catalysts. Thus, a broad variety of chiral Pd pincer complexes have been prepared by the introduction of various stereochemical centers in the pincer skeletons. These chiral Pd pincer complexes have been successfully applied to many asymmetric catalytic reactions such as hydrophosphination reactions, allylation of aldehydes and imines, Michael and aldol reactions, Suzuki-Miyaura reactions as well as reactions of nitrile compounds with imines. This review focuses on the synthetic methods and the applications of chiral Pd pincer complexes in asymmetric catalysis.

19.
Org Biomol Chem ; 17(20): 5029-5037, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31045200

RESUMO

The first nickel(ii)-catalyzed direct sulfuration/annulation of C(sp2)-H bonds with elemental sulfur has been achieved by using 2-amino alkylbenzimidazole (MBIP-amine) as a N,N-bidentate directing group. This strategy tolerates a wide range of functional groups, furnishing structurally diverse benzoisothiazolone derivatives with benzimidazole skeletons in moderate to excellent yields in a simple and efficient way.

20.
Biotechnol Appl Biochem ; 66(4): 591-596, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31050059

RESUMO

Glucose-6-phosphate dehydrogenase (G6PDH) has been used in enzyme multiplied immunoassay technique (EMIT) assays for detecting small molecule metabolites such as cholyglycine (CG). A key parameter for successful EMIT CG assay development is the inhibition rate of the G6PDH-CG conjugate, measured as the decrease in enzyme activity upon CG antibody binding. Several commonly used G6PDH cysteine mutants including A45C and K55C have been labeled with CG-maleimide derivative, but inhibition rates of are unsatisfactory. Herein, we investigated whether other mutation sites can achieve better inhibition rates. We generated eight cysteine mutants (K106C, Y155C, A201C, T258C, D306C, D375C, G426C, and D480C) of G6PDH, measured their inhibition rates, and evaluated the performance of the D306C mutant using EMIT CG assays. One of the eight mutants (D306C) displayed improved inhibition rate, whereas all others exhibited inhibition similar to or lower than that of A45C and K55C. The enhanced inhibition rate of D306C improved the EMIT CG assay calibration curve, using an Abbott c16000 automated biochemical analyzer, resulting in better repeatability, precision, and linearity than with K55C assays and a commercially available EMIT CG kit. The G6PDH mutant D306C has a higher inhibition rate in EMIT CG assays and improves assay performance.

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