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1.
J Agric Food Chem ; 67(45): 12382-12392, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31635461

RESUMO

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is a promising target for herbicide discovery. Search for new compounds with novel chemotypes is a key objective for agrochemists. Here, we describe the discovery and systematic SAR-based structure optimization of novel N-isoxazolinylphenyltriazinones 5-9 as PPO inhibitors. The in vivo herbicidal activity and in vitro Nicotiana tabacum PPO (NtPPO) inhibitory activity were explored in detail. A number of the new synthetic compounds displayed strong PPO inhibitory activity with Ki values in the nanomolar range. Some compounds exhibited excellent and broad-spectrum weed control at the rate of 9.375-37.5 g ai/ha by postemergence application and showed improved monocotyledonous weed control compared to saflufenacil. Most promisingly, ethyl 3-(2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluorophenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate, 5a, with a Ki value of 4.9 nM, displayed over 2- and 6-fold higher potency than saflufenacil (Ki = 10 nM) and trifludimoxazin (Ki = 31 nM), respectively. Moreover, 5a showed excellent and broad-spectrum weed control against 32 kinds of weeds at 37.5-75 g ai/ha. Rice exhibited relative tolerance to 5a at 150 g ai/ha by postemergence application, indicating that 5a could be a potential herbicide candidate for weed control in paddy fields.


Assuntos
Inibidores Enzimáticos/farmacologia , Herbicidas/química , Herbicidas/farmacologia , Proteínas de Plantas/antagonistas & inibidores , Protoporfirinogênio Oxidase/antagonistas & inibidores , Descoberta de Drogas , Inibidores Enzimáticos/química , Cinética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Plantas Daninhas/química , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/enzimologia , Protoporfirinogênio Oxidase/química , Protoporfirinogênio Oxidase/metabolismo , Relação Quantitativa Estrutura-Atividade , Tabaco/química , Tabaco/efeitos dos fármacos , Tabaco/enzimologia , Controle de Plantas Daninhas
2.
Chem Commun (Camb) ; 55(79): 11888-11891, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31528874

RESUMO

A novel type of oxime phosphonate was synthesized and used in the intermolecular cascade radical addition reaction of alkenes to access ß-aminophosphonates via visible-light-driven N-centered iminyl radical-mediated and redox-neutral selective C-P single-bond cleavage in an active phosphorus radical route. The procedure is characterized by its ability to achieve the construction of Csp3-P and Csp3-N bonds without the requirement for oxidants and bases.

3.
Ying Yong Sheng Tai Xue Bao ; 30(6): 1919-1926, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31257764

RESUMO

Microbial oxidation is the only biological sink of atmospheric methane (CH4). It is essential to understand the variation of CH4 fluxes among different grassland use types for developing low-emission management system. Here, we measured the CH4 flux and the soil methane-oxidizing bacteria abundance in a typical steppe under grazing, mowing and fencing management in central Inner Mongolia, with the aims to determine the effects of these grassland use types on CH4 flux, and to test the hypothesis that pmoA functional gene abundance regulates CH4 fluxes. The measurements were conducted on the experimental grassland that had experienced four grassland use treatments over five years. The treatments were whole growing season grazing from May to September (T1), spring and summer grazing (twice in May and July)(T2), autumn mowing (T3) and enclosure (T0). We measured CH4 flux using static chamber method, and quantified the abundance of pmoA functional genes using molecular techniques. Moreover, we measured plant biomass and soil physicochemical properties. The results showed that moderate grazing significantly enhanced CH4 uptake rate and the methane-oxidizing bacteria abundance (i.e., the pmoA gene copy number per gram of dry soil). The pmoA gene copy number ranged from 6.9×104 to 3.9×105 per gram of dry soil in growing season. The CH4 uptake rate was (68.21±3.01) µg·m-2·h-1 under T1, which was 22.1%, 37.5% and 30.9% higher than that under T2, T3 or T0 , respectively. The CH4 uptake rate was positively correlated with abundance of CH4 oxidizing bacteria and soil sand content, but negatively correlated with soil silt content, soil moisture, NH4+-N and NO3--N content, and plant biomass. These results suggested that the steppe ecosystem is a CH4 sink under all land-use types in central Inner Mongolia, and that moderate grazing would enhance methane-oxidizing bacteria abundance and CH4 uptake by improving soil sand content, reducing soil mineral nitrogen content and plant production in the typical steppe ecosystem. These results were of significance for the development of low-emission grassland management system.


Assuntos
Ecossistema , Metano/análise , Methylococcaceae/fisiologia , China , Solo
4.
Org Biomol Chem ; 17(20): 4970-4974, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31049547

RESUMO

With H2WO4 as the catalyst and H2O2 as the oxidant, we herein report a deconstructive difunctionalization of the C-N bond in unstrained, benzo cyclic amines to generate an ester group and nitro group simultaneously. The preliminary mechanistic studies suggested that the corresponding hydroxamic acid is the key intermediate for this transformation. Importantly, with the utilization of this transformation, we achieved an interesting approach for the ring contraction of quinoline to indole, an example of scaffold hopping in a hetero-aromatic system.

5.
Eur J Med Chem ; 167: 472-484, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30784880

RESUMO

Since pyrithiobac (PTB) is a successful commercial herbicide with very low toxicity against mammals, it is worth exploring its derivatives for an extensive study. Herein, a total of 35 novel compounds were chemically synthesized and single crystal of 6-6 was obtained to confirm the molecular structure of this family of compounds. The novel PTB derivatives were fully evaluated against various biological platforms. From the bioassay results, the best AHAS inhibitor 6-22 displayed weaker herbicidal activity but stronger anti-Candida activity than PTB did. For plant pathogenic fungi, 6-26 showed excellent activity at 50 mg/L dosage. Preliminary insecticidal activity and antiviral activity were also observed for some title compounds. Strikingly, 6-5 exhibited a promising inhibitory activity against SARS-CoV Mpro with IC50 of 4.471 µM and a low cellular cytotoxicity against mammalian 293 T cells. Based on the results of molecular modeling, HOMO-1 was considered to be a factor that affects AHAS inhibition and a possible binding mode of 6-5 with SARS-CoV Mpro was predicted. This is the first time that PTB derivatives have been studied as biological agents other than herbicides. The present research hence has suggested that more attentions should be paid to compounds belonging to this family to develop novel agrochemicals or medicines.


Assuntos
Benzoatos/síntese química , Benzoatos/farmacologia , Fungos/efeitos dos fármacos , Herbicidas/síntese química , Acetolactato Sintase/antagonistas & inibidores , Antivirais/síntese química , Antivirais/farmacologia , Benzoatos/química , Desenho de Drogas , Herbicidas/farmacologia , Herbicidas/uso terapêutico , Modelos Moleculares , Estrutura Molecular , Vírus da SARS/efeitos dos fármacos
6.
J Sports Med Phys Fitness ; 59(11): 1798-1804, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30722652

RESUMO

BACKGROUND: Stereopsis is the most important part of depth perception, especially in athletic population. At present, there are few studies on how to comprehensively evaluate athletes' stereoscopic function and how the impairment of stereoscopic function affects sports performance. METHODS: Twenty-two professional table-tennis players from Sichuan Province Team were recruited as player group and 23 age-matched students were recruited as the controls. All subjects were measured the habitual visual acuity, best corrected visual acuity, dominant eye, retinoscopy and three stereo acuity tests. Both groups completed two motor skills tasks: Purdue Pegboard and beads threading with habitual binocular viewing and monocular viewing by covering dominant eye. In addition, the player group was asked to complete a brief questionnaire and catch balls served by the auto table-tennis machine under two viewing conditions. RESULTS: The player group had better stereo acuity with median values of 60, 25 and 40 arc sec in TNO, Butterfly, and Frisby tests, respectively. There had statistically correlations between stereo acuity and two motor skills tasks. Both the two tasks were statistically significant different between binocular and monocular viewings in both groups. The player group had better performance on Purdue Pegboard task with binocular viewing (16±1.1, P=0.006) compared to the control group, while no statistical difference was found under monocular condition in beads threading task. In player group, the brief questionnaire demonstrated very negative feeling of players under monocular viewing and the number of catching balls had statistically significant difference between binocular (9.9±0.3) and monocular (6.9±1.6) viewings (P<0.001). CONCLUSIONS: Stereopsis plays an important role in sports performance, the stereo tests combined with Purdue pegboard can be used to evaluate athletes' stereoscopic function comprehensively.

7.
Urol Oncol ; 37(1): 71-77, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30446465

RESUMO

PURPOSE: There are limited therapeutic options for patients with advanced penile squamous cell carcinoma (PSCC) after chemotherapy failure. Thus, we evaluated the feasibility of salvage treatment using the epidermal growth factor receptor (EGFR) mono-antibody nimotuzumab in chemotherapy-failed PSCC patients and explored potential response or resistance biomarkers. MATERIALS AND METHODS: Six chemotherapy-failed PSCC patients with locally advanced disease or distant metastasis were enrolled consecutively to nimotuzumab treatment. Clinical responses and side effects were evaluated, and genetic characteristics of cancer specimens were analyzed through the next-generation sequencing of hotspot regions in cancer-related genes. RESULTS: Two of 6 patients showed partial responses, one was identified as having stable disease, while the other 3 had disease progression after nimotuzumab therapy. Side effects were all welltolerated. Genetic analysis revealed that TP53, CDKN2A, RB1, SMAD4, FLT3, and PIK3CA were the most frequently mutated genes in PSCC specimens, while altered KRAS, HRAS, EGFR, ERBB2, and FLT3 may be correlated with nimotuzumab resistance. Furthermore, 3 patients that were human papillomavirus-positive each showed clinical response or stable disease. CONCLUSIONS: EGFR mono-antibody may be a potential modality for locally advanced PSCC patients after chemotherapy failure. Further large-scale clinical studies are needed to elucidate the role of human papillomavirus status and critical gene mutations in the clinical response to EGFR-targeted therapy.


Assuntos
Neoplasias Penianas/terapia , Terapia de Salvação/métodos , Adulto , Idoso , Receptores ErbB , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Penianas/patologia
8.
Cancer Commun (Lond) ; 38(1): 68, 2018 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-30470255

RESUMO

BACKGROUND: The 8th American Joint Committee on Cancer tumor-node-metastasis (AJCC-TNM) staging system is based on a few retrospective single-center studies. We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular embolization could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer. METHODS: A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system. The internal validation was analyzed by bootstrap-corrected C-indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation. RESULTS: A survivorship overlap was observed between T2 and T3 patients (P = 0.587) classified according to the 8th AJCC-TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P < 0.001). Based on the multivariate analysis, only lymphovascular embolization showed a significant influence on cancer-specific survival (CSS) (hazard ratio = 1.587, 95% confidence interval = 1.253-2.011; P = 0.001). T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascular embolization (P < 0.001). Therefore, a modified clinicopathological staging system was proposed, with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows: t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion, and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion. The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories (all P < 0.005) and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system (C-index, 0.739 vs. 0.696). These results were confirmed in the external validation cohort. CONCLUSIONS: T2-3 penile cancers are heterogeneous, and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system. Trial registration This study was retrospectively registered on Chinese Clinical Trail Registry: ChiCTR16008041 (2016-03-02). http://www.chictr.org.cn.


Assuntos
Metástase Linfática/patologia , Neoplasias Penianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Penianas/patologia , Prognóstico , Análise de Sobrevida , Adulto Jovem
9.
Clin Cancer Res ; 24(24): 6319-6330, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30305293

RESUMO

PURPOSE: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial-mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells' EMT and explored their regulatory mechanisms and clinical significance in UCBs. EXPERIMENTAL DESIGN: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells' EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA). RESULTS: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis. CONCLUSIONS: CircPRMT5 exerts critical roles in promoting UCB cells' EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.


Assuntos
Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Proteína-Arginina N-Metiltransferases/genética , RNA , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Caderinas/metabolismo , Carcinoma de Células de Transição/metabolismo , Linhagem Celular Tumoral , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Interferência de RNA , Transdução de Sinais , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Neoplasias da Bexiga Urinária/metabolismo
10.
Cancer Manag Res ; 10: 2983-2995, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214293

RESUMO

Purpose: Molecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC. Patients and methods: This study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan-Meier analysis with a log-rank test was used for the survival analysis. Results: LAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer. Conclusion: These findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients.

11.
Cancer Lett ; 435: 10-22, 2018 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-30075204

RESUMO

Clinically, most of human urothelial carcinoma of the bladder (UCB)-related deaths result from tumor metastasis, but the underlying molecular mechanisms are largely unknown. Recently, a growing number of tripartite motif (TRIM) family members have been suggested to be important regulators for tumorigenesis. However, the impact of most TRIM members on UCB pathogenesis is unclear. In this study, TRIM65 was first screened as an important oncogenic factor of UCB from the Cancer Genome Atlas (TCGA) database and was validated by a large cohort of clinical UCB tissues. By in vitro and in vivo experiments, we demonstrated that TRIM65 promotes UCB cell invasive and metastatic capacities. Notably, we showed that TRIM65 modulates cytoskeleton rearrangement and induces UCB cells epithelial-mesenchymal transition by the ubiquitination of ANXA2, ultimately leading to an enhanced invasiveness of UCB cells. Importantly, UCBs with high expression of TRIM65 and low expression of ANXA2 showed the poorest outcome. Collectively, our results suggest that the overexpression of TRIM65 has an essential oncogenic role via ubiquitination of ANXA2 in UCB pathogenesis, and that such could be used as a novel prognostic marker and/or therapeutic target for UCB.


Assuntos
Anexina A2/genética , Carcinoma de Células de Transição/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Neoplasias da Bexiga Urinária/genética , Animais , Anexina A2/metabolismo , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteólise , Transdução de Sinais/genética , Transplante Heterólogo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
12.
Org Lett ; 20(8): 2382-2385, 2018 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-29624398

RESUMO

A new approach to the synthesis of 2-phosphinoylindoles through photoredox catalysis without external oxidants has been developed. Promoted by a ruthenium photoredox catalyst, a broad scope of 2-phosphinoylindoles can be synthesized through phosphinoylation/cyclization of diphenylphosphine oxide at room temperature under irradiation without external oxidants. The estrone skeleton isocyan is also an amenable substrate for this cyclization, yielding a molecule that has potential medicinal applications.

13.
Oncotarget ; 8(31): 51542-51550, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28881666

RESUMO

PURPOSE: In this study, we assess the CK2α expression in human penile squamous cell carcinoma (SCC) and its clinical significance. METHODS: A total of 157 human penile SCC tissue samples were immunohistochemically analyzed. In addition, 12 human penile SCC and adjacent normal tissues were examined for CK2α protein and mRNA expression by Western blotting and real-time quantitative PCR, respectively. Survival was analyzed using the Kaplan-Meier test and the log-rank test. Multivariate Cox proportional hazard regression analysis was performed to determine the impacts of CK2α expression and the clinicopathological features on patient disease-specific survival (DSS). Likelihood ratios (LRs), Akaike information criterion (AIC) values, and concordance indexes (C-indexes) were investigated to evaluate the accuracies of the factors. Bootstrap-corrected C-indexes were used for internal validation (with sampling 1000 times). RESULTS: A significant difference in the distribution of CK2α was observed between the normal and penile carcinoma tissues (P<0.001). CK2α expression was associated with the pathological T and N stages in the penile cancer tissues (P<0.001). High CK2α expression was with significantly poorer DSS compared with low expression one (P<0.001). Western blotting and real-time quantitative PCR also confirmed that CK2α expression was increased in the penile cancer tissues. In multivariate Cox regression analysis, CK2α overexpression still was one of independent prognostic factors for penile SCC (P=0.005). The predictive accuracy of CK2α was verified by analysis of the C-indexes. CONCLUSION: High protein kinase CK2α expression is associated with several prognostic factors and is thus a significant indicator of poor prognosis for penile cancer.

14.
Drug Des Devel Ther ; 11: 2387-2397, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28860710

RESUMO

Alginate oligosaccharide (AOS) has recently demonstrated the ability to protect against acute doxorubicin cardiotoxicity and neurodegenerative disorders by inhibiting oxidative stress and endoplasmic reticulum (ER) stress-mediated apoptosis, which are both involved in myocardial ischemia/reperfusion (I/R) injury. In the present study, we investigated whether pretreatment with AOS protects against myocardial I/R injury in mice and explored potential cardioprotective mechanisms. AOS pretreatment significantly decreased the infarct size, reduced the cardiac troponin-I concentration, and ameliorated the cardiac dysfunction. Accompanied with the reduced cardiac injury, AOS pretreatment clearly decreased I/R-induced myocardial apoptosis. With regard to mechanism, AOS pretreatment markedly attenuated nitrative/oxidative stress, as evidenced by decreases in 3-nitrotyrosine content and superoxide generation, and downregulated inducible nitric oxide synthase, NADPH oxidase2, and 4-hydroxynonenal. Moreover, AOS pretreatment decreased myocardial apoptosis by inhibiting the ER stress-mediated apoptosis pathway, which is reflected by the downregulation of C/EBP homologous protein, glucose-regulated protein 78, caspase-12, and Bcl-2-associated X protein, and by the upregulation of the anti-apoptotic protein B-cell lymphoma-2. Collectively, these findings demonstrate that AOS renders the heart resistant to I/R injury, at least in part, by inhibiting nitrative/oxidative stress and ER stress-mediated apoptosis.


Assuntos
Alginatos/química , Cardiotônicos/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Oligossacarídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Cardiotônicos/química , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/patologia , Estresse Nitrosativo/efeitos dos fármacos , Oligossacarídeos/química , Estresse Oxidativo/efeitos dos fármacos , Superóxidos/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo
15.
J Agric Food Chem ; 65(35): 7661-7668, 2017 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-28813155

RESUMO

The degradation issue of sulfonylurea (SU) has become one of the biggest challenges that hamper the development and application of this class of herbicides, especially in the alkaline soils of northern China. On the basis of the previous discovery that some substituents on the fifth position of the benzene ring in Chlorsulfuron could hasten its degradation rate, apparently in acidic soil, this work on Metsulfuron-methyl showed more convincing results. Two novel compounds (I-1 and I-2) were designed and synthesized, and they still retained potent herbicidal activity in tests against both dicotyledons and monocotyledons. The half-lives of degradation (DT50) assay revealed that I-1 showed an accelerated degradation rate in acidic soil (pH 5.59). Moreover, we delighted to find that the degradation rate of I-1 was 9-10-fold faster than that of Metsulfuron-methyl and Chlorsulfuron when in alkaline soil (pH 8.46), which has more practical value. This research suggests that a modified structure that has potent herbicidal activity as well as accelerated degradation rate could be realized and this approach may provide a way to improve the residue problem of SUs in farmlands with alkaline soil.


Assuntos
Herbicidas/química , Poluentes do Solo/química , Compostos de Sulfonilureia/química , China , Cinética , Solo/química
16.
BMC Surg ; 17(1): 8, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-28095848

RESUMO

BACKGROUND: Many studies have reported the oncological outcomes between open radical nephroureterectomy (ONU) and laparoscopic radical nephroureterectomy (LNU) of upper tract urothelial carcinoma (UTUC). However, few data have focused on the oncological outcomes of LNU in the subgroup of localized and/or locally advanced UTUC (T1-4/N0-X). The purpose of this study was to compare the oncological outcomes of LNU vs. ONU for the treatment in patients with T1-4/N0-X UTUC. METHODS: We collected and analyzed the data and clinical outcomes retrospectively for 265 patients who underwent radical nephroureterectomy for T1-4/N0-X UTUC between April 2000 and April 2013 at two Chinese tertiary hospitals. Survival was estimated using the Kaplan-Meier method. Cox's proportional hazards model was used for univariate and multivariate analysis. RESULTS: The mean patient age was 62.0 years and the median follow-up was 60.0 months. Of the 265 patients, 213 (80.4%) underwent conventional ONU, and 52 (19.6%) patients underwent LNU. The groups differed significantly in their presence of previous hydronephrosis, presence of previous bladder urothelial carcinoma, and management of distal ureter (P < 0.05). The predicted 5-year intravesical recurrence- free survival (RFS) (79% vs. 88%, P = 0.204), overall RFS (47% vs. 59%, P = 0.076), cancer-specific survival (CSS) (63% vs. 70%, P = 0.186), and overall survival (OS) (61% vs. 55%, P = 0.908) rates did not differ between the ONU and LNU groups. Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with intravesical RFS (odds ratio [OR] 1.23, 95% confidence interval [CI] 0.46-3.65, P = 0.622), Overall RFS (OR 0.99, 95% CI 0.54-1.83, P = 0.974), CSS (OR 1.38, 95% CI 0.616-3.13, P = 0.444), or OS (OR 1.61, 95% CI 0.81-3.17, P = 0.17). CONCLUSIONS: The results of this retrospective study showed no statistically significant differences in intravesical RFS, overall RFS, CSS, or OS between the laparoscopy and the open groups. Thus, LNU can be an alternative to the open procedure for T1-4/N0-X UTUC. Further studies, including a multi-institutional, prospective study are required to confirm these findings.


Assuntos
Carcinoma de Células de Transição/cirurgia , Laparoscopia , Nefrectomia , Neoplasias Ureterais/cirurgia , Idoso , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/patologia
17.
J Cancer Res Clin Oncol ; 143(2): 329-335, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27771796

RESUMO

BACKGROUND: Current guidelines recommend pelvic lymphadenectomy (PLND) for patients with pelvic lymph node metastasis and special state. However, these data and recommendations do not distinguish the role of PLND in different patient groups and confirm the final benefits. The aim of this study was to confirm the efficacy of pelvic lymphadenectomy (PLND) for the different groups of patients. METHODS: Data obtained from 7 centers were retrospectively analyzed. Of the patients, 190 pN2-3 penile carcinoma patients confirmed by bilateral inguinal lymph node excision were included in this study. Sixty-nine and 121 of these patients did and did not undergo bilateral PLND, respectively. The baseline differences from the patients were matched by propensity score analysis. RESULTS: In this study, the Kaplan-Meier estimated disease-specific survival (DSS) was not significantly different between the PLND and no-PLND groups (P = 0.796). According to the propensity score matching for T stage, N stage, grade, adjuvant therapies, and lymph node stage (number of inguinal lymph node metastasis and extranodal extension), 48 patients were selected for each group. Among the pN2 patients, the PLND group showed higher DSS rates than the no-surgery group (P = 0.030). However, even after matching, survival did not differ between the PLND and no-PLND patients among all patients (P = 0.609) and pN3 patients (P = 0.417) with comparable DSS. CONCLUSION: Bilateral PLND may improve survival in pN2 patients. Men with pN3 may not benefit from bilateral PLND.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Linfonodos/cirurgia , Neoplasias Penianas/cirurgia , Adulto , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Terapia Combinada , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pelve , Neoplasias Penianas/mortalidade , Neoplasias Penianas/patologia , Estudos Retrospectivos , Resultado do Tratamento
18.
Bioorg Med Chem Lett ; 26(19): 4661-4665, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27575481

RESUMO

A series of novel 5-substituted-1,3,4-oxadiazole Mannich bases and bis-Mannich bases have been conveniently synthesized in good yields. Their structures were characterized by IR, (1)H NMR, (13)C NMR and elemental analysis. The preliminary bioassay results indicated that some of the compounds showed promising in vitro fungicidal activities towards several test plant fungi; some of them exhibited significant herbicidal activities against Brassica campestris and excellent in vitro inhibitory activities against rice ketol-acid reductoisomerase (KARI). Among 14 novel compounds, 8c, 8d and 8m showed potent KARI inhibitory activities with Ki value of (0.96±0.42), (3.86±0.49) and (3.10±0.71) µmol/L, respectively, and were comparable with IpOHA. These compounds could be novel KARI inhibitors for further investigation. The density functional theory (DFT) calculations and molecular docking were carried out to study the structure-activity relationship (SAR) of the active inhibitors in this Letter.


Assuntos
Inibidores Enzimáticos/farmacologia , Cetol-Ácido Redutoisomerase/antagonistas & inibidores , Bases de Mannich/síntese química , Bases de Mannich/farmacologia , Oxidiazóis/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Bases de Mannich/química , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Espectrofotometria Infravermelho , Relação Estrutura-Atividade
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(5): 701-4, 2016 May.
Artigo em Chinês | MEDLINE | ID: mdl-27222189

RESUMO

OBJECTIVE: To evaluate the efficacy of periprostatic nerve block anesthesia (PPNB) for pain relief in transrectal ultrasound-guided systematic prostate biopsy (PBx). METHODS: We reviewed the data of patients undergoing initial PBx at our center from November, 2013 to January, 2015. Only the patients with 12-core systemic PBx were included and 111 patients were eligible for this study, among whom 52 patients received PPNB and 59 did not. PPNB was achieved by an injection of 5 mL of 1% lidocaine at the angle between the seminal vesicle and base of the prostate on each side before biopsy. The DRE pain score, probe insert pain score, and biopsy pain score were assessed by visual analogue scale (VAS) immediately after the biopsy. The complications were recorded and evaluated immediately after and at 7 days after the biopsy. RESULTS: The mean age, prostate volume, total prostate specific antigen (tPSA), free PSA (fPSA), and abnormal DRE were comparable between the 2 groups (P>0.05). Immediately after the biopsy, no difference was found between the 2 groups in DRE pain score (1.40±0.98 vs 1.39±0.91, P=0.102) or probe insert pain score (2.07±0.96 vs 2.03±0.90, P=0.960), but the biopsy pain score was significantly lower in PPNB group than in no PPNB group (2.54±1.42 vs 3.07±1.43, P=0.033). The incidence of the procedure-related complications was similar between the 2 groups (P>0.05). CONCLUSION: PPNB can significantly lower the biopsy pain score in PBx without increasing the incidence of complications.


Assuntos
Biópsia , Lidocaína/uso terapêutico , Bloqueio Nervoso , Manejo da Dor/métodos , Próstata/diagnóstico por imagem , Humanos , Masculino , Dor/prevenção & controle , Medição da Dor , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Ultrassonografia
20.
Eur J Med Chem ; 117: 167-78, 2016 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-27092414

RESUMO

A series of novel carboxamide compounds 19a-19j, 20a-20j and 22a-22d containing piperazine and arylsulfonyl moieties have been synthesized. The bioassay results showed that some compounds exhibited favorable herbicidal activities against dicotyledonous plants and many of them possessed excellent antifungal activities. Among 24 novel compounds, some showed superiority over the commercial fungicides Chlorothalonil, Dimethomorph, Thiophanate-methyl, Iprodione, and Zhongshengmycin at 500 mg/L concentration. Some compounds also exhibited high KARI inhibitory activity at 100 µg/mL concentration and could be used as new KARI lead inhibitors for further studies. Moreover, SAR of these new compounds were comprehensively investigated using different computational methods in which 3D-QSAR model obtained provided useful information for further structural optimization for the discovery of new fungicides. The results of this research will contribute to explore comprehensive biological activities of piperazine-containing compounds in different areas of chemistry.


Assuntos
Amidas/síntese química , Antifúngicos/síntese química , Herbicidas/síntese química , Relação Quantitativa Estrutura-Atividade , Amidas/farmacologia , Antifúngicos/farmacologia , Ácidos Arilsulfônicos/química , Herbicidas/farmacologia , Piperazina , Piperazinas/química
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