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1.
Food Chem ; 304: 125446, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31491715

RESUMO

Fused coumarins recently attracted strong scientific interest due to their potent pharmacological activities. In this study, density functional theory (DFT) calculations were performed to evaluate the antiradical activities of a series of coumarin-fused coumarins. By calculating the thermodynamic parameters, three primary mechanisms including hydrogen atom transfer (HAT), electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) were examined. It was found that in the gas and benzene phases, the studied compounds prefer to undergo HAT mechanism, while SPLET is more favored in polar media. The results also reveal the possibility of double HAT and double SPLET mechanisms for compound CC-6. Interestingly, a new polycyclic compound was generated by forming a new C5-O5' bond during the second HAT process at the 5'-OH in CC-6-R6 radical. In addition, the SPLHAT mechanism is proposed as a competitive pathway for radical scavenging by CC-4, CC-5 and CC-6.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31564529

RESUMO

BACKGROUND: To evaluate and compare the results of three different cervical cancer screening strategies including cytology screening, HR-HPV screening which taking HR-HPV testing as primary test and co-testing which taking both tests at the same time, then provide evidence to explore whether the cervical cancer screening can be conducted in community healthcare centers in Beijing. METHODS: 182,119 women aged between 35 and 64, who were screened in the primary healthcare facilities of nine districts in Beijing from January 2014 to March 2015, were enrolled in this study. Cytology screening was performed in participants during January 2014 and December 2014 as a conventional arm. HR-HPV screening strategy and co-testing were randomly allocated to participants on districts level as experimental arm 1 and 2 during January 2015 and March 2015. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN 2+) was defined as endpoint. The screening results and costs to detect a case of three strategies were calculated. RESULTS: The positivity rate, colposcopy referral rate and biopsy referral rate of co-testing were 8.46%, 6.36% and 4.65% respectively, which were all significantly higher than the other two screening strategies. The detection rate of CIN 2+ by co-testing was 5.06‰ and was much more than the other two screening strategies, while the HR-HPV screening had the highest PPV of 14.40%. The HR-HPV screening ignores some lesion which can be found by co-testing. Co-testing refers a woman to colposcopy with a positive screening result at the least cost, but it costs the most to detect a CIN 2+ case. CONCLUSIONS: To detect more cases of CIN 2+, co-testing performs better although with the most cost. And the primary healthcare facilities in Beijing have the capability to carry out the cervical cancer screen programs and prompts women with positive screen results to the hospital.

4.
Platelets ; : 1-6, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498027

RESUMO

Single-spin methods of preparation of platelet-rich plasma are used widely in private practice, yet they have not been extensively studied and compared. The use of platelet-rich plasma (PRP) by the private practitioner can be facilitated by efficient and predictable PRP preparation. The primary purpose of this study was to study common methods of single-spin PRP preparation to determine their efficiency and variability. Six single-spin methods of PRP production from whole blood were analyzed. The primary measures were mean yield and standard deviation as the quotient of total platelet count in PRP produced divided by total platelet count in whole blood utilized. Each sample was analyzed in triplicate and the results were averaged. Secondary measures included red blood cell count (RBC) and white blood cell count (WBC), concentration ratio, and variable cost per million platelets produced. Sixty-four volunteers provided samples from 30 June 2017 to 30 September 2018. Seventeen to twenty six samples were utilized to assess each method. Yields for the six preparation methods (PMs) varied from 53(±18)% to 72(±13)%. Differences were observed for WBC count (1.8 to 14), Hematocrit (0.8 to 32), platelet concentration (568 to 1062), and variable cost per billion platelets produced ($1.55 to $44.31). All six methods evaluated provided a platelet yield of more than 50%, although two methods were less efficient than the others. Two methods were able to produce leukocyte-poor PRP. Variability was moderate across all methods, suggesting that estimation of platelet yield should be feasible from a baseline platelet count for all methods.

5.
Diabetes Educ ; 45(5): 544-552, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31486339

RESUMO

PURPOSE: The purpose of this study is to identify patient-specific factors, easily obtainable from the electronic medical record (EMR), that are associated with nonattendance to a group Diabetes Self-Management Education and Support (DSMES) program among an adult population with type 2 diabetes. METHODS: This study used a retrospective cohort design, with attendance to a group DSMES session as the primary outcome. The study included adult patients with diagnosed type 2 diabetes who were scheduled for a group DSMES session between March 1, 2013, and June 30, 2017. Patients who were pregnant or who had other types of diabetes (eg, type 1 diabetes, prediabetes, gestational diabetes) were excluded. RESULTS: A higher A1C, required copay for DSMES, low socioeconomic status, increased number of diabetes medications prescribed, the presence of a prescription for any insulin, and a higher calculated total daily dose of insulin were all associated with a decreased likelihood of attendance. Only older age was associated with an increased likelihood of attendance. CONCLUSION: Using the EMR to identify patients who need more intensive intervention strategies can help programs direct resources to those who need them most. Having identified these at-risk individuals, a targeted communication and outreach strategy can be developed to assist these individuals with overcoming barriers to attending DSMES.

6.
Int J Cardiol ; 296: 129-135, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31439425

RESUMO

BACKGROUND: The therapeutic potential of doxorubicin (DOX) is limited by cardiotoxicity. Rubicon is an inhibitory interacting partner of autophagy protein UVRAG. Currently, the role of Rubicon in DOX-induced cardiotoxicity is unknown. In this study, we test the hypothesis that loss of Rubicon attenuates DOX-induced cardiotoxicity. METHODS: A mouse model of acute DOX-induced cardiotoxicity was established by a single intraperitoneal injection of DOX at a dose of 20 mg/kg. Rubicon expression was detected by Western blot. Cardiac damage was determined by measuring activities of lactate dehydrogenase and myocardial muscle creatine kinase in the serum, cytoplasmic vacuolization, collagen deposition, ROS levels, ATP content and mitochondrial damage in the heart. Cardiac morphometry and function were assessed by echocardiography. Markers for autophagy, mitophagy and mitochondrial dynamics were evaluated by Western blot and real time reverse transcription polymerase chain reaction. RESULTS: Rubicon expression was reduced in the heart 16 h after DOX treatment. DOX induced accumulation of cytoplasmic vacuolization and collagen, increased serum activities of lactate dehydrogenase and myocardial muscle creatine kinase, enhanced ROS levels, reduced ATP content, pronounced mitochondrial damage and greater left ventricular wall thickness in wild type mice, which were mitigated by Rubicon deficiency. Mechanistically, loss of Rubicon improved DOX-induced impairment of autophagic flux, Parkin-mediated mitophagy and mitochondrial fission and fusion in the heart. CONCLUSIONS: Loss of Rubicon ameliorates DOX-induced cardiotoxicity through enhancement of mitochondrial quality by improving autophagic flux, mitophagy and mitochondrial dynamics. Rubicon is a potential molecular target for prevention and therapy of DOX cardiotoxicity.

7.
Microb Drug Resist ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31441704

RESUMO

ZTW-41, an indolizinoquinoline-5,12-dione derivative, was investigated for antibacterial activity against Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA). In our study, the MIC90s (minimum inhibitory concentrations) of ZTW-41 against MRSA (MRSA, n = 200), methicillin-sensitive S. aureus (MSSA, n = 100), Enterococcus faecalis (E. faecalis, n = 32), and Enterococcus faecium (E. faecium n = 32) were 0.25, 0.25, 0.125, and 8 µg/mL, respectively, whereas the MBC90s (minimum bactericidal concentrations) were 2, 1, 1, and >32 µg/mL, respectively. ZTW-41 maintained its potency at different pH levels (range 5-9) and in starting inoculum size up to 107 CFU/mL. The presence of human serum (25-75%) increased ZTW-41 MICs by two- to eightfold. Time-kill curves showed that ZTW-41 had bactericidal activity against MRSA, MSSA, and E. faecalis strains within 8 hours, and rebound growth occurred after 8 hours except at higher multiples of the MIC (4 × and 8 × ). In the acute toxicity study, no mortality or signs of toxicity was noted in mice after 14 days of observation at doses <50 mg/kg. ZTW-41 exhibited good selectivity indices (SIs) (SI = IC50/MIC90) ranging from 1.12 to 71.76 against clinical isolates, demonstrating excellent therapeutic selectivity in MRSA, MSSA, and E. faecalis strains. Moreover, the in vivo efficacy (effective dose [ED]50 = 6.59 mg/kg) of ZTW-41 was found comparable with vancomycin. Collectively, our favorable results supported ZTW-41 as a promising investigational candidate for treating drug-resistant bacteria infection.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31281800

RESUMO

The frequent emergence of azole-resistant strains has increasingly led azoles to fail in treating candidiasis. Combination with other drugs is a good option to effectively reduce or retard its incidence of resistance. Natural products are a promising synergist source to assist azoles in treating resistant candidiasis. Eucalyptal D (ED), a formyl-phloroglucinol meroterpenoid, is one of the natural synergists, which could significantly enhance the anticandidal activity of fluconazole (FLC) in treating FLC resistant C. albicans. The checkerboard microdilution assay showed their synergistic effect. The agar disk diffusion test illustrated the key role of ED in synergy. The rhodamine 6G (R6G) efflux assay reflected ED could reduce drug efflux, but quantitative reverse transcription PCR analysis revealed the upregulation of CDR1 and CDR2 genes in ED treating group. Efflux pump-deficient strains were hyper-susceptible to ED, thus ED was speculated to be the substrate of efflux pump Cdr1p and Cdr2p to competitively inhibit the excretion of FLC or R6G, which mainly contributed to its synergistic effect.

9.
Am J Chin Med ; 47(5): 1113-1131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31352786

RESUMO

Pulmonary fibrosis (PF) is characterized by myofibroblast activation, which can be triggered by oxidative stress. In this study, we investigated the antifibrotic effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on PF and examined the underlying molecular mechanism. EASM suppressed myofibroblast activation with reduced extracellular matrix deposition in the lungs of mice subjected to bleomycin (BLM) challenge, demonstrating the inhibitory effects on PF. EASM positively alleviated oxidative stress by upregulating nuclear factor-erythroid 2-related factor 2 (Nrf2) and concomitantly downregulating NADPH oxidase 4 (Nox4) in the lungs of BLM-treated mice. This effect was also observed in an in vitro model of transforming growth factor beta 1 (TGF-ß1)-stimulated fibroblast activation. EASM reduced reactive oxygen species (ROS) generation in fibroblasts by stabilizing Nrf2 protein with promoting kelch-like ECH-associated protein 1 (Keap1) degradation. Nrf2 knockdown in the lungs of BLM-treated mice diminished the inhibitory effects of EASM on fibrosis, providing evidence in vivo to address the unique role of Nrf2. Additionally, EASM inhibited TGF-ß1/Smad3 signaling by downregulating protein kinase C delta (PKC-δ) and Smad3 phosphorylation (p-Smad3), which led to suppression of the TGF-ß1-induced fibrogenic response. These results indicate that EASM exhibits potent antifibrotic activity in vitro and in vivo, which might be associated with activation of Nrf2 pathway and inhibition of TGF-ß1/Smad3 pathway. Our findings support that EASM may act as an effective antifibrotic remedy for PF.

10.
Eur J Med Chem ; 178: 81-92, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176097

RESUMO

DNA topoisomerase IB (TOP1) regulates DNA topological structure in many cellular metabolic processes and is a validated target for development of antitumor agents. Our previous study revealed that the benzophenanthridone scaffold is a novel chemotype for the discovery of TOP1 inhibitors. In this work, a series of novel 5-aminoethyl substituted benzophenanthridone derivatives have been synthesized and evaluated for TOP1 inhibition and cytotoxicity. Compound 12 exhibits the most potent TOP1 inhibition (+++) and cytotoxicity in human cancer cell lines with GI50 values at nanomolar concentration range. 12 induces the cellular TOP1cc formation and DNA damage, resulting in HCT116 cell apoptosis. The pharmacokinetics, acute toxicity and antitumor efficiency in vivo of 12 were also studied.


Assuntos
Antineoplásicos/farmacocinética , Benzofenantridinas/farmacocinética , Inibidores da Topoisomerase I/farmacocinética , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Benzofenantridinas/síntese química , Benzofenantridinas/metabolismo , Benzofenantridinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , DNA Topoisomerases Tipo I/química , DNA Topoisomerases Tipo I/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos Nus , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/metabolismo , Inibidores da Topoisomerase I/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Eur J Dermatol ; 29(2): 160-166, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31106759

RESUMO

Sporothrix schenckii strains are the aetiological agents of sporotrichosis, which is endemic in China. The most common clinical manifestation of sporotrichosis is cutaneous and subcutaneous nodular lesions with lymphangitis involvement. Currently, antifungal therapy is commonly used to treat sporotrichosis, however, drug resistance and complications are the major concerns, especially in patients who have asymptomatic liver injury or existing liver disorders, children, and pregnant women. To assess the in vitro and in vivo antifungal efficacy of photodynamic therapy (PDT) using photosensitizer methylene blue against Sporothrix strains isolated from patients. A light-emitting diode (LED) lamp was used as the light source with a wavelength of 640 ± 10 nm. For the in vitro study, the presence of five Sporothrix strains was assayed following LED irradiation with and without photosensitizer (L + M + , L + M-), with photosensitizer alone (L-M + ), or no exposure to LED light or photosensitizer (L-M-). For the in vivo study, mice were infected with the fungi and then treated with sodium chloride (control group), antifungal itraconazole alone (itraconazole group), and a combination of antifungal itraconazole and PDT (itraconazole +PDT group), or PDT alone (PDT group). The results showed that, in vitro, PDT (L + M + ) effectively inhibited fungal growth at an energy density of 40 J/cm2. In vivo, itraconazole + PDT effectively inhibited growth of the fungus with the highest level of efficacy. PDT with methylene blue is an effective adjuvant therapy for resistant infections of Sporothrix.

12.
J Int Assoc Provid AIDS Care ; 18: 2325958219838858, 2019 Jan-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30950300

RESUMO

BACKGROUND:: After diagnosis, a substantial number of people with HIV disease fall out of care. Effective interventions are needed for this priority population. METHODS:: The "Peers Keep It Real" study aimed to help adults who were disengaged from HIV treatment. Peers, lay individuals living with HIV, facilitated intervention sessions. Participants were randomized to immediately receive the peer-facilitated intervention or were wait-listed. RESULTS:: Considerable attrition occurred in the control group. Pre-/postanalyses showed that among participants (n = 23) who received the intervention, 65% had viral load suppression and 100% remained in care at 12 months postintervention. Impact on viral load was significant ( P = .0326), suggesting that peers are effective change agents who positively impacted outcomes for individuals struggling with adherence to HIV treatment. CONCLUSION:: Future endeavors should consider providing all individuals from this priority population with an active peer intervention from the onset to enhance retention and adherence.

13.
Mol Cell Biol ; 39(12)2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988156

RESUMO

Long noncoding RNAs (lncRNAs) are involved in various human diseases. Recently, H19 was reported to be upregulated in fibrotic rat lung and play a stimulative role in bleomycin (BLM)-induced pulmonary fibrosis in mice. However, its expression in human fibrotic lung tissues and mechanism of action remain unclear. Here, our observations showed that H19 expression was significantly upregulated and that of microRNA 140 (miR-140) was markedly reduced in pulmonary fibrotic tissues from idiopathic pulmonary fibrosis (IPF) patients and transforming growth factor ß1 (TGF-ß1)-induced HBE and A549 cells. Moreover, the expression of H19 was negatively correlated with the expression of miR-140 in IPF tissues. H19 knockdown attenuated TGF-ß1-induced pulmonary fibrosis in vitro Furthermore, animal experiments showed that H19 knockdown attenuated BLM-induced pulmonary fibrosis in mice. The study of molecular mechanisms showed that H19 functioned via reduction of miR-140 expression by binding to miR-140. The increase of miR-140 inhibited TGF-ß1-induced pulmonary fibrosis, and H19 upregulation diminished the inhibitory effects of miR-140 on TGF-ß1-induced pulmonary fibrosis, which was involved in the TGF-ß/Smad3 pathway. Taken together, our findings showed that H19 knockdown attenuated pulmonary fibrosis via the regulatory network of lncRNA H19-miR-140-TGF-ß/Smad3 signaling, and H19 and miR-140 might represent therapeutic targets and early diagnostic and prognostic biomarkers for patients with pulmonary fibrosis.

14.
Zhongguo Zhen Jiu ; 39(2): 173-8, 2019 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-30942037

RESUMO

OBJECTIVE: To observe the effects of herbal-cake-separated moxibustion on the repair of damaged vascular endothelium structure and the content of stromal cells derived factor 1 (SDF-1) in rabbits with atherosclerosis. METHODS: A total of 75 rabbits were randomly divided into a normal group, a model group, a direct moxibustion group, an atorvastatin calcium group and a herbal-cake-separated moxibustion group, 15 rabbits in each one. The rabbits in the normal group were fed with normal diet, and the remaining rabbits were fed with high-cholesterol diet for 12 weeks to prepare atherosclerotic model. Two groups of acupoints, one was "Juque" (CV 14), "Tianshu" (ST 25) and "Fenglong" (ST 40), the other one was "Xinshu" (BL 15), "Ganshu" (BL 18) and "Pishu" (BL 20), were applied in the direct moxibustion group and herbal-cake-separated moxibustion group; the two groups of acupoints were selected alternatively every other day. The moxibustion was given for 30 min per treatment, once a day for 4 weeks. The rabbits in the atorvastatin calcium group were treated with atorvastatin calcium tablets (1.96 mg•kg-1•d-1) which were crushed into powder and mixed into breakfast. After modeling, the rabbits in the normal group and model group received no treatment, and immobilized at the time when moxibustion was applied in other three groups. The levels of total cholesterol (TC) and triglyceride (TG) were measured by enzymic method; the low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by colorimetric method; the morphological structure of aortic wall was observed under optical microscope; the serum level of SDF-1 was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: After treatment, compared with the normal group, the levels of TC, TG and LDL-C were significantly increased in the model group (all P<0.01), and the level of HDL-C was decreased (P<0.01). Compared with the model group, the levels of TC, TG and LDL-C were significantly decreased (all P<0.01), and the level of HDL-C was significantly increased in the direct moxibustion group, atorvastatin calcium group and herbal-cake-separated moxibustion group (P<0.01, P<0.05). Compared with the normal group, the morphological structure of aortic wall was significantly damaged in the model group. Compared with the model group, the vascular endothelial structure was improved in the atorvastatin calcium group and herbal-cake-separated moxibustion group, and the pathological change of aorta endothelial in the direct moxibustion group was relieved. After treatment, compared with the model group, the level of SDF-1 was increased in the direct moxibustion group, atorvastatin calcium group and herbal-cake-separated moxibustion group (P<0.05, P<0.01); the level of SDF-1 in the herbal-cake- separated moxibustion group was higher than that in the direct moxibustion group (P<0.05). CONCLUSION: The herbal- cake-separated moxibustion can promote the expression of SDF-1 in serum and repair the damaged aortic endothelial structure.


Assuntos
Aterosclerose , Hiperlipidemias , Moxibustão , Pontos de Acupuntura , Animais , Endotélio Vascular , Coelhos
15.
Mayo Clin Proc ; 94(5): 820-832, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878157

RESUMO

OBJECTIVE: To assess the efficacy and longer-term effectiveness of dextrose prolotherapy injections in participants with temporomandibular dysfunction. PATIENTS AND METHODS: A randomized controlled trial with masked allocation was conducted from January 14, 2013, through December 19, 2015. Forty-two participants (with 54 joints) meeting temporomandibular dysfunction criteria were randomized (1:1) to 3 monthly intra-articular injections (20% dextrose/0.2% lidocaine or 0.2% lidocaine) followed by as-needed dextrose/0.2% lidocaine injections through 1 year. Primary and secondary outcome measures included a 0 to 10 Numerical Rating Scale score for facial pain and jaw dysfunction; maximal interincisal opening (MIO) measured in millimeters, percentage of joints with 50% or more change (improvement) in pain and function, and satisfaction. RESULTS: Randomization produced a control group with more female participants (P=.03), longer pain duration (P=.01), and less MIO (P=.01). Upon 3-month analysis, including pertinent covariates, dextrose group participants reported decreased jaw pain (4.3±2.9 points vs 1.8±2.7 points; P=.02), jaw dysfunction (3.5±2.8 points vs 1.0±2.1 points; P=.008), and improved MIO (1.5±4.1 mm vs -1.8±5.1 mm; P=.006). Control group participants received dextrose injections beginning at 3 months. No between-group differences were noted at 12 months; pooled data suggested that jaw pain, jaw function, and MIO improved by 5.2±2.7 points (68%), 4.1±2.8 points (64%), and 2.1±5.5 mm, respectively. Pain and dysfunction improved by at least 50% in 38 of 54 (70%) and 39 of 54 (72%) jaws, respectively. CONCLUSION: Intra-articular dextrose injection (prolotherapy) resulted in substantial improvement in jaw pain, function, and MIO compared with masked control injection at 3 months; clinical improvements endured to 12 months. Satisfaction was high. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01706172.


Assuntos
Glucose/administração & dosagem , Proloterapia/métodos , Síndrome da Disfunção da Articulação Temporomandibular/tratamento farmacológico , Adulto , Idoso , Estudos Cross-Over , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do Tratamento
16.
J Enzyme Inhib Med Chem ; 34(1): 818-822, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30907213

RESUMO

DNA topoisomerase IB (TOP1) is a validated target for discovery and development of antitumor agents. Four TOP1 poisons are clinically used for tumor treatment now. In spite of their effectiveness in solid tumors, these camptothecin (CPT) poisons suffer from many shortcomings. Therefore, many investigations have focused on the discoveries of non-CPT poisons and catalytic inhibitors. Herein, we systematically study the antitumor activity of CYB-L10, a novel indolizinoquinolinedione TOP1 catalytic inhibitor discovered in our laboratory. The results indicated that CYB-L10 mainly acts on TOP1 in cancer cells and is not a substrate of the P-glycoprotein. In addition, CYB-L10 can induce apoptosis of HCT116 cells, shows high cytotoxicity against 60 human clinical cancer cell lines (NCI60) with the mean-graph midpoint for growth inhibition of all cancer cell lines of 0.050 µM concentration and obvious antitumor efficiency in vivo in the HCT116 xenograft model.


Assuntos
Antineoplásicos/farmacologia , DNA Topoisomerases Tipo I/metabolismo , Indolizinas/farmacologia , Quinolinas/farmacologia , Inibidores da Topoisomerase I/farmacologia , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indolizinas/química , Camundongos , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Quinolinas/química , Inibidores da Topoisomerase I/química , Células Tumorais Cultivadas
17.
Planta ; 250(1): 105-114, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30927053

RESUMO

MAIN CONCLUSION: Rice phytochrome-interacting factor-like protein OsPIL15 regulates tiller angle through light and gravity signals in rice. Tiller angle of cereal crops is a key agronomic trait that contributes to grain production. An understanding of how tiller angle is controlled is helpful for achieving ideal plant architecture to improve grain yield. Phytochrome-interacting factors (PIFs) are known to regulate seed germination, seedling skotomorphogenesis, shade avoidance, and flowering in Arabidopsis thaliana. Here, we report that OsPIL15 is, indeed, a rice PIF that negatively regulates tiller angle. Dominant-negative OsPIL15 plants displayed a larger tiller angle, which was associated with reduced shoot gravitropism. Phytochrome B (phyB) is the main photoreceptor perceiving the low red:far-red ratio of shade light. Compared with wild-type rice plants, loss-of-function phyB plants and OsPIL15-overexpressing plants showed smaller tiller angles and enhanced shoot gravitropism. In addition, more OsPIL15 protein accumulated in phyB plants than in wild-type plants. Light regulates the level of the OsPIL15 protein negatively, depending on phyB partially. We propose that OsPIL15 integrates light and gravity signals to regulate tiller angle in rice.


Assuntos
Regulação da Expressão Gênica de Plantas , Gravitropismo/genética , Oryza/fisiologia , Fitocromo/metabolismo , Proteínas de Plantas/metabolismo , Gravitropismo/efeitos da radiação , Luz , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/efeitos da radiação , Proteínas de Plantas/genética , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/fisiologia , Brotos de Planta/efeitos da radiação , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/fisiologia , Plântula/efeitos da radiação
18.
J Assoc Nurses AIDS Care ; 30(3): 362-371, 2019 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30829894

RESUMO

Few studies have examined perceived social support among the subgroup of the HIV population that struggles with adherence to HIV care and treatment. A secondary analysis from 2 HIV medication adherence intervention studies was conducted using a mixed method design. Participants were not taking HIV medications as prescribed or had fallen out of HIV care. Two major themes emerged from the qualitative data analysis: extreme isolation and constant turmoil. Overall social support scores were low, as measured by the Medical Outcomes Study Social Support Survey. Convergent qualitative data excerpt corresponded with low scores on every dimension of the Medical Outcomes Study Social Support Survey. Findings from our study indicate that adults living with HIV who struggled with taking HIV medications lacked social support in many areas of their lives. Interventions that focus on perceptions of available social support may be helpful for individuals with ongoing HIV medication adherence challenges.

19.
Biol Res Nurs ; 21(3): 237-244, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30722677

RESUMO

INTRODUCTION: Patients admitted to the hospital with sepsis are 8 times more likely to die than patients with other diagnoses. There is no diagnostic test that clearly identifies the presence of the dysregulated host response that is central to sepsis. Researchers have identified serum albumin as a possible predictor of mortality in a number of critically ill patient populations. However, these studies primarily focus on the levels on admission, neglecting the clinically significant decrease that occurs subsequently. The purpose of this study was to examine the relationship between the trend of serum albumin over time and mortality in adults admitted to the intensive care unit (ICU) with sepsis. METHODS: This retrospective, correlational study used existing medical record data. All patients admitted to the ICU at a Midwestern regional medical center with a primary sepsis diagnosis were included in the initial sample. Logistic regression analysis was used to assess the ability of serum albumin to predict mortality. RESULTS: Serum albumin trend, admission serum albumin level, and lowest serum albumin level were significant unique predictors of mortality. The probability of survival decreases by 70.6% when there is a strong negative trend in serum albumin level, by 63.4% when admission serum albumin is ≤2.45 g/dl, and by 76.4% when the lowest serum albumin is ≤1.45 g/dl. CONCLUSION: Clinicians are encouraged to measure serum albumin levels in patients with sepsis. Low serum albumin levels and a strong negative trend in serial measurements should instigate aggressive monitoring and treatment in this population.


Assuntos
Sepse/mortalidade , Albumina Sérica/análise , Idoso , Idoso de 80 Anos ou mais , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Meio-Oeste dos Estados Unidos , Valor Preditivo dos Testes , Estudos Retrospectivos , Sepse/diagnóstico , Sepse/fisiopatologia
20.
Bioorg Chem ; 85: 1-17, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30599408

RESUMO

Aberrant overexpression of heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key feature in oncogenesis and progression of many human cancers. hnRNP K has been found to be a transcriptional activator to up-regulate c-myc gene transcription, a critical proto-oncogene for regulation of cell growth and differentiation. Therefore, down-regulation of c-myc transcription by inhibiting hnRNP K through disrupting its binding to c-myc gene promoter is a potential approach for cancer therapy. In the present study, we synthesized and screened a series of Quinoline derivatives and evaluated their binding affinity for hnRNP K. Among these derivatives, (E)-1-(4-methoxyphenyl)-3-(4-morpholino-6-nitroquinolin-2-yl)prop-2-en-1-one (compound 25) was determined to be the first-reported hnRNP K binding ligand with its KD values of 4.6 and 2.6 µM measured with SPR and MST, respectively. Subsequent evaluation showed that the binding of compound 25 to hnRNP K could disrupt its unfolding of c-myc promoter i-motif, resulting in down-regulation of c-myc transcription. Compound 25 showed a selective anti-proliferative effect on human cancer cell lines with IC50 values ranged from 1.36 to 3.59 µM. Compound 25 exhibited good tumor growth inhibition in a Hela xenograft tumor model, which might be related to its binding with hnRNP K. These findings illustrated that inhibition of DNA-binding protein hnRNP K by compound 25 could be a new and selective strategy of regulating oncogene transcription instead of targeting promoter DNA secondary structures such as G-quadruplexes or i-motifs.

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