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1.
New Phytol ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33586157

RESUMO

Plants control water use efficiency (WUE) by regulating water loss and CO2 diffusion through stomata. Variation in stomatal control has been reported among lineages of vascular plants, thus giving raise to the possibility that different lineages may show distinct WUE dynamics in response to water stress. Here, we compared the response of gas exchange to decreasing leaf water potential among four ferns and nine seed plant species exposed to a gradually intensifying water deficit. The data collected were combined with those from 339 phylogenetically diverse species obtained from previous studies. In well-watered angiosperms, the maximum stomatal conductance was high and greater than that required for maximum WUE, but drought stress caused a rapid reduction in stomatal conductance and an increase in WUE in response to elevated levels of abscisic acid. However, in ferns stomata did not open beyond the optimum point corresponding to maximum WUE and actually exhibited a steady WUE in response to dehydration. Thus, seed plants showed improved photosynthetic WUE under water stress. The ability of seed plants to increase WUE may provide them with an advantage over ferns under drought conditions, thereby, presumably increasing their fitness under selection pressure by drought.

2.
J Asian Nat Prod Res ; : 1-5, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33463380

RESUMO

Two new benzo[de]isoquinoline derivatives, 4-phenyl-benzo[de]isoquinoline-1,3-dione (1) and 4-(4-hydroxyphenyl)-benzo[de]isoquinoline-1,3-dione (2), were isolated from 70% ethanol extract of the rhizomes of Musa basjoo. Their chemical structures were elucidated by HRESIMS, 1 D and 2 D spectra.

3.
Anal Chem ; 93(5): 2974-2981, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33476115

RESUMO

Metal-organic gels (MOGs) are new soft materials with the characteristics of high colloidal stability, superb luminescence properties, and facile synthesis. Herein, we develop for the first time a host-guest interaction-based and MOG-based biosensor with aggregation-induced electrochemiluminescence (ECL) enhancement for M.SssI methyltransferase (M.SssI MTase) assay. This biosensor employs a MOG as the luminophor and potassium persulfate as the coreactant, and the formation of the Ag-MOG from the aggregation of silver nanoclusters can induce significant ECL enhancement. Two complementary single-stranded DNAs (ssDNAs, i.e., biotinylated DNA-1 and Fc-labeled DNA-2) that contain specific recognition sequence 5'-CCGG-3' can form a double-stranded DNA (dsDNA) probe. In the absence of M.SssI MTase, the dsDNA probe will be digested by restriction endonuclease HpaII, leading to the release of Fc from magnetic beads (MBs). The ß-CD can specifically recognize the released Fc through guest-host interaction, resulting in the quenching of an ECL signal. In contrast, the presence of M.SssI MTase enables the formation of fully methylated dsDNA, which cannot be cleaved by HpaII, making Fc remain on the MB surface and consequently generating an improved ECL signal. This biosensor can specifically detect M.SssI MTase with a linear range of 0.05-100 U mL-1 and a limit of detection of 3.5 × 10-3 U mL-1, and it enables accurate detection of M.SssI MTase in human serum. In addition, it can be used for inhibitor screening, with wide applications in drug discovery and disease diagnosis.

4.
Toxins (Basel) ; 13(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466634

RESUMO

Protobothrops mucrosquamatus poses a serious medical threat to humans in Southern and Southeastern Asia. Hemorrhage is one of the conspicuous toxicities related to the pathology of P. mucrosquamatus envenoming. Previous in vitro and in vivo studies showed that a silica-derived reagent, sodium silicate complex (SSC), was able to neutralize hemorrhagic and proteolytic activities induced by pit viper venoms, including Crotalus atrox, Agkistrodon contortrix contortrix and Agkistrodon piscivorus leucostoma. In this study, we validated that SSC could neutralize enzymatic and toxic effects caused by the venom of P. mucrosquamatus. We found that SSC inhibited the hemolytic and proteolytic activities induced by P. mucrosquamatus venom in vitro. In addition, we demonstrated that SSC could block intradermal hemorrhage caused by P. mucrosquamatus venom in a mouse model. Finally, SSC could neutralize lethal effects of P. mucrosquamatus venom in the mice. Therefore, SSC is a candidate for further development as a potential onsite first-aid treatment for P. mucrosquamatus envenoming.

5.
Amino Acids ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398528

RESUMO

Elevated phenylalanine has been observed in patients with advanced heart failure (HF) and in community cohorts at risk of HF, and has been shown to have prognostic value. This study aimed to explore the factors associated with elevated phenylalanine in HF patients. Mass spectrometry was performed on blood from 669 participants, including 75 normal controls and 594 HF patients (stages A, B, and C). We measured phenylalanine and associated degradation products on the catecholamine pathway, C-reactive protein, valerylcarnitine, methionine sulfoxide, estimated glomerular filtration rate (eGFR), and B-type natriuretic peptide. Longitudinal analysis was conducted on 61 stage C HF patients who had recovered systolic function after 1 year. Phenylalanine and tyrosine levels increased from normal through stages A, B and C. Cross-sectional analysis in patients at stage C showed that phenylalanine levels were related to total bilirubin, eGFR, valerylcarnitine, methionine sulfoxide, C-reactive protein, and male gender. Longitudinal analysis in the patients at stage C with recovered systolic function after 1 year revealed that phenylalanine, tyrosine, methionine sulfoxide, total bilirubin, and C-reactive protein levels significantly decreased from baseline to 12 months. Based on a generalized estimating equations analysis model with time interaction considered, the only significant factor associated with changes in phenylalanine was changes in C-reactive protein concentrations from baseline to 12 months [B (coefficient) = 0.81, P < 0.001] after adjusting for methionine sulfoxide and total bilirubin levels. In conclusion, phenylalanine levels respond sensitively to HF improvement. Our findings suggest that inflammation plays a pivotal role in the elevation of phenylalanine levels in patients with HF.

6.
Food Chem ; 347: 129023, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33484959

RESUMO

This study developed a novel surface-enhanced Raman spectroscopy (SERS) method coupled with cellulose nanofiber (CNF)-based SERS wipers that were fabricated on quartz papers coated with a mixture of silver nanoparticle (AgNP) and gold nanostar (AuNS). A "drop-wipe-test" protocol was developed for rapid detection of pesticide residues in vegetables by SERS. Tremendously enhanced Raman scattering signals were obtained from the quartz/CNF/mixture (AgNP + AuNS) substrate, which were much higher than the paper/mixture (AgNP + AuNS) substrate. This method was used to detect ferbam on kale leaves within a few minutes and the detection limit was 50 µg/kg based on the PLS models (R2 = 0.89). The enhancement factor of the SERS substrate was calculated to be ~ 104 with satisfactory reproducibility. Satisfactory SERS performance could be achieved within 1-month storage period. These results demonstrate that this CNF-based SERS/wiper method is a practical approach for rapid detection of chemical contaminants in fresh produce.

7.
J Formos Med Assoc ; 120(1 Pt 1): 83-92, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32863084

RESUMO

The COronaVIrus Disease 2019 (COVID-19), which developed into a pandemic in 2020, has become a major healthcare challenge for governments and healthcare workers worldwide. Despite several medical treatment protocols having been established, a comprehensive rehabilitation program that can promote functional recovery is still frequently ignored. An online consensus meeting of an expert panel comprising members of the Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation was held to provide recommendations for rehabilitation protocols in each of the five COVID-19 stages, namely (1) outpatients with mild disease and no risk factors, (2) outpatients with mild disease and epidemiological risk factors, (3) hospitalized patients with moderate to severe disease, (4) ventilator-supported patients with clear cognitive function, and (5) ventilator-supported patients with impaired cognitive function. Apart from medications and life support care, a proper rehabilitation protocol that facilitates recovery from COVID-19 needs to be established and emphasized in clinical practice.


Assuntos
Protocolos Clínicos/normas , Controle de Infecções , Reabilitação , /epidemiologia , /reabilitação , Consenso , Humanos , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Recuperação de Função Fisiológica , Reabilitação/métodos , Reabilitação/normas , Taiwan
8.
ACS Nano ; 15(1): 884-893, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33370534

RESUMO

Structuring pores into stable membrane and controlling their opening is extremely useful for applications that require nanopores as channels for material exchange and transportation. In this work, nanoporous vesicles with aggregation-induced emission (AIE) properties were developed from the amphiphilic polymer PEG550-TPE-Chol, in which the hydrophobic part is composed of a tetraphenylethene (TPE) group and a cholesterol moiety and the hydrophilic block is a poly(ethylene glycol) (PEG, Mn = 550 Da). Two stereoisomers, trans-PEG550-TPE-Chol and cis-PEG550-TPE-Chol, were successfully synthesized. These thermally stable stereoisomers showed distinct self-assembly behavior in water: trans-PEG550-TPE-Chol formed classical vesicles, while cis-PEG550-TPE-Chol self-assembled into cylindrical micelles. Interestingly, trans/cis mixtures of PEG550-TPE-Chol (trans/cis = 60/40), either naturally synthesized without isomers' separation during the synthesis or intentionally mixed using trans- and cis-isomers, constructed perforated vesicles with nanopores. Moreover, under the illumination of high intensity UV light (365 nm, 15 mW/cm2), the classical vesicles of trans-PEG550-TPE-Chol were perforated by its cis counterparts generated from the trans-cis photoisomerization, while the cylindrical micelles of cis-PEG550-TPE-Chol interweaved to form meshes and nanoporous membranes due to the trans-isomers produced by cis-trans photoisomerization. All of these assemblies in water emitted bright cyan fluorescence under UV light, while their constituent molecules were not fluorescent when solubilized in organic solvent. The AIE fluorescent normal vesicles and nanoporous vesicles may find potential applications in biotechnology as light-gated delivery vehicles and capsules with nanochannels for material exchange.

10.
Zhongguo Zhong Yao Za Zhi ; 45(21): 5143-5149, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33350229

RESUMO

Yinshan Mountains stands on the southern edge of the Inner Mongolia Plateau, which stretches 1 200 km from east to west and 50 to 100 km from north to south. The rich and varied topographic environment of the Yinshan Mountains has created a variety of vegetation floras, which also makes the species of medicinal plant resources in this area unevenly distributed. Therefore, studying the spatial distribution difference of medicinal plant resources among various banners, counties, and districts in the Yinshan area is of great significance to formulate the protection policy and promote the industry development of medicinal plant. This study is based on the fourth national survey of traditional Chinese medicine resources in Inner Mongolia, regarding the results of the third national survey of traditional Chinese medicine resources. The species of medicinal plant resources in the Yinshan area around 31 banners, counties and districts were counted in detail. Then, using exploratory spatial data analysis(ESDA), trend surface analysis, spatial autocorrelation, geographical detector and other geostatistical analysis methods to analyze the differences in the spatial distribution of medicinal plant resources of the Yinshan area in Inner Mongolia. After discussing and analyzing the experimental results to account for the reasons for the overall trend of change and the degree of aggregation, the author further put forward relevant constructive suggestions. The results show that the areas with the most abundant and concentrated distribution of medicinal plant resources in the Yinshan area are located in Guyang county, Shiguai District of Baotou city, Tutou right banner, and Tuoketuo county; the higher richness and concentrated distribution of medicinal plant resources is in Wulate front banner, Wulate middle banner, Wulate back banner; areas with relatively low abundance and concentrated distribution of medicinal plant resources located in Qingshan district of Baotou city, Saihan district and Yuquan district of Hohhot city; areas with the lowest abundance and concentrated distribution of medicinal plant resources are located in Xincheng district and Huimin district of Hohhot city. It can be concluded that the horizontal distribution difference of multiple ecological factors, the special wetland environment of the river, the vertical difference of elevation, the farmland and other factors have an important influence on the richness of the medicinal plant resources species.


Assuntos
Plantas Medicinais , China , Medicina Tradicional Chinesa
11.
Cell Microbiol ; : e13294, 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33222390

RESUMO

Gametogenesis, the formation of gametes from gametocytes, an essential step for malaria parasite transmission, is targeted by transmission-blocking drugs and vaccines. We identified a conserved protein (PBANKA_0305900) in Plasmodium berghei, which encodes a protein of 22 kDa (thus named Pb22) and is expressed in both asexual stages and gametocytes. Its homologues are present in all Plasmodium species and its closely related, Hepatocystis, but not in other apicomplexans. Pb22 protein was localised in the cytosols of schizonts, as well as male and female gametocytes. During gamete-to-ookinete development, Pb22 became localised on the plasma membranes of gametes and ookinetes. Compared to the wild-type (WT) parasites, P. berghei with pb22 knockout (KO) showed a significant reduction in exflagellation (~89%) of male gametocytes and ookinete number (~97%) during in vitro ookinete culture. Mosquito feeding assays showed that ookinete and oocyst formation of the pb22-KO line in mosquito midguts was almost completely abolished. These defects were rescued in parasites where pb22 was restored. Cross-fertilisation experiments with parasite lines defective in either male or female gametes confirmed that the defects in the pb22-KO line were restricted to the male gametes, whereas female gametes in the pb22-KO line were fertile at the WT level. Detailed analysis of male gametogenesis showed that 30% of the male gametocytes in the pb22-KO line failed to assemble the axonemes, whereas ~48.9% of the male gametocytes formed flagella but failed to egress from the host erythrocyte. To explore its transmission-blocking potential, recombinant Pb22 (rPb22) was expressed and used to immunise mice. in vitro assays showed that the rPb22-antisera significantly inhibited exflagellation by ~64.8% and ookinete formation by ~93.4%. Mosquitoes after feeding on rPb22-immunised mice also showed significant decreases in infection prevalence (83.3-93.3%) and oocyst density (93.5-99.6%). Further studies of the Pb22 orthologues in human malaria parasites are warranted.

12.
Chin J Integr Med ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170942

RESUMO

Medicinal plants have provided numerous medicinal active ingredients for thousands of years and these ingredients have been used in Chinese medicine (CM) and traditional pharmacologies worldwide. Recently, the exploitation and utilisation of medicinal plant resources has increased significantly. The results of the studies have led to the identification of many active components, such as steroidal alkaloids, saponins, terpenoids, and glycosides, in various medicinal plants with different evolutionary levels. Moreover, research on the chemical classification, molecular phylogeny, and pharmacological activity of medicinal plants is increasing in popularity. Pharmacophylogeny is an interdisciplinary topic that studies the correlation between plant phylogeny, chemical composition, and curative effects (pharmacological activity and the traditional curative effect) of medicinal plants. In addition, it provides the basic tools to enable research and development of CM resources. This literature review, based on the genetic relationship between phytogroup and species, highlights the formation process, research content, applications, and future directions of pharmacophylogeny.

13.
Plant Cell Environ ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33131059

RESUMO

Drought is a cyclical phenomenon in natural environments. During dehydration, stomatal closure is mainly regulated by abscisic acid (ABA) dynamics that limit transpiration in seed plants, but following rehydration, the mechanism of gas exchange recovery is still not clear. In this study, leaf water potential (ψleaf ), stomatal conductance (gs ), leaf hydraulic conductance (Kleaf ), foliar ABA level, ethylene emission rate in response to dehydration and rehydration were investigated in four Caragana species with isohydric (Caragana spinosa and C. pruinosa) and anisohydric (C. intermedia and C. microphylla) traits. Two isohydric species with ABA-induced stomatal closure exhibited more sensitive gs and Kleaf to decreasing ψleaf than two anisohydric species which exhibited a switch from ABA to water potential-driven stomatal closure during dehydration. Following rehydration, the recovery of gas exchange was not associated with a decrease in ABA level but was strongly limited by the degradation of the ethylene emission rate in all species. Furthermore, two anisohydric species with low drought-induced ethylene production exhibited more rapid recovery in gas exchange upon rehydration. Our results indicated that ethylene is a key factor regulating the drought-recovery ability in terms of gas exchange, which may shape species adaptation to drought and potential species distribution.

15.
Int J Biol Macromol ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33130268

RESUMO

Apoptosis is a cellular defense mechanism used for the elimination of host cells infected by viruses. Viruses have evolved corresponding inhibitors of apoptosis genes to promote their replication. Anti-apoptosis-related genes, involved in baculovirus proliferation, have been proposed but it is unclear whether these genes can be manipulated in gene therapy. We constructed a transgenic silkworm, using the CRISPR/Cas9 system to knock out the BmNPV inhibitor of apoptosis 2 (iap2). The sequencing results showed that all the sequences could edit the target site of BmNPV iap2 gene. There were no differences in economic traits and growth tests between the BmNPV iap2 knockout strain transgenic silkworm lines and the control groups. However, the mortality rate was significantly reduced, the median lethal dose (LD50) was about 100 times higher than the control group, and the onset time was prolonged by 1-2 days after knocking out BmNPV iap2. In addition, the expression levels of apoptotic-related genes Bmiap2, BmICE and BmDreed were significantly affected and the activity of caspase 9 was increased after BmNPV iap2 being edited in transgenic silkworm. These results demonstrated that gene editing BmNPV iap2 could significantly inhibit BmNPV replication and proliferation. This approach provides a new strategy for antiviral research.

16.
Adv Healthc Mater ; : e2001157, 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33251762

RESUMO

Recent studies emphasize on developing immune tolerance by an interim administration of various immunosuppressive drugs. In this study, a robust protocol is reported for local immunomodulation using a single-dose of FK506 microspheres and clodronate liposomes (mFK+CLO) in a xenogeneic model of islet transplantation. Surprisingly, the single-dose treatment with mFK+CLO induce tolerance to the islet xenograft. The recipient mice display tolerogenic dendritic cells (tDCs) with decreased antigen presenting ability and T cell activation capacity. Furthermore, a reduced percentage of CD4+ and CD8+ T cells and an impaired differentiation of naïve CD4+ T cells into interferon-γ producing Th1 and interleukin-17 producing Th17 cells are observed. In addition, the immunosuppressive protocol leads to the generation of Foxp3+ regulatory T cells (Tregs) which are required for the long-term graft survival. The enhanced generation of tDCs and Tregs by the single treatment of mFK+CLO cause xenograft tolerance, suggesting a possible clinical strategy which may pave the way towards improving therapeutic outcomes of clinical islet transplantation.

17.
Appl Soft Comput ; 97: 106790, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33071685

RESUMO

During the outbreak of the novel coronavirus pneumonia (COVID-19), there is a huge demand for medical masks. A mask manufacturer often receives a large amount of orders that must be processed within a short response time. It is of critical importance for the manufacturer to schedule and reschedule mask production tasks as efficiently as possible. However, when the number of tasks is large, most existing scheduling algorithms require very long computational time and, therefore, cannot meet the needs of emergency response. In this paper, we propose an end-to-end neural network, which takes a sequence of production tasks as inputs and produces a schedule of tasks in a real-time manner. The network is trained by reinforcement learning using the negative total tardiness as the reward signal. We applied the proposed approach to schedule emergency production tasks for a medical mask manufacturer during the peak of COVID-19 in China. Computational results show that the neural network scheduler can solve problem instances with hundreds of tasks within seconds. The objective function value obtained by the neural network scheduler is significantly better than those of existing constructive heuristics, and is close to those of the state-of-the-art metaheuristics whose computational time is unaffordable in practice.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33039642

RESUMO

BACKGROUND: Bullous skin disorders are induced by different pathomechanisms and several are emergent, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Rapid diagnostic methods for SJS/TEN or cytotoxic T-lymphocyte (CTL)-mediated bullous disorders are crucial for early treatment. Granulysin, primarily expressed by CTLs, is a specific cytotoxic protein responsible for SJS/TEN and similar skin reactions. OBJECTIVE: To assess granulysin levels in blister fluids to differentiate SJS/TEN and similar CTL-mediated bullous reactions from other autoimmune bullous disorders. METHODS: Using ELISA, we measured granulysin in blister fluids from patients with bullous skin disorders, including SJS/TEN, erythema multiforme major, bullous fixed-drug eruption, bullous lupus erythematosus, paraneoplastic pemphigus, pemphigus vulgaris, bullous pemphigoid, purpura fulminans-related bullae, and hand-foot syndrome/hand-foot-skin reactions. We compared serum and blister granulysin levels in patients with SJS/TEN presenting varying severity, monitoring serial granulysin levels from acute to late stages. RESULTS: Overall, 144 patients presenting with bullous skin disorders were enrolled. Blister granulysin levels (mean ± SD) in CTL-mediated disorders, including TEN (n = 28; 3938.7 ± 3475.7), SJS-TEN overlapping (n = 22; 1440.4 ± 1179.6), SJS (n = 14; 542.0 ± 503.2), erythema multiforme major (n = 7; 766.3 ± 1073.7), generalized bullous fixed-drug eruption (n = 10; 720.4 ± 858.3), and localized bullous fixed-drug eruption (n = 16; 69.0 ± 56.4), were significantly higher than in non-CTL-mediated bullous disorders (P < .0001), including bullous lupus erythematosus (n = 3; 22.7 ± 20.1), paraneoplastic pemphigus (n = 3; 20.3 ± 8.6), pemphigus vulgaris (n = 3; 4.4 ± 2.8), bullous pemphigoid (n = 18; 4.0 ± 2.7), purpura fulminans (n = 4; 5.9 ± 5.5), and hand-foot syndrome/hand-foot-skin reactions (n = 6; 4.6 ± 3.5). Blister granulysin levels correlated with clinical severity of SJS/TEN (P < .0001). CONCLUSIONS: Determination of blister granulysin levels is a noninvasive and useful tool for rapid differential diagnosis of SJS/TEN and other similar CTL-mediated bullous skin disorders for treatment selection.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33057610

RESUMO

Importance: Although the survival impact of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is well known, there has been conflicting and scarce evidence on the role of HPV in non-OPSCC. Objective: To undertake a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant systematic review and meta-analysis of all published studies on the association between HPV status and survival outcomes in patients with non-OPSCC, analyzing each site separately. Data Sources: PubMed, CINAHL, and Embase were searched from 1946 to December 16, 2019, for English-language articles. Study Selection: Analysis comprised randomized clinical trials or observational studies that each included at least 10 patients with non-OPSCC in which the presence of HPV was analyzed, survival outcomes were reported, and a clinical follow-up of 1 year or more was performed. Studies excluded were those in which data on OPSCC and non-OPSCC were not distinguished between both cohorts and studies on patients with distant metastatic tumors at diagnosis. Final analysis included outcomes that were analyzed in at least 3 studies. Data Extraction and Synthesis: Two reviewers independently abstracted the data. Risk of bias was estimated with the Newcastle-Ottawa Scale. Meta-analysis was performed using the random-effects model. Main Outcomes and Measures: The primary end point was overall survival (OS); secondary end points were disease-specific survival (DSS) and disease-free survival (DFS). Results: Of the 3947 articles screened, a total of 22 observational and 2 randomized clinical trials were included in the analysis, representing 24 854 patients. In oral cavity locations, OS was not significantly associated with HPV positivity (hazard ratio [HR], 1.16; 95% CI, 0.83-1.61; I2 = 71%); however, HPV-positive tumors showed worse DFS (HR, 1.81; 95% CI, 1.12-2.91; I2 = 47%). Laryngeal and hypopharyngeal HPV-positive tumors were associated with improved OS (HR, 0.71; 95% CI, 0.54-0.92; I2 = 38% and HR, 0.60; 95% CI, 0.47-0.76; I2 = 0%), respectively, whereas, in nasopharyngeal locations HPV was not associated with OS (HR, 0.82; 95% CI, 0.49-1.38; I2 = 46%) or DSS (HR, 0.55; 95% CI, 0.22-1.42; I2 = 65%). Conclusions and Relevance: In this meta-analysis of 24 studies, HPV was associated with improved OS in laryngeal and hypopharyngeal locations but not in the oral cavity and the nasopharynx. This information may be useful for future clinical studies of laryngeal and hypopharyngeal tumors and whether HPV status should be incorporated in prognostication of patients with these cancers.

20.
Eur J Med Chem ; 209: 112889, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33045660

RESUMO

To identity fast-acting, multistage antimalarial agents, a series of pyridylvinylquinoline-triazole analogues have been synthesized via CuAAC. Most of the compounds display significant inhibitory effect on the drug-resistant malarial Dd2 strain at low submicromolar concentrations. Among the tested analogues, compound 60 is the most potent molecule with an EC50 value of 0.04 ± 0.01 µM. Our current study indicates that compound 60 is a fast-acting antimalarial compound and it demonstrates stage specific action at the trophozoite phase in the P. falciparum asexual life cycle. In addition, compound 60 is active against both early and late stage P. falciparum gametocytes. From a mechanistic perspective, compound 60 shows good activity as an inhibitor of ß-hematin formation. Collectively, our findings suggest that fast-acting agent 60 targets dual life stages of the malarial parasites and warrant further investigation of pyridylvinylquinoline hybrids as new antimalarials.

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