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1.
Parasite Immunol ; 46(3): e13029, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465509

RESUMO

Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-ß1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.


Assuntos
Esquistossomose Japônica , Esquistossomose , Humanos , Camundongos , Animais , Interleucina-4 , Cirrose Hepática , Esquistossomose/complicações , Fígado , Citocinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Imunidade
2.
Br J Nutr ; 131(10): 1777-1785, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38287709

RESUMO

Previous studies revealed that consuming spicy food reduced mortality from CVD and lowered stroke risk. However, no studies reported the relationship between spicy food consumption, stroke types and dose­response. This study aimed to further explore the association between the frequency of spicy food intake and the risk of stroke in a large prospective cohort study. In this study, 50 174 participants aged 30­79 years were recruited. Spicy food consumption data were collected via a baseline survey questionnaire. Outcomes were incidence of any stroke, ischaemic stroke (IS) and haemorrhagic stroke (HS). Multivariable-adjusted Cox proportional hazard models estimated the association between the consumption of spicy food and incident stroke. Restricted cubic spline analysis was used to examine the dose­response relationship. During the median 10·7-year follow-up, 3967 strokes were recorded, including 3494 IS and 516 HS. Compared with those who never/rarely consumed spicy food, those who consumed spicy food monthly, 1­2 d/week and 3­5 d/week had hazard ratio (HR) of 0·914 (95 % CI 0·841, 0·995), 0·869 (95 % CI 0·758, 0·995) and 0·826 (95 % CI 0·714, 0·956) for overall stroke, respectively. For IS, the corresponding HR) were 0·909 (95 % CI 0·832, 0·994), 0·831 (95 % CI 0·718, 0·962) and 0·813 (95 % CI 0·696, 0·951), respectively. This protective effect showed a U-shaped dose­response relationship. For obese participants, consuming spicy food ≥ 3 d/week was negatively associated with the risk of IS. We found the consumption of spicy food was negatively associated with the risk of IS and had a U-shaped dose­response relationship with risk of IS. Individuals who consumed spicy food 3­5 d/week had a significantly lowest risk of IS.


Assuntos
AVC Isquêmico , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , Estudos Prospectivos , Adulto , Idoso , AVC Isquêmico/prevenção & controle , AVC Isquêmico/epidemiologia , AVC Isquêmico/etiologia , Fatores de Risco , Modelos de Riscos Proporcionais , Dieta , Especiarias , Incidência , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia
3.
Langmuir ; 39(38): 13588-13598, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37703860

RESUMO

Chemotherapy is one of the available cancer treatments which has been successfully employed to prolong the survival of cancer patients. However, it remains a major challenge to develop effective chemotherapeutic agents by reducing off-target toxicity, improving bioavailability, and effectively prolonging blood circulation. The pH profile of tumor cells is abnormal to that of normal cells, making it a potential breakthrough for designing effective chemotherapeutic drug agents. Here, the pH-activatable charge-reversal supramolecular nanocarriers, named MI7-ß-CD/SA NPs, were prepared through a simple and "green" constructive process. MI7-ß-CD/SA NPs possess both pH-induced charge-reversal and disassembly properties that were exploited to investigate the loading, delivery, and pH-responsive controlled release of the antitumor compound celastrol (CSL). CSL@MI7-ß-CD/SA NPs displayed low hemolysis, good biocompatibility, and targeted uptake. Furthermore, CSL@MI7-ß-CD/SA NPs exhibited superior apoptosis rates against SMMC-7721 cell lines compared with CSL, when CSL@MI7-ß-CD/SA NPs and CSL were administered at a mass concentration of 5.0 µg/mL, i.e., the CSL content in CSL@MI7-ß-CD/SA NPs was relatively lower than that of intact CSL. We expected that MI7-ß-CD/SA NPs featuring pH-triggered charge reversal could offer a promising controlled release strategy that would then facilitate the clinical conversion of antitumor drugs.


Assuntos
Apoptose , Polímeros , Humanos , Preparações de Ação Retardada , Transporte Biológico , Concentração de Íons de Hidrogênio
4.
BMC Gastroenterol ; 23(1): 271, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553605

RESUMO

BACKGROUND: The purpose of this study was to investigate the differences between the clinical characteristics and the factors influencing liver injury in patients with the Omicron subvariant BA.5.2 (Omicron BA.5.2) and the prototype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Between December 30, 2019 and November 30, 2022, 157 patients infected with the SARS-CoV-2 prototype and 199 patients infected with the Omicron BA.5.2 were included in this case-control, single-center, retrospective study. Differences in clinical characteristics and liver injury between the Omicron BA.5.2 patients and the prototype patients were subsequently analyzed. RESULTS: None of the Omicron BA.5.2 patients reached the critical state, and showed relatively milder symptoms including fever, cough, headache, muscle soreness, nausea or vomiting, diarrhea, anorexia and hypoxia. The Omicron BA.5.2 had a lower effect on body temperature (T), white blood cell (WBC) count, hematocrit (HCT), C-reactive protein (CRP) level, D-dimer, finger pulse oxygen saturation (SpO2) and lung lesions. The differences in liver injury between the two groups were related to the severity of the disease, T, blood oxygen levels, albumin (ALB), CRP, and medication usage. Gender, body mass index, and CRP levels influenced liver damage in the Omicron BA.5.2 patients. In particular, CRP was an independent risk factor for liver injury. Because the severity of liver function damage was considerably low, only a small number of Omicron BA.5.2 patients required liver-protective treatment. CONCLUSION: Liver injury is expected in the COVID-19 patients. The Omicron BA.5.2 patients showed milder symptoms of liver injury than the prototype patients. However, dynamic monitoring of liver function is warranted, especially for individuals presenting with elevated levels of CRP.


Assuntos
COVID-19 , Fígado , SARS-CoV-2 , Humanos , Albuminas , COVID-19/complicações , Fígado/lesões , Estudos Retrospectivos
5.
BMC Infect Dis ; 23(1): 440, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37386364

RESUMO

BACKGROUND: Hydrogen/oxygen therapy contribute to ameliorate dyspnea and disease progression in patients with respiratory diseases. Therefore, we hypothesized that hydrogen/oxygen therapy for ordinary coronavirus disease 2019 (COVID-19) patients might reduce the length of hospitalization and increase hospital discharge rates. METHODS: This retrospective, propensity-score matched (PSM) case-control study included 180 patients hospitalized with COVID-19 from 3 centers. After assigned in 1:2 ratios by PSM, 33 patients received hydrogen/oxygen therapy and 55 patients received oxygen therapy included in this study. Primary endpoint was the length of hospitalization. Secondary endpoints were hospital discharge rates and oxygen saturation (SpO2). Vital signs and respiratory symptoms were also observed. RESULTS: Findings confirmed a significantly lower median length of hospitalization (HR = 1.91; 95% CIs, 1.25-2.92; p < 0.05) in the hydrogen/oxygen group (12 days; 95% CI, 9-15) versus the oxygen group (13 days; 95% CI, 11-20). The higher hospital discharge rates were observed in the hydrogen/oxygen group at 21 days (93.9% vs. 74.5%; p < 0.05) and 28 days (97.0% vs. 85.5%; p < 0.05) compared with the oxygen group, except for 14 days (69.7% vs. 56.4%). After 5-day therapy, patients in hydrogen/oxygen group exhibited a higher level of SpO2 compared with that in the oxygen group (98.5%±0.56% vs. 97.8%±1.0%; p < 0.001). In subgroup analysis of patients received hydrogen/oxygen, patients aged < 55 years (p = 0.028) and without comorbidities (p = 0.002) exhibited a shorter hospitalization (median 10 days). CONCLUSION: This study indicated that hydrogen/oxygen might be a useful therapeutic medical gas to enhance SpO2 and shorten length of hospitalization in patients with ordinary COVID-19. Younger patients or those without comorbidities are likely to benefit more from hydrogen/oxygen therapy.


Assuntos
COVID-19 , Humanos , Estudos de Casos e Controles , Estudos Retrospectivos , COVID-19/terapia , Oxigênio/uso terapêutico , Hidrogênio/uso terapêutico
6.
Microb Pathog ; 171: 105735, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36007846

RESUMO

To improve the identification and subsequent intervention of COVID-19 patients at risk for ICU admission, we constructed COVID-19 severity prediction models using logistic regression and artificial neural network (ANN) analysis and compared them with the four existing scoring systems (PSI, CURB-65, SMARTCOP, and MuLBSTA). In this prospective multi-center study, 296 patients with COVID-19 pneumonia were enrolled and split into the General-Ward-Care group (N = 238) and the ICU-Admission group (N = 58). The PSI model (AUC = 0.861) had the best results among the existing four scoring systems, followed by SMARTCOP (AUC = 0.770), motified-MuLBSTA (AUC = 0.761), and CURB-65 (AUC = 0.712). Data from 197 patients (training set) were analyzed for modeling. The beta coefficients from logistic regression were used to develop a severity prediction model and risk score calculator. The final model (NLHA2) included five covariates (consumes alcohol, neutrophil count, lymphocyte count, hemoglobin, and AKP). The NLHA2 model (training: AUC = 0.959; testing: AUC = 0.857) had similar results to the PSI model, but with fewer variable items. ANN analysis was used to build another complex model, which had higher accuracy (training: AUC = 1.000; testing: AUC = 0.907). Discrimination and calibration were further verified through bootstrapping (2000 replicates), Hosmer-Lemeshow goodness of fit testing, and Brier score calculation. In conclusion, the PSI model is the best existing system for predicting ICU admission among COVID-19 patients, while two newly-designed models (NLHA2 and ANN) performed better than PSI, and will provide a new approach for the development of prognostic evaluation system in a novel respiratory viral epidemic.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , COVID-19/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Humanos , Redes Neurais de Computação , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
7.
J Neurosci Res ; 99(9): 2074-2090, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34031910

RESUMO

Extensive alterations in gene regulatory networks are a typical characteristic of Huntington's disease (HD); these include alterations in protein-coding genes and poorly understood non-coding RNAs (ncRNAs), which are associated with pathology caused by mutant huntingtin. Long non-coding RNAs (lncRNAs) are an important class of ncRNAs involved in a variety of biological functions, including transcriptional regulation and post-transcriptional modification of many targets, and likely contributed to the pathogenesis of HD. While a number of changes in lncRNAs expression have been observed in HD, little is currently known about their functions. Here, we discuss their possible mechanisms and molecular functions, with a particular focus on their roles in transcriptional regulation. These findings give us a better insight into HD pathogenesis and may provide new targets for the treatment of this neurodegenerative disease.


Assuntos
Encéfalo/metabolismo , Redes Reguladoras de Genes/fisiologia , Proteína Huntingtina/metabolismo , Doença de Huntington/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Encéfalo/patologia , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Doença de Huntington/patologia , RNA Longo não Codificante/genética
8.
Analyst ; 146(1): 262-269, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33118581

RESUMO

While numerous sensing strategies have been applied in the determination of Acetaminophen (AP), dopamine (DA), and ascorbic acid (AA), the selectivity is always a critical challenge based on their similar structure and function. Accordingly, the development of a highly selective sensing method is not only necessary but also crucial. In this study, a novel electrochemical sensing platform for the simultaneous determination of AP and DA has been successfully constructed based on a multifunctional nanocomposite (WP6-Pd-COF) of water-soluble pillar[6]arene (WP6), ultrafine Pd nanoparticles, and triethylene glycol-modified covalent organic framework (COF). Pd nanoparticles with an average size of 4.2 nm are prepared by reducing K2PdCl4 under the stabilization of oxygen-rich COF, which shows superior catalytic activity in electrochemical detection. A supramolecular host-guest recognition system introduced between WP6 and analytes (AP, DA, and AA) can effectively recognize AP and DA, implying the simultaneous determination of AP and DA by this approach. The electrode, best operated at a working potential range from -0.2 to 0.8 V (vs. Hg/Hg2Cl2), works in the concentration ranges of 0.2-8 µM for DA and 0.1-7.5 µM for AP, and has a detection limit of 0.06 µM for DA and 0.03 µM for AP (S/N = 3). Therefore, this study presents potential application values in sensing, catalysis, and other fields.


Assuntos
Técnicas Biossensoriais , Grafite , Estruturas Metalorgânicas , Nanocompostos , Nanopartículas , Acetaminofen , Ácido Ascórbico , Dopamina , Técnicas Eletroquímicas , Eletrodos , Compostos de Amônio Quaternário , Água
9.
Nutr J ; 20(1): 46, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034769

RESUMO

BACKGROUND: Could nutritional status serve as prognostic factors for coronavirus disease 2019 (COVID-19)? The present study evaluated the clinical and nutritional characteristics of COVID-19 patients and explored the relationship between risk for malnutrition at admission and in-hospital mortality. METHODS: A retrospective, observational study was conducted in two hospitals in Hubei, China. Confirmed cases of COVID-19 were typed as mild/moderate, severe, or critically ill. Clinical data and in-hospital death were collected. The risk for malnutrition was assessed using the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the Controlling Nutritional Status (CONUT) via objective parameters at admission. RESULTS: Two hundred ninety-five patients were enrolled, including 66 severe patients and 41 critically ill patients. Twenty-five deaths were observed, making 8.47% in the whole population and 37.88% in the critically ill subgroup. Patients had significant differences in nutrition-related parameters and inflammatory biomarkers among three types of disease severity. Patients with lower GNRI and PNI, as well as higher CONUT scores, had a higher risk of in-hospital mortality. The receiver operating characteristic curves demonstrated the good prognostic implication of GNRI and CONUT score. The multivariate logistic regression showed that baseline nutritional status, assessed by GNRI, PNI, or CONUT score, was a prognostic indicator for in-hospital mortality. CONCLUSIONS: Despite variant screening tools, poor nutritional status was associated with in-hospital death in patients infected with COVID-19. This study highlighted the importance of nutritional screening at admission and the new insight of nutritional monitoring or therapy.


Assuntos
COVID-19/epidemiologia , Mortalidade Hospitalar , Desnutrição/epidemiologia , Avaliação Nutricional , Estado Nutricional , SARS-CoV-2 , Adulto , Idoso , China/epidemiologia , Comorbidade , Estado Terminal/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X
10.
J Fish Dis ; 44(7): 881-892, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33560558

RESUMO

Target identification is important for drug discovery. Unfortunately, no drug targets have been found in Ichthyophthirius multifiliis until now and further limited development of the novel drug for Ichthyophthiriasis. In this study, an iTRAQ-based quantitative proteomic analysis was used to find the target of malachite green (MG), exhibiting greater efficacy than the existing drugs, against I. multifiliis trophonts in situ. We also verified the proteomic results by RT-qPCR, TEM and cell apoptosis assay. Our results showed that major variations in protein abundance were found among many of the ribosome proteins, indicating ribosome might be a candidate target. Furthermore, GO and KEGG pathway analyses of differentially expressed proteins (DEPs) revealed that ribosome and PI3K-Akt signalling pathway were remarkably enriched. Taken together, the above DEPs were also verified by RT-qPCR and morphological observations. This study provides insights into the key proteins enriched in PI3K-Akt signal pathway and ribosome pathway as potential targets of MG killing I. multifiliis, which could be served as targets for other less toxic drugs and be tested as potential treatments for I. multifiliis.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Carpas , Infecções por Cilióforos/veterinária , Doenças dos Peixes/tratamento farmacológico , Hymenostomatida/efeitos dos fármacos , Corantes de Rosanilina/uso terapêutico , Animais , Anti-Infecciosos Locais/farmacologia , Infecções por Cilióforos/tratamento farmacológico , Infecções por Cilióforos/parasitologia , Doenças dos Peixes/parasitologia , Proteômica , Corantes de Rosanilina/farmacologia
11.
J Am Chem Soc ; 142(23): 10314-10318, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32433880

RESUMO

Fluorides have been widely applied in pharmaceutical, medicinal, and materials science as well as in fine chemical manufacturing. The performance of fluorides, however, can be markedly affected by the water content. One previous study (Maiti, A.; et al. Phys. Chem. Chem. Phys. 2008, 10, 5050) suggested that anhydrous 1,3-dimethylimidazolium fluoride ([DMIm]F) was unstable since the fluoride undergoes a self-decomposition reaction. Herein we first show quantum-chemical calculation evidence that although gas-phase [DMIm]F is unstable, the bulk phase of anhydrous [DMIm]F is quite stable. We then demonstrate the successful synthesis of the anhydrous [DMIm]F compound via the reaction between 1,3-dimethylimidazolium iodide and silver fluoride. Importantly, we find that anhydrous [DMIm]F possesses a high dissolution capability toward 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), although it is known that TATB is hardly dissolved in many common organic solvents. Our Born-Oppenheimer molecular dynamics (BOMD) simulations further show that the high dissolving ability of anhydrous [DMIm]F toward TATB can be attributed to the chemical reaction between the F- anion and the TATB molecules, which disrupts the strong hydrogen-bonding interaction among the TATB molecules. Alternatively, water molecules in hydrous [DMIm]F tend to form a hydration layer around the F- anion, thereby preventing F- from reacting with the TATB molecule. This result explains why TATB is barely dissolved in hydrous [DMIm]F.

12.
Langmuir ; 36(48): 14676-14685, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33227210

RESUMO

In this study, we constructed a highly sensitive and selective electrochemical sensing strategy for l-ascorbic acid (AA) based on a covalent organic framework (COF)-loading non-noble transition metal Co ion and macrocyclic cationic pillar[6]arene (CP6) nanocomposite (CP6-COF-Co). The COF plays a crucial role in anchoring the Co ion according to its crystalline porous and multiple coordination sites and has an outstanding performance for building an electrochemical sensing platform based on a unique two-dimensional structure. Accordingly, the transition-metal Co ion can be successfully anchored on the framework of COF and shows strong catalytic activity for the determination of AA. Moreover, introduction of host-guest recognition based on CP6 and AA can bring new properties for enhancing selectivity, sensitivity, and practical application in real environment. Host-guest interactions between CP6 and AA were evaluated by the 1H NMR spectrum. When compared with other literatures, our method displayed a lower determination limit and broader linear range. To the best of our knowledge, this is the first study carried out for the non-noble transition-metal Co ion, COF, and pillar[6]arene hybrid material in sensing field, which has a potential value in sensing, catalysis, and preparation of advanced multifunction materials.

13.
J Org Chem ; 85(4): 2092-2102, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-31876415

RESUMO

Herein, we describe an efficient copper-catalyzed coupling of sulfonamides with alkylamines to synthesize (E)-N-sulfonylformamidines. The reaction is accomplished under mild conditions without the use of a corrosive acid or base as an additive. It tolerates a broad scope of substrates and generates the products with exclusive (E)-stereoselectivity.

14.
Nanotechnology ; 31(13): 135705, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-31816606

RESUMO

While tremendous advancements in 2D materials anchoring Au nanoparticles have been made, it is an urgent challenge to explore a green and facile approach for obtaining small-size Au nanoparticles. The rise of 2D covalent organic framework (COF) presents more-promising candidates for constructing excellent sites for loading metal nanoparticles. In this study, a novel 2D heterogeneous hybrid nanomaterial (P6-Au-COF) based on COF and pillar[6]arene (P6) reduced Au nanoparticles (P6-Au) is prepared by a simple and green procedure. The Au nanoparticles with an average small diameter of 2-3 nm are homogeneously dispersed on the surface of the COF. The P6-Au-COF hybrid material shows highly catalytic performance for the reduction of nitrophenol isomers when compared with commercial Pd/C catalyst and other reported materials. The P6-Au-COF hybrid material exhibits durable recyclablility and stability during the catalytic reaction. Considering the outstanding merits of the heterogeneous 2D catalyst of P6-Au-COF as well as the simple and green preparation, this research might not only present enormous opportunities for stabilized, high-performance and sustainable catalysts, but be applied in other frontier study of sustainable functionalized nanocomposites and advanced materials.

15.
Anal Bioanal Chem ; 412(11): 2391-2397, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32076786

RESUMO

By adding 6 thymines to lengthen the parent aptamer combined with the change of "on" and "off" induced by the target for an assistant stem-loop DNA probe (ASP-SLP-MB), a new folding-type electrochemical kanamycin (Kana) aptamer-engineering dual-probe-based sensor (sensor d) was developed. By purposefully reducing the background current and increasing the electron transfer efficiency of methylene blue (MB), the sensor obtained significantly enhanced detection sensitivity compared with non-aptamer-engineering one-probe-based sensor (sensor a). Such efficacy was validated by a big decrease from 530.6 to 210.2 nA for the background current signal and from 360 to 0.3 nM for the detection limit. In addition to the improved sensitivity, the sensor also exhibited good selectivity, anti-fouling detection performance, and potential quantitative analysis ability, showing a feasible potential practical analytical application in real-life complicated samples, for example, milk and serum. The released results prove that the aptamer-engineering method is effective in improving the analytical performance of folding-type sensors and provides a methodological guidance for the design and fabrication of other high-performance folding-type aptasensors. Graphical abstract.


Assuntos
Antibacterianos/análise , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Canamicina/análise , Leite/química , Animais , Antibacterianos/sangue , Bovinos , Sondas de DNA/química , Técnicas Eletroquímicas/métodos , Canamicina/sangue , Hibridização de Ácido Nucleico
16.
J Nanobiotechnology ; 18(1): 32, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070333

RESUMO

Gold nanoparticles (GNPs) are one of the most widely used nanomaterials in various fields. Especially, the unique chemical and physical properties make them as the promising candidates in drug target identification, unfortunately, little is known about their application in parasites. In this paper, GNPs were employed as new solid support to identify drug targets of natural bioactive compound arctigenin (ARG) against fish monogenean parasite Gyrodactylus kobayashi. Before target identification, GNPs with ARG on the surface showed the ability to enter the live parasites even the nucleus or mitochondria, which made the bound compounds capable of contacting directly with target proteins located anywhere of the parasites. At the same time, chemically modified compound remained the anthelminthic efficacy against G. kobayashii. The above results both provide assurance on the reliability of using GNPs for drug target-binding specificity. Subsequently, by interrogating the cellular proteome in parasite lysate, myosin-2 and UNC-89 were identified as the potential direct target proteins of ARG in G. kobayashii. Moreover, results of RNA-seq transcriptomics and iTRAQ proteomics indicated that myosin-2 expressions were down-regulated after ARG bath treatment both in transcript and protein levels, but for UNC-89, only in mRNA level. Myosin-2 is an important structural muscle protein expressed in helminth tegument and its identification as our target will enable further inhibitor optimization towards future drug discovery. Furthermore, our findings demonstrate the power of GNPs to be readily applied to other parasite drugs of unknown targets, facilitating more broadly therapeutic drug design in any pathogen or disease model.


Assuntos
Furanos/metabolismo , Ouro/química , Lignanas/metabolismo , Nanopartículas Metálicas/química , Platelmintos/parasitologia , Proteoma/metabolismo , Animais , Transporte Biológico , Descoberta de Drogas , Peixes , Regulação da Expressão Gênica/efeitos dos fármacos , Mitocôndrias/metabolismo , Estrutura Molecular , Miosinas/genética , Miosinas/metabolismo , Ligação Proteica , Proteômica , RNA Mensageiro/efeitos dos fármacos , Reprodutibilidade dos Testes , Relação Estrutura-Atividade , Propriedades de Superfície
17.
BMC Ecol ; 20(1): 22, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295587

RESUMO

BACKGROUND: Chlorops oryzae is an important pest of rice crops. There have been frequent outbreaks of this pest in recent years and it has become the main rice pest in some regions. To elucidate the molecular mechanism of frequent C. oryzae outbreaks, we estimated the genetic diversity and genetic differentiation of 20 geographical populations based on a dataset of ISSR markers and COI sequences. RESULTS: ISSR data revealed a high level of genetic diversity among the 20 populations as measured by Shannon's information index (I), Nei's gene diversity (H), and the percentage of polymorphic bands (PPB). The mean coefficient of gene differentiation (Gst) was 0.0997, which indicates that only 9.97% genetic variation is between populations. The estimated gene flow (Nm) value was 4.5165, indicating a high level of gene flow and low, or medium, genetic differentiation among some populations. The results of a Mantel test revealed no significant correlation between genetic and geographic distance among populations, which means there is no evidence of significant genetic isolation by distance. An UPGMA (unweighted pair-group method with arithmetic averages) dendrogram based on genetic identity, did not indicate any major geographic structure for the 20 populations examined. mtDNA COI data indicates low nucleotide (0.0007) and haplotype diversity (0.36) in all populations. Fst values suggest that the 20 populations have low, or medium, levels of genetic differentiation. And the topology of a Neighbor-Joining tree suggests that there are no independent groups among the populations examined. CONCLUSIONS: Our results suggest that C. oryzae populations have high genetic diversity at the species level. There is evidence of frequent gene flow and low, or medium, levels of genetic differentiation among some populations. There is no significant correlation between genetic and geographic distance among C. oryzae populations, and therefore no significant isolation by distance. All results are consistent with frequent gene exchange between populations, which could increase the genetic diversity, and hence, adaptability of C. oryzae, thereby promoting frequent outbreaks of this pest. Such knowledge may provide a scientific basis for predicting future outbreaks.


Assuntos
Dípteros , Animais , China , DNA Mitocondrial , Fluxo Gênico , Variação Genética , Haplótipos , Filogenia
18.
Reprod Health ; 17(1): 84, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487257

RESUMO

BACKGROUND: Sexual and Reproductive Health (SRH) targets have been included as part of the United Nations Sustainable Development Goals and indictors are important to monitor progress towards these targets. SRH indicators are recommended for setting norms and measuring progress globally. However, given the diverse political, socioeconomic and cultural contexts in different countries, and lack of global agreement on broad indicators, it is important to select appropriate indicators for specific countries. Based on internationally recommended indicators and data availability in China, this paper selected four indictors to reflect SRH in China and interpreted these indictors by analyzing the underlying factors. METHODS: We employed secondary data analysis and key informant interviews. Secondary data were obtained from the China Health Statistical Yearbook (2005-2017), China Statistical Yearbook (2005-2017), and the sub-national estimates of the Global Burden Diseases Study 2016. We interviewed 36 key informants at national and sub-national levels. RESULTS: The four selected SRH indicators are contraceptive prevalence rate (CPR), adolescent birth rate, abortion rate, and availability of school sex education. CPR of married women has remained above 75% over the last three decades, indicating a high level of access to family planning (FP) services; however, unmarried but sexually active women have significant unmet needs for FP services. Although adolescent birth rates in China remain low, the abortion rate, abortion numbers, and the ratio of abortions to births increased from 2014 to 2016 while FP policy was relaxed. This suggests that abortion among unmarried women is a significant contributor to overall figures. Qualitative analysis of the availability of school sex education, reveals an absence of policy due to conservative attitudes of key stakeholders. CONCLUSION: Since SRH challenges vary significantly between contexts, indicators for measuring progress towards SRH targets should be selected based on country context. The CPR and abortion rate are currently available and important indicators to monitor the most basic part of SRH in China, but require modification to ensure they reflect universal access to quality reproductive healthcare by all reproductive age women, regardless of their marriage status. Policy and indicators on sex education need to be carefully developed to fit the context in China.


Assuntos
Aborto Induzido/estatística & dados numéricos , Comportamento Contraceptivo/estatística & dados numéricos , Gravidez na Adolescência/estatística & dados numéricos , Saúde Reprodutiva , Educação Sexual/estatística & dados numéricos , Saúde Sexual , Adolescente , China , Anticoncepção , Serviços de Planejamento Familiar , Feminino , Humanos , Gravidez
19.
BMC Surg ; 20(1): 182, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778094

RESUMO

BACKGROUND: The clinical incidence of appendiceal mucinous adenocarcinoma is low. Moreover, the case reports of postoperative relapse after surgery are rarely based on literature search results. Here, we report such a case spanning nearly 7 years and and review the relevant literature. CASE PRESENTATION: A 50-year-old female underwent additional surgery after appendectomy, and pathological examination confirmed mucinous adenocarcinoma. The patients underwent HIPEC (hyperthermic intraoperative chemotherapy) and adjuvant chemotherapy. Twenty-six months after the previous surgeries, another surgery, HIPEC, and adjuvant chemotherapy were performed again due to tumour recurrence. To date, the follow-up time is 43 months, and no recurrence or metastasis has been found. CONCLUSIONS: Appendix mucinous adenocarcinoma has a poor prognosis and the diagnosis depends on pathological and immunohistochemical examinations. Its clinical manifestations are non-specific, and CRS + HIPEC should be used for treatment, which is safe and effective.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias do Apêndice , Apêndice , Hipertermia Induzida , Neoplasias Peritoneais , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Apêndice/tratamento farmacológico , Neoplasias do Apêndice/cirurgia , Apêndice/cirurgia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Reoperação , Estudos Retrospectivos
20.
Fish Shellfish Immunol ; 93: 380-386, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374312

RESUMO

White spot syndrome virus (WSSV) is a serious epidemic pathogen of crustaceans and cause severe economic losses to aquaculture. However, no commercial drugs presently available to control WSSV infection. Genipin (GN) is a bioactive compound extracted from the fruit of Gardenia jasminoides and exhibits potential antiviral activity. In the study, the antiviral activity of GN against WSSV was investigated in crayfish Procambarus clarkii and in shrimp Litopenaeus vannamei. In vitro antiviral test showed that GN could inhibit WSSV replication in crayfish and in shrimp, and the highest inhibition on WSSV was over 99% when treatment with 50 mg/kg of GN for 24 h. In vivo antiviral test proved that GN could be used to treat and prevent WSSV infection. GN could also effectively protect crayfish from WSSV infection by reducing the mortality rate of WSSV-infected crayfish. Moreover, GN attenuated the WSSV-induced oxidative stress and inflammatory by upregulation the expression of antioxidant-related genes and downregulation the expression of inflammatory-related genes, respectively. Mechanically, GN inhibited WSSV replication at least via decreasing STAT (signal transducer and activator of transcription) gene expression to block WSSV immediate-early gene ie1 transcription. Additionally, the inhibition of BI-1 (Bax inhibitor-1) gene expression also played an important role in the suppression of WSSV infection. In conclusion, GN represented a potential therapeutic and preventive agent to block WSSV infection.


Assuntos
Antivirais/farmacologia , Astacoidea/fisiologia , Iridoides/farmacologia , Penaeidae/fisiologia , Vírus da Síndrome da Mancha Branca 1/efeitos dos fármacos , Animais , Astacoidea/virologia , Relação Dose-Resposta a Droga , Penaeidae/virologia , Distribuição Aleatória
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