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1.
Prev Vet Med ; 196: 105477, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34482152

RESUMO

Abattoir surveillance is an integral component of a bovine tuberculosis (bTB) eradication programme. The objective of this study was to determine the prevalence of bTB among culled adult dairy cows in Wuhan, China and to further assess two diagnostic procedures as an adjunct to the confirmation of M. bovis in animals with TB-like lesions. The study was conducted in an abattoir located in Wuhan, China over a period of 41 days from June to July 2019. A total of 171 culled adult dairy cows were sampled and inspected, and blood samples collected from 134 of these. The viscera and lymph nodes of the carcasses were visually inspected and palpated for TB-like lesions. A total of 28.1 % (48/171) of the carcasses had gross TB-like lesions. 89.6 % (43/48) of the animals with TB-like lesions were positive to a PCR procedure for bTB. The sensitivity and specificity for post-mortem examination for TB-like lesions using a Bayesian latent class analysis model was estimated to be 60.8 % and 86.6 %, respectively. A seroprevalence of 20.9 % (28/134) was recorded for antibody response to M. bovis antigens MPB70 and MPB83 based on an ELISA procedure. There was a low-moderate agreement between the ELISA and PCR results in the detection of bTB (Kappa = 0.46, 95 % CI: 0.24-0.67). The study confirms a high prevalence of bTB among culled adult dairy cows in the abattoir and highlights the need to implement surveillance for bTB based on post-mortem examination and ELISA and PCR methods in association with backward tracing of infected dairy herds.


Assuntos
Mycobacterium bovis , Tuberculose Bovina , Matadouros , Abate de Animais , Animais , Teorema de Bayes , Bovinos , China/epidemiologia , Indústria de Laticínios , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Reação em Cadeia da Polimerase/veterinária , Prevalência , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Tuberculose Bovina/epidemiologia
2.
Nanomicro Lett ; 13(1): 43, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34138226

RESUMO

Inspired by the nature, lotus leaf-derived gradient hierarchical porous C/MoS2 morphology genetic composites (GHPCM) were successfully fabricated through an in situ strategy. The biological microstructure of lotus leaf was well preserved after treatment. Different pores with gradient pore sizes ranging from 300 to 5 µm were hierarchically distributed in the composites. In addition, the surface states of lotus leaf resulted in the Janus-like morphologies of MoS2. The GHPCM exhibit excellent electromagnetic wave absorption performance, with the minimum reflection loss of - 50.1 dB at a thickness of 2.4 mm and the maximum effective bandwidth of 6.0 GHz at a thickness of 2.2 mm. The outstanding performance could be attributed to the synergy of conductive loss, polarization loss, and impedance matching. In particularly, we provided a brand-new dielectric sum-quotient model to analyze the electromagnetic performance of the non-magnetic material system. It suggests that the specific sum and quotient of permittivity are the key to keep reflection loss below - 10 dB within a certain frequency range. Furthermore, based on the concept of material genetic engineering, the dielectric constant could be taken into account to seek for suitable materials with designable electromagnetic absorption performance.

4.
Am J Transl Res ; 13(4): 3337-3343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017507

RESUMO

BACKGROUND: One of the major postoperative complications of esophageal cancer is acute respiratory distress syndrome (ARDS), which poses a great threat to patients' lives. In this research, the cause of ARDS after esophageal cancer surgery was explained from the aspect of the single-nucleotide polymorphism at rs7873784, rs10759930 and rs10983755 of the Toll-like receptor 4 (TLR4) gene. METHODS: A total of 75 patients complicated with ARDS after esophageal cancer surgery in our hospital were collected as the ARDS group and 150 patients without ARDS after surgery as the control group. Deoxyribonucleic acids (DNAs) in the peripheral blood of patients were extracted, and the polymorphism loci (rs7873784, rs10759930 and rs10983755) of the TLR4 gene were amplified through polymerase chain reaction (PCR) and sent to a company for sequencing. The concentration of serum TLR4 was detected by kits. RESULTS: The frequencies of the G allele at rs7873784 (P=0.011) and C allele at rs10759930 (P=0.000) in the ARDS group were remarkably lower than those in the control group. Besides, the frequencies of GG genotype at rs7873784 (P=0.000) and CC and CT genotypes at rs10759930 (P=0.000) in the control group were notably higher than those in the ARDS group, while the frequency of AA genotype at rs10983755 (P=0.001) in the ARDS group was clearly lower than that in control group. The survival status of patients with complications of ARDS was notably correlated with CT genotype at rs10759930 of the TLR4 gene since patients with genotype CT were more likely to die (P=0.001). The GG genotype at rs10983755 of the TLR4 gene was remarkably related to the mean mechanical ventilation time (P=0.003) and the average length of intensive care unit (ICU) stay (P=0.018). The ARDS group had a lower frequency of GCG haplotype (P=0.009) and a higher frequency of GTA haplotype (P=0.001) than the control group. The linkage disequilibrium D' was 0.781 between rs7873784 and rs10759930 of the TLR4 gene, and two loci were linked to each other. In addition, the concentration of serum TRL4 in patients with genotype CC at rs7873784 (P=0.034), genotype CT at rs7873784 (P=0.000) and genotype GG at rs10983755 (P=0.000) of the TLR4 gene in the ARDS group was higher than that in the control group. CONCLUSION: The single-nucleotide polymorphisms at rs7873784, rs10759930 and rs10983755 of the TLR4 gene are significantly related to ARDS after esophageal cancer surgery.

5.
Heart Surg Forum ; 24(2): E282-E292, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33798050

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common complication of cardiovascular surgery. The aim of this study was to investigate the correlation between Vasoactive-Inotropic Score (VIS) and postoperative acute kidney injury in adult patients with cardiovascular surgery. METHODS: We retrospectively reviewed the data of 1935 adult patients who underwent cardiovascular surgery between September 2017 and May 2019. The data of patients included demographic data, laboratory findings, intraoperative details, and postoperative clinical outcomes. We calculated VIS-max by using the highest doses of vasoactive and inotropic medications during the first 24h after cardiovascular surgery. Logistic regression model was used to evaluate whether the VIS-max was independently associated with postoperative AKI. Additionally, improvements in risk reclassification and discrimination were evaluated by calculating the net reclassification improvement (NRI), C-index and the integrated discrimination improvement (IDI) with the addition of the VIS-max to a baseline model of the Society of Thoracic Surgeons (STS) score for analyzing the association of VIS-max with postoperative AKI. RESULTS: In 1935 patients, 291 patients (15.0%) developed postoperative AKI from the second to seventh day after cardiovascular surgery, and 30 patients (1.6%) needed renal replacement therapy (RRT). In 291 patients with AKI, 3 patients (0.2%) with AKI class 1, 12 patients (0.6%) with AKI class 2, and 15 patients (0.8%) with AKI class 3 needed RRT. Multivariate logistic regression analysis showed that VIS-max was associated with postoperative AKI (odds ratio [OR]: 1.19, 95% confidence interval [CI]: 1.11-1.34, P < 0.001) and the need for RRT in AKI patients (OR: 1.29, 95%CI: 1.01-1.83, P = 0.007). The area under the ROC curves (AUROC) of VIS-max combining STS score for predicting postoperative AKI (AUROC: 0.84, 95%CI: 0.81-0.87, P < 0.001) and need of RRT (AUROC: 0.91, 95%CI: 0.86-0.96, P < 0.001) significantly were higher than the AUC of VIS-max, STS score and EuroSCORE. Inclusion of VIS-max into basic risk model of STS score provided an increase in all indexes of prognostic accuracy for postoperative AKI and need of RRT: C-statistic: 0.721, NRI: 21.8%, IDI: 4.9%; and C-statistic: 0.745, NRI: 24.7%, IDI: 5.6%, respectively. CONCLUSION: VIS-max is an independent predictor of postoperative AKI in adult patients after cardiovascular surgery and increases prognostic accuracy of STS score, allowing a risk reclassification.


Assuntos
Injúria Renal Aguda/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias , Medição de Risco/métodos , Vasoconstrição/fisiologia , Injúria Renal Aguda/fisiopatologia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
6.
ChemMedChem ; 16(11): 1740-1743, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-33522135

RESUMO

A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766, exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.

7.
Transbound Emerg Dis ; 68(3): 1216-1228, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32767733

RESUMO

Eliminating rabies is challenging in many developing countries, especially in rural areas. In contrast to the annual decline of human cases in China in last decade, the incidence of rabies in livestock has been increasingly reported. This paper reports the rabies outbreaks in beef cattle (Angus) in Shaanxi Province, China, which caused 31 and 5 deaths at an attack rate of 19.4% (95% CI: 13.6%-26.4%) and 0.25% (95% CI: 0.1%-0.6%) in a satellite cow farm (farm A) and a core intensive farm (farm B), respectively. The rabies infection was confirmed by several laboratory tests, and rabies virus (RABV) strains SXBJ15 and SXYL15 were isolated and characterized from farm A and B, respectively. The two strains were found to have a high genomic sequence similarity to the dog-associated China clade I strains previously identified in the neighbouring area. SXBJ15 was shown to have a higher mouse pathogenicity (1.07) than SXYL15 (0.45). RABV was also detected in the saliva and salivary glands from the affected cattle. The potential causes were investigated on the farm, and the biosecurity scores were 20 and 64 (a full score of 82) for farms A and B, respectively. The rabies infection is likely to result from rabid free-roaming dogs (FRDs). On farm A with more cow deaths, the rabies transmission between animals can be attributed to the improper disposal of aborted foetuses and placental materials as a food source for rabid FRDs, high stocking density and drinking water sharing. Additionally, vaccinating cattle with a canine vaccine was shown to help stop the spread of rabies in herds. These results indicate that the occurrence of RABV on cattle farms can be prevented by improving biosecurity measures to control the entry of rural FRDs on the farm and immunizing farm cattle against rabies.


Assuntos
Doenças dos Bovinos/epidemiologia , Surtos de Doenças/veterinária , Fazendas , Vírus da Raiva/genética , Vírus da Raiva/isolamento & purificação , Raiva/veterinária , Animais , Bovinos/virologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/transmissão , Doenças dos Bovinos/virologia , China/epidemiologia , Doenças do Cão/epidemiologia , Cães , Feminino , Genoma Viral , Humanos , Gado , Camundongos , Placenta , Gravidez , Raiva/epidemiologia , Raiva/transmissão , Raiva/virologia , Vacinas Antirrábicas , Vírus da Raiva/patogenicidade
8.
Pathogens ; 9(10)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086687

RESUMO

The objective of this study was to estimate the fecal carriage of Salmonella spp. among culled adult dairy cows presented to an abattoir in Wuhan, China and to evaluate their antimicrobial resistance profiles. Rectal swabs from 138 culled cows were cultured. Laboratory analysis involved the identification of Salmonella, the susceptibility assessment and the presence of Extended Spectrum ß-lactamases and mcr genes in the isolates. An overall prevalence of Salmonella of 29.0% was recorded with 63.4% (26/41) and 2.4% (1/41) of the isolates identified as S. Typhimurium and S. Dublin, respectively. The occurrence of Salmonella was higher (odd ratios: 3.3) in culled cows originating from the northeast zone of China than cows originating from the central and north zones. Twenty multi-drug resistant strains (resistant to three or more antimicrobial agents) were detected (48.8%) and overall, a high resistance to ampicillin (36/41) and tetracycline (15/41) was observed. Extended Spectrum ß-lactamases phenotypes were found in 7/41 isolates, of which all contained the blaCTX-M resistance gene, and no mcr genes were found by polymerase chain reaction. The high prevalence of Salmonella fecal carriage and antimicrobial resistance may contribute to an increased risk of Salmonella transmission to food.

9.
Microb Pathog ; 148: 104456, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32810556

RESUMO

Tripartite motif 25 (TRIM25) is a TRIM family member which is involved in innate immunity. However, its role in the modulation of host defense against Mycobacterium tuberculosis (M.tb) infection has not been investigated. Therefore, this study aimed to demonstrate the significance of TRIM25 in the regulation of macrophage responses to M.tb infection. TRIM25 was found to be significantly overexpressed (3.476-fold) in peripheral blood mononuclear cells (PBMCs) of 67 patients with pulmonary tuberculosis compared with 48 healthy controls. TRIM25 expression was enhanced following M.tb infection of RAW264.7 cells, a macrophage cell line. Overexpression of TRIM25 in M.tb-infected RAW264.7 cells led to a significant increase in phosphorylated p38 levels; however, the production of IL-6, IL-1ß, and TNF-α were significantly reduced. Finally, M.tb intracellular survival increased by 90% at 12 h post-infection (PI) (p < 0.01). To validate the previous results, TRIM25 levels in M.tb-infected RAW264.7 macrophages were down-regulated using small interfering RNA (siRNA). Therefore, it was concluded that TRIM25 promotes intracellular survival of M.tb in RAW264.7 cells, likely by enhancing p38 pathways and thereby inhibiting the production of proinflammatory cytokines. These results contribute to the further understanding of the host defense against M.tb infection.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Leucócitos Mononucleares , Transdução de Sinais , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases , Regulação para Cima
10.
Microb Pathog ; 149: 104303, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32504845

RESUMO

Dendritic cells (DCs) are critical for both innate and adaptive immunity. Meanwhile, nitric oxide (NO) is a member of reactive nitrogen species (RNS) generally considered to play a key role in the bactericidal process in innate immunity against Mycobacterium tuberculosis complex infection. The present study therefore investigated the mechanism of NO production in murine DCs induced by Mycobacterium bovis (M.bovis) and its attenuated strain Bacillus Calmette-Guérin (BCG) infection. The expression of genes Slc7A1, Slc7A2, iNOS, and ArgI essential to NO synthesis was up-regulated in M.bovis/BCG infected DCs. IFN-γ addition further increased, while the iNOS inhibitor L-NMMA significantly inhibited their expression. Accordingly, the end products of arginine metabolism, NO and urea, were found to be significantly increased. In addition, BCG induced significantly higher levels of apoptosis in DCs compared to M.bovis shown by higher levels of DNA fragmentation using flow cytometry and release of mitochondrial Cytochrome C, and up-regulation of the genes caspase-3, caspase-8, caspase-9 and dffa critical to apoptosis by qRT-PCR detection and western blot analysis. Furthermore, IFN-γ increased, but L-NMMA decreased apoptosis of M.bovis/BCG infected DCs. In addition, mycobacterial intracellular survival was significantly reduced by IFN-γ treatment in BCG infected DCs, while slightly increased by L-NMMA treatment. Taken altogether, our data show that NO synthesis was differentially increased and associated with apoptosis in M.bovis/BCG infected DCs. These findings may significantly contribute to elucidate the pathogenesis of M.bovis.


Assuntos
Mycobacterium bovis , Animais , Apoptose , Caspases , Células Dendríticas , Camundongos , Óxido Nítrico
11.
Artigo em Inglês | MEDLINE | ID: mdl-32325799

RESUMO

The interior noise and vibration of metro vehicles have been the subject of increasing concern in recent years with the development of the urban metro systems. However, there still is a lack of experimental studies regarding the interior noise and vibration of metro vehicles. Therefore, overnight field experiments of the interior noise and vibration of a standard B-type metro train running on a viaduct were conducted on metro line 14 of Guangzhou (China). Both the A-weighted sound pressure level and linear sound pressure level were used to evaluate the interior noise signals in order to revel the underestimation of the low-frequency noise components. The results show that the interior noise concentrates in the low-to-middle frequency range. Increasing train speeds have significant effects on the sound pressure level inside the vehicle. However, two obvious frequency ranges (125-250 Hz and 400-1000 Hz) with respective corresponding center frequencies (160 Hz and 800 Hz) of the interior noise are nearly independent of train speed. The spectrum analysis of the vehicle body vibration shows that the frequency peak of the floor corresponds to the first frequency peak of the interior noise spectrum. There are two frequency peaks around 40 Hz and 160 Hz of the sidewall's acceleration level. The frequency peaks of the acceleration level are also independent of the train speeds. It hopes that the field measurements in this paper can provide a data set for researchers for further investigations and can contribute to the countermeasures for reducing interior noise and vibration of a metro vehicle.


Assuntos
Veículos Automotores , Ruído , Vibração , Aceleração , China
12.
Microorganisms ; 8(4)2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32316659

RESUMO

: Mycobacterium tuberculosis is considered a successful pathogen with multiple strategies to undermine host immunity. The YrbE3A is encoded by Rv1964 within the RD15 region present in the genome of Mtb, but missing in M. bovis, M. bovis BCG (Pasteur) strain, and M. smegmatis (Ms). However, little is known about its function. In this study, the YrbE3A gene was cloned into pMV261 and expressed in Ms and BCG, while the strains with the vector served as the controls. The YrbE3A was expressed on the mycobacterial membrane, and the purified protein could stimulate RAW264.7 cells to produce IL-6. Furthermore, the effect of the recombinant strains on cytokine secretion by RAW264.7 was confirmed, which varied with the host strains. Ms_YrbE3A increased significantly higher levels of TNF-α and IL-6 than did Ms_vec, while BCG_YrbE3A enhanced higher TNF-α than BCG_vec. The pathways associated with NF-κB p65 and MAPK p38/JNK, other than Erk1/2, regulated this process. In addition, mice were infected with Ms_YrbE3A and Ms-vec and were kinetically examined. Compared to Ms-vec, Ms_YrbE3A induced more serious inflammatory damage, higher levels of TNF-α and IL-6, higher numbers of lymphocytes, neutrophils, and monocytes in a time-dependent way, but lower lung bacterial load in lung. These findings may contribute to a better understanding of Mtb pathogenesis.

13.
Sensors (Basel) ; 20(3)2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32013099

RESUMO

This paper focuses on the dynamic responses of a metro train-bridge system under train-braking. Experiments were performed on the elevated Metro Line 21 of Guangzhou (China). A continuous, three-span, rigid-frame bridge (42 m + 65 m + 42 m) and a standard B-type metro train were selected. The acceleration signals were measured at the center-points of the main span and one side-span, and the acceleration signals of the car body and the bogie frame were measured simultaneously. The train-bridge system's vibration characteristics and any correlations with time and frequency were investigated. The Choi-Williams distribution method and wavelet coherence were introduced to analyze the obtained acceleration signals of the metro train-bridge system. The results showed that the Choi-Williams distribution provided a more explicit understanding of the time-frequency domain. The correlations between different parts of the bridge and the train-bridge system under braking conditions were revealed. The present study provides a series of measured dynamic responses of the metro train-bridge system under train-braking, which could be used as a reference in further investigations.

14.
Microorganisms ; 8(2)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023904

RESUMO

Mycobacterium bovis (M. bovis) is a zoonotic pathogen that causes bovine and human tuberculosis. Dendritic cells play a critical role in initiating and regulating immune responses by promoting antigen-specific T-cell activation. Prostaglandin E2 (PGE2)-COX signaling is an important mediator of inflammation and immunity and might be involved in the pathogenesis of M. bovis infection. Therefore, this study aimed to reveal the character of PGE2 in the differentiation of naïve CD4+ T cells induced by infected dendritic cells (DCs). Murine bone marrow-derived DCs were pre-infected with M. bovis and its attenuated strain M. bovis bacillus Calmette-Guérin (BCG). Then, the infected DCs were co-cultured with naïve CD4+ T cells with or without the cyclooxygenase (COX) inhibitor indomethacin. Quantitative RT-PCR analysis and protein detection showed that PGE2/COX-2 signaling was activated, shown by the upregulation of PGE2 production as well as COX-2 and microsomal PGE2 synthase (mPGES1) transcription in DCs specifically induced by M. bovis and BCG infection. The further co-culture of infected DCs with naïve CD4+ T cells enhanced the generation of inflammatory cytokines IL-17 and IL-23, while indomethacin suppressed their production. Following this, the differentiation of regulatory T cells (Treg) and Th17 cell subsets was significantly induced by the infected DCs rather than uninfected DCs. Meanwhile, M. bovis infection stimulated significantly higher levels of IL-17 and IL-23 and the differentiation of Treg and Th17 cell subsets, while BCG infection led to higher levels of TNF-α and IL-12, but lower proportions of Treg and Th17 cells. In mice, M. bovis infection generated more bacterial load and severe abnormalities in spleens and lungs, as well as higher levels of COX-2, mPGE2 expression, Treg and Th17 cell subsets than BCG infection. In conclusion, PGE2/COX-2 signaling was activated in DCs by M. bovis infection and regulated differentiation of Treg and Th17 cell subsets through the crosstalk between DCs and naive T cells under the cytokine atmosphere of IL-17 and IL-23, which might contribute to M. bovis pathogenesis in mice.

15.
Mol Carcinog ; 59(4): 447-461, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32096299

RESUMO

Effective therapeutic targets for triple-negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration-approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR-155 is upregulated in BC, but whether and how miR-155 regulates DCA resistance is unclear. In this study, we demonstrated that miR-155 was upregulated in CD24- CD44+ BC stem cells (BCSCs). In addition, the overexpression of miR-155 increased the number of CD24- CD44+ CSCs, DCA resistance and tumor clone formation in MDA-231 and BT-549 BC cells, and knockdown of miR-155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR-155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin-5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR-155 in promoting stemness and DCA resistance in BC cells. Our data show that miR-155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR-155/TSPAN5 signaling axis in the treatment of TNBC.


Assuntos
Decitabina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , Tetraspaninas/genética , Neoplasias de Mama Triplo Negativas/genética , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Tetraspaninas/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-31991884

RESUMO

Uranium (U) mining activities, which lead to contamination in soils and waters (i.e., leachate from U mill tailings), cause serious environmental problems. However, limited research works have been conducted on U pollution associated with a whole soil-water system. In this study, a total of 110 samples including 96 solid and 14 water samples were collected to investigate the characteristics of U distribution in a natural soil-water system near a U mining tailings pond. Results showed that U concentrations ranged from 0.09 ± 0.02 mg/kg to 2.56 × 104± 23 mg/kg in solid samples, and varied greatly in different locations. For tailings sand samples, the highest U concentration (2.56× 104 ± 23 mg/kg) occurred at the depth of 80 cm underground, whereas, for paddy soil samples, the highest U concentration (5.22 ± 0.04 mg/kg) was found at surface layers. Geo-accumulation index and potential ecological hazard index were calculated to assess the hazard of U in the soils. The calculation results showed that half of the soil sampling sites were moderately polluted. For groundwater samples, U concentrations ranged from 0.55 ± 0.04 mg/L to 3.36 ± 0.02 mg/L with a mean value of 2.36 ± 0.36 mg/L, which was significantly lower than that of percolating waters (ranging from 4.56 ± 0.02 mg/L to 12.05 ± 0.04 mg/L, mean 7.91 ± 0.98 mg/L). The results of this study suggest that the distribution of U concentrations in a soil-water system was closely associated with hydrological cycles and U concentrations decreased with circulation path.


Assuntos
Monitoramento Ambiental , Água Subterrânea/análise , Poluentes Radioativos do Solo/análise , Urânio/análise , Poluentes Radioativos da Água/análise , China , Mineração
17.
J Pharm Sci ; 108(10): 3348-3358, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31103789

RESUMO

Vincristine (VCR) has been used in the treatment of lung cancer. To improve its efficacy, the designs of elevating lung exposure to drug and decreasing the clearance with extended time were brought out. Pulmonary delivery is regarded as a good choice in pulmonary diseases treatment. Spray-drying is a technology for the preparation of drugs that can be delivered to lung via a dry powder inhaler. The results showed an appropriate particle size and shape for the pulmonary delivery. The aerosol behaved a sustained-release profile while VCR solution released rapidly within 10 h. The antitumor activity was characterized by 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide assay, and half maximal inhibitory concentration values of VCR-liposomes spray-dried powder were 24.42 ± 1.88 nM and 55.28 ± 4.76 nM in MCF-7 and A549 cells, respectively. Compared with the free VCR, the aerosol performed better pharmacokinetic behavior: increased maximum concentration (630.8%) and systemic exposure (429.6%) and decreased elimination half-life (81.1%). The clearance was decreased by 83.2%. Comprehensively, the pulmonary delivery seemed to be a recommendable way to effectively treat the pulmonary disease.


Assuntos
Lipossomos/química , Pulmão/efeitos dos fármacos , Pós/química , Pós/farmacocinética , Vincristina/química , Vincristina/farmacocinética , Células A549 , Administração por Inalação , Aerossóis/química , Aerossóis/farmacocinética , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Inaladores de Pó Seco/métodos , Humanos , Células MCF-7 , Tamanho da Partícula
18.
Pulm Pharmacol Ther ; 55: 50-61, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30738974

RESUMO

Pulmonary delivery of anti-cancer drugs in the form of nanoparticulate dry powders is considered a promising modality for treating lung cancer. However, it is not known whether the pharmacodynamics and pharmacokinetics of nano-preparations are altered after co-spray drying. In this study, we compared the physicochemical property, anti-cancer activity, tumor targeting and pharmacokinetic behavior of docetaxel-loaded folic acid-conjugated liposomes (LPs-DTX-FA) with those of dry powder prepared by co-spray-drying LPs-DTX-FA. The particle size and PDI after re-dispersion of the powder were increased. The re-dispersed liposomes showed increased cellular uptake via micropinocytosis and exhibited higher cytotoxicity than LPs-DTX-FA. Tumor targeting of re-dispersed liposomes was less effective compared with LPs-DTX-FA but the metabolism of re-dispersed liposomes was decreased. Tracheal administration resulted in a 45-fold higher concentration of docetaxel in the lung of Sprague Dawley rats at 30 min as compared with intravenous administration. Our results indicated that co-spray drying did change the properties, while tracheal administration of the dry powder provided higher drug exposure at the tumor site without increasing the exposure of other organs. Thus, inhaled dry powders might be clinically effective for treatment of lung cancer.


Assuntos
Antineoplásicos/administração & dosagem , Docetaxel/administração & dosagem , Ácido Fólico/química , Neoplasias Pulmonares/tratamento farmacológico , Administração por Inalação , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Docetaxel/química , Docetaxel/farmacocinética , Sistemas de Liberação de Medicamentos , Inaladores de Pó Seco , Lipossomos , Masculino , Tamanho da Partícula , Pós , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
19.
Plant Physiol ; 178(4): 1657-1678, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30309966

RESUMO

KEA4, KEA5, and KEA6 are members of the Arabidopsis (Arabidopsis thaliana) K+ efflux antiporter (KEA) family that share high sequence similarity but whose function remains unknown. Here, we show their gene expression pattern, subcellular localization, and physiological function in Arabidopsis. KEA4, KEA5, and KEA6 had similar tissue expression patterns, and the three KEA proteins localized to the Golgi, the trans-Golgi network, and the prevacuolar compartment/multivesicular bodies, suggesting overlapping roles of these proteins in the endomembrane system. Phenotypic analyses of single, double, and triple mutants confirmed functional redundancy. The triple mutant kea4 kea5 kea6 had small rosettes, short seedlings, and was sensitive to low K+ availability and to the sodicity imposed by high salinity. Also, the kea4 kea5 kea6 mutant plants had a reduced luminal pH in the Golgi, trans-Golgi network, prevacuolar compartment, and vacuole, in accordance with the K/H exchange activity of KEA proteins. Genetic analysis indicated that KEA4, KEA5, and KEA6 as well as endosomal Na+/H+exchanger5 (NHX5) and NHX6 acted coordinately to facilitate endosomal pH homeostasis and salt tolerance. Neither cancelling nor overexpressing the vacuolar antiporters NHX1 and NHX2 in the kea4 kea5 kea6 mutant background altered the salt-sensitive phenotype. The NHX1 and NHX2 proteins in the kea4 kea5 kea6 mutant background could not suppress the acidity of the endomembrane system but brought the vacuolar pH close to wild-type values. Together, these data signify that KEA4, KEA5, and KEA6 are endosomal K+ transporters functioning in maintaining pH and ion homeostasis in the endomembrane network.


Assuntos
Antiporters/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Potássio/metabolismo , Antiporters/genética , Arabidopsis/citologia , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Compartimento Celular/fisiologia , Regulação da Expressão Gênica de Plantas , Complexo de Golgi/metabolismo , Homeostase/fisiologia , Concentração de Íons de Hidrogênio , Lítio/farmacologia , Plantas Geneticamente Modificadas , Potássio/farmacologia , Estresse Salino/genética , Vacúolos/genética , Vacúolos/metabolismo , Rede trans-Golgi/metabolismo
20.
Mar Drugs ; 16(8)2018 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-30081563

RESUMO

Natural angiotensin converting enzyme (ACE)-inhibitory peptides, which are derived from marine products, are useful as antihypertensive drugs. Nevertheless, the activities of these natural peptides are relatively low, which limits their applications. The aim of this study was to prepare efficient ACE-inhibitory peptides from sea cucumber-modified hydrolysates by adding exogenous proline according to a facile plastein reaction. When 40% proline (w/w, proline/free amino groups) was added, the modified hydrolysates exhibited higher ACE-inhibitory activity than the original hydrolysates. Among the modified hydrolysates, two novel efficient ACE-inhibitory peptides, which are namely PNVA and PNLG, were purified and identified by a sequential approach combining a sephadex G-15 gel column, reverse-phase high-performance liquid chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS), before we conducted confirmatory studies with synthetic peptides. The ACE-inhibitory activity assay showed that PNVA and PNLG exhibited lower IC50 values of 8.18 ± 0.24 and 13.16 ± 0.39 µM than their corresponding truncated analogs (NVA and NLG), respectively. Molecular docking showed that PNVA and PNLG formed a larger number of hydrogen bonds with ACE than NVA and NLG, while the proline at the N-terminal of peptides can affect the orientation of the binding site of ACE. The method developed in this study may potentially be applied to prepare efficient ACE-inhibitory peptides, which may play a key role in hypertension management.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Peptídeos/farmacologia , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/química , Pepinos-do-Mar , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Desenho de Fármacos , Ensaios Enzimáticos , Hipertensão/tratamento farmacológico , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Peptídeos/química , Peptídeos/isolamento & purificação , Prolina/química , Hidrolisados de Proteína/farmacologia , Relação Estrutura-Atividade , Especificidade por Substrato , Espectrometria de Massas em Tandem/métodos
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