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Respiratory syncytial virus (RSV) causes lower respiratory tract diseases and bronchiolitis in children and elderly individuals. There are no effective drugs currently available to treat RSV infection. In this study, we report that Licochalcone A (LCA) can inhibit RSV replication and mitigate RSV-induced cell damage in vitro, and that LCA exerts a protective effect by reducing the viral titer and inflammation in the lungs of infected mice in vivo. We suggest that the mechanism of action occurs through pathways of antioxidant stress and inflammation. Further mechanistic results demonstrate that LCA can induce nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus, activate heme oxygenase 1 (HO-1), and inhibit reactive oxygen species-induced oxidative stress. LCA also works to reverse the decrease in I-kappa-B-alpha (IкBα) levels caused by RSV, which in turn inhibits inflammation through the associated nuclear factor kappa B and tumor necrosis factor-α signaling pathways. The combined action of the two cross-talking pathways protects hosts from RSV-induced damage. To conclude, our study is the first of its kind to establish evidence of LCA as a viable treatment for RSV infection.
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Chalconas , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Animais , Camundongos , Chalconas/farmacologia , Chalconas/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , InflamaçãoRESUMO
Constructing van der Waals (vdW) heterostructures provides an effective and feasible method for 2D materials to improve their properties and extend their possible applications. Using first-principles calculations, we explored the atomic and electronic structures of Janus In2SeX (X = S or Te) and revealed the existence of a vertical internal intrinsic electric field in these Janus monolayers. Then, we stacked the pristine InSe and Janus In2SeX (X = S or Te) with black phosphorus (BP) vertically to construct vdW heterostructures with a mismatch of less than 5% and systematically investigated their interface atomic structures and possible applications in photovoltaics. The calculation results reveal that the constructed vdW heterostructures can be synthesized experimentally, and the type-II band alignment can be found in all vdW heterostructures, which is independent of the internal electric field of Janus monolayers, the built-in dipole at the interface between two domains, and the number of layers. In addition, the vdW heterostructures show stronger light absorption compared to monolayer individuals, and the type-II band alignment can help the photo-excited carriers to separate and achieve an excellent photovoltaic power conversion efficiency of up to about 21% in these heterostructures. These extraordinary results suggest that these vdW heterostructures have great potential for more efficient solar photovoltaic applications.
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OBJECTIVE: This study sought to investigate the effect of miR-5191 on proliferation, invasion and metastasis in salivary adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: The differential expression level of miR-5191 between 5 primary tumor and adjacent non-neoplastic samples, and in two SACC cell lines was detected by quantitative real-time PCR. Cell proliferation, invasion, and migration were performed, followed by luciferase reporter assay and western analysis. The effect of miR-5191 on cell proliferation and apoptosis was evaluated by cell growth and apoptosis assay. The function of miR-5191 in SACC tumorigenesis and metastasis in vivo was investigated by nude mice experiment. The associations between miR-5191/Notch-2 expression and clinicopathological features were analyzed. RESULTS: miR-5191 was downregulated in primary tumor tissues and SACC-LM cells. By targeting Notch-2, miR-5191 expression level affected the migration, invasion, and proliferation of SACC cells. Overexpression of miR-5191 inhibited the expression levels of Notch-2, followed by the decreased expression of c-Myc, Bcl-2, Hes-1, Hey-1, and Cyclin D1. In vivo, miR-5191 overexpression suppressed the SACC tumorigenesis and pulmonary metastasis in mice. In SACC patients, higher expression of miR-5191 was related to better prognoses and lower possibility of metastasis. CONCLUSIONS: miR-5191 acts as a tumor suppressor in SACC by targeting Notch-2.
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Carcinoma Adenoide Cístico , MicroRNAs , Receptor Notch2/metabolismo , Neoplasias das Glândulas Salivares , Animais , Carcinogênese , Carcinoma Adenoide Cístico/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Neoplasias das Glândulas Salivares/patologiaRESUMO
BACKGROUND: Rice (Oryza sativa L.) Chalkiness, the opaque part in the kernel endosperm formed by loosely piled starch and protein bodies. Chalkiness is a complex quantitative trait regulated by multiple genes and various environmental factors. Phytohormones play important roles in the regulation of chalkiness formation but the underlying molecular mechanism is still unclear at present. RESULTS: In this research, Xiangzaoxian24 (X24, pure line of indica rice with high-chalkiness) and its origin parents Xiangzaoxian11 (X11, female parent, pure line of indica rice with high-chalkiness) and Xiangzaoxian7 (X7, male parent, pure line of indica rice with low-chalkiness) were used as materials. The phenotype, physiological and biochemical traits combined with transcriptome analysis were conducted to illustrate the dynamic process and transcriptional regulation of rice chalkiness formation. Impressively, phytohormonal contents and multiple phytohormonal signals were significantly different in chalky caryopsis, suggesting the involvement of phytohormones, particularly ABA and auxin, in the regulation of rice chalkiness formation, through the interaction of multiple transcription factors and their downstream regulators. CONCLUSION: These results indicated that chalkiness formation is a dynamic process associated with multiple genes, forming a complex regulatory network in which phytohormones play important roles. These results provided informative clues for illustrating the regulatory mechanisms of chalkiness formation in rice.
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Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Oryza/genética , Oryza/fisiologia , Reguladores de Crescimento de Plantas/farmacologia , Transcrição Gênica/efeitos dos fármacos , Endosperma/efeitos dos fármacos , Endosperma/metabolismo , Endosperma/ultraestrutura , Perfilação da Expressão Gênica , Ontologia Genética , Oryza/efeitos dos fármacos , Fenótipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reprodutibilidade dos Testes , Amido/metabolismo , Amido/ultraestrutura , Sacarose/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: To evaluate the clinical outcomes of reconstruction of maxillary class III defect using 3D-printed titanium mesh. METHODS: Twelve patients with maxillary class III defect from April 2015 to December 2016 were retrospectively studied. A 3D individualized maxillary stereo model based on mirror images of the unaffected maxilla was obtained to fabricate an anatomically adapted titanium mesh using computer-assisted design and manufacture. The individual titanium mesh was inserted into the maxillary class III defect after total maxillectomy. The incidence of postoperative complications was evaluated. The postoperative orbital volume and protrusion degree of eye were measured. RESULTS: All patients were satisfied with their postoperative facial symmetry, without developing diplopia or endophthalmos. The postoperative orbital volumes were 26.41 ± 0.52 mL on the affected side and 26.55 ± 0.45 mL on the unaffected side. The postoperative protrusion degrees of affected and unaffected eyes were 16.21 ± 0.48 and 16.82 ± 0.79 mm, respectively. Titanium mesh exposure was observed in 2 patients and mild limitation of mouth opening was observed in 4 patients who underwent postoperative radiotherapy. CONCLUSION: Reconstruction of maxillary class III defect with 3D-printed titanium mesh can achieve successful clinical outcomes, which recovered orbital volume and protrusion degree of eye. Twelve patients with maxillary class III defect were satisfied with their postoperative facial symmetry, without developing diplopia or endophthalmos. We investigated that reconstruction of maxillary class III defect with 3D-printed titanium mesh can achieve successful clinical outcomes.
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Materiais Biocompatíveis , Neoplasias Ósseas/cirurgia , Maxila/cirurgia , Impressão Tridimensional , Alicerces Teciduais , Titânio , Humanos , Masculino , Teste de Materiais , Osteossarcoma/cirurgia , Adulto JovemRESUMO
The aim of this study was to investigate the clinical outcomes of orbital blowout fracture repair by using the three-dimensional (3D) printing-assisted fabrication of individual titanium mesh. Clinical and radiologic data were analyzed for 12 patients with orbital floor and/or medial wall fractures. Lower eyelid incision was used to expose the fractures. Preoperative computed tomographic data were input into an imaging software to rebuild a 3D orbit and mirror the unaffected side into the affected side to replace the demolished orbit. A resin model of the reshaped orbit was generated and used to develop an individual titanium mesh for repairing the fractured orbital. The surgical results were assessed by value of enophthalmos and a comparison of preoperative and postoperative orbital volume difference. All patients had a successful treatment outcome without any complications. Clinical significant enophthalmos were not observed after treatment, and diplopia were solved within 2 weeks postoperative. No extraocular muscle limitation was observed. Postoperative computed tomography scans demonstrated appropriate positioning of titanium mesh and there was no implant displacement. The postoperative orbital volume and enophthalmos difference between the 2 eyes decreased significantly than preoperative (Pâ<â0.001). Three-dimensional printing-assisted fabrication of individual titanium mesh is appropriate for use in orbital blowout fracture.
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Fraturas Orbitárias/diagnóstico por imagem , Impressão Tridimensional , Adulto , Diplopia/etiologia , Enoftalmia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas Orbitárias/complicações , Fraturas Orbitárias/cirurgia , Software , Titânio , Tomografia Computadorizada por Raios X/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
Testis-specific gene 13 (TSGA13) is abundantly expressed in testis. As previous studies of TSGA13 expression pattern have all been based on mRNA analysis, it is imperative to investigate its actual protein expression. Here, we first examined TSGA13 gene tree and protein homology among species, and found that TSGA13 is relatively well conserved. Next, we detected its protein expression in normal human tissues as well as in a limited number of malignant tumors by immunohistochemistry (IHC). It was demonstrated that, in addition to testis, high expression of TSGA13 could also be observed in multiple normal tissues, including stomach, larynx, spleen, bladder, tonsil, liver and thyroid. Notably, most types of human carcinoma tissues displayed reduced expression of TSGA13 rather than their adjacent normal tissues except glioblastoma and lung cancer. Hence, the data from the current study strongly suggest the association between TSGA13 and tumor malignancy.
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Proteínas de Neoplasias/genética , Neoplasias/genética , Especificidade de Órgãos , Proteínas/genética , Especificidade de Anticorpos/imunologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Immunoblotting , Imuno-Histoquímica , Masculino , Proteínas de Neoplasias/metabolismo , Neoplasias/patologia , Filogenia , Proteínas/metabolismo , Reprodutibilidade dos Testes , Homologia de Sequência de Aminoácidos , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , TestículoRESUMO
Infant colic, excessive crying of unknown cause, is a major burden to families and effects about 10-30 % of infants. Despite decades of research, the exact cause and treatment of infant colic has remained elusive. The use of Lactobacillus reuteri (DSM 17938) in infant colic is somewhat controversial and hence, we designed this study to evaluate its efficacy in infantile colic. We recruited predominantly or exclusively breastfed infants, aged less than 4 months in a placebo controlled observational randomized study. Participants' were assigned to receive L. reuteri at a dose 10(8) colony forming units (n = 21) and placebo (n = 21). Placebo was an identical formulation without live micro-organisms. Treatment was given to subjects for 21 days and they were followed for 4 weeks. Treatment success (primary outcome), daily reduction in crying time, parent satisfaction and reduction in maternal depression (secondary outcomes) were assessed at the end of study period. Treatment success was observed in all infants (100 %) of the probiotic group while it was seen in 15.7 % of the placebo group. Mean daily crying time was more significantly reduced to 32.1 ± 8.3 min/day (P < 0.01) from 200.9 ± 6.3 min/day in the probiotic group as compared to the placebo group (120.6 ± 20.0 min/day). Moreover, throughout the study period, parent's satisfaction and improvement in maternal depression (Edinburgh postnatal depression scale) was also significantly higher in the probiotic group. In our study population, reduction in crying time was significant (P < 0.01) even during first week of initiation of therapy. We conclude that L. reuteri (DSM 17938) reduces daily crying time and maternal depression during infantile colic. We suggest L. reuteri may be a safe and efficacious option for reducing infant colic.
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Dor Abdominal/prevenção & controle , Dor Abdominal/psicologia , Cólica/prevenção & controle , Cólica/psicologia , Depressão/prevenção & controle , Limosilactobacillus reuteri , Probióticos/administração & dosagem , Humanos , Lactente , Recém-Nascido , Mães , Placebos/administração & dosagem , Distribuição Aleatória , Resultado do TratamentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia. AIM OF THE STUDY: To evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO. MATERIALS AND METHODS: CGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR. RESULTS: (E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 µg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment. CONCLUSIONS: The findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO.
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ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Guizhi decoction (CGD) is a classic Traditional Chinese Medicine (TCM) prescription for the treatment of influenza and fever, composes of Bupleuri Radix (Chaihu), Cinnamomi Ramulus (Guizhi), Scutellariae Radix (Huangqin), Codonopsis Radix (Dangshen), Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle (Zhigancao), Pinelliae Rhizoma Praeparatum (Fabanxia), Zingiberis Rhizoma Recens (Shengjiang), Paeoniae Radix Alba (Baishao) and Jujubae Fructus (Dazao) in the ratio of 12:4.5:4.5:4.5:3:6:4.5:4.5:4. The efficacy of TCM, if there are differences, depends on the different extraction methods and extracted components. AIM OF THE STUDY: This study was to evaluate the anti-influenza virus effect of CGD extracts with different extraction methods, analyze the components and explore their correlation. MATERIALS AND METHODS: CGD were prepared with four extraction methods respectively, the traditional decoction (TD), two steps alcohol-water extraction (AWE), alcohol reflux extraction (AE) and water reflux extraction (WE). Based on the influenza mouse model, the efficacy of anti-influenza virus in vivo of the four CGD extracts were evaluated with the therapeutic index of body weight, rectal temperature, lung index, thymus index and lung viral load of mice. The chemical components in four CGD extracts, and compounds absorbed in rats blood with prototypes or metabolites were identified by UPLC-Q-Exactive/MS. The partial least squares (PLS) method was used to explore the correlation between the components variation in CGD extracts and the comprehensive efficacy index. The potential effective components were further accessed by molecular docking. RESULTS: Comparing with the other three extracts, AWE has the best anti-influenza effect. It could ameliorate the symptoms caused by influenza virus infection in mice, increase body weight and rectal temperature, reduce the lung index and virus load in lung tissue. 129, 144, 140 and 129 components were identified from TD, AWE, AE, and WE respectively. The identified components were mainly including flavonoids, terpenoids, organic acids, phenylpropanoids, amino acids, nucleosides, phenols, alkaloids, etc. 43 prototypes and 49 metabolites of CGD were detected in rat plasma after oral administration. Seven components, cinnamaldehyde, wogonoside, baicalin, baicalein, gallic acid, oroxylinA-7-O-glucuronide and coumarin, showed significant correlation with anti-influenza effects, all of which had good binding activity with NA, IL-6, STAT3, AKT1, EGFR and TNF. CONCLUSION: Two steps alcohol-water extraction was optimal for CGD preparation. Cinnamaldehyde, wogonoside, oroxylinA-7-O-glucuronide, coumarin, gallic acid, baicalein and baicalin play a certain essential role in anti-influenza effects and may be taken as a potential maker compounds for quality evaluation of CGD.
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Medicamentos de Ervas Chinesas , Influenza Humana , Ratos , Camundongos , Animais , Humanos , Simulação de Acoplamento Molecular , Glucuronídeos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Peso Corporal , Cumarínicos , Ácido Gálico , ÁguaRESUMO
BACKGROUND: Wheat crown rot (WCR), primarily caused by Fusarium pseudograminearum has become more and more prevalent in winter wheat areas in China. However, limited fungicides have been registered for the control of WCR in China so far. Pyraclostrobin is a representative quinone outside inhibitor (QoI) with excellent activity against Fusarium spp. There is currently limited research on the resistance risk and resistance mechanism of F. pseudograminearum to pyraclostrobin. RESULTS: Here, we determined the activity of pyraclostrobin against F. pseudograminearum. The EC50 values ranged from 0.022 to 0.172 µg mL-1 with an average EC50 value of 0.071 ± 0.030 µg mL-1. Four highly pyraclostrobin-resistant mutants were obtained from two sensitive strains by ultraviolet (UV) mutagenesis in the laboratory. The mutants showed decreased mycelial growth rate and virulence as compared with the corresponding wild-type strains, indicating that pyraclostrobin resistance suffered a fitness penalty in F. pseudograminearum. It was found that the high resistance of four mutants was caused by the G143S mutation in Cytb. Molecular docking analysis also further confirms that the G143S mutation in Cytb decreased the binding affinity between pyraclostrobin and Cytb. CONCLUSION: The resistance risk of F. pseudograminearum to pyraclostrobin could be low to medium. Although a mutation at the G143S position of Cytb could potentially occur, this mutation decreases the fitness of the mutant, which may reduce its survival in the environment. Therefore, the negative consequences of a possible mutation are lower. This makes pyraclostrobin a good candidate for controlling crown rot in wheat. © 2024 Society of Chemical Industry.
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Both lung and gut belong to the common mucosal immune system (CMIS), with huge surface areas exposed to the external environment. They are the main defense organs against the invasion of pathogens and play a key role in innate and adaptive immunity. Recently, more and more evidence showed that stimulation of one organ can affect the other, as exemplified by intestinal complications during respiratory disease and vice versa, which is called lung-gut crosstalk. Intestinal microbiota plays an important role in respiratory and intestinal diseases. It is known that intestinal microbial imbalance is related to inflammatory bowel disease (IBD), this imbalance could impact the integrity of the intestinal epithelial barrier and leads to the persistence of inflammation, however, gut microbial disturbances have also been observed in respiratory diseases such as asthma, allergy, chronic obstructive pulmonary disease (COPD), and respiratory infection. It is not fully clarified how these disorders happened. In this review, we summarized the latest examples and possible mechanisms of lung-gut crosstalk in respiratory disease and IBD and discussed the strategy of shaping intestinal flora to treat respiratory diseases.
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Asma , Doenças Inflamatórias Intestinais , Doença Pulmonar Obstrutiva Crônica , Humanos , Inflamação , PulmãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Qingjin Huatan Decoction (QJHTT) consists of 11 herbal medicines: Scutellaria baicalensis Georgi, Gardenia jasminoides J.Ellis, Platycodon grandiflorus (Jacq.) A.DC., Ophiopogon japonicus (Thunb.) Ker Gawl., Morus alba L., Fritillaria thunbergii Miq., Anemarrhena asphodeloides Bunge, Trichosanthes kirilowii Maxim., Citrus reticulata Blanco, Poria cocos (Schw.) Wolf, and Glycyrrhiza uralensis Fisch. As a traditional compound Chinese medicinal formula, QJHTT has been used for more than 400 years in China. Historically, it was used to treat respiratory diseases and had shown beneficial clinical results for diseases related to lung inflammation. AIM OF THE STUDY: To investigate the therapeutic effect of QJHTT on influenza A virus (IAV) pneumonia in mice and explore its possible mechanism of action. MATERIALS AND METHODS: The components in QJHTT were analyzed by UPLC-Q-TOF-MS and some antiviral active components reported in the literature were determined and quantified by HPLC. The protective effects of QJHTT were investigated using lethal and sublethal doses (2 LD50 or 0.8 LD50 viral suspension, separately) of H1N1-infected mice. Mortality and lung lesions in H1N1-infected mice were used to evaluate the efficacy of QJHTT. The potential mechanism of QJHTT in the treatment of viral pneumonia was determined at the gene level by RNA sequencing and validated by qRT-PCR. Following this, the changes in protein levels of JAK2/STAT3 were analyzed since it is a key downstream target of the chemokine signaling pathways. Preliminary elucidation of the mechanism of QJHTT to protect mice against IAV pneumonia through this pathway was conducted. RESULTS: In this study, 12 antiviral active constituents including baicalin, geniposide, and mangiferin were identified from QJHTT. In vivo treatment of QJHTT reduced the virus titers of lung tissue significantly and improved the survival rate, lung index, and pulmonary histopathological changes; additionally, a reduction in the serum levels of TNF-α, IL-1ß, IL-6, and IFN-γ inflammatory factors in H1N1-infected mice was observed. RNA-seq analysis and qRT-PCR showed that QJHTT primarily reversed the activities CCL2, CCL7, CCR1, and other chemokines and their reception-related genes, suggesting that QJHTT may produce disease-resistant pneumonia by inhibiting the downstream JAK2/STAT3 pathway. Western blot analysis confirmed that QJHTT effectively reduced the protein levels of JAK2, STAT3, and related phosphorylated products in the lung tissue of H1N1-infected mice. CONCLUSIONS: Our results indicated that QJHTT alleviated IAV pneumonia in mice by regulating related chemokines and their receptor-related genes in lung tissue, thereby inhibiting JAK2/STAT3 pathway. This could pave way for the design of novel therapeutic strategies to treat viral pneumonia.
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Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Infecções por Orthomyxoviridae , Pneumonia Viral , Animais , Camundongos , Pneumonia Viral/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Quimiocinas , Transdução de SinaisRESUMO
Chitosan (CH), partially N-deacetylated chitin, is a biodegradable and biocompatible polymer that has shown great potential in drug delivery and tissue engineering applications. Although bioadhesive, CH has limited mucoadhesion in wet conditions due to weak interactions with biological surfaces. DOPA (3,4-dihydroxy-L-phenylalanine), a catechol-containing molecule naturally present in marine mussel foot proteins, has been shown to increase the mucoadhesion of several polymers. We report here a simple and bioinspired approach to enhance CH mucoadhesion in wet conditions by preparing mixed hydrogels including CH and different catechol-containing compounds, namely DOPA, hydrocaffeic acid (HCA), and dopamine (DA). We characterized the hydrogels for their swelling, release kinetics of the catechol compounds, and mucoadhesive strength to rabbit small intestine. The swelling of the hydrogels was pH dependent with maximum swelling at pH 1. The hydrogel swelling was higher in the presence of the DOPA and DA but lower in the presence of HCA. HCA/CH hydrogel also showed the slowest catechol release, most likely due to electrostatic interactions between CH and HCA. Lower hydrogel swelling and slower HCA release resulted in increased mucoadhesion: HCA/CH showed more than 2-fold enhancement of mucoadhesion to rabbit small intestine compared to CH alone. Since it is known that catechol compounds can be oxidized, we analyzed the oxidation of DOPA, HCA, and DA at different pH values and its effect on mucoadhesion. We found that oxidation occurring before contact with the intestinal mucosa did not improve mucoadhesion, while oxidation occurring during the contact further increased the mucoadhesion of HCA/CH hydrogels. These results show that mucoadhesion of CH hydrogels can be increased with a simple bioinspired approach, which has the potential to be applied to other polymers since it does not require any chemical modification.
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Materiais Biocompatíveis/química , Quitosana/química , Ácidos Cafeicos/química , Di-Hidroxifenilalanina/química , Dopamina/química , Hidrogéis/síntese química , Hidrogéis/química , Concentração de Íons de Hidrogênio , Cinética , OxirreduçãoRESUMO
Polysaccharides are important natural biomacromolecules. In particular, microbial exopolysaccharides have received much attention. They are produced by a variety of microorganisms, and they are widely used in the food, pharmaceutical, and chemical industries. The Candida glabrata mutant 4-C10, which has the capacity to produce exopolysaccharide, was previously obtained by random mutagenesis. In this study we aimed to further enhance exopolysaccharide production by systemic fermentation optimization. By single factor optimization and orthogonal design optimization in shaking flasks, an optimal fermentation medium composition was obtained. By optimizing agitation speed, aeration rate, and fed-batch fermentation mode, 118.6 g L-1 of exopolysaccharide was obtained by a constant rate feeding fermentation mode, with a glucose yield of 0.62 g g-1 and a productivity of 1.24 g L-1 h-1. Scaling up the established fermentation mode to a 15-L fermenter led to an exopolysaccharide yield of 113.8 g L-1, with a glucose yield of 0.60 g g-1 and a productivity of 1.29 g L-1 h-1.
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BACKGROUND: Rice blast, caused by Magnaporthe oryzae, is a destructive disease threatening the production of staple foods worldwide. Quinone outside inhibitors (QoIs) are a group of chemicals exhibiting excellent activity against a majority of plant pathogens, with the disadvantage that pathogens can easily develop resistance to QoIs. RESULTS: Here, we investigated the activity of picoxystrobin against M. oryzae, which showed a great inhibitory effect on 100 strains of M. oryzae with half-maximal effective concentrations (EC50 ) ranging from 0.0251 to 0.1337 µg ml-1 . The EC50 values showed a continuous unimodal distribution that was identical to the normal distribution, suggesting the potency of our study to represent baseline sensitivity. In addition, nine resistant mutants were obtained by exposing M. oryzae to a high dosage of picoxystrobin in the laboratory; all of them showed cross-resistance to the other five QoI fungicides. Although some mutants showed a decreased resistance factor after ten successive cultures on fungicide-free medium, the resistance to picoxystrobin was still inheritable. Amino acid substitution of G143S was detected in eight of nine picoxystrobin-resistant mutants, and G143A was detected in only one of nine mutants. A fitness penalty was found in the mutants carrying G143S rather than G143A. CONCLUSION: Our findings suggested that M. oryzae had a mid to high risk of resistance to picoxystrobin. Considering this, we should be vigilant to the resistance risk and apply picoxystrobin sensibly in the field. © 2022 Society of Chemical Industry.
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Ascomicetos , Fungicidas Industriais , Magnaporthe , Ascomicetos/metabolismo , Citocromos b/genética , Citocromos b/metabolismo , Fungicidas Industriais/metabolismo , Fungicidas Industriais/farmacologia , Magnaporthe/genética , Doenças das Plantas , Estrobilurinas/farmacologiaRESUMO
Two-dimensional materials with excellent surface-volume ratios and massive reaction sites recently have been receiving attention for gas sensing. With first-principles calculations, we explored the performance of monolayer Sc2CF2 as a gas sensor. We investigated how molecule adsorption affects its electronic structure and optical properties. It is found that a large charge transfer quantity happens between Sc2CF2 and NO2, which results from the fact that the lowest unoccupied molecular orbital (LUMO) of NO2 is below the valence band maximum (VBM) of Sc2CF2. Moreover, the MD simulation shows that NO2 can adsorb on the Sc2CF2 surface stably at room temperature. We explored the effect of biaxial strain on the adsorption energy and charge transfer quantity of each system, and the results show that the biaxial strain can enhance both the adsorption energy and charge transfer quantity of the NO2 system and thus can improve the sensitivity of Sc2CF2 in detecting the NO2 molecule. Furthermore, we investigated the adsorption behavior and charge transfer of polar polyatomic molecules at the Sc2CF2 surface with h-BN as a substrate, and the results demonstrate that the h-BN substrate can hardly modify the main results. Our result predicts that Sc2CF2 can be a promising selective and sensitive sensor to detect the NO2 molecule, and could also give a theoretical guide for other terminated MXenes used for gas sensors or detectors.
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Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) samples were successfully foamed using supercritical carbon dioxide as a physical foaming agent. PHBV sheets were first saturated at 175 °C followed by a foaming process at different temperatures (145 to 165 °C) and different CO2 pressures (10 to 29 MPa). It was found that microcellular structures with average cell sizes ranging from 6 to 22 µm and cell densities ranging from 108 to 1.2 × 109 cells/cm3 could be controllably prepared by selecting suitable foaming conditions. To investigate crystallization behavior during the foaming process and explore the corresponding foaming mechanism, differential scanning calorimetry, wide angle X-ray diffraction, and small-angle X-ray scattering characterizations were carried out. Stretching behavior during the cell growth stage may increase the crystal nucleation rate, and the generated crystal nucleus accelerates the crystallization rate as well as thickens PHBV crystal lamellae.
RESUMO
KIAA0101, previously identified as PCNA-associated factor, is overexpressed among almost majority of human cancers and has emerged as an important regulator of cancer progression; however, its function in human nasopharyngeal carcinoma (NPC) remain unknown. Integrated bioinformatics approaches were employed to determine the KIAA0101 expressions in the NPC samples. Lentiviral vectors carrying KIAA0101 shRNA were constructed and stable transfected cells were validated by qRT-PCR and western blot. Cellular functions were then evaluated by MTT, colony formation, Brdu staining, and flow cytometry. Mechanistic studies were systematically investigated by UCSC Genome Browser, GEO, UALCAN, QIAGEN, PROMO and JASPAR, ChIP, and the cBioPortal, et al. The results showed that KIAA0101 ranked top overexpressed gene lists in GSE6631 dataset. KIAA0101 was highly expressed in NPC tissues and cell lines. Furthermore, knockdown of KIAA0101 significantly inhibited cell proliferation and DNA replication, promoted apoptosis and cell cycle arrest in vitro. Meanwhile, the mechanistic study revealed that MAP kinase phosphorylation-dependent activation of ELK1 may enhance neighbor gene expressions of KIAA0101 and TRIP4 by binding both promotor regions in the NPC cells. Taken together, our findings indicate that overexpression of KIAA0101 activated by MAP kinase phosphorylation-dependent activation of ELK1 may play an important role in NPC progression.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Elk-1 do Domínio ets/metabolismo , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Técnicas de Transferência de Genes , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Proteínas de Neoplasias/metabolismoRESUMO
Copy number variation (CNV) may have phenotypic effects by altering the expression level of the gene(s) or regulatory element(s) contained. It is believed that CNVs play pivotal roles in controlling plant architecture and other traits in plant. However, the effects of CNV contributing to special traits remain largely unknown. Here we report a CNV involved in rice architecture by modulating tiller number and leaf angle. In the genome of Oryza sativa ssp. japonica cv. Nipponbare, we found a locus Loc_Os08g34249 is derived from a 13,002-bp tandem duplication in the nearby region of OsMTD1, a gene regulating tillering in rice. Further survey of 230 rice cultivars showed that the duplication occurred in only 13 japonica rice cultivars. Phenotypic investigation indicated that this CNV region may contribute to tiller number. Moreover, we revealed that OsMTD1 not only influences rice tiller number and leaf angle, but also represses pri-miR156f transcription in the CNV region. Intriguingly, this CNV performs function through both the dosage and position effects on OsMTD1 and pri-miR156f. Thus, our work identified a CNV and revealed a molecular regulatory basis for its effects on plant architecture, implying this CNV may possess importance and application potential in molecular breeding in rice.