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It's urgent to discover new antibiotics along with the increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens. In the present investigation, morusin exhibited rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) by targeting the phospholipid of bacterial inner membrane, increasing membrane rigidity and disrupting bacterial homeostasis together with the membrane permeability, which caused fundamental metabolic disorders. Furthermore, morusin can also accumulate ROS, suppress H2S production, and aggravate oxidative damage in bacteria. Importantly, morusin also inhibited the spread of wounds and reduced the bacterial burden in the mouse model of skin infection caused by MRSA. It's a chance to meet the challenge of existing antibiotic resistance and avoid the development of bacterial resistance, given the multiple targets of morusin.
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Staphylococcus aureus Resistente à Meticilina , Morus , Animais , Camundongos , Antibacterianos/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: The hard double-walled structure of Ganoderma lucidum spore powder (GLSP) is difficult for the human body to digest, so it is very important to break the wall of GLSP. In this study, the wall of GLSP was broken by mechanical milling at room temperature (MM-R) and ultra-fine grinding at low temperature (UFG-L), respectively. RESULTS: Compared with MM-R, UFG-L could better retain the sporangium powder's morphological and structural integrity. During in vitro digestion, compared with unbroken GLSP, the released amounts of polysaccharides and triterpenes from broken GLSP were significantly increased, and they increased with the increase of specific surface area. The bioaccessibility of polysaccharide and triterpene from unbroken GLSP after the intestinal stage were 29.52% and 5.37%, respectively. The bioaccessibility of polysaccharides and triterpene from broken GLSP by MM-R after the intestinal phase were 39.73-72.45% and 16.44-24.97%, while those by UFG-L were 44.53-104.18% and 12.96-32.90%, respectively. CONCLUSION: The active ingredients of broken GLSP showed better digestion and absorption abilities than unbroken GLSP. Moreover, the specific surface area of GLSP by UFG-L was lower than that by MM-R, and the bioaccessibility of GLSP by UFG-L was higher than that by MM-R. © 2024 Society of Chemical Industry.
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Digestão , Polissacarídeos , Pós , Reishi , Esporos Fúngicos , Reishi/metabolismo , Reishi/química , Reishi/crescimento & desenvolvimento , Esporos Fúngicos/metabolismo , Esporos Fúngicos/química , Pós/química , Humanos , Polissacarídeos/química , Polissacarídeos/metabolismo , Triterpenos/metabolismo , Triterpenos/química , Nutrientes/metabolismo , Modelos Biológicos , Manipulação de Alimentos/métodosRESUMO
Monoterpene indole alkaloids exhibit structural diversity in herbal resources and have been developed as promising drugs owing to their significant biological activities. Confidential identification and quantification of monoterpene indole alkaloids is the key to quality control of target plants in industrial production but has rarely been reported. In this study, quantitative performance of three data acquisition modes of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry including full scan, auto-MS2 and target-MS2 , was evaluated and compared for specificity, sensitivity, linearity, precision, accuracy, and matrix effect using five monoterpene indole alkaloids (scholaricine, 19-epi-scholaricine, vallesamine, picrinine, and picralinal). Method validations indicated that target-MS2 mode showed predominant performance for simultaneous annotation and quantification of analytes, and was then applied to determine monoterpene indole alkaloids in Alstonia scholaris (leaves, barks) after extraction procedures optimization using Box-Behnken design of response surface methodology. The variations of A. scholaris monoterpene indole alkaloids in different plant parts, harvest periods, and post-handling processes, were subsequently investigated. The results indicated that target-MS2 mode could improve the quantitative capability of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry for structure-complex monoterpene indole alkaloids in herbal matrices. Alstonia scholaris, monoterpene indole alkaloids, quadrupole time of flight mass spectrometry, qualitative and quantitative analysis, ultra-high-performance liquid chromatography.
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Alstonia , Alcaloides de Triptamina e Secologanina , Cromatografia Líquida de Alta Pressão , Alstonia/química , Alcaloides Indólicos/química , Espectrometria de Massas/métodos , MonoterpenosRESUMO
OBJECTIVE: Refractory rifampicin-resistant/multidrug resistant/extensively-drug resistant tuberculosis (RR/MDR/XDR-TB) were defined as patients infected with Mycobacterium tuberculosis (MTB) resistant to rifampicin(RR-TB), or at least resistant to rifampicin and isoniazid (MDR-TB) or added resistant to fluoroquinolones (FQs) and one of second line injectable agents (XDR-TB), a patient for whom an effective regimen (fewer than 4 effective agents due to adverse events (AEs) or multiple drug resistances) cannot be developed. To compare the effectiveness and safety of bedaquiline (BDQ)-containing and BDQ-free regimens for treatment of patients with refractory RR/MDR/XDR-TB. METHODS: Patients with refractory RR/MDR/XDR-TB receiving BDQ-containing regimens (BDQ group, n = 102) and BDQ-free regimens (non-BDQ group, n = 100) satisfied with included criteria were strictly included in this retrospective historical control study across East China. Culture conversion, treatment outcome, cavity closing rate, and AEs were compared between two groups. RESULTS: The baseline characteristics involved all possible aspects of patients were well balanced between two groups (p > 0.05). Culture conversion rates in the BDQ group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs 65.0%) were all significantly higher than those in non-BDQ group (p < 0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs 8.0%, p = 0.0) and month 12 (39.2% vs 15.0%, p < 0.001). Patients receiving BDQ-containing regimens had more treatment success than those receiving BDQ-free regimens (p < 0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%); the use of BDQ and combined with Linezolid or Clofazimine or Cycloserine were identified as independent predictors of treatment success and no culture reversion (P < 0.05). AEs were similarly reported in 26.5% of patients in the BDQ group and 19.0% in the non-BDQ group (p = 0.2). CONCLUSIONS: BDQ-containing regimens resulted in better treatment outcomes and similar safety relative to BDQ-free regimens for patients with refractory pulmonary RR/MDR/XDR-TB.
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Tuberculose Extensivamente Resistente a Medicamentos , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Antituberculosos/efeitos adversos , Diarilquinolinas , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Humanos , Estudos Retrospectivos , Rifampina/efeitos adversos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
INTRODUCTION: The structural annotation of target relies on high-resolution mass spectrometry (HRMS) information resulting in dubious identities in most cases. The accurate annotation of isomeric structures is still challenging to be confirmed with significant bottleneck. OBJECTIVE: This study focused on the improvement of structural annotation of candidate structures via four pairs of isomeric flavanone-7-O-diglucosides and their basic flavanone aglycones commonly detected in citrus products. METHOD: An integrated liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) approach merging retention time, accurate mass, tandem mass spectrometry (MS/MS) information (diagnostic ions), ion ratio at selected collision energy was established successfully. RESULTS: Feasibility of this approach was validated confidently in biological samples with relative standard deviation (RSD) of ion ratio range from 3.91 to 12.28%. Differences of fragmentation patterns of citrus flavanones were illustrated reasonably. MS/MS fragments of (S)-hesperetin and (S)-isosakuranetin were complicated and showed typical radical ion [1,2 A - H]â¢- (m/z 164) in negative ESI mode due to the methoxyl group on B-ring, which showed huge difference with (R)-hesperetin and (R)-isosakuranetin. CONCLUSION: This study integrated multiple levels to boost the confidence of structural annotation relied on LC-HRMS, and provided important values in practice for precise identification of citrus flavanones in biological matrices.
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Citrus , Flavanonas , Cromatografia Líquida , Flavanonas/análise , Humanos , Isomerismo , Espectrometria de Massas em TandemRESUMO
The stress-induced unfolded protein response (UPR) in the endoplasmic reticulum (ER) involves various signaling cross-talks and controls cell fate. B-cell receptor (BCR) signaling, which can trigger UPR, induces gammaherpesvirus lytic replication and serves as a physiological mechanism for gammaherpesvirus reactivation in vivo However, how the UPR regulates BCR-mediated gammaherpesvirus infection is unknown. Here, we demonstrate that the ER stressors tunicamycin and thapsigargin inhibit BCR-mediated murine gammaherpesvirus 68 (MHV68) lytic replication by inducing expression of the UPR mediator Bip and blocking activation of Akt, ERK, and JNK. Both Bip and the downstream transcription factor ATF4 inhibited BCR-mediated MHV68 lytic gene expression, whereas UPR-induced C/EBP homologous protein (CHOP) was required for and promoted BCR-mediated MHV68 lytic replication by suppressing upstream Bip and ATF4 expression. Bip knockout was sufficient to rescue BCR-mediated MHV68 lytic gene expression in CHOP knockout cells, and this rescue was blocked by ectopic ATF4 expression. Furthermore, ATF4 directly inhibited promoter activity of the MHV68 lytic switch transactivator RTA. Altogether, we show that ER stress-induced CHOP inhibits Bip and ATF4 expression and that ATF4, in turn, plays a critical role in CHOP-mediated regulation of BCR-controlled MHV68 lytic replication. We conclude that ER stress-mediated UPR and BCR signaling pathways are interconnected and form a complex network to regulate the gammaherpesvirus infection cycle.
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Fator 4 Ativador da Transcrição/metabolismo , Linfócitos B/virologia , Estresse do Retículo Endoplasmático , Gammaherpesvirinae/fisiologia , Proteínas de Choque Térmico/metabolismo , Receptores de Antígenos de Linfócitos B/agonistas , Fator de Transcrição CHOP/metabolismo , Fator 4 Ativador da Transcrição/antagonistas & inibidores , Fator 4 Ativador da Transcrição/genética , Animais , Antivirais/farmacologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linhagem Celular Transformada , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Gammaherpesvirinae/efeitos dos fármacos , Gammaherpesvirinae/crescimento & desenvolvimento , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Proteínas de Choque Térmico/antagonistas & inibidores , Proteínas de Choque Térmico/genética , Lisogenia/efeitos dos fármacos , Camundongos , Chaperonas Moleculares/antagonistas & inibidores , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Regiões Promotoras Genéticas/efeitos dos fármacos , Receptores de Antígenos de Linfócitos B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tapsigargina/farmacologia , Fator de Transcrição CHOP/antagonistas & inibidores , Fator de Transcrição CHOP/genética , Tunicamicina/farmacologia , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/genética , Proteínas Virais/metabolismo , Ativação Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
The Koopman operator has received attention for providing a potentially global linearization representation of the nonlinear dynamical system. To estimate or control the original system, the invertibility problem is introduced into the data-driven modeling, i.e., the observables are required to be reconstructed the original system's states. Existing methods cannot solve this problem perfectly. Only linear or nonlinear but lossy reconstruction can be achieved. This paper proposed a novel data-driven modeling approach, denoted as the Extended Dynamic Mode Decomposition with Invertible Dictionary Learning (EDMD-IDL) to address this issue, which can be interpreted as a further extension of the classical Extended Dynamic Mode Decomposition (EDMD). The Invertible Neural Network (INN) is introduced in the proposed method, where its inverse process provides the explicit inverse on the dictionary functions, thus allowing the nonlinear and lossless reconstruction. An iterative algorithm is designed to solve the extended optimization problem defined by the Koopman operator and INN by combining the optimization algorithm based on the gradient descent and the classical EDMD method, making the method successfully obtain the finite-dimensional approximation of the Koopman operator. The method is tested on various canonical nonlinear dynamical systems and is shown that the predictions obtained in a linear fashion and the ground truth match well over the long-term, where only the initial status is provided. Comparison experiments highlight the superiority of the proposed method over the other EDMD-based methods. Notably, a typical example in fluid dynamics, cylinder wake, illustrates the potential of the method to be further extended to the high-dimensional system with tens of thousands of states. By combining the Proper Orthogonal Decomposition technique, nontrivial Kármán vortex sheet phenomenon is perfectly reconstructed. Our proposed method provides a new paradigm for solving the finite-dimensional approximation of the Koopman operator and applying it to data-driven modeling.
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Algoritmos , Tetranitrato de Pentaeritritol , Aprendizagem , Dinâmica não Linear , Redes Neurais de ComputaçãoRESUMO
BACKGROUND: Insomnia and depressive disorder are two common symptoms with a reciprocal causal relationship in clinical practice, which are usually manifested in comorbid form. Several medications have been widely used in the treatment of insomnia and depression, but most of these drugs show non-negligible side effects. Currently, many treatments are indicated for insomnia and depressive symptom, including Chinese herbal medicine such as Gastrodia elata Blume (G. elata), which has excellent sedative-hypnotic and antidepressant effects in clinical and animal studies. PURPOSE: To summarize the mechanisms of insomnia and depression and the structure-activity mechanism for G. elata to alleviate these symptoms, particularly by hypothalamic-pituitary-adrenal (HPA) axis and intestinal flora, aiming to discover new approaches for the treatment of insomnia and depression. METHODS: The following electronic databases were searched from the beginning to November 2023: PubMed, Web of Science, Google Scholar, Wanfang Database, and CNKI. The following keywords of G. elata were used truncated with other relevant topic terms, such as depression, insomnia, antidepressant, sedative-hypnotic, neuroprotection, application, safety, and toxicity. RESULTS: Natural compounds derived from G. elata could alleviate insomnia and depressive disorder, which is involved in monoamine neurotransmitters, inflammatory response, oxidative stress, and gut microbes, etc. Several clinical trials showed that G. elata-derived natural compounds that treat depression and insomnia have significant and safe therapeutic effects, but further well-designed clinical and toxicological studies are needed. CONCLUSION: G. elata exerts a critical role in treating depression and insomnia due to its multi-targeting properties and fewer side effects. However, more clinical and toxicological studies should be performed to further explore the sedative-hypnotic and antidepressant mechanisms of G. elata and provide more evidence and recommendations for its clinical application. Our review provides an overview of G. elata treating insomnia with depression for future research direction.
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Gastrodia , Distúrbios do Início e da Manutenção do Sono , Animais , Extratos Vegetais/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Antidepressivos/farmacologia , Antidepressivos/uso terapêuticoRESUMO
Zanthoxylum motuoense (Tibetan prickly ash, MTHJ), different from the Chinese prickly ash species, is distributed only in the Tibet. Now the chemical characterization and antibacterial activity of MTHJ extracts were analyzed for the first time. As a result, Schinifoline (12), γ-Fagarine (8), (2E,7E,9E)-6 S-Hydroxy-N-(2-methylpropyl)-11-oxo-2, 7, 9-Dodecatrienamide (6), and Neoechinulin A (17) were found to be the major different factors by untarget LC-MS metabolomics together with quantitative analysis on target. These four compounds were also the major antibacterial constituents. Then, the antimicrobial activity of MTHJ fractions was evaluated with colony forming units (CFU), fluorescence microscopy imaging, SEM and investigating the potential food preservation. Nutritional composition, colour and sensory evaluation of extract-treated samples were evaluated along storage time. The results suggested the MTHJ may be used for meat products preservation, and the scores were significantly higher for its unique flavor, which offered a promising choice for food safety, preservation and reducing foodborne illness.
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The abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1-4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4-8 µg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time.
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Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25-1.00 µg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin.
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Antibacterianos , Flavonoides , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Enterococos Resistentes à Vancomicina , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/química , Flavonoides/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Animais , Camundongos , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a Droga , Infecções Estafilocócicas/tratamento farmacológico , HumanosRESUMO
In this study, the effects of particle size on the microstructure, nutrient components and antioxidant activities of bee pollen were evaluated. Moreover, the in vitro simulated digestion model was used to explore whether there was a size effect on the release behavior of phenolic compounds from the bee pollen matrix. Results showed that the greater the damage degree of the bee pollen wall, the smaller the bee pollen particle became. The decrease in the bee pollen particle size promoted the release and extractability of sugar, protein, phenolics and flavonoids, and improved their antioxidant activities. In addition, during simulated digestion, the dissolution of total phenolics and flavonoids, as well as the antioxidant activities of bee pollen, increased with the decrease in the particle size. Results showed that minimizing the particle size of bee pollen was not always beneficial for bioaccessible phenolic compounds because their content and bioavailability decreased when the particle size became smaller than 200 µm.
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Fagopyrum , Estupro , Rosa , Abelhas , Animais , Antioxidantes/farmacologia , Tamanho da Partícula , Flavonoides/químicaRESUMO
Two unique windmill-like aziridine-containing indole alkaloids, possessing an unprecedented 6/5/5/6/6/5/3 rigid ring system and an unusual azabicyclo[3.1.0]hexane core, were isolated from Alstonia scholaris. Their structures were established by spectroscopy, X-ray diffraction, and electronic circular dichroism calculations. The novel compounds exhibited significant anti-inflammatory bioactivity in vitro and alleviated LPS-induced acute lung injury in mice.
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Alstonia , Plantas Medicinais , Camundongos , Animais , Alstonia/química , Alcaloides Indólicos , Anti-Inflamatórios , Difração de Raios X , Estrutura Molecular , Folhas de Planta/químicaRESUMO
Three new steroidal alkaloids, veratrasines A - C (1-3), along with ten known analogues (4-13) were isolated from the roots of Veratrum stenophyllum. Their structures were elucidated by NMR and HRESIMS data and comparison with the reported data in the literatures. A plausible biosynthetic pathway for 1 and 2 were proposed. Compounds 1, 3, and 8 showed moderate cytotoxic activity against MHCC97H and H1299 cell lines.
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Alcaloides , Veratrum , Veratrum/química , Estrutura Molecular , Raízes de Plantas , Esteroides , Alcaloides de Veratrum/químicaRESUMO
Veratrazine A (1), a steroidal alkaloid with a unique 6/5/5 triheterocyclic scaffold as the side chain, was isolated from Veratrum stenophyllum, and its structure was established via spectroscopic analyses and X-ray diffraction. A plausible biosynthetic pathway for 1 is proposed. Bioassy exhibits moderate anti-inflammatory activities in vitro and in vivo.
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Alcaloides , Antineoplásicos , Veratrum , Alcaloides/farmacologia , Alcaloides/química , Extratos Vegetais/química , Veratrum/química , Esteroides/farmacologia , Anti-Inflamatórios , Estrutura MolecularRESUMO
OBJECTIVE: To study the correlation between polymorphisms of genes with susceptibility to tuberculosis and the clinical characteristics of tuberculosis in Han population. METHODS: Four hundred and fifty-nine tuberculosis inpatients of Han population in Shanghai Pulmonary Hospital from Jan 2007 to Dec 2008 were recruited. The clinical characteristics of tuberculosis (gender, fever, extent of lesions, cavity formation, hemoptysis, initial treatment and retreatment) were observed. The polymorphisms of VDR gene (variants in FokI and TaqI), NRAMP1 gene (variants in INT4, D543N and 3 UTR), MBL gene (variants in HL, YX and QP) and IFNG gene (variants in 874AT) were genotyped by a variety of SNP genotyping techniques. The correlation between polymorphisms of genes with susceptibility to tuberculosis and the clinical characteristics of the disease was analyzed by ANOVAs. RESULTS: The frequency of CC, CT and TT variants of FokI in VDR gene in cases with fever were 54.7% (29/53), 13.2% (7/53) and 32.1% (17/53), respectively, compared to 40.6% (52/128), 30.5% (39/128) and 28.9% (37/128) in cases without fever, the difference being significant (χ² = 6.183, P < 0.05). In patients with CT variants, 15.2% (7/46) had fever, while in patients with non-CT variants, 34.1% (46/135) had fever (χ² = 5.891, P < 0.05), suggesting that patients with CT variants were less likely to have fever. The frequencies of TT + TC and CC variants of QP in the MBL gene in initial treatment cases were 28.3% (60/212) and 71.7% (152/212), respectively, compared to 19.1% (41/215) and 80.9% (174/215) in retreatment cases, the difference being significant (χ² = 5.038, P < 0.05). No significant correlation was observed between the other variants and the clinical characteristics of tuberculosis (χ² = 0.001 - 2.732, P > 0.05). CONCLUSIONS: The polymorphisms of FokI in VDR gene was associated with fever among the clinical characteristics of tuberculosis, and patients with CT variants might be protected from fever. The polymorphisms of QP in MBL gene might be associated with recurrence of tuberculosis.
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Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Tuberculose/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , China , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Calcitriol/genética , Adulto JovemRESUMO
The effects of air pollution on population health are currently a hot topic. However, few studies have examined the physical and mental health effects of air pollution jointly in China. Using data from the China Health and Retirement Longitudinal Study (CHARLS) in 2015 and 2018, this study explores how air pollution affects the physical and mental health of middle-aged and elderly residents. The empirical results highlight that air pollution can negatively affect both physical and mental health. In terms of physical health, those exposed to chronic shock are likely to suffer more adverse effects from air pollution than those exposed to acute shock. In terms of mental health, those exposed to depression suffer greater adverse effects than those exposed to episodic memory and mental cognition. Besides, heterogeneity analysis also shows that air pollution affects the mental and physical health of males more than females. Furthermore, the increase in air pollution is expected to result in huge hospitalization costs. Therefore, the Chinese government should formulate differentiated public health policies to reduce the effects of air pollution on the health of middle-aged and elderly residents.
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Poluição do Ar , Saúde da População , Idoso , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , AposentadoriaRESUMO
BACKGROUND: The prognosis of lung cancer patients is poor without useful prognostic and diagnostic biomarker. To search for novel prognostic and diagnostic markers, we previously found homeobox-A13 (HOXA13) as a promising candidate in lung cancer. OBJECTIVE: To determine the precisely clinical feature, prognostic and diagnostic value, possible role and mechanism of HOXA13. METHODS: Gene-expression was explored by real-time quantitative-PCR, western-blot and tissue-microarray. The associations were analyzed by Chi-square test, Kaplan-Meier and Cox-regression. The roles and mechanisms were evaluated by MTS, EdU, transwell, xenograft tumor and luciferase-reporter assays. RESULTS: HOXA13 expression is increased in tumors, and correlated with age of patients. HOXA13 expression is associated with unfavorable overall survival and relapse-free survival of patients in four cohorts. Interestingly, HOXA13 has different prognostic significance in adenocarcinoma (ADC) and squamous-cell carcinoma (SCC), and is a sex- and smoke-related prognostic factor only in ADC. Importantly, HOXA13 can serve as a diagnostic biomarker for lung cancer, especially for SCC. HOXA13 can promote cancer-cell proliferation, migration and invasion in vitro, and facilitate tumorigenicity and tumor metastasis in vivo. HOXA13 acts the oncogenic roles on tumor growth and metastasis by regulating P53 and Wnt/ß-catenin signaling activities in lung cancer. CONCLUSIONS: HOXA13 is a new prognostic and diagnostic biomarker associated with P53 and Wnt/ß-catenin signaling pathways.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias Pulmonares/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Via de Sinalização Wnt , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/fisiologia , Expressão Gênica , Xenoenxertos , Proteínas de Homeodomínio/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Transfecção , Proteína Supressora de Tumor p53/genéticaRESUMO
Two rearranged triterpenoids, representing new subtypes of pentacyclic triterpenoids, with unique 6/6/6/7/5 and 6/6/5/6/6/6 ring systems were isolated from Alstonia scholaris. Their structures were established by spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Both compounds exhibited potent antihyperuricemic bioactivity in vitro and in vivo.
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Alstonia/química , Supressores da Gota/farmacologia , Triterpenos/farmacologia , Cristalografia por Raios X , Supressores da Gota/análise , Supressores da Gota/química , Folhas de Planta/química , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
Microwavable plastic food containers (MPFCs) are extensively used for food storage, cooking, rapid heating and as take-out containers. There is an urgent need to investigate whether MPFCs pose potential health risks, as a result of the migration of chemicals into foods. Herein, 42 intentionally added substances (IAS) and > 100 non-IAS (NIAS) migrating from MPFCs were identified in food simulants according to Regulation (EU). The migration of major IAS and NIAS was higher in 95% ethanol compared to other simulants, and gradually decreased following repeated use. NIAS, including Cramer class III toxic compounds, such as PEG oligomers of N,N-bis(2-hydroxyethyl) alkyl(C8-C18)amines, isomers of hexadecanamide and oleamide, and Irgafos 168 OXO were detected and exceeded the recommended limits in some MPFCs. Furthermore, microplastics (MPs) were detected with high values of over one million particles/L in some MPFCs in a single test, and migration behaviors of MPs in different MPFCs were diverse. Surprisingly, this rigorous migration might result in an annual intake of IAS/NIAS up to 55.15 mg and 150 million MPs particles if take-out food was consumed once a day. Multi-safety evaluation studies on the migration of various chemicals from MPFCs to foodstuffs during food preparation should be assessed.