RESUMO
Sporopollenin, a critical innovation in the evolution of terrestrial plants, is the core building brick for the outer wall of land-plant spores and pollen. Despite its significance, the basic structure of sporopollenin remains elusive due to its extreme chemical inertness. In this study, we used ethanolamine to completely dissolve rape sporopollenin and successfully identified a total of 22 components, including fatty acids, p-coumaric acid, sterols and polymeric phenylpropanoid derivatives. After that, using NaOH treatment and partial dissolution, alongside Arabidopsis mutants analysis and spectroscopic methods, we determined that polymeric phenylpropanoid derivatives crosslinked by hydroxyl fatty acids serve as the core structure of sporopollenin. The free hydroxyl groups and carboxyl groups of the polymeric phenylpropanoid derivatives can be modified by other fatty acids (C16:0, C18:0 and C18:3) as well as alcohols/phenols (for example, naringenin, ß-sitosterol), resulting in a structure that protects pollen from terrestrial stresses. This discovery provides a basis for further exploration of sporopollenin's role in plant reproduction and evolution.
RESUMO
We conducted a large-scale survey of arboviruses in mosquitoes and biting midges to assess the presence and spread of mosquito-borne pathogens currently circulating on Hainan Island, China. RT-PCR assays were used to detect the arbovirus species, distribution, and infection rates in mosquitoes and biting midges. Cell inoculation and high throughput sequencing were performed to isolate the viruses and assemble full viral genomes. Phylogenetic analysis was conducted to identify the viral genotypes and evolutionary relationships with known viruses. During 2019-2023, 32,632 mosquitoes and 21,000 biting midges were collected from 14 of 18 cities/counties on Hainan Island. Japanese encephalitis virus (JEV) was detected in Culex mosquitoes from five cities/counties, where the minimum infection rate (MIR) was 1.6 (0.6-2.6) per 1,000 females tested. Tembusu virus (TMUV) was detected in Culex mosquitoes from three cities/counties with MIR1.0 (0-2.2) per 1,000. Getah virus (GETV) was detected in Armigeres mosquitoes from Qionghai city with MIR 7.1 (0-15.2) per 1,000. Oya virus (OYAV) and Bluetongue virus (BTV) were detected in biting midges from Wanning city with MIRs of 0.4 (0-1.2) and 0.1 (0-10.2) per 1,000, respectively. Three JEV strains were isolated and clustered within the genotype I group, which is presently the dominant genotype in China. Three TMUV strains were isolated for the first time on Hainan Island that belonged to Cluster 3. Three isolated GETVs were identified as Group 3. BTV was reported for the first time on Hainan Island, and the complete genome for one BTV strain was successfully assembled, which was classified as serotype 1 based on the sequences of segment 2. These results stress the need to develop adequate surveillance plan measures to better control the public health threat of arboviruses carried by mosquitoes and biting midges in local regions.
RESUMO
Poly(ADP-ribose) polymerase 1 (PARP1) is a crucial member of the PARP family, which modifies targets through ADP-ribosylation and plays key roles in a variety of biological processes. PARP inhibitors (PARPis) hinder ADP-ribosylation and lead to the retention of PARP1 at the DNA lesion (also known as trapping), which underlies their toxicity. However, inhibitors and mutations that make PARP1 inactive do not necessarily correlate with trapping potency, challenging the current understanding of inactivation-caused trapping. Recent studies on mouse models indicate that both trapping and non-trapping inactivating mutations of PARP1 lead to embryonic lethality, suggesting the unexpected toxicity of the current inhibition strategy. The allosteric model, complicated automodification, and various biological functions of PARP1 all contribute to the complexity of PARP1 inactivation.
RESUMO
BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%. CONCLUSION: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.
Assuntos
Endometriose , Fibrinogênio , Neutrófilos , Humanos , Feminino , Endometriose/sangue , Endometriose/complicações , Endometriose/diagnóstico , Adulto , Estudos Retrospectivos , Estudos de Casos e Controles , Fibrinogênio/análise , Tempo de Tromboplastina Parcial , Coagulação Sanguínea/fisiologia , Índice de Gravidade de Doença , Antígeno Ca-125/sangue , Curva ROC , Linfócitos , Biomarcadores/sangueRESUMO
BACKGROUND: Due to the complexity of the metabolic pathway network of active ingredients, precise targeted synthesis of any active ingredient on a synthetic network is a huge challenge. Based on a complete analysis of the active ingredient pathway in a species, this goal can be achieved by elucidating the functional differences of each enzyme in the pathway and achieving this goal through different combinations. Lignans are a class of phytoestrogens that are present abundantly in plants and play a role in various physiological activities of plants due to their structural diversity. In addition, lignans offer various medicinal benefits to humans. Despite their value, the low concentration of lignans in plants limits their extraction and utilization. Recently, synthetic biology approaches have been explored for lignan production, but achieving the synthesis of most lignans, especially the more valuable lignan glycosides, across the entire synthetic network remains incomplete. RESULTS: By evaluating various gene construction methods and sequences, we determined that the pCDF-Duet-Prx02-PsVAO gene construction was the most effective for the production of (+)-pinoresinol, yielding up to 698.9 mg/L after shake-flask fermentation. Based on the stable production of (+)-pinoresinol, we synthesized downstream metabolites in vivo. By comparing different fermentation methods, including "one-cell, one-pot" and "multicellular one-pot", we determined that the "multicellular one-pot" method was more effective for producing (+)-lariciresinol, (-)-secoisolariciresinol, (-)-matairesinol, and their glycoside products. The "multicellular one-pot" fermentation yielded 434.08 mg/L of (+)-lariciresinol, 96.81 mg/L of (-)-secoisolariciresinol, and 45.14 mg/L of (-)-matairesinol. Subsequently, ultilizing the strict substrate recognition pecificities of UDP-glycosyltransferase (UGT) incorporating the native uridine diphosphate glucose (UDPG) Module for in vivo synthesis of glycoside products resulted in the following yields: (+)-pinoresinol glucoside: 1.71 mg/L, (+)-lariciresinol-4-O-D-glucopyranoside: 1.3 mg/L, (+)-lariciresinol-4'-O-D-glucopyranoside: 836 µg/L, (-)-secoisolariciresinol monoglucoside: 103.77 µg/L, (-)-matairesinol-4-O-D-glucopyranoside: 86.79 µg/L, and (-)-matairesinol-4'-O-D-glucopyranoside: 74.5 µg/L. CONCLUSIONS: By using various construction and fermentation methods, we successfully synthesized 10 products of the lignan pathway in Isatis indigotica Fort in Escherichia coli, with eugenol as substrate. Additionally, we obtained a diverse range of lignan products by combining different modules, setting a foundation for future high-yield lignan production.
Assuntos
Vias Biossintéticas , Escherichia coli , Glicosídeos , Lignanas , Lignanas/biossíntese , Lignanas/metabolismo , Glicosídeos/biossíntese , Glicosídeos/metabolismo , Escherichia coli/metabolismo , Escherichia coli/genética , Engenharia Metabólica/métodos , Fermentação , Biologia Sintética/métodos , Furanos/metabolismoRESUMO
Background: Polygonum capitatum Buch.-Ham. ex D. Don (P. capitatum), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties. Materials and Methods: Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS. Results: Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins. Conclusion: Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin's action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.
Assuntos
Diabetes Mellitus Experimental , Hipoglicemiantes , Metaboloma , Ratos Sprague-Dawley , Estreptozocina , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Ratos , Hipoglicemiantes/farmacologia , Masculino , Metaboloma/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
BACKGROUND: Mosquito-borne viruses cause various infectious diseases in humans and animals. Oya virus (OYAV) and Ebinur Lake virus (EBIV), belonging to the genus Orthobunyavirus within the family Peribunyaviridae, are recognized as neglected viruses with the potential to pose threats to animal or public health. The evaluation of vector competence is essential for predicting the arbovirus transmission risk. METHODS: To investigate the range of mosquito vectors for OYAV (strain SZC50) and EBIV (strain Cu20-XJ), the susceptibility of four mosquito species (Culex pipiens pallens, Cx. quinquefasciatus, Aedes albopictus, and Ae. aegypti) was measured through artificial oral infection. Then, mosquito species with a high infection rate (IR) were chosen to further evaluate the dissemination rate (DR), transmission rate (TR), and transmission efficiency. The viral RNA in each mosquito sample was determined by RT-qPCR. RESULTS: The results revealed that for OYAV, Cx. pipiens pallens had the highest IR (up to 40.0%) among the four species, but the DR and TR were 4.8% and 0.0%, respectively. For EBIV, Cx. pipiens pallens and Cx. quinquefasciatus had higher IR compared to Ae. albopictus (1.7%). However, the EBIV RNA and infectious virus were detected in Cx. pipiens pallens, with a TR of up to 15.4% and a transmission efficiency of 3.3%. CONCLUSIONS: The findings indicate that Cx. pipiens pallens was susceptible to OYAV but had an extremely low risk of transmitting the virus. Culex pipiens pallens and Cx. quinquefasciatus were susceptible to EBIV, and Cx. pipiens pallens had a higher transmission risk to EBIV than Cx. quinquefasciatus.
Assuntos
Aedes , Culex , Mosquitos Vetores , Orthobunyavirus , Animais , Mosquitos Vetores/virologia , Aedes/virologia , Culex/virologia , Orthobunyavirus/genética , Orthobunyavirus/classificação , Orthobunyavirus/isolamento & purificação , RNA Viral/genética , Infecções por Bunyaviridae/transmissão , Infecções por Bunyaviridae/virologiaRESUMO
Orthobunyavirus is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored the antiviral effects of two broad-spectrum antiviral drugs, favipiravir and ribavirin, in a BALB/c mouse model. Favipiravir significantly improved the clinical symptoms of infected mice, reduced viral titer and RNA copies in serum, and extended overall survival. The median survival times of mice in the vehicle- and favipiravir-treated groups were 5 and 7 days, respectively. Favipiravir significantly reduced virus titers 10- to 100-fold in sera at all three time points compared to vehicle-treated mice. And favipiravir treatment effectively reduced the virus copies by approximately 10-fold across the three time points, relative to vehicle-treated mice. The findings expand the antiviral spectrum of favipiravir for orthobunyaviruses in vivo.
Assuntos
Amidas , Antivirais , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Pirazinas , Carga Viral , Animais , Pirazinas/uso terapêutico , Pirazinas/farmacologia , Amidas/farmacologia , Amidas/uso terapêutico , Antivirais/uso terapêutico , Antivirais/farmacologia , Camundongos , Carga Viral/efeitos dos fármacos , Feminino , Ribavirina/uso terapêutico , Ribavirina/farmacologia , Infecções por Vírus de RNA/tratamento farmacológico , Infecções por Vírus de RNA/virologiaRESUMO
Mosquito-borne viruses cause various infectious diseases in humans and animals. Tibet orbivirus (TIBOV), a newly identified arbovirus, efficiently replicates in different types of vertebrate and mosquito cells, with its neutralizing antibodies detected in cattle and goats. However, despite being isolated from Culicoides midges, Anopheles, and Culex mosquitoes, there has been a notable absence of systematic studies on its vector competence. Thus, in this study, Aedes aegypti and Culex pipiens pallens were reared in the laboratory to measure vector susceptibility through blood-feeding infection. Furthermore, RNA sequencing was used to examine the overall alterations in the Ae. aegypti transcriptome following TIBOV infection. The results revealed that Ae. aegypti exhibited a high susceptibility to TIBOV compared to Cx. p. pallens. Effective replication of the virus in Ae. aegypti midguts occurred when the blood-feeding titer of TIBOV exceeded 105 plaque-forming units mL-1. Nevertheless, only a few TIBOV RNA-positive samples were detected in the saliva of Ae. aegypti and Cx. p. pallens, suggesting that these mosquito species may not be the primary vectors for TIBOV. Moreover, at 2 dpi of TIBOV, numerous antimicrobial peptides downstream of the Toll and Imd signaling pathways were significantly downregulated in Ae. aegypti, indicating that TIBOV suppressed mosquitos' defense to survive in the vector at an early stage. Subsequently, the stress-activated protein kinase JNK, a crucial component of the MAPK signaling pathway, exhibited significant upregulation. Certain genes were also enriched in the MAPK signaling pathway in TIBOV-infected Ae. aegypti at 7 dpi.IMPORTANCETibet orbivirus (TIBOV) is an understudied arbovirus of the genus Orbivirus. Our study is the first-ever attempt to assess the vector susceptibility of this virus in two important mosquito vectors, Aedes aegypti and Culex pipiens pallens. Additionally, we present transcriptome data detailing the interaction between TIBOV and the immune system of Ae. aegypti, which expands the knowledge about orbivirus infection and its interaction with mosquitoes.
Assuntos
Aedes , Culex , Mosquitos Vetores , Orbivirus , Animais , Aedes/virologia , Aedes/genética , Culex/virologia , Culex/genética , Mosquitos Vetores/virologia , Mosquitos Vetores/genética , Orbivirus/genética , Orbivirus/fisiologia , Feminino , Replicação Viral , Saliva/virologia , Transcriptoma , TibetRESUMO
Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as antiatopic dermatitis agents. 3',4-O-dimethylcedrusin (DCN) is a natural dihydrobenzofuran neolignan isolated from Magnolia biondii with moderate potency against PDE4 (IC50 = 3.26 ± 0.28 µM) and a binding mode similar to that of apremilast, an approved PDE4 inhibitor for the treatment of psoriasis. The structure-based optimization of DCN led to the identification of 7b-1 that showed high inhibitory potency on PDE4 (IC50 = 0.17 ± 0.02 µM), good anti-TNF-α activity (EC50 = 0.19 ± 0.10 µM), remarkable selectivity profile, and good skin permeability. The topical treatment of 7b-1 resulted in the significant benefits of pharmacological intervention in a DNCB-induced atopic dermatitis-like mice model, demonstrating its potential for the development of novel antiatopic dermatitis agents.
Assuntos
Dermatite Atópica , Lignanas , Inibidores da Fosfodiesterase 4 , Camundongos , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/uso terapêutico , Dinitroclorobenzeno/farmacologia , Dinitroclorobenzeno/uso terapêutico , Lignanas/farmacologia , Lignanas/uso terapêutico , Inibidores do Fator de Necrose Tumoral/farmacologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Citocinas/farmacologia , PeleRESUMO
Artemisinin is primarily synthesized and stored in the subepidermal space of the glandular trichomes of Artemisia annua. The augmentation of trichome density has been demonstrated to enhance artemisinin yield. However, existing literature lacks insights into the correlation between the stratum corneum and trichomes. This study aims to unravel the involvement of TrichomeLess Regulator 3 (TLR3), which encodes the transcription factor, in artemisinin biosynthesis and its potential association with the stratum corneum. TLR3 was identified as a candidate gene through transcriptome analysis. The role of TLR3 in trichome development and morphology was investigated using yeast two-hybrid, pull-down analysis, and RNA electrophoresis mobility assay. Our research revealed that TLR3 negatively regulates trichome development. It modulates the morphology of Arabidopsis thaliana trichomes by inhibiting branching and inducing the formation of abnormal trichomes in Artemisia annua. Overexpression of the TLR3 gene disrupts the arrangement of the stratum corneum and reduces artemisinin content. Simultaneously, TLR3 possesses the capacity to regulate stratum corneum development and trichome follicle morphology by interacting with TRICHOME AND ARTEMISININ REGULATOR 1, and CycTL. Consequently, our findings underscore the pivotal role of TLR3 in the development of glandular trichomes and stratum corneum biosynthesis, thereby influencing the morphology of Artemisia annua trichomes.
RESUMO
Background: Risk factors for colorectal cancer (CRC) affect the way patients are subsequently treated and their prognosis. Dual-energy computerized tomography (DECT) is an advanced imaging technique that enables the quantitative evaluation of lesions. This study aimed to evaluate the quality of DECT images based on the Mono+ algorithm in CRC, and based on this, to assess the value of DECT in the diagnosis of CRC risk factors. Methods: This prospective study was performed from 2021 to 2023. A dual-phase DECT protocol was established for consecutive patients with primary CRC. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), overall image quality, lesion delineation, and image noise of the dual-phase DECT images were assessed. Next, the optimal energy-level image was selected to analyze the iodine concentration (IC), normalized iodine concentration (NIC), effective atomic number, electron density, dual-energy index (DEI), and slope of the energy spectrum curve within the tumor for the high- and low-risk CRC groups. A multifactor binary logistic regression analysis was used to construct a differential diagnostic regression model for high- and low-risk CRC, receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated to assess the diagnostic value of the model. Results: A total of 74 patients were enrolled in this study, of whom 41 had high-risk factors and 33 had low-risk factors. The SNR and CNR were best at 40 keV virtual monoenergetic imaging (VMI) based on the Mono+ algorithm (VMI+) (SNR 8.79±1.27, P<0.001; CNR 14.89±1.77, P=0.027). The overall image quality and lesion contours were best at 60 keV VMI+ and 40 keV VMI+, respectively (P=0.001). Among all the DECT parameters, the arterial phase (AP)-IC, NIC, DEI, energy spectrum curve, and venous phase-NIC differed significantly between the two groups. The AP-IC was the optimal DECT parameter for predicting high- and low-risk CRC with AUC, sensitivity, specificity, and cut-off values of 0.96, 97.06%, 87.80%, and 2.94, respectively, and the 95% confidence interval (CI) of the AUC was 0.88-0.99. Integrating the clinical factors and DECT parameters, the AUC, sensitivity, specificity, and predictive accuracy of the model were 0.99, 100.00%, 92.68%, and 94.67%, respectively, and the 95% CI of the AUC was 0.93-1.00. Conclusions: The DECT parameters based on 40 keV noise-optimized VMI+ reconstruction images depicted the CRC tumors best, and the clinical DECT model may have significant implications for the preoperative prediction of high-risk factors in CRC patients.
RESUMO
Studying the mechanisms of the spin Hall effect (SHE) is essential for the fundamental understanding of spintronic physics. By now, despite the intensive studies of SHE on heavy metal (HM)/metallic magnet heterostructures, the SHE on HM/ferrimagnetic insulator (FMI) heterostructures still remains elusive. Here, we study the mechanism of SHE in the Pt/Tm3Fe5O12 (TmIG) heterostructure. We first tune the crystallinity and resistivity of Pt by an annealing method, and then study the spin-orbit torque (SOT) in the tuned-Pt/TmIG devices. The SOT generation efficiency per unit electric field and spin Hall angle were obtained, which are insensitive to the annealing temperature. We further demonstrate that the intrinsic contribution in the moderately dirty regime is responsible for the SHE in our Pt/TmIG bilayer. Our study provides an important piece of information for the SHE in FMI-based spintronic physics.
RESUMO
BACKGROUND: Airway epithelium is the first barrier against environmental insults, and epithelial barrier dysfunction caused by cigarette smoke (CS) is particularly relevant to chronic obstructive pulmonary disease (COPD) progression. Our study was to determine whether Azithromycin (AZI) ameliorates CS-induced airway epithelial barrier dysfunction and the underlying mechanisms. METHODS: Primary bronchial epithelial cells (PBECs), human bronchial epithelial cells (HBECs), Sprague Dawley rats and nuclear factor erythroid 2-related factor 2 (Nrf2)-/- mice were pretreated with AZI and subsequently exposed to CS. Transepithelial electronic resistance (TEER), junction proteins as well as pro-inflammatory cytokines and apoptosis markers were examined to assess epithelial barrier dysfunction. Metabolomics study was applied to explore the underlying mechanism of AZI. RESULTS: CS-induced TEER decline and intercellular junction destruction, accompanied with inflammatory response and cell apoptosis in PBECs were restored by AZI dose-dependently, which were also observed in CS-exposed rats. Mechanistically, GSH metabolism pathway was identified as the top differentially impacted pathway and AZI treatment upregulated the activities of glutamate cysteine ligase (GCL) and the contents of metabolites in GSH metabolic pathway. Furthermore, AZI apparently reversed CS-induced Nrf2 suppression, and similar effects on airway epithelial barrier dysfunction were also found for Nrf2 agonist tert-butylhydroquinone and vitamin C. Finally, deletion of Nrf2 in both HBECs and C57BL/6N mice aggravated CS-induced GSH metabolism imbalance to disrupt airway epithelial barrier and partially deprived the effects of AZI. CONCLUSION: These findings suggest that the clinical benefits of AZI for COPD management are related with the protection of CS-induced airway epithelial barrier dysfunction via activating Nrf2/GCL/GSH pathway, providing potential therapeutic strategies for COPD.
Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Animais , Humanos , Camundongos , Ratos , Azitromicina/farmacologia , Azitromicina/uso terapêutico , Glutamato-Cisteína Ligase , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2 , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Ratos Sprague-Dawley , Transdução de Sinais , Glutationa/metabolismoRESUMO
This work was aimed to elucidate the mechanism of action of Han-Shi-Yu-Fei-decoction (HSYFD) for treating patients with mild coronavirus disease 2019 (COVID-19) based on clinical symptom-guided network pharmacology. Experimentally, an ultra-high performance liquid chromatography technique coupled with quadrupole time-of-flight mass spectrometry method was used to profile the chemical components and the absorbed prototype constituents in rat serum after its oral administration, and 11 out of 108 compounds were identified. Calculatingly, the disease targets of Han-Shi-Yu-Fei symptoms of COVID-19 were constructed through the TCMIP V2.0 database. The subsequent network pharmacology and molecular docking analysis explored the molecular mechanism of the absorbed prototype constituents in the treatment of COVID-19. A total of 42 HSYFD targets oriented by COVID-19 clinical symptom were obtained, with EGFR, TP53, TNF, JAK2, NR3C1, TH, COMT, and DRD2 as the core targets. Enriched pathway analysis yielded multiple COVID-19-related signaling pathways, such as the PI3K/AKT signaling pathway and JAK-STAT pathway. Molecular docking showed that the key compounds, such as 6-gingerol, 10-gingerol, and scopoletin, had high binding activity to the core targets like COMT, JAK2, and NR3C1. Our work also verified the feasibility of clinical symptom-guided network pharmacology analysis of chemical compounds, and provided a possible agreement between the points of views of traditional Chinese medicine and western medicine on the disease.
RESUMO
With the broad application of sequencing technologies, many novel virus-like sequences have been discovered in arthropods, including mosquitoes. The two main categories of these new mosquito-associated viruses are "mosquito-borne viruses (MBVs)" and "mosquito-specific viruses (MSVs)". These novel viruses might be pathogenic to both vertebrates and mosquitoes, or they could just be symbiotic with mosquitoes. Entity viruses are essential to confirm the biological characters of these viruses. Thus, a detailed protocol has been described here for virus isolation and amplification from field-collected mosquitoes. First, the mosquito samples were prepared as supernatants of mosquito homogenates. After centrifugation twice, the supernatants were then inoculated into either mosquito cell line C6/36 or vertebrate cell line BHK-21 for virus amplification. After 7 days, the supernatants were collected as the P1 supernatants and stored at -80 °C. Next, P1 supernatants were passaged twice more in C6/36 or BHK-21 cells while the cell status was being checked daily. When cytopathogenic effect (CPE) on the cells was discovered, these supernatants were collected and used to identify viruses. This protocol serves as the foundation for future research on mosquito-associated viruses, including MBVs and MSVs.
Assuntos
Culicidae , Flavivirus , Vírus , Animais , Vírus Satélites , VertebradosRESUMO
The mortality rate of the recent global pandemic corona virus disease 2019 (COVID-19) is currently as high as 7%. The SARS-CoV-2 virus is the culprit behind COVID-19. SARS-CoV-2 is an enveloped single-stranded RNA virus, the genome encodes four types of the structural proteins: S protein, E protein (envelope protein), M protein (matrix protein) and N protein (nucleocapsid protein). In COVID-19, monoclonal antibodies have played a significant role in diagnosis and treatment. This article briefly introduced the development of monoclonal antibodies targeting on S protein and N protein, which represents the main direction of monoclonal antibody drugs used in the diagnosis and treatment of COVID-19. Meanwhile, the traditional Chinese medicine also plays important role in the fight against COVID-19 by regulating human immunity. The article introduced the use of traditional Chinese medicine in fighting against COVID-19.
RESUMO
[This corrects the article DOI: 10.3389/fphar.2022.788388.].
RESUMO
Background: COVID-19 is a respiratory illness caused by SARS-CoV-2. The most recent variant is Omicron (line B.1.1.529), which was first identified in South Africa in November 2021. The concern with this variant is the ineffectiveness of vaccines currently available. We aim to systematically evaluate the effectiveness of the currently available COVID-19 vaccines and boosters for the Omicron variant. Methods: We searched the PubMed, Embase, the Cochrane Library and Web of Science databases from inception to June 5th, 2022. Studies that examined the effectiveness of SARS-CoV-2 vaccines against the Omicron variant infection were included. Random-effects model was used to estimate the pooled vaccine effectiveness against the Omicron variant. Results: A total of 13 studies were included to evaluate the effectiveness of the vaccine against the Omicron variant, and 11 studies were included to compare the effectiveness between the two-dose and three-dose (booster) vaccinations. Full vaccination (two-dose with or without booster) showed a protective effect against the Omicron variant compared to no vaccination (OR = 0.62, 95% CI: 0.56-0.69), while the effectiveness decreased significantly over 6 months after the last dose. The two-dose vaccination plus booster provided better protection against the Omicron variant compared to the two-dose vaccination without booster (OR = 0.60, 95% CI: 0.52-0.68). Additional analysis was performed for the most commonly used vaccines in the United Staes: BNT162b2(Pfizer) (OR = 0.65, 95% CI: 0.52-0.82) and mRNA-1273(Moderna) (OR = 0.67, 95% CI: 0.58-0.88) vaccines in the US, which showed similar effectiveness compared to no vaccination. Conclusions: The full dose of SARS-CoV-2 vaccination effectively reduces infection from the SARS-CoV-2 Omicron variant; however, the effectiveness wanes over time. The booster vaccine provides additional protection against the Omicron variant.
Assuntos
COVID-19 , Vacinas Virais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Eficácia de VacinasRESUMO
Current knowledge about the transformation of total mercury and methylmercury (MeHg) in aerobic composting process is limited. In this study, the composition and transformation of mercury and dissovled organic matter (DOM) in aerobic composting process of municipal sewage sludge were were comprehensively characterized, and the differences among the three C/N ratio (20, 26 and 30) were investigated. The main form of mercury in C/N 20 and 26 was organo-chelated Hg (F3, 46%-60%); while the main form of mercury in C/N 30 was mercuric sulfide (F5, 64%-70%). The main component of DOM in C/N 20 and 26 were tyrosine-like substance (C1, 53%-76%) while the main fractions in C/N 30 were tyrosine-like substance (C1, 28%-37%) and fulvic-like substance (C2, 17%-39%). The mercury and DOM varied significantly during the 9 days composting process. Compared to C/N 20 and 26, C/N 30 produced the less MeHg after aerobic composting process, with values of 658% (C/N 20), 1400% (C/N 26) and 139% (C/N 30) of the initial, respectively. Meanwhile, C/N 30 produced the best compost showed greater degree of DOM molecular condensation and humification. Hg fraction had been altered by DOM, as indicated by a significant correlation between mercury species and DOM components. Notably, C/N 30 should be used as an appropriate C/N ratio to control the methylation processes of mercury and degration of DOM.