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A crystalline silicon thin-film solar cell with a three-layer sinusoidal grating structure is studied. The structure has a double-layer antireflection layer, and the three-layer grating is located in the double-layer antireflection layer and the passivation layer, respectively. The related parameters of the grating structure are optimized by scanning using finite-difference time-domain. The optimization results show that cutting the sinusoidal grating structure can significantly improve the light absorption efficiency of the cell for near-infrared light (750-1100 nm), and the enhancement effect is mainly in the transverse electric (TE)-polarized light. This is because the localized surface plasmon resonance and optical waveguide mode under TE-polarized light can be fully excited after the sinusoidal structure is cut. The short-circuit current density (J S C ) of the optimized three-layer sinusoidal grating structure is 19.82m A/c m 2, which is 112.43% higher than that of the planar structure with the same parameters and 23.18% higher than that of the uncut sinusoidal grating structure with the same parameters.
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α-Synuclein (α-syn)-induced neurotoxicity has been generally accepted as a key step in the pathogenesis of Parkinson's disease (PD). Microtubule-associated protein tau, which is considered second only to α-syn, has been repeatedly linked with PD in association studies. However, the underlying interaction between these two PD-related proteins in vivo remains unclear. To investigate how the expression of tau affects α-syn-induced neurodegeneration in vivo, we generated triple transgenic mice that overexpressed α-syn A53T mutation in the midbrain dopaminergic neurons (mDANs) with different expression levels of tau. Here, we found that tau had no significant effect on the A53T α-syn-mediated mDANs degeneration. However, tau knockout could modestly promote the formation of α-syn aggregates, accelerate the severe and progressive degeneration of parvalbumin-positive (PV+) neurons in substantia nigra pars reticulata (SNR), accompanied with anxiety-like behavior in aged PD-related α-syn A53T mice. The mechanisms may be associated with A53T α-syn-mediated specifically successive impairment of N-methyl-d-aspartate receptor subunit 2B (NR2B), postsynaptic density-95 (PSD-95) and microtubule-associated protein 1A (MAP1A) in PV+ neurons. Our study indicates that MAP1A may play a beneficial role in preserving the survival of PV+ neurons, and that inhibition of the impairment of NR2B/PSD-95/MAP1A pathway, may be a novel and preferential option to ameliorate α-syn-induced neurodegeneration.
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Mutação , Degeneração Neural , Doença de Parkinson/etiologia , Parvalbuminas/análise , Substância Negra/patologia , alfa-Sinucleína/genética , Proteínas tau/fisiologia , Animais , Proteína 4 Homóloga a Disks-Large/fisiologia , Proteínas de Homeodomínio/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/fisiologia , Doença de Parkinson/patologia , Fragmentos de Peptídeos/fisiologia , Agregados Proteicos , Receptores de N-Metil-D-Aspartato/fisiologia , Fatores de Transcrição/fisiologia , alfa-Sinucleína/fisiologia , Proteínas tau/química , Proteínas tau/genéticaRESUMO
We propose a dual-layer split nanograting structure in crystalline silicon thin-film solar cells (TFSCs). The split nanograting is designed by introducing two partitioning factors and split times. By employing the finite-difference time-domain method, the light trapping performance and relevant parameters of TFSCs are analyzed and optimized. Numerical computation of optical and electrical simulation shows that the optimal dual-layer split nanograting structure has demonstrated great enhanced light absorption compared with the planar structure. Enhancement of the light trapping effect is associated with light coupling to waveguide modes. The short-circuit current density is reached at 21.66mA/cm2 with an improvement of 54.6% over the planar structure. All results provide a parting thought for the design of TFSC grating structures.
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A low-cost rodent model of HIV infection and which presents high application value is an effective tool to investigate HIV infection and pathogenesis. However, development of such a small animal model has been hampered by the unsuitability of rodent cells for HIV-1 replication given that the retrovirus HIV-1 has high selectivity to its host cell. Our study used the mouse leukemia cell lines L615 and L1210 that were induced by murine leukemia virus and transfected with hCD4/CCR5 loaded-lentiviral vector. Lentiviral vectors containing the genes hCD4/CCR5 under the transcriptional control of cytomegalovirus promoter were designed. Transfection efficiencies of human CD4 and CCR5 in L615 and L1210 cells were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) and Western blot assay. Results showed that hCD4 and CCR5 proteins were expressed on the cell surface, demonstrating that the L615 and L1210 cells were humanized and that they possess the characteristics necessary for HIV infection of human host cells. Moreover, the sensitivity of human CD4/CCR5 transgenic mouse cells to HIV infection was confirmed by RT-PCR and ELISA. Mouse leukemia cell lines that could express hCD4 and CCR5 were thus established to facilitate normal entry of HIV-1 so that a human CD4/CCR5 transgenic mice cell model can be used to investigate the transmission and pathogenesis of HIV/AIDS and potential antiviral drugs against this disease.
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Antígenos CD4/biossíntese , Infecções por HIV/genética , Vírus da Leucemia Murina/genética , Receptores CCR5/biossíntese , Animais , Antígenos CD4/genética , Modelos Animais de Doenças , Regulação Viral da Expressão Gênica , Vetores Genéticos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/genética , HIV-1/patogenicidade , Humanos , Lentivirus/genética , Camundongos , Camundongos Transgênicos , Receptores CCR5/genética , TransfecçãoRESUMO
BACKGROUND: Recently, there have been some reports of seizures related with COVID-19 vaccinations. However, no studies have systematically investigated the relationship between seizures and various COVID-19 vaccines. RESEARCH DESIGN AND METHODS: This research aimed to analyze the characteristics and risk signals of new-onset seizures in children caused by various COVID-19 vaccines based on the data of the Vaccine Adverse Event Reporting System (VAERS). To identify potential risk signals, a disproportionality analysis was conducted. The reporting odds ratio (ROR) and the Proportional Reporting Ratio (PRR) were used to detect signals. RESULTS: A total of 695 children with new-onset seizures events associated with COVID-19 vaccinations were retrieved from the VAERS database. Compared with influenza vaccinations, the percentage and rate of COVID-19 vaccinations related seizures was all reduced. The median onset time of seizures was 1 day after COVID-19 vaccines. No signal was detected for an association between the COVID-19 vaccines and new-onset seizures, neither when compared with influenza vaccines nor with non-COVID-19 vaccines. CONCLUSION: No statistically significant risk signal of COVID-19 vaccine-related seizures was found in this study. However, it is still necessary to monitor the possibility of new-onset seizures when children are immunized with COVID-19 vaccines.
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ETHNOPHARMACOLOGICAL RELEVANCE: Alcohol misuse persists as a prevalent societal concern and precipitates diverse deleterious consequences, entailing significant associated health hazards including acute alcohol intoxication (AAI). Binge drinking, a commonplace pattern of alcohol consumption, may incite neurodegeneration and neuronal dysfunction. Clinicians tasked with managing AAI confront a dearth of pharmaceutical intervention alternatives. In contrast, natural products have garnered interest due to their compatibility with the human body and fewer side effects. Lingjiao Gouteng decoction (LGD), a classical traditional Chinese medicine decoction, represents a frequently employed prescription in cases of encephalopathy, although its efficacy in addressing acute alcoholism and alcohol-induced brain injury remains inadequately investigated. AIM OF THE STUDY: To investigate the conceivable therapeutic benefits of LGD in AAI and alcohol-induced brain injury, while delving into the underlying fundamental mechanisms involved. MATERIALS AND METHODS: We established an AAI mouse model through alcohol gavage, and LGD was administered to the mice twice at the 2 h preceding and 30 min subsequent to alcohol exposure. The study encompassed the utilization of the loss of righting reflex assay, histopathological analysis, enzyme-linked immunosorbent assays, and cerebral tissue biochemical assays to investigate the impact of LGD on AAI and alcohol-induced brain injury. These assessments included a comprehensive evaluation of various biomarkers associated with the inflammatory response and oxidative stress. Finally, RT-qPCR, Western blot, and immunofluorescence staining were carried out to explore the underlying mechanisms through which LGD exerts its therapeutic influence, potentially through the regulation of the RhoA/ROCK2/NF-κB signaling pathway. RESULTS: Our investigation underscores the therapeutic efficacy of LGD in ameliorating AAI, as evidenced by discernible alterations in the loss of righting reflex assay, pathological analysis, and assessment of inflammatory and oxidative stress biomarkers. Furthermore, the results of RT-qPCR, Western blot, and immunofluorescence staining manifest a noteworthy regulatory effect of LGD on the RhoA/ROCK2/NF-κB signaling pathway. CONCLUSIONS: The present study confirmed the therapeutic potential of LGD in AAI and alcohol-induced brain injury, and the protective effects of LGD against alcohol-induced brain injury may be intricately linked to the RhoA/ROCK2/NF-κB signaling pathway.
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Intoxicação Alcoólica , Alcoolismo , Lesões Encefálicas , Camundongos , Humanos , Animais , NF-kappa B/metabolismo , Intoxicação Alcoólica/tratamento farmacológico , Transdução de Sinais , Etanol/farmacologia , Lesões Encefálicas/tratamento farmacológico , Biomarcadores , Quinases Associadas a rho/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Coronavirus Disease 2019 (COVID-19) is a grave and pervasive global infectious malady brought about by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), posing a significant menace to human well-being. Qingfei Paidu decoction (QFPD) represents a pioneering formulation derived from four classical Chinese medicine prescriptions. Substantiated evidence attests to its efficacy in alleviating clinical manifestations, mitigating the incidence of severe and critical conditions, and reducing mortality rates among COVID-19 patients. AIM OF THE STUDY: This study aims to investigate the protection effects of QFPD in mice afflicted with a coronavirus infection, with a particular focus on determining whether its mechanism involves the NLRP3 signaling pathway. MATERIALS AND METHODS: The coronavirus mice model was established through intranasal infection of Kunming mice with Hepatic Mouse Virus A59 (MHV-A59). In the dose-effect experiment, normal saline, ribavirin (80 mg/kg), or QFPD (5, 10, 20 g/kg) were administered to the mice 2 h following MHV-A59 infection. In the time-effect experiment, normal saline or QFPD (20 g/kg) was administered to mice 2 h post MHV-A59 infection. Following the assessment of mouse body weights, food consumption, and water intake, intragastric administration was conducted once daily at consistent intervals over a span of 5 days. The impact of QFPD on pathological alterations in the livers and lungs of MHV-A59-infected mice was evaluated through H&E staining. The viral loads of MHV-A59 in both the liver and lung were determined using qPCR. The expression levels of genes and proteins related to the NLRP3 pathway in the liver and lung were assessed through qPCR, Western Blot analysis, and immunofluorescence. RESULTS: The administration of QFPD was shown to ameliorate the reduced weight gain, decline in food consumption, and diminished water intake, all of which were repercussions of MHV-A59 infection in mice. QFPD treatment exhibited notable efficacy in safeguarding tissue integrity. The extent of hepatic and pulmonary injury, when coupled with QFPD treatment, demonstrated not only a reduction with higher treatment dosages but also a decline with prolonged treatment duration. In the dose-effect experiment, there was a notable, dose-dependent reduction in the viral loads, as well as the expression levels of IL-1ß, NLRP3, ASC, Caspase 1, Caspase-1 p20, GSDMD, GSDMD-N, and NF-κB within the liver of the QFPD-treated groups. Additionally, in the time-effects experiments, the viral loads and the expression levels of genes and proteins linked to the NLRP3 pathway were consistently lower in the QFPD-treated groups compared with the model control groups, particularly during the periods when their expressions reached their zenith in the model group. Notably, IL-18 showed only a modest elevation relative to the blank control group following QFPD treatment. CONCLUSIONS: To sum up, our current study demonstrated that QFPD treatment has the capacity to alleviate infection-related symptoms, mitigate tissue damage in infected organs, and suppress viral replication in coronavirus-infected mice. The protective attributes of QFPD in coronavirus-infected mice are plausibly associated with its modulation of the NLRP3 signaling pathway. We further infer that QFPD holds substantial promise in the context of coronavirus infection therapy.
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COVID-19 , Lesão Pulmonar , Camundongos , Humanos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR , Solução Salina , SARS-CoV-2 , Transdução de Sinais , FígadoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine (TCM) prescription widely used in treating mental retardation and neurodegenerative diseases with kidney deficiency, has been reported to attenuate oxidative stress-related neuronal apoptosis. Chronic cerebral hypoperfusion (CCH) is considered to be related to cognitive and emotional disorders. However, it remains to be clarified that the effect of BSYZ on CCH and its underlying mechanism. AIM OF THE STUDY: In the present study, we aimed to investigate the therapeutic effects and underlying mechanisms of BSYZ on CCH- injured rats based on the domination of oxidative stress balance and mitochondrial homeostasis through inhibiting abnormal excessive mitophagy. MATERIALS AND METHODS: The in vivo rat model of CCH was established by bilateral common carotid artery occlusion (BCCAo), while the in vitro PC12 cell model was exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) condition, and a mitophagy inhibitor (chloroquine) by decreasing autophagosome-lysosome fusion was used as reverse validation in vitro. The protective role of BSYZ on CCH-injured rats was measured by open field test, morris water maze test, analysis of amyloid fibrils and apoptosis, and oxidative stress kit. The expression of mitochondria-related and mitophagy-related proteins was evaluated by Western blot, immunofluorescence, JC-1 staining assay and Mito-Tracker Red CMXRos assay. The components of BSYZ extracts were identified by HPLC-MS. The molecular docking studies were used to investigate the potential interactions of characteristic compounds in BSYZ with lysosomal membrane protein 1 (LAMP1). RESULTS: Our result indicated that BSYZ improved the cognition and memory abilities of the BCCAo rats by diminishing the occurrence of apoptosis and abnormal amyloid deposition accumulation, suppressing oxidative stress damage for abnormal excessive mitophagy activation in the hippocampus. Moreover, in OGD/R-damaged PC12 cells, BSYZ drug serum treatment substantially enhanced the PC12 cell viability and suppressed intracellular reactive oxygen species (ROS) accumulation for protecting against oxidative stress, along with the improvement of mitochondrial membrane activity and lysosomal proteins. Our studies also showed that inhibiting of autophagosome-lysosome fusion to generate autolysosomes by using chloroquine abrogated the neuroprotective effects of BSYZ on PC12 cells regarding the modulation of antioxidant defence and mitochondrial membrane activity. Furthermore, the molecular docking studies supported the direct bindings between lysosomal associated membrane protein 1 (LAMP1) and compounds in BSYZ extract to inhibit excessive mitophagy. CONCLUSION: Our study demonstrated that BSYZ played a neuroprotective role in rats with CCH and reduced neuronal oxidative stress via promoting the formation of autolysosomes to inhibit abnormal excessive mitophagy.
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Isquemia Encefálica , Fármacos Neuroprotetores , Ratos , Animais , Mitofagia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Simulação de Acoplamento Molecular , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , ApoptoseRESUMO
OBJECTIVE: Observational studies have posited a strong correlation between chronic gastritis (CG) and major depressive disorder (MDD), but the nature of this association remains uncertain, owing to the challenges of establishing the temporal sequence. The present study sought to elucidate the elusive relationship between CG and MDD by employing a bidirectional two-sample Mendelian randomization (MR) approach. METHODS: We extracted instrumental variants for MDD and CG from published genome-wide association study data, focusing on individuals of primarily European descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. RESULTS: For MDD and CG, 221 and 5 genetic variants, respectively, were selectively extracted as instrumental variants. The results suggest that MDD is causally associated with an elevated risk of CG (IVW: 23andMe, OR = 1.33; 95% CI = 1.15-1.54; p = 1.06 × 10-4); conversely, no strong evidence was found to corroborate that CG exerts a causal effect on the incidence of MDD (IVW: OR = 1.01; 95% CI = 0.95-1.07; p = 0.68). CONCLUSIONS: These findings provide novel insights into the causal relationship between CG and MDD, which may have implications for clinical decision-making in patients with MDD and CG.
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Transtorno Depressivo Maior , Gastrite , Humanos , Transtorno Depressivo Maior/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Bases de Dados Factuais , Gastrite/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: To investigate the traditional Chinese Medicine (TCM) etiology and pathogenesis of acquired immune deficiency syndrome (AIDS) by 18-month observation of Chinese rhesus macaques infected with simian immunodeficiency virus (SIV) mac239. METHODS: Thirty-five healthy Chinese rhesus macaques were divided into a model group (n = 30) and a control group (n = 5). The model was established by inoculating monkeys intravenously with SIVmac239. Changes in TCM symptoms after SIV infection within 18 months were then observed and recorded. Routine blood tests, SIV viral load, T-lymphocyte subsets, plasma triiodothyronine (T3), tetraiodothyronine (T4), adrenocorticotropic hormone (ACTH) and cortisol (Cor) were tested periodically during the experiment. RESULTS: During the acute infection period of SIV, model monkeys temporarily showed clinical symptoms such as diarrhea, dysphoria and slight weight loss. Decrease percentages of CD4+ T-lymphocytes were observed but levels of T3, T4, Cor, and ACTH were relatively unchanged. Monkeys in the model group during the early and middle periods of infection showed no obvious symptoms, except few monkeys exhibited transient diarrhea and reduced food intake. All variables at this stage showed normal fluctuations. In the middle period model group monkeys showed chronic and persistent diarrhea, weight loss, reduced food intake and low levels of T3 and Cor. In the late period, symptoms including emaciation, weight loss, listlessness, crouching in corners and low levels of T3 appeared. CONCLUSION: The results suggest that the rhesus monkey SIV/SAIDS model can be applied to research on TCM etiology and pathogenesis of AIDS. According to this model, the etiology of disease is the SIV virus. The pathogenesis manifests as the invasion of SIV virus, incubation of the virus, balance between virus and healthy "Qi", damage to spleen and kidney as the disease progressed, exhaustion of vitality and finally the failure of five zang and six fu organs.
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Síndrome da Imunodeficiência Adquirida/patologia , Modelos Animais de Doenças , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/virologia , Animais , HIV-1/fisiologia , Humanos , Masculino , Medicina Tradicional Chinesa , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologiaRESUMO
The molecular detection of SARS-CoV-2 is extremely important for the discovery and prevention of pandemic dissemination. Because SARS-CoV-2 is not always present in the samples that can be collected, the sample chosen for testing has inevitably become the key to the SARS-CoV-2 positive cases screening. The nucleotide amplification strategy mainly includes Q-PCR assays and isothermal amplification assays. The Q-PCR assay is the most used SARS-CoV-2 detection assay. Due to heavy expenditures and other drawbacks, isothermal amplification cannot replace the dominant position of the Q-PCR assay. The antibody-based detection combined with Q-PCR can help to find more positive cases than only using nucleotide amplification-based assays. Pooled testing based on Q-PCR significantly increases efficiency and reduces the cost of massive-scale screening. The endless stream of variants emerging across the world poses a great challenge to SARS-CoV-2 molecular detection. The multi-target assays and several other strategies have proved to be efficient in the detection of mutated SARS-CoV-2 variants. Further research work should concentrate on: (1) identifying more ideal sample plucking strategies, (2) ameliorating the Q-PCR primer and probes targeted toward mutated SARS-CoV-2 variants, (3) exploring more economical and precise isothermal amplification assays, and (4) developing more advanced strategies for antibody/antigen or engineered antibodies to ameliorate the antibody/antigen-based strategy.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Reação em Cadeia da Polimerase , NucleotídeosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication (AAI) is a ubiquitous emergency worldwide, whereas the searching for both effective and safe drugs is still a task to be completed. Modified Lvdou Gancao decoction (MLG), a traditional Chinese medicine decoction, has been confirmed to be valid to alcohol-induced symptoms and hepatotoxicity clinically, whereas its protective mechanisms have not been determined. MATERIALS AND METHODS: AAI mice model was established by alcohol gavage (13.25 mL/kg) and MLG (5, 10, 20 g/kg BW) was administered to mice 2 h before and 30 min after the alcohol exposure. Assay kits for alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamine transferase (GGT), total superoxide dismutase (T-SOD), malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidase (GSH-Px), as well as histopathology were used to explore the effects of MLG on acute alcohol-induced intoxication and hepatotoxicity. Mechanisms of MLG on oxidative stress and inflammatory were evaluated with RT-qPCR and Western Blot. RESULTS: MLG remarkably decreased the drunkenness rate, prolonged the tolerance time and shortened the sober-up time of AAI mice. After acute alcohol exposure, MLG treatment induced significant increment of ADH, ALDH, T-SOD and GSH-Px activities in liver, while serum ALT, AST, GGT and NO levels as well as hepatic MDA activity were reduced, in a dose-dependent manner. In contrast to the model group, the mRNA expression of TNFα, IL-1ß and NF-κB in the MLG treated groups had a downward trend while the Nrf-2 showed an upward trend simultaneously. Furthermore, the protein levels of p65, p-p65, p-IκBα in the MLG treated groups were considerably diminished, with HO-1 and Nrf2 elevated. To sum up, our results suggested that MLG could efficaciously ameliorate AAI via accelerating the metabolism of alcohol, alleviating acute hepatotoxicity, and weakening the oxidative stress coupled with inflammation response, which might be attributed to the inhibition of the NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway. CONCLUSIONS: Taken together, our present study verified the protective effect and mechanisms of MLG to AAI mice, and we further conclude that MLG may be a potent and reliable candidate for the prevention and treatment of AAI.
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Intoxicação Alcoólica , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/farmacologia , Glycyrrhiza , Fator 2 Relacionado a NF-E2/metabolismo , Álcool Desidrogenase/metabolismo , Intoxicação Alcoólica/tratamento farmacológico , Intoxicação Alcoólica/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Monitoramento de Medicamentos/métodos , Heme Oxigenase-1/metabolismo , Testes de Função Hepática/métodos , Proteínas de Membrana/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
AIDS, a serious fatal disease caused by the human immunodeficiency virus (HIV), is an epidemic disease for which no effective vaccine has been established. The current therapeutic interventions for AIDS have limited efficacy because they are unable to clear HIV infections and the continuous occurrence of resistant HIV strains. Therefore, the exploitation of new drugs to prevent the spread of AIDS remains a high priority. In this study, the effects of icariin and its metabolite anhydroicaritin on SIV/HIV replication were investigated. In CEM × 174 cells and PBMC cells, both icariin and anhydroicaritin can significantly inhibit HIV-1 or SIVmac251 replication. Furthermore, molecular docking studies revealed that icariin and anhydroicaritin can act on both HIV reverse transcriptase and protease but could not bind to integrase. Reverse transcriptase and protease inhibition biological assays showed that both icariin and anhydroicaritin could significantly inhibit only HIV reverse transcriptase. In summary, the two compounds can significantly inhibit HIV/SIV in vitro and their targets may be mainly involved with HIV reverse transcriptase.
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Fármacos Anti-HIV/farmacologia , Benzopiranos/farmacologia , Flavonoides/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/química , Benzopiranos/química , Linhagem Celular , Protease de HIV/metabolismo , Transcriptase Reversa do HIV/química , Transcriptase Reversa do HIV/metabolismo , HIV-1/enzimologia , HIV-1/crescimento & desenvolvimento , Humanos , Masculino , Simulação de Acoplamento Molecular , Inibidores de Proteases/farmacologia , Conformação Proteica , Inibidores da Transcriptase Reversa/química , Vírus da Imunodeficiência Símia/enzimologia , Vírus da Imunodeficiência Símia/crescimento & desenvolvimento , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacosRESUMO
OBJECTIVE: To observe the impacts of the formula of Suoquanwan (SQW) on the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney of rat polyuria model of Yang-deficiency. METHODS: The model rats were induced by adenine (250 mg/kg) for 4 weeks, then treated respectively with SQW or dDAVP. The expression of AQP-2 mRNA and AVPR-V2 mRNA in kidney of Yang-deficiency model by realtime fluorescence quantitative PCR method were investigated. RESULTS: In model rats, the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney decreased, dDAVP and SQW high dose could increased the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney. The others had no influence on the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney. CONCLUSION: SQW can increase the expression of AQP-2 mRNA and AVPR-V2 mRNA in the kidney of rat polyuria model of Yang-deficiency.
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Aquaporina 2/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Poliúria/tratamento farmacológico , Receptores de Vasopressinas/metabolismo , Deficiência da Energia Yang/tratamento farmacológico , Animais , Aquaporina 2/genética , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Medicina Tradicional Chinesa , Plantas Medicinais/química , Reação em Cadeia da Polimerase/métodos , Poliúria/induzido quimicamente , Poliúria/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de Vasopressinas/genética , Deficiência da Energia Yang/induzido quimicamente , Deficiência da Energia Yang/metabolismoRESUMO
Friend leukemia virus (FLV), a murine retrovirus, has been used as a model for elucidation of human immunodeficiency virus (HIV) immunopathogenesis and evaluation of anti-HIV drug effects for several decades. However, no method for direct detection of the plasma viral load has yet been reported. In this study, a TaqMan real-time quantitative reverse transcriptase PCR (qRT-PCR) assay was established for the rapid detection and quantitation of FLV. Measurement of the absolute FLV load was achieved through synthesis of a standard RNA from within the FLV envelope gene for generation of a standard curve. The assay allows quantitation over a range from 20 to 2 x 10(8) RNA copies per reaction in a two-step real-time quantitative reverse transcriptase PCR protocol. The relationships between the initially injected FLV dose and the plasma FLV load and spleen index were explored. Following this, the in vivo effects of zidovudine, adefovir dipivoxil, and entecavir on mice infected with FLV were evaluated. The results showed that the plasma FLV load was not proportional to the spleen index over the same FLV injection dosage series, although a trend was observed. When evaluated using plasma viral load, high dose (15 mg/(kg d)) adefovir dipivoxil was capable of significant inhibition of FLV replication in mice. The qRT-PCR assay described here allows specific, sensitive and direct detection of FLV and may also provide more precise measurement of FLV load.
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Vírus da Leucemia Murina de Friend/fisiologia , RNA Viral/sangue , Infecções por Retroviridae/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Infecções Tumorais por Vírus/virologia , Carga Viral , Animais , Antirretrovirais/uso terapêutico , Feminino , Vírus da Leucemia Murina de Friend/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Retroviridae/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , ViremiaRESUMO
BACKGROUND: Adult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis. Although various treatments have been reported, the immune-mediated tissue regeneration driven by biomaterial offers an attractive regenerative strategy for damaged tissue repair. METHODS: In this research, we investigated a specific bone marrow-derived mesenchymal stem cell (BMSC) sheet that was induced by the Traditional Chinese Medicine curcumin (CS-C) and its immunomodulatory effects on wound repair. Comparisons were made with the BMSC sheet induced without curcumin (CS-N) and control (saline). RESULTS: In vitro cultured BMSC sheets (CS-C) showed that curcumin promoted the proliferation of BMSCs and modified the features of produced extracellular matrix (ECM) secreted by BMSCs, especially the contents of ECM structural proteins such as fibronectin (FN) and collagen I and III, as well as the ratio of collagen III/I. Two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging of mouse implantation revealed superior engraftment of BMSCs, maintained for 35 days in the CS-C group. Most importantly, CS-C created a favorable immune microenvironment. The chemokine stromal cell-derived factor 1 (SDF1) was abundantly produced by CS-C, thus facilitating a mass migration of leukocytes from which significantly increased expression of signature TH1 cells (interferon gamma) and M1 macrophages (tumor necrosis factor alpha) genes were confirmed at 7 days post-operation. The number of TH1 cells and associated pro-inflammatory M1 macrophages subsequently decreased sharply after 14 days post-operation, suggesting a rapid type I immune regression. Furthermore, the CS-C group showed an increased trend towards M2 macrophage polarization in the early phase. CS-C led to an epidermal thickness and collagen deposition that was closer to that of normal skin. CONCLUSIONS: Curcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a pro-regenerative immune microenvironment for cutaneous wound healing.
Assuntos
Células da Medula Óssea/imunologia , Microambiente Celular/efeitos dos fármacos , Curcumina/farmacologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Cicatrização/imunologia , Ferimentos e Lesões/terapia , Aloenxertos , Animais , Células da Medula Óssea/patologia , Microambiente Celular/imunologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Células Th1/imunologia , Células Th1/patologia , Ferimentos e Lesões/imunologia , Ferimentos e Lesões/patologiaRESUMO
Accumulating evidence has revealed the imprinting of insulin-like growth factor-2 gene (IGF2) is maintained by binding of CCCTC binding factor (CTCF) to the unmethylated imprinting control region (ICR) between IGF2 and H19 genes. We have previously reported that high-density lipoprotein binding protein (HDLBP/vigilin), a multiKH-domain protein, interacts with CTCF and coexists with it at several CTCF-binding sites on the ICR to regulate general gene expression of IGF2. However, the impact of the interaction on imprinting of IGF2 remains unclear. Here, we demonstrate that cooperation of vigilin and CTCF protects IGF2 from losing of imprinting. Pull-down experiments show that KH1-7 domains of vigilin interact with zinc-finger domains of CTCF. We also display that some RNAs participate in the vigilin-CTCF interaction, one of which is H19 long noncoding RNA (lncRNA). Furthermore, we confirm that H19 lncRNA-knockdown alters the imprinting of IGF2. These data suggest that vigilin interacts with CTCF, mediated by H19 lncRNA, to keep the imprinting of IGF2.
Assuntos
Fator de Ligação a CCCTC/metabolismo , Impressão Genômica , Fator de Crescimento Insulin-Like II/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/metabolismo , Alelos , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Ligação Proteica , Dedos de ZincoRESUMO
AIM: To investigate if iron deposition and fat accumulation in the liver play a pathogenetic role in dimethylnitrosamine (DMN)-induced liver fibrosis in rat. METHODS: Thirty rats were treated with DMN at does consecutive days of 10 microL/kg daily, i.p., for 3 consecutive day each week for 4 wk. Rats (n=30) were sacrificed on the first day (model group A) and 21(st) d (model group B) after cessation of DMN injection. The control group (n=10) received an equivalent amount of saline. Liver tissues were stained with hematoxylin and eosin (HE) and Masson and Prussian blue assay and observed under electron microscopy. Serum alanine aminotransferase (ALT) and liver tissue hydroxyproline (Hyp) content were tested. RESULTS: The liver fibrosis did not automatically reverse, which was similar to previous reports, the perilobular deposition of iron accompanied with collagen showed marked characteristics at both the first and 21(st) d after cessation of DMN injection. However, fat accumulation in hepatocytes occurred only at the 21(st) d after cessation of DMN injection. CONCLUSION: Iron deposition and fat accumulation may play important roles in pathological changes in DMN-induced rat liver fibrosis. The detailed mechanisms of these characteristics need further research.
Assuntos
Ferro/metabolismo , Metabolismo dos Lipídeos/fisiologia , Cirrose Hepática/metabolismo , Alanina Transaminase/sangue , Animais , Colágeno/metabolismo , Dimetilnitrosamina , Feminino , Hidroxiprolina/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To compare the sensitivity and reproducibility of Allglo and TaqMan probe in the detection of simian immunodeficiency virus (SIV) using fluorescence quantitative RT-PCR (QPCR). METHODS: The reference sample of SIV was diluted to 6 gradient concentrations; at each concentration 12 samples were tested to analyze the variations within batches, and each sample was tested for 12 times for analysis of variations between batches by QRT-PCR using TaqMan probe and Allglo probe. The results of QPCR using the two probes were analyzed with ABI7300 PCR system software. RESULTS: In QPCR using TaqMan and Allglo probe, the lower limit of sensitivity for SIV detection was both 50 copies/mL. Assessment of the reproducibility of the tests showed that the maximum and minimum coefficients of variation between batches were 0.63% and 0.33% with Allglo probe, respectively, as compared with 1.33% and 0.2% with TaqMan probe. The maximum and minimum coefficients of inter-batch variation was 1.77% and 0.95% with Allglo probe, respectively, as compared with 1.86% and 1.03% with TaqMan probe. CONCLUSION: Allglo probe shows a better performance then TaqMan probe in detection of SIV QPCR.
Assuntos
Sondas de DNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vírus da Imunodeficiência Símia/isolamento & purificação , Animais , Fluorescência , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
AIM: To observe the Lamivudine resistance character of a DHBV strain in vitro and in vivo, and to analyze if the Lamivudine resistance character is caused by gene mutation or by abnormity of the Lamivudine metabolism. METHODS: Congenitally DHBV-negative Guangdong brown ducks and duck embryo liver cells were respectively taken as animal and cell model. The Lamivudine-susceptive DHBV and Lamivudine-resistant DHBV (LRDHBV) were infected and Lamivudine was administrated according to the divided groups. The changes of DHBV quantity in the animal and cell model were tested. Three Lamivudine-resistant and two Lamivudine-susceptive DHBV complete genomes were successfully amplified, sequenced and then submitted to GenBank. All the DHBV complete sequences in the GenBank at present were taken to align with the three LRDHBV to analyze the mutational points related to the Lamivudine-resistant mutation. RESULTS: Both the animal and cell model showed that the large and the small dosage Lamivudine have no significant inhibitory effect on the LRDHBV. Five sequences of DHBV complete genomes were successfully cloned. The GenBank accession numbers of the three sequences of LRDHBV are AY521226, AY521227, and AY433937. The two strains of Lamivudine-susceptive DHBV are AY392760 and AY536371. The correlated mutational points are KorR86Q and AorE591T in the P protein. CONCLUSION: The Lamivudine resistance character of this DHBV strain is caused by genome mutation; the related mutational points are KorR86Q and AorE591T and have no relations with the YMDD motif mutation.