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1.
Proc Natl Acad Sci U S A ; 119(11): e2118278119, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35263220

RESUMEN

SignificanceThe photosensitizer is one of the important components in the photocatalytic system. Molecular photosensitizers have well-defined structures, which is beneficial in revealing the catalysis mechanism and helpful for further structural design and performance optimization. However, separation and recycling of the molecular photosensitizers is a great problem. Loading them into/on two/three-dimensional supports through covalent bonds, electrostatic interactions, and supramolecular interactions is a method that enhances their separation and recycling capability. Nonetheless, the structures of the resulting composites are unclear. Thus, the development of highly crystalline heterogeneity methods for molecular photosensitizers, albeit greatly challenging, is meaningful and desirable in photocatalysis, through which heterogeneous photosensitizers with well-defined structures, definite catalysis mechanisms, and good catalytic performance would be expected.


Asunto(s)
Fármacos Fotosensibilizantes , Catálisis , Estructura Molecular , Fármacos Fotosensibilizantes/química
2.
Proc Natl Acad Sci U S A ; 119(35): e2119267119, 2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-35998222

RESUMEN

A carbazolide-bis(NHC) NiII catalyst (1; NHC, N-heterocyclic carbene) for selective CO2 photoreduction was designed herein by a one-stone-two-birds strategy. The extended π-conjugation and the strong σ/π electron-donation characteristics (two birds) of the carbazolide fragment (one stone) lead to significantly enhanced activity for photoreduction of CO2 to CO. The turnover number (TON) and turnover frequency (TOF) of 1 were ninefold and eightfold higher than those of the reported pyridinol-bis(NHC) NiII complex at the same catalyst concentration using an identical Ir photosensitizer, respectively, with a selectivity of ∼100%. More importantly, an organic dye was applied to displace the Ir photosensitizer to develop a noble-metal-free photocatalytic system, which maintained excellent performance and obtained an outstanding quantum yield of 11.2%. Detailed investigations combining experimental and computational studies revealed the catalytic mechanism, which highlights the potential of the one-stone-two-birds effect.

3.
Int J Colorectal Dis ; 39(1): 99, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926205

RESUMEN

PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.


Asunto(s)
Terapia Neoadyuvante , Neoplasias del Recto , Microambiente Tumoral , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Quimioradioterapia , Resultado del Tratamiento , Estudios Retrospectivos
4.
Appl Microbiol Biotechnol ; 108(1): 182, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38285115

RESUMEN

Mammalian cell lines are frequently used as the preferred host cells for producing recombinant therapeutic proteins (RTPs) having post-translational modified modification similar to those observed in proteins produced by human cells. Nowadays, most RTPs approved for marketing are produced in Chinese hamster ovary (CHO) cells. Recombinant therapeutic antibodies are among the most important and promising RTPs for biomedical applications. One of the issues that occurs during development of RTPs is their degradation, which caused by a variety of factors and reducing quality of RTPs. RTP degradation is especially concerning as they could result in reduced biological functions (antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity) and generate potentially immunogenic species. Therefore, the mechanisms underlying RTP degradation and strategies for avoiding degradation have regained an interest from academia and industry. In this review, we outline recent progress in this field, with a focus on factors that cause degradation during RTP production and the development of strategies for overcoming RTP degradation. KEY POINTS: • The recombinant therapeutic protein degradation in CHO cell systems is reviewed. • Enzymatic factors and non-enzymatic methods influence recombinant therapeutic protein degradation. • Reducing the degradation can improve the quality of recombinant therapeutic proteins.


Asunto(s)
Apoptosis , Industrias , Animales , Cricetinae , Humanos , Células CHO , Cricetulus , Proteolisis
5.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2585-2596, 2024 May.
Artículo en Zh | MEDLINE | ID: mdl-38812159

RESUMEN

This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1ß), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1ß, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1ß, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1ß, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.


Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Ciclooxigenasa 2 , Hígado , FN-kappa B , Panax , Saponinas , Transducción de Señal , Animales , Acetaminofén/efectos adversos , Acetaminofén/toxicidad , Ratones , Panax/química , Masculino , Saponinas/farmacología , Saponinas/administración & dosificación , FN-kappa B/genética , FN-kappa B/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Transducción de Señal/efectos de los fármacos , Humanos , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología
6.
Angew Chem Int Ed Engl ; : e202405451, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-39031893

RESUMEN

Hydrogen-bonded organic frameworks (HOFs) are outstanding candidates for photocatalytic hydrogen evolution. However, most of reported HOFs suffer from poor stability and photocatalytic activity in the absence of Pt cocatalyst. Herein, a series of metal HOFs (Co2-HOF-X, X = COOMe, Br, tBu and OMe) have been rationally constructed based on dinuclear cobalt complexes, which exhibit exceptional stability in the presence of strong acid (12 M HCl) and strong base (5 M NaOH) for at least 10 days. More impressively, by varying the -X groups of the dinuclear cobalt complexes, the microenvironment of Co2-HOF-X can be modulated, giving rise to obviously different photocatalytic H2 production rates, following the -X group sequence of -COOMe > -Br > -tBu > -OMe. The optimized Co2-HOF-COOMe shows H2 generation rate up to 12.8 mmol g-1 h-1 in the absence of any additional noble-metal photosensitizers and cocatalysts, which is superior to most reported Pt-assisted photocatalytic systems. Experiments and theoretical calculations reveal that the -X groups grafted on Co2-HOF-X possess different electron-withdrawing ability, thus regulating the electronic structures of Co catalytic centres and proton activation barrier for H2 production, and leading to the distinctly different photocatalytic activity.

7.
J Immunol ; 207(1): 200-209, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34162722

RESUMEN

Melanization and encapsulation are prominent defense responses against microbes detected by pattern recognition receptors of their host insects. In the ghost moth Thitarodes xiaojinensis, an activated immune system can melanize and encapsulate the fungus Cordyceps militaris However, these responses were hardly detected in the host hemolymph postinfection of another fungus Ophiocordyceps sinensis The immune interaction between O. sinensis and the host remains largely unknown, which hinders the artificial cultivation of Chinese cordyceps. We found that T. xiaojinensis ß-1,3-glucan recognition protein-1 (ßGRP1) was needed for prophenoloxidase activation induced by C. militaris Failure of ßGRP1 to recognize O. sinensis is a primary reason for the lack of melanization in the infected host. Lyticase or snailase treatment combined with binding and immunofluorescence detection showed the existence of a protective layer preventing the fungus from ßGRP1 recognition. Coimmunoprecipitation and mass spectrometry analysis indicated that ßGRP1 interacted with immulectin-8 (IML8) via binding to C. militaris IML8 promotes encapsulation. This study suggests the roles of T. xiaojinensis ßGRP1 and IML8 in modulating immune responses against C. militaris Most importantly, the data indicate that O. sinensis may evade melanization by preventing ßGRP1 recognition.


Asunto(s)
Cordyceps/inmunología , Proteínas de Insectos/inmunología , Mariposas Nocturnas/inmunología , Animales , Mariposas Nocturnas/microbiología
8.
Ecotoxicol Environ Saf ; 267: 115650, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37939555

RESUMEN

Benzophenones (BPs) have wide practical applications in real human life due to its presence in personal care products, UV-filters, drugs, food packaging bags, etc. It enters the wastewater by daily routine activities such as showering, impacting the whole aquatic system, then posing a threat to human health. Due to this fact, the monitoring and removal of BPs in the environment is quite important. In the past decade, various novel analytical and removal techniques have been developed for the determination of BPs in environmental samples including wastewater, municipal landfill leachate, sewage sludge, and aquatic plants. This review provides a critical summary and comparison of the available cutting-edge pretreatment, determination and removal techniques of BPs in environment. It also focuses on novel materials and techniques in keeping with the concept of "green chemistry", and describes on challenges associated with the analysis of BPs, removal technologies, suggesting future development strategies.


Asunto(s)
Benzofenonas , Contaminantes Químicos del Agua , Humanos , Aguas Residuales , Embalaje de Alimentos , Aguas del Alcantarillado
9.
Pharm Biol ; 61(1): 1343-1363, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37623313

RESUMEN

CONTEXT: Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage. OBJECTIVE: To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms. MATERIALS AND METHODS: TA concentrations of 1.563-25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats. RESULTS: TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression. DISCUSSION AND CONCLUSIONS: TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment.


Asunto(s)
MicroARNs , Triterpenos , Animales , Ratas , Ratas Sprague-Dawley , Frutas , Triterpenos/farmacología , Citocinas , Quimiocina CXCL12
10.
Small ; 18(20): e2200332, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35451165

RESUMEN

2D lamellar materials can offer high surface area and abundant reactive sites, thus showing an appealing prospect in photocatalytic hydrogen evolution. However, it is still difficult to build cost-efficient photocatalytic hydrogen evolution systems based on 2D materials. Herein, an in situ growth method is employed to build 2D/2D heterojunctions, with which 2D Ni-based metal-organic layers (Ni-MOLs) are closely grown on 2D porous CdS (P-CdS) nanosheets, affording traditional P-CdS/Ni-MOL heterojunction materials. Impressively, the optimized P-CdS/Ni-MOL catalyst exhibits superior photocatalytic hydrogen evolution performance, with an H2 yield of 29.81 mmol g-1 h-1 . This value is 7 and 2981 times higher than that of P-CdS and Ni-MOLs, respectively, and comparable to those of reported state of the art catalysts. Photocatalytic mechanism studies reveal that the enhanced photocatalytic performance can be attributed to the 2D/2D intimate interface between P-CdS and Ni-MOLs, which facilitates the fast charge carriers' separation and transfer. This work provides a strategy to develop 2D MOL-based photocatalysts for sustainable energy conversion.

11.
Clin Lab ; 68(10)2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36250845

RESUMEN

BACKGROUND: Leukopenia is the most common adverse event in chemotherapy, which natural products can prevent and treat. The aim of this study was to investigate the clinical efficacy of potato extract for alleviating chemoradiotherapy-induced leukopenia in cancer patients. METHODS: This was a single-blinded randomized placebo-controlled trial that enrolled 184 cancer patients. The participants were scheduled to undergo chemoradiotherapy in two hospitals, where they were randomized to receive potato extract or a placebo in a 1:1 ratio for a period of 49 days. Change in leukocyte value was considered the primary outcome of this clinical trial. Secondary outcomes included tumor response rate, blood test, and quality of life score. RESULTS: The leukopenia was relieved in the potato extract group compared with the placebo group. Of note, a significant difference in leukopenia between the two groups was found after 14 days (p = 0.04). In addition, there was no statistically significant difference in leucocyte levels in the potato extract group (before and after potato extract treatment; p = 0.13), but in the placebo group, the leukocyte value significantly decreased compared to before treatment (p = 0.06). CONCLUSIONS: Potato extract can alleviate chemoradiotherapy-induced leukopenia in cancer patients. These results show the potential function of potato extract as a protective agent in management of cancer chemoradiotherapy.


Asunto(s)
Productos Biológicos , Leucopenia , Neoplasias , Solanum tuberosum , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Método Doble Ciego , Humanos , Leucopenia/inducido químicamente , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Calidad de Vida , Método Simple Ciego , Resultado del Tratamiento
12.
Angew Chem Int Ed Engl ; 61(51): e202215187, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36316808

RESUMEN

Dual-atom catalysts (DACs) have emerged as efficient electrocatalysts for CO2 reduction owing to the synergistic effect between the binary metal sites. However, rationally modulating the electronic structure of DACs to optimize the catalytic performance remains a great challenge. Herein, we report the electronic structure modulation of three Ni2 DACs (namely, Ni2 -N7 , Ni2 -N5 C2 and Ni2 -N3 C4 ) by the regulation of the coordination environments around the dual-atom Ni2 centres. As a result, Ni2 -N3 C4 exhibits significantly improved electrocatalytic activity for CO2 reduction, not only better than the corresponding single-atom Ni catalyst (Ni-N2 C2 ), but also higher than Ni2 -N7 and Ni2 -N5 C2 DACs. Density functional theory (DFT) calculations revealed that the high electrocatalytic activity of Ni2 -N3 C4 for CO2 reduction could be attributed to the electronic structure modulation to the Ni centre and the resulted proper binding energies to COOH* and CO* intermediates.

13.
Cell Tissue Res ; 386(3): 661-677, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34599689

RESUMEN

Determining the source of primary cells is conductive to enriching sufficient cells with immortal potential thereby improving the success rate of establishing cell lines. However, most of the existing insect cell lines are established by mixing and fragmentation of explants. At present, the origin of cell lines can only be determined according to the cultured tissues, so it is impossible to determine which cell types they come from. In this study, a new cell line designated IOZCAS-Myse-1 was generated from pupal ovaries of the migratory pest Mythimna separata by explant tissues to derive adherent cultures. This paper mainly shows the further descriptive information on the origin of primary cells in the process of ovarian tissue isolation and culture. Phospho-histone H3 antibody-labeled cells with mitotic activity showed that the rapidly developing somatic cells in vivo gradually stopped proliferation when cultured ex vivo. The primary cells dissociated outside the tissue originated from the lumen cells, rather than the germ cells or the follicular epithelium cells. The results suggest that the newly established cell line IOZCAS-Myse-1 had two possible sources. One is the mutation of lumen cells in the vitellarium, and the other is the stem cells with differentiation potential in the germarium of the ovarioles. Moreover, the newly established cell line is sensitive to the infection of Autographa californica multiple nucleopolyhedrovirus, responds to 20-hydroxyecdysone and has weak encapsulation ability. Therefore, the new cell line can be a useful platform for replication of viral insecticides, screening of hormone-based insecticides and immunology research.


Asunto(s)
Línea Celular/fisiología , Ovario/fisiología , Animales , Femenino , Lepidópteros , Pupa
14.
J Clin Lab Anal ; 35(2): e23685, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33576536

RESUMEN

BACKGROUND: Pneumonia caused by the 2019 novel Coronavirus (COVID-2019) shares overlapping signs and symptoms, laboratory findings, imaging features with influenza A pneumonia. We aimed to identify their clinical characteristics to help early diagnosis. METHODS: We retrospectively retrieved data for laboratory-confirmed patients admitted with COVID-19-induced or influenza A-induced pneumonia from electronic medical records in Ningbo First Hospital, China. We recorded patients' epidemiological and clinical features, as well as radiologic and laboratory findings. RESULTS: The median age of influenza A cohort was higher and it exhibited higher temperature and higher proportion of pleural effusion. COVID-19 cohort exhibited higher proportions of fatigue, diarrhea and ground-glass opacity and higher levels of lymphocyte percentage, absolute lymphocyte count, red-cell count, hemoglobin and albumin and presented lower levels of monocytes, c-reactive protein, aspartate aminotransferase, alkaline phosphatase, serum creatinine. Multivariate logistic regression analyses showed that fatigue, ground-glass opacity, and higher level of albumin were independent risk factors for COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count were independent risk factors for influenza A pneumonia. CONCLUSIONS: In terms of COVID-19 pneumonia and influenza A pneumonia, fatigue, ground-glass opacity, and higher level of albumin tend to be helpful for diagnosis of COVID-19 pneumonia, while older age, higher temperature, and higher level of monocyte count tend to be helpful for the diagnosis of influenza A pneumonia.


Asunto(s)
COVID-19/diagnóstico , COVID-19/virología , Técnicas de Laboratorio Clínico , Virus de la Influenza A/fisiología , Neumonía/diagnóstico , Neumonía/virología , SARS-CoV-2/fisiología , COVID-19/diagnóstico por imagen , Diagnóstico Diferencial , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neumonía/diagnóstico por imagen , Factores de Riesgo , Tomografía Computarizada por Rayos X
15.
J Infect Dis ; 222(3): 443-455, 2020 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-32115640

RESUMEN

BACKGROUND: Encephalitis in hand, foot, and mouth disease (HFMD) is a serious threat to children's health and life. Toll-like receptor 3 (TLR3) is an innate immune-recognition receptor that can recognize virus and initiate innate immune responses. Emodin has the effects of anti-inflammatory and regulating immune function, but the mechanism is not very clear. METHODS: Cells and mice were pretreated with coxsackievirus B3m (CVB3) and treated with emodin. The messenger ribonucleic acid (mRNA) and protein levels of TLR3 and downstream molecules were detected by quantitative real-time polymearse chain reaction and western blotting analysis, respectively. TLR3 expression was also downregulated by anti-TLR3 antibody (TLR3Ab) or small interfering RNA (siRNA). Pathological changes were assessed with hematoxylin and eosin staining. Immunohistochemistry was used to examine the expression of TLR3 in brain tissues. The expression of interleukin (IL)-6, nuclear factor (NF)-κB, and interferon (IFN)-ß in serum were tested with enzyme-linked immunosorbent assay. RESULTS: Emodin decreased the mRNA and protein levels of TLR3 and downstream molecules in vitro and in vivo. After downregulating TLR3 using anti-TLR3Ab or siRNA, emodin could still decrease the mRNA and protein levels of TLR3 and downstream molecules. Emodin also displayed notable effects on pathology, TLR3 protein in brain tissues, and expression of IL-6, NF-κB, IFN-ß, in serum. CONCLUSIONS: Emodin exerts a protective effect in CVB3-mediated encephalitis in HFMD by inhibiting the TLR3 pathway.


Asunto(s)
Emodina/farmacología , Encefalitis/tratamiento farmacológico , Enfermedad de Boca, Mano y Pie/virología , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 3/metabolismo , Animales , Western Blotting , Células Cultivadas , Encefalitis/inmunología , Encefalitis/virología , Enterovirus/inmunología , Ensayo de Inmunoadsorción Enzimática , Inmunidad Innata , Interferón beta/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , ARN Mensajero/efectos de los fármacos , Receptor Toll-Like 3/genética
16.
Zhongguo Zhong Yao Za Zhi ; 46(18): 4782-4792, 2021 Sep.
Artículo en Zh | MEDLINE | ID: mdl-34581089

RESUMEN

This study investigated the protective effect of total triterpenoids from Chaenomeles speciosa against Helicobacter pylori(Hp)-induced gastritis in mice and explored its possible mechanism. The chronic atrophic gastritis(CAG) model mice were randomly divided into four groups of model, total triterpenoids from C. speciosa(50 and 100 mg·kg~(-1)) and triple therapy, with C57 BL/6 J mice without Hp infection taken as the normal group. Mice in the treatment groups were given corresponding drugs once a day for 4 weeks. Then the following indexes were detected: the contents of reactive oxygen species(ROS), monocyte chemotactic protein 1(MCP-1), keratinocyte chemokines(KC), TNF-α, IL-1ß, IL-6, IL-18, IL-4 and IL-10 in blood and gastric tissue, the activities and contents of LDH, MPO, SOD, GSH-Px, CAT and MDA in gastric tissue and the activities of ß-glucuronidase, ß-galactosidase, cathepsins B and D in blood, gastric tissue and lysosome. Besides, the mRNA expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), Bcl-2, Bcl-xl, Bax and Bad in gastric tissue were determined by quantitative real-time PCR. Western blot was employed to detect the protein expression levels of TLR4, MyD88, p-IKKß, p-IκBα, NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein(ASC), pro-caspase-1, caspase-1, thioredoxin-interacting protein(TXNIP), pro-IL-1ß, pro-IL-18, Bcl-2, Bcl-xl, Bax, Bad, cytochrome C, apoptotic protease-activating factor-1(Apaf-1), pro-caspase-9, pro-caspase-3, cleaved-caspase-9, cleaved-caspase-3, poly(ADP-ribose) polymerase 1(PARP-1), cleaved-PARP-1 and cytosol and nucleus NF-κB p65 in gastric tissue. The results indicated that the total triterpenoids from C. speciosa significantly suppressed Hp proliferation, alleviated the damage to gastric mucosa and improved lymphocyte infiltration and gland atrophy. They were also effective in reducing the activities of ß-glucuronidase, ß-galactosidase, cathepsins B and D in blood and gastric tissue, elevating the activities of ß-glucuronidase and cathepsin D in lysosomal organelles, decreasing the contents of ROS, MCP-1, KC, TNF-α, IL-1ß, IL-6, IL-18 in blood, MDA content and MPO and LDH activities in gastric tissue and increasing the contents of IL-4 and IL-10 in blood and activities of SOD, CAT and GSH-Px in gastric tissue. Other phenomena were also observed after the treatment with total triterpenoids from C. speciosa, including the down-regulation of the mRNA and protein expression levels of TLR4, MyD88, Bax and Bad, the protein expression levels of p-IKKß, p-IκBα, NLRP3, ASC, pro-caspase-1, caspase-1, TXNIP, pro-IL-1ß, pro-IL-18, cytochrome C, Apaf-1, cleaved-caspase-9, cleaved-caspase-3, cleaved-PARP-1 and nuclear NF-κB p65, reduction of p-IKKß/IKKß and p-IκBα/IκBα ratios and up-regulation of the mRNA and protein expression levels of Bcl-2 and Bcl-xl, up-regulation of pro-caspase-9, pro-caspace-3, cytosol NF-κB p65 protein expression levels and Bcl-2/Bax and Bcl-xl/Bad ratios in gastric tissue. These aforementioned results suggest that the total triterpenoids from C. speciosa have significant protective effects against CAG induced by Hp, and its mechanism may be related to enhancing the function of endogenous antioxidant system, suppressing the oxidative stress and inflammatory reaction induced by Hp, correcting lysosomal dysfunction and inflammatory activation of TLR4/NF-κB/NLRP3 inflammasome signaling pathway and thus inhibiting mitochondria-mediated apoptosis.


Asunto(s)
Gastritis , Helicobacter pylori , Rosaceae , Triterpenos , Animales , Gastritis/tratamiento farmacológico , Ratones , FN-kappa B/genética
17.
Biotechnol Lett ; 42(2): 187-196, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31776751

RESUMEN

OBJECTIVES: Previously, we have found that the matrix attachment region (MAR) may confer a 'distance effect' on transgene expression. This work aims to systematically explore the increased transgene expression in transfected Chinese hamster ovary (CHO) cells due to the characteristics of MAR and its mechanism. RESULTS: Compared with the control vector, 500 and 1000 bp DNA distances between MAR and the cytomegalovirus promoter can increase transgene expression by 1.77- and 1.56-fold, respectively. Meanwhile, transgene expression was not affected when 2000 and 2500 bp spacer DNAs were inserted, but a declining trend was observed when a 1500 bp spacer DNA was inserted. The vector containing a 500 bp DNA distance significantly increased the expression of the enhanced green fluorescent protein, and this increase was not related to transgene copy numbers. CONCLUSIONS: A short DNA distance-containing MAR confers high transgene expression level in transfected CHO cells, but a distance threshold does not exist in the vector system.


Asunto(s)
Clonación Molecular/métodos , Proteínas Recombinantes/metabolismo , Transgenes , Animales , Células CHO , Cricetinae , Cricetulus , Expresión Génica , Regiones de Fijación a la Matriz , Regiones Promotoras Genéticas , Transfección
18.
Sensors (Basel) ; 20(4)2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32079364

RESUMEN

Due to the flourishing development of vehicle-to-vehicle (V2V) communications and autonomous driving, interference between radar sensing and communication signals becomes a challenging issue. We propose a transmit beamforming based spectrum sharing scheme to achieve peaceful coexistence between automotive multiple-input multiple-out (MIMO) radar and communication systems. Our objective is to maximize the signal-to-interference-plus-noise ratio (SINR) of the automotive radar receiver subject to the communication capacity and the transmitted power budget constraints to optimize both the communication covariance matrix and the radar transmit precoder. The formulated optimization problem is non-convex, which is converted to convex by introducing a new slack variable and then solving it using the block coordinate descent, also called alternation optimization, approach. Additionally, the ellipsoid sub-gradient method is then employed to reduce the computational complexity. Simulation results demonstrate that our proposed scheme outperforms the conventional schemes.

19.
Opt Express ; 27(10): 13694-13705, 2019 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-31163829

RESUMEN

In this study, we design a T-shaped quantum router that comprises two-level systems (TLSs), an infinite coupled resonator waveguide (CRW), and a semi-infinite CRW. The loss (absorption) and gain (amplification) of the energy levels of the TLSs can be considered as energy exchange between the system and its environment. Considering loss in the ground state and gain in the excited state of the TLSs and loss of cavities, the system is non-energy-conserving and non-Hermitian. Loss in the system consists of loss of cavities and TLSs. The total transmission probabilities (TPs) of photons in the system are equal to 1 or lower when the system has loss only. Loss causes a bounce-back phenomenon in the TPs. The TPs have a divergent point when the TLSs have gain, and we obtain this divergent condition. The reflection probability has a minimal point only when photons are incident from the semi-infinite CRW and the system has loss. The TPs of the non-Hermitian router are increased by gain, decreased by loss, and conserved under certain conditions.

20.
BMC Neurol ; 19(1): 210, 2019 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-31462223

RESUMEN

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, which is the most common type of autoimmune encephalitis, is caused by the production of autoantibodies against NMDA receptor. Anti-NMDAR encephalitis patients present with various non-specific symptoms, such as abnormal psychiatric or behaviour, speech dysfunction, cognitive dysfunction, seizures, movement disorders, decreased level of consciousness, and central hypoventilation or autonomic dysfunction. CASE PRESENTATION: A 67-year-old man presented with new-onset focal seizures. The brain magnetic resonance imaging (MRI) plain scan and enhanced scan showed abnormal signal on the proximal midline frontoparietal junction region. Anti-NMDAR antibody was detected in cerebrospinal fluid (CSF) and serum using a commercial kit (Euroimmune, Germany) by indirect immunofluorescence testing (IIFT) according to the manufacturer's instructions for twice. Both of the test results were positive in CSF and serum. The patient was diagnosed as anti-NMDAR encephalitis and then was treated repeatedly with large dose of intravenous corticosteroids and gamma globulin. Accordingly, the refractory nature of seizures in this case may be attributed to NMDAR autoantibodies. When the patient presented at the hospital for the third time, the brain MRI revealed an increase in the size of the frontal parietal lesion and one new lesion in the left basal ganglia. The patient underwent a surgical biopsy and astrocytoma was confirmed by histopathology. CONCLUSIONS: Although the sensitivity and specificity of anti-NMDAR-IgG antibodies in CSF to diagnose anti-NMDAR encephalitis are close to 100%, it is not absolute. Anti-NMDAR antibodies were positive, which might make the diagnosis more complex. The diagnosis of atypical presentation of anti-NMDAR encephalitis requires reasonable exclusion of other disorders.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Anciano , Autoanticuerpos/sangre , Errores Diagnósticos , Alemania , Humanos , Masculino
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