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1.
Organ Transplantation ; (6): 120-2022.
Article in Chinese | WPRIM | ID: wpr-907042

ABSTRACT

Graft-versus-host disease (GVHD) is a major cause that prevents widespread application of allogeneic hematopoietic stem cell transplantation. GVHD is a complication that can affect all systems of the body, such as skin, liver, lung and gastrointestinal tract, among which skin is the most vulnerable organ. At present, the pathogenesis of skin GVHD has not been fully elucidated, and no effective treatment has been established. Severe or extensive chronic GVHD significantly affects the quality of life of the recipients. Consequently, it is urgent to unravel the pathogenesis of skin GVHD and explore novel therapeutic treatment. Cytokines, such as interleukin (IL)-22, IL-17, IL-6 and interferon (IFN)-γ, have been proven to play pivotal roles in the progression of skin GVHD. Nevertheless, the specific mechanism remains elusive. In this article, research progresses at home and abroad on the mechanism underlying the roles of these cytokines in skin GVHD were reviewed, aiming to provide novel ideas for the prevention and treatment of skin GVHD.

2.
Organ Transplantation ; (6): 80-2022.
Article in Chinese | WPRIM | ID: wpr-907037

ABSTRACT

Objective To investigate the predictive and diagnostic value of absolute value and function of different lymphocyte subsets in evaluating the risk of early viral infection after kidney transplantation. Methods Ninety-five kidney transplant recipients were enrolled in this prospective observational cohort study, and divided into the stable group (n=77) and infection group (n=18) according to postoperative immune status. Peripheral blood samples were collected for flow cytometry before operation, and 2 weeks, 1 month, 2 months and 6 months after operation. The dynamic changes of the absolute values of CD4+T cells, CD8+T cells and natural killer (NK) cells were compared between two groups. The function of lymphocyte subsets in two groups was evaluated by detecting the proportion of interferon (IFN)-γ+CD4+T cells, IFN-γ+CD8+T cells and IFN-γ+NK cells. The value of the absolute values and function of lymphocyte subsets in predicting and diagnosing viral infection in the early stage after kidney transplantation was evaluated. Results During viral infection, the absolute values of CD4+T cells, CD8+T cells and NK cells in the infection group were at a relatively low level. At 2 months after operation, the absolute values of CD4+T cells and NK cells in the infection group were lower than those in the stable group. At 6 months after operation, the absolute values of CD4+T cells and CD8+T cells in the infection group were significantly lower compared with those in the stable group (all P < 0.05). During viral infection, the proportion of IFN-γ+CD4+T cells, IFN-γ+CD8+T cells and IFN-γ+NK cells in the infection group were all at a relatively low level, especially that of IFN-γ+CD8+T cells decreased most significantly. At postoperative 2 months, the proportion of IFN-γ+CD8+T cells and IFN-γ+NK cells in the infection group was significantly higher than those in the stable group. At 6 months after operation, the proportion of IFN-γ+CD4+T cells and IFN-γ+CD8+T cells in the infection group was significantly higher than those in the stable group (all P < 0.05). Logistic regression analysis showed that the increasing proportion of IFN-γ+CD8+T cells and IFN-γ+NK cells was correlated with the increasing risk of viral infection at 2 months after operation (both P < 0.05). The receiver operating characteristic (ROC) curve demonstrated that the diagnostic value of absolute values of lymphocyte subsets combined with IFN-γ secretion function for viral infection in the immunocompromised recipients was significantly higher than that of absolute values of lymphocyte subsets alone (P < 0.05). Conclusions Dynamic monitoring of the changes of absolute values and function of lymphocyte subsets provides critical reference value for the prediction, diagnosis and medication guidance of viral infection.

3.
Article in Chinese | WPRIM | ID: wpr-920546

ABSTRACT

Upper respiratory tract is directly connected with the external environment, and its natural immune system is the first line of defense against pathogens. In antiviral infection, interferon (IFN) is the main component of the antiviral natural immune system and IFN-λ is a newly discovered immune effector molecule that is mainly produced in the mucosal barrier. IFN-λ exerts a biological role through Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathway, and plays an important part in regulating innate and acquired immunity of respiratory mucosa. IFN-λ principally expresses on the mucosal barrier with a long-lasting antiviral impact and controls immune-inflammatory damage, which is becoming a new focus of antiviral immunity research in the upper respiratory tract, especially in fighting against 2019 novel coronavirus diseases (COVID-19). Thus, we summarize the research progress of IFN-λ antiviral immunity in the upper respiratory tract to provide new insight in the prevention and treatment of viral infection in the upper respiratory tract.

4.
Journal of Clinical Hepatology ; (12): 180-186, 2022.
Article in Chinese | WPRIM | ID: wpr-913138

ABSTRACT

Hepatitis B virus (HBV) infection is closely associated with the adverse events such as liver cirrhosis, liver cancer, and liver failure and remains a serious threat to human health. Pegylated interferon is an indispensable drug for the treatment of chronic hepatitis B (CHB), and interferon-stimulated genes are associated with a variety of viruses, but few studies have mentioned their association with hepatitis B and their predictive effect after the treatment of hepatitis B with interferon. This article introduces the predictive factors for interferon treatment of CHB and summarizes the association of interferon-stimulated genes with hepatitis B and their predictive effect, so as to provide a reference for clinical work and basic research.

5.
Braz. J. Pharm. Sci. (Online) ; 58: e18984, 2022. graf
Article in English | LILACS | ID: biblio-1364429

ABSTRACT

Interferon-ß-1a (INF-ß-1a) has gained significant attention due to its emerging applications in the treatment of different human diseases. Therefore, many researchers have attempted to produce it in large quantities and also in a biologically active form using different expression systems. In the present study, we aimed to improve the expression level of INF-ß-1a by Pichia pastoris using optimization of culture conditions. The codon-optimized INF-ß- 1a gene was cloned into pPICZαA plasmid under the control of alcohol oxidase I (AOX1) promoter. The protein expression was induced using different concentrations of methanol at different pHs and temperatures. The biological activity of produced protein was evaluated by anti-proliferative assay. The ideal culture conditions for the expression of INF-ß-1a by P. pastoris were found to be induction with 2% methanol at pH 7.0 culture medium at 30 C which yielded a concentration of 15.5 mg/L INF-ß-1a in a shake flask. Our results indicate that differences in glycosylation pattern could result in different biological activities as INF- ß-1a produced by P. pastoris could significantly more reduce the cell viability of HepG-2 cells, a hepatocellular carcinoma cell line, than a commercially available form of this protein produced by CHO


Subject(s)
Pichia/classification , Interferon-beta/agonists , Carcinoma, Hepatocellular/pathology , Process Optimization , Codon , Cells , Carcinoma, Hepatocellular , Hydrogen-Ion Concentration
6.
J. pediatr. (Rio J.) ; 97(6): 617-622, Nov.-Dec. 2021. tab, graf
Article in English | LILACS | ID: biblio-1350978

ABSTRACT

Abstract Objective: To investigate the impact of recombinant human interferon α1b (rhIFNα1b) treatment in infants hospitalized with lower respiratory tract infections on subsequent wheezing. Methods: The clinical data of infants (n = 540) with viral pneumonia, wheezy bronchitis, or bronchiolitis hospitalized in 19 Chinese hospitals from June 2009 to June 2015 were retrospectively analyzed. The parameters relevant to wheezing episodes within the last year were collected by telephone and questionnaires. The rhIFNα1b treatment group (n = 253) and control group (n = 287) were compared in terms of wheezing episodes within the last year. Moreover, the wheezing group (95 cases) and non-wheezing group (445 cases) were compared. Results: Out of 540 cases, 95 (17.6%) experienced wheezing episodes, 13.8% (35/253) cases treated with rhIFNα1b, and 20.9% (60/287) cases without rhIFNα1b experienced wheezing episodes within the last year. The rhIFNα1b treatment significantly improved wheezing episodes within the last year, compared with the control peers (p = 0.031). Single-factor regression showed statistically significant differences between the wheezing and non-wheezing groups in terms of age, rhIFNα1b use, childhood and family history of allergy, housing situation, and feeding history (p < 0.05). Binary logistic regression showed a childhood history of allergy (OR = 2.14, p = 0.004), no rhIFNα1b use (OR = 1.70, p = 0.028), and living in a crowded house (OR = 1.92, p = 0.012) might be risk factors of subsequent wheezing. Accordingly, breastfeeding (OR = 0.44, p = 0.008) and hospitalization age of 1-year-old (OR = 0.58, p = 0.024) were protective factors. Conclusions: Early use of rhIFNα1b in infants hospitalized with lower respiratory tract infections and breastfeeding could prevent subsequent wheezing. Living in a crowded house could promote subsequent wheezing.


Subject(s)
Humans , Female , Infant , Respiratory Tract Infections/drug therapy , Bronchiolitis , Respiratory Sounds , Retrospective Studies , Risk Factors , Interferons
7.
Rev. bras. ginecol. obstet ; 43(9): 682-689, Sept. 2021. graf
Article in English | LILACS | ID: biblio-1351778

ABSTRACT

Abstract Objective The aim of the present study was to compare the local and systemic expression of the factors linked to the interferon alpha (IFN-α) activation pathway in different degrees of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods A total of 128 patients with CIN I, CIN II, CIN III and cervical cancer was evaluated. The real-time polymerase chain reaction (RT-PCR) technique was used to evaluate the gene expression of IFNR1, IFNR2, IFN-α, oligoadenylate synthase (2'5′OAS), cytokine signal suppressor 1 (SOCS) 1, SOCS3, signal transducer and transcription activator 1 (STAT1), and IRF9 from 128 biopsies. A total of 46 out of 128 samples were evaluated by flow cytometry for IFNAR1, IFNAR2, STAT1, IRF7 and IFN-α in peripheral blood cells. Results Patients with CIN II and III (63 samples) had a low local expression of IFNR1, but not IFNR2. Patients with some degree of injury showed high expression of SOCS1 and SOCS3. Systemically, patients with CIN II and III (20 samples) had a significant increase in IFNR1, IFNR2, STAT1, IRF7, and IFN-α in helper, cytotoxic T lymphocytes, and in monocytes. Conclusion Patients with high-grade lesions have increased systemic expression of IFN-α and its activation pathways in helper and cytotoxic T lymphocytes, as well as in monocytes due to an exacerbation of the immune response in these patients. This phenomenon is not accompanied by resolution of the lesion due to a defect in the IFN-α activation pathway that revealed by low local IFNAR1 expression and high local expression of SOCS1 and SOCS3.


Resumo Objetivo O objetivo do presente estudo foi comparar a expressão local e sistêmica dos fatores ligados à via de ativação do interferon alfa (IFN-α) em diferentes graus de neoplasia intraepitelial cervical (NIC) e câncer cervical (CA) Métodos Foram avaliados 128 pacientes com NIC I, NIC II, NIC III e CA. A técnica de reação de cadeia de polimerase em tempo real (RT-PCR, na sigla em inglês) foi realizada para avaliar a expressão gênica do receptor de interferon (IFNR) 1, IFNR2, IFN-α, 2′-5′- oligoadenilato sintetase (2′5′OAS), supressor de sinalização de citocina (SOCS)1, SOCS3, transdutor de sinal e ativador de transcrição 1 (STAT1) e fator regulador de interferon 9 (IRF9) das 128 biópsias. Das 128 amostras, 46 foram avaliadas por citometria de fluxo para IFNAR1, IFNAR2, STAT1, IRF7 e IFN-α em células de sangue periférico. Resultados Pacientes com NIC II e III (63 amostras) tiveram baixa expressão local de IFNR1 mas não de IFNR2. Pacientes com algum grau de lesão apresentaram alta expressão de SOCS1 e SOCS3. Sistemicamente, os pacientes com NIC II e III (20 amostras) tiveram um aumento significativo de IFNR1, IFNR2, STAT1, IRF7 e IFN-α em linfócitos T auxiliares, citotóxicos e monócitos. Conclusão Pacientes com lesões de alto grau apresentam expressão sistêmica aumentada de IFN-α e suas vias de ativação em linfócitos T auxiliares e citotóxicos, bem como em monócitos, devido à exacerbação da resposta imune nesses pacientes. Este fenômeno não é acompanhado pela resolução da lesão devido a um defeito na via de ativação do IFN-α que é revelado pela baixa expressão local de IFNR1 e alta expressão local de SOCS1 e SOCS3.


Subject(s)
Humans , Female , Uterine Cervical Neoplasms/genetics , Cervical Intraepithelial Neoplasia/genetics , Interferon-alpha , Suppressor of Cytokine Signaling Proteins/metabolism
8.
Braz. j. otorhinolaryngol. (Impr.) ; 87(3): 260-268, May-Jun. 2021. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1285685

ABSTRACT

Abstract Introduction Chronic rhinosinusitis is currently classified into two types: chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps. In the West, approximately 80% of chronic rhinosinusitis with nasal polyps cases are characterized by a predominantly eosinophilic cell infiltrate and a Th2 cytokine pattern. Objective To evaluate the effect of Interferon-α on cytokine levels of the eosinophilic nasal polyp cell culture supernatant. Methods Cell cultures were performed based on nasal polypoid tissue samples collected from 13 patients with eosinophilic chronic rhinosinusitis with nasal polyps. Polyps were considered eosinophilic according to the histopathological examination. Cell cultures were stimulated with 3000 IU of interferon-α. Before and after the stimulus, concentrations of Interferon-γ, tumor necrosis factor αand IL 2, 4, 6 and 10, using cytometric bead array, were assessed. Results Cell samples from eosinophilic nasal polyps from 13 patients were included in the study. Twenty-four hours after interferon-α stimulation, eosinophilic nasal polyp culture supernatants showed significantly decreased IL-4 concentrations and increase in interferon-γ, IL-10 and IL-6 concentrations compared to controls. There were no significant differences in tumor necrosis factor -α and IL-2 concentrations. Conclusion We demonstrated that interferon-α in vitro alters the pattern of cytokines in cell cultures of eosinophilic nasal polyps. Analysis of these alterations suggests that interferon-α promotes a rebalancing of inflammatory profiles in cell cultures, favoring the expression of Th1 and regulatory cytokines over Th2 cytokines.


Resumo Introdução A rinossinusite crônica, atualmente, é classificada em dois tipos: Rinossinusite Crônica sem Pólipos Nasais (RSCsPN) e Rinossinusite Crônica com Pólipos Nasais (RSCcPN). No Ocidente, cerca de 80% dos casos de RSCcPN caracterizam-se por um infiltrado celular predominantemente eosinofílico e um padrão de citocinas Th2. Objetivo Avaliar o efeito do Interferon-alpha nos níveis de citocinas do sobrenadante de culturas celulares de pólipos nasais eosinofílicos. Método Foram feitas culturas celulares a partir de amostras de tecido polipoide nasal coletadas de 13 pacientes com RSCcPN eosinofílica. Os pólipos eram considerados eosinofílicos segundo exame histopatológico. As culturas celulares foram estimuladas com 3000 UI de IFN-α. Antes e após tal estímulo, foram avaliadas, no sobrenadante das culturas celulares, as concentrações do Interferon-γ (IFN-γ), do Fator de Necrose Tumoral alfa (TNF-α) e das Interleucinas (IL) 2, 4, 6 e 10, usou-se o Cytometric Bead Array. Resultados Foram incluídas no estudo amostras celulares dos pólipos nasais eosinofílicos de 13 pacientes. Vinte e quatro horas após o estímulo com IFN-α, os sobrenadantes das culturas dos pólipos nasais eosinofílicos apresentaram, de forma significante, diminuição da concentração de IL-4 e aumento das concentrações de IFN-γ, IL-10 e IL-6, em relação ao controle. Não houve diferença significante nas concentrações de TNF-α e IL-2. Conclusão Demonstramos que o IFN-α, in vitro, altera o padrão de citocinas nas culturas celulares de pólipos nasais eosinofílicos. A análise do conjunto dessas alterações sugere que o IFN-α promove, nas culturas celulares, um rebalanceamento dos perfis inflamatórios, favorece a expressão de citocinas Th1 e regulatórias, em detrimento de citocinas do padrão Th2.

9.
Gac. méd. espirit ; 23(1): 35-45, ene.-abr. 2021. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1250004

ABSTRACT

RESUMEN Fundamento: El carcinoma basocelular periocular es una lesión tumoral que surge de las células basales de la epidermis y los folículos pilosos, con un alto potencial de destrucción local, pueden ser desfigurantes e invaden el tejido que los rodea dando lugar a deformidades o pérdida de la función del órgano afectado. En orden de aparición es más común en el párpado inferior, el canto medial, el párpado superior y el canto temporal. Objetivo: Describir los resultados de la aplicación del HeberFERON en una serie de casos con carcinoma basocelular periocular que acudieron a consulta de dermatología del Policlínico Centro, de enero de 2017 a diciembre del 2020. Metodología: Se realizó un estudio de serie de casos clínicos con carcinoma basocelular periocular que acudieron a la consulta de dermatología del Policlínico Centro. Se incluyeron 17 casos con diagnóstico clínico, dermatoscópico e histopatológico. Se realizó una evaluación inicial, durante y 16 semanas después del tratamiento; se administró 10.5 UI de HeberFERON 3 veces por semana perilesional e intradérmica hasta completar 9 dosis. Las variables principales fueron la respuesta al tratamiento y la presencia o no de eventos adversos. Resultados: Predominó el sexo masculino, el fototipocutáneo II, la localización en párpado inferior, el subtipo clínico nódulo ulcerativo y el histológico sólido, se logró respuesta completa en la mayoría de los pacientes. Como eventos adversos se presentaron dolor en el sitio de inyección, fiebre, mal estar general, edema y eritema perilesional. Conclusiones: La respuesta al tratamiento fue favorable en la mayoría de los pacientes tratados con HeberFERON.


ABSTRACT Background: Periocular basal cell carcinoma is a tumor lesion arising from the epidermis and hair follicles basal cells, with a high potential local destruction, can be disfiguring and invade the surrounding tissue leading to deformities or loss of function of the affected organ. In order of appearance it is most common in the lower eyelid, medial edge, upper eyelid and temporal edge. Objective: To describe the results of the application of HeberFERON in a case series with periocular basal cell carcinoma who attended dermatology appointment at the Policlínico Centro, from January 2017 to December 2020. Methodology: A series study of clinical cases with periocular basal cell carcinoma who attended the dermatology appointment at the Policlínico Centro was conducted. 17 cases with clinical, dermatoscopic and histopathological diagnosis were included. A baseline evaluation was conducted, during and 16 weeks after treatment; 10.5 IU of HeberFERON was administered 3 times a week perilesional and intradermally until completing 9 doses. The main variables were the treatment response and the presence or absence of adverse events. Results: Male sex, phototypocutaneous II, lower eyelid location, clinical subtype ulcerative nodule and solid histological subtype predominated, complete response was achieved in most patients. Adverse events were pain at the injection site, fever, general malaise, edema and perilesional erythema. Conclusions: Treatment response was favorable in most patients treated with HeberFERON.

10.
Rev. argent. reumatolg. (En línea) ; 32(1): 16-20, mar. 2021. ilus, tab
Article in Spanish | LILACS, BINACIS | ID: biblio-1279754

ABSTRACT

Introducción: El interferón (IFN) tipo I es una citoquina que juega un rol fundamental en la patogenia del Lupus Eritematoso Sistémico (LES). Diferentes niveles de esta citoquina podrían explicar la heterogeneidad de esta patología y ser útil para evaluar la actividad de la misma. Objetivos: Determinar los niveles de IFN tipo I sérico en pacientes con LES y evaluar su utilidad como biomarcador de actividad. Material y Métodos: 16 pacientes con LES (ACR 1997) y 16 controles. Métodos: Actividad de la enfermedad (SLEDAI-2K), daño orgánico (SLICC), IFN tipo I (HEK-Blue-IFNα/β), anticuerpos anti-DNAdc (Inmunofluorescencia Indirecta), anticuerpos anti-ENA (ELISA), C3-C4 (Inmunoturbidimetría). Estadística: InfoStat/Instat/MedCalc. Valores de p<0,05 fueron considerados estadísticamente significativos. Resultados: Se observó un aumento de la concentración de IFN en el grupo LES con respecto al control (p<0,05). Los pacientes con valores de IFN superiores al punto de corte, se asociaron con la presencia de anticuerpos anti-DNAdc (OR:13,33; p<0,05). Pacientes con hipocomplementemia y aquellos con puntaje de SLEDAI-2K mayor a 8 presentaron mayores niveles de IFN comparados con pacientes con complemento normal y menor puntaje de índice, respectivamente (p<0,05). Conclusiones: Estos resultados sugieren la importancia que podría tener la determinación de IFN tipo I para el monitoreo de la actividad del LES.


Introduction: Type I interferon (IFN) is a cytokine that plays a fundamental role in the pathogenesis of Systemic Lupus Erythematosus (SLE). Different levels of this cytokine could explain the heterogeneity of this pathology and be useful to evaluate its activity. Objectives: To determine the serum type I IFN levels in patients with SLE and evaluate its usefulness as a biomarker of activity. Material and Method: 16 patients with SLE (ACR 1997) and 16 controls. Methods: Disease activity (SLEDAI-2K), organ damage (SLICC), type I IFN (HEK-Blue-IFNα/β), anti-dsDNA antibodies (Indirect Immunofluorescence), anti-ENA antibodies (ELISA), C3-C4 (Immunoturbidimetry). Statistics: InfoStat/Instat/MedCalc. P values <0.05 were statistically significant. Results: An increase in IFN concentration was observed in the SLE group respect to the control (p <0.05). Patients with IFN values above the cut-off point were associated with the presence of anti-dsDNA antibodies (OR: 13.33; p<0.05). Hypocomplementemic patients and those with a SLEDAI-2K score greater than 8 had higher IFN levels compared to patients with normal complement and a lower index score, respectively (p<0.05). Conclusions: These results suggest the importance that the determination of IFN type I could have for the monitoring of SLE activity.


Subject(s)
Humans , Lupus Erythematosus, Systemic , Interferon Type I , Antibodies
11.
Article in Chinese | WPRIM | ID: wpr-909592

ABSTRACT

OBJECTIVE Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints which can be induced by interferon-γ(IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells. METHODS Expressions of PD-L1 and major histocompatibility complex-I (MHC-I) were evaluated by flow cytometry and Western blotting, and the expression of IDO1 was measured by Western blotting. qRT-PCR was used to detect their mRNA levels. The function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line that overexpressing PD-1. Molecular docking analysis, Western blotting and immunofluorescence were used for mechanism study. RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells, while didn't show obvious effect on the expression of MHC-I. In addition, MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells in the co-culture system. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression, supporting the potential of MY in anti-tumor immunotherapy.

12.
Article in Chinese | WPRIM | ID: wpr-908735

ABSTRACT

Objective:To explore the expression and detection significance of peripheral blood interferon-gamma (IFN-γ) and hepcidin-25 (Hepc-25) in primary gastric cancer combined with thalassemia minor.Methods:One hundred and fifty primary gastric cancer combined with thalassemia minor patients admitted to of Jiangsu Province Official Hospital from January 2017 to December 2019 were selected as the research group, and 150 cases of primary gastric cancer without thalassemia minor admitted in the same period were selected as the control group. The levels of peripheral blood IFN-γ and Hepc-25 in the two groups were determined by enzyme-linked immunosorbent assay, and the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic sensitivity and specificity of peripheral blood IFN-γ and Hepc-25 on primary gastric cancer combined with thalassemia minor. The level of hemoglobin (Hb) was measured by the cyanmethemoglobin method, and the Pearson correlation analysis was used to analyzed the relationship among the peripheral blood IFN-γ, Hepc-25 and Hb levels in the research group.Results:The levels of peripheral blood IFN-γ and Hb in the research group were lower than those in the control group: (115.18 ± 27.05) ng/L vs. (137.17 ± 35.66) ng/L, (88.44 ± 10.71) g/L vs. (120.60 ± 29.46) g/L; the level of Hepc-25 in the research group was higher than that in the control group: (49.32 ± 15.05) μg/L vs. (32.66 ± 12.22) μg/L, and the differences were statistically significant ( P<0.05). There were no significant differences in the levels of peripheral blood IFN-γ, Hepc-25 and Hb between the patients with α-thalassemia and β-thalassemia ( P>0.05). The area under the curve (AUC) of thalassemia predicted by of peripheral blood IFN-γ level was 0.709.When the cut-off value was≤138.89 ng/L, its diagnostic sensitivity and specificity were 81.33% and 70.67% respectively, and when the serum AUC of Hepc-25 was 0.811 and cut-off value was ≥ 40.13 μg/L, its diagnostic sensitivity and specificity were 75.33% and 74.00% respectively. Pearson correlation analysis showed that in the research group IFN-γ and Hb had positive correlation ( r = 0.245, P<0.05), Hepc-25 and IFN-γ had negative correlation ( r = - 0.378, P<0.05); Hepc-25 and Hb had negative correlation ( r = - 0.647, P<0.05). Conclusions:The low level of IFN-γ and the high level of Hepc-25 in peripheral blood of patients with primary gastric cancer combined with thalassemia minor are related to Hb and have certain diagnostic value for thalassemia.

13.
Acta Pharmaceutica Sinica B ; (6): 3244-3261, 2021.
Article in English | WPRIM | ID: wpr-922791

ABSTRACT

Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death (ICD) to provoke a robust immune response for metastasis control. Here, a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation, chemodynamic (CDT) and photothermal therapy. Ultrasmall FeS-GOx nanodots were synthesized with glucose oxidase (GOx) as template and induced by paclitaxel (PTX) to form self-assembling FeS-GOx@PTX (FGP)

14.
Acta Pharmaceutica Sinica B ; (6): 2983-2994, 2021.
Article in English | WPRIM | ID: wpr-922779

ABSTRACT

Genomic instability remains an enabling feature of cancer and promotes malignant transformation. Alterations of DNA damage response (DDR) pathways allow genomic instability, generate neoantigens, upregulate the expression of programmed death ligand 1 (PD-L1) and interact with signaling such as cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. Here, we review the basic knowledge of DDR pathways, mechanisms of genomic instability induced by DDR alterations, impacts of DDR alterations on immune system, and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy.

15.
Protein & Cell ; (12): 877-888, 2021.
Article in English | WPRIM | ID: wpr-922482

ABSTRACT

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M


Subject(s)
Antiviral Agents/therapeutic use , Binding Sites , COVID-19/virology , Coronavirus Papain-Like Proteases/metabolism , Crystallography, X-Ray , Drug Evaluation, Preclinical , Drug Repositioning , High-Throughput Screening Assays/methods , Humans , Imidazoles/therapeutic use , Inhibitory Concentration 50 , Molecular Dynamics Simulation , Mutagenesis, Site-Directed , Naphthoquinones/therapeutic use , Protease Inhibitors/therapeutic use , Protein Structure, Tertiary , Recombinant Proteins/isolation & purification , SARS-CoV-2/isolation & purification
16.
Acta Pharmaceutica Sinica B ; (6): 3983-3993, 2021.
Article in English | WPRIM | ID: wpr-922454

ABSTRACT

Unfolded protein response (UPR) is a stress response that is specific to the endoplasmic reticulum (ER). UPR is activated upon accumulation of unfolded (or misfolded) proteins in the ER's lumen to restore protein folding capacity by increasing the synthesis of chaperones. In addition, UPR also enhances degradation of unfolded proteins and reduces global protein synthesis to alleviate additional accumulation of unfolded proteins in the ER. Herein, we describe a cell-based ultra-high throughput screening (uHTS) campaign that identifies a small molecule that can modulate UPR and ER stress in cellular and

17.
Chinese Journal of Biotechnology ; (12): 3201-3210, 2021.
Article in Chinese | WPRIM | ID: wpr-921417

ABSTRACT

In order to study the signal pathway secreting type Ⅰ interferon in porcine alveolar macrophages (PAMs) infected with porcine circovirus type 2 (PCV2), the protein and the mRNA expression levels of cGAS/STING pathways were analyzed by ELISA, Western blotting and quantitative reverse transcriptase PCR in PAMs infected with PCV2. In addition, the roles of cGAS, STING, TBK1 and NF-κB/P65 in the generation of type I interferon (IFN-I) from PAMs were analyzed by using the cGAS and STING specific siRNA, inhibitors BX795 and BAY 11-7082. The results showed that the expression levels of IFN-I increased significantly at 48 h after infection with PCV2 (P<0.05), the mRNA expression levels of cGAS increased significantly at 48 h and 72 h after infection (P<0.01), the mRNA expression levels of STING increased significantly at 72 h after infection (P<0.01), and the mRNA expression levels of TBK1 and IRF3 increased at 48 h after infection (P<0.01). The protein expression levels of STING, TBK1 and IRF3 in PAMs infected with PCV2 were increased, the content of NF-κB/p65 was decreased, and the nuclear entry of NF-κB/p65 and IRF3 was promoted. After knocking down cGAS or STING expression by siRNA, the expression level of IFN-I was significantly decreased after PCV2 infection for 48 h (P<0.01). BX795 and BAY 11-7082 inhibitors were used to inhibit the expression of IRF3 and NF-κB, the concentration of IFN-I in BX795-treated group was significantly reduced than that of the PCV2 group (P<0.01), while no significant difference was observed between the BAY 11-7028 group and the PCV2 group. The results showed that PAMs infected with PCV2 induced IFN-I secretion through the cGAS/STING/TBK1/IRF3 signaling pathway.


Subject(s)
Animals , Cells, Cultured , Circovirus , Interferon Type I/genetics , Macrophages, Alveolar/virology , Membrane Proteins/metabolism , Nucleotidyltransferases/metabolism , Signal Transduction , Swine
18.
Article in Chinese | WPRIM | ID: wpr-912118

ABSTRACT

Rotavirus (RV) is one of the leading causes of acute gastroenteritis in infants and young animals worldwide. Rotavirus infection has obvious species specificity and mainly causes diarrhea in infants and young animals. The host innate responses suppress the infection and replication of rotavirus through activating multiple signaling pathways. Meanwhile, rotavirus also antagonizes the innate immune responses in various ways. This article reviewed the mechanisms of host innate immune responses to rotavirus infection and the antagonistic mechanism of rotavirus against host innate immunity with a view to providing reference for the development of therapeutic drugs and the prevention of rotavirus infection.

19.
Article in Chinese | WPRIM | ID: wpr-912069

ABSTRACT

Enterovirus 71 (EV71) is one of the main pathogens causing hand, foot and mouth disease (HFMD), which seriously threatens the health of infants and young children and causes major infectious diseases in the Asia-Pacific region. The host′s innate immune response is the most effective way to fight against viral infections. However, EV71 has evolved a series of strategies, escaping from innate immune surveillance and destroying its antiviral function in the process of gaming with the host. This article mainly focuses on the research progress of EV71′s innate immune escape mechanism, and provides help for the development of anti-EV71 infection drugs.

20.
Chinese Journal of Dermatology ; (12): 878-883, 2021.
Article in Chinese | WPRIM | ID: wpr-911545

ABSTRACT

Objective:To investigate the role of folliculin in apoptosis of and chemokine secretion by melanocytes mediated by interferon-γ (IFN-γ) .Methods:Normal primary melanocytes were isolated from circumcised foreskin tissues from a healthy male child, and primary vitiliginous melanocytes were isolated from normally pigmented suction-blistered epidermis from patients with vitiligo after suction blister epidermal grafting. Western blot analysis was performed to determine the folliculin protein expression in normal primary melanocytes, primary vitiliginous melanocytes and a human primary melanocyte line PIG1. PIG1 cells stimulated with 10 ng/ml IFN-γ for 48 hours served as induction group, and untreated PIG1 cells served as control group. Real-time quantitative RCR (qRT-PCR) was performed to determine the mRNA expression of folliculin, autophagy-related microtubule-associated protein 1 light chain 3 (LC3) -Ⅱ and Beclin genes, and Western blot analysis to determine the protein expression of folliculin, Beclin1 and LC3Ⅱ/Ⅰ, as well as phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in the above cells. Furthermore, the melanocytes stimulated with 10 ng/ml IFN-γ for 48 hours were divided into several groups: negative control group infected with an empty lentiviral vector, folliculin inhibition group infected with a folliculin-inhibiting lentivirus, autophagy enhancement group infected with a folliculin-inhibiting lentivirus followed by 2-hour treatment with a mTOR inhibitor, autophagy inhibition group infected with a folliculin-inhibiting lentivirus followed by 2-hour treatment with an AMPK inhibitor. Then, flow cytometry was conducted to detect apoptosis of PIG1 cells, and enzyme-linked immunosorbent assay to measure the concentration of chemokines CXCL10 and CCL20 in the culture supernatant of PIG1 cells in the above groups. Measurement data were compared among multiple groups by using one-way analysis of variance, and multiple comparisons were carried out by using least significant difference- t test. Results:The relative protein expression level of folliculin significantly differed among the normal primary melanocytes (0.850 ± 0.120) , primary vitiliginous melanocytes (1.507 ± 0.170) and PIG1 cells (0.697 ± 0.130; F = 50.09, P < 0.001) , and was significantly higher in the primary vitiliginous melanocytes than in the normal primary melanocytes and PIG1 cells ( t = 4.06, 5.89, respectively, both P < 0.01) . Compared with the control group, the induction group showed significantly increased relative mRNA and protein expression levels of folliculin (both P < 0.01) , but significantly decreased relative mRNA and protein expression levels of LC3Ⅱ and Beclin (all P < 0.01) ; moreover, the induction group showed significantly decreased LC3Ⅱ/Ⅰ levels (0.72 ± 0.02) and AMPK phosphorylation levels (0.714 ± 0.023) in the PIG1 cells compared with the control group (1.13 ± 0.02, 1.176 ± 0.002, t = 7.34, 6.67, respectively, both P < 0.01) , but significantly increased mTOR phosphorylation levels (1.051 ± 0.023) compared with the control Group (0.451 ± 0.016, t = 3.81, P = 0.009) . There were significant differences in the PIG1 cell apoptosis rate and concentrations of CXCL10 and CCL20 among the control group, induction group and other treatment groups (all P < 0.001) ; specifically, the PIG1 cell apoptosis rate and concentrations of CXCL10 and CCL20 were significantly higher in the induction group than in the control group, lower in the folliculin inhibition group than in the negative control group, lower in the autophagy enhancement group than in the folliculin inhibition group, and higher in the autophagy inhibition group than in the folliculin inhibition group (all P < 0.05) . Conclusions:Folliculin is highly expressed in vitiliginous melanocytes. Folliculin expression and downstream signaling pathways are regulated by IFN-γ, and folliculin may participate in IFN-γ-mediated melanocyte apoptosis and chemokine secretion via regulating autophagy.

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