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ObjectiveTo investigate the change and potential role of Mindin protein in the treatment of chronic hepatitis B （CHB） with PEG-IFNα-2b. MethodsA total of 29 CHB patients who received the treatment with PEG-IFNα-2b in The Second Affiliated Hospital of Xi’an Jiaotong University from January 2018 to December 2019 were enrolled， and according to their clinical outcome， they were divided into cured group with 17 patients and uncured group with 12 patients. Peripheral blood samples were collected from both groups at baseline， 12 weeks， and 24 weeks to measure blood routine indices， liver function parameters， hepatitis B markers， and Mindin protein. HBsAg， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Mindin protein at different time points were compared between the two groups. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； a Spearman correlation analysis was used to investigate correlation； a multiple linear regression analysis was used to investigate the influence of HBsAg and ALT on the content of Mindin protein. ResultsThe analysis of baseline data showed that there were significant differences in the levels of HBsAg， HBeAb， albumin， and albumin/globulin ratio between the cured group and the uncured group （all P<0.05）. The cured group tended to have a gradual increase in the level of Mindin， and the level of Mindin at 24 weeks was significantly higher than that at baseline （P<0.05）. The cured group had a significantly higher level of Mindin protein than the uncured group at 24 weeks （P=0.019）. The cured group had a significantly lower level of HBsAg than the uncured group （P<0.05）， with a significant change from baseline to each time point within the cured group （P<0.05）. In addition， the levels of ALT and AST in the cured group tended to first increase and then decrease， and the expression levels at 12 weeks were significantly higher than those at baseline （P<0.05）. At 12 weeks， there was a strong linear correlation between Mindin protein levels and ALT in the untreated group （r=0.760 8， P<0.05）， and further multiple linear regression analysis also demonstrated a linear relationship between the two （b=1.571， P=0.019）. ConclusionThere is a significant difference in the level of Mindin protein between the cured group and the non-cured group after 24 weeks of PEG-IFNα-2b antiviral treatment， and therefore， detecting the dynamic changes of Mindin protein can better predict the treatment outcome of CHB， which provides a reference for clinical practice.
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ABSTRACT The aim of this study was to alert the ophthalmic community to an atypical manifestation of ocular surface squamous neoplasia, which may delay diagnosis and treatment and result in a guarded visual prognosis and significant sequelae. A 61-year-old immunocompetent man presented with an initial diagnosis of necrotizing scleritis in the right eye for 3 months. He was treated with systemic prednisone but experienced persistent pain and low visual acuity. Conjunctival biopsy of the affected region confirmed the diagnosis of invasive ocular surface squamous neoplasia, which progressed with intraocular and orbital invasion; thus, exenteration was performed. Masquerade syndrome should be suspected in patients with nodulo-ulcerative lesions of the conjunctiva and sclera. This clinical can be more aggressive, with a greater likelihood of intraocular and orbital involvement. The earlier the diagnosis and treatment, the better the patient prognosis.
RESUMO O objetivo é alertar a comunidade oftalmológica sobre uma manifestação atípica de neoplasia escamosa da superfície ocular (OSSN) que pode levar a um atraso no diagnóstico e tratamento, evoluindo com prognóstico reservado e significativas sequelas. Homem, imunocompetente, 61 anos com diagnóstico inicial de esclerite necrosante em olho direito há 3 meses, em tratamento com prednisona sistêmica porém com persistência da dor e baixa acuidade visual. Realizado biópsia conjuntival em região acometida e diagnosticado como neoplasia escamosa da superfície ocular invasiva. Evolui com invasão intraocular e orbital sendo submetido a exenteração. Assim sendo, deve-se suspeitar de síndrome mascarada frente a um paciente com lesões nódulo-ulcerativas da conjuntiva e esclera. Essa forma clínica pode ser mais agressiva, com maior chance de comprometimento intraocular e orbital. Quanto mais precoces o diagnóstico e o tratamento, melhor o prognóstico para o paciente.
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@#Objective To evaluate the pharmacodynamics of human interferon(IFN)α1b against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron strain in vitro.Methods Total four drugs human IFNα1b bulk,human IFNα1b eye drops,human IFNα1b spray and Remdesivir were detected for cytotoxicity by CCK-8 assay.The inhibitory effect of human IFNα1b on SARS-CoV-2 Omicron strains(BA.5/BA.2/BA.1)was determined by qPCR.Results Human IFNα1b bulk of the maximum concentration(1 × 107IU/mL)and Remdesivir of the maximum concentration(150 μmol/L)did not achieve half cytotoxicity to Vero cells;The median cytotoxicity concentrations(CC_(50))of human IFNα1b eye drops and human IFNα1b sprays were 29 958 and 37 550 IU/mL,respectively,showing toxicity to Vero cells.The median effective concentrations(EC_(50))of human IFNα1b against virus strains BA.1,BA.2 and BA.5 after incubation for 2 h in advance were 9.30,13.38 and 12.33 IU/mL and those of Remdesivir were 0.314 7,0.291 0 and0.300 3 μmol/L.When incubation with virus simultaneously,the EC_(50)of human IFNα1b to BA.1,BA.2 and BA.5 were19.68,10.91 and 18.84 IU/mL and those of the control drug Remdesivir were 0.320 5,0.274 4 and 0.304 1 μmol/L,respectively.Conclusion At the cell level in vitro,human IFNα1b of very low activity showed a good inhibitory effect on SARS-CoV-2 Omicron strain,which was expected to be a clinical specific drug for the treatment of SARS-CoV-2 Omicron strain infection.
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@#Objective To knockout interferon alpha/beta receptor subunit 1(IFNAR1) gene in human colorectal adenocarcinoma cells Caco-2 using clustered regularly interspaced short palinmic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system to construct IFNAR1 knockout Caco-2 cell line.Methods The single guide RNA(sgRNA)sequence was designed to specifically recognize the exon region of IFNAR1 gene using CRISPR/Cas9 technology,and the LentiCRISPRv2-IFNAR1-sgRNA recombinant plasmid was constructed.Caco-2 cells were infected with the plasmid packaged by lentivirus and screened by puromycin resistance.The obtained monoclonal cell lines were cultured by limited dilution method,which were verified for the effect of IFNAR1 gene knockout by target gene sequencing and Western blot,and detected for the mRNA levels of CXC chemokine ligand 10(CXCL10)and interferon-stimulatd gene 20(ISG20)in IFNAR1knockout cells by adding exogenous IFNβ.Results Sequencing results of plasmid LentiCRISPRv2-IFNAR1-sgRNA showed that the insertion sites were all located at the sticky end of BsmBⅠenzyme digestion.Two IFNAR1 knockout monoclonal cell lines were obtained.The sequencing results showed that Caco-2-IFNAR1-KO1 had 5 bp deletion in the sixth exon of IFNAR1,and Caco-2-IFNAR1-KO2 had 18 bp deletion and 1 bp insertion in the seventh exon.Compared with wild-type Caco-2 cells,Caco-2-IFNAR1-KO1 and Caco-2-IFNAR1-KO2 cells showed no expression of IFNAR1 protein.Compared with no IFNβ stimulation,the mRNA levels of CXCL10 gene(t = 0.566 and 1.268 respectively,P>0.05)and ISG20 gene(t =1.522 and 1.733 respectively,P>0.05)in Caco-2-IFNAR1-KO1 and Caco-2-IFNAR1-KO2 cells stimulated by 50 ng/mL IFNβ showed no significant increase.While compared with those of wild-type Caco-2 cells,the mRNA levels of CXCL10gene(t = 6.763 and 6.777 respectively,P<0.05)and ISG20 gene(t = 5.664 and 5.65 respectively,P<0.05)in Caco-2-IFNAR1-KO1 and Caco-2-IFNAR1-KO2 cells decreased significantly under the stimulation of 50 ng/mL exogenous IFNβ.Conclusion Caco-2 cell line with IFNAR1 knockout was successfully constructed by using CRISPR/Cas9 technology,and the downstream molecules activated by IFNAR(interferon alpha/beta receptor)in this cell line were obviously inhibited,which provided a powerful tool for further exploration of the innate immune response and replication packaging mechanism of Caco-2 cells after virus infection.
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@#Objective To investigate the effects of recombinant human interferon α2a(rhIFNα2a) suppository on the levels of inflammatory factors in the cervical mucus of patients infected with human papillomavirus(HPV).Methods A total of60 HPV-positive patients admitted to the Second Affiliated Hospital of Xi'an Jiaotong University from March to August in 2022 were selected as study objects,and then divided into observation and control groups,30 cases for each group,according to the random number table method.The observation group was given rhIFNα2a suppository therapy by vaginal medication,once every other day,continuous 10 times a month as a course of treatment,and 3 consecutive courses of treatment.The control group did not use drugs.The cervical secretions were collected and the levels of IL-1β,IL-2R,IL-6,IL-8,IL-10 and tumor necrosis factor-α(TNF-α) were measured by chemiluminescence assay.Results After 3 months of treatment,the levels inflammatory factors IL-1β,IL-6,IL-8 and TNF-α in cervical mucus of patients in the observation group were significantly lower than those in the control group(t=-2.717,-2.686,-3.178 and-3.25,respectively,each P <0.05).Compared with before treatment,the levels of IL-1β,IL-6,IL-8 and TNF-α in cervical mucus of patients in the observation group also decreased significantly(t=5.934,4.092,6.495 and 3.287,respectively,each P <0.01),while in the control group,only the level of IL-8 in cervical mucus was significantly different(t=2.345,P=0.024).Conclusion rhIFNα2a suppository can reduce the level of inflammatory factors in cervical mucus,attenuate the inflammatory response and accelerate the clearance of HPV.
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Objective:To investigate the efficacy of recombinant human interferon α2b in the adjuvant treatment of neonatal pneumonia.Methods:A total of 60 children with neonatal pneumonia who received treatment in Lingbi County People's Hospital from January 2020 to January 2022 were included in this study. They were randomly divided into study and control groups ( n = 30/group). The control group was treated with conventional therapy and the study group was treated with recombinant human interferon α2b and conventional therapy. All children were treated for 7 days. The time to clinical symptom remission, total response rate, and inflammatory factor levels were compared between the two groups. Results:Before treatment, there were no significant differences in general data between the study and control groups (all P > 0.05). After treatment, the time to body temperature recovery, rale disappearance, cough disappearance, and shortness of breath disappearance in the study group were (4.03 ± 1.27) days, (5.13 ± 1.72) days, (4.96 ± 1.64) days, and (5.45 ± 1.52) days, respectively, which were significantly shorter than (5.13 ± 1.52) days, (6.73 ± 1.85) days, (6.73 ± 1.82) days, and (6.82 ± 1.74) days, respectively in the control group ( t = 3.04, 3.46, 3.95, 3.24, all P < 0.05). The total response rate in the study group was 93.3% (28/30), which was significantly higher than 80.0% (24/30) in the control group, and clinical efficacy was better in the study group than that in the control group ( Z = 2.40, P = 0.016). High-sensitivity C-reactive protein, procalcitonin, interleukin-6, and serum amyloid A in the study group were (2.96 ± 0.84) mg/L, (0.72 ± 0.33) μg/L, (6.25 ± 2.18) mg/L, and (3.48 ± 1.13) mg/L, respectively, which were significantly lower than (4.02 ± 1.53) mg/L, (1.16 ± 0.47) μg/L, (8.04 ± 2.06) ng/L, and (6.42 ± 2.03) mg/L, respectively in the control group ( t = 3.32, 4.19, 3.26, 6.93, all P < 0.05). Conclusion:Recombinant human interferon α2b for the adjuvant treatment of neonatal pneumonia can shorten the time to clinical symptom remission, decrease inflammatory factor levels, and improve clinical efficacy.
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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.
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Humans , Female , Uterine Cervical Neoplasms/genetics , /genetics , Interferon-alpha , Suppressor of Cytokine Signaling Proteins/metabolismABSTRACT
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.
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Skin Neoplasms/therapy , Carcinoma, Basal Cell/therapy , Interferon alpha-2/therapeutic use , Dermatitis, Perioral/therapyABSTRACT
Chronic hepatitis B caused by hepatitis B virus (HBV) infection is a global public health issue. Antiviral therapy for chronic HBV infection plays a critical role, and the goal of antiviral therapy is mainly defined by virological, serological, and biochemical parameters. As the two types of antiviral drugs approved for marketing, both interferon and nucleos(t)ide analogues can alleviate liver inflammation and liver fibrosis and reduce the incidence rates of liver cirrhosis and hepatocellular carcinoma. However, the ideal goal of antiviral therapy is functional cure, which significantly improves the long-term outcome of chronic hepatitis B. The limitation of current treatment is that it can inhibit HBV replication, but cannot clear the virus, with low serological clearance rates of HBeAg and HBsAg. Development of new drugs with the goal of functional cure and evaluation of the synergistic and combined effects of existing drugs are important directions for HBV treatment and development.
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RESUMEN Fundamento: el carcinoma basocelular es el cáncer cutáneo más frecuente. El tratamiento de elección es quirúrgico, existen otras terapéuticas. El HeberFERON es una formulación farmacéutica que contiene una mezcla de interferones alfa2b y Y en proporciones sinérgicas de actividad anti-tumoral. Objetivo: caracterizar los pacientes con carcinoma basocelular tratados con HeberFERON. Métodos: se realizó un estudio observacional descriptivo transversal. El universo lo constituyeron 22 pacientes con diagnóstico clínico e histológico de carcinoma basocelular, que asistieron a consulta de Dermatología del Hospital Universitario Manuel Ascunce Domenech de la provincia Camagüey, durante el periodo de estudio se administró 3,5 millones UI de HeberFERON, perilesional, tres veces por semana en días alternos, durante tres semanas, seguidos cada 15 días durante 13 semanas, con evaluación final a la semana 16. Las variables estudiadas fueron: sexo, foto tipo cutáneo, localización, tamaño de las lesiones, subtipo clínico, ocupación laboral, respuesta clínica, efecto cosmético y reacciones adversas. La información obtenida fue procesada mediante el paquete estadístico SPSS v21.Los métodos empleados fueron estadística descriptiva con distribución de frecuencias absolutas y relativas. Los resultados se expusieron en tablas y gráficos. Resultados: predominó el sexo masculino, foto tipo cutáneo III en más de la mitad de los enfermos. Las lesiones en cara predominaron en más de las cuatro quintas partes de ellos, casi las dos terceras medían menos de dos centímetros. Prevaleció el subtipo clínico nodular en la mitad de estos, igual que los trabajadores expuestos al sol. Todos tuvieron respuesta clínica favorable, con respuesta completa en los dos tercios, y parcial en un tercio, igual que el efecto cosmético aceptable. La mayoría presentó escalofríos como reacción adversa, seguida de fiebre. Conclusiones: el HeberFERON resultó un medicamento eficaz y seguro para tratar el carcinoma basocelular; ofrece una alternativa en enfermos que no pueden ser sometidos a cirugía.
ABSTRACT Background: basal cell carcinoma is the most frequent skin cancer. The treatment of choice is surgical, but there are other therapies. HeberFERON is a pharmaceutical formulation containing a mixture of interpheron alpha2b and IFN-Y in synergistic proportions of anti-tumor activity. Objective: to characterize patients with basal cell carcinoma treated with HeberFeron. Methods: a transversal, observational, descriptive study was carried out in which 22 patients were clinically and histologically diagnosed with basal cell carcinoma, who attended a Dermatology consultation at the University Hospital Manuel Ascunce Domenech, Camagüey, Cuba. 3.5 million IU of HeberFeron, was administered, near the lesion, three times a week on alternate days for three weeks, followed biweekly for 13 weeks, with final evaluation at week 16. The variables studied were: sex, skin photo-type, tumor site, size of lesions, clinical subtype, occupation, clinical response, cosmetic effect and adverse reactions. The information obtained was processed using the statistical package SPSS v21. The methods used were descriptive statistics with distribution of absolute and relative frequencies. The results were presented in tables and graphs. Results: male sex, cutaneous photo-type III, predominated in more than half of the patients. Face lesions predominated in more than four fifths of them, and almost two thirds measured less than two centimeters. The nodular clinical subtype prevailed in half of these, just like workers exposed to the sun. All had a favorable clinical response, with a complete response in two thirds, and partial in a third, as well as an acceptable cosmetic effect. Most presented chills as an adverse reaction, followed by fever. Conclusions: the HeberFERON was an effective and safe medicine to treat basal cell carcinoma, and offer an alternative in patients who cannot be operated on.
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ObjectiveTo investigate the effect of synergistic intervention of interferonα (IFNα) and thymopentin (TP5) on the mRNA expression of apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B) in HepG2.2.15 cells. MethodsHepG2.2.15 cells were divided into blank control group, IFNα treatment group, TP5 treatment group, and IFNα+TP5 treatment group, and at 12, 24, 48, and 72 hours of treatment, quantitative real-time PCR was used to measure the mRNA expression of APOBEC3A and APOBEC3B in HepG2.2.15 cells. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the blank control group, the IFNα treatment group and the IFNα+TP5 treatment group had a significant increase in the mRNA expression of APOBEC3A at 12, 24, 48, and 72 hours of treatment (all P＜0001). Compared with the IFNα treatment group, the IFNα+TP5 treatment group had a significant increase in the mRNA expression of APOBEC3A at these four time points (all P＜0.001). TP5 treatment had no significant influence on the mRNA expression of APOBEC3A at each time point (all P＞0.05). There was no significant difference in the mRNA expression of APOBEC3B between the blank control group and the treatment groups (all P＞0.05). ConclusionIFNα combined with TP5 can significantly upregulate the mRNA expression of APOBEC3A in HepG2.2.15 cells.
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Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed aftertreatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterallyovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX?OA control, OVX?OA ? diclofenac (5 mg/kg) (positive control), OVX?OA ? LP leaf extract (150 and300 mg/kg) and healthy sham control. After 8 weeks’ treatment, their conditions were evaluated via serum biomarkers,knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilageerosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenacand the non-treated OA. The cartilage catabolic markers’ (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa,CASP3 and HIF-2a) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased byLP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilageprotective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondralbone restoration. The cartilage ERa over-expression showed a strong positive correlation with MMP-13, COL10a1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.
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ABSTRACT We analyzed the management and outcomes of pregnancies of patients with chronic myeloid leukemia at a single center over fifteen years. Among the 203 CML female patients, there were ten pregnancies in seven women, all of them not planned. In three cases, the chronic myeloid leukemia diagnosis was made during pregnancy. Five patients received tyrosine kinase inhibitors in the first weeks of pregnancy and the drug was interrupted until delivery. One patient lost complete cytogenetic response, and two patients lost the hematological response. A patient with a stable major molecular response had two successful pregnancies without loss of response. There were four premature births. There were no maternal adverse events, fetal malformation or death. All patients received Interferon-alpha during gestation, and two received hydroxyurea for a short period. Leukapheresis was performed in two patients for hyperleukocytosis control. One patient with sickle cell disease died from disease progression six months after delivery. Conclusions: The tyrosine kinase inhibitors ministration should be interrupted during pregnancy. Patients should be advised to achieve a stable and deep molecular response if they plan to conceive, to avoid the risk of disease progression.
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Humans , Female , Pregnancy , Pregnancy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Interferon-alpha , Imatinib Mesylate , Dasatinib , HydroxyureaABSTRACT
Objective@#To investigate the effects of recombinant human interferon alpha 2b injection(P.putida)and hydroxyethyl starch inhalation on physiological indexes and tissues and organs of SD rats, such as lungs, trachea and bronchus, and thus to explore the safety of the drug and excipients for inhalation.@*Methods@#Rats were randomly divided into two groups(hydroxyethyl starch 40 group and recombinant human interferon alpha 2b group).5 million IU/ml recombinant human interferon alpha 2b injection or 6% hydroxyethyl starch 40 injection were given respectively, which were diluted with 0.9% sodium chloride injection in a radio of 1: 2.Both groups were given aerosol inhalation for 30 minutes once a day for 14 days.Within 14 days after administration, the behavior of rats and the degree of toxicity were continuously observed.During the drug administration and recovery period, the clinical signs of the rats in each group were observed daily, and the body weight and food consumption were measured once a week.At the end of drug administration and the end of recovery period, hematology test, blood biochemical test, gross anatomical observation, organ weight determination, and histopathological examination were performed.@*Results@#The mass median aerodynamic diameter(MMAD)of the drug mist was 3.56 μm, and the geometric standard deviation(GSD)was 1.84 μm, which met the particle size requirements of arrival and deposition in the lower respiratory tract via atomization inhalation.No abnormality in clinical signs, body weight and food consumption, hematology and blood biochemical indexes were found in hydroxyethyl starch 40 group and recombinant human interferon alpha 2b group.No abnormal histopathological changes were observed in oral mucosa, tongue, nasal cavity(paranasal sinus), larynx, trachea, main bronchial tube, lung, heart, liver, spleen, kidney, reproductive system and other organs or tissues examined.@*Conclusion@#Results suggest the drug particle size of recombinant human interferon alpha 2b injection(pseudomonas)can reach the lower respiratory tract and deposit in the lower respiratory tract.Continuous atomization inhalation for 14 days has a good safety, and the excipient hydroxyethyl starch 40 has a high safety.
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Objective To investigate the effects of recombinant human interferon alpha 2b injection ( P. putida) and hydroxyethyl starch inhalation on physiological indexes and tissues and organs of SD rats, such as lungs, trachea and bronchus, and thus to explore the safety of the drug and excipients for inhalation. Meth-ods Rats were randomly divided into two groups ( hydroxyethyl starch 40 group and recombinant human inter-feron alpha 2b group). 5 million IU/ml recombinant human interferon alpha 2b injection or 6％ hydroxyethyl starch 40 injection were given respectively, which were diluted with 0. 9％ sodium chloride injection in a radio of 1: 2. Both groups were given aerosol inhalation for 30 minutes once a day for 14 days. Within 14 days after administration, the behavior of rats and the degree of toxicity were continuously observed. During the drug ad-ministration and recovery period, the clinical signs of the rats in each group were observed daily, and the body weight and food consumption were measured once a week. At the end of drug administration and the end of re-covery period, hematology test, blood biochemical test, gross anatomical observation, organ weight determi-nation, and histopathological examination were performed. Results The mass median aerodynamic diameter ( MMAD) of the drug mist was 3. 56 μm, and the geometric standard deviation ( GSD ) was 1. 84 μm, which met the particle size requirements of arrival and deposition in the lower respiratory tract via atomization inhalation. No abnormality in clinical signs, body weight and food consumption, hematology and blood bio-chemical indexes were found in hydroxyethyl starch 40 group and recombinant human interferon alpha 2b group.No abnormal histopathological changes were observed in oral mucosa, tongue, nasal cavity ( paranasal sinus) , larynx, trachea, main bronchial tube, lung, heart, liver, spleen, kidney, reproductive system and other or-gans or tissues examined. Conclusion Results suggest the drug particle size of recombinant human interferon alpha 2b injection (pseudomonas) can reach the lower respiratory tract and deposit in the lower respiratory tract. Continuous atomization inhalation for 14 days has a good safety, and the excipient hydroxyethyl starch 40 has a high safety.
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The persistence of covalently closed circular DNA (cccDNA) in the nucleus of liver cells is a key factor that hinders the cure of chronic hepatitis B. However,it is difficult to eliminate cccDNA with existing anti-HBV therapy. Recent studies have found that serum HBV RNA may be a new indicator reflecting the activity of cccDNA in hepatocytes and evaluating the clinical efficacy of CHB patients . This article reviews recent advances in the properties,detection methods,and clinical significance of HBV RNA, particularly the application of antiviral therapy in CHB patients.
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Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal central nervous system disorder resulting from persistent measles virus infection. Long-term data are scarce, with a maximum follow-up period of 10 years. Interferon-alpha (IFN-α) is a protein that exerts its antiviral activity via enhancement of cellular immune response and is reported to be an effective drug for the treatment of SSPE. However, there is currently no consensus regarding the optimal duration of IFN-α therapy. Here, we present a case report of a patient with SSPE treated with long-term intraventricular IFN-α therapy, which facilitated clinical improvement and neurological stabilization without causing serious adverse effects. To the best of our knowledge, this is one of the longest follow-up studies investigating a patient with SSPE receiving intraventricular INF-α treatment. Further studies are necessary to validate the benefits and safety of long-term intraventricular IFN-α treatment in patients with SSPE.
Subject(s)
Humans , Central Nervous System , Consensus , Follow-Up Studies , Immunity, Cellular , Interferon-alpha , Measles , Measles virus , Subacute Sclerosing Panencephalitis , SurvivorsABSTRACT
Objective To assess the efficacy and clinical value of immunoglobulin combined with interferon ( IFN) α-2b in treatment of patients with glucocorticoid refractory subacute thyroiditis. Methods Thirty-five cases of subacute thyroiditis (12 males, 23 females, age (58.1±12.0) years) from January 2016 to May 2017 were retrospectively analyzed. Patients were resistant to the treatment of glucocorticoid and as-pirin, or were not suitable for that treatment because of accompany diseases. Thirty-four healthy controls (16 males,18 females, age (57.0±10.0) years) were included. Thyroid hormone, C-reactive protein (CRP), erythrocyte sedimentation rate ( ESR) and 24 h iodine uptake rate tests, as well as 99 Tcm O-4 thyroid imaging and thyroid ultrasonography were performed before and after co-administration of immunoglobulin and IFNα-2b. Paired t test or Wilcoxon signed rank test, two-sample t test or Wilcoxon rank test were used for data anal-ysis. Results The levels of free triiodothyronine ( FT3 ) , free thyroxine ( FT4 ) and thyroid stimulating hor-mone ( TSH) 4 weeks after immunology intervention were restored compared with the levels before treatment ( t:4.81, 7.76, z=4.60, all P<0.01) and were not significantly different compared with those in the con-trol group ( t:0.02, 0.33, z=0.37, all P>0.05) . CRP and ESR were sharply decreased compared to those before treatment (t:9.59, 13.78, both P<0.01). The 24 h iodine uptake rate was restored 4 weeks after treatment (t=13.92, P<0.01). The positive result was found in 1 patient (2.9％, 1/35) by 24 h iodine uptake rate test, and 5.7％(2/35) of patients were positive in 99TcmO-4 static imaging and 1 patient(2.9％, 1/35) had positive ultrasonography result. The 3-month follow-up showed that 32 cases were cured and the treatment was effective in all 35 patients. Only 1 case recurred after 12-month follow-up, and the effective rate was 96.9％(31/32, 3 cases were lost to follow-up). Conclusion Immunology intervention is an effective way to treat glucocorticoid refractory subacute thyroiditis and should be applied extensively in clinical treatment.
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Background: In different studies the correlation between systemic lupus erythematosus (SLE) and disease activity with vitamin D has been shown. The role of different interferons especially interferon alpha (IFN-?) in lupus pathogenesis have been previously shown. Considering the role of vitamin D and IFN-?, it is possible that these two could demonstrate the SLE activity. This study aimed to investigate the association between vitamin D levels and IFN-? with disease activity index in Ardabil city SLE patients.Methods: In this case control study, 50 SLE patients and 50 age and sex matched healthy subjects were recruited. Patients had serum 25-OH Vitamin D concentration and disease activity recorded. Vitamin D and IFN-? levels were compared between two groups and also, levels of anti-dsDNA, and SLEDAI in case group was measured. Statistical methods were used to determine the correlation between vitamin D and IFN-? with disease activity index at baseline.Results: Vitamin D deficiency (<40 nmol/L) was detected in 20% of SLE patients. Vitamin D level in case group significantly lower than control group (23.94±11.93 vs. 29.10±11.40 ng/ml, p=0.02). The IFN-? amount in case group significantly upper than control group (396.60±54.73 vs. 200.38±14.42, p=0.001). There was significantly negative correlation between vitamin D with IFN-? (r=-0.413, p=0.003), SLEDAI (r=-0.492, p<0.001) and anti-dsDNA (r=-0.417, p=0.003). There was positive correlation between IFN-? with SLEDAI (r=0.358, p=0.01) and anti-dsDNA (p=0.297, p=0.03).Conclusions: Results showed that the low vitamin D was associated with a higher disease activity in SLE patients. Also, it seems that, the improvement of vitamin D levels by decreasing IFN-? could help in controlling disease activity in future.
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Background & objectives: Genetic aberrations disrupting toll-like receptor and interferon homeostasis enhance the risk of systemic lupus erythematosus (SLE). Raised serum interferon-alpha (IFN-?) levels in SLE patients have been ascribed to polymorphism (rs2004640 G/T) in interferon regulatory factor 5 (IRF5) gene, resulting in enhanced transcript splicing. A positive association between IRF5 polymorphism and SLE risk has been reported in many populations. This study was aimed to find out frequency of IRF5 rs2004640 G/T polymorphism in patients with SLE and healthy controls and to assess its influence on susceptibility, clinical and serological characteristics of SLE. Methods: IRF5 rs2004640 (G/T) polymorphism was analyzed in 300 SLE patients and 460 age and sex matched controls by real-time PCR. Results: The IRF5 rs2004640 (G/T) polymorphism did not confer risk of SLE or influence clinical or serological phenotype. However, the mutant allele conferred a borderline risk to develop thrombocytopenia (odds ratio: 2.05, 95% confidence interval: 0.97�3, P=0.06) in patients with SLE. Interpretation & conclusions: Our study revealed that the IRF5 rs2004640 polymorphism was not a risk factor for SLE in population from south India. It may, however, be a useful genetic marker for thrombocytopenia in SLE patients. Although we could not demonstrate susceptibility toward lupus in the presence of IRF5 rs2004640 (G/T) polymorphism, further exploration of the genetic variability of IRF5 may help uncover its pathogenic role in Indian SLE patients.