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1.
Chinese Journal of Microbiology and Immunology ; (12): 390-395, 2022.
Article in Chinese | WPRIM | ID: wpr-934058

ABSTRACT

Objective:To analyze the incidence of human papillomavirus (HPV) infection in 1 902 patients and to evaluate the efficacy of drug treatment in 266 patients, aiming to provide reference for the treatment of HPV infection.Methods:The subtypes of HPV isolated from 1 902 patients aged 15-86 years visiting the venereology outpatient clinic of Tianjin Medical University General Hospital from October 2019 to May 2021 were identified by polymerase chain reaction-reverse dot blot hybridization. Drug treatment efficacy in 266 patients of them was retrospectively analyzed.Results:The overall incidence of HPV infection in the 1 902 patients was as high as 53.84% (1 024/1 902). It was 52.60% (689/1 310) in males and 56.59% (335/592) in females. There was no significant difference in the incidence between males and females ( P>0.05). The most common HPV genotype in males and females was HPV6 [15.27% (200/1 310) and 21.96% (130/592)], followed by HPV16 [10.61% (139/1 310) and 9.46% (56/592)], HPV11 [9.31% (122/1 310) and 8.61% (51/592)], HPV52 [6.79% (89/1 310) and 8.95% (53/592)] and HPV43 [5.64% (87/1 310) and 8.45% (50/592)]. The majority of HPV-positive patients were aged between 20 and 39 years. There were 476 cases (25.03%, 476/1 902) of single-type infection and 548 cases (28.81%, 548/1 902) of multiple infection. The incidence of multiple infection was higher than that of single-type infection ( P<0.05). The incidence of multiple infection in females was higher than that in males ( P<0.05). Among the 266 patients, 106 were treated with Paiteling, a traditional Chinese medicine (TCM) preparation, and 68 of them tested negative (64.15%) after treatment. Fifty-eight patients were treated with recombinant human interferon α2b and 22 of them (37.93%) tested negative after treatment. Twenty out of the 56 subjects treated with imiquimod tested negative after treatment. Eight out of the 46 patients without treatment also turned negative. Conclusions:The incidence of HPV infection in the 1 902 patients visiting the venereology outpatient clinic was very high, and most of them were young adults. Multiple infection was more common than single-type infection. Topical application of drugs such as Paiteling, recombinant human interferon α2b and imiquimod was effective in treating HPV infection.

2.
Journal of Pharmaceutical Analysis ; (6): 308-316, 2022.
Article in Chinese | WPRIM | ID: wpr-931259

ABSTRACT

Recombinant human interferon α2b(rhIFNα2b)is widely used as an antiviral therapy agent for the treatment of hepatitis B and hepatitis C.The current identification test for rhIFNα2b is complex.In this study,an anti-rhIFNα2b nanobody was discovered and used for the development of a rapid lateral flow strip for the identification of rhIFNα2b.RhIFNα2b was used to immunize an alpaca,which established a phage nanobody library.After five steps of enrichment,the nanobody I22,which specifically bound rhIFNα2b,was isolated and inserted into the prokaryotic expression vector pET28a.After subsequent purification,the physicochemical properties of the nanobody were determined.A semiquantitative detection and rapid identification assay of rhIFNα2b was developed using this novel nanobody.To develop a rapid test,the nanobody I22 was coupled with a colloidal gold to produce lateral-flow test strips.The developed rhIFNα2b detection assay had a limit of detection of 1 μg/mL.The isolation of I22 and successful construction of a lateral-flow immunochromatographic test strip demonstrated the feasibility of performing ligand-binding assays on a lateral-flow test strip using recombinant protein products.The principle of this novel assay is generally applicable for the rapid testing of other com-mercial products,with a great potential for routine use in detecting counterfeit recombinant protein products.

3.
Journal of Peking University(Health Sciences) ; (6): 1166-1170, 2020.
Article in Chinese | WPRIM | ID: wpr-942134

ABSTRACT

Behcet syndrome (BS) is a chronic systemic inflammatory disorder involving vessels of all sizes, characterized by relapsing episodes of oral and/or genital ulcers, as well as skin lesions. Ocular, vascular, gastrointestinal, neurological system involvement can cause significant morbidity and mortality. Glucocorticoids and immunosuppressants are the cornerstones for the management of BS. Biologic agents has been recommended for severe and/or refractory BS. Interferon-α (IFN-α) had multiple biological effects, such as antiviral and antiproliferative, that could regulate both innate and adaptive immunity in BS. Growing evidence showed the efficacy of IFN-α in severe and/or refractory BS. Many studies have demonstrated that IFN-α has comparable effectiveness and tolerance profiles as anti-tumor necrosis factor (TNF) agents for Behcet's uveitis with a much lower cost and steroid-and immunosuppressant-sparing effects. IFN-α has been recommended as second-line therapy for ocular involvement of BS in EULAR (The European League Against Rheumatism) 2018. IFN-α also improves mucocutaneous lesions in BS with the dosage from 3 to 9-12 million IU three times per week. A few cases indicated the therapeutic potential of IFN-α in intestinal BS. As a new trial of IFN-α in vascular BS (VBS), a recent study revealed the lower relapse rate and higher recanalization rate with IFN-α in lower extremity deep vein thrombosis (DVT). Another two case reports presented the efficacy of IFN-α in pulmonary artery involvement in BS. Also, case reports have shown successful treatment in refractory neurological involvement. There are two subtypes of IFN-α commonly used in autoimmune diseases, named IFN-α2a and IFN-α2b. IFN-α2a seemed more effective than IFN-α2b, especially in ocular and mucocutaneous involvement of BS. Side effects of IFN-α are dose-dependent and not severe. The most frequent side effects are flu-like syndrome, mild leukopenia and alopecia. Considering the potential risk of tuberculosis (TB) and hepatitis B virus (HBV) reactivation of TNF-α inhibitors, IFN-α is safe due to its anti-HBV effect and protective effect on TB. In conclusion, IFN-α is a promising choice for severe and/or refractory BS patients, especially for those who are intolerant or contraindicant to other biological agents, such as TNF inhibitors. Further prospective controlled studies are warranted to confirm the efficacy and safety of IFN-α in BS.


Subject(s)
Humans , Behcet Syndrome/drug therapy , Glucocorticoids , Immunosuppressive Agents , Uveitis , Venous Thrombosis
4.
Article | IMSEAR | ID: sea-207294

ABSTRACT

Chronic myeloid leukemia (CML) is a rare condition during reproductive age. Still, women may present with pre-existing or newly diagnosed CML during pregnancy. The management of chronic myeloid leukemia during pregnancy requires balancing the well-being of the mother with that of fetus. Tyrosine Kinase inhibitors are considered the most effective drug against CML but they are still not considered safe during pregnancy and breast feeding. So, there is a need for management of CML with alternate drugs during pregnancy. Here we report a case of a 26-year-old lady who was diagnosed with chronic myelogenous leukemia (CML) at 20 weeks of gestation and had an atypical chromosome translocation t (9:22). She was managed jointly by obstetrician and haemato-oncologist for the remainder of her pregnancy and eventually she delivered a healthy baby at term.

5.
Article | IMSEAR | ID: sea-203649

ABSTRACT

This study aimed to investigate relationship of the HCV genome structure and treatment with Pegylated Interferonα/Ribavirin (peg-IFNα/RBV) Egyptian patient. Mutations in two sites of HCV genome; the internal ribosome entry site(IRES) and the interferon sensitivity determining region (ISDR) of HCV genotype 4a were studied in details including DNAsequences and mutations detection in response to treatment. Ninety patients, responders and non-responders, to treatmentwith peg-IFN α /RBV were included in this study. IRES and ISDR regions were amplified by RT-PCR using specific designedprimers, and amplified regions were sequenced. The data obtained were aligned with published sequences in GenBank usingBLAST program. Results of this study have revealed that there are different mutations in the studied sequences in both ISDRand IRES regions. The predicted amino acids sequences in the ISDR region showed significant differences ranging from oneup to more than eight mutations in the HCV Genome sequences. Although there was a significant difference betweensequences of HCV RNA isolated from responders and non-responders, these data were not able to give an absolute answerwhether response to interferon therapy is directly/relates to the structure of the HCV genome

6.
Journal of International Pharmaceutical Research ; (6): 456-460, 2019.
Article in Chinese | WPRIM | ID: wpr-845289

ABSTRACT

Objective: To investigate the aerodynamic characteristics of the nebulized recombinant human inter- feron α1b(rhIFN α1b)injection and its delivery in different respiratory modes both in vitro. Methods: The particle size distribution and aerodynamic properties of the nebulized rhIFN α1b injection for inhalation were evaluated with Spraytec STP5313 and the next generation pharmaceutical impactor(NGI). The total delivered dose and delivery rate were deter- mined using a breathing simulator. Results:After atomization, the D50 of rhIFN α1b droplets was 2.74 μm, the fine par- ticle fraction(FPF)was 77.49%, the mass median aerodynamic diameter(MMAD)was 3.26 μm, and the geometric standard deviation(GSD)was 1.93. In neonatal, infant, and child breathing modes, the delivered total amount of rhIFN α1b by spraying for 220 seconds was 2.10, 2.44, and 3.51 μg, respectively. Conclusion: After atomization, the particle size of rhIFN α1b injection was small enough to be transmitted to the lung, and the total delivered dose and delivery rate showed a tendency of increase in turn in the neonatal, infant, and child breathing modes, indicating that the effective dose of the drug and the age of patients should be considered when formulating the clinical treatment plan.

7.
Frontiers of Medicine ; (4): 354-364, 2019.
Article in English | WPRIM | ID: wpr-771263

ABSTRACT

The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon-α (IFN- α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI), was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after allo-HSCT were studied (n = 47). The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms' tumor gene 1 expression is present in a single bone marrow sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P = 0.377) and 9.1% and 0.0% (P = 0.985) for patients in the IFN-α and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P = 0.891) and 84.3% and 84.6% (P = 0.972) for patients in the IFN-α and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN-α treatment.

8.
International Journal of Pediatrics ; (6): 541-544, 2019.
Article in Chinese | WPRIM | ID: wpr-751509

ABSTRACT

Recombinant human interferon αl b (rhIFN-1 b) is the first internationally unique novel genetic engineering medicine in China.In the previous article,it has been summarized that it is a major interferon subtype that is naturally antiviral in human body,and has high safety and broad-spectrum antiviral effect.A number of pediatric consensus and guidelines of clinical experts have formed in China's national conditions.This article summarizes its innovative research and achievements in the clinical treatment of pediatric diseases,and further discusses the problems that need to be solved in the clinical application of rhIFN-α1b in pediatrics.

9.
International Journal of Pediatrics ; (6): 461-464, 2019.
Article in Chinese | WPRIM | ID: wpr-751491

ABSTRACT

Recombinant human interferonα1b (IFN-α1b) is the first internationally unique novel ge-netic engineering medicine in China. As a major interferon subtype with natural antiviral activity, IFN-α1b has high safety and broad-spectrum antiviral effect, so it has broad application prospects in the treatment of viral diseases. Chinese pediatric doctors have taken the lead globally in conducting clinical research of IFN-α1b in the treatment of respiratory syncytial virus ( RSV) pneumonia、 bronchiolitis、 hand-foot-mouth disease, her-petic angina、 viral diarrhea, etc. A series of clinical guidance and expert consensus have been published which are in line with China's national conditions. This article summarizes the innovative research of IFN-α1b and proposes common issues and potential application in pediatric clinical applications.

10.
Frontiers of Medicine ; (4): 238-249, 2019.
Article in English | WPRIM | ID: wpr-772707

ABSTRACT

The efficacy of salvage interferon-α (IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI) (n = 24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2-3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and > 2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Beijing , Graft Survival , Graft vs Host Disease , Mortality , Hematopoietic Stem Cell Transplantation , Interferon-alpha , Therapeutic Uses , Leukemia, Myeloid, Acute , Mortality , Therapeutics , Lymphocyte Transfusion , Myelodysplastic Syndromes , Mortality , Therapeutics , Neoplasm, Residual , Recurrence , Salvage Therapy , Survival Analysis , Transplantation Conditioning , Transplantation, Homologous
11.
Journal of Southern Medical University ; (12): 150-155, 2019.
Article in Chinese | WPRIM | ID: wpr-772106

ABSTRACT

OBJECTIVE@#To evaluate the therapeutic effects of entecavir (ETV) and interferon- (IFN-) treatments for 48 weeks for chronic hepatitis B (CHB) in patients with different baseline alanine aminotransferase (ALT) levels.@*METHODS@#We retrospectively analyzed the data of 369 CHB patients receiving ETV and IFN- treatments for 48 weeks. We compared the virological response rates, HBsAg clearance, and HBsAg reduction between the patients receiving ETV and IFN- treatments with different baseline ALT levels[≤ 5×upper limits of normal (ULN) level (subgroup 1), 5-10×ULN (subgroup 2), and > 10× ULN (subgroup 3)].@*RESULTS@#In patients receiving ETV treatment, the virological response rate was 83.3% in subgroup 1, 91.4% in subgroup 2, and 95.5% in subgroup 3, as compared with 19.7%, 40%, and 42.9% in the 3 subgroups with IFN- treatment, respectively, showing significantly differences both among different subgroups with the same treatment and between the same subgroup with different treatments ( < 0.05). HBeAg clearance rates in the 3 subgroups were 8.3%, 16.7% and 35.5% in patients with ETV treatment and were 1.8%, 41.9%, and 38.1% in patients with IFN- treatment, respectively, showing significant differences among the 3 subgroups with the same treatment ( < 0.05); in the same subgroups with different treatments, the rates differed significantly only between subgroups 2 ( < 0.05). In ETV group, the rate of HBsAg reduction to below 200 IU/ml was 2.5% in subgroup 1 and 13.8% in subgroup 2, showing no significant difference between the two subgroups; in IFN- group, the rates were also similar between subgroups 1 and 2 (30.6% 33.3%, > 0.05); but the rates differed significantly between the same subgroups with different treatments ( < 0.05).@*CONCLUSIONS@#In all the subgroups with different baseline ALT levels, ETV treatment for 48 weeks results in significantly higher virological response rates than IFN- treatment in patients with CHB. In patients with a baseline ALT of 5-10 ×ULN, IFN- can result in a higher HBeAg clearance rate than ETV. In patients with comparable baseline ALT level, IFN- more effectively reduces HBsAg level than ETV. The patients with a relatively high baseline ALT level (> 5 × ULN) show better responses to both ETV and IFN- treatment than those with ALT level below 5×ULN. We thus recommend IFN- for patients with a baseline ALT of 5-10×ULN and ETV for patients with a baseline ALT either below 5 × ULN or beyond 10×ULN.


Subject(s)
Humans , Alanine Transaminase , Blood , Antiviral Agents , Therapeutic Uses , DNA, Viral , Guanine , Therapeutic Uses , Hepatitis B Surface Antigens , Blood , Hepatitis B e Antigens , Blood , Hepatitis B virus , Allergy and Immunology , Hepatitis B, Chronic , Drug Therapy , Allergy and Immunology , Virology , Interferon-alpha , Therapeutic Uses , Retrospective Studies , Time Factors , Treatment Outcome , Viral Load
12.
Chinese Journal of Biotechnology ; (12): 1029-1040, 2019.
Article in Chinese | WPRIM | ID: wpr-771825

ABSTRACT

To evaluate the optimal administration frequency for interferon-α (IFN-α) and the effect of its combined use with inactive virus on chicken flocks, the prokaryotic expression plasmid pET-22b-ChIFN-α was constructed and transferred into Escherichia coli BL21(DE3) host bacteria to induce the expression of chicken IFN-α and to harvest recombinant proteins inclusion bodies. The expression of recombinant chicken IFN-α was confirmed by SDS-PAGE, and the results demonstrated that the chicken IFN-α (20 kDa) was highly expressed using the prokaryotic expression vector with a concentration of 0.2 mg/mL in the medium. Chicken IFN-α was diluted to 2.5×10⁴ U/fowls and administered to immunized specific-pathogen-free chickens orally in combination with inactivated H9N2 subtype influenza virus. Chicken that received chicken IFN-α were safe after three repeated immunizations (96 h). In addition, chicken IFN-α could induce higher levels of antiviral-related inducible genes in peripheral blood, spleen, and thymus of chicken flocks. The results of a challenge assay revealed that the lowest detoxification rates of chicken IFN-α ranged from three to five days, suggesting a higher capacity to resist H9N2 subtype avian influenza virus. The present study obtained the optimal immune frequency and immunization period for chicken IFN-α to provide theoretical support for the optimal clinical application of IFN-α.


Subject(s)
Animals , Humans , Administration, Oral , Chickens , Influenza A Virus, H9N2 Subtype , Interferon-alpha , Virus Replication
13.
Asian Pacific Journal of Tropical Medicine ; (12): 214-221, 2018.
Article in English | WPRIM | ID: wpr-825836

ABSTRACT

Objective:To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus (CHIKV) infection.Methods:Using flow cytometry and immunoblotting assay, in vitro viral protein expression was studied in THP-1 cells line. In Balb/c mouse neonates, viral RNA copy number was determined by real time PCR.Results:The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells, Vero cells and THP-1 cell line. In vivo, andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number. Further, andrographolide also increased cytotoxic T lymphocytes both in vitro and in vivo. Andrographolide also activated host innate immune pathways, viz., protein kinase R, phosphorylated eukaryotic initiation factor 2α , retinoic acid inducible gene-I and interferon regulatory factor 3/7, thereby increasing IFN- α secretion. CHIKV-induced nuclear factor κ light chain enhancer of activated B cells and tumor necrosis factor- α was also reduced on andrographolide treatment.Conclusion:Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.

14.
Chinese Journal of Infectious Diseases ; (12): 101-106, 2018.
Article in Chinese | WPRIM | ID: wpr-707222

ABSTRACT

Objective To evaluate the curative effect of recombinant human Interferon α2b (rhIFN α2b) spray in hand,foot and mouth disease (HMFD).Methods In total,313 HMFD children were enrolled from Beijing Ditan Hospital affiliated to Capital Medical University,Tianjing Second People's Hospital,Hebei Children's Hospital,the Second Hospital affiliated to Wenzhou Medical College,Kunming Maternal and Child Health Hospital and Guiyang Public Health Treatment Center from March,2015 to February,2017.They were divided into rhIFN α2b group (148 cases) and ribavirin group (165 cases).The children in rhIFN α2b group were given with the rhIFN α2b spray,and those in ribavirin group were given with the ribavirin spray.Meanwhile,the children were given unified standard interventions for basic treatment.The curative effect and safety between two groups was compared.The t test was used for intergroup comparison and the Wilcoxon rank test was used for non-normal quantitative data.Results At the end of the follow-up period,all kids reached the recovery level,with 144 cases in the rhIFN α2b group and 164 cases in the ribavirin group.Fever,herpes and rashes all disappeared with 7-day follow-up.The total efficiency of the rhIFN α2b group measured at the 72h after treatment was 74.15%,which showed significant differences compared with the ribavirin group with 49.09 % efficiency (Z=4.44,P<0.01).As the secondary outcome measures,the complete disappearance time of fever and the immediate disappearance time of fever in the rhIFN α2b group were significantly shorter than those in the ribavirin group ([27.03±21.99] vs [33.21±26.71],t=-2.13;[23.56±13.96] vs [28.51±18.84],t=-2.07,both P<0.05).The appetite improvement and the disappearance times of oral herpes and rashes in the rhIFN α2b group were shorter than those in the ribavirin group,with significant differences (x2 =4.94,3.17 and 3.55,respectively,all P=0.000).No adverse event in both groups.Conclusions rhIFN α2b spray treatment in HMFD is proved significantly effective,particularly,it can evidently relieve fever symptoms and promote the disappearance of oral herpes symptoms,and no adverse event is observed throughout the study,which indicates a good safety of the rhIFN α2b spray.Clinical trial registration Chinese Clinical Trial Registry,ChiCTR-OIN-17013182.

15.
Chinese Journal of Applied Clinical Pediatrics ; (24): 1361-1365, 2018.
Article in Chinese | WPRIM | ID: wpr-696597

ABSTRACT

As the first class Ⅰ novel genetic engineering medical product in China,recombinant human interferon alpha 1b (IFNα1b) shows unique biological significance and clinical value.Especially in the field of pediatrics,IFNα1 b has been used in the treatment of viral pneumonia,viral hepatitis,bronchiolitis,herpetic angina,hand-footmouth disease and some tumors in children and shown definite efficacy and good safety.It is also used in the prevention and treatment of virus-related wheezing and major infectious diseases,such as influenza.With a greater application prospect,IFNα1b plays an important role in promoting children's health in China.Now,IFNα1b's gene and molecular characteristics,new delivery methods,and the frontier clinical research will be discussed.

16.
Basic & Clinical Medicine ; (12): 944-949, 2018.
Article in Chinese | WPRIM | ID: wpr-694014

ABSTRACT

Objective To explore the role of cytidine/uridine monophosphate kinase 2( CMPK2) in the immune-mediated antitumor effect of IFNα in hepatocellular carcinoma. Methods RT-qPCR and Western blot were used to analyze the expression of CMPK2 in Huh7 after the treatment of IFNα. The CMPK2 overexpressing Huh7 cells were generated by stably infecting with lentivirus. The ATP level in the cells and the supernatant of CMPK2 overexpress-ing Huh7 cells were measured by CellTiter-Glo ATP fluorescence assay. RT-qPCR was applied to test the expression of inflammatory cytokines in macrophages under the treatment of the supernatant of CMPK2 overexpress-ing Huh7 cells. Results The transcription and protein level of CMPK2 were significantly enhanced after the treat-ment of IFNα for 6 hours ( P<0.01) . CMPK2 increased the ATP level in the cells and supernatant of Huh7 cells ( P<0.01) . The supernatant of CMPK2 overexpressing Huh7 cells activated the expression of IL1β, IL6 and CCL5 in macrophages( P<0.01) . Conclusions IFNα increases the expression of CMPK2 in Huh7 cells to activate the expression of inflammatory cytokines in macrophages.

17.
Asian Pacific Journal of Tropical Medicine ; (12): 214-221, 2018.
Article in Chinese | WPRIM | ID: wpr-972472

ABSTRACT

Objective: To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus (CHIKV) infection. Methods: Using flow cytometry and immunoblotting assay, in vitro viral protein expression was studied in THP-1 cells line. In Balb/c mouse neonates, viral RNA copy number was determined by real time PCR. Results: The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells, Vero cells and THP-1 cell line. In vivo, andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number. Further, andrographolide also increased cytotoxic T lymphocytes both in vitro and in vivo. Andrographolide also activated host innate immune pathways, viz., protein kinase R, phosphorylated eukaryotic initiation factor 2α , retinoic acid inducible gene-I and interferon regulatory factor 3/7, thereby increasing IFN- α secretion. CHIKV-induced nuclear factor κ light chain enhancer of activated B cells and tumor necrosis factor- α was also reduced on andrographolide treatment. Conclusion: Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.

18.
Chinese Medical Journal ; (24): 1813-1818, 2018.
Article in English | WPRIM | ID: wpr-773971

ABSTRACT

Background@#Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB).@*Methods@#Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis.@*Results@#IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = -0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = -2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ = 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = -1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ = 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = -0.358, t = -2.308, P = 0.024), HBsAg (β = -0.359, t = -2.288, P = 0.025), and HBeAg contents (β = -0.355, t = -2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = -0.459, t = -4.225, P = 0.000; β = -0.616, t = -6.334, P = 0.000; and β = -0.290, t = -2.433, P = 0.018; respectively).@*Conclusions@#IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.


Subject(s)
Adult , Female , Humans , Male , Young Adult , Alanine Transaminase , Blood , Antigens, Surface , Case-Control Studies , Cytokines , Blood , DNA, Viral , Hepatitis B , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus , Hepatitis B, Chronic , Blood , Allergy and Immunology
19.
Chinese Journal of Infection and Chemotherapy ; (6): 177-183, 2018.
Article in Chinese | WPRIM | ID: wpr-702609

ABSTRACT

Objective To explore the antiviral effect and mechanism of interferon-α (IFN-α) in chronic HBV infection mouse model by hydrodynamic tail vein injection. Methods Chronic HBV infection mouse model was constructed with C57BL/6j mice by hydrodynamic tail vein injection of pAAV-HBV1.2 plasmid. Serum IFN-α was determined by ELISA after injection of IFNα- expressing plasmid (i.e., plasmid pKCMvint.IFN-α-2a) or control plasmid pKCMvint. HBsAg and HBeAg levels were assayed on Abbot ARCHITECT i2000SR. Total lymphocytes in liver or spleen were counted and the frequency and function of CD8+T cells and HBV-specific CD8+T cells were analyzed by flow cytometry. Results Serum IFN-α expression level was significantly higher in the animals injected with pKCMvint.IFN-α-2a plasmid than in control group (P<0.01). Serum HBsAg decreased quickly 12 days after injection and significantly lower than control group. Serum HBeAg was undetectable after IFN-α expression. Interestingly, the frequency of CD8+T cells in the liver of animals injected with pKCMvint.IFN-α-2a plasmid was significant higher than control group (P<0.05), while total liver lymphocytes and HBV-specific CD8+T cells had a similar trend. Consistently, the HBV-specific CD8+T cells in IFN-α-expressing animals showed higher level of producing IFN-γ, TNF-α and IL-2 than control group. IFN-γ production was significantly different between IFN-α- expressing group and control group (P<0.05). Conclusions IFN-α can increase the frequency and function of liver CD8+T cells to inhibit HBV gene expression in chronic HBV infection mouse model.

20.
Chinese Journal of Primary Medicine and Pharmacy ; (12): 1022-1025, 2018.
Article in Chinese | WPRIM | ID: wpr-701882

ABSTRACT

Objective To study the clinical efficacy of Baofukang suppository and recombinant human inter -feron α-2b in the treatment of HPV infection with chronic cervicitis ,and to observe the prognosis ,thus to provide reference for its clinical treatment .Methods 120 patients with chronic cervicitis with HPV infection were selected . All patients were divided into observation group and control group by random number table method ,60 cases in each group.The observation group was treated with Baofukang combined with recombinant human interferon α-2b,and the control group was treated with recombinant human interferon α-2b.The patients were evaluated before treatment ,at the end of treatment and 3 months after treatment.The cure rate,total effective rate,recurrence rate,incidence rate of adverse reactions were observed and compared .Results In the observation group ,26 cases were cured ,the cure rate was 43.33%.In the control group ,15 cases were cured ,the cure rate was 25%.The cure rate of the observation group was higher than that of the control group ,the difference was statistically significant (χ2 =4.482,P<0.05).The total effective rate of the observation group was 98.33%,which was higher than 80.00% of the control group,the differ-ence was statistically significant (χ2 =10.438,P <0.05).The negative rate of HPV in the control group was 38.33%,which was lower than 56.67% in the observation group,the difference was statistically significant (χ2 = 4.043,P<0.05).The incidence rate of adverse reactions in the observation group was 11.67%,which in the control group was 10.00%,the difference was not statistically significant (χ2 =0.086,P >0.05).After treatment for 3 months,the recurrence rate was 0.00%in the observation group and 1.67%in the control group,the difference was not statistically significant (χ2 =1.008,P >0.05).Conclusion The combination of Baofukang suppository and recombinant human interferon α-2b showed good curative effect and prognosis in the treatment of chronic cervicitis with HPV infection ,and it is worthy to be popularized in clinical practice .

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