interferon

摘要： BACKGROUND Persistent inflammation on histology after successful hepatitis C(HCV)treatment has been reported.However,data regarding the long-term impact in liver transplant recipients is limited,particularly after using direct-acting antiviral(DAA)therapies.AIM To evaluate the impact of successful treatment with DAAs on histological changes and occult HCV and to describe the clinical course of residual inflammation in liver transplant recipients.METHODS We conducted a case series of 13 chronic HCV infected liver transplant recipients successfully treated with DAAs between December 2013 and May 2014.All patients were treated for 24 wk and had non-detectable serum HCV RNA by the time of biopsy.Only patients with at least one liver biopsy at or after treatment were included.We examined liver biopsies for evidence of residual inflammation and the presence of intrahepatic HCV RNA.RESULTS Persistent inflammation was seen in 12/13 patients on end of treatment biopsy.Inflammation was still seen in the available five follow-up biopsies(range 38-48 wk after the end of treatment).Intrahepatic HCV RNA was undetectable in all biopsies.All patients had preserved graft function for a mean follow-up of 2.5 years,except one that developed chronic rejection.CONCLUSION After successful HCV treatment with DAAs,liver transplant recipients may have persistent inflammation on biopsy without evidence of intracellular RNA.The clinical outcome remained favorable in most patients.Further studies with a larger number and longer follow-up are needed to establish the implication of this finding on long-term graft function.

摘要： Most neurological diseases are associated with a tissue injury that is detected by the innate immune response(IIR),leading to an inflammatory component.The IIR is activated through conserved Pattern Recognition Receptors,including membrane bound Toll like receptors(TLRs),intracellular nucleotide-binding oligomerization domain like receptors and the receptors for advanced glycation end-products(Amor et al.,2010;Heppnerrt et al.,2015).These receptors detect highly conserved structural motifs of damaged or stressed tissues(danger-associated molecular patterns(DAMP)).Cytosolic receptors of nucleic acids,such as cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)and melanoma differentiation associated gene 5(MDA-5)can also trigger IIR activation leading to interferon(IFN)and IFN stimulated gene(ISG)expression through DNA/RNA sensing signaling pathways(Yang and Li,2020).

摘要： The need for effective therapeutic options for patients has received increasing attention in response to the prevalence of COVID 19.Although there are several options for the prevent of COVID-19,including vaccines,monoclonal antibodies,oligonucleotide-based therapies,peptides,and interferon therapies,no treatment for coronaviruses has yet been approved[1].

摘要： Hepatitis B virus(HBV)infection is one of the main causes of morbidity and mortality worldwide.Most children acquire the infection perinatally or during early childhood and develop a chronic hepatitis characterized by a high viral replication and a low-inflammation phase of infection,with normal or only slightly raised aminotransferases.Although a conservative approach in children is usually recommended,different therapies exist and different therapeutic approaches are possible.The main goals of antiviral treatment for children with chronic HBV infection are to suppress viral replication and to warn the disease progression to cirrhosis and hepatocellular carcinoma,although these complications are rare in children.Both United States Food and Drug Administration(USFDA)and European Medicines Agency(EMA)have approved interferon alfa-2b for children aged 1 year and older,pegylated interferon alfa-2a and lamivudine for children aged 3 years and older,entecavir for use in children aged 2 years and older,and adefovir for use in those 12 years of age and older.Tenofovir disoproxil fumarate is approved by EMA for children aged 2 years and older and by USFDA for treatment in children aged 12 years and older.Finally,EMA has approved the use of tenofovir alafenamide for treatment of children aged 12 years and older or for children weighing more than 35 kg independent of age.This narrative review will provide the framework for summarizing indications to antiviral therapy in the management of chronic HBV infection in children and adolescents.

摘要： Chronic infection with hepatitis C virus(HCV)is one of the leading causes of liver disease globally,affecting approximately 71 million people.The majority of them are infected with genotype(GT)1 but infections with GT3 are second in frequency.For many years,GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon(IFN)-based regimen.However,the growing evidence of a higher rate of steatosis,more rapid progression of liver fibrosis,and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this conviction.This review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals(DAA).The way from a standard of care therapy with pegylated IFNalpha(pegIFNα)and ribavirin(RBV)through a triple combination of pegIFNα+RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead ends.Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection,there is still room for improvement,especially in patients with liver cirrhosis and those who fail to respond to DAA therapies,particularly those containing inhibitors of HCV nonstructural protein 5A.

摘要： Objective:This study conducted a systematic review of randomized controlled trials in order to evaluate the efficacy and safety of Baofukang Suppository(保妇康栓)combined with interferon on cervical high-risk human papillomavirus(HR-HPV)infection.Methods:Data comes from China National Knowledge Infrastructure(CNKI),Wanfang database,the VIP information database,Chinese Biomedical Literature Database,PubMed,Cochrane Library,Web of Science and Embase.Primary and secondary outcome measures were extracted from 13 included randomized controlled trials:number of HR-HPV turning negative and effective,time of HPV turning negative,duration of abnormal vaginal secretions and adverse events.Results:Baofukang Suppository combined with interferon were better than interferon alone in improving the negative rate of HR-HPV(RR=1.42,95%CI[1.28,1.58],P<0.00001)and the effective rate of HR-HPV RR=1.3,95%CI[1.24,1.37],P<0.00001),time of HR-HPV turning negative(MD=-8.32,95%CI[-9.17,-7.47],P<0.00001),duration of abnormal vaginal secretions(MD=-8.95,95%CI[-11.34,-6.56],P<0.00001).However,there was no statistical difference in improving inflammatory factor(TNF-α:SMD=-0.49,95%CI[-1.02,0.03],Z=1.83,P=0.07;IL-6:SMD=-13.69,95%CI[-41.98,14.6],Z=0.95,P=0.34)and adverse events(RR=-0.73,95%CI[0.48,1.11,P=0.15)between two groups.Conclusion:The results showed that the efficacy of Baofukang Suppository combined with interferon were better than interferon alone in improving the negative and effective rate of HR-HPV,shortening the time of HR-HPV turning negative and duration of abnormal vaginal secretion and reducing adverse events.

摘要： In a recent single cell transcriptomic investigation of the peripheral immune responses of the patients with severe COVID-19[1],no substantial expression of pro-inflammatory cytokines has been identified in the peripheral monocytes and lymphocytes,while these peripheral immune cells exhibit phenotypes of heterogeneously expressed interferon-stimulated genes in certain COVID-19 patients.These genes may contribute to the inhibitory response to the viral entry,translation,replication and egress.Questions remain regarding why the peripheral cytokine production is constrained,what additional roles these peripheral immune cells may play in COVID-19 pathophysiology,and which potential targets can be explored for facilitating COVID-19 therapeutics.

摘要： BACKGROUND An increased amount of Fusobacterium nucleatum(F.nucleatum)is frequently detected in the gastric cancer-associated microbiota of the Taiwanese population.F.nucleatum is known to exert cytotoxic effects and play a role in the progression of colorectal cancer,though the impact of F.nucleatum colonization on gastric cancer cells and patient prognosis has not yet been examined.AIM To identify F.nucleatum-dependent molecular pathways in gastric cancer cells and to determine the impact of F.nucleatum on survival in gastric cancer.METHODS Coculture of F.nucleatum with a gastric cancer cell line was performed,and changes in gene expression were investigated.Genes with significant changes in expression were identified by RNA sequencing.Pathway analysis was carried out to determine deregulated cellular functions.A cohort of gastric cancer patients undergoing gastrectomy was recruited,and nested polymerase chain reaction was performed to detect the presence of F.nucleatum in resected cancer tissues.Statistical analysis was performed to determine whether F.nucleatum colonization affects patient survival.RESULTS RNA sequencing and subsequent pathway analysis revealed a drastic interferon response induced by a high colonization load.This response peaked within 24 h and subsided after 72 h of incubation.In contrast,deregulation of actin and its regulators was observed during prolonged incubation under a low colonization load,likely altering the mobility of gastric cancer cells.According to the clinical specimen analysis,approximately one-third of the gastric cancer patients were positive for F.nucleatum,and statistical analysis indicated that the risk for colonization increases in late-stage cancer patients.Survival analysis demonstrated that F.nucleatum colonization was associated with poorer outcomes among patients also positive for Helicobacter pylori(H.pylori).CONCLUSION F.nucleatum colonization leads to deregulation of actin dynamics and likely changes cancer cell mobility.Cohort analysis demonstrated that F.nucleatum colonization leads to poorer prognosis in H.pylori-positive patients with late-stage gastric cancer.Hence,combined colonization of F.nucleatum and H.pylori is a predictive biomarker for poorer survival in late-stage gastric cancer patients treated with gastrectomy.

摘要： Hepatitis C virus (HCV) infection is one of the major causes of end-stage liver disease and hepatocellular carcinoma (HCC). Before the use of direct acting antivirals (DAAs) against HCV, liver transplantation was one of the best ways to achieve long-term survival and a better prognosis in patients with HCV infection and advanced liver fibrosis (1). In the interferon era, it is difficult for HCV infected patients with advanced liver fibrosis to achieve sustained virological response (SVR) because interferon therapy causes severe adverse events and these completely hamper this treatment in these patients.

摘要： BACKGROUND Interferons(IFNs)are characterized by a wide range of biological effects,which justifies their potential therapeutic use in several pathologies,but also elicit a wide array of adverse effects in almost every organ system.Among them,renal involvement is probably one of the most complex to identify.CASE SUMMARY We describe four cases of kidney damage caused by different IFN formulations:IFN-β-related thrombotic microangiopathy,IFN-β-induced systemic lupus erythematosus,and two cases of membranous nephropathy secondary to pegylated-IFN-α2B.In each case,we carefully excluded any other possible cause of renal involvement.Once suspected as the casual relationship between drug and kidney damage,IFN treatment was immediately discontinued.In three cases,we observed a complete and persistent remission of clinical and laboratory abnormalities after IFN withdrawal,while the patient who developed thrombotic microangiopathy,despite IFN withdrawal and complement-inhibitor therapy with eculizumab,showed persistent severe renal failure requiring dialysis.CONCLUSION This case series highlights the causal relationship between IFN treatment and different types of renal involvement and enables us to delineate several peculiarities of this association.

摘要： 本发明涉及一种重组马Interferon‑alpha‑1的制备方法，将经过密码子优化的编码马Interferon‑alpha‑1的核苷酸序列构建入酵母细胞诱导表达载体中，然后转入酵母细胞进行培养后诱导表达，并进行纯化，从而获得重组马Interferon‑alpha‑1，较佳地，酵母细胞诱导表达载体是分泌表达载体，在诱导表达后，培养得到细胞发酵上清液，上清液采用液相柱层析方法进行纯化，本发明设计巧妙，从而可以高表达、高纯度地获得具有生物学活性的重组马Interferon‑alpha‑1，进而可以在预防马匹病毒感染时应用，以增强动物抵抗病毒的免疫反应。

摘要： 本发明涉及一种重组马Interferon‑alpha‑1的制备方法，将经过密码子优化的编码马Interferon‑alpha‑1的核苷酸序列构建入酵母细胞诱导表达载体中，然后转入酵母细胞进行培养后诱导表达，并进行纯化，从而获得重组马Interferon‑alpha‑1，较佳地，酵母细胞诱导表达载体是分泌表达载体，在诱导表达后，培养得到细胞发酵上清液，上清液采用液相柱层析方法进行纯化，本发明设计巧妙，从而可以高表达、高纯度地获得具有生物学活性的重组马Interferon‑alpha‑1，进而可以在预防马匹病毒感染时应用，以增强动物抵抗病毒的免疫反应。