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Advances in newly developing therapy for chronic hepatitis C virus infection

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《医学前沿（英文）》 2014年 第8卷 第2期   页码 166-174 doi: 10.1007/s11684-014-0334-2

摘要：

Chronic hepatitis C virus (HCV) infection afflicts a reported 170 million people worldwide and is often complicated by cirrhosis and hepatocellular carcinoma. Morbidity and mortality are decreased with the successful treatment of chronic HCV infection. Increased understanding of the HCV has allowed further development of new direct-acting antiviral (DAA) agents against the HCV and has also allowed the development of IFN-free oral treatment regimens. In late 2013 the first nucleotide polymerase inhibitor regimen with RBV alone for genotypes 2/3 and in combination with a 12-week regimen of PEG-IFN+RBV for genotypes 1, 4 was approved for use in the US. A number of promising new DAA regimens which are IFN-free are in phase 3 development and the first will likely be approved for use in the US in 2014. The currently approved regimens are discussed in detail and currently available data on future regimens are reviewed herein.

关键词： direct-acting antiviral (DAA)     nucleotide polymerase inhibitors     protease inhibitors    

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Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 502-508 doi: 10.1007/s11684-017-0590-z

摘要：

Although the efficacy of nucleos(t)ide analogue (NA) has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus (HBV) are integrated into the life cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA (cccDNA), particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen (HBsAg) that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a “para-functional cure,” a status nearly close to the functional cure of chronic hepatitis B, to distinguish the “functional cure” characterized as serum HBsAg loss with or without anti-HBs seroconversion.

关键词： chronic hepatitis B     serum HBV RNA     nucleos(t)ide analogs     virological response     para-functional cure    

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Current recommendations of managing HBV infection in preconception or pregnancy

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 158-165 doi: 10.1007/s11684-014-0340-4

摘要：

Hepatitis B remains a leading cause of cirrhosis, hepatocellular carcinoma and liver transplantation worldwide. Management of chronic hepatitis B during pregnancy is challenging. Transmission of hepatitis B to infants still occurs perinatally although immunoprophylaxis is widely available for infants born to mothers with chronic hepatitis B infection. The emerging data suggest that initiation of antiviral therapy in the beginning of the third trimester in highly viremic mothers can prevent immunoprophylaxis failure in their infants. The available drug safety data show that lamivudine, telbivudine and tenofovir are generally safe to be used during the pregnancy. In order to minimize the fetal exposure to the antiviral medication, antiviral therapy during the pregnancy should be limited to a selected group of patients with cirrhosis, high hepatitis B viral load, or prior history immunoprophylaxis failure. An elective Caesarean section may reduce the risk of perinatal transmission. For those females planning for pregnancy or in early stage of pregnancy, communication and follow-up among obstetrician, gastroenterologist, and primary care physician are important. In this article, we will review the features of hepatitis B infection before, during and after the pregnancy; the risk factors that increase mother-to-child transmission; safety data on antiviral drug use during pregnancy; and the potential role of Caesarean section in selected cases.

关键词： antiviral therapy     Caesarean section     cirrhosis     hepatitis B     immunoprophylaxis     mother-to-child transmission     pregnancy     prevention    

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Direct acting antiviral-induced dynamic reduction of serum

Tung Huynh, Ke-Qin Hu

《医学前沿（英文）》 2019年 第13卷 第6期   页码 658-666 doi: 10.1007/s11684-019-0707-7

摘要： Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12–213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (>5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP>5.5 was associated with the presence of cirrhosis ( =0.001), co-existing non-alcoholic steatohepatitis (NASH) ( = 0.035), and GT 1 ( = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis ( = 0.003), Child–Pugh score<6 ( = 0.015), and baseline AFP<10 ( = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child–Pugh score<6, and baseline AFP<10.

关键词： chronic hepatitis C     α fetoprotein     direct acting antiviral treatment     cirrhosis    

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ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

《农业科学与工程前沿（英文）》 2022年 第9卷 第1期 doi: 10.15302/J-FASE- 2021390

摘要：

It has previously been shown that tryptophan, the biosynthesis precursor of Peganum harmala alkaloids, and its derivatives have anti-TMV activity both in vitro and in vivo. Further exploration of this led to the identification of NK0238 as a highly effective agent for the prevention and control of diseases caused by plant viruses, but the existing routes are unsuitable for its large-scale synthesis. This study optimized a route for two-step synthesis of this virucide candidate via reaction of l-tryptophan with triphosgene to produce l-tryptophan-N-carboxylic anhydride, which then reacts with n-octylamine to give NK0238 at up to 94% yield and nearly 97% HPLC purity. In addition, the route was used for the preparation of NK0238 on a>40 g scale permitting further assessment of its antivirus activity in the greenhouse and field experiments, and toxicity tests. NK0238 exhibited useful antiviral activities against a variety of viruses both in greenhouse and field experiments. The toxicity tests showed that NK0238 was not acutely toxic to birds, fish, honey bees and silkworms. The optimized route provides a solid foundation for its large-scale synthesis and subsequent efficacy and toxicity studies, its excellent activity and safety make NK0238 a promising drug candidate for further development.

 

关键词： antiviral plant protectant / antiviral in the greenhouse / field evaluation / l-trp-NCA / synthesis optimization / toxicity tests    

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Design, synthesis, and antiviral properties of 2-aryl-1H-benzimidazole-4-carboxamide derivatives

Xianjin LUO, Zhonglü ZHANG, Yutian YANG, Fei XUE, Naiyun XIU, Yuanbin SHE

《化学科学与工程前沿（英文）》 2009年 第3卷 第3期   页码 305-309 doi: 10.1007/s11705-009-0021-z

摘要： A series of new benzimidazole derivatives were designed and synthesized. Their chemical structures were testified by H NMR, infrared spectroscopy (IR), mass spectrography (MS), and elemental analysis. Their potent antiviral properties indicated the prospect of new drugs. Compound , , , , , , and were identified as novel antivirus with much better selective activity and inhibitory activity than the comparable ribavirin against Coxsackie virus B in VERO cells.

关键词： benzimidazole     coxsackie virus B3     antiviral properties    

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ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

Wentao XU, Hao TIAN, Hongjian SONG, Yuxiu LIU, Yongqiang LI, Qingmin WANG

《农业科学与工程前沿（英文）》   页码 110-119 doi: 10.15302/J-FASE-2021390

摘要： It has previously been shown that tryptophan, the biosynthesis precursor of alkaloids, and its derivatives have anti-TMV activity both and . Further exploration of this led to the identification of NK0238 as a highly effective agent for the prevention and control of diseases caused by plant viruses, but the existing routes are unsuitable for its large-scale synthesis. This study optimized a route for two-step synthesis of this virucide candidate via reaction of L-tryptophan with triphosgene to produce L-tryptophan- -carboxylic anhydride, which then reacts with -octylamine to give NK0238 at up to 94% yield and nearly 97% HPLC purity. In addition, the route was used for the preparation of NK0238 on a > 40 g scale permitting further assessment of its antivirus activity in the greenhouse and field experiments, and toxicity tests. NK0238 exhibited useful antiviral activities against a variety of viruses both in greenhouse and field experiments. The toxicity tests showed that NK0238 was not acutely toxic to birds, fish, honey bees and silkworms. The optimized route provides a solid foundation for its large-scale synthesis and subsequent efficacy and toxicity studies, its excellent activity and safety make NK0238 a promising drug candidate for further development.

关键词： antiviral plant protectant     antiviral in the greenhouse     field evaluation     L-trp-NCA     synthesis optimization     toxicity tests    

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Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 260-267 doi: 10.15302/J-FASE-2016116

摘要： The innate immune response is the first line of defense against viral invasion and pro-inflammatory chemokines and cytokines have a critical function in the innate immune responses against virus infections. The ability of a rabies virus (RABV) to induce the expression of chemokines and cytokines can lead to viral clearance from the central nervous system (CNS), whereas the ability to evade such expression and activation contributes to virulence and pathogenicity. In this review, the crucial contribution of chemokines/cytokines to clearing RABV from the CNS is discussed, including recruiting leukocytes into the CNS, enhancement of blood brain barrier permeability and activation of various immune cells that are essential for viral clearance. In addition, recombinant RABV expressing cytokines and chemokines can induce elevated innate and adaptive immune responses which result in clearing an established wild-type RABV infection in the CNS.

关键词： antiviral     blood brain barrier     chemokines and cytokines     innate immunity     rabies virus    

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ANTIVIRAL EFFECTS OF BACTERIOCIN AGAINST ANIMAL-TO-HUMAN TRANSMITTABLE MUTATED SARS-COV-2: A SYSTEMATIC

《农业科学与工程前沿（英文）》 2021年 第8卷 第4期   页码 603-622 doi: 10.15302/J-FASE -2021397

摘要：

The COVID-19 infections caused by SARS-CoV-2 have resulted in millions of people being infected and thousands of deaths globally since November 2019. To date, no unique therapeutic agent has been developed to slow the progression of this pandemic. Despite possessing antiviral traits the potential of bacteriocins to combat SARS-CoV-2 infection has not been fully investigated. This review summarizes the mechanisms by which bacteriocins can be manipulated and implemented as effective virus entry blockers with infection suppression potential properties to highly transmissible viruses through comprehensive immune modulations that are potentially effective against COVID-19. These antimicrobial peptides have been suggested as effective antiviral therapeutics and therapeutic supplements to prevent rapid virus transmission. This review also provides a new insight into the cellular and molecular alterations which have made SARS-CoV-2 self-modified with diversified infection patterns. In addition, the possible applications of antimicrobial peptides through both natural and induced mechanisms in infection prevention perspectives on changeable virulence cases are comprehensively analyzed. Specific attention is given to the antiviral mechanisms of the molecules along with their integrative use with synthetic biology and nanosensor technology for rapid detection. Novel bacteriocin based therapeutics with cutting-edge technologies might be potential substitutes for existing time-consuming and expensive approaches to fight this newly emerged global threat.

 

关键词： antimicrobial proteins / antiviral profiling of bacteriocins / antiviral therapeutics / immunomodulation / nanosensor technology / mutated SARS-CoV-2    

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How to judge the association of postmenopausal hormone therapy and the risk of breast cancer

Ling XU

《医学前沿（英文）》 2010年 第4卷 第3期   页码 290-293 doi: 10.1007/s11684-010-0093-7

摘要： The relevance of postmenopausal hormone therapy (HT) for breast cancer risk has been long debated, although it is one of the most important barriers for women to accept HT. Various opinions have been reported from recent randomized clinical trials and epidemiological studies. These unanswered questions include: whether HT has a positive impact on breast cancer; whether risks of therapy with unopposed estrogen and combined estrogen-progestin are different; and whether different types and routes of estrogen and progestogens, as well as the duration and cessation of HT use, have different impacts on this disorder. Recently, there has been some good news such as the following: the currently available data do not provide sufficient evidence to prove a causal relationship between postmenopausal HT and breast cancer; breast cancer in postmenopausal women using HT usually has better prognosis than that of nonusers. In conclusion, HT is still the most effective method of relieving climacteric symptoms for many postmenopausal women. However, a possible risk of breast cancer associated with long-term HT usage should not be ignored. With respect to prevention of breast cancer, regular evaluation of individual breast cancer susceptibility and close follow-up through mammography and/or breast sonography are necessary strategies for the safety of HT use.

关键词： breast cancer     postmenopausal hormone therapy     unopposed estrogen therapy     combined estrogen-progestin therapy    

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Particle therapy for cancers: a new weapon in radiation therapy

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《医学前沿（英文）》 2012年 第6卷 第2期   页码 165-172 doi: 10.1007/s11684-012-0196-4

摘要：

Particle irradiation started to draw attention in the past decade and has now become a hotspot in the radiation oncology community. This article reviews the most advanced developments in particle irradiation, focusing on the characteristics of proton and carbon ions in radiation physics and radiobiology. The Bragg peak of physical dose distribution causes proton and carbon beams to optimally meet the requirement for cancer irradiation because the Bragg peak permits the accurate concentration of the dose on the tumor, thus sparing the adjacent normal tissues. Moreover, carbon ion has more radiobiological benefits than photon and proton beams. These benefits include stronger sterilization effects on intrinsic radio-resistant tumors and more effective killing of hypoxic, G0, and S phase cells. Compared with the most advanced radiation techniques using photon, such as three-dimensional conformal radiation therapy and intensity-modulated radiation therapy, proton therapy has yielded more promising outcomes in local control and survival for head and neck cancers, prostate carcinoma, and pediatric cancers. Carbon therapy in Japan showed even more promising results than proton therapy. The local controls and overall survivals were as good as that treated by surgery in early stages of non-small cell lung cancer, hepatocellular carcinoma, prostate carcinoma, and head and neck cancers, especially for such highly resistant tumors as melanoma. The non-invasive nature of particle therapy affords more patients with chances to receive and benefit from treatment. Particle therapy is gradually getting attention from the oncology community. However, the cost of particle therapy facilities has limited the worldwide use of this technology.

关键词： radiation therapy     particle therapy     proton     carbon     cancer    

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Oral administration of

Sufen ZHAO,Yuanyuan JIA,Weiwei ZHANG,Lili WANG,Yunfei MA,Kedao TENG

《农业科学与工程前沿（英文）》 2015年 第2卷 第4期   页码 318-326 doi: 10.15302/J-FASE-2015080

摘要： Garlic ( Liliaceae) has been safely used for more than 5000 years, and research on garlic extract is rapidly increasing because of its multiple biological functions. The effects of oral administration of garlic mixture (GM, water-soluble extract) on infectious bursal disease virus (IBDV)-infected specific pathogen free male white leghorn chicken were examined through histopathological, immunohistochemical, and Western blot analyses, and enzyme-linked immunosorbent assay. The results confirmed the protective effects of oral administration of 5 mg·kg BW GM (Group GM1) on bursal lesions after IBDV infection. In particular, protein expression of IBDV in the bursa decreased in Group GM1, indicating that GM administration decreased IBDV replication in the bursa. Furthermore, immunoglobulin M- and A-bearing B lymphocytes significantly increased 7 days post infection in bursae in Group GM1 ( <0.01), suggesting that the oral administration of 5 mg·kg GM offers moderate protection against B cell destruction after IBDV infection. During infection, the concentration of bursal interferon gamma (IFN-g) increased and peaked in Group GM1 earlier than in Group T (IBDV-exposed), demonstrating that GM administration prompted the production of IFN-g to protect against IBDV infection.

关键词： garlic     infectious bursal disease virus (IBDV)     antiviral effect     IgM-bearing B lymphocyte    

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Passive antibody therapy in emerging infectious diseases

《医学前沿（英文）》 doi: 10.1007/s11684-023-1021-y

摘要： The epidemic of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 and its variants of concern (VOCs) has been ongoing for over 3 years. Antibody therapies encompassing convalescent plasma, hyperimmunoglobulin, and neutralizing monoclonal antibodies (mAbs) applied in passive immunotherapy have yielded positive outcomes and played a crucial role in the early COVID-19 treatment. In this review, the development path, action mechanism, clinical research results, challenges, and safety profile associated with the use of COVID-19 convalescent plasma, hyperimmunoglobulin, and mAbs were summarized. In addition, the prospects of applying antibody therapy against VOCs was assessed, offering insights into the coping strategies for facing new infectious disease outbreaks.

关键词： SARS-CoV-2     COVID-19     convalescent plasma     hyperimmunoglobulin     neutralizing monoclonal antibodies    

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mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?

Shi-Yong Sun

《医学前沿（英文）》 2021年 第15卷 第2期   页码 221-231 doi: 10.1007/s11684-020-0812-7

摘要： The mammalian target of rapamycin (mTOR) critically regulates several essential biological functions, such as cell growth, metabolism, survival, and immune response by forming two important complexes, namely, mTOR complex 1 (mTORC1) and complex 2 (mTORC2). mTOR signaling is often dysregulated in cancers and has been considered an attractive cancer therapeutic target. Great efforts have been made to develop efficacious mTOR inhibitors, particularly mTOR kinase inhibitors, which suppress mTORC1 and mTORC2; however, major success has not been achieved. With the strong scientific rationale, the intriguing question is why cancers are insensitive or not responsive to mTOR-targeted cancer therapy in clinics. Beyond early findings on induced activation of PI3K/Akt, MEK/ERK, and Mnk/eIF4E survival signaling pathways that compromise the efficacy of rapalog-based cancer therapy, recent findings on the essential role of GSK3 in mediating cancer cell response to mTOR inhibitors and mTORC1 inhibition-induced upregulation of PD-L1 in cancer cells may provide some explanations. These new findings may also offer us the opportunity to rationally utilize mTOR inhibitors in cancer therapy. Further elucidation of the biology of complicated mTOR networks may bring us the hope to develop effective therapeutic strategies with mTOR inhibitors against cancer.

关键词： mTOR     cancer therapy     resistance     GSK3     protein degradation     E3 ubiquitin ligase     PD-L1    

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Targeted therapy of desmoid-type fibromatosis: mechanism, current situation, and future prospects

Zhen Wang, Jianhui Wu, Xiuyun Tian, Chunyi Hao

《医学前沿（英文）》 2019年 第13卷 第4期   页码 427-437 doi: 10.1007/s11684-018-0672-6

摘要： Desmoid-type fibromatosis (DF) is a rare monoclonal fibroblastic proliferation that is characterized by locally infiltrative but rarely metastatic lesions. Tyrosine kinase and γ-secretase inhibitors are primarily used in the targeted therapy of DF. The use of these drugs, however, is mainly based on the recommendations of retrospective studies with small sample sizes. Previous studies that focused on the mechanism, efficacy, and safety of targeted therapy for DF were reviewed to provide references for clinical applications and research. The efficacy and safety of targeted therapy were compared with those of other systemic therapy options. Targeted therapy does not provide considerable advantages in efficacy and safety over other medical treatments and is usually applied after the failure of antihormonal therapies, nonsteroidal anti-inflammatory drugs, and chemotherapy. Further studies are required to explore the mechanism, indications, and appropriate drug dosage of the targeted therapy of DF.

关键词： targeted therapy     desmoid-type fibromatosis     tyrosine kinase inhibitor     γ-secretase inhibitor    

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标题 作者 时间 类型 操作

Advances in newly developing therapy for chronic hepatitis C virus infection

null

期刊论文

Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide

null

期刊论文

Current recommendations of managing HBV infection in preconception or pregnancy

null

期刊论文

Direct acting antiviral-induced dynamic reduction of serum

Tung Huynh, Ke-Qin Hu

期刊论文

ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

期刊论文

Design, synthesis, and antiviral properties of 2-aryl-1H-benzimidazole-4-carboxamide derivatives

Xianjin LUO, Zhonglü ZHANG, Yutian YANG, Fei XUE, Naiyun XIU, Yuanbin SHE

期刊论文

ROUTE DEVELOPMENT, ANTIVIRAL STUDIES, FIELD EVALUATION AND TOXICITY OF AN ANTIVIRAL PLANT PROTECTANT

Wentao XU, Hao TIAN, Hongjian SONG, Yuxiu LIU, Yongqiang LI, Qingmin WANG

期刊论文

Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

期刊论文

ANTIVIRAL EFFECTS OF BACTERIOCIN AGAINST ANIMAL-TO-HUMAN TRANSMITTABLE MUTATED SARS-COV-2: A SYSTEMATIC

期刊论文

How to judge the association of postmenopausal hormone therapy and the risk of breast cancer

Ling XU

期刊论文

Particle therapy for cancers: a new weapon in radiation therapy

null

期刊论文

Oral administration of

Sufen ZHAO,Yuanyuan JIA,Weiwei ZHANG,Lili WANG,Yunfei MA,Kedao TENG

期刊论文

Passive antibody therapy in emerging infectious diseases

期刊论文

mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?

Shi-Yong Sun

期刊论文

Targeted therapy of desmoid-type fibromatosis: mechanism, current situation, and future prospects

Zhen Wang, Jianhui Wu, Xiuyun Tian, Chunyi Hao

期刊论文