1.Recent progress of the aptamer-based antiviral drugs.
Yao ZHU ; Yinghui Lü ; Huiyong YANG ; Junsheng LIN ; Qizhao WANG
Acta Pharmaceutica Sinica 2013;48(4):447-56
Aptamers are capable of binding a wide range of biomolecular targets with high affinity and specificity. It has been widely developed for diagnostic and therapeutic purposes. Because of unique three dimensional structures and cell-membrane penetration, aptamers inhibit virus infection not only through binding specific target, such as the viral envelope, genomic site, enzyme, or other viral components, but also can be connected to each other or with siRNA jointly achieve antiviral activity. Taking human immunodeficiency virus and hepatitis C virus as examples, this paper reviewed the effects and mechanisms of aptamers on disturbing viral infection and replication steps. It may provide an insight to the development of aptamer-based new antiviral drugs.
2.Ribozyme riboswitch based gene expression regulation systems for gene therapy applications: progress and challenges.
Jingxian FENG ; Jiawen WANG ; Junsheng LIN ; Yong DIAO
Acta Pharmaceutica Sinica 2014;49(11):1504-11
Robust and efficient control of therapeutic gene expression is needed for timing and dosing of gene therapy drugs in clinical applications. Ribozyme riboswitch provides a promising building block for ligand-controlled gene-regulatory system, based on its property that exhibits tunable gene regulation, design modularity, and target specificity. Ribozyme riboswitch can be used in various gene delivery vectors. In recent years, there have been breakthroughs in extending ribozyme riboswitch's application from gene-expression control to cellular function and fate control. High throughput screening platforms were established, that allow not only rapid optimization of ribozyme riboswitch in a microbial host, but also straightforward transfer of selected devices exhibiting desired activities to mammalian cell lines in a predictable manner. Mathematical models were employed successfully to explore the performance of ribozyme riboswitch quantitively and its rational design predictably. However, to progress toward gene therapy relevant applications, both precision rational design of regulatory circuits and the biocompatibility of regulatory ligand are still of crucial importance.
3.Early diagnosis and interventional therapy of acute renal infarction
Yunhua LIN ; Junsheng WANG ; Yongguang JIANG ; Yunpeng CHI
Chinese Journal of Urology 2012;(11):851-855
Objective To discuss the early diagnosis and interventional therapy of acute renal infarction.Methods The diagnosis and therapy of 5 cases of acute renal infarction were retrospectively analyzed.There were 4 male and 1 female patients,aged 38-68 years.The symptoms were severe back pain or upper abdominal pain,with or without nausea and vomiting and the time to hospital was 1 to 16 h.Four cases had rheumatic heart disease and 4 cases had artrial fibrillation history.The lab assay results: WBC 8.9-15.8 × 109/L,urine RBC-to + + +,albumin + to + + +,serum creatinin 66-216 μmol/L,serum LDH 350-920 U/L.The doppler ultrasound and CT scan showed large infarction in 3 cases and focal infarction in 2 cases.Percutaneous arteriography,thrombolytic therapy and thrombosuction via catheter were applied promptly.Results The 5 cases were diagnosed and treated timely and effectively.The emboli were cleared.Four patients were followed up for 3-12 months.The creatinin recovered to 53-122 μmol/L,and the blood perfusion of the infarction lesion was satisfactory.Conclusions Early diagnosis and interventional therapy is important for achieving satisfactory recovery of the acute renal infarction.Three dimensional CT angiography could conduce to early diagnosis and follow-up.Thrombosuction via catheter plus thrombolytic therapy is efficient for greater embolus.
4.THE NUTRITION SURVEY OF DIETARY STRUCTURE AND VITAMIN A STATUS IN LONG-HAUL TRUCK DRIVERS
Zejian FU ; Wenling MA ; Dongyi TAO ; Guangfei XU ; Jing LIN ; Junsheng GUO
Acta Nutrimenta Sinica 1956;0(01):-
Objective To investigate the dietary structure in long-haul truck drivers,especially their vitamin A(VA) intake,food sources and serum level.Method One hundred and forty-five long-haul truck drivers were enrolled.A 24-hour dietary recall was conducted by food frequency questionnaire using three-dimensional food models.Serum VA was measured by HPLC.Results The average intake of energy,protein,fat and carbohydrate in working days was 3.95 MJ(945 kcal/d,35.0%RNI),40.7g/d(17.2% energy),20.5g/d(19.5% energy),134.5g/d(56.9% energy) respectively.In rest days,the average intake of energy,protein,fat and carbohydrate was 11.72 MJ(2802 kcal/d,116.8%RNI),118.5g/d(15.0% energy),92.4g/d(37.7% energy),307.2g/d(38.9% energy) respectively.VA intake was 252.6?gRE/d(31.5% RNI) in working days compared to 602.3?gRE/d(75.2% RNI) in rest days.The average serum VA concentration was 583 ?g RE/L,and the prevalence of serum VA
5.Lateral ligament of the rectum-anatomical or surgical terminology
Moubin LIN ; Weiguo CHEN ; Zhiming JIN ; Jindi NI ; Junsheng NI ; Zhaofang BAO ; Lu YIN
Chinese Journal of General Surgery 2008;23(9):686-688
Objective To study the clinical topography of lateral ligament of the rectum in the relation to surgical procedures in rectal carcinoma. Method Twenty-three pelvises(12 males,11 females)harvested from embalmed cadavers were studied by topographic dissection. Results The lateral rectal ligamem were identiffed bilaterally in all cadavers between the rectum and visceral fascia.Unilateral middle rectal arteries was found in 8 cadavers and bilateral arteries was found in 2 cadavers.The rectal branches from the pelvic plexus were uniformly constant structure within lateral ligament of the rectum.Conclusion The lateral rectal ligament is located between rectum and visceral fascia.The cleavage between visceral fascia and pelvic plexus is the appropriate plane for lateral rectal dissection of rectal cancers.
6.Osteogenesis and angiogenesis of tissue-engineered biomimetic periosteum constructed by combination of small intestinal submucosa matrix with bone marrow mesenchymal stem cells in rabbits
Lin ZHAO ; Shuanke WANG ; Ping DONG ; Junsheng WANG ; Jia LIU ; Junlong HAO ; Meng WU
Chinese Journal of Tissue Engineering Research 2009;13(51):10079-10082
OBJECTIVE: To investigate the in vivo possibility of osteogenesis and angiogenesis of tissue-engineered periosteum in rabbits.METHODS: The marrow mesenchymal stem cells (MSCs) derived from New Zealand rabbits were adhered to small intestinal submucosa (SIS) to fabricate the tissue-engineered periosteum. Totally 12 New Zealand rabbits were received critical bone defect in bilateral radii to prepare models. The tissue-engineered periosteum was randomly implanted in one side of bone defect,and the other side was treated by SIS. At 4 weeks after operation, the angiogenesis of tissue engineered bone was detected by Tetracycline fluorescence microscopy and formaldehyde-ink perfusion method; simultaneously, the new bone formation was firmed by haematoxylin-eosin staining.RESULTS: Animals showed normal daily behaviors and non-infection wounds healing. The gross observation showed that bone defects in the experimental side were bridged with newly formed bone; while the defects of the control side were remained empty.Tetracycline fluorescence microscopy and hisotological examination could confirm the new bone tissue formation in the experimental side. The ink staining in new bone specimens suggested that there were abundant of neovasculization in tissue-engineered bone.CONCLUSION: Tissue-engineered periosteum can form new bone in allogenic rabbits and can be vascularized by some inherent mechanism for new bone tissue survivor.
7.Association of ABO genotype with acute rejection in renal transplantation
Lixin YU ; Youcheng LIN ; Wenfeng DENG ; Yibin WANG ; Junsheng YE ; Yun MIAO ; Lulu XIAO
Chinese Journal of Urology 2010;31(12):814-817
Objective To investigate a possible association of donor-recipient compatibility for ABO blood group alleles with acute rejection (AR) in renal transplantation. Methods A study comprising 87 pairs of donor and recipient was performed. The ABO genotype A1, A2, O1, O2, and B alleles of renal transplanted recipients and their respective donors were assessed by PCR amplification with sequence-specific primers (PCR-SSP). Accordingly, recipients were divided into donor-recipient ABO genotype matched and mismatched groups. Results The PCR-SSP based types of all cases showed total concordance with their serologically assigned ABO groups. Fifty pairs (57. 5%) were matched for ABO genotype among the 87 pairs of donor and recipient while 37 (42. 5%) were mismatched, including 1 allele mismatch in 31 pairs (83.8%), 2 alleles mismatches in 6 pairs (16. 2%).The incidence of AR was 12.0% (6 cases) and 29. 7% (11 cases) for ABO genotype matched and mismatched transplant patients, respectively ( P < 0.05). After high dose methylprednisolone (MP)treatment, all cases exepienced reversion of AR except a A2O1 recipient receiving kidney from a A1O1enced 4 AR episodes within 3-10 months, and the period of AR was gradually shortened. After high dose MP was administered empirically, even though short-term improvement of renal function was observed, the serum creatinine continued to increase progressively with decreased efficacy of high dose MP. One year after operation the serum creatinine rose to 441 μmol/L. Conclusions Simultaneous definition of the ABO genotype and HLA is highly feasible. The A2 patient is suitable for receiving kidneys from blood group O donors. DNA mismatch for ABO genotype of renal transplant recipients and their respective donors is an independent risk factor for AR. Genotyping of ABO blood group is conducive to prevent AR.
8.Expression of human long-acting FSH in CHO cell and its bioactivity in vivo.
Xiaoping HUANG ; Xiao WANG ; Chunxue YANG ; Dongfang JIA ; Junsheng LIN ; Yong DIAO
Chinese Journal of Biotechnology 2014;30(6):954-961
Follicle-stimulating hormone (FSH) is a pituitary glycoprotein hormone that is essential for the development of ovarian follicles and testicular seminiferous tubules. The relatively short half-life of FSH in vivo requires daily injections for more than 10 days that is inconvenient and possibly contribute to the stress perceived by the patients. The goal of the present study was to increase FSH glycosylation, in order to develop a long-acting recombinant FSH. The cDNA of native alpha and beta subunit of human FSH was linked by a sequence with two N-linked glycosylation sites, and the resulted DNA was inserted into pcDNA3.1 vector to generate a recombinant vector of pcDNA3.1-FSH. The pcDNA3.1-FSH was linearized and transfected into CHO-K1, positive transformants were selected by G418 and confirmed by PCR and Western blotting. A single chain recombinant FSH was expressed, with molecular weight of about 49 kDa. The recombinant FSH expression level in CHO-K1 cell strain in serum-free culture was 3 mg/L. Single injection of this recombinant FSH could induce folliculogenesis and ovulation in rats, the efficacy was similar with the commercially available FSH preparation (Folltropin-V) administrated 8 times consecutively. The results suggested a long-acting FSH was produced successfully.
Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Female
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Follicle Stimulating Hormone, Human
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biosynthesis
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Genetic Vectors
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Half-Life
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Humans
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Ovarian Follicle
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drug effects
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Ovulation
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drug effects
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Rats
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Recombinant Proteins
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biosynthesis
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Transfection
9.The effect of Connexin43 downregulation on biological functions of HUVEC.
Caizhen ZHANG ; Xiaofeng MU ; Xianxiang XU ; Fei QIU ; Junsheng LIN ; Yong DIAO
Acta Pharmaceutica Sinica 2015;50(3):298-304
Connexin43 has been shown to play a pivotal role in wound healing process. Wound repair is enhanced by acute downregulation of connexin43, by increasing proliferation and migration of keratinocyte and fibroblast. Angiogenesis is also a central feature of wound repair, but little is known about the effects of connexin43 modulation on functions of endothelial cells. We used connexin43 specific small interference RNA (siRNA) to reduce the expression of connexin43 in human umbilical vein endothelial cell (HUVEC), and investigated the effects of connexin43 downregulation on intercellular communication, viability, proliferation, migration and angiogenic activity of HUVEC. Treatment of siRNA markedly reduced the expression of connexin43 by -80% in HUVEC (P < 0.05), and decreased the intercellular communication by -65% (P < 0.05). The viability, proliferation, migration and angiogenic activity of HUVEC decreased significantly (P < 0.05), compared with that of the normal cells. The results suggest that temporally downregulation of connexin43 expression at early stage of wound to inhibit the abnormal angiogenesis characterized with leaky and inflamed blood vessels, maybe a prerequisite for coordinated normal healing process.
10.Long-term efficacy of low dose leflunomide in the treatment of rheumatoid arthritis
Jun WANG ; Biya ZU ; Deshuai LIN ; Junsheng YANG ; Xueyong QIN ; Ming LIAO
Clinical Medicine of China 2012;28(4):364-367
Objective To perspectively evaluate the long-term efficacy of low dose leflunomide in treatment of rheumatoid arthritis.Methods Twenty-eight patients with rheumatoid arthritis were randomly divided into treatment group( n =15 ) and control group ( n =13 ).The patients in treatment group were treated with low dose leflunomide( omitting the loading dose) and with maintenance dose of 10 mg/day.And the patients in control group were treated with sulphasalazine in the dose of 1.5 ~ 2.0 g/d.The observation lasted for 18 months and the observed indicator were as follows:( 1 ) The primary efficacy indicators:counts of swollen and tender joints,overall assessment of disease status made by patients and physicians; ( 2 ) Secondary efficacy indicators:pain visual analogue scale,duration of morning stiffness,health assessment questionnaire (HAQ),Creaction protein,the American College of Rheumatology Outcome Assessment (ACR20,50).Results Eighteen months after treatment,the primary efficacy indicators in the treatment group were superior to the control group ( swollen joint counts:( - 8.5 ± 6.3 ) vs ( - 7.9 ± 6.4) ; overall assessment by patients:( - 1.4 ± 0.8 ) points vs ( - 1.2 ± 0.6) points; overall assessment by physicians:( - 1.4 ± 1.2 ) points vs ( - 1.3 ± 0.9 ) points; P <0.01 ).In the secondary efficacy indicators,pain visual analogue scale,duration of morning stiffness and health assessment questionnaire(HAQ) in the treatment group were significantly improved compared with the control group(VAS score:( - 32.4 ± 23.7) points vs ( - 31.6 ± 24.8) points; duration of morning stiffness:( [ - 97.8 ± 6.2 ] min vs [ - 92.4 ± 5.2 ] min; HAQ:[ - 0.62 ± 0.08 ] points vs [ - 0.57 ± 0.02 ] points,P <0.01 ),there was no significant difference on the percentage of patients achieving ACR20 standard between the treatment group and the control group (76.9% vs 75.0%,P > 0.05 ),but there was significant difference on the percentage of patients achieving ACRS0 standard between the treatment group and the control group( 61.5% vs 47.0%,P < 0.05 ).The gastrointestinaladverse reactions for patients in the treatment group were mild and there were 2 cases of elevated blood pressure,2 cases of elevated liver enzymes and 2 cases out of the trail,in the control group,there was 1 case out of the trial.Conclusion The long-term treatment of active rheumatoid arthritis with low dose leflunomide can achieve exact efficacy and good tolerability compared with the treatment with sulfasalasine.