Recombinant Platelet-Activating Factor–Acetylhydrolase Attenuates Paracetamol-Induced Liver Oxidative Stress,Injury, and Regeneration

The aim of this study was to investigate the effects of platelet-activating factor (PAF) inactivator, recombinant PAF-acetylhydrolase (rPAF-AH), on post–paracetamol treatment functional outcome of the liver in the rat. Fifty male Wistar rats were divided into two groups: the control group received a toxic dose of paracetamol (3.5 g/kg body weight [BW]) by gastric tube and the rPAF-AH-treated group received the same dose of paracetamol followed by a dose of rPAF-AH (10 mg/kg BW) intraperitoneally. The animals were sacrificed at time points of 56, 66, 72, 84, and 96 hr after paracetamol treatment. Hepatic injury was evaluated by determination of AST, ALT, and ALP activities and degree of necrosis and apoptosis. Liver regeneration was estimated by [³H]thymidine incorporation into hepatic DNA, liver thymidine kinase activity, and hepatocyte mitotic index. Hepatic levels of malondialdehyde (MDA) and serum cholesterol/high-density lipoprotein cholesterol fraction were also measured as parameters of oxidant–antioxidant balance. The positive effects of rPAF-AH were expressed by (1) reduction of oxidative stress, (2) large decrease in hepatic injury, and (3) diminution of regenerating activity. These results indicate that the use of PAF inactivator enhances the liver’s recovery from paracetamol intoxication and attenuates the severity of experimental liver injury, providing important means of improving liver function following paracetamol intoxication.     

Recombinant protein of tissue inhibitor of metaIloproteinase-3 induces apoptosis of mouse MC3T3-E1 osteoblasts

Objective To investigate the action of recombinantprotein of tissue inhibitor of metalloproteinase-3 (TIMP-3) on apoptosis of MC3T3-E1 osteoblasts. Methods Cell survival rate and apoptosis were measured by MTT and ELISA respectively. The expressions of Fas, FasL, Bel-2, Bax, caspase-3 , caspase-8, cytochrome c and phosphorylations of JNK, p38 and extracellular signalregulated kinase (ERK) 1/2 were analysed by Western blotting. Results TIMP-3 reduced survival rate of MC3T3-E1 cells and promoted apoptosis of MC3T3-E1     

Oncosuppressive Effects of Natural and Recombinant Parvoviruses

The infection of animals with certain autonomous parvoviruses has been shown to have an onco-sup-pressive effect, whilst the viruses themselves have a preferred tropism for transformed cells (oncotropism). However, in many instances, the level of this response is not sufficient for complete suppression of tumorigenesis. Our goal is to enhance the antitumor potential by combining both the intrinsic oncosuppressive and oncotropic determinants of the virus with an additional therapeutic gene in a recombinant parvoviral vector.     

Recombinant factor VIIa: a universal hemostatic agent?

Recombinant factor VIIa (rVIIa) has proved effective for the treatment and prevention of hemorrhage in patients with inherited hemophilia A and B who develop inhibitors to factor VIII or IX, and patients with acquired hemophilia A. More recently, there is evidence that rVIIa may also be effective in the control of abnormal bleeding in a variety of other conditions, such as inherited factor VII deficiency, thrombocytopenia, Glanzmann's thrombasthenia, and liver disease. In some of the reports, rVIIa appeared to be effective in controlling massive hemorrhage in which there was no response to conventional measures. It is now considered by some to be potentially the first universal hemostatic agent. However, further prospective, controlled, and adequately powered clinical studies are clearly required. It will be of particular interest to determine the efficacy of rVIIa in conditions such as severe thrombocytopenia, severe von Willebrand disease, severe defects in platelet activation, and severe deficiencies of factors V, X, II, and fibrinogen in which effectiveness would seem to be unlikely based on our current understanding of mechanisms of action of rVIIa.     

原发性肝癌FT3,FT4,TT3测定的临床意义

４０例原发性肝癌（ＰＨＣ）施行肝动脉栓塞前、后测定了ＦＴ３、ＦＴ４、ＴＴ３、ＴＴ４和ＴＳＨ水平。结果：ＴＡＥ前，ＦＴ３、ＦＴ４、ＴＴ３水平均低于正常人水平（Ｐ〈０．０１）。而ＴＴ４、ＴＳＨ两项有后无差异。本组结果还可见ＴＡＥ后ＦＴ３、ＦＴ４水平下降明显，与ＴＡＥ前差异有显著性意义（Ｐ〈０．０１）。而ＴＴ３与ＴＡＥ前的ＴＴ３相比，差异无显著差异（Ｐ〈０．０５）。另外，ＦＴ３、ＦＴ４值的降低与白蛋白呈     

健康老人血中25OHD3,iPTH,CT,T3,T4水平的变化

血中25羟维生素D_3(25OHD_3)、免疫活性甲状旁腺激素(iPTH)、降钙素(CT)和甲状腺激素(T_3、T_4)直接与钙磷代谢和骨代谢相关,而上述激素浓度变化又与成年后与年龄相关的骨质丢失密切相关。本文以45例80～100岁的健康老人为对象,综合观察其血中25OHD_3、iPTH、CT、T_3和T_4浓度的变化,并特别以32例3～17岁儿童和青少年作为对照进行观察。     

Recombinant Allergen Immunotherapy: Clinical Evidence of Efficacy—A Review

Recombinant allergens for immunotherapy aim to overcome the problems of natural extracts as they can be produced in unlimited amounts with exact physiochemical and immunological properties. These can be modified to have more favourable characteristics including reduced IgE reactivity or enhanced immunogenicity. Different types of recombinant allergens have been evaluated in clinical phase II and III trials whilst others are currently under development. In this review, we identified double-blind, placebo-controlled randomised clinical trials assessing the efficacy and safety of various recombinant allergen preparations. The majority of studies have up to now focused on cat, grass, birch, ragweed and bee venom allergens. Some studies have shown some of these preparations to be effective and well tolerated. However, there are still outstanding issues regarding optimum doses, minimising side effects and long-term effects.     

Recombinant adeno-associated virus carrying thymosin β4 suppresses experimental colitis in mice

AIM To investigate the protective effect of a recombinant adeno-associated virus carrying thymosin β4(AAV-Tβ4) on murine colitis via intracolonic administration.METHODS AAV-Tβ4 was prepared and intracolonically used to mediate the secretory expression of Tβ4 in mouse colons. Dextran sulfate sodium(DSS) was applied to induce the murine ulcerative colitis, and 2,4,6-trinitrobenzene sulfonic acid(TNBS) was used to establish a mouse colitis model resembling Crohn's disease. The disease severity and colon injuries were observed and graded to reveal the effects of AAV-Tβ4 on colitis. The activities of myeloperoxidase(MPO) and superoxide dismutase(SOD) and the content of malondialdehyde(MDA) were determined using biochemical assays. Colonic levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-10 were measured using ELISA, and mucosal epithelial cell apoptosis andproliferation were detected by TUNEL assay and immunochemistry, respectively.RESULTS Recombinant AAVs efficiently delivered Lac Z and Tβ4 into the colonic tissues of the mice, and AAV-Tβ4 led to a strong expression of Tβ4 in mouse colons. In both the DSS and TNBS colitis models, AAV-Tβ4-treated mice displayed distinctly attenuated colon injuries and reduced apoptosis rate of colonic mucosal epithelia. AAV-Tβ4 significantly reduced inflammatory cell infiltrations and relieved oxidative stress in the inflamed colons of the mice, as evidenced by decreases in MPO activity and MDA content and increases in SOD activity. AAV-Tβ4 also modulated colonic TNF-α, IL-1β and IL-10 levels and suppressed the compensatory proliferation of colonic epithelial cells in DSS- and TNBS-treated mice.CONCLUSION Tβ4 exerts a protective effect on murine colitis, indicating that AAV-Tβ4 could potentially be developed into a promising agent for the therapy of inflammatory bowel diseases.     

Recombinant LSDV Strains in Asia: Vaccine Spillover or Natural Emergence?

From 2017 to 2019, several vaccine-like recombinant strains of lumpy skin disease virus (LSDV) were discovered in Kazakhstan and neighbouring regions of Russia and China. Shortly before their emergence, the authorities in Kazakhstan launched a mass vaccination campaign with the Neethling-based Lumpivax vaccine. Since none of the other countries in the affected region had used a homologous LSDV vaccine, it was soon suspected that the Lumpivax vaccine was the cause of these unusual LSDV strains. In this study, we performed a genome-wide molecular analysis to investigate the composition of two Lumpivax vaccine batches and to establish a possible link between the vaccine and the recent outbreaks. Although labelled as a pure Neethling-based LSDV vaccine, the Lumpivax vaccine appears to be a complex mixture of multiple CaPVs. Using an iterative enrichment/assembly strategy, we obtained the complete genomes of a Neethling-like LSDV vaccine strain, a KSGP-like LSDV vaccine strain and a Sudan-like GTPV strain. The same analysis also revealed the presence of several recombinant LSDV strains that were (almost) identical to the recently described vaccine-like LSDV strains. Based on their InDel/SNP signatures, the vaccine-like recombinant strains can be divided into four groups. Each group has a distinct breakpoint pattern resulting from multiple recombination events, with the number of genetic exchanges ranging from 126 to 146. The enormous divergence of the recombinant strains suggests that they arose during seed production. The recent emergence of vaccine-like LSDV strains in large parts of Asia is, therefore, most likely the result of a spillover from animals vaccinated with the Lumpivax vaccine.     

病毒性心肌炎的3个感染期,转归,治疗

各种病毒包括人类免疫缺陷病毒 (HIV)均可引起病毒性心肌炎 (VMC) ,其中肠道病毒 (EV )和柯萨奇 B3病毒(CVB3)是引起 VMC最常见的感染因子 ,在急性病毒感染期大约有 5 %的人群引起局限性或弥漫性心肌炎性病变。 VMC的感染过程因人而异 ,可有 3个期 :即病毒感染早期、病毒感染后期、病毒持续感染期。1　病毒感染早期病毒感染后第 1周嗜心肌病毒直接溶解、损伤心肌细胞 ,病毒在心肌细胞内大量复制。动物试验证明 :大鼠心肌感染病毒后 2～ 5天内心肌细胞搏动逐渐减慢以至停止搏动 ,细胞变圆、团缩崩解 ;感染后 48小时心肌酶 :乳酸脱氢…     

Recombinant human interferonsα,β andγ reduce the antiproliferative action of cytarabine in K562 human myeloid leukaemia clonogenic cells

Summary The effects of recombinant human interferons , and (IFN) on the antiproliferative activity of cytarabine in K562 human myeloid leukaemia clonogenic cells were studied in an agar capillary microassay. The addition of IFN- did not affect the antiproliferative activity of cytarabine in K562 cultures treated with low concentrations of cytarabine (10–50 nM), whereas in those treated with high concentrations (100–150 nM) IFN increased the IC₅₀ of cytarabine on day 5 from 102 nM to 214 nM, i.e., cytarabine combined with IFN was about two-fold less potent than cytarabine alone. Similarly, low concentrations of IFN and IFN did not affect the antiproliferative activity of cytarabine on K562 colonies, but high concentrations of these two interferons: 4×10³ U/ml and 10⁴ U/ml respectively, increased the IC₅₀ of cytarabine on day 5 to 304 nM and to 316 nM respectively, i.e. cytarabine combined with IFN or IFN was about threefold less potent than cytarabine alone. The evaluation of the present negative interactions of interferons with cytarabine is warranted in fresh cells from myeloid leukaemia patients in primary culture.Abbreviation IFN interferon     

Gene Delivery to Intestinal Epithelial Cells In vitro and In vivo with Recombinant Adeno-Associated Virus Types 1, 2 and 5

Intestinal disorders such as inflammatory bowel disease (IBD) result in chronic illness requiring lifelong therapy. Our aim was to evaluate the efficacy of recombinant adeno-associated virus (AAV) vector-mediated gene delivery to intestinal epithelial cells in vitro and in vivo. Human colon epithelial cell lines and colon biopsies were transduced using AAV pseudotypes 2/1, 2/2, and 2/5 encoding green fluorescence protein (GFP). Mice were administered the same vectors through oral, enema, intraperitoneal (IP) injection and superior mesenteric artery (SMA) injection routes. Tropism and efficiency were determined by microscopy, flow cytometry, immunohistochemistry and PCR. Caco2 cells were more permissive to AAV transduction. Human colon epithelial cells in organ culture were more effectively transduced by AAV2/2. SMA injection provided the most effective means of vector gene transfer to small intestine and colonic epithelial cells in vivo. Transgene detection 80 days post AAV treatment suggests transduction of crypt progenitor cells. This study shows the feasibility of AAV-mediated intestinal gene delivery, applicable for the investigation of IBD pathogenesis and novel therapeutic options, but also revealed the need for further studies to identify more efficient pseudotypes. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Recombinant interferon-α may retard progression of early primary myelofibrosis: a preliminary report

The limited effects of current treatments of primary myelofibrosis (PM) led us to prospectively evaluate recombinant interferon-α (rIFNα) in "early" PM patients with residual hematopoiesis and only grade 1 or 2 myelofibrosis. Seventeen patients meeting World Health Organization PM diagnostic criteria received either rIFNα-2b 500 000 to 3 million units 3 times weekly, or pegylated rIFNα-2a 45 or 90 μg weekly. International Working Group for Myelofibrosis Research and Treatment criteria for prognosis and response were used. Eleven patients were women and 6 were men. Their median age at diagnosis was 57 years. Eleven patients were low risk and 6 were intermediate-1 risk. Two achieved complete remission, 7 partial, 1 clinical improvement, 4 stable disease, and 3 had progressive disease. Thus, more than 80% derived clinical benefit or stability. Improvement in marrow morphology occurred in 4. Toxicity was acceptable. These results, with documented marrow reversion because of interferon treatment, warrant expanded evaluation.