Excess dietary Lys reduces feed intake, stimulates jejunal CCK secretion and alters essential and non‑essential blood AA profile in pigs

Background Commercial diets are frequently formulated to meet or exceed nutrient levels including those of lim-iting essential amino acids(AA)covering potential individual variations within the herd.However,the provision of dietary excess of AA,such as Lys,may lead to reduced appetite and growth in pigs.The mechanisms modulat-ing these responses have not been extensively investigated.This study evaluated the effect of Lys dietary excesses on performance and satiety biomarkers in post weaning pigs.Methods Twenty-four pigs aged 21 d and weighing 6.81±0.12kg(mean±SEM)were individually housed and offered 1 of 4 dietary treatments for 3weeks:a diet containing a standardized ileal digestible Lys reaching 100%(T0),120%(T1),150%(T2)or 200%(T3)of the NRC(2012)requirements.At the end of the experiment,blood samples from the cephalic vein of the T0 and T3 groups were obtained for AA analysis.In addition,primary intestinal cultures from T0 pigs were used,following their humane killing,to evaluate the effect of Lys on gut hormone secretion and AA sensors gene expression under ex vivo conditions.Results Feed intake was linearly reduced(P<0.001)and the weight gain to feed ratio reduced(P<0.10)with increased dietary levels of Lys during the third-and first-week post weaning,respectively.Cholecystokinin con-centration(P<0.05)and the metabotropic glutamate receptor 1 and the solute carrier family 7 member 2(P<0.10)gene expression was enhanced in proximal jejunum tissues incubated with Lys at 20mmol/L when compared to the control(Lys 0mmol/L).Plasma Lys and Glu(P<0.05)concentration increased in the T3 compared to T0 pigs.In contrast,plasma levels of His,Val,Thr,Leu(P<0.05)and Gln(P<0.10)were lower in T3 than T0 pigs.Conclusion The present results confirm that excess dietary Lys inhibits hunger in pigs.Moreover,the results provide evidence of pre-and post-absorptive mechanisms modulating these responses.Lys dietary excesses should be nar-rowed,when possible,to avoid negative effects of the AA on appetite in pigs.

Detection and Analysis of Routine Blood Indexes in Guike Pig

[Objectives] In this study,routine blood indexes of Guike pig were detected to clarify quantity variation and morphology distribution of different functional cells（ red blood cells,white blood cells and platelets）,thus providing reference data for immunological evaluation and disease resistance research of Guike pig. [Methods] Blood samples were collected from forty-four 49-day-old healthy Guike pigs（ 22 males and 22 females） once a week for seven consecutive weeks to detect routine blood indexes,and the results were compared with routine blood indexes of Landrace pig and Enshi black pig. [Results]Among red blood cell indexes of Guike pig at different day ages,red blood cell count（ RBC） and hemoglobin count（ HGB） both reached the lowest levels（ 6. 85 × 10^12/L and 97. 1 g/L）at 70 days of age,which were significantly lower than the corresponding indexes at 49,56,63,84 and 91 days of age（ P 〈 0. 05,similarly hereinafter）; mean corpuscular hemoglobin（ MCH） and mean corpuscular hemoglobin concentration（ MCHC） demonstrated basically the same variation pattern,which both reached the lowest levels（ 15. 11 pg and 275. 70 g/L） at 70 days of age and reached the highest levels（ 16. 40 pg and 314. 30 g/L） at 91 days of age; hematocrit（ HCT）,mean corpuscular volume（ MCV） and red blood cell distribution width（ RDW） exhibited relatively stable changes with no significant differences among different day ages（ P 〉 0. 05,similarly hereinafter）. Among white blood cell indexes of Guike pig at different day ages,white blood cell count（ WBC） reached the lowest level（ 13. 71 × 10^9/L） at 63 days of age and reached the highest level（ 17. 52 × 10^9/L） at 84 days of age,with significant differences; neutrophil count（ NEUT）reached the lowest level（ 3. 61 × 10^9/L） at 70 days of age,which was significantly lower than that at 49,56 and 77 days of age; lymphocyte count（ LYMPH） exhibited relatively stable changes and was not significantly affected by the increase in day age. Among platelet indexes of Guike pig at different day ages,platelet count（ PLT）,thrombocytocrit（ PCT） and platelet volume distribution width（ PDW） exhibited relatively stable changes among different day ages,which were not significantly affected by the increase in day age. Compared to 35-day-old Landrace pig and 5-month-old Enshi black pig,most routine blood indexes of Guike pig were similar to or ranged between those of Landrace pig and Enshi black pig except HCT,mean platelet volume（ MPV）,PCT and PDW. [Conclusions]Guike pig has a certain uniqueness in routine blood indexes,which has developed a stable immune system at 49-91 days of age.

Assessment of the Acute Effects of DEE （Diesel Exhaust Emitted） on Blood Parameters in Guinea Pigs Cavia porcellus

The acute （15 minutes-4 hours） effects of exposure to the inhaled DEE （diesel exhaust emitted） on blood parameters of Guinea pigs Cavia porcellus were assessed via CBC （complete blood count） as an indicator using an automated blood analyzer machines （Cell DYN 1700）. The results showed significant changes in some parameters in comparison with control animals started as early as 15 minutes and intensified by the continuous exposure time, leading to significant increase （p 〈 0.05） in the number of both WBC （white blood cells）, PLT （blood platelets） and decrease in numbers of RBC （red blood corpuscles） while hemoglobin percentages （Hb%） showed an insignificant （p 〉 0.05） fluctuating rhythm. The percentages of both Neutrophil and Lymphocyt recorded a significant increase （p 〈 0.05） 1 hour post-exposure to the DEE while other WBCs showed less changes. It is concluded that blood components are so sensitive to DEE and do respond quicker to inhaled pollutants via changes in some components of WBC% but decrease in RBC% and the likelihood of blood clotting due to increase in blood platelets. These results indicate the acute toxic risks of the exposure to DEE of mechanics and technicians who work in vicinity of DEE sources or/and spend most daily hours in semi closed areas.

Optimization of Chelation Process for Complex Microelement Iron Supplement Derived from Pig Blood by Response Surface Methodology

[Objectives]This study aimed to optimize the chelation process for complex microelement iron supplement derived from pig blood by response surface methodology.[Methods]On the basis of single-factor test,p H value,concentration of polypeptide solution and volume ratio of polypeptide solution to FeCl_2 solution were selected as influencing factors with Fe(II)chelation rate as the indicator for Box-Behnken central composite experimental design with three factors and three levels.The effects of three factors on the response value were analyzed by response surface methodology.[Results]The optimized chelation process for complex microelement iron supplement derived from pig blood by response surface methodology was as follows:pH 5.40,polypeptide solution concentration 2.27%,volume ratio of polypeptide solution to FeCl_2 solution 2.16∶1.Under this condition,the predictive Fe(II)chelation rate of iron supplement was 79.37%,while the actual value was 79.41%.[Conclusions]The optimized process may provide new thoughts for the development and utilization of complex microelement iron supplement derived from pig blood.

Serum anti‑blood type IgG/IgM binding and cytotoxicity to pig PBMC and RBC

Objective: TO investigate the killing differences of human blood group antibodies IgG and IgM on PBMC and RBC in peripheral blood of genetically modified pigs, and provide theoretical basis for the selection of pig blood group for clinical application of porcine xenotransplantation. Methods: Serum samples were collected from 20 healthy subjects, 20 patients with end‑stage renal disease and 20 brain dead organ donors, and divided into 4 groups on the basis of ABO blood group (A: n=20;B: n=17;AB: n=7;O: n=16). Flow cytometry was used to detect antibody binding or complement dependent cytotoxicity test (CDC) between human serum and O blood group Wild‑type (WT), α1, 3‑galactosyltransferase gene‑knockout(GTKO), cytidine monophosphate‑N‑acetylneuraminic acid hydroxylase gene‑knockout (GTKO/β4GalNT2KO), β‑1, 4N‑acetylgalactosaminyltransferase gene‑knockout(GTKO/CMAHKO) and mononuclear cells (PBMC) and red blood cells (RBC) of Triple knockout (TKO/hCD55) porcine peripheral blood, respectively. Results: There was no significant difference in binding and killing of human serum antibodies with blood group A, B, AB and O on PBMC of WT pigs, GTKO pigs, GTKO/β4GalNT2KO pigs, GTKO/CMAHKO pigs and TKO/hCD55 pigs, respectively. There was no significant difference in RBC binding with RBC of WT pig, GTKO pig, GTKO/β4GalNT2KO pig, GTKO/CMAHKO pig and TKO/hCD55 pig. Conclusion: The selection of recipients of pigs with type O blood group can be done without considering blood group.

The relationship of tension and blood flow of the expanded pedicled fasciocutaneous flap in pig

Objective To evaluate the effect of wound closure tension on the blood flow of the expanded pedicled fasciocutaneous flap,so as to find the best tension for the blood supply of the flap.Methods 8 piglets,aged 9-12 months,were used.On

Isolation,Screening and Identification of High-temperature Cellulolytic Microbes in Pig Manure

[Objective] The research aimed to lay the foundation for high-efficiency biological degradation microbial inoculums. [Method] under the 60℃ temperature the cellulolytic microbes in pig manure were isolated and determined the CMCase and Fpase,then proceeded the 16S rRNA gene analysis. [Result]The results showed that:BC1 and BC3 strains characterized higher carboxymethyl cellulose enzyme activity and higher filter paper activity,but their difference was small,then the 16S rDNA sequence of BC1 and BC3 strains were related to pseudomonas sp. (98% and 99% similarities,respectively).[Conclusion] the experiment laid foundation for high-efficiency biological heating agent.

献血者HBVs基因变异的生物信息学分析

目的分析HBV DNA+/HBsAg-献血者的传染性指标、S区基因序列突变情况及生物信息学特征变化。方法通过PCR方法筛查出1份HBV DNA+/HBsAg-的标本,应用酶联免疫和化学发光方法检测该标本乙肝病毒5项指标,对该标本HBVs区基因片段测序并分析变异情况,应用分析软件对所测序列进行生物信息学分析。结果该标本HBV DNA+、HBsAg-、HBsAb+、HBeAg+、HBeAb-、HBcAb+;HBVs区基因序列内发生氨基酸单位点突变(P151L),空间结构发生改变。结论HBVs区基因序列空间结构改变,可能是导致检测结果出现血清学HBsAg-/HBsAb+/HBV DNA+的原因。

The potential of genetically-engineered pigs in providing an alternative source of organs and cells for transplantation

There is a critical shortage of organs, cells, and corneas from deceased human donors worldwide. There are also shortages of human blood for transfusion. A potential solution to all of these problems is the transplantation of organs, cells, and corneas from a readily available animal species, such as the pig, and the transfusion of red blood cells from pigs into humans. However, to achieve these ends, major immunologic and other barriers have to be overcome. Considerable progress has been made in this respect by the genetic modification of pigs to protect their tissues from the primate immune response and to correct several molecular incompatibilities that exist between pig and primate. These have included knockout of genes responsible for the expression of major antigenic targets for primate natural anti-pig antibodies, insertion of human complement- and coagulation-regulatory transgenes, and knockdown of swine leukocyte antigens that stimulate the primate＇s adaptive immune response. As a result of these manipulations, the administration of novel immunosuppressive agents, and other innovations, pig hearts have now functioned in baboons for 6-8 months, pig islets have maintained normoglycemia in diabetic monkeys for 〉 1 year, and pig corneas have maintained transparency for several months. Clinical trials of pig islet trans- plantation are already in progress. Future developments will involve further genetic manipulations of the organ- source pig, with most of the genes that are likely to be beneficial already identified.

S-100β CysC和NF-κB对急性缺血性脑卒中患者静脉溶栓后出血转化的预测价值

目的 探讨急性缺血性脑卒中(AIS)外周血中S-100β、CysC和NF-κB水平对静脉溶栓后出血转化的影响及预测价值。方法 收集2019-03—2022-03接受溶栓治疗的AIS患者140例,根据溶栓后24 h是否发生出血转化(HT)将患者分为非HT组(n=112)和HT组(n=28)。比较2组一般临床资料,采用多因Logistic回归分析影响HT发生的危险因素,受试者工作特征(ROC)曲线评估S-100β、CysC和NF-κB预测HT发生的价值。结果 HT组与非HT组相比,患者年龄、发病至溶栓时间、房颤、TOAST分型、C反应蛋白、凝血酶原时间、S-100β、CysC、NF-κB、白质高信号和脑微出血等均有统计学差异(P<0.05)。Logistic多因素回归分析显示,房颤、S-100β、CysC和NF-κB为影响HT发生的危险因素。S-100β、CysC和NF-κB预测AIS患者静脉溶栓后出血转化的曲线下面积分别为0.915(0.902~0.923)、0.874(0.856~0.882)和0.789(0.771~0.796),均具有一定的预测价值。结论 S-100β、CysC和NF-κB为AIS患者静脉溶栓后HT发生的危险因素,对HT发生具有一定的预测价值。

LARGELY IMPROVED BLOOD COMPATIBILITY OF POLYURETHANE BY BLENDING WITH FLUORINATED PHOSPHATIDYLCHOLINE POLYURETHANE

The improvement of biocompatibility of polyurethanes was investigated.The results demonstrate that the blood compatibility of polyurethanes can be further improved by just simply mixing with the fluorinated phosphatidylcholine poly(carbonate urethane)s(FPCPCUs).The solution blending was done by mixing poly(ether urethane)(PEU)with FPCPCU in different compositions.An increased blood compatibility of the blend films was observed with the increase of FPCPCU content,and when FPCPCU content reached to 40 wt%(40F...

Gastric emptying, postprandial blood pressure, glycaemia and splanchnic flow in Parkinson's disease

AIM: To determine gastric emptying, blood pressure, mesenteric artery blood flow, and blood glucose responses to oral glucose in Parkinson’s disease.METHODS: Twenty-one subjects (13 M, 8 F; age 64.2 ± 1.6 years) with mild to moderate Parkinson’s disease (Hoehn and Yahr score 1.4 ± 0.1, duration of known disease 6.3 ± 0.9 years) consumed a 75 g glucose drink, labelled with 20 MBq 99mTc-calcium phytate. Gastric emptying was quantified with scintigraphy, blood pressure and heart rate with an automated device, superior mesenteric artery blood flow by Doppler ultrasonography and blood glucose by glucometer for 180 min. Autonomic nerve function was evaluated with cardiovascular reflex tests and upper gastrointestinal symptoms by questionnaire.RESULTS: The mean gastric half-emptying time was 106 ± 9.1 min, gastric emptying was abnormally delayed in 3 subjects (14%). Systolic and diastolic blood pressure fell (P < 0.001) and mesenteric blood flow and blood glucose (P < 0.001 for both) increased, following the drink. Three subjects (14%) had definite autonomic neuropathy and 8 (38%) had postprandial hypotension. There were no significant relationships between changes in blood pressure, heart rate or mesenteric artery blood flow with gastric emptying. Gastric emptying was related to the score for autonomic nerve function (R = 0.55, P < 0.01). There was an inverse relationship between the blood glucose at t = 30 min (R = -0.52, P < 0.05), while the blood glucose at t = 180 min was related directly (R = 0.49, P < 0.05), with gastric emptying.CONCLUSION: In mild to moderate Parkinson’s disease, gastric emptying is related to autonomic dysfunction and a determinant of the glycaemic response to oral glucose.

Emotion processing in Parkinson's disease: a blood oxygenation level-dependent functional magnetic resonance imaging study

Parkinson's disease is a neurodegenerative disorder caused by loss of dopamine neurons in the substantia nigra pars compacta. Tremor, rigidity, and bradykinesia are the major symptoms of the disease. These motor impairments are often accompanied by affective and emotional dysfunctions which have been largely studied over the last decade. The aim of this study was to investigate emotional processing organization in the brain of patients with Parkinson's disease and to explore whether there are differences between recognition of different types of emotions in Parkinson's disease. We examined 18 patients with Parkinson's disease(8 men, 10 women) with no history of neurological or psychiatric comorbidities. All these patients underwent identical brain blood oxygenation level-dependent functional magnetic resonance imaging for emotion evaluation. Blood oxygenation level-dependent functional magnetic resonance imaging results revealed that the occipito-temporal cortices, insula, orbitofrontal cortex, basal ganglia, and parietal cortex which are involved in emotion processing, were activated during the functional control. Additionally, positive emotions activate larger volumes of the same anatomical entities than neutral and negative emotions. Results also revealed that Parkinson's disease associated with emotional disorders are increasingly recognized as disabling as classic motor symptoms. These findings help clinical physicians to recognize the emotional dysfunction of patients with Parkinson's disease.

Correlations of PCBs, DIOXIN, and PBDE with TSH in Children's Blood in Areas of Computer E-waste Recycling

Objective To study correlations of polychlorinated biphenyls （PCBs）, DIOXIN, and polybrominated diphenyl ethers （PBDE） with thyroid stimulating hormone（TSH） in children, and assess the impact on children＇s health. Methods Three hundred and sixty nine children aged from 6 to 8, including 195 from Luqiao, the computer E‐waste recycling area, and 174 from Longyou, the control area, were selected for this investigation to elucidate the correlation of PCBs, DIOXIN, and PBDE with TSH in children’s blood samples. The children had a physical examination and their blood levels of PCBs, DIOXIN, PBDE, and TSH were detected after sample collection. Results In the E‐waste recycling area, the contents of PCBs, PBDE, DIOXIN, and TSH in the blood samples of children were 484.00±84.86 ng·g ‐1 lipid weight, 664.28±262.38 ng·g ‐1 lipid weight, 26.00±19.58 ng·g ‐1 lipid weight and 1.88±0.42 μIU/mL （serum） respectively, while in the control area, the PCBs, PBDE, DIOXIN, and TSH contents were 255.38±95 ng·g ‐1 lipid weight, 375.81±262.43 ng·g ‐1 lipid weight, 39.64±31.86 ng·g ‐1 lipid weight, and 3.31±1.04 μIU/mL respectively. Conclusion The health status of children in the control area are better than that in the contaminated area. Among children who are exposed to persistent organic pollutants, the pollutant content increases significantly in their serum, and the distribution of TSH levels in their bodies are also affected.

Prognostic significance of red blood cell distribution width in gastrointestinal disorders

The red blood cell distribution width(RDW) is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis. Recently,the baseline RDW was found to have clinical significance for assessing clinical outcome and severity of various pathological conditions including cardiovascular diseases,sepsis,cancers,leukemia,renal dysfunction and respiratory diseases. A myriad of factors,most of which ill-defined,have an impact on the red cell population dynamics(i.e.,production,maturation and turnover). A delay in the red blood cell clearance in pathological conditions represents one of the leading determinants of increased anisocytosis. Further study of RDW may reveal new insight into inflammation mechanisms. In this review,we specifically discuss the current literature about the association of RDW in various disease conditions involving the gastrointestinal and hepatobiliary systems. We also present some of the related measurements for their value in predicting clinical outcomes in such conditions. According to our data,RDW was found to be a valuable prognostic index in gastrointestinal disorders along with additional inflammatory biomarkers(i.e.,C reactive protein,erythrocyte sedimentation rate,and platelet count) and current disease severity indices used in clinical practice.

Effects of dietary Hermetia illucens meal inclusion on cecal microbiota and small intestinal mucin dynamics and infiltration with immune cells of weaned piglets

Background: The constant interaction between diet and intestinal barrier has a crucial role in determining gut health in pigs. Hermetia illucens(HI) meal(that represents a promising, alternative feed ingredient for production animals) has recently been demonstrated to influence colonic microbiota, bacterial metabolite profile and mucosal immune status of pigs, but no data about modulation of gut mucin dynamics are currently available. The present study evaluated the effects of dietary HI meal inclusion on the small intestinal mucin composition of piglets, as well as providing insights into the cecal microbiota and the mucosal infiltration with immune cells.Results: A total of 48 weaned piglets were randomly allotted to 3 dietary treatments(control diet [C] and 5% or10% HI meal inclusion [HI5 and HI10], with 4 replicate boxes/treatment and 4 animals/box) and slaughtered after61 days of trial(3 animals/box, 12 piglets/diet). The cecal microbiota assessment by 16 S r RNA amplicon based sequencing showed higher beta diversity in the piglets fed the HI-based diets than the C(P < 0.001). Furthermore,the HI-fed animals showed increased abundance of Blautia, Chlamydia, Coprococcus, Eubacterium, Prevotella,Roseburia, unclassified members of Ruminococcaceae, Ruminococcus and Staphylococcus when compared to the C group(FDR < 0.05). The gut of the piglets fed the HI-based diets showed greater neutral mucin percentage than the C(P < 0.05), with the intestinal neutral mucins of the HI-fed animals being also higher than the sialomucins and the sulfomucins found in the gut of the C group(P < 0.05). Furthermore, the piglets fed the HI-based diets displayed lower histological scores in the jejunum than the other gut segments(ileum [HI5] or ileum and duodenum [HI10], P < 0.05).Conclusions: Dietary HI meal utilization positively influenced the cecal microbiota and the small intestinal mucin dynamics of the piglets in terms of selection of potentially beneficial bacteria and preservation of mature mucin secretory architecture, without determining the development of gut inflammation. These findings further confirm the suitability of including insect meal in swine diets.

Cerebrospinal fluid and blood biomarkers in Alzheimer’s disease

Due to an ever aging society and growing prevalence of Alzheimer’s disease(AD),the challenge to meet social and health care system needs will become increasingly difficult.Unfortunately,a definite ante mortem diagnosis is not possible.Thus,an early diagnosis and identification of AD patients is critical for promising,early pharmacological interventions as well as addressing health care needs.The most advanced and most reliable markers areβ-amyloid,total tau and phosphorylated tau in cerebrospinal fluid(CSF).In blood,no single biomarker has been identified despite an intense search over the last decade.The most promising approaches consist of a combination of several bloodbased markers increasing the reliability,sensitivity and specificity of the AD diagnosis.However,contradictory data make standardized testing methods in longitudinal and multi-center studies extremely difficult.In this review,we summarize a range of the most promising CSF and blood biomarkers for diagnosing AD.

The effects of anisodamine and dobutamine on gut mucosal blood flow during gut ischemia/reperfusion

AIM: To determine if anisodamine is able to augment mucosal perfusion during gut I/R ischemia-reperfusion. METHODS: A jejunal sac was formed in Sprague Dawley rat. A Laser Doppler probe and a tonometer were inserted into the sac which was filled with saline. The superior mesenteric artery was occluded (SMAO)for 60 minutes followed by 90 minutes of reperfusion. At the end of 60 minutes of SMAO, either 0.2 mg/kg of anisodmine or dobutamine was injected into the jejunal sac. Laser Doppler mucosal blood flow and regional PCO2 (PrCO2)measurements were made. RESULTS: Mucosal blood flow was significantly increased at 30,60 and 90 minutes of reperfusion (R30, R60, R90) when intraluminal anisodamine or dobutamine was present compared to intraluminal saline only(44+/-3.3% or 48+/-4.1% vs 37+/-2.6% at R30, 57+/-5.0% or 56+/-4.7% vs 45+/-2.7% at R60, 64+/-3.3% or 56+/-4.2% vs 48+/-3.4% at R90,respectively P【0.05). Blood flow changes were also reflected by lowering of jejunal PrCO2 measurements after intraluminal anisodamine or dobutamine compared with that of the saline controls (41+/-3.1 mmHg or 44+/-3.0 mmHg vs 49+/-3.7 mmHg at R30,38+/-3.7 mmHg or 40+/-2.1 mmHg vs 47+/-3.8 mmHg at R60,34+/-2.1 mmHg or 39+/-3.0 mmHg vs 46+/-3.4 mmHg at R90, respectively, P【0.05). Most interesting finding was that there were significantly higher mucosal blood flow and lower jejunal PrCO2 in anisodamine group than those in dobutamine group at 90 minutes of reperfusion(64+/-3.3% vs 56+/-4.2% for blood flow or 34+/-2.1 mmHg vs 39+/-3.0 mmHg for PrCO2, respectively, P【0.05), suggesting that anisodamine had a more lasting effect on mucosal perfusion than dobutamine. CONCLUSION: Intraluminal anisodamine and dobutamine can augment mucosal blood flow during gut I/R and alleviate mucosal acidosis. The results provided beneficial effects on the treatment of splanchnic hypoperfusion following traumatic or burn shock.

Gene-modified leucoconcentrate for personalized ex vivo gene therapy in a mini pig model of moderate spinal cord injury

We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy for neurodegenerative diseases,neurotrauma,and stroke.In this study,using a mini pig model of spinal cord injury,we proposed for the first time the use of gene-modified leucoconcentrate prepared from peripheral blood in the plastic blood bag for personalized ex vivo gene therapy.Leucoconcentrate obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector(Ad5/35 F)that carried an enhanced green fluorescent protein(EGFP)reporter gene in the plastic blood bag.The day after blood donation,the mini pigs were subjected to moderate SCI and four hours post-surgery they were intravenously autoinfused with gene-modified leucoconcentrate.A week after gene-modified leucoconcentrate therapy,fluorescent microscopy revealed EGFP-expressing leucocytes in spinal cord at the site of contusion injury.In the spleen the groups of EGFP-positive cells located in the lymphoid follicles were observed.In vitro flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by leucocytes.Thus,the efficacy of leucocytes transduction in the plastic blood bag and their migratory potential suggest their use for temporary production of recombinant biologically active molecules to correct certain pathological conditions.This paper presents a proof-of-concept of simple,safe and effective approach for personalized ex vivo gene therapy based on gene-modified leucoconcentrate autoinfusion.The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee(approval No.5)on May 27,2014.

Young blood products:emerging treatment for Alzheimer's disease?

Alzheimer＇s disease is the most common neurodegenerative disorder and no disease-modifying treatment is currently available.Research has shown that while brain neurogenesis continues in adult life,it declines with age.Using parabiosis,plasma transfusions and direct administration of neural growth factors,animal studies have demonstrated the positive impact of exposure to young blood products on neurogenesis and synaptic plasticity in an aging brain.The hippocampus and the sub-ventricular zones were identified as the main regions affected.Promising findings have prompted researchers to experiment their effects in subjects with an established neurocognitive disorder,such as Alzheimer＇s disease.They argued that modification of brain vasculature,reactivation of adult neural stem cells,and remodeling of their synaptic activity/plasticity may lead to cognitive enhancement and increased neurogenesis.One pilot human study found that young donor plasma infusion protocols for adults with Alzheimer＇s disease were safe and feasible;however,no statistically significant improvements in cognition were detected.There is a need to conduct additional placebo-controlled human studies in larger samples.Future studies should focus on identifying an “optimal age” at which an intervention in humans may yield significant cognitive enhancement,as well as determining the types of transfusions with the best efficacy and tolerability profiles.