Our brain is constantly active.Even at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information processing.Thi...Our brain is constantly active.Even at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information processing.This resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance imaging.This technique measures subtle changes in blood flow,volume,and oxygenation that occur over time.Although vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.展开更多
As a key contributor to memory storage,the synapse is one of the earliest affected neuronal components in Alzheimer′s disease(AD).Under physiological conditions,the synaptic connections between neurons undergo activi...As a key contributor to memory storage,the synapse is one of the earliest affected neuronal components in Alzheimer′s disease(AD).Under physiological conditions,the synaptic connections between neurons undergo activity-dependent functional and morphological re-organisation.This dynamic,‘plastic’neural ability critically depends on the structural integrity of the synapse.Thus,proteins that are implicated in preserving the organisation and dynamics of synaptic connections。展开更多
A critical function of flow cytometry is to count the concentration of blood cells,which helps in the diagnosis of certain diseases.However,the bulky nature of commercial flow cytometers makes such tests only availabl...A critical function of flow cytometry is to count the concentration of blood cells,which helps in the diagnosis of certain diseases.However,the bulky nature of commercial flow cytometers makes such tests only available in hospitals or laboratories,hindering the spread of point-of-care testing(POCT),especially in underdeveloped areas.Here,we propose a smart Palm-size Optofluidic Hematology Analyzer based on a miniature fluorescence microscope and a microfluidic platform to lighten the device to improve its portability.This gadget has a dimension of 35×30×80 mm and a mass of 39 g,less than 5%of the weight of commercially available flow cytometers.Additionally,automatic leukocyte concentration detection has been realized through the integration of image processing and leukocyte counting algorithms.We compared the leukocyte concentration measurement between our approach and a hemocytometer using the Passing-Bablok analysis and achieved a correlation coefficient of 0.979.Through Bland-Altman analysis,we obtained the relationship between their differences and mean measurement values and established 95%limits of agreement,ranging from−0.93×10^(3)to 0.94×10^(3)cells/μL.We anticipate that this device can be used widely for monitoring and treating diseases such as HIV and tumors beyond hospitals.展开更多
Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous system.Glial progenitor cells can respond to diverse environme...Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous system.Glial progenitor cells can respond to diverse environmental signals and transform into distinct populations,each serving specific functions.Notably,the adult spinal cord hosts various populations of glial progenitors,a region integral to the central nervous system.During development,glial progenitors express glial fibrillary acidic protein(GFAP;Dimou and Gotz,2014).However,the specific identities of GFAP-expressing progenitors in the adult spinal cord were not thoroughly investigated.展开更多
AIM:To investigate the effect of transgenic expression of kallistatin(Kal) on carbon tetrachloride(CCl 4)induced liver injury by intramuscular(im) electrotransfer of a Kal-encoding plasmid formulated with poly-Lglutam...AIM:To investigate the effect of transgenic expression of kallistatin(Kal) on carbon tetrachloride(CCl 4)induced liver injury by intramuscular(im) electrotransfer of a Kal-encoding plasmid formulated with poly-Lglutamate(PLG).METHODS:The pKal plasmid encoding Kal gene was formulated with PLG and electrotransferred into mice skeletal muscle before the administration of CCl 4.The expression level of Kal was measured.The serum biomarker levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),malonyldialdehyde(MDA),and tumor necrosis factor(TNF)-α were monitored.The extent of CCl 4-induced liver injury was analyzed histopathologically.RESULTS:The transgene of Kal was sufficiently expressed after an im injection of plasmid formulated with PLG followed by electroporation.In the Kal gene-transferred mice,protection against CCl 4-induced liver injury was reflected by significantly decreased serum ALT,AST,MDA and TNF-α levels compared to those in control mice(P < 0.01 to 0.05 in a dose-dependent manner).Histological observations also revealed that hepatocyte necrosis,hemorrhage,vacuolar change and hydropic degeneration were apparent in mice after CCl 4 administration.In contrast,the damage was markedly attenuated in the Kal gene-transferred mice.The expression of hepatic fibrogenesis marker transforming growth factor-β1 was also reduced in the pKal transferred mice.CONCLUSION:Intramuscular electrotransfer of plasmid pKal which was formulated with PLG significantly alleviated the CCl 4-induced oxidative stress and inflammatory response,and reduced the liver damage in a mouse model.展开更多
Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complication...Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications,including decompensation,bleeding and liver cancer.Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease.Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis,while cirrhosis requires a specif ic follow-up including screening for esophageal varices and hepatocellular carcinoma.Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive,costly and prone to sampling errors.Recently,blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis.However,there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available.This is due to an unsatisfactory accuracy for some of them,and to an incomplete validation for others.Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they are combined.Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement non-invasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.展开更多
All retinoids, which can be natural and synthetic, are chemically related to vitamin A. Both natural and synthetic retinoids use specific nuclear receptors such as retinoic acid receptors and retinoid X receptors to a...All retinoids, which can be natural and synthetic, are chemically related to vitamin A. Both natural and synthetic retinoids use specific nuclear receptors such as retinoic acid receptors and retinoid X receptors to activate specific signaling pathways in the cells. Retinoic acid signaling is extremely important in the central nervous system. Impairment of retinoic acid signaling pathways causes severe pathological processes in the central nervous system, especially in the adult brain. Retinoids have major roles in neural patterning, differentiation, axon outgrowth in normal development, and function of the brain. Impaired retinoic acid signaling results in neuroinflammation, oxidative stress, mitochondrial malfunction, and neurodegeneration leading to progressive Alzheimer’s disease, which is pathologically characterized by extra-neuronal accumulation of amyloid plaques(aggregated amyloid-beta) and intra-neurofibrillary tangles(hyperphosphorylated tau protein) in the temporal lobe of the brain. Alzheimer’s disease is the most common cause of dementia and loss of memory in old adults. Inactive cholinergic neurotransmission is responsible for cognitive deficits in Alzheimer’s disease patients. Deficiency or deprivation of retinoic acid in mice is associated with loss of spatial learning and memory. Retinoids inhibit expression of chemokines and neuroinflammatory cytokines in microglia and astrocytes, which are activated in Alzheimer’s disease. Stimulation of retinoic acid receptors and retinoid X receptors slows down accumulation of amyloids, reduces neurodegeneration, and thereby prevents pathogenesis of Alzheimer’s disease in mice. In this review, we described chemistry and biochemistry of some natural and synthetic retinoids and potentials of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer’s disease.展开更多
Dietary restriction(DR) can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver functio...Dietary restriction(DR) can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver function of mice with hyperlipidemia. To investigate these effects, hyperlipidemia mouse models were established with high-fat diet(HFD)(34% of energy), then randomly divided into HFD group, DR30% group and DR50% group. Mice in DR30% and DR50% group were respectively supplied with HFD as much as about 70% and 50% of the consumption of HFD in the mice of HFD group. Rats in control group were fed routinely. After DR for 5 weeks, the average body weight, liver weight, liver index, serum lipids and glucose levels in both DR groups decreased significantly as compared with the HFD group(P<0.05 or P<0.01), so did alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH) levels and the ratio of LDL-C/HDL-C in the DR50% group(P<0.05 or P<0.01). Histopathology examination of liver tissues further proved ameliorative effect of DR on liver function. Western blotting showed that DR significantly increased the expression of silent mating type information regulation 2 homolog 1(SIRT1) in liver and adipose, while notably decreased the expression of peroxisome proliferators-activated receptors-gamma(PPARγ) in adipose(P<0.05 or P<0.01). The increase of SIRT1 and decrease of PPARγ may be a mechanism by which DR reduces blood lipids and ameliorates liver function.展开更多
AIM: To investigate the inhibitory effect of kallistatin (KAL) on angiogenesis and HCT-116 xenograft tumor growth. METHODS: Heterotopic tumors were induced by subcutaneous injection of 2 × 106 HCT-11 cells in mic...AIM: To investigate the inhibitory effect of kallistatin (KAL) on angiogenesis and HCT-116 xenograft tumor growth. METHODS: Heterotopic tumors were induced by subcutaneous injection of 2 × 106 HCT-11 cells in mice. Seven days later, 2 × 1011 rAAV-GFP or rAAV-KAL was injected intratumorally (n = 5 for each group). The mice were sacrificed at d 28, by which time the tumors in the rAAV-GFP group had grown to beyond 5% of the total body weight. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density (MVD) by immunohistology. Tumor cell proliferation was assessed by Ki-67 staining. RESULTS: Intratumor injection of rAAV-KAL inhibited tumor growth in the treatment group by 78% (171 ± 52 mm3) at d 21 after virus infection compared to the control group (776 ± 241 mm3). Microvessel density was significantly inhibited in tumor tissues treated with rAAV-KAL. rAAV-KAL also decreased the proportion of proliferating cells (Ki-67 positive cells) in tumors compared with the control group.CONCLUSION: rAAV-mediated expression of KAL inhibits the growth of colon cancer by reducing angiogenesis and proliferation of tumor cells, and may provide a promising anti-angiogenesis-based approach to the treatment of metastatic colorectal cancer.展开更多
AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt) mice were given 5...AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelialinjury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modu-lated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.展开更多
瞄准：为了测试交付为改善作为一个 DNA 疫苗的助手编码 IL-15 的一个原生质标志的可行性，有免疫力的回答由肝炎 B 核心基因 DNA 疫苗导致了。方法：我们使用了 RT-PCR 开发 IL-15 表示构造的基于的策略。我们首先证实基因能由于 IL-15...瞄准：为了测试交付为改善作为一个 DNA 疫苗的助手编码 IL-15 的一个原生质标志的可行性，有免疫力的回答由肝炎 B 核心基因 DNA 疫苗导致了。方法：我们使用了 RT-PCR 开发 IL-15 表示构造的基于的策略。我们首先证实基因能由于 IL-15 的差的表示在埃希氏杆菌属关口 i 被表示。然后， IL-15 原生质标志表示产品的简历活动被 CTLL-2 增长试金识别。从每 IL-15 的 DNA 的 100 微克真核细胞的表示原生质标志和怀有编码 HBV 核心基因(缩短的 pHBc144 ) 的 N 终点的 144 氨基酸的 DNA 的 recombinant 原生质标志习惯于共同使免疫 C57 BL/6 老鼠。anti-HBcIgG 的效价被 ELISA 检测，抗原特定的 CD8 (+) T 房间(CD8 (+) IFN-gamma (+) T 房间) 被在不同时间点染色的细胞内部的 cytokine 检测。结果：在由 pIL-15 和老鼠的抗原特定的 CD8 (+) 房间逐渐地增加了的 pHBc144 DNA 疫苗的合作免疫以后，有免疫力的反应的第一座山峰出现了 14 d 以后，然后，抗原特定的 CD8 (+) T 房间的数字逐渐地减少了并且在 3 瞬间在稳定的水平维持了。在增加以后，抗原特定的 CD8 (+) T 房间的数字到达了第二座山峰与以后的 10 d 一第一山峰双，然后，抗原特定的 CD8 (+) T 房间的数字慢慢地减少了。一个基因助手没在体液的有免疫力的回答上有重要效果的 IL-15 由肝炎 B 核心基因 DNA 疫苗导致了，但是增加了抗原特定的 CD8 (+) T 房间由肝炎 B 核心基因 DNA 疫苗导致了的记忆。结论：HBc Ag 1-144 氨基酸构造的 DNA 疫苗导致交付 plasmid 的 IL-15 提高的有效房间免疫，和 cytokine CD8 (+) T 房间的长寿。展开更多
Background:Since the use of antibiotics in animal feed has become a critical concern worldwide due to severe threats to human health and environment,we are in need of finding alternatives to antibiotics in pig breedin...Background:Since the use of antibiotics in animal feed has become a critical concern worldwide due to severe threats to human health and environment,we are in need of finding alternatives to antibiotics in pig breeding,maintaining the health of pigs,and getting high-quality pork.As traditional Chinese herbs(TCH)are rich natural resources in China and show great benefits to human health we propose to transfer this abundant resource into animal production industry as additives.Methods:Three groups of Chinese herbs(groups A,B,and C)were used as feed additives in the diet for pigs.In total 32 pigs were arranged in four groups(groups A,B,C,and control group,NC),fed in the same facility,eight pigs(one group)in each colony,free drinking,for 120 days.The feed:gain ratio(F/G),meat quality,total protein,and amino acid concentration of muscle were checked in the experiments.Results:After 120 days of feeding,the feed:gain ratio(F/G)of pigs in groups A,B,and C was decreased 17.56%,9.31%,and 13.86%compared with NC treatment,respectively.The diets supplemented with Chinese herbs improved meat quality,increased loin eye area(especially group A and C showed significant difference,P<.001),the total protein(increased ratio vs NC was A=4.54%,B=0.38%and C=3.53%),amino acid concentration of muscle,increased the villus height:crypt depth ratio,and induced positive effects on serum biochemical parameters and immune function(serum TC and TG concentrations were significantly lower than those in the NC group,P<.05.).Conclusions:The use of Chinese herbal feed additives can reduce the cost of pig breeding and produce high-quality pock.The combination of these effects would contribute to better absorption ability of the intestinal tract and yield a better growth performance.展开更多
AIM:To identify the genes related to lymph node metastasis in human hepatocellular carcinoma(HCC),32 HCC patients with or without lymph node metastasis were investigated by high-throughput microarray comprising 886 ge...AIM:To identify the genes related to lymph node metastasis in human hepatocellular carcinoma(HCC),32 HCC patients with or without lymph node metastasis were investigated by high-throughput microarray comprising 886 genes.METHODS:The samples of cancerous and non-cancerous paired tissue were taken from 32 patients with HCC who underwent hepatectomy with lymph node dissection.Total RNA was extracted from the cells obtained by means of laser microdissection(LCM) and was amplified by the T7-based amplification system.Then,the amplifi ed samples were applied in the cDNA microarray comprising of 886 genes.RESULTS:The results demonstrated that 25 up-regulated genes such as cell membrane receptor,intracellular signaling and cell adhesion related genes,and 48 down-regulated genes such as intracellular signaling and cell cycle regulator-related genes,were correlated with lymph node metastasis in HCC.Amongst them were included some interesting genes,such as MET,EPHA2,CCND1,MMP2,MMP13,CASP3,CDH1,and PTPN2.Expression of 16 genes(MET,CCND1,CCND2,VEGF,KRT18,RFC4,BIRC5,CDC6,MMP2,BCL2A1,CDH1,VIM,PDGFRA,PTPN2,SLC25A5 and DSP) were further confirmed by real-time quantitative reverse transcriptional polymerase chain reaction(RT-PCR).CONCLUSION:Tumor metastasis is an important biological characteristic,which involves multiple genetic changes and cumulation.This genome-wide information contributes to an improved understanding of molecular alterations during lymph node metastasis in HCC.It may help clinicians to predict metastasis of lymph nodes and assist researchers in identifying novel therapeutic targets for metastatic HCC patients.展开更多
Objective: The combination of both nuclear and fluorescent reporters provides unique opportunities for noninvasive nuclear imaging with subsequent fluorescence image-guided resection and pathology. Our objective was t...Objective: The combination of both nuclear and fluorescent reporters provides unique opportunities for noninvasive nuclear imaging with subsequent fluorescence image-guided resection and pathology. Our objective was to synthesize and optimize a dual-labeled trastuzumab-based imaging agent that can be used to validate an optical imaging agent with potential use in identifying tumor metastases in human epidermal growth factor receptor 2(HER2) positive breast cancer patients.Methods: [111In]-DTPA-trastuzumab-IRDye 800 was synthesized by a three-step procedure. Purity, stability, immunoreactivity, internalization and biodistribution were explored in HER2+ SKBR-3 cells. Biodistribution of [111In]-DTPA-trastuzumab-IRDye 800 was performed in a SKBR-3 xenograft model.Results: [111In]-DTPA-trastuzumab-IRDye 800 demonstrated high purity by both chemical and fluorometric determinations. Both flow cytometry and the Lindmo assay demonstrated a high binding affinity of [111In]-DTPA-trastuzumab-IRDye 800 to HER2-overexpressing cells. The dual-labeled conjugate was stable in PBS, but not in serum after 24 h at 37 ℃. Larger molecules(>150 k D) were seen after a 24 h-incubation in human serum. Biodistribution studies revealed tumor-specific accumulation of [111In]-DTPAtrastuzumab-IRDye 800 in SKBR-3 tumors, and tumor uptakes at 24 and 48 h were(12.42±1.72)% and(9.96±1.05)%, respectively, following intravenous administration. The tumor-to-muscle ratio was 9.13±1.68 at 24 h, and increased to 12.79±2.13 at 48 h. Liver and kidney showed marked uptake of the dual-labeled imaging agent.Conclusions: [111In]-DTPA-trastuzumab-IRDye 800 is an effective diagnostic biomarker that can be used to validate dual-labeled, molecularly targeted imaging agents and can allow these agents to be translated into clinical practice for identifying HER2+ lesions.展开更多
A number of studies conducted over many years have shown that hepatitis C virus(HCV)can infect a variety of cell types.In vivo infection of monocytes,macrophages,and dendritic cells by HCV has been frequently shown by...A number of studies conducted over many years have shown that hepatitis C virus(HCV)can infect a variety of cell types.In vivo infection of monocytes,macrophages,and dendritic cells by HCV has been frequently shown by a number of researchers.These studies have demonstrated replication of HCV by detecting the presence of both negative genomic strands and a variety of non-structural HCV proteins in infected cells.In addition,analyses of genome sequences have also shown that different cell types can harbor different HCV variants.Investigators have also done preliminary studies of which cellular genes are affected by HCV infection,but there have not yet been a sufficient number of these studies to understand the effects of infection on these cells.Analyses of in vitro HCV replication have shown that monocytes,macrophages and dendritic cells can be infected by HCV from patient sera or plasma.These studies suggest that entry and cellular locations may vary between different cell types.Some studies suggest that macrophages may preferentially allow HCV genotype 1 to replicate,but macrophages do not appear to select particular hypervariable regions.Overall,these studies agree with a model where monocytes and macrophages act as an amplification system,in which these cells are infected and show few cytopathic effects,but continuously produce HCV.This allows them to produce virus over an extended time and allows its spread to other cell types.展开更多
Over the last decades, nitric oxide(NO) has been definitively recognised as one of the key players involved in immunity and inflammation. NO generation was originally described in activated macrophages, which still re...Over the last decades, nitric oxide(NO) has been definitively recognised as one of the key players involved in immunity and inflammation. NO generation was originally described in activated macrophages, which still represent the prototype of NO-producing cells. Notwithstanding, additional cell subsets belonging to both innate and adaptive immunity have been documented to sustain NO propagation by means of the enzymatic activity of different nitric oxide synthase isoforms. Furthermore, due to its chemical characteristics, NO could rapidly react with other free radicals to generate different reactive nitrogen species(RNS), which have been intriguingly associated with many pathological conditions. Nonetheless, the plethora of NO/RNS-mediated effects still remains extremely puzzling. The aim of this manuscript is to dig into the broad literature on the topic to provide intriguing insights on NO-mediated circuits within immune system. We analysed NO and RNS immunological clues arising from their biochemical properties, immunomodulatory activities and finally dealing with their impact on different pathological scenarios with far prompting intriguing perspectives for their pharmacological targeting.展开更多
Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro.It has recently been observed that MSC may also exert a profound immunosuppressive and an...Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro.It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders.We present the case of a patient suffering from childhood-onset, multidrug resistant and steroiddependent Crohn's disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient's peripheral blood mononuclear cells.Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation.The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.展开更多
Myocardial siderosis is known as the major cause of death in thalassemia major(TM) patients since it can lead to iron overload cardiomyopathy.Although this condition can be prevented if timely effective intensive chel...Myocardial siderosis is known as the major cause of death in thalassemia major(TM) patients since it can lead to iron overload cardiomyopathy.Although this condition can be prevented if timely effective intensive chelation is given to patients,the mortality rate of iron overload cardiomyopathy still remains high due to late detection of this condition.Various direct and indirect methods of iron assessment,including serum ferritin level,echocardiogram,non-transferrin-bound iron,cardiac magnetic resonance T2*,heart rate variability,and liver biopsy and myocardial biopsy,have been proposed for early detection of cardiac iron overload in TM patients.However,controversial evidence and limitations of their use in clinical practice exist.In this review article,all of these iron assessment methods that have been proposed or used to directly or indirectly determine the cardiac iron status in TM reported from both basic and clinical studies are comprehensively summarized and presented.Since there has been growing evidence in the past decades that cardiac magnetic resonance imaging as well as cardiac autonomic status known as the heart rate variability can provide early detection of cardiac involvement in TM patients,these two methods are also presented and discussed.The existing controversy regarding the assessment of cardiac involvement in thalassemia is also discussed.展开更多
AIM:To suggest infliximab(IFX) is effective for acute severe ulcerative colitis,from real-life clinical practice.METHODS:All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single cent...AIM:To suggest infliximab(IFX) is effective for acute severe ulcerative colitis,from real-life clinical practice.METHODS:All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single centre were included.Data were extracted from clinical records in order to assess response to IFX therapy.The primary endpoint was colectomy-free survival,and secondary outcomes included glucocorticosteroid-free remission and safety,which was evaluated by recording deaths and adverse events.Demographic and clinical characteristics of those who underwent colectomy and those who were colectomy-free,both at discharge from their index admission,and during follow-up after an initial response to IFX were compared.RESULTS:Forty-four patients(16 females,mean age 36 years) received IFX between May 2006 and January 2012 for acute severe ulcerative colitis.The median duration of follow-up post-first infusion was 396 d(interquartile range = 173-828 d).There were 21(47.7%) patients with < 1 year of follow-up,10(22.7%) with 1 years to 2 years of follow-up,and 13(29.5%) with > 2 years of follow-up post-first infusion of IFX.Overall,35(79.5%) responded to IFX,avoiding colectomy during their index admission,29(65.9%) were colectomyfree at last point of follow-up(median follow-up 396 d),and 25(56.8%) were in glucocorticosteroid-free remission at end of follow-up.There was one death from post-operative sepsis,20 d after a single IFX infusion.Colectomy rates were generally lower among those "bridging" to thiopurine.Of 18 patients "bridged" to thiopurine therapy,17(94.4%) were colectomyfree,and 15(83.3%) were in glucocorticosteroid-free remission at study end.No predictors of response were identified.CONCLUSION:IFX is effective for acute severe ulcerative colitis in real-life clinical practice.Two-thirds of patients avoided colectomy,and more than 50% were in glucocorticosteroid-free remission.展开更多
文摘Our brain is constantly active.Even at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information processing.This resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance imaging.This technique measures subtle changes in blood flow,volume,and oxygenation that occur over time.Although vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.
基金supported by grant SDU2020 to Prof.Bente Finsen and Prof.Martin R.Larsen(COPING AD–Collaborative Project on the Interaction between Neurons and Glia in Alzheimer’s Disease)
文摘As a key contributor to memory storage,the synapse is one of the earliest affected neuronal components in Alzheimer′s disease(AD).Under physiological conditions,the synaptic connections between neurons undergo activity-dependent functional and morphological re-organisation.This dynamic,‘plastic’neural ability critically depends on the structural integrity of the synapse.Thus,proteins that are implicated in preserving the organisation and dynamics of synaptic connections。
基金supported by the National Natural Science Foundation of China (grant no.62305083 to W.Z.,grant no.T2222009 to H.L.,grant no.32227802 to H.L.)China Postdoctoral Science Foundation (grant no.2023T160163 to W.Z.grant no.2022M720971 to W.Z.)+2 种基金the Heilongjiang Provincial Postdoctoral Science Foundation (grant no.LBH-Z22027 to W.Z.)the National Key Research and Development Program of China (grant no.2022YFC3400600 to H.L.)the Natural Science Foundation of Heilongjiang Province (grant no.YQ2021F013 to H.L.).
文摘A critical function of flow cytometry is to count the concentration of blood cells,which helps in the diagnosis of certain diseases.However,the bulky nature of commercial flow cytometers makes such tests only available in hospitals or laboratories,hindering the spread of point-of-care testing(POCT),especially in underdeveloped areas.Here,we propose a smart Palm-size Optofluidic Hematology Analyzer based on a miniature fluorescence microscope and a microfluidic platform to lighten the device to improve its portability.This gadget has a dimension of 35×30×80 mm and a mass of 39 g,less than 5%of the weight of commercially available flow cytometers.Additionally,automatic leukocyte concentration detection has been realized through the integration of image processing and leukocyte counting algorithms.We compared the leukocyte concentration measurement between our approach and a hemocytometer using the Passing-Bablok analysis and achieved a correlation coefficient of 0.979.Through Bland-Altman analysis,we obtained the relationship between their differences and mean measurement values and established 95%limits of agreement,ranging from−0.93×10^(3)to 0.94×10^(3)cells/μL.We anticipate that this device can be used widely for monitoring and treating diseases such as HIV and tumors beyond hospitals.
基金supported by grants from the NIH,United States (R01AG078728-01 and R21NS113068)Fund-the UTHSC Senator Lloyd and B.A.Bentsen Center for Stroke Research (to JQW)。
文摘Glial progenitor cells were reported to have the capacity to generate various types of cells in both the central nervous system(CNS)and peripheral nervous system.Glial progenitor cells can respond to diverse environmental signals and transform into distinct populations,each serving specific functions.Notably,the adult spinal cord hosts various populations of glial progenitors,a region integral to the central nervous system.During development,glial progenitors express glial fibrillary acidic protein(GFAP;Dimou and Gotz,2014).However,the specific identities of GFAP-expressing progenitors in the adult spinal cord were not thoroughly investigated.
基金Supported by The State High Technology Research and Development Program of China (863 Program),No.2008AA02Z135the Important National Science and Technology Specific Projects,No.2009ZX09103-643the Natural Science Foundation of China,No.30973591
文摘AIM:To investigate the effect of transgenic expression of kallistatin(Kal) on carbon tetrachloride(CCl 4)induced liver injury by intramuscular(im) electrotransfer of a Kal-encoding plasmid formulated with poly-Lglutamate(PLG).METHODS:The pKal plasmid encoding Kal gene was formulated with PLG and electrotransferred into mice skeletal muscle before the administration of CCl 4.The expression level of Kal was measured.The serum biomarker levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),malonyldialdehyde(MDA),and tumor necrosis factor(TNF)-α were monitored.The extent of CCl 4-induced liver injury was analyzed histopathologically.RESULTS:The transgene of Kal was sufficiently expressed after an im injection of plasmid formulated with PLG followed by electroporation.In the Kal gene-transferred mice,protection against CCl 4-induced liver injury was reflected by significantly decreased serum ALT,AST,MDA and TNF-α levels compared to those in control mice(P < 0.01 to 0.05 in a dose-dependent manner).Histological observations also revealed that hepatocyte necrosis,hemorrhage,vacuolar change and hydropic degeneration were apparent in mice after CCl 4 administration.In contrast,the damage was markedly attenuated in the Kal gene-transferred mice.The expression of hepatic fibrogenesis marker transforming growth factor-β1 was also reduced in the pKal transferred mice.CONCLUSION:Intramuscular electrotransfer of plasmid pKal which was formulated with PLG significantly alleviated the CCl 4-induced oxidative stress and inflammatory response,and reduced the liver damage in a mouse model.
基金Supported by An unrestricted grant from Roche-Italia
文摘Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications,including decompensation,bleeding and liver cancer.Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease.Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis,while cirrhosis requires a specif ic follow-up including screening for esophageal varices and hepatocellular carcinoma.Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive,costly and prone to sampling errors.Recently,blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis.However,there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available.This is due to an unsatisfactory accuracy for some of them,and to an incomplete validation for others.Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they are combined.Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement non-invasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.
基金supported in part by an award from the Soy Health Research Program(SHRP,United Soybean Board,Chesterfield,MO,USA)(to SKR)a grant(SCIRF-2015-I-01) from South Carolina Spinal Cord Injury Research Fund(Columbia,SC,USA)(to SKR)earlier R01 grants(CA-091460,and NS-057811)(to SKR) from the National Institutes of Health(Bethesda,MD,USA)
文摘All retinoids, which can be natural and synthetic, are chemically related to vitamin A. Both natural and synthetic retinoids use specific nuclear receptors such as retinoic acid receptors and retinoid X receptors to activate specific signaling pathways in the cells. Retinoic acid signaling is extremely important in the central nervous system. Impairment of retinoic acid signaling pathways causes severe pathological processes in the central nervous system, especially in the adult brain. Retinoids have major roles in neural patterning, differentiation, axon outgrowth in normal development, and function of the brain. Impaired retinoic acid signaling results in neuroinflammation, oxidative stress, mitochondrial malfunction, and neurodegeneration leading to progressive Alzheimer’s disease, which is pathologically characterized by extra-neuronal accumulation of amyloid plaques(aggregated amyloid-beta) and intra-neurofibrillary tangles(hyperphosphorylated tau protein) in the temporal lobe of the brain. Alzheimer’s disease is the most common cause of dementia and loss of memory in old adults. Inactive cholinergic neurotransmission is responsible for cognitive deficits in Alzheimer’s disease patients. Deficiency or deprivation of retinoic acid in mice is associated with loss of spatial learning and memory. Retinoids inhibit expression of chemokines and neuroinflammatory cytokines in microglia and astrocytes, which are activated in Alzheimer’s disease. Stimulation of retinoic acid receptors and retinoid X receptors slows down accumulation of amyloids, reduces neurodegeneration, and thereby prevents pathogenesis of Alzheimer’s disease in mice. In this review, we described chemistry and biochemistry of some natural and synthetic retinoids and potentials of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer’s disease.
基金supported by a grant from the Social Development Research Program of Science and Technology Agency of Jiangsu Province(No.BE2015646)
文摘Dietary restriction(DR) can delay senescence, prolong lifespan of mammals and improve their learning-memory activity. The purpose of the study was to explore the effects of DR on hypolipidemic action and liver function of mice with hyperlipidemia. To investigate these effects, hyperlipidemia mouse models were established with high-fat diet(HFD)(34% of energy), then randomly divided into HFD group, DR30% group and DR50% group. Mice in DR30% and DR50% group were respectively supplied with HFD as much as about 70% and 50% of the consumption of HFD in the mice of HFD group. Rats in control group were fed routinely. After DR for 5 weeks, the average body weight, liver weight, liver index, serum lipids and glucose levels in both DR groups decreased significantly as compared with the HFD group(P<0.05 or P<0.01), so did alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH) levels and the ratio of LDL-C/HDL-C in the DR50% group(P<0.05 or P<0.01). Histopathology examination of liver tissues further proved ameliorative effect of DR on liver function. Western blotting showed that DR significantly increased the expression of silent mating type information regulation 2 homolog 1(SIRT1) in liver and adipose, while notably decreased the expression of peroxisome proliferators-activated receptors-gamma(PPARγ) in adipose(P<0.05 or P<0.01). The increase of SIRT1 and decrease of PPARγ may be a mechanism by which DR reduces blood lipids and ameliorates liver function.
基金Hong Kong University Foundation (special donation from Madame Cho So Man)Huaqiao University Foundation B105
文摘AIM: To investigate the inhibitory effect of kallistatin (KAL) on angiogenesis and HCT-116 xenograft tumor growth. METHODS: Heterotopic tumors were induced by subcutaneous injection of 2 × 106 HCT-11 cells in mice. Seven days later, 2 × 1011 rAAV-GFP or rAAV-KAL was injected intratumorally (n = 5 for each group). The mice were sacrificed at d 28, by which time the tumors in the rAAV-GFP group had grown to beyond 5% of the total body weight. Tumor growth was measured by calipers in two dimensions. Tumor angiogenesis was determined with tumor microvessel density (MVD) by immunohistology. Tumor cell proliferation was assessed by Ki-67 staining. RESULTS: Intratumor injection of rAAV-KAL inhibited tumor growth in the treatment group by 78% (171 ± 52 mm3) at d 21 after virus infection compared to the control group (776 ± 241 mm3). Microvessel density was significantly inhibited in tumor tissues treated with rAAV-KAL. rAAV-KAL also decreased the proportion of proliferating cells (Ki-67 positive cells) in tumors compared with the control group.CONCLUSION: rAAV-mediated expression of KAL inhibits the growth of colon cancer by reducing angiogenesis and proliferation of tumor cells, and may provide a promising anti-angiogenesis-based approach to the treatment of metastatic colorectal cancer.
基金Supported by Instituto de Salud Carlos Ⅲ (C03/02), FEDER funds, Fundación Canaria de Investigación (PI 21/02), and Spanish Ministry of Education to CM (EX2004-0396)
文摘AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelialinjury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modu-lated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.
基金the National High Technology Research and Development Program of China (863 Program), No.G1999054105the National Natural Science Foundation of China, No. 30070693
文摘瞄准：为了测试交付为改善作为一个 DNA 疫苗的助手编码 IL-15 的一个原生质标志的可行性，有免疫力的回答由肝炎 B 核心基因 DNA 疫苗导致了。方法：我们使用了 RT-PCR 开发 IL-15 表示构造的基于的策略。我们首先证实基因能由于 IL-15 的差的表示在埃希氏杆菌属关口 i 被表示。然后， IL-15 原生质标志表示产品的简历活动被 CTLL-2 增长试金识别。从每 IL-15 的 DNA 的 100 微克真核细胞的表示原生质标志和怀有编码 HBV 核心基因(缩短的 pHBc144 ) 的 N 终点的 144 氨基酸的 DNA 的 recombinant 原生质标志习惯于共同使免疫 C57 BL/6 老鼠。anti-HBcIgG 的效价被 ELISA 检测，抗原特定的 CD8 (+) T 房间(CD8 (+) IFN-gamma (+) T 房间) 被在不同时间点染色的细胞内部的 cytokine 检测。结果：在由 pIL-15 和老鼠的抗原特定的 CD8 (+) 房间逐渐地增加了的 pHBc144 DNA 疫苗的合作免疫以后，有免疫力的反应的第一座山峰出现了 14 d 以后，然后，抗原特定的 CD8 (+) T 房间的数字逐渐地减少了并且在 3 瞬间在稳定的水平维持了。在增加以后，抗原特定的 CD8 (+) T 房间的数字到达了第二座山峰与以后的 10 d 一第一山峰双，然后，抗原特定的 CD8 (+) T 房间的数字慢慢地减少了。一个基因助手没在体液的有免疫力的回答上有重要效果的 IL-15 由肝炎 B 核心基因 DNA 疫苗导致了，但是增加了抗原特定的 CD8 (+) T 房间由肝炎 B 核心基因 DNA 疫苗导致了的记忆。结论：HBc Ag 1-144 氨基酸构造的 DNA 疫苗导致交付 plasmid 的 IL-15 提高的有效房间免疫，和 cytokine CD8 (+) T 房间的长寿。
基金This work was financially supported by Fujian Provincial Publicinterest Scientific Institution Basal Research Fund(2019R1021-5)the Scientific and Technological Innovation Team of FAAS,PR China(STIT2017-1-9)the China Agriculture Research System(CARS-22).
文摘Background:Since the use of antibiotics in animal feed has become a critical concern worldwide due to severe threats to human health and environment,we are in need of finding alternatives to antibiotics in pig breeding,maintaining the health of pigs,and getting high-quality pork.As traditional Chinese herbs(TCH)are rich natural resources in China and show great benefits to human health we propose to transfer this abundant resource into animal production industry as additives.Methods:Three groups of Chinese herbs(groups A,B,and C)were used as feed additives in the diet for pigs.In total 32 pigs were arranged in four groups(groups A,B,C,and control group,NC),fed in the same facility,eight pigs(one group)in each colony,free drinking,for 120 days.The feed:gain ratio(F/G),meat quality,total protein,and amino acid concentration of muscle were checked in the experiments.Results:After 120 days of feeding,the feed:gain ratio(F/G)of pigs in groups A,B,and C was decreased 17.56%,9.31%,and 13.86%compared with NC treatment,respectively.The diets supplemented with Chinese herbs improved meat quality,increased loin eye area(especially group A and C showed significant difference,P<.001),the total protein(increased ratio vs NC was A=4.54%,B=0.38%and C=3.53%),amino acid concentration of muscle,increased the villus height:crypt depth ratio,and induced positive effects on serum biochemical parameters and immune function(serum TC and TG concentrations were significantly lower than those in the NC group,P<.05.).Conclusions:The use of Chinese herbal feed additives can reduce the cost of pig breeding and produce high-quality pock.The combination of these effects would contribute to better absorption ability of the intestinal tract and yield a better growth performance.
文摘AIM:To identify the genes related to lymph node metastasis in human hepatocellular carcinoma(HCC),32 HCC patients with or without lymph node metastasis were investigated by high-throughput microarray comprising 886 genes.METHODS:The samples of cancerous and non-cancerous paired tissue were taken from 32 patients with HCC who underwent hepatectomy with lymph node dissection.Total RNA was extracted from the cells obtained by means of laser microdissection(LCM) and was amplified by the T7-based amplification system.Then,the amplifi ed samples were applied in the cDNA microarray comprising of 886 genes.RESULTS:The results demonstrated that 25 up-regulated genes such as cell membrane receptor,intracellular signaling and cell adhesion related genes,and 48 down-regulated genes such as intracellular signaling and cell cycle regulator-related genes,were correlated with lymph node metastasis in HCC.Amongst them were included some interesting genes,such as MET,EPHA2,CCND1,MMP2,MMP13,CASP3,CDH1,and PTPN2.Expression of 16 genes(MET,CCND1,CCND2,VEGF,KRT18,RFC4,BIRC5,CDC6,MMP2,BCL2A1,CDH1,VIM,PDGFRA,PTPN2,SLC25A5 and DSP) were further confirmed by real-time quantitative reverse transcriptional polymerase chain reaction(RT-PCR).CONCLUSION:Tumor metastasis is an important biological characteristic,which involves multiple genetic changes and cumulation.This genome-wide information contributes to an improved understanding of molecular alterations during lymph node metastasis in HCC.It may help clinicians to predict metastasis of lymph nodes and assist researchers in identifying novel therapeutic targets for metastatic HCC patients.
基金supported by Beijing Natural Science Foundation (No. 7132037)NIH R01
文摘Objective: The combination of both nuclear and fluorescent reporters provides unique opportunities for noninvasive nuclear imaging with subsequent fluorescence image-guided resection and pathology. Our objective was to synthesize and optimize a dual-labeled trastuzumab-based imaging agent that can be used to validate an optical imaging agent with potential use in identifying tumor metastases in human epidermal growth factor receptor 2(HER2) positive breast cancer patients.Methods: [111In]-DTPA-trastuzumab-IRDye 800 was synthesized by a three-step procedure. Purity, stability, immunoreactivity, internalization and biodistribution were explored in HER2+ SKBR-3 cells. Biodistribution of [111In]-DTPA-trastuzumab-IRDye 800 was performed in a SKBR-3 xenograft model.Results: [111In]-DTPA-trastuzumab-IRDye 800 demonstrated high purity by both chemical and fluorometric determinations. Both flow cytometry and the Lindmo assay demonstrated a high binding affinity of [111In]-DTPA-trastuzumab-IRDye 800 to HER2-overexpressing cells. The dual-labeled conjugate was stable in PBS, but not in serum after 24 h at 37 ℃. Larger molecules(>150 k D) were seen after a 24 h-incubation in human serum. Biodistribution studies revealed tumor-specific accumulation of [111In]-DTPAtrastuzumab-IRDye 800 in SKBR-3 tumors, and tumor uptakes at 24 and 48 h were(12.42±1.72)% and(9.96±1.05)%, respectively, following intravenous administration. The tumor-to-muscle ratio was 9.13±1.68 at 24 h, and increased to 12.79±2.13 at 48 h. Liver and kidney showed marked uptake of the dual-labeled imaging agent.Conclusions: [111In]-DTPA-trastuzumab-IRDye 800 is an effective diagnostic biomarker that can be used to validate dual-labeled, molecularly targeted imaging agents and can allow these agents to be translated into clinical practice for identifying HER2+ lesions.
文摘A number of studies conducted over many years have shown that hepatitis C virus(HCV)can infect a variety of cell types.In vivo infection of monocytes,macrophages,and dendritic cells by HCV has been frequently shown by a number of researchers.These studies have demonstrated replication of HCV by detecting the presence of both negative genomic strands and a variety of non-structural HCV proteins in infected cells.In addition,analyses of genome sequences have also shown that different cell types can harbor different HCV variants.Investigators have also done preliminary studies of which cellular genes are affected by HCV infection,but there have not yet been a sufficient number of these studies to understand the effects of infection on these cells.Analyses of in vitro HCV replication have shown that monocytes,macrophages and dendritic cells can be infected by HCV from patient sera or plasma.These studies suggest that entry and cellular locations may vary between different cell types.Some studies suggest that macrophages may preferentially allow HCV genotype 1 to replicate,but macrophages do not appear to select particular hypervariable regions.Overall,these studies agree with a model where monocytes and macrophages act as an amplification system,in which these cells are infected and show few cytopathic effects,but continuously produce HCV.This allows them to produce virus over an extended time and allows its spread to other cell types.
基金Supported by Grant from the Italian Ministry of Health,BANDO GIOVANI RICERCATORI,No.2009-GR-2009-1558698Agnellini AHR was granted by Cariparo Fundation Fellowship
文摘Over the last decades, nitric oxide(NO) has been definitively recognised as one of the key players involved in immunity and inflammation. NO generation was originally described in activated macrophages, which still represent the prototype of NO-producing cells. Notwithstanding, additional cell subsets belonging to both innate and adaptive immunity have been documented to sustain NO propagation by means of the enzymatic activity of different nitric oxide synthase isoforms. Furthermore, due to its chemical characteristics, NO could rapidly react with other free radicals to generate different reactive nitrogen species(RNS), which have been intriguingly associated with many pathological conditions. Nonetheless, the plethora of NO/RNS-mediated effects still remains extremely puzzling. The aim of this manuscript is to dig into the broad literature on the topic to provide intriguing insights on NO-mediated circuits within immune system. We analysed NO and RNS immunological clues arising from their biochemical properties, immunomodulatory activities and finally dealing with their impact on different pathological scenarios with far prompting intriguing perspectives for their pharmacological targeting.
文摘Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro.It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders.We present the case of a patient suffering from childhood-onset, multidrug resistant and steroiddependent Crohn's disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient's peripheral blood mononuclear cells.Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation.The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders.
基金Acknowledgments We thank M Hamaguchi （Nagoya Univ., Japan） and T Iwahara （Osaka Bioscience Institute, Japan） forJak null MEFs, and N Gotoh （Tokyo Univ., Japan）, H Higashi （Hokkaido Univ., Japan）, N Mochizuki （National Cardiovascular Cent. Res. Inst., Japan）, H Hanafusa （Prof. emeritus, The Rockefeller Univ., USA and Direc- tor em., OBI, Japan）, SK Hanks （Vanderbilt Univ., USA）, and M Matsuda （Kyoto Univ., Japan） for plasmids. We also thank K Sasai （Hokkaido Univ., Japan） and Y Ohba （Hokkaido Univ., Japan） for valuable discussion. This work was supported in part by grants-in- aid from the Ministry of Education, Science, Culture, and Sports, and the Ministry of Health, Labor, and Welfare, Japan, as well as Suhara Memorial Foundation （Sapporo, Japan）, and the Mochida Medical Science Foundation （Tokyo, Japan）. The work of SF and TK is supported by grants from Cancer Research UK and the Brit- ish Cancer Charity ＂Heads Up＂. We dedicate this work to our great mentor Hidesaburo Hana- fusa, professor emeritus of the Rockefeller University, who passed away on March 15, 2009 at the age of 79. He devoted his life to science and in particular to creating the oncogene research field, to teaching and to providing profound affection to his students and postdocs. All of the alumni of Saburo＇s laboratory pride them- selves in having been his apprentices and we would like to hereby express our deeply felt
gratitude to Saburo.
基金Supported by Thailand Research Fund grants RTA5580006 and BRG5480003
文摘Myocardial siderosis is known as the major cause of death in thalassemia major(TM) patients since it can lead to iron overload cardiomyopathy.Although this condition can be prevented if timely effective intensive chelation is given to patients,the mortality rate of iron overload cardiomyopathy still remains high due to late detection of this condition.Various direct and indirect methods of iron assessment,including serum ferritin level,echocardiogram,non-transferrin-bound iron,cardiac magnetic resonance T2*,heart rate variability,and liver biopsy and myocardial biopsy,have been proposed for early detection of cardiac iron overload in TM patients.However,controversial evidence and limitations of their use in clinical practice exist.In this review article,all of these iron assessment methods that have been proposed or used to directly or indirectly determine the cardiac iron status in TM reported from both basic and clinical studies are comprehensively summarized and presented.Since there has been growing evidence in the past decades that cardiac magnetic resonance imaging as well as cardiac autonomic status known as the heart rate variability can provide early detection of cardiac involvement in TM patients,these two methods are also presented and discussed.The existing controversy regarding the assessment of cardiac involvement in thalassemia is also discussed.
文摘AIM:To suggest infliximab(IFX) is effective for acute severe ulcerative colitis,from real-life clinical practice.METHODS:All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single centre were included.Data were extracted from clinical records in order to assess response to IFX therapy.The primary endpoint was colectomy-free survival,and secondary outcomes included glucocorticosteroid-free remission and safety,which was evaluated by recording deaths and adverse events.Demographic and clinical characteristics of those who underwent colectomy and those who were colectomy-free,both at discharge from their index admission,and during follow-up after an initial response to IFX were compared.RESULTS:Forty-four patients(16 females,mean age 36 years) received IFX between May 2006 and January 2012 for acute severe ulcerative colitis.The median duration of follow-up post-first infusion was 396 d(interquartile range = 173-828 d).There were 21(47.7%) patients with < 1 year of follow-up,10(22.7%) with 1 years to 2 years of follow-up,and 13(29.5%) with > 2 years of follow-up post-first infusion of IFX.Overall,35(79.5%) responded to IFX,avoiding colectomy during their index admission,29(65.9%) were colectomyfree at last point of follow-up(median follow-up 396 d),and 25(56.8%) were in glucocorticosteroid-free remission at end of follow-up.There was one death from post-operative sepsis,20 d after a single IFX infusion.Colectomy rates were generally lower among those "bridging" to thiopurine.Of 18 patients "bridged" to thiopurine therapy,17(94.4%) were colectomyfree,and 15(83.3%) were in glucocorticosteroid-free remission at study end.No predictors of response were identified.CONCLUSION:IFX is effective for acute severe ulcerative colitis in real-life clinical practice.Two-thirds of patients avoided colectomy,and more than 50% were in glucocorticosteroid-free remission.
