Role of Plasma MMP 9 levels in the Pathogenesis of Chronic Pancreatitis

Pancreatic fibrosis is a key pathological feature in the etiology of chronic pancreatitis that leads to obliteration of exocrine and endocrine pancreatic tissues and its replacement by fibrous tissue resulting in clinical manifestations. Matrix metalloproteinase 9 is a member of the MMP family that is also known as gelatinase B, degrades type IV collagen of extracellular matrix and basal membrane. The present study is aimed at evaluating the clinical significance of plasma concentration of MMP-9 in chronic pancreatitis. The samples were obtained from 112 chronic pancreatitis patients and an equal number of age and sex matched healthy controls. MMP-9 levels were quantitatively measured by ELISA assay. Statistical analysis was applied to test the significance of results. The present study revealed a significant increase of plasma MMP 9 levels in chronic pancreatitis patients compared to control subjects. Elevated levels were also observed in all the patient groups compared to control subjects with regard to sex, age, addictions etc. MMP-9 degrades the type IV collagens in normal basement membrane, which in turn activates the pancreatic stellate cells which promote the development of pancreatitic fibrosis. Thus, elevated plasma levels of MMP-9 may act as a susceptibility factor for the development of chronic pancreatitis.     

棉花胚珠中生长素水平的时空调控提高了棉花纤维的产量和品质

棉花是我国最重要的经济作物之一,同时,中国又是世界上最大的纺织品生产国和消费国。棉花生产涉及2亿棉农的生计和近2千万纺织工人的就业,因此,棉花在我国国民经济中具有举足轻重的地位。但是,随着棉纺织业的发展,目前我国棉花生产面临总量严重不足和纤维品质偏低等问题。提高棉花的产量、改进其品质,对增加棉农收入、促进我国纺织业持续健康的发展,具有十分重要的意义。     

康脑液对脑缺血再灌注损伤大鼠血管内皮生长因子、脑源性神经生长因子、基质金属蛋白酶表达的影响

目的：通过康脑液干预观察其对脑缺血再灌注损伤大鼠血管内皮生长因子（vascular endothelial growth factor,VEGF）、脑源性神经生长因子（brain derived neurotrophic factor,BDNF）、基质金属蛋白酶（matrix metalloproteinase-9,MMP-9）表达的影响,探讨康脑液对脑缺血再灌注损伤的保护机制.方法：将雄性SD大鼠随机分为假手术组、脑缺血再灌注模型组及康脑液28.6、14.3、7.15 g·kg-1·d-1剂量组（灌胃给药7 d）,改进Longa等线栓法制备大鼠右侧大脑中动脉阻塞（middle cerebral artery occlusion,MCAO）再灌注模型.于缺血2h后再灌注（分别于再灌注后6h、12h、24 h、72 h、7d处死大鼠）;采用TTC染色法观察大鼠的脑梗死面积;免疫组织化学法观察大鼠脑组织VEGF、BDNF、MMP-9的表达.结果：比较各组缺血再灌注24 h大鼠脑梗死灶面积,发现28.6、14.3 g·kg--1·d-1剂量组较脑缺血再灌注模型组明显减小（P＜0.05）;与脑缺血再灌注模型组相比,28.6、14.3 g·kg--1·d-1剂量组各时间点的VEGF、BDNF表达量明显上调（P＜0.01）,MMP-9表达的阳性细胞明显减少（P＜0.01）,差异有统计学意义.结论：康脑液可促进大鼠局灶性脑缺血后脑组织中VEGF,BDNF的表达,同时抑制脑内MMP-9的表达,缩小脑梗死面积,发挥对神经血管单元（neurovascular unit,NVU）的保护作用,减轻脑缺血再灌注损伤.     

亨廷顿舞蹈症、氧化应激与胶质细胞

氧化应激的产生与胞浆内活性氧簇的升高密切相关,过多生成的活性氧簇能够造成脂质过氧化,损伤蛋白质甚至DNA,而这些物质的受损与疾病发生相关,尤其是神经退行性疾病.神经退行性疾病经常被描述为进行性的神经元丢失,伴随神经元或者胶质细胞中出现标志性寡聚体.在神经退行性疾病中,胶质细胞可能以一种抗氧化应激的方式在神经元功能维持以及生存上发挥重要作用.反之,神经元也能够通过不同途径反馈调节胶质细胞.该文主要探讨在亨廷顿舞蹈症中胶质细胞的特点和功能,阐明氧化应激与亨廷顿舞蹈症的关系,概括这三者之间的关系进而论证胶质细胞在亨廷顿舞蹈症中的抗氧化应激保护作用.     

尼克酰胺与exendin-4诱导胰腺干细胞向β细胞定向分化研究

目的体外分离胰腺干细胞,选择最佳培养条件探索胰腺干细胞在体外环境下向β细胞的分化情况.方法取SD大鼠胰腺组织,胶原酶消化,密度梯度离心获得纯化的胰腺导管上皮细胞.采用分步诱导法诱导胰腺导管上皮细胞向胰岛β细胞分化;用胰岛素释放实验检测胰岛功能,免疫荧光法检测nestin,PDX-1,CK-19,CK-20胰岛素及胰高血糖素等的表达.结果胰腺消化培养6～12h,可看到胰腺导管上皮细胞贴壁生长,通过4步诱导培养,nestin阳性细胞快速生长,并可分泌胰岛素.结论体外分离的成人胰岛前体细胞,在诱导因子的作用下,胰腺干细胞可定向分化为β细胞,有望应用于糖尿病的治疗.     

Clinical implications of exercise immunology

Maintaining leanness and a physically active lifestyle during adulthood reduces systemic inflammation, an underlying factor in multiple chronic diseases. The anti-inflammatory influence of near-daily physical activity in lowering C-reactive protein, total blood leukocytes, interleukin-6, and other inflammatory cytokines may play a key role in lowering risk of cardiovascular disease, certain types of cancer, type 2 diabetes, sarcopenia, and dementia. Moderate exercise training causes favorable perturbations in immunity and a reduction in incidence of upper respiratory tract infection (URTI). During each bout of moderate exercise, an enhanced recirculation of immunoglobulins, neutrophils, and natural killer cells occurs that persists for up to 3-h post-exercise. This exercise-induced surge in immune cells from the innate immune system is transient but improves overall surveillance against pathogens. As moderate exercise continues on a near-daily basis for 12–15 weeks, the number of symptoms days with URTI is decreased 25%–50% compared to randomized sedentary controls. Epidemiologic and animal studies support this inverse relationship between URTI risk and increased physical activity.     

Danshen protects endothelial progenitor cells from oxidized low-density lipoprotein induced impairment

In this study,we examined the protective effects of Danshen both on endothelial progenitor cells(EPCs) in patients with hypercholesterolemia and on in-vitro EPCs of healthy volunteers.In the clinical study,we randomly divided 24 subjects with hypercholesterolemia into two groups(the control group and the Danshen-treated group).At the end of two weeks of treatment,the EPC cellular functions of both groups were tested.The results indicated that,compared to the control group,EPCs in the Danshen-treated group showed significantly better cellular functions,which was manifested in the cloning number,the proliferation capacity,the number of EPC adhesions,and cell migration.In the subsequent in-vitro experiments,EPCs were treated with vehicle,oxidized low-density lipoprotein(Ox-LDL,100 μg/ml),or Ox-LDL(100 μg/ml) plus different concentrations of Danshen(Danshensu 2,10,or 50 μg/ml,respectively) for 24 h.The results showed that Danshen treatments can prevent the detrimental effects of Ox-LDL on EPC cellular functions measured by proliferation capacity(0.24±0.08,0.37±0.11,0.30±0.04 vs.0.13±0.02,P0.05,P0.01,and P0.01,respectively),and adhesion ability(63.00±11.60,70.00±10.80,85.50±11.41 vs.40.50±6.85,all P0.01).Compared to the group treated with Ox-LDL alone,Danshen treatment significantly decreased the lipid peroxidation end product malondialdehyde(MDA) [(4.34±0.54),(3.98±0.47),(3.46±0.31) vs.(5.57±0.64) nmol/ml,all P0.01],increased the production of superoxide dismutase(SOD) [(29.74±0.71),(31.09±0.83),(30.41±0.65) vs.(14.76±3.99) U/ml,all P0.01],and lowered the expression of interleukin-6(IL-6) [(24.62±7.69),(27.04±3.14),(33.38±18.86) vs.(230.67±33.53) pg/ml,all P0.01] and tumor necrosis factor-α(TNF-α) [(41.72±6.10),(17.02±6.82),(3.73±2.26) vs.(228.71±41.53) pg/ml,all P0.01] in Ox-LDL treated EPCs.These results suggest that Danshen may exert a protective effect through its antioxidant and anti-inflammatory features.     

Effect of interrupted endogenous BMP/Smad signaling on growth and steroidogenesis of porcine granulosa cells

Bone morphogenetic proteins (BMPs) play a critical role in the growth and steroidogenesis of granulosa cells (GCs). BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors. Upon ligand binding, BMPs activate intracellular Smad proteins and regulate growth and apoptosis in various cell types. The objective of this study was to demonstrate the effects of BMP/Smad signal on growth and steroidogenesis of porcine GCs. A strategy of RNA interference (RNAi)-mediated ‘gene silencing’ of Smad4, a core molecule mediating the intracellular BMP/Smad signal transduction pathways, was used to interrupt endogenous BMP/Smad signaling. Results indicate that Smad4-small interfering RNA (siRNA) caused specific inhibition of Smad4 mRNA and protein expression after transfection. Interrupted endogenous BMP/Smad signaling significantly inhibited growth, and induced apoptosis of porcine GCs, while decreasing estradiol production. In addition, interrupted BMP/Smad signaling significantly (P<0.05) changed the expression of Cyclin D2, CDK4, Bcl-2, and Cyp19a1. These findings provide new insights into how BMP/Smad signaling regulates the growth and steroidogenesis of porcine GCs.     

Arachnoid cell involvement in the mechanism of coagulation-initiated inflammation in the subarachnoid space after subarachnoid hemorrhage

Objective: To assess if arachnoid cells have the capability to present antigen and activate T-lymphocytes after stimulation by bloody cerebrospinal fluid (CSF), and to illuminate the mechanism of coagulation-initiated inflammation in the subarachnoid space after subarachnoid hemorrhage (SAH). Methods: Arachnoid cells were cultured, characterized, and examined by immunofluorescence for the basal expression of human leukocyte antigen-DR (HLA-DR). Expression of HLA-DR, after co-culturing arachnoid cells in vitro with bloody CSF, was investigated by immunofluorescence and flow cytometry (FCM). The variation of arachnoid cells' ultrastructure was observed by transmission electron microscope (TEM). Arachnoid cells were co-cultured with peripheral blood mononuclear cells (PBMCs). The content of soluble interleukin-2 receptor (sIL-2r) in culture medium was detected by enzyme-linked immunosorbent assay (ELISA). Results: (1) Arachnoid cells were successfully cultured for many passages. The immunofluorescent staining was positive for HLA-DR in over 95% of the human arachnoid cells. The punctate HLA-DR was distributed in cytoplasm and not in the karyon. (2) After co-culturing arachnoid cells in vitro with bloody CSF, numerous particles with strong fluorescence appeared in the cytoplasm on Day 6. On Day 8, the quantity of particles and fluorescent intensity were maximal. FCM showed that the percentage of HLA-DR expressing cells was (2.5±0.4)% at the first 5 d, increasing to (60.8±3.6)% on Day 7. (3) After co-culturing arachnoid cells in vitro with bloody CSF, many lysosome and secondary lysosome particles were present in the cytoplasm. Hyperplasia of rough endoplasmic reticulum and enlarged cysts were observed, with numerous phagocytizing vesicles also observed at the edge of the arachnoid cells. (4) Arachnoid cells stimulated by bloody CSF were co-cultured in vitro with PBMCs. The content of sIL-2r in the culture medium, having been maintained at around 1.30 ng/ml during the first 3 d, had increased by Day 4. The content of sIL-2r peaked 7.53 ng/ml on Day 7 and then reduced gradually. Conclusions: (1) Basic HLA-DR expression is present in arachnoid cells. (2) After stimulation by bloody CSF, arachnoid cells have the potential to serve as antigen presenting cells (APCs) and the ability to activate T-lymphocytes, indicating that arachnoid cells are involved in the mechanism of coagulation-initiated inflammation in the subarachnoid space after SAH.     

Edaravone protects PC12 cells from ischemic-like injury via attenuating the damage to mitochondria

Background： Edaravone had been validated to effectively protect against ischemic injuries. In this study, we investigated the protective effect of edaravone by observing the effects on anti-apoptosis, regulation of Bcl-2/Bax protein expression and recovering from damage to mitochondria after OGD （oxygen-glucose deprivation）-reperfusion. Methods： Viability of PC 12 cells which were injured at different time of OGD injury, was quantified by measuring MTT （2-（4,5-dimethylthia-zol-2-yl）-2,5-diphenyltetrazolium bromide） staining. In addition, PC 12 cells＇ viability was also quantified after their preincubation in different concentration of edaravone for 30 min followed by （OGD）. Furthermore, apoptotic population of PC 12 cells that reinsulted from OGD-reperfusion with or without preincubation with edaravone was determined by flow cytometer analysis, electron microscope and Hoechst/Pl staining. Finally, change of Bcl-2/Bax protein expression was detected by Western blot. Results： （1） The viability of PC12 cells decreased with time （1-12 h） after OGD. We regarded the model of OGD 2 h, then replacing DMEM （Dulbecco＇s Modified Eagle＇s Medium） for another 24 h as an OGD-reperfusion in this research. Furthermore, most PC 12 cells were in the state of apoptosis after OGD-reperfusion. （2） The viability of PC 12 cells preincubated with edaravone at high concentrations （1, 0.1, 0.01 μmol/L） increased significantly with edaravone protecting PC 12 cells from apoptosis after OGD-reperfusion injury. （3） Furthermore, edaravone attenuates the damage of OGD-reperfusion on mitochondria and regulated Bcl-2/Bax protein imbalance expression after OGD-reperfusion. Conclusion： Neuroprotective effects of edaravone on ischemic or other brain injuries may be partly mediated through inhibition of Bcl-2/Bax apoptotic pathways by recovering from the damage of mitochondria.