Effects of maternal diabetes on trophoblast cells

Diabetes mellitus(DM)is a health condition characterized by hyperglycemia over a prolonged period.There are three main types of DM:DM type 1(DM1),DM2 and gestational DM(GDM).Maternal diabetes,which includes the occurrence of DM1 and DM2 during pregnancy or GDM,increases the occurrence of gesttional complications and adverse fetal outcomes.The hyperglycemic intrauterine environment affects not only the fetus but also the placental development and function in humans and experimental rodents.The underlying mechanisms are still unclear,but some evidence indicates alterations in trophoblast proliferation,apoptosis and cell cycle control in diabetes.A proper coordination of trophoblast proliferation,differentiation and invasion is required for placental development.Initially,increased expression of proliferative markers in junctional and labyrinth zones of rat placentas and villous cytotrophoblast,syncytiotrophoblast,stromal cells and fetal endothelial cells in human placentas is reported among diabetics.Moreover,reduced apoptotic index and expression of some apoptotic genes are described in placentas of GDM women.In addition,cell cycle regulators including cyclins and cyclin-dependent kinase inhibitors seem to be affected by the hyperglycemic environment.More studies are necessary to check the balance between proliferation,apoptosis and differentiation in trophoblast cells during maternal diabetes.

Promoter hypermethylation of CDH1, FHIT, MTAP and PLAGL1 in gastric adenocarcinoma in individuals from Northern Brazil

AIM：To evaluate the methylation status of CDH1, FHIT, MTAP and PLAGL1 promoters and the association of these findings with clinico-pathological characteristics.METHODS： Methylation-specific PCR （MSP） assay was performed in 13 nonneoplastic gastric adenocarcinorna, 30 intestinal-type gastric adenocarcinorna and 35 diffuse-type gastric adenocarcinorna samples from individuals in Northern Brazil. Statistical analyses were performed using the chi-square or Fisher＇s exact test to assess associations between rnethylation status and clinico-pathological characteristics.RESULTS： Hypermethylation frequencies of CDH1, FHIT, MTAPand PLAGL1 promoter were 98.7%, 53.9%, 23.1% and 29.5%, respectively. Hyperrnethylation of three or four genes revealed a significant association with diffuse-type gastric cancer compared with nonneoplastic cancer. A higher hyperrnethylation frequency was significantly associated with H pylori infection in gastric cancers, especially with diffuse-type. Cancer samples without lymph node metastasis showed a higher FHIT hypermethylation frequency. MTAP hypermethylation was associated with H pylori in gastric cancer samples, as well as with diffuse-type compared with intestinal-type. In diffuse-type, MTAP hypermethylation was associated with female gender.CONCLUSION： Our findings show differential gene methylation in tumoral tissue, which allows us to conclude that hypermethylation is associated with gastric carcinogenesis. MTAP promoter hypermethylation can be characterized as a marker of diffuse-type gastric cancer, especially in women and may help in diagnosis, prognosis and therapies. The H pylori infectious agent was present in 44.9% of the samples. This infection may be correlated with the carcinogenic process through the gene promoter hypermethylation, especially the MTAP promoter in diffuse-type. A higher H pylori infection in diffuse-type may be due to greater genetic predisposition.

Classification and guidelines of hemorrhoidal disease: Present and future

Classification and guidelines of hemorrhoidal disease are based on the subdivision in Grades of prolapse followed by any aspect related to both the treatment and its technique. When taking the proposals for classification and guidelines issued by prolific scientific societies into consideration, it is evident that strong contradictions and interpretative limits emerge in finding the best treatment to be adopted. After a critical examination of these limitations, a methodological proposal is shared to achieve a new classification, which plays a part in forming a new guideline for hemorrhoidal disease, identifying its evolution, dynamism of the prolapse, symptomatology, enteropathogenesis and gender characteristics.

Validation of a novel imaging approach using multi-slice CT and cone-beam CT to follow-up on condylar remodeling after bimaxillary surgery

The main goal of this study was to introduce a novel three-dimensional procedure to objectively quantify both inner and outer condylar remodelling on preoperative multi-slice computed tomography （MSCT） and postoperative cone-beam computed tomography （CBCT） images. Second, the reliability and accuracy of this condylar volume quantification method was assessed. The mandibles of 20 patients （11 female and 9 male） who underwent bimaxillary surgery were semi-automatically extracted from MSCT/CBCT scans and rendered in 3D. The resulting condyles were spatially matched by using an anatomical landmark-based registration procedure. A standardized sphere was created around each condyle, and the condylar bone volume within this selected region of interest was automatically calculated. To investigate the reproducibility of the method, inter- and intra-observer reliability was calculated for assessments made by two experienced radiologists twice five months apart in a set of ten randomly selected patients. To test the accuracy of the bone segmentation, the inner and outer bone structures of one dry mandible, scanned according to the clinical set-up, were compared with the gold standard, micro-CT. Thirty-eight condyles showed a significant （P〈O.05） mean bone volume decrease of 26.4%_ 11.4% （502.9 mm3＋ 268.1 mm3）. No significant effects of side, sex or age were found. Good to excellent （ICC〉 0.6） intra- and inter-observer reliability was observed for both MSCT and CBCT. Moreover, the bone segmentation accuracy was less than one voxel （0.4 mm） for MSCT （0.3 mm __. 0.2 mm） and CBCT （0.4 mm _ 0.3 mm）, thus indicating the clinical potential of this method for objective follow-up in pathological condylar resorption.

Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis

The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.

Activation of autophagy in photoreceptor necroptosis after experimental retinal detachment

AIM:To investigate whether photoreceptor necroptosis induced by z-VAD-FMK(pan caspase inhibitor) was involved the activation of autophagy and whether Necrostatin-1, a specific necroptosis inhibitor, could inhibit this induction of autophagy after experimental retinal detachment.METHODS:Experimental retinal detachment models were created in Sprague-Dawley rats by subretinal injection of sodium hyaluronate and subretinal injections of z-VAD-FMK, vehicle or z-VAD-FMK plus Necrostatin-1.Three days after retinal detachment, morphologic changes were observed by transmission electron microscopy. In other animals, retinas were subjected to immunoprecipitation and Western Blotting, then probed with anti-RIP1, phosphoserine, LC-3II or caspase 8antibody.RESULTS:It was proved by immunoprecipitation and western blotting, that photoreceptor necroptosis was mediated by caspase-8 inhibition and receptor interacting protein kinase(RIP1) phosphorylation activation. Transmission electron microscope and western blotting results indicated that photoreceptornecroptosis was involved the LC-3II and autophagosomes induction. We also discovered Necrostatin-1 could inhibit RIP1 phosphorylation and LC-3II induction.CONCLUSION:These data firstly indicate photoreceptor necroptosis is associated with the activation of autophagy. Necrostatin-1 protects photoreceptors from necroptosis and autophagy by down-regulation of RIP1 phosphorylation and LC-3II.

Clinical implication of 14-3-3 epsilon expression in gastric cancer

AIM:To evaluate for the first time the protein and mRNA expression of 14-3-3εin gastric carcinogenesis.METHODS:14-3-3εprotein expression was determined by western blotting,and mRNA expression was examined by real-time quantitative RT-PCR in gastric tumors and their matched non-neoplastic gastric tissue samples.RESULTS:Authors observed a significant reduction of 14-3-3εprotein expression in gastric cancer(GC)samples compared to their matched non-neoplastic tissue.Reduced levels of 14-3-3εwere also associated with diffuse-type GC and early-onset of this pathology.Our data suggest that reduced 14-3-3εmay have a role in gastric carcinogenesis process.CONCLUSION:Our results reveal that the reduced 14-3-3εexpression in GC and investigation of 14-3-3ε interaction partners may help to elucidate the carcino-genesis process.

Alteration of P2X3 expression in dorsal root ganglia after sciatic nerve ligation

BACKGROUND： The expressions of P2X3 receptor in dorsal root ganglia （DRG） after different peripheral nerve injuries are diverse. It indicates the different roles of P2X3 in different models-caused neuropathologic pains. OBJECTIVE： To observe the expressions of P2X3 in corresponding DRG after sciatic nerve ligation in rots. DESIGN： Controlled observation experiment. SETTING： Department of Morphology, Hunan Traditional Chinese Medical College; Department of Human Anatomy and Neurobiology, Xiangya Medical College, Central South University. MATERIALS： Thirty-five healthy adult SD rots of clean grade an d either gender, weighing （ 200 ± 20 ） g, were involved. According to the random digits table, the involved rats were randomized into 3 groups： normal group （n =5）, sham-operated group （n =5） and experimental group （n =25）. The experimental group were subdivided into 3, 7, 14, 21, 28 days groups according to different surviving time after operation, 5 rots at each time point. Polyclonal rabbit anti-P2X3 antibody （ABCAM company）; biotinylated goat anti-rabbit IgG （Zhongshanjingqiao Biotechnical Co., Ltd., Beijing）; Motic fluorescence microscope （Motic, Germany）. METHODS： The experiments were carried out in the Department of Human Anatomy and Neurobiology, Xiangya Medical College, Central South University from June to December 2006. ① Rats of experimental group were created into models by ligation of right sciatic nerve according to the method of Seltzer et al. Left sciatic nerve was used as self-control. As for rats in the sham-operated group, ligation of sciatic nerve was omitted, but other procedures were the same as those in the experimental group. Rats of normal group were untouched, ② Rats of the normal group and sham-operated group survived for 14 days separately, and those of experimental group survived for corresponding time. After being deeply anesthetized by intraperitoneal injection of over-dose sodium pentobarbital, the rots of experimental group were transcardially perfused. L4- 6 corresponding DRG connected to sciatic nerve were taken for preparing transverse sections serially. ③P2X3 expression in L4-6 DRG was detected by immunohistochemistry, immunofluorescence and image analysis techniques. MAIN OUTCOME MEASURES： P2X3 expression in L4-6 DRG of rots in each group. RESULTS： Thirty-five SD rats were involved in the final analysis. ① P2X3 expression in DRG： In normal DRG of rots, there were abundant P2X3 immuno-positive small- and medium-sized primary sensory neurons, especially the small ones, which mostly received the input from C fibers. There were only a few large neurons expressing P2X3. The immuno-positive products mostly were located in the cytoplasm and processes. The expression of P2X3 had a slight but significant decrease in ipsilateml L4-6 DRG 3 days after sciatic nerve ligation, and a decreasing tendency was observed with the elongation of time. At 28 days, the expression had not returned to base line, and still maintained at a low level. ② P2X3 immuno-positive gray scale in DRG： P2X3 immuno-positive gray scale in ipsilateral side L4-6 DRG was 117.74±2.38, 129.12± 4.86, 133.56±3.79, 148.75±6.90 and 150.49±5.15, respectively at 3,7,14, 21 and 28 days after sciatic nerve ligation, which was significantly higher than that in the normal group and sham-operated group （ 105.11 ±3.52, 104.22 ± 5.41, F =78.861, P 〈 0.05 ） , also significantly higher than that in the contralateral side （105.53±5.85, 108.54±3.70, 104.07±4.16, 106.55±2.02, 106.29±5.19, t=3.48- 13.95, P〈 0.05 ） ; There were no significant differences when comparing sham-operated group or contralateral side at each time point with normal group （P 〉 0.05） CONCLUSION： P2X3 is significantly down regulated in L4-6 DRG after sciatic nerve ligation. It may exert certain effects in neuropathic pain.

Exercise sustains the hallmarks of health

Exercise has long been known for its active role in improving physical fitness and sustaining health.Regular moderate-intensity exercise improves all aspects of human health and is widely accepted as a preventative and therapeutic strategy for various diseases.It is well-documented that exercise maintains and restores homeostasis at the organismal,tissue,cellular,and molecular levels to stimulate positive physiological adaptations that consequently protect against various pathological conditions.Here we mainly summarize how moderate-intensity exercise affects the major hallmarks of health,including the integrity of barriers,containment of local perturbations,recycling and turnover,integration of circuitries,rhythmic oscillations,homeostatic resilience,hormetic regulation,as well as repair and regeneration.Furthermore,we summarize the current understanding of the mechanisms responsible for beneficial adaptations in response to exercise.This review aimed at providing a comprehensive summary of the vital biological mechanisms through which moderate-intensity exercise maintains health and opens a window for its application in other health interventions.We hope that continuing investigation in this field will further increase our understanding of the processes involved in the positive role of moderate-intensity exercise and thus get us closer to the identification of new therapeutics that improve quality of life.

Role of calcium in polycystic kidney disease:From signaling to pathology

Autosomal dominant polycystic kidney disease （ADPKD） is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1 （PC1）, a large multi-functional memb-rane receptor protein able to regulate ion channel complexes, whereas polycystin-2 （PC2）, encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum （ER）. In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this feld could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.

Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats

AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia(HEEP) leaves on gastric ulcer healing.METHODS In this rat study involving males, intact(cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.RESULTS Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males(52.44%), intact females(85.22%), and ovariectomized females(65.47%), confirming that HEEP accelerates the healing of acetic acidinduced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor(intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2(intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed.CONCLUSION In gastric ulcers, HEEP-induced healing(modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.

Low-level laser therapy enhances the number of osteocytes in calvaria bone defects of ovariectomized rats

Background : Osteoporosis can make bone repair difficult. Low-level laser therapy( LLLT) has been shown to be a promising tool for bone neoformation. This study aimed to analyze the effect of LLLT on calvaria bone defects of ovariectomized rats using stereology. Methods : Fifty-four Wistar rats were subjected to bilateral ovariectomy, and bone defects were created in calvaria after 150 days. The animals were divided into nine groups(n = ?6 per group), and 24 hours after the bone defects were created they received three, six or 12 sessions of LLLT at 0, 20 or 30 J/cm 2, using a 780-nm low-intensity GaAlAs laser. One-way ANOVA followed by Tukey ' s post hoc test was used for data processing. A difference of P < 0.05 was considered statistically significant. The parameters evaluated were osteocyte density( Nv_(ost)), total osteocyte number( Nto ost), trabecular surface density( Sv_t), and trabecular surface area( Sa_t). Results : Data obtained showed that Nto ost, Sv t, and Sa t in group G2 rats were significantly different from G1(0 J/cm^2)( P < 0.05). Compared to group G4, G5 presented higher values for the parameters Sv t and Sa t, and G6 presented significantly higher values for almost all the analyzed parameters( Nv _(ost), Nto_(ost), Sv_t, and Sa t)( P < 0.05). Compared to group G7, G8 showed a higher value only for the parameter Sa t, and G9 showed significantly higher values for parameters Nv ost, Nto ost, Sv_t, and Sa_t. Conclusion : We conclude that LLLT stimulated bone neoformation and contributed to an increase in the total number of osteocytes, especially with a laser energy density of 30 J/cm^2 given for six and 12 sessions.

Peri-implantitis and periodontitis: Use of bacteriological test in dental practice

Peri-implantitis has been defined as an inflamematory condition involving dental implants, surrounding mucosa and bone, which lose supporting bone. Although high success rates for endosseous implants have been reported, failures occur, and some implants are lost or removed. At least 10% of the failures have been suggested to be the result of peri-implantitis. One of the major causes of the peri-implantitis is the bacterial colonization of implant surfaces but additional risk factors such as periodontitis, poor oral hygiene, tobacco consumption, prepost operative therapies and genetic susceptibility should be considered. In the present study a real-time PCR bases assay was designed to detect and quantify red complex species, then used to investigate 307 periodontal pocket samples from 127 periodontitis patients and 180 controls. Results demonstrated a significant higher prevalence of red complex species and increased amount of Porphyromonas gingivalis and Treponema denticolain periodontal pocket of periodontitis. Since a higher risk of peri-implantitis occurs in periodontally affected patients, detection and treatment of bacteria is a fundamental objective to ensure dental implant survival.

Effect of gestational protein restriction on left ventricle hypertrophy and heart angiotensin II signaling pathway in adult offspring rats

Maternal protein restriction may be a risk factor for cardiovascular disorders in adulthood. The RAS (renin-angiotensin-system) plays a pivotal role in cardiac remodeling. Components of the RAS, including angiotensin II (AngII) and its receptors type 1 (AT1R) and 2 (AT2R) are expressed in the heart. This study investigates whether gestational protein restriction alters the expression and localization of AT1R and AT2R and RAS signaling pathway proteins in parallel with left ventricle hypertrophy and systemic hypertension in male offspring. Dams were kept on normal (NP, 17% protein) or low (LP, 6% protein) protein diet during pregnancy. Systolic blood pressure (SBP) of male offspring was measured from the 8th to 16th week and left ventricles of 16-wk-old rats were processed for histology, morphometric, immunoblotting and immunohistochemistry. LP offspring showed a significant reduction in birth body weight and SBP increased significantly from the 8th week. Left ventricle mass and cardiomyocytes area were also significantly higher in LP animals. Widespread perivascular fibrosis was not detected in the heart tissue. Analysis by immunoblotting and immunohistochemistry demonstrated a significant enhance in cardiomyocyte expression of AT1R and ERK1 in LP offspring. Expression of PI3K in LP was significantly reduced in cardiomyocytes and in the intramural coronary wall, while AT2R expression was unchanged in the NP group. We also found reduced LP expression of JAK2 and STAT3. In conclusion, our data also suggest that changes in the RAS may play a role in the ventricular growth through upregulation of the AT1-mediated ERK1/2 response, despite unchanged AT2R expression.

Buyuan Congnao decoction decreases hippocampal beta-amyloid expression in a rat model of Alzheimer's disease

A mixture of ibotenic acid and β-amyloid 1-42 was injected into the hippocampus of a rat model of Alzheimer＇s disease, followed by intragastric administration of a traditional Chinese medicine Buyuan Congnao decoction （main components included radix astragali, radix polygoni multiflori preparata, rhizoma acori talarinowii, radix polygalae, fructus alpiniae oxyphyllae, and radix glycyrrhizae preparata） and a piracetam suspension. Following treatment with traditional Chinese medicine or western medicine, β-amyloid expression decreased and neuronal morphology was normal in the rat hippocampal CA1 region, in addition to significantly shortened average latency in the Morris water navigation task. These findings suggested that compound prescription of Buyuan Congnao decoction, similar to the curative effects of piracetam, decreased hippocampal β-amyloid expression in a rat model of Alzheimer＇s disease, as well as improved learning and memory.

On the origin of cardiac mucosa: A histological and immunohistoc-hemical study of cytokeratin expression patterns in the developing esophagogastric junction region and stomach

AIM： To examine the fetal and neonatal esophagogastric junction region （EGJ） histologically for the presence of an equivalent to adult cardiac mucosa （CM）; to study the expression patterns of all cytokeratins （CK） relevant to the EGJ during gestation; to compare the CK profile of the gestational and the adult EGJ; and to determine the degree of development in the adult EGJ histology and CK profile during gestation. METHODS： Forty-eight fetal autopsy specimens of the EGJ were step-sectioned and stained with hematoxylin and eosin （H＆E） to select sections showing the mucosal lining. Immunohistochemistry for CK5, 7, 8, 13, 18, 19, and 20 was performed. Antibody staining was then graded for location, intensity, and degree. RESULTS： The distal esophagus was lined by simple columnar epithelium from 12-wk gestational age （GA）. The proximal part of this segment consisted of mucusproducing epithelium, devoid of parietal cells. CK5 and 13 were present exclusively in multilayered epithelia and CK8, 18, and 19 predominantly in simple columnar epithelium. There were no differences in the frequencies of the coordinate CK7＋/20＋ and the CK7-/20- immunophenotypes between different locations. The prevalence of the CK7＋/ 20- immunophenotype decreased, and that of the CK7-/ 20＋ immunophenotype increased significantly from the distal esophagus to the distal stomach. CONCLUSION： Fetal columnar-lined lower esophagus （fetal CLE） may be the equivalent and precursor of the short segments of columnar epithelium found in the distal esophagus of some normal adult subjects. Esophageal simple columnar epithelium without parietal cells （ESN） may be the precursor of adult CM. The similarities between the fetal and adult EGJ and stomach CK expression pattems support the conclusion that adult CN has an identifiable precursor in the fetus. This would then indicate that at least a part of the adult CM has a congenital origin.

TREATMENT OF 37 CASES OF SCAPULOHUMERAL PERIARTHRITIS BY NEEDLE-KNIFE THERAPY

Scapulohumeral 仙子关节炎，通常并且经常遇到的疾病在之中中年并且老，造成很多麻烦到 suffers 的生活和工作。Inmodern 药它被止痛剂的非外科的本地温柔的点块治疗，或口头的管理管理，治疗学的结果是相反的。作者从 1998 年 9 月与按摩在联合由针刀治疗对待疾病的 37 个案例到 2002 年 12 月并且获得了满足的结果。处理在下列被报导。

Precise tissue bioengineering and niches of mesenchymal stem cells:Their size and hierarchy matter

Stem cell microterritories(niches),as a specialized part of the extracellular matrix(ECM),are considered an important target and tool for the development of new materials,medical implants,and devices.However,tissue bioengineering products that have stem cell niches of known size on the surface or in the bulk structure of artificial materials are practically unknown.This brief review attempts to draw attention to the problematic aspects of niches as specific parts of the ECM,such as their hierarchy and size for mesenchymal stromal/stem cells(MSCs).These parameters arise directly from numerous definitions of stem cell niches as specialized morphological microterritories found in various tissues.The authors of this review analyze the known information on the hierarchy of MSC microterritories by analogy with that of hematopoietic stem cells.Occasional reports on the size of artificial MSC niches compared to natural niche candidates are summarized.A consensus on a hierarchy and optimal range of niche sizes for MSCs and other stem cells is needed to accelerate the development of prototyping technologies and additive manufacturing in applications to precise tissue bioengineering and regenerative medicine.

THE STUDY ON RELATION BETWEEN CD1a^+ CELLS AND INFILTRATIVE CD3 ^+ AND CD8 ~ + CELLS IN RENAL TISSUE OF GLOMERULONEPHRITIS

Objective To discuss the role of dendritic cell s (DCs) in cellular immunity pathogenesis of glomerulonephritis (GN). Meth ods 114 patients with GN were selected randomly and divided into two gr oups, primary GN (pGN) and secondry GN (sGN). CD1a +, CD3 + and CD8 + cells in bioptic renal tissues were examined immunohistochemically. The di stribution of CD1a + cells and the infiltration of CD3 + and CD8 + cells in renal tissues were observed. Results There was no si gnificant difference of CD1a +, CD3 +, and CD8 + cells between pG N and sGN group (P>0.05). CD1a + cells had significant positive correla tion with the infiltrative CD3 + and CD8 + cells, respectively (P< 0.01). The infiltrative CD3 + cells had significant positive correlation wi th the CD8 + cells in the same area, respectively (P<0.01). CD1a + cells, CD3 + cells infiltrating in both glomeruli and renal interstitial t issues, and CD8 + cells only infiltrating in renal interstitial tissues, al l of them had significant positive correlation with the degree of glomerular pro liferation, respectively (P<0.05). The infiltrative CD3 + and CD8 + cells in renal interstitial tissues had significant positive correlation with the degree of glomerular sclerosis and the lesion degree of renal tubule and in terstitial, respectively (P<0.05). There were significant positive correlati on between CD1a + cells and the lesion degree of renal interstitial (P< 0.05). Conclusion DCs could activate T lymphocyte by presenting antigen, then the activated T lymphocyte participate in the pathogenesis of GN through releasing cytokine and/or directly damaging the renal tubule and interst itial, which produce more serious glomerular lesion.

Enhancement of TRAIL cytotoxicity by AG-490 in human ALL cells is characterized by downregulation of cIAP-1 and cIAP-2 through inhibition of Jak2/Stat3

The ability of death-inducing tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） to selectively kill a variety of cancer cells has been largely described, but one of the major concerns with the treatment is the occurrence of drug resistance and possible toxic side effects. Here, we report that TRAIL induces apoptosis in Jurkat and SUPT1 T cell lines and in human T-ALL blasts but not in healthy subject-derived peripheral blood mononuclear cells. In parallel, the treatment with TRAIL and Tyrphostin （AG-490）, a selective Janus kinase 2 inhibitor, produces an evident enhancement of cytotoxicity, characterized by a significant inhibition of Stat3 phosphorylation compared to controls or to TRAIL alone-treated samples, and associated with a dramatic decrease of both clAP-1 and clAP-2 mRNA levels. Downregulation of clAP-1 and cIAP-2 by specific small interference RNAs significantly amplifies TRAIL-reduced cytotoxicity. All together, these findings strongly indicate that clAP-1 and clAP-2 downregulation is a fundamental step in the signaling pathways mediating the combinatorial effect of TRAIL and AG-490 on T cell leukemia. These findings may help to open new routes for the development of less toxic pharmacological strategies in the treatment of patients affected by TRAIL-sensitive leukemias.