S100 proteins and their implication in the thalamus: an integrative review / Las proteínas S100 y su implicación en el tálamo: una revisión integradora

SUMMARY: S100 proteins belong group of calcium-binding proteins and are present in physiological intracellular and extracellular regulatory activities, such as cell differentiation, and act in inflammatory and neoplastic pathological processes. Recently, its expressions in the nervous system have been extensively studied, seeking to elucidate its action at the level of the thalamus: A structure of the central nervous system that is part of important circuits, such as somatosensory, behavioral, memory and cognitive, as well as being responsible for the transmission and regulation of information to the cerebral cortex. This article is an integrative review of scientific literature, which analyzed 12 studies present in Pubmed. The analysis showed that the relationship of S100 proteins and the thalamus has been described in neoplastic processes, mental disorders, hypoxia, trauma, stress, infection, Parkinson's disease and epilepsy. In summary, it is possible to conclude that this protein family is relevant as a marker in processes of thalamic injury, requiring further studies to better understand its clinical, preclinical meanings and its prognostic value.

Las proteínas S100 pertenecen al grupo de proteínas fijadoras de calcio y están presentes en actividades reguladoras fisiológicas intracelulares y extracelulares, como la diferenciación celular, y actúan en procesos patológicos inflamatorios y neoplásicos. Recientemente, sus expresiones en el sistema nervioso han sido ampliamente estudiadas, buscando dilucidar su acción a nivel del tálamo: una estructura del sistema nervioso central que forma parte de importantes circuitos, como el somatosensorial, conductual, de memoria y cognitivo, así como además de ser responsable de la transmisión y regulación de la información a la corteza cerebral. Este artículo es una revisión integradora de la literatura científica, que analizó 12 estudios presentes en Pubmed. El análisis mostró que la relación de las proteínas S100 y el tálamo ha sido descrita en procesos neoplásicos, trastornos mentales, hipoxia, trauma, estrés, infección, enfermedad de Parkinson y epilepsia. En resumen, es posible concluir que esta familia de proteínas es relevante como marcador en procesos de lesión talámica, requiriendo más estudios para comprender mejor su significado clínico, preclínico y su valor pronóstico.

Expression of CD44 in Tumor Tissue and Serum of Small Cell Lung Cancer and Its Clinical Prognostic Significance / 中国肺癌杂志

BACKGROUND@#Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth, early metastasis and acquired therapeutic resistance, and the prognosis is extremely poor. Studies have proved that the stem cell marker CD44 is correlated with tumor recurrence and treatment resistance, however, there are limited reports yet concerning on the CD44 expression and its clinical prognostic significance in SCLC patients. The purpose of this study is to investigate the expression of CD44 in tumor tissues as well as serum of SCLC patients and explore its correlation with the clinical characteristics, therapeutic effect and prognosis.@*METHODS@#The tumor tissues and serum samples of 47 newly diagnosed SCLC patients were collected. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to detect CD44. The relationship between CD44 level and the clinical characteristics as well as prognosis of the patients was analyzed.@*RESULTS@#The stem cell marker CD44 was detectable both in serum sample and tumor tissue of SCLC patients. The positive rate of CD44 in tumor tissue was significantly higher in patients with performance status (PS) 2 than that of patients with PS 0-1 (85.71% vs 30%, P=0.017). Patients were divided in to different groups according to the treatment efficacy. The CD44 immunohistochemical score and serum level in the disease progression group were significantly higher than those in the disease control group, and the differences were statistically significant (P=0.006, P=0.034), Univariate analysis depicted that the progression-free survival (PFS) of CD44 positive patients was significantly shorter than that of CD44 negative patients (5.23 mon vs 9.03 mon, P=0.036).@*CONCLUSIONS@#The positive expression of CD44 in tumor tissues of pre-treatment SCLC patients is correlated with poor PFS. The clinical significance of CD44 is worthy to be further studied.

Clinicopathological correlation of cancer stem cell markers Oct-4 and CD133 expression as prognostic factor in malignant lesions of gallbladder: An immunohistochemical study

Background: Gallbladder cancer (GBC) is the most frequent biliary tract cancer, with high morbidity and poor prognosis, and shows early metastasis and invasiveness. No reliable biomarkers are available for detection of GBC progression. Aim: To investigate the immunohistochemical expression of Oct-4 and CD133 in malignant and nonneoplastic lesions of gallbladder and to analyze the clinical significance of the expressions related to clinicopathological parameters. Settings and Design: This is a prospective case control study, conducted in medical college background. Materials and Methods: A total of 103 cases of gallbladder were grouped into malignant lesions (n = 48) and nonneoplastic lesions (simple epithelial hyperplasia; n = 35 and chronic cholecystitis; n = 20). All tissue samples were evaluated for expression of Oct-4 and CD133 using immunohistochemistry in an effort to elucidate the correlation between their expressions with clinicopathological parameters. Statistical Analysis: The final score was calculated by multiplying the intensity to the percentage of positive cells. The scores ?2 were considered as positive. Results: Significant positive correlation of higher expression levels of Oct-4 and CD133 were observed in malignant as compared to nonneoplastic lesions of gallbladder (P < 0.0001). High expression of Oct-4 and CD133 were significantly associated with tumor grading (Oct-4, P = 0.04; CD133, P = 0.02), staging (Oct-4, P = 0.03; CD133, P = 0.02), and liver metastasis (Oct-4, P = 0.01; CD133, P = 0.007). Significantly reduced survival was observed with high expression of Oct-4 (P = 0.002). No significant correction was observed between CD 133 and survival. Conclusion: This study revealed that high expression level of Oct-4 may provide a new insight for the prognosis of the disease in terms of clinical staging and grade.

The feasibility of PKH26-marked human adipose derived mesenchymal stem cells and intraocular trace / 中华实验眼科杂志

Objective@#To evaluate the feasibility of PKH26 marked human adipose derived mesenchymal stem cells (hADSCs) in vitro and intraocular.@*Methods@#HADSCs were cultured in vitro and marked with PKH26.Eighteen C57BL/6J mice were divided into normal control group (6 mice), labeled cell group (9 mice) and unlabeled cell group (3 mice) by using sortition randomization method, labeled cells were injected intravitreally in C57BL/6J mice as labeled cell group, and the unlabeled cells were injected intravitreally in C57BL/6J mice as unlabeled cell group.After 1 month, retinal slab was checked to contrast the results of intraocular labeling.The retina was taken out for hematoxylin-eosin staining and electron microscopy to observe the toxicity.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.@*Results@#In vitro, red fluorescent was found in the cytomembranes after hADSCs were labeled by PKH26.Retinal patch of labeled cell group showed red fluorescence of hADSCs were in front of the retina.Hematoxylin-eosin staining of retinal tissue and optic ganglion cells showed that cell degeneration and proliferation were not found in labeled cell group.The hADSCs in vivo and in vitro marked enhancement results showed that, no fluorescent was found in the unlabeled cell group, the color positive rate were both 0, while red fluorescence was found in the labeled cell group, the color positive rate were both 100%.@*Conclusions@#PKH26 can be used to mark and intraocular trace of hADSCs.Also, it has no morphology toxic reaction.

Effects of Buyang Huanwu Decoction on Endothelial-mesenchymal Transformation of Lung Tissue in Idiopathic Pulmonary Fibrosis Model Rats and Mechanism Study / 中国药房

OBJECTIVE： To investigate the effects of Buyang huanwu decoction on endothelial-mesenchymal transformation （EndMT） of lung tissue in idiopathic pulmonary fibrosis （IPF） model rats， and to explore its potential mechanism. METHODS： Male SD rats were randomly divided into normal group， model gorup， dexamethasone group [0.405 mg/（kg·d）]， Buyang huanwu decoction low-dose， medium-dose and high-dose groups [6.435， 12.87， 25.74 g/（kg·d）， by raw material]， with 8 rats in each group. Except for normal group， other groups were given endotracheal injection of bleomycin to induce IPF model. On the second day after modeling， normal group and model group were given water intrgastrically [10 mL/（kg·d）]； administration groups were given relevant medicine intragastrically， once a day， for consecutive 28 days. 24 h after last medication， the expression of endothelial cell markers [platelet endothelial cell adhesion molecule 1， vascular endothelial cell cadherin] and interstitial cell markers [α-smooth muscle actin， fibroblast specific protein 1] were detected by immunohistochemistry method. The expression of Notch4 and DLL4 in lung tissue of rats were detected by Western blotting assay. RESULTS： Compared with normal group， the expression of endothelial cell markers were decreased significantly in lung tissue of model group， while the expressipon of interstitial cell markers， Notch4 and DLL4 were increased significantly （P＜0.01）. Compared with model group， the expression of endothelial cell markers in lung tissue of rats were increased significantly in administration groups， while Buyang huanwu decoction low-dose group was significantly lower than dexamethasone group； the expression of interstitial cell markers， Notch4 and DLL4 were decreased significantly， while Buyang huanwu decoction low-dose group was significantly higher than dexamethasone group （P＜0.05 or P＜0.01）. CONCLUSIONS： Buyang huanwu decoction can relieve IPF of model rats by intervening in EndMT， the mechanism of which may be associated with inhibiting DLL4/Notch4 singaling pathway.

Advances in the role of microRNAs in liver cancer stem cells / 中华肝胆外科杂志

Liver cancer stem cells have the abilities of infinite proliferation,self-renewal,chemoradiation tolerance,high tumorigenicity and stem cell characteristics.The proportion of liver cancer stem cells is positively correlated with the malignancy of the tumor.MicroRNAs (miRNA) can regulate the expression of many genes by degrading mRNA or inhibiting mRNA translation.MicroRNAs also play an important role in a series of life activities such as embryogenesis,tissue and organ development,cell growth and differentiation,apoptosis,disease development.In-depth study of specific miRNA in the occurrence and development of liver cancer and its role in LCSCs,it may provide a new target for prevention and treatment of recurrence and metastasis of liver cancer.

Research progress of AIDS treatment / 中国人兽共患病学报

AIDS antiviral therapy (ART) has achieved great success.Originaly,AIDS had been regarded as a fatal disease,but it has become a kind of infectious disease that could be cured and administrated.Global HIV / AIDS cases were still up to about 38 million,but more than half have been effectively treated.In addition to drug treatment,at present,some new technologies and new methods,such as genome editing,have also been involved in the treatment of AIDS,and in the humanized animal experiment has shown very good results.There is no doubt that AIDS will eventually be stopped its epidemic.However,with the continuous development of AIDS antiviral treatment,the most fundamental problem is that HIV latent library has become increasingly prominent one,whether molecular therapy and hybrid cure have being developed for AIDS treatment,there are still such problem existence.Great efforts shoud be made to continuously search for new markers of latent viral cells and to reduce the latent pool.In addition,despite the prevention and treatment of AIDS has made great achievements,but the world still produces nearly 6000 cases of HIV/AIDS every day.Therefore,the development of safe and effective vaccine,whether in the field of prevention,or in clinical treatment,has its positive significance.

RESULTS OF CULTURING STEM CELLS DERIVED FROM MOUSE BONE MARROW UNDER VARYING OXYGEN CONDITIONS / Шинэ санаа Шинэ нээлт

@#BACKGROUND: In the recent years, mesenchymal stem cells have become increasingly utilized in regenerative medicine and tissue engineering applications because of their properties for self-renewal, differentiation and immunoregulation. The use of stem cells of various clinical applications is highly expected and the production of good quality stem cells is very critical for basic studies. In the bone marrow, hematopoietic and mesenchymal stem cells from an unique niche in which the oxygen tension is low. Hypoxia may have a role in maintaining stem cell fate, self renewal and multi-potency. We investigated whether low oxygen culture would be beneficial for hematopoietic stem cell and mesenchymalstemcell. MATERIAL: BMCs from 8-12 week aged, 15 mice were subjected to hypoxic conditioning by culture for 8-10 days in 20%, 3%, 1% oxygen. For culture 1x105cell/ml were seeded in colony forming assay and 2x106cell/ml were seeded in L-glutamin mediain chamber slide. We counted cell colonies under different hypoxic condiontins by Olympus IX71 fluorescence microscope. After cell culture in chamber slide, we stained cells by anti-CD90 and anti-CD105 then counted positive cells by Olympus IX71 fluorescence microscope. RESULTS: Compared to normoxic cells and hypoxic cells well morphologically differentiated and counted by Olympus IX71 microscope. More colonies were observed at 3%, 1% oxygen. Statistical significances were identified with granulocytes and macrophage colony (p<0.05) in hypoxic condition. More anti-CD90 and anti-CD105 markers were observed at 3% oxygen condition. Statistical significances were identified in 3% oxygen condition with cell markers(p<0.001). CONCLUSIONS: Our data suggests low physiological oxygen culture could improve the stemness of macrophage and granulocytes colony and improve the differentiation of mesenchymal cells. Long term culturewith additional cell markers will be necessary to confirm whether low physiological oxygen levels also improve genomic stability

Stem Cell Therapy in Dentistry: An Overview.

Cells with a unique capacity for self-renewal and potency are called stem cells. With appropriate biochemical signals stem, cells can be transformed into desirable cells. Regeneration of oral and maxillofacial structures is earned out by using stem cell therapy, and this has gained momentum in recent days. Future tissues like tissue engineered bone grafts, engineered joints and cranial sutures can be developed with stem cell therapy. We have described the properties, types and advantages of dental stem cells. Emphasis is been given to the possibilities of stem cell therapy in the oral and maxillofacial region including regeneration of tooth and craniofacial defects.

Isolation and tumorigenicity of CD133 + subpopulation in human hepatocellular carcinoma / 中华肝胆外科杂志

Objective To separate the CD133 + subpopulation in human hepatocellular carcinoma (HCC) and investigate the tumorigenicity.Methods The human liver cancer tissues were subcutaneously transplanted into nude mice to generate xenograft tumors which were then isolated to prepare single cell suspension.The expression of CD133 + subpopulation was further detected using flow cytometry.The CD133 + subpopulations were separated and depurated with magnetic-activated cell sorting system.Immunofluorescence was performed to identify the histological phenotype of CD133 + subpopulation.The in vitro and in vivo clone formation assay and in vivo xenograft formation assay were performed, respectively.Results Flow cytometry analysis revealed that a percentage of (4.1 ± 0.6) ％ CD133 + cells were detected in xenografts.Immunofluorescence studies showed that (86.8 ± 7.5) ％ of the isolated cells were CD133 +.Compared with CD133-population, CD133 + cells showed a higher capability to generate clone sphere in vitro and a higher tumorigenicity in nude mice (P ＜ 0.05).Conclusion The CD133 + subpopulation in human hepatocellular carcinoma had a potent tumorigenicity and was enriched in cancer stem cells.

Culture mesenchymal stem cells under hypoxic conditions / Эрүүл мэндийн лаборатори

Background:Mesenchymal stem cells derived from bone marrow and adipose tissue are being applied to tissue engineering and cell therapy. The use of stem cells of various clinical applications is highly expected and the production of good quality stem cells is very critical for basic studies. In the bone marrowmesenchymal stem cells from an unique niche in which the oxygen tension is low. Hypoxia may have a role in maintaining stem cell fate, self renewal and multi-potency. We investigated whether low oxygen culture would be beneficial for mesenchymal stem cell. Results:BMCs from 8-10 week aged, 6 mice were subjected to hypoxic conditioning by culture for 7 days in 20%, 3%, 1% oxygen. For culture 1x106 cell/ml were seeded in media with L-glutamine in each dish. During the culturing, cell colonies were checked once in three days. After cell culture, we stained cells by CD90 then counted CD90 positive cells by fluorescence microscope. More colonies and mesenchymal cells were observed at 3%, 1% oxygen and also colonies were bigger in hypoxic condition. Statistical significances were identified mesenchymal cells (p<0.05) in hypoxic condition. Conclusions:Our data suggests low physiological oxygen culture could improve the differentiation of mesenchymal cells. Long term culture will be necessary to confirm whether low physiological oxygen levels also improve genomic stability.

Research progress of cancer stem cell markers in colorectal cancer / 肿瘤研究与临床

Now that the cancer stem cell (CSC) theory has been verified for many scholars.The key to the identification of CSC is to find specific stem cell surface markers.The study of colorectal CSC continues to show progress.In recent years,many stem cell markers were discovered,such as CD44,SOX9,ALDH1,OCT-4 and so on.This article will discuss the relationship between those makers and colorectal cancer.

Cyclooxygenase 2 in Gastric Carcinoma Is Expressed in Doublecortin- and CaM Kinase-Like-1-Positive Tuft Cells

BACKGROUND/AIMS: Doublecortin and CaM kinase-like-1 (DCAMKL1) is a marker of stem cells expressed predominantly in the crypt base in the intestine. However, DCAMKL1-positive cells have been shown to be differentiated tuft cells rather than quiescent progenitors. Tuft cells are the only epithelial cells that express cyclooxygenase 2 (COX-2) in the normal intestinal epithelium. We previously generated Cdx2-transgenic mice as model mice for intestinal metaplasia and gastric carcinoma. In the current study, we investigated the association between COX-2 and DCAMKL1 in gastric carcinoma. METHODS: We examined the association between COX-2 and DCAMKL1 expression in gastric carcinomas in clinical samples (early gastric well-differentiated adenocarcinoma) and Cdx2-transgenic mice; and the DCAMKL1-transgenic mouse stomach using immunohistochemistry and quantitative real-time polymerase chain reaction. RESULTS: The COX-2-expressing cells were scattered, not diffusely expressed, in gastric carcinomas from humans and Cdx2-transgenic mice. DCAMKL1-positive cells were also scattered in the gastric carcinomas, indicating that tuft cells could still be present in gastric carcinoma. COX-2 was expressed in DCAMKL1-positive tuft cells in Cdx2- and DCAMKL1-transgenic mouse stomachs, whereas the Sox9 transcription factor was ubiquitously expressed in gastric carcinomas, including COX-2-positive cells. CONCLUSIONS: COX-2 is expressed in DCAMKL1-expressing quiescent tuft cells in gastric carcinoma.

Correlação da expressão do receptor do fator de crecimento do epitélio vascular (VEGRF1) e do KI-67, em pacientes com câncer de mama, com variáveis histopatológicas / Correlations of the expression of the receptor of vascular endothelial growth factor (VEGF) and ki-67 with phatological variables in breast cancer patients

Correlação da expressão do receptor do fator de crescimento do epitélio vascular - vascular endothelial growth factor (VEGF) e do KI-67, em pacientes com câncer de mama, com variáveis histopatológicas. Introdução: proteínas que influam na proliferação celular, como o VEGF e o KI-67, são alvo de estudos. O VEGF está implicado na angiogênese, que é necessária ao crescimento tumoral. Objetivo: Analisar a correlação do VEGF e do KI-67 com variáveis histopatológicas. Métodos: entre 15/03/2008 e 14/0412009, incluímos 41 pacientes com câncer de mama inicial, rumores T1 e T2, para estudo, usando a coloração H & E na análise do tumor, grau histológico e invasão vascular e a imunoperoxidade para a avaliação imuno-histoquímica com anticorpos específicos para os receptores de VEGF, KI-67, p53 e receptor de estrogênio (RE), usando escore qualitativo até 3+ na avaliação da intensidade da coloração e/ou quantitativo até 5+, para avaliar a expressão percentual das células coradas. O escore total, soma das duas, pode chegar ao máximo de 8+. Apenas o KI-67 foi categorizado pelo percentual de células coradas na IHQ e considerado positivo a partir de 20%. Resultados: O receptor do VEGFR1, tanto no escore intensidade de cor quanto no escore total, apresenta correlação positiva com os tumores T1 (p=.01), com o receptor estrogênico positivo (p=.01) e com a expressão negativa do KI-67 (p=.02). A expressão do KI-67 apresenta correlação positiva com p53 (p=.00) e com o receptor hormonal negativo (RE-) (p=.04) e correlação fraca com a invasão vascular (p=.09) e o grau histológico indiferenciado (G3) (p=.07). Discussão: A avaliação de marcadores tumorais que possam responder à terapia alvo é um objetivo a ser perseguido. A correlação positiva do VEGF com o status do RE ja foi relatada e está de acordo com nossos resultados. A expressão do KI-67 é associada à pobre evento. Os resultados controversos dos marcadores refletem a dificuldade em padronizar as avaliações (reagentes)...

Correlation of the expression of the receptor of vascular endothelial growth factor (VEGP) and KI-67 with pathological variables in breast cancer patients. Background: Many studies have been conducted on proteins that have action on cell proliferation, such as VEGP and KI-67. VEGP acts in the angiogenesis required for tumor growth. The KI-67 correlates with proliferation of tumor cells, probably reflecting its aggressiveness. Objective: To analyze the correlation of VEGPR1 and KI-67 with pathological variables. Methods: The study was approved by the Committee on Ethics in research, University Hospital of Porto Alegre (RS). Between March 2008 and April 2009 we included 41 patients with early breast cancer (T1 and T2). We used H & E staining for tumor analysis, histological grade and vascular invasion, and immunohistochemistry evaluation with antibodies specific for VEGP receptors, KI-67, p53, estrogen receptor (ER), using quality score until 3+ of the evaluation of intensity of stain and quantitative untiI 5+, to evaluate the expression percentage of stained cells. The total score, add either, can reach 8+ Only the KI-67 was categorized by percentage of stained cells in the IHC and considered positive above 20%. Statistics: correlation and pearson's chi square and, for the significant variables, used the multivariate analysis. Results: The receptor VEGPR1 in both color intensity score and the total score, correlated positively with T1 tumors (p=.01), with the estrogen receptor positive (p=.01) and negative expression of KI-67 (p=.02). The expression of KI-67 correlates positively with p53 (p=.00) and with estrogen receptor negative (p=.04) and weak correlation with vascular invasion (p=.09) and histological grade undifferentiated (p=.07). Discussion: evaluation of tumor markers that may respond to targeted therapy is a goal to be pursued. The positive correlation of VEGP with the status of ER has been reported and is consistent with our results...

The current status and future in limbal stem cells research / 眼科

The discovery of limbal stem cells is the key advancement in ophthalmology in the 20th century.Many clinical researches have proved that limbal stem cells transplantation is an effective method to treat severe ocular surface diseases.However, some important issues associated with the identification,isolation,standardized culture in vitro and differentiation after transplantation are still not clear and need to be paid more attention.Strengthening the underlaying research in this field will play important role in treating corneal blindness.

Macrophage/dendritic Cell Marker Staining Characteristics of Langerhans cell Granulomatosis(Histiocytosis X)

Histiocytosis X is characterized by aggregates of Langerhans cells with other inflammatory cells. These Langerhans cells are antigen-presenting cells to T lymphocytes and identified by characteristic morphology, ultrastructural demonstration of Birbeck granules and immunologic reactivity with OKT-6 and HLA-DR antibodies. In this report, the tumor arising in a 2-years-old baby was examined byimmunostaining with several macrophage/dendritic cell markers. The main tumor cells showed cytoplasmic and nuclear staining with S-100 protein and ring-like surface and paranuclear staining with PNA. However, they were negative for follicular dendritic cell marker CD21, macrophage markers lysozyme, Mac 387, alpha-1 antitrypsin and CD68, and interdigitating reticulum cell marker ID4 and ID5. These observations demonstrate the usefulness of S-100 protein and PNA for the identification of Langerhans cells in paraffin-embedded tissue.