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Colorectal cancer (CRC) is the third most prevalent cancer in the world. The PD-1/PD-L1 pathway plays a crucial role in modulating immune response to cancer, and PD-L1 expression has been observed in tumor and immune cells within the tumor microenvironment of CRC. Thus, immunotherapy drugs, specifically checkpoint inhibitors, have been developed to target the PD-1/PD-L1 signaling pathway, thereby inhibiting the interaction between PD-1 and PD-L1 and restoring T-cell function in cancer cells. However, the emergence of resistance mechanisms can reduce the efficacy of these treatments. To counter this, monoclonal antibodies (mAbs) have been used to improve the efficacy of CRC treatments. mAbs such as nivolumab and pembrolizumab are currently approved for CRC treatment. These antibodies impede immune checkpoint receptors, including PD-1/PD-L1, and their combination therapy shows promise in the treatment of advanced CRC. This review presents a concise overview of the use of the PD-1/PD-L1 blockade as a therapeutic strategy for CRC using monoclonal antibodies and combination therapies. Additionally, this article outlines the function of PD-1/PD-L1 as an immune response suppressor in the CRC microenvironment as well as the potential advantages of administering inflammatory agents for CRC treatment. Finally, this review analyzes the outcomes of clinical trials to examine the challenges of anti-PD-1/PD-L1 therapeutic resistance.
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Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50%of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine le-sions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glio-blastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell char-acteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.
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OBJECTIVE Baicalin is a major flavonoid component of Scutellaria baicalensis, and has been used in the treatment of liver diseases for many years. However, the role of baicalin in estrogen-induced cholestasis (EIC) remains to be elucidated. This present study explored the protective effect of baicalin against estrogen-induced liver injury and further elucidated the mechanisms involved both in vivo and in vitro. METHODS We conducted a series of experiments using 17α-ethinylestradiol (EE) induced cholestatic rats and cultured HepG2 cells. Serum, bile, and liver samples were collected for biochemical and histological analyses. Bile acid composition in liver was analyzed by LC-MS/MS. The mechanisms underlying the hepatoprotective of baicalin were investigated by RT-PCR, Western blotting analyses and immunohistochemistry. RESULTS Baicalin showed obvious hepatoprotective effects in EIC rats by reducing serum bio?markers and increasing the bile flow rate, as well as by alleviating liver histology and restoring the abnormal composition of hepatic bile acids (BAs). In addition, baicalin protected against EE induced liver injury by up-regulation of the expres?sion of hepatic efflux transporters and down-regulation of hepatic uptake transporters. Furthermore, baicalin increased the expression of hepatic BA synthase (CYP27A1) and metabolic enzymes (Bal, Baat and Sult2a1) in EIC rats. We showed that baicalin significantly inhibited hepatic inflammatory responses in EIC rats through reducing elevated levels of TNF-α, IL-1β, IL-6 and NF-κB. Finally, we confirmed that baicalin maintains BA homeostasis and alleviates inflamma?tion through Sirt1/HNF-1α/FXR signaling pathway. CONCLUSION Baicalin protects against estrogen-induced cholestatic liver injury, and the underlying mechanism involved is related to activation of the Sirt1/HNF-1α/FXR signaling pathway.
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Objective:To explore the genetic diversity and population structure of <italic>Erigeron breviscapus</italic>, so as to provide a scientific basis for its resource protection and rational utilization. Method:Twelve pairs of simple sequence repeat(SSR) primers were screened out from 243 individuals in 16 natural populations to calculate the genetic diversity parameters of <italic>E. breviscapus</italic>, which were then subjected to principal coordinate analysis and cluster analysis. Result:Twelve SSR markers generated 209 alleles, with an average of 17.417 alleles per locus. Based on 12 SSR markers and 16 populations of <italic>E. breviscapus</italic>, the observed heterozygosity (<italic>H</italic><sub>0</sub>) values were determined to be 0.603 and 0.613, the expected heterozygosity (<italic>H</italic><sub>e</sub>)to be 0.658 and 0.659, and the Shannon's information index (<italic>I</italic>) to be 1.443 and 1.446, respectively. The Wright's fixation index (<italic>F</italic><sub>st</sub>) was 0.123 and gene flow (<italic>N</italic><sub>m</sub>) was 2.077. Analysis of molecular variance (AMOVA) and genetic differentiation revealed that genetic variation within populations was the main source of total variation. The Nei's genetic distance and genetic identity coefficients were within the ranges of 0.107 (YA and XY)-0.713 (SZ and XZD) and 0.490 (SZ and XZD)-0.899 (YA and XY), respectively. As demonstrated by the principal coordinate analysis and cluster analysis, the 16 populations of <italic>breviscapus </italic>were divided into two clusters. Conclusion:The genetic diversity of <italic>E. breviscapus</italic> was relatively high and there existed certain genetic differentiation and gene flow within and among populations. The genetic variation was mainly present within populations. All these have provided reference for subsequent study on good germplasm selection of <italic>E. breviscapus.</italic>
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Screening suitable reference genes is the premise of quantitative Real-time PCR(qRT-PCR)for gene expression analysis. To provide stable reference genes for expression analysis of genes in Aconitum vilmorinianum, this study selected 19 candidate re-ference genes(ACT1, ACT2, ACT3, aTUB1, aTUB2, bTUB, 18S rRNA, UBQ, eIF2, eIF3, eIF4, eIF5, CYP, GAPDH1, GAPDH2, PP2A1, PP2A2, ACP, and EF1α) based on the transcriptome data of A. vilmorinianum. qRT-PCR was conducted to profile the expression of these genes in the root, stem, leaf, and flower of A. vilmorinianum. The Ct values showed that 18S rRNA with high expression level and GAPDH2 with large expression difference among organs were not suitable as the reference genes. NormFinder and geNorm showed similar results of the expression stability of the other candidate reference genes and demonstrated PP2A1, EF1α, and CYP as the highly stable ones. However, BestKeeper suggested EF1α, ACT3, and PP2A1 as the top stable genes. In view of the different results from different softwares, the geometric mean method was employed to analyze the expression stability of the candidate re-ference genes, the results of which indicated that PP2A1, EF1α, and ACT3 were the most stable. Based on the comprehensive analysis results of geNorm, NormFinder, BestKeeper, and geometric mean method, PP2A1 and EF1α presented the most stable expression in different organs of A. vilmorinianum. PP2A1 and EF1α were the superior reference genes for gene expression profiling in different organs of A. vilmorinianum.
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Aconitum , Perfilación de la Expresión Génica , Genes de Plantas/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estándares de Referencia , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Urban wastewater treatment plants are considered important greenhouse gas resources with massive emissions of carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) during operation. Based on the emission factor approach of pollutant reduction, the 2014 emission inventory of greenhouse gases (CO2, CH4, and N2O) from urban wastewater treatment plants in China was established. In addition, the temporal and spatial distribution and influencing factors of greenhouse gas emissions were analyzed in this study. The results showed that total emissions of greenhouse gas from urban wastewater treatment plants in China was 7348.60 Gg (CO2-eq) in 2014, which included CO2, CH4, and N2O emissions of 6054.57 Gg, 27.47 Gg (769.08 Gg, CO2-eq), and 1.98 Gg (524.95 Gg, CO2-eq), respectively. The difference in greenhouse gas emissions among provinces was significant:high emissions appeared in the eastern areas of China, low emissions were observed in the northwest, and hardly any emissions were found in Xizang. From 2005 to 2014, annual greenhouse gas emissions from urban sewage treatment plants in China increased by 229.4%, and the rates of CO2, CH4, and N2O increased by 217.9%, 217.9%, and 520.3%, respectively. The regional economic development level and number of wastewater treatment plants were correlated the most with the emissions of greenhouse gasses, and the per-capita protein supply was closely related with the N2O emission.
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Psammosilene tunicoides is one of the main ingredients of the "Yunnan Baiyao". P. tunicoides is an endangered species included in the secondary protection list in China Plant Red Data Book as well as the endemic species in Southwest China. Its natural resources could not meet the needs of pharmaceutical production. Construction of core collection of P. tunicoides will lay the foundation for germplasm improvement and molecular breeding. The sequence variation of the key enzymes gene locus (β-AS) were carried out to survey the population structure and population history of the species. Among the 11 populations across its geographical range, 36 haplotypes were identified. The levels of haplotype diversity (Hd=0.905) were high, while the levels of population differentiation (GST=0.280) were low. Analysisof molecular variance (AMOVA) indicated that a significantly greater proportion of total genetic variationpartitioned among populations thanwithin populations (values of 77.43% and 22.57%, respectively). These results in combination with the star-like phylogenetic network analysis indicate that Hap1 as an ancestral haplotypewas shared in four populations, Hap2, Hap4, Hap15 and Hap16 are occurred in two populations, the remains as private haplotype only distributed in single population. The strategy of core collection was constructed in order to maximumpreserve genetic diversity of P. tunicoides.
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Caryophyllaceae , Genética , China , Variación Genética , Genética de Población , Haplotipos , Filogenia , Plantas Medicinales , GenéticaRESUMEN
Objective: To explore the relationship between plasma Jagged1 protein level and coronary collateral circulation (CCC) formation in patients with coronary artery disease(CAD). Methods: According to coronary angiography (CAG) examination, our research was categorized in 2 groups: CAD group, n=89 patients with at least one of left anterior descending (LAD), left circumflex(LCX) or right coronary artery(RCA) stenosis ≥ 95% and Control group, n=30 subjects without abnormal findings by CAG. Based on Rentrop grading system, CAD group was further divided into 2 subgroups: Good CCC subgroup, n=42 patients with Rentrop grade ≥ 2 and Poor CCC subgroup, n=47 patients with Rentrop grade≤1. Plasma levels of Jagged1 protein,vascular endothelial growth factor (VEGF) were measured by ELISA and the relevant correlation study was conducted by multivariate regression analysis. Results: Compared with Control group, CAD group had increased plasma levels of Jagged1 protein (38.74±10.60)ng/L vs (23.04±8.97)ng/L and elevated VEGF (113.98±30.80)pg/L vs (72.73±14.55)pg/L. Compared with Poor CCC subgroup, Good CCC subgroup presented increased Jagged1 protein (46.77±8.49)ng/L vs (31.56±6.26)ng/L and elevated VEGF (128.10±20.24) pg/L vs (92.43±21.09)pg/L. Correlation study showed that Jagged1 protein was positively related to VEGF in CAD patients (r=0.730, P<0.01); multivariate regression analysis indicated that Jagged1 protein (OR=1.318, P=0.000) and VEGF (OR=1.043, P=0.043) were the independent predictors for CCC processing.Conclusion: CAD patients with good CCC had the higher plasma Jagged1 protein level than the patients with poor CCC which implied that Jagged1 protein played important role in CCC processing, such finding may provide a new direction for treating CAD patients in clinical practice.
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·Glaucoma is a progressive optic neurodegenerative disease with specific characteristics of structural optic nerve head ( ONH) and with changes in the inner retinal layer (ganglion cell complex) along with the presence of corresponding functional visual field ( VF) changes that are irreversible. Obstructive sleep apnea hypopnea syndrome ( OSAHS ) is characterized by recurrent complete or partial interruption of normal breathing due to functional occlusion or collapse of upper airway during sleep that leads to apnea or hypopnea and hypoxia. This causes decrease in the arterial oxygen ( O2) saturation and a rise in the carbon dioxide saturation during sleep and results in transient hypoxia and increased vascular resistance in body tissues. OSAHS is an independent risk factor for cardiovascular and cerebrovascular, and many reports showed that OSAHS is one of the systemic risk factors for glaucoma which causes irreversible visual field damage, but lacks a systematic analysis of the relationship between the two. Comprehensive glaucoma evaluation should be recommended in patients with OSAHS.
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·Delayed absorption of limited subretinal fluid occurs in some patients with rhegmatogenous retinal detachment (RRD) after scleral buckling. The macular-off patients may be effected more on visual function. The progress of recent researches on the epidemiology, diagnosis, pathogenesis and treatment of persistent subretinal fluid with rhegmatogenous retinal detachment has been summarized in this article. 视网膜下积液延迟吸收的情况,黄斑区受累者可能对视功能的影响更显著.本文就近年来RRD术后持续性视网膜下液(persistent subretinal fluid,PSF)的流行病学、检查方法、致病因素及发病机制、治疗及预防等方面的研究进展进行综述.
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<p><b>OBJECTIVE</b>To systematically investigate the efficacy and safety of glucocorticoids (GCs) combined with intravenous injection of immunoglobulin (IVIG) in the initial treatment of Kawasaki disease (KD).</p><p><b>METHODS</b>EDLINE Database, PubMed Database, CNKI, Wanfang Data, and VIP Database were searched to collect prospective or retrospective controlled studies on the combination of GCs and IVIG as the initial treatment of KD, which were published up to March 2016. Two investigators independently screened the literature, extracted data, and assessed the quality of the articles included. Then, a Meta analysis was performed using RevMan 5.2 software.</p><p><b>RESULTS</b>A total of 11 articles in English were included, with 7 prospective studies and 4 retrospective studies. The results of the Meta analysis showed that compared with the group using IVIG alone, the combination group had a significantly lower incidence rate of coronary artery lesion (CAL) (OR=0.44, 95%CI 0.23-0.86, P=0.02) and a significantly shorter duration of fever (MD=-1.66, 95%CI -2.32 to -1.01, P<0.00001). The combination group had a significantly lower rate of no response to initial treatment than the IVIG alone group (OR=0.37, 95%CI 0.27-0.51, P<0.00001). The recurrence rate of KD and the incidence rate of adverse events showed no significant differences between the two groups.</p><p><b>CONCLUSIONS</b>GCs combined with IVIG as the initial treatment for KD can reduce the incidence rate of CAL and the rate of no response to initial treatment and shorten the duration of fever, and does not increase the recurrence rate of KD and the incidence rate of adverse events.</p>
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Humanos , Enfermedad de la Arteria Coronaria , Quimioterapia Combinada , Glucocorticoides , Inmunoglobulinas Intravenosas , Síndrome Mucocutáneo Linfonodular , Quimioterapia , RecurrenciaRESUMEN
Lysostaphin is highly effective on eliminating methicillin resistant Staphylococcus aureus (MRSA). In order to achieve controlled release of lysostaphin, a biocompatible drug carrier is needed. Hydroxyapatite/chitosan (HA/CS) composites were chosen to carry lysostaphin and sample composites with different weight ratios of HA to CS, including 80/20, 70/30, 60/40, and 40/60, were prepared. Multiple analyses were performed to determine the structural and physicochemical properties of the composites, including scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. We immersed HA/CS composites loaded with 1 wt% lysostaphin to test in vitro release activity and cultured MC3T3-E1 cells to carry out biocompatibility test. The result of the release behavior of the composites revealed that the controlled release of lysostaphin from 60/40 HA/CS composites was the highest release rate of (87.4 ± 2.8)%, which lasted for 120 hours. In biocompatibility testing, MC3T3-E1 cells were able to proliferate on the surface of these composites, and the extract liquid from the composites could increase the growth of the cells. These results demonstrate the controlled release of lysostaphin from HA/CS composites and their biocompatibility, suggesting the potential application of these composites to bone injury and infection applications.
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Animales , Ratones , Células 3T3 , Materiales Biocompatibles , Quitosano , Química , Preparaciones de Acción Retardada , Portadores de Fármacos , Química , Durapatita , Química , Lisostafina , Farmacología , Ensayo de Materiales , Staphylococcus aureus Resistente a Meticilina , Microscopía Electrónica de Rastreo , Difracción de Rayos XRESUMEN
<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and safety of glyceryl trinitrate (GTN) ointment in the treatment of anal fissure.</p><p><b>METHODS</b>In this multi-center, randomized, double-blind and placebo-controlled trial, 240 chronic anal fissure patients from 7 clinical centers were randomized to receive eight-week treatment with GTN ointment (treatment group) or vaseline ointment (control group) respectively. Healing rate, visual analogue score (VAS), maximum anal resting pressure (MARP) and adverse reactions were recorded and compared.</p><p><b>RESULTS</b>A total of 221 patients (92.1%) finished the trial, including 114 patients in treatment group (95.0%, 114/120) and 107 in control group (89.2%, 107/120). At the endpoint of treatment (56 d), 90 patients in treatment group (78.9%, 90/114) healed completely compared to 31 patients in control group (29.0%, 31/107), and decrease rates of VAS in the two groups were (94.8±15.7)% and (61.2±35.7)% respectively, both differences were statistically significant (P<0.01). MARP after first administration was (20.2±18.5) mm Hg in treatment group (n=12) and (7.1±14.7) mm Hg in control group (n=6), which was not significantly different (P=0.152). Adverse reaction incidence was higher in treatment group (42.1% vs. 9.3%, P<0.05), while these adverse reactions were mainly headache and fullness in head, which were self-limiting.</p><p><b>CONCLUSION</b>GTN ointment can effectively promote healing and relieve pain in anal fissure with safety and tolerance.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Doble Ciego , Fisura Anal , Quimioterapia , Nitroglicerina , Usos Terapéuticos , Resultado del TratamientoRESUMEN
<p><b>BACKGROUND</b>Epidemiological study showed that the use of angiotensin-converting enzyme inhibitors was associated with higher bone mineral density (BMD) in older people, especially male subjects, which suggested that angiotensin II may have a detrimental effect on bone. Therefore, blocking its effect may have a beneficial effect on bone health.</p><p><b>METHODS</b>Six-month-old male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used. Animals of each model were randomly assigned to the following four groups: Group 1, SHAM operated+vehicle; Group 2, orchidectomy (ORX)+vehicle; Group 3, ORX+low-dose losartan (10 mg×kg(-1)×d(-1)); and Group 4, ORX+high-dose losartan (25 mg×kg(-1)×d(-1)). Blood pressure was recorded weekly. SHAM and ORX operations were performed, followed by daily losartan and vehicle treatment from day 4 after operation for 16 weeks. Serum and 24-hour urine samples were collected for measurement of bone turnover markers before euthanasia and then the left femur was collected for measurements of BMD and microarchitecture before mechanical test.</p><p><b>RESULTS</b>Urine deoxypyridinoline/urine creatinine (DPD/Cr) ratio was significantly higher in SHR than in WKY. BMD and microarchitecture parameters also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration decreased and urine DPD/Cr ratio increased significantly accompanied by a significant decrease in cortical and trabecular BMD and cortical bone thickness in both WKY and SHR. High-dose losartan significantly increased DPD in urine in both SHR and WKY. Apart from marginal favorable changes in bone architecture in WKY treated with high-dose losartan, losartan did not show significant effect on BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and WKY.</p><p><b>CONCLUSION</b>Angiotensin II type I receptor blocker losartan was not able to demonstrate significant effect on ORX-induced bone deterioration in both hypertensive and normotensive rats.</p>
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Animales , Masculino , Ratas , Bloqueadores del Receptor Tipo 1 de Angiotensina II , Usos Terapéuticos , Densidad Ósea , Huesos , Patología , Hipertensión , Quimioterapia , Patología , Losartán , Usos Terapéuticos , Orquiectomía , Ratas Endogámicas SHR , Ratas Endogámicas WKY , SístoleRESUMEN
<p><b>BACKGROUND</b>The ability of pneumoperitoneum in laparoscopic surgery to promote proliferation and metastasis of colorectal cancer has become a focus of research in the field of minimally invasive surgery. The aim of this research was to investigate the effect of CO2 pneumoperitoneum under different pressures and exposed times on the expression of chemokine receptors in colorectal carcinoma cells.</p><p><b>METHODS</b>We constructed an in vitro pneumoperitoneum model. SW480 colon carcinoma cells were exposed to CO2 pneumoperitoneum under different pressures (6, 9, 12, and 15 mmHg) for 1, 2, and 4 hours. These cells were then cultivated under the same conditions as normal SW480 colon carcinoma cells without CO2 pneumoperitoneum (control group), treated at 37°C, and 5% CO2. The expression of the chemokine receptors CXC receptor 4 (CXCR4) and chemokine C receptor 7 (CCR7) was detected by immunocytochemistry and reverse transcriptase polymerase chain reaction after being cultivated for 0, 24, 48, and 72 hours.</p><p><b>RESULTS</b>Immunocytochemistry showed that CXCR4 expression in SW480 cells was significantly decreased in the 6, 9, 12, and 15 mmHg CO2 pneumoperitoneum-treated groups for the same exposure times compared with controls (P < 0.05). CCR7 expression in SW480 cells was significantly decreased in the 12 and 15 mmHg CO2 pneumoperitoneum-treated groups compared with controls (P < 0.05). CXCR4 and CCR7 expression increased up to the level of the control group after 24 and 48 hours (P > 0.05). If the CO2 pneumoperitoneum pressure increased, CXCR4 and CCR7 expression decreased at all exposure times. If the CO2 pneumoperitoneum exposure time prolonged, there were no significant differences in CXCR4 and CCR7 expression under the same pressure. Under all exposure times, CXCR4 and CCR7 mRNA expression was significantly decreased in the 6, 9, 12, and 15 mmHg CO2 pneumoperitoneum-treated groups (P < 0.05) compared with controls, and it increased up to the level of controls after being cultivated for 48 hours (P > 0.05). If the CO2 pneumoperitoneum pressure increased (with all exposure times) and exposure time prolonged (under the same pressure), there were no significant differences in CXCR4 and CCR7 expression.</p><p><b>CONCLUSIONS</b>CXCR4 and CCR7 expression is temporarily affected after continuous CO2 pneumoperitoneum treatment. The high pressure of CO2 pneumoperitoneum plays an important role in suppressing the expression of these chemokine receptors. Different lengths of time of exposure to a CO2 pneumoperitoneum-like environment do not change CXCR4 and CCR7 expression.</p>
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Humanos , Dióxido de Carbono , Línea Celular Tumoral , Neoplasias Colorrectales , Metabolismo , Receptores CCR7 , Metabolismo , Receptores CXCR4 , Metabolismo , Retroneumoperitoneo , MetabolismoRESUMEN
Amphipathic α-helical antimicrobial peptides comprise a class of broad-spectrum agents that are used against pathogens. We designed a series of antimicrobial peptides, CP-P (KWKSFIKKLTSKFLHLAKKF) and its derivatives, and determined their minimum inhibitory concentrations (MICs) against Pseudomonas aeruginosa, their minimum hemolytic concentrations (MHCs) for human erythrocytes, and the Therapeutic Index (MHC/MIC ratio). We selected the derivative peptide K11, which had the highest therapeutic index (320) among the tested peptides, to determine the MICs against Gram-positive and Gram-negative bacteria and 22 clinical isolates including Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Klebsiella pneumonia. K11 exhibited low MICs (less than 10 µg/mL) and broad-spectrum antimicrobial activity, especially against clinically isolated drug-resistant pathogens. Therefore, these results indicate that K11 is a promising candidate antimicrobial peptide for further studies.
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Objective To explore the expression ofapoptosis inducing factor (AIF) and the apoptosis ofnervous cells in infectious brain injury rat models induced by pneumolysin (PLY) and their significance.Methods A total of 80 infant SD rats were randomly divided into normal saline treatment group (NS group,n=40) and PLY treatment group (PLY group,n=40).Each group was divided into 4 subgroups:NS observation subgroups at the 6,12,24 and 48 h of treatment and PLY observation subgroups at the 6,12,24 and 48 h of treatment (n=10).Five rats in these subgroups were injected with Evan' s blue (EB) to determine the damage of BBB by measuring the content of EB in the brain tissues;the other 5 rats in these subgroups were not given EB,and their brain tissues were obtained to detect the protein expressions of NSE,GFAP and AIF by immunohistochemistry,and their apoptosis was examined by TUNEL staining.Results As compared with those in the NS treatment subgroups,the brain EB content and the expression levels of NSE,GFAP and AIF in the PLY treatment subgroups were significantly higher,and the number of apoptotic cells was significantly increased (P<0.05).The number of apoptotic cells was positively correlated to the protein expression level of AIF in the PLY treatment group (r=0.959,P=0.000).Conclusion Apoptosis plays a role in the formation and development of infectious brain injury of rats and AIF might involve in the apoptosis ofneurocyte.
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<p><b>OBJECTIVE</b>To screen potential serum marker proteins of osteosarcoma, and to make a preliminary bioinformatics analysis of RNA polymerase III polypeptide F (POLR3F).</p><p><b>METHODS</b>Gene chip and SELDI-TOF MS was used to screen genes differentially expressed in osteosarcoma. The associations of potential biomarkers from SELDI data and microarray analysis were further inferred by link-test to identify biomarkers that could likely be used for diagnosis. MATLAB was used to search transcription factors binding site in the promoter region and miRNAs binding site in 3'-UTR of POLR3F, respectively.</p><p><b>RESULTS</b>653 differentially expressed genes were found in osteosarcoma cells, while six differentially expressed protein peaks with significant statistical significances were detected by SELDI-TOF MS in patient's serum. 13 potential biomarkers for early diagnosis of osteosarcoma were screened by link-test. A conserved STAT3 binding site and a miRNA target site were found in proximal promoter regions and 3'-UTR region of POLR3F, respectively.</p><p><b>CONCLUSIONS</b>Link-test is a effective method to identify osteosarcoma biomarkers from both microarray and SELDI-TOF MS database. The results confirmed that POLR3F may be a promising biomarker for early diagnosis and a therapy target of osteosarcoma.</p>
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Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Adulto Joven , Sitios de Unión , Biomarcadores de Tumor , Sangre , Proteínas Sanguíneas , Neoplasias Óseas , Genética , Metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Análisis de Secuencia por Matrices de Oligonucleótidos , Osteosarcoma , Genética , Metabolismo , Péptidos , Genética , Metabolismo , Regiones Promotoras Genéticas , Genética , Unión Proteica , Subunidades de Proteína , Genética , Metabolismo , ARN Polimerasa III , Genética , Metabolismo , ARN Mensajero , Genética , Factor de Transcripción STAT3 , Metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
<p><b>BACKGROUND</b>Presacral tumors are highly infrequent tumors located in the space known as presacral or retrorectal space. Although there have been substantial improvements in the prognosis of patients with malignant presacral tumors, the development of newer surgical strategy is likely to further improve the oncologic outcomes of malignant presacral tumors. The aim of this article was to report our experience in 33 cases, and to review the surgical strategy, pathological features and the prevention of complications from our experience.</p><p><b>METHODS</b>A retrospective analysis was conducted on 33 cases (20 male and 13 female) with presacral tumors surgically treated in our hospital between January 1998 and April 2009. The surgical approaches included trans-abdominal in 10 cases (30%), trans-sacral in 18 cases (55%) and combined abdominal-sacral in 5 cases (15%). All patients got followed up (14 - 123 months, mean of 45.1 months). At last, the general information, clinical symptoms, histodiagnosis, surgical types and postoperative complications of all cases in our series were assessed.</p><p><b>RESULTS</b>Ages of 33 patients ranged from 18 to 71 years, with an average of 48.5 years.</p><p><b>PATHOLOGICAL FINDINGS</b>6 epidermoid cysts, 5 teratomas, 3 leiomyomas, 9 neurofibromas, 5 neurilemmomas, 1 enterogenous cyst, 1 liposarcoma, 1 leiomyosarcoma, 1 angiosarcoma, and 1 neurofibrosarcoma. All tumors were excised with no perioperative death. A colostomy was taken in one case with angiosarcoma involving the rectum because of the intraoperative injury of the rectum. Blood loss during surgery was 400 - 11 000 ml (mean of 2400 ml). Four (12%) cases had local recurrence during follow-up: 2 because of inadequate drainage after dermoidectomy, both of them were cured by surgical resection and drainage; recurrence occurred in a case of teratoma in 18 months after surgery, cured by a trans-sacral excision; local recurrence and lung metastasis occurred simultaneously in a case of angiosarcoma in 6 months postoperatively and the patient died one month later of respiratory failure.</p><p><b>CONCLUSIONS</b>The main treatment of most presacral tumors is surgical resection. Selection of surgical approach is very important for complete resection of the presacral tumors. The location, size and peculiarities of tumors, conditions of the skin and soft tissues and the patients' somatotype are all determinative factors. Multidisciplinary cooperation is also very necessary.</p>
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Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Neoplasias Retroperitoneales , Patología , Cirugía General , Estudios Retrospectivos , Región Sacrococcígea , Patología , Cirugía GeneralRESUMEN
<p><b>BACKGROUND</b>Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) could be induced to differentiate into insulin producing cells (IPCs) in vitro, which have good application potential in the cell replacement treatment of type-1 diabetes. However, the mechanisms regulating this differentiation have remained largely unknown. Notch signaling is critical in cell differentiation. This study investigated whether Notch signaling could regulate the IPCs differentiation of human UCB-MSCs.</p><p><b>METHODS</b>Using an interfering Notch signaling protocol in vitro, we studied the role of Notch signaling in differentiation of human UCB-MSCs into IPCs. In a control group the induction took place without interfering Notch signaling.</p><p><b>RESULTS</b>Human UCB-MSCs expressed the genes of Notch receptors (Notch 1 and Notch 2) and ligands (Jagged 1 and Deltalike 1). Human UCB-MSCs with over-expressing Notch signaling in differentiation resulted in the down-regulation of insulin gene level, proinsulin protein expression, and insulin-positive cells percentage compared with the control group. These results showed that over-expressing Notch signaling inhibited IPCs differentiation. Conversely, when Notch signaling was attenuated by receptor inhibitor, the induced cells increased on average by 3.06-fold (n = 4, P < 0.001) in insulin gene level, 2.60-fold (n = 3, P < 0.02) in proinsulin protein expression, and 1.62-fold (n = 6, P < 0.001) in the rate of IPCs compared with the control group. Notch signaling inhibition significantly promoted IPCs differentiation with about 40% of human UCB-MSCs that converted to IPCs, but these IPCs were not responsive to glucose challenge very well both in vitro and in vivo. Hence, further research has to be carried out in the future.</p><p><b>CONCLUSIONS</b>Notch signaling may be an important mechanism regulating IPCs differentiation of human UCB-MSCs in vitro and Notch signaling inhibition may be an efficient way to increase the number of IPCs, which may resolve the shortage of islet of cell replacement treatment of type-1 diabetes.</p>