Effects of methionine deficiency on B7H3-DAP12-CAR-T cells in the treatment of lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is a subtype of lung cancer for which precision therapy is lacking. Chimeric antigen receptor T-cells (CAR-T) have the potential to eliminate cancer cells by targeting specific antigens. However, the tumor microenvironment (TME), characterized by abnormal metabolism could inhibit CAR-T function. Therefore, the aim of this study was to improve CAR-T efficacy in solid TME by investigating the effects of amino acid metabolism. We found that B7H3 was highly expressed in LUSC and developed DAP12-CAR-T targeting B7H3 based on our previous findings. When co-cultured with B7H3-overexpressing LUSC cells, B7H3-DAP12-CAR-T showed significant cell killing effects and released cytokines including IFN-γ and IL-2. However, LUSC cells consumed methionine (Met) in a competitive manner to induce a Met deficiency. CAR-T showed suppressed cell killing capacity, reduced cytokine release and less central memory T phenotype in medium with lower Met, while the exhaustion markers were up-regulated. Furthermore, the gene NKG7, responsible for T cell cytotoxicity, was downregulated in CAR-T cells at low Met concentration due to a decrease in m5C modification. NKG7 overexpression could partially restore the cytotoxicity of CAR-T in low Met. In addition, the anti-tumor efficacy of CAR-T was significantly enhanced when co-cultured with SLC7A5 knockdown LUSC cells at low Met concentration. In conclusion, B7H3 is a prospective target for LUSC, and B7H3-DAP12-CAR-T cells are promising for LUSC treatment. Maintaining Met levels in CAR-T may help overcome TME suppression and improve its clinical application potential.

THOC3 interacts with YBX1 to promote lung squamous cell carcinoma progression through PFKFB4 mRNA modification.

The THO complex (THOC) is ubiquitously involved in RNA modification and various THOC proteins have been reported to regulate tumor development. However, the role of THOC3 in lung cancer remains unknown. In this study, we identified that THOC3 was highly expressed in lung squamous cell carcinoma (LUSC) and negatively associated with prognosis. THOC3 knockdown inhibited LUSC cell growth, migration, and glycolysis. THOC3 expression was regulated by TRiC proteins, such as CCT8 and CCT6A, which supported protein folding. Furthermore, THOC3 could form a complex with YBX1 to promote PFKFB4 transcription. THOC3 was responsible for exporting PFKFB4 mRNA to the cytoplasm, while YBX1 ensured the stability of PFKFB4 mRNA by recognizing m5C sites in its 3'UTR. Downregulation of PFKFB4 suppressed the biological activities of LUSC. Collectively, these findings suggest that THOC3, folded by CCT proteins can collaborate with YBX1 to maintain PFKFB4 expression and facilitate LUSC development. Therefore, THOC3 could be considered as a novel promising therapeutic target for LUSC.

Regenerative plantlets with improved agronomic characteristics caused by anther culture of tetraploid potato (Solanum tuberosum L.).

Objective: As the primary means of plant-induced haploid, anther culture is of great significance in quickly obtaining pure lines and significantly shortening the potato breeding cycle. Nevertheless, the methods of anther culture of tetraploid potato were still not well established. Methods: In this study, 16 potato cultivars (lines) were used for anther culture in vitro. The corresponding relation between the different development stages of microspores and the external morphology of buds was investigated. A highly-efficient anther culture system of tetraploid potatoes was established. Results: It was shown in the results that the combined use of 0.5 mg/L 1-Naphthylacetic acid (NAA), 1.0 mg/L 2,4-Dichlorophenoxyacetic acid (2,4-D), and 1.0 mg/L Kinetin (KT) was the ideal choice of hormone pairing for anther callus. Ten of the 16 potato cultivars examined could be induced callus with their respective anthers, and the induction rate ranged from 4.44% to 22.67% using this hormone combination. According to the outcome from the orthogonal design experiments of four kinds of appendages, we found that the medium with sucrose (40 g/L), AgNO3 (30 mg/L), activated carbon (3 g/L), potato extract (200 g/L) had a promotive induction effect on the anther callus. In contrast, adding 1 mg/L Zeatin (ZT) effectively facilitated callus differentiation. Conclusion: Finally, 201 anther culture plantlets were differentiated from 10 potato cultivars. Among these, Qingshu 168 and Ningshu 15 had higher efficiency than anther culture. After identification by flow cytometry and fluorescence in situ hybridization, 10 haploid plantlets (5%), 177 tetraploids (88%), and 14 octoploids (7%) were obtained. Some premium anther-cultured plantlets were further selected by morphological and agronomic comparison. Our findings provide important guidance for potato ploidy breeding.

New Glycosyltransferases in Panax notoginseng Perfect Main Ginsenosides Biosynthetic Pathways.

Ginsenosides, the main bioactive ingredients of the Panax genus, are dammarane or oleanane triterpenoids with glycosylated modifications at C3/C6/C20 hydroxyls or C28 carboxyl, and their diverse glycosylation pattern has attracted great attention. However, the biosynthesis of some important saponins is still unclear. In this study, six UGTs were characterized, two of which were novel. PnUGT71A3 catalyzes not only the C6 hydroxyl glycosylation of protopanaxatriol (PPT) and F1 to form Rh1 and Rg1, respectively, but also the C20 hydroxyl glycosylation of protopanaxadiol (PPD)-type Rg3 to generate Rd. Especially, PnUGT94M1 is UDP-ß-l-rhamnose (UDP-Rha)-dependent, regioselectively catalyzing the C2' hydroxyl rhamnosylation of C6 glucose of the PPT-type ginsenosides Rg1 and Rh1 to generate ginsenosides Re and Rg2, respectively. Site-directed mutagenesis showed that His21, Asp120, Ser363, and Pro372 are key residues, and the triple mutant (G344S/G345S/L346T) highly improved the activity toward Rg1 and Rh1. The findings in this study, perfect main ginsenosides biosynthetic pathways in the Panax genus, expand the biocatalyst toolbox for ginsenoside production and show that the PSPG motif is one of the options to modify UGTs to improve their activities.

Sensitive Organic Vapor Sensors Based on Flexible Porous Conductive Composites with Multilevel Pores and Thin, Rough, Hollow-Wall Structure.

Advanced organic vapor sensors that simultaneously have high sensitivity, fast response, and good reproducibility are required. Herein, flexible, robust, and conductive vapor-grown carbon fibers (VGCFs)-filled polydimethylsiloxane (PDMS) porous composites (VGCFs/PDMS sponge (CPS)) with multilevel pores and thin, rough, and hollows wall were prepared based on the sacrificial template method and a simple dip-spin-coating process. The optimized material showed outstanding mechanical elasticity and durability, good electrical conductivity and hydrophobicity, as well as excellent acid and alkali tolerance. Additionally, CPS exhibited good reproducible sensing behavior, with a high sensitivity of ~1.5 × 105 s-1 for both static and flowing organic vapor, which was not affected in cases such as 20% squeezing deformation or environment humidity distraction (20~60% RH). Interestingly, both the reproducibility and sensitivity of CPS were better than those of film-shaped VGCFs/PDMS (CP), which has a thickness of two hundred microns. Therefore, the contradiction between the reproducibility and high sensitivity was well-solved here. The above excellent performance could be ascribed to the unique porous structures and the rough, thin, hollow wall of CPS, providing various gas channels and large contact areas for organic vapor penetration and diffusion. This work paves a new way for developing advanced vapor sensors by optimizing and tailoring the pore structure.

High prevalence and low awareness of hyperuricemia in hypertensive patients among adults aged 50-79 years in Southwest China.

INTRODUCTION: This study was aimed to assess the prevalence of hyperuricemia and its associated risk factors among hypertensive patients in Southwest China. METHODS: From September 2013 to March 2014, a multistage, stratified sampling was conducted on 3505 hypertensive people aged 50-79 years who lived in urban communities within Chengdu and Chongqing, using a questionnaire and performing physical and biochemical measurements. RESULTS: In the study population, approximately 18.2% of all hypertensive participants had hyperuricemia (638/3505), with a prevalence rate of 21.5% in men and 16.2% in women (p < 0.05). Multivariate logistic regression analysis showed that aging, without spouse, current drinking, preferring hotpot, hypertriglyceridemia, BMI ≥ 25 kg/ m2, and central obesity were all positively correlated with hyperuricemia, whereas female gender was negatively correlated with hyperuricemia. The prevalence of hyperuricemia among hypertensive patients in urban adults aged 50-79 years in southwestern China was high, while levels of awareness were extremely low. DISCUSSION: Improved hyperuricemia health knowledge should be delivered to improve public awareness of the disease and it may need aggressive strategies aiming at the prevention and treatment of hyperuricemia. It is may necessary to encourage people to check blood uric acid levels when they first time to be diagnosed with hypertension, especially in the elderly.

2D Indium Phosphorus Sulfide (In2 P3 S9 ): An Emerging van der Waals High-k Dielectrics.

2D van der Waals (vdW) semiconductors hold great potentials for more-than-Moore field-effect transistors (FETs), and the efficient utilization of their theoretical performance requires compatible high-k dielectrics to guarantee the high gate coupling efficiency. The deposition of traditional high-k dielectric oxide films on 2D materials usually generates interface concerns, thereby causing the carrier scattering and degeneration of device performance. Here, utilizing a space-confined epitaxy growth approach, the authors successfully obtained air-stable ultrathin indium phosphorus sulfide (In2 P3 S9 ) nanosheets, the thickness of which can be scaled down to monolayer limit (≈0.69 nm) due to its layered structure. 2D In2 P3 S9 exhibits excellent insulating properties, with a high dielectric constant (≈24) and large breakdown voltage (≈8.1 MV cm-1 ) at room temperature. Serving as gate insulator, ultrathin In2 P3 S9 nanosheet can be integrated into MoS2 FETs with high-quality dielectric/semiconductor interface, thus providing a competitive electrical performance of device with subthreshold swings (SS) down to 88 mV dec-1 and a high ON/OFF ratio of 105 . This study proves an important strategy to prepare 2D vdW high-k dielectrics, and greatly facilitates the ongoing research of 2D materials for functional electronics.

Brain-derived neurotrophic factor enhances the therapeutic effect of oleuropein in the lipopolysaccharide-induced models of depression.

Major depressive disorder (MDD) is a heterogeneous disease, involving multiple mechanisms and factors, which commonly result in injury to the psychosocial function of the central nervous system, and even suicidality of patients. However, effective treatment for MDD is still lacking. Oleuropein is a newly discovered natural compound extracted from olive leaves, which has a strong antioxidative effect by reducing the production of reactive oxygen species (ROS). Oleuropein also reduces blood pressure in humans and experimental animals, and protects blood vessels. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which supports the function of the central nervous system. BDNF plays an important role in the development of the nervous system via the regulation of cellular differentiation, survival neurogenesis and synaptic plasticity; therefore, we hypothesized that overexpression of BDNF might contribute to the therapeutic effect of oleuropein. Here, we first demonstrated that oleuropein reverses depressive-like behaviour and restores the inflammatory response in a mouse lipopolysaccharide (LPS) model of MDD. We further established a cell model of BDNF overexpression and inhibition in SH-SY5Y cells, and found that the concentration of intercellular calcium was increased after treatment with oleuropein combined with BDNF overexpression, which may be mediated by the BDNF-TrkB-CaMKII signalling pathway. In addition, we observed that the expression of neurotrophic factors, including epidermal growth factor (EGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), was increased, which may be mediated by inhibition of the RhoA-ROCK signalling pathway.

Effect of glycated hemoglobin index and mean arterial pressure on acute ischemic stroke prognosis after intravenous thrombolysis with recombinant tissue plasminogen activator.

To determine whether glycated hemoglobin and mean arterial pressure (MAP) during thrombolysis are prognostic factors of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke (AIS).A total of 125 AIS patients, who received rt-PA intravenous thrombolysis in our hospital, were included into the present study, and divided into good prognosis group and poor prognosis group. Univariate and multivariate logistic regression analyses were used to determine the prognostic factors of AIS treated by rt-PA thrombolysis, Spearman correlation analysis was used to analyze the correlation of the accumulated cigarette consumption in the smoking subgroup and glycated hemoglobin in the diabetic subgroup with the prognosis after intravenous thrombolysis and the symptomatic intracranial hemorrhage (sICH).Univariate analysis revealed that the interval from onset to thrombolysis, baseline National Institutes of Health Stroke Scale (NIHSS) score, MAP during thrombolysis and DRAGON score were prognostic factors. Multivariate logistic regression analysis revealed that baseline NIHSS score and MAP during thrombolysis were independent prognostic factors for rt-PA thrombolysis. Furthermore, the glycated hemoglobin index was positively correlated with the incidence of sICH.The NIHSS score before thrombolysis and MAP during thrombolysis were independent factors for the prognosis of AIS treated by thrombolysis. The higher the glycated hemoglobin index of diabetic patients, the more likely they are to develop sICH, the glycated hemoglobin index was negatively correlated with the prognosis after intravenous thrombolysis. The accumulated cigarette consumption was negatively correlated with the prognosis after intravenous thrombolysis.

Placenta-specific protein 1 promotes cell proliferation and invasion in non-small cell lung cancer.

Pulmonary carcinoma-associated proteins have emerged as crucial players in governing fundamental biological processes such as cell proliferation, apoptosis and metastasis in human cancers. Placenta-specific protein 1 (PLAC1) is a cancer-related protein, which is activated and upregulated in a variety of malignant tissues, including prostate cancer, gastric adenocarcinoma, colorectal, epithelial ovarian and breast cancer. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression are still unknown. In the present study, we found that PLAC1 was significantly upregulated in NSCLC tissues, and its expression level was associated with advanced pathological stage and it was also correlated with shorter progression-free survival of lung cancer patients. Furthermore, knockdown of PLAC1 expression by siRNA inhibited cell proliferation, induced apoptosis and impaired invasive ability in NSCLC cells partly via regulation of epithelial-mesenchymal transition (EMT)-related protein expression. Our findings present that increased PLAC1 could be identified as a negative prognostic biomarker in NSCLC and regulate cell proliferation and invasion. Thus, we conclusively demonstrated that PLAC1 plays a key role in NSCLC development and progression, which may provide novel insights on the function of tumor-related gene-driven tumorigenesis.

Long intergenic non-coding RNA 00152 promotes lung adenocarcinoma proliferation via interacting with EZH2 and repressing IL24 expression.

BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown. METHODS: Quantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24. RESULTS: LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD. CONCLUSIONS: Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.

The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB.

Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.

Evaluation of shoulder function in clavicular fracture patients after six surgical procedures based on a network meta-analysis.

Purpose Using a network meta-analysis approach, our study aims to develop a ranking of the six surgical procedures, that is, Plate, titanium elastic nail (TEN), tension band wire (TBW), hook plate (HP), reconstruction plate (RP) and Knowles pin, by comparing the post-surgery constant shoulder scores in patients with clavicular fracture (CF). Methods A comprehensive search of electronic scientific literature databases was performed to retrieve publications investigating surgical procedures in CF, with the stringent eligible criteria, and clinical experimental studies of high quality and relevance to our area of interest were selected for network meta-analysis. Statistical analyses were conducted using Stata 12.0. Results A total of 19 studies met our inclusion criteria were eventually enrolled into our network meta-analysis, representing 1164 patients who had undergone surgical procedures for CF (TEN group = 240; Plate group = 164; TBW group = 180; RP group = 168; HP group = 245; Knowles pin group = 167). The network meta-analysis results revealed that RP significantly improved constant shoulder score in patients with CF when compared with TEN, and the post-operative constant shoulder scores in patients with CF after Plate, TBW, HP, Knowles pin and TEN were similar with no statistically significant differences. The treatment relative ranking of predictive probabilities of constant shoulder scores in patients with CF after surgery revealed the surface under the cumulative ranking curves (SUCRA) value is the highest in RP. Conclusion The current network meta-analysis suggests that RP may be the optimum surgical treatment among six inventions for patients with CF, and it can improve the shoulder score of patients with CF. Implications for Rehabilitation RP improves shoulder joint function after surgical procedure. RP achieves stability with minimal complications after surgery. RP may be the optimum surgical treatment for rehabilitation of patients with CF.

Comparison of the Clinical Effectiveness of PFNA, PFLCP, and DHS in Treatment of Unstable Intertrochanteric Femoral Fracture.

In this study, a randomized trial was conducted to compare the clinical effectiveness of proximal femoral locking compression plate (PFLCP), dynamic hip screw (DHS), and proximal femoral nail antirotation (PFNA) for unstable intertrochanteric femoral fracture treatment. Ninety patients diagnosed with unstable intertrochanteric femoral fracture were enrolled in this study at the department of orthopedics at Linyi Second People's Hospital between May 2010 and May 2012. Fractures were classified according to Tronzo-Evans classification, and the patients were randomly divided into 3 groups, PFLCP, DHS, and PFNA, with 30 patients in each group. The length of incision, operative time, intraoperative blood loss, postoperative drainage, postoperative weight-bearing ambulation time, and duration of fracture union were significantly lower in patients who underwent PFNA and PFLCP compared to patients treated with DHS. Furthermore, when the same clinical parameters were used for comparison, the PFNA group showed markedly lower values compared with the PFLCP group. The total incidence of postoperative complications was significantly different among the PFNA, PFLCP, and DHS groups, with the PFNA group exhibiting markedly lower complication rates compared with PFLCP and DHS groups. However, PFLCP and DHS groups did not show significant differences in the incidence of postoperative complications. Notably, the Harris hip score of PFNA group was markedly higher than the DHS group. In conclusion, our results provide convincing evidence that PFNA may be the most effective internal fixation treatment of unstable intertrochanteric femoral fracture.

The pseudogene DUXAP10 promotes an aggressive phenotype through binding with LSD1 and repressing LATS2 and RRAD in non small cell lung cancer.

Pseudogenes have been considered as non-functional transcriptional relics of human genomic for long time. However, recent studies revealed that they play a plethora of roles in diverse physiological and pathological processes, especially in cancer, and many pseudogenes are transcribed into long noncoding RNAs and emerging as a novel class of lncRNAs. However, the biological roles and underlying mechanism of pseudogenes in the pathogenesis of non small cell lung cancer are still incompletely elucidated. This study identifies a putative oncogenic pseudogene DUXAP10 in NSCLC, which is located in 14q11.2 and 2398 nt in length. Firstly, we found that DUXAP10 was significantly up-regulated in 93 human NSCLC tissues and cell lines, and increased DUXAP10 was associated with patients poorer prognosis and short survival time. Furthermore, the loss and gain of functional studies including growth curves, migration, invasion assays and in vivo studies verify the oncogenic roles of DUXAP10 in NSCLC. Finally, the mechanistic experiments indicate that DUXAP10 could interact with Histone demethylase Lysine specific demethylase1 (LSD1) and repress tumor suppressors Large tumor suppressor 2 (LATS2) and Ras-related associated with diabetes (RRAD) transcription in NSCLC cells. Taken together, these findings demonstrate DUXAP10 exerts the oncogenic roles through binding with LSD1 and epigenetic silencing LATS2 and RRAD expression. Our investigation reveals the novel roles of pseudogene in NSCLC, which may serve as new target for NSCLC diagnosis and therapy.

Long non-coding RNA LINC01133 represses KLF2, P21 and E-cadherin transcription through binding with EZH2, LSD1 in non small cell lung cancer.

Long non-coding RNAs are emerging as crucial regulators and prognostic markers in multiple cancers including non small cell lung cancer (NSCLC). In this study, we screened LINCO1133 as a new candidate lncRNA which promotes NSCLC development and progression, in two independent datasets (GSE18842 and GSE19804) from the Gene Expression Omnibus (GEO). LINC01133 is previously found to be over-expressed in lung squamous cell cancer (LSCC) and knockdown its expression inhibits LSCC cells invasion. However, its' molecular mechanism and downstream targets involving in regulation of cancer cells phenotype is not known. Here, we found that LINC01133 expression is up-regulated in NSCLC tissues, and its' over-expression is associated with patients poor prognosis and short survival time. LINC01133 knockdown decreased NSCLC cells proliferation, migration, invasion and induced cell cycle G1/S phase arrest and cell apoptosis. Mechanistic investigations showed that LINC01133 could interact with EZH2, LSD1 and recruit them to KLF2, P21 or E-cadherin promoter regions to repress their transcription. Furthermore, rescue experiments demonstrated that LINC01133 oncogenic function is partly through regulating KLF2. Lastly, we found that there was negative correlation between LINC01133 and KLF2, P21 or E-cadherin in NSCLC. Overall, our findings illuminate how LINC01133 over-expression confers an oncogenic function in NSCLC that may offer a novel therapy target in this disease.

[Post-transplant kidney from C-III donation after cardiac death of children: a clinicopathologic study of 20 cases].

OBJECTIVE: To study the clinical and histopathologic features of post-transplant kidney biopsy tissues from pediatric C-III donors. METHODS: The clinical and pathologic features of 20 cases (22 case-times) of renal transplant biopsies from pediatric cadaveric donors were analyzed by light microscopy and immunohistochemistry according to the Banff system of working classification of renal allograft pathology. Biopsies were compared to those from adult C-III donors and adult cadaveric donors. RESULTS: Sixteen cases (72.7%) showed renal allograft drug toxicity damage by Tacrolimus, seven cases (31.8%) showed degeneration and necrosis of renal tubular epithelial cells, four cases (18.2%) showed T cell-mediated acute rejection and six cases (27.3%) showed renal interstitial inflammation. There were two cases (9.1%) of renal dysplasia and one case (4.5%) of renal infarction. There was insufficient evidence for diagnosis of renal allograft nephropathy. Compared to post-transplant kidney from adult C-III donors, the proportion of drug toxicity damage was higher (P<0.05). Compared to post-transplant kidney from adult cadavers, the proportions of drug toxicity damage, degeneration and necrosis of renal tubular epithelial cells were higher (P<0.05) while the proportion of acute rejection was lower (P<0.05). CONCLUSIONS: The pathologic changes in the post-transplant kidneys from pediatric donors are different from those from adult donors. Optimal long-term outcome can be accomplished by effective treatment based on timely or procedural biopsy.

Decreased long noncoding RNA MIR31HG is correlated with poor prognosis and contributes to cell proliferation in gastric cancer.

Long noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in the development of several human cancers. MIR31HG, an lncRNA located in 9p21.3 and 2166 bp in length, has been found to be upregulated in breast cancer and contributes to cell proliferation and invasion. However, the expression pattern and biological function of MIR31HG in gastric cancer are still not well documented. In this study, we found that MIR31HG expression is decreased in gastric cancer tissues and associated with larger tumor size and advanced pathological stage. Patients with lower MIR31HG expression had a relatively poor prognosis. Furthermore, ectopic over-expression of MIR31HG could inhibit gastric cancer (GC) cell proliferation both in vitro and in vivo, while knockdown of MIR31HG by small interfering RNA (siRNA) promoted cell proliferation in GC cells partly via regulating E2F1 and p21 expression. Our findings present that decreased MIR31HG is involved in GC development and could be identified as a poor prognostic biomarker in GC patients.

Involvement of lncRNA dysregulation in gastric cancer.

Benefiting from the fast development of sequencing technique and bioinformatics methods, more and more new long non-coding RNAs (lncRNAs) are discovered and identified. lncRNAs were firstly thought to be transcription noise that from genome desert without biological function; however, as the discovery of lncRNA XIST and HOTAIR uncovers the emerging roles of lncRNAs in development and tumorigenesis. In the past decades, accumulating evidence have indicated that lncRNAs involve in a wide range of biological functions, such as X-chromosome inactivation, reprogramming stem cell pluripotency, regulation of the immune response and carcinogenesis. Although lots of studies have demonstrated that dysregulation of lncRNAs involve in diverse diseases including cancers, the underlying molecular mechanisms of lncRNAs are not well documented. Interestingly, our previous studies and others' have shown that numerous of lncRNAs expression was misregulated in gastric cancer. In this review, we will focus on the dysregulated lncRNAs and their biological function and underlying pathways or mechanisms in GC. Finally, we will discuss the potential roles of lncRNAs acting as biomarkers or therapeutic targets in GC patients.

Decreased long noncoding RNA SPRY4-IT1 contributing to gastric cancer cell metastasis partly via affecting epithelial-mesenchymal transition.

BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in tumorigenesis. SPRY4-IT1 (SPRY4 intronic transcript 1), a lncRNA derived from an intron within SPRY4 gene, involves in multiple cancers development. However, the expression pattern and biological function of SPRY4-IT1 in gastric cancer is still not well documented. Hence, we carried out the present study to investigate the potential role of SPRY4-IT1 in gastric carcinogenesis. METHODS: QRT-PCR was performed to detect the expression of SPRY4-IT1 in 61 pairs of gastric cancer samples. Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of SPRY4-IT1. The effect of SPRY4-IT1 on proliferation was evaluated by MTT and colony formation assays. Gastric cancer cells transfected with pCDNA-SPRY4-IT1 were injected into nude mice to study the effect of SPRY4-IT1 on tumorigenesis and metastasis in vivo. Protein levels of SPRY4-IT1 targets were determined by western blot or fluorescence immunohistochemistry. ChIP assays were performed to investigate the effect of DNMT1 on SPRY4-IT1 expression. Differences between groups were tested for significance using Student's t test (two-tailed). RESULTS: SPRY4-IT1 expression is decreased in gastric cancer tissues and associated with larger tumor size, advanced pathological stage, deeper depth of invasion and lymphatic metastasis. Patients with lower SPRY4-IT1 expression had a relatively poor prognosis. DNA methylation may be a key factor in controlling the SPRY4-IT1 expression. Furthermore, SPRY4-IT1 contributed to gastric cancer cells metastasis might partly via regulating epithelial-mesenchymal transition (EMT) process. CONCLUSION: Low expression of SPRY4-IT1 is involved in progression and metastasis of gastric cancer and may represent a novel biomarker of poor prognosis in patients with gastric cancer.