The Ability of Clinically Relevant Chemotherapeutics to Induce Immunogenic Cell Death in Squamous Cell Carcinoma.

BACKGROUND: Immunogenic cell death (ICD) is a crucial mechanism for triggering the adaptive immune response in cancer patients. Damage-associated molecular patterns (DAMPs) are critical factors in the detection of ICD. Chemotherapeutic drugs can cause ICD and the release of DAMPs. The aim of this study was to assess the potential for paclitaxel and platinum-based chemotherapy regimens to induce ICD in squamous cell carcinoma (SCC) cell lines. In addition, we examined the immunostimulatory effects of clinically relevant chemotherapeutic regimens utilized in the treatment of SCC. METHODS: We screened for differentially expressed ICD markers in the supernatants of three SCC cell lines following treatment with various chemotherapeutic agents. The ICD markers included Adenosine Triphosphate (ATP), Calreticulin (CRT), Annexin A1 (ANXA 1), High Mobility Group Protein B1 (HMGB1), and Heat Shock Protein 70 (HSP70). A vaccination assay was also employed in C57BL/6J mice to validate our in vitro findings. Lastly, the levels of CRT and HMGB1 were evaluated in Serum samples from SCC patients. RESULTS: Addition of the chemotherapy drugs cisplatin (DDP), carboplatin (CBP), nedaplatin (NDP), oxaliplatin (OXA) and docetaxel (DOC) increased the release of ICD markers in two of the SCC cell lines. Furthermore, mice that received vaccinations with cervical cancer cells treated with DDP, CBP, NDP, OXA, or DOC remained tumor-free. Although CBP induced the release of ICD-associated molecules in vitro, it did not prevent tumor growth at the vaccination site in 40% of mice. In addition, both in vitro and in vivo results showed that paclitaxel (TAX) and LBP did not induce ICD in SCC cells. CONCLUSION: The present findings suggest that chemotherapeutic agents can induce an adjuvant effect leading to the extracellular release of DAMPs. Of the agents tested here, DDP, CBP, NDP, OXA and DOC had the ability to act as inducers of ICD.

Circular RNA Circ_0000119 promotes gastric cancer progression via circ_0000119/miR-502-5p/MTBP axis.

Dysregulated circular RNAs (circRNAs) are significantly related with tumor initiation and progression. However, biological activity and potential molecular mechanism of circRNAs in gastric cancer (GC) deserve further exploration. We carried out total RNA sequencing and acquired the expression profiles of circRNAs. Quantitative real-time PCR as well as RNA in situ hybridization helped to validate circ_0000119 dysregulation. Various in vitro experiments were utilized to investigate the biological activities of circ_0000119 in GC, and the clinical relation of circ_0000119 in vivo was identified through nude mouse xenograft models. Finally, the molecular mechanism of circ_0000119 was clarified via luciferase assays, western blot, and rescue experiments. Compared with adjacent normal tissues, the study found an increase in the expression of circ_0000119 as well as its host linear gene MAN1A2 in GC tissues. Circ_0000119 overexpression promoted proliferation and migration of GC cells in vitro and in vivo, whereas circ_0000119 suppression had the opposite effect. Mechanistically, circ_0000119 sponged miR-502-5p which played an inhibitory role in tumors. Furthermore, we found that miR-502-5p alleviated GC progression through targeting MTBP and downregulating its expression at mRNA and protein levels. In conclusion, our findings reveal a new regulatory mechanism for circ_0000119, which sponges the miR-502-5p, suppresses MTBP expression, and finally promotes GC progression.

LINC00659 cooperated with ALKBH5 to accelerate gastric cancer progression by stabilising JAK1 mRNA in an m6 A-YTHDF2-dependent manner.

BACKGROUND: N6-methyladenosine (m6 A) RNA modification is known as a common epigenetic regulation form in eukaryotic cells. Emerging studies show that m6 A in noncoding RNAs makes a difference, and the aberrant expression of m6 A-associated enzymes may cause diseases. The demethylase alkB homologue 5 (ALKBH5) plays diverse roles in different cancers, but its role during gastric cancer (GC) progression is not well known. METHODS: The quantitative real-time polymerase chain reaction, immunohistochemistry staining and western blotting assays were used to detect ALKBH5 expression in GC tissues and human GC cell lines. The function assays in vitro and xenograft mouse model in vivo were used to investigate the effects of ALKBH5 during GC progression. RNA sequencing, MeRIP sequencing, RNA stability and luciferase reporter assays were performed to explore the potential molecular mechanisms involved in the function of ALKBH5. RNA binding protein immunoprecipitation sequencing (RIP-seq), RIP and RNA pull-down assays were performed to examine the influence of LINC00659 on the ALKBH5-JAK1 interaction. RESULTS: ALKBH5 was highly expressed in GC samples and associated with aggressive clinical features and poor prognosis. ALKBH5 promoted the abilities of GC cell proliferation and metastasis in vitro and in vivo. The m6 A modification on JAK1 mRNA was removed by ALKBH5, which resulted in the upregulated expression of JAK1. LINC00659 facilitated ALKBH5 binding to and upregulated JAK1 mRNA depending on an m6 A-YTHDF2 manner. Silencing of ALKBH5 or LINC00659 disrupted GC tumourigenesis via the JAK1 axis. JAK1 upregulation activated the JAK1/STAT3 pathway in GC. CONCLUSION: ALKBH5 promoted GC development via upregulated JAK1 mRNA expression mediated by LINC00659 in an m6 A-YTHDF2-dependent manner, and targeting ALKBH5 may be a promising therapeutic method for GC patients.

Loss of miR-26b-5p promotes gastric cancer progression via miR-26b-5p-PDE4B/CDK8-STAT3 feedback loop.

BACKGROUND: Chronic inflammation is a well-known risk factor for the development of gastric cancer (GC). Nevertheless, the molecular mechanisms underlying inflammation-related GC progression are incompletely defined. METHODS: Bioinformatic analysis was performed based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and the expression of miR-26b-5p in GC cells and tissues was validated by quantitative real-time PCR (qRT-PCR). Cell proliferation was examined through Cell Counting Kit-8 (CCK8), 5-Ethynyl-2'-deoxyuridine (EdU), colony formation, flow cytometry, and tumor xenografts. Correlation between miR-26b-5p and Cyclin dependent kinase 8 (CDK8) or Phosphodiesterase 4B (PDE4B) was analyzed by dual-luciferase reporter assays, qRT-PCR, and Western blot. The effect of miR-26b-5p on the Signal transducer and activator of transcription 3 (STAT3) pathway was investigated using Western blot, immunofluorescence (IF), and immunohistochemistry (IHC). The impact of STAT3 on miR-26b-5p was determined by dual-luciferase reporter assays and qRT-PCR. RESULTS: The expression of miR-26b-5p was significantly downregulated in Helicobacter Pylori (H. pylori)-infected GC cells. The decreased expression of miR-26b-5p was also detected in GC cells and tissues compared to normal gastric epithelium cells (GES1) and normal adjacent gastric tissues. The low expression of miR-26b-5p promoted GC proliferation in vitro and in vivo and was related to the poor outcome of GC patients. In terms of mechanism, miR-26b-5p directly targeted PDE4B and CDK8, resulting in decreased phosphorylation and nuclear translocation of STAT3, which was associated with the regulation of GC proliferation by miR-26b-5p. Notably, miR-26b-5p was transcriptionally suppressed by STAT3, thus forming the miR-26b-5p-PDE4B/CDK8-STAT3 positive feedback loop. CONCLUSION: The newly identified miR-26b-5p-PDE4B/CDK8-STAT3 feedback loop plays an important role in inflammation-related GC progression and may serve as a promising therapeutic target for GC.

APE1 controls DICER1 expression in NSCLC through miR-33a and miR-130b.

Increasing evidence suggests different, not completely understood roles of microRNA biogenesis in the development and progression of lung cancer. The overexpression of the DNA repair protein apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is an important cause of poor chemotherapeutic response in lung cancer and its involvement in onco-miRNAs biogenesis has been recently described. Whether APE1 regulates miRNAs acting as prognostic biomarkers of lung cancer has not been investigated, yet. In this study, we analyzed miRNAs differential expression upon APE1 depletion in the A549 lung cancer cell line using high-throughput methods. We defined a signature of 13 miRNAs that strongly correlate with APE1 expression in human lung cancer: miR-1246, miR-4488, miR-24, miR-183, miR-660, miR-130b, miR-543, miR-200c, miR-376c, miR-218, miR-146a, miR-92b and miR-33a. Functional enrichment analysis of this signature revealed its biological relevance in cancer cell proliferation and survival. We validated DICER1 as a direct functional target of the APE1-regulated miRNA-33a-5p and miR-130b-3p. Importantly, IHC analyses of different human tumors confirmed a negative correlation existing between APE1 and Dicer1 protein levels. DICER1 downregulation represents a prognostic marker of cancer development but the mechanisms at the basis of this phenomenon are still completely unknown. Our findings, suggesting that APE1 modulates DICER1 expression via miR-33a and miR-130b, reveal new mechanistic insights on DICER1 regulation, which are of relevance in lung cancer chemoresistance and cancer invasiveness.

Exosome-transmitted miR-769-5p confers cisplatin resistance and progression in gastric cancer by targeting CASP9 and promoting the ubiquitination degradation of p53.

BACKGROUND: Cisplatin resistance is the main cause of poor clinical prognosis in patients with gastric cancer (GC). Yet, the exact mechanism underlying cisplatin resistance remains unclear. Recent studies have suggested that exocrine miRNAs found in the tumor microenvironment participate in tumor metastasis and drug resistance. METHODS: Exosomes isolated from BGC823 and BGC823/DDP culture medium were characterized by transmission electron microscopy and differential ultracentrifugation, and miRNA expression profiles of BGC823 and BGC823/DDP cells derived exosomes were analyzed using miRNA microarray. In vivo and in vitro assays were used to identify roles of exosomal miR-769-5p and clarify the mechanism of exosomal miR-769-5p regulated the crosstalk between sensitive and resistant GC cells. RESULTS: In this study, we found that cisplatin-resistant GC cells communicated with the tumor microenvironment by secreting microvesicles. MiR-769-5p was upregulated in GC tissues and enriched in the serum exosomes of cisplatin-resistant patients. The biologically active miR-769-5p could be integrated into exosomes and delivered to sensitive cells, spreading cisplatin resistance. Underlying cellular and molecular mechanism was miR-769-5p targeting CASP9, thus inhibiting the downstream caspase pathway and promoting the degradation of the apoptosis-related protein p53 through the ubiquitin-proteasome pathway. Targeting miR-769-5p with its antagonist to treat cisplatin-resistant GC cells can restore the cisplatin response, confirming that exosomal miR-769-5p can act as a key regulator of cisplatin resistance in GC. CONCLUSIONS: These findings indicate that exosome-transmitted miR-769-5p confers cisplatin resistance and progression in gastric cancer by targeting CASP9 and promoting the ubiquitination degradation of p53. These findings reveal exosomal miR-769-5p derived from drug-resistant cells can be used as a potential therapeutic predictor of anti-tumor chemotherapy to enhance the effect of anti-cancer chemotherapy, which provides a new treatment option for GC.

Targeting IL8 as a sequential therapy strategy to overcome chemotherapy resistance in advanced gastric cancer.

Systemic chemotherapy with multiple drug regimens is the main therapy option for advanced gastric cancer (GC) patients. However, many patients develop relapse soon. Here, we evaluated the therapeutic potential of targeting interleukin-8 (IL8) to overcome resistance to chemotherapy in advanced GC. RNA sequencing revealed crucial molecular changes after chemotherapy resistance, in which the expression of IL8 was significantly activated with the increase in drug resistance. Subsequently, the clinical significance of IL8 expression was determined in GC population specimens. IL8-targeted by RNA interference or reparixin reversed chemotherapy resistance with limited toxicity in vivo and vitro experiments. Sequential treatment with first-line, second-line chemotherapy and reparixin inhibited GC growth, reduced toxicity and prolonged survival. Collectively, our study provides a therapeutic strategy that targeting IL8 as a sequential therapy after chemotherapy resistance in advanced GC.

Crosstalk between Environmental Inflammatory Stimuli and Non-Coding RNA in Cancer Occurrence and Development.

There is a clear relationship between inflammatory response and different stages of tumor development. Common inflammation-related carcinogens include viruses, bacteria, and environmental mutagens, such as air pollutants, toxic metals, and ultraviolet light. The expression pattern of ncRNA changes in a variety of disease conditions, including inflammation and cancer. Non-coding RNAs (ncRNAs) have a causative role in enhancing inflammatory stimulation and evading immune responses, which are particularly important in persistent pathogen infection and inflammation-to-cancer transformation. In this review, we investigated the mechanism of ncRNA expression imbalance in inflammation-related cancers. A better understanding of the function of inflammation-associated ncRNAs may help to reveal the potential of ncRNAs as a new therapeutic strategy.

Exosomal circSHKBP1 promotes gastric cancer progression via regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation.

BACKGROUND: Circular RNAs (circRNAs) play important regulatory roles in the development of various cancers. However, biological functions and the underlying molecular mechanism of circRNAs in gastric cancer (GC) remain obscure. METHODS: Differentially expressed circRNAs were identified by RNA sequencing. The biological functions of circSHKBP1 in GC were investigated by a series of in vitro and in vivo experiments. The expression of circSHKBP1 was evaluated using quantitative real-time PCR and RNA in situ hybridization, and the molecular mechanism of circSHKBP1 was demonstrated by western blot, RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. Lastly, mouse xenograft and bioluminescence imaging were used to exam the clinical relevance of circSHKBP1 in vivo. RESULTS: Increased expression of circSHKBP1(hsa_circ_0000936) was revealed in GC tissues and serum and was related to advanced TNM stage and poor survival. The level of exosomal circSHKBP1 significantly decreased after gastrectomy. Overexpression of circSHKBP1 promoted GC cell proliferation, migration, invasion and angiogenesis in vitro and in vivo, while suppression of circSHKBP1 plays the opposite role. Exosomes with upregulated circSHKBP1 promoted cocultured cells growth. Mechanistically, circSHKBP1 sponged miR-582-3p to increase HUR expression, enhancing VEGF mRNA stability. Moreover, circSHKBP1 directly bound to HSP90 and obstructed the interaction of STUB1 with HSP90, inhibiting the ubiquitination of HSP90, resulting in accelerated GC development in vitro and in vivo. CONCLUSION: Our findings demonstrate that exosomal circSHKBP1 regulates the miR-582-3p/HUR/VEGF pathway, suppresses HSP90 degradation, and promotes GC progression. circSHKBP1 is a promising circulating biomarker for GC diagnosis and prognosis and an exceptional candidate for further therapeutic exploration.

Role of hypoxia in cancer therapy by regulating the tumor microenvironment.

AIM: Clinical resistance is a complex phenomenon in major human cancers involving multifactorial mechanisms, and hypoxia is one of the key components that affect the cellular expression program and lead to therapy resistance. The present study aimed to summarize the role of hypoxia in cancer therapy by regulating the tumor microenvironment (TME) and to highlight the potential of hypoxia-targeted therapy. METHODS: Relevant published studies were retrieved from PubMed, Web of Science, and Embase using keywords such as hypoxia, cancer therapy, resistance, TME, cancer, apoptosis, DNA damage, autophagy, p53, and other similar terms. RESULTS: Recent studies have shown that hypoxia is associated with poor prognosis in patients by regulating the TME. It confers resistance to conventional therapies through a number of signaling pathways in apoptosis, autophagy, DNA damage, mitochondrial activity, p53, and drug efflux. CONCLUSION: Hypoxia targeting might be relevant to overcome hypoxia-associated resistance in cancer treatment.

The value of miR-155 as a biomarker for the diagnosis and prognosis of lung cancer: a systematic review with meta-analysis.

BACKGROUND: Recently, a growing number of studies have reported the coorelation between miR-155 and the diagnosis and prognosis of lung cancer, but results of these researches were still controversial due to insufficient sample size. Thus, we carried out the systematic review and meta-analysis to figure out whether miR-155 could be a screening tool in the detection and prognosis of lung cancer. METHODS: A meta-analysis of 13 articles with 19 studies was performed by retrieving the PubMed, Embase and Web of Science. We screened all correlated literaters until December 1st, 2018. For the diagnosis analysis of miR-155 in lung cancer, sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve (AUC) were pooled to evaluate the accuracy of miRNA-155 in the diagnosis of lung cancer. For the prognosis analysis of miR-155 in lung cancer, the pooled HRs and 95% CIs of miR-155 for overall survival/disease free survival/progression-free survival (OS/DFS/PFS) were calculated. In addition, Subgroup and meta-regression analyses were performed to distinguish the potential sources of heterogeneity between studies. RESULTS: For the diagnostic analysis of miR-155 in lung cancer, the pooled SEN and SPE were 0.82 (95% CI: 0.72-0.88) and 0.78 (95% CI: 0.71-0.84), respectively. Besides, the pooled PLR was 3.75 (95% CI: 2.76-5.10), NLR was 0.23 (95% CI: 0.15-0.37), DOR was 15.99 (95% CI: 8.11-31.52) and AUC was 0.87 (95% CI: 0.84-0.90), indicating a significant value of miR-155 in the lung cancer detection. For the prognostic analysis of miR-155 in lung cancer, up-regulated miRNA-155 expression was not significantly associated with a poor OS (pooled HR = 1.26, 95% CI: 0.66-2.40) or DFS/PFS (pooled HR = 1.28, 95% CI: 0.82-1.97). CONCLUSIONS: The present meta-analysis demonstrated that miR-155 could be a potential biomarker for the detection of lung cancer but not an effective biomarker for predicting the outcomes of lung cancer. Furthermore, more well-designed researches with larger cohorts were warranted to confirm the value of miR-155 for the diagnosis and prognosis of lung cancer.

miR-942 promotes tumor migration, invasion, and angiogenesis by regulating EMT via BARX2 in non-small-cell lung cancer.

Epithelial-mesenchymal transition (EMT) has an important function in cancer. Recently, microRNAs have been reported to be involved in EMT by regulating target genes. miR-942 is considered a novel oncogene in esophageal squamous cell carcinoma. However, its role in non-small-cell lung cancer (NSCLC) has not been investigated. In this study, the expression of miR-942 in NSCLC patients tumor and paired adjacent tissues were assessed by quantitative real-time polymerase chain reaction and in situ hybridization. Transwell, wound healing, tube formation, and tail vein xenograft assays were conducted to assess miR-942's function in NSCLC. Potential miR-942 targets were confirmed using dual-luciferase reporter assays, immunohistochemistry, immunoblot, and rescue experiments. The results showed miR-942 is relatively highly expressed in human NSCLC tissues and cells. In vitro assays demonstrated that overexpression of miR-942 promoted cell migration, invasion, and angiogenesis. Tail vein xenograft assays suggested that miR-942 contributed to NSCLC metastasis in vivo. Three bioinformatics software was searched, and BARX2 was predicted as a downstream target of miR-942. Direct interaction between them was validated by dual-luciferase assays. Rescue experiments further confirmed that BARX2 overexpression could reverse functional changes caused by miR-942. Moreover, miR-942 increased EMT-associated proteins N-cadherin and vimentin by inhibiting BARX2, while E-cadherin expression is reduced. In summary, this study reveals that miR-942 induces EMT-related metastasis by directly targeting BARX2, which may provide a potential therapeutic strategy for NSCLC.

Viability loss pattern under rapid dehydration of Antiaris toxicaria axes and its relation to oxidative damage.

The relation between oxidative damage and viability loss of excised embryonic axes of Antiaris toxicaria subjected to rapid drying with silica gel at 15 degrees C was studied. Changes of survival rate, accumulation of thiobarbituric acid-reactive substances (TBARs), activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR) and the permeability of cell membrane that was determined as relative electrolyte leakage (REL) were measured. The half-life moisture content (MC(L50)) was 0.41 g H2O/g DW (dry weight basis). During drying, the activities of SOD, CAT and APX increased until MC(L50), and declined thereafter. The generation speed of (.)O2(-), and content of H2O2 and TBARs remained steadily or even decreased at MC levels higher than MC(L50), demonstrating a low oxidative level in these axes. There was no significant correlation between viability loss and accumulation of reactive oxygen species or lipid peroxidation within the dehydration process until MC(L50). Whereas the increase in REL from the beginning of the drying process indicated that the cell membrane was damaged. In conclusion, under rapid drying with silica gel the viability loss of excised recalcitrant A. toxicaria axes seemed to be triggered by mechanical or physical damage, rather than metabolic damage.

Memory impairment in early sensorimotor deprived rats is associated with suppressed hippocampal neurogenesis and altered CREB signaling.

Sensorimotor function is important for cognitive development; however, little experimental evidence exists to support this assumption. In this study we tested the hypothesis that altered cAMP response element binding (CREB) protein induction and activity-regulated cytoskeletal-associated gene (Arc) expression may underlie the suppression of hippocampal neurogenesis and memory impairment associated with early sensorimotor deprivation. Associated memory was evaluated in sensorimotor deprived (T) and sham operated (C) rats using a contextual fear-conditioning task. Hippocampal dentate gyrus (DG) neurogenesis was assessed by Brdu and NeuN labeling. Hippocampal DG CREB signaling was examined by measuring protein and mRNA levels of CREB and activity-regulated cytoskeletal-associated gene (Arc). Contextual freezing responses in the 1-day recall test were significantly lower in 25- and 35-day-old group T compared to C rats (P<0.01), indicating that hippocampal-dependent memory impairment was caused by early sensorimotor deprivation. Furthermore, group T rats exhibited significantly decreased CREB and Arc activation in the hippocampal DG at 25 and 35 days compared to in group C rats (P<0.01 for both). These changes may underlie decreased neurogenesis and impaired memory. No significant between groups differences were apparent in 45- and 60-day-old rats. These results suggest that early sensorimotor deprivation may alter CREB signaling, decrease Arc activation, suppress neurogenesis and ultimately impair memory.

Mitochondrial damage in the soybean seed axis during imbibition at chilling temperatures.

The development of mitochondria during seed germination is essential for plant growth. However, the developmental process is still poorly understood. Temperature plays a key role in soybean germination, and in this study we characterized the mitochondrial ultrastructure and proteome after imbibition at 22, 10 and 4 degrees C for 24 h. The mitochondria from the soybean seed axis can be divided into light and heavy mitochondria by Percoll density gradient centrifugation. The axes imbibed at 4 degrees C mainly contained light mitochondria, which had lower levels of specific mitochondrial enzymes and oxidative phosphorylation activity. In contrast, the axes imbibed at 22 degrees C mainly contained heavy mitochondria, which exhibited higher metabolism. Electron microscopy revealed that mitochondria in the axes imbibed at 4 degrees C had a poorly developed internal membrane system with few cristae, while the mitochondria in the axes imbibed at 22 degrees C developed more normally. Furthermore, we compared the axis mitochondrial proteomes during imbibition at different temperatures. The differentially expressed proteins were identified using ESI-Q-TOF-MS/MS (electrospray ionization quadrupole time-of-flight tandem mass spectrometry). Proteins involved in mitochondrial metabolites including malate dehydrogenase (tricarboxylic acid cycle enzyme), putative ATP synthase subunit (oxidative phosphorylation complex subunits), mitochondrial chaperonin-60 (heat shock protein), arginase (urea cycle enzyme) and mitochondrial elongation factor Tu (mitochondrial genome transcript enzyme) were identified. The reduced expression of these proteins might not support normal mitochondrial metabolism. We conclude that chilling during imbibition causes mitochondrial damage at both ultrastructural and metabolic levels.

GMCHI, cloned from soybean [Glycine max (L.) Meer.], enhances survival in transgenic Arabidopsis under abiotic stress.

Plants respond to cold stress by modifying the expression of a battery of cold-responsive genes. Using cDNA-AFLP techniques, GMCHI (G lycine m ax chilling-inducible) (accession no. EU699765) was isolated from the embryonic axis of a chilling-resistant cultivar of soybean seed imbibed at 4 degrees C for 24 h. The full-length GMCHI cDNA which consisted of a single open reading frame (ORF) encoded a putative polypeptide of 129 amino acids. Sequence analysis revealed neither significant similarity of GMCHI to known proteins, nor any conserved domains found. Soybean seed imbibed at 4 degrees C dramatically enhanced transcript level of GMCHI after 1 h, and reached a maximum at 18 h, while the expression was only detected in the embryonic axis. GMCHI expression was strongly induced by treatment with ABA and PEG, but weakly by 250 mM NaCl which suggests that GMCHI is probably regulated by ABA-dependent signal transduction pathway during cold acclimation. Overexpression of GMCHI in Arabidopsis under the control of CaMV35S promoter enhanced the tolerance to cold, drought and NaCl stresses. Therefore, GMCHI may play an important role in the adaptation of chilling-resistant soybean seed to chilling imbibition.

The influence of forepaw palmar sensorimotor deprivation on learning and memory in young rats.

This study examined the effects of early palmar forepaw sensorimotor deprivation on learning and memory in rats. Sensorimotor deprivation was performed on 18-day-old male rats. Controls were sham operated. Studies were performed on rats aged 18, 25, 35, 45 and 60 days. Morris water maze testing was used to assess learning and memory. Long-term potentiation (LTP) was assessed by electrophysiological means in slices obtained from the hippocampal Schaffer collateral pathway. Nissl staining was performed to assess pyramidal cell number in hippocampal CA1 and CA3 regions. Hippocampal N-methyl-d-aspartate receptor 1 (NMDAR1) mRNA and protein levels were assessed. Learning and short-term memory were significantly depressed in 25 and 35 day old sensorimotor deprived rats (P<0.01). LTP was also significantly depressed in sensorimotor deprived rats at these ages, while hippocampal CA1 pyramidal cell counts were significantly decreased (P<0.05). CA3 cell numbers were significantly lower in 25-day-old sensorimotor deprived rats (P<0.05). Both NMDAR1 mRNA and protein levels were significantly lower in sensorimotor deprived rats aged 25 and 35 days (P<0.05). These findings indicate that palmar surface forepaw sensorimotor deprivation impairs subsequent learning and memory in young rats. Decreased hippocampal pyramidal cell numbers and altered NMDAR1 expression may underlie this impairment.

Child body mass index in four cities of East China compared to Western references.

BACKGROUND: The rising trends in child obesity worldwide are poorly documented in China. AIM: The present study compared the distribution of body mass index (BMI) by age in children from four cities in East China with Western references. SUBJECTS AND METHODS: 94 370 boys and 90 048 girls aged 0-19 years from Shanghai, Jinan, Xuzhou and Hefei were measured in 1999-2004 for length/height and weight. The LMS method was used to construct BMI centiles for each city. Shanghai children aged 0-6 years in 1986 and US and UK BMI references were used for comparison. RESULTS: The median BMI curves for the four cities differed in shape from those for the USA and UK. Chinese boys were fatter than US boys in early to mid-childhood but less so in adolescence, and US boys were fatter at age 18. Within China the adiposity rebound was earlier in boys than girls. Shanghai children were appreciably fatter in 2000 than in 1986, and boys more so than girls. CONCLUSIONS: The roots of child obesity lie in early life, particularly in boys, and are linked to economic development, which has important implications for both the aetiology of child obesity and the health of current and future Chinese children.

[Effects of osmoconditioning on membrane lipid components and fatty acid content of cold-sensitive soybean seeds].

Cold-sensitive soybean (Glycisne max Zhonghuang No.22) seeds were used to investigate the effects of osmoconditioning for invigoration of seeds chilling tolerance and the changes in membrane lipid by thin layer chromatography and gas chromatography to disclose the role of membrane lipid played in imbibitional chilling resistance capacity. Results are as follows: being treated with 33% PEG6000, seeds germination index, vigor index and root dry weight presented the trend of upward as the osmocondition time prolonged. In 72 h, the percentage of unsaturated phospholipid (e.g. PC and PE) in soybean seed increased, composition of lipid fatty acid changed: the saturated fatty acid 16:0 content in PC, PE, PI significantly decreased, while unsaturated fatty acid 18:2 increased greatly, which led to increase index of unsaturation fatty acid of lipid. These changes were positively corrected with osmoconditioning time. After treated with PEG, membrane fluidity increased to provide precondition for preventing imbibitional chilling, keeping the integrity of membrane system and normal metabolism.