LncRNA CHROMR/miR-27b-3p/MET axis promotes the proliferation, invasion, and contributes to rituximab resistance in diffuse large B-cell lymphoma.

Long non-coding RNAs (LncRNAs) could regulate chemoresistance through sponging microRNAs (miRNAs) and sequestering RNA binding proteins. However, the mechanism of lncRNAs in rituximab resistance in diffuse large B-cell lymphoma (DLBCL) is largely unknown. Here, we investigated the functions and molecular mechanisms of lncRNA CHROMR in DLBCL tumorigenesis and chemoresistance. LncRNA CHROMR is highly expressed in DLBCL tissues and cells. We examined the oncogenic functions of lncRNA CHROMR in DLBCL by a panel of gain-or-loss-of-function assays and in vitro experiments. LncRNA CHROMR suppression promotes CD20 transcription in DLBCL cells and inhibits rituximab resistance. RNA immunoprecipitation, RNA pull-down, and dual luciferase reporter assay reveal that lncRNA CHROMR sponges with miR-27b-3p to regulate mesenchymal-epithelial transition factor (MET) levels and Akt signaling in DLBCL cells. Targeting the lncRNA CHROMR/miR-27b-3p/MET axis reduces DLBCL tumorigenesis. Altogether, these findings provide a new regulatory model, lncRNA CHROMR/miR-27b-3p/MET, which can serve as a potential therapeutic target for DLBCL.

Comparison of tucidinostat with CHOP-like versus CHOP-like in first-line treatment of peripheral T-cell lymphoma: a single-center real-world study.

Tucidinostat has been approved by the Chinese FDA for relapsed/refractory Peripheral T cell lymphoma (PTCL), but its efficacy in newly diagnosed PTCL has not been confirmed. In this study, we aimed to compare the efficacy of tucidinostat combined with CHOP-like (C + CHT) versus CHOP-like alone (CHT) in newly diagnosed PTCL patients. Of the PTCL patients, 109 were newly diagnosed. Patients in the C + CHT group who achieved objective response received tucidinostat maintenance therapy. A total of 36 pairs (n = 72) were matched at a ratio of 1:1 using propensity scoring. The matching criteria included: whether the Prognostic index for the peripheral T-cell lymphoma-not otherwise specified subtype (PIT) was ≥ 2, the pathological subtype, age > 60 years, and gender (matching tolerance = 0.024). A significantly higher objective response rate (ORR) (P = 0.016), 2-year progression-free survival (PFS) (P = 0.026), and 2-year survival rate (P = 0.017) was observed for the C + CHT group as compared to the CHT group. After propensity score matching (PSM), the C + CHT group as compared to the CHT group displayed significantly longer PFS (P = 0.035) and overall survival (OS) (P = 0.029). For the C + CHT group in the per-protocol set, the effect values showed a significant benefit in terms of both PFS (P = 0.027) and OS (P = 0.019). Common grade 3-4 haematological adverse events (AEs), had comparable incidence in each group; while common non-haematological AEs, including elevated AST and ALT were higher in the C + CHT group than in the CHT group. Our study suggests that the tucidinostat with CHOP-like regimen and sequential tucidinostat maintenance after objective remission provides a promising therapeutic approach for treating newly diagnosed PTCL patients.

Mitochondrion-encoded circular RNAs are widespread and translatable in plants.

Nucleus-encoded circular RNAs (ncircRNAs) have been widely detected in eukaryotes, and most circRNA identification algorithms are designed to identify them. However, using these algorithms, few mitochondrion-encoded circRNAs (mcircRNAs) have been identified in plants, and the role of plant mcircRNAs has not yet been addressed. Here, we developed a circRNA identification algorithm, mitochondrion-encoded circRNA identifier, based on common features of plant mitochondrial genomes. We identified 7,524, 9,819, 1,699, 1,821, 1,809, and 5,133 mcircRNAs in maize (Zea mays), Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa), tomato (Solanum lycopersicum), cucumber (Cucumis sativus), and grape (Vitis vinifera), respectively. These mcircRNAs were experimentally validated. Plant mcircRNAs had distinct characteristics from ncircRNAs, and they were more likely to be derived from RNA degradation but not intron backsplicing. Alternative circularization was prevalent in plant mitochondria, and most parental genomic regions hosted multiple mcircRNA isoforms, which have homogenous 5' termini but heterogeneous 3' ends. By analysis of mitopolysome and mitoribosome profiling data, 1,463 mcircRNAs bound to ribosomes were detected in maize and Arabidopsis. Further analysis of mass spectrometry-based proteomics data identified 358 mcircRNA-derived polypeptides. Overall, we developed a computational pipeline that efficiently identifies plant mcircRNAs, and we demonstrated mcircRNAs are widespread and translated in plants.

Treatment-related outcome from patient report outcome (PRO) of children with severe and moderate hemophilia A in China: An analysis report of registration data from patient organization "hemophilia home care center".

OBJECTIVES: To assess current treatment-related outcomes for children with severe and moderate haemophilia A (cHA) in China. METHODS: This cross-section Patient Report Outcome (PRO) report collected PRO data of severe and moderate cHAs registered in the 'Hemophilia Home Care Center' database (http://web.bjxueyou.cn) between January 2021 and November 2022. Data included records of bleeding, activities, and concentrates consumption. All patients had a confirmed diagnosis of moderate or severe haemophilia A (FVIII: C ≤ 5%) and were < 18 years old. RESULTS: Among 1038 analysable cases, 9.6% of children with inhibitors had a higher rate of intracranial haemorrhage, dropout school rate, and higher FVIII consumption than children without inhibitors. Among 100 children with inhibitors, 36 patients were treated without immune tolerance induction (ITI), 14 patients with irregular treatment and 50 patients received ITI. Children with ITI had a lower ABR (2.4 (0,6.6) vs. 13.4 (9.5, 26.6), p<.001) and AJBR (0 (0, 3.1) vs. 8.9 (1.6, 19.3), p < .001) compared to those without ITI. Among 938 children without inhibitors, 28.5% received on-demand treatment and 71.5% received prophylaxis. Of 528 children with 1343.8 (1050.4, 2922.9)IU/kg/year median FVIII consumption, 43.0% received low-dose, 43.2% received intermediate-dose, and 13.8% received high-dose regimen; these children with prophylaxis had a lower ABR (3.1 (0, 10.7) vs. 12.8 (2.4, 45.5), p < .001), AJBR (0.5 (0, 3.9) vs. 3.0 (0, 12.0), p < .001) and disability rate (9.0% vs.18.5%, p = .032) compared to children who received on-demand treatment. CONCLUSION: The high rate of drop-out of school and disability still present a huge gap to meet the needs in China. It is necessary to improve the level of medical accessibility and medicine affordability and strengthen the patient/parent's education in China.

Drug-related adverse events potentially predict the efficacy of apatinib on advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide every year, and most HCC patients are diagnosed with advanced disease and can only receive systemic treatment. TKIs are the most important components of the systemic treatment of HCC and have both good efficacy and adverse events (AEs).  METHODS: This analysis included 207 patients with locally advanced unresectable or metastatic HCC who received oral treatment with apatinib. We analyzed the overall survival (OS) and progression-free survival (PFS) of patients with or without corresponding AEs to evaluate which AEs can predict the efficacy of apatinib. RESULTS: Patients with hand-foot syndrome (HFS; p = 0.005), proteinuria (p = 0.006) and diarrhea (p < 0.001) had significantly better OS than those without corresponding AEs, and the appearance of HFS (p = 0.006) and proteinuria (p = 0.004) was associated with longer PFS. CONCLUSION: Among all the AEs induced by apatinib in the treatment of advanced HCC, proteinuria could potentially predict PFS, and diarrhea was a potential predictor of OS.

Evaluation of the Effect of Nano-Sodium Alginate-Bioglass on Cardiac Function of Myocardial Infarction Based on Cardiac Ultrasound.

In cardiovascular diseases, myocardial infarction is the most important cause of chronic heart failure. According to reports, more than 70% of patients with chronic heart failure suffer from myocardial infarction. Nano sodium alginate-bioglass has attracted more and more attention in the treatment of myocardial infarction due to its good cell proliferation. In order to understand the effect of nano-sodium alginate-bioglass on myocardial infarction, we added nano-sodium alginate-bioglass in the treatment process. The calcium ions released by the bio-glass during the slurry preparation process partially cross-link the sodium alginate, which helps to restore the heart function of myocardial infarction. Add nano-seaweed Sodium-bioglass can significantly promote the proliferation of heart cells. Through the test of different groups and the results of cell experiments, we have obtained the best recovery effect of myocardial infarction when the bioglass content is about 30%, and the changes in the vitality of heart cells can be seen most clearly.

A Chloroplast-Localized Glucose-6-Phosphate Dehydrogenase Positively Regulates Stripe Rust Resistance in Wheat.

Glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme of the pentose phosphate pathway (PPP), plays a pivotal role in plant stress responses. However, the function and mechanism of G6PDHs in crop plants challenged by fungal pathogens remain poorly understood. In this study, a wheat G6DPH gene responding to infection by Puccinia striiformis f. sp. tritici (Pst), designated TaG6PDH2, was cloned and functionally identified. TaG6PDH2 expression was significantly upregulated in wheat leaves inoculated with Pst or treated with abiotic stress factors. Heterologous mutant complementation and enzymatic properties indicate that TaG6PDH2 encodes a G6PDH protein. The transient expression of TaG6PDH2 in Nicotiana benthamiana leaves and wheat protoplasts revealed that TaG6PDH2 is a chloroplast-targeting protein. Silencing TaG6PDH2 via the barley stripe mosaic virus (BSMV)-induced gene silencing (VIGS) system led to compromised wheat resistance to the Pst avirulent pathotype CYR23, which is implicated in weakened H2O2 accumulation and cell death. In addition, TaG6PDH2 was confirmed to interact with the wheat glutaredoxin TaGrxS4. These results demonstrate that TaG6PDH2 endows wheat with increased resistance to stripe rust by regulating reactive oxygen species (ROS) production.

Physiological effects of different stubble height and freeze-thaw stress on Secale cereale L. seedlings.

BACKGROUND: As a biennial plant, Secale cereale L is usually harvested in the autumn in the northern part of China where the temperature difference between day and night is of great disparity Through the pot experiment, the seedlings were cut to 2, 6 and 10 cm stubble height, and the simulated freeze-thaw (FT) stress (10/- 5 °C) was carried out after 6 days regrowth. The physiological effects of FT with different stubble height were revealed by analyzing the relative water content (RWC), osmotic adjustment substance concentration (soluble sugar and protein), membrane peroxidation (MDA) and catalase (CAT) activity. RESULTS: The results demonstrated that under freeze stress (- 5 °C), the content of soluble protein and MDA decreased and the seedlings of 2 cm treatment kept higher level of soluble protein and MDA, while the seedlings of 6 and 10 cm treatments kept higher level of the RWC, soluble sugar content, and CAT activity. After FT stress, the content of soluble sugar and protein, RWC in the 6 cm treatment were higher than those in 2 cm and 10 cm treatments, and the CAT activity in 10 cm treatment was the highest while the MDA content is lower. CONCLUSION: These data suggest that keeping high stubble height is more adaptive for short-term FT stress.

Clinical observation of two bone cement distribution modes after percutaneous vertebroplasty for osteoporotic vertebral compression fractures.

BACKGROUND: Current findings suggest that percutaneous vertebroplasty(PVP) is a suitable therapeutic approach for osteoporotic vertebral compression fractures (OVCFs). The present retrospective study aimed to investigate the differences in clinical efficacy and related complications between the two bone cement distribution modes. METHODS: We retrospectively reviewed the medical records of the patients with single-segment OVCFs who underwent bilateral percutaneous vertebroplasty. Patients were divided into blocky and spongy group according to the type of postoperative bone cement distribution. Clinical efficacy and related complications was compared between the two bone cement distribution modes on 24 h after the operation and last follow-up. RESULTS: A total of 329 patients with an average follow up time of 17.54 months were included. The blocky group included 131 patients, 109 females(83.2 %) and 22 males(16.8 %) with a median age of 72.69 ± 7.76 years, while the Spongy group was made up of 198 patients, 38 females(19.2 %) and 160 males(80.8 %) with a median age of 71.11 ± 7.36 years. The VAS and ODI after operation improved significantly in both two groups. The VAS and ODI in the spongy group was significantly lower than that in the blocky group, 24 h postoperatively, and at the last follow-up. There were 42 cases (12.8 %) of adjacent vertebral fractures, 26 cases (19.8 %) in the blocky group and 16 cases (8.1 %) in the spongy group. There were 57 cases (17.3 %) of bone cement leakage, 18 cases (13.7 %) in blocky group and 39 cases (19.7 %) in the spongy group. At 24 h postoperatively and at the last follow-up, local kyphosis and anterior vertebral height were significantly corrected in both groups, but gradually decreased over time, and the degree of correction was significantly higher in the spongy group than in the block group. The change of local kyphosis and loss of vertebral body height were also less severe in the spongy group at the last follow-up. CONCLUSIONS: Compared with blocky group, spongy group can better maintain the height of the vertebral body, correct local kyphosis, reduce the risk of the vertebral body recompression, long-term pain and restore functions.

Adaptive Compaction Construction Simulation Based on Bayesian Field Theory.

The compaction construction process is a critical operation in civil engineering projects. By establishing a construction simulation model, the compaction duration can be predicted to assist construction management. Existing studies have achieved adaptive modelling of input parameters from a Bayesian inference perspective, but usually assume the model as parametric distribution. Few studies adopt the nonparametric distribution to achieve robust inference, but still need to manually set hyper-parameters. In addition, the condition of when the roller stops moving ignores the impact of randomness of roller movement. In this paper, a new adaptive compaction construction simulation method is presented. The Bayesian field theory is innovatively adopted for input parameter adaptive modelling. Next, whether rollers have offset enough distance is used to determine the moment of stopping. Simulation experiments of the compaction process of a high earth dam project are demonstrated. The results indicate that the Bayesian field theory performs well in terms of accuracy and efficiency. When the size of roller speed dataset is 787,490, the Bayesian field theory costs only 1.54 s. The mean absolute error of predicted compaction duration reduces significantly with improved judgment condition. The proposed method can contribute to project resource planning, particularly in a high-frequency construction monitoring environment.

Slit2/Robo1 signaling is involved in angiogenesis of glomerular endothelial cells exposed to a diabetic-like environment.

Abnormal angiogenesis plays a pathological role in diabetic nephropathy (DN), contributing to glomerular hypertrophy and microalbuminuria. Slit2/Robo1 signaling participates in angiogenesis in some pathological contexts, but whether it is involved in glomerular abnormal angiogenesis of early DN is unclear. The present study evaluated the effects of Slit2/Robo1 signaling pathway on angiogenesis of human renal glomerular endothelial cells (HRGECs) exposed to a diabetic-like environment or recombinant Slit2-N. To remove the effect of Slit2 derived from mesangial cells, human renal mesangial cells (HRMCs) grown in high glucose (HG) medium (33 mM) were transfected with Slit2 siRNA and then the HG-HRMCs-CM with Slit2 depletion was collected after 48 h. HRGECs were cultured in the HG-HRMCs-CM or recombinant Slit2-N for 0, 6, 12, 24, or 48 h. The mRNA and protein expressions of Slit2/Robo1, PI3K/Akt and HIF-1α/VEGF signaling pathways were detected by quantitative real-time PCR, western blotting, and ELISA, respectively. The CCK-8 cell proliferation assay, flow cytometry and the scratch wound-healing assay were used to assess cell proliferation, cycles, and migration, respectively. Matrigel was used to perform a tubule formation assay. Our results showed that the HG-HRMCs-CM with Slit2 depletion enhanced the activation of Slit2/Robo1, PI3K/Akt, and HIF-1α/VEGF signaling in HRGECs in time-dependent manner (0-24 h post-treatment). In addition, the HG-HRMCs-CM with Slit2 depletion significantly promoted HRGECs proliferation, migration, and tube formation. Pretreatment of HRGECs with Robo1 siRNA suppressed the activation of PI3K/Akt and HIF-1α/VEGF signaling and inhibited angiogenesis, whereas PI3K inhibitor suppressed HIF-1α/VEGF signaling, without influencing Robo1 expression. In the HRGECs treated with Slit2-N, Slit2-N time-dependently enhanced the activation of Robo1/PI3K/Akt/VEGF pathway but not HIF-1α activity, and promoted HRGECs proliferation, migration, and tube formation. The effects induced by Slit2 were also abolished by Robo1 siRNA and PI3K inhibitor. Taken together, our findings indicate that in a diabetic-like environment, in addition to mesangial cells, autocrine activation of Slit2/Robo1 signaling of HRGECs may contribute to angiogenesis of HRGECs through PI3K/Akt/VEGF pathway; therefore, Slit2/Robo1 signaling may be a potent therapeutic target for the treatment of abnormal angiogenesis in early DN and may have broad implications for the treatment of other diseases dependent on pathologic angiogenesis.

Telmisartan attenuates hydrogen peroxide-induced apoptosis in differentiated PC12 cells.

The present study investigated the protective actions of telmisartan, an angiotensin II type 1 receptor blocker (ARBs), against the cell apoptosis induced by exposure to hydrogen peroxide (H2O2) in differentiated PC12 cells. Preincubation of PC12 cells with telmisartan prevented H2O2-induced cytotoxicity as indicated by increased MTT (3,(4,5-dimethylthiazole-2-yl)2,5-diphenyl-tetrazolium bromide) reduction, decreased lactate dehydrogenase (LDH) release, and improved morphological changes. Hoechst 33,258 staining showed that telmisartan markedly reduced shrunken nuclei of the cells, and Western blot analysis indicated that telmisartan significantly attenuated caspase-3 activity, as indicated by decreased ratio of cleaved Caspase-3 to its precursor and increased ratio of Bcl-2/Bax. The present findings showed that telmisartan protected against cellular oxidative damages by inhibiting apoptotic response.

[Analysis of TGFBI gene mutation in a Chinese pedigree affected with lattice corneal dystrophy].

OBJECTIVE: To explore the clinical features and mutation of TGFBI gene in a Chinese pedigree affected with lattice corneal dystrophy (LCD). METHODS: Genomic DNA was extracted from 35 members including 11 patients from the pedigree. The 17 exons and splicing region of introns of the TGFBI gene were amplified by PCR. The products were directly sequenced and compared with GenBank database to identify potential mutation. Bioinformatic analysis was carried out to predict the effect of mutation on proteins. RESULTS: A heterozygous mutation (p.R124C) was found in exon 4 of the TGFBI gene in all patients from the pedigree but not among unaffected members. The mode of inheritance of corneal dystrophy in this pedigree was identified as autosomal dominant. Bioinformatics analysis predicted that the p.R124C mutation may be functionally deleterious. The phenotype of corneal dystrophy in the pedigree was determined to be LCD I type. CONCLUSION: The p.R124C mutation of the TGFBI gene probably underlies the pathogenesis of LCD in this Chinese pedigree. Genetic testing can facilitate proper diagnosis of this type of corneal dystrophy.

Synthesis and cardiovascular protective effects of quercetin 7-O-sialic acid.

Oxidative stress and inflammation play important roles in the pathogenesis of cardiovascular disease (CVD). Oxidative stress-induced desialylation is considered to be a primary step in atherogenic modification, and therefore, the attenuation of oxidative stress and/or inflammatory reactions may ameliorate CVD. In this study, quercetin 7-O-sialic acid (QA) was synthesized aiming to put together the cardiovascular protective effect of quercetin and the recently reported anti-oxidant and anti-atherosclerosis functions of N-acetylneuraminic acid. The biological efficacy of QA was evaluated in vitro in various cellular models. The results demonstrated that 50 µM QA could effectively protect human umbilical vein endothelial cells (HUVEC, EA.hy926) against hydrogen peroxide- or oxidized low-density lipoprotein-induced oxidative damage by reducing the production of reactive oxygen species. QA attenuated hydrogen peroxide-induced desialylation of HUVEC and lipoproteins. QA decreased lipopolysaccharide-induced secretion of tumour necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), and it significantly reduced the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, TNF-α and MCP-1. Furthermore, QA effectively promoted cholesterol efflux from Raw 264.7 macrophages to apolipoprotein A-1 and high-density lipoprotein by up-regulating ATP-binding cassette transporter A1 and G1, respectively. Results indicated that the novel compound QA exhibited a better capacity than quercetin for anti-oxidation, anti-inflammation, cholesterol efflux promotion and biomolecule protection against desialylation and therefore could be a candidate compound for the prevention or treatment of CVD.

Analysis of the VSX1 gene in sporadic keratoconus patients from China.

BACKGROUND: Keratoconus normally presents as a sporadic disease. Although different studies have found sequence variants of the visual system homeobox 1 (VSX1) gene associated with keratoconus in humans, no research has detected such variants in sporadic keratoconus patients from China. To investigate the possibility of VSX1 being a candidate susceptibility gene for Chinese patients with sporadic keratoconus, we performed sequence screening of this gene in such patients. METHODS: Whole DNA was obtained from the leukocytes in the peripheral venous blood of 50 patients with sporadic keratoconus and 50 control subjects without this ocular disorder. Polymerase chain reaction single-strand conformation polymorphism analysis and direct DNA sequencing technology were used to detect sequence variation in the five exons and splicing regions of the introns of the VSX1 gene. The sequencing results were analyzed using DNAstar software. RESULTS: One novel missense heterozygous sequence variant (p.Arg131Pro) was found in the first exon of the VSX1 gene in one keratoconus patient. Another heterozygous sequence variant (p.Gly160Val) in the second exon was found in two keratoconus patients. These variants were not detected in the control subjects. In the third intron of the VSX1 gene, c.8326G > A nucleotide substitution (including heterozygous and homozygous change) was also discovered. The frequency of this variation did not differ significantly between patients and controls, it should belong to single-nucleotide polymorphism of the VSX1 gene. Bioinformatic analysis also predicted that one missense sequence variation (p.Arg131Pro) may not cause a pathogenic change. CONCLUSIONS: In this study, we added one novel missense sequence variation (p.Arg131Pro) in the coding region of the VSX1 gene to the range of VSX1 coding region variations observed in patients with sporadic keratoconus from China. Our work suggests that VSX1 sequence variants might be involved in the pathogenesis of sporadic keratoconus, but their precise role in disease causation requires further investigation.

[Analysis of TGFBI gene mutation in a Chinese family affected with Reis-Bucklers corneal dystrophy].

OBJECTIVE: To analyze the clinical features and TGFBI gene mutation in a Chinese family affected with Reis-Bucklers corneal dystrophy. METHODS: Genomic DNA was extracted from 53 members including 9 patients from the family. The 17 exons and splice region of introns of the TGFBI gene were amplified by PCR and directly sequenced. All family members were subjected to ophthalmologic examination. RESULTS: A heterozygous mutation (R124L) was found in exon 4 of the TGFBI gene among all patients from the family. The same mutation was not found among unaffected family members. The inheritance pattern of the family was identified as autosomal dominant, and the Reis-Bucklers corneal dystrophy in the family was diagnosed as the geographic type. CONCLUSION: The R124L mutation of the TGFBI gene probably underlies the pathogenesis of Reis-Bucklers corneal dystrophy in this Chinese family. Molecular genetic approach is useful for the proper diagnosis of this type of corneal dystrophy.

An extracellular Zn-only superoxide dismutase from Puccinia striiformis confers enhanced resistance to host-derived oxidative stress.

Accumulation of reactive oxygen species (ROS) following plant-pathogen interactions can trigger plant defence responses and directly damage pathogens. Thus, it is essential for pathogens to scavenge host-derived ROS to establish a parasitic relationship. However, the mechanisms protecting pathogens from host-derived oxidative stress remain unclear. In this study, a superoxide dismutase (SOD) gene, PsSOD1, was cloned from a wheat-Puccinia striiformis f. sp. tritici (Pst) interaction cDNA library. Transcripts of PsSOD1 were up-regulated in the early infection stage. Heterologous mutant complementation and biochemical characterization revealed that PsSOD1 encoded a Zn-only SOD. The predicted signal peptide was functional in an invertase-mutated yeast strain. Furthermore, immunoblot analysis of apoplastic proteins in Pst-infected wheat leaves and bimolecular fluorescence complementation suggested that PsSOD1 is a secreted protein that potentially forms a dimer during Pst infection. Overexpression of PsSOD1 enhanced Schizosaccharomyces pombe resistance to exogenous superoxide. Transient expression of PsSOD1 in Nicotiana benthamiana suppressed Bax-induced cell death. Knockdown of PsSOD1 using a host-induced gene silencing (HIGS) system reduced the virulence of Pst, which was associated with ROS accumulation in HIGS plants. These results suggest that PsSOD1 is an important pathogenicity factor that is secreted into the host-pathogen interface to contribute to Pst infection by scavenging host-derived ROS.

Down-regulation of a wheat alkaline/neutral invertase correlates with reduced host susceptibility to wheat stripe rust caused by Puccinia striiformis.

Numerous studies have found that sucrose (Suc) metabolism plays a crucial role in the environmental stress response of many plant species. The majority of Suc metabolism-associated reports refer to acid invertases (Ac-Invs). However, alkaline/neutral Invs (A/N-Invs) have been poorly studied. In this study, a wheat A/N-Inv gene, Ta-A/N-Inv1, with three copies located on chromosomes 4A, 4B, and 4D, was cloned from a wheat-Puccinia striiformis f. sp. tritici (Pst) interaction cDNA library. Transcripts of the three Ta-A/N-Inv1 copies were up-regulated in wheat leaves that were infected by Pst or had experienced certain abiotic treatments. Furthermore, the expression of Ta-A/N-Inv1 was decreased by treatment with exogenous hormones. Heterologous mutant complementation and subcellular localization revealed that Ta-A/N-Inv1 is a cytoplasmic invertase. Knocking down all three copies of Ta-A/N-Inv1 using the barley stripe mosaic virus-induced gene silencing system reduced the susceptibility of wheat to the Pst virulent pathotype CYR31, which is associated with pathogen-induced H2O2 accumulation and enhanced necrosis. Interestingly, 48h dark treatment of the Ta-A/N-Inv1-knockdown plants immediately after inoculation abrogated their enhanced resistance, suggesting that H2O2 production and its associated cell death and resistance in the Ta-A/N-Inv1-silenced plants require light. Consistent with this observation, photosynthesis and reactive oxygen species (ROS)-related genes were significantly up-regulated in the Ta-A/N-Inv1-knockdown plants infected by CYR31 under light exposure. These results suggest that Ta-A/N-Inv1 might act as a negative regulator in wheat disease resistance to Pst by increasing cytoplasmic hexose accumulation and downregulating photosynthesis of the leaves to avoid cell death due to excessive ROS production.

Telmisartan treatment ameliorates memory deficits in streptozotocin-induced diabetic mice via attenuating cerebral amyloidosis.

Telmisartan, an angiotensin II type 1-receptor blocker (ARBs), has been reported to exert beneficial effects on the central nervous system (CNS). However, the effect of telmisartan on cognitive impairment associated with type 1 diabetes is not well known. Here, we examined the possibility that telmisartan could improve memory function in a type 1 diabetic mouse model, streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice subjected to the Morris Water Maze (MWM) task exhibited a significant decline of spatial learning and memory. Oral administration of telmisartan at two nonhypotensive doses (0.7 or 0.35 mg/kg) significantly improved memory deficits in STZ-induced diabetic mice. Telmisartan treatment markedly reduced Aß42, APP, BACE1, RAGE, and NF-κB p65 of the hippocampus and cortex, but did not beneficially affect hyperglycemia and hypoinsulinemia in the STZ-induced diabetic mice compared with untreated diabetic mice. Taken together, our findings suggest that telmisartan ameliorates memory deficits in type 1 diabetic mice, at least partly because of attenuation of amyloidosis in the brain.

Role of methotrexate exposure in apoptosis and proliferation during early neurulation.

Apoptosis and proliferation play important roles in embryonic development and are required for neural tube closure. The antifolate drug methotrexate (MTX) induces folate dysmetabolism by inhibition of dihydrofolate reductase and causes abnormal apoptosis and proliferation. In this study, we established an animal model of neural tube defects (NTDs) using MTX to investigate the role of apoptosis and proliferation in NTDs caused by folate deficiency. Differential gene expressions were studied by microarray and reverse transcription-polymerase chain reaction in the NTD animal model. Results showed that 30.8% of NTDs were caused by using MTX in treatment regimens. Microarray indicated that 166 genes were significantly different between the control and NTD mice, including four apoptosis-related genes (Endog, Trp53, Casp3, Bax) and three proliferation-related genes (Ptch1, Pla2g4a, Foxg1). Levels of Endog, Trp53, Casp3, Bax (fold change>1.5) were upregulated but Ptch1, Pla2g4a, Foxg1 (fold change<0.67) were downregulated (P<0.05). These results were confirmed by reverse transcription-polymerase chain reaction. TUNEL, immunohistochemical assays and Western blot were further used to detect apoptosis and proliferation in the NTD animal model. It was found that apoptosis in neuroepithelial cells was increased as determined by TUNEL (P<0.05). Expressions of caspase-3 were significantly enhanced (P<0.05) but expressions of phosphohistone H3 were greatly decreased (P<0.05). These results concluded that MTX caused a folate and folate-associated dysmetabolism, and further induced abnormal apoptosis and proliferation, which may play a critical role in the occurrence of NTDs caused by folate deficiency.