AtHD2D is involved in regulating lateral root development and participates in abiotic stress response in Arabidopsis.

Roots are essential to terrestrial plants, as their growth and morphology are crucial for plant development. The growth of the roots is affected and regulated by several internal and external environmental signals and metabolic pathways. Among them, chromatin modification plays an important regulatory role. In this study, we explore the potential roles of the histone deacetylase AtHD2D in root development and lay the foundation for further research on the biological processes and molecular mechanisms of AtHD2D in the future. Our study indicates that AtHD2D affects the root tip microenvironment homeostasis by affecting the gene transcription levels required to maintain the root tip microenvironment. In addition, we confirmed that AtHD2D is involved in regulating Arabidopsis lateral root development and further explained the possible role of AtHD2D in auxin-mediated lateral root development. AtHD2D can effectively enhance the resistance of Arabidopsis thaliana to abiotic stress. We believe that AtHD2D is involved in coping with abiotic stress by promoting the development of lateral roots. Overexpression of AtHD2D promotes the accumulation of reactive oxygen species (ROS) in roots, indicating that AtHD2D is also involved in developing lateral roots mediated by ROS. Previous studies have shown that the overexpression of AtHD2D can effectively enhance the resistance of Arabidopsis thaliana to abiotic stress. Based on our data, we believe that AtHD2D participates in the response to abiotic stress by promoting the development of lateral roots. AtHD2D-mediated lateral root development provides new ideas for studying the mechanism of HDAC protein in regulating root development.

HD2A and HD2C co-regulate drought stress response by modulating stomatal closure and root growth in Arabidopsis.

Histone deacetylase 2 (HD2) is a unique family of histone deacetylases (HDACs) in plants. Despite evidence that certain HD2 family HDACs play an important role in plant growth and stress response, the coordination of HD2s in these processes remains largely unknown. We found that HD2-type, HD2A and HD2C coordinate to play a role in drought stress response in Arabidopsis. We showed that the hd2a.hd2c double mutant (Mac16) exhibit decreased drought survival and increased water loss as compared to the single mutants, hd2a and hd2c. Gene expression analysis showed that the ABI1 and ABI2 genes were upregulated and SLAC1 was downregulated which led to the modified stomatal functioning in the Mac16 as compared to the single mutants. Overexpression of HD2A and HD2C showed enhanced drought survival and decreased water loss. We also showed that the GA2ox1 and GA2ox2 genes, which are involved in the catabolism of bioactive gibberellic acids, were upregulated in the Mac16 as compared to the single mutants, which led to a decreased root growth in the Mac16. Furthermore, we showed that HD2A and HD2C can physically interact and increased genome-wide H3K9 acetylation was observed in the Mac16, compared to the single mutants. Overall, our investigation revealed that HD2A and HD2C coordinate to play a cumulative role in drought stress response and root growth in Arabidopsis.

An efficient and specific CRISPR-Cas9 genome editing system targeting soybean phytoene desaturase genes.

BACKGROUND: Genome editing by CRISPR/Cas9 has become a popular approach to induce targeted mutations for crop trait improvement. Soybean (Glycine max L. Merr.) is an economically important crop worldwide. Although gene editing has been demonstrated in soybean, its utilization in stably transformed plants through whole plant regeneration is still not widespread, largely due to difficulties with transformation or low mutation efficiencies. RESULTS: We sought to establish a simple, efficient, and specific CRISPR/Cas9 system to induce heritable mutations in soybean through stable transformation. We targeted phytoene desaturase (PDS) genes due to the distinctive dwarf and albino phenotypes of the loss of function mutant. To evaluate gene editing efficiency and specificity, three constructs targeting each of the two homologous soybean PDS genes specifically, as well as two constructs targeting both simultaneously with one guide RNA were created. Instead of using cotyledonary nodes from germinated seedlings, we used 'half-seed' explants derived from imbibed seeds for Agrobacterium-mediated transformation of cultivar Williams 82. Transformed plants for all five constructs were recovered. Dwarf and albino phenotypes were observed in transgenic plants harboring the constructs targeting both PDS genes. Gene editing at the desired loci was detected in the majority of T0 transgenic plants, with 75-100% mutation efficiencies. Indel frequencies varied widely among plants (3-100%), with those exhibiting visible mutant phenotypes showing higher frequencies (27-100%). Deletion was the predominant mutation type, although 1-nucleotide insertion was also observed. Constructs designed to target only one PDS gene did not induce mutation in the other homologous counterpart; and no mutation at several potential off-target loci was detected, indicating high editing specificity. Modifications in both PDS genes were transmitted to T1 progenies, including plants that were negative for transgene detection. Strong mutant phenotypes were also observed in T1 plants. CONCLUSIONS: Using simple constructs containing one guide RNA, we demonstrated efficient and specific CRISPR/Cas9-mediated mutagenesis in stably transformed soybean plants, and showed that the mutations could be inherited in progenies, even in plants that lost transgenes through segregation. The established system can be employed to edit other genes for soybean trait improvement.

Differential Gene Expression of Brachypodium distachyon Roots Colonized by Gluconacetobacter diazotrophicus and the Role of BdCESA8 in the Colonization.

Alternatives to synthetic nitrogen fertilizer are needed to reduce the costs of crop production and offset environmental damage. Nitrogen-fixing bacterium Gluconacetobacter diazotrophicus has been proposed as a possible biofertilizer for monocot crop production. However, the colonization of G. diazotrophicus in most monocot crops is limited and deep understanding of the response of host plants to G. diazotrophicus colonization is still lacking. In this study, the molecular response of the monocot plant model Brachypodium distachyon was studied during G. diazotrophicus root colonization. The gene expression profiles of B. distachyon root tissues colonized by G. diazotrophicus were generated via next-generation RNA sequencing, and investigated through gene ontology and metabolic pathway analysis. The RNA sequencing results indicated that Brachypodium is actively involved in G. diazotrophicus colonization via cell wall synthesis. Jasmonic acid, ethylene, gibberellin biosynthesis. nitrogen assimilation, and primary and secondary metabolite pathways are also modulated to accommodate and control the extent of G. diazotrophicus colonization. Cellulose synthesis is significantly downregulated during colonization. The loss of function mutant for Brachypodium cellulose synthase 8 (BdCESA8) showed decreased cellulose content in xylem and increased resistance to G. diazotrophicus colonization. This result suggested that the cellulose synthesis of the secondary cell wall is involved in G. diazotrophicus colonization. The results of this study provide insights for future research in regard to gene manipulation for efficient colonization of nitrogen-fixing bacteria in Brachypodium and monocot crops.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Development of a Csy4-processed guide RNA delivery system with soybean-infecting virus ALSV for genome editing.

BACKGROUND: A key issue for implementation of CRISPR-Cas9 genome editing for plant trait improvement and gene function analysis is to efficiently deliver the components, including guide RNAs (gRNAs) and Cas9, into plants. Plant virus-based gRNA delivery strategy has proven to be an important tool for genome editing. However, its application in soybean which is an important crop has not been reported yet. ALSV (apple latent spherical virus) is highly infectious virus and could be explored for delivering elements for genome editing. RESULTS: To develop a ALSV-based gRNA delivery system, the Cas9-based Csy4-processed ALSV Carry (CCAC) system was developed. In this system, we engineered the soybean-infecting ALSV to carry and deliver gRNA(s). The endoribonuclease Csy4 effectively releases gRNAs that function efficiently in Cas9-mediated genome editing. Genome editing of endogenous phytoene desaturase (PDS) loci and exogenous 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) sequence in Nicotiana. benthamiana (N. benthamiana) through CCAC was confirmed using Sanger sequencing. Furthermore, CCAC-induced mutagenesis in two soybean endogenous GW2 paralogs was detected. CONCLUSIONS: With the aid of the CCAC system, the target-specific gRNA(s) can be easily manipulated and efficiently delivered into soybean plant cells by viral infection. This is the first virus-based gRNA delivery system for soybean for genome editing and can be used for gene function study and trait improvement.

HD2-type histone deacetylases: unique regulators of plant development and stress responses.

Plants have developed sophisticated and complex epigenetic regulation-based mechanisms to maintain stable growth and development under diverse environmental conditions. Histone deacetylases (HDACs) are important epigenetic regulators in eukaryotes that are involved in the deacetylation of lysine residues of histone H3 and H4 proteins. Plants have developed a unique HDAC family, HD2, in addition to the RPD3 and Sir2 families, which are also present in other eukaryotes. HD2s are well conserved plant-specific HDACs, which were first identified as nucleolar phosphoproteins in maize. The HD2 family plays important roles not only in fundamental developmental processes, including seed germination, root and leaf development, floral transition, and seed development but also in regulating plant responses to biotic and abiotic stresses. Some of the HD2 members coordinate with each other to function. The HD2 family proteins also show functional association with RPD3-type HDACs and other transcription factors as a part of repression complexes in gene regulatory networks involved in environmental stress responses. This review aims to analyse and summarise recent research progress in the HD2 family, and to describe their role in plant growth and development and in response to different environmental stresses.

Characterization of the Role of SPL9 in Drought Stress Tolerance in Medicago sativa.

Extreme environmental conditions, such as drought, are expected to increase in frequency and severity due to climate change, leading to substantial deficiencies in crop yield and quality. Medicago sativa (alfalfa) is an important crop that is relied upon as a staple source of forage in ruminant feed. Despite its economic importance, alfalfa production is constrained by abiotic stress, including drought. In this report, we investigate the role of Squamosa Promoter Binding Protein-Like 9 (SPL9), a target of miR156, in drought tolerance. Transgenic alfalfa plants with RNAi-silenced MsSPL9 (SPL9-RNAi) were compared to wild-type (WT) alfalfa for phenotypic changes and drought tolerance indicators. In SPL9-RNAi plants, both stem thickness and plant height were reduced in two- and six-month-old alfalfa, respectively; however, yield was unaffected. SPL9-RNAi plants showed less leaf senescence and had augmented relative water content under drought conditions, indicating that SPL9-RNAi plants had greater drought tolerance potential than WT plants. Interestingly, SPL9-RNAi plants accumulated more stress-alleviating anthocyanin compared to WT under both drought and well-watered control conditions, suggesting that MsSPL9 may contribute to drought tolerance in alfalfa, at least in part, by regulating anthocyanin biosynthesis. The results suggest that targeting MsSPL9 is a suitable means for improving alfalfa resilience towards drought conditions.

BdHD1, a histone deacetylase of Brachypodium distachyon, interacts with two drought-responsive transcription factors, BdWRKY24 and BdMYB22.

Histone deacetylases (HDACs) play an important role in plant stress response. In Brachypodium distachyon, which is model species for molecular biology research on monocot plants, the histone deacetylase BdHD1, homologous to AtHDAC1 of the RPD3/HDA1 class, functions as a positive regulator in the plant drought stress response. AtHDAC1 has been found to interact with transcription factors to regulate gene expression. However, the drought-responsive transcription factors that interact with BdHD1 have not been identified yet. Previously, we identified BdWRKY24 and BdMYB22 as drought responsive transcription factors in Brachypodium. In this study, we used yeast two-hybrid (Y2 H) and bimolecular fluorescence complementation (BiFC) assays to show that BdHD1 interacts with BdWRKY24 and BdMYB22. Our findings provides a base to investigate BdHD1-transcription factor complexes in the context of drought stress response in Brachypodium.

Therapy With Carboplatin and Anti-PD-1 Antibodies Before Surgery Demonstrates Sustainable Anti-Tumor Effects for Secondary Cancers in Mice With Triple-Negative Breast Cancer.

Patients with triple-negative breast cancer (TNBC) suffer an unfavorable prognosis. Carboplatin (CBDCA) as a cytotoxic reagent has been widely administered to patients with cancer including TNBC. Programmed cell death protein 1 (PD-1) is an immune checkpoint, blockade of which unleashes T cell functions that kill cancer cells. However, the efficacy of CBDCA combined with anti-PD-1 antibodies in TNBC has not been determined. Patient-derived xenografts (PDX) were implanted to immune-deficient mice. Three mouse TNBC cell lines (4T1, EMT6, and E0771) were seeded to immune-competent mice. Tumor volumes and survival rates were monitored. CBDCA and anti-PD-1 antibodies were administered by intra-peritoneal injection at designated time points. Total CD8+ T cells, memory CD8+ T cells, and CD103+ dendritic cells (DC) in the tumor were measured by flow cytometry. Tumor-specific CD8+ T cells were quantified by the ELISpot assay. Administration of CBDCA to PDX-bearing mice induced increased levels of tumor cell necrosis and reduced tumor size. Treatment with CBDCA and anti-PD-1 antibodies reduced TNBC tumor volumes and slightly improved survival rates. More importantly, therapy with CBDCA and anti-PD-1 antibodies before surgery showed a remarkably improved, sustainable protection against a secondary tumor after surgery by a CD8+- T-cell-dependent manner, which required CCL4 expressed in the tumor and subsequently CD103+ DC recruited to the tumor microenvironment. Immunochemotherapy with CBDCA and anti-PD-1 antibodies before surgery improves the outcome of a secondary tumor after surgery via increasing the number of tumor-specific CD8+ T cells in the tumor microenvironment of murine TNBC. These results highlight the possibility to utilize this regimen in clinical practice.

Roxatidine inhibits fibrosis by inhibiting NF­κB and MAPK signaling in macrophages sensing breast implant surface materials.

Capsular contracture is an important complication after silicone mammary implant surgery. Fibroblasts and macrophages play critical roles in the pathogenesis of capsular contracture, making these two cell types therapeutic targets. It has been reported that inhibiting histamine receptors results attenuates fibrosis, but the role of roxatidine (a histamine receptor 2 inhibitor) in preventing fibrosis caused by breast implant materials remains unknown. The aim of the present study was to assess the hypothesis that roxatidine might have a prophylactic effect in capsular contracture induced by implant material. Inflammation induced by breast implant materials was mimicked by co­culturing macrophages or fibroblasts with these materials in vitro. Capsular contracture was modeled in mice by planting breast implant materials in a subcutaneous pocket. Roxatidine was added in the culture medium or administered to mice bearing breast implant materials. By co­culturing macrophages or fibroblasts with common breast implant materials (micro­textured or smooth breast implants), the present study demonstrated that macrophages respond to these materials by producing pro­inflammatory cytokines, a process that was abolished by addition of roxatidine to the culture medium. Although fibroblasts did not respond to implant surface materials in the same way as macrophages, the conditioned media of macrophages induced proliferation of fibroblasts. Mechanistically, administration of roxatidine inhibited activation of NF­κB and p38/mitogen­activated protein kinase (MAPK) signaling in macrophages. Furthermore, treatment with roxatidine in implant­bearing mice reduced serum concentrations of transforming growth factor­ß and the abundance of fibroblasts around the implant. The present study concluded that roxatidine plays an important role in preventing fibrosis by inhibiting activation of NF­κB and p38/MAPK signaling in macrophages.

Macrophages on the Peritoneum are involved in Gastric Cancer Peritoneal Metastasis.

Tumor-associated macrophages (TAM) have been shown to support tumor growth and progression by various mechanisms. However, the roles of TAM in gastric cancer (GC) peritoneal metastasis remain elusive. To explore the roles of macrophages in the process of GC peritoneal metastasis, we performed the present study. Samples from the primary GC tumor beds, surgical margins, peritoneal metastatic lesions and surrounding tissue, and the Pouch of Douglas, were collected, fixed by formalin, and embedded with paraffin. Immunohistochemistry staining for macrophages markers was performed. The peritoneal lavage was obtained from a fraction of patients to analyze the ratios of epidermal growth factor (EGF)- and vascular endothelial growth factor (VEGF)-secreting macrophages in the peritoneal cavity. GC patients with peritoneal metastasis had increased levels of macrophages and alternatively activated macrophages in the peritoneum compared to those without dissemination. Patients bearing more macrophages in the peritoneum had a poorer prognosis. GC patients bearing peritoneal metastasis harbored an increased level of angiogenesis. Macrophages in the peritoneal cavity were a source of EGF and VEGF. Macrophages in the peritoneum of GC patients play a supportive role for peritoneal metastasis by producing EGF and VEGF. Macrophages in the peritoneum might be a therapeutic target in the future.

Brachypodium histone deacetylase BdHD1 positively regulates ABA and drought stress responses.

Despite recent evidence that HDACs are involved in the environmental stress responses of plants, their roles in the abiotic stress responses of monocot plants remain largely unexplored. We investigated a HDAC gene, Bradi3g08060 (BdHD1), in Brachypodium distachyon. The Brachypodium BdHD1-overexpression plants displayed a hypersensitive phenotype to ABA and exhibited better survival under drought conditions. On the other hand, the RNA-interference plants were insensitive to ABA and showed low survival under drought stress. At the genome-wide level, overexpression of BdHD1 led to lower H3K9 acetylation at the transcriptional start sites of 230 genes than in the wild type plants under the drought treatment. We validated our ChIP-Seq data on 10 selected transcription factor genes from the 230 drought-specific genes. These genes exhibited much lower expression in the BdHD1-overexpression plants compared to the wild type plants under drought stress. We further identified an ABA-inducible transcription factor gene BdWRKY24 that was repressed in BdHD1-OE plants, but highly expressed in RNA-interference plants under drought stress. These results indicate that BdHD1 plays a positive role in ABA sensitivity and drought stress tolerance and they provide a link between the role of BdHD1 and the drought stress response at a genome-wide level in Brachypodium.

Identification and molecular characterization of the Brachypodium distachyon NRT2 family, with a major role of BdNRT2.1.

The small monocot plant Brachypodium distachyon is rapidly emerging as a powerful model system to study questions unique to the monocot crops. An extensive BLAST search was carried to identify putative orthologues of the Arabidopsis NRT2 genes in the fully sequenced Brachypodium genome. Seven genes encoding putative high-affinity nitrate transporters (BdNRT2) were identified. Transcriptional analysis of individual BdNRT2 gene under various nitrogen sources and levels in the wild-type and a T-DNA mutant of BdNRT2.1 were performed. A transgenic approach was taken to complement the bdnrt2.1 mutant. BdNRT2.1 and BdNRT2.2 were strongly induced by nitrate resupply to nitrogen-starved plants and were classified as inducible genes. BdNRT2.5 was found to be repressed by nitrate resupply whereas other members were constitutively expressed in the root. Interestingly, higher ammonium concentrations also triggered similar gene expression regulation, suggesting BdNRT2 gene expression was also governed by internal nitrogen status, not just external nitrate concentrations. In bdnrt2.1 mutant, the high-affinity transporter system (HATS) was reduced by 30% and BdNRT2.2 and BdNRT2.6 were differentially regulated. This pioneering research demonstrates that genes in the BdNRT2 family have diverse roles, differing from the Arabidopsis AtNRT2 family, in response to various nitrogen conditions. BdNRT2.1 serves as a key member of the family.

A Golden Gate and Gateway double-compatible vector system for high throughput functional analysis of genes.

A major research topic nowadays is to study and understand the functions of the increasing number of predicted genes that have been discovered through the complete genome sequencing of many plant species. With the aim of developing tools for rapid and convenient gene function analysis, we have developed a set of "pGate" vectors based on the principle of Golden gate and Gateway cloning approaches. These vectors combine the positive aspects of both Golden gate and Gateway cloning strategies. pGate vectors can not only be used as Golden gate recipient vectors to assemble multiple DNA fragments in a pre-defined order, but they can also work as an entry vector to transfer the assembled DNA fragment(s) to a large number of already-existing, functionally diverse, Gateway compatible destination vectors without adding additional nucleotides during cloning. We show the pGate vectors are effective and convenient in several major aspects of gene function analyses, including BiFC (Bimolecular fluorescence complementation) to analyze protein-protein interaction, amiRNA (artificial microRNA) candidate screening and as assembly of CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats, CRISPR-associated protein-9 nuclease) system elements together for genome editing. The pGate system is a practical and flexible tool which can facilitate plant gene function research.

Trichostatin A and 5-Aza-2'-Deoxycytidine influence the expression of cold-induced genes in Arabidopsis.

The expression of cold-induced genes is critical for plants to survive under freezing stress. However, the underlying mechanisms for the decision of when, where, and which genes to express are unclear when a plant meets a sudden temperature drop. Previous studies have demonstrated epigenetics to play a central role in the regulation of gene expression in plant responses to environmental stress. DNA methylation and histone deacetylation are the two most important epigenetic modifications. This study was conducted to investigate the effects of inhibiting DNA methylation and histone deacetylation on gene expression, and to explore the potential role of epigenetics in plant responses to cold stress. The results revealed that histone deacetylase inhibitors (trichostatin A) and DNA methylation inhibitors (5-Aza-2'-deoxycytosine) treatment enhanced cold tolerance. DNA microarray analysis and the gene ontology method revealed 76 cold-induced differently expressed genes in Arabidopsis thaliana seedlings that were treated to 0°C for 24 h following Trichostatin A and 5-Aza-2'-Deoxycytidine. Furthermore, analyses of metabolic pathways and transcription factors of 3305 differentially expressed genes were performed. Each four metabolic pathways were significantly affected (p < 0.01) by Trichostatin A and 5-Aza-2'-Deoxycytidine. Finally, 10 genes were randomly selected and verified via qPCR analysis. Our study indicated that Trichostatin A and 5-Aza-2'-Deoxycytidine can improve the plant cold resistance and influence the expression of the cold-induced gene in A. thaliana. This result will advance our understanding of plant freezing responses and may provide a helpful strategy for cold tolerance improvement in crops.

Histone deacetylase HD2D is involved in regulating plant development and flowering time in Arabidopsis.

HD2D is one of the 4 plant specific HD2 family histone deacetylases (HDAC) identified in Arabidopsis and it is distantly related to the other HD2 members. At this time, little is known about the function of HD2D in plants. Here we provide evidence that HD2D is involved in the control of flowering time. Flowering was delayed in transgenic plants overexpressing HD2D and hd2d mutant plants flowered earlier compared with wild-type in both long day and short day conditions. Expression of several floral identity genes was altered in these plants. Taken together, our findings suggest that HD2D is a negative regulator of flowering that modulates the transition of vegetative to reproductive growth in a photoperiod independent manner.

C-C motif chemokine 22 ligand (CCL22) concentrations in sera of gastric cancer patients are related to peritoneal metastasis and predict recurrence within one year after radical gastrectomy.

BACKGROUND: Gastric cancer is a common cancer with a poor prognosis. Chemokines play important roles in the tumor microenvironments to support tumor growth and metastasis. The effects of C-C motif chemokine ligand 22 (CCL22) in gastric cancer remain unclear. MATERIALS AND METHODS: Between January 1, 2014 and April 31, 2014, a total of 298 gastric cancer patients were recruited to this study. Circulating concentrations of CCL22 were measured in gastric cancer patients before surgery, at discharged and during follow-up visits. The expression of CCL22 in gastric cancer tumor beds was measured by immunohistochemistry. The proportion of CD3+CD4+CD25+Foxp3+ regulatory T cells in tumor sites was assessed by flow cytometry. RESULTS: Gastric cancer patients had higher serum CCL22 levels compared to healthy controls (P < 0.001). Immunohistochemistry indicated that the gastric cancer tumor beds were the source of serum CCL22, as gastric cancer patients had an increased proportion of strong expression of CCL22 (P < 0.01), and immunohistochemistry scores were positively correlated with levels of circulating CCL22 (P < 0.001). Gastric cancer tissue harbored a higher percentage of regulatory T cells compared to normal tumor-free stomach margins (P < 0.001), and this abundance of regulatory T cells was positively correlated with circulating levels of CCL22 (P < 0.001). Gastric cancer patients with peritoneal metastasis showed increased levels of circulating CCL22 before surgery compared to metastasis-free patients (P < 0.001). Gastric cancer patients with the recurrence within the first year after surgery had elevated serum CCL22 concentrations at different time points compared to those of recurrence-free patients (P < 0.001). Logistic regression analysis indicated that high CCL22 circulating levels before surgery is a risk factor for peritoneal metastasis and an independent risk factor for an early recurrence after surgery. CONCLUSIONS: CCL22 plays an important role in supporting gastric cancer development presumably by increasing the percentage of regulatory T cells in the tumor microenvironments. CCL22 levels in sera have a predictive value for gastric cancer peritoneal metastasis and the early recurrence. Therefore, CCL22 may be a therapeutic target for gastric cancer.

C-C motif chemokine ligand 5 (CCL5) levels in gastric cancer patient sera predict occult peritoneal metastasis and a poorer prognosis.

Gastric cancer is one of the most common cancers and the third leading cause of cancer death worldwide. A number of chemokines and cytokines play important roles in the progress of gastric cancer. The roles of C-C motif chemokine ligand 5 (CCL5) in gastric cancer remain unclear. Here, we retrospectively report an analysis of 105 patients with gastric cancer. Increased levels of CCL5 in circulation were correlated with more advanced T and N stages, poorly- or un-differentiated histological types, peritoneal metastasis, higher rates of residual tumor, and shorter survivals. Patients in the CCL5 High Group had stronger CCL5 immunohistochemistry (IHC) staining in tumor beds. Circulating CCL5 concentrations before surgery are a good biomarker for occult peritoneal metastasis. Elevated levels of serum CCL5, along with strong IHC CCL5 staining and poorly- or un-differentiated cancer are predictors for poorer outcomes. In conclusion, increased serum levels of CCL5 can be used to predict peritoneal dissemination and a poorer prognosis.

Interleukin (IL)-4 -590C>T polymorphism is not associated with the susceptibility of gastric cancer: An updated meta-analysis.

Gastric cancer (GC) is a common cancer affecting patients around the world. The pathogenesis of gastric cancer has not been understood completely. Genetic mutations and the inflammation induced by Helicobacter pylori (HP) seem to play important roles. The cytokine Interleukin-4 (IL-4) has effects in inflammation, allergies and cancer including GC. The association of IL-4 -590 C>T polymorphism and gastric cancer has been studied in different populations with inconsistent results. Here, we report this meta-analysis showing that the polymorphism of IL-4 -590C>T might not be associated with the GC susceptibility in both Asian and Caucasian populations.

AtHD2D Gene Plays a Role in Plant Growth, Development, and Response to Abiotic Stresses in Arabidopsis thaliana.

The histone deacetylases play important roles in the regulation of gene expression and the subsequent control of a number of important biological processes, including those involved in the response to environmental stress. A specific group of histone deacetylase genes, HD2, is present in plants. In Arabidopsis, HD2s include HD2A, HD2B, HD2C, and HD2D. Previous research showed that HD2A, HD2B, and HD2C are more related in terms of expression and function, but not HD2D. In this report, we studied different aspects of AtHD2D in Arabidopsis with respect to plant response to drought and other abiotic stresses. Bioinformatics analysis indicates that HD2D is distantly related to other HD2 genes. Transient expression in Nicotiana benthamiana and stable expression in Arabidopsis of AtHD2D fused with gfp showed that AtHD2D was expressed in the nucleus. Overexpression of AtHD2D resulted in developmental changes including fewer main roots, more lateral roots, and a higher root:shoot ratio. Seed germination and plant flowering time were delayed in transgenic plants expressing AtHD2D, but these plants exhibited higher degrees of tolerance to abiotic stresses, including drought, salt, and cold stresses. Physiological studies indicated that the malondialdehyde (MDA) content was high in wild-type plants but in plants overexpressing HD2D the MDA level increased slowly in response to stress conditions of drought, cold, and salt stress. Furthermore, electrolyte leakage in leaf cells of wild type plants increased but remained stable in transgenic plants. Our results indicate that AtHD2D is unique among HD2 genes and it plays a role in plant growth and development regulation and these changes can modulate plant stress responses.