Thermal injury-plus-sepsis contributes to a substantial deletion of intestinal mesenteric lymph node CD4 T cell via apoptosis

Thermal injury (TI) with septic complications continues to be a serious clinical problem. One of the main concerns in such patients is immunosuppression related to functional derangements in intestinal CD4+ T lymphocytes. Extensive previous studies in thermal injury/septic patients and animal models of thermal injury/sepsis have shown decreased responsiveness of intestinal CD4+ T cells to antigen/mitogen. This hyporesponsiveness could significantly contribute to increase injured host susceptibility to pathogens including those translocating from host's gut lumen. Our previous studies indicated that while thermal injury or sepsis alone lead to suppressed proliferation and IL-2 production of intestinal CD4+ T cells, this study showed a substantial deletion via apoptosis of the Mesenteric Lymph Nodes (MLN) CD4+ T cells. Hence, thermal injury-plus-sepsis contributes not only to suppressed CD4+ T proliferation/IL-2 production but also to a substantial modulation of CD4+ T cell survivability. These findings allow us to conclude that while thermal injury alone can produce attenuated cell mediated responses without an overt change in CD4+ T cell survival, thermal injury with septic complications causes CD4+ T cell death and an irreversible loss of cell-mediated responses. The latter happening could be responsible for high morbidity and mortality in the injured host afflicted with thermal injury plus a critical infection.     

The host niches of soybean rather than genetic modification or glyphosate application drive the assembly of root-associated microbial communities

Plant roots significantly influence soil microbial diversity, and soil microorganisms play significant roles in both natural and agricultural ecosystems. Although the genetically modified (GM) crops with enhanced insect and herbicide resistance are thought to have unmatched yield and stress resistance advantages, thorough and in-depth case studies still need to be carried out in a real-world setting due to the potential effects of GM plants on soil microbial communities. In this study, three treatments were used: a recipient soybean variety Jack, a triple transgenic soybean line JD321, and the glyphosate-treated JD321 (JD321G). Three sampling stages (flowering, seed filling and maturing), as well as three host niches of soybean rhizosphere [intact roots (RT), rhizospheric soil (RS) and surrounding soil (SS)] were established. In comparison to Jack, the rhizospheric soil of JD321G had higher urease activity and lower nitrite reductase at the flowering stage. Different treatments and different sampling stages existed no significant effects on the compositions of microbial communities at different taxonomic levels. However, at the genus level, the relative abundance of three plant growth-promoting fungal genera (i.e. Mortierella, Chaetomium and Pseudombrophila) increased while endophytic bacteria Chryseobacterium and pathogenic bacteria Streptomyces decreased from the inside to the outside of the roots (i.e. RT → RS → SS). Moreover, two bacterial genera, Bradyrhizobium and Ensifer were more abundant in RT than in RS and SS, as well as three species, Agrobacterium radiobacter, Ensifer fredii and Ensifer meliloti, which are closely related to nitrogen-fixation. Furthermore, five clusters of orthologous groups (COGs) associated to nitrogen-fixation genes were higher in RT than in RS, whereas only one COG annotated as dinitrogenase iron-molybdenum cofactor biosynthesis protein was lower. Overall, the results imply that the rhizosphere host niches throughout the soil–plant continuum largely control the composition and function of the root-associated microbiome of triple transgenic soybean.     

Primary ovarian cancer cell inhibition by human Wharton's Jelly stem cells (hWJSCs): Mapping probable mechanisms and targets using systems oncology

Ovarian cancer is one of the most lethal gynaecological cancers. Its subtle onset and absence of symptoms in early stages are associated with poor prognosis and high mortality. Identification of early biomarkers would aid in ovarian cancer control. Mesenchmal stem cells (MSCs) and/or their secretory products are identified to have cancer inhibitory properties. Therefore, it is of interest to study the anticancer properties of human Wharton''s jelly stem cells conditioned medium (hWJSCs-CM) on primary ovarian carcinoma cells in vitro. Primary cultures of epithelial ovarian carcinoma cells (EOCs) and hWJSCs were used in this study. EOCs were exposed to hWJSC-CM (100%) for 24h-72h and changes in mophology and cell proliferation were monitored. Treatment with hWJSC-CM showed altered morphological changes that resulted in death of EOCs. Colorimetric assay [MTT, (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide)] showed mean decreases in EOC proliferation by 16.21%, 23.89% and 40.08% at 24h, 48h and 72h respectively compared to control. Ingenuity Pathway Analysis (IPA, Igenuity Systems, USA) deduced important molecular pathways and signaling networks associated with cancer cell death and these correlated with significant expression of tumour suppresors and apoptotic genes in hWJSCs. Secretory products of hWJSC-CM induced cell death of EOCs via apoptosis. IPA identification of canonical genes/pathways involved in EOCs that overlap with hWJSCs tumour suppressors and apoptosis genes further support this hypotheis. Additional in vitro and in vivo studies are necessary to validate EOCs inhibition with hWJSC-extracts towards their mechanism of action.     

Helicobacter pylori activate epidermal growth factor receptor- and phosphatidylinositol 3-OH kinase-dependent Akt and glycogen synthase kinase 3beta phosphorylation

The signalling pathways leading to the development of Helicobacter pylori -induced gastric cancer remain poorly understood. We tested the hypothesis that H. pylori infections involve the activation of Akt signalling in human gastric epithelial cancer cells. Immunoblot, immunofluorescence and kinase assays show that H. pylori infection of gastric epithelial cells induced phosphorylation of Akt at Ser 473 and Thr 308. Mutations in the H. pylori virulence factor OipA dramatically reduced phosphorylation of Ser 473, while the cag pathogenicity island mutants predominantly inhibited phosphorylation of Thr 308. As the downstream of Akt activation, H. pylori infection inactivated the inactivation of glycogen synthase kinase 3β at Ser 9 by its phosphorylation. As the upstream of Akt activation, H. pylori infection activated epidermal growth factor receptor (EGFR) at Tyr 992, phosphatidylinositol 3-OH kinase (PI3K) p85 subunit and PI3K-dependent kinase 1 at Ser 241. Pharmacologic inhibitors of PI3K or mitogen-activated protein kinase kinase (MEK), Akt knock-down and EGFR knock-down showed that H. pylori infection induced the activation of EGFR→PI3K→PI3K-dependent kinase 1→Akt→extracellular signal-regulated kinase signalling pathways, the inactivation of glycogen synthase kinase 3β and interleukin-8 production. The combined functions of cag pathogenicity island and OipA were necessary and sufficient for full activation of signalling at each level. We propose activation of these pathways as a novel mechanism for H. pylori -mediated carcinogenesis.     

Association study of CCR6 rs3093024 with Rheumatoid Arthritis in a Pakistani cohort

C-C Chemokine receptor 6 (CCR6), an important protein in inflammatory and immunological responses, has been previously reported to be associated with rheumatoid arthritis (RA). Therefore, in order to replicate these findings, a case-control study was conducted on 500 subjects (including 250 RA patients and 250 healthy controls) of Pakistani origin. The aim of this study was to determine the association of CCR6 rs3093024 variant with RA and identify its role in splicing events using bioinformatics tools. The clinical and demographic characteristics of the patients were collected using a well-designed questionnaire. The genotype frequencies of CCR6 rs3093024 variant were determined using tetra-primer ARMS-PCR (amplification of refractory mutation system-polymerase chain reaction) method. A significant difference was found between CCR6 rs3093024 genotype frequencies [P = 0.0016, χ² = 12.915]. Similarly, a significant difference in the allele frequencies between RA patients and healthy controls was also observed [P = 0.0003 and OR (95% CI) = 0.63 (0.49–0.80)]. The stratification of patients showed that there was a significant increase in AA genotype against AG + GG in patients [P = 0.0014, OR (95% CI) = 2.0 (1.32–3.02)]. Furthermore, using bioinformatics analysis, it was found that CCR6 rs3093024 variant might create a potential splicing enhancer motif (SF2/ASF (IgM-BRCA1) with score of 77.92; Threshold 70.53), which might have important impact on the product of this gene. This study suggests that the A variant of CCR6 rs3093024 variant is significantly associated with RA-risk and its G variant is protective in Pakistani population but a multi-cohort large sized population study is needed to elucidate these results. Moreover, functional studies are needed to highlight the effects of this polymorphism on the function of CCR6 gene.     

The Genus Pluchea: Phytochemistry,Traditional Uses,and Biological Activities

In this review, literature data on phytochemical and biological investigations on the genus Pluchea are compiled. Pluchea is a genus of flowering plants in the Asteraceae family and comprises ca. 80 species distributed mainly in Northern and Southern America, Africa, Asia, and Australia. Sesquiterpenoids and flavonoids are the main constituents of this genus. Compounds isolated from plants of the Pluchea genus display a variety of biological properties, viz., anticancer, antileishmanial, immunosuppressive, antioxidant, anti‐acetylcholinesterase, antimicrobial, trypanocidal, hepatoprotective, cytotoxic, larvicidal, anti‐ulcer, anti‐inflammatory, and antinociceptive activities.