A state-of-the-art review on cadmium uptake, toxicity, and tolerance in rice: From physiological response to remediation process.

Cadmium (Cd), a major contaminant of concern, has been extensively reviewed and debated for its anthropogenic global shifts. Cadmium levels in rice grains raise wide food safety concerns. The aim of this review is therefore to capture the dynamics of Cd in paddy soil, translocation pathways of Cd from soil to consumption rice, and assess its bio-accessibility in human consumption. In crop plants, Cd reduces absorption of nutrients and water, triggers oxidative stress, and inhibits plant metabolism. Understanding the mechanisms and behaviour of Cd in paddy soil and rice allows to explain, predict and intervene in Cd transferability from soil to grains and human exposure. Factors affecting Cd movement in soil, and further to rice grain, are elucidated. Recently, physiological and molecular understanding of Cd transport in rice plants have been advanced. Morphological-biochemical characteristics and Cd transporters of plants in such a movement were also highlighted. Ecologically viable remediation approaches, including low input cost agronomic methods, phytoremediation and microbial bioremediation methods, are emerging.

FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer.

Low-affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa) is a cell surface protein that belongs to a family of Fc receptors that facilitate the protective function of the immune system against pathogens. However, the role of FcγRIIIa in prostate cancer (PCa) progression remained unknown. In this study, we found that FcγRIIIa expression was present in PCa cells and its level was significantly higher in metastatic lesions than in primary tumors from the PCa cohort (P = 0.006). PCa patients with an elevated level of FcγRIIIa expression had poorer biochemical recurrence (BCR)-free survival compared with those with lower FcγRIIIa expression, suggesting that FcγRIIIa is of clinical importance in PCa. We demonstrated that overexpression of FcγRIIIa increased the proliferative ability of PCa cell line C4-2 cells, which was accompanied by the upregulation of androgen receptor (AR) and phosphatidylinositol-4-phosphate 5-kinase alpha (PIP5Kα), which are the key players in controlling PCa progression. Conversely, targeted inhibition of FcγRIIIa via siRNA-mediated knockdown or using its inhibitory antibody suppressed growth of xenograft PC-3 and PC-3M prostate tumors and reduced distant metastasis in xenograft mouse models. We further showed that elevated expression of AR enhanced FcγRIIIa expression, whereas inhibition of AR activity using enzalutamide led to a significant downregulation of FcγRIIIa protein expression. Similarly, inhibition of PIP5K1α decreased FcγRIIIa expression in PCa cells. FcγRIIIa physically interacted with PIP5K1α and AR via formation of protein-protein complexes, suggesting that FcγRIIIa is functionally associated with AR and PIP5K1α in PCa cells. Our study identified FcγRIIIa as an important factor in promoting PCa growth and invasion. Further, the elevated activation of FcγRIII and AR and PIP5K1α pathways may cooperatively promote PCa growth and invasion. Thus, FcγRIIIa may serve as a potential new target for improved treatment of metastatic and castration-resistant PCa.

Establishment of Prostate Tumor Growth and Metastasis Is Supported by Bone Marrow Cells and Is Mediated by PIP5K1α Lipid Kinase.

Cancer cells facilitate growth and metastasis by using multiple signals from the cancer-associated microenvironment. However, it remains poorly understood whether prostate cancer (PCa) cells may recruit and utilize bone marrow cells for their growth and survival. Furthermore, the regulatory mechanisms underlying interactions between PCa cells and bone marrow cells are obscure. In this study, we isolated bone marrow cells that mainly constituted populations that were positive for CD11b and Gr1 antigens from xenograft PC-3 tumor tissues from athymic nu/nu mice. We found that the tumor-infiltrated cells alone were unable to form tumor spheroids, even with increased amounts and time. By contrast, the tumor-infiltrated cells together with PCa cells formed large numbers of tumor spheroids compared with PCa cells alone. We further utilized xenograft athymic nu/nu mice bearing bone metastatic lesions. We demonstrated that PCa cells were unable to survive and give rise to colony-forming units (CFUs) in media that were used for hematopoietic cell colony-formation unit (CFU) assays. By contrast, PC-3M cells survived when bone marrow cells were present and gave rise to CFUs. Our results showed that PCa cells required bone marrow cells to support their growth and survival and establish bone metastasis in the host environment. We showed that PCa cells that were treated with either siRNA for PIP5K1α or its specific inhibitor, ISA-2011B, were unable to survive and produce tumor spheroids, together with bone marrow cells. Given that the elevated expression of PIP5K1α was specific for PCa cells and was associated with the induced expression of VEGF receptor 2 in PCa cells, our findings suggest that cancer cells may utilize PIP5K1α-mediated receptor signaling to recruit growth factors and ligands from the bone marrow-derived cells. Taken together, our study suggests a new mechanism that enables PCa cells to gain proliferative and invasive advantages within their associated host microenvironment. Therapeutic interventions using PIP5K1α inhibitors may not only inhibit tumor invasion and metastasis but also enhance the host immune system.

Utility and pitfalls of high field 3 tesla intraoperative MRI in neurosurgery: A single centre experience of 100 cases.

OBJECTIVE: In India, few centers are using 1.5 Tesla intraoperative MRI systems. We are using a 3 Tesla iMRI system. We share our initial experience of 3T iMRI in neurosurgical procedures with evaluation of its utility and pitfalls. METHODS: A prospective observational study conducted between August 2017 to July 2018 at Yashoda Hospital, Secunderabad. All patients undergoing iMRI guided resection of intracranial SOL were included. RESULTS: First 100 patients with various intracranial SOLs were included. The mean time required in shifting and image acquisition was 85.6 minutes in first 20 cases which was reduced to 37.4 minutes in next the next cases. Primary GTR was achieved in 44% cases, and residues were detected in 56%, secondary GTR was achieved in 37% cases, and surgery was discontinued in 19%. Maximum residues were detected in intraaxial sols and pituitary macroadenomas. No major iMRI associated complications were seen, minor issues involving transportation and minor contact burns were seen in 4 cases, insignificant anesthetic procedure related complications in 19 cases. CONCLUSION: As per our experience iMRI is an excellent tool to guide and improve the extent of safe resection by 37% in brain tumor surgeries. Good image quality, less time for image acquisition was observed advantages of 3T system. iMRI success depends on multidepartment coordinated teamwork and multiple iterations of the process to smoothen the workflow.

Effects of water deficit stress on agronomic and physiological responses of rice and greenhouse gas emission from rice soil under elevated atmospheric CO2.

Rice is the foremost staple food in the world, safeguarding the global food and nutritional security. Rise in atmospheric carbon dioxide (CO2) and water deficits are threatening global rice productivity and sustainability. Under real field conditions these climatic factors often interact with each other resulting in impacts that are remarkably different compared to individual factor exposure. Rice soils exposed to drought and elevated CO2 (eCO2) alters the biomass, diversity and activity of soil microorganisms affecting greenhouse gas (GHG) emission dynamics. In this review we have discussed the impacts of eCO2 and water deficit on agronomic, biochemical and physiological responses of rice and GHGs emissions from rice soils. Drought usually results in oxidative stress due to stomatal closure, dry weight reduction, formation of reactive oxygen species, decrease in relative water content and increase in electrolyte leakage at almost all growth and developmental phases of rice. Elevated atmospheric CO2 concentration reduces the negative effects of drought by improving plant water relations, reducing stomatal opening, decreasing transpiration, increasing canopy photosynthesis, shortening crop growth period and increasing the antioxidant metabolite activities in rice. Increased scientific understanding of the effects of drought and eCO2 on rice agronomy, physiology and GHG emission dynamics of rice soil is essential for devising adaptation options. Integration of novel agronomic practices viz., crop establishment methods and alternate cropping systems with improved water and nutrient management are important steps to help rice farmers cope with drought and eCO2. The review summarizes future research needs for ensuring sustained global food security under future warmer, drier and high CO2 conditions.

ETS1 and PAX5 transcription factors recruit AID to Igh DNA.

B lymphocytes optimize antibody responses by class switch recombination (CSR), which changes the expressed constant region exon of the immunoglobulin heavy chain (IgH), and by somatic hypermutation (SH) that introduces point mutations in the variable regions of the antibody genes. Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates both these antibody diversification processes by deaminating cytosine to uracil. Here we asked the question if transcription factors can mediate the specific targeting of the antibody diversification by recruiting AID. We have recently reported that AID is together with the transcription factors E2A, PAX5 and IRF4 in a complex on key sequences of the Igh locus. Here we report that also ETS1 is together with AID in this complex on key sequences of the Igh locus in splenic B cells of mice. Furthermore, we show that both ETS1 and PAX5 can directly recruit AID to DNA sequences from the Igh locus with the specific binding site for the transcription factor. Taken together, our findings support the notion of a targeting mechanism for the selective diversification of antibody genes with limited genome wide mutagenesis by recruitment of AID by PAX5 and ETS1 in a transcription factor complex.

Spontaneous Isolated Inferior Mesenteric Artery Dissection With Chronic Mesenteric Ischemia: Case Report and Endovascular Management.

We report the clinical details, imaging findings, and management for a 39-year-old female presenting with recurrent episodes of pain in abdomen due to systemic lupus erythematous vasculitis associated with spontaneous isolated inferior mesenteric dissection. Spontaneous mesenteric artery dissection is an uncommon cause of mesenteric ischemia. Symptomatic spontaneous isolated inferior mesenteric artery (IMA) dissection is a rare condition, and its association with systemic lupus erythematosus is not previously described in the English literature. The optimal treatment options are debatable and include medical management, surgical reconstruction, and endovascular therapy. We wish to highlight spontaneous isolated IMA dissection as a rare etiology for chronic mesenteric ischemia and its management by endovascular methods.

Modulation of Trehalose Dimycolate and Immune System by Rv0774c Protein Enhanced the Intracellular Survival of Mycobacterium smegmatis in Human Macrophages Cell Line.

Mycobacterium tuberculosis Rv0774c protein was reported previously to express under stress conditions. Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. The bacterial colonies expressing Rv0774c (Ms_rv0774c) were larger, smoother, more moist, and flatter than the control ones (Ms_ve). Enhanced survival of Ms_rv0774c after treatment with streptomycin was observed when compared with control. The cell envelope of Ms_rv0774c was demonstrated to have more trehalose di-mycolate (TDM) and lesser amount of mycolylmannosylphosphorylheptaprenol (Myc-PL) in comparison to control. Higher intracellular survival rate was observed for Ms_rv0774c as compared to Ms_ve in the THP-1 cells. This could be correlated to the reduction in the levels of reactive NO and iNOS expression. Infection of macrophages with Ms_rv0774c resulted in significantly increased expression of TLR2 receptor and IL-10 cytokines. However, it lowered the production of pro-inflammatory cytokines such as IL-12, TNF-α, IFN-γ, and MCP-1 in Ms_rv0774c infected macrophages in comparison to the control and could be associated with decreased phosphorylation of p38 MAPK. Though, predicted with high antigenicity index bioinformatically, extracellular in nature and accessible to host milieu, Rv0774c was not able to generate humoral response in patient samples. Overall, the present findings indicated that Rv0774c altered the morphology and streptomycin sensitivity by altering the lipid composition of M. smegmatis as well as modulated the immune response in favor of bacterial persistence.

The immunosuppressive effects of a novel recombinant LipQ (Rv2485c) protein of Mycobacterium tuberculosis on human macrophage cell lines.

Mycobacterium tuberculosis (MTB), an intracellular pathogen, still represents a major global health challenge. A number of mycobacterial macromolecules have been shown to target biological processes within host macrophages; however, the exact mechanism for the majority of these host pathogen interactions is still poorly understood. Moreover, the lipid metabolic pathway is one of the most important physiologic pathways that plays a vital role in the survival and infection of Mycobacterium tuberculosis. In present study, we investigated the effect of rLipQ from Mycobacterium tuberculosis H37Rv on macrophage functions in vitro.Our results demonstrate that rLipQ significantly lowers the expression level of pro-inflammatory cytokines (TNF-α& IFN-γ) and augments the level of anti inflammatory cytokines such as IL-4 & IL-10as compared to LPS stimulated macrophages. An up-regulation of anti-inflammatory and down-regulation of pro-inflammatory cytokines levels in rLipQ pretreated macrophages implies immuno-modulatory functions in TB patients. Interestingly, rLipQ also inhibited the expression of iNOS, TLR-2 and transcription factor NF-kB in LPS stimulated macrophages whereas the expression of TLR-4 remains unchanged. The inhibition in the expression of these signaling molecules has been correlated to the inhibition of NO production in macrophages. Taken together, these studies demonstrate that rLipQ is a novel lipase that is highly immunogenic and may play an important role in the virulence and pathogenesis of M. tuberculosis infection, by altering the balance of cytokines, which might help to assess prognosis and contribute to a better understanding against host-pathogen interactions.

Screening for Thalassemia Carrier Status in Pregnancy and Pre-Natal Diagnosis.

This hospital-based study reports the results of antenatal screening for thalassemia in pregnant women visiting a hospital in Jodhpur, Rajasthan, India. Eighty-eight (5.9%) of 1500 women screened for thalassemia had thalassemia trait. Twenty at-risk couples were identified and two fetuses were detected to be having thalassemia major.

Role of vitamin e in prevention of oral cancer:-a review.

Oral cancer is one of the major global threads to public health. The development of oral cancer is tobacco related mainly. Vitamin-E can inhibit reaction of the tobacco specific nitrosamine which undergoes specific activation, detoxification process. Dietary substitute such as vitamin-E can prevent oral cancer at a very early stage that is in premalignant lesions, in premalignant conditions. Main action of vitamin E includes increase immunity, controls free radicals mediated cell disturbances, maintains membrane integrity, inhibit cancer cell growth, cytotoxicity. Many past studies suggest the role of antioxidant (vitamin-E) in treatment of oral mucosal lesions particularly includes oral leukoplakia, oral lichen planus, oral submucous fibrosis and oral cancer. Vitamin-E as an antioxidant helps in prevention and slow the growth of Head and Neck cancer, improve the effects of cancer chemotherapy and reduce the side effects from both chemotherapy and radiation therapy for cancer patients. As prevention modality use of Vitamin-E may be beneficial for human beings.

Hyperglycemia of tumor microenvironment modulates stage-dependent tumor progression and multidrug resistance: implication of cell survival regulatory molecules and altered glucose transport.

Using a murine tumor model, we demonstrate that tumor cells display a tumor stage-dependent differential glucose utilization associated with an altered GLUT-1 expression. Hyperglycemic tumor microenvironment modulates the tumorigenic ability, survival, apoptosis, and glucose utilization of tumor cells in late tumor-bearing stage accompanied by an altered tumor acidosis and expression of cell survival regulatory molecules: HIF-1α, p53, Bcl2, caspase-activated DNase, IL-4, IL-6, IL-10, IFN-γ, TGF-ß, and VEGF. Glucose-exposed tumor cells of late tumor-bearing stage also show a declined susceptibility to the cytotoxic action of chemotherapeutic drugs: cisplatin and methotrexate, accompanied by an increased expression of MDR-1 gene. Taken together the results show that hyperglycemic tumor microenvironment differentially alters tumor growth depending on the stage of tumor progression.

Priming effect of aspirin for tumor cells to augment cytotoxic action of cisplatin against tumor cells: implication of altered constitution of tumor microenvironment, expression of cell cycle, apoptosis, and survival regulatory molecules.

The present study was conducted to investigate if anti-inflammatory drug aspirin could alter the cytotoxic action of cisplatin on tumor cells. Using a transplantable T cell lymphoma in a murine model, we demonstrate that exposure to aspirin exerts a priming action on tumor cells, rendering them susceptible to induction of cell death by cisplatin with consequences on retardation of tumor progression. The priming action of aspirin on tumor cells was found to be dependent on an altered constitution of tumor microenvironment with respect to decline of acidosis and modulation in the expression of cell cycle and survival regulatory molecules like cyclin B1, cyclin D, bcl-2, bcl-xL, p53, and cytokines: IL-4, IL-10, IFN- γ & VEGF. The study also discusses possible mechanisms underlying augmentary action of aspirin on cisplatin-mediated tumor cells killing. This is the first report showing that pre-exposure of tumor cells to aspirin lowers the concentration of cisplatin to exert its cytotoxic action. The finding of this study will help in designing novel antitumor protocols with reduced dose of cisplatin.

Myelopotentiating effect of curcumin in tumor-bearing host: role of bone marrow resident macrophages.

The present investigation was undertaken to study if curcumin, which is recognized for its potential as an antineoplastic and immunopotentiating agent, can also influence the process of myelopoiesis in a tumor-bearing host. Administration of curcumin to tumor-bearing host augmented count of bone marrow cell (BMC) accompanied by an up-regulated BMC survival and a declined induction of apoptosis. Curcumin administration modulated expression of cell survival regulatory molecules: Bcl2, p53, caspase-activated DNase (CAD) and p53-upregulated modulator of apoptosis (PUMA) along with enhanced expression of genes of receptors for M-CSF and GM-CSF in BMC. The BMC harvested from curcumin-administered hosts showed an up-regulated colony forming ability with predominant differentiation into bone marrow-derived macrophages (BMDM), responsive for activation to tumoricidal state. The number of F4/80 positive bone marrow resident macrophages (BMM), showing an augmented expression of M-CSF, was also augmented in the bone marrow of curcumin-administered host. In vitro reconstitution experiments indicated that only BMM of curcumin-administered hosts, but not in vitro curcumin-exposed BMM, augmented BMC survival. It suggests that curcumin-dependent modulation of BMM is of indirect nature. Such prosurvival action of curcumin is associated with altered T(H1)/T(H2) cytokine balance in serum. Augmented level of serum-borne IFN-γ was found to mediate modulation of BMM to produce enhanced amount of monokines (IL-1, IL-6, TNF-α), which are suggested to augment the BMC survival. Taken together the present investigation indicates that curcumin can potentiate myelopoiesis in a tumor-bearing host, which may have implications in its therapeutic utility.

Effect of aspirin administration on reversal of tumor-induced suppression of myelopoiesis in T-cell lymphoma bearing host.

The present investigation studied the effect of aspirin administration in tumor-bearing hosts on bone marrow cellularity and myelopoiesis. Aspirin administration to mice bearing a transplantable T-cell lymphoma, designated as Dalton's lymphoma (DL), augmented proliferation of bone marrow cells (BMC). BMC of aspirin-administered tumor-bearing mice were found to be predominantly in the S phase of cell cycle releasing them from G0/G1 arrest. Aspirin-exposed BMC also showed an altered expression of survival and cell cycle regulatory proteins p53, bcl2, caspase-activated deoxyribonuclease (CAD), cyclin B1 and cyclin D. Moreover, the BMC of aspirin-administered tumor-bearing mice showed an augmented colony-forming ability and differentiation in the macrophage lineage with an activated phenotype of bone marrow-derived macrophages (BMDM) with respect to macrophage-mediated tumoricidal activity and production of nitric oxide, IL-1ß, TNFα and VEGF. On the other hand aspirin administration to normal mice showed little effect on bone marrow cellularity and myeloid differentiation. In this model, aspirin had a myelopoetic action in tumor-bearing host.

Anti-neoplastic action of aspirin against a T-cell lymphoma involves an alteration in the tumour microenvironment and regulation of tumour cell survival.

The present study explores the potential of the anti-neoplastic action of aspirin in a transplantable murine tumour model of a spontaneously originated T-cell lymphoma designated as Dalton's lymphoma. The antitumour action of aspirin administered to tumour-bearing mice through oral and/or intraperitoneal (intratumoral) routes was measured via estimation of survival of tumour-bearing mice, tumour cell viability, tumour progression and changes in the tumour microenvironment. Intratumour administration of aspirin examined to assess its therapeutic potential resulted in retardation of tumour progression in tumour-bearing mice. Oral administration of aspirin to mice as a prophylactic measure prior to tumour transplantation further primed the anti-neoplastic action of aspirin administered at the tumour site. The anti-neoplastic action of aspirin was associated with a decline in tumour cell survival, augmented induction of apoptosis and nuclear shrinkage. Tumour cells of aspirin-treated mice were found arrested in G0/G1 phase of the cell cycle and showed nuclear localization of cyclin B1. Intratumoral administration of aspirin was accompanied by alterations in the biophysical, biochemical and immunological composition of the tumour microenvironment with respect to pH, level of dissolved O2, glucose, lactate, nitric oxide, IFNγ (interferon γ), IL-4 (interleukin-4), IL-6 and IL-10, whereas the TGF-ß (tumour growth factor-ß) level was unaltered. Tumour cells obtained from aspirin-treated tumour-bearing mice demonstrated an altered expression of pH regulators monocarboxylate transporter-1 and V-ATPase along with alteration in the level of cell survival regulatory molecules such as survivin, vascular endothelial growth factor, heat-shock protein 70, glucose transporter-1, SOCS-5 (suppressor of cytokine signalling-5), HIF-1α (hypoxia-inducible factor-1α) and PUMA (p53 up-regulated modulator of apoptosis). The study demonstrates a possible indirect involvement of the tumour microenvironment in addition to a direct but limited anti-neoplastic action of aspirin in the retardation of tumour growth.

Gender-specific antitumor action of aspirin in a murine model of a T-cell lymphoma bearing host.

Aspirin is an anti-inflammatory drug demonstrated to possess a tremendous anticancer potential. As progression of some tumors is influenced by sex hormones, we investigated if the antineoplastic action of aspirin shows gender dependence. Using a murine model of T-cell lymphoma, the present investigation was undertaken to study if the antitumor actions of aspirin against lymphoma cells display gender dimorphism. The findings of the present investigation indicate that aspirin administration to male and female tumor-bearing hosts resulted in gender dependent differential tumor growth retardation. Such gender dichotomy of aspirin's antitumor action was associated with a differential impact on cell cycle progression and expression of cell survival regulatory molecules. Aspirin administration was also found to modulate crucial parameters of tumor microenvironment, including contents of glucose, lactate and cell growth regulatory cytokines, in a gender specific manner. Aspirin was found to reverse estrogen-dependent augmentation of tumor cell survival in vitro. Taken together the results of the present study suggest that the antineoplastic action of aspirin is gender-dependent and should be considered in designing of gender-specific therapeutic applications of aspirin.

Role of curcumin-dependent modulation of tumor microenvironment of a murine T cell lymphoma in altered regulation of tumor cell survival.

Using a murine model of a T cell lymphoma, in the present study, we report that tumor growth retarding action of curcumin involves modulation of some crucial parameters of tumor microenvironment regulating tumor progression. Curcumin-administration to tumor-bearing host caused an altered pH regulation in tumor cells associated with alteration in expression of cell survival and apoptosis regulatory proteins and genes. Nevertheless, an alteration was also observed in biophysical parameters of tumor microenvironment responsible for modulation of tumor growth pertaining to hypoxia, tumor acidosis, and glucose metabolism. The study thus sheds new light with respect to the antineoplastic action of curcumin against a tumor-bearing host with progressively growing tumor of hematological origin. This will help in optimizing application of the drug and anticancer research and therapy.