The road-map for establishment of a prognostic molecular marker panel in glioma using liquid biopsy: current status and future directions.

Gliomas are primary intracranial tumors with defined molecular markers available for precise diagnosis. The prognosis of glioma is bleak as there is an overlook of the dynamic crosstalk between tumor cells and components of the microenvironment. Herein, different phases of gliomagenesis are presented with reference to the role and involvement of secreted proteomic markers at various stages of tumor initiation and development. The secreted markers of inflammatory response, namely interleukin-6, tumor necrosis factor-α, interferon-ϒ, and kynurenine, proliferation markers human telomerase reverse transcriptase and microtubule-associated-protein-Tau, and stemness marker human-mobility-group-AThook-1 are involved in glial tumor initiation and growth. Further, hypoxia and angiogenic factors, heat-shock-protein-70, endothelial-growth-factor-receptor-1 and vascular endothelial growth factor play a major role in promoting vascularization and tumor volume expansion. Eventually, molecules such as matrix-metalloprotease-7 and intercellular adhesion molecule-1 contribute to the degradation and remodeling of the extracellular matrix, ultimately leading to glioma progression. Our study delineates the roadmap to develop and evaluate a non-invasive panel of secreted biomarkers using liquid biopsy for precisely evaluating disease progression, to accomplish a clinical translation.

Curcumin in Combination with Other Adjunct Therapies for Brain Tumor Treatment: Existing Knowledge and Blueprint for Future Research.

Malignant brain tumors proliferate aggressively and have a debilitating outcome. Surgery followed by chemo-radiotherapy has been the standard procedure of care since 2005 but issues of therapeutic toxicity and relapse still remain unaddressed. Repurposing of drugs to develop novel combinations that can augment existing treatment regimens for brain tumors is the need of the hour. Herein, we discuss studies documenting the use of curcumin as an adjuvant to conventional and alternative therapies for brain tumors. Comprehensive analysis of data suggests that curcumin together with available therapies can generate a synergistic action achieved through multiple molecular targeting, which results in simultaneous inhibition of tumor growth, and reduced treatment-induced toxicity as well as resistance. The review also highlights approaches to increase bioavailability and bioaccumulation of drugs when co-delivered with curcumin using nano-cargos. Despite substantial preclinical work on radio-chemo sensitizing effects of curcumin, to date, there is only a single clinical report on brain tumors. Based on available lab evidence, it is proposed that antibody-conjugated nano-curcumin in combination with sub-toxic doses of conventional or repurposed therapeutics should be designed and tested in clinical studies. This will increase tumor targeting, the bioavailability of the drug combination, reduce therapy resistance, and tumor recurrence through modulation of aberrant signaling cascades; thus improving clinical outcomes in brain malignancies.

Novel sulphur-oxidizing bacteria consummate sulphur deficiency in oil seed crop.

Plants absorb sulphate, the oxidized form of elemental sulphur (S°), from soil. Sulphur-oxidizing bacteria play a key role in transformation of sulphur in soil. Oil seed crops require high amount of sulphur and it plays an important role in the formation of proteins, vitamins and enzymes. It increases yield, oil content and protein content in oil seed crops. Sulphur is the important constituent of amino acids, viz. methionine, cystine, and cysteine. It necessitates various enzymatic, metabolic processes such as photosynthesis and nitrogen fixation. In the last few years, the prominence of sulphur in oil seed crop nutrition has been accepted as widespread occurrence of its inadequacy in agricultural soil. Approximately 41% of Indian soil is deficient in sulphur. The soil microbial population is the major enforcement behind sulphur transformation. They mineralize, immobilize, oxidize and reduce the elemental and other reduced forms of sulphur. The main step in transformation is oxidation carried out by microorganisms to convert sulphur into sulphate. The chemolithotrophic bacteria belonging to genus Thiobacillus are of primary importance; there are heterotrophic bacteria also which can oxidize sulphur in soil. The pH reduction at the time of oxidation helps in mineralization and absorption of other essential nutrients also. This property of sulphur-oxidizing bacteria (SOB) shows their potential to be used as bioinoculants. Bioformulations prepared using carrier-based formulations, immobilization, biostimulation, etc., are sustainable forms of fertilizers. These SOB inoculants can be used to increase the fertility and sulphate production in soil.

Facets of rhizospheric microflora in biocontrol of phytopathogen Macrophomina phaseolina in oil crop soybean.

The use of microbial bioinoculants for managing plant diseases and promoting plant growth is an effective alternative approach to integrated farming. One of the devastating phytopathogens is Macrophomina phaseolina (Tassi) Goid. It is an omnipresent fungus infecting more than 500 plant species. It causes charcoal rot disease in soybean leading to 30-50% yield loss. Soybean Glycine max (L.) oil seed crop produced globally is highly susceptible to M. phaseolina. India is the fifth largest producer of soybean in the world. Madhya Pradesh is the largest soybean-producing state in India; Around 70% yield loss of soybean is accounted to M. phaseolina infection in India. Control of charcoal rot is the requisite of the current situation. Chemical control is not feasible due to saprophytic nature and prolonged survival of Macrophomina phaseolina. Chemical fungicides are expensive, toxic, hazardous, and cause pollution. Biological control is an effective approach to control this devastating fungus. The rhizosphere of soil is rich in beneficial microflora competent to suppress plant pathogens and also promote plant growth. PGPR have well-developed mechanisms that impart antagonistic traits to them. PGPR produces various antifungal metabolites siderophores and HCN which inhibit fungal growth, and can be used as potent BCA. Pseudomonas and Bacillus species have been reported effective against M. phaseolina. The mechanisms and antifungal compounds produced by these bacteria to control charcoal rot can be studied extensively. BCA or the metabolites secreted by them have the potential to develop effective bioformulations for soybean at the commercial level for sustainable agriculture.

Expression of H19 long non-coding RNA is down-regulated in oral squamous cell carcinoma.

Long non-coding RNAs (lncRNAs) are a group of non-protein-coding RNAs which are longer than 200 nucleotides. LncRNAs play important roles in epigenetic modification, transcription and post-transcriptional regulation, maintenance of normal tissue development and differentiation. LncRNA could serve as a biomarker for diagnosis and prognosis as well as a molecular target for therapy in oral squamous cell carcinoma (OSCC). Therefore, we have determined the expression profile of 5-lncRNAs namely UCA1, TUG1, HOTAIR, MALAT1, and H19 by quantitative real-time PCR in tumor tissues and adjacent normal tissue of 32 OSCC patients. To determine the expression, methylation status and genomic alterations in lncRNAs across pancancer, TCGA datasets were analyzed by UALCAN, MEXPRESS and cBioPortal database. Then, we determined the association between lncRNA expression and clinicopathological attributes of patients by Spearman's rank test. Expression of UCA1 and TUG1 genes was up-regulated in 54.83 % and 53.12 % OSCC tumors, respectively. Importantly, expression of MALAT1 and H19 was down-regulated in tumor tissues of 62.5 % and 81.25 % respectively of OSCC patients. Except for MALAT1, our experimental data showed concordance with the TCGA analysis. Expression of HOTAIR in OSCC tumors was positively correlated with tumor volume, whereas MALAT1 and H19 negatively correlated with the smoking status of patients.

siRNAs targeting PB2 and NP genes potentially inhibit replication of Highly Pathogenic H5N1 Avian Influenza Virus.

Highly Pathogenic Avian Influenza (HPAI) H5N1 virus is a threat to animal and public health worldwide. Till date, the H5N1 virus has claimed 402 human lives, with a mortality rate of 58 percent and has caused the death or culling of millions of poultry since 2003. In this study, we have designed three siRNAs (PB2-2235, PB2-479 and NP-865) targeting PB2 and NP genes of avian influenza virus and evaluated their potential, measured by hemagglutination (HA), plaque reduction and Real time RT-PCR assay, in inhibiting H5N1 virus (A/chicken/Navapur/7972/2006) replication in MDCK cells. The siRNAs caused 8- to 16-fold reduction in virus HA titers at 24 h after challenged with 100TCID50 of virus. Among these siRNAs, PB2-2235 offered the highest inhibition of virus replication with 16-fold reduction in virus HA titer, 80 percent reduction in viral plaque counts and 94 percent inhibition in expression of specific RNA at 24 h. The other two siRNAs had 68-73 percent and 87-88 percent reduction in viral plaque counts and RNA copy number, respectively. The effect of siRNA on H5N1 virus replication continued till 48h (maximum observation period). These findings suggest that PB2-2235 could efficiently inhibit HPAI H5N1 virus replication.

A comparison of the variation in Indian populations of pigeonpea cyst nematode, Heterodera cajani revealed by morphometric and AFLP analysis.

The cyst nematode Heterodera cajani is one of the major endemic diseases of pigeonpea, an important legume for food security and protein nutrition in India. It occurs in several pulse crops grown over a range of Indian agro climatic conditions but the extent of its intraspecific variation is inadequately defined. In view of this, 11 populations of Heterodera cajani were analyzed using morphometrics and the results correlated with those obtained from an AFLP approach using 24 primer pair combinations that amplified a total of 1278 AFLP markers. The cluster solution from this binary data indicated similarities for five populations that differed from those suggested by morphometrics. The differences obtained could not be related to geographic distance between populations. The data suggests that recent and long distance dispersal has occurred whose causes need to be defined to restrict further field introductions. Four AFLP primer pairs clustered the populations similarly to that generated using all 24 primer pairs. This simplified approach may provide a rapid basis for discriminating populations for their future management and help to check further distribution in agricultural trade. It may also have potential to determine differences in populations that relate to host range or virulence to resistance genes.