Mutant crtRB1 gene negates the unfavourable effects of opaque2 gene on germination and seed vigour among shrunken2-based biofortified sweet corn genotypes.

Sweet corn is one of the most popular vegetables worldwide. However, traditional shrunken2 (sh2 )-based sweet corn varieties are poor in nutritional quality. Here, we analysed the effect of (1) ß-carotene hydroxylase1 (crtRB1 ), (2) opaque2 (o2 ) and (3) o2+crtRB1 genes on nutritional quality, germination, seed vigour and physico-biochemical traits in a set of 27 biofortified sh2 -based sweet corn inbreds. The biofortified sweet corn inbreds recorded significantly higher concentrations of proA (16.47µg g-1 ), lysine (0.36%) and tryptophan (0.09%) over original inbreds (proA: 3.14µg g-1 , lysine: 0.18%, tryptophan: 0.04%). The crtRB1 -based inbreds had the lowest electrical conductivity (EC), whereas o2 -based inbreds possessed the highest EC. The o2 +crtRB1 -based inbreds showed similar EC to the original inbreds. Interestingly, o2 -based inbreds also had the lowest germination and seed vigour compared to original inbreds, whereas crtRB1 and o2 +crtRB1 introgressed sweet corn inbreds showed similar germination and seed vigour traits to their original versions. This suggested that the negative effect of o2 on germination, seed vigour and EC is nullified by crtRB1 in the double mutant sweet corn. Overall, o2 +crtRB1 -based sweet corn inbreds were found the most desirable over crtRB1 - and o2 -based inbreds alone.

First report of 'Candidatus phytoplasma asteris' (16SrI) from Cassia fistula showing symptoms of flat stem and witches'-broom in India.

Cassia fistula commonly known as 'golden shower tree' is a deciduous tree with a greenish-gray bark and complex leaves with lovely clusters of yellow blossoms that is also utilized for several purposes in traditional medicine offer therapeutic characteristics (Pawar et al., 2017). Random spotting of flat stem symptoms along with unopened flower beds was observed in C. fistula plant during March 2022 in IISER (Indian Institute of Science Education and Research), Thiruvananthapuram, Kerala, India and during May 2022 in SKUAST (Sher-e-Kashmir University of Agricultural Sciences and Technology), Jammu, which were suggestive of phytoplasma infection (Fig. 1 a-e). Surge of leaf hoppers was also observed in and around the tree. The leaf samples were collected from 3 individual C. fistula trees showing suspected symptoms of phytoplasma and one sample from asymptomatic plant of both the states. Leafhopper (LH) species were collected using sweep net method from both the locations. DNA was extracted using CTAB (Cetyl trimethyl ammonium bromide) method and nested universal PCR primers P1/P7 and R16F2n/R16R2 for the 16S rRNA gene (Deng and Hiruki 1991; Gundersen and Lee 1996) and secAfor1/secArev3 and SecAfor2/ SecArev3 for SecA gene (Hodgetts et al. 2008) were employed for the analysis of the phytoplasma strain association. The symptomatic plants and leaf hopper species showed positive bands of 1.2kb and 480bp for 16S rRNA and SecA gene respectively along with. Purified PCR products of both the genes (16Sr RNA and sec A) were ligated into pGEM ®T vector and cloned in Escherichia coli (DH5-α) were sequenced at Agri Genome labs, Kerala, India. The comparative sequence analysis using the BLASTn tool results showed 16S rRNA sequences acquired from plant samples (GenBank Acc. No. OP950857, OP950858) and the leafhoppers Hishimonus phycitis (OP538583) and Orosius albicinctus (OP538584) of Kerala had the minimum of 99.84% of similarity with Bitter gourd little leaf phytoplasma from Myanmar and maximum sequence identity (100%) with the Rapeseed phyllody phytoplasma strain from Taiwan. The sequences of phytoplasma strains from Jammu trees (Genbank Acc. No. OP801671 & OP801672) and H. phycitis (OP801673) shared 100% similarity with each other as well as with North American grapevine yellows and a minimum of 97.65% with Beta vulgaris phytoplasma from Poland. The pairwise comparison results were completely supported by the corresponding phylogenetic sequence analysis of 16S rRNA and SecA gene sequences of all the isolates in the study which clustered with 16SrI-B subgroup related strains. Virtual RFLP analysis through iPhyClassifer results that were derived from in silico digestions of R16F2n/R2 region of 16S rRNA gene using 17 restriction endonucleases enzymes indicated that all the samples produced similar virtual RFLP profiles identical to the reference strain of 16SrI-B phytoplasma subgroup (aster yellows: Acc. No. M30790) with a similarity coefficient value of 1.0. To the best of our knowledge, this is the first report of the phytoplasma association of 'Ca. P. asteris' (16SrI-B) subgroup with Cassia fistula in the world.

A superior gene allele involved in abscisic acid signaling enhances drought tolerance and yield in chickpea.

Identifying potential molecular tags for drought tolerance is essential for achieving higher crop productivity under drought stress. We employed an integrated genomics-assisted breeding and functional genomics strategy involving association mapping, fine mapping, map-based cloning, molecular haplotyping and transcript profiling in the introgression lines (ILs)- and near isogenic lines (NILs)-based association panel and mapping population of chickpea (Cicer arietinum). This combinatorial approach delineated a bHLH (basic helix-loop-helix) transcription factor, CabHLH10 (Cicer arietinum bHLH10) underlying a major QTL, along with its derived natural alleles/haplotypes governing yield traits under drought stress in chickpea. CabHLH10 binds to a cis-regulatory G-box promoter element to modulate the expression of RD22 (responsive to desiccation 22), a drought/abscisic acid (ABA)-responsive gene (via a trans-expression QTL), and two strong yield-enhancement photosynthetic efficiency (PE) genes. This, in turn, upregulates other downstream drought-responsive and ABA signaling genes, as well as yield-enhancing PE genes, thus increasing plant adaptation to drought with reduced yield penalty. We showed that a superior allele of CabHLH10 introgressed into the NILs improved root and shoot biomass and PE, thereby enhancing yield and productivity during drought without compromising agronomic performance. Furthermore, overexpression of CabHLH10 in chickpea and Arabidopsis (Arabidopsis thaliana) conferred enhanced drought tolerance by improving root and shoot agro-morphological traits. These findings facilitate translational genomics for crop improvement and the development of genetically tailored, climate-resilient, high-yielding chickpea cultivars.

Rice Pangenome Genotyping Array: an efficient genotyping solution for pangenome-based accelerated genetic improvement in rice.

The advent of the pangenome era has unraveled previously unknown genetic variation existing within diverse crop plants, including rice. This untapped genetic variation is believed to account for a major portion of phenotypic variation existing in crop plants. However, the use of conventional single reference-guided genotyping often fails to capture a large portion of this genetic variation leading to a reference bias. This makes it difficult to identify and utilize novel population/cultivar-specific genes for crop improvement. Thus, we developed a Rice Pangenome Genotyping Array (RPGA) harboring probes assaying 80K single-nucleotide polymorphisms (SNPs) and presence-absence variants spanning the entire 3K rice pangenome. This array provides a simple, user-friendly and cost-effective (60-80 USD per sample) solution for rapid pangenome-based genotyping in rice. The genome-wide association study (GWAS) conducted using RPGA-SNP genotyping data of a rice diversity panel detected a total of 42 loci, including previously known as well as novel genomic loci regulating grain size/weight traits in rice. Eight of these identified trait-associated loci (dispensable loci) could not be detected with conventional single reference genome-based GWAS. A WD repeat-containing PROTEIN 12 gene underlying one of such dispensable locus on chromosome 7 (qLWR7) along with other non-dispensable loci were subsequently detected using high-resolution quantitative trait loci mapping confirming authenticity of RPGA-led GWAS. This demonstrates the potential of RPGA-based genotyping to overcome reference bias. The application of RPGA-based genotyping for population structure analysis, hybridity testing, ultra-high-density genetic map construction and chromosome-level genome assembly, and marker-assisted selection was also demonstrated. A web application (http://www.rpgaweb.com) was further developed to provide an easy to use platform for the imputation of RPGA-based genotyping data using 3K rice reference panel and subsequent GWAS.

Impact of age and gender disparity on CD4+ cell counts to control disease progression using specific HAART in HIV-1 positive patients: A case-control study.

BACKGROUND: Highly Active Antiretroviral Therapy (HAART) is composed of several drugs in the antiretroviral class to better treat human immunodeficiency virus type 1 (HIV-1) patients. The estimation of CD4+ T cell counts and HIV-1 viral load in plasma is required to evaluate the treatment success of a specific HAART. METHODOLOGY: The study included the effects of NRTIs (nucleoside reverse transcriptase inhibitors) and novel protease inhibitors (HAART) on normal control subjects and HIV-1 positive subjects from SGPGIMS, Lucknow, with different age groups and genders. Furthermore, the study was conducted by the estimation of HIV through ELISA, measurement of absolute CD4+ cell count, and the measurement of viral load through qRT-PCR. Furthermore, NRTIs (Retrovir and Epivir) were administered orally one tablet daily in the morning followed by newly FDA-approved protease inhibitors (fosamprenavir and darunavir) orally in the evening at the same dose. Furthermore, CD4+T cell counts and HIV-1 viral load were investigated and correlated in patients with different genders and age groups. RESULT: Administration of NRTIs and novel protease inhibitors (HAART) in HIV patients had a significant effect on the CD4+ cell count in various age intervals among males and females. The mean comparison of viral load distribution based on gender in CD4 +ve patients in the case group exhibited a viral load higher in females compared to males, indicating a statistically significant difference between males and females (p<0.05). A notable association between virological and immunological parameters was observed with a reciprocal relationship between viral load and CD4 cell count in CD4 +ve patients, demonstrating multiple correlation coefficients with an R-value of 0.853. CONCLUSION: The administration of specific HAART (NRTIs and novel protease inhibitors) in HIV patients had a notable improvement in the CD4+ cell count and viral load with significant age and gender disparity.

Characterization of crtRB1- and vte4-based biofortified sweet corn inbreds for seed vigour and physico-biochemical traits.

Sweet corn possessing recessive shrunken2 (sh2) gene is popular worldwide. Traditional sweet corn is poor in vitamin A and vitamin E. Plant breeders during the selection of sweet corn genotypes mainly emphasize on plant architecture and yield. Seed germination and seedling vigour play important role for early establishment in field, thereby increasing yield and income. Here, we analysed a set of 15 sh2-based biofortified sweet corn inbreds with crtRB1 (ß-carotene hydroxylase1) and vte4 (γ-tocopherol methyltransferase) genes and three traditional sh2-based sweet corn inbreds for nutritional quality, seed vigour and various physico-biochemical traits. The newly developed inbreds possessed significantly higher provitamin A (proA: 15.60 µg/g) and vitamin E [α-tocopherol (α-T): 20.42 µg/g] than the traditional sweet corn inbreds (proA: 2.51 µg/g, α-T: 11.16 µg/g). The biofortified sweet corn inbreds showed wide variation for germination (80.67-87.33%), vigour index-I (2097.17-2925.28 cm), vigour index-II (134.27-216.19 mg) and electrical conductivity (10.19-13.21 µS cm-1 g-1). Wide variation was also observed for dehydrogenase (1.29-1.59 OD g-1 ml-1), super oxide dismutase (4.01-9.82 g-1), peroxidase (11.66-16.47 µM min-1 g-1), esterase (22.98-34.76 nM min-1 g-1) and α-amylase (5.91-8.15 OD g-1 ml-1). Enrichment of proA and vitamin E in sweet corn did not affect seed vigour and physico-biochemical traits. Correlation analysis revealed that electrical conductivity and α-amylase activity was the reliable indicator for assessing seed germination and vigour. The study identified superior biofortified sweet corn genotypes that would contribute to better vigour and establishment in field. This is the first report of analysis of biofortified sweet corn genotypes for seed vigour and physico-biochemical traits.

Molecular profiling of BADH2 locus reveals distinct functional allelic polymorphism associated with fragrance variation in Indian aromatic rice germplasm.

Allelic variability of the aroma gene, betaine aldehyde dehydrogenase 2 (BADH2) was studied in a random subset of indigenous aromatic rice germplasm along with a few exotic aromatic accessions. Use of functional markers of four badh2 alleles identified that the test panel possessed only two alleles, badh2-E7 and badh2-p-5'UTR. Two other alleles, badh2.2 and badh2-E4-5.2 were absent. Based on the alleles present, four functional polymorphisms (FP) were detected, namely FP1 to FP4. 188 genotypes possessed FP1 having both the badh2-p-5'UTR and badh2-E7 (71.8%) alleles. The badh2 allele with FP1 is named badh2-E7-p. 39 genotypes (14.9%) possessed only the badh2-p-5'UTR allele (FP3), while three genotypes were found to carry only the badh2-E7 allele (FP2). We also found that 32 genotypes (12.2%) did not have any of the target aroma alleles tested in this study (FP4). Interestingly, for badh2-p-5'UTR marker, the expected 198 bp amplicon for the non-aromatic allele could not be detected among any of the genotypes tested. Instead, an amplicon of 456 bp length appeared with 100% presence in the non-aromatic checks. Notwithstanding, the 456 bp allele also showed a 16% presence among the aromatic lines. This article forms the first report of this allele, named badh2-p1, among aromatic rice. Quantification of 2-Acetyl-1-Pyrroline (2AP) content and sensory evaluation among the test genotypes showed that those with FP1 are highly aromatic than the genotypes carrying other types of FPs. But, a few strongly aromatic lines showed lower 2AP content. The BADH2 characterization carried out in this study is suggestive of identifying the additional gene(s)/ allele(s) governing aroma among the Indian fragrant rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01181-9.

Impact of the Combined Application of Biochar and Compost on Mine Soil Quality and Growth of Lady's Finger (Abelmoschus esculentus).

Amelioration of mine soil is challenging because of the lack of biologically active organic matter. The study was aimed to recycle yard waste into compost and biochar and to use them to reclaim mine soil. Biochar prepared at 350 °C showed the highest stable organic matter yield index and was used for the experiments. Lady's finger was grown on mine soil amended with biochar (1%-5%), compost (2%-10%), and biochar-compost mixtures (2%-10%). Mine soil pH increased in all treatments. Mine soil dehydrogenase activity (42%-224%), microbial biomass carbon (4%-257%), and hydrolase activity (3%-230%) increased by combined application of biochar and compost. Lady's finger plant height, biomass, and fruit yield were superior in biochar-compost mixtures compared to biochar and compost alone treatment. Thus the use of compost along with biochar could be recommended for reclamation of mine soil.

Mechanistic exploration of the activities of poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid against hepatocellular carcinoma at cellular and molecular levels.

The effectiveness of betulinic acid (B) and PLGA loaded nanoparticles of B (Bnp) against hepatocellular carcinoma (HCC) was established and reported earlier. In continuation of our previous report, the present study described the molecular mechanisms of their antineoplastic responses. In this context, the antineoplastic properties of both B and Bnp were evaluated on DEN-induced HCC rat model. The quantitative real-time polymerase chain reaction and western blot analyses revealed that HCC was developed through lower expressions of e-NOS, BAX, BAD, Cyt C and higher expressions of i-NOS, Bcl-xl, Bcl-2. B and Bnp normalised the expressions of these apoptogenic markers. Particularly, both activated i-NOS and e-NOS mediated Bcl-2 family proteins→CytC→Caspase 3 and 9 signalling cascades. The 1H-NMR-based metabolomics study also demonstrated that the perturbed metabolites in DEN-induced rat serum restored to the normal level following both treatments. Moreover, the antineoplastic potential of Bnp was found to be comparable with the marketed product, 5-flurouracil.

Sulphur in Jharia and Raniganj coalfields: Chemical fractionation and its environmental implications.

In coal, total sulphur content is not the only important factor for the industry, but also the forms of sulphur and their distributions should be considered before utilizing any coal for a particular use. In Jharia and Raniganj coalfields, sulphur is present in the forms of organic sulphur (OS), pyritic sulphur (PS), and sulphate sulphur (SS). In this perspective, the present study aims to know the different forms of sulphur in coking and non-coking coals of Jharia and Raniganj coalfields. Twenty samples were collected from both the mining areas. The total sulphur content in coking coals varied from 0.28% to 0.55% and in non-coking coals it varied from 0.33% to 0.54%. The distribution pattern of sulphur showed that PS and OS are dominating in both the coalfields. The OS in Jharia field varied from 0.13% to 0.47%, and in Raniganj coalfield it varied from 0.19% to 0.41%. This depicts that both the coalfields were formed under freshwater condition. Similarly, PS varied from 0.01% to 0.21% and from 0.06% to 0.29%, and SS varied from 0.0052% to 0.01% and 0.005%-0.02% in the above fields, respectively. It is noticed that the content of sulphate sulphur is less than 0.1 wt%, which is lower than other forms of sulphur. In the past two decades, sulphur emission has increased with the increase of thermal power plants due to more demand for power, which is one of the causes of global warming. During coal combustion, H2S and SOx, are produced and that can react with O2 and H2O to form H2SO3, H2SO4 or H2S. Thus, sulphur release can respond within the ecosystem in the form of acidic precipitation that may acidify and affect lakes and streams, sub-surface water and historical monuments. In India, coal consumption and ecological contaminations are increasing day by day due to the rapid energy consumption. Therefore, special attention should be given to adopt clean coal technologies though the coal contains less sulphur.

Drought Tolerant Near Isogenic Lines of Pusa 44 Pyramided With qDTY2.1 and qDTY3.1, Show Accelerated Recovery Response in a High Throughput Phenomics Based Phenotyping.

Reproductive stage drought stress (RSDS) is a major challenge in rice production worldwide. Cultivar development with drought tolerance has been slow due to the lack of precise high throughput phenotyping tools to quantify drought stress-induced effects. Most of the available techniques are based on destructive sampling and do not assess the progress of the plant's response to drought. In this study, we have used state-of-the-art image-based phenotyping in a phenomics platform that offers a controlled environment, non-invasive phenotyping, high accuracy, speed, and continuity. In rice, several quantitative trait loci (QTLs) which govern grain yield under drought determine RSDS tolerance. Among these, qDTY2.1 and qDTY3.1 were used for marker-assisted breeding. A set of 35 near-isogenic lines (NILs), introgressed with these QTLs in the popular variety, Pusa 44 were used to assess the efficiency of image-based phenotyping for RSDS tolerance. NILs offered the most reliable contrast since they differed from Pusa 44 only for the QTLs. Four traits, namely, the projected shoot area (PSA), water use (WU), transpiration rate (TR), and red-green-blue (RGB) and near-infrared (NIR) values were used. Differential temporal responses could be seen under drought, but not under unstressed conditions. NILs showed significant level of RSDS tolerance as compared to Pusa 44. Among the traits, PSA showed strong association with yield (80%) as well as with two drought tolerances indices, stress susceptibility index (SSI) and tolerance index (TOL), establishing its ability in identifying the best drought tolerant NILs. The results revealed that the introgression of QTLs helped minimize the mean WU per unit of biomass per day, suggesting the potential role of these QTLs in improving WU-efficiency (WUE). We identified 11 NILs based on phenomics traits as well as performance under imposed drought in the field. The study emphasizes the use of phenomics traits as selection criteria for RSDS tolerance at an early stage, and is the first report of using phenomics parameters in RSDS selection in rice.

Race to arsenal COVID-19 therapeutics: Current alarming status and future directions.

The on-going pandemic of COVID-19 wreaked by a viral infection of SARS-CoV-2, has generated a catastrophic plight across the globe. Interestingly, one of the hallmarks of COVID-19 is the so-called 'cytokine storm' due to attack of SARS-Cov-2 in the lungs. Considering, mesenchymal stem cells (MSCs) therapy could contribute against SARS-CoV-2 viruses attack because of their immune modulatory and anti-inflammatory ability linked to their stemness, to the arsenal of treatments for COVID-19. Another novel therapeutic strategies include the blockade of rampant generation of pro-inflammatory mediators like acute respiratory distress syndrome (ARDS), degradation of viral protein capsids by PROTACs, composed of Ubiquitin-proteasome framework, and ubiquitination-independent pathway directing the SARS-CoV-2 nucleocapsid protein (nCoV N) and proteasome activator (PA28γ), etc. This review is consequently an endeavour to highlight the several aspects of COVID-19 with incorporation of important treatment strategies discovered to date and putting the real effort on the future directions to put them into the perspective.

Heterologous expression and characterization of novel manganese superoxide dismutase (Mn-SOD) - A potential biochemical marker for heat stress-tolerance in wheat (Triticum aestivum).

Heat stress causes oxidative bursts damaging the organelles and nascent proteins. Plants have inherited antioxidant defense system to neutralize the effect of reactive oxygen species. Superoxide dismutase provides first line of defense against the HS by regulating the accumulation of peroxide radicals inside the cells. Here, we report identification and cloning of putative manganese superoxide dismutase (Mn-SOD) gene of ~733 nt from wheat cv. HD2985 through de novo assembly. The gene was observed to localize on Chr 6D with a mitochondrial targeting peptide sequence and iron/manganese domain. We predicted 147 homologs of Mn-SOD in eukaryotes with diverse speciation nodes. A recombinant Mn-SOD protein of ~25.5 kDa was purified through heterologous expression system. Kinetics assay of recombinant protein showed optimum pH of 8.0, optimum temperature of 35 °C and Km and Vmax values of 1.51 µM and 9.45 U/mg proteins, respectively. Maximum expression and activity of Mn-SOD was observed in leaves from Raj3765, as compared to stem and spike during milky-ripe stage under differential HS. In gel activity assay showed the appearance of all the three isoforms of SOD in thermotolerant cv. under HS. Mn-SOD, being active at pivotal position, can be also used as potential biochemical marker in wheat breeding program.

Genome-wide analysis of polymorphisms identified domestication-associated long low-diversity region carrying important rice grain size/weight quantitative trait loci.

Rice grain size and weight are major determinants of grain quality and yield and so have been under rigorous selection since domestication. However, the genetic basis for contrasting grain size/weight trait among Indian germplasms and their association with domestication-driven evolution is not well understood. In this study, two long (LGG) and two short grain (SGG) genotypes were resequenced. LGG (LGR and PB 1121) differentiated from SGG (Sonasal and Bindli) by 504 439 single nucleotide polymorphisms (SNPs) and 78 166 insertion-and-deletion polymorphisms. The LRK gene cluster was different and a truncation mutation in the LRK8 kinase domain was associated with LGG. Phylogeny with 3000 diverse rice accessions revealed that the four sequenced genotypes belonged to the japonica group and were at the edge of the clades indicating them to be the potential source of genetic diversity available in Indian rice germplasm. Six SNPs were significantly associated with grain size/weight and the top four of these could be validated in mapping a population, suggesting this study as a valuable resource for high-throughput genotyping. A contiguous long low-diversity region (LDR) of approximately 6 Mb carrying a major grain weight quantitative trait loci (harbouring OsTOR gene) was identified on Chromosome 5. This LDR was identified as an evolutionary important site with significant positive selection and multiple selection sweeps, and showed association with many domestication-related traits, including grain size/weight. The aus population retained more allelic variations in the LDR than the japonica and indica populations, suggesting it to be one of the divergence loci. All the data and analyses can be accessed from the RiceSzWtBase database.

Supra-patellar nailing for isolated closed tibial shaft fractures: Medium term functional outcomes from an Academic Level 1 Trauma centre.

Aims The aim of this study was to assess functional outcome, at medium-term follow up, in patients undergoing intra-medullary nailing of tibial shaft fractures, using the supra-patellar approach. Materials and methods The study included patients with intra-medullary nailing, for diaphysial tibia fractures, between March 2013 to August 2015. An initial audit compared short-term functional outcomes at 15 months, between the supra and infra-patellar approaches, using a cohort of 20 patients (10 in each group). Subsequently, a larger cohort of 22 patients with supra-patellar nailing, were reviewed for medium term assessment of their functional outcomes at average 60 months (50 - 78 months) and the results between all 3 groups were compared. All patients were assessed using the Kujala and Oxford Knee Scores. Results The mean age of the cohorts was 38 years (18-87years). The mean follow-up was 15 months for the initial audit and 60 months for the medium-term results. The initial audit showed that the supra-patellar group had statistically significantly better Oxford and Kujala scores when compared to infra-patellar group (p < 0.05). At 5 years following supra-patellar nailing, the medium-term cohort showed improved outcome scores compared to the infra-patellar group at 1 year (p < 0.01) but showed no difference with the supra-patellar group at 1 year (p value >0.1). Conclusion Our study suggests that patients undergoing supra-patellar tibial nailing have better outcomes at 15 months compared to traditional infra-patellar nailing and more importantly, they continue to do well even at 5 years, despite perceived risks associated with this technique.

Author Correction: Novel Indole-fused benzo-oxazepines (IFBOs) inhibit invasion of hepatocellular carcinoma by targeting IL-6 mediated JAK2/STAT3 oncogenic signals.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Deciphering signalling network in broad spectrum Near Isogenic Lines of rice resistant to Magnaporthe oryzae.

Disease resistance (R) genes like Pi9, Pita, Pi21, Pi54 are playing important role for broad spectrum blast resistance in rice. Development of near isogenic lines (NILs) using these type of broad spectrum genes and understanding their signalling networks is essential to cope up with highly evolving Magnaporthe oryzae strains for longer duration. Here, transcriptional-level changes were studied in three near-isogenic lines (PB1 + Pi1, PB1 + Pi9 and PB1 + Pi54) of rice resistant to blast infection, to find the loci that are unique to resistant lines developed in the background of Pusa Basmati 1 (PB1). The pathway analysis of loci, unique to resistant NILs compared to susceptible control revealed that plant secondary metabolite synthesis was the common mechanism among all NILs to counter against M. oryzae infection. Comparative transcriptome analysis helped to find out common clusters of co-expressed significant differentially expressed loci (SDEL) in both PB1 + Pi9 and PB1 + Pi54 NILs. SDELs from these clusters were involved in the synthesis and degradation of starch; synthesis and elongation of fatty acids; hydrolysis of phospholipids; synthesis of phenylpropanoid; and metabolism of ethylene and jasmonic acid. Through detailed analysis of loci specific to each resistant NIL, we identified a network of signalling pathways mediated by each blast resistance gene. The study also offers insights into transcriptomic dynamics, points to a set of important candidate genes that serve as module to regulate the changes in resistant NILs. We suggest that pyramiding of the blast resistance gene Pi9 with Pi54 will lead to maximum broad spectrum resistance to M. oryzae.

Antineoplastic properties of zafirlukast against hepatocellular carcinoma via activation of mitochondrial mediated apoptosis.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwideand haslimited treatment options. In view of this, zafirlukast (ZAF) was administered orally to DEN-induced HCC rats to evaluate its antineoplastic properties. ELISA, qRT-PCR and Western blot were used to determine the molecular mechanism associated with ZAF therapy for HCC. We found that HCC developed as a result of lower expression of caspases 3 and 9, but their levels returned to normal when the expression of eNOS, BAX, BAD, and Cyt C was decreased and when the expression of iNOS, Bcl-xl, and Bcl-2 was increased. Again, ZAF (80 mg/kg dose) treatment normalized the expression of caspase-mediated apoptotic factors, i.e. BAX and Bcl-2 proteins, as established through Western blot analysis. Later, 1H NMR-based serum metabolomics study revealed that levels of perturbed metabolites in DEN-induced rat serum returned to normal after ZAF administration. Altogether, the antineoplastic potential of ZAF was found to be comparable, and to some degree better, than the marketed chemotherapeutic 5-flurouracil, which may be beneficial for anti-HCC treatment from a future drug design perspective.

Zolmitriptan attenuates hepatocellular carcinoma via activation of caspase mediated apoptosis.

A preclinical study using DEN-induced HCC rat model was attempted to evaluate the antitumor potential of zolmitriptan (ZOL). The molecular insights were investigated using ELISA, qRT-PCR and Western blot techniques. The result confirmed that the HCC condition was developed in response to lower expressions of caspase 3 and 9 which, in turn, was due to the upstream regulation of iNOS, Bcl-xl and Bcl-2, and downstream regulation of eNOS, BAX, BAD and Cyt C. The treatment with ZOL caused the significant activation of caspase mediated apoptotic signals that could be responsible for its anti-HCC potential. Later, 1H NMR based serum metabolomics study confirmed that ZOL restored the perturbed metabolites associated with DEN-induced HCC. The antineoplastic potential of ZOL was found comparable or to some degree better than the marketed chemotherapeutics, 5-flurouracil.