In vitro cytotoxicity, in vivo pharmacokinetic studies and tissue distribution studies of multifunctional citric acid dendrimers using the drug Cytarabine

Dendrimers are considered the emerging polymeric architectures, known for their well defined molecular-weight, polydispersity, uniformity and high-surface functionality. These nano-architectures are capable of encapsulating low-high molecular-weight drug moieties in their interior or exterior through covalent bonding and host-guest interactions. Further, large surface volume made researchers to implicate dendrimers in biomedical and therapeutic applications. Regardless of the massive applications, sometimes its use is limited because of the cytotoxicity produced.  Considering this, the present research is focused on the synthesis and PEGylation of citric acid dendrimers. PEGylation is an act of conjugating polyethylene glycol to dendrimers that completely eliminates the toxicity issues associated with dendrimers and render them biocompatible. Cytarabine was loaded in the dendritic architecture to target specifically the tumor cells. Dendrimers are made tumor specific by incorporating certain agents that get cleaved in tumor environment. Synthesized dendrimers were studied for its effect on acute cytotoxicity, tissue-distributions and pharmacokinetic parameters

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy

Efficacy of Major Plant Extracts/Molecules on Field Insect Pests

Insect pests are considered the major hurdle in enhancing the production and productivity of any farming system. The use of conventional synthetic pesticides has led to the emergence of pesticide-resistant insects, environmental pollution, and negative effects on natural enemies, which have caused an ecological imbalance of the predator-prey ratio and human health hazards; therefore, eco-friendly alternative strategies are required. The plant kingdom, a rich repertoire of secondary metabolites, can be tapped as an alternative for insect pest management strategies. A number of plants have been documented to have insecticidal properties against various orders of insects in vitro by acting as antifeedants, repellents, sterilant and oviposition deterrents, etc. However, only a few plant compounds are applicable at the field level or presently commercialised. Here, we have provided an overview of the broad-spectrum insecticidal activity of plant compounds from neem, Annona, Pongamia, and Jatropha. Additionally, the impact of medicinal plants, herbs, spices, and essential oils has been reviewed briefl

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Not AvailableThe aim of the present study was to ascertain the effectiveness of seminal plasma mRNAs as markers to assess the reproductive performance of bulls. Semen samples (33 ejaculates) from 11 bulls were evaluated for sperm kinematic and functional parameters. Total RNA was isolated from cell-free seminal (cfs) using TRIzol LS reagent and the concentration of cfs-RNA was 24.4±2.3µgmL-1 seminal plasma. The cfs-RNA was fragmented to a size of 25-500bp. Of the cfs-mRNAs screened using real time PCR, expression of protamine 1 (PRM1) was positively (P2.5μm and straightness >85%) in raw semen was positively (P<0.05) associated with bone morphogenetic protein 2 (BMP2), ubiquitin conjugating enzyme E2D3 (UBE2D3), tumour-associated necrotic factor-associated death domain (TRADD) and caspase-3 (CASP3) expression. Nerve growth factor (NGF) expression was positively (P<0.05) associated with the maintenance of post-thaw functional membrane integrity in spermatozoa and could be used to assess the cryotolerance of bull semen. In conclusion, the expression of cfs mRNAs can be used to assess the reproductive performance of males and to predict the sensitivity of spermatozoa to cryoinjury.Not Availabl

Isolation and enrichment of putative spermatogonial stem cells from ram (Ovis aries) testis

Not AvailableThe present study aimed to isolate and enrich putative SSCs from ram testes, which are positive for promyelocytic leukaemia zinc-finger protein (PLZF). The putative SSCs were isolated using a combination of enzymes with different concentrations, collagenase (1 and 2 mg/ml), hyaluronidase (1 mg/ml) and trypsin (0.25 and 0.5 mg/ml). The isolated SSCs were purified using an extracellular matrix such as laminin (20 μg/ml), DSA-lectin (5 μg/ml) and gelatin (0.2%) in combination with BSA (0.5 mg/ml). The number of putative SSCs/ tubule was significantly (p < 0.05) higher in prepubertal (3.1 ± 0.51) and adult (3.45 ± 0.58) than the number of gonocytes/tubule in neonatal (0.59 ± 0.03) testis. Optimum enzyme combinations required for isolation of putative SSCs from prepubertal testis (collagenase; 2 mg/ml and trypsin; 0.5 mg/ml) were different from adult testis (collagenase; 1 mg/ml, trypsin; 0.25 mg/ml and hyaluronidase; 1 mg/ml). Though the number of putative SSCs/tubule was comparable in prepubertal and adult animals, a significantly (p < 0.05) higher percentage of putative SSCs (7.33 Vs 0.47%) were isolated from prepubertal testis than the adult. Differential plating using laminin along with BSA resulted in a significantly (p < 0.05) higher number of putative SSCs. The enzyme combinations suitable for isolation of putative SSCs from prepubertal testis are different from adult ram testis and the laminin has been found to be effective for purification of putative SSCs from testicular cells isolatesICAR-NIAN

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Not AvailableBacterial blight (BB) of rice caused by the pathogen Xanthomonas oryzae pv. oryzae and the insect gall midge (GM) (Orseolia oryzae) are two major constraints of rice production. The present study was carried out to improve RPHR-1005, a stable restorer line of the fine-grain-type rice hybrid DRRH-3, for BB and GM resistance through marker-assisted backcross breeding (MABB). Two major GM resistance genes, Gm4 and Gm8, and a major BB resistance gene, Xa21, were selected as target genes for transfer to RPHR-1005. Two sets of backcrosses were carried out to combine either Xa21 + Gm4 or Xa21+ Gm8 into RPHR-1005 using breeding lines in the genetic background of ISM possessing either Gm4 or Gm8 along with Xa21. Foreground selection was performed for Xa21, Gm4, Gm8, and the major fertility restorer genes Rf3 and Rf4 using gene-specific markers, while 61 polymorphic simple sequence repeat (SSR) markers were used for background selection and marker-assisted backcrossing was continued until BC2 generation. A promising homozygous backcross-derived plant at the BC2F2 generation possessing Xa21 + Gm4, and another possessing Xa21 + Gm8, were intercrossed to stack the target resistance genes. At ICF 4 (inter-crossed F4) , three promising lines possessing the three target resistance genes in a homozygous condition along with fine-grain type, complete fertility restoration, and better panicle exsertion than RPHR-1005 have been identified. Among these, a single line, # RPIC-16-65-125, showed better yield, was highly resistant to BB and GM, was of medium–slender grain type, and had complete fertility restoration along with better panicle exsertion and taller plant type than RPHR-1005. This is the first report of combining resistance against BB and GM in the genetic background of a hybrid rice parental line.Department of Biotechnology (DBT), Government of India # BT/PR11705/AGR/02/646/200