Intramuscular (infiltrating) Lipoma

Intraoral lipomas are benign and relatively rare tumors, although they occur with higher frequencies in other areas, most especially the back, abdomen and shoulders of adults. They have no gender predilection and predominantly affect the buccal mucosa. This paper describes a case of intramuscular (infiltrating) lipoma on the buccal mucosa of a 60-year old male which is relatively rare when compared to simple lipoma of buccal mucosa, and review pertinent literature

Development, characterization, efficacy and repeated dose toxicity of nanoemulsified ethanolic extract of Enicostemma littorale in Streptozotocin-induced diabetes rats.

Alginate nanocapsules of ethanolic extract of Enicostemma littorale (NEL) were prepared by emulsification, cross linking with calcium chloride and solvent removal. Based on total phenol content the loading efficiency of the nanocapsules was 89% at an optimum concentration of 2: 18 (mg ml -1) for plant extract: olive oil. The photon correlation spectroscopy (PCS) revealed that the mean particle diameter of optimized formulation was 233 nm and scanning electron microscopy (SEM) showed a spherical morphology. When subjected to Fourier transform infrared spectroscopy (FT-IR) for the compatability analysis between plant extract and sodium alginate, it revealed that the phytoconstituents were stable. The purpose of the present study was to compare the anti-diabetic activity of NEL and E.littorale (EL) in streptozoticin induced male rats. An oral dose of NEL (20 mg/kg b.w) and EL (2000 mg/kg b.w) showed a relatively similar antidiabetic effect, reducing the blood glucose, triglycerides, cholesterol, creatinine, ALT, AST, and ALP. Moreover, NEL is 100 times less than EL exhibiting better results within 10 days of treatment. These biochemical assessments were supported by rat biopsy examinations. In conclusion, the nanoemulsification method can be applied for poor water-soluble ethanolic herbal extracts to reduce the dosage and time

DEVELOPMENT OF STABILITY INDICATING RP-HPLC METHOD FOR THE SIMULTANEOUS ESTIMATION OF AMBROXOL HYDROCHLORIDE AND LEVOCETIRIZINE DIHYDROCHLORIDE

A simple, precise and accurate method has been developed for simultaneous estimation of Ambroxol hydrochloride and Levocetirizine dihydrochloride. The proposed RP-HPLC method utilises Enable C18 G column (250 x 4.6mm, 5m), mobile phase consisting of Phosphate buffer pH 3.0: Methanol in the ratio of 20:80 (v/v) and UV detection at 236nm using a photodiode array detector. ambroxol hydrochloride and levocetirizine dihydrochloride were exposed to acidic, alkali, oxidative, thermal and photolytic stress conditions and the stressed samples were analysed by the proposed method. Peak homogeneity data of ambroxol hydrochloride and levocetirizine dihydrochloride in the stressed samples demonstrated the specificity of the method for their estimation in presence of degradants. The described method was linear over a range of 15 45 g/mL for ambroxol hydrochloride and 1 3 g/mL for levocetirizine dihydrochloride respectively. The method validation data showed excellent results for accuracy, precision, linearity, specificity, limit of detection, limit of quantification and robustness. The present method can be successfully used for routine quality control and stability studies

Grain Legumes: Biotechnological Interventions in Crop Improvement for Adverse Environments

Grain legumes are the major food crops grown and consumed mostly by the poor farmers as an important source of protein in the drylands of the world. The ensuing climate change has posed serious potential threats to the cultivation of these crops that are important for the sustainable livelihoods of the poorest of the poor in these regions. There is evidence to suggest that the ecological dynamics and equilibriums are likely to be affected as a result of changing climate, either by making these crops susceptible to new diseases or by increasing the intensities of diseases, pests, and parasites. Despite many uncertainties, there is a growing consensus that these adversities could lead to an overall increase in the disease and pest pressure besides harsher abiotic stresses. Since most of the grain legumes have a narrow genetic base and levels of resistance to some biotic and abiotic constraints are low, making crop improvement an overarching research-for-development challenge for maximizing the benefits that grain legumes offer to smallholder farmers. Running against the headwinds, grain legume research has been immensely benefited by applications of modern biotechnological tools and approaches that have the potential to develop solutions for destructive diseases, besides making headway against the complex problems of drought. Similarly, identifying novel genes/traits and assessing their suitability as candidate genes for genetic engineering options will be important for future breeding programs in order to achieve remarkable impacts in these grain legume crops globally. This chapter mainly provides a comprehensive picture of the different biotechnological interventions adopted for addressing various constraints in gain legume productivity and improvement, highlighting the pitfalls and possible solutions that can be taken through an integrated approach to combat the altered environmental conditions

Breeding tomato (Solanum lycopersicum L.) for resistance to biotic and abiotic stresses

Tomato (Solanum lycopersicum L.) is an important vegetable crop cultivated in the tropical and sub-tropical regions of the world. Low productivity in India is due to occurrence of both biotic and abiotic stresses. Among the biotic stresses, tomato leaf curl disease, bacterial wilt, early blight and Groundnut Bud Necrosis Virus disease have become serious production constraints causing considerable yield loss in the major tomato growing areas of the country. Adoption of multiple disease resistant varieties or F1 hybrids would be the most appropriate way to address these diseases. At ICAR-IIHR, Bengaluru systematic breeding strategies were employed to pyramid genes for resistance to early blight, bacterial wilt and tomato leaf curl diseases and to develop advanced breeding lines& F1 hybrids with triple disease resistance. Stable source of resistance to early blight and bi-partite begomo-virus (Tomato Leaf Curl New Delhi Virus) has been identified in Solanum habrochaites LA-1777. Validation with molecular markers linked to tomato leaf curl virus resistance revealed that LA-1777 carryTy2 and other putative resistant genes. Several high yielding dual purpose hybrids were also developed for fresh market and processing with high level of resistance to multiple diseases. Cherry tomato lines have also been bred for high TSS, total carotenoids, total phenols, flavonoids, vitamin C, acidity and lycopene content. IIHR-249-1, IIHR-2101 (Solanum habrochaites LA-1777), IIHR- 2866 and IIHR-2864 recorded high values for quality parameters like total carotenoids, lycopene, vitamin C, total phenols, flavonoids and TSS. Drought tolerant root stock has been developed by an interspecific cross between S. habrochaites LA-1777 and S. lycopersicum (15 SB SB). Resistant sources have also been identified against Tuta absoluta, a serious insect pest reported from major tomato growing areas in the country in recent time. High temperature tolerant breeding lines are in pipe line

Nocardia transvalensis keratitis: an emerging pathology among travelers returning from Asia

<p>Abstract</p> <p>Background</p> <p>The incidence rate of <it>Nocardia </it>keratitis is increasing, with new species identified thanks to molecular methods. We herein report a case of <it>Nocardia transvalensis </it>keratitis, illustrating this emerging pathology among travellers returning from Asia.</p> <p>Case presentation</p> <p>A 23-year-old man presented with a 10-week history of ocular pain, redness, and blurred vision in his right eye following a projectile foreign body impacting the cornea while motor biking in Thaïland. At presentation, a central epithelial defect with a central whitish stromal infiltrate associated with pinhead satellite infiltrates was observed. Identification with 16S rRNA PCR sequencing and microbiological culture of corneal scraping and revealed <it>N. transvalensis </it>as the causative organism. Treatment was initiated with intensive topical amikacin, oral ketoconazole and oral doxycycline. After a four-week treatment period, the corneal infiltrate decreased so that only a faint subepithelial opacity remained.</p> <p>Conclusion</p> <p><it>Nocardia </it>organisms should be suspected as the causative agent of any case of keratitis in travelers returning from Asia. With appropriate therapy, <it>Nocardia </it>keratitis resolves, resulting in good visual outcome.</p

Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

Tumor oncogenes include transcription factors that co-opt the general transcriptional machinery to sustain the oncogenic state1, but direct pharmacological inhibition of transcription factors has thus far proven difficult2. However, the transcriptional machinery contains various enzymatic co-factors that can be targeted for development of new therapeutic candidates3, including cyclin-dependent kinases (CDKs)4. Here we present the discovery and characterization of the first covalent CDK7 inhibitor, THZ1, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7. Cancer cell line profiling indicates that a subset of cancer cell lines, including T-ALL, exhibit exceptional sensitivity to THZ1. Genome-wide analysis in Jurkat T-ALL shows that THZ1 disproportionally affects transcription of RUNX1 and suggests that sensitivity to THZ1 may be due to vulnerability conferred by the RUNX1 super-enhancer and this transcription factor’s key role in the core transcriptional regulatory circuitry of these tumor cells. Pharmacological modulation of CDK7 kinase activity may thus provide an approach to identify and treat tumor types exhibiting extreme dependencies on transcription for maintenance of the oncogenic state

Systemic Inflammation and the Increased Risk of Inflamm-Aging and Age-Associated Diseases in People Living With HIV on Long Term Suppressive Antiretroviral Therapy.

The ART program in low- and middle-income countries (LMIC) like India, follows a public health approach with a standardized regimen for all people living with HIV (PLHIV). Based on the evidence from high-income countries (HIC), the risk of an enhanced, and accentuated onset of premature-aging or age-related diseases has been observed in PLHIV. However, very limited data is available on residual inflammation and immune activation in the populations who are on first-generation anti-HIV drugs like zidovudine and lamivudine that have more toxic side effects. Therefore, the aim of the present study was to evaluate the levels of systemic inflammation and understand the risk of age-associated diseases in PLHIV on long-term suppressive ART using a large number of biomarkers of inflammation and immune activation. Blood samples were obtained from therapy naïve PLHIV (Pre-ART, = 43), PLHIV on ART for >5 years (ART, = 53), and HIV-negative healthy controls (HIVNC, = 41). Samples were analyzed for 92 markers of inflammation, sCD14, sCD163, and telomere length. Several statistical tests were performed to compare the groups under study. Multivariate linear regression was used to investigate the associations. Despite a median duration of 8 years of successful ART, sCD14 ( < 0.001) and sCD163 ( = 0.04) levels continued to be significantly elevated in ART group as compared to HIVNC. Eleven inflammatory markers, including 4E-BP1, ADA, CCL23, CD5, CD8A, CST5, MMP1, NT3, SLAMF1, TRAIL, and TRANCE, were found to be significantly different ( < 0.05) between the groups. Many of these markers are associated with age-related co-morbidities including cardiovascular disease, neurocognitive decline and some of these markers are being reported for the first time in the context of HIV-induced inflammation. Linear regression analysis showed a significant negative association between HIV-1-positivity and telomere length ( < 0.0001). In ART-group CXCL1 ( = 0.048) and TGF-α ( = 0.026) showed a significant association with the increased telomere length and IL-10RA was significantly associated with decreased telomere length ( = 0.042). This observation warrants further mechanistic studies to generate evidence to highlight the need for enhanced treatment monitoring and special interventions in HIV-infected individuals

Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

Tumour oncogenes include transcription factors that co-opt the general transcriptional machinery to sustain the oncogenic state, but direct pharmacological inhibition of transcription factors has so far proven difficult. However, the transcriptional machinery contains various enzymatic cofactors that can be targeted for the development of new therapeutic candidates, including cyclin-dependent kinases (CDKs). Here we present the discovery and characterization of a covalent CDK7 inhibitor, THZ1, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7. Cancer cell-line profiling indicates that a subset of cancer cell lines, including human T-cell acute lymphoblastic leukaemia (T-ALL), have exceptional sensitivity to THZ1. Genome-wide analysis in Jurkat T-ALL cells shows that THZ1 disproportionally affects transcription of RUNX1 and suggests that sensitivity to THZ1 may be due to vulnerability conferred by the RUNX1 super-enhancer and the key role of RUNX1 in the core transcriptional regulatory circuitry of these tumour cells. Pharmacological modulation of CDK7 kinase activity may thus provide an approach to identify and treat tumour types that are dependent on transcription for maintenance of the oncogenic state.National Institutes of Health (U.S.) (Grant HG002668)National Institutes of Health (U.S.) (Grant CA109901

High Resolution Methylome Map of Rat Indicates Role of Intragenic DNA Methylation in Identification of Coding Region

DNA methylation is crucial for gene regulation and maintenance of genomic stability. Rat has been a key model system in understanding mammalian systemic physiology, however detailed rat methylome remains uncharacterized till date. Here, we present the first high resolution methylome of rat liver generated using Methylated DNA immunoprecipitation and high throughput sequencing (MeDIP-Seq) approach. We observed that within the DNA/RNA repeat elements, simple repeats harbor the highest degree of methylation. Promoter hypomethylation and exon hypermethylation were common features in both RefSeq genes and expressed genes (as evaluated by proteomic approach). We also found that although CpG islands were generally hypomethylated, about 6% of them were methylated and a large proportion (37%) of methylated islands fell within the exons. Notably, we obeserved significant differences in methylation of terminal exons (UTRs); methylation being more pronounced in coding/partially coding exons compared to the non-coding exons. Further, events like alternate exon splicing (cassette exon) and intron retentions were marked by DNA methylation and these regions are retained in the final transcript. Thus, we suggest that DNA methylation could play a crucial role in marking coding regions thereby regulating alternative splicing. Apart from generating the first high resolution methylome map of rat liver tissue, the present study provides several critical insights into methylome organization and extends our understanding of interplay between epigenome, gene expression and genome stability