Innovations in nanoscience for the sustainable development of food and agriculture with implications on health and environment.

A rapid increase in world population is leading to the rise in global demand of food and agriculture (agri) products. Nanotechnology and its applications have emerged as one of the most pioneering and promising technology for transforming conventional food and agri industries, with the aim of sustainable farming, improving the food security, quality and safety which could revolutionize the food and agri industries. Current developments in nanotechnology have led to the new paths progressively and bringing the radical changes the way food is perceived throughout the farming, transportation, processing, packaging, storage, monitoring and consumption. This review brings the current updates on novel nanomaterials in food and agri industries. Emphasis is given on the importance of nanotechnological applications, offering complete food solutions from farm to fork; including nutraceutical and functional foods, improving bioavailability, efficiency, nutritional status, nano-additives, food texture, color, taste and packaging. Agricultural sector also witnessed several nano-based products, such as nano-fertilizer, nano-pesticide, nano growth promoters and many more for the development of sustainable farming and crop improvement. Despite of numerous advantages of nanotechnology, there are still toxicity challenges, safety concerns, which needs to be addressed and demands transformations in regulatory policies. Rapid development is projected to transform several foods and agri sectors, with rapid increase in market stake and investment. Government agencies, private research centers as well as academicians are also coming together to explore the benefits of nanotechnology to improve food scarcity in the coming years.

HIV-1 Escape from Small-Molecule Antagonism of Vif.

The HIV-1 accessory protein Vif, which counteracts the antiviral action of the DNA-editing cytidine deaminase APOBEC3G (A3G), is an attractive and yet unexploited therapeutic target. Vif reduces the virion incorporation of A3G by targeting the restriction factor for proteasomal degradation in the virus-producing cell. Compounds that inhibit Vif-mediated degradation of A3G in cells targeted by HIV-1 would represent a novel antiviral therapeutic. We previously described small molecules with activity consistent with Vif antagonism. In this study, we derived inhibitor escape HIV-1 variants to characterize the mechanism by which these novel agents inhibit virus replication. Here we show that resistance to these agents is dependent on an amino acid substitution in Vif (V142I) and on a point mutation that likely upregulates transcription by modifying the lymphocyte enhancing factor 1 (LEF-1) binding site. Molecular modeling demonstrated a docking site in the Vif-Elongin C complex that is disrupted by these inhibitors. This docking site is lost when Vif acquires the V142I mutation that leads to inhibitor resistance. Competitive fitness experiments indicated that the V142I Vif and LEF-1 binding site mutations created a virus that is better adapted to growing in the presence of A3G than the wild-type virus.IMPORTANCE Although antiretroviral therapy can suppress HIV-1 replication effectively, virus reservoirs persist in infected individuals and virus replication rapidly rebounds if therapy is interrupted. Currently, there is a need for therapeutic approaches that eliminate, reduce, or control persistent viral reservoirs if a cure is to be realized. This work focuses on the preclinical development of novel, small-molecule inhibitors of the HIV-1 Vif protein. Vif inhibitors represent a new class of antiretroviral drugs that may expand treatment options to more effectively suppress virus replication or to drive HIV-1 reservoirs to a nonfunctional state by harnessing the activity of the DNA-editing cytidine deaminase A3G, a potent, intrinsic restriction factor expressed in macrophage and CD4+ T cells. In this study, we derived inhibitor escape variants to characterize the mechanism by which these novel agents inhibit virus replication and to provide evidence for target validation.

Outcome of focal treatment to residual retinoblastoma after chemotherapy (Experience with Focal Treatment of Retinoblastoma).

We report a prospective case series on the anatomical, and functional outcomes, and complications of focal treatment of retinoblastoma to residual tumors in patients who had already received chemotherapy. We examined the patients of retinoblastoma under general anaesthesia with Ret Cam II. Patients with lesions from Group 1 to Group 5 of Reese Ellsworth classification at presentation. They were first given chemotherapy according to VEC (Vincristine, Etoposide and Carboplatin) protocol and then focal treatment. Solid State Green laser photocoagulation and/or cryotherapy were applied to the lesions with help of indirect ophthalmoscope. Thirty one eyes of 26 children were treated. The mean age at presentation was 35.5 ± 6.4 (median = 24, IQR = 36) months. Fourteen (57.7%) were male and 12 (42.3%) were female. Twenty three (88.5%) children had bilateral retinoblastoma and 3 (11.5%) had unilateral involvement. Complete regression was achieved in 25 (80.6%) eyes. Only 6 (19.4%) eyes had to be enucleated. Final mean LogMAR visual acuity after treatment was0.6 ± 0.64. Transient Corneal oedema was the most commonly observed adverse effect seen immediately after laser photocoagulation in 12 (38.7%) eyes. Focal treatment is a good and effective adjuvant to systemic treatment and ophthalmologists should be aware of this modality of treatment and competent enough to use these modalities appropriately to improve the outcome of RB patients in our population.

1,2,3-Triazoles as Amide Bioisosteres: Discovery of a New Class of Potent HIV-1 Vif Antagonists.

RN-18 based viral infectivity factor (Vif), Vif antagonists reduce viral infectivity by rescuing APOBEC3G (A3G) expression and enhancing A3G-dependent Vif degradation. Replacement of amide functionality in RN-18 (IC50 = 6 µM) by isosteric heterocycles resulted in the discovery of a 1,2,3-trizole, 1d (IC50 = 1.2 µM). We identified several potent HIV-1 inhibitors from a 1d based library including 5ax (IC50 = 0.01 µM), 5bx (0.2 µM), 2ey (0.4 µM), 5ey (0.6 µM), and 6bx (0.2 µM).

8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells.

Ras converting enzyme 1 (Rce1) is an endoprotease that catalyzes processing of the C-terminus of Ras protein by removing -aaX from the CaaX motif. The activity of Rce1 is crucial for proper localization of Ras to the plasma membrane where it functions. Ras is responsible for transmitting signals related to cell proliferation, cell cycle progression, and apoptosis. The disregulation of these pathways due to constitutively active oncogenic Ras can ultimately lead to cancer. Ras, its effectors and regulators, and the enzymes that are involved in its maturation process are all targets for anti-cancer therapeutics. Key enzymes required for Ras maturation and localization are the farnesyltransferase (FTase), Rce1, and isoprenylcysteine carboxyl methyltransferase (ICMT). Among these proteins, the physiological role of Rce1 in regulating Ras and other CaaX proteins has not been fully explored. Small-molecule inhibitors of Rce1 could be useful as chemical biology tools to understand further the downstream impact of Rce1 on Ras function and serve as potential leads for cancer therapeutics. Structure-activity relationship (SAR) analysis of a previously reported Rce1 inhibitor, NSC1011, has been performed to generate a new library of Rce1 inhibitors. The new inhibitors caused a reduction in Rce1 in vitro activity, exhibited low cell toxicity, and induced mislocalization of EGFP-Ras from the plasma membrane in human colon carcinoma cells giving rise to a phenotype similar to that observed with siRNA knockdowns of Rce1 expression. Several of the new inhibitors were more effective at mislocalizing K-Ras compared to a potent farnesyltransferase inhibitor (FTI), which is significant because of the preponderance of K-Ras mutations in cancer.

Shellfish allergy and relation to iodinated contrast media: United Kingdom survey.

AIM: To assess current practice of United Kingdom cardiologists with respect to patients with reported shellfish/iodine allergy, and in particular the use of iodinated contrast for elective coronary angiography. Moreover we have reviewed the current evidence-base and guidelines available in this area. METHODS: A questionnaire survey was send to 500 senior United Kingdom cardiologists (almost 50% cardiologists registered with British Cardiovascular Society) using email and first 100 responses used to analyze practise. We involved cardiologists performing coronary angiograms routinely both at secondary and tertiary centres. Three specific questions relating to allergy were asked: (1) History of shellfish/iodine allergy in pre-angiography assessment; (2) Treatments offered for shellfish/iodine allergy individuals; and (3) Any specific treatment protocol for shellfish/iodine allergy cases. We aimed to establish routine practice in United Kingdom for patients undergoing elective coronary angiography. We also performed comprehensive PubMed search for the available evidence of relationship between shellfish/iodine allergy and contrast media. RESULTS: A total of 100 responses were received, representing 20% of all United Kingdom cardiologists. Ninety-three replies were received from consultant cardiologists, 4 from non-consultant grades and 3 from cardiology specialist nurses. Amongst the respondents, 66% routinely asked about a previous history of shellfish/iodine allergy. Fifty-six percent would pre-treat these patients with steroids and anti-histamines. The other 44% do nothing, or do nonspecific testing based on their personal experience as following: (1) Skin test with 1 mL of subcutaneous contrast before intravenous contrast; (2) Test dose 2 mL contrast before coronary injection; (3) Close observation for shellfish allergy patients; and (4) Minimal evidence that the steroid and anti-histamine regime is effective but it makes us feel better. CONCLUSION: There is no evidence that allergy to shellfish alters the risk of reaction to intravenous contrast more than any other allergy and asking about such allergies in pre-angiogram assessment will not provide any additional information except propagating the myth.

Extra-luminal Air Fluid Level on Abdominal X-ray of a Patient with Isolated Jejunal Blow Out: Case report.

Patients with trivial blunt abdominal trauma may present with isolated jejunal blow out (IJBO). A high index of suspicion is required as delayed presentation or delayed diagnosis may increase morbidity. Presentation with frank perforation peritonitis can be diagnosed by abdominal X-rays. We report the case of a patient who presented with features of peritonitis 10 days after being injured by a knee kick trauma. An erect abdominal X-ray showed extraluminal air-fluid levels, suggesting a hollow viscous injury which on exploration was found to be IJBO.

Lipoprotein(a) and SYNTAX Score Association with Severity of Coronary Artery Atherosclerosis in North India.

OBJECTIVES: This cross-sectional study investigated the association of lipoprotein(a) [Lp(a)] levels as an atherosclerosis predictor and their relationship to the severity of coronary artery disease (CAD). METHODS: 360 consecutive patients at Sanjay Gandhi Postgraduate Institute of Medical Sciences and King George's Medical University hospitals, Lucknow, North India, with chest pains, CAD symptoms and on lipid-lowering therapy were enrolled between June 2009 and October 2011. Before coronary artery angiography (CAG), a fasting blood sample was assessed for lipid and Lp(a) levels. The synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score was calculated according to the CAG results. Patients were divided into 3 groups based on CAD severity and SYNTAX scores. RESULTS: Angiography revealed CAD in 270 patients. Lp(a) levels were higher in CAD compared to non-CAD patients (48.7 ± 23.8 mg/dl versus 18.9 ± 11.1 mg/dl [P <0.0001]). The levels of Lp(a) were lower in single than in double and triple vessels (39.3 ± 18.4 mg/dl versus 58.0 ± 23.0 mg/dl, and 69.2 ± 24.1 mg/dl, [P <0.05]). Lp(a) levels were significantly higher in severe CAD with SYNTAX score >30 (88.0±24.0 mg/dl). Lp(a) levels correlated significantly with SYNTAX scores (r = 0.70, P <0.0001). CONCLUSION: In this study, Lp(a) levels were positively associated with a patient's SYNTAX score in diseased vessels. Furthermore, an elevated Lp(a) level was a causal, independent risk factor of CAD. Lowering Lp(a) levels would reduce CAD in primary and secondary prevention settings. There is an urgent need to define more precisely which patients to treat and which to target for earlier interventions.

SAR and Lead Optimization of an HIV-1 Vif-APOBEC3G Axis Inhibitor.

We describe structure-activity relationship and optimization studies of RN-18, an HIV-1 Vif-APOBEC3G axis inhibitor. Targeted modifications of RN-18 ring-C, ring-B, ring-A, bridge A-B, and bridge B-C were performed to identify the crucial structural features, which generated new inhibitors with similar (4g and 4i) and improved (5, 8b, and 11) activities. Two potent water-soluble RN-18 analogues, 17 and 19, are also disclosed, and we describe the results of pharmacological studies with compound 19. The findings described here will be useful in the development of more potent Vif inhibitors and in the design of probes to identify the target protein of RN-18 and its analogues.