Cancer remains a deadly disease for effective treatment. Although anomalous tumor microenvironment is now widely exploited for targeted chemotherapy, safe and efficacious drug delivery to tumor cells ...is not still warranted. Liposomes are promising biodegradable and biocompatible nanocarriers having potential amenability for surface and internal modifications, and extraordinary capability to carry both hydrophilic as well as hydrophobhic drugs. Meticulous fabrication of liposomes with tumor selective ligand(s) and PEGylation reduces immunogenicity and increase target-specificity. This review focuses on critical developmental aspects of liposomes to target cancer cells exploiting Enhanced Permeability and Retention (EPR) effect and tumor-selective ligands such as folate, transferrin, peptides etc. Moreover, stimuli-responsive smart liposomes (triggers: pH, temperature, enzymes, magnetic field, ultrasound, and redox potential etc.) are also investigated for enhancement of drug delivery to tumors. This review summarizes advances in tumor-targeted liposomes via various means of targeting. This knowledgeable assemblage of advances in liposomal approaches will render new insights to formulators and budding scientists to design cancer targeted liposomes.
In this work, we explored the acid-induced unfolding pathway of non-porin outer membrane protein (OMP), an immunogenic protein from Salmonella Typhi, by monitoring the conformational changes over a ...pH range of 1.0–7.0 by circular dichroism, intrinsic fluorescence, ANS binding, acrylamide quenching, and dynamic light scattering. The spectroscopic measurements showed that OMP in its native state at pH 7.0 exists in more stable and compact conformation. In contrast, at pH 2.0, OMP retains substantial amount of secondary structure, disrupted side chain interactions, increased hydrodynamic radii, and nearly four-fold increase in ANS fluorescence with respect to the native state, indicating that MG state exists at pH 2.0. Quenching of tryptophan fluorescence by acrylamide further confirmed the accumulation of a partially unfolded state between native and unfolded state. The effect of pH on the conformation and thermostability of OMP points towards its heat resistance at neutral pH (T ₘ ~ 69 °C at pH 7.0, monitored by change in MRE₂₂₂ ₙₘ). Acid unfolded state was also characterized by the lack of a cooperative thermal transition. All these results suggested that acid-induced unfolded state of OMP at pH 2.0 represented the molten globule state. The chemical denaturation studies with GuHCl and urea as denaturants showed dissimilar results. The chemical unfolding experiments showed that in both far-UV CD and fluorescence measurements, GuHCl is more efficient than urea. GuHCl is characterized by low C ₘ (~1 M), while urea is characterized by high C ₘ (~3 M). The fully unfolded states were reached at 2 M GuHCl and 4 M urea concentration, respectively. This study adds to several key considerations of importance in the development of therapeutic agents against typhoid fever for clinical purposes.
Salinity tolerance in rice is highly desirable to sustain production in areas rendered saline due to various reasons. It is a complex quantitative trait having different components, which can be ...dissected effectively by genome-wide association study (GWAS). Here, we implemented GWAS to identify loci controlling salinity tolerance in rice. A custom-designed array based on 6,000 single nucleotide polymorphisms (SNPs) in as many stress-responsive genes, distributed at an average physical interval of <100 kb on 12 rice chromosomes, was used to genotype 220 rice accessions using Infinium high-throughput assay. Genetic association was analysed with 12 different traits recorded on these accessions under field conditions at reproductive stage. We identified 20 SNPs (loci) significantly associated with Na(+)/K(+) ratio, and 44 SNPs with other traits observed under stress condition. The loci identified for various salinity indices through GWAS explained 5-18% of the phenotypic variance. The region harbouring Saltol, a major quantitative trait loci (QTLs) on chromosome 1 in rice, which is known to control salinity tolerance at seedling stage, was detected as a major association with Na(+)/K(+) ratio measured at reproductive stage in our study. In addition to Saltol, we also found GWAS peaks representing new QTLs on chromosomes 4, 6 and 7. The current association mapping panel contained mostly indica accessions that can serve as source of novel salt tolerance genes and alleles. The gene-based SNP array used in this study was found cost-effective and efficient in unveiling genomic regions/candidate genes regulating salinity stress tolerance in rice.
In the present investigation, GO was prepared by exfoliation of graphite using modified Hummer's method and then reduced using hydrazine hydrate (reducing agent) to produce rGO. XRD, FESEM, Raman, ...FTIR spectrophotometer and TGA were used for characterization of GO and rGO. XRD images reveal crystalline structure for both GO and rGO. The d‐spacing is observed to be reduced for rGO as compared to that for GO because of removal of oxygen containing functional groups. Raman excitation peaks were obtained for two laser wavelengths 532 and 785 nm. Ratio of intensities of D and G bands (ID/IG) increase for rGO due to increase in order by reduction, implying restoration of the p‐conjugation. The bands are narrower for rGO.TGA thermograms show a higher overall loss of weight for GO in the temperature range 0–1000 °C under N2 flow. Intensity of FTIR peaks of oxide, hydroxyl and alkoxy groups decreases significantly on reduction. FESEM image shows more corrugated surface of rGO as compared to GO. It is expected that this investigation would be useful to develop GO/rGO based gas sensors to detect minute concentration of gases.
Induction of tumor cell death is the therapeutic goal for most anticancer drugs. Yet, a mode of drug-induced cell death, known as immunogenic cell death (ICD), can propagate antitumoral immunity to ...augment therapeutic efficacy. Currently, the molecular hallmark of ICD features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Here, we show that gemcitabine, a standard chemotherapy for various solid tumors, triggers hallmark immunostimualtory DAMP release (e.g., calreticulin, HSP70, and HMGB1); however, is unable to induce ICD. Mechanistic studies reveal gemcitabine concurrently triggers prostaglandin E
release as an inhibitory DAMP to counterpoise the adjuvanticity of immunostimulatory DAMPs. Pharmacological blockade of prostaglandin E
biosythesis favors CD103
dendritic cell activation that primes a Tc1-polarized CD8
T cell response to bolster tumor rejection. Herein, we postulate that an intricate balance between immunostimulatory and inhibitory DAMPs could determine the outcome of drug-induced ICD and pose COX-2/prostaglandin E
blockade as a strategy to harness ICD.
Type 2 diabetes mellitus (T2DM) worldwide continues to increase, in particular in India. Early T2DM diagnosis followed by appropriate management will result in more cardiovascular event free life ...years. However, knowledge of the cardiovascular profile of newly diagnosed T2DM patients is still limited. The aim of this study was to understand the extent of cardiovascular disease (CVD) risk of newly diagnosed T2DM patients in India.
A cross sectional observational study was conducted to evaluate clinical laboratory and socio-demographic parameters of 5,080 newly diagnosed T2DM patients (48.3 ± 12.8 years of age; 36.7% female). In addition, we determined their cardiovascular risk according to the guidelines of the Lipid Association of India (LAI) and the criteria of the QRISK3 score.
Of the newly T2DM diagnosed patients in India 2,007(39.5%) were classified as "High risk" and 3,073 (60.5%) were classified as "Very high risk" based on LAI criteria. On average, patients had 1.7 ± 0.9 major atherosclerotic cardiovascular disease (ASCVD) risk factors. Low HDL-C value was the most frequent major risk (2,823; 55.6%) followed by high age (2,502; 49.3%), hypertension (2,141; 42.1%), smoking/tobacco use (1,078; 21.2%) and chronic kidney disease stage 3b or higher (568; 11.2%). In addition, 4,192 (82.5%) patients appeared to have at least one cholesterol abnormality and, if the latest LAI recommendations are applied, 96.5% (4,902) presented with lipid values above recommended targets. Based on the QRISK3 calculation Indian diabetes patients had an average CVD risk of 15.3 ± 12.3%, (12.2 ± 10.1 vs. 17.1 ± 13.5 p<0.001 for females and males, respectively).
Newly diagnosed Indian T2DM patients are at high ASCVD risk. Our data therefore support the notion that further extension of nationwide ASCVD risk identification programs and prevention strategies to reduce the occurrence of cardiovascular diseases are warranted.
Realizing the threat of rapid spread, China implemented a lockdown in Wuhan city, the epi-centre, to prevent further spread, even as cases started rising and more Chinese provinces were affected3, ...leading to declaration of a PHEIC on January 30, 20204. ...March 21, 2020, a total of 292,142 confirmed cases of COVID-19 had been reported to the WHO from 192 countries, with 12,784 deaths10. A more focal community transmission may be presently underway in these countries, as well as in cruise ships. ...the global outbreak is now undergoing a remarkable and ominous shift. The Integrated Disease Surveillance Programme (IDSP) based at the National Centre for Disease Control (NCDC), Delhi, has been conducting entry screening for all passengers arriving from other countries and has augmented community surveillance for severe acute respiratory illnesses. The planning and preparedness for the next phase of the outbreak is indeed critical, currently seen in many countries reporting focal clusters of cases in the community and rapid escalation of the situation for the worst. ...preparedness and readiness to have a public health surge capacities is urgently needed in the country.
The GRAPES-3 muon telescope located in Ooty, India records rapid (∼10 min) variations in the muon intensity during major thunderstorms. Out of a total of 184 thunderstorms recorded during the ...interval of April 2011-December 2014, the one on December 1, 2014 produced a massive potential of 1.3 GV. The electric field measured by four well-separated (up to 6 km) monitors on the ground was used to help estimate some of the properties of this thundercloud, including its altitude and area that were found to be 11.4 km above mean sea level and ≥380 km^{2}, respectively. A charging time of 6 min to reach 1.3 GV implied the delivery of a power of ≥2 GW by this thundercloud that was moving at a speed of ∼60 km h^{-1}. This work possibly provides the first direct evidence for the generation of gigavolt potentials in thunderclouds that could also possibly explain the production of highest-energy (100 MeV) gamma rays in the terrestrial gamma-ray flashes.
Iminodiacetic acid functionality has been introduced on styrene–divinyl benzene co-polymeric beads and characterized by FT-IR in order to develop weak acid based cation exchange resin. This resin was ...evaluated for the removal of different heavy metal ions namely Cd(II), Cr(VI), Ni(II) and Pb(II) from their aqueous solutions. The results showed greater affinity of resin towards Cr(VI) for which 99.7% removal achieved in optimal conditions following the order Ni(II)
>
Pb(II)
>
Cd(II) with 65%, 59% and 28% removal. Experiments were also directed towards kinetic studies of adsorption and found to follow first order reversible kinetic model with the overall rate constants 0.3250, 0.2393, 0.4290 and 0.2968 for Cr(VI), Ni(II), Pb(II) and Cd(II) removal respectively. Detailed studies of Cr(VI) removal has been carried out to see the effect of pH, resin dose and metal ion concentration on adsorption and concluded that complexation enhanced the chromium removal efficacy of resin drastically, which is strongly pH dependent. The findings were also supported by the comparison of FT-IR spectra of neat resin with the chromium-adsorbed resin.
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