Synthesis of chitosan succinate-g-amine functionalized mesoporous silica: Inorganic-organic nanohybrid for antibacterial assessment, antioxidant activity and pH-controlled drug delivery.

An innovative and proficient inorganic-organic nanohybrid was synthesized by using amine modified MCM-41 as an inorganic precursor combined with organic moiety, a derivative of chitosan i.e. chitosan succinate through amide bond. These nanohybrids can be used in diverse applications due to potential combination of desired properties of inorganic and organic components. The nanohybrid was characterized by FTIR, TGA, small angle powder XRD, zeta potential, particle size distribution, BET, proton NMR and 13C NMR techniques to confirm its formation. The synthesized hybrid was loaded with curcumin drug to check its potential application for controlled drug release, showing 80 % drug release in acidic medium (i.e. pH -5.0), while physiological pH -7.4 shows only 25 % release. The encapsulation efficiency of nanohybrid is 87.24 %. The results of antibacterial performances are demonstrated in terms of ZOI (zone of inhibition) which depicts that hybrid material shows better ZOI in gram negative (E. coli) than for gram positive (B. subtilis) bacteria. Nanohybrid was also tested for the antioxidant activity by using two different methods (DPPH and ABTS) radical scavenging methods. The ability of nano-hybrid to scavenge DPPH radicals was found 65 %, and ability to scavenge ABTS radicals was 62.47 %.

Utility of myxedema score as a predictor of mortality in myxedema coma.

OBJECTIVE: Myxedema crisis (MC) is a rare condition. There is a dearth of data regarding the predictors of mortality in MC. Predictive scores for mortality specific to the clinical and biochemical profile of MC are still lacking. DESIGN AND METHODS: All consecutive patients presenting with MC from September 2006 to December 2020 comprised the new cohort. Patients managed between January 1999 and August 2006 comprised the old cohort. Both cohorts were compared for the determination of secular trends. Combined analysis of both the cohorts was done for clinico-demographic profile and predictors of mortality. Myxedema score (MS) and qSOFA (Quick Sequential Organ Failure Assessment) score were evaluated in all the patients. RESULTS: A total of forty-one patients (new cohort; n = 18 and old cohort; n = 23) were enrolled into the study. There was a female predominance (80.5%). Nearly half (51.2%) of the patients were newly diagnosed with hypothyroidism on admission. Overall mortality was 60.9%. On comparative analysis among survivors and non-survivors, female gender (OR 20.4, p value 0.018), need for mechanical ventilation (OR16.4, p value 0.009), in-hospital hypotension (OR 9.1, p value 0.020), and high qSOFA score (OR 7.1, p value 0.023) predicted mortality. MS of > 90 had significantly higher mortality (OR-11.8, p value - 0.026) while MS of > 110 had 100% mortality. There was no change in secular trends over last 20 years. There was no difference in outcome of patients receiving oral or IV levothyroxine. CONCLUSION: Myxedema crisis is associated with high mortality despite improvement in health care services. The current study is first to elucidate the role of the MS in predicting mortality in patients with MC.

A photocatalyst-free visible-light-mediated solvent-switchable route to stilbenes/vinyl sulfones from ß-nitrostyrenes and arylazo sulfones.

Photocatalyst-free visible-light-mediated reactions, based on the presence of a visible-light-absorbing functional group in the starting material itself in order to exclude the often costly, hazardous, degradable and difficult to remove or recover photoredox catalysts, have been gaining momentum recently. We have employed this approach to develop a denitrative photocatalyst-free visible-light-mediated protocol for the arylation/sulfonylation of ß-nitrostyrenes employing arylazo sulfones (bench-stable photolabile compounds) in a switchable solvent-controlled manner. Arylazo sulfones served as the aryl and sulfonyl radical precursors under blue LED irradiation for the synthesis of trans-stilbenes and (E)-vinyl sulfones in CH3CN and dioxane/H2O 2 : 1, respectively. The absence of any metal, photocatalyst and additive; excellent selectivity (E-stereochemistry) and solvent-switchability; and the use of visible light and ambient temperature are the prime assets of the developed method. Moreover, we report the first photocatalyst-free visible light-driven route to synthesize stilbenes and vinyl sulfones from readily available ß-nitrostyrenes.

Remission in Cushing's disease is predicted by cortisol burden and its withdrawal following pituitary surgery.

AIM: To ascertain the predictors of remission and relapse in patients of Cushing's disease (CD) undergoing pituitary transsphenoidal surgery (TSS). METHODS: Patients with CD subjected to TSS over 35 years at a tertiary care center were included. Patients were grouped into remission and persistent disease at 1 year after surgery, and were further followed up for relapse. Demographic, clinical, biochemical, histological, radiological and post-operative follow-up parameters were analyzed. RESULTS: Of the 152 patients of CD, 145 underwent TSS. Remission was achieved in 95 (65.5%) patients at 1 year. Patients in remission had shorter duration of symptoms prior to presentation (p = 0.009), more frequent presence of proximal myopathy (p = 0.038) and a tumor size of < 2.05 cm (p = 0.016) in comparison to those with persistent disease. Post-TSS, immediate post-operative 0800-h cortisol (< 159.85 nmol/L; p = 0.001), histological confirmation of tumor (p = 0.045), duration of glucocorticoid replacement (median 90 days; p = 0.001), non-visualization of tumor on MRI (p = 0.003), new-onset hypogonadism (p = 0.001), 3-month 0800-h cortisol (< 384.9 nmol/L; p = 0.001), resolution of diabetes (p = 0.001) and hypertension (p = 0.001), and recovery of hypothalamic-pituitary-adrenal axis (p = 0.018) favored remission. In logistic regression model, requirement of glucocorticoid replacement (p = 0.033), and resolution of hypertension post-TSS (p = 0.003) predicted remission. None of the parameters could predict relapse. CONCLUSION: The study could ascertain the predictors of remission in CD. Apart from the tumor characteristics, surgical aspects and low post-operative 0800-h cortisol, the results suggest that baseline clinical parameters, longer glucocorticoid replacement, and resolution of metabolic complications post-TSS predict remission in CD. Long-term follow-up is essential to look for relapse.

Chitosan based ZnO nanoparticles loaded gallic-acid films for active food packaging.

Chitosan (Ch) and zinc oxide nanoparticles loaded gallic-acid films, (Ch-ZnO@gal) have been prepared aiming for their exploitation as environmentally benign food packaging material. The chitosan films with varying quantities of zinc oxide nanoparticles loaded gallic-acid (ZnO@gal) content were synthesized in order to evaluate the effect of ZnO@gal on their optimum mechanical and biological potential. The characteristic results have shown that the incorporation of ZnO@gal into chitosan films remarkably enhanced the desired mechanical property of the chitosan films. Other noticeable physical properties such as oxygen and water vapor permeability (WVP), swelling, water solubility and UV-vis light transmittance have also been found to improve positively. SEM analysis of the films indicates a good material compatibility between chitosan and ZnO@gal matrices. Ch-ZnO@gal films possess significant antibacterial potential and strong antioxidant behavior compared to pristine chitosan. The overall results suggested that the prepared biocomposite chitosan films may be considered for active food packaging applications.

A systematic study on chitosan-liposome based systems for biomedical applications.

The advent of liposome technology with its unique features has led researchers to work relentlessly on the successful development of novel drug delivery vehicles based on liposomes. But still there are some limitations of using liposomes for biomedical applications because of their poor stability that is primarily the cause of rapid leakage of drugs incorporated within the said matrices. Therefore, a considerable interest has been paid on modification of surface of liposomes by combining it with several compounds of interest. Although chitosan-liposome based systems are not yet well-documented. Hence, in this review, we exclusively focused on the discussion about the preparation of various chitosan-liposome based systems and their suitable biomedical applications as well.

Green synthesis, characterization and biological evaluation of chitin glucan based zinc oxide nanoparticles and its curcumin conjugation.

A well-organized, simplistic, and green route of chitin-glucan based zinc oxide nanoparticles (ChGC@ZnONPs) was synthesized using reducing and capping agent both in one as chitin-glucan complex (ChGC). Herein we report the bio-synthesis of Cur-ChGC@ZnONPs by the conjugation of curcumin (Cur) with ChGC@ZnONPs for the improvement of antioxidant and antibacterial activity. The synthesized nanoparticles were characterized by the UV-Visible (UV-Vis), particle size analyser, scanning electron microscope (SEM) with Energy-dispersive X-ray spectroscopy (EDX), Transmission electron microscope (TEM), X-ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FT-IR). Structure analysis, shape and crystalline size of nanomaterials were confirmed by scanning electron microscopy (SEM) and Transmission Electron Microscopy (TEM). The particle size analyser showed the particle size of nanomaterials and stability. Crystalline nature of both ChGC@ZnONPs and Cur-ChGC@ZnONPs were confirmed by the XRD spectra and FT-IR spectrum was used to examine the functional groups of nanomaterials. The antioxidant potential of conjugated nanomaterials were estimated using a DPPH free radical scavenging assay and ABTS+⁎ assay. This analysis showed that after loading of Cur, antioxidant activity increases. The antibacterial assessment of conjugated nanomaterials were tested by different microorganisms and showed excellent antibacterial activity.

Preparation, physicochemical and biological evaluation of quercetin based chitosan-gelatin film for food packaging.

Ecofriendly chitosan-gelatin (Ch-ge) bio-composite films containing Quercetin-starch (Q) were synthesized using solution casting method. Physicochemical characteristics and mechanical properties of the resulting chitosan-gelatin containing Quercetin-starch films (Ch-ge-Q) were studied using UV, FTIR, XRD and SEM techniques. The films were also investigated for their swelling, water-vapor permeability (WVP), water solubility properties. The FTIR spectra confirmed the chemical interactions between the chitosan-gelatin and Q. Surface morphology of prepared film was analyzed by the SEM imaging while XRD spectra suggest the expanded crystallinity of the film with the addition of Q. The film also showed enhanced barrier property against UV rays. The reduction of water-vapor permeability and increase in tensile strength while a decrease in elongation at break has been observed in the Ch-ge-Q film compared to Ch-ge film. The antibacterial activity of Ch-ge-Q film against both gram positive (B. substilis) and gram negative (E. coli) bacteria suggested the Q loaded Ch-ge films as more feasible antibacterial candidate especially against the strain E. coli. The antioxidant activity of the Ch-ge-Q film was evaluated using the DPPH and ABTS as standards and corresponded to 81.45% of DPPH and 72.2% of ABTS scavenging activities. It was observed that the film containing Quercetin-starch presented superior antioxidant activity results in comparison to Ch-ge film promising its application in food packaging.

Methyl methacrylate modified chitosan: Synthesis, characterization and application in drug and gene delivery.

A methyl methacrylate (MMA) modified chitosan (CS) conjugate (CSMMA) has been synthesized by a green method via Michael addition reaction between CS and MMA in ethanol. The synthesized conjugate was characterized by FT-IR, 1H NMR, X-ray diffraction spectrometry and SEM analysis. The results confirmed that CS was covalently linked to MMA yielding a highly porous framework. The uses of CSMMA were analyzed as a potential gene and drug delivery agent. CSMMA proved to be a reasonably good gene delivery agent based on transfection efficiency studies in mammalian cancer cell lines (A549, HeLa and HepG2). For drug delivery studies, nanoparticles of the CSMMA biopolymer were prepared by ionic gelation method with sodium tripolyphosphate (TPP). The prepared nanoparticles were characterized in terms of FE-SEM, DLS and zeta potential. In vitro drug release study of curcumin loaded CSMMA nanoparticles showed its maximal entrapment efficiency up to 68% and the drug release was more rapid at a pH (5.0) lower than physiological pH.

Health risks from PAHs and potentially toxic elements in street dust of a coal mining area in India.

Polycyclic aromatic hydrocarbons (PAHs) and potentially toxic elements (PTEs) (Ba, Zn, Pb, Cu, Cr, Ni, As, Co) were determined in the road dusts of a coal mining area (Dhanbad, India) to assess their content and potential human health risks. Dust samples were collected from sign boards of the heavy traffic road connecting Dhanbad and Sindri. The total PAHs (∑PAHs, all values in mg/kg) content in the road dust samples varied from 3.98 to 13.1, with carcinogenic PAHs content of 14.8-34.4% of the ∑PAHs. Phenanthrene (2.72), fluorene (0.715) and pyrene (0.575) are the major PAHs. Principal component analysis revealed that these PAHs are probably originated from pyrogenic (coal combustion and traffic emission) and petrogenic (coal dust, tyre and road particles) sources. Among the PTEs, the mean content was higher for Ba (293 mg/kg) followed by Zn (224), Pb (128), Cu (52.6), Cr (45.2), Ni (22.0), As (17.5) and Co (8.11). The overall pollution load index varied from 0.43 to 1.0. Source analysis showed that PTEs in the road dust of the study site were derived from traffic emission (Zn, Fe, Mn, Co and Pb), coal dust (Cr, As and Ni) and soil (K, Mg, Ba, Sr and Ca). In general, the PTEs are lower, but the PAHs contents were elevated in the road dust samples. Although the exposure risks from PTEs are low, the risk to children (expressed as hazardous quotient) for As and Pb is near to the permissible limit of 1.0. Cancer risk from PAHs for adult (4.8 × 10-6) and child (5.3 × 10-6) has exceeded the acceptable limit of 10-6.

Chitosan grafted graphene oxide aerogel: Synthesis, characterization and carbon dioxide capture study.

We have demonstrated a superficial, environmentally friendly and sustainable development of chitosan (CS) grafted graphene oxide aerogels for adsorption of CO2 gas. The CS is grafted into the carbonaceous materials like graphene oxide, multi-walled carbon nanotubes etc. to provide the large surface area, high porosity and a large number of amine group which facilitates the adsorption of CO2 gas. CS and carbonaceous materials undergo crosslinking by using cross-linker reagents, and freeze-drying technique to yield CS based aerogels with ordered porous structures. Crosslinking between CS and carbonaceous materials was confirmed by FT-IR. Physical properties of the CS-based aerogels were studied using SEM, TGA, XRD, BET isotherm analysis. The adsorption capacity of CO2 gas by CS grafted graphene oxide aerogels is around 0.257 mmol g-1 at 1 bar, that is significantly higher in comparison to the adsorption capacity of pure CS. We believe that this study helps to reduce the cost of adsorbents due to the large availability of marine waste (CS) and thus aims to reduce the anthropogenic CO2 gas at low cost, favourable temperature and pressure as compared to previously reported.

Metamagnetic transition and observation of spin-fluctuations in the antiferromagnetic Heusler compound Pd2MnIn.

We report detailed investigations on the structural, magnetic, magneto-transport and calorimetric aspects of a partially ordered Heusler compound Pd2MnIn. The sample shows antiferomagnetic (AFM) state below around 120 K, though positive paramagnetic Curie temperature signifies a complex magnetic ground state with the presence of both ferromagnetic (FM) and AFM correlations. A clear spin-flop type metamagnetic transition is observed as evident from the magnetization and resistivity data. However, non-saturation of magnetization even at 145 kOe of applied field implies that the high field state may be a spin canted state, originating from the enhanced FM correlations by field induced conduction electron spin polarization. The sample shows a profound quadratic temperature dependence of resistivity below about 20-25 K indicating a spin-fluctuation dominated low temperature region. Previous electronic structure calculations show the existence of a subtle balance between superexchange mediated AFM state and an RKKY (Ruderman-Kittel-Kasuya-Yoshida) interaction mediated FM state in Pd2MnIn. Such competing AFM-FM correlations can be accounted for the observed spin fluctuations.

Synthesis of chitin-glucan-aldehyde-quercetin conjugate and evaluation of anticancer and antioxidant activities.

In the present study, we have synthesized chitin-glucan-aldehyde-quercetin (chi-glu-ald-que) conjugate via condensation reaction. Synthesis of chitin-glucan-aldehyde (chi-glu-ald) complex was facilitated by the oxidation of chitin-glucan (chi-glu) complex. Formation of conjugate was confirmed by Proton nuclear magnetic resonance spectroscopy (1H NMR) and Fourier-transform infrared spectroscopy (FT-IR). Morphological studies showed that after grafting of quercetin, several changes on surface were depicted and a more crystalline nature was observed. The chi-glu-ald-que conjugate displayed strong antioxidant activity. It showed 69% of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical, DPPH* scavenging activity at 1 mg/mL and 72% of 2, 2-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical cation, ABTS*+ scavenging activity at 1 mg/mL concentration, which are much higher than that of chi-glu complex. The anticancer activity of chi-glu-ald-que conjugate was performed in Macrophage cancer cell lines (J774) and biocompatibility was performed in Peripheral blood mononuclear cells (PBMCs). The chi-glu-ald-que conjugate showed excellent cytotoxicity against J774 cell lines but no cytotoxicity towards PBMCs.

Effect of Linagliptin on Incretin-axis and Glycaemic Variability in T1DM.

BACKGROUNDS AND OBJECTIVES: Short-term studies have demonstrated potential therapeutic efficacy of dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors) in patients with poorly controlled T1DM. In this study we evaluated the effect of DPP4 inhibitor, linagliptin, on glycaemic control and variability, and incretinaxis in well controlled T1DM patients to mitigate the effect of glucotoxicity on incretin secreting cells. METHODS: Twenty T1DM patients were randomized to receive either linagliptin (10 patients, dose-5 mg/day) or placebo (10 patients), in addition to insulin for 3 months. HbA1C, continuous glucose monitoring (CGM) and mixed meal test (MMT) were performed before and at the end of the study period. RESULTS: HbA1C reduction and change in glycaemic variability and insulin requirement in the linagliptin group did not attain the level of statistical significance. The increase in AUC GLP1 (Area under curve for GLP1) and decrease in AUC glucagon (Area under curve for glucagon) during the MMT in linagliptin group were also statistically insignificant. INTERPRETATIONS AND CONCLUSIONS: Linagliptin is not effective in reducing HbA1C and glycaemic variability in relatively well controlled T1DM patients.

First report of Chikungunya virus circulation during a dengue outbreak in Arunachal Pradesh, a Northeastern state of India.

Dengue has become a major public health problem in Pasighat, Arunachal Pradesh since 2012 outbreak. This region is rich in Aedes mosquitoes, the common vector for Dengue and Chikungunya (CHIK), however, active surveillance of CHIK is lacking in this part of India. Therefore, this study has been undertaken to detect the presence of CHIKV infection during 2014 and 2015 dengue outbreak in Arunachal Pradesh. A total of 116 (52 during 2014 and 64 during 2015 outbreak) dengue negative serum samples were collected from General Hospital, Pasighat and were screened for the presence of CHIK IgM antibodies. All the samples were further processed for CHIKV RNA detection by RT-PCR using specific primers. Phylogenetic tree was constructed by Neighbor Joining method using Kimura-2 parameter model. A total of 8 samples were found to be positive for IgM antibodies. RT-PCR showed CHIKV RNA positivity in 2 samples. Both of these samples belonged to 2014 outbreak. Phylogenetic tree revealed that the CHIKV circulating during the outbreak belonged to Eastern, Central and Southern African genotype. Sequence analysis showed two uniform nucleotide substitutions. Circulation of CHIKV masked by dengue is reported from this study. Therefore, CHIKV diagnosis should be made as a routine test in areas where dengue is already endemic so as to prevent misdiagnosis of the disease and to check its accomplishment before commencing an outbreak.

Curcumin loaded chitin-glucan quercetin conjugate: Synthesis, characterization, antioxidant, in vitro release study, and anticancer activity.

In this study, we have synthesized chitin-glucan quercetin conjugate (ChGCQ) by an easy and facile free radical grafting reaction. The structure of ChGCQ was confirmed by proton nuclear magnetic resonance (1H NMR) and Fourier transforms infrared spectroscopy (FT-IR). Curcumin was loaded into ChGCQ to study its anti-cancer efficiency. The biocompatibility of ChGCQ and curcumin loaded ChGCQ (Cu-ChGCQ) were analysed by different assays in Peripheral blood mononuclear cells (PBMCs) and cytotoxicity test was performed in a macrophage cancer cell line (J774). The result shows tremendous biocompatibility of ChGCQ and Cu-ChGCQ in peripheral blood mononuclear cells and excellent cytotoxity in macrophage cancer cell line (J774). Chitin-glucan complex (ChGC), ChGCQ and Cu-ChGCQ showed 51%, 66% and 74% of DPPH radical-scavenging activity at 1mg/ml respectively, which are much higher than that of ChGC and in ABTS*+ assay 58%, 71% and 83% show radical-scavenging activity at 1mg/ml. Antioxidant assay of Cu-ChGCQ conjugate expressed much higher antioxidant activity than ChGCQ and ChGC. In vitro drug release study of Cu-ChGCQ conjuagate showed faster drug release in acidic medium in comparison to PBS of physiological pH and anticancer activity in vitro assay showed more anticancer activity of Cu-ChGCQ in comparison to ChGCQ conjugate.

Cu(II)-carboxymethyl chitosan-silane schiff base complex grafted on nano silica: Structural evolution, antibacterial performance and dye degradation ability.

O-Carboxymethyl chitosan (OCMC) Schiff's base was utilized for a new class of organic-inorganic hybrid material by grafting it on nano-silica-silane and further metallated with Cu (II). Here (3-Aminopropyl) triethoxysilane (APTES) was used as a linker and 2-hydroxy-1-naphthaldehyde (HN) for Schiff's base formation. The hybrid was characterized by FTIR, TGA, powder XRD, SEM, CHN, DLS, ICP-AES, diffuse reflectance UV-vis and EDX spectroscopic techniques. Magnetization measurements were carried out by VSM at room temperature. This study explored the possible synergic effect of unique properties of carboxymethyl chitosan, Schiff's base Cu (II) complex and nano-silica towards antibacterial activity and in dye degradation studies. The antibacterial performance of nano-hybrid material was examined against both Gram-positive (Escherichia coli) and Gram-negative (Bacillus subtilis) bacteria. The catalytic activity of the hybrid was tested for degradation of reactive black 5 (RB5) through advanced oxidation processes using H2O2 as oxidant. The results show a high dye degradation efficiency of 93% in 130min by the hybrid catalyst with reusability. As per published reports, Chitosan-Schiff's bases show strong antimicrobial activity and their Cu complexes exhibit good catalytic and anticancer activities. Therefore, it is expected that the new organic-inorganic hybrid would be highly applicable in environmental as well as biomedical fields.

Phenolic compounds based conjugates from dextran aldehyde and BSA: Preparation, characterization and evaluation of their anti-cancer efficacy for therapeutic applications.

Here, we have synthesized phenolic compounds (pc) based on conjugates from dextran aldehyde (dex-ald) and bovine serum albumin (BSA) and screening their potential activity as therapeutic agents in cancer disease. The synthesized conjugates were analyzed by UV-vis, FT-IR, XRD and SEM analysis. UV-vis spectra of conjugates showed the shifting of spectral peak at UV to visible region revealed the enhanced conjugation due to formation of linkage. The XRD peaks of conjugates found broader and indicating the amorphous phase of conjugating materials in compared to free components. The SEM images showed that the conjugated materials having numerous pores on its surface, which proved its porous nature. The amount of phenolic compounds conjugated with (dex-ald-pc) and (BSA-pc) were found to be 65.4 and 73.91mg/g of conjugates, respectively. Cells viability was significantly decreased approximately 80-85% at concentration of 100µg conjugates whereas the free polymers or phenolics did not affect the viability of cancer cells. Generation of high quantity of reactive oxygen species (ROS) in cells treated with conjugate materials, which may caused cell apoptosis in cancer cell line. The results clearly showed that conjugation of phenolic compounds were an effective method to improve the functional properties for therapeutic applications.