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Background: NSAIDs are the most widely prescribed medications worldwide for their anti-inflammatory, antipyretic, and analgesic effects. However, their chronic use can lead to several adverse drug events including GI toxicity. The selective COX-2 inhibitors developed as gastrosparing NSAIDs also suffer from serious adverse effects which limit their efficacy. Objective: Local generation of reactive oxygen species is implicated in NSAID-mediated gastric ulceration and their combination with H2 antagonists like famotidine reduces the risk of ulcers. The objective of this work was to design and synthesize novel methanesulphonamido isoxazole derivatives by hybridizing the structural features of NSAIDs with those of antiulcer drugs (ranitidine, famotidine, etc.) to utilize a dual combination of anti-inflammatory activity and reducing (antioxidant) potential. Method: The designing process utilized three dimensional similarity studies and utilized an isoxazole core having a potential for anti-inflammatory as well as radical scavenging antioxidant activity. The compounds were assayed for their anti-inflammatory activity in established in vivo models. The in vitro antioxidant activity was assessed in potassium ferricyanide reducing power (PFRAP) assay employing ascorbic acid as the standard drug. Results: Compounds 5, 6, 9 and 10 showed antiinflammatory activity comparable to the standard drugs and were also found to be non-ulcerogenic at the test doses. Compounds 6-10 exhibited good antioxidant effect in the concentration range of 1.0- 50.0 μmol/ml. The test compounds were also found to comply with the Lipinski rule suggesting good oral absorption. Conclusion: A new series of isoxazole based compounds is being reported with good antiinflammatory activity coupled with antioxidant potential as gastro-sparing anti-inflammatory agents.

Background:NSAIDs are used as first-line drugs for the treatment of various inflammatory disorders. Chronic use of NSAIDs is known to be associated with gastrointestinal and renal toxicity. Local generation of reactive oxygen species finally resulting in cellular apoptosis is one of the accepted mechanisms for NSAID-induced toxicity.Objective:The objective of the present study was to design and synthesize a series of 2-methane sulfonamido substituted arylthiazole derivatives by including structural features of combined antiulcer and anti-inflammatory activity utilizing as the structural core, thiazole nucleus with potential for antioxidant effect.Methods:Compounds were designed based on three dimensional and field similarity studies. The synthesized compounds were evaluated for their anti-inflammatory activity in carrageenan-induced rat paw edema model. Rofecoxib and indomethacin were taken as standard drugs for comparison. The in vitro antioxidant activity was assessed in potassium ferricyanide reducing power (PFRAP) assay employing ascorbic acid as the standard drug.Results:The compounds 6 and 7 showed good anti-inflammatory activity comparable to the standard group and were also non ulcerogenic at the test doses. Compounds 1-7 displayed varying degrees of reducing power in the PFRAP) assay and the methanesulphonamido derivatives 4-7 showed the highest antioxidant activity (EC50 values 3.7-5.1 μmol/ml vs ascorbic acid 7.4 μmol/ml). Theoretical ADME profiling of the compounds based on selected physicochemical properties showed excellent compliance with Lipinski’s rule.Conclusion:A series of compounds have been designed and synthesized having dual antioxidant and anti-inflammatory activity with activities comparable to standard drugs.

Diabetic kidney disease (DKD) occurs in approximately 20–40% of patients with type 2 diabetes mellitus. Patients with DKD have a higher risk of cardiovascular and all-cause mortality. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antihyperglycemic drugs form the mainstay of DKD management and aim to restrict progression to more severe stages of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) control hyperglycemia by blocking renal glucose reabsorption in addition to preventing inflammation, thereby improving endothelial function and reducing oxidative stress; consequently, this class of prescription medicines is emerging as an important addition to the therapeutic armamentarium. The EMPA-REG OUTCOME, DECLARE TIMI 58, and CANVAS trials demonstrated the renoprotective effects of SGLT2i, such as restricting decline in glomerular filtration rate, in the progression of albuminuria, and in death due to renal causes. The renoprotection provided by SGLT2i was further confirmed in the CREDENCE study, which showed a 30% reduction in progression of chronic kidney disease, and in the DELIGHT study, which demonstrated a reduction in albuminuria with dapagliflozin compared with placebo (− 21.0%, confidence interval [CI] − 34.1 to − 5.2, p = 0.011). Furthermore, a meta-analysis demonstrated a reduced risk of dialysis, transplantation, or death due to kidney disease (relative risk 0.67; 95% CI 0.52–0.86; p = 0.0019) and a 45% risk reduction in worsening of renal function, end-stage renal disease, or renal death (hazard ratio 0.55, CI 0.48–0.64, p

The human pathogen Mycobacterium tuberculosis (Mtb) harbors a well-orchestrated Clp (caseinolytic protease) proteolytic machinery consisting of two oligomeric segments, a barrel-shaped heterotetradecameric protease core comprising the ClpP1 and ClpP2 subunits, and hexameric ring-like ATP-dependent unfoldases composed of ClpX or ClpC1. The roles of the ClpP1P2 protease subunits are well-established in Mtb, but the potential roles of the associated unfoldases, such as ClpC1, remain elusive. Using a CRISPR interference–mediated gene silencing approach, here we demonstrate that clpC1 is indispensable for the extracellular growth of Mtb and for its survival in macrophages. The results from isobaric tags for relative and absolute quantitation–based quantitative proteomic experiments with clpC1- and clpP2-depleted Mtb cells suggested that the ClpC1P1P2 complex critically maintains the homeostasis of various growth-essential proteins in Mtb, several of which contain intrinsically disordered regions at their termini. We show that the Clp machinery regulates dosage-sensitive proteins such as the small heat shock protein Hsp20, which exists in a dodecameric conformation. Further, we observed that Hsp20 is poorly expressed in WT Mtb and that its expression is greatly induced upon depletion of clpC1 or clpP2. Remarkably, high Hsp20 protein levels were detected in the clpC1(−) or clpP2(−) knockdown strains but not in the parental bacteria, despite significant induction of hsp20 transcripts. In summary, the cellular levels of oligomeric proteins such as Hsp20 are maintained post-translationally through their recognition, disassembly, and degradation by ClpC1, which requires disordered ends in its protein substrates.

Starch is a polymer derived from plants that have various applications. There are various types of starch available like potato, maize, tapioca, and wheat, etc. We have studied and successfully differentiated tapioca and maize starch using polarized light microscopy and bright field techniques with the help of Iodine staining. Starch granules are suspended in aqueous or non-aqueous media for polarized light and bright field microscopy. The botanical source of the starch is identified according to the shape and size of granules, granule surface marking, the position of hilum, iodine staining, and the presence of maltase crosses under polarized light.

Background There is a constant search for an ideal treatment for vitiligo. Platelet-rich plasma (PRP) is a novel modality for treating stable vitiligo. Presently, literature regarding the efficacy of combining either PRP or platelet-poor plasma (PPP) with psoralen+sunlight (PUVASOL) in vitiligo does not exist. Objective This study compares the safety and efficacy of combining PUVASOL with either PRP or PPP against PUVASOL alone in patients with stable nonsegmental vitiligo. Patients and methods This prospective, open-labeled, comparative study was done in 20 patients with stable nonsegmental vitiligo, each having at least three vitiligo patches of similar shape and size. All the patients received PUVASOL as standard treatment modality. PRP or PPP was injected into two separate study patches as an adjuvant treatment with PUVASOL; however, the third patch acted as a control and was treated by PUVASOL alone. These patients were followed up for 4 weeks after the end of four treatment sessions. Results Compared with control areas (exposed to PUVASOL only), statistically significant more repigmentation was seen in areas treated with a platelet preparation (either PRP or PPP) along with PUVASOL. However, there was no significant difference between PRP and PPP arm (P=0.824) as per qualitative and quantitative assessment. Conclusion Addition of a platelet preparation (either PRP or PPP) had an additive beneficial effect on the response of PUVASOL therapy in patients with stable vitiligo at the study end point of 16 weeks. However, PRP and PPP showed comparable efficacy at the study end point in terms of repigmentation when used in conjunction with PUVASOL.

We report the effects of zinc metal substitution on the molecular dynamics of protoporphyrin-IX in dichloromethane solvent by spectrally resolving the femtosecond photon echo spectrum. We have found that the coherence and population dynamics change due to the presence of Zn metal in the protoporphyrin-IX system. Zinc metal reduces the conformational disorder in the molecular structure of protoporphyrin-IX and in turn increases the planarity of the molecule resulting in better delocalization of π-electrons in the system. This effect decreases the inhomogeneous broadening of the photon echo spectra of Zn-substituted protoporphyrin-IX.

An ionic liquid catalyzed dual C–N/C–C coupled cyclization of a three component assembly is demonstrated to access 3,4-dihydropyrimidin-2(1H)-one (DHPM) analogues under solvent-free green conditions. Innovative new organic materials are introduced with pure and mixed DHPM using LB high surface pressure, AFM and photophysical studies.

Introduction: Glycated hemoglobin (HbA1c) can be altered in different conditions. We hypothesize that HbA1c levels may change due to altered thyroid status, possibly due to changes in red blood cell (RBC) turnover. Objectives: The objective of this study was to determine the effects of altered thyroid status on HbA1c levels in individuals without diabetes, with overt hyper- and hypo-thyroidism, and if present, whether such changes in HbA1c are reversed after achieving euthyroid state. Methods: Euglycemic individuals with overt hypo- or hyper-thyroidism were selected. Age- and sex-matched controls were recruited. Baseline HbA1c and reticulocyte counts (for estimation of RBC turnover) were estimated in all the patients and compared. Thereafter, stable euthyroidism was achieved in a randomly selected subgroup and HbA1c and reticulocyte count was reassessed. HbA1c values and reticulocyte counts were compared with baseline in both the groups. Results: Hb A1c in patients initially selected was found to be significantly higher in hypothyroid group. HbA1c values in hyperthyroid patients were not significantly different from controls. HbA1c reduction and rise in reticulocyte count were significant in hypothyroid group following treatment without significant change in glucose level. Hb A1c did not change significantly following treatment in hyperthyroid group. The reticulocyte count, however, decreased significantly. Conclusion: Baseline HbA1c levels were found to be significantly higher in hypothyroid patients, which reduced significantly after achievement of euthyroidism without any change in glucose levels. Significant baseline or posttreatment change was not observed in hyperthyroid patients. Our study suggests that we should be cautious while interpreting HbA1c data in patients with hypothyroidism.

Excellent Langmuir-Blodgett films (LB) of non-amphiphilic coronene (COR) have been prepared by mixing with a long chain fatty acid, viz., arachidic acid (AA) and an inert polymer such as poly methyl methacrylate (PMMA) separately. Miscibility of the guest and host molecules in the mixed monolayer of COR and AA/PMMA have been studied with excess area criterion. Both the attractive and repulsive interactions are present in the COR/AA mixed monolayer, whereas only repulsive interaction is active between the component molecules of COR/PMMA mixed monolayer. Spectroscopic properties of COR in solution and mixed LB films have been compared by UV-Vis absorption spectroscopy. Surface morphology of mixed LB films has been examined by atomic force microscopy (AFM). Absorption spectroscopic study complemented with AFM image suggests the formation of some kind of aggregates in the mixed LB films.

This paper reports the monolayer characteristics of cationic octadecylamine (ODA) on both distilled water and aqueous Erythrosine B (EB) dye solution at the air-water interface. From the pressure-area isotherms at various pHs, EB anions in the subphase were found to interact with the insoluble monolayer of cationic octadecylamine (ODA). Adsorption kinetics shows that the amount of dye adsorbed depends on the concentration of the dye present in the subphase. It was observed that the adsorption process mainly occurred due to the electrostatic interaction between the cationic amino group of long chain amine and the anionic part of EB. The spectroscopic characteristics of the mixed LB films, solution, have been compared using UV-vis absorption and fluorescence spectroscopic data. These studies indicate the formation of aggregates in the thin films. Scanning electron microscopic study certainly confirms the presence of aggregates of EB dye in the (ODA-EB) mixed LB films.

Background and objective: Metformin is often used as a first-line therapy for Type 2 diabetes mellitus (T2DM), but the glycemic response to metformin is variable in patients. Here, we aimed to assess the inter-patient variability in terms of glycemic response to metformin in the state of West Bengal, India. Material and methods: We enrolled newly diagnosed treatment naive 113 patients with T2DM. Patients were subjected to assay of glycated hemoglobin (HbA1c), fasting blood glucose (FBG), postprandial blood glucose (PP) and measurement of body mass index (BMI), waist circumstances (WC) before and after the end of 3 months of immediate release metformin (2000mg/day) therapy. Results: Out of 113 patients, 111 (58 male and 53 female; average age 43.13 years) were provided with 3 months of metformin therapy. 102 individuals responded to metformin, but HbA1c levels of 9 patients did not improve after 3 months of drug therapy. Conclusions: In the present study, metformin lead to improvements in glycemic control in 92% of newly diagnosed T2DM patients but in 8% does not which is much less in this part of India.

Mixed films of a polycylic aromatic hydrocarbon 1-pyrene-carboxaldehyde (PyCHO) and a polymer matrix, viz. isotactic poly(methyl methacrylate) (PMMA) were studied at the air–water interface by surface pressure versus area per molecule (π-A) isotherms. The diagrams obtained by plotting the mean area per molecule as a function of the molar fraction of PyCHO showed positive deviations from ideal conditions with a small exception indicating a repulsive type of interaction between PyCHO and PMMA molecules, resulting in the formation of aggregates. Spectroscopic as well as scanning electron microscopy (SEM) studies revealed that aggregates were present when the mixed film was transferred onto quartz substrates at different mole ratios of PyCHO.

Nonamphiphilic 2-aminoanthracene has been incorporated within the Langmuir monolayer and Langmuir–Blodgett (LB) films when mixed with behenic acid (BA). Miscibility of 2-aminoanthracene and BA at the air—water (A–W) interface has been studied by using surface phase rule and excess area criterion. Our studies reveal that repulsive type interactions exist between the component molecules in mixed monolayer and this may facilitate the formation of aggregates. Spectroscopic as well as morphological studies of mixed LB films of 2-aminoanthracene and BA undoubtedly confirms the formation of aggregates.

A systematic study is reported on the monolayer characteristics of 2,2′-p-phenylenebis (5-phenyloxazol) (POPOP) mixed with arachidic acid (AA) at the air-water interface, using surface pressure versus area per molecule (π-A) isotherms complemented with absorption spectroscopy as well as scanning electron microscopy. The (π-A) isotherms of POPOP mixed with AA at different mole fractions show a plateau like region at very low surface pressure, which suggests a phase transition corresponding to a reorientation of the POPOP molecules at the air-water interface. The mixing behavior was obtained from surface pressure-area isotherms by using the surface phase rule and excess area criterion. Results show that POPOP is immiscible in AA, leading to the formation of aggregates. These observations are confirmed by ultraviolet-visible absorption spectroscopy and scanning electron microscopy. Absorption spectra of the mixed LB films reveal that I-type of aggregates play their prominent role in the mixed LB films.

The behavior of binary mixed Langmuir monolayers from the mixture of non-amphiphilic bathophenanthroline (BPH) and behenic acid (BA)/poly(methyl methacrylate) (PMMA) spread on aqueous subphase was investigated on the basis of the analysis of surface pressure–average area per molecule (π–A) isotherms complemented with UV–vis absorption spectroscopy and scanning electron microscopy. In addition, the miscibility of the components in the two investigated mixed systems (BPH/BA and BPH/PMMA) was also tested by using additivity and surface phase rules. The plots of area per molecule versus mole fraction suggest that BPH and BA are immiscible, whereas BPH and PMMA mixtures show non-ideal behavior at low surface pressures and complete miscibility or immiscibility at higher surface pressures. Spectroscopic study reveals that J-type of aggregates is formed in the mixed films. Scanning electron microscopic study supports the presence of aggregates.

This paper reports the incorporation of an inhibitor of Human Immunodeficiency Virus (HIV), viz. Chicago Sky Blue (CSB) dye within an insoluble cationic octadecylamine (ODA) Langmuir monolayer. A surface pressure-area isotherm study confirmed the strong interaction between long chain amine and CSB dye. At higher surface pressure, CSB molecules tend to squeeze out from the octadecylamine monolayer. SEM study confirms this observation. Adsorption kinetics shows that the amount of dye adsorbed depends on the concentration of the dye present in the subphase. It was observed that the absorption process mainly occurred due to the electrostatic interaction between the cationic amino group of long chain amine and the sulphonate group of CSB dye. UV-Vis absorption spectroscopic study indicates the formation of aggregates of CSB dye in the mixed (ODA-CSB) LB films.

An ionic liquid catalyzed dual C–N/C–C coupled cyclization of a three component assembly is demonstrated to access 3,4-dihydropyrimidin-2(1H)-one (DHPM) analogues under solvent-free green conditions. Innovative new organic materials are introduced with pure and mixed DHPM using LB high surface pressure, AFM and photophysical studies.

Multilayer films can be precisely engineered on solid substrate via layer-by-layer (LbL) self-assemble technique using negatively charged organic dye and positively charged polyelectrolytes or surfactants. This communication first time reports the successful incorporation of an anionic dye Niagara blue (NB) in Polyallylamine hydrochloride (PAH) by electrostatic sequential alternative LbL adsorption. The photo-physical characteristics of LbL films are investigated by varying different parameters such as number of deposited layer, dipping time in dye solution, pH of PAH solution, concentration of the dye, etc. In addition, the interaction of NB with double tail surfactant Didodecyl dimethyl ammonium bromide (DDAB) at different concentrations is also studied in the light of UV–Vis absorption spectroscopy. Spectroscopic analysis reveals that NB has been successfully anchored to PAH or DDAB through electrostatic self-assembled technique and forms molecular aggregates. The formation of aggregates is further confirmed by atomic force microscopic (AFM) study.

We have studied the coherence and population dynamics of Astaxanthin solution in methanol and acetonitrile by spectrally resolving their photon echo signals. Our experiments indicate that methanol has a much stronger interaction with the ultrafast dynamics of Astaxanthin in comparison to that of acetonitrile.

Hydraulic fracturing of rocks is a frequently practiced technique in upstream hydrocarbon industry. However, the phenomena relates to brittle fracture. Fracture formation in visco-elastic materials is a relatively poorly understood process. Inspired by hydraulic fracturing of rocks, fluid fracturing of viscoelastic materials is the proposed technique for the development of micro fractures or pores in a viscoelastic material which is not only simple but effective too. In this method fluid is injected inside the material and at sufficient pressure fractures are observed. In our research, we have found that this method can be used to develop micro fractures of controlled morphology, size and orientation, and thus can have vital applications. Micro fracture development can find a wide range of application including micro filtration, microfluidics, micro reactors, adsorption etc. This paper discusses the basic methodology and the results of experiments conducted on cross-linked polydimethylsiloxane (PDMS), mainly focussing upon the morphology and size variation of fracture depending upon the degree of cross linking and fluid injection pressure.

Anti-malarial methylene blue (MB) doped in arachidic acid (AA) have been incorporated in the Langmuir monolayer at the air–water interface and also in the Langmuir–Blodgett films deposited on quartz substrate. The pressure–area (π–A) isotherm studies at different concentrations of MB pointed out that pure MB could not form stable monolayer at the air–water interface and collapse readily at very low surface pressures. However, mixture of MB with AA formed stable monolayers and they could be transferred into solid quartz substrate to form mono/multi layered films of MB. The area per molecule of floating mixed monolayers was systematically decreased with the increasing concentrations of MB in the mixture. The pressure–time (π - t) isotherm study indicated the interaction kinetics between MB and AA. Higher the concentration of MB, higher is the increase in pressure. The spectroscopic characteristics of the mixed LB films have been compared with that of pure MB solution, microcrystal and layer-by-layer self assembled film with UV-Vis absorption spectroscopy. Surface morphology of the mixed LB and LbL film of MB was measured with atomic force microscopy (AFM).

This communication reports the successful fabrication and the comparative study of Langmuir and Langmuir–Blodgett (LB) films of nonamphiphilic phenanthrene derivative, 1, 10 phenanthroline (bathophenanthroline) (BATH), when incorporated to a long chain fatty acid viz. heptadecanoic acid and stearic acid. Measurements of compressibility modulus from the surface pressure versus area per molecule isotherm indicate that the mixed film of BATH and SA is harder than that with HA. The plot of area per molecule versus mole fraction is the indication of some repulsive interactions between binary components of the mixed monolayer which facilitates the formation of aggregates. UV–Vis absorption spectroscopy and steady-state fluorescence spectroscopy confirms the formation of microcrystalline aggregates in the mixed LB films. Scanning electron microscopic study supports this observation. The dependence of various LB parameters in the mixed films such as mole fraction, number of layers and surface pressure of lifting have also been investigated in the light of electronic absorption spectroscopy.

We have observed two photon fluorescence resonance energy transfer (FRET) from optically trapped bead coated with multiple dyes. The fluorescence obtained from trapped particles is useful to measure biomechanical property of that confined system.