Polymorphism Dependent Cytotoxicity, Cellular Uptake, and Live Cell Imaging Studies on Napthalimide-Vinyl-Phenothiazine Conjugate.

Polymorphism-dependent cytotoxicity and cellular uptake of drug molecules have been studied for the past two decades. However, the visualization of polymorph-dependent cellular uptake and cytotoxicity using microscopy imaging techniques has not yet been reported. The luminescent polymorph is an ideal candidate to validate the above hypothesis. Herein, we report the polymorph-dependent cellular uptake, cytotoxicity, and bio-imaging functions of polymorphs 1Y and 1R of a naphthalimide-phenothiazine dyad. These polymorphs show different luminescence colors in the solid state and exhibit aggregation-induced enhanced emission (AIEE) in the DMSO-Water mixture. Bioimaging, cytotoxicity assay, and fluorescence-activated cell sorting (FACS) studies revealed that these polymorphs show different levels of cytotoxicity, cellular uptake, localization, and imaging potential. Detailed photophysical, morphological, and biological studies revealed that the difference in molecular conformation in these polymorphs enables them to form aggregates of different sizes and morphology, which leads to the differential uptake of these into the cells and consequently shows different cytotoxicity and imaging potentials.

Synthesis of 6-alkoxy and 6-hydroxy-alkyl amine derivatives of braylin as vasorelaxing agents.

Braylin (10b) is a 8,8-dimethyl chromenocoumarin present in the plants of the family Rutaceae and Meliaceae and possesses vasorelaxing and anti-inflammatory activities. In this study, six 6-alkoxy (10b, 15-19), and twelve 6-hydroxy-alkyl amine (20a-20l) derivatives of braylin (11 and 12) were synthesized to delineate its structural requirement for vasorelaxing activity. The synthesized compounds were evaluated for vasorelaxation response in preconstricted intact rat Main Mesenteric Artery (MMA). The compounds showed l-type VDCC channel blockade depended and endothelium-independent vasorelaxation within the range of Emax < 50.00-96.70 % at 30 µM. Amongst all, 6-alkoxy derivatives were more active than 6-hydroxy-alkyl amine derivatives. The structural refinements about braylin showed that deletion of its methoxy group or homologation beyond ethoxy group presented deleterious effect on vasorelaxation response of braylin. Interestingly, substituting the ethoxy group in 10b presented the best activity and selectivity towards l-type VDCC channel blockade, a specific target cardiovascular function.

A substrate-dependent reaction of 1-aryl-2-alkyl-1,2-diketones with 2-aroyl-1-chlorocyclopropanecarboxylates: selective access to 2',5'-dicyclopropoxy-1,1':4',1''-teraryls and pentafulvenes.

An interesting substrate-controlled one-pot approach to highly substituted 2',5'-dicyclopropoxy-1,1':4',1''-teraryls and 6-hydroxypentafulvenes involving various 1,2-diketones and 2-aroyl-1-chlorocyclopropanecarboxylates as 3C Michael acceptors triggered by Cs2CO3 has been developed. We noticed that 1,2-diketones play a decisive role in this reaction to determine the product's selectivity. For example, aryl rings having electron-poor functionalities at the para and meta-positions of 1,2-diketones led to 2,5-diarylhydroquinones selectively via a cyclodimerization/double oxa-Michael process with highly strained cyclopropenes. However, when 1-naphthyl/electron-donating aryl/ortho-aryl-substituted 1,2-diketones were chosen, the Michael-initiated ring expansion reaction (C-C and CC bonds) took place under the same conditions that gave the corresponding pentafulvenes predominately. Moreover, this reaction has several imperative features such as good to high diastereoselectivities, wide substrate scope, good functional group tolerance, transition metal-free process, etc.

Osmo-air drying of banana slices: multivariate analysis, process optimization and product quality characterization.

In the present work, osmotic dehydration (OD) was applied as a pretreatment to hot air drying of banana slices and the effect of OD parameters on mass transfer characteristics, color profile was analysed. Principal component analysis (PCA) of OD process revealed that solid gain, weight reduction, water loss and total soluble solids were positively correlated with each other but were found to be negatively correlated with moisture content (MC) of sample. Response surface methodology was used for optimizing the OD of banana slices and and the optimum conditions were 61.26°Brix sucrose concentration at 50 °C for 6 h, resulting in moisture reduction from 75 to 49.78%. PCA-biplot of osmo-air drying (OAD) process showed the association among response parameters, which further revealed a positive correlation of MC with bioactive components. Additionally, OAD samples were also studied for microstructure and Fourier Transform Infra-red analysis. Addition of calcium lactate to sucrose solution resulted in preserving the firmness and bioactive components during osmosis, in addition to fortifying the sample with calcium. The present study provides new possibilities for food industries in preserving the ripe banana and developing calcium fortified functional food products.

Extrusion of fermented rice-black gram flour for development of functional snacks: Characterization, optimization and sensory analysis.

Considering the health benefits of fermentation, extrusion of fermented rice black gram mix flour can lead to developing nutritionally rich expanded snack. Hence, present study details the effect of various extrusion process variables, barrel temperature (100, 110, 120 °C), screw speed (250, 300, 350 rpm) and die opening diameter (3, 3.5 mm) on physicochemical and bioactive properties of extrudates from fermented rice-black gram flour (Rice flour: black gram flour = 3:1). Results indicated that temperature rise led to the production of a more expanded product with higher water solubility index (WSI) and lower water absorption index (WAI). Higher puffing, WSI, and bioactive content were observed in 3 mm die opening extrudates. Interestingly, extrusion cooking of fermented flour has shown a remarkable increment in phenolic content and antioxidant activity from 63.47 up to 210.3 and 7.28 up to 13.889 mg GAE/100 g, respectively. However, rise in barrel temperature showed a negative impact on bioactive attributes. Further, the optimal conditions determined by numerical optimization method for development of fermented flour-based extrudates having superior functional and enhanced bioactive properties were found to be 100 °C temperature, 289 rpm of screw and 3 mm die diameter. Principal component analysis indicated that bulk density-moisture content and phenolic content-antioxidant activity were highly positively correlated, while expansion ratio-bulk density was negatively correlated. The microstructure of extrudates showed continuous and compact structure lacking starch granules. The fuzzy logic analysis revealed that fermented flour-based extruded product had superior overall acceptability over unfermented flour extrudates.

Comprehensive Understanding of the Eco-Friendly Synthesis of Zeolites: Needs of 21st Century Sustainable Chemical Industries.

Zeolites have taken a leading position in petrochemical, fine, and bulk chemical industries due to their porous architecture, pore sizes, tunable acidity, and thermal stability. Various strategies of zeolites preparation, including template-free, solvent-free, and toxic mineral-free strategies are summarized. Moreover, the zeolite synthesis using naturally occurring minerals and sustainable natural templates is also discussed, which involves the synthesis of nanocrystalline zeolites of different framework structures using plant-based natural templates and biomass-derived renewable chemicals. Overall this personal account provides the fundamentals of various sustainable synthetic strategies reported in the literature for the synthesis of zeolites with suitable examples that will be useful for the students and will motivate experienced researchers to develop various novel sustainable methods for the synthesis of zeolites and other inorganic materials of industrial relevance.

Modelling of moisture migration during convective drying of pineapple slice considering non-isotropic shrinkage and variable transport properties.

The present work aims to develop a 3-dimensional finite element (FE) model to analyze moisture migration during drying of pineapple ring considering moisture dependent diffusion coefficient (D) and mass transfer coefficient (hm) along with radial and longitudinal shrinkage. Pineapple rings were dried at 70 °C temperature and 0.6 m/s air velocity to study the moisture loss and shrinkage kinetics during drying. Thickness, outer radius and inner radius of hollow cylindrical pineapple slices were reduced by 79.3%, 32.2%, and 51.2%, respectively due to the occurrence of shrinkage during drying. Non-linear regression analysis showed the quadratic model to best fitted to the experimental moisture ratio data for explaining the shrinkage phenomenon in pineapple slice during drying. Shrinkage was accommodated into FE modelling using the arbitrary lagrange-eulerian method. Consideration of variable D showed better agreement with the experimental data than consideration of constant D, however constant and variable hm predicted similar results. Incorporation of shrinkage phenomena during modelling led to prediction of more accurate result showing 0.06% deviation from experimental curve, but neglecting the shrinkage resulted in a 17% deviation. Hence, model developed with consideration of shrinkage along with variable D and hm presented best fit with experimental drying curve. Developed model allowed the visualization of spatial moisture profile within the sample during drying, which would be useful for estimating the correct drying time, optimizing and designing of drying process.

Effect of ultrasound and chemical pretreatment on drying characteristics and quality attributes of hot air dried pineapple slices.

Drying of food materials is a time consuming activity making the process cost and energy intensive and hence, several pretreatments are used to improve the drying rate. The present study aims to study the effect of potassium metabisulphite (KMS solution, 0.25% w/v) and ultrasound (20 and 30 min) pretreatment on hot air drying characteristics and quality of pineapple slices. The results indicated that pretreated samples provided higher drying rate, enhanced moisture diffusivity, brighter color and lower hardness than that of untreated dried sample. It was observed that KMS and ultrasound pretreatment for 20 and 30 min reduced the drying time by 23.8%, 19% and 14.3%, respectively. Further, ten thin layer drying models were applied to the experimental drying data and logarithmic model was best fitted to explain the drying behavior of pretreated and untreated samples. Additionally, the effect of shrinkage on moisture transfer mechanism was also studied. Results highlighted that instantaneous moisture diffusivity was increased during drying while shrinkage was not accounted. However, shrinkage consideration reduced the average moisture diffusivity values by 72-83%. Overall color change (13.95 ± 0.92) and browning index (36.02 ± 2.45) were found to be lowest in ultrasound (30 min) pretreated dried sample, highlighting better color stability. Scanning electron microscopy presented noticeable effects of pretreatment on alterations of microstructure of pineapple slices. It can be interpreted that KMS pretreatment was found to be more effective for improvement of drying characteristics of pineapple slices as compared to ultrasound pretreatment.

Psiguanol, a novel α-pyrone derivative from Psidium guajava leaves and vasorelaxant activity in rat aorta cells through intracellular cGMP-dependent opening of calcium-activated potassium channels.

The phytochemical investigation of Psidium guajava leaves led to the isolation of total nineteen compounds which belongs to meroterpenoids, flavonoid, phenolics, and triterpenoids. The compounds were isolated using extensive chromatography techniques and identified as psiguanol (4), as new compound along with guajadial (1), psidial A (2), ß-caryophyllene (3), quercetin (5), avicularin (6), guaijaverin (7), hyperin (8), rutin (9), ursolic acid (10), corosolic acid (11), asiatic acid (12), ß-sitosterol (13), ß-sitosterol-D-glucoside (14), ellagic acid (15), 3,3',4'-trimethylellagic acid 4-O-glucoside (16), protocatechuic acid (17), gallic acid (18), and tricosanoic acid (19) as known molecules. The compound 16 was isolated for the first time from this plant. The isolated compounds were evaluated for vasorelaxation activity in rat aorta cells and it was observed that compound 4 exhibited the most potent vasorelaxation response in the ex-vivo model in isolated rat aorta cells. Mechanistically, the vasorelaxation activity of 4 was mediated through cGMP-dependent BKCa channel opening.

Designing novel anti-plasmodial quinoline-furanone hybrids: computational insights, synthesis, and biological evaluation targeting Plasmodium falciparum lactate dehydrogenase.

To combat resistance against current antimalarials, modifying key pharmacophores and exploring novel parasite-specific drug targets remained one of the key drug design strategies. The resistance to quinoline-based antimalarials arises often due to the efflux of the drug. Hence, the development of newer agents containing bulkier pharmacophores will enable medicinal chemists to counteract drug resistance. In view of this, herein we designed bulkier quinoline-furanone hybrids. Initially, virtual drug-likeness and ADMET screening were conducted to optimize physicochemical properties followed by docking of the hybrids against the Plasmodium falciparum lactate dehydrogenase (PfLDH) enzyme. The most potent hybrids that emerged from the computational screening were synthesized and screened for their bioactivity against the resistant strain of Plasmodium through Schizont Maturation Inhibition assays. Among the compounds tested, 5g and 6e demonstrated the best activity, with IC50 values similar to chloroquine (CQ), and 5g exhibited superior LDH inhibition compared to CQ. Compounds 5f, 7a, and 7f showed IC50 values comparable to CQ and moderate LDH inhibition. Structure-activity relationship (SAR) analysis revealed that halogen substitutions, particularly Br and Cl, enhanced antimalarial activity, while strong electron-withdrawing (-NO2) or -donating (-OH) groups led to diminished activity. Additionally, bulkier aromatic substitutions were favoured for antimalarial activity and LDH inhibition. The investigation successfully found potent anti-plasmodial quinoline-furanone hybrids, demonstrating promising prospects for combating malaria.

Construction of an amperometric TG biosensor based on AuPPy nanocomposite and poly (indole-5-carboxylic acid) modified Au electrode.

A method is described for construction of an amperometric triglyceride (TG) biosensor based on covalent co-immobilization of lipase, glycerol kinase and glycerol-3-phosphate oxidase onto gold polypyrrole nanocomposite decorated poly indole-5-carboxylic acid electrodeposited on the surface of a gold electrode. The enzyme electrode was characterized by transmission electron microscopy, scanning electron microscopy, electrochemical impedance studies, Fourier transform infrared spectroscopy and cyclic voltammetry. Biosensor showed optimum response within 4 s at pH 6.5 and 35 °C, when polarized at +0.1 V against Ag/AgCl. There was a linear relationship between sensor response and triolein concentration in the range 50-700 mg/dl. Biosensor was employed for determination of TG in serum. Detection limit of the biosensor was 20 mg/dl. Biosensor was evaluated with 91-95 % recovery of added triolein in sera and 4.14 and 5.85 % within and between batch coefficients of variation, respectively. There was a good correlation (r = 0.99) between sera TG values by standard method (Enzymic colorimetric) and the present method. The biosensor was unaffected by a number of serum substances at their physiological concentration. Biosensor lost 50 % of its initial activity after its 100 uses over 7 months, when stored at 4 °C.

Inherited thrombophilia: undetected comorbidity complicating COVID-19 infection.

The relation between the severity of COVID-19 and coexisting undiagnosed underlying thrombophilic conditions is not yet established. It may be possible that undiagnosed thrombophilia exaggerates an already pro-thrombotic state in COVID-19 patients and may be responsible for severe disease in absence of any known co-morbidity. The aim was to analyze the association of underlying thrombophilia with the severity of COVID-19 infection in post-COVID patients after a minimum of 6 weeks of recovery and to compare thrombophilia profile in severe versus non-severe COVID-19 patients. Forty severe and 40 non-severe COVID patients at least 6 weeks post recovery were selected for thrombophilia profile and complete blood count evaluation. The data were analyzed using Stata software, USA; version 13. The Chi-square test and Student's t-test were used to compare proportions and mean respectively. A total of 14/80 (17.5%) were positive for the thrombophilia screen. Protein C deficiency was noted in 6/40 (15%) severe COVID patients but not in the non-severe group. The Protein S deficiency was seen in 7/40 (17.5%) severe patients and only 1 patient was deficient in the non-severe group (2.5%). The mean Protein C and Protein S levels of severe and non-severe COVID patients were statistically significant (P-0.002) and (P-0.007) respectively. The difference in mean anti-COVID IgG antibody titer of severe and non-severe COVID patients was also statistically significant (P-0.0001). To Conclude, Protein C & S deficiencies were the commonest abnormalities detected in severe COVID patients. Positive thrombophilia profile and higher titers of anti-IgG COVID-19 antibodies were seen in a significant number of patients who had suffered from Severe COVID-19 than in non-severe infection, even after 6 weeks of recovery. Thereby, suggesting that underlying thrombophilia might have affected the severity of the disease.

Correlation of T-regulatory Cells and Iron Status in ß-Thalassemia Major Patients.

Background The increased risk of infections in transfusion-dependent ß-thalassemia major (TDT) patients is mainly due to underlying immune dysfunction; however, its cause is largely unidentified. There is sufficient evidence to suggest immune changes due to iron deficiency; however, similar studies demonstrating the effects of iron excess on immune cells in these cases are limited. Aim and objectives To analyze the correlation between T-regulatory cells and iron stores in ß-thalassemia major patients. Methods In this study, 20 ß-thalassemia major cases and 20 healthy controls were studied for complete hemogram, iron profile, and flow cytometric immunophenotyping for CD3+, CD4+, CD8+, and T-regulatory cells markers (CD4+CD25+ and CD4+CD25+FOXP3+). Result Significantly higher levels of serum iron, ferritin, transferrin saturation, and CD4+ cell percentage were observed in cases than in controls. In 70% of cases with serum ferritin cut-off levels of less than 1000 µg/L, the T-regulatory cell marker CD4+CD25+ and serum ferritin revealed a significant moderate positive correlation (p=0.031, r=0.627). These same 70% cases also demonstrated a moderately significant positive correlation between serum iron and absolute lymphocyte count (r=0.529, p=0.042). Conclusion The results suggest that serum ferritin in excess amounts can increase T-regulatory cells, which may further alter the immune status of TDT patients; however, the absence of such a correlation in cases with serum ferritin of more than 1000 µg/L remains unanswered. It is important to understand immune system alterations as this will help provide new modalities for managing thalassemia patients in the form of immunoregulatory therapies.

Vasorelaxant property of 2-phenyl ethyl alcohol isolated from the spent floral distillate of damask rose (Rosa damascena Mill.) and its possible mechanism.

ETHNOBOTANICAL RELEVANCE: Rosa damascena Mill. (Rosaceae), commonly known as damask rose, is an ancient medicinal and perfumery plant used in Traditional Unani Medicine due to various therapeutic effects, including cardiovascular benefits. AIM OF THE STUDY: This study aimed to evaluate the vasorelaxant effect of the 2-phenyl ethyl alcohol (PEA) isolated from the spent flowers of R. damascena which remain after the extraction of essential oil. MATERIALS AND METHODS: The freshly collected flowers of R. damascena were hydro-distilled in a Clevenger's type apparatus to extract the rose essential oil (REO). After removing the REO, the spent-flower hydro-distillate was collected and extracted with organic solvents to yield a spent-flower hydro-distillate extract (SFHE), which was further purified by column chromatography. The SFHE and its isolate were characterized by gas chromatography (GC-FID), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) techniques. The PEA, isolated from SFHE, was evaluated for vasorelaxation response in conduit blood vessels like rat aorta and resistant vessels like mesenteric artery. The preliminary screening of PEA was done in aortic preparation pre-constricted with phenylephrine/U46619. Further, a concentration-dependent relaxation response to PEA has been elicited in both endothelium-intact and endothelium-denuded arterial rings, and the mode of action was explored. RESULTS: The SFHE revealed the presence of PEA as the main constituent (89.36%), which was further purified by column chromatography to a purity of 95.0%. The PEA exhibited potent vasorelaxation response both in conduit vessels like the rat aorta and resistance vessels like the mesenteric artery. The relaxation response is mediated without any involvement of vascular endothelium. Further, TEA sensitive BKCa channel was found to be the major target for PEA-induced relaxation response in these blood vessels. CONCLUSIONS: The spent flowers of R. damascena, which remain after the extraction of REO, could be used to extract PEA. The PEA possessed marked vasorelaxation properties in both aorta and mesenteric artery and showed promise for development into an herbal product against hypertension.

The influence of non-thermal technologies on color pigments of food materials: An updated review.

The color of any food is influenced by several factors, such as food attributes (presence of pigments, maturity, and variety), processing methods, packaging, and storage conditions. Thus, measuring the color profile of food can be used to control the quality of food and examine the changes in chemical composition. With the advent of non-thermal processing techniques and their growing significance in the industry, there is a demand to understand the effects of these technologies on various quality attributes, including color. This paper reviews the effects of novel, non-thermal processing technologies on the color attributes of processed food and the implications on consumer acceptability. The recent developments in this context and a discussion on color systems and various color measurement techniques are also included. The novel non-thermal techniques, including high-pressure processing, pulsed electric field, ultrasonication, and irradiation which employ low processing temperatures for a short period, have been found effective. Since food products are processed at ambient temperature by subjecting them to non-thermal treatment for a very short time, there is no possibility of damage to heat-sensitive nutrient components in the food, any deterioration in the texture of the food, and any toxic compounds in the food due to heat. These techniques not only yield higher nutritional quality but are also observed to maintain better color attributes. However, suppose foods are exposed to prolonged exposure or processed at a higher intensity. In that case, these non-thermal technologies can cause undesirable changes in food, such as oxidation of lipids and loss of color and flavor. Developing equipment for batch food processing using non-thermal technology, understanding the appropriate mechanisms, developing processing standards using non-thermal processes, and clarifying consumer myths and misconceptions about these technologies will help promote non-thermal technologies in the food industry.

Platelets orchestrate remote tissue damage after mesenteric ischemia-reperfusion.

Ischemia-reperfusion (I/R) injury is a leading cause of morbidity and mortality. A functional role for platelets in tissue damage after mesenteric I/R is largely unknown. The hypothesis that mesenteric I/R local and remote injury are platelet dependent was tested. Using a murine mesenteric I/R model, we demonstrate that platelets orchestrate remote lung tissue damage that follows mesenteric I/R injury and also contribute, albeit to a lesser degree, to local villi damage. While lung damage is delayed compared with villi damage, it increased over time and was characterized by accumulation of platelets in the pulmonary vasculature early, followed by alveolar capillaries and extravasation into the pulmonary space. Both villi and lung tissues displayed complement deposition. We demonstrate that villi and lung damage are reduced in mice made platelet deficient before I/R injury and that platelet transfusion into previously platelet-depleted mice before I/R increased both villi and lung tissue damage. Increased C3 deposition accompanied platelet sequestration in the lung, which was mostly absent in platelet-depleted mice. In contrast, C3 deposition was only minimally reduced on villi of platelet-depleted mice. Our findings position platelets alongside complement as a significant early upstream component that orchestrates remote lung tissue damage after mesenteric I/R and strongly suggest that reperfusion injury mitigating modalities should consider the contribution of platelets.

Inhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injury.

Tissue injury following ischemia-reperfusion (I/R) occurs as a consequence of actions of soluble factors and immune cells. Growing evidence supports a role for platelets in the manifestation of tissue damage following I/R. Spleen tyrosine kinase has been well documented to be important in lymphocyte activation and more recently in platelet activation. We performed experiments to evaluate whether inhibition of platelet activation through inhibition of spleen tyrosine kinase prevents tissue damage after mesenteric I/R injury. Platelets isolated from C57BL/6J mice fed with R788 for 10 days were transfused into C57BL/6J mice depleted of platelets 2 days before mesenteric I/R injury. Platelet-depleted mice transfused with platelets from R788-treated mice before mesenteric I/R displayed a significant reduction in the degree of remote lung damage, but with little change in the degree of local intestinal damage compared with control I/R mice. Transfusion of R788-treated platelets also decreased platelet sequestration, C3 deposition, and immunoglobulin deposition in lung, but not in the intestine, compared with control groups. These findings demonstrate that platelet activation is a requisite for sequestration in the pulmonary vasculature to mediate remote tissue injury after mesenteric I/R. The use of small-molecule inhibitors may be valuable to prevent tissue damage in remote organs following I/R injury.