Multispectroscopic and Theoretical Investigation on the Binding Interaction of a Neurodegenerative Drug, Lobeline with Human Serum Albumin: Perturbation in Protein Conformation and Hydrophobic-Hydrophilic Surface.

Lobeline (LOB), a naturally occurring alkaloid, has a broad spectrum of pharmacological activities and therapeutic potential, including applications in central nervous system disorders, drug misuse, multidrug resistance, smoking cessation, depression, and epilepsy. LOB represents a promising compound for developing treatments in various medical fields. However, despite extensive pharmacological profiling, the biophysical interaction between the LOB and proteins remains largely unexplored. In the current article, a range of complementary photophysical and cheminformatics methodologies were applied to study the interaction mechanism between LOB and the carrier protein HSA. Steady-state fluorescence and fluorescence lifetime experiments confirmed the static-quenching mechanisms in the HSA-LOB system. "K" (binding constant) of the HSA-LOB system was determined to be 105 M-1, with a single preferable binding site in HSA. The forces governing the HSA-LOB stable complex were analyzed by thermodynamic parameters and electrostatic contribution. The research also investigated how various metal ions affect complex binding. Site-specific binding studies depict Site I as probable binding in HSA by LOB. We conducted synchronous fluorescence, 3D fluorescence, and circular dichroism studies to explore the structural alteration occurring in the microenvironment of amino acids. To understand the robustness of the HSA-LOB complex, we used theoretical approaches, including molecular docking and MD simulations, and analyzed the principal component analysis and free energy landscape. These comprehensive studies of the structural features of biomolecules in ligand binding are of paramount importance for designing targeted drugs and delivery systems.

Binding Interaction of Coumarin Derivative Daphnetin with Ovalbumin: Molecular Insights into the Complexation Process and Effects of Metal Ions and pH in the Binding and Antifibrillation Studies.

This study investigates the interaction between daphnetin and ovalbumin (OVA) as well as its potential to inhibit OVA fibrillation using both spectroscopic and computational analysis. A moderate binding affinity of 1 × 104 M-1 was observed between OVA and daphnetin, with a static quenched mechanism identified during the fluorescence quenching processes. Metal ions' (Cu2+ and Zn2+) presence led to an increase in the binding affinities of daphnetin toward OVA, mirroring a similar trend observed with the pH variation. Synchronous and 3D fluorescence studies indicated an increase in the polarity of the microenvironment surrounding the Trp residues during binding. Interestingly, circular dichroism and Fourier transform infrared studies showed a significant change in the secondary structure of OVA upon binding with daphnetin. The efficacy of daphnetin in inhibiting protein fibrillation was confirmed through thioflavin T and Congo Red binding assays along with fluorescence microscopic imaging analysis. The thermodynamic assessment showed positive ΔH° [+(29.34 ± 1.526) kJ mol-1] and ΔS° [+(181.726 ± 5.465) J mol-1] values, indicating the presence of the hydrophobic forces, while negative ΔG° signifies spontaneous binding interactions. These experimental findings were further correlated with computational analysis, revealing daphnetin dynamics within the binding site of OVA.

Interactions of Turmeric- and Curcumin-Functionalized Gold Nanoparticles with Human Serum Albumin: Exploration of Protein Corona Formation, Binding, Thermodynamics, and Antifibrillation Studies.

In order to better understand the bioavailability and biocompatibility of polyphenol-assisted surface-modified bioengineered nanoparticles in nanomedicine applications, here, we address a series of photophysical experiments to quantify the binding affinity of serum albumin toward polyphenol-capped gold nanoparticles. For this, two different gold nanoparticles (AuNPs) were synthesized via the green synthesis approach, where curcumin and turmeric extract act as reducing as well as capping agents. The size, surface charge, and surface plasmon bands of the AuNPs were highly affected by the adsorption of human serum albumin (HSA) during protein corona formation, which was investigated using dynamic light scattering (DLS), ξ-potential, ultraviolet-visible (UV-vis) spectroscopy, and transmission electron microscopy (TEM) measurements. Fluorescence-based methods, absorbance, and SERS experiments were carried out to evaluate the binding aspects of AuNPs with HSA. We found that the AuNPs show moderate binding affinity toward HSA (Kb ∼ 104 M-1), irrespective of the capping agents on the surface. Hydrophobic association, along with some contribution of electrostatic interaction, played a key role in the binding process. The binding interaction was more toward the subdomain IIA region of HSA, as indicated by the competitive displacement studies using site-specific binders (warfarin and flufenamic acid). Because of the large surface curvature of small-sized AuNPs, the secondary structural conformations of HSA were slightly altered, as revealed by circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopy, and surface-enhanced Raman scattering (SERS) measurements. Additionally, the findings of the binding interactions were re-evaluated using molecular dynamics (MD) simulation studies by determining the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and changes in the binding energy of HSA upon complexation with AuNPs. To determine the tentative evidence for pharmacokinetic administration, these biocompatible AuNPs were applied to inhibit the amyloid fibril formation of HSA and monitored by using the thioflavin T (ThT) assay, ANS fluorescence assay, fluorescence microscopic imaging, and FESEM. AuNPs were found to show better resistance toward fibrillation of the adsorbed protein.

Formation of CdTe core and CdTe@ZnTe core-shell quantum dots via hydrothermal approach using dual capping agents: deciphering the food dye sensing and protein binding applications.

Excessive use of food coloring agents in the food industry to make the food more attractive or improve the taste has caused various health and ecological problems. Therefore, it is necessary to develop a reliable, sensitive, and selective sensing probe to detect food dyes in different food products for future industrial processing and biosafety. In recent decades, surface-functionalized quantum dots (QDs), owing to their unique optical properties, have gained tremendous interest for a wide range of applications, including biomedical, bioimaging and sensing applications. Herein, we have reported the synthesis of excellent colloidal stable and highly luminescent CdTe core and CdTe@ZnTe core-shell QDs using dual functionalizing agents, polyvinyl pyrrolidone and vitamin C. The synthesized QDs were explored as excellent sensing probes for the food dyes carmoisine, Ponceau 4R and tartrazine with limit of detection (LOD) values of 0.097 ± 0.006, 0.147 ± 0.001 and 0.044 ± 0.001 µM for CdTe-PVP QDs and 0.079 ± 0.001, 0.114 ± 0.002 and 0.042 ± 0.001 µM for CdTe@ZnTe-PVP QDs, respectively. The sensitivity of the synthesized QDs for the food dyes was also investigated in real samples (soft drinks and medications). Moreover, considering the potential effects of QDs as therapeutics or nano-drug carriers, the interactions between the synthesized QDs and carrier protein human serum albumin (HSA) were investigated. The binding affinity was observed to be in the order of 104 M-1. QDs were found to quench the intrinsic fluorescence of HSA, and both types of quenching (static and dynamic) occur via electrostatic interactions in association with hydrophobic forces without any significant alteration in the protein structure.

Evaluation of prescriptions from tertiary care hospitals across India for deviations from treatment guidelines & their potential consequences.

BACKGROUND OBJECTIVES: Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription have potential to improve prescribing practices. In this context, the present study aimed to capture and evaluate the prevalence of deviations from treatment guidelines in the prescriptions, potential consequence/s of the deviations and corrective actions recommended by clinicians. METHODS: It was a cross-sectional observational study conducted in the outpatient departments of tertiary care hospitals in India wherein the 13 Indian Council of Medical Research Rational Use of Medicines Centres are located. Prescriptions not compliant with the standard treatment guidelines and incomplete prescriptions with respect to formulation, dose, duration and frequency were labelled as 'prescriptions having deviations'. A deviation that could result in a drug interaction, lack of response, increased cost, preventable adverse drug reaction (ADR) and/or antimicrobial resistance was labelled as an 'unacceptable deviation'. RESULTS: Against all the prescriptions assessed, about one tenth of them (475/4838; 9.8%) had unacceptable deviations. However, in 2667/4838 (55.1%) prescriptions, the clinicians had adhered to the treatment guidelines. Two thousand one hundred and seventy-one prescriptions had deviations, of which 475 (21.9%) had unacceptable deviations with pantoprazole (n=54), rabeprazole+domperidone (n=35) and oral enzyme preparations (n=24) as the most frequently prescribed drugs and upper respiratory tract infection (URTI) and hypertension as most common diseases with unacceptable deviations. The potential consequences of deviations were increase in cost (n=301), ADRs (n=254), drug interactions (n=81), lack of therapeutic response (n=77) and antimicrobial resistance (n=72). Major corrective actions proposed for consideration were issuance of an administrative order (n=196) and conducting online training programme (n=108). INTERPRETATION CONCLUSIONS: The overall prevalence of deviations found was 45 per cent of which unacceptable deviations was estimated to be 9.8 per cent. To minimize the deviations, clinicians recommended online training on rational prescribing and administrative directives as potential interventions.

Usage Pattern of Fixed-dose Combinations at ICMR Network of Rational Use of Medicine Centres across India: Recommendations for Policymakers and Prescribers.

AIM: Irrational use of medicines is a global problem. In India, one contributing factor is the availability of a large number of fixed-dose combinations (FDCs). To improve rational use and to strengthen policies, it is important to assess the usage patterns and rationality of FDCs. METHODS: This study was conducted as part of a 1-year prospective cross-sectional analysis of prescriptions in the outpatient clinics of broad specialities from 13 tertiary care hospitals across India. Five most commonly prescribed FDCs in each center were analyzed. In addition, all the prescribed FDCs were classified as per the Kokate Committee classification and it was noted whether any of the FDCs were irrational or banned as per the reference lists released by regulatory authorities. RESULTS: A total of 4,838 prescriptions were analyzed. Of these, 2,093 (43.3%) prescriptions had at least one FDC. These 2,093 prescriptions had 366 different FDCs. Of the 366 FDCs, 241 were rational; 10 were irrational; 14 required further data generation; and the remaining 96 FDCs could not be categorized into any of the above. Vitamins and minerals/supplements, antibacterial for systemic use, and drugs for gastroesophageal reflux disease (GERD) and peptic ulcer were the most used FDCs. CONCLUSION: Based on the finding that some prescriptions contained irrational FDCs, it is recommended that a rigorous, regular, and uniform method of evaluation be implemented to approve/ban FDCs and that prescribers be periodically notified about the status of the bans.

The effect of Bacillus coagulans Unique IS-2 supplementation on plasma amino acid levels and muscle strength in resistance trained males consuming whey protein: a double-blind, placebo-controlled study.

PURPOSE: The aim of the present study was to assess the effect of Bacillus coagulans Unique IS-2 supplementation on absorption and utilization of protein in resistance-trained males. METHODS: In this double blind, placebo-control trial, resistance-trained males (21.08 ± 2.84 years) were randomized to consume, either 20 g of whey protein powder {80% whey protein concentrate (WPC80), amounting to 15.4 g protein} with 2 billion CFU Bacillus coagulans Unique IS-2 (supplemental group) or 20 g of whey protein powder and lactose instead of Bacillus coagulans (placebo group) once daily for 60 days with a controlled resistance exercise protocol. The whey protein concentrate (WPC-80) given to both groups had a lactose content of 6.8%. Plasma-free amino acids (PFAAs) were determined at baseline, at 30 and 60 days of supplementation. Muscle strength, hypertrophy, VO2 max, and body composition, and other biochemical parameters were assessed at baseline and end line. RESULTS: A positive effect of probiotic Bacillus coagulans Unique IS-2 supplementation was observed on protein absorption as evidenced by an increase in total PFAA by + 16.1% (p = 0.004). Branched chain amino acids (BCAA) comprising isoleucine (p = 0.016), leucine (p = 0.001), and valine (p = 0.002) were increased by + 33.1% in ITT analysis as compared to placebo after 60 days. At 30 days an increase in isoleucine by + 35% (p = 0.113), leucine by + 43% (p = 0.032), and valine by + 32% (p = 0.017) was observed in ITT analysis. Probiotic effect was shown on exercise performance as evidenced by an increase in one RM of leg press and vertical jump power by + 16.61% (p = 0.024) and + 7.86% (p = 0.007), respectively. CONCLUSION: Significantly increased absorption of BCAA with supplementation of B. coagulans Unique IS-2 along with whey protein and improvement in leg press and vertical jump power was noted indicating the positive effect of the probiotic on muscle power in the lower body. TRIAL REGISTRATION NUMBER: CTRI/2017/03/008117; Date:16.03.2017.

Interaction properties of biosynthesized cadmium sulphide quantum dots with human serum albumin: further investigation of antibacterial activities and sensing applications.

The synthesis of small-sized quantum dots (QDs) (1-10 nm) via the green route has garnered great interest regarding their prospective use in many biological applications (diagnosis, drug delivery and in vivo sensing); this is difficult to achieve using chemical synthesis methods, which produce larger size QD particles and also require hazardous reagents. Here, we synthesized biogenic cadmium sulphide (CdS) QDs using green tea extract as the reducing agent to produce particles that were homogeneous and a smaller size of 2-4 nm. We also elucidated the (a) protein binding, (b) antibacterial use and (c) sensing applications of biogenic CdS QDs in this present work. The biosynthesized CdS QDs were found to have extensive antibacterial activity against both Gram-negative Escherichia coli and Gram-positive Enterococcus faecalis bacterial strains. The introduction of QDs in biological medium can lead to the formation of protein-QD complexes; therefore we investigated the binding interaction of CdS QDs with the carrier protein human serum albumin (HSA) in vitro. The synthesized CdS QDs quenched the intrinsic fluorescence of HSA through a static quenching mechanism and the binding constant (Kb ) was in the order of 104 M-1 . It was also observed that the presence of biogenic CdS QDs affected the HSA-ligand interactions in vitro. The synthesized CdS made highly effective sensors for tetracycline, rifampicin, and bilirubin with limit of detection (LOD) values of 99, 141 and 29 ng/ml, respectively.

Multispectroscopic studies on the molecular interactions between bovine γ-globulin and borohydride-capped silver nanoparticles.

Interactions between bovine γ-globulin (BGG) and borohydride-capped silver nanoparticles (BAgNPs) were studied using dynamic light scattering (DLS) and spectroscopic techniques such as UV-vis spectroscopy, fluorescence, and circular dichroism. The results were compared with earlier reported interactions between γ-globulin and citrate-coated AgNPs (CAgNPs). BAgNPs were synthesized and characterized. Irrespective of the coating on AgNPs, nanoparticles had formed ground-state complexes with the protein. CAgNPs, as well as BAgNPs had caused static quenching of tryptophan (Trp) fluorescence of the protein. The change in the capping agent from citrate to borohydride weakened the binding of nanoparticles with the protein. But the same change in capping agent had increased the fluorescence quenching efficiency of AgNPs. Hydrogen bonding and van der Waals interactions were involved in BGG-BAgNPs complex similar to the CAgNPs complex with γ-globulin. Polarity of the Trp microenvironment in BGG was not altered using BAgNPs as opposed to CAgNPs, as supported using synchronous and three-dimensional fluorescence. Resonance light scattering experiments also suggested nano-bio conjugation. Far-UV and near-UV circular dichroism (CD) spectra respectively pointed towards changes in the secondary and tertiary structure of BGG by BAgNPs, which was not observed for CAgNPs.

Deciphering the interactions of phytochemicals with ovalbumin, the major food allergen from egg white: spectroscopic and computational studies.

Ovalbumin (OVA), the major component of egg white, has been used as a model carrier protein to study the interaction of four bioactive phytochemicals 6-hydroxyflavone, chrysin, naringin, and naringenin. A static quenching mechanism was primarily associated with the complexation of the flavonoids with OVA. Hydrophobic forces play a major part in the stability of the complexes. The structural changes within the protein in response to flavonoid binding revealed a decrease in OVA's α-helical content. The hypothesized binding site for flavonoids in OVA overlaps with one or more immunoglobulin E-binding epitopes that may have some effect in the immunoglobulin E response pathway. The flavonoids remain in the same binding site throughout the simulation time and impart protein stability by forming different noncovalent interactions. This study presents comprehensive information about the interaction of the flavonoids with OVA and the associated structural variations after the binding, which might help researchers better comprehend similar medication pharmacodynamics and provide critical information for future therapeutic development.

Role of cooked green banana in home management of acute diarrhea in under-5 children.

BACKGROUND: Acute diarrhea is an important contributor to under-5 mortality. Green banana is traditionally used as a home-based remedy for diarrhea. OBJECTIVES: To identify the effect of green banana on duration, recovery and prevention of severe dehydration in under-5 children with acute watery diarrhea with no/some dehydration. METHODS: This study was conducted in the rural field practice area of a tertiary care center between January 2020 and December 2021 in under-5 children presenting with acute diarrhea with no/some dehydration. One hundred fifty-three children were divided into group A (received cooked green banana supplementation along with standard management) and group B (received only standard management). Duration of diarrhea, proportion of children recovered, requirement of hospitalization, development of persistent diarrhea and number of diarrheal episodes in 1 year follow-up period were compared between two groups. RESULTS: Green banana supplementation was significantly associated with reduction in duration [median (interquartile range)-4 (1.5) day versus 5.5 (1) day, P < 0.001] of diarrhea, less hospitalization (9.2% versus 22.1%, P = 0.03) and early recovery, both at day 3 (17.1% versus 3.9%, P = 0.007) and day 7 (90.8% versus 77.9%, P = 0.03). Green banana also protected children from the development of persistent diarrhea (7.9% versus 19.5%, P = 0.04). It also reduced future episodes of diarrhea by 40.5%. CONCLUSION: Green banana supplementation could be a promising adjunct therapy in acute diarrhea and thereby it might reduce under-5 mortality.

Acute diarrhea is the second leading cause of under-5 mortality excluding neonatal causes in India where green banana has traditionally been used as a home-based remedy for diarrhea since ancient days. Some of the previous literatures have found promising results of green banana supplementation in prolonged diarrhea, dysentery and hospital management of acute diarrhea but none have considered it in the home management of diarrhea and have not reviewed its role on duration, recovery and prevention of severe dehydration in under-5 children with acute watery diarrhea with no/some dehydration. These issues along with the possible role of green banana in preventing future episodes of diarrhea have been addressed in our study. One hundred fifty-three under-5 children presenting with acute diarrhea with no/some dehydration were studied over 2 years dividing into group A (received cooked green banana supplementation along with standard management) and group B (received only standard management). Green banana supplementation was significantly associated with reduction in duration of diarrhea, less hospitalization and early recovery, lesser incidences of development of persistent diarrhea, and it also significantly reduced the future episodes of diarrhea. Hence, green banana could be a promising adjunct therapy in acute diarrhea and might reduce under-5 mortality.

Effect of structured training in improving the ergonomic stress in laparoscopic surgery among general surgery residents.

BACKGROUND: Minimal access surgery has fast become the standard of care for many operative procedures, but is associated with lot of ergonomic stress to the surgeons performing these procedures, which may result in reduction in surgeon's performance and work capacity. In this study, we evaluated the impact of structured training program in improving the ergonomic stress in trainee laparoscopic surgeons. METHODS: Laparoscopic surgeons were divided in 2 groups: trainee surgeons (ten) and expert surgeons (three). Baseline surface electromyography (sEMG) data were collected from bilateral deltoid, biceps brachii, forearm extensors, and pronator teres during a predefined suturing task on Tuebingen trainer with integrated porcine organs in both the groups. Trainee surgeons underwent 20 h of laparoscopic intra-corporeal suturing training and surface electromyography data were recorded at the end of training again and compared with baseline. RESULTS: Experts were found to have lower muscle activation (p < 0.05) and muscle work (p < 0.05) and better bimanual dexterity than the trainee surgeons at baseline. After training, the trainee surgeons showed significant improvement (p = 0.01), but still did not reach the values of the expert surgeons (p = 0.01). Right deltoid and pronator teres muscles were found to have maximal activity while performing intra-corporeal suturing. CONCLUSION: Structured and focused training outside operation theater can significantly reduce unnecessary muscle activation of trainee laparoscopic surgeons and better dexterity leading on to lesser ergonomic stress and thus possibly may reduce the risk of development of future musculo-skeletal disorders.

Targeting the heme protein hemoglobin by (-)-epigallocatechin gallate and the study of polyphenol-protein association using multi-spectroscopic and computational methods.

In this work, the interaction of a bioactive tea polyphenol (-)-epigallocatechin gallate (EGCG) with bovine hemoglobin (BHb) along with its anti-oxidative behavior and the anti-glycation property have been explored using multi-spectroscopic and computational techniques. The binding affinity for EGCG towards BHb was observed to be moderate in nature with an order of 104 M-1, and the fluorescence quenching mechanism was characterized by an unusual static quenching mechanism. The binding constant (Kb) showed a continuous enhancement with temperature from 3.468 ± 0.380 × 104 M-1 at 288 K to 6.017 ± 0.601 × 104 M-1 at 310 K. The fluorescence emission measurements along with molecular docking studies indicated that EGCG binds near the most dominant fluorophore of BHb (ß2-Trp37, at the interface of α1 and ß2 chains) within the pocket formed by the α1, α2 and ß2 chains. The sign and magnitude of the thermodynamic parameters, changes in enthalpy (ΔH = +17.004 ± 1.007 kJ mol-1) and in entropy (ΔS = +146.213 ± 2.390 J K-1 mol-1), indicate that hydrophobic forces play a major role in stabilizing the BHb-EGCG complex. The micro-environment around the EGCG binding site showed an increase in hydrophobicity upon ligand binding. The binding of EGCG with BHb leads to a decrease in the α-helical content, whereas that of the ß-sheet increased. FTIR studies also indicated that the secondary structure of BHb changed upon binding with EGCG, along with providing further support for the presence of hydrophobic forces in the complexation process. Molecular docking studies indicated that EGCG binds within the cavity of α1, α2, and ß2 chains surrounded by residues such as α1- Lys99, α1-Thr134, α1-Thr137, α1-Tyr140, α2-Lys127 and ß2-Trp37. Molecular dynamics simulation studies indicated that EGCG conferred additional stability to BHb. Furthermore, moving away from the binding studies, EGCG was found to prevent the glyoxal (GO)-mediated glycation process of BHb, and it was also found to act as a potent antioxidant against the photo-oxidative damage of BHb.

Effect of Virgin Coconut Oil Application on the Skin of Preterm Newborns: A Randomized Controlled Trial.

BACKGROUND: Preterm constitutes a major part of neonatal mortality, particularly in India. Due to dermal immaturity, preterm neonates are susceptible to various complications like infection, hypothermia, etc. Emollient application is a traditional practice in our subcontinent. AIMS: To find out the efficacy of coconut oil application for skin maturity, prevention of sepsis, hypothermia and apnea, its effect on long-term neurodevelopment and adverse effect of it, if any. MATERIAL AND METHODS: A randomized controlled trial was conducted in the rural field practice area of Department of Community Medicine, Burdwan Medical College from March 2014 to August 2018. Preterm born in the study period was divided into Group A (received virgin coconut oil application) and Group B (received body massage without any application). Neonatal skin condition was assessed on 7th, 14th, 21st and 28th day of life. Neurodevelopmental status was assessed on 3rd, 6th and 12th months. RESULTS: A total of 2294 preterm were included in the study. Groups A and B consisted of 1146 and 1148 preterm infants, consecutively. Mean gestational age of the study population was 31.9 ± 3.4 weeks and 50.4% were male. Mean weight loss in first few days was less in group A but mean weight gain per day was higher in group B. Lesser incidences of hypothermia and apnea, and better skin maturity and neurodevelopmental outcome were noted in group A. No significant adverse effect was noted with coconut oil application. CONCLUSION: Use of coconut oil helps in dermal maturity and better neurodevelopmental outcome. Further studies are warranted for universal recommendation.

Electrochemical Energy Storage Properties of Ni-Mn-Oxide Electrodes for Advance Asymmetric Supercapacitor Application.

In this work, we report a facile one-spot synthesis process and the influence of compositional variation on the electrochemical performance of Ni-Mn-oxides (Ni:Mn = 1:1, 1:2, 1:3, and 1:4) for high-performance advanced energy storage applications. The crystalline structure and the morphology of these synthesized nanocomposites have been demonstrated using X-ray diffraction, field emission scanning electron microscopy, and transmission electron Microscopy. Among these materials, Ni-Mn-oxide with Ni:Mn = 1:3 possesses a large Brunauer?Emmett?Teller specific surface area (127 m2 g?1) with pore size 8.2 nm and exhibits the highest specific capacitance of 1215.5 F g?1 at a scan rate 2 mV s?1 with an excellent long-term cycling stability (?87.2% capacitance retention at 10 A g?1 over 5000 cycles). This work also gives a comparison and explains the influence of different compositional ratios on the electrochemical properties of Ni-Mn-oxides. To demonstrate the possibility of commercial application, an asymmetric supercapacitor device has been constructed by using Ni-Mn-oxide (Ni:Mn = 1:3) as a positive electrode and activated carbon (AC) as a negative electrode. This battery-like device achieves a maximum energy density of 132.3 W h kg?1 at a power density of 1651 W kg?1 and excellent coulombic efficiency of 97% over 3000 cycles at 10 A g?1.

Lysozyme-luteolin binding: molecular insights into the complexation process and the inhibitory effects of luteolin towards protein modification.

In the proposed work, the complexation of bioactive flavonoid luteolin with hen egg white lysozyme (HEWL) along with its inhibitory influence on HEWL modification has been explored with the help of multi-spectroscopic and computational methods. The binding affinity has been observed to be moderate in nature (in the order of 104 M-1) and the static quenching mechanism was found to be involved in the fluorescence quenching process. The binding constant (Kb) shows a progressive increase with the increase in temperature from (4.075 ± 0.046 × 104 M-1) at 293 K to (6.962 ± 0.024 × 104 M-1) at 313 K under experimental conditions. Spectroscopic measurements along with molecular docking calculations suggest that Trp62 is involved in the binding site of luteolin within the geometry of HEWL. The positive changes in enthalpy (ΔH = +19.99 ± 0.65 kJ mol-1) as well as entropy (ΔS = +156.28 ± 2.00 J K-1 mol-1) are indicative of the presence of hydrophobic forces that stabilize the HEWL-luteolin complex. The micro-environment around the Trp residues showed an increase in hydrophobicity as indicated by synchronous fluorescence (SFS), three dimensional fluorescence (3D) and red edge excitation (REES) studies. The % α-helix of HEWL showed a marked reduction upon binding with luteolin as indicated by circular dichroism (CD) and Fourier-transform infrared spectroscopy (FTIR) studies. Moreover, luteolin is situated at a distance of 4.275 ± 0.004 nm from the binding site as indicated by FRET theory, and the rate of energy transfer kET (0.063 ± 0.004 ns-1) has been observed to be faster than the donor decay rate (1/τD = 0.606 ns-1), which is indicative of the non-radiative energy transfer during complexation. Leaving aside the binding study, luteolin showed promising inhibitory effects towards the d-ribose mediated glycation of HEWL as well as towards HEWL fibrillation as studied by fluorescence emission and imaging studies. Excellent correlation with the experimental observations as well as precise location and dynamics of luteolin within the binding site has been obtained from molecular docking and molecular dynamics simulation studies.

Planning, implementation, and evaluation of multicomponent, case-based learning for first-year Indian medical undergraduates.

Didactic lecture is an effective method to quickly pass on a high volume of information to a large number of students. However, if not well designed, lectures can be monotonous and provide only passive learning, with little scope for higher order learning skills. To address this drawback of lectures, we supplemented it with case-based learning (CBL), which has been shown to promote self-learning. After giving an overview of gastrointestinal physiology through lectures, CBL on peptic ulcer disease was implemented for first-year Bachelor of Medicine, Bachelor of Surgery students. The present study aimed to evaluate the students' and teachers' opinions on the notion of supplementing lectures with CBL. In previous reports, discussion using clinical cases was primarily employed as the solitary component for conducting CBL. In the present study, three different but mutually exclusive components, such as case discussion, concept map, and critical thinking exercise on a specific topic in gastrointestinal pathophysiology, were integrated to form the multicomponent CBL (MC-CBL). Students reported that MC-CBL could promote application of the knowledge learned in lectures in a more appropriate context (92.42% positive response), enhance their learning efficiency (98.46% positive response), promote their active participation in the learning process (98.48% positive response), and help them in integrating physiological concepts with clinical science (98.46% positive response). Teachers observed that MC-CBL could promote active learning, analytic, and problem-solving skills of students. In conclusion, MC-CBL appeared to be an effective supplement for the lectures, providing an opportunity for the students to relate the knowledge learned during lectures.

Molecular recognition of bio-active flavonoids quercetin and rutin by bovine hemoglobin: an overview of the binding mechanism, thermodynamics and structural aspects through multi-spectroscopic and molecular dynamics simulation studies.

The binding of two bio-active flavonoids, quercetin and rutin, with bovine hemoglobin (BHb) was investigated by multi-spectroscopic and computational (molecular docking and molecular dynamics simulation) studies. The two flavonoids were found to quench the intrinsic fluorescence of BHb through a static quenching mechanism. The binding constants at 288 K were observed to be (14.023 ± 0.73) × 104 M-1 and (7.848 ± 0.20) × 104 M-1, respectively for quercetin and rutin binding with BHb. Both rutin and quercetin were observed to increase the polarity around the Trp residues of BHb as indicated by synchronous and 3D spectral studies. No significant alterations in the secondary structural components of the protein were caused during the binding of the flavonoids as studied by CD and FTIR studies. The negative molar Gibbs free energies indicated the spontaneity of the interaction processes while the binding processes were characterized by a negative enthalpy change (ΔH) and a positive entropy change (ΔS). The possibility of energy transfer from the donor (BHb) to the acceptor molecules (flavonoids) was indicated by the FRET studies. According to the fluorescence studies, the flavonoids interact near to the ß2-Trp37 residue of BHb. Excellent correlations with the experimental studies were observed from the molecular docking and molecular dynamics (MD) simulation studies. Further investigations established that these flavonoids are efficient in the inhibition of glucose mediated glycation of BHb.

Non-covalent binding interaction of bioactive coumarin esculetin with calf thymus DNA and yeast transfer RNA: A detailed investigation to decipher the binding affinities, binding location, interacting forces and structural alterations at a molecular level.

Esculetin is a well-known coumarin derivative found abundantly in nature possessing an extensive array of pharmacological and therapeutic properties. Consequently, to comprehend its molecular recognition mechanism, our objective is to conduct a complete investigation of its interactions with the nucleic acid, specifically ct-DNA, and t-RNA, using spectroscopic and computational techniques. The intrinsic fluorescence of esculetin is quenched when it interacts with ct-DNA and t-RNA, and this occurs through a static quenching mechanism. The thermodynamic parameters demonstrated that the interaction is influenced by hydrogen bonding and weak van der Waals forces. CD and FT-IR results revealed no conformational changes in ct-DNA and t-RNA structure on binding with esculetin. Furthermore, competitive displacement assay with ethidium bromide, melting temperature, viscosity measurement, and potassium iodide quenching experiments, reflected that esculetin probably binds to the minor groove of ct-DNA. The molecular docking results provided further confirmation for the spectroscopic findings, including the binding location of esculetin and binding energies of esculetin complexes with ct-DNA and t-RNA. Molecular dynamics simulation studies demonstrated the conformational stability and flexibility of nucleic acids.

The Effects of Short- and Long-Term Ingestion of Plastic Toxin Bisphenol A on Gastrointestinal Transit Time in Rats.

Introduction Exposure to bisphenol A (BPA), a toxic chemical released from plastic, affects various body functions, including reproduction, metabolism, and development. The most common route of exposure to BPA is oral, and the gastrointestinal (GI) tract is, therefore, the first body system to be exposed to BPA. BPA has been well-documented to impair gut contractility in rats, in vitro. It may therefore be hypothesized that BPA may adversely affect GI motility and hence slow down the movement of food, resulting in the increased transit of food bolus in the GI tract. There are no reports so far on the effects of BPA on GI transit time. Objectives The present study was undertaken to examine the impact of exposure to BPA by a single oral dose (termed as short-term ingestion of BPA) and chronic (28-day) oral dose (termed as long-term ingestion of BPA) on the transit time of food bolus in the gut of adult male albino rats. Methods and materials The study was conducted in the Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. In one set of experiments, each animal was fed a food pellet, once (short-term ingestion) containing BPA (2 µg/kg and 50 µg/kg in different groups), and in another set of experiments, each animal was fed a food pellet containing BPA (50 µg/kg/day) for 28 consecutive days (long-term ingestion). Control rats in both sets were fed food pellets without BPA. Subsequently, the gastric transit index (GTI), ileocecal transit index (ICTI), and colonic transit time (CTT) were determined by the standard charcoal marker method. Results One-time ingestion of a food pellet containing BPA caused a significant (p < 0.05) drop in the GTI and ICTI and an increase in the CTT with both doses of BPA (2 and 50 µg/kg). Similarly, after chronic (28-day), oral BPA exposure, a significant decrease in the GTI and ICTT and an increase in CTT were observed. Conclusion Both short-term (one-time) and long-term (28-day) oral exposure to BPA-containing food harmed GI transit. Slow GI transit may lead to metabolic disorders and GI motility disorders, such as constipation.