Beyond the ordinary: exploring the synergistic effect of iodine and nickel doping in cobalt hydroxide for superior energy storage applications.

This study explores the iodine and nickel-doped cobalt hydroxide (I & Ni-co-doped-Co(OH)2) as a potential material for energy storage and conversion applications owing to its excellent electrochemical characteristics. According to our analysis, it was revealed that this material exhibits pseudocapacitive-like behavior, as evident from distinct redox peaks observed in cyclic voltammetry, which confirms its ability to store charges. The diffusion coefficient analysis reveals that this material possesses conductivity and rapid diffusion kinetics, making it particularly advantageous compared to materials synthesized in previous studies. Charge-discharge measurements were performed to analyze the charge storage capacity and stability of this material after 3000 consecutive cycles, showing its excellent stability with minimum loss of capacitance. Furthermore, its anodic and cathodic linear sweep voltammetry curves were measured to evaluate its oxygen evolution and hydrogen evolution reaction performance. The results showed that the material exhibited an excellent water splitting performance, which suggests its potential practical application for hydrogen production. This increased activity was attributed to the doping of α-Co(OH)2, which improved its structural stability, electrical conductivity, and charge transfer efficiency. Thus, I & Ni-co-doped-Co(OH)2 possesses enhanced properties that make it an excellent material for both energy storage and hydrogen generation applications.

Green synthesized silver nanoparticles from Phoenix dactylifera synergistically interact with bioactive extract of Punica granatum against bacterial virulence and biofilm development.

The global rise of antibiotic resistance poses a substantial risk to mankind, underscoring the necessity for alternative antimicrobial options. Developing novel drugs has become challenging in matching the pace at which microbial resistance is evolving. Recently, nanotechnology, coupled with natural compounds, has emerged as a promising solution to combat multidrug-resistant bacteria. In the present study, silver nanoparticles were green-synthesized using aqueous extract of Phoenix dactylifera (variety Ajwa) fruits and characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) coupled with Energy dispersive X-ray analysis (EDX), Transmission electron microscopy (TEM) and Thermogravimetric-differential thermal analysis (TGA-DTA). The in-vitro synergy of green synthesized P. dactylifera silver nanoparticle (PD-AgNPs) with selected antibiotics and bioactive extract of Punica granatum, i.e., ethyl acetate fraction (PGEF), was investigated using checkerboard assays. The most effective synergistic combination was evaluated against the QS-regulated virulence factors production and biofilm of Pseudomonas aeruginosa PAO1 by spectroscopic assays and electron microscopy. In-vivo anti-infective efficacy was examined in Caenorhabditis elegans N2 worms. PD-AgNPs were characterized as spherical in shape with an average diameter of 28.9 nm. FTIR analysis revealed the presence of functional groups responsible for the decrease and stabilization of PD-AgNPs. The signals produced by TGA-DTA analysis indicated the generation of thermally stable and pure crystallite AgNPs. Key phytocompounds detected in bioactive fractions include gulonic acid, dihydrocaffeic acid 3-O-glucuronide, and various fatty acids. The MIC of PD-AgNPs and PGEF ranged from 32 to 128 µg/mL and 250-500 µg/mL, respectively, against test bacterial strains. In-vitro, PD-AgNPs showed additive interaction with selected antibiotics (FICI 0.625-0.75) and synergy with PGEF (FICI 0.25-0.375). This combination inhibited virulence factors by up to 75 % and biofilm formation by 84.87 % in P. aeruginosa PAO1. Infected C. elegans worms with P. aeruginosa PAO1 had a 92.55 % survival rate when treated with PD-AgNPs and PGEF. The combination also reduced the reactive oxygen species (ROS) level in C. elegans N2 compared to the untreated control. Overall, these findings highlight that biosynthesized PD-AgNPs and bioactive P. granatum extract may be used as a potential therapeutic formulation against MDR bacteria.

Exploring the mechanism of interaction of glipizide with DNA: Combined in vitro and bioinformatics approach.

DNA, vital for biological processes, encodes hereditary data for protein synthesis, shaping cell structure and function. Since revealing its structure, DNA has become a target for various therapeutically vital molecules, spanning antidiabetic to anticancer drugs. These agents engage with DNA-associated proteins, DNA-RNA hybrids, or bind directly to the DNA helix, triggering diverse downstream effects. These interactions disrupt vital enzymes and proteins essential for maintaining cell structure and function. Analysing drug-DNA interactions has significantly advanced our understanding of drug mechanisms. Glipizide, an antidiabetic drug, is known to cause DNA damage in adipocytes. However, its extract mechanism of DNA interaction is unknown. This study delves into the interaction between glipizide and DNA utilizing various biophysical tools and computational technique to gain insights into the interaction mechanism. Analysis of UV-visible and fluorescence data reveals the formation of complex between DNA and glipizide. The binding affinity of glipizide to DNA was of moderate strength. Examination of thermodynamic parameters at different temperatures suggests that the binding was entropically spontaneous and energetically favourable. Various experiments such as thermal melting assays, viscosity measurement, and dye displacement assays confirmed the minor grove nature of binding of glipizide with DNA. Molecular dynamics studies confirmed the glipizide forms stable complex with DNA when simulated by mimicking the physiological conditions. The binding was mainly favoured by hydrogen bonds and glipizide slightly reduced nucleotide fluctuations of DNA. The study deciphers the mechanism of interaction of glipizide with DNA at molecular levels.

Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1.

SARS-CoV-2 and filovirus enter cells via the cell surface angiotensin-converting enzyme 2 (ACE2) or the late-endosome Niemann-Pick C1 (NPC1) as a receptor. Here, we screened 974 natural compounds and identified Tubeimosides I, II, and III as pan-coronavirus and filovirus entry inhibitors that target NPC1. Using in-silico, biochemical, and genomic approaches, we provide evidence that NPC1 also binds SARS-CoV-2 spike (S) protein on the receptor-binding domain (RBD), which is blocked by Tubeimosides. Importantly, NPC1 strongly promotes productive SARS-CoV-2 entry, which we propose is due to its influence on fusion in late endosomes. The Tubeimosides' antiviral activity and NPC1 function are further confirmed by infection with SARS-CoV-2 variants of concern (VOC), SARS-CoV, and MERS-CoV. Thus, NPC1 is a critical entry co-factor for highly pathogenic human coronaviruses (HCoVs) in the late endosomes, and Tubeimosides hold promise as a new countermeasure for these HCoVs and filoviruses.

Riboflavin (vitamin B2) sensitized photooxidation of ascorbic acid (vitamin C): A kinetic study.

Ascorbic acid (AH2) photoxidation sensitized by riboflavin (RF) has been studied between pH 2.0 and 12.0 in ambient air and anaerobic environment using UV and visible irradiation sources. The kinetics of AH2 degradation in aqueous medium along with RF is found to be first-order for its photodegradation. AH2 photolysis rate constants in aerobic and anaerobic conditions with RF (1.0-5.0 × 10-5 M) are 0.14-3.89 × 10-2 and 0.026-0.740 × 10-2 min-1, respectively. The rate constants (k2) of second-order kinetics for AH2 and RF photochemical interaction in aerobic and anaerobic conditions are in the range of 0.24-3.70 to 0.05-0.70 × 10-3 M-1 min-1, respectively, which manifests that increasing the RF concentration also increases the rate of photodegradation (photooxidation) of AH2. The k2 versus pH graph is bell-shaped which indicates that increasing the pH increases photolytic degradation rate of AH2 with RF. Increasing the pH results in the increased ionization of AH2 (ascorbyl anion, AH-) and redox potential which leads to the higher rates of photodegradation of AH2. Two-component spectrophotometric (243 and 266 nm, AH2 and RF, respectively) and high-performance liquid chromatography (HPLC) methods have been used to determine the concentration of AH2 and RF in pure and degraded solutions. The results obtained from these two methods are compared using a student t-test which showed no noteworthy difference between them.

Modulation of quorum sensing and biofilm of Gram-negative bacterial pathogens by Cinnamomum zeylanicum L.

The development of antibiotic resistant microbial pathogens has become a global health threat and a major concern in modern medicine. The problem of antimicrobial resistance (AMR) has majorly arisen due to sub-judicious use of antibiotics in health care and livestock industry. A slow progress has been made in last two decades in discovery of new antibiotics. A new strategy in combatting AMR is to modulate or disarm the microbes for their virulence and pathogenicity. Plants are considered as promising source for new drugs against AMR pathogens. In this study, fraction-based screening of the Cinnamomum zeylanicum extract was performed followed by detailed investigation of antiquorum sensing and antibiofilm activities of the most active fraction that is, C. zeylanicum hexane fraction (CZHF). More than 75% reduction in violacein pigment of C. violaceum 12472 was overserved. CZHF successfully modulated the virulence of Pseudomonas aeruginosa PAO1 by 60.46%-78.35%. A similar effect was recorded against Serratia marcescens MTCC 97. A broad-spectrum inhibition of biofilm development was found in presence of sub-MICs of CZHF. The colonization of bacteria onto the glass coverslips was remarkably reduced apart from the reduction in exopolymeric substances. Alkaloids and terpenoids were found in CZHF. GC/MS analysis revealed the presence of cinnamaldehyde dimethyl acetal, 2-propenal, coumarin, and α-copaene as major phytocompounds. This study provides enough evidence to support potency of C. zeylanicum extract in targeting the virulence of Gram -ve pathogenic bacteria. The plant extract or active compounds can be developed as successful drugs after careful in vivo examination to target microbial infections. RESEARCH HIGHLIGHTS: Hexane fraction of Cinnamomum zeylanicum is active against QS and biofilms. The broad-spectrum antibiofilm activity was further confirmed by microscopic analysis. Dimethyl acetal, 2-propenal, coumarin, α-copaene, and so forth are major phytocompounds.

Management of virulence in Pseudomonas aeruginosa and Serratia marcescens using environmentally-friendly titanium dioxide nanoparticles.

Antimicrobial resistance (AMR), a condition in which the efficacy of antimicrobial drugs in fighting microorganisms is reduced, has become a global challenge. Multidrug resistance (MDR) has been developing in microorganisms, where they can resist multiple medications. In particular, there has been a rise in MDR as well as extensively drug-resistant (XDR) strains of Pseudomonas aeruginosa in some regions, with prevalence rates ranging from 15% to 30%. The application of nanotechnology ranges from diagnostics to drug-delivery systems, revolutionizing healthcare, and improving disease treatment. We aimed to investigate the efficacy of titanium dioxide nanoparticles (TiO2-NPs) against various virulent traits of P. aeruginosa and S. marcescens. More than 50% reduction in the production of virulent pigments of P. aeruginosa was recorded following the treatment of TiO2-NPs. Additionally, elastases and exoproteases were inhibited by 58.21 and 74.36%, respectively. A similar result was observed against the rhamnolipid production and swimming motility of P. aeruginosa. The effect of TiO2-NPs was also validated against another opportunistic pathogen, S. marcescens, where the production of prodigiosin was reduced by 64.78%. Also, a roughly 75% attenuation of proteolytic activity and more than 50% reduction in swarming motility were found. In the control group, the cell surface hydrophobicity was 77.72%, which decreased to 24.67% with the addition of 64 µg ml-1 TiO2-NPs in culture media. The hydrophobicity index of microorganisms is crucial for their initial attachment and the formation of biofilms. In conclusion, TiO2-NPs demonstrated potential in a multi-target approach against P. aeruginosa and S. marcescens, suggesting their advantages in the prevention and treatment of infections. These nanomaterials could have vital importance in the development of novel antibacterial agents to combat drug-resistant bacteria.

Efflux Pump Inhibition-Based Screening and Anti-Infective Evaluation of Punica granatum Against Bacterial Pathogens.

Drug efflux pumps contribute to bacterial multidrug resistance (MDR), reducing antibiotic effectiveness and causing treatment failures. Besides their role in MDR, efflux pumps also assist in the transportation of quorum sensing (QS) signal molecules and increased the tolerance of biofilms. Recently, the search for efflux pump inhibitors from natural sources, including anti-infective plants, has gained attention as a potential therapy against drug-resistant bacteria. In this study, 19 traditional Indian medicinal plants were screened for their efflux pump inhibitory activity against Escherichia coli TGI. The promising extract, i.e., Punica granatum was subsequently fractioned in the solvents of increasing polarity. Among them, at sub-MIC active EPI fraction was PGEF (P. granatum ethyl acetate fraction), further investigated for anti-infective potential against Chromobacterium violaceum 12,472, Pseudomonas aeruginosa PAO1, and Serratia marcescens MTCC 97. PGEF was also evaluated for in vivo efficacy in Caenorhabditis elegans model. Major phytocompounds were analyzed by mass spectroscopic techniques. At respective Sub-MIC, PGEF reduced violacein production by 71.14% in C. violaceum 12,472. Moreover, PGEF inhibited pyocyanin (64.72%), pyoverdine (48.17%), protease (51.35%), and swarming motility (44.82%) of P. aeruginosa PAO1. Furthermore, PGEF reduced the production of prodigiosin and exoprotease by 64.73% and 61.80%, respectively. Similarly, at sub-MIC, PGEF inhibited (≥ 50%) biofilm development in all test pathogens. The key phytocompounds detected in active fraction include 5-hydroxymethylfurfural, trans-p-coumaric acid 4- glucoside, (-)-Epicatechin 3'-O-glucuronide, and ellagic acid. Interestingly, PGEF also demonstrated anti-infective efficacy against the PAO1-infected C. elegans test model and highlighting its therapeutic potential as an anti-infective agent to combat drug-resistant problems.

Multi-targeting of virulence factors of P. aeruginosa by ß-lactam antibiotics to combat antimicrobial resistance.

Antimicrobial resistance poses a significant challenge to public health, especially in developing countries, due to a substantial rise in bacterial resistance. This situation has become so concerning that we are now at risk of losing the effectiveness of antibiotics altogether. Recent research has firmly established that bacteria engage in a process called quorum sensing (QS). QS regulates various functions, including nutrient scavenging, immune response suppression, increased virulence, biofilm formation and mobility. Pseudomonas aeruginosa, an opportunistic bacterial pathogen, plays a significant role in various medical conditions such as chronic wounds, corneal infections, burn wounds and cystic fibrosis. While antibiotics are effective in killing bacteria, only a few antibiotics, particularly those from the ß-lactam group, have been studied for their impact on the quorum sensing of P. aeruginosa. Given the lack of concentrated efforts in this area, we have investigated the role of ß-lactam antibiotics on various potential targets of P. aeruginosa. Based on their toxicological profiles and the average binding energy obtained through molecular docking, azlocillin and moxalactam have emerged as lead antibiotics. The binding energy for the docking of azlocillin and moxalactam with LasA was determined to be -8.2 and -8.6 kcal/mol, respectively. Molecular simulation analysis has confirmed the stable interaction of both these ligands with all three target proteins (LasI, LasA and PqsR) under physiological conditions. The results of this research underscore the effectiveness of azlocillin and moxalactam. These two antibiotics may be repurposed to target the quorum sensing of P. aeruginosa.Communicated by Ramaswamy H. Sarma.

Human Retinal Ganglion Cells Respond to Evolutionarily Conserved Chemotropic Cues for Intra Retinal Guidance and Regeneration.

Retinal ganglion cells (RGCs) connect the retina with the higher centers in the brain for visual perception. Their degeneration leads to irreversible vision loss in patients with glaucoma. The mechanism underlying human RGCs (hRGCs) axon growth and guidance remains poorly understood because hRGCs are born during development and connections with the central targets are established before birth. Here, using RGCs directly generated from human embryonic stem cells, we demonstrate that hRGCs express a battery of guidance receptors. These receptors allow hRGCs to read the spatially arrayed chemotropic cues in the developing rat retina for the centripetal orientation of axons toward the optic disc, suggesting that the mechanism of intraretinal guidance is conserved in hRGCs. The centripetal orientation of hRGCs axons is not only in response to chemorepulsion but also involves chemoattraction, mediated by Netrin-1/DCC interaction. The spatially arrayed chemotropic cues differentially influence hRGCs physiological responses, suggesting that neural activity of hRGCs and axon growth may be coupled during inter-retinal guidance. In addition, we demonstrate that Netrin-1/DCC interaction, besides promoting axon growth, facilitates hRGCs axon regeneration by recruiting the mTOR signaling pathway. The diverse influence of Netrin-1/DCC interaction ranging from axon growth to regeneration may involve recruitment of multiple intracellular signaling pathways as revealed by transcriptome analysis of hRGCs. From the perspective of ex vivo stem cell approach to glaucomatous degeneration, our findings posit that ex vivo generated hRGCs can read the intraretinal cues for guidance toward the optic disc, the first step required for connecting with the central target to restore vision.

Umbelliferone modulates the quorum sensing and biofilm of Gram - ve bacteria: in vitro and in silico investigations.

In last two decades, the world has seen an exponential increase in the antimicrobial resistance (AMR), making the issue a serious threat to human health. The mortality caused by AMR is one of the leading causes of human death worldwide. Till the end of the twentieth century, a tremendous success in the discovery of new antibiotics was seen, but in last two decades, there is negligible progress in this direction. The increase in AMR combined with slow progress of antibiotic drug discovery has created an urgent demand to search for newer methods of intervention to combat infectious diseases. One of such approach is to look for biofilm and quorum sensing (QS) inhibitors. Plants are excellent source of wide class compounds that can be harnessed to look for the compounds with such properties. This study proves a broad-spectrum biofilm and QS inhibitory potential of umbelliferone. More than 85% reduction in violacein production Chromobacterium violaceum 12472 was found. All tested virulent traits of Pseudomonas aeruginosa PAO1 and Serratia marcescens MTCC 97 were remarkably inhibited that ranged from 56.62% to 86.24%. Umbelliferone also successfully prevented the biofilm of test bacteria at least by 67.68%. Umbelliferone interacted at the active site of many proteins of QS circuit, which led to the mitigation of virulent traits. The stable nature of complexes of umbelliferone with proteins further strengthens in vitro results. After examining the toxicological profile and other drug-like properties, umbelliferone could be potentially developed as new drug to target the infections caused by Gram - ve bacteria.Communicated by Ramaswamy H. Sarma.

Reproducible generation of human retinal ganglion cells from banked retinal progenitor cells: analysis of target recognition and IGF-1-mediated axon regeneration.

The selective degeneration of retinal ganglion cells (RGCs) is a common feature in glaucoma, a complex group of diseases, leading to irreversible vision loss. Stem cell-based glaucoma disease modeling, cell replacement, and axon regeneration are viable approaches to understand mechanisms underlying glaucomatous degeneration for neuroprotection, ex vivo stem cell therapy, and therapeutic regeneration. These approaches require direct and facile generation of human RGCs (hRGCs) from pluripotent stem cells. Here, we demonstrate a method for rapid generation of hRGCs from banked human pluripotent stem cell-derived retinal progenitor cells (hRPCs) by recapitulating the developmental mechanism. The resulting hRGCs are stable, functional, and transplantable and have the potential for target recognition, demonstrating their suitability for both ex vivo stem cell approaches to glaucomatous degeneration and disease modeling. Additionally, we demonstrate that hRGCs derived from banked hRPCs are capable of regenerating their axons through an evolutionarily conserved mechanism involving insulin-like growth factor 1 and the mTOR axis, demonstrating their potential to identify and characterize the underlying mechanism(s) that can be targeted for therapeutic regeneration.

Effects of Repeated in-vitro Exposure to Saudi Honey on Bacterial Resistance to Antibiotics and Biofilm Formation.

Introduction: Although Sumra and Sidr Saudi honey is widely used in traditional medicine due to its potent activity, it is unknown whether its prolonged usage has impact upon bacterial virulence or leading to reduced antibiotic sensitivity. Thus, the study aims to investigate the effect of prolonged (repeated) in-vitro exposure to Saudi honey on the antibiotic susceptibility profiles and biofilm formation of pathogenic bacteria. Methods: Several bacteria, including Staphylococcus aureus, Escherichia coli, and Acinetobacter baumannii, were in-vitro exposed ten times [passaged (P10)]to Sumra and Sider honey individually to introduce adapted bacteria (P10). Antibiotic susceptibility profiles of untreated (P0) and adapted (P10) bacteria were assessed using disc diffusion and microdilution assays. The tendency regarding biofilm formation following in-vitro exposure to honey (P10) was assessed using the Crystal violet staining method. Results: Adapted (P10) bacteria to both Sumra and Sidr honey showed an increased sensitivity to gentamicin, ceftazidime, ampicillin, amoxycillin/clavulanic acid, and ceftriaxone, when compared with the parent strains (P0). In addition, A. baumannii (P10) that was adapted to Sidr honey displayed a 4-fold increase in the minimal inhibitory concentration of the same honey following in-vitro exposure. 3-fold reduction in the tendency toward biofilm formation was observed for the Sumra-adapted (P10) methicillin resistant S. aureus strain, although there was a lower rate of reduction (1.5-fold) in biofilm formation by both the Sumra- and Sidr-adapted A. baumannii (P10) strains. Conclusion: The data highlight the positive impact of prolonged in-vitro exposure to Saudi honey (Sumra and Sider) for wound-associated bacteria since they displayed a significant increase in their sensitivity profiles to the tested antibiotic and a reduction in their ability to form biofilm. The increased bacterial sensitivity to antibiotics and a limited tendency toward biofilm formation would suggest the great potential therapeutic use of this Saudi honey (Sumra and Sidr) to treat wound infections.

Large-scale sonochemical fabrication of a Co3O4-CoFe2O4@MWCNT bifunctional electrocatalyst for enhanced OER/HER performances.

Herein, we have prepared a mixed-phase Co3O4-CoFe2O4@MWCNT nanocomposite through a cheap, large-scale, and facile ultrasonication route followed by annealing. The structural, morphological, and functional group analyses of the synthesized catalysts were performed by employing various characterization approaches such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The resultant samples were tested for bifunctional electrocatalytic activity through various electrochemical techniques: cyclic voltammetry (CV), linear sweep voltammetry (LSV), and electrochemical impedance spectroscopy (EIS). The prepared Co3O4-CoFe2O4@MWCNT nanocomposite achieved a very high current density of 100 mA cm-2 at a lower (290 mV and 342 mV) overpotential (vs. RHE) and a smaller (166 mV dec-1 and 138 mV dec-1) Tafel slope in the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively, compared to Co3O4-CoFe2O4. The excellent electrochemical activity of the as-prepared electrocatalyst was attributed to the uniform incorporation of Co3O4-CoFe2O4 over MWCNTs which provides high redox active sites, a greater surface area, better conductivity, and faster charge mobility. Furthermore, the enhanced electrochemical active surface, low charge-transfer resistance (Rct), and higher exchange current density (J0) of the Co3O4-CoFe2O4@MWCNT ternary composite are attributed to its superior behavior as a bifunctional electrocatalyst. Conclusively, this study demonstrates a novel and large-scale synthesis approach for bifunctional electrocatalysts with a high aspect ratio and abundance of active sites for high-potential energy applications.

Synergistic effects of biofilm-producing PGPR strains on wheat plant colonization, growth and soil resilience under drought stress.

Drought stress substantially impedes crop productivity throughout the world. Microbial based approaches have been considered a potential possibility and are under study. Based on our prior screening examination, two distinct and novel biofilm-forming PGPR strains namely Bacillus subtilis-FAB1 and Pseudomonas azotoformans-FAP3 are encompassed in this research. Bacterial biofilm development on glass surface, microtiter plate and seedling roots were assessed and characterized quantitatively and qualitatively by light and scanning electron microscopy. Above two isolates were further evaluated for their consistent performance by inoculating on wheat plants in a pot-soil system under water stresses. Bacterial moderate tolerance to ten-day drought was recorded on the application of individual strains with wheat plants; however, the FAB1 + FAP3 consortium expressively improved wheat survival during drought. The strains FAB1 and FAP3 displayed distinct and multifunctional plant growth stimulating attributes as well as effective roots and rhizosphere colonization in combination which could provide sustained wheat growth during drought. FAB1 and FAP3-induced alterations cooperatively conferred improved plant drought tolerance by controlling physiological traits (gs, Ci, E, iWUE and PN), stress indicators (SOD, CAT, GR, proline and MDA content) and also maintained physico-chemical attributes and hydrolytic enzymes including DHA, urease, ALP, protease, ACP and ß glucosidase in the soil. Our findings could support future efforts to enhance plant drought tolerance by engineering the rhizobacterial biofilms and associated attributes which requires in-depth exploration and exploiting potential native strains for local agricultural application.

Synergistic Antibacterial Screening of Cymbopogon citratus and Azadirachta indica: Phytochemical Profiling and Antioxidant and Hemolytic Activities.

Current studies were performed to investigate the phytochemistry, synergistic antibacterial, antioxidant, and hemolytic activities of ethanolic and aqueous extracts of Azadirachta indica (EA and WA) and Cymbopogon citratus (EC and WC) leaves. Fourier transform infrared data verified the existence of alcoholic, carboxylic, aldehydic, phenyl, and bromo moieties in plant leaves. The ethanolic extracts (EA and EC) were significantly richer in phenolics and flavonoids as compared to the aqueous extracts (WA and WC). The ethanolic extract of C. citratus (EC) contained higher concentrations of caffeic acid (1.432 mg/g), synapic acid (6.743 mg/g), and benzoic acid (7.431 mg/g) as compared to all other extracts, whereas chlorogenic acid (0.311 mg/g) was present only in the aqueous extract of A. indica (WA). Food preservative properties of C. citratus can be due to the presence of benzoic acid (7.431 mg/g). -Gas chromatography-mass spectrometry analysis demonstrated the presence of 36 and 23 compounds in A. indica and C. citratus leaves, respectively. Inductively coupled plasma analysis was used to determine the concentration of 26 metals (Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Mo, Na, Ni, Pb, Sb, Se, Si, Sn, Sr, V, Zn, Zr, Ti); the metal concentrations were higher in aqueous extracts as compared to the ethanolic extracts. The extracts were generally richer in calcium (3000-7858 ppm), potassium (13662-53,750 ppm), and sodium (3181-8445 ppm) and hence can be used in food supplements as a source of these metals. Antioxidant potential (DDPH method) of C. citratus ethanolic extract was the highest (74.50 ± 0.66%), whereas it was the lowest (32.22 ± 0.28%) for the aqueous extract of A. indica. Synergistic inhibition of bacteria (Staphylococcus aureus and Escherichia coli) was observed when the aqueous extracts of both the plants were mixed together in certain ratios (v/v). The highest antibacterial potential was exhibited by the pure extract of C. citratus, which was even higher than that of the standard drug (ciprofloxacin). The plant extracts and their mixtures were more active against S. aureus as compared to E. coli. No toxic hemolytic effects were observed for the investigated extracts indicating their safe medicinal uses for human beings.

Pharmaceutical based cosmetic serums.

The growth and demand for cosmeceuticals (cosmetic products that have medicinal or drug-like benefits) have been enhanced for the last few decades. Lately, the newly invented dosage form, i.e., the pharmaceutical-based cosmetic serum has been developed and widely employed in various non-invasive cosmetic procedures. Many pharmaceutical-based cosmetic serums contain natural active components that claim to have a medical or drug-like effect on the skin, hair, and nails, including anti-aging, anti-wrinkle, anti-acne, hydrating, moisturizing, repairing, brightening and lightening skin, anti-hair fall, anti-fungal, and nail growth effect, etc. In comparison with other pharmaceutical-related cosmetic products (creams, gels, foams, and lotions, etc.), pharmaceutical-based cosmetic serums produce more rapid and incredible effects on the skin. This chapter provides detailed knowledge about the different marketed pharmaceutical-based cosmetic serums and their several types such as facial serums, hair serums, nail serums, under the eye serum, lip serum, hand, and foot serum, respectively. Moreover, some valuable procedures have also been discussed which provide prolong effects with desired results in the minimum duration of time after the few sessions of the serum treatment.

Human Retinal Ganglion Cells Respond to Evolutionarily Conserved Chemotropic Cues for Intra Retinal Guidance and Regeneration.

Retinal ganglion cells (RGCs) connect the retina with the higher centers in the brain for visual perception. Their degeneration leads to irreversible vision loss in glaucoma patients. Since human RGCs (hRGCs) are born during fetal development and connections with the central targets are established before birth, the mechanism underlying their axon growth and guidance remains poorly understood. Here, using RGCs directly generated from human embryonic stem cells, we demonstrate that hRGCs express a battery of guidance receptors. These receptors allow hRGCs to read the spatially arrayed chemotropic cues in the developing rat retina for the centripetal orientation of axons toward the optic disc, suggesting that the mechanism of intra-retinal guidance is conserved in hRGCs. The centripetal orientation of hRGCs axons is not only in response to chemo-repulsion but also involves chemo-attraction, mediated by Netrin-1/DCC interactions. The spatially arrayed chemotropic cues differentially influence hRGCs physiological responses, suggesting that neural activity of hRGCs may facilitate axon growth during inter-retinal guidance. Additionally, we demonstrate that Netrin-1/DCC interactions, besides promoting axon growth, facilitate hRGCs axon regeneration by recruiting the mTOR signaling pathway. The diverse influence of Netrin-1/DCC interactions ranging from axon growth to regeneration may involve recruitment of multiple intracellular signaling pathways as revealed by transcriptome analysis of hRGCs. From the perspective of ex-vivo stem cell approach to glaucomatous degeneration, our findings posit that ex-vivo generated human RGCs are capable of reading the intra-retinal cues for guidance toward the optic disc, the first step toward connecting with the central target to restore vision.

In silico screening and in vitro validation of phytocompounds as multidrug efflux pump inhibitor against E. coli.

Multiple drug resistance (MDR) in bacteria has increased globally in recent times. This has reduced the efficacy of antibiotics and increasing the rate of therapeutic failure. Targeting efflux pump by natural and synthetic compounds is one of the strategies to develop an ideal broad-spectrum resistance-modifying agent. Very few inhibitors of AcrB from natural sources have been reported till date. In the current study, 19 phytocompounds were screened for efflux pump inhibitory activity against AcrB protein of E. coli TG1 using molecular docking studies. The molecular dynamics simulation provided stability the protein (AcrB) and its complex with chlorogenic acid under physiological conditions. Moreover, the detailed molecular insights of the binding were also explored. The Lipinski rule of 5 and the drug-likeness prediction was determined using Swiss ADME server, while toxicity prediction was done using admetSAR and PROTOX-II webservers. Chlorogenic acid showed the highest binding affinity (-9.1 kcal mol-1) with AcrB protein among all screened phytocompounds. Consequently, all the phytocompounds that accede to Lipinski's rule, demonstrated a high LD50 value indicating that they are non-toxic except the phytocompound reserpine. Chlorogenic acid and capsaicin are filtered out based on the synergy with tetracycline having FIC index of 0.25 and 0.28. The percentage increase of EtBr fluorescence by chlorogenic acid was 36.6% followed by piperine (24.2%). Chlorogenic acid may be a promising efflux pump inhibitor that might be employed in combination therapy with tetracycline against E. coli, based on the above relationship between in silico screening and in vitro positive efflux inhibitory activity.Communicated by Ramaswamy H. Sarma.

Microglia: Friends or Foes in Glaucoma? A Developmental Perspective.

Glaucoma is the most prevalent form of optic neuropathy where a progressive degeneration of retinal ganglion cells (RGCs) leads to irreversible loss of vision. The mechanism underlying glaucomatous degeneration remains poorly understood. However, evidence suggests that microglia, which regulate RGC numbers and synaptic integrity during development and provide homeostatic support in adults, may contribute to the disease process. Hence, microglia represent a valid cellular target for therapeutic approaches in glaucoma. Here, we provide an overview of the role of microglia in RGC development and degeneration in the backdrop of neurogenesis and neurodegeneration in the central nervous system and discuss how pathological recapitulation of microglia-mediated developmental mechanisms may help initiate or exacerbate glaucomatous degeneration.