Sulfonium-Cross-Linked Hyaluronic Acid-Based Self-Healing Hydrogel: Stimuli-Responsive Drug Carrier with Inherent Antibacterial Activity to Counteract Antibiotic-Resistant Bacteria.

Augmentation of the activity of Food and Drug Administration-approved antibiotics by an adjuvant or antibiotic carrier is considered one of the promising strategies to fight against antibiotic-resistant bacteria. This study reports the development of sulfonium-cross-linked hyaluronic acid (HA)-based polymer (HA-SS-HA) as an inherent antimicrobial agent and antibiotic carrier. The HA-SS-HA polymer offers the potential for encapsulating various classes of antibiotics and accomplishing a stimuli-responsive release profile in the presence of hyaluronidase produced by bacterial cells within their extracellular environment. Systematic antibacterial studies reveal that the HA-SS-HA-encapsulated antibiotics (vancomycin, amoxicillin, and tetracycline) restore its activity against the antibiotic-resistant bacterial cells methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), and Pseudomonas aeruginosa. The HA-SS-HA gel shows robust efficacy in eradicating the mature biofilm of Staphylococcus aureus (S. aureus). The membrane-disrupting activity reveals that HA-SS-HA can also counteract the antibiotic resistance mechanism of the bacterial cells. The in vivo studies reveal excellent wound-healing activity of HA-SS-HA in albino laboratory-bred (BALB/c) mice. The outcome of additional antibacterial studies reveals that antibiotics-encapsulated HA-SS-HA hydrogel can effectively combat Gram-negative, Gram-positive, and antibiotic-resistant bacterial strains. Therefore, revitalizing the activity of commercial antibiotics by HA-SS-HA can be considered a valuable and economically effective strategy to fight against antibiotic-resistant bacteria.

Combating Staphylococcus aureus biofilm formation: the inhibitory potential of tormentic acid and 23-hydroxycorosolic acid.

Plant extracts have been used to treat microbiological diseases for centuries. This study examined plant triterpenoids tormentic acid (TA) and 23-hydroxycorosolic acid (HCA) for their antibiofilm effects on Staphylococcus aureus strains (MTCC-96 and MTCC-7405). Biofilms are bacterial colonies bound by a matrix of polysaccharides, proteins, and DNA, primarily impacting healthcare. As a result, ongoing research is being conducted worldwide to control and prevent biofilm formation. Our research showed that TA and HCA inhibit S. aureus planktonic growth by depolarizing the bacterial membrane. In addition, zone of inhibition studies confirmed their effectiveness, and crystal violet staining and biofilm protein quantification confirmed their ability to prevent biofilm formation. TA and HCA exhibited substantial reductions in biofilm formation for S. aureus (MTCC-96) by 54.85% and 48.6% and for S. aureus (MTCC-7405) by 47.07% and 56.01%, respectively. Exopolysaccharide levels in S. aureus biofilm reduced significantly by TA (25 µg/mL) and HCA (20 µg/mL). Microscopy, bacterial motility, and protease quantification studies revealed their ability to reduce motility and pathogenicity. Furthermore, TA and HCA treatment reduced the mRNA expression of S. aureus virulence genes. In silico analysis depicted a high binding affinity of triterpenoids for biofilm and quorum-sensing associated proteins in S. aureus, with TA having the strongest affinity for TarO (- 7.8 kcal/mol) and HCA for AgrA (- 7.6 kcal/mol). TA and HCA treatment reduced bacterial load in S. aureus-infected peritoneal macrophages and RAW264.7 cells. Our research indicates that TA and HCA can effectively combat S. aureus by inhibiting its growth and suppressing biofilm formation.

Novel Insight into the Cellular and Molecular Signalling Pathways on Cancer Preventing Effects of Hibiscus sabdariffa: A Review.

A category of diseases known as cancer includes abnormal cell development and the ability to infiltrate or spread to other regions of the body, making them a major cause of mortality worldwide. Chemotherapy, radiation, the use of cytotoxic medicines, and surgery are the mainstays of cancer treatment today. Plants or products produced from them hold promise as a source of anti-cancer medications that have fewer adverse effects. Due to the presence of numerous phytochemicals that have been isolated from various parts of the Hibiscus sabdariffa (HS) plant, including anthocyanin, flavonoids, saponins, tannins, polyphenols, organic acids, caffeic acids, citric acids, protocatechuic acid, and others, extracts of this plant have been reported to have anti-cancer effects. These compounds have been shown to reduce cancer cell proliferation, induce apoptosis, and cause cell cycle arrest. They also increase the expression levels of the cell cycle inhibitors (p53, p21, and p27) and the pro-apoptotic proteins (BAD, Bax, caspase 3, caspase 7, caspase 8, and caspase 9). This review highlights various intracellular signalling pathways involved in cancer preventive potential of HS.

Quinoline Thiourea-Based Zinc Ionophores with Antibacterial Activity.

The increasing resistance of bacteria to commercially available antibiotics threatens patient safety in healthcare settings. Perturbation of ion homeostasis has emerged as a potential therapeutic strategy to fight against antibacterial resistance and other channelopathies. This study reports the development of 8-aminoquinoline (QN) derivatives and their transmembrane Zn2+ transport activities. Our findings showed that a potent QN-based Zn2+ transporter exhibits promising antibacterial properties against Gram-positive bacteria with reduced hemolytic activity and cytotoxicity to mammalian cells. Furthermore, this combination showed excellent in vivo efficacy against Staphylococcus aureus. Interestingly, this combination prevented bacterial resistance and restored susceptibility of gentamicin and methicillin-resistant S. aureus to commercially available ß-lactam and other antibiotics that had lost their activity against the drug-resistant bacterial strain. Our findings suggest that the transmembrane transport of Zn2+ by QN derivatives could be a promising strategy to combat bacterial infections and restore the activity of other antibiotics.

Vitexin alters Staphylococcus aureus surface hydrophobicity to obstruct biofilm formation.

Cell Surface hydrophobicity is one of the determinant biophysical parameters of bacterial aggregation for being networked to form a biofilm. Phytoconstituent, like vitexin, has long been in use for their antibacterial effect. The present work demonstrates the role of vitexin in modulating Staphylococcus aureus surface hydrophobicity while aggregating to form biofilm and pathogenesis in a host. In planktonic form, vitexin shows minimum inhibitory concentration at 252 µg/ml against S. aureus. Sub-MIC doses of vitexin and antibiotics (26 µg/ml of vitexin, 55 µg/ml of azithromycin, and 2.5 µg/ml of gentamicin) were selected to treat S. aureus. Dead cell counts after treatment were studied through flow cytometry. As dead cell counts were minimal (<5 %), these doses were considered for all subsequent experiments. While studying aggregating cells, it was observed that vitexin reduces S. aureus surface hydrophobicity and membrane permeability at the sub-MIC dose of 26 µg/ml. The in silico binding analysis showed a higher binding affinity of vitexin with surface proteins (IcaA, DltA, and SasG) of S. aureus. Down-regulation of dltA and icaAB expression, along with the reduction in membrane potential with a sub-MIC dose of vitexin, explains reduced S. aureus surface hydrophobicity. Vitexin was found to interfere with S. aureus biofilm-associated protein biomass, EPS production, and swarming movement. Subsequently, the suppression of proteases production and down-regulation of icaAB and agrAC gene expression with a sub-MIC dose of vitexin explained the inhibition of S. aureus virulence in vitro. Besides, vitexin was also found to potentiate the antibiofilm activity of sub-MIC doses of gentamicin and azithromycin. Treatment with vitexin exhibits a protective response in S. aureus infected macrophages through modulation of expression of cytokines like IL-10 and IL-12p40 at protein and mRNA levels. Furthermore, CFU count and histological examination of infected mouse tissue (liver and spleen) justify the in vivo protective effect of vitexin from S. aureus biofilm-associated infection. From this study, it can be inferred that vitexin can reduce S. aureus surface hydrophobicity, leading to interference with aggregation at the time of biofilm formation and subsequent pathogenesis in a host.

Tryptophan interferes with the quorum sensing and cell surface hydrophobicity of Staphylococcus aureus: a promising approach to inhibit the biofilm development.

Staphylococcus aureus, a Gram-positive bacterium has been implicated in a plethora of human infections by virtue of its biofilm-forming ability. Inhibition in microbial biofilm formation has been found to be a promising approach towards compromising microbial pathogenesis. In this regard, various natural and synthetic molecules have been explored to attenuate microbial biofilm. In this study, the role of an amino acid, L-tryptophan was examined against the biofilm-forming ability of S. aureus. The compound did not execute any antimicrobial characteristics, instead, showed strong antibiofilm activity with the highest biofilm inhibition at a concentration of 50 µg/mL. Towards understanding the underlying mechanism of the same, efforts were given to examine whether tryptophan could inhibit biofilm formation by interfering with the quorum-sensing property of S. aureus. A molecular docking analysis revealed an efficient binding between the quorum-sensing protein, AgrA, and tryptophan. Moreover, the expression of the quorum-sensing gene (agrA) got significantly reduced under the influence of the test compound. These results indicated that tryptophan could interfere with the quorum-sensing property of the organism thereby inhibiting its biofilm formation. Further study revealed that tryptophan could also reduce the cell surface hydrophobicity of S. aureus by downregulating the expression of dltA. Moreover, the tested concentrations of tryptophan did not show any significant cytotoxicity. Hence, tryptophan could be recommended as a potential antibiofilm agent to manage the biofilm-associated infections caused by S. aureus. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02924-3.

Interdependencies between Toll-like receptors in Leishmania infection.

Multiple pathogen-associated molecular patterns (PAMPs) on a pathogen's surface imply their simultaneous recognition by the host cell membrane-located multiple PAMP-specific Toll-like receptors (TLRs). The TLRs on endosomes recognize internalized pathogen-derived nucleic acids and trigger anti-pathogen immune responses aimed at eliminating the intracellular pathogen. Whether the TLRs influence each other's expression and effector responses-termed TLR interdependency-remains unknown. Herein, we first probed the existence of TLR interdependencies and next determined how targeting TLR interdependencies might determine the outcome of Leishmania infection. We observed that TLRs selectively altered expression of their own and of other TLRs revealing novel TLR interdependencies. Leishmania major-an intra-macrophage parasite inflicting the disease cutaneous leishmaniasis in 88 countries-altered this TLR interdependency unfolding a unique immune evasion mechanism. We targeted this TLR interdependency by selective silencing of rationally chosen TLRs and by stimulation with selective TLR ligands working out a novel phase-specific treatment regimen. Targeting the TLR interdependency elicited a host-protective anti-leishmanial immune response and reduced parasite burden. To test whether this observation could be used as a scientific rationale for treating a potentially fatal L. donovani infection, which causes visceral leishmaniasis, we targeted the inter-TLR dependency adopting the same treatment regimen. We observed reduced splenic Leishman-Donovan units accompanied by host-protective immune response in susceptible BALB/c mice. The TLR interdependency optimizes TLR-induced immune response by a novel immunoregulatory framework and scientifically rationalizes targeting TLRs in tandem and in sequence for redirecting immune responses against an intracellular pathogen.

Attenuation of Pseudomonas aeruginosa biofilm by thymoquinone: an individual and combinatorial study with tetrazine-capped silver nanoparticles and tryptophan.

Microbial biofilm indicates a cluster of microorganisms having the capability to display drug resistance property, thereby increasing its proficiency in spreading diseases. In the present study, the antibiofilm potential of thymoquinone, a black seed-producing natural molecule, was contemplated against the biofilm formation by Pseudomonas aeruginosa. Substantial antimicrobial activity was exhibited by thymoquinone against the test organism wherein the minimum inhibitory concentration of the compound was found to be 20 µg/mL. Thereafter, an array of experiments (crystal violet staining, protein count, and microscopic observation, etc.) were carried out by considering the sub-MIC doses of thymoquinone (5 and 10 µg/mL), each of which confirmed the biofilm attenuating capacity of thymoquinone. However, these concentrations did not show any antimicrobial activity. Further explorations on understanding the underlying mechanism of the same revealed that thymoquinone accumulated reactive oxygen species (ROS) and also inhibited the expression of the quorum sensing gene (lasI) in Pseudomonas aeruginosa. Furthermore, by taking up a combinatorial approach with two other reported antibiofilm agents (tetrazine-capped silver nanoparticles and tryptophan), the antibiofilm efficiency of thymoquinone was expanded. In this regard, the highest antibiofilm activity was observed when thymoquinone, tryptophan, and tetrazine-capped silver nanoparticles were applied together against Pseudomonas aeruginosa. These combinatorial applications of antibiofilm molecules were found to accumulate ROS in cells that resulted in the inhibition of biofilm formation. Thus, the combinatorial study of these antibiofilm molecules could be applied to control biofilm threats as the tested antibiofilm molecules alone or in combinations showed negligible or very little cytotoxicity.

Lupeol and amphotericin B mediate synergistic anti-leishmanial immunomodulatory effects in Leishmania donovani-infected BALB/c mice.

Leishmania donovani, a protozoan parasite, inflicts the disease Visceral leishmaniasis (VL) Worldwide. The only orally bioavailable drug miltefosine is toxic, whereas liposomal amphotericin B (AmpB) is expensive. Lupeol, a triterpenoid from Sterculia villosa bark, was exhibited immunomodulatory and anti-leishmanial activity in experimental VL. Herein, we evaluated synergism between sub-optimum dose of AmpB and lupeol in anti-leishmanial and immunomodulatory effects in L. donovani-infected BALB/c mice. We observed that a combination of sub-optimum dose of lupeol and AmpB significantly reduced the hepatic and splenic parasitic burden accompanied by enhanced nitric oxide production, robust induction of Th1 cytokines (IL-12 and IFN-γ) but suppressed Th2 cytokine (IL-10 and TGF- ß) production. The treatment with the lupeol-AmpB combination enhanced p38mitogen-activated protein kinase (p38MAPK), but reduced extracellular signal-related kinase (ERK-1/2), phosphorylation and up-regulated pro-inflammatory response. The present work thus indicates a lupeol-AmpB-mediated immunotherapeutic approach for eliminating the parasite-induced immunosuppression.

Conundrums in leishmaniasis.

Parasites of the genus Leishmania cause the disease leishmaniasis. As the sandfly vector transfers the promastigotes into the skin of the human host, the infection is either cured or exacerbated. In the process, there emerge several unsolved paradoxes of leishmaniasis. Chronologically, as the infections starts in skin, the role of the salivary proteins in supporting the infection or the host response to these proteins influencing the induction of immunological memory becomes a conundrum. As the parasite invokes inflammation, the infiltrating neutrophils may act as "Trojan Horse" to transfer parasites to macrophages that, along with dendritic cells, carry the parasite to lymphoid organs to start visceralization. As the visceralized infection becomes chronic, the acutely enhanced monocytopoiesis takes a downturn while neutropenia and thrombocytopenia ensue with concomitant rise in splenic colony-forming-units. These responses are accompanied by splenic and hepatic granulomas, polyclonal activation of B cells and deviation of T cell responses. The granuloma formation is both a containment process and a form of immunopathogenesis. The heterogeneity in neutrophils and macrophages contribute to both cure and progression of the disease. The differentiation of T-helper subsets presents another paradox of visceral leishmaniasis, as the counteractive T cell subsets influence the curing or non-curing outcome. Once the parasites are killed by chemotherapy, in some patients the cured visceral disease recurs as a cutaneous manifestation post-kala azar dermal leishmaniasis (PKDL). As no experimental model exists, the natural history of PKDL remains almost a black box at the end of the visceral disease.

Central and local controls of monocytopoiesis influence the outcome of Leishmania infection.

Leishmaniases represent a complex of tropical and subtropical diseases caused by an intracellular protozoon of the genus Leishmania. The principal cells controlling the interaction between the host and the parasite Leishmania are monocytes and macrophages, as these cells play a decisive role in establishing the pathogenesis or cure. These cells are involved in controlling the growth of Leishmania and in modulating the adaptive immune responses. The heterogeneity and extensive plasticity of monocytes allow these cells to adjust their functional phenotypes in response to the pathogen-directed immunological cues. In Leishmania-infected host, the rate of myelopoiesis is augmented by enhanced monocytic lineage commitment and proliferation of myeloid progenitor cells both in the BM and at the site of infection. These newly generated monocytes play as "safe haven" for the parasite and also as the antigen-presenting cells for T cells to cause deregulated cytokine production. This altered monocytopoiesis is characterized by tissue-specific immune responses, spatiotemporal dynamics of immunoregulation and functional heterogeneity. In the presence of Th1 cytokines, monocytes exhibit a pro-inflammatory phenotype that protects the host from Leishmania. By contrast, in an environment of Th2 cytokines, monocytes display anti-inflammatory phenotype with pro-parasitic functions. In this review, we summarize the involvement of cytokines in the regulation of monocytopoiesis and differentiation of macrophages during leishmanial infection. Understanding the role of cytokines in regulating interactions between Leishmania and the host monocytes is key to developing new therapeutic interventions against leishmaniases.

Barley beta-Glucan and Zymosan induce Dectin-1 and Toll-like receptor 2 co-localization and anti-leishmanial immune response in Leishmania donovani-infected BALB/c mice.

Toll-like receptors (TLRs), TLR2 in particular, are shown to recognize various glycans and glycolipid ligands resulting in various immune effector functions. As barley ß-glucan and zymosan are the glycans implicated in immunomodulation, we examined whether these ligands interact with Dectin-1, a lectin-type receptor for glycans, and TLR2 and induce immune responses that can be used against Leishmania infection in a susceptible host. The binding affinity of barley ß-glucan and zymosan with Dectin-1 and TLR2 was studied in silico. Barley ß-glucan- and zymosan-induced dectin-1 and TLR2 co-localization was studied by confocal microscopy and co-immunoprecipitation. These ligands-induced signalling and effector functions were assessed by Western blot analyses and various immunological assays. Finally, the anti-leishmanial potential of barley ß-glucan and zymosan was tested in Leishmania donovani -infected macrophages and in L. donovani-infected BALB/c mice. Both barley ß-glucan and zymosan interacted with TLR2 and dectin-1, but with a much stronger binding affinity for the latter, and therefore induced co-localization of these two receptors on BALB/c-derived macrophages. Both ligandsactivated MyD88- and Syk-mediated downstream pathways for heightened inflammatory responses in L. donovani-infected macrophages. These two ligands induced T cell-dependent host protection in L. donovani-infected BALB/c mice. These results establish a novel modus operandi of ß-glucans through dectin-1 and TLR2 and suggest an immuno-modulatory potential against infectious diseases.

The anti-biofilm potential of triterpenoids isolated from Sarcochlamys pulcherrima (Roxb.) Gaud.

Formation of biofilm is the major cause of Pseudomonas aeruginosa associated pathological manifestations in the urinary tract, respiratory system, gastrointestinal tract, skin, soft tissues etc. Triterpenoid group of compounds have shown their potential in reducing planktonic and biofilm form of bacteria. Sarcochlamys pulcherrima (Roxb.) Gaud. is an ethnomedicinal plant traditionally used for its anti-microbial and anti-inflammatory property. In the present study two triterpenoids, have been isolated from this plant, characterised and evaluated for their antibacterial and antibiofilm potential against P. aeruginosa. Compounds were characterised as 2α, 3ß, 19α-trihydroxy-urs-12-ene-28-oic acid (Tormentic acid) and 2α, 3ß, 23-trihydroxyurs-12-ene-28-oic acid (23-hydroxycorosolic acid) through spectroscopic studies viz. infrared (IR), nuclear magnetic resonance (NMR) and mass spectroscopy (MS). Depolarization of bacterial membrane and zone of inhibition studies revealed that both the compounds inhibited the growth of planktonic bacteria. Compounds were also found to inhibit the formation of P. aeruginosa biofilm. Inhibition of biofilm found to be mediated through suppressed secretion of pyoverdin, protease and swarming motility of P. aeruginosa. Gene expression study, in silico binding analysis, in vivo bacterial load and tissue histology observations also supported the antibiofilm activity of both the compounds. In vitro and in vivo study showed that both compounds were non-toxic. The study has explored the antibacterial and antibiofilm effect of two triterpenes isolated for the first time from S. pulcherrima.

Free radical stress induces DNA damage response in RAW264.7 macrophages during Mycobacterium smegmatis infection.

Genomic instability resulting from oxidative stress responses may be traced to chromosomal aberration. Oxidative stress suggests an imbalance between the systemic manifestation of reactive free radicals and biological system's ability to repair resulting DNA damage and chromosomal aberration. Bacterial infection associated insult is considered as one of the major factors leading to such stress conditions. To study free radical responses by host cells, RAW 264.7 macrophages were infected with non-pathogenic M. smegmatis mc2155 at different time points. The infection process was followed up with an assessment of free radical stress, cytokine, toll-like receptors (TLRs) and the resulting DNA damage profiles. Results of CFU count showed that maximum infection in macrophages was achieved after 9 h of infection. Host responses to the infection across different time periods were validated from nitric oxide quantification and expression of iNOS and were plotted at regular intervals. IL-10 and TNF-α expression profile at protein and mRNA level showed a heightened pro-inflammatory response by host macrophages to combat M. smegmatis infection. The expression of TLR4, a receptor for recognition of mycobacteria, in infected macrophages reached the highest level at 9 h of infection. Furthermore, comet tail length, micronuclei and γ-H2AX foci recorded the highest level at 9 h of infection, pointing to the fact that breakage in DNA double strands in macrophage reaches its peak at 9 h of infection. In contrast, treatment with ROS inhibitor N-acetyl-L-cysteine (NAC) prevented host cell death through reduction in oxidative stress and DNA damage response during M. smegmatis infection. Therefore, it can be concluded that enhanced oxidative stress response in M. smegmatis infected macrophages might be correlated with DNA damage response.

Modulation of S. aureus and P. aeruginosa biofilm: an in vitro study with new coumarin derivatives.

Coumarin is an important heterocyclic molecular framework of bioactive molecules against broad spectrum pathological manifestations. In the present study 18 new coumarin derivatives (CDs) were synthesized and characterized for antibiofilm activity against two model bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. It was observed that all the CDs executed significant effect in moderating activities against both planktonic and biofilm forms of these selected bacteria. Hence, to interpret the underlying probable reason of such antibiofilm effect, in-silico binding study of CDs with biofilm and motility associated proteins of these organisms were performed. All CDs have shown their propensity for occupying the native substrate binding pocket of each protein with moderate to strong binding affinities. One of the CDs such as CAMN1 showed highest binding affinity with these proteins. Interestingly, the findings of in-silico studies coincides the experimental results of antibiofilm and motility affect of CDs against both S. aureus and P. aeruginosa. Moreover, in-silico studies suggested that the antibiofilm activity of test CDs may be due to the interference of biofilm and motility associated proteins of the selected model organisms (PilT from P. aeruginosa and TarK, TarO from S. aureus). The detailed synthesis, characterization, methodology and results of biological screening along with computational studies have been reported. This study could be of greater interest in the context of the development of new anti-bacterial agent in the future.

Free tryptophan residues inhibit quorum sensing of Pseudomonas aeruginosa: a potential approach to inhibit the development of microbial biofilm.

Microbial biofilm reveals a cluster of microbial population aggregated on a surface. Pseudomonas aeruginosa, a strong biofilm forming organism, often causes several human diseases. Microorganism-based diseases become more difficult to manage when the causative organism develops biofilm during the course of disease progression as the organism attains alarming drug resistance in biofilm form. Agents inhibiting microbial biofilm formation could be considered as a potential tool to weaken the extent of microbial pathogenesis. Tryptophan has already been reported as a promising agent against the biofilm development by P. aeruginosa. In the current study, we had focused on the underlying mechanism of microbial biofilm inhibition of P. aeruginosa under the influence of tryptophan. The expression level of the mRNA of the genes (lasR, lasB and lasI) associated with quorum sensing was compared between tryptophan treated and untreated cells under similar conditions using real time polymerase chain reaction (RT-PCR). The results showed that the tested concentrations of tryptophan considerably reduced the expression of those genes (lasR, lasB and lasI) that are required during the occurrence of quorum sensing in P. aeruginosa. Molecular docking also revealed that tryptophan can interact with the proteins responsible for the occurrence of quorum sensing in P. aeruginosa. The cytotoxicity assay was carried out wherein we observed that the tested concentration of tryptophan did not show any considerable cytotoxicity against the RAW 264.7 macrophage cell line. From this study, it may be concluded that the tryptophan-mediated inhibition of biofilm formation is associated with interference of quorum sensing in P. aeruginosa. Hence, tryptophan could be used as a potential agent against the microbial biofilm mediated pathogenesis.

Obesity and Associated Cardiometabolic Risk among Women from Tripura - A Northeastern State of India.

INTRODUCTION: Cardiometabolic health status of women is a serious public health concern. Markers of body fat content and their distribution are important indicators of cardiometabolic health risk in participants. In addition, socio-demographic status plays a determinant role. The aim of the study was to evaluate the influence of adiposity markers and socio-demographic determinants on various cardiovascular and metabolic risk factors in Indian women. MATERIALS AND METHODS: The study was conducted on 388 women (age 25-65 years) from Tripura, a Northeastern state of India. Various obesity and atherogenic markers such as body mass index (BMI), waist circumference (WC), waist-hip ratio, waist - height ratio, high density lipoprotein-cholesterol (HDL-C)/total cholesterol, HDL-C/low density lipoprotein cholesterol, triglyceride/HDL-C ratio and traditional cardiometabolic risk factors such as high blood pressure, dyslipidemia, and glucose intolerance were evaluated in participant. The socio-demographic status included the level of education and monthly family income. RESULTS: The cardiometabolic risk in postmenopausal women were higher than premenopausal women. The risk increases with age in both groups. Women with lower educational level and higher income group were found to be prone to higher cardiometabolic risk. Receiver operating characteristics analysis revealed central obesity marked by increased WC was a better predictor of cardiometabolic risk than general obesity marked by increased BMI. CONCLUSION: The cardiometabolic risk among both premenopausal and postmenopausal women are associated with central obesity which can be predicted by increased WC in the subject. Socio-demographic status of the participant plays a definitive role in determining cardiometabolic risk in women.

Nanoscale wide-band semiconductors for photocatalytic remediation of aquatic pollution.

Water pollution is a serious challenge to the public health. Among different forms of aquatic pollutants, chemical and biological agents create paramount threat to water quality when the safety standards are surpassed. There are many conventional remediatory strategies that are practiced such as resin-based exchanger and activated charcoal/carbon andreverse osmosis. Newer technologies using plants, microorganisms, genetic engineering, and enzyme-based approaches are also proposed for aquatic pollution management. However, the conventional technologies have shown impending inadequacies. On the other hand, new bio-based techniques have failed to exhibit reproducibility, wide specificity, and fidelity in field conditions. Hence, to solve these shortcomings, nanotechnology ushered a ray of hope by applying nanoscale zinc oxide (ZnO), titanium dioxide (TiO2), and tungsten oxide (WO3) particles for the remediation of water pollution. These nanophotocatalysts are active, cost-effective, quicker in action, and can be implemented at a larger scale. These nanoparticles are climate-independent, assist in complete mineralization of pollutants, and can act non-specifically against chemically and biologically based aquatic pollutants. Photocatalysis for environmental remediation depends on the availability of solar light. The mechanism of photocatalysis involves the formation of electron-hole pairs upon light irradiations at intensities higher than their band gap energies. In the present review, different methods of synthesis of nanoscale ZnO, TiO2, and WO3 as well as their structural characterizations have been discussed. Photodegradation of organic pollutants through mentioned nanoparticles has been reviewed with recent advancements. Enhancing the efficacy of photocatalysis through doping of TiO2 and ZnO nanoparticles with non-metals, metals, and metal ions has also been documented in this report.

miRNAs in Alzheimer Disease - A Therapeutic Perspective.

BACKGROUND: Alzheimer's disease is a neurodegenerative disorder which generally affects people who are more than 60 years of age. The disease is clinically characterised by dementia, loss of cognitive functions and massive neurodegeneration. The presence of neurofibrilary tangles and amyloid plaques in the hippocampal region of the brain are the hallmarks of the disease. Current therapeutic approaches for the treatment of Alzheimer's disease are symptomatic and disease modifying, none of which provide any permanent solution or cure for the disease. Dysregulation of miRNAs is one of the major causes of neurodegeneration. CONCLUSION: In the present review, the roles of different miRNAs such as miR-9, miR-107, miR-29, miR-34, miR-181, miR-106, miR-146a, miR132, miR124a, miR153 has been discussed in detail in the pathogenesis of various neurodegenerative diseases with special focus on AD. The probability of miRNAs as an alternative and more sensitive approach for detection and management of the AD has also been discussed.

Antileishmanial and immunomodulatory activities of lupeol, a triterpene compound isolated from Sterculia villosa.

Visceral leishmaniasis (VL) is one of the most severe forms of leishmaniasis, caused by the protozoan parasite Leishmania donovani. Nowadays there is a growing interest in the therapeutic use of natural products to treat parasitic diseases. Sterculia villosa is an ethnomedicinally important plant. A triterpenoid was isolated from this plant and was screened for its antileishmanial and immunomodulatory activities in vitro and in vivo. Biochemical colour test and spectroscopic data confirmed that the isolated pure compound was lupeol. Lupeol exhibited significant antileishmanial activity, with IC50 values of 65 ± 0.41 µg/mL and 15 ± 0.45 µg/mL against promastigote and amastigote forms, respectively. Lupeol caused maximum cytoplasmic membrane damage of L. donovani promastigote at its IC50 dose. It is well known that during infection the Leishmania parasite exerts its pathogenicity in the host by suppressing nitric oxide (NO) production and inhibiting pro-inflammatory responses. It was observed that lupeol induces NO generation in L. donovani-infected macrophages, followed by upregulation of pro-inflammatory cytokines and downregulation of anti-inflammatory cytokines. Lupeol was also found to reduce the hepatic and splenic parasite burden through upregulation of the pro-inflammatory response in L. donovani-infected BALB/c mice. Strong binding affinity of lupeol was observed for four major potential drug targets, namely pteridine reductase 1, adenine phosphoribosyltransferase, lipophosphoglycan biosynthetic protein and glycoprotein 63 of L. donovani, which also supported its antileishmanial and immunomodulatory activities. Therefore, the present study highlights the antileishmanial and immunomodulatory activities of lupeol in an in vitro and in vivo model of VL.