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The study aimed at enhancing the oral bioavailability of the BCS class 2 drug Ibrutinib (IBR), which exhibits low solubility (0.002 mg/mL) and high permeability (3.9% oral bioavailability). This was achieved through the formulation and evaluation of Ibrutinib-loaded Glycyrrhizic acid conjugated egg ovalbumin nanoparticles (IBR-GA-EA NPs) and Ibrutinib-Glycyrrhizic acid complex (IBR-GA-COMP). The formulation of Ibrutinib-Glycyrrhizic acid complex aimed to enhance the oral bioavailability of Ibrutinib. Lyophilized Ibrutinib-Glycyrrhizic acid complex was prepared and characterized through various studies including DSC, FTIR, in vitro release, and in vivo pharmacokinetics studies. DSC and FTIR confirmed successful formulation development. The nanoparticles exhibited spherical morphology with favourable characteristics: particle size of 194.10 nm, PDI of 0.22, and zeta potential of -33.96 mV. Encapsulation efficiency was 82.88%. In vitro release study displayed major improvement in drug release pattern compared to the free drug suspension. In vivo pharmacokinetic studies demonstrated 3.21-fold and 3.41-fold increase in the oral bioavailability of IBR-GA-EA NPs and IBR-GA-COMP, respectively, compared to IBR suspension alone. The formulated IBR-GA-EA NPs and IBR-GA-COMP are promising drug delivery methods as they successfully improve the solubility and oral bioavailability of Ibrutinib.

Photocatalysis is recognized to be one of the most promising ways to address energy and environmental issues by utilizing visible light. Graphitic carbon nitride (g-C 3 N 4 ), with a moderate band gap (∼2.7 eV) has been the flashpoint in environmental photocatalysis as it can work better under visible light, can be synthesized by a facile synthesis process using low-cost materials, thermally and chemically stable. Still the photocatalytic performance of g-C 3 N 4 is not satisfactory because of certain limitations such as insufficient visible light absorption capacity, low electron-hole separation efficiency, high recombination rate, poor surface area. Introduction of doping, band structure engineering, defecting and designing of heterojunction, composites etc. were investigated to amplify its applications. Among all these modifications, elemental doping is a suitable and successful alternative for the enhancement of the photocatalytic activity by changing the optical and electronic properties. This review emphasizes on advancement and trends of elemental doping and its application on photocatalytic organic pollutant remediation in aqueous medium. The fundamental photocatalytic activity of heterogeneous photocatalysis and specifically g-C 3 N 4 -based photocatalysis have been discussed. The benfits of non-metal doping, enhanced photocatalytic performance by doping element, mechanism invloved in doping, advantages of co-doping has been explained. Mono, bi, and tri non-metal doped g-C 3 N 4 and their application for the removal of organic pollutants from water medium by visible light photocatalysis has been summerized. Life cycle assessment (LCA) of photocatalytic system has been highlighted. Future research should focus on the large-scale application of the photocatalysis process considering the economic aspects. A rigorous life cycle assessment for deploying the non-metal doped g-C 3 N 4 -based photocatalysis technology for successful commercial application is recommended., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC 50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO 3 ). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment., (© 2024. The Author(s).)

Background: One of the major objectives of orthodontic treatment is to improve facial attractiveness. To orthodontists, this means that the nose, lips, and chin form an attractive outline when the faces are viewed from one side. The aim of the study is to evaluate the influence of lip inclination on perceived attractiveness using North Indian observer ratings on profile silhouettes., Materials and Methods: A profile photograph of an Indian male and female were converted to silhouettes for the study using computer software. The lip inclination of the idealized profile image was altered in two-degree increments to create a series of profiles with different upper lip inclination angles and rated by laypersons on a Likert scale., Results: An angle of 79° was deemed to be neither attractive nor unattractive. Therefore, within the range of 65°-75°, the pictures were deemed acceptable. Angles above or below this range, up to 91° were perceived as slightly unattractive, and anything outside the range of 93°-105° was deemed very unattractive., Limitations: The study is not generalizable to ethnic groups other than the North Indian population. Another limitation is the inability to visualize the entire face for a complete facial analysis., Conclusion: An upper lip inclination of 75°-85° in the male profile was associated with perceived attractiveness in all three groups whereas it was in the range of 65°-75° for a female profile. An upper lip inclination angle ranging from 95° to 105° was associated with unattractiveness in all three groups of observers and requires correctional intervention., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Orthodontic Science.)

Ethnopharmacological Relevance: Nyctanthes arbor-tristis L. is a mythical plant used in traditional Indian medicinal systems for the treatment of inflammation, rheumatoid arthritis, and pain-related responses. However, its bioactive compounds and underlying mechanism of action have not been fully elucidated., Aim of the Study: This investigation aimed to study the anti-inflammatory and anti-nociceptive effects of the bioactive extract of N. arbor-tristis (NATE), both in vitro and in vivo, elucidate the possible mechanism of action, and determine its chemicals., Materials and Methods: We studied the anti-inflammatory and anti-nociceptive activities of NATE on lipopolysaccharide-stimulated RAW264.7 macrophages, paw-ear edema, and acetic acid-induced pain in rats and analysed its chemical components using Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC-ESI-MS)., Results: NATE efficiently reduced the production of various inflammatory mediators and factors, such as free radicals, lipid peroxidation, nitrous oxide (NO), reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1beta (IL-1β), and IL-10, as well as their corresponding mRNA expression in LPS-induced RAW264.7 cells (p < 0.001). Furthermore, NATE inhibited the activation of a key signaling pathway, nuclear factor-kappa B (NF-kB), as it caused a decrease in the degradation of inhibitor of kB alpha (IkBa). Administration of NATE significantly inhibited carrageenan-induced paw edema (p < 0.001), TPA-induced ear edema, and the production of inflammatory factors (p < 0.01). NATE revealed anti-nociceptive impacts in acetic acid-induced writhing and tail immersion experiments (p < 0.001) as well as no toxicity signs. A total of six compounds, namely iridoid glycoside (6,7-di-O-benzonylnyctanthoside), arborsides A, arborsides C, betulinic acid, kaempferol 3-O-glucoside, and kaempferol 3-O-rutinoside, were characterized through the examination of their mass spectra in correlation with those documented in a database of mass spectra., Conclusions: The present study furnishes scientific corroboration of the inhibitory potency of N. arbor-tristis as a promising herbal treatment for inflammation and pain responses without toxicity, offering a scientific basis for future drug development strategies aimed at ameliorating inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The relationship between nasal obstruction and obstructive sleep apnea has raised interest among otolaryngologists since years. There are studies that suggest that surgical correction of nasal obstruction improves sleep quality and reduces symptoms of sleep apnea. This lead to our study to understand the effect of nasal surgery on obstructive sleep apnea hypopnea syndrome (OSAHS)., Aim: To assess the effect of nasal surgery in improvement in Obstructive Sleep Apnoea Hypopnoea Syndrome in patients with nasal obstruction by Polysomnography (PSG)., Material and Methods: This study included 30 patients with nasal obstruction who underwent septoplasty and/or turbinate reduction procedure with pre and post operative assessment of respiratory distress index (RDI) including apnoea hypopnoea index (AHI), obstructive apnoea index (OAI), Snoring Index (SI) using polysomnography (PSG)., Result: Nasal correction surgery showed statistically significant improvement (p-value < 0.001) in RDI from 13.66 to 6.66, OAI from 6.34 to 3.18 and Snoring Index from 161.77 to 62.23 as assessed by polysomnography. There was statistically significant improvement in minimal saturation levels (during sleep) and positional sleep apnoea., Conclusion: Isolated nasal surgery like septoplasty and/or turbinate reduction improved sleep parameters and alleviated OSA symptoms in patients with static nasal obstruction and obstructive sleep apnoea/hypopnoea syndrome. However, patients with multilevel or dynamic airway obstruction may need further intervention., Competing Interests: Conflict of InterestThe Authors declare that there is no conflict of interest., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Justification: Neurodevelopmental disorders, as per DSM-V, are described as a group of conditions with onset in the development period of childhood. There is a need to distinguish the process of habilitation and rehabilitation, especially in a developing country like India, and define the roles of all stakeholders to reduce the burden of neurodevelopmental disorders., Process: Subject experts and members of Indian Academy of Pediatrics (IAP) Chapter of Neurodevelopmental Pediatrics, who reviewed the literature on the topic, developed key questions and prepared the first draft on guidelines. The guidelines were then discussed by the whole group through online meetings, and the contentious issues were discussed until a general consensus was arrived at. Following this, the final guidelines were drafted by the writing group and approved by all contributors., Objectives: These guidelines aim to provide practical clinical guidelines for pediatricians on the prevention, early diagnosis and management of neurodevelopmental disorders (NDDs) in the Indian settings. It also defines the roles of developmental pediatricians and development nurse counselor., Statement: There is a need for nationwide studies with representative sampling on epidemiology of babies with early NDD in the first 1000 days in India. Specific learning disability (SLD) has been documented as the most common NDD after 6 years in India, and special efforts should be made to establish the epidemiology of infants and toddlers at risk for SLD, where ever measures are available. Preconception counseling as part of focusing on first 1000 days; Promoting efforts to organize systematic training programs in Newborn Resuscitation Program (NRP); Lactation management; Developmental follow-up and Early stimulation for SNCU/ NICU graduates; Risk stratification of NICU graduates, Newborn Screening; Counseling parents; Screening for developmental delay by trained professionals using simple validated Indian screening tools at 4, 8, 12, 18 and 24 months; Holistic assessment of 10 NDDs at child developmental clinics (CDCs) / district early intervention centre (DEICs) by multidisciplinary team members; Confirmation of diagnosis by developmental pediatrician/developmental neurologist/child psychiatrist using clinical/diagnostic tools; Providing parent guided low intensity multimodal therapies before 3 years age as a center-based or home-based or community-based rehabilitation; Developmental pediatrician to seek guidance of pediatric neurologist, geneticist, child psychiatrist, physiatrist, and other specialists, when necessary; and Need to promote ongoing academic programs in clinical child development for capacity building of community based therapies, are the chief recommendations.

Activated microglial cells in the central nervous system (CNS) are the main contributors to neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Inhibiting their activation will help in reducing inflammation and oxidative stress during pathogenesis, potentially limiting the progression of the diseases. The immunomodulation properties of dental pulp-derived stem cells (DPSC) make it a promising therapy for neurodegenerative disorders. This study aims to determine whether secretory factors of DPSC (DPSC ℗ ) inhibit inflammation and proliferation of microglial cells and define the molecular mechanisms. Our quantitative RT-PCR analysis showed that the DPSC ℗ reduced the markers of the inflammation and induced anti-inflammatory molecules in microglial cells. DPSC ℗ reduced the intracellular and mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential in microglial cells. In addition, DPSC ℗ decreased the cellular bioenergetics parameters related to oxygen consumption rate (OCAR) and extracellular acidification rate (ECAR). We found that DPSC ℗ inhibited microglial cell proliferation by activating a checkpoint molecule, Chk1 leading an arrest at the G1 phase of the cell cycle. To define the mechanism, we performed the western blot analysis and observed that the MAPK P38 pathway was inhibited by DPSC ℗ . Furthermore, a System biology analysis revealed that the BDNF and GDNF, secretory factors of DPSC, blocked at the phosphorylation site (Tyr 182) of the P38 molecule resulting in the inhibition of downstream signaling of inflammation. These data suggest that the DPSC ℗ may be a potential therapeutic agent for neurodegenerative diseases., Competing Interests: Declaration of Competing Interest The authors do not have any potential conflict of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Cyanobacterial polyhydroxybutyrate (PHB) is preferred over bacteria for low-cost production due to its photoautotrophic nature and lower carbon requirement. Considering its impact on the environment and circular economy, the valorization of fruit waste is the need of the hour. In the present study, fruit peels of banana, orange, pea, jackfruit, watermelon and waste flowers were tried as carbon sources for mangrove-isolated cyanobacteria Limnothrix planktonica to accumulate PHB. Alterations in the ASN-III culture medium and the introduction of untreated and pre-treated (acid/alkali-treated) peels as carbon sources are tried to enhance PHB. Banana peel showed the maximum PHB accumulation potential of 25.73 mg/L on the 12th day of incubation, followed by jackfruit (22.46 mg/L) and watermelon peels (20.72 mg/L); whereas, commercial carbon sources showed lower PHB accumulation up to 19.26 mg/L and 18.21 mg/L with fructose and glucose respectively. PHB accumulation was boosted to 5-fold higher (39.39 mg/L) in NP deficiency medium along with banana peel supplement, as compared to photoautotrophic conditions (8.49 mg/L) after the 9th day of incubation. Additionally, the PHB obtained by using the fruit wastes has a higher molecular weight than the PHB accumulated during photoautotrophic conditions. Optimization of parameters using fruit wastes and characterization of PHB would lead to its potential use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Dental pulp-derived stem cells (DPSC) is a promising therapy as they modulate the immune response, so we evaluated the inhibitory effect of DPSC secretome (DPSC ℗ ) on the proliferation and inflammation in human glioblastoma (GBM) cells (U-87 MG) and elucidated the concomitant mechanisms involved., Methods: The U87-MG cells were cultured with DPSC ℗ for 24 h and assessed the expression of inflammatory molecules using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), generation of reactive oxygen species (ROS), and mitochondrial functionality using a seahorse flux analyzer. MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay and cell cycle analysis were performed to evaluate the proliferation and cell cycle. Finally, the protein levels were determined by western blot., Results: DPSC ℗ reduced the inflammation and proliferation of U-87 MG cells by down-regulating the pro-inflammatory markers and up-regulating anti-inflammatory markers expressions through ROS-mediated signaling. Moreover, DPSC ℗ significantly reduced the mitochondrial membrane potential (MMP) in the cells. The cellular bioenergetics revealed that all the parameters of oxygen consumption rate (OCAR) and the extracellular acidification rate (ECAR) were significantly decreased in the GBM cells after the addition of DPSC ℗ . Additionally, DPSC ℗ decreased the GBM cell proliferation by arresting the cell cycle at the G1 phase through activation (phosphorylation) of checkpoint molecule CHK1. Furthermore, mechanistically, we found that the DPSC ℗ impedes the phosphorylation of the mitogen-activated protein kinases (P38 MAPK) and protein kinase B (AKT) pathway., Conclusion: Our findings lend the first evidence of the inhibitory effects of DPSC ℗ on proliferation and inflammation in GBM cells by altering the P38 MAPK-AKT pathway.

The gut epithelium has a remarkable ability to recover from damage. We employed a combination of high-throughput sequencing approaches, mouse genetics, and murine and human organoids and identified a role for TGFB signaling during intestinal regeneration following injury. At 2 days following irradiation (IR)-induced damage of intestinal crypts, a surge in TGFB1 expression is mediated by monocyte/macrophage cells at the location of damage. The depletion of macrophages or genetic disruption of TGFB signaling significantly impaired the regenerative response. Intestinal regeneration is characterized by the induction of a fetal-like transcriptional signature during repair. In organoid culture, TGFB1 treatment was necessary and sufficient to induce the fetal-like/regenerative state. Mesenchymal cells were also responsive to TGFB1 and enhanced the regenerative response. Mechanistically, pro-regenerative factors, YAP/TEAD and SOX9, are activated in the epithelium exposed to TGFB1. Finally, pre-treatment with TGFB1 enhanced the ability of primary epithelial cultures to engraft into damaged murine colon, suggesting promise for cellular therapy., Competing Interests: Declaration of interests L.C. and M.P.V are listed inventors of a provisional patent application 63392365., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Transplantation of stem cells for treating neurodegenerative disorders is a promising future therapeutic approach. However, the molecular mechanism underlying the neuronal differentiation of dental pulp-derived stem cells (DPSC) remains inadequately explored. The current study aims to define the regulatory role of KLF2 (Kruppel-like factor 2) during the neural differentiation (ND) of DPSC., Methods: We first investigated the transcriptional and translational expression of KLF2, autophagy, and mitophagy-associated markers during the ND of DPSC by using quantitative RT-PCR and western blot methods. After that, we applied the chemical-mediated loss- and gain-of-function approaches using KLF2 inhibitor, GGPP (geranylgeranyl pyrophosphate), and KLF2 activator, GGTI-298 (geranylgeranyl transferase inhibitor-298) to delineate the role of KLF2 during ND of DPSC. The western blot, qRT-PCR, and immunocytochemistry were performed to determine the molecular changes during ND after KLF2 deficiency and KLF2 sufficiency. We also analyzed the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) using the Seahorse XFe24 analyzer., Results: Our study demonstrated that the expression level of KLF2, autophagy, and mitophagy-associated markers were significantly elevated during the ND of DPSC. Next, we found that the KLF2 inhibitor, GGPP significantly reduced the ND of DPSC. Inversely, KLF2 overexpression accelerated the molecular phenomenon of DPSC's commitment towards ND, indicating the crucial role of KLF2 in neurogenesis. Moreover, we found that the KLF2 positively regulated autophagy, mitophagy, and the Wnt5a signaling pathway during neurogenesis. Seahorse XFe24 analysis revealed that the ECAR and OCR parameters were significantly increased during ND, and inhibition of KLF2 marginally reversed them towards DPSC's cellular bioenergetics. However, KLF2 overexpression shifted the cellular energy metabolism toward the quiescent stage., Conclusion: Collectively, our findings provide the first evidence that the KLF2 critically regulates the neurogenesis of DPSC by inducing autophagy and mitophagy., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Contrast sensitivity (CS) evaluation is very much necessary for the diagnosis and management of eye conditions. Several disadvantages seen in the traditionally used Pelli-Robson (PR) chart persuaded us to develop a novel digital device for the evaluation of CS at various levels of visual acuity (VA) for early detection of deteriorating vision., Materials and Methods: The new chart was constructed on the Debian software. Letters were constructed at each level of VA from 6/60 to 6/6 with a contrast of 0-2.25 logCS. The newly constructed chart was validated against the PR chart. The data were analyzed on the SPSS software version 23. The Pearson's correlation test was used to find out the correlation between the digital CS chart (DCSC) and PR charts., Results: On successful construction of a DCSC with varying VA, 56 participants were examined with a mean age of 20.43 ± 1.44 years. The mean CS with PR was 1.84 ± 0.13 logCS, whereas DCSC was 2.09 ± 0.14 logCS. The correlation between the two charts was moderate having r = 0.489 with P = 0 (confidence interval 95%)., Conclusion: A newly developed CS chart is efficient in examining the CS in clinical practice and has good repeatability; it may help in the early detection and monitoring of ocular diseases., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Oman Ophthalmic Society.)

Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects. Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality. Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis. However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC. This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Astrocytes have been implicated in the onset and complication of various central nervous system (CNS) injuries and disorders. Uncontrolled astrogliosis (gliosis), while a necessary process for recovery after CNS trauma, also causes impairments in CNS performance and functions. The ability to preserve astrocyte health and better regulate the gliosis process could play a major role in controlling damage in the aftermath of acute insults and during chronic dysfunction. Here in, we demonstrate the ability of dental pulp-derived stem cells (DPSCs) in protecting the health of astrocytes during induced gliosis. First of all, we have characterized the expression of genes in primary astrocytes that are relevant to the pathological conditions of CNS by inducing gliosis. Subsequently, we found that astrocytes co-cultured with DPSCs reduced ROS production, NRF2 and GCLM expressions, mitochondrial membrane potential, and mitochondrial functions compared to the astrocytes that were not co-cultured with DPSCs in gliosis condition. In addition, hyperactive autophagy was also decreased in astrocytes that were co-cultured with DPSCs compared to the astrocytes that were not co-cultured with DPSCs during gliosis. This reversal and mitigation of gliosis in astrocytes were partly due to induction of neurogenesis in DPSCs through enhanced expressions of the neuronal genes like GFAP, NeuN, and Synapsin in DPSCs and by secretion of higher amounts of neurotropic factors, such as BDNF, GDNF, and TIMP-2. Protein-Protein docking analysis suggested that BDNF and GDNF can bind with CSPG4 and block the downstream signaling. Together these findings demonstrate novel functions of DPSCs to preserve astrocyte health during gliosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Arsenic contamination is a severe issue because of its toxicity and related health risks. This review article presents an overview of the sources, health hazards, and treatment options for arsenic pollution. Conventional approaches to achieving the permitted level of 10 ppb set by the WHO, such as chemical oxidation, biological oxidation, and coagulation-flocculation, are ineffective and time-consuming. The paper analyses the advantages and disadvantages of various advanced treatment technologies, including membrane filtration, ion exchange, advanced oxidation, phytoremediation, and adsorption. This paper summarized the effectiveness of hybrid arsenic remediation techniques in removing arsenic and its operating conditions. This study is a helpful tool for putting remediation strategies into practice. This article describes arsenic pollution's damaging effects on human health, underscoring the necessity for careful treatment. The article addresses numerous treatment technologies, each with advantages and disadvantages preventing widespread use. Due to these limitations, deciding the best technique for arsenic remediation is difficult. As a result, hybrid treatment systems are urgently needed, with photocatalysis-adsorption being the most popular approach. The relevance of adaptable, user-friendly, low-maintenance hybrid technologies that are versatile, easy to use, and provide affordable arsenic removal options, especially for poor populations, is highlighted by prospects.

Vaccination has been a hot topic in the present COVID-19 context. The government, public health stakeholders and media are all concerned about how to get the people vaccinated. The study was intended to explore the perception and emotions of the Indians citizens toward COVID-19 vaccine from Twitter messages. The tweets were collected for the period of 6 months, from mid-January to June, 2021 using hash-tags and keywords specific to India. Topics and emotions from the tweets were extracted using Latent Dirichlet Allocation (LDA) method and National Research Council (NRC) Lexicon, respectively. Theme, sentiment and emotion wise engagement and reachability metrics were assessed. Hash-tag frequency of COVID-19 vaccine brands were also identified and evaluated. Information regarding ' Co-WIN app and availability of vaccine' was widely discussed and also received highest engagement and reachability among Twitter users. Among the various emotions, trust was expressed the most, which highlights the acceptance of vaccines among the Indian citizens. The hash-tags frequency of vaccine brands shows that Covishield was popular in the month of March 2021, and Covaxin in April 2021. The results from the study will help stakeholders to efficiently use social media to disseminate COVID-19 vaccine information on popular concerns. This in turn will encourage citizens to be vaccinated and achieve herd immunity. Similar methodology can be adopted in future to understand the perceptions and concerns of people in emergency situations., Supplementary Information: The online version contains supplementary material available at 10.1007/s42001-023-00203-0., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Osteoarthritis (OA) is a common and debilitating joint disorder that leads to progressive joint breakdown and loss of articular cartilage. Accompanied by a state of low-grade inflammation, its etiology extends beyond that of a wear-and-tear disease, and the immune system might have a role in its initiation and progression. Obesity, which is directly associated with an increased incidence of OA, alters adipokine release, increases pro-inflammatory macrophage activity, and affects joint immune regulation. Studying inflammatory macrophage expression and strategies to inhibit inflammatory macrophage phenotype polarization might provide insights into disease pathogenesis and therapeutic applications. In pre-clinical studies, the detection of OA in its initial stages was shown to be possible using imaging techniques such as SPECT-CT, and advances are made to detect OA through blood-based biomarker analysis. In this review, obesity-induced osteoarthritis and its mechanisms in inducing joint degeneration are summarized, along with an analysis of the current developments in patient imaging and biomarker use for diagnostic and therapeutic strategies.

Microbial polysaccharides (MPs) offer immense diversity in structural and functional properties. They are extensively used in advance biomedical science owing to their superior biodegradability, hemocompatibility, and capability to imitate the natural extracellular matrix microenvironment. Ease in tailoring, inherent bio-activity, distinct mucoadhesiveness, ability to absorb hydrophobic drugs, and plentiful availability of MPs make them prolific green biomaterials to overcome the significant constraints of cancer chemotherapeutics. Many studies have demonstrated their application to obstruct tumor development and extend survival through immune activation, apoptosis induction, and cell cycle arrest by MPs. Synoptic investigations of MPs are compulsory to decode applied basics in recent inclinations towards cancer regimens. The current review focuses on the anticancer properties of commercially available and newly explored MPs, and outlines their direct and indirect mode of action. The review also highlights cutting-edge MPs-based drug delivery systems to augment the specificity and efficiency of available chemotherapeutics, as well as their emerging role in theranostics., Competing Interests: Declaration of Competing Interest The authors do not have any conflicts of interest to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A natural plant product, epigallocatechin-3-gallate (EGCG), was evaluated for its effectiveness in the regulation of osteoclastogenesis. We found that EGCG inhibited the osteoclast (OC) differentiation in vitro, and in primary bone marrow cells in a dose-dependent manner. Quantitative RT-PCR studies showed that the EGCG reduced the expression of OC differentiation markers. DCFDA, MitoSOX, and JC-1 staining revealed that the EGCG attenuated the reactive oxygen species (ROS), and mitochondrial membrane potential; and flux analysis corroborated the effect of EGCG. We further found that the EGCG inhibited mRNA and protein expressions of mitophagy-related molecules. We confirmed that the OC differentiation was inhibited by EGCG by modulating mitophagy through AKT and p38MAPK pathways. Furthermore, in silico analysis revealed that the binding of RANK and RANKL was blocked by EGCG. Overall, we defined the mechanisms of osteoclastogenesis during arthritis for developing a new therapy using a natural compound besides the existing therapeutics., (© 2022. The Author(s).)

This work aimed to validate the potential use of dental pulp-derived stem cells (DPSCs) for the treatment of inflammation by defining their mechanisms of action. We planned to investigate whether priming of DPSC with proinflammatory molecules had any impact on their behavior and function. In the first step of our validation in vitro, we showed that priming of DPSCs with the bioactive agents LPS, TNF-α, or IFN-γ altered DPSCs' immunologic properties by increasing their expression levels of IL-10, HGF, IDO, and IL-4 and by decreasing their mitochondrial functions. Moreover, DPSCs induced accelerated wound healing irrespective of priming, as determined by using a gut epithelial cell line in a scratch wound assay. Wound healing of gut epithelial cells was mediated by regulating the expressions of AKT, NF-κB, and ERK1/2 proteins compared to the control epithelial cells. In addition, primed DPSCs altered monocyte polarization toward an immuno-suppressive phenotype (M2), where monocytes expressed higher levels of IL-4R, IL-6, Arg1, and YM-1 compared to monocytes cultured with control DPSCs. In silico analysis revealed that this was accomplished in part by the interaction between kynurenine and PPARγ, which regulated the expression of M2 differentiation-related genes. Collectively, these data provided evidence that the DPSCs reduced inflammation, induced M2 polarization of myeloid cells, and healed damaged gut epithelial cells through inactivation of inflammation and modulating constitutively active signaling pathways., Competing Interests: The authors declare no conflict of interest.

Osteoblast differentiation is critically reduced in various bone-related pathogenesis, including arthritis and osteoporosis. For future development of effective regenerative therapeutics, herein, we reveal the involved molecular mechanisms of a phytoestrogen, ferutinin-induced initiation of osteoblast differentiation from dental pulp-derived stem cell (DPSC). We demonstrate the significantly increased expression level of a transcription factor, Kruppel-like factor 2 (KLF2) along with autophagy-related molecules in DPSCs after induction with ferutinin. The loss-of-function and the gain-of-function approaches of KLF2 confirmed that the ferutinin-induced KLF2 modulated autophagic and OB differentiation-related molecules. Further, knockdown of the autophagic molecule (ATG7 or BECN1) from DPSC resulted not only in a decreased level of KLF2 but also in the reduced levels of OB differentiation-related molecules. Moreover, mitochondrial membrane potential-related molecules were increased and induction of mitophagy was observed in DPSCs after the addition of ferutinin. The reduction of mitochondrial as well as total ROS generations; and induction of intracellular Ca 2+ production were also observed in ferutinin-treated DPSCs. To test the mitochondrial respiration in DPSCs, we found that the cells treated with ferutinin showed a reduced extracellular acidification rate (ECAR) than that of their vehicle-treated counterparts. Furthermore, mechanistically, chromatin immunoprecipitation (ChIP) analysis revealed that the addition of ferutinin in DPSCs not only induced the level of KLF2, but also induced the transcriptionally active epigenetic marks (H3K27Ac and H3K4me3) on the promoter region of the autophagic molecule ATG7. These results provide strong evidence that ferutinin stimulates OB differentiation via induction of KLF2-mediated autophagy/mitophagy., (© 2022. The Author(s).)

Interleukin-mediated deep cytokine storm, an aggressive inflammatory response to SARS-CoV-2 virus infection in COVID-19 patients, is correlated directly with lung injury, multi-organ failure, and poor prognosis of severe COVID-19 patients. Curcumin (CUR), a phenolic antioxidant compound obtained from turmeric ( Curcuma longa L.), is well-known for its strong anti-inflammatory activity. However, its in vivo efficacy is constrained due to poor bioavailability. Herein, we report that CUR-encapsulated polysaccharide nanoparticles (CUR-PS-NPs) potently inhibit the release of cytokines, chemokines, and growth factors associated with damage of SARS-CoV-2 spike protein (CoV2-SP)-stimulated liver Huh7.5 and lung A549 epithelial cells. Treatment with CUR-PS-NPs effectively attenuated the interaction of ACE2 and CoV2-SP. The effects of CUR-PS-NPs were linked to reduced NF-κB/MAPK signaling which in turn decreased CoV2-SP-mediated phosphorylation of p38 MAPK, p42/44 MAPK, and p65/NF-κB as well as nuclear p65/NF-κB expression. The findings of the study strongly indicate that organic NPs of CUR can be used to control hyper-inflammatory responses and prevent lung and liver injuries associated with CoV2-SP-mediated cytokine storm.

The human digestive tract is the cottage to trillions of live microorganisms, which regulate health and illness. A healthy Gut Microbiota (GM) is necessary for preventing microbial growth, body growth, obesity, cancer, diabetes, and enhancing immunity. The equilibrium in GM's composition and the presence/absence of critical species enable specific responses to be essential for the host's better health condition. Research evidences revealed that the dietary plants and their bioactive phytochemicals (BPs) play an extensive and critical role in shaping the GM to get beneficial health effects. BPs are also known to improve gastrointestinal health and reduce the risk of several diseases by modulating GM-mediated cellular and molecular processes. Regular intake of BPs-rich vegetables, fruits, and herbal preparations promotes probiotic bacteria, including Bifidobacteria and Lactobacillus species, while inhibiting unwanted gut residents' development Escherichia coli, and Salmonella typhimurium etc. Upon consumption, BPs contact the GM that gets transformed before being absorbed from the gastrointestinal tract. Biotransformation of BPs by GM is linked with the enhancement of bioactivity/toxicity diminishment of the BPs compared to parental phytochemicals. Therefore, the current review focuses on the role of BPs in shaping GM for the prevention and treatment of human diseases., Competing Interests: Declaration of competing interest Not applicable., (Copyright © 2021. Published by Elsevier B.V.)

Existing drugs have limited success in managing obesity in human due to their low efficacy and severe side-effects. Surface-modified gold nanoparticles have now received considerable attention of researchers for efficient biomedical applications owing to their superior uptake by cells, biocompatibility, hydrophilicity and non-immunogenicity. Here we prepared Cinnamomum verum derived bioactives-functionalized gold nanoparticles (Au@P-NPs) and assessed their impact on obesity and related immune-metabolic complications in high-fat diet (HFD)-induced obese mice using metabolic experiments along with 16S RNA gene-based gut microbial profiling and faecal microbiota transplantation (FMT). Au@P-NPs treatment prevented weight gain, decreased fat deposition, reduced metabolic inflammation and endotoxaemia in HFD-fed mice. Au@P-NPs-treated group exhibited better glucose tolerance and insulin sensitivity than HFD-fed control mice, and got completely protected against hepatic steatosis. These impacts were related to increased energy expenditure and enhanced Ucp1 expression in the brown adipose tissues of Au@P-NPs-administered animals, which strongly linked with the mRNA expression of the membrane bile acid receptor TGR5. Treatment of HFD-fed animals with Au@P-NPs altered plasma bile acid profile, and increased Akkermansia muciniphila and decreased Lactobacillus populations in the faeces. Au@P-NPs-treated animals revealed altered plasma bile acid profile, and increased Akkermansia muciniphila and decreased Lactobacillus populations in the faeces. FMT experiments showed lesser weight gain and greater energy expenditure in the mice fed with faecal suspension from Au@P-NPs-treated animals than that from HFD-fed mice. These results clearly establish that gold nanoparticles functionalized with bioactive compounds of C. verum have high potential to be an anti-obesity drug., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Ltd.)

Nanotechnology is an innovative area of science that deals with things smaller than 100 nanometers. The influence of nanotechnology in the cosmetic industry is overwhelming since it can enhance the properties attained by the particles at the nano level, including color, solubility, etc, and can also promote the bioavailability of API. A plethora of nanomaterials can be employed in cosmetics, including organic and inorganic nanoparticles. Unlike orthodox carriers, they facilitate easy penetration of the product into the skin, thereby increasing the stability and allowing a controlled drug release so that they can permeate deeper into the skin and start revitalizing it. Nanomaterials rejuvenate the skin by forming an occlusive barrier to inhibit the loss of water from the skin's surface and thereby moisturize the skin. Nano-cosmeceuticals are used to provide better protection against UV radiation, facilitate deeper skin penetration, and give long-lasting effects. Although they still have some safety concerns, hence detailed characterization or risk assessments are required to fulfill the standard safety requirements. In this review, an attempt is made to make a brief overview of various nanocosmeceuticals skincare and anti-aging products., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hepatocellular Carcinoma is one of the most frequently diagnosed cancer and highly refractory for chemotherapeutics agents. Therefore, the study aims to explore the new therapeutic agents for HCC. Phenolics rich fraction of leaves of P. lanceifolium was studied against hepatic cancer cell lines (HepG2) and NDEA-induced HCC rat model system. The obtained results showed that PLE induces reactive oxygen species (ROS) generation and chromatin condensation in nucleus and, alters the mitochondrial membrane potential (MMP) in HepG2 cell lines. The acridine orange/propidium iodide analysis and annexin-V FITC/PI analysis confirms that PLE induces apoptosis-mediated cell death in HepG2-cell lines. In In Vivo analysis, the administration of PLE in NDEA-induced rats declined the elevated biochemicals markers (ALT, AST, ALP, and GGT), interleukins, TNF-α, α-fetoprotein, carcinoembryonic antigen, and total bilirubin. PLE reinstated the level of antioxidant enzyme (GSH, GST, catalase, SOD, and GPX) and the expression of pro-apoptotic (p53, caspase-3, caspase-9, and Bax) and anti-apoptotic (Bcl-2) genes in a dose-dependent manner. The GC-MS analysis of Pterospermum lanceifolium fraction (PLE) represents the presence of palmitic acid, myristic acid, β-sitosterol, and catechin as major bioactive phytocompounds. The study discloses the new lead for HCC that can be further useful for development of new chemopreventive agent.

The unprecedented quick spreading of newly emerged SARS-CoV-2, the virus responsible for causing COVID-19 has put the whole world in vast crisis. Several prophylactic interventions are being performed to discover the effective anti-COVID-19 agent. Thus, the present study aims to identify the cryptogamic secondary metabolites (CSMs) as potent inhibitors of two major targets of SARS-Cov2, namely 3-chymotrypsin-like protease (3CL pro ) and receptor-binding domain (RBD) of spike glycoprotein (SGP), by implementing a computational approach. Molecular docking was carried out on Autodock 4.2 software with the 3CL pro (PDB ID:6LU7) and RBD of SGP (PDB ID:6W41) of the virus. Lopinavir and Arbidol were taken as positive controls to compare the efficacy of randomly selected 53 CSMs. The drug-likeness and pharmacokinetics properties of all metabolites were accessed to discern the anti-COVID 19 activity acting well at the physiological conditions. The docking results predicted that Marchantin E and Zeorin would potentially block the catalytic site of 3CL pro with the interaction energy values of -8.42 kcal/mol and -9.04 kcal/mol, respectively. In addition, Usnic acid revealed its ability to combat the interaction of RBD of SGP to angiotensin-converting enzyme-2 in docking analysis. To certify the potent metabolites for both targets of SARS-CoV-2, MD analysis was performed for 100 ns. The results confirmed that Marchantin E could inhibit SARS-CoV-2 3CL pro and RBD of SGP as well as reveals excellent pharmacokinetic properties. The present study suggests that the identified CSMs could be quickly positioned for further experimental validation to propose promising inhibitors of SARS-CoV-2., Competing Interests: The authors declare that there are no conflicts of interest. Dr. Brahma Nand Singh reports financial support was provided by DBT and CSIR and DBT, India. Dr. B.N. Singh reports a relationship with CSIR-NBRI, Lucknow that includes: employment., (© 2021 Elsevier B.V. All rights reserved.)

Lichens are composite organisms, comprising of a fungus (mycobiont) and a blue-green alga (photobiont). Along with the mycobiont, numerous non-obligate microfungi live in lichen thalli. These microfungi are called endolichenic fungi (ELF). In recent years, the ELF are emerging as promising natural sources because of their capability to exert unique drug molecules. The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents. Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics. The isolated ELF was identified by amplifying the long subunit region of the fungal genome. The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling. Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1. The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52. The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1. The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner. The MELE also disturbed biofilm formation of P. aeruginosa PAO1. The 3-D analysis of biofilm architecture showed that the thickness and surface area covered by microcolonies was decreased as the concentration of MELE was increased. The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE. The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest among them., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: To compare refractive measurements of noncycloplegic photoscreener Plusoptix S12R with cycloplegic retinoscopy, noncycloplegic autorefractor, and cycloplegic autorefractor in children., Methods: The study population (200 eyes of 100 children) was divided into two groups: Group 1 (age 3-7 years) and Group 2 (age 8-15 years). In Group 1, Plusoptix was compared with cycloplegic retinoscopy. In Group 2, Plusoptix was compared with cycloplegic retinoscopy and autorefraction. The second group was made because the younger group was found to be uncooperative for autorefraction. Paired t-test and Pearson's correlation were used for statistical analysis., Results: The mean difference in sphere (DS), spherical equivalent (DSE), and cylinder (DC) between cycloplegic retinoscopy and Plusoptix in Group 1 was 0.68 ± 0.55 (P < 0.001), 0.77 ± 0.61 (P < 0.001), and 0.18 ± 0.28 (P < 0.001), respectively. In Group 2, DS, DSE, and DC between cycloplegic retinoscopy and Plusoptix were 0.86 ± 0.49 (P < 0.001), 0.97 ± 0.51 (P < 0.001), and 0.23 ± 0.28 (P < 0.001); between cycloplegic autorefractor and Plusoptix were 0.69 ± 0.47 (P < 0.001), 0.74 ± 0.49 (P < 0.001), and 0.10 ± 0.31 (P = 0.002); and between noncycloplegic autorefractor and Plusoptix were - 0.25 ± 0.39 (P < 0.001), -0.19 ± 0.41 (P < 0.001), and 0.11 ± 0.31 (P < 0.001), respectively. Pearson's correlation coefficients of S, SE, and C between Plusoptix and cycloplegic retinoscopy were 0.948, 0.938, and 0.924 in Group 1 and 0.972, 0.972, and 0.946 in Group 2, and these values were statistically significant. Bland-Altman plots showed good agreement between cycloplegic retinoscopy and Plusoptix in both groups. Plusoptix gave axis values within 10° of cycloplegic retinoscopy in 81.56% of eyes in Group 1 and in 71.44% of eyes in Group 2., Conclusion: Plusoptix photoscreener can be used for prescription of axis of cylinder in children; however, other refractive measurements must be refined by cycloplegic retinoscopy., Competing Interests: There are no conflicts of interest.

Purpose: To compare short-term visual outcomes (best corrected visual acuity [BCVA]), visual axis opacification, anterior (ACCC) and posterior (PCCC) continuous curvilinear capsulorhexis size, shape, and extension, and their decentration between manual capsulorhexis and 25-gauge vitrectorhexis in pediatric cataract surgery with intraocular lens (IOL) implantation., Methods: Thirty eyes of children aged 3 to 8 years with developmental cataract were randomly selected for ACCC and PCCC by manual capsulorhexis forceps and 25-gauge vitrectomy cutter followed by IOL implantation and limited anterior vitrectomy. The size of the ACCC and PCCC was measured intraoperatively with calibrated capsulorhexis forceps. Patients were followed up for 3 months postoperatively and were evaluated for BCVA and visual axis opacification. Slit-lamp photographs of operated eyes were taken in retroillumination. The size in millimeters and decentration of the ACCC and PCCC from the center of the IOL were measured with the help of the Python imaging library., Results: There was no statistically significant difference between BCVA (P > .05), visual axis opacification (P > .05), size of the ACCC (P > .05) and its decentration (P > .05), extension of the rhexis (P > .05), and size of the PCCC (P > .05) and its decentration (P > .05) between the two methods., Conclusions: In both groups, BCVA, visual axis opacification, and ACCC and PCCC size, shape, and decentration from the center of the IOL were comparable, making 25-gauge vitrectorhexis a good alternative to manual capsulorhexis. [J Pediatr Ophthalmol Strabismus. 2019;56(5):327-332.]., (Copyright 2019, SLACK Incorporated.)

The indiscriminate and excessive use of antibiotics has ultimately led to the emergence of bacterial resistant mutants or superbugs. These superbugs are difficult to control with conventional antibiotics. Disabling quorum sensing (QS), a population-density-dependent cell-to-cell communication process used by bacteria to coordinate the expression of virulence genes and biofilm formation, with dietary phytochemicals is emerging as a non-antibiotic strategy to inhibit bacterial pathogenicity. Although curcumin is an anti-QS agent and its delivery to cells has been a challenge due to poor bioavailability, ZnO/curcumin nanocomposites (ZnC-NCs) were fabricated with enhanced delivery of curcumin inside the bacterial superbug Pseudomonas aeruginosa PAO1 for effective inhibition of its QS and biofilm formation. Sustained release of curcumin from ZnC-NCs was observed where 51% curcumin at pH 7.2 and 83% curcumin at pH 5.5 were released within 48 h. ZnC-NCs also decreased the production of virulence factors and biofilm formation without affecting planktonic cell growth. Both LasR and RhlR QS systems were inhibited by ZnC-NCs. ZnC-NCs were also capable of protecting both mice as well as lung epithelial cells from killing by PAO1. The superoxide anions (O 2 · - ) were also found as key players in suppressing PAO1 QS systems by ZnC-NCs. Overall, ZnC-NCs enhanced curcumin bioavailability for effective inhibition of QS signaling in P. aeruginosa via LasR-RhlR suppression and O 2 · - generation.

The indiscriminate use of antibiotics has led to the emergence of drug-resistant bacteria which has become one of the biggest challenges of the twenty-first century for the researchers to combat and in turn search for novel targets which could lead to the development of effective and sustainable therapies. Inhibition of biofilm formation and virulence of bacterial pathogens is an emerging approach to address the challenges related to bacterial infections. To suppress the virulence and biofilm formation by Escherichia coli O157:H7 (ECOH), we developed stable nanoemulsion (NE) of Gaultheria fragrantissima Wall. essential oil's (EO) bioactive compounds, viz., eugenol (E-NE) and methyl salicylate (MS-NE) that showed significantly higher anti-biofilm and anti-virulence activities as compared to eugenol and methyl salicylate without affecting ECOH planktonic cell growth. Transcriptional analysis showed that E-NE and MS-NE reduced the expression of genes, including curli, type I fimbriae, Shiga-like toxins, quorum sensing, and ler-controlled toxins, which are needed for biofilm formation, pathogenicity, and attachment. E-NE and MS-NE loaded hydrogel coatings showed superior anti-biofilm activity against ECOH on glass, plastic and meat surfaces as compared to eugenol and methyl salicylate loaded coatings. Conclusively, NE-loaded hydrogel coatings could be used in combating ECOH infection on solid surfaces through anti-biofilm and anti-virulence strategies.

During biotic stress, plants use several mechanisms to protect themselves that include the production of reactive oxygen species (ROS), induction of pathogenesis-related proteins and cell death. Some plant growth promoting rhizobacteria (PGPR) are known to act as bio-control agents that protect crops against pathogens. The biocontrol activity of PGPR Paenibacillus lentimorbus (B-30488) against Sclerotium rolfsii showed previously where several defense-related genes were upregulated with ROS induction in tomato. We further evaluate the other possibility, i.e. role of autophagy in enhancing defense in tomato using PGPR. Confocal microscopy revealed the presence of an acidotropic dye Mono Dansyl Cadaverine (MDC) stained autophagosomes in B-30488 treated healthy and infected plants. These autophagosomes almost disappeared in plants treated with an autophagy inhibitor chloroquine. The results were also confirmed by ultrastructural analysis of leaf tissues using transmission electron microscopy. Enhanced expression of autophagy-related genes was also monitored in B-30488 primed fungal infected tissues as compared to control by qRT-PCR. Results of ROS accumulation, fluorescence, confocal and transmission electron microscopy and gene expression analysis revealed induction of autophagy using B-30488 as a biocontrol agent suggesting a role in enhancing disease resistance in tomato. Overall, the present study indicated a role of B-30488 as a biocontrol in enhancing disease resistance in tomato and also assists a better understanding of fungal pathogenesis that is expected to be useful in developing new strategies for disease control., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background. The present study was undertaken to evaluate the incidence of dentinal cracks during root canal preparation with different periodontal ligament simulating materials in vitro. Methods. Seventy freshly extracted human mandibular first premolars were selected and divided into 7 groups in terms of simulating material: group 1: polyether impression material; group 2: polyvinyl acetate adhesive; group 3: polyvinyl siloxane impression material; group 4: cyanoacrylate adhesive; group 5: epoxy resin adhesive; group 6: positive control, without any periodontal ligament simulation; and group 7: negative control, where neither a periodontal ligament simulating material was used nor canal preparation was carried out. Root canal preparation was carried out in all the groups followed by sectioning of roots at 3 mm, 6 mm and 9 mm. The sections were evaluated under a stereomicroscope at ×2.5 for the presence or absence of cracks. Chi-squared test was used to compare the appearance of defective roots between the different experimental groups. Results. The least number of cracks were found in the negative control group, followed by group 1 where polyether impression material was used for periodontal ligament simulation. The difference was significant with a P-value of 0.002 for coronal sections. Conclusion. Under the limitation of the present study, polyether and polyvinyl siloxane (light body) can both be used for simulation of periodontal ligament.

The present investigation for the first time explains the anti biofilm and anti virulence potential of Kaffir lime oil (KLO) and its major constituent, Citronellal (3,7-dimethyloct-6-enal) against Xanthomonas oryzae pv. oryzae, causal organism of bacterial blight disease of rice. KLO at 500 ppm showed potential activity against X. oryzae pv. oryzae. Among the major components identified, citronellal (CIT) at 75 μM concentration was found to significantly inhibit biofilm along with the swimming and swarming potential of X. oryzae pv. oryzae. In contrary, CIT did not affect the metabolic status and growth kinetics of the bacterial cells. Gene expression analysis showed down regulation in motA, cheD, cheY, flgF, gumC, xylanase, endogluconase, cellulose, cellobiosidase, virulence and rpfF transcript levels by citronellal treatment. However, an insignificant effect of 75 μM CIT treatment was observed on motB, flgE, pilA, estY, pglA, protease and lytic genes expression. Finally, the observations recorded were in confirmity with the virulence leaf clip test as lesion length was significantly decreased (39%) in CIT treatment as compared to the control leaves inoculated with only X. oryzae pv. oryzae. Overall, the findings obtained advocate the use of CIT for promising anti biofilm and anti virulence activity which in turn can be used for managing the blight disease in rice., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Despite several conventional potent antibacterial therapies, bacterial infections pose a significant threat to human health because they are emerging as the leading cause of death worldwide. Due to the development of antibiotic resistance in bacteria, there is a pressing demand to discover novel approaches for developing more effective therapies to treat multidrug-resistant bacterial strains and biofilm-associated infections. Therefore, attention has been especially devoted to a new and emerging branch of science "nanotechnology" to design non-conventional antimicrobial chemotherapies. A range of nanomaterials and nano-sized carriers for conventional antimicrobial agents have fully justified their potential to combat bacterial diseases by reducing cell viability, by attenuating quorum sensing, and by inhibiting/or eradicating biofilms. This communication summarizes emerging nano-antimicrobial therapies in treating bacterial infections, particularly using antibacterial, quorum quenching, and anti-biofilm nanomaterials as new approaches to tackle the current challenges in combating infectious diseases.

Honey is an excellent source of polyphenolic compounds that are effective in attenuating quorum sensing (QS), a chemical process of cell-to-cell communication system used by the opportunistic pathogen Pseudomonas aeruginosa to regulate virulence and biofilm formation. However, lower water solubility and inadequate bioavailability remains major concerns of these therapeutic polyphenols. Its therapeutic index can be improved by using nano-carrier systems to target QS signaling potently. In the present study, we fabricated a unique drug delivery system comprising selenium nanoparticles (SeNPs; non-viral vectors) and polyphenols of honey (HP) for enhancement of anti-QS activity of HP against P. aeruginosa PAO1. The developed selenium nano-scaffold showed superior anti-QS activity, anti-biofilm efficacy, and anti-virulence potential in both in-vitro and in-vivo over its individual components, SeNPs and HP. LasR is inhibited by selenium nano-scaffold in-vitro . Using computational molecular docking studies, we have also demonstrated that the anti-virulence activity of selenium nano-scaffold is reliant on molecular binding that occurs between HP and the QS receptor LasR through hydrogen bonding and hydrophobic interactions. Our preliminary investigations with selenium-based nano-carriers hold significant promise to improve anti-virulence effectiveness of phytochemicals by enhancing effective intracellular delivery.

Background and Objective: To evaluate retinal nerve fiber layer (RNFL) thickness after conventional brilliant blue (BB) assisted macular hole (MH) surgery versus BB selective staining using whole blood (WB) in MH surgery., Patients and Methods: Sixty eyes with stage 4 idiopathic MH with a clear media were randomly divided into two equal groups. Group A eyes underwent sequential intraoperative use of autologous heparinized WB followed by BB dye for staining internal limiting membrane, whereas eyes in group B were subjected to conventional BB staining. Clinical examination and spectral-domain optical coherence tomography was done preoperatively and postoperatively up to 6 months., Results: Mean global RNFL thickness and mean temporal RNFL thickness decreased in both groups postoperatively, but the reduction in RNFL thickness in group B was greater than group A at all postoperative visits (P < .05)., Conclusion: BB toxicity may be responsible for reduction of RNFL thickness and WB appears to protect RNFL against dye toxicity. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:436-442.]., (Copyright 2016, SLACK Incorporated.)