Curcumin coating: a novel solution to mitigate inherent carbon nanotube toxicity.

Multi-walled Carbon Nanotubes (MWCNTs) are inert structures with high aspect ratios that are widely used as vehicles for targeted drug delivery in cancer and many other diseases. They are largely non-toxic in nature however, when cells are exposed to these nanotubes for prolonged durations or at high concentrations, they show certain adverse effects. These include cytotoxicity, inflammation, generation of oxidative stress, and genotoxicity among others. To combat such adverse effects, various moieties can be attached to the surface of these nanotubes. Curcumin is a known anti-inflammatory, antioxidant and cytoprotective compound derived from a medicinal plant called Curcuma longa. In this study, we have synthesized and characterized Curcumin coated-lysine functionalized MWCNTs and further evaluated the cytoprotective, anti-inflammatory, antioxidant and antiapoptotic effect of Curcumin coating on the surface of MWCNTs. The results show a significant decrease in the level of inflammatory molecules like IL-6, IL-8, IL-1ß, TNFα and NFκB in cells exposed to Curcumin-coated MWCNTs as compared to the uncoated ones at both transcript and protein levels. Further, compared to the uncoated samples, there is a reduction in ROS production and upregulation of antioxidant enzyme-Catalase in the cells treated with Curcumin-coated MWCNTs. Curcumin coating also helped in recovery of mitochondrial membrane potential in the cells exposed to MWCNTs. Lastly, cells exposed to Curcumin-coated MWCNTs showed reduced cell death as compared to the ones exposed to uncoated MWCNTs. Our findings suggest that coating of Curcumin on the surface of MWCNTs reduces its ability to cause inflammation, oxidative stress, and cell death.

Computational insights into VacA toxin inhibition: harnessing FDA-approved antibiotics against Helicobacter pylori.

Cancer is a condition in which a few of the body's cells grow beyond its control and spread to other outward regions. Globally, gastric cancer (GC) is third most common cause of cancer-related mortality and the fourth most common kind of cancer. Persistent infection of VacA-positive Helicobacter pylori (H. pylori) modulates cellular physiology and leads to GC. About ∼70% of H. pylori are positive for vacuolating cytotoxin-A (VacA), and it infects ∼80-90% of world populations. Herein, for first time, we repurposed FDA-approved gram-negative antibiotics, which are feasible alternatives to existing regimens and may be used in combinatorial treatment against VacA-positive H. pylori. Out of 110 FDA-approved antibiotics, we retrieved 92 structures, which were screened against the VacA protein. Moreover, we determined that the top eight hit antibiotics viz; cefpiramide, cefiderocol, eravacycline, doxycycline, ceftriaxone, enoxacin, tedizolid, and cefamandole show binding free energies of -9.1, -8.9, -8.1, -8.0, -7.9, -7.8, -7.8 and -7.8 Kcal/mol, respectively, with VacA protein. Finally, we performed 100 ns duplicate MD simulations on the top eight selected antibiotics showing strong VacA binding. Subsequently, five antibiotics, including cefiderocol, cefpiramide, doxycycline, enoxacin, and tedizolid show stable ligand protein distance and good binding affinity revealed by the MM-PBSA scheme. Among the five antibiotics cefiderocol act as the most potent inhibitor (-28.33 kcal/mol). Furthermore, we also identified the hotspot residue like Asn-506, Tyr-529, and Phe-483 which control the interaction. Concisely, we identified antibiotics that can be repurposed against VacA of H. pylori and explored their molecular mechanism of interaction with VacA.Communicated by Ramaswamy H. Sarma.

SARS-CoV-2 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1.

SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated necrotic cell death in E protein transfected cells. Our study revealed the role of the necroptotic marker RIPK1 in cell death. Additionally, inhibition of RIPK1 by its specific inhibitor Nec-1s exhibits recovery from cell death and inflammation manifested by reduced phosphorylation of NFκB. The E-transfected cells' conditioned media induced inflammation with differential expression of inflammatory markers compared to direct transfection in the gastrointestinal-lung axis. In conclusion, SARS-CoV-2 E mediates inflammation and necroptosis through RIPK1, and the E-expressing cells' secretion can modulate the gastrointestinal-lung axis. Based on the data of the present study, we believe that during severe COVID-19, necroptosis is an alternate mechanism of cell death besides ferroptosis, especially when the disease is not associated with drastic increase in serum ferritin.

Epigallocatechin Gallate: A Multifaceted Molecule for Neurological Disorders and Neurotropic Viral Infections.

Epigallocatechin-3-gallate (EGCG), a polyphenolic moiety found in green tea extracts, exhibits pleiotropic bioactivities to combat many diseases including neurological ailments. These neurological diseases include Alzheimer's disease, multiple sclerosis, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. For instance, in the case of Alzheimer's disease, the formation of a ß-sheet in the region of the 10th-21st amino acids was significantly reduced in EGCG-induced oligomeric samples of Aß40. Its interference induces the formation of Aß structures with an increase in intercenter-of-mass distances, reduction in interchain/intrachain contacts, reduction in ß-sheet propensity, and increase in α-helix. Besides, numerous neurotropic viruses are known to instigate or aggravate neurological ailments. It exerts an effect on the oxidative damage caused in neurodegenerative disorders by acting on GSK3-ß, PI3K/Akt, and downstream signaling pathways via caspase-3 and cytochrome-c. EGCG also diminishes these viral-mediated effects, such as EGCG delayed HSV-1 infection by blocking the entry for virions, inhibitory effects on NS3/4A protease or NS5B polymerase of HCV and potent inhibitor of ZIKV NS2B-NS3pro/NS3 serine protease (NS3-SP). It showed a reduction in the neurotoxic properties of HIV-gp120 and Tat in the presence of IFN-γ. EGCG also involves numerous viral-mediated inflammatory cascades, such as JAK/STAT. Nonetheless, it also inhibits the Epstein-Barr virus replication protein (Zta and Rta). Moreover, it also impedes certain viruses (influenza A and B strains) by hijacking the endosomal and lysosomal compartments. Therefore, the current article aims to describe the importance of EGCG in numerous neurological diseases and its inhibitory effect against neurotropic viruses.

Prediction of Rab5B inhibitors through integrative in silico techniques.

Rab5B is a small monomeric G protein that regulates early endocytosis and controls signaling pathways related to cell growth, survival, and apoptosis. Dysregulation of Rab5B protein expression has been linked to the development of several cancers such as leukemia, lymphoma, kidney, prostate, ovarian, breast cancer, etc. Our research shows the first attempt to identify inhibitors that can target Rab5B GTPase. In this study, we performed molecular docking using Autodock Vina 1.5.6 and identified eight molecules with docking scores ranging from -9.8 to -10.6 kcal/mol. Thereafter, we examined the pharmacological characteristics of these compounds, and selected compounds were further analyzed for their conformational dynamics and thermodynamic stability using molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA)-based free energy calculations. Notably, our findings revealed that strychnine had the highest binding affinity to Rab5B followed by anonaine, helioxanthin, and taiwanin E, with a ΔGbind value of -21.43, -17.11, -15.11, and -14.09 kcal/mol respectively. The binding free energy calculations showed that Van der Waals interactions are the primary contributor to the binding between Rab5B and the inhibitor. The interaction between the inhibitor and Rab5B was shown to be controlled by certain hot spot residues, including Phe45, Tyr48, Ala64, and Ala30. Overall, we believe that these findings could facilitate the exploration and development of potential hits against Rab5B, subject to optimization and further research. Rab5B inhibitory binding affinity of natural plants active compounds.

Comprehensive insight into altered host cell-signaling cascades upon Helicobacter pylori and Epstein-Barr virus infections in cancer.

Cancer is characterized by mutagenic events that lead to disrupted cell signaling and cellular functions. It is one of the leading causes of death worldwide. Literature suggests that pathogens, mainly Helicobacter pylori and Epstein-Barr virus (EBV), have been associated with the etiology of human cancer. Notably, their co-infection may lead to gastric cancer. Pathogen-mediated DNA damage could be the first and crucial step in the carcinogenesis process that modulates numerous cellular signaling pathways. Altogether, it dysregulates the metabolic pathways linked with cell growth, apoptosis, and DNA repair. Modulation in these pathways leads to abnormal growth and proliferation. Several signaling pathways such RTK, RAS/MAPK, PI3K/Akt, NFκB, JAK/STAT, HIF1α, and Wnt/ß-catenin are known to be altered in cancer. Therefore, this review focuses on the oncogenic roles of H. pylori, EBV, and its associated signaling cascades in various cancers. Scrutinizing these signaling pathways is crucial and may provide new insights and targets for preventing and treating H. pylori and EBV-associated cancers.

A Systematic Review on Traumatic Brain Injury Pathophysiology and Role of Herbal Medicines in its Management.

BACKGROUND: Traumatic brain injury (TBI) is a worldwide problem. Almost about sixtynine million people sustain TBI each year all over the world. Repetitive TBI linked with increased risk of neurodegenerative disorder such as Parkinson, Alzheimer, traumatic encephalopathy. TBI is characterized by primary and secondary injury and exerts a severe impact on cognitive, behavioral, psychological and other health problem. There were various proposed mechanism to understand complex pathophysiology of TBI but still there is a need to explore more about TBI pathophysiology. There are drugs present for the treatment of TBI in the market but there is still need of more drugs to develop for better and effective treatment of TBI, because no single drug is available which reduces the further progression of this injury. OBJECTIVE: The main aim and objective of structuring this manuscript is to design, develop and gather detailed data regarding about the pathophysiology of TBI and role of medicinal plants in its treatment. METHOD: This study is a systematic review conducted between January 1995 to June 2021 in which a consultation of scientific articles from indexed periodicals was carried out in Science Direct, United States National Library of Medicine (Pubmed), Google Scholar, Elsvier, Springer and Bentham. RESULTS: A total of 54 studies were analyzed, on the basis of literature survey in the research area of TBI. CONCLUSION: Recent studies have shown the potential of medicinal plants and their chemical constituents against TBI therefore, this review targets the detailed information about the pathophysiology of TBI and role of medicinal plants in its treatment.

Relationship of Nasolabial Angle with Maxillary Incisor Proclination and Upper Lip Thickness in North Indian Population.

Aim: The aim of the study was to evaluate the relationship between nasolabial angle (NLA) with maxillary incisor proclination (U1-NA) and upper lip thickness (ULT). Materials and methods: Pretreatment lateral cephalometric radiographs of 120 patients were taken, and NLA, U1-NA, and basic ULT measurements were obtained for each patient. Descriptive statistics were calculated for all the variables involved in the study. The correlation was found using the Pearson correlation coefficient (r) test. p < 0.01 was considered statistically significant. Results: The mean values of NLA, upper incisor proclination, and ULT were found to be 91.38° ± 7.10°, 34.21° + 5.17°, and 15.38 ± 1.76 mm, respectively. r (r = -0.583) was found between NLA and upper incisor proclination and (r = -0.040) for NLA and ULT. Conclusion: There is a statistically significant relationship between NLA and U1-NA. How to cite this article: Garg H, Khundrakpam D, Saini V, et al. Relationship of Nasolabial Angle with Maxillary Incisor Proclination and Upper Lip Thickness in North Indian Population. Int J Clin Pediatr Dent 2022;15(5):489-492.

Exploration of fluorescence behavior of an imidazolium-based chemosensor in solution and in the solid state and its turn-on response to Al3+ in pure aqueous medium.

An imidazolium-based quinoline Schiff base ImSB was developed and fully characterized by FT-IR, 1H and 13C NMR spectroscopy, mass spectrometry, and X-ray crystallography. The fluorescence behaviour of ImSB in solution and in the solid state, keto-enol stability at different concentrations and pH in aqueous medium were investigated. The UV-visible and fluorescence studies were performed to determine the response of ImSB towards different ions in aqueous medium. ImSB showed a turn-on fluorescence behaviour with high selectivity towards Al3+ over various cations and anions due to chelation-enhanced fluorescence (CHEF), inhibition of photoinduced electron transfer (PET) and restriction of C[double bond, length as m-dash]N isomerization. The low detection limit for Al3+ was 54 nM and Job's plot confirmed 1 : 1 stoichiometry between ImSB and Al3+ with a high binding constant value of 4.16 × 106 M-1. Monitoring of Al3+ was also demonstrated in real water samples (mineral, river and tap water). The structural and electronic parameters of ImSB and ImSB-Al3+ were also studied theoretically.

Freeze dried solid dispersion of exemestane: A way to negate an aqueous solubility and oral bioavailability problems.

This study was envisaged to demonstrate the potential of exemestane loaded phospholipid/sodium deoxycholate solid dispersions (EXE-PL/SDC-SDs) on the solubility and oral bioavailability of EXE. Initial studies were performed to screen the best suitable phospholipid among lysophosphatidylcholine, Phospholipon® P80H and Lipoid® E80S for solid dispersion preparation. Further studies were carried out to optimize the molar concentration of phospholipid and sodium deoxycholate (SDC) for EXE-PL/SDC-SDs preparation. Optimized EXE-PL/SDC-SDs was prepared using Lipoid® E80S and SDC in 1:4M concentration, respectively and lyophilized using 10% w/w 2-hydroxypropyl-ß-cyclodextrin (2-HPCD). The physical state of EXE in lyophilized formulation was confirmed by DSC and PXRD. Lyophilized formulation exhibits a significant increase in solubility and dissolution rate as compared to free drug EXE. Apparent permeability study was performed on Caco-2 cell line for 2h. The lyophilized EXE-PL/SDC-SDs exhibits 4.6-fold increase in absorptive transport as compared to EXE. Pharmacokinetic study in fasted female Sprague-Dawley rats revealed a 2.3-fold increase in AUC0-72h. Thus, the results suggest that PL/SDC-SDs is a promising carrier for EXE delivery.

Preoperative steroid use and the risk of infectious complications after neurosurgery.

BACKGROUND AND PURPOSE: The association between preoperative corticosteroid use and infectious complications after neurosurgical procedures is unclear. We aim to determine whether corticosteroids increase the risk of infectious complications after neurosurgery. METHODS: We examined the association between preoperative corticosteroid use and postoperative infectious complications in a cohort of adults who underwent a neurosurgical procedure between 2005 and 2010 at centers participating in the National Surgical Quality Improvement Program. Corticosteroid use was defined as at least 10 days of oral or parental therapy in the 30 days prior to surgery. Our primary outcome was a composite of any infectious complications occurring within 30 days of surgery. We used propensity score analysis to examine the independent association between preoperative corticosteroid use and postoperative infections. RESULTS: Among 26 634 neurosurgical procedures, 1228 (4.61%, 95% confidence interval [CI], 4.36-4.86) were preceded by preoperative corticosteroid use and 1469 (5.52%; 95% CI, 5.24-5.79) were followed by postoperative infections. In a propensity score analysis controlling for comorbidities, illness severity, and preexisting preoperative infections, corticosteroid use was independently associated with subsequent postoperative infections (odds ratio, 1.38; 95% CI, 1.11-1.70). Our results were unchanged in sensitivity analyses controlling for central nervous system tumors or active treatment with chemotherapy. CONCLUSION: Our results suggest that preoperative corticosteroid use is associated with an increased risk of infectious complications after neurosurgery. These findings may aid physicians with preoperative treatment decisions and risk stratification. Future randomized trials are needed to guide preoperative use of corticosteroids in this population.