Corrigendum to "Tanshinone-I for the treatment of uterine fibroids: Molecular docking, simulation, and density functional theory investigations" [Saudi Pharm. J. 31(6) (2023) 1061-1067].

[This corrects the article DOI: 10.1016/j.jsps.2023.05.002.].

Tanshinone-I for the treatment of uterine fibroids: Molecular docking, simulation, and density functional theory investigations.

Uterine fibroids (UF), most prevalent gynecological disorder, require surgery when symptomatic. It is estimated that between 25 and 35 percent of women wait until the symptoms have worsened like extended heavy menstrual bleeding and severe pelvic pain. These UF may be reduced in size through various methods such as medical or surgical intervention. Progesterone (prog) is a crucial hormone that restores the endometrium and controls uterine function. In the current study, 28 plant-based molecules are identified from previous literature and docked onto the prog receptors with 1E3K and 2OVH. Tanshinone-I has shown the best docking score against both proteins. The synthetic prog inhibitor Norethindrone Acetate is used as a standard to evaluate the docking outcomes. The best compound, tanshinone-I, was analyzed using molecular modeling and DFT. The RMSD for the 1E3K protein-ligand complex ranged from 0.10 to 0.42 Å, with an average of 0.21 Å and a standard deviation (SD) of 0.06, while the RMSD for the 2OVH protein-ligand complex ranged from 0.08 to 0.42 Å, with an average of 0.20 Å and a SD of 0.06 showing stable interaction. In principal component analysis, the observed eigen values of HPR-Tanshinone-I fluctuate between -1.11 to 1.48 and -1.07 to 1.25 for PC1 and PC2, respectively (1E3K), and the prog-tanshinone-I complex shows eigen values of -38.88 to -31.32 and -31.32 to 35.87 for PC1 and PC2, respectively (2OVH), which shows Tanshinone-I forms a stable protein-ligand complex with 1E3K in comparison to 2OVH. The Free Energy Landscape (FEL) analysis shows the Gibbs free energy in the range of 0 to 8 kJ/mol for Tanshinone-I with 1E3K and 0 to 14 kJ/mol for Tanshinone-I with the 2OVH complex. The DFT calculation reveals ΔE value of 2.8070 eV shows tanshinone-I as a stable compound. 1E3K modulates the prog pathway, it may have either an agonistic or antagonistic effect on hPRs. Tanshinone-I can cause ROS, apoptosis, autophagy (p62 accumulation), up-regulation of inositol requiring protein-1, enhancer-binding protein homologous protein, p-c-Jun N-terminal kinase (p-JNK), and suppression of MMPs. Bcl-2 expression can change LC3I to LC3II and cause apoptosis through Beclin-1 expression.

Novel archetype in cancer therapeutics: exploring prospective of phytonanocarriers.

This paper reports various types of cancer, their incidence, and prevalence all over the globe. Along with the discovery of novel natural drugs for cancer treatment, these present a promising option which are eco-friendly, safe, and provide better acceptability in comparison to synthetic agents that carries multiple side effects. This paper provides an idea about various nanocarriers and phytochemicals, along with how their solubility and bioavailability can be enhanced in nanocarrier system. This report combines the data from various literature available on public domain including PubMed on research articles, reviews, and along with report from various national and international sites. Specialized metabolites (polyphenols, alkaloids, and steroids etc) from medicinal plants are promising alternatives to existing drugs. Studies have suggested that the treatment of cancer using plant products could be an alternative and a safe option. Studies have shown with the several cell lines as well as animal models, that phytomolecules are important in preventing/treating cancer. Phytochemicals often outperform chemical treatments by modulating a diverse array of cellular signaling pathways, promoting cell cycle arrest, apoptosis activation, and metastatic suppression, among others. However, limited water solubility, bioavailability, and cell penetration limit their potential clinical manifestations. The development of plant extract loaded nanostructures, rendering improved specificity and efficacy at lower concentrations could prove effective. Nanocarriers, such as liposomes, nanostructured lipids, polymers, and metal nanoparticles, have been tested for the delivery of plant products with enhanced effects. Recent advances have achieved improvement in the the stability, solubility, bioavailability, circulation time, and target specificity by nanostructure-mediated delivery of phytochemicals. Nanoparticles have been considered and attempted as a novel, targeted, and safe option. Newer approaches such as phyto-nanocarriers with carbohydrates, lignin, and polymers have been considered even more selective and effective modes of drug delivery in biomedical or diagnostic applications.

Comparative study on eucalyptol and camphor rich essential oils from rhizomes of Hedychium spicatum Sm. and their pharmacological, antioxidant and antifungal activities.

The aim of present study was to evaluate chemical composition and different biological activities viz., pharmacological and antioxidant activities of essential oils. The chemical composition of essential oils was determined by gas chromatography/mass spectrometry while biological activities were evaluated by standard protocols. Essential oils of Hedychium spicatum Sm. from two different ecological niches viz; Nainital (Site-I) and Himachal Pradesh (Site-II) of India revealed the qualitative and quantitative chemo-diversity. Both the oils were dominated by oxygenated terpenoids. Major marker compounds identified were eucalyptol, camphor, linalool, α-eudesmol, 10-epi-γ-eudesmol, and iso-borneol. Both the oils exhibited anti-inflammatory activity suppressing 17.60 % to 33.57 % inflammation at 100mg/kg b. wt. dose levels compared to ibuprofen-treated group (40.06 %). The sub-acute inflammation in oils-treated mice groups (50 and 100 mg/kg b. wt.) increased on day 2 but showed a gradual decrease from day 3 onwards and then recovered to normal by day 10. The antinociception percentage for doses (50 and 100 mg/kg b. wt.) ranged from 33.70-40.46 % in Site-I and 30.34-42.39 % in Site-II compared to standard drug, ibuprofen (43.08 %). The oils also showed a good antipyretic effect by suppressing Brewer's yeast (Saccharomyces cerevisiae) induced pyrexia after oil dose injection. The oils also exhibited good antioxidant activity.

A Comparative Evaluation of Xylitol Chewing Gum and a Combination of IgY + Xylitol Chewable Tablet on Salivary Streptococcus mutans Count in Children: A Double-blind Randomized Controlled Trial.

Aim: The study was designed for evaluation and comparison of the efficacy of Xylitol chewing gum and a combination of IgY + Xylitol chewable tablet (Nodecay TM) against the "salivary Streptococcus mutans " count in children. Materials and methods: About 120 children belonging to 6-12 years age-group were enrolled into this "double-blind randomized control clinical trial" according to the selection criteria. They were randomly assigned to three groups of 40 each: Group I-Xylitol chewing gum, Group II-IgY + Xylitol Chewable tablet (Nodecay TM), and Group III-Control. Children in all the groups had to chew the gum/tablet twice daily for 5 minutes during the 15-day period. The salivary samples at baseline, 15 days, 1, 2, and 3 months were inoculated on mitis salivarius bacitracin agar with potassium tellurite medium and the number of colony-forming units (CFUs) of Streptococcus mutans were determined. The data obtained was subjected to statistical analysis. Result: There was a "significant" difference in the number of "S. mutans CFUs" amongst the three groups at 15 days, 1st month, 2nd month, 3rd month with highest levels of S. mutans CFUs in Group III-Control and least in Group II-IgY + Xylitol (NodecayTM). Conclusion: The combination of IgY + Xylitol (NodecayTM) when administered for 15 days had significant efficacy against "S. mutans" when compared to Xylitol and control group. Clinical significance: Passive immunization with immunoglobulin Y is known not only to decrease the S. mutans count but also confers extended immunity by preventing recolonization of the tooth surface by persistence of the antibodies in saliva. How to cite this article: Jain RL, Tandon S, Rai TS, et al. A Comparative Evaluation of Xylitol Chewing Gum and a Combination of IgY + Xylitol Chewable Tablet on Salivary Streptococcus mutans Count in Children: A Double-blind Randomized Controlled Trial. Int J Clin Pediatr Dent 2022;15(S-2):S212-S220.

Quantification and distribution of heavy metals from small-scale industrial areas of Kanpur city, India.

Kanpur city has large number of small-scale industries (SSIs), primarily comprising of textile and leather industries. This study inventorises the presence of heavy metals in the samples collected from Panki and Jajmau Industrial Areas of Kanpur city. The bulk concentration of heavy metals found in solid waste samples was Fe as 1885 and 2340 mg/kg, Mn 173 and 445 mg/kg, Zn 233 and 132 mg/kg, Cu 20 and 28 mg/kg, Cd 1.4 and 1.1mg/kg, Ni 26 and 397 mg/kg, Pb 107 and 19 mg/kg, Cr 1323 and 734 mg/kg, respectively. Heavy metal concentration was also found to be high in soil and road dust samples viz. Ni and Pb were in higher concentration in few samples, whereas Cr was found in higher concentration in all samples than the recommended values of USEPA and specifications for compost quality contained in the Indian Municipal Solid Wastes (Management and Handling) Rules, 2000. The heavy metal pollution so detected is indicative of contamination in ground and surface water and food chain. This raises concerns pertaining to adverse consequences to environment and human health.

Formulation optimization of double emulsification method for preparation of enzyme-loaded Eudragit S100 microspheres.

The present study aimed to develop an oral sustained release microparticulate system for acid labile enzyme-Serratiopeptidase. A 3(2) full factorial experiment was designed to study the effects of the external aqueous phase volume and stabilizer (Tween 80) concentration on the entrapment and size of Eudragit S100 microspheres prepared by a modified double emulsion solvent evaporation technique. The results of analysis of variance tests for both effects indicated that the test is significant. The effect of external aqueous phase volume was found to be higher on the entrapment efficiency of microspheres (SSY(1) = 1362.63; SSY(2) = 250.13), whereas Tween 80 produced a significant effect on size of microspheres (SSY(1) = 944.01; SSY(2) = 737.26). Scanning electron microscopy of microspheres demonstrated smooth surface spherical particles. The effect of formulation variables on the integrity of enzyme was confirmed by in vitro proteolytic activity. Microspheres having maximum drug encapsulation (81.32 ± 3.97) released 4-5% enzyme at pH 1.2 in 2 h. The release of enzyme from microspheres followed Higuchi kinetics (R(2) = 0.987). In phosphate buffer, microspheres showed an initial burst release of 25.65 ± 2.35% in 1 h with an additional 62.96 ± 4.09% release in the next 5 h. Thus, formulation optimization represents an economical approach for successful preparation of Eudragit S100 microspheres involving fewest numbers of experiments.

Lipid carriers: a versatile delivery vehicle for proteins and peptides.

Lipid based carriers have attracted increasing scientific and commercial attention during the last few years as an alternative material for the delivery of peptides and proteins concerned with stability issues. This article presents an overview of different types of biocompatible and versatile lipid-based carriers employed for the delivery of therapeutic proteins and peptides. Such delivery systems are discussed and exemplified regarding both more traditional lipid based delivery systems such as liposomes and lipid emulsions as well as more novel structures, e.g., lipid microtubules, microbubbles, and solid lipid nanoparticles.

Development and in vitro evaluation of alginate gel-encapsulated, chitosan-coated ceramic nanocores for oral delivery of enzyme.

The successful administration of protein and peptide drugs by oral route maintaining their active conformation remains a key challenge in the field of pharmaceutical technology. In the present study, we propose the use of a nanosize ceramic core-based system for effective oral delivery of acid-labile model enzyme, serratiopeptidase (STP). Ceramic core was prepared by colloidal precipitation and sonication of disodium hydrogen phosphate solution and calcium chloride solution at room temperature. The core was coated with chitosan under constant stirring and Fourier-Transform Infra Red Spectroscopy (FTIR) confirmed phosphoric groups of calcium phosphate linked with ammonium groups of chitosan in the nanoparticles; then the enzyme was adsorbed over the preformed nanocore. Protein-loaded nanocore was further encapsulated into alginate gel for enzyme protection. Prepared system was characterized for size, shape, loading efficiency, and in vitro release profile (pH 1.2 and pH 7.4). The effect of processing variables on the size of the core was evaluated to form small, uniform, and discrete nanocores. Stability and integrity of enzyme during processing steps was assessed by in vitro proteolytic activity. The prepared system was examined to be spherical in shape with diameter 925 +/- 6.81 nm using TEM. The in vitro release data followed the Higuchi model, showing a low amount (26% +/- 2.4%) of diffusion-controlled drug release (R(2) = 0.9429) in acidic buffer up to a period of 2 to 6 hours, signifying the integrity of alginate gel in acid. In the alkaline medium sustained and nearly complete first order release of protein was observed up to a 6 hours. It is inferred that the protein-loaded ceramic core acts as a reservoir of the adsorbed enzyme and alginate gel provides protection to STP for controlled release in intestinal pH when compared to the enzyme solution.

Methane emission and heavy metals quantification from selected landfill areas in India.

In this study, an attempt has been made to study methane flux and quantification of heavy metals from Municipal Solid Waste (MSW) landfill areas of selected cities in India. During the period of study, the average value of methane flux was estimated from these landfill areas varied from 146-454 mg/m2/h. Methane emission from landfill is of serious environmental global concern as it accounts for approximately 15 percentages of current Greenhouse gas emissions. It has been estimated that methane emission, from landfill areas in the world, in next two decades would be same as that what is emitted from paddy fields presently. Besides, the estimation of methane flux, quantification of some heavy metals was conducted to analyse the suitability of using MSW as compost. The average values for metals were observed to be both within the range of USEPA and Indian standards for MSW disposal in landfill areas and to be used as compost respectively.

Influence of selected formulation variables on the preparation of enzyme-entrapped Eudragit S100 microspheres.

The aim of this work is to study the influence of formulation parameters in the preparation of sustained release enzyme-loaded Eudragit S100 microspheres by emulsion solvent diffusion technique. A 3(2) full factorial experiment was designed to study the effects of the amount of solvent (dichloromethane) and stabilizers (Tween 20, 40, or 80) on the drug content and microsphere size. The results of analysis of variance test for both effects indicated that the test is significant. The effect of amount of stabilizer was found to be higher on both responses (SS(Y1) = 45.60; SS(Y2) = 737.93), whereas solvent concentration comparatively produced significant effect on the size of microspheres (SS(Y1) = 0.81; SS(Y2) = 358.83). Scanning electron microscopy of microspheres with maximum drug content (2.5 mL dichloromethane and 0.1 mL Tween 80) demonstrated smooth surface spherical particles with mean diameter of 56.83 +/- 2.88 microm. The effect of formulation variables on the integrity of enzyme was confirmed by in vitro proteolytic activity. The enteric nature of microspheres was evaluated and results demonstrated ~6% to 7% release of enzyme in acidic medium. The release of enzyme from microspheres followed Higuchi kinetics. In phosphate buffer, microspheres showed an initial burst release of 20.34% +/- 2.35% in 1 hour with additional 58.79% +/- 4.32% release in the next 5 hours. Three dimensional response graphs were presented to visualize the effect of independent variables on the chosen response. Thus, Eudragit S100 microspheres can be successfully prepared for oral delivery of enzymes with desirable characters in terms of maximum loading and diffusion release pattern.

Nanocarriers: promising vehicle for bioactive drugs.

Development of new delivery systems that deliver the potential drug specifically to the target site in order to meet the therapeutic needs of the patients at the required time and level remains the key challenge in the field of pharmaceutical biotechnology. Developments in this context to achieve desired goal has led to the evolution of the multidisciplinary field nanobiotechnology which involves the combination of two most promising technologies of 21st century--biotechnology and nanotechnology. Nanobiotechnology encompasses a wide array of different techniques to improve the delivery of biotech drugs, and nanoparticles offer the most suitable form whose properties can be tailored by chemical methods. This review highlights the different types of nanoparticulate delivery systems employed for biotech drugs in the field of molecular medicine with a short overlook at its applications and the probable associated drawbacks.

Inventory compilation and distribution of heavy metals in wastewater from small-scale industrial areas of Delhi, India.

Delhi has the highest cluster of small-scale industries (SSI) in India. There are generally less stringent rules for the treatment of waste in SSI due to less waste generation within each individual industry. This results in SSI disposing of their wastewater untreated into drains and subsequently into the river Yamuna, which is a major source of potable water in Delhi, thus posing a potential health and environmental risk to the people living in Delhi and downstream. To study the quantity, quality and distribution of heavy metals in liquid waste from industrial areas, wastewater, suspended materials and bed sediments were collected from industrial areas and from the river Yamuna in Delhi. This study has also focused on the efficiency of production processes in small-scale industries in India. Heavy metals such as Fe, Mn, Cu, Zn, Ni, Cr, Cd, Co and Pb were detected using a GBC 902 atomic absorption spectrometer. The concentration of heavy metals observed was as follows: Fe 2-212, Mn 0.3-39, Cu 0.2-20, Zn 0.2-5, Ni 0.6-6, Cr 0.2-53, Cd 0.08-0.2, Co 0.013-0.55, Pb 0.3-0.7 mg L(-1) in wastewater; Fe 5842-78 000, Mn 585-10 889, Cu 206-7201, Zn 406-9000, Ni 22-3621, Cr 178-10 533, Co 17-114, Cd 13-141, Pb 67-50 171 mg kg(-1) in suspended material; and Fe 3000-84000, Mn 479-1230, Cu 378-8127, Zn 647-4010, Ni 164-1582, Cr 139-3281, Co 20-54, Cd 37-65, Pb 228-293 mg kg(-1) in bed residues. This indicates that SSI could be one of the point sources of metals pollution in the river system.