Mutagenicity and safety evaluation of Ashwagandha (Withania somnifera) root aqueous extract in different models.

Withania somnifera (Ashwagandha) also called as Indian ginseng, a revered herb from Indian traditional system of medicine is a rejuvenator and tonic (Rasayana) used for its varied benefits. The roots of ashwagandha exhibit properties like anti-inflammatory, aphrodisiac, anthelmintic, astringent, diuretic, stimulant and thermogenic. However, data of ashwagandha on its mutagenic effects are lacking. In the present study, in-vitro genotoxicity tests were used to evaluate the mutagenic potential of Ashwagandha Root Extract (ARE). Concentrations of 0.156 to 5.00 mg/plate ARE were used for conducting Bacterial reverse mutation test (BRMT). For chromosome aberration (CA) test ARE was used in concentrations of 0.25 to 2.00 mg/ml, and for micronucleus (MN) tests ARE concentrations of 500/1000/2000 mg/kg were used. Acute oral toxicity was conducted in Wistar rats (n = 25) as per the OECD guideline (#423) with doses of 500/1000/2000 mg/kg body weight in male Swiss albino mice for morbidity and mortality for 3 days. The BRMT and CA tests were conducted with and without metabolic activation (S9). The study was approved by the institutional ethics committee (IEC) and institutional animal ethics committee (IAEC). ARE failed to show any mutagenic effects up to a dose of 5 mg/plate in BRMT. Also, ARE did not show any clastogenic activity in doses up to 2 mg/ml in CA test and in micronucleus test up to 2000 mg/kg body weight. These results were observed with and without metabolic activation (S9) under the stated experimental conditions. No mortality, morbidity, or any clinical signs were observed up to 3 days following ARE administration. Ashwagandha root extract failed to show any mortality in doses up to 2000 mg/kg oral dosage and did not show any mutagenic (genotoxic) effects in high concentrations.

An insight into the cytotoxic, antimicrobial, antioxidant, and biocontrol perspective of novel Iron(III) complexes of substituted benzimidazoles: Inhibition kinetics and molecular simulations.

Mononuclear complexes [FeCl3L2(OH2)] (L = L1, L2) were designed and synthesized by combining FeCl3 with 2-(3'-Aminophenylbenzimidazole) (L1) and 2-[(3'-N-Salicylidinephenyl)benzimidazole] (L2) and were characterized by physico-analytical strategies. The redox properties of the complexes were disclosed by the cyclic voltammetric method. Further, the interactions of complexes with proteins were studied by performing molecular docking engaging protein models of common cancer therapeutic targets to foresee their affinity to bind to these proteins. The complexes evidenced better protein-ligand docking (-8.4 and -9.0 kcal mol-1) and higher binding energies than their ligands. However, the L1 complex displayed improved binding free energy (-33.576 ± 1.01 kcal mol-1) compared to the other complexes and individual ligands. These compounds were screened for in vitro cytotoxic assays against triple-negative breast cancer cell lines (MDA-MB-468 cells), anti-inflammatory, antimicrobial, and antioxidant properties. The in vitro study complemented the in silico assay; therefore, these compounds may be a viable choice for expanding anticancer therapy. Additionally, the L2 showed better biocontrol activity owing to the enhanced growth of Trichoderma and inhibited the growth of Fusarium oxysporum.Communicated by Ramaswamy H. Sarma.

Nanohydroxyapatite in dentistry: A comprehensive review.

Enamel, being the hardest and the highest mineralized tissue of the human body, contains nearly 96% inorganic components and 4% organic compounds and water. Dentin contains 65% inorganic components and 35% organic and water content. The translucency and white appearance of enamel are attributed to Hydroxyapatite (HA), which constitutes the major part of the inorganic component of dental hard tissue. With the advent of nanotechnology, the application of Nanohydroxyapatite (nHA) has piqued interest in dentistry due to its excellent mechanical, physical, and chemical properties. Compared to HA, nHA is found to have superior properties such as increased solubility, high surface energy and better biocompatibility. This is due to the morphological and structural similarity of nanosized hydroxyapatite particles to tooth hydroxyapatite crystals. These nanoparticles have been incorporated into various dental formulations for different applications to ensure comprehensive oral healthcare. To prevent dental caries, several nHA based dentifrices, mouth rinsing solutions and remineralizing pastes have been developed. nHA-based materials, such as nanocomposites, nano impression materials, and nanoceramics, have proven to be very effective in restoring tooth deformities (decay, fracture, and tooth loss). The nHA coating on the surface of the dental implant helps it bind to the bone by forming a biomimetic coating. A recent innovative strategy involves using nHA to reduce dentinal hypersensitivity and to reconstruct periodontal bone defects. The purpose of the present review is to discuss the different applications of nHA in dentistry, especially in preventive and restorative dentistry, dental implantology, bleaching and dentine hypersensitivity management.

Ninety-day repeated dose toxicity of Ashwagandha (Withania somnifera) root extract in Wistar rats.

Many pharmacological studies have been carried out to describe multiple biological properties of Ashwagandha (Withania somnifera) and the additional safety information on repeated dose toxicity is limited. Therefore, the aim of this study was to obtain safety data for KSM-66 Ashwagandha Root Extract (ARE) through repeated-dose toxicity in Wistar rats according to the Organisation for Economic Co-operation and Development (OECD) test guideline (TG 408). ARE was orally administered to rats at doses of 0, 500, 1000, and 2000 mg/kg body weight/day for 90-day and reversibility of effects of 0 and 2000 mg/kg body weight/day was assessed for 14 days. All the animals from treated, control, recovery control and recovery groups were observed for clinical signs of toxicity once daily, detailed clinical examination every week after dosing and before necropsy day. Mortality/Morbidity was observed twice daily. In addition, observations were noted in the detailed sensory reactivity, functional assessments, body weight, food consumption, ophthalmological examination, hematological parameters, biochemical parameters, organ weights, histopathological findings. The present results show that the no observed adverse effect level (NOAEL) of KSM-66 Ashwagandha Root Extract was considered to be 2000 mg/kg body weight/day in rats after repeated oral administration for 90-day under the present study conditions.

Molecular pathways of oral submucous fibrosis and its progression to malignancy.

OBJECTIVE: The review aims to comprehend various factors engaged in the alteration of molecular events resulting in Oral submucous fibrosis (OSMF) and its malignant transformation. DESIGN: Literature pertinent to pathways involved in OSMF were explored in databases such as PubMed, Scopus and Google Scholar. The relevant literature was reviewed and critically appraised in this narrative review. RESULTS: Areca nut components influence myriad of cellular molecules such as cytokines, growth factors, myofibroblasts, non-coding RNAs and alter their expression. These aberrantly expressed molecules drive the progression of OSMF from localized inflammation to fibrosis of buccal mucosa. The oral tissue suffers from oxidative stress, hypoxia, autophagy, aberration of cell cycle and DNA damage. Apoptosis of epithelial layer results in its atrophy facilitating deeper penetration of areca nut elements. With the advance of disease, epithelial-mesenchymal transition eventuates and promotes dysplasia. The jeopardized expression of various cellular molecules, suppressed apoptosis, along with increased genetic alterations and neovascularization favors the malignant transformation. CONCLUSION: OSMF is a progressive disorder with complex mechanism of pathogenesis initiated by inflammation of oral mucosa. Continuous habit of areca nut chewing and the resulting insult to the tissues prevents healing process and is destined to debilitating disease which affects the quality of life with a higher probability of progression to malignancy.

Interfacial interaction driven enhancement in the colossal magnetoresistance property of ultra-thin heterostructure of Pr0.6Sr0.4MnO3 in proximity with Pr0.5Ca0.5MnO3.

The ultra-thin heterostructure of Pr0.6Sr0.4MnO3(15 nm)/Pr0.5Ca0.5MnO3(15 nm)/SrTiO3 fabricated using pulsed laser deposition technique exhibits the phase-segregated nature wherein the ferromagnetism of Pr0.6Sr0.4MnO3, and the antiferromagnetic state of Pr0.5Ca0.5MnO3 coexist in proximity. The observation of two exciting phenomena in the grown ultra-thin heterostructure, namely, the kinetic arrest and training effect, confirms its phase-segregated nature. The melting of the antiferromagnetic state in Pr0.5Ca0.5MnO3 into a ferromagnetic state due to the interfacial interaction arising from the magnetic proximity of the ferromagnetic clusters of Pr0.6Sr0.4MnO3 have been observed. A metal-insulator transition (TMIT) found at 215 K, close to its Curie temperature (TCurie) observed at 230 K, reveals a strong correlation between the electrical transport and the magnetization of the ultra-thin heterostructure. The electrical conduction in the high-temperature regime is explained in terms of the adiabatic small polaron hopping model. While the resistance in the metallic regime for temperatures above 100 K is contributed by the inelastic scattering due to the two-magnons, in the metallic regime below 100 K, the one-magnon inelastic scattering contribution is prevalent. An enhanced colossal magnetoresistance property near room temperature is obtained in the ultra-thin heterostructure arising from the proximity-driven interfacial interaction, making it a suitable candidate for technological applications near room temperature.

Glycosylated Fibronectin Point-of-care Test for Triage and Surveillance of Hypertension in Pregnancy Cases: A Retrospective Observational Case Control Study.

Purpose of the Study: To evaluate the usefulness of glycosylated fibronectin (GlyFn) as point-of-care (POC) test for triaging and managing hypertension cases in pregnancy. Materials and Methods: It is a retrospective case control study done in 51 cases of hypertension (HTN) and pre-eclampsia (PE) where patients with GlyFn levels more than 350 µg/ml were included in the study group and GlyFn less than 350 µg/ml were included in the control group. Maternal and fetal outcomes were evaluated and compared. Results: Maternal and fetal morbidity leading to delivery within 10 days of testing (p value-0.0035, 95% CI 4.05 to 19.13) and worsening of Dopplers (p value-0.0031) is significantly high in study group. Gestational age (Mean 35 weeks vs. 32 weeks, p value of 0.0008, 95% CI 1.31-4.65) and birth weight (Mean 2.2 kg vs. 1.48 kg, p value 0.0009 95% CI 0.32 to 1.16) are significantly less in the study group despite there is no difference in the gestational age at testing (Mean 32.25 weeks vs. 30.9 weeks, p value 0.203, 95% CI - 0.75 to 3.42). Abnormal PE laboratory parameters (PE profile) are seen only in the study group and none in the control group (p value 0.015). Conclusion: Our results demonstrate that in pregnant women with hypertension, glycosylated fibronectin is useful for predicting maternal and fetal morbidity occurring within 10 days of testing. In low-resource settings, it will be a useful cost-effective tool for appropriate triage and improved outcomes.

Zinc Oxide Nanoparticles: A Review on Its Applications in Dentistry.

Nanotechnology in modern material science is a research hot spot due to its ability to provide novel applications in the field of dentistry. Zinc Oxide Nanoparticles (ZnO NPs) are metal oxide nanoparticles that open new opportunities for biomedical applications that range from diagnosis to treatment. The domains of these nanoparticles are wide and diverse and include the effects brought about due to the anti-microbial, regenerative, and mechanical properties. The applications include enhancing the anti-bacterial properties of existing restorative materials, as an anti-sensitivity agent in toothpastes, as an anti-microbial and anti-fungal agent against pathogenic oral microflora, as a dental implant coating, to improve the anti-fungal effect of denture bases in rehabilitative dentistry, remineralizing cervical dentinal lesions, increasing the stability of local drug delivery agents and other applications.

Influence of multi valent states of vanadium ions in ZnO doped novel calcium fluoro phosphate bio glasses.

ZnO-CaF2-P2O5 glasses doped with different concentrations of V2O5 (ranging from 0 to 1.0 mol %) were prepared. The prepared bio glasses are soaked in SBF for duration of 2, 3, 7 and 10 days in separate plastic containers and then kept in incubator maintained at body temperature 36.5 °C. The influence of valence states of vanadium ions (V4+/V5+) with respect to the structural aspects by means of FTIR and Raman Spectra, elastic properties by means of relevant parameters, the thermal stability by means of DTA studies and other spectroscopic properties by using OA and ESR studies are studied. The raise in wavenumber and comparative areas of the two absorption bands corresponding to electronic transitions 2B2g → E2g, 2B2g → 2B1g respectively in optical absorption spectra of these CZPV glasses clearly indicate that vanadium ions have octahedral co-ordination with tetragonal compression due to modifier action of V2O5in the glass network. The optical absorption and ESR studies have revealed that vanadium ions exist in V4+ states. The characteristic temperatures of these prepared glasses obtained from DTA curves explain modifications taking place in the structure of glass network. The structural changes are explained with the aid of FTIR and Raman studies. The bio active nature of the titled glasses is evident from dissociation and pH studies by SEM &EDS of these glasses before and after immersion into SBF.

Drivers of human-megaherbivore interactions in the Eastern and Western Ghats of southern India.

The global effort to protect megaherbivore populations is largely dependent on how human-wildlife conflict is identified, prioritized, and remedied. We examined the socio-ecological and landscape-scale factors determining spatial patterns of human-megaherbivore (Asian elephant Elephas maximus and gaur Bos gaurus) interactions across sixteen Forest Divisions in Tamil Nadu, India. Using a systematic grid-based design, we conducted questionnaire-based surveys of 1460 households at the human-wildlife interface adjacent to Protected Areas, Reserve Forest and Fringe Areas. We specifically collected information on elephant and gaur conflict incidents (e.g., human death/injuries, property damage, and crop-raiding), cropland type, extent of crop area and area lost to crop-raiding, from each household. We found that human-elephant conflict increased with percentage of crop cover, diversity of major and minor crops grown, proximity to water source, flat terrain, and lower rates of precipitation. Human-gaur conflict was greatest with a high diversity of major crops, proximity to water source, moderate precipitation, and more undulating terrain. We identified ca. 7900 km2 hotspot area of contiguous high-intensity elephant conflict. For gaur, we identified high-frequency conflict hotspot areas covering ca. 625 km2, which were patchily distributed, highly localised, and attributed mostly to the recent changing land-use patterns. Our findings will help policymakers and park managers in developing landscape-scale human-wildlife conflict mitigation plans in the identified conflict hotspots.

Molecular docking analysis of long-chain alkanes with the ß-lactamase BEL-1 from P. aeruginosa.

Pseudomonas aeruginosa is a gram-negative opportunistic bacterium that is a concern worldwide due to its innate antibiotic resistance properties. This warrants the development of non-antibiotic compounds that can potentially address the growing concern. Therefore, it is of interest to document the molecular docking analysis data of three long-chain alkanes, namely, eicosane, triacontane, and nonadecane with ß-lactamase BEL-1. Data shows that nonadecane have good binding features and drug-likeness when compared to triacontane and nonadecane. It is well known that nonadecane is a compound that is abundantly available from natural resources for further consideration.

Platelet-rich fibrin and collagen matrix for the regeneration of infected necrotic immature teeth.

Revitalization of an immature necrotic tooth is possible under conditions of total canal disinfection. This case report describes an immature tooth #21 with periapical pathology which was treated through revascularization using 3% sodium hypochlorite and 17% ethylenediaminetetraacetic acid as irrigants; calcium hydroxide was placed as an intracanal medicament, platelet-rich fibrin as a scaffold, and collagen matrix was placed as a barrier. On follow-up at 2 years, healing of periapical lesion, apical closure could be appreciated. Based on the results, we conclude that regeneration of necrotic tooth is possible under efficient disinfection. RELEVANCE FOR PATIENTS: This article documents the 2-year outcome of regenerative endodontic treatment in necrotic immature teeth. The successful outcome of this case shows that regenerative endodontic teeth can be a viable treatment option in immature teeth.

Assessment of Heavy Metals Pollution in Noyyal and Chinnar Rivers, Western Ghats of Tamil Nadu, India with Reference to Crabs (Gecarcinucidae)-A Baseline Study.

In the present study, heavy metals (Cd, Cu, Pb, and Zn) level in the water, sediment, and crabs were analyzed from Noyyal and Chinnar Rivers of the Western Ghats in Tamil Nadu, India. Based on our results, Noyyal River is considered as polluted environment due to the discharge of contaminants by various anthropogenic activities, whereas, Chinnar River maintained as unpolluted one due to its tributary nature of Noyyal River located in Western Ghats hills. The results showed that the heavy metals in water and sediments were higher in Noyyal River. Also, the level of bioaccumulation of studied metals and biochemical constituents were higher in the crab Spiralothelphusa hydrodroma sampled from Noyyal River than Barytelphusa cunicularis collected from Chinnar River. The present findings revealed that the crab sampled from Noyyal River had elevated heavy metals which lead to a significant increase in biochemical constituents to overcome the stress.

Bioaccumulation of heavy metals, antioxidants, and metabolic enzymes in the crab Scylla serrata from different regions of Tuticorin, Southeast Coast of India.

The present study was performed to analyze the bioaccumulation of heavy metals, biochemical constituents, antioxidants, and metabolic enzymes in the crab Scylla serrata from different regions of Tuticorin, Southeast Coast of India. The study area consists of Threspuram and Harbour Beach which were polluted environments due to the discharge of industrial effluents and domestic sewage into them. Punnakayal, which is a low-polluted environment where the in-situ culture of S. serrata is carried out by local fish farmers, was selected as well. The results revealed that the level of heavy metals, biochemical constituents, antioxidants, and metabolic enzymes were significantly high in the crabs collected from Threspuram and Harbour Beach compared to the crabs collected from Punnakayal. This study indicates that crabs from polluted environments have significant heavy metals bioaccumulation which leads to elevated antioxidants and metabolic enzyme levels. This implies that the crabs are under oxidative and metabolic stress.

Hierarchical Black Hole Mergers in Active Galactic Nuclei.

The origins of the stellar-mass black hole mergers discovered by LIGO/Virgo are still unknown. Here we show that if migration traps develop in the accretion disks of active galactic nuclei (AGNs) and promote the mergers of their captive black holes, the majority of black holes within disks will undergo hierarchical mergers-with one of the black holes being the remnant of a previous merger. 40% of AGN-assisted mergers detected by LIGO/Virgo will include a black hole with mass ≳50M_{⊙}, the mass limit from stellar core collapse. Hierarchical mergers at traps in AGNs will exhibit black hole spins (anti)aligned with the binary's orbital axis, a distinct property from other hierarchical channels. Our results suggest, although not definitively (with odds ratio of ∼1), that LIGO's heaviest merger so far, GW170729, could have originated from this channel.

Utilization of marine fisheries wastes for the production of the freshwater fish Cyprinus carpio.

The present study was aimed to assess the effects of complete replacement of fish meal with fisheries waste meals on survival, growth performance, digestive enzyme activities, and muscle compositions of the freshwater fish Cyprinus carpio. The proximate composition and mineral contents of three different fisheries wastes, such as Rastrelliger kanagurta, Sphyraena barracuda, and Fenneropenaeus indicus were analyzed. Based on the nutrient content of these fisheries waste, one control fish meal diet and three different complete fish meal replacement diets (diet 1, diet 2, and diet 3 formulated with R. kanagurta, S. barracuda, and F. indicus waste meals, respectively) were formulated. Fingerlings C. carpio were fed with these diets for a period of 6 weeks. Results from feeding experiments showed insignificant (p > 0.05) differences in survival, growth, and feed intake of C. carpio fed with control and three different fisheries waste diets. However, the digestive enzyme activity and muscle biochemical compositions were significantly (p < 0.05) altered in F. indicus waste meal fed C. carpio compared to other fisheries waste meal and control diets fed fish groups. Therefore, the present study suggests that R. kanagurta, S. barracuda, and F. indicus waste meals can be considered as alternative feed ingredients for fish meal to formulate low-cost feeds for C. carpio culture.

Antiurolithiatic Effect of Sirupeelai Samoola Kudineer: A Polyherbal Siddha Decoction on Ethylene Glycol-induced Renal Calculus in Experimental Rats.

BACKGROUND: Sirupeelai Samoola Kudineer (SK), a polyherbal decoction containing four medicinal plants has been used in Siddha system of medicine, practiced in Southern parts of India for the management of urolithiasis. OBJECTIVE: The present study is carried out to scientifically validate the traditional claim and to study the mechanism of action of the drug. MATERIALS AND METHODS: In the present study, anti-urolithiatic effect of SK was evaluated in Sprague-Dawley rats using ethylene glycol through drinking water and intraperitoneal injection of sodium oxalate. Renal damage was confirmed by the increased production of thiobarbituric acid reactive substance (TBARS). RESULTS: Co-treatment with SK to urolithiatic rats for 21 days significantly prevented the elevation of renal and urinary stone biomarkers in plasma and renal tissue thereby preventing renal damage and the formation of renal calculi. Administration of SK at all doses and cystone restored the antioxidant (glutathione) levels by preventing the elevation of TBARS in the kidney tissue, which was further confirmed by histological sections. CONCLUSIONS: SK treatment promotes diuresis which leads to flushing of the renal stones and maintains the alkaline environment in the urinary system which probably mediates the antilithiatic activity. SK provides structural and functional protection to the kidneys by enhancing its physiological function against stone formation and validates its clinical use. SUMMARY: SK exhibited antilithiatic and diuretic potential in ethylene glycol and sodium oxalate induced urolithiasis in ratsElevated urinary stone markers (Calcium, oxalate, uric acid, magnesium and phosphates) in plasma and renal tubular enzymes (LDH, GGT, ALP, AST ALT) in urolithiatic rats were reversed by SK treatmentSK administration significantly reduced the level of renal stress markers like Urea, Creatinine, LPO and elevated SOD, GPx, GSH levels aiding in nephroprotectionSK also provides structural and functional protection against ethylene glycol- induced renal calculus in rats as evidenced by histopathological studies. Abbreviations used: SK: Sirupeelai Samoola Kudineer; TBARS: ThioBarbituric Acid Reactive Substances; SOD: SuperOxide Dismutase; GPx: Gluthathione peroxidase; GSH- Glutathione; LPO: Lipid peroxidation as measured as TBARS; AST: Aspartate AminoTransferase; ALT: Alanine Amino transferase; GGT: Gamma Glutamyl Transferase; LDH: Lactate Dehydrogenase.

Anti-arthritic potential of marine macroalgae Turbinaria ornata in Complete Freund's Adjuvant induced rats.

T. ornata a macroalgae rich in bioactive molecules possess various biological activities. Herein, the aim of the study is to evaluate the aqueous extract and the sulphated polysaccharide isolated from T. ornata for its anti-arthritic potential in Complete Freund's Adjuvant (CFA) induced arthritis in rats. Anti-arthritic potential of aqueous T. ornata (ATO) and T. ornata sulphated polysaccharide (TSP) was evidenced by the significant reduction in paw volume and arthritic score. Inflammatory and antioxidant markers were found to be restored in the drug treated groups which was found to be in line with dexamethasone a standard anti-inflammatory drug. The histopathological and radiological examination adds on the support to the above findings confirming the anti-arthritic potential of ATO and TSP. It is interesting to note that the sulphated polysaccharide inhibits inflammation and bone damage at very low dose itself. Hence, TSP could be considered as a better candidate in the management of chronic inflammatory diseases like rheumatoid arthritis.

A study for the development of K-sound based automatic blood pressure device using PVDF film.

Traditional indirect standard measurement of blood pressure is based on hearing Korotkoff sounds to determine systolic and diastolic blood pressure. However, the problem exists among different types of automatic blood pressure monitoring devices because of no standard algorithm for estimating accurate blood pressure values. Aim of the study was to develop an automatic blood pressure measurement device based on Korotkoff sounds. PVDF(poliyvinylidene fluoride) film was used as a contact microphone to detect Korotkoff sounds on the brachial artery, and pressure sensor was used to obtain cuff pressure. With those two variables, an algorithm to determine systolic and diastolic blood pressure was established. Correlation coefficients between auscultatory method and developed device were 0.977 and 0.968 for systolic and diastolic, respectively. Validation results based on the international protocol shows 95% and 91.6% of accuracies.