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Abstract Background 6-Gingerol (6-G) is the primary active phytocomponent of ginger and has been shown to regulate multiple targets against cancer and its treatment. Androgen receptors (ARs) remain critical in the progression of prostate cancer (PCa). This study focuses on investigating 6-G as a promising anti-cancerous agent that inhibits AR activity significantly. Methods In this study, molecular docking simulation was done to investigate the binding affinity of 6-G and control drug Bicalutamide (BT) against oncogenic AR and tumor suppressor estrogen receptor β (ERβ). The crystal structure of AR and ERβ was retrieved from Protein Data Bank (PDB) and docked with 3D Pubchem structures of 6-G using iGEMDOCK and AutoDock. Further in vitro study was done to evaluate the antioxidant, anti-cancerous, apoptotic, and wound healing potential of 6-G. Results The result displays that 6-G shows good binding affinity with AR and ERβ. Condensation of the nucleus, change in mitochondrial membrane potential (MMP) and the ability to induce reactive oxygen species (ROS) were done in human PCa PC-3 cells. Results from the MTT assay demonstrated that 6-G and control drug BT showed significant (p

In the original publication [...]

Introduction: Moringa oleifera is known as a ‘natural nutrition of the tropics’ because it provides vital nutritional supplements and a variety of pharmacological benefits. The focus of this study was to elucidate the dose dependent effects of Moringa oleifera leaf (MOL) extract on the growth of the human osteoblast-like osteosarcoma SaOS-2 cell line and primary osteoblast cells. Methods: Trypan blue & tetrazolium assay, intracellular ROS generation, chromatin condensation, cell cycle analysis, alkaline phosphatase (ALP), mineralization, and osteogenic gene expression were tested on both treated and untreated osteosarcoma SaOS-2 cells. Results: As revealed by cell viability assay, growth activity was observed at concentrations 25 and 50 μg/mL of MOL extract, whereas 100 and 200 μg/mL doses decreased the proliferation activity, resulting in ROS production and chromatin condensation. Cell cycle study revealed that MOL extract at 50 and 100 μg/mL concentrations arrested the cells in the G2/M phase. Low doses increased the ALP levels, mineralization, and expression of the bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (Runx2) genes in osteoblast-like SaOS-2 cells, however, high doses inhibited the proliferation properties of MOL extract. Through AutoDock Vina and iGEMDOCK 2.1, the interaction of active components of MOL, such as β-sitosterol, quercetin and kaempferol, with BMP2 and Runx2 proteins revealed a reasonable binding affinity. Moreover, these components did not show any Lipinski's rule of five violation and showed predictable pharmacokinetic properties. Conclusion: The results of the biphasic dose-response of MOL extract on the growth activity of osteoblast-like SaOS-2 cells and in silico binding interface, may provide a therapeutic and/or preventive implication in prospective drug development.

Background: Tropical pulmonary eosinophilia (TPE) is a type of eosinophilic lung disease, and it is associated with a hypersensitivity response to Wuchereria bancrofti and Brugia malayi's microfilariae. Any systemic data regarding its clinical, demographic, and radiological profile in patients of this part of the world are sparse. This study aimed to study the clinical and demographic profile of TPE patients in this geographical area. Materials and Methods: This is a prospective observational study done over 1 year period in patients with TPE-like features in a tertiary care center of Bihar. After appropriate clinical and blood examination, absolute eosinophil count (AEC), serum total immunoglobulin E (IgE), spirometry, filarial antigen, and filarial antibody and chest radiology were done. Results: Among 77 cases of TPE, 54 were male (70.1%) and 23 were female (29.9%), in a ratio of 2.35:1. The majority of cases 43 (55.9%) were found in age less than 30 years. Most of our participants were students 28 (36.4%), homemakers 19 (24.7%), and farmers 17 (22.1%). The most common clinical feature was cough 77 (100%). Filarial antibody was raised in all (100%) while antigen was positive in 96.1%. Chest radiology was normal in 71.4%. Mean AEC and IgE ± standard deviation were 6730.71 + 4671.12 and 7983.14 ± 7279.60 kU/L, respectively. Spirometric findings were mild restriction 25 (32.5%). Conclusion: The prevalence of TPE is supposed to be higher in endemic areas. The patient should be evaluated in detail if having raised eosinophil count (>3000/mm3) with increased IgE level (>1000 kU/L) along with suggestive clinical features. Timely diagnosis and treatment can cure the disease and prevent its complications.

Although, zinc oxide nanoparticles (ZRTs) as an anti-cancer agent have been the subject of numerous studies, none of the reports has investigated the impact of the reaction entry time of ion-carriers on the preparation of ZRTs. Therefore, we synthesized variants of ZRTs by extending the entry time of NaOH (that acts as a carrier of hydroxyl ions) in the reaction mixture. The anti-proliferative action, morphological changes, reactive oxygen species (ROS) production, and nuclear apoptosis of ZRTs on human A431 skin carcinoma cells were observed. The samples revealed crystallinity and purity by X-ray diffraction (XRD). Scanning electron microscopy (SEM) images of ZRT-1 (5 min ion carrier entry) and ZRT-2 (10 min ion carrier entry) revealed microtubule like morphology. On prolonging the entry time for ion carrier (NaOH) introduction in the reaction mixture, a relative ascent in the aspect ratio was seen. The typical ZnO band with a slight shift in the absorption maxima was evident with UV-visible spectroscopy. Both ZRT-1 and ZRT-2 exhibited non-toxic behavior as evident by RBC lysis assay. Additionally, ZRT-2 showed better anti-cancer potential against A431 cells as seen by MTT assay, ROS generation and chromatin condensation analyses. At 25 μM of ZRT-2, 5.56% cells were viable in MTT test, ROS production was enhanced to 166.71%, while 33.0% of apoptotic cells were observed. The IC50 for ZRT-2 was slightly lower (6 μM) than that for ZRT-1 (8 μM) against A431 cells. In conclusion, this paper presents a modest, economical procedure to generate ZRT nano-structures exhibiting strong cytotoxicity against the A431 cell line, indicating that ZRTs may have application in combating cancer.

Let A be a unital ∗-algebra over the complex fields C. For any H1,H2∈A, a product [H1,H2]•=H1H2−H2H1* is called the skew Lie product. In this article, it is shown that if a map ξ : A→A (not necessarily linear) satisfies ξ(Pn(H1,H2,…,Hn))=∑i=1nPn(H1,…,Hi−1,ξ(Hi),Hi+1,…,Hn)(n≥3) for all H1,H2,…,Hn∈A, then ξ is additive. Moreover, if ξ(ie2) is self-adjoint, then ξ is ∗-derivation. As applications, we apply our main result to some special classes of unital ∗-algebras such as prime ∗-algebra, standard operator algebra, factor von Neumann algebra, and von Neumann algebra with no central summands of type I1.

Stress-related neuropsychiatric disorders affect nearly all people worldwide irrespective of the age and sex of the person. Females are supposed to experience a higher stress and anxiety as compared to the male individuals. The role of serotonin receptor in stress and anxiety condition is supposed to affect this sex-based difference in stress and anxiety condition between male and female animals. Serotonin receptor system is one of the most important molecular mechanism in brain function involved in a number of vital functions such as apetite, sleep, thermoregulation, aggression, learning, mood, cognition as well as in stress and anxiety. The current preclinical study is analyzing the role of serotonin 5HT-5A and 5B receptor in stress and anxiety in male and female rodents. The study suggests here a differential region specific association of both the serotonin receptor under stressful condition between male and female animals.

Abstract Background The present study was designed to examine the role of isoflavone genistein (GS) on bone formation, regulating oxidative stress and cell cycle in primary osteoblasts, as well as attenuation of osteoclast formation. Methods Primary calvaria osteoblasts were isolated from 2 to 3 days old neonatal rat pups (n = 6–8) of Sprague Dawley rats. Osteoblasts were incubated with varying concentrations of GS and different assays viz. cell proliferation, differentiation, calcium deposition, cell cycle progression, antioxidant ability, and osteogenic gene expression were performed. Tartrate-resistant acid phosphatase (TRAP) staining and immunolocalization of cathepsin K protein were assessed in bone marrow-derived osteoclasts. Results Results revealed that GS markedly induced cell growth and osteoblast differentiation depending upon dose. The fluorescent dye DCFH-DA staining data proved the antioxidant ability of GS, which reduced the H2O2- induced intracellular oxidative stress in osteoblasts. Quantitative real-time PCR analysis revealed that GS treatment upregulated the expression of osteoblastic genes of Runt-related transcription factor 2 (Runx2), bone morphogenetic proteins 2 (BMP2), and osteocalcin. Immunolocalization of BMP2 also indicated the osteogenic efficacy of GS. Furthermore, TRAP staining and cathepsin K expression depicted that GS inhibited multinucleated osteoclasts formation. Conclusions In conclusion, GS isoflavone might impart protective effects against oxidative stress-induced bone loss and thus, could maintain skeletal growth.

Introduction: Drug Resistant Tuberculosis (DR-TB) is a rapidly escalating problem. Vitamin D and calcium serum levels can be an important determinant of Multidrug-Resistant Tuberculosis (MDR-TB) infection, progression to disease. The link between the serum level of 25-hydroxy vitamin-D {25(OH) D and MDR-TB is an emerging area for conducting evidence-based research. Aim: To assess the serum 25(OH)D and calcium levels and its deficiency in all the patients with drug resistant tuberculosis. Materials and Methods: This retrospective, observational study was conducted in the Department of Pulmonary Medicine, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India, from October 2019 to October 2020, in the newly detected 100 patients experiencing DR-TB. Patients sputum/body fluid samples were subjected for GeneXpert/Line Probe Assay (LPA) examinations to confirm resistance to anti-tubercular drugs. The frequency and prevalence of mean serum vitamin D and mean serum calcium levels were recorded based on age and gender. DR-TB categorised into H-Mono resistance, MDR-TB, Pre-Extensively Drug Resistant (Pre-XDR) and Extensively Drug Resistance Pulmonary Tuberculosis (XDR-PTB), based on GeneXpert and LPA of sputum/body fluid. Descriptive statistics were used to determine the characteristics of all the patients. All the statistical analysis was done using the Statistical Software for Data Sciences (STATA) software. Results: Mean age of study population was 31.12±15.49 years. Among them 63 were males and 37 were females. The mean serum vitamin D level of 10.87±8.49 ng/mL (deficient) and serum calcium level of 8.62±0.82 mg/dL (normal) was reported. Mean serum vitamin D levels were deficient in all the four types of DR-TB (p-value=0.04), while changes in mean serum calcium level was non significant (p-value=0.15). Conclusion: All patients with DR-TB have significant propensity to vitamin D deficiency. While changes in mean serum calcium level was non significant.

Northern corn leaf blight (NCLB) of maize, caused by Exserohilum turcicum (Pass.) Leonard and Suggs., is an important foliar disease common across maize-producing areas of the world, including Bihar, India. In this study, virulence and distribution of races were observed against Ht-resistant genes and also identified the E. turcicum race population distribution in Bihar. For that, 45 E. turcicum isolates were collected from maize fields in Bhagalpur, Begusarai, Khagaria, Katihar and Samastipur districts between 2020 and 2022. These isolates were screened on maize differential lines containing Ht1, Ht2, Ht3 and HtN1 resistance genes. Five different physiological races were observed based on the symptoms response of the differential maize lines. These races are race 0, race 1, race 3, race 23N and race 123N. E. turcicum race 3 was the most prevalent race having 26.6% frequency followed by race 0 (24.4%) and race 1 (22.2%) and the least prevalent races were race 23N and 123N having 13.3% each. Varied resistance response of different isolates was observed on differential lines having different resistant genes. Despite the fact that virulence was seen against all Ht resistance genes, NCLB control might be increased by combining qualitative Ht resistance genes with quantitative resistance.

Objective The development of self nano emulsifying co-delivery system of doxorubicin and Nigella sativa oil for potentiating the anticancer effects against HepG2 cell lines.Materials and methods SNEDDS were formulated by using Labrafil and N. sativa oil (3:2% w/w), Kolliphor RH40 (15% w/w), glycerol (5% w/w) as oil phase, surfactant and co-surfactant while deionized water (75% v/v) used as an aqueous phase. Optimized SNEDDS was evaluated for drug release and in vitro anticancer efficacy in liver cancer (HepG2) cell line.Results and discussion The selected formulation (F6) has a mean particle size of 79.7 nm with PDI 0.098 and the minimum viscosity of 16.42 cps with % transmittance of 1.332 with maximum drug release of 96.968% in 32 h as compared to DOX alone. Stability data showed stable emulsion in both 250C and -40C. F6 showed improved efficacy in HepG2 cells by cytotoxicity, showed significant results p

Maize is considered the third most important cereal crop in Asia after rice and wheat. Many diseases affect this crop due to the cultivation of various hybrids. This research aimed to characterize the causative agent of northern corn leaf blight disease in Bihar, India, caused by Exserohilum turcicum (Passerini) Leonard and Suggs. Leaf samples were collected from infected fields in five maize growing districts of Bihar in 2020–2022. A total of 45 fungal isolates from 135 samples were examined for cultural, morphological, and molecular characteristics and were identified as E. turcicum. The isolates were grouped into four groups based on colony color, i.e., olivaceous brown, blackish brown, whitish black, and grayish, and into two groups based on regular and irregular margins. The conidial shapes were observed to be elongated and spindle-shaped with protruding hilum, with conidial septa ranging from 2–12. Similarly, conidial length varied from 52.94 μm to 144.12 μm. β-tubulin gene sequences analysis made it possible to verify the identities of fungal strains and the phylogenetic relationships of all isolates, which were clustered in the same clade. The β-tubulin gene sequences of all the isolates showed a high level of similarity (100%) with reference isolates from GenBank accession numbers KU670342.1, KU670344.1, KU670343.1, KU670341.1, and KU670340.1. The findings of this study will serve as a baseline for future studies and will help to minimize yield losses.

Introduction: Amplification of airway inflammation and its destruction due to oxidative stress is a major step in the pathogenesis of chronic obstruction pulmonary disease (COPD). Exhaled carbon monoxide (eCO) may be quantified to evaluate the airway inflammation and oxidative stress in such patients. Objectives: To assess the disease severity of COPD and treatment response by measuring eCO as a biomarker. Materials and Methods: COPD patients diagnosed according to the global initiative for chronic obstructive lung disease guidelines and healthy individuals as controls were selected. One hundred and fifty patients with COPD and 125 controls were included in the study. Participants were further subdivided on the basis of their smoking habits. Clinical examinations and spirometry were done to diagnose COPD by following the standard protocol. eCO was measured using a piCO + Smokerlyzer (Breath CO Monitor, Bedfont Scientific Ltd., Kent, UK). It was a single-center cross-sectional study. Results: Mean (± standard error of mean) CO levels in ex-smokers with COPD were higher (5.21 ± 1.546 ppm; P < 0.05) than in nonsmoking controls (1.52 ± 0.571 ppm) but were lower than in current smokers with COPD (12.55 ± 4.514 ppm; P < 0.05). eCO levels were higher in current smokers with COPD (12.55 ± 4.514 ppm; P < 0.05) compared to healthy smokers (9.71 ± 5.649). There was a negative correlation between eCO and forced expiratory volume in 1 s (FEV1) in COPD (r = −0.28; P < 0.05). The mean eCO level was decreased (6.291–4.332; P < 0.001) with improvement in lung function (FEV1 38.75%–50.65%: P < 0.05) after treatment with inhaled steroid. Conclusion: Our study concludes that quantification of eCO level in COPD varies with different grades of airway obstruction and to measure the treatment response. Measuring the level of eCO can be used to assess the indirect assessment of airway inflammation, oxidative stress, and severity of airway obstruction in COPD patients.

In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC50 values of 9.2 and 21.8 µmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.

Exserohilum turcicum is an emerging pathogen of maize causing the northern leaf blight (NLB) disease with severe losses. The disease prevails all over the area under production but has varying severity. A temperature of 13°C to 33°C, along with 75-84% relative humidity, favours the pathogen development and growth. Thus, the present investigation was carried out to assess the prevalence of the disease in Bihar and the cultural, morphological, and pathogenic variability among the population through extensive field surveys conducted in maize-growing areas of seven major maize-producing districts of Bihar, India. A total of twenty-one isolates were identified as E. turcicum, which showed varying colony characteristics, colony margin, margin colour, pigmentation, growth pattern, sporulation, conidial shape, conidial size, and conidial septa. However, all the isolates produced characteristic symptoms of cigar-shaped necrotic lesions with variation in disease reaction on the leaves of susceptible maize inbred line CM-202. The isolates were categorized into three phylogenetic clusters with a coefficient of 0.42 based on their variations. A similar trend was observed, and three clusters with a coefficient of 0.52 were confirmed based on the disease reaction under field conditions. The isolates constituting Cluster I were deemed high virulent, followed by Cluster II as moderate virulent, and Cluster III as low virulent. All the isolates were further identified as Setosphaeria turcica, a teleomorph stage of E. turcicum, through molecular identification using ITS sequence analysis. Conclusively, a higher variability among the pathogen population was present, thus leading to the disease emergence, and their virulence assessment will aid in the identification of races and simultaneously accelerate the resistance breeding programmes in maize.

Phrenic nerve palsy causing hemidiaphragm paralysis is a very uncommon feature of thoracic aortic aneurysm. In one case, a 30 year male complained of chronic dull aching chest pain, and hoarseness of voice; posteroanterior view chest radiograph revealed large spherical radiopacity on the left upper lung zone with smooth lobulated margin with elevated left hemidiaphragm. On Colour Doppler sonography, lesion was anechoic on gray scale sonography but on Doppler analysis revealed intense internal vascularity within it with characteristic "Ying Yang" sign. The finding favor the vascular origin of the lesion and a diagnosis of an arterial aneurysm was made Contrast-enhanced computed tomography (CT) of the thorax revealed a large well defined spherical lesion of 8 × 10 cm size with smooth well defined margin arising from the aortic arch and attenuation of impending rupture or dissection were lesion on immediate post contrast and delayed scan was similar to that of aorta. Left hemidiaphragm elevation was explained by the gross mass effect of the aneurysm causing right phrenic nerve palsy.

A series of fluorinated 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles (2a–2i) was synthesized by condensation of various substituted 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiols (1a–1i) with penta fluoro benzoic acid in good yields (60–80%). The synthesized compounds were screened for anticancer activity against three cancerous cell lines MCF7 (human breast cancer), SaOS-2 (human osteosarcoma) and K562 (human myeloid leukemia). The compounds showed moderate to good antiproliferative potency against the studied cell lines. Among these, compound 2b showed higher antiproliferative activity (IC50 22.1, 19 and 15 μM against MCF7, SaOS-2 and K562, respectively) while 2a exhibited least antiproliferative activity (IC50 30.2, 39 and 29.4 μM against MCF7, SaOS-2 and K562 cells, respectively). Therefore, the present study demonstrates that fluorine substituted 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles would be a better prospective in the development of anticancer drugs.

Acute myocardial infarction or myocardial infarction (MI) is a major health problem, due to diminished flow of blood to the heart, leads to higher rates of mortality and morbidity. The most specific markers for cardiac injury are cardiac troponin I (cTnI) and cardiac troponin T (cTnT) which have been considered as ‘gold standard’. Due to higher specificity, determination of the level of cardiac troponins became a predominant indicator for MI. Currently, field-effect transistor (FET)-based biosensors have been main interest to be implemented in portable sensors with the ultimate application in point-of-care testing (POCT). In this paper, we review on the FET-based biosensor based on its principle of operation, integration with nanomaterial, surface functionalization as well as immobilization, and the introduction of additional gate (for ambipolar conduction) on the device architecture for the detection of cardiac troponin I (cTnI) biomarker.

Aluminium (Al) is the third most abundant element in the earth's crust and its compounds are used in the form of house hold utensils, medicines and in antiperspirant etc. Increasing number of evidences suggest the involvement of Al+3 ions in a variety of neurodegenerative disorders including Alzheimer's disease. Here, we have attempted to investigate the role of Al in endoplasmic reticulum stress and the regulation of p53 during neuronal apoptosis using neuroblastoma cell line. We observed that Al caused oxidative stress by increasing ROS production and intracellular calcium levels together with depletion of intracellular GSH levels. We also studied modulation of key pro- and anti-apoptotic proteins and found significant alterations in the levels of Nrf2, NQO1, pAKT, p21, Bax, Bcl2, Aβ1-40 and Cyt c together with increase in endoplasmic reticulum (ER) stress related proteins like CHOP and caspase 12. However, with respect to the role of p53, we observed downregulation of its transcript as well as protein levels while analysis of its ubiquitination status revealed no significant changes. Not only did Al increase the activities of caspase 9, caspase 12 and caspase 3, but, by the use of peptide inhibitors of specific and pan-caspases, we observed significant protection against neuronal cell death upon inhibition of caspase 12, demonstrating the prominent role of endoplasmic reticulum stress generated responses in Al toxicity. Overall our findings suggest that Al induces ER stress and ROS generation which compromises the antioxidant defenses of neuronal cells thereby promoting neuronal apoptosis in p53 independent pathway.

A natural predominant flavanone naringenin, especially abundant in citrus fruits, has a wide range of pharmacological activities. The search for antiproliferative agents that reduce skin carcinoma is a task of great importance. The objective of this study was to analyze the anti-proliferative and apoptotic mechanism of naringenin using MTT assay, DNA fragmentation, nuclear condensation, change in mitochondrial membrane potential, cell cycle kinetics and caspase-3 as biomarkers and to investigate the ability to induce reactive oxygen species (ROS) initiating apoptotic cascade in human epidermoid carcinoma A431 cells. Results showed that naringenin exposure significantly reduced the cell viability of A431 cells (p

Vehicular Ad-Hoc Networks (VANETs) play an essential role in the intelligent transportation era, furnishing users with essential roadway data to facilitate optimal route selection and mitigate the risk of accidents. However, the network exposure makes VANETs susceptible to cyber threats, making authentication crucial for ensuring security and integrity. Therefore, joining entity verification is essential to ensure the integrity and security of communication in VANETs. However, to authenticate the entities, authentication time should be minimized to guarantee fast and secure authentication procedures. We propose an authentication system for VANETs using blockchain and Kerberos for storing authentication messages in a blockchain ledger accessible to Trusted Authentication Servers (TASs) and Roadside Units (RSUs). We evaluate the system in three diverse network scenarios: suburban, urban with 1 TAS, and urban with 2 TASs. The findings reveal that this proposal is applicable in diverse network scenarios to fulfill the network requirements, including authentication, handover, and end-to-end delay, considering an additional TAS for an increasing number of vehicles. The system is also practicable in storing the authentication message in blockchain considering the gas values and memory size for all scenarios.