Search

In this study, we successfully synthesized ethyl 2-(3-methoxybenzyl) acrylate-substituted pyrazolones derivative (EMH) through the reaction of Baylis-Hillman acetate with pyrazolones. We conducted comprehensive screenings to evaluate its invitro antifungal, antibacterial, and antioxidant properties. The molecule demonstrated notable in vitro antifungal and antibacterial activities attributed to the presence of anisole, enhancing absorption rates through increased lipid solubility and improving pharmacological effects. Structure-activity relationship (SAR) studies supported these findings. Additionally, insilico studies delved into the molecular interactions of the synthesized molecule with DNA Gyrase, Lanosterol 14 alpha demethylase, and KEAP1-NRF2 proteins, revealing strong binding interactions at specific sites. Furthermore, we employed ab-initio techniques to theoretically estimate the photophysical properties of the compounds. Ground state optimization, dipole moment, and HOMO-LUMO energy levels were calculated using the DFT-B3LYP-6-31G(d) basis set. The theoretical HOMO-LUMO values indicated high electronegativity and electrophilicity index. NBO analysis confirmed the presence of intermolecular ON...H hydrogen bonds resulting from the interaction of the lone pair of oxygen with the anti-bonding orbital. Overall, our results suggest that anisole-substituted pyrazolones derivatives exhibit promising applications in both photophysical and biological domains.

Background: Soybean is important oil seed crop. Poor seed germination is a major constraint for increasing the productivity of soybean. Seed quality enhancement will enhance the germination. Treating the seeds with chemicals may cause harmful effects to ecosystems and also to human beings. Using botanicals for seed treatment is safe. The present study was taken with a view to assess the seed quality of soybean by using different botanicals treatments (ball milled and commercial grade) along with shaking and without shaking. Methods: Experiment was conducted to evaluate the effect of seed treatment with different ball milled botanicals and commercial grade along with shaking (60 min) and without shaking of soybean seeds on quality attributes. Botanical powders of fenugreek (Trigonella foenum-graecum L.) seed, leafs of ashwagandha (Withania somnifera), tea (Camellia sinensis) and noni (Morinda citrifolia) were ball milled for 1 h to bring into near nano size and treated with seeds @ 2 g kg-1 for 60 min. Without ball milling was served as commercial grade. Among these two methods (commercial grade and near nano size) highest values were observed in seeds treated with near nano size powder. Generally shaking of seeds with botanicals was performed better than without shaking. Result: In this experiment, botanical fenugreek seed powder perfrmed well. In interaction, soybean seeds treated with near nano size fenugreek seed powder @ 2 g kg-1 with shaking of 60 min showed highest seed quality parameters. The per cent increase over control for germination, shoot length, root length, dry matter production and vigour index were 17.8, 27.7, 43.9, 47.6 and 45.3%, respectively. [ABSTRACT FROM AUTHOR]

PURPOSE: To measure the pupillary dynamics and accommodative response in individuals with mild traumatic brain injury (mTBI) as compared to age‑matched controls. MATERIALS AND METHODS: This prospective comparative study was carried out at the neuro‑optometry clinic of a tertiary eye care hospital. Sixty‑three subjects with a history of mTBI and ninety age‑matched controls were enrolled in this study. Subjects in the age range of 18–35 years were included in the study. A comprehensive neuro‑optometric assessment was performed followed by pupillary dynamics and accommodation response measurements using NeurOptics® pupillary light reflex™‑3000 and Grand-Seiko WAM-5500 binocular accommodation auto ref/keratometer | shigiya machinery works LTD. RESULTS: A statistically significant difference was noticed for constriction percentage (%): 32.73 ± 9.20 versus 39.93 ± 7.36 (P < 0.001), average constriction velocity (mm/s): 2.24 ± 0.85 versus 2.62 ± 0.68 (P = 0.002), maximum constriction velocity (mm/s): 3.82 ± 1.33 versus 4.42 ± 0.93 (P = 0.004) and T75 (recovery period to 75% of the baseline pupillary diameter in sec): 1.38 ± 0.36 versus 2.0 ± 0.82 (P < 0.001) in mTBI compared to age‑matched controls. A statistically significant difference was noted for accommodative response (in D) as well as in the sample as compared to age‑matched controls: −1.12 ± 0.64 versus − 1.39 ± 0.47 (P < 0.001). CONCLUSION: Pupillary constriction velocities and accommodative response are significantly affected in mTBI. These findings have important clinical implications in being able to understand the visual symptoms following an mTBI. [ABSTRACT FROM AUTHOR]

Macrophages are highly responsive to the environmental cues and are the primary responders to tissue stress and damage. While much is known about the role of macrophages during inflammatory disease progression; the initial series of events that set up the inflammation remains less understood. In this study, we use next generation sequencing (NGS) of embryonic skin macrophages and the niche cells - skin epithelia and stroma in the epidermis specific knockout of integrin beta 1 (Itgβ1) model to uncover specific roles of each cell type and identify how these cell types communicate to initiate the sterile inflammatory response. We demonstrate that while the embryonic skin fibroblasts in the Itgβ1 knockout skin are relatively inactive, the keratinocytes and macrophages are the critical responders to the sterile inflammatory cues. The epidermis expresses damage associated molecular patterns (DAMPs), stress response genes, pro-inflammatory cytokines, and chemokines that aid in eliciting the inflammatory response. The macrophages, in-turn, respond by acquiring enhanced M2-like characteristics expressing ECM remodeling and matrisome signatures that exacerbate the basement membrane disruption. Depletion of macrophages by blocking the CSF1 receptor (CSF1R) results in improved basement membrane integrity and reduced ECM remodeling activity in the KO skin. Further, blocking the skin inflammation with celecoxib reveals that the acquired fate of macrophages in the KO skin is dependent on its interaction with the epidermal compartment through COX2 dependent cytokine production. Taken together, our study highlights a critical crosstalk between the epithelia and the dermal macrophages that shapes macrophage fate and initiates sterile inflammation in the skin. The insights gained from our study can be extrapolated to other inflammatory disorders to understand the early events that set up the disease.

This study aimed to synthesize a new magnetic photocatalytic nanosystem composed of Ag-CuFe2O4@rGO and to investigate its photodegradation efficiency for two organic pollutants of methylene blue (MB) 4-nitrophenol (4-NP) under visible light irradiation. The synthesized Ag-CuFe2O4@rGO nanocomposites were fully characterized by XRD, TEM, HRTEM, XPS, FTIR, UV and PL analysis which shows well controlled small sized (∼ 10 nm from Scherrer formula) CuFe2O4 NPs with dense and compact loading over rGO sheets. XRD results reveal that cubic spinel structure of CuFe2O4 with nanoparticles (5–10 nm) in shape, which is uniformly, decorated on the surface of the rGO sheets. The band gap energy values of CuFe2O4, Ag-CuFe2O4 and Ag-CuFe2O4@rGO nanoparticles are calculated as 2.76, 2.27 and 2.03 eV, respectively. After incorporation of Ag and rGO into CuFe2O4, the specific surface area was significantly improved to 154 m2/g for Ag-CuFe2O4@rGO nanocomposite. Upon inclusion of the photocatalysts, photodegradation efficiency increased and the Ag-CuFe2O4@rGO composite showed the highest efficiency towards MB (99.5%) and 4-NP (88.7%) followed by the Ag-CuFe2O4. With addition of rGO, the electron-hole recombination declines, thus resulting in a more optimum photocatalytic performance. The rate constant of Ag-CuFe2O4@rGO composite was found to be 0.0985 min−1 for MB and 0.0542 min−1 for 4-NP, respectively. Moreover, the effect of pH, catalyst dosage, and long term stability was thoroughly determined. The improved performance could be attributed to the positive synergistic effect between CuFe2O4 nanoparticles and rGO. The samples were further evaluated by EIS and dynamic photoresponse in order to identify the charge transfer efficiency. The improved photocatalytic mechanism was also explained briefly. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been responsible for the cause of global pandemic Covid-19 and to date, there is no effective treatment available. The spike ‘S’ protein of SARS-CoV-2 and ACE2 of the host cell are being targeted to design new drugs to control Covid-19. Similarly, a transmembrane serine protease, TMPRSS2 of the host cell plays a significant role in the proteolytic cleavage of viral ‘S’ protein helpful for the priming of ACE2 receptors and viral entry into human cells. However, three-dimensional structural information and the inhibition mechanism of TMPRSS2 is yet to be explored experimentally. Hence, we have used a molecular dynamics (MD) simulated homology model of TMPRSS2 to study the inhibition mechanism of experimentally known inhibitors Camostat mesylate, Nafamostat and Bromhexine hydrochloride (BHH) using molecular modeling techniques. Prior to docking, all three inhibitors were geometry optimized by semi-empirical quantum chemical RM1 method. Molecular docking analysis revealed that Camostat mesylate and its structural analogue Nafamostat interact strongly with residues His296 and Ser441 present in the catalytic triad of TMPRSS2, whereas BHH binds with Ala386 along with other residues. Comparative molecular dynamics simulations revealed the stable behavior of all the docked complexes. MM-PBSA calculations also revealed the stronger binding of Camostat mesylate to TMPRSS2 active site residues as compared to Nafamostat and BHH. Thus, this structural information could be useful to understand the mechanistic approach of TMPRSS2 inhibition, which may be helpful to design new lead compounds to prevent the entry of SARS-Coronavirus 2 in human cells.

The extracellular matrix (ECM) is a complex network of proteins and proteoglycans secreted by keratinocytes, fibroblasts and immune cells. The function of the skin ECM has expanded from being a scaffold that provides structural integrity, to a more dynamic entity that is constantly remodeled to maintain tissue homeostasis. The ECM functions as ligands for cell surface receptors such as integrins, dystroglycans, and toll-like receptors (TLRs) and regulate cellular signaling and immune cell dynamics. The ECM also acts as a sink for growth factors and cytokines, providing critical cues during epithelial morphogenesis. Dysregulation in the organization and deposition of ECMs lead to a plethora of pathophysiological conditions that are exacerbated by aberrant ECM-immune cell interactions. In this review, we focus on the interplay between ECM and immune cells in the context of skin diseases and also discuss state of the art therapies that target the key molecular players involved.