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Aim: The present study aimed to compare and evaluate debris and irrigant extrusion from curved root canals using different rotary systems. Materials and Methods: 30 single-rooted mandibular canines were used in this study. The crown was decoronated, working length and initial apical diameter were established. A 1.5% agar gel model was used in this study. Samples were assigned randomly into 3 groups (n = 10 teeth per group). Protaper Next, OneShape, and Hanudent files were used according to the manufacturers' instructions for canal instrumentation. Apically extruded debris and irrigant was were computed by deducting the initial weight of the test apparatus without a tooth from its weight after the biomechanical preparation. Comparative analysis of the amount of apically extruded debris and irrigant for each of the instruments and the experimental models was performed. Results: The statistically significant difference was found between the three experimental groups. (P < .05). Among all the groups least extrusion was observed in the Protaper Next group when used in combination with conventional irrigation. Conclusion: All the instruments produced apically extruded debris and irrigant, but the maximum was seen with OneShape among the experimental groups. [ABSTRACT FROM AUTHOR]

Purpose. Effectively controlling the accumulation of adipose tissue can be a therapeutic strategy for treating obesity, which is a global problem. The present study was designed for comparative assessment of in vitro antiobesity activities of the Psoralea corylifolia-dichloromethane seed extract (DCME) and the isolated phytochemicals, bakuchiol, isopsoralen, and psoralen, through antiadipogenesis and pancreatic lipase (PL) inhibition assays. Material and Methods. In vitro pancreatic lipase activity was determined spectrophotometrically by measuring the hydrolysis of p-nitrophenyl butyrate (p-NPB) to p-nitrophenol at 405 nm, and adipogenesis was assayed in 3 T3-L1 adipocytes (by using Oil Red O staining) using P. corylifolia-dichloromethane seed extract (DCME) and individual compounds, isolated from the extract. Result. Antilipase as well as antiadipogenesis activity was displayed by both the DCME and the compounds. Maximum antilipase property was recorded in DCME (26.02 ±.041 %) at 100 μg/ml, while, among the isolated compounds, bakuchiol exhibited a higher activity (24.2 ± 0.037 %) at 100 μg/ml concentration, compared to other isolates. DCME was found to exhibit antiadipogenesis property, 75 ± 0.003 % lipid accumulation, compared to the control at 100 μg/ml dose. Bakuchiol, isopsoralen, and psoralen inhibited the lipid accumulation in 3T3-L1 preadipocytes, 78.06 ± 0.002 %, 80.91 ± 0.004 %, and 80.91 ± 0.001 %, respectively, lipid accumulation in comparison to control at 25 μM dose. Conclusion. The present study highlights the antiobesity potential of P. corylifolia and its active constituents. Thus, it can be concluded that P. corylifolia has the potential to treat obesity and related diseases; however, further research on dose standardization and clinical trials are required. [ABSTRACT FROM AUTHOR]

Background: Inadequate obturation techniques of the root canal system have been found to be the most frequent reason of failure post root canal treatment. An ideal endodontic sealer should fulfill all ideal requisites. The present study aimed to compare apical sealing ability between bioceramic (BC) sealer, GuttaFlow, and AH Plus. Methodology: One hundred and twenty-five curved roots of maxillary and mandibular third molar teeth with fully formed apex were collected for this study. The root canals were cleaned and shaped using a standard single-cone preparation to file at the established working length and divided into five groups of 25 each. Dye leakage was carried out. Group A: with GP, using EndoSequence BC sealer with conventional with 4% gutta-percha (Brasseler USA, Savannah, Georgia, USA); Group B: with ceramic coated with 4% gutta-percha (Brasseler USA, Savannah, Georgia, USA); Group C: with GP, using AH Plus sealer (Dentsply, De-Trey Konstanz, Germany) with 4% gutta-percha; Group D: with GuttaFlow bioseal (Roeko-Coltène/Whaledent, Langenau, Germany) with 4% Gutta-percha; and Group E is a negative control group. Statistical analysis was done using the Statistical Package for the Social Sciences software and Student's unpaired t-test. Results: The group AH Plus showed more leakage values than the GuttaFlow group and of two groups of BC sealer and negative control. Student's unpaired t-test disclosed no significant difference (P < 0.05) between the groups. Conclusion: None of the sealers used in the study could completely seal the apical foramen to have a fluid-tight seal. [ABSTRACT FROM AUTHOR]

Dental caries is a chronic, widespread, and infectious disease affecting the large population. Anticariogenic effects of different herbs and natural products are observed, cinnamon among these, showed the ability to inhibit Streptococcus mutans biofilm. Objectives: The aim of this study was to assess the cinnamon water extract use on nicotine exposed S. mutans biolfilms. Materials and Methods: Microtiter plates having S. mutans culture were treated using varying nicotine concentration range (0-32 mg/ml). These were then either subjected to cinnamon water (2.5 mg/ml) extract or no treatment and analyzed using a spectrophotometer to see planktonic growth, total growth absorbance, and biofilm formation. Results: About 2.5 mg/ml of cinnamon water inhibits the S. mutans biofilm (nicotine-induced) considerably at various nicotine levels (0-32 mg/ml). Conclusion: Cinnamon water extract has a powerful inhibitory effect for S. mutans growth. Nicotine-induced S. mutans growth is markedly reduced by treating with cinnamon water extract. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study is to compare the fracture resistance of endodontic treated tooth restored with GIC, amalgam, and composite cements. Materials and Methods: Forty teeth were divided into 4 groups of 10 teeth each. Group I teeth were restored with silver amalgam. Group II teeth were restored with GIC. Group III teeth were restored with composite and Group IV teeth were control in which no alteration was performed. Testing machine applied force on teeth to detect fracture resistance. Results: The mean fracture resistance was maximum in Group IV (1050.2 N) followed by Group III (956.2 N), Group I (836.4 N), and Group II (766.4 N). The difference was statistically significant (P < 0.05). The mean difference of fracture resistance was significant (P > 0.05). Conclusion: Composite resin possesses highest fractures resistance as compared to GIC and silver amalgam. [ABSTRACT FROM AUTHOR]

Herbal polyphenols have gained increased significance because of the promises they hold in the prevention and treatment of cancer. There exists an enormous opportunity for the screening and valuation of natural dietary compounds in the development of an effective chemopreventive drug and radiosensitizer that may be of practical use for patients undergoing cancer therapy. This study describes the effect of the flavonoid ellagic acid (EA) on gamma-irradiated human breast cancer MCF-7 cellsin vitrowhen administered alone or in combination with radiation. It was interesting to find the radioprotective effect of EA on NIH3T3, which is a normal cell line. Irradiation of breast tumor cells in the presence of EA (10 μM) to doses of 2 and 4-Gy gamma radiation produced a marked synergistic tumor cytotoxicity while it was found to aid recovery from the radiation damage to NIH3T3 cells. When cells were given a combined treatment of EA and radiation, the cell death increased to 21.7% and 20.7% in the 2 and 4-Gy-treated cells respectively, significantly (P< 0.05) reducing the capacity of MCF-7 cells to form colonies. Even at 24 h, 38 foci/cell were observed in samples that were given the combined treatment, suggesting the cells' inability in repairing the damage. Also, increased apoptosis in EA+ 2Gy (50%) and EA+ 4 Gy (62%)-treated cells was observed in the the sub-G1 phase of the cell cycle. A 6.2-fold decrease in the mitochondrial membrane potential was observed in the combined treatment of EA and IR that facilitated the upregulation of pro-apopttotic Bax and downregulation of Bcl-2, pushing the MCF-7 cells to undergo an apoptotic cell death. It is suggested that EA may be a potential drug adjuvant for improving cancer radiotherapy by increasing tumor toxicity and reducing the normal cell damage caused by irradiation. [ABSTRACT FROM PUBLISHER]

Akt, a serine/threonine protein kinase, is often hyper activated in breast and prostate cancers, but with poor prognosis. Allosteric inhibitors regulate aberrant kinase activity by stabilizing the protein in inactive conformation. Several natural compounds have been reported as inhibitors for kinases. In this study, to identify potential natural allosteric inhibitor for Akt1, we generated a seven-point pharmacophore model and screened it through natural compound library. Quercetin-7- O -β- d -glucopyranoside or Q7G was found to be the best among selected molecules based on its hydrogen bond occupancy with key allosteric residues, persistent polar contacts and salt bridges that stabilize Akt1 in inactive conformation and minimum binding free energy during molecular dynamics simulation. Q7G induced dose-dependent inhibition of breast cancer cells (MDA MB-231) and arrested them in G1 and sub-G phase. This was associated with down-regulation of anti-apoptotic protein Bcl-2, up-regulation of cleaved caspase-3 and PARP. Expression of p-Akt (Ser473) was also down-regulated which might be due to Akt1 inhibition in inactive conformation. We further confirmed the Akt1 and Q7G interaction which was observed to have a dissociation constant (K d ) of 0.246 μM. With these computational, biological and thermodynamic studies, we suggest Q7G as a lead molecule and propose for its further optimization. [ABSTRACT FROM AUTHOR]

Amyloid deposits are common in various tissues as a consequence of misfolded proteins. However, secretory protein and peptides are often stored in membrane coated granules as functional amyloids. In this article, we present a detailed characterization of in vitro generated amyloid fibrils from human parathyroid hormone (hPTH(1–84)). Fully mature fibrils could be obtained after a short lag phase within less than one hour at 65 °C. These fibrils showed all characteristic of a cross-β structure. Protease cleavage combined with mass spectrometry identified the central region of the peptide hormone involved in the fibril core formation. EGCG, an inhibitor of amyloid fibril formation, showed binding to residues in the peptide monomers corresponding to the later fibril core and thus explaining the inhibition of the fibril growth. Conformational and dynamic studies by solid-state NMR further corroborated the cross-β core of the fibrils, but also identified highly mobile segments with a random coil structure not belonging to the rigid fibril core. [ABSTRACT FROM AUTHOR]

• A series of nitro- and methoxy-2-phenylbenzofuran was synthesized. • Compounds displayed activity against monoamine oxidase enzymes. • Relevance of number/position of methoxyl substitution in enzyme activity. • Importance of nitro substitution in MAO-A enzyme activity. • Physicochemical properties are suitable for good bioavailability. • Docking studies assisted in explaining the structure-activity relationship. A new series of 2-phenylbenzofuran derivatives were designed and synthesized to determine relevant structural features for the MAO inhibitory activity and selectivity. Methoxy substituents were introduced in the 2-phenyl ring, whereas the benzofuran moiety was not substituted or substituted at the positions 5 or 7 with a nitro group. Substitution patterns on both the phenyl ring and the benzofuran moiety determine the affinity for MAO-A or MAO-B. The 2-(3-methoxyphenyl)-5-nitrobenzofuran 9 was the most potent MAO-B inhibitor (IC 50 = 0.024 µM) identified in this series, whereas 7-nitro-2-phenylbenzofuran 7 was the most potent MAO-A inhibitor (IC 50 = 0.168 µM), both acting as reversible inhibitors. The number and position of the methoxyl groups on the 2-phenyl ring, have an important influence on the inhibitory activity. Molecular docking studies confirmed the experimental results and highlighted the importance of key residues in enzyme inhibition. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XO) plays a critical role in purine catabolism, catalyzing the conversion of hypoxanthine to xanthine and xanthine to uric acid, contributing to superoxide anion production. This process is implicated in various human diseases, particularly gout. Traditional XO inhibitors, such as allopurinol and febuxostat, while effective, may present side effects. Our study focuses on Asphodelus microcarpus , a plant renowned for traditional anti-inflammatory uses. Recent investigations into its phenolic-rich flowers, notably abundant in luteolin derivatives, reveal its potential as a natural source of XO inhibitors. In the present research, XO inhibition by an ethanolic flowers extract from A. microcarpus is reported. In silico docking studies have highlighted luteolin derivatives as potential XO inhibitors, and molecular dynamics support that luteolin 7- O -glucoside has the highest binding stability compared to other compounds and controls. In vitro studies confirm that luteolin 7- O -glucoside inhibits XO more effectively than the standard inhibitor allopurinol, with an IC 50 value of 4.8 μg/mL compared to 11.5 μg/mL, respectively. These findings underscore the potential therapeutic significance of A. microcarpus in managing conditions related to XO activity. The research contributes valuable insights into the health-promoting properties of A. microcarpus and its potential application in natural medicine, presenting a promising avenue for further exploration in disease management. • A. microcarpus flower extract inhibits xanthine oxidase (XO) via mixed-type inhibition. • Luteolin-7- O -glucoside stably binds XO in AutoDock and 250ns molecular dynamics. • Luteolin 7- O -glucoside demonstrates in vitro XO inhibition (IC 50 4.8 μg/mL). [ABSTRACT FROM AUTHOR]

Epidemiological studies promote the inclusion of natural-products in diet due to their inhibitory effects on various types of cancer. Among them, Achyranthes aspera L. (Family Amaranthaceae) is a medicinal plant in Ayurvedic pharmacopeia, found in India, Southeast Asia, America, and Sub-Saharan Africa. It is endowed with anti-inflammatory, anti-oxidant, and anti-cancer activities. However, its potential effect on Non-Hodgkin lymphomas (NHLs), has not yet been clarified. In the present study, we aimed to investigate the effect of Achyranthes aspera L. leaf extracts on highly aggressive murine NHL called Dalton's Lymphoma (DL) in vitro and in vivo. GC-HRMS analysis was carried out for the identification of compounds present in A. aspera leaf extract. The cytotoxicity of various A. aspera leaf extracts was evaluated on DL cells by MTT assay. Chromatin condensation, nuclear fragmentation, and morphological changes were observed by microscopy technique. Flow cytometry was used to measure the changes in mitochondrial membrane potential (ΔΨm) and apoptosis. In addition, the expressions of apoptosis-related proteins were detected by western blotting. Meanwhile, the in vivo anti-tumor effect of leaf extract was tested in DL induced Balb/c mice. GC-HRMS analysis of A. aspera methanolic leaf extract (AAML) revealed the presence of ten pharmacologically active compounds. The results showed that AAML suppressed cell proliferation, decreased mitochondrial membrane potential, changed the morphological structure, and induced apoptosis. Moreover, AAML could promote the release of cytochrome c by regulating Bcl-2 family proteins and then activated caspase-9/ -3 to triggered cell apoptosis. At the same time in DL cells treated with AAML, the protein kinase Cα (PKCα) pathway was inhibited in a concentration-dependent manner. Remarkably, in vivo , AAML mediated suppression of DL growth in Balb/c mice was accompanied by attenuation of the PKCα pathway and induction of apoptosis. Our result suggested that AAML promotes mitochondrial apoptotic cascade in DL cells by suppressing the PKCα signaling pathway. The study suggests that AAML could potently suppress DL progression by promoting apoptosis via mitochondrial-cascade and attenuation of the PKCα signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]