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Heart failure is a condition in which the heart's one or both ventricles are unable to either receive an adequate amount of blood or eject an adequate amount of blood. Diabetes is considered one of the major risk factors for cardiovascular diseases. The current research is designed to evaluate the cardioprotective effects of dapagliflozin in streptozotocin and isoproterenol-induced comorbid rats. The COX-2, TNF-α, NF-Κ B, NLRP3, PPAR-γ, CKMB, TROP-I, AR, GP and SGLT were docked against dapagliflozin, propranolol and metformin. Dapagliflozin restored adequate blood flow and halted myofibril damage. Moreover, it's evident from this study that dapagliflozin significantly decreased serum concentration of various blood markers, decreased relative growth rate and QT interval prolongation, as compared to the negative control group. However, it improved the ventricular ejection fraction in rats of the treatment group. The GST, GSH and CAT levels were increased, as compared to normal. On the contrary, a decrease in LPO concentrations was observed. Evaluation of the coronal section of heart tissues showed the anti-inflammatory expressions evaluated through H & E staining and immunohistochemical techniques and with ELISA and PCR. In a nutshell, dapagliflozin reverses myocardial necrosis and apoptosis. [ABSTRACT FROM AUTHOR]

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect. [ABSTRACT FROM AUTHOR]

The pentacyclic triterpenoids (PTs) of plant origin are reputed to restrain prostate cancer (PCa) cell proliferation. This study aims to assess 3-epifriedelinol (EFD) isolated from aerial part of Ipomoea batatas against PCa and its potential mechanism, in vitro and in vivo. Molecular docking affirms good binding affinity of the compound with target proteins exhibiting binding energy of −7.9 Kcal/mol with BAX, −8.1 Kcal/mol (BCL-2), −1.9 Kcal/mol (NF-κB) and −8.5 Kcal/mol with P53. In the MTT assay, EFD treatment (3–50 µM) showed a significant (p < 0.05 and p < 0.01) dose and time dependent drop in the proliferative graph of DU145 and PC3, and an upsurge in apoptotic cell population. EFD displayed substantial IC50 against DU145 (32.32 ± 3.72 µM) and PC3 (35.22 ± 3.47 µM). According to Western blots, EFD administration significantly enhanced the cleavage of caspases and PARP, elevated BAX and P53 and decreased BCL-2 and NF-κB expression, thereby triggering apoptosis in PCa cells. When male Sprague Dawley rats were intoxicated with Bisphenol A (BPA), an apparent increase in prostate mass (0.478 ± 0.08 g) in comparison to control (0.385 ± 0.03 g) indicates prostatitis. Multidose treatment of EFD (10 mg/kg) significantly reduced prostate size (0.404 ± 0.05 g). EFD exhibited substantial curative potential in vivo, as hematological, hormonal and histopathological parameters have been significantly improved. Reduced peroxidation (TBARS), and suppression of inflammatory markers i.e., NO, IL-6 and TNF-α, signposts substantial antiinflammatory potential of the compound. Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or adjuvant therapy against PCa and toxins-induced gonadotoxicity. [ABSTRACT FROM AUTHOR]

Pyrimidine 2, 4, 6-trione derivatives are known to have L-type calcium channel blockade activity due to which they are quite effective in cardiovascular diseases along with cancer, epilepsy and inflammatory disorders. The chemoinformatics prediction for test compounds: 5-(3-Hydroxybenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-5), 5-(4-Hydroxybenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-8), 5-(3-Chlorobenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-9) and 5-(4-Chlorobenzylidene)-2, 4, 6(1H, 3H, 5H)-pyrimidinetrione (SR-10) was investigated. The druglikeliness and pharmacokinetic properties (PKs) of test compounds calculated using Molinspiration & Swiss ADME online servers. These test drugs subjected to molecular docking analysis and molecular dynamic (MD) simulation to calculate their binding energies with hypertensive and platelet aggregatory proteinaceous targets and their stability against calcium channel. The druggability and PKs of selected compounds exhibited that these compounds could be represented as potential candidates for further development into antihypertensive-like agents. The docking results indicated that binding energies ranged between -5 and -8.8 kcal/mol. Compounds showed good binding energies against calcium channels (CC) and subjected to molecular dynamic simulation to assess the stability of proteinligand complex. The results showed that all the ligands form stable complexes with the CC, though SR-9 and SR-10 had enhanced stability when compared to SR-5 and SR-8. [ABSTRACT FROM AUTHOR]

Background: To explore the association between obesity and tooth wear among American adults and the role of sugar-sweetened acidic drinks consumption in explaining that association. Methods: We analyzed data from 3541 adult participants in the National Health and Nutrition Examination Survey. Obesity was determined using the body mass index and tooth wear was assessed using the modified tooth wear index. Daily intake of four categories of drinks was estimated as the average (drinks/day) of two consecutive 24-h dietary recalls. The association between obesity and number of surfaces with moderate-to-severe tooth wear was assessed in hurdle models adjusting for sociodemographic factors, acid reflux medication, and dental insurance. Results: Overweight and obese adults had more surfaces with moderate-to-severe tooth wear than those with normal body size, after adjusting for confounders. The consumption of sugar-sweetened acidic drinks explained part, but not all the above association. More specifically, the estimate for obesity was fully attenuated, whereas the estimate for overweight was slightly attenuated but remained significant. Conclusion: Obesity was positively associated with tooth wear in American adults. This association was only partially accounted for by the consumption of sugar-sweetened acidic drinks, a common risk factor for both conditions. Practical implications: Dentists must be aware of the health consequences of sugar-sweetened acidic drinks and advocate for reduction in consumption and/or substitution with healthier alternatives. [ABSTRACT FROM AUTHOR]