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The study aimed to enhance the solubility, dissolution, and oral bioavailability of standardized Piper longum fruits ethanolic extract (PLFEE) via fourth-generation ternary solid dispersion (SD) for melanoma therapy. With the use of solvent evaporation method, the standardized PLFEE was formulated into SD, optimized using Box-Wilson's Central Composite Design (CCD), and evaluated for pharmaceutical performance and in-vivo anticancer activity against melanoma (B16F10) bearing C57BL/6 mice. The optimized SD showed good accelerated stability, high yield, drug content, and content uniformity for bioactive marker piperine (PIP). The X-ray diffraction (XRD), Differential scanning calorimetry (DSC), Polarized Light Microscopy (PLM), and selected area electron diffraction (SAED) analysis revealed its amorphous nature. The Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and High-Performance Thin Layer Chromatography (HPTLC) revealed the compatibility of excipients with the PLFEE. The contact angle measurement and in-vitro dissolution study revealed good wetting of SD and improved dissolution profile as compared to the plain PLFEE. The in-vivo oral bioavailability of SD reflected a significant (prel = 188.765%) as compared to plain extract. The in-vivo tumor regression study revealed the improved therapeutic activity of SD as compared to plain PLFEE. Further, the SD also improved the anticancer activity of Dacarbazine (DTIC) as an adjuvant therapy. The overall result revealed the potential of developed SD for melanoma therapy either alone or as an adjuvant therapy with DTIC.

The present study identified the probable mechanism behind the anti-cancer activity of the hexane fraction of Pleurotus osteratus (HFPO) using network pharmacology and experimental validation. HFPO myco-metabolites targets and targets related to the cancer were mined from the online web server, and overlapping targets were screened. Out of the 74 overlapping targets, 33 targets were identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of cancer. Furthermore, the main active myco-metabolites and hub targets were identified by network analysis of the compound-targets network and protein-protein interaction (PPI), respectively. Molecular docking results showed good binding affinity of the hub targets with their respective myco-metabolites. HFPO induced in-vitro anti-cancer activity by affecting the PI3K-AKT-mTOR pathway, besides time-dependent cell cytotoxicity and apoptotic cell body formation. Additionally, tumor volume reduction was observed in HFPO-treated Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice. Overall, HFPO induces anti-cancer potential by modulating the PI3K-AKT-mTOR signaling pathway.

Background: The aim of the present study was to study the effect of percutaneous balloon mitral valvuloplasty (PBMV) on P wave dispersion and to test the correlation between P-maximum and P-dispersion to right ventricular function and pulmonary artery pressure before and after PMBV. Also to study the impact of P-maximum and P-wave dispersion on the short term clinical outcome after successful PBMV in patients with mitral stenosis (MS) and sinus rhythm. Methods: 75 patients undergoing PMBV were enrolled in this study. We evaluated P-maximum, P-minimum and P-wave dispersion before and one month and one year after PBMV . We studied the changes in pulmonary arterial pressure (PAP), left atrial (LA) dimension, mitral diastolic gradient, and mitral valve area, in addition to the changes in right ventricular function utilizing tissue Doppler assessment both before and after PMBV, in addition the role of the P-wave dispersion in prediction of late cardiac events. Results: There were significant decrease in mean diastolic gradient, PAP, and LA size and significant improvement in right ventricular tissue Doppler indices after PMBV. Accompany these hemodynamic changes after PMBV. P-maximum and P-wave dispersion were found to be decreased (P < 0.001). Conclusion: Successful PBMV was associated with a decrease in Pmax and PWD. These simple electrocardiographic indices may predict the success of the procedure immediately after PBMV. The P-maximum and P-wave dispersion changes were correlated with significant impairment of right dysfunction and the degree of pulmonary artery pressure. Keywords: PBMV.PAP,LA

Background: Patients of coronary artery disease require medical treatment to optimize their lipid profile. The present analysis evaluates the lipid profile among CAD patients receiving statin therapy. To study THE STATUS OF LIPID PROFILE CONTROL IN CORONARY ARTERY DISEASE PATIENTS AT A TERTIARY CARE HOSPITAL Methods: Our study included 1016 patients with documented CAD by coronary angiography in Department of cardiology SMS medical college and associated group of hospitals. Patients treated with statin therapy for at least 3 months were included. We compared data relating to demographic parameters and other cardiovascular risk factors. Results: In a total of 1016 patients (730 males and 286 females), (mean age 57.2 ± 8.8 years). Complete lipid profiles of 1016 patients were recorded. Regarding the CAD patients with complete lipid profiles, 72% had lag in lipid profile control as against the current guidelines in at least one of the three main lipid parameters: low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and/or triglycerides. LDLc was not within target levels in 64.2% of these high risk patients; HDLc was abnormal in 35%, and triglycerides were elevated in 25% despite monthly follow up at the opd. Conclusion: Most of the patients treated with statins, especially those with a high cardiovascular risk, do not meet recommended lipid targets and/or have a high frequency of abnormal HDLc and TG levels. The results of this study show that significant differences exist between the recommendations in the guidelines and clinical practice, as well as highlighting the need for a more intensive and integrated management of dyslipidemia in high-risk patients. Keywords: Lipid profile, CAD, Lipoprotein

Background: Advances in both X-ray sources and X-ray optics have dramatically improved the feasibility of these techniques in various fields. Aims: We aimed to evaluate the frequency of dentinal microcracks observed after root canal preparation with ProTaper Gold (PTG), Hyflex electrodischarge machining (HEDM), Reciproc (RPC), and WaveOne Gold (WOG) using synchrotron radiation-based micro-computed tomographic (SR-μCT) analysis. Subjects and Methods: Forty mandibular molars were assigned to 4 experimental groups (n = 10) according to the file system used for the root canal preparation: Group 1: PTG (25/0.08), Group 2: HEDM (25/0.08), Group 3: RPC (25/0.08), and Group 4: WOG (25/0.07). The specimens were scanned on SR-μCT system before and after root canal preparation. The pre- and postoperative cross-sectional images (N = 183,200) of the mesial roots were screened to identify the presence of dentinal microcracks. The number of microcracks was determined as a percentage for each group. Statistical Analysis: There was no necessity of statistical analysis in the present study. The number of microcracks was determined as a percentage for each group. Results: Among the four file systems tested, HEDM (0.9%) has shown a fewer number of new dentinal microcracks. Conclusions: SR-μCT can be used as a reliable diagnostic tool for further implications.

Background: Left ventricular remodeling (LVR) after ST-elevation myocardial infarction (STEMI) harbingers poor prognosis. Three-dimensional echocardiography (3DE) is more accurate than 2 D echo for the assessment of left ventricle (LV) shape. We assessed LV geometry with 3D ECHO 6 months after STEMI in patients who had primary angioplasty. Materials and Methods: In this prospective study, morphological and functional analysis of LV with 3D ECHO (volumes, LVEF, 3D sphericity index [SI]) was assessed up to 7 days and 6 months in 42 STEMI patients. The LVR was considered for increase >15% of the end diastolic volume of the LV (LVEDV) 6 months after the STEMI, compared to the LVEDV up to 7 days of it. Results: Sixteen (38%) patients had LVR. 3D Echocardiographic measurements up to 7 days after the acute myocardial infarction (AMI) 1-LVEDV in ventricular remodeling group was 99.8 ± 19.1 ml and in no ventricular remodeling group was 87 ± 18.2 mL (P = 0.037); 2-LVEF was 0.48 ± 0.01 and 51 ± 0.02 (P