Designing, Synthesis, and Anti-Breast Cancer Activity of a Series of New Quinazolin-4(1H)-one Derivatives.

The inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) protein could be a promising treatment for breast cancer. In this regard, docking studies were accomplished on various functionalized organic molecules. Among them, several derivatives of quinazolin-4(1H)-one exhibited anti-breast cancer activity and satisfied the drug likeliness properties. Further, the in vitro inhibitory studies by a series of 2-(2-phenoxyquinolin-3-yl)-2,3-dihydroquinazolin-4(1H)-one molecules showed strong anti-cancer activity than the currently available drug, wortmannin. The MTT cytotoxicity assay was used to predict the anti-proliferative activity of these drugs against MCF-7 cancer cells by inhibiting the PIK3CA protein. The dose-dependent analysis showed a striking decrease in cancer cell viability at 24 h with inhibitory concentrations (IC50 ) of 3b, 3c, 3d, 3f and 3m are 15±1, 17±1, 8±1, 10±1 and 60±1 (nanomoles), respectively. This is the first report in the literature on the inhibition of PIK3CA protein by quinazolinone derivatives that can be used in the treatment of cancer. Quinazolinone analogs have the potential to be safe and economically feasible scaffolds if they are produced using a chemical technique that is both straightforward and amenable to modification. From the cancer research perspective, this study can eventually offer better care for cancer patients.

Lectins from plants and algae act as anti-viral against HIV, influenza and coronaviruses.

BACKGROUND: Carbohydrate-lectin interactions are extremely specific as the lectin is capable of recognising monomeric and oligomeric sugars in a reversible manner. It has been known for a long time that lectins have antibacterial, antifungal, and insecticidal activities. Recently, it has been reported that many lectins can prevent the virus growth by interacting with the viral envelop surface glycoprotein. Spike protein, which is found on the surface of some enveloped viruses, is heavily mannosylated and will have strong affinity for mannose specific lectins. According to the findings, lectins have a high binding affinity for the glycans of the SARS-CoV-2 spike glycoprotein, which contains N-glycosylation sites. As a result, various lectins are being researched and developed as anti-viral agents. RESULTS: According to our in silico studies, the amino acid residues Asn487, Tyr489, Gln493, Lys417, and Tyr505 of the receptor binding domain (RBD) of SARS-CoV-2 formed an interaction with the model lectin Lablab purpureus lectin. Similar interaction for SARS-CoV-2 spike protein was observed with Griffithsin lectin (algal source) as well. These observations demonstrate that lectins could be one of the potential molecules for neutralising coronavirus infection. CONCLUSION: This review focuses on anti-viral lectins isolated and characterized from plants and algae (last 5 years) and showed anti-viral properties against HIV, Influenza, and coronaviruses.

Purification, biochemical characterization, and DPP-IV and α-amylase inhibitory activity of Berberine from Cardiospermum halicacabum.

Diabetes mellitus (DM) has spread across the globe, increasing the risk of obesity, cardiovascular disease, and other comorbidities. Despite substantial research into the development of diabetic treatments that are effective in lowering blood glucose levels, their efficiency is short-lived due to unpleasant side effects such as weight gain and hypoglycemia. The discovery of secondary metabolites in the prevention and treatment of diabetes and its complications has an incentive to take interest in plant-based medications, and enzyme inhibitors have the potential to aid in the treatment and management of DM. This study aims to isolate, characterize, and analyse the influence of berberine-like alkaloids from alcoholic Cardiospermum halicacabum extract in vitro and in silico, as a possible inhibitor of Dipeptidyl peptidase-IV (DPP-IV) and α-amylase, two essential enzymes involved in diabetes. The alkaloid from C. halicacabum was identified as berberine, with an m/z of 336.1263. Purified berberine inhibits DPP-IV with an IC50 of 16.328 ± 1.344 µM and inhibits α-amylase by 72% at 10 µg/mL. In-silico studies demonstrated that berberine was found to bind to the active site of both DPP-IV and α-amylase. The precise mechanism underlying the observation has to be researched further in order to investigate C. halicacabum's anti-diabetic effects and argue for its possible application as alternative medicine.

Biochemical Characterization of Lactose Binding Entadin Lectin from Entada rheedii Seeds with Cytotoxic Activity against Cancer Cell Lines.

A novel Entadin lectin was isolated, purified, and characterized from the seeds of Entada rheedii by ammonium sulfate precipitation, followed by lactose affinity chromatography. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the purified Entadin lectin appeared as a single band (monomeric in nature) with a molecular mass of approximately 20 kDa in both reducing and nonreducing conditions. Mass spectroscopic analysis confirms the molecular weight of Entadin lectin as 19,333 Da. Entadin lectin showed a highest titer value in agglutination against human blood group B red blood cells, and its hemagglutination activity was inhibited by lactose, cellobiose, and galactose. Periodic acid Schiff staining confirmed the glycoprotein nature of Entadin lectin with an approximately 5% carbohydrate content. This lectin is highly stable even after incubation at a wide range of temperatures (30-60 °C) and pHs (6-10). The antiproliferative effect of Entadin lectin against lung cancer cells A549 and cervical cancer cells HeLa showed IC50 values of 28 and 32 µg/mL, respectively, and no antiproliferative activity against normal cells was observed. Cell morphological studies revealed that Entadin lectin induced apoptosis in both A549 and HeLa cancer cells, which was confirmed by acridine orange/ethidium bromide and Hoechst (33258) nuclear counterstaining.

Adverse childhood experiences in families with multiple members diagnosed to have psychiatric illnesses.

OBJECTIVE: Adverse childhood experiences are linked to the development of a number of psychiatric illnesses in adulthood. Our study examined the pattern of adverse childhood experiences and their relation to the age of onset of major psychiatric conditions in individuals from families that had ⩾2 first-degree relatives with major psychiatric conditions (multiplex families), identified as part of an ongoing longitudinal study. METHODS: Our sample consisted of 509 individuals from 215 families. Of these, 268 were affected, i.e., diagnosed with bipolar disorder (n = 61), obsessive-compulsive disorder (n = 58), schizophrenia (n = 52), substance dependence (n = 59) or co-occurring diagnoses (n = 38), while 241 were at-risk first-degree relatives who were either unaffected (n = 210) or had other depressive or anxiety disorders (n = 31). All individuals were evaluated using the Adverse Childhood Experiences - International Questionnaire and total adverse childhood experiences exposure and severity scores were calculated. RESULTS: It was seen that affected males, as a group, had the greatest adverse childhood experiences exposure and severity scores in our sample. A Cox mixed effects model fit by gender revealed that a higher total adverse childhood experiences severity score was associated with significantly increased risk for an earlier age of onset of psychiatric diagnoses in males. A similar model that evaluated the interaction of diagnosis revealed an earlier age of onset in obsessive-compulsive disorder and substance dependence, but not in schizophrenia and bipolar disorder. CONCLUSION: Our study indicates that adverse childhood experiences were associated with an earlier onset of major psychiatric conditions in men and individuals diagnosed with obsessive-compulsive disorder and substance dependence. Ongoing longitudinal assessments in first-degree relatives from these families are expected to identify mechanisms underlying this relationship.

Biochemical characterisation of lectin from Indian hyacinth plant bulbs with potential inhibitory action against human cancer cells.

This work describes purification and characterisation of a monocot mannose-specific lectin from Hyacinth bulbs. The purified lectin has a molecular mass of ∼30kDa in reducing as well as in non-reducing SDS-PAGE. In hydrodynamic studies by Dynamic Light Scattering (DLS) showed that purified lectin was monomeric in nature with a molecular size of 2.38±0.03nm. Agglutination activity of purified lectin was confirmed by rabbit erythrocytes and its agglutination activity was inhibited by d-mannose and a glycoprotein (ovalbumin). Glycoprotein nature of purified lectin was confirmed by Periodic Acid Schiff's (PAS) stain. Purified lectin showed moderate pH and thermal stability by retaining hemagglutination activity from pH 6-8 and temperature up to 60°C. It also suppressed the growth of human colon cancer cells (Caco-2) and cervical cancer cells (HeLa) with IC50 values of 127µg/mL and 158µg/mL respectively, after 24-h treatment. Morphological studies of treated cells (Caco-2 and HeLa) with hyacinth lectin by AO/EB dual staining indicated that purified lectin is capable of inducing apoptosis.

Age- and sex-related differences in the tissue Doppler imaging parameters of left ventricular diastolic dysfunction.

BACKGROUND: The effect of age and gender on tissue Doppler imaging measurements comparing the septal and mitral annulus needs to be investigated. METHODS: We investigated in 276 outpatients in a university cardiology practice the relationship of age and gender to left atrial (LA) size, LA volume, mitral pulse-wave Doppler E/A ratio, E/Ea ratios by tissue Doppler image of mitral annular velocity (TDI), and left ventricular diastolic dysfunction (LVDD) by TDI. RESULTS: Mitral E/A inflow was statistically decreased with age. E/Ea ratios of the lateral and mean of both lateral and septal annulus showed a statistical increase with age, while the E/Ea ratio of the septal annulus did not correlate with age. When comparing men and women of all ages, the mean LA volume for men was 59.2 cm3 +/- 24.36 cm3 versus 48.54 cm3 +/- 16.14 cm3 (P-value < 0.0001) and the mean LA size was 4.0 + 0.51 cm for men and 3.65 + 0.47 for women (P-value < 0.0001). There was no statistical difference between men and women when looking at mitral E/A inflow ratio, deceleration time, E/Ea ratio of the septal annulus, E/Ea ratio of the lateral annulus, E/Ea ratio of the mean of both septal and lateral annulus, and grades of LVDD. CONCLUSION: In patients 70 years of age or older, the mean diastolic grade was mild-to-moderate LVDD when using lateral or mean of septal and lateral annular measurements. When only the septal annular measurements were used to determine diastolic grade, all four age groups showed a mean of mildly to moderately impaired LVDD and showed no correlation with age. There were no differences in tissue Doppler imaging measurements between men and women.

Differences of lateral and septal mitral annulus velocity by tissue Doppler imaging in the evaluation of left ventricular diastolic function.

Left ventricular diastolic dysfunction (LVDD) was investigated in 276 outpatients at a university cardiology practice by tissue Doppler imaging of mitral valve annular velocity. The well-investigated parameters of mitral inflow were used as the standard. Using septal E/Ea ratios, 62 patients (22%) had no LVDD, 44 patients (16%) had mild LVDD, 126 patients (46%) had moderate LVDD, 25 patients (9%) had severe LVDD, and 19 patients (7%) had indeterminate LVDD. Using lateral E/Ea ratios, 131 patients (48%) had no LVDD, 40 patients (14%) had mild LVDD, 62 patients (22%) had moderate LVDD, 9 patients (3%) had severe LVDD, and 12 patients (13%) had indeterminate LVDD. In conclusion, the use of septal tissue Doppler imaging tends to overestimate the severity of LVDD compared with the use of lateral tissue Doppler imaging.

Intraoperative radiofrequency maze procedure for treating atrial fibrillation at the time of valve surgery or coronary artery bypass grafting.

We investigated the prevalence of sinus rhythm at long-term follow-up of 35 patients with atrial fibrillation who had an intraoperative radiofrequency maze procedure at the time of valve surgery or coronary artery bypass grafting. The 35 patients included 22 men and 13 women, mean age 71+/-10 years. Postoperatively, sinus rhythm was present in 24 of 35 patients (69%). In-hospital mortality occurred in 4 of 35 patients (11%). At 29-month follow-up, 28 of 31 in-hospital survivors (90%) were alive. Of the 28 survivors, 18 (64%) were in sinus rhythm.

Colorectal polyps and cancers in asymptomatic average-risk patients: evaluation with CT colonography.

PURPOSE: To compare thin-section multi-detector row computed tomographic (CT) colonography with conventional colonoscopy in the evaluation of colorectal polyps and cancer in asymptomatic average-risk patients. MATERIALS AND METHODS: Sixty-eight asymptomatic men (age > 50 years) scheduled to undergo screening colonoscopy were enrolled in this study. CT colonography was followed by conventional colonoscopy, performed on the same day. Supine and prone CT colonography were performed after colonic insufflation with room air. A gastroenterologist measured all polyps, which were categorized as 1-5, 6-9, or over 10 mm. Biopsy and histologic evaluation were performed of all polyps. CT colonography and colonoscopy results were compared for location, size, and morphology of detected lesions. Point estimates and 95% CIs were provided for specificity and sensitivity of CT by using results at conventional colonoscopy as the reference standard. RESULTS: At colonoscopy, 98 polyps were identified in 39 patients; 21 (21.4%) of 98 were detected at CT colonography. Sensitivity was 11.5% (nine of 78) for polyps 1-5 mm, 52.9% (nine of 17) for polyps 6-9 mm, and 100% (three of three) for polyps over 10 mm. Results at colonoscopy were normal in 29 (42.6%) of 68 patients; at CT colonography, results were correctly identified as normal in 26 of these 29 patients. In one of these patients, a lesion larger than 10 mm was detected at CT colonography. The per-patient specificity of CT was 89.7% (26 of 29; 95% CI: 72.7%, 97.8%). The mean time for CT image interpretation was 9 minutes. CONCLUSION: In patients at average risk for colorectal cancer, CT colonography is a sensitive and specific screening test for detecting polyps 10 mm or larger; the sensitivity for detecting smaller polyps is decreased. Examination findings can be interpreted in a clinically feasible amount of time.