In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer.

Introduction: Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments. Material and Methods: For in vitro study we used thin layer chromatography (TAC) for phytochemical screening, total antioxidant capacity (TLC) assay for antioxidant capacity, and hemolytic activity test for toxicity of Neuropilins (NRPs). We performed bioinformatic analyses to predict protein structures, molecular docking, pharmacophore modeling, and virtual screening to reveal interactions with oncogenes. We conducted 200 ns Molecular Dynamics (MD) simulations and MMGBSA calculations to assess the complex dynamics and stability. Results: We identified phytochemical constituents in Nigella sativa leaves, including tannins, saponins, steroids, and cardiac glycosides, while phlobatannins and terpenoids were absent. The leaves contained 9.4% ± 0.04% alkaloids and 1.9% ± 0.05% saponins. Methanol extract exhibited the highest yield and antioxidant capacity, with Total Flavonoid Content at 127.51 ± 0.76 mg/100 g and Total Phenolic Content at 134.39 ± 0.589 mg GAE/100 g. Hemolysis testing showed varying degrees of hemolysis for different extracts. In-silico analysis indicated stable Neuropilin complexes with key signaling pathways relevant for anti-cancer therapy. Molecular docking scores at different possesses (0, C-50, C -80, C-120,C -150, C -200 ns) revealed strong hydrogen bonding in the complexes and showed -12.9, -11.6, and -11.2 binding Affinities (kcal/mol) to support their stability. Our MD simulations analysis at 200ns confirmed the stability of Neuropilin complexes with the signaling pathways protein PI3K. The calculated binding free energies using MMGBSA provided valuable quantitative information on ligand potency on different time steps. These findings highlight the potential health benefits of N. sativa leaves and their possible role in anti-cancer treatments targeting angiogenesis. Conclusion: Nigella sativa leaves have shown significant medical potential due to their bioactive compounds, which exhibit strong properties in supporting organogenic processes related to cancer. Furthermore, studies have highlighted the promising role of neuropilins in anticancer treatment, demonstrating stable interactions and potential as targeted therapy specifically for breast cancer.

A review on extraction, composition, structure, and biological activities of polysaccharides from different parts of Nelumbo nucifera.

Nelumbo nucifera (lotus plant) is an important member of the Nelumbonaceae family. This review summarizes the studies conducted on it since the past 15 years to provide an understanding on future areas of focus. Different parts of this plant, that is, leaves, roots, and seeds, have been used as food and for the treatment of various diseases. Polysaccharides have been extracted from different parts using different methods. The manuscript reviews the methods of extraction of polysaccharides used for leaves, roots, and seeds, along with their yield. Some methods can provide better yield while some provide better biological activity with low yield. The composition and structure of extracted polysaccharides have been determined in some studies. Although monosaccharide composition has been determined in various studies, too little information about the structure of polysaccharides from N. nucifera is available in the current literature. Different useful biological activities have been explored using in vivo and in vitro methods, which include antioxidant, antidiabetic, antitumor, anti-osteoporotic, immunomodulatory, and prebiotic activities. Antitumor activity from polysaccharides of lotus leaves is yet to be explored, besides lotus root has been underexplored as compared to other parts (leaves and seeds) according to our literature survey. Studies dedicated to the successful use of combination of extraction methods can be conducted in future. The plant provides a therapeutic as well as nutraceutical potential; however, antimicrobial activity and synergistic relationships of polysaccharides from different parts of the plant need further exploration.

Solitary Rectal Ulcer Syndrome in Patients Presenting With Lower Gastrointestinal Bleeding: A Tertiary-Care Hospital Experience.

BACKGROUND: Solitary rectal ulcer syndrome (SRUS) is a benign rectal condition associated with defecation disorder that has multifactor pathologies and variable findings on presentation, endoscopy, and histopathology. A diagnostic dilemma with an overlap of differentials and step-wise management that starts with conservative therapies and goes up to repeated surgeries in case of failure of the conservative approach. OBJECTIVE: This study aims to observe clinical, endoscopic, and histological features of SRUS in patients presenting with lower gastrointestinal bleeding. MATERIAL AND METHODS: The study was conducted at the Department of Gastroenterology, Medical Teaching Institute, Lady Reading Hospital Peshawar from October 2018 to April 2020. After written informed consent, 257 patients (149 males and 108 females) from ages 15 to 70 who presented with lower GI bleeding were included via non-probability convenient sampling. Sociodemographic details were recorded in a pre-designed proforma. A colonoscopy was performed with the Colonoscope CF200 Z, Olympus Tokyo, Japan, and findings were noted. Suspected lesions were magnified, dyed with 0.2% indigo carmine, biopsied from the middle and edges of the ulcer, and sent for histopathology. All data were recorded and analyzed in SPSS-20. The mean with SD was calculated for quantitative variables, and frequency and percentages were calculated for qualitative variables. The chi-square test was used to check the significance, and a p-value of <0.05 was considered statistically significant. RESULTS: SRUS was found in 17 (6.6%) patients with lower GI bleeding, with a male predominance of 57% (n=11). Perirectal bleeding, constipation, mucous discharge, abdominal pain, and anemia were common clinical findings. Solitary lesions, ulceration, and anterior rectum location were the most common endoscopy findings. Obliterated lamina propria with collagen, ulceration, crypt distortion, and inflammatory infiltrates were common histopathological findings. CONCLUSION: SRUS is a benign defecation disorder commonly presenting with lower GI bleeding, constipation, straining, and abdominal pain. It needs a stepwise approach with conservative management, medical management, biofeedback, and surgeries as a last resort.

Breast Cancer Dataset, Classification and Detection Using Deep Learning.

Incorporating scientific research into clinical practice via clinical informatics, which includes genomics, proteomics, bioinformatics, and biostatistics, improves patients' treatment. Computational pathology is a growing subspecialty with the potential to integrate whole slide images, multi-omics data, and health informatics. Pathology and laboratory medicine are critical to diagnosing cancer. This work will review existing computational and digital pathology methods for breast cancer diagnosis with a special focus on deep learning. The paper starts by reviewing public datasets related to breast cancer diagnosis. Additionally, existing deep learning methods for breast cancer diagnosis are reviewed. The publicly available code repositories are introduced as well. The paper is closed by highlighting challenges and future works for deep learning-based diagnosis.

Blue honeysuckle extracts retarded starch digestion by inhibiting glycosidases and changing the starch structure.

Blue honeysuckle rich in anthocyanins can inhibit starch-digesting enzyme activity. This study evaluated the inhibitory effect and mechanism of blue honeysuckle extract (BHE) on glycosidases (α-amylase and α-glucosidase). BHE was a mixed glycosidase inhibitor with an IC50 of 2.36 ± 0.14 and 0.06 ± 0.01 for α-amylase and α-glucosidase, respectively. Fourier transform infrared (FTIR) spectroscopy, multi-fluorescence spectroscopy, and isothermal titration calorimetry (ITC) confirmed that BHE caused the secondary structure change and static fluorescence quenching of glycosidases, and the interaction was an enthalpy-driven exothermic reaction. Molecular docking proved that the main anthocyanin monomers in BHE interacted with glycosidases through hydrogen bonds and van der Waals forces. Moreover, BHE changed the starch structure and prevented starch from being digested by glycosidases. In vivo, BHE and starch-BHE complexes effectively slowed postprandial hyperglycemia. This research provided a theoretical basis for BHE in antidiabetic healthy food research and development.

Apple phlorizin attenuates oxidative stress in Drosophila melanogaster.

Apple phlorizin has a lot of applications owing to its antioxidant and hepatoprotective properties. This study explored the antioxidant effects and life span-prolonging activity of apple phlorizin in Drosophila melanogaster. Treatment with apple phlorizin was found to significantly extend the life span and ameliorate the age-related decline of locomotor function. This life span-extending activity was associated with the increased activity of superoxide dismutase, catalase, mRNA expression of glutamate-cysteine ligase catalytic subunit, cap-n-collar (cnc, homologue of mammalian Nrf2 gene), Keap1, and deacetylase sir2, as well as the downregulation of methuselah. Computational analysis suggested phlorizin could work as a Nrf2 activator and exert its biological activities by interfering with the Keap1 and Nrf2 binding. Therefore, it was concluded that the antioxidant and anti-aging effects of phlorizin might, at least in part, be mediated through the cooperation with the endogenous stress defense system. PRACTICAL APPLICATIONS: Phlorizin, from apple peel, has been used as a nutrient for over 100 years. To date, despite extensive research on phlorizin, a report on its effect on the antioxidant system in fruit flies is yet lacking. This report demonstrates that phlorizin can exert a protective effect on antioxidant issues and prolong life in fruit flies, which is valuable in the rational utilization of phlorizin in functional foods.

Stenting the complex patent ductus arteriosus in tetralogy of Fallot with pulmonary atresia: challenges and outcomes.

Patent ductus arteriosus (PDA) stenting has gained acceptance for palliation in cyanotic congenital heart disease. The PDA in tetralogy of Fallot with pulmonary atresia (ToF-PA) arises, in the left aortic arch, from underneath the arch and connects to the proximal left pulmonary artery, often resulting in stenosis. The PDA is usually elongated and tortuous, making stent implantation challenging. Shorter duration of palliation, aggravation of branch pulmonary artery stenosis resulting in poor growth and difficulty at surgery makes ductal stenting controversial. Access via the carotid and axillary artery reduces complexity of the procedure and improves success, with recent data demonstrating good pulmonary artery growth. Advances in bioresorbable stents offer future promise and will likely resolve some controversies surrounding PDA stenting in ToF-PA.

Colonization and Gut Flora Modulation of Lactobacillus kefiranofaciens ZW3 in the Intestinal Tract of Mice.

This study evaluated the distribution and colonization of Lactobacillus kefiranofaciens ZW3 and determined its capacity to modulate the gut microbiota in an animal model. Based on (1) fluorescence imaging, (2) flow cytometry, and (3) qPCR, we found that ZW3 successfully adhered to mouse mucous tissue and colonized the mouse ileum. Gut microbiota profiling was performed using high-throughput sequencing. After continuous intubation with ZW3 for 1 week, the proportion of Lachnospiraceae, a family of butyric acid-producing bacteria, increased at day 7 (11.9% at day 0 versus 18.4% at day 7). In addition, Lactobacillaceae showed an increasing trend (4% at day 0 versus 13% at day 7) that was accompanied by an observable decline in the Rikenellaceae family (1.58% at day 7, 0.14% at day 14, and 0.75% at day 21) in the tested mouse. The results demonstrate that ZW3 could successfully adhere to and colonize the mouse gut throughout the course of the experiment. The profiling analysis of the gut microbiota also provided evidence supporting the function of ZW3 in improving the intestinal flora of mice.

Rosemary Extract-Mediated Lifespan Extension and Attenuated Oxidative Damage in Drosophila melanogaster Fed on High-Fat Diet.

Rosemary extract has a potent antioxidant activity and is widely used in the food industry. In this study, the lifespan prolonging and antioxidant activity of rosemary extract was evaluated by high-fat-induced oxidative damage in Drosophila melanogaster. The results revealed that the lifespan and climbing ability of fruit flies was enhanced significantly by feeding rosemary extract. Furthermore, feeding with rosemary extract significantly increased the enzyme activity of superoxide dismutase (SOD) and catalase (CAT), and significantly decreased the level of malonaldehyde. The gene expression of SOD, CAT, and nuclear factor erythroid-2 related factor 2 was enhanced and that for methuselah was significantly reduced. The comet assay showed that high-fat diet-induced DNA lesion was significantly reduced in larvae treated with the rosemary extract. Our results suggest that feeding with rosemary extract is effective to the extended lifespan in fruit flies by strengthening of the resistance to high-fat-induced oxidative stress and by stimulating, at least in part, the endogenous antioxidant response.

Techniques for transcatheter retrieval of the occlutech ASD device United Kingdom-European multicenter report.

AIMS: To gather current experience in Occlutech ASD device retrieval, to determine whether snaring is an effective technique and to highlight alternative retrieval techniques; METHODS AND RESULTS: United Kingdom and European Occlutech ASD device implanters reported their experience in dealing with device embolization and retrieval. Six operators reported 12 retrieval cases. Retrieval was successful in 92% (11/12), although in most cases it was not straightforward and required multiple attempts using different techniques and equipment. When each different technique or equipment combination was considered separately, there were a total of 23 retrieval attempts. Fifteen attempts involved snaring the ball on the right atrial disc of the device ("the RA pin"). In 12/15 of these attempts the snare slipped off the RA pin. In 8/15 attempts snaring eventually failed. In two cases retrieval was facilitated by elongating the device in a blood vessel. In three cases retrieval was achieved by grasping the RA pin with the jaws of the Occlutech Flex II delivery cable; CONCLUSIONS: Snares do not grip the RA pin sufficiently to reliably retrieve the device. Funnelling the device into a blood vessel or grasping the RA pin with the jaws of the delivery cable may be successful alternatives. © 2016 Wiley Periodicals, Inc.