Search

Breast cancer stands as the leading cause of cancer-related fatalities among women globally, presenting a diverse landscape of histological and molecular c characteristics, treatment response, and prognosis. This investigation examined the impact of soyasaponin IV, a natural product, on mice carrying Ehrlich’s ascites carcinoma (EAC), exploring its potential in blostering the hosts’ defense against cancer. The isolated compounds underwent scrutiny for their cytotoxic effects on breast cancer cell line, with Doxorubicin as the reference standard. Notably, Soyasaponin IV exhibited the highest cytotoxicity. Evaluation of its in vivo antitumor efficacy against EAC revealed a substantial reduction in tumor weight and volume, accompanied by improved histological features of tumor cells. EAC-induced abnormalities, including elevated levels of Malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and nuclear factor-kappa B (NF-κB) were all shown to be upregulated by EAC, while glutathione (GSH), were mitigated in a dose-dependent manner by soyasaponin IV treatment. Soyasaponin IV emerged as a promising strategy for suppressing EAC by impeding the NF-κB and VEGF pathways.

Objective: To evaluate curve correctability, complications, and rate of growth following treatment. Background: Distraction-founded techniques such as traditionally growing rods or magnetically controlled growing rods are the almost globally accepted management patterns for early onset scoliosis. However, periodic lengthening operations are still needed. Moreover, an MCGR is difficult to contour, and implant-associated problems are common. We developed concave side apical control of the growing rod in which an additional anchor site is inserted at the apex to enhance stability and assist in the adjustment of axial deformity. Methods: Entirely skeletally immature early onset scoliosis (EOS) cases with a progressive curve of >40° and without bone or soft tissue weakness were appropriate for this study. Coronal Cobb angle, sagittal parameters, complications, spinal length, and reoperations were documented with at least a 3-year follow-up. Results: In this study, 15 patients were involved. The mean age was 7 years. The mean preoperative Cobb angle was 48°, which postoperatively became 12° with the percentage of coronal correction reaching 75.73%. The mean Cobb angle degrees of correction were 39°. T1-S1 height increased by 10 mm/year. Postoperative complications occurred in two cases with single rod technique and rod breakage. Conclusions: The concave side apical control of the growing rod seems to be a hopeful surgical procedure for the management of EOS. Curve correctability in patients was 60% and can be sustained for a minimum of 2 years. Reoperations and complications might not be constricted, but the complication frequency looks more reasonable than in the current systems.

This study aimed to evaluate the xanthine oxidase (XO) inhibitory activities of seven compounds identified in the potent antioxidant ethyl acetate fraction of Ambrosia maritima L. using various computational tools. Physicochemical properties and density functional theory (DFT) analyses were performed. Subsequently, XO molecular docking was performed to identify the most promising leads. The water solubility of the compounds varied among highly soluble, moderately soluble, and soluble compounds. Four compounds were predicted to have no mutagenic or tumorigenic effect. All compounds were found to have lower binding energies than the oxypurinol standard, indicating their potential as XO inhibitors. The predicted inhibitory interactions, physicochemical properties, and DFT results suggest that two of the compounds (Kaempferol-3-O-glucoside and escululin) are promising drugs or drug leads for the treatment of certain diseases related to increased levels of XO.

Abstract Background Dementia is a pressing problem for families and society. In 2019, a total of 57.4 million people worldwide were estimated to be living with dementia, and this number will almost double every 20 years, especially in Africa and the Middle East. This study aimed to investigate knowledge about dementia among the Egyptian population. A cross-sectional online survey was conducted among a sample of adult Egyptians using a socio-demographics data sheet and a designed dementia knowledge questionnaire. Results Nearly one-third (33.4%) had a poor knowledge score. The items most often answered incorrectly were the sudden onset of cognitive problems as characteristic of dementia (59.3%). The highest percentage of good knowledge was in the manifestations and prevention domains (62.20% and 67.18%, respectively). On the other hand, the lowest rate of good knowledge was in the treatment and life impact domains (35.23% and 25.70%, respectively). Not working in the medical field (OR 2.656, 95% CI: 1.504–4.688, p

The correlation between epigenetic alterations and the pathophysiology of human infertility is progressively being elucidated with the discovery of an increasing number of target genes that exhibit altered expression patterns linked to reproductive abnormalities. Several genes and molecules are emerging as important for the future management of human infertility. In men, microRNAs (miRNAs) like miR-34c, miR-34b, and miR-122 regulate apoptosis, sperm production, and germ cell survival, while other factors, such as miR-449 and sirtuin 1 (SIRT1), influence testicular health, oxidative stress, and mitochondrial function. In women, miR-100-5p, miR-483-5p, and miR-486-5p are linked to ovarian reserve, PCOS, and conditions like endometriosis. Mechanisms such as DNA methylation, histone modification, chromatin restructuring, and the influence of these non-coding RNA (ncRNA) molecules have been identified as potential perturbators of normal spermatogenesis and oogenesis processes. In fact, alteration of these key regulators of epigenetic processes can lead to reproductive disorders such as defective spermatogenesis, failure of oocyte maturation and embryonic development alteration. One of the primary factors contributing to changes in the key epigenetic regulators appear to be oxidative stress, which arises from environmental exposure to toxic substances or unhealthy lifestyle choices. This evidence-based study, retracing the major epigenetic processes, aims to identify and discuss the main epigenetic biomarkers of male and female fertility associated with an oxidative imbalance, providing future perspectives in the diagnosis and management of infertile couples.

Abstract Background Genomic insights in settings where tumour sample sizes are limited to just hundreds or even tens of cells hold great clinical potential, but also present significant technical challenges. We previously developed the DigiPico sequencing platform to accurately identify somatic mutations from such samples. Results Here, we complete this genomic characterisation with copy number. We present a novel protocol, PicoCNV, to call allele-specific somatic copy number alterations from picogram quantities of tumour DNA. We find that PicoCNV provides exactly accurate copy number in 84% of the genome for even the smallest samples, and demonstrate its clinical potential in maintenance therapy. Conclusions PicoCNV complements our existing platform, allowing for accurate and comprehensive genomic characterisations of cancers in settings where only microscopic samples are available.

Pin1 is a pivotal player in interactions with a diverse array of phosphorylated proteins closely linked to critical processes such as carcinogenesis and tumor suppression. Its axial role in cancer initiation and progression, coupled with its overexpression and activation in various cancers render it a potential candidate for the development of targeted therapeutics. While several known Pin1 inhibitors possess favorable enzymatic profiles, their cellular efficacy often falls short. Consequently, the pursuit of novel Pin1 inhibitors has gained considerable attention in the field of medicinal chemistry. In this study, we employed the Phase tool from Schrödinger to construct a structure-based pharmacophore model. Subsequently, 449,008 natural products (NPs) from the SN3 database underwent screening to identify compounds sharing pharmacophoric features with the native ligand. This resulted in 650 compounds, which then underwent molecular docking and binding free energy calculations. Among them, SN0021307, SN0449787 and SN0079231 showed better docking scores with values of −9.891, −7.579 and −7.097 kcal/mol, respectively than the reference compound (−6.064 kcal/mol). Also, SN0021307, SN0449787 and SN0079231 exhibited lower free binding energies (−57.12, −49.81 and −46.05 kcal/mol, respectively) than the reference ligand (−37.75 kcal/mol). Based on these studies, SN0021307, SN0449787, and SN0079231 showed better binding affinity that the reference compound. Further the validation of these findings, molecular dynamics simulations confirmed the stability of the ligand-receptor complex for 100 ns with RMSD ranging from 0.6 to 1.8 Å. Based on these promising results, these three phytochemicals emerge as promising lead compounds warranting comprehensive biological screening in future investigations. These compounds hold great potential for further exploration regarding their efficacy and safety as Pin1 inhibitors, which could usher in new avenues for combating cancer.

Summary: The study of fallopian tube (FT) function in health and disease has been hampered by limited knowledge of FT stem cells and lack of in vitro models of stem cell renewal and differentiation. Using optimized organoid culture conditions to address these limitations, we find that FT stem cell renewal is highly dependent on WNT/β-catenin signaling and engineer endogenous WNT/β-catenin signaling reporter organoids to biomark, isolate, and characterize these cells. Using functional approaches, as well as bulk and single-cell transcriptomics analyses, we show that an endogenous hormonally regulated WNT7A-FZD5 signaling axis is critical for stem cell renewal and that WNT/β-catenin pathway-activated cells form a distinct transcriptomic cluster of FT cells enriched in extracellular matrix (ECM) remodeling and integrin signaling pathways. Overall, we provide a deep characterization of FT stem cells and their molecular requirements for self-renewal, paving the way for mechanistic work investigating the role of stem cells in FT health and disease.

Abstract Background Several researches have examined the impact of inhalation anesthetics, intravenous anesthetics, and muscle relaxants on spectral entropy, but many did not evaluate the extent of neuromuscular block. Besides, they did not inspect the impact of distinct degrees of neuromuscular blockade on spectral entropy under dissimilar saturations of isoflurane inhalation. Hence, this study has evaluated variant degrees of minimum alveolar concentration (MAC) to estimate the isoflurane concentration, along with various levels of neuromuscular blockade. This study aims to evaluate the effect of muscle relaxants (atracurium and rocuronium) on entropy readings (state, response entropy, and response-state difference) during isoflurane anesthesia. This is a prospective randomized study, as forty patients have been included and divided into two study groups: patients in group A received atracurium, while patients in group R received rocuronium. Under 50% and 100% neuromuscular blockage, state and response entropy were observed at MACs of 0.8% and 1%, respectively. Results There was a positive correlation between state (SE) and response entropy (RE) at baseline, different MACs, and different trains of four (TOF) for both atracurium and rocuronium. State and response entropy decreased with increasing MAC of isoflurane (P < 0.001), while atracurium and rocuronium at TOF 50% and 100% showed no effect on SE, RE, or RE-SE (P > 0.05). Conclusions State and response entropy can be used effectively to evaluate the depth of anesthesia at different isoflurane MAC and atracurium or rocuronium doses. Registration number ClinicalTrials.gov identifier: NCT 05097508, Registered October 5, 2021 (prospectively registered), http://www.ClinicalTrial.gov

Purpose: Although there is an established role for microbiome dysbiosis in the pathobiology of colorectal cancer (CRC), CRC patients of various race/ethnicities demonstrate distinct clinical behaviors. Thus, we investigated microbiome dysbiosis in Egyptian, African American (AA), and European American (EA) CRC patients. Patients and methods: CRCs and their corresponding normal tissues from Egyptian (n = 17) patients of the Alexandria University Hospital, Egypt, and tissues from AA (n = 18) and EA (n = 19) patients at the University of Alabama at Birmingham were collected. DNA was isolated from frozen tissues, and the microbiome composition was analyzed by 16S rRNA sequencing. Differential microbial abundance, diversity, and metabolic pathways were identified using linear discriminant analysis (LDA) effect size analyses. Additionally, we compared these profiles with our previously published microbiome data derived from Kenyan CRC patients. Results: Differential microbiome analysis of CRCs across all racial/ethnic groups showed dysbiosis. There were high abundances of Herbaspirillum and Staphylococcus in CRCs of Egyptians, Leptotrichia in CRCs of AAs, Flexspiria and Streptococcus in CRCs of EAs, and Akkermansia muciniphila and Prevotella nigrescens in CRCs of Kenyans (LDA score >4, adj. p-value

Tropomyosin-receptor kinase A (TrkA) is the primary isoform among the tropomyosin-receptor kinases that have been associated with human cancer development, contributing to approximately 7.4% of all cancer cases. TrkA represents an attractive target for cancer treatment; however, currently available TrkA inhibitors face limitations in terms of resistance development and potential toxicity. Hence, the objective of this study was to identify new allosteric-approved inhibitors of TrkA that can overcome these challenges and be employed in cancer therapy. To achieve this goal, a screening of 9,923 drugs from the ChEMBL database was conducted to assess their repurposing potential using molecular docking. The top 49 drug candidates, exhibiting the highest docking scores (−11.569 to −7.962 kcal/mol), underwent MM-GBSA calculations to evaluate their binding energies. Delanzomib and tibalosin, the top two drugs with docking scores of −10.643 and −10.184 kcal/mol, respectively, along with MM-GBSA dG bind values of −67.96 and −50.54 kcal/mol, were subjected to 200 ns molecular dynamic simulations, confirming their stable interactions with TrkA. Based on these findings, we recommend further experimental evaluation of delanzomib and tibalosin to determine their potential as allosteric inhibitors of TrkA. These drugs have the potential to provide more effective and less toxic therapeutic alternatives. The approach employed in this study, which involves repurposing drugs through molecular docking and molecular dynamics, serves as a valuable tool for identifying novel drug candidates with distinct therapeutic uses. This methodology can contribute to reducing the attrition rate and expediting the process of drug discovery.

Salinity is one of abiotic stress that affects plant growth and production. The objective of this study was to investigate the effect of salinity and vermicompost on morphology and physiology parameters of Calliandra haematocephala. The experiment was carried out with salinity treatments at 1000, 2000 3000 ppm in addition to the control (tap water, 280 ppm), vermicompost treatments at 5%, 10%, 15%, and 20% in addition to the control. The results indicated that increasing level of salinity resulted in reduction in vegetative growth and flowering parameters (plant height, number of branches/plant, stem diameter, root length, fresh and dry weights of leaves and roots/plant, number of flowers /plant, as well as fresh and dry weights of flowers /plant), total chlorophylls, total carbohydrates, K+%, Ca2+%, and K+/Na+ ratio, while increased proline, Na+ and Cl−% in the plants. Catalase (CAT), superoxide dismutase (SOD), Ascorbate peroxidase (APX) enzyme activities significantly increased with elevating salinity level from 0 to 3000 ppm. Application of vermicompost with any concentration had a positive effect on vegetative growth and flowering parameters, total chlorophylls, total carbohydrates, nutrient uptake, K+/Na+ ratio, proline content, enzyme activities and reducing accumulation of Na+ and Cl−% toxic ions in leaves. Based on the results, application of vermicompost at 20% recommended for alleviating the harmful efects of salinity on Calliandra haematocephala plants irrigated with saline water at concentration up to 3000 ppm.

Vaginal atrophy is a commonly encountered problem among young cancer survivors. Patients suffer from vaginal dryness, irritation, and dyspareunia secondary to oestrogen deficiency. Oestrogenbased hormone replacement therapy is effective, but unfortunately health concerns or contraindications in cancer survivors frequently limit its use. A 35-year-old female patient with dyspareunia that markedly affected her sexual relationship was referred to the gynaecology clinic. Treatment using topical oestrogen cream and sexual counselling were not successful. We treated her using two submucosal injections of PRP-non-cross-linked hyaluronic acid injections into the vestibule and lower third of the anterior vaginal wall mucosa, spaced a month apart. The patient reported marked reduction of dyspareunia and demonstrated an improvement of FSFI total score 1 month after the second injection. Both the patient and her husband showed an improvement of the index of sexual satisfaction score one month after the second injection compared to their pretreatment scores. Examination of the vaginal mucosa showed improvement of thickness and integrity of the mucosa and increased lubrication. PRP-non-cross-linked hyaluronic acid submucosal injections can be effective for cancer therapy-related vaginal atrophy, coitus-related pain, and sexual satisfaction.

Background: Meniscal lesions are the commonest lesions in the knee, and usually caused by athletic activities. Meniscal lesions diagnosis may need costly imaging modalities like magnetic resonance imaging [MRI]. However, MRI is not available in all medical facilities, especially peripheral and rural continents. Thus, there is a need for a readily available imaging tool. Knee ultrasound may be used as diagnostic modality as it is devoid of economic burden of MRI.Aim of the work: The current work aimed to estimate the diagnostic accuracy of knee ultrasound and to correlate it with the results of MRI for diagnosis of knee meniscal lesions.Patients and methods: Fourty patients with acute or chronic knee pain, swelling or movement restrictions were included. All were assessed by referral physician and submitted to knee ultrasound and MRI. Then results of ultrasound were correlated with that of MRI and diagnostic accuracy measures of ultrasound were calculated [sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV] and overall accuracy].Result: Out of included patients, 28 were males. Their mean age was 36.7 ± 14.4 years [ranged from 15 to 60 years]. The ultrasound detected meniscal tear in 90%, degeneration in 47.5%, Para-meniscal cyst in 25% and discoid meniscus in 40%. The MRI detected meniscal tear in 80%, degeneration in 65%, para-meniscal cyst in 25% and discoid meniscus in 37.5%. For meniscal tear, the ultrasound had 83.3% sensitivity, 50.0% specificity, 93.7% PPV, 25.0% NPV and overall accuracy of 80.0%. Otherwise, the overall accuracy was 75.0% for degenerative changes and 95.0% for para meniscal cyst. Finally, it was 67.5% for discoid meniscus.Conclusion: Ultrasound has shown reasonable diagnostic accuracy in detecting meniscal lesions. It could be used as a screening tool to prevent unnecessary and costly MRI.

Kaolinite was subjected to advanced exfoliation processes to form separated nano-silicate sheets (EXK) with enhanced physicochemical properties as adsorbents. This involved the incorporation of different exfoliating agents, urea (U/EXK), KNO3 (N/EXK), and CTAB (C/EXK), highlighting their impacts on their textural and surficial properties as adsorbents for safranin dye. The applied characterization techniques confirmed the higher exfoliating degree of C/EXK, followed by N/EXK and U/EXK. This appeared significantly in the determined surface area (55.7 m2/g (C/EXK), 36.7 m2/g (U/EXK), and 47.1 m2/g (N/EXK)) and adsorption performances. The C/EXK structure displayed a better safranin uptake capacity (273.2 mg/g) than N/EXK (231 mg/g) and U/EXK (178.4 mg/g). Beside the remarkable differences in textural properties, the advanced mathematical modeling and the corresponding steric and energetic parameters illustrate the mentioned uptake properties. The interface of C/EXK is highly saturated by active uptake sites (Nm = 158.8 mg/g) as compared to N/EXK (109.3 mg/g) and U/EXK (93.4 mg/g), which is in agreement with the characterization findings and the expected higher exposure of siloxane groups. Each of these sites can be filled with four dye molecules using C/EXK and N/EXK, which implies the vertical orientation of these adsorbed ions and the effective operation of multi-molecular mechanisms. The energetic (ΔE < 40 kJ/mol) and thermodynamic investigations indicate the spontaneous, physical, and exothermic uptake of safranin molecules by EXK particulates. These mechanisms might involve dipole bonding (2–29 kJ/mol), electrostatic attraction (2–50 kJ/mol), van der Waals forces (4–10 kJ/mol), and hydrogen bonding (<30 kJ/mol). [ABSTRACT FROM AUTHOR]