Novel combinatorial approach: Harnessing HIV protease inhibitors to enhance amphotericin B's antifungal efficacy in cryptococcosis.

Cryptococcosis is a fungal infection that is becoming increasingly prevalent worldwide, particularly among individuals with compromised immune systems, such as HIV patients. Amphotericin B (AmB) is the first-line treatment mainly combined with flucytosine. The scarcity and the prohibitive cost of this regimen urge the use of fluconazole as an alternative, leading to increased rates of treatment failure and relapses. Therefore, there is a critical need for efficient and cost-effective therapy to enhance the efficacy of AmB. In this study, we evaluated the efficacy of the HIV protease inhibitors (PIs) to synergize the activity of AmB in the treatment of cryptococcosis. Five PIs (ritonavir, atazanavir, saquinavir, lopinavir, and nelfinavir) were found to synergistically potentiate the killing activity of AmB against Cryptococcus strains with Æ©FICI ranging between 0.09 and 0.5 against 20 clinical isolates. This synergistic activity was further confirmed in a time-kill assay, where different AmB/PIs combinations exhibited fungicidal activity within 24 hrs. Additionally, PIs in combination with AmB exhibited an extended post-antifungal effect on treated cryptococcal cells for approximately 10 hrs compared to 4 hours with AmB alone. This promising activity against cryptococcal cells did not exhibit increased cytotoxicity towards treated kidney cells, ruling out the risk of drug combination-induced nephrotoxicity. Finally, we evaluated the efficacy of AmB/PIs combinations in the Caenorhabditis elegans model of cryptococcosis, where these combinations significantly reduced the fungal burden of the treated nematodes by approximately 2.44 Log10 CFU (92.4%) compared to the untreated worms and 1.40 Log10 ((39.4%) compared to AmB alone. The cost-effectiveness and accessibility of PIs in resource-limited geographical areas compared to other antifungal agents, such as flucytosine, make them an appealing choice for combination therapy.

Associations Between Food Insecurity and Diet Quality Among Graduate Students and Postdoctoral Trainees in the Health Sciences at a Private University in Boston: A Cross-Sectional Study.

Background: Food insecurity is a pivotal determinant of health outcomes. Little evidence exists on the association between food insecurity and health behaviors and outcomes, including diet quality, among graduate students or postdoctoral trainees. Objectives: This study aimed to examine the association between food insecurity and diet quality among graduate students and postdoctoral trainees at 3 health-focused graduate schools (public health, medical, and dental medicine) within Harvard University. Methods: Between April and June 2023, 1287 graduate students and 458 postdoctoral trainees at the health-focused schools within Harvard University completed a web-based survey. The primary exposure was food security status, assessed using the United States Household Food Security Survey Module. The primary outcome was diet quality, measured using the 30-day Prime Diet Quality Score screener (ranges from 0 to 126, with higher scores indicating healthier diets). The associations between food insecurity and diet quality were examined using multivariable regression models, adjusting for sociodemographic covariates. Results: Among graduate students, compared with those with high food security, diet quality was significantly lower among those experiencing marginal food security [ß: -4.7; 95% confidence interval (CI): -6.5, -2.9], low food security (ß: -5.4; 95% CI: -7.6, -3.3), and very low food security (ß: -4.4; 95% CI: -7.4, -1.4). Poor diet quality included lower intake frequencies of vegetables, fruits, beans/peas/soy products, nuts/seeds, poultry, fish, low-fat dairy, and liquid oils, and higher intake frequencies of refined grains/baked products, sugar-sweetened beverages, and fried foods. Among postdoctoral trainees, compared with those with high food security, diet quality was significantly lower among those experiencing low food security (ß: -5.1; 95% CI: -8.8, -1.4), and very low food security (ß: -5.2; 95% CI: -10.2, -0.2). Poor diet quality included lower intake frequencies of dark green leafy vegetables, other fruits, and whole grains. Conclusions: Graduate students and postdoctoral trainees who experienced degrees of food insecurity reported lower diet quality. These observations underscore the need for policies and interventions to simultaneously reduce food insecurity and improve diet quality.

Adaptive robotic system for the inspection of aerospace slat actuator mount.

Introduction: Robotics uptake in the aerospace industry is low, mainly due to the low-volume/high-accuracy production that aerospace manufacturers require. Furthermore, aerospace manufacturing and assembly sites are often unstructured environments not specifically suitable for robots to operate in. Methods: This paper introduces a robotic visual inspection system using off-the-shelf components able to inspect the mounting holes for wing slat actuators without the need for fixed-coordinate programming; the part just needs to be left within reach of the robot. Our system sets one of the opposed pairs of mounting holes as a reference (the "datum") and then compares the tilt of all other pairs of mounting holes with respect to it. Under the assumption that any deviation in the mounting hole tilt is not systematic but due to normal manufacturing tolerances, our system will either guarantee the correct alignment of all mounting holes or highlight the existence of misaligned holes. Results and Discussion: Computer-vision tilt measurements are performed with an error of below 0.03° using custom optimization for the sub-pixel determination of the center and radius of the mounting holes. The error introduced by the robot's motion from the datum to each of the remaining hole pairs is compensated by moving back to the datum and fixing the orientation again before moving to inspect the next hole pair. This error is estimated to be approximately 0.05°, taking the total tilt error estimation for any mounting hole pair to be 0.08° with respect to the datum. This is confirmed by manually measuring the tilt of the hole pairs using a clock gauge on a calibrated table (not used during normal operation).

Modeling of brain tumors using in vitro, in vivo, and microfluidic models: A review of the current developments.

Brain cancers are some of the most complex diseases to treat, despite the numerous advances science has made in cancer chemotherapy and research. One of the key obstacles to identifying potential cures for this disease is the difficulty in emulating the complexity of the brain and the surrounding microenvironment to understand potential therapeutic approaches. This paper discusses some of the most important in vitro, in vivo, and microfluidic brain tumor models that aim to address these challenges.

Food Insecurity and Ideal Cardiovascular Health Risk Factors Among US Adolescents.

BACKGROUND: Food insecurity, a social and economic condition of limited availability of healthy food, is a risk factor for adverse cardiovascular health outcomes among adults; few studies have been conducted in adolescents. This study explores the association between food insecurity and cardiovascular health risk factors among a nationally representative sample of US adolescents, adopting the American Heart Association's Life's Essential 8 metric. METHODS AND RESULTS: We analyzed data from 2534 adolescents aged 12 to 19 years from the 2013 to 2018 National Health and Nutrition Examination Surveys. In the sample, 24.8% of adolescents lived in food-insecure households. After multivariable adjustment, food insecurity was associated with a 3.23-unit lower total Life's Essential 8 score (95% CI, -6.32, -0.15) and lower scores on diet quality (ß=-5.39 [95% CI, -8.91, -1.87]) and nicotine exposure (ß=-4.85 [95% CI, -9.24, -0.45]). Regarding diet, food insecurity was associated with 5% lower Healthy Eating Index-2015 scores [95% CI, -7%, -2%], particularly lower intakes of whole grains and seafood/plant proteins and marginally higher intake of added sugar. Regarding nicotine exposure, food insecurity was associated with ever use of a tobacco product among m (odds ratio, 1.74 [95% CI, 1.20-2.53]). Compared with their food-secure counterparts, food-insecure male (odds ratio, 1.98 [95% CI, 1.07-3.65]) and female (odds ratio, 3.22 [95% CI, 1.60-6.45]) adolescents had higher odds of living with a current indoor smoker. CONCLUSIONS: In this nationally representative sample of adolescents, food insecurity was associated with multiple indicators of cardiovascular health risk. These findings underscore the need for public health interventions and policies to reduce food insecurity and improve cardioprotective behaviors during adolescence, with particular efforts targeting diet quality and nicotine exposure.

Energy drink consumption among medical students in Jordan - prevalence, attitudes, and associated factors: a cross-sectional study.

Background: Energy drinks (ED) are popular beverages that contain high levels of caffeine, sugar, and other supplements, such as vitamins, which are marketed to enhance mental alertness and physical performance. Studies have shown that energy drink consumption is prevalent among medical students. Therefore, this study aimed to assess the prevalence, attitudes, and factors associated with energy drink consumption among medical students in Jordan. Materials and methods: A cross-sectional study was conducted among medical students from six public universities in Jordan. A total of 307 students were included in the study, and data were collected using an expert-validated questionnaire. The collected data were analyzed using SPSS version 25. Results: The study found that 50% of the sample had consumed ED, half of them started consuming them at the age of 16-18, and learned about them from friends. The primary reasons for consuming ED were to stay awake at night and the majority of them increase their consumption during exams to increase alertness. Regular energy drink consumption was significantly associated with being a student at the university located in the south governorate of Jordan (P=0.021), living alone (P=0.000), drinking alcohol (P=0.049), drinking coffee daily (P=0.043), and consuming more than 10 cans of soft drinks weekly (P=0.001). However, sex, age, academic achievement, and smoking status had no significant association with regular energy drink consumption. Students with regular energy drink consumption experienced daytime sleepiness, decreased concentration, fatigue, and reduced performance more than students with no regular energy drink consumption. Conclusion: The prevalence of energy drink consumption among medical students in Jordan is high, with factors such as social influences, lifestyle behaviors, and academic pressure being significant contributors. This study highlights the need for interventions to promote healthy behaviors and raise awareness about the potential harms of ED among medical students.

Facile sonochemically-assisted bioengineering of titanium dioxide nanoparticles and deciphering their potential in treating breast and lung cancers: biological, molecular, and computational-based investigations.

Combining sonochemistry with phytochemistry is a modern trend in the biosynthesis of metallic nanoparticles (NPs), which contributes to the sustainability of chemical processes and minimizes hazardous effects. Herein, titanium dioxide (TiO2) NPs were bioengineered using a novel and facile ultrasound-assisted approach utilizing the greenly extracted essential oil of Ocimum basilicum. FTIR and UV-Vis spectrophotometry were used to confirm the formation of TiO2 NPs. The X-ray diffraction (XRD) analysis showed the crystalline nature of TiO2 NPs. TEM analysis revealed the spherical morphology of the NPs with sizes ranging from 5.55 to 13.89 nm. Energy-dispersive X-ray (EDX) confirmed the purity of the greenly synthesized NPs. TiO2 NPs demonstrated outstanding antitumor activity against breast (MCF-7) and lung (A-549) cancer cells with estimated IC50 values of 1.73 and 4.79 µg mL-1. The TiO2 NPs were cytocompatible to normal cells (MCF-10A) with a selectivity index (SI) of 8.77 for breast and 3.17 for lung cancer. Biological assays revealed a promising potential for TiO2 NPs to induce apoptosis and arrest cells at the sub-G1 phase of the cell cycle phase in both cancer cell lines. Molecular investigations showed the ability of TiO2 NPs to increase apoptotic genes' expression (Bak and Bax) and their profound ability to elevate the expression of apoptotic proteins (caspases 3 and 7). Molecular docking demonstrated strong binding interactions for TiO2 NPs with caspase 3 and EGFR-TK targets. In conclusion, the greenly synthesized TiO2 NPs exhibited potent antitumor activity and mitochondrion-based cell death against breast and lung cancer cell lines while maintaining cytocompatibility against normal cells.

Elastin recoil is driven by the hydrophobic effect.

Elastin is an extracellular matrix material found in all vertebrates. Its reversible elasticity, robustness, and low stiffness are essential for the function of arteries, lungs, and skin. It is among the most resilient elastic materials known: During a human lifetime, arterial elastin undergoes in excess of 2 × 109 stretching/contracting cycles without replacement, and slow oxidative hardening has been identified as a limiting factor on human lifespan. For over 50 y, the mechanism of entropic recoil has been controversial. Herein, we report a combined NMR and thermomechanical study that establishes the hydrophobic effect as the primary driver of elastin function. Water ordering at the solvent:protein interface was observed as a function of stretch using double quantum 2H NMR, and the most extensive thermodynamic analysis performed to date was obtained by measuring elastin length and volume as a function of force and temperature in normal water, heavy water and with cosolvents. When stretched, elastin's heat capacity increases, water is ordered proportional to the degree of stretching, the internal energy decreases, and heat is released in excess of the work performed. These properties show that recoil in elastin under physiological conditions is primarily driven by the hydrophobic effect rather than by configurational entropy as is the case for rubber. Consistent with this conclusion are decreases in the thermodynamic signatures when cosolvents that alter the hydrophobic effect are introduced. We propose that hydrophobic effect-driven recoil, as opposed to a configurational entropy mechanism where hardening from crystallization can occur, is the origin of elastin's unusual resilience.

Food Insecurity Among Graduate Students and Postdoctoral Trainees.

Importance: Food insecurity on college campuses has emerged as an urgent public health priority; however, there has been a lack of studies focused on graduate students or postdoctoral trainees, particularly those enrolled at private academic institutions. Objective: To estimate the prevalence of and factors associated with food insecurity among graduate students and postdoctoral trainees at a private academic university in Boston, Massachusetts. Design, Setting, and Participants: In this cross-sectional survey study, a survey on food insecurity was sent to graduate students and postdoctoral trainees at 3 health-focused graduate schools at Harvard University during the end of the spring 2023 academic term (April to June). Participants were studying medicine, dental medicine, or public health. Data analysis was performed from July to September 2023. Exposure: Sociodemographic characteristics of graduate students and postdoctoral trainees. Main Outcomes and Measures: The primary outcome was food insecurity as assessed using the US Household Food Security Survey Module. Food insecurity also encompassed low and very low food security. Bidirectional stepwise logistic regression models were conducted to estimate the factors associated with food insecurity for graduate students and postdoctoral trainees. Results: The analytic sample included 1745 participants (response rate, 55%): 1287 were graduate students and 458 were postdoctoral trainees. The median age of respondents was 29.0 (IQR, 7.0) years, and more than half (1073 [61.5%]) identified as female. A total of 694 respondents (39.8%) identified as Asian, 625 (35.8%) as White, and 426 (24.4%) as being of other race or ethnicity. The prevalence of food insecurity was 17.4% (224 of 1287) among graduate students and 12.7% (58 of 458) among postdoctoral trainees. Among graduate students, factors associated with food insecurity included being Asian (OR, 1.06 [95% CI, 1.01-1.11]) or of other race or ethnicity (OR, 1.07 [95% CI, 1.02-1.13]), receiving financial aid (OR, 1.09 [95% CI, 1.05-1.13]), and having housing instability (OR, 1.53 [95% CI, 1.45-1.61]). Among postdoctoral trainees, factors associated with food insecurity included receiving Supplemental Nutrition Assistance Program benefits (OR, 1.59 [95% CI, 1.28-1.97]), having housing instability (OR, 1.33 [95% CI, 1.22-1.45]), and not owning a car (OR, 1.11 [95% CI, 1.04-1.18]). Conclusions and Relevance: In this study, a substantial proportion of graduate students and postdoctoral trainees at a private academic institution experienced food insecurity during the academic year. These findings underscore the need for national and institutional interventions to address the complex, structural factors related to food insecurity in these distinct populations.

Relations between Parental Acceptance-Rejection and Forgiveness/Vengeance as Mediated by Psychological Adjustment among Egyptian Adults.

The study investigated relations among parental (maternal and paternal) acceptance-rejection and dispositions toward forgiveness and vengeance, as mediated by psychological (mal)adjustment. Data were collected using convenience sampling from 341 adults (87% females) ranging from 18 years to above 52 years old. Measures used were short forms of the maternal and paternal Adult Parental Acceptance-Rejection Questionnaires (PARQ) to investigate recollections of parental acceptance-rejection, the short form of the Adult Personality Assessment Questionnaire (PAQ) to evaluate which participants were psychologically (mal)adjusted, the Heartland Forgiveness Scale (HFS), the Vengeance Scale (VS-10) to investigate levels of forgiveness and vengeance respectively, and a Personal Information Form (PIF). The results indicated that participants perceived significant signs of paternal rejection and substantial maternal acceptance during childhood. Men and women self-reported fair psychological adjustment. Women reported having no disposition toward vengeance, whereas men slightly leaned toward vengeance. Participants were equally likely to be unforgiving as forgiving. Psychological adjustment mediated the relations between maternal acceptance (but not paternal acceptance) and forgiveness among men and women. Psychological maladjustment mediated the relations between maternal rejection and vengeance among women, but not men. Psychological maladjustment did not mediate relations between paternal rejection and vengeance. Limitations and implications of the findings are discussed.

The Role of Apolipoproteins in the Commonest Cancers: A Review.

Apolipoproteins (APOs) are vital structural components of plasma lipoproteins that are involved in lipid metabolism and transport. Recent studies have reported an association between apolipoprotein dysregulation and the onset of a variety of human cancers; however, the role of certain APOs in cancer development remains unknown. Based on recent work, we hypothesize that APOs might be involved in the onset of cancer, with a focus on the most common cancers, including breast, lung, gynecological, colorectal, thyroid, gastric, pancreatic, hepatic, and prostate cancers. This review will focus on the evidence supporting this hypothesis, the mechanisms linking APOs to the onset of cancer, and the potential clinical relevance of its various inhibitors.

Anthropometric and Cephalometric Facial Characteristics of Adult Saudi Patients with Skeletal Class III Malocclusions.

Objectives: We aimed to assess adult Saudi patients' facial anthropometry and cephalometric characteristics with skeletal Class III malocclusions compared to Class I malocclusion patients. Materials and Methods: Our cross-sectional study included a review of the orthodontic records of 108 patients: 54 patients with skeletal Class III malocclusions and 54 patients with skeletal Class I malocclusions, equally distributed between males and females. Using anthropometric landmarks, seven angular and eight linear measurements were recorded and compared between Class III and Class I patients. In addition, we compared three horizontal facial proportions and three horizontal neoclassical canons between the two groups. Finally, we used Student's t-tests to compare continuous variables and Chi-square tests for categorical variables. Results: Class III patients had significantly larger mandibular length, mandibular plane angle, mid- and lower-anterior face height, and posterior face height (P < 0.05) compared to Class I patients. Class III patients had significantly proclined upper incisors, retroclined lower incisors, and an obtuse interincisal angle (P < 0.05). The mouth: nose ratio differed significantly between skeletal Class III and I patients (P = 0.008). The orbital canon was valid in 14.8% of Class I and 9.3% of Class III patients, respectively. The orbitonasal proportion applied only to 31.5% and 20.4% of Class I and III patients, respectively. The naso-oral canon occurred in 18.5% and 1.9% of Class I and III patients, respectively. Conclusion: Saudis with Class III skeletal profiles have some distinctive Class III characteristics not observed in most other ethnic groups. The established horizontal facial proportions, neoclassical facial canons, and Class III skeletal profile did not apply to Saudis with skeletal Class I malocclusions, indicating that these proportions and characteristics may not be suitable as references when planning the surgical treatment for these patients.

Perspectives on healthy eating practices and acceptance of WIC-approved foods among parents of young children enrolled in WIC.

INTRODUCTION: The prevalence of childhood obesity remains high in the United States, particularly among children living in low-income households. Diet quality plays an important role in obesity prevention, particularly among mothers as they serve as role models. Those served by the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) receive nutrient-rich foods aimed at increasing diet quality, yet redemption is low. Digital interventions targeting WIC parents show potential for behavior change and could be used for childhood obesity prevention. METHODS: This study describes the formative research conducted to understand perspectives on healthy eating practices, acceptance of WIC-approved foods, and preferences for the use of digital tools to improve the purchasing and consumption of WIC-approved foods to improve diet quality. In-depth interviews were conducted with 13 WIC parents and caregivers. RESULTS: A variety of definitions for and misconceptions about healthy eating exist among WIC caregivers. Most purchased foods were fruits, vegetables, milk, cheese, and eggs and the least purchased foods were yogurt and peanut butter. The biggest facilitator for purchasing WIC-approved foods was the preference of children and caregivers, whereas the biggest barrier was children's picky eating behaviors. Most caregivers reported using their phone to get nutrition information. Most caregivers reported their interest in receiving weekly text messages and indicated preferences about receiving recipes. CONCLUSION: A text messaging program that includes sending weekly messages, recipes, and nutrition tips is hypothesized to improve diet quality and increase redemption of WIC-approved foods.

Epithelial-Myoepithelial Carcinoma of the Maxilla Arising From Minor Salivary Glands of Hard Palate: A Rare Case Report.

Epithelial-myoepithelial carcinoma is a rare malignant neoplasm of salivary glands. It is specifically found in the major salivary glands. The cases that emerge from minor salivary glands are rarely described. Histologically, it commonly exhibits a characteristic biphasic pattern consisting of epithelial and myoepithelial components. The histopathological resemblance to other benign and malignant neoplasms that also display myoepithelial characteristics makes the differential diagnosis challenging. Each differential diagnosis requires a very different management approach. Considering the difficulties of anatomopathological diagnosis and the rarity of epithelial-myoepithelial carcinomas emerging from minor salivary glands, we report a rare epithelial-myoepithelial carcinoma case of minor salivary glands in a 58-year-old woman. She was referred for a palatal swelling, evolving for more than 35 years, and reported recent pain and nasal obstruction. The mucosal swelling was located in the left maxilla within the hard palate, of a 45-mm-long axis crossing the medial line and extending to the premaxilla, without cervical lymph node involvement. A computed tomography scan revealed a palatal lesion involving the left and the right maxilla. Furthermore, the superior alveolar process, both left and right maxillary sinuses, the nasal cavities, and the nasal septum were included in the lesion. The final diagnosis was difficult to confirm despite multiple biopsies and was determined only from the excised specimen. The diagnosis of this tumor was challenging due to the clinical and histological similarities with other salivary tumors. The aim of this case report is to shed light on the distinctive features of these tumors and explore optimal screening and related management strategies.

Effect of phospholipid head group on ultrasound-triggered drug release and cellular uptake of immunoliposomes.

Liposomes are the most successful nanoparticles used to date to load and deliver chemotherapeutic agents to cancer cells. They are nano-sized vesicles made up of phospholipids, and targeting moieties can be added to their surfaces for the active targeting of specific tumors. Furthermore, Ultrasound can be used to trigger the release of the loaded drugs by disturbing their phospholipid bilayer structure. In this study, we have prepared pegylated liposomes using four types of phospholipids with similar saturated hydrocarbon tails including a phospholipid with no head group attached to the phosphate head (DPPA) and three other phospholipids with different head groups attached to their phosphate heads (DPPC, DPPE and DPPG). The prepared liposomes were conjugated to the monoclonal antibody trastuzumab (TRA) to target the human epidermal growth factor receptor 2 (HER2) overexpressed on HER2-positive cancer cells (HER2+). We have compared the response of the different formulations of liposomes when triggered with low-frequency ultrasound (LFUS) and their cellular uptake by the cancer cells. The results showed that the different formulations had similar size, polydispersity, and stability. TRA-conjugated DPPC liposomes showed the highest sensitivity to LFUS. On the other hand, incubating the cancer cells with TRA-conjugated DPPA liposomes triggered with LFUS showed the highest uptake of the loaded calcein by the HER2+ cells.

Nedaplatin/Peganum harmala Alkaloids Co-Loaded Electrospun, Implantable Nanofibers: A Chemopreventive Nano-Delivery System for Treating and Preventing Breast Cancer Recurrence after Tumorectomy.

Currently, the main pillars in treating breast cancer involve tumorectomy pursued by hormonal, radio, or chemotherapies. Nonetheless, these approaches exhibit severe adverse effects and might suffer from tumor recurrence. Therefore, there is a considerable demand to fabricate an innovative controlled-release nano-delivery system to be implanted after tumor surgical removal to guard against cancer recurrence. In addition, combining platinum-based drugs with phytochemicals is a promising approach to improving the anticancer activity of the chemotherapeutics against tumor cells while minimizing their systemic effects. This study designed polycaprolactone (PCL)-based electrospun nanofiber mats encapsulating nedaplatin (N) and Peganum harmala alkaloid-rich fraction (L). In addition to physicochemical characterization, including average diameters, morphological features, degradation study, thermal stability, and release kinetics study, the formulated nanofibers were assessed in terms of cytotoxicity, where they demonstrated potentiated effects and higher selectivity towards breast cancer cells. The dual-loaded nanofiber mats (N + L@PCL) demonstrated the highest antiproliferative effects against MCF-7 cells with a recorded IC50 of 3.21 µg/mL, as well as the topmost achieved selectivity index (20.45) towards cancer cells amongst all the tested agents (N, L, N@PCL, and L@PCL). This indicates that the dual-loaded nanofiber excelled at conserving the normal breast epithelial cells (MCF-10A). The combined therapy, N + L@PCL treatment, resulted in a significantly higher percent cell population in the late apoptosis and necrosis quartiles as compared to all other treatment groups (p-value of ≤0.001). Moreover, this study of cell cycle kinetics revealed potentiated effects of the dual-loaded nanofiber (N + L@PCL) at trapping more than 90% of cells in the sub-G1 phase and reducing the number of cells undergoing DNA synthesis in the S-phase by 15-fold as compared to nontreated cells; hence, causing cessation of the cell cycle and confirming the apoptosis assay results. As such, our findings suggest the potential use of the designed nanofiber mats as perfect implants to prevent tumor recurrence after tumorectomy.

CTP-based estimated ischemic core: A comparative multicenter study between Olea and RAPID software.

BACKGROUND AND PURPOSE: CTP is increasingly used to assess eligibility for endovascular therapy (EVT) in patients with large vessel occlusions (LVO). There remain variability and inconsistencies between software packages for estimation of ischemic core. We aimed to use heterogenous data from four stroke centers to perform a comparative analysis for CTP-estimated ischemic core between RAPID (iSchemaView) and Olea (Olea Medical). METHODS: In this retrospective multicenter study, patients with anterior circulation LVO who underwent pretreatment CTP, successful EVT (defined TICI ≥ 2b), and follow-up MRI included. Automated CTP analysis was performed using Olea platform [rCBF < 25% and differential time-to-peak (dTTP)>5s] and RAPID (rCBF < 30%). The CTP estimated core volumes were compared against the final infarct volume (FIV) on post treatment MRI-DWI. RESULTS: A total of 151 patients included. The CTP-estimated ischemic core volumes (mean ± SD) were 18.7 ± 18.9 mL on Olea and 10.5 ± 17.9 mL on RAPID significantly different (p < 0.01). The correlation between CTP estimated core and MRI final infarct volume was r = 0.38, p < 0.01 for RAPID and r = 0.39, p < 0.01 for Olea. Both software platforms demonstrated a strong correlation with each other (r = 0.864, p < 0.001). Both software overestimated the ischemic core volume above 70 mL in 4 patients (2.6%). CONCLUSIONS: Substantial variation between Olea and RAPID CTP-estimated core volumes exists, though rates of overcalling of large core were low and identical. Both showed comparable core volume correlation to MRI infarct volume.

Transferrin-Targeted Liposomes in Glioblastoma Therapy: A Review.

Glioblastoma (GBM) is a highly aggressive brain tumor, and its treatment is further complicated by the high selectivity of the blood-brain barrier (BBB). The scientific community is urgently seeking innovative and effective therapeutic solutions. Liposomes are a promising new tool that has shown potential in addressing the limitations of chemotherapy, such as poor bioavailability and toxicity to healthy cells. However, passive targeting strategies based solely on the physicochemical properties of liposomes have proven ineffective due to a lack of tissue specificity. Accordingly, the upregulation of transferrin receptors (TfRs) in brain tissue has led to the development of TfR-targeted anticancer therapeutics. Currently, one of the most widely adopted methods for improving drug delivery in the treatment of GBM and other neurological disorders is the utilization of active targeting strategies that specifically target this receptor. In this review, we discuss the role of Tf-conjugated liposomes in GBM therapy and present some recent studies investigating the drug delivery efficiency of Tf-liposomes; in addition, we address some challenges currently facing this approach to treatment and present some potential improvement possibilities.

Charting the Evolution of Chemoenzymatic Strategies in the Syntheses of Complex Natural Products.

Bolstered by recent advances in bioinformatics, genetics, and enzyme engineering, the field of chemoenzymatic synthesis has enjoyed a rapid increase in popularity and utility. This Perspective explores the integration of enzymes into multistep chemical syntheses, highlighting the unique potential of biocatalytic transformations to streamline the synthesis of complex natural products. In particular, we identify four primary conceptual approaches to chemoenzymatic synthesis and illustrate each with a number of landmark case studies. Future opportunities and challenges are also discussed.

Co-Delivery of Ylang Ylang Oil of Cananga odorata and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer.

Smart pH-responsive niosomes loaded with either Oxaliplatin (Ox), Ylang ylang essential oil (Y-oil), or co-loaded with both compounds (Ox-Y) (Ox@NSs, Y@NSs, and Ox-Y@NSs, respectively) were formulated utilizing the thin film method. The developed nanocontainers had a spherical morphology with mean particle sizes lower than 170 nm and showed negative surface charges, high entrapment efficiencies, and a pH-dependent release over 24 h. The prepared pH-responsive niosomes' cytotoxicity was tested against the invasive triple-negative breast cancer (MDA-MB-231) cells, compared to free OX and Y-oil. All niosomal formulations loaded with Ox and/or Y-oil significantly improved cytotoxic activity relative to their free counterparts. The Ox-Y@NSs demonstrated the lowest IC50 (0.0002 µg/mL) when compared to Ox@NSs (0.006 µg/mL) and Y@NSs (18.39 µg/mL) or unloaded Ox (0.05 µg/mL) and Y-oil (29.01 µg/mL). In addition, the percentages of the MDA-MB-231 cell population in the late apoptotic and necrotic quartiles were profoundly higher in cells treated with the smart Ox-Y@NSs (8.38% and 5.06%) than those exposed to free Ox (7.33% and 1.93%) or Y-oil (2.3% and 2.13%) treatments. Gene expression analysis and protein assays were performed to provide extra elucidation regarding the molecular mechanism by which the prepared pH-sensitive niosomes induce apoptosis. Ox-Y@NSs significantly induced the gene expression of the apoptotic markers Tp53, Bax, and Caspase-7, while downregulating the antiapoptotic Bcl2. As such, Ox-Y@NSs are shown to activate the intrinsic pathway of apoptosis. Moreover, the protein assay ascertained the apoptotic effects of Ox-Y@NSs, generating a 4-fold increase in the relative protein quantity of the late apoptotic marker Caspase-7. Our findings suggest that combining natural essential oil with synthetic platinum-based drugs in pH-responsive nanovesicles is a promising approach to breast cancer therapy.