6-Bromo quinazoline derivatives as cytotoxic agents: design, synthesis, molecular docking and MD simulation.

Based on unselectively, several side effects and drug resistance of available anticancer agents, the development and research for novel anticancer agents is necessary. In this study, a new series of quinazoline-4(3H)-one derivatives having a thiol group at position 2 of the quinazoline ring (8a-8 h) were designed and synthesized as potential anticancer agents. The Chemical structures of all compounds were characterized by 1H-NMR, 13C-NMR, and Mass spectroscopy. The antiproliferative activity of all derivatives were determined against two cancer cell lines (MCF-7 and SW480) and one normal cell lines (MRC-5) by the MTT method. Cisplatin, Erlotinib and Doxorubicin were used as positive controls. The results of in vitro screening showed that 8a with an aliphatic linker to SH group was the most potent compound with IC50 values of 15.85 ± 3.32 and 17.85 ± 0.92 µM against MCF-7 and SW480 cell lines, respectively. 8a indicated significantly better potency compared to Erlotinib in the MCF-7 cell line. The cytotoxic results obtained from testing compound 8a on the normal cell line, revealing an IC50 value of 84.20 ± 1.72 µM, provide compelling evidence of its selectivity in distinguishing between tumorigenic and non-tumorigenic cell lines. Structure-activity relationship indicated that the variation in the anticancer activities of quinazoline-4(3H)-one derivatives was affected by different substitutions on the SH position. Molecular docking and MD simulation were carried out for consideration of the binding affinity of compounds against EGFR and EGFR-mutated. The binding energy of compounds 8a and 8c were calculated at -6.7 and - 5.3 kcal.mol- 1, respectively. Compounds 8a and 8c were found to establish hydrogen bonds and some other important interactions with key residue. The DFT analysis was also performed at the B3LYP/6-31 + G(d, p) level for compounds 8a, 8c and Erlotinib. Compound 8a was thermodynamically more stable than 8c. Also, the calculated theoretical and experimental data for the IR spectrum were in agreement. The obtained results delineated that the 8a can be considered an appropriate pharmacophore to develop as an anti-proliferative agent.

An Evaluation of the User Experience and Privacy Concerns of Individuals Misusing Opioids Using a Location Tracking Mobile Application.

Opioid use disorder is a growing public health concern in the United States, causing economic burden and hindered by stigma. New forms of data, including location data, may improve the effectiveness of interventions for preventing and treating opioid use disorder and/or misuse, increase access to treatment and address racial and ethnic disparities. This qualitative study aimed to identify factors that contribute to users' experience with a publicly available location-tracking mobile app - and investigate their privacy and ethical concerns. The study was conducted through two 15-minute interviews within a 48-h time frame. Participants were recruited from a pool of past research participants, Facebook ads, and referrals, and had to meet certain inclusion criteria related to opioid use disorder and/or misuse. The study had a final sample of 30 participants, 15 male and 15 female. The study suggests that a simple onboarding process and convenient experience can enhance participant adherence to the study app and other similar location-based research apps. However, the study also found that participants had concerns about privacy and transparency about locational privacy when sharing their location data. To improve the app, researchers suggest incorporating user behavior earlier in the app development stage. The study also highlights the importance of addressing ethical and privacy concerns such as limiting the types of collected data, incorporating data encryption and retention strategies, giving access to research staff only, and not sharing the data with third-party companies or law enforcement agencies to increase user satisfaction.

Biomaterials coated with zwitterionic polymer brush demonstrated significant resistance to bacterial adhesion and biofilm formation in comparison to brush coatings incorporated with antibiotics.

A critical problem with the use of biomaterial implants is associated with bacterial adhesion on the surface of implants and in turn the biofilm formation. Among different strategies that have been reported to resolve this dilemma, surface design combined with both antiadhesive and antimicrobial properties has proven to be highly effective. Physiochemical properties of polymer brush coatings possess non-adhesive capability against bacterial adhesion and create a niche for further functionalization. The current study aims to evaluate the effect of antibiotics incorporated into the polymer brush on bacterial adhesion and biofilm formation. Brushes made of zwitterionic polymers were synthesized, functionalized with vancomycin via both physical and chemical conjugation, and grafted onto the silicon rubber surfaces. Antibacterial and antiadhesive measurements of designed coated biomaterials were mediated through the use of a parallel plate flow chamber against biofilm growth developed by Staphylococcus aureus and Escherichia coli over a period of 24 h. The analysis of biofilm growth on designed coated biomaterials showed that the pristine coated zwitterionic brushes are significantly resistant to bacterial adhesion and biofilm formation but not in the polymer brush coating incorporated with antibiotics.

Exploring mobility data for enhancing HIV care engagement in Black/African American and Hispanic/Latinx individuals: a longitudinal observational study protocol.

INTRODUCTION: Increasing engagement in HIV care among people living with HIV, especially those from Black/African American and Hispanic/Latinx communities, is an urgent need. Mobility data that measure individuals' movements over time in combination with sociostructural data (eg, crime, census) can potentially identify barriers and facilitators to HIV care engagement and can enhance public health surveillance and inform interventions. METHODS AND ANALYSIS: The proposed work is a longitudinal observational cohort study aiming to enrol 400 Black/African American and Hispanic/Latinx individuals living with HIV in areas of the USA with high prevalence rates of HIV. Each participant will be asked to share at least 14 consecutive days of mobility data per month through the study app for 1 year and complete surveys at five time points (baseline, 3, 6, 9 and 12 months). The study app will collect Global Positioning System (GPS) data. These GPS data will be merged with other data sets containing information related to HIV care facilities, other healthcare, business and service locations, and sociostructural data. Machine learning and deep learning models will be used for data analysis to identify contextual predictors of HIV care engagement. The study includes interviews with stakeholders to evaluate the implementation and ethical concerns of using mobility data to increase engagement in HIV care. We seek to study the relationship between mobility patterns and HIV care engagement. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Institutional Review Board of the University of California, Irvine (#20205923). Collected data will be deidentified and securely stored. Dissemination of findings will be done through presentations, posters and research papers while collaborating with other research teams.

The effect of induced hypertension in aneurysmal subarachnoid hemorrhage: A narrative review.

Aneurysmal subarachnoid hemorrhage (aSAH) accounts for 2-5% of all strokes, and 10%-15% of aSAH patients will not survive until hospital admission. Induced hypertension (IH) is an emerging therapeutic option being used for the treatment of vasospasm in aSAH. For patients with cerebral vasospasm (CVS) consequent to SAH, IH is implemented to increase systolic blood pressure (SBP) in order to optimize cerebral blood flow (CBF) and prevent delayed cerebral ischemia (DCI). Prophylactic use of IH has been associated with the development of vasospasm and cerebral ischemia in SAH patients. Various trials have defined several different parameters to help clinicians decide when to initiate IH in a SAH patient. However, there is insufficient evidence to recommend therapeutic IH in aSAH due to the possible serious complications like myocardial ischemia, development of posterior reversible encephalopathy syndrome (PRES), pulmonary edema, and even rupture of another unsecured aneurysm. This narrative review showed the favorable impact of IH therapy on aSAH patients; however, it is crucial to conduct further clinical and molecular experiments to shed more light on the effects of IH in aSAH.

A Mobile Health Application Using Geolocation for Behavioral Activity Tracking.

The increasing popularity of mHealth presents an opportunity for collecting rich datasets using mobile phone applications (apps). Our health-monitoring mobile application uses motion detection to track an individual's physical activity and location. The data collected are used to improve health outcomes, such as reducing the risk of chronic diseases and promoting healthier lifestyles through analyzing physical activity patterns. Using smartphone motion detection sensors and GPS receivers, we implemented an energy-efficient tracking algorithm that captures user locations whenever they are in motion. To ensure security and efficiency in data collection and storage, encryption algorithms are used with serverless and scalable cloud storage design. The database schema is designed around Mobile Advertising ID (MAID) as a unique identifier for each device, allowing for accurate tracking and high data quality. Our application uses Google's Activity Recognition Application Programming Interface (API) on Android OS or geofencing and motion sensors on iOS to track most smartphones available. In addition, our app leverages blockchain and traditional payments to streamline the compensations and has an intuitive user interface to encourage participation in research. The mobile tracking app was tested for 20 days on an iPhone 14 Pro Max, finding that it accurately captured location during movement and promptly resumed tracking after inactivity periods, while consuming a low percentage of battery life while running in the background.

The synthesis and development of poly(ε-caprolactone) conjugated polyoxyethylene sorbitan oleate-based micelles for curcumin drug release: an in vitro study on breast cancer cells.

BACKGROUND: it is now known that curcumin (Cur) has a broad range of biological properties; however, photosensitivity, as well as low bioavailability and short half-life, have limited its clinical application. To overcome these problems the synthesis of poly(ε-caprolactone)-Tween 80 (PCL-T) copolymers was performed. METHODS: the copolymers of PCL-T were created using the solvent evaporation/extraction technique. Then Cur was loaded in PCL-T micelles (PCL-T-M) by a self-assembly method. The characterization of copolymer and micelles was assessed by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1HNMR), differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and dynamic light scattering (DLS) methods. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was used to indicate the cytotoxicity of the free Cur, PCL-T-M, and Cur-loaded PCL-T-M. RESULTS: TEM analysis showed monodispersed and spherical shapes with a size of about 90 nm. Cur was released from PCL-T-M at pH 7.4 (45%) and 5.5 (90%) during 6 days. After 24 and 48 h, the IC50 of the free Cur, PCL-T-M, and Cur-loaded PCL-T-M on MCF-7 cells were 80.86 and 54.45 µg mL-1, 278.30 and 236.19 µg mL-1, 45.47 and 19.05 µg mL-1, respectively. CONCLUSION: this study showed that, in the same concentration, the effectiveness of the Cur-loaded PCL-T-M is more than the free Cur, and the nano-system has been able to overcome delivery obstacles of Cur drug. Thus, PCL-T-M can be a candidate as a drug carrier for the delivery of Cur and future therapeutic investigations on breast cancer.

A novel hydrogel containing 4-methylcatechol for skin regeneration: in vitro and in vivo study.

Skin damages are usual physical injuries and different studies have been done to improve wound healing. Hydrogel due to its properties like a moist environment and cooling wound site is a good option for wound treatment. In this study, we evaluated the consequence of using alginate/chitosan hydrogel contained various dosages of 4-Methylcatechol (0, 0.1, 1% (W/W)) on wound healing. After hydrogel fabrication, different tests like SEM, swelling, release, weight loss, and hemo- and cytocompatibility were done to characterize fabricated hydrogels. Finally, the rat model was used to assess Alginate/Chitosan hydrogel's therapeutic function containing 0.1 and 1% of 4-Methylcatechol. The pore size of hydrogel was between 24.5 ± 9 and 62.1 ± 11.63 µm and about 90% of hydrogel was lost after 14 days in the weight loss test. Blood compatibility and MTT assay showed that hydrogels were nontoxic and improved cell proliferation. In vivo test showed that Alginate/Chitosan/0.1%4-Methylcatechol improved wound healing and the results were significantly better than the gauze-treated wound. Our results showed dose depending effect of 4-Methylcatechol on wound healing. This study shows the treatment effect of 4-Methylcatechol on wound healing and the possibility of using it for treating skin injuries.

pH-sensitive HPMCP-chitosan nanoparticles containing 5-aminosalicylic acid and berberine for oral colon delivery in a rat model of ulcerative colitis.

Ulcerative colitis (UC) with continuous and extensive inflammation is limited to the colon mucosa and can lead to abdominal pain, diarrhea, and rectal bleeding. Conventional therapies are associated with several limitations, such as systemic side effects, drug degradation, inactivation, and limited drug uptake, leading to poor bioavailability. These restrictions necessitate drug delivery to the colon so that the drug passes through the stomach unchanged and has selective access to the colon. The present study aimed to formulate 5-aminosalicylic acid (5-ASA) and berberine (BBR) in chitosan nanoparticles cross-linked by HPMCP (hydroxypropyl methylcellulose phthalate) as a colon drug delivery system for UC. Spherical nanoparticles were prepared. They showed appropriate drug release in the simulated intestinal fluid (SIF), while the release did not occur in the simulated gastric fluid (SGF). They improved disease activity parameters (DAI) and ulcer index, increased the length of the colon, and decreased the wet weight of the colon. Furthermore, histopathological colon studies showed an improved therapeutic effect of 5-ASA/HPMCP/CSNPs and BBR/HPMCP/CSNPs. In conclusion, although 5-ASA/HPMCP/CSNPs showed the best effect in the treatment of UC, BBR/HPMCP/CSNPs, and 5-ASA/BBR/HPMCP/CSNPs were also effective in vivo study, and this study anticipated they could be helpful in future clinical applications for the management of UC.

Potential Role of Conversational Agents in Encouraging PrEP Uptake.

Approximately 1.2 million people are living with HIV, with many of them unaware of their infection. Pre-exposure prophylaxis (PrEP) is available to minimize transmission among those at high risk for infection, including men who have sex with men, people who inject drugs, and female sex workers. Despite its availability, there is low usage of PrEP. To address this problem, various digital tools have been examined in HIV research. Among those, conversational agents are still underused and their capacity warrants examination to reach at-risk populations. In this paper, we discuss the potential of conversational agents in increasing uptake of PrEP by addressing barriers experienced among those at high risk for infection.

Neuroblastoma: Essential genetic pathways and current therapeutic options.

Neuroblastoma is a very diverse pediatric tumor that starts from the neural crest, and it is responsible over more than 15% of all juvenile cancer deaths. Clinical signs and symptoms are highly dependent on tumor origin and spread. Bone, lymph nodes, liver, intracranial and orbital tissues, lungs, and the central nervous system are frequently involved in metastatic neuroblastoma. Neuroblastoma enhances with contrast in Computed Tomography (CT) scans as a solid heterogeneous mass which might invade to adjacent ipsilateral or contralateral lymph nodes, tissues, and vessels. Whereas the Magnetic Resonance Imaging (MRI) acquires an acceptable diagnostic accuracy for detection of spinal cord and musculoskeletal metastases. Lorlatinib, a novel ALK inhibitor designed to overcome this resistance, is currently being tested in the New Approaches to Neuroblastoma Therapy (NANT) consortium. Aurora kinase inhibitors have been reported to disrupt MYCN, which is particularly attractive considering the lack of direct inhibitors targeting this driver in neuroblastoma. Sorafenib, a RAF kinase inhibitor, and newer PI3K inhibitors are being tested in children with neuroblastoma in an attempt to block the RAS pathway. Despite various therapies including chemotherapy, radiotherapy, immunotherapy and autologous stem cell transplantation in different neuroblastoma risk groups, most patients undergo surgical removal of the tumoral mass. This review is aimed to summarize the updated knowledge about the neuroblastoma, pathogenesis, it's essential genetic pathways and the current available therapeutic options for neuroblastoma.

Paroxysmal sympathetic hyperactivity during traumatic brain injury.

Traumatic brain injury (TBI) is one of the leading causes of disability, morbidity, and mortality worldwide. Some of the more common etiologies of TBI include closed head injury, penetrating head injury, or an explosive blast head injury. Neuronal damage in TBI is related to both primary injury (caused by mechanical forces), and secondary injury (caused by the subsequent tissue and cellular damages). Recently, it has been well established that Paroxysmal Sympathetic Hyperactivity (PSH), also known as "Sympathetic Storm", is one of the main causes of secondary neuronal injury in TBI patients. The clinical manifestations of PSH include recurrent episodes of sympathetic hyperactivity characterized by tachycardia, systolic hypertension, hyperthermia, tachypnea with hyperpnea, and frank diaphoresis. Given the diverse manifestations of PSH and its notable impact on the outcome of TBI patients, we have comprehensively reviewed the current evidence and discussed the pathophysiology, clinical manifestations, time of onset and duration of PSH during TBI. This article reviews the different types of head injuries that most commonly lead to PSH, possible approaches to manage and minimize PSH complications in TBI and the current prognosis and outcomes of PSH in TBI patients.

Childbearing Intention and its Associated Factors among Adolescent Girls: A Narrative Review.

BACKGROUND: Childbearing is an important phenomenon among adolescents. Studies that have evaluated teenagers' reproductive patterns have found that many adolescents are ambivalent regarding sexual activity and childbearing. In order to assess the patterns of adolescents' reproductive health and pregnancy to conduct interventions, every country needs to collect specific data about childbearing intentions. This study was conducted to determine the factors that may affect the childbearing intentions of adolescents. MATERIALS AND METHODS: This article was a narrative review. Articles derived from PubMed, Scopus, and Web of Science from January of 2000 to February 2015 were assessed. Moreover, gray literature, such as conference abstracts, theses, and the result of technical reports were also used. RESULTS: In total, 15 studies were included in the review. The findings of this study showed that childbearing motives are affected by several factors. According to the results of the qualitative studies, some of the most important effective factors were women's decision-making power and financial issues. In this regard, the quantitative studies noted that the cultural and economic factors were more effective than other factors in determining the childbearing motives of adolescents. CONCLUSIONS: Fertility expectations are affected by several factors and are compatible with a variety of conditions. Moreover, access to precise information on the effects of each factor (positive or negative) is necessary and useful for demographers, policymakers, and other planners in any community.

Effects of biologically produced gold nanoparticles: toxicity assessment in different rat organs after intraperitoneal injection.

Gold nanoparticles (GNPs) have different usage in the medical field. The plan of the present research was to evaluate the influence of the biologically produced GNPs on some rat organs. GNPs were produced using Fusarium oxysporum and their presence was confirmed using spectrophotometer, transmission electron microscope (TEM) and X-ray diffraction (XRD) analyses. The non-toxic and toxic doses of GNPs were determined using MTT assay and were injected intraperitoneally into rats in 3 continuous days and their effects on the kidney, liver and testis were analyzed using microscopic technique. Results revealed that GNPs that were produced had 525 nm absorbance peak and average sizes of about 50 nm, with round and hexagonal shapes. Results from the XRD analysis showed the presence of GNPs in the reaction mixture. MTT assay results revealed that GNPs had somehow toxic effects which depend on their doses. Histological examinations indicated that based on the tested organ, the distribution and effects of GNPs were different which in the testis, the non-toxic dose had no effects and in some parts of the liver and kidney, it induced mild changes. The toxic dose of the GNPs in all the three tested organs induced mild changes. In conclusion, the in vitro and in vivo behaviors of the produced GNPs were different and GNPs even in high concentration induced low changes in the rat organs. This may be due to the short exposure and the use of the biologically produced GNPs.

Optimized fabrication of newly cholesterol biosensor based on nanocellulose.

A novel and sensitive electrochemical cholesterol biosensor was developed based on immobilization cholesterol oxidase (ChOx) on the polyaniline/crystalline nanocellulose/ionic liquid modified Screen-Printed Electrode (PANi/CNC/IL/SPE). A thin layer of ionic liquid (IL) was spin coated on the modified electrode to enhance the electron transferring. Crystalline nanocellulose was prepared from Semantan bamboo (Gigantochloa scortechinii) via acid hydrolysis and it was used to synthesize a nanocomposite of PANi/CNC via in situ oxidative polymerization process. FESEM and TEM images showed high porosity of the nanostructure with no phase separation, revealing the homogenous polymerization of the monomer on the surface of the crystalline cellulose. Research surface methodology (RSM) was carried out to optimize the parameters and conditions leading to maximize the performance and sensitivity of biosensors. The PANi/CNC/IL/GLU/ChOx-modified electrode showed a high sensitivity value of 35.19 µA mM/cm-2 at optimized conditions. The proposed biosensor exhibited a dynamic linear range of 1 µM to 12 mM (R2 = 0.99083) with the low Limit of Detection of 0.48 µM for cholesterol determination. An acceptable reproducibility (RSDs ≤3.76%) and repeatability (RSDs ≤3.31%) with the minimal interference from the coexisting electroactive compounds such as ascorbic acid, uric acid and glucose was observed for proposed biosensor.

Phylogenetic analysis of PR genes in some pome fruit species with the emphasis on transcriptional analysis and ROS response under Erwinia amylovora inoculation in apple.

Attempts were made to identify eight pathogenesis related (PR) genes (i.e., PR-1a, PR3-ch1, PR3-Ch2, PR3-Ch3, PR3-Ch4, PR3-Ch5, PR-5 and PR-8) from 27 genotypes of apple, quince and pear, which are induced in response to inoculation with the pathogen Erwinia amylovora, the causal agent of fire blight. Totally, 32 PR genes of different families were obtained, excepting PR3-Ch2 (amplified only in apple) and PR3-Ch4 (amplified only in apple and pear), the others were successfully amplified in all the genotypes of apple, quince and pear. Evolutionary, the genes of each family exhibited significant homology with each other, as the corresponded phylogenetic neighbor-joining-based dendrograms were taken into consideration. Meanwhile, according to the expression assay, it was deduced that the pathogen activity can significantly affect the expression levels of some selected PR genes of PR3-Ch2, PR3-Ch4, PR3-Ch5 and particularly Cat I in both resistant (MM-111) and semi-susceptible (MM-106) apple rootstocks. Lastly, it was concluded that the pathogen E. amylovora is able to stimulate ROS response, particularly using generation of hydrogen peroxide (H2O2) in both aforementioned apple rootstock.