Comparison of Pre-eclampsia Screening Algorithms in the First Trimester of Pregnancy Being Used in Thai Nguyen Province.

Objective To compare the rates of pregnancies in high-risk groups for preeclampsia recommended for aspirin prophylactic when screened using various common algorithms. Methods This cross-sectional study was conducted on 1726 pregnant women from 11 to 13 weeks six days of gestation receiving antenatal care at two hospitals: Thai Nguyen National Hospital and a hospital in Thai Nguyen Province from October 2022 to October 2023. All participants provided consent for the study. We collected maternal characteristics, obstetric history, mean arterial pressure (MAP), mean uterine artery-PI (UtA-PI), and placental growth factor serum (PLGF). Screening performance estimates were calculated using the Fetal Medicine Foundation (FMF) and National Institute for Health and Care Excellence (NICE) guidelines. All pregnant women in the study had their preeclampsia risk assessed using all three algorithms with two cut-off points. Our data was collected, entered and analyzed using SPSS software 20.0 (IBM Corp., Armonk, NY). Categorical data was reported as frequency and percentage. McNemar's test was used for analyzing differences in the sizes of individual groups. Results In our study, the most common high-risk factor identified was the history of preeclampsia, 132 cases (7.6%). According to the NICE guideline, BMI ≥ 35 (kg/m²) is considered a moderate risk factor for preeclampsia. Several risk factors, such as BMI ≥ 35 kg/m² and history of diabetes mellitus type 1, were not present in any participants. Only one pregnant woman had chronic kidney disease (0.06%). Out of the 1726 pregnant women surveyed, the rates of high-risk preeclampsia were as follows: 9.9% (171 cases) based on algorithm 1; 10.8% (187 cases) based on algorithm 2 with a cut-off point > 1/100, 11.8% (203 cases) with a cut-off point > 1/150; 10.3 % (178 cases) based on algorithm 3 with a cut-off point > 1/100, and 11.6% (201 cases) with a cut-off point > 1/150. Among these algorithms, pregnant women in the high-risk preeclampsia group were advised to consider taking low-dose aspirin. Conclusion Screening for pre-eclampsia based on NICE recommendations resulted in a lower number of high-risk pregnant women requiring prophylactic aspirin use compared to other algorithms. This means that some pregnant women at risk of developing preeclampsia are not recommended to use aspirin as a preventive measure. Adding PLGF to the screening strategy will help us get closer to pregnant women who are truly at risk of progressing to preterm preeclampsia.

Integrated Antigenic and Nucleic Acid Detection in Single Virions and Extracellular Vesicles with Viral Content.

Virion-mediated outbreaks are imminent and despite rapid responses, continue to cause adverse symptoms and death. Therefore, tunable, sensitive, high-throughput assays are needed to help diagnose future virion-mediated outbreaks. Herein, we developed a tunable in situ assay to selectively enrich virions and extracellular vesicles (EVs) and simultaneously detect antigens and nucleic acids at a single-particle resolution. The Biochip Antigen and RNA Assay (BARA) enhanced sensitivities compared to quantitative reverse-transcription polymerase chain reaction (qRT-PCR), enabling the detection of virions in asymptomatic patients, genetic mutations in single virions, and enabling the continued long-term expression of viral RNA in the EV-enriched subpopulation in the plasma of patients with post-acute sequelae of COVID-19. BARA revealed highly accurate diagnoses of COVID-19 by simultaneously detecting the spike glycoprotein and nucleocapsid-encoding RNA in saliva and nasopharyngeal swab samples. Altogether, the single-particle detection of antigens and viral RNA provides a tunable framework for the diagnosis, monitoring, and mutation screening of current and future outbreaks. This article is protected by copyright. All rights reserved.

Adjustment of optical absorption in phosphorene through electron-phonon coupling and an electric field.

This study investigates the optical absorption of monolayer phosphorene, focusing on its response to the electron-phonon coupling (EPC) and an electric field. Using a tight-binding Hamiltonian model based on the Barisic-Labbe-Friedel-Su-Schrieffer-Heeger model and the Kubo formula, we calculate the electronic band structure and optical absorption characteristics. The anisotropic dispersion of carriers along armchair and zigzag directions leads to distinct optical responses. Positive and negative EPC effects increase and decrease hopping parameters, respectively, enlarging and reducing/closing the band gap. Moreover, both EPCs cause an admixture of blue and red shift spectrum along the armchair direction, while a red (blue) shift spectrum is observed for positive (negative) EPC along the zigzag direction. Incorporating electric field effects in the EPC increases band gaps for both positive and negative EPC activities, resulting in shifted optical peaks along both directions.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Engineering a tunable micropattern-array assay to sort single extracellular vesicles and particles to detect RNA and protein in situ.

The molecular heterogeneity of extracellular vesicles (EVs) and the co-isolation of physically similar particles, such as lipoproteins (LPs), confounds and limits the sensitivity of EV bulk biomarker characterization. Herein, we present a single-EV and particle (siEVP) protein and RNA assay (siEVP PRA) to simultaneously detect mRNAs, miRNAs, and proteins in subpopulations of EVs and LPs. The siEVP PRA immobilizes and sorts particles via positive immunoselection onto micropatterns and focuses biomolecular signals in situ. By detecting EVPs at a single-particle resolution, the siEVP PRA outperformed the sensitivities of bulk-analysis benchmark assays for RNA and protein. To assess the specificity of RNA detection in complex biofluids, EVs from various glioma cell lines were processed with small RNA sequencing, whereby two mRNAs and two miRNAs associated with glioblastoma multiforme (GBM) were chosen for cross-validation. Despite the presence of single-EV-LP co-isolates in serum, the siEVP PRA detected GBM-associated vesicular RNA profiles in GBM patient siEVPs. The siEVP PRA effectively examines intravesicular, intervesicular, and interparticle heterogeneity with diagnostic promise.

An immunogold single extracellular vesicular RNA and protein (Au SERP) biochip to predict responses to immunotherapy in non-small cell lung cancer patients.

Conventional PD-L1 immunohistochemical tissue biopsies only predict 20%-40% of non-small cell lung cancer (NSCLC) patients that will respond positively to anti-PD-1/PD-L1 immunotherapy. Herein, we present an immunogold biochip to quantify single extracellular vesicular RNA and protein (Au SERP) as a non-invasive alternative. With only 20 µl of purified serum, PD-1/PD-L1 proteins on the surface of extracellular vesicles (EVs) and EV PD-1/PD-L1 messenger RNA (mRNA) cargo were detected at a single-vesicle resolution and exceeded the sensitivities of their bulk-analysis conventional counterparts, ELISA and qRT-PCR, by 1000 times. By testing a cohort of 27 non-responding and 27 responding NSCLC patients, Au SERP indicated that the single-EV mRNA biomarkers surpass the single-EV protein biomarkers in predicting patient responses to immunotherapy. Dual single-EV PD-1/PD-L1 mRNA detection differentiated responders from non-responders with an accuracy of 72.2% and achieved an NSCLC diagnosis accuracy of 93.2%, suggesting the potential for Au SERP to provide enhanced immunotherapy predictions and cancer diagnoses within the clinical setting.

Microfluidic harvesting of breast cancer tumor spheroid-derived extracellular vesicles from immobilized microgels for single-vesicle analysis.

Investigating cellular and vesicular heterogeneity in breast cancer remains a challenge, which encourages the development of controllable in vitro systems that mimic the tumor microenvironment. Although three-dimensional cell culture better recapitulates the heterogeneity observed in tumor growth and extracellular vesicle (EV) biogenesis, the physiological relevance is often contrasted with the control offered by two-dimensional cell culture. Therefore, to challenge this misconception we developed a novel microfluidic system harboring highly tunable three-dimensional EV microbioreactors (EVµBRs) to model micrometastatic EV release in breast cancer while capitalizing on the convenient, low-volume, and sterile interface provided by microfluidics. The diameter and cellular occupancy of the EVµBRs could be precisely tailored to various configurations, supporting the formation of breast cancer tumor spheroids. To immobilize the EVµBRs within a microchannel and facilitate EV extraction, oxygen inhibition in free-radical polymerization was repurposed to rapidly generate two-layer hydrodynamic traps in situ using a digital-micromirror device (DMD)-based ultraviolet (UV) projection system. Breast cancer tumor spheroid-derived EVs were harvested with as little as 20 µL from the microfluidic system and quantified by single-EV immunofluorescence for CD63 and CD81. Despite the low-volume extraction, differences in biomarker expression and coexpression of the tetraspanins on single EVs were observed. Furthermore, the EVµBRs were capable of recapitulating heterogeneity at a cellular and vesicular degree, indicating the utility and robustness of the microfluidic system to investigate physiologically relevant EVs in breast cancer and other disease models.

Drop-off behaviour of Bt-resistant and Bt-susceptible Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) larvae on Bt-cotton and non-Bt cotton plants.

The highest natural mortality rate of larval Lepidoptera in field populations occurs in the first instar, but it is highly variable. The pattern and degree of survival is not easily predicted but depends on their ability to establish on host plants. Lepidopteran larval dispersal behaviour, known as 'drop-off', happens when the host is unsuitable for larvae to settle and begin feeding. Understanding drop-off behaviour of Helicoverpa armigera (Hübner) with and without physiological resistance to Bt toxins on Bt and non-Bt cotton plants is an important component for resistance management strategies for this insect. We examined the drop-off behaviour of H. armigera to determine: (1) whether they move the same way or differently in response to Bt and non-Bt, and (2) could H. armigera larvae detect Bt toxin levels in cotton plants or did they move independently of toxin levels? In this study, we assessed the drop-off behaviour of Bt-resistant and Bt-susceptible H. armigera neonates on artificial diets and cotton plants with and without Bt toxin during the first 12 h after hatching. Bt-resistant and Bt-susceptible H. armigera neonates behaved differently on Bt and non-Bt substrates. The percentages of Bt-resistant larvae that dropped off Bt and non-Bt cotton plants were not significantly different. In contrast, significantly more Bt-susceptible larvae dropped off Bt cotton than non-Bt cotton plants over time. Although Bt-susceptible larvae could not detect Bt toxin, they showed preference on non-Bt toxin substrates and were more likely to drop off substrates with Bt toxin.

Effects of a Novel Erectogenic Condom on Men and Women's Sexual Pleasure: Randomized Controlled Trial.

We tested whether CSD500 (Futura Medical; Guildford, UK), a novel condom containing erectogenic gel designed to increase penile firmness, penile size, and erection duration, results in greater sexual pleasure. In 2017-2020, we randomized heterosexual couples in Thanh Hoa, Vietnam to use CSD500 (N = 248) or standard condoms (N = 252) and followed them up for six months. Women completed the Quality of Sexual Experience (QSE) scale; men completed the QSE, Sexual Experience Questionnaire (SEX-Q), and 11 condom acceptability items. Female participants' mean age was 32.1 years (SD = 0.24; range 21-46). QSE scores were higher among women (B, 0.12; 95% CI, 0.03-0.21) and men (B, 0.21; 95% CI, 0.08-0.35) in the CSD500 relative to the control arm. SEX-Q scores were higher among men in the CSD500 compared to the control arm (B, 3.22; 95% CI, 1.53-4.91). Higher proportions of men in the CSD500 relative to the control arm reported the condom felt "natural" during sex (68.6% vs. 32.3%; p < .01) and that sex with the condom felt "a lot better" than condomless sex (15.5% vs. 5.3%; p < .01). Compared with standard condoms, CSD500 use was associated with higher reports of sexual pleasure and condom acceptability.

Liposome interaction with macrophages and foam cells for atherosclerosis treatment: effects of size, surface charge and lipid composition.

Liposomes are potential drug carriers for atherosclerosis therapy due to low immunogenicity and ease of surface modifications that allow them to have prolonged circulation half-life and specifically target atherosclerotic sites to increase uptake efficiency. However, the effects of their size, charge, and lipid compositions on macrophage and foam cell behaviour are not fully understood. In this study, liposomes of different sizes (60 nm, 100 nm and 180 nm), charges (-40 mV, -20 mV, neutral, +15 mV and +30 mV) and lipid compositions (1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, L-a-phosphatidylcholine, and egg sphingomyelin) were synthesized, characterized and exposed to macrophages and foam cells. Compared to 100 nm neutral 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) liposomes, flow cytometry and confocal imaging indicated that cationic liposomes and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DSPC) liposomes were internalized more by both macrophages and foam cells. Through endocytosis inhibition, phagocytosis and clathrin-mediated endocytosis were identified as the dominant mechanisms of uptake. Anionic and DSPC liposomes induced more cholesterol efflux capacity in foam cells. These results provide a guide for the optimal size, charge, and lipid composition of liposomes as drug carriers for atherosclerosis treatment.

Keratin-Alginate Sponges Support Healing of Partial-Thickness Burns.

Deep partial-thickness burns damage most of the dermis and can cause severe pain, scarring, and mortality if left untreated. This study serves to evaluate the effectiveness of crosslinked keratin-alginate composite sponges as dermal substitutes for deep partial-thickness burns. Crosslinked keratin-alginate sponges were tested for the ability to support human dermal fibroblasts in vitro and to support the closure and healing of partial-thickness burn wounds in Sus scrofa pigs. Keratin-alginate composite sponges supported the enhanced proliferation of human dermal fibroblasts compared to alginate-only sponges and exhibited decreased contraction in vitro when compared to keratin only sponges. As dermal substitutes in vivo, the sponges supported the expression of keratin 14, alpha-smooth muscle actin, and collagen IV within wound sites, comparable to collagen sponges. Keratin-alginate composite sponges supported the regeneration of basement membranes in the wounds more than in collagen-treated wounds and non-grafted controls, suggesting the subsequent development of pathological scar tissues may be minimized. Results from this study indicate that crosslinked keratin-alginate sponges are suitable alternative dermal substitutes for clinical applications in wound healing and skin regeneration.

Anti-inflammatory potential of simvastatin loaded nanoliposomes in 2D and 3D foam cell models.

Atherosclerosis is a multifactorial disease triggered and sustained by risk factors such as high cholesterol, high blood pressure and unhealthy lifestyle. Inflammation plays a pivotal role in atherosclerosis pathogenesis. In this study, we developed a simvastatin (STAT) loaded nanoliposomal formulation (LIPOSTAT) which can deliver the drug into atherosclerotic plaque, when administered intravenously. This formulation is easily prepared, stable, and biocompatible with minimal burst release for effective drug delivery. 2D and 3D in vitro models were examined towards anti-inflammatory effects of STAT, both free and in combination with liposomes. LIPOSTAT induced greater cholesterol efflux in the 2D foam cells and significantly reduced inflammation in both 2D and 3D models. LIPOSTAT alleviated inflammation by reducing the secretion of early and late phase pro-inflammatory cytokines, monocyte adherence marker, and lipid accumulation cytokines. Additionally, the 3D foam cell spheroid model is a convenient and practical approach in testing various anti-atherosclerotic drugs without the need for human tissue.

Analyzing Inter-Leukocyte Communication and Migration In Vitro: Neutrophils Play an Essential Role in Monocyte Activation During Swarming.

Neutrophils are known to be the first responders to infection or injury. However, as inflammation progresses, other leukocytes become increasingly important in inflammation propagation, tissue reconstruction, and inflammation resolution. In recent years, there has been an increase in publications that analyze neutrophil behavior in vitro, but there remains a gap in the literature for in vitro technologies that enable quantitatively measuring interactions between different types of human leukocytes. Here, we used an in vitro platform that mimics inflammation by inducing neutrophil swarming to analyze the behavior of various leukocytes in a swarming setting. Using human peripheral blood leukocytes isolated directly from whole blood, we found that myeloid cells and lymphoid cells had different migratory behaviors. Myeloid cells, which are predominately neutrophils, exhibited swarming behavior. This behavior was not seen with lymphoid cells. We perturbed the peripheral blood leukocyte system by adding exogenous leukotriene B4 (LTB4) to the medium. Notably, only the myeloid cell compartment was significantly changed by the addition of LTB4. Additionally, LTB4 had no significant impact on myeloid cell migration during the recruitment phase of swarming. To further investigate the myeloid cell compartment, we isolated neutrophils and monocytes to analyze their interaction on the platform. We found that neutrophils increase monocyte migration toward the bioparticle clusters, as measured through speed, chemotactic index, track straightness, and swarm size. These results were confirmed with in vivo mouse experiments, where monocyte accumulation only occurred when neutrophils were present. Additionally, we found that both neutrophils and monocytes release the monocyte chemoattractant proteins CCL2 and CCL3 in the presence of Staphylococcus aureus bioparticles. Furthermore, extracellular vesicles from swarming neutrophils caused monocyte activation. These findings suggest that neutrophils play an essential role in the onset of inflammation not only by sealing off the site of infection or injury, but also by recruiting additional leukocytes to the site.

Prevalence and genotype distribution of JC polyomavirus in urine from patients with hematological malignancies in Vietnam.

JC virus (JCV) causes progressive multifocal leukoencephalopathy in immunocompromised patients. The prevalence and genotype patterns of JCV vary between different geographical regions. This study was done to investigate the prevalence and genotype distribution of JCV in patients with hematological malignancies in Vietnam. A total of 48 urine samples were collected from patients with hematological malignancies. DNA was extracted and detection of JCV was by nested-polymerase chain reaction. Sequence analysis was obtained and a phylogenetic tree was constructed for genotyping of JCV. Twenty-seven (56.25%) urine samples tested positive for JCV. JCV genotype 7 was only observed in this study. Subtype analysis showed that JCV subtype 7A was the most commonly prevalent, followed by 7B1 and 7C1. Other subtypes were not detected in this population. There were no significant differences associated with age, gender, and biochemical parameters between patients with JCV and without JCV excretion in urine. The present study showed a high prevalence of JCV in the urine of patients with hematologic malignancies. The most common genotype found in this population was JCV subtype 7A.

Immunomagnetic sequential ultrafiltration (iSUF) platform for enrichment and purification of extracellular vesicles from biofluids.

Extracellular vesicles (EVs) derived from tumor cells have the potential to provide a much-needed source of non-invasive molecular biomarkers for liquid biopsies. However, current methods for EV isolation have limited specificity towards tumor-derived EVs that limit their clinical use. Here, we present an approach called immunomagnetic sequential ultrafiltration (iSUF) that consists of sequential stages of purification and enrichment of EVs in approximately 2 h. In iSUF, EVs present in different volumes of biofluids (0.5-100 mL) can be significantly enriched (up to 1000 times), with up to 99% removal of contaminating proteins (e.g., albumin). The EV recovery rate by iSUF for cell culture media (CCM), serum, and urine corresponded to 98.0% ± 3.6%, 96.0% ± 2.0% and 94.0% ± 1.9%, respectively (p > 0.05). The final step of iSUF enables the separation of tumor-specific EVs by incorporating immunomagnetic beads to target EV subpopulations. Serum from a cohort of clinical samples from metastatic breast cancer (BC) patients and healthy donors were processed by the iSUF platform and the isolated EVs from patients showed significantly higher expression levels of BC biomarkers (i.e., HER2, CD24, and miR21).

Sociodemographic Factors Associated with Request for Labor Epidural Analgesia in a Tertiary Obstetric Hospital in Vietnam.

This study is aimed at examining the sociodemographic factors associated with the utilization of labor epidural analgesia at a large obstetric and gynecology hospital in Vietnam. This was a cross-sectional study of women who underwent vaginal delivery in September 2018 at the Hanoi Obstetrics and Gynecology Hospital. The utilization of epidural analgesia during labor was determined. Univariate and multivariate regression models were applied to evaluate the association between patient demographic and socioeconomic factors and request for labor epidural analgesia. A total of 417 women had vaginal deliveries during the study period. 207 women utilized epidural analgesia for pain relief during labor, and 210 did not. Parturients older than 35 years of age (OR 2.84, 95% CI 1.11-8.17), multiparous women (OR 2.8 95% CI 1.85-4.25), women living from an urban area, women with higher income (OR 6.47, 95% CI 2.59-19.23), and women with higher level of education were more likely to utilize labor epidurals. Factors related to a parturient request for epidural analgesia during labor at our tertiary obstetric hospital included age greater than 35 years, multiparity, and high income and education levels. Educational outreach to women about the benefits of epidural analgesia can target women who do not share these demographic characteristics.

Palladin isoforms 3 and 4 regulate cancer-associated fibroblast pro-tumor functions in pancreatic ductal adenocarcinoma.

Pancreatic Ductal Adenocarcinoma (PDAC) has a five-year survival under 10%. Treatment is compromised due to a fibrotic-like stromal remodeling process, known as desmoplasia, which limits therapeutic perfusion, supports tumor progression, and establishes an immunosuppressive microenvironment. These processes are driven by cancer-associated fibroblasts (CAFs), functionally activated through transforming growth factor beta1 (TGFß1). CAFs produce a topographically aligned extracellular matrix (ECM) that correlates with reduced overall survival. Paradoxically, ablation of CAF populations results in a more aggressive disease, suggesting CAFs can also restrain PDAC progression. Thus, unraveling the mechanism(s) underlying CAF functions could lead to therapies that reinstate the tumor-suppressive features of the pancreatic stroma. CAF activation involves the f-actin organizing protein palladin. CAFs express two palladin isoforms (iso3 and iso4) which are up-regulated in response to TGFß1. However, the roles of iso3 and iso4 in CAF functions remain elusive. Using a CAF-derived ECM model, we uncovered that iso3/iso4 are required to sustain TGFß1-dependent CAF activation, secrete immunosuppressive cytokines, and produce a pro-tumoral ECM. Findings demonstrate a novel role for CAF palladin and suggest that iso3/iso4 regulate both redundant and specific tumor-supportive desmoplastic functions. This study highlights the therapeutic potential of targeting CAFs to restore fibroblastic anti-tumor activity in the pancreatic microenvironment.

Crystal structures of glutathione- and inhibitor-bound human GGT1: critical interactions within the cysteinylglycine binding site.

Overexpression of γ-glutamyl transpeptidase (GGT1) has been implicated in an array of human diseases including asthma, reperfusion injury, and cancer. Inhibitors are needed for therapy, but development of potent, specific inhibitors of GGT1 has been hampered by a lack of structural information regarding substrate binding and cleavage. To enhance our understanding of the molecular mechanism of substrate cleavage, we have solved the crystal structures of human GGT1 (hGGT1) with glutathione (a substrate) and a phosphate-glutathione analog (an irreversible inhibitor) bound in the active site. These are the first structures of any eukaryotic GGT with the cysteinylglycine region of the substrate-binding site occupied. These structures and the structure of apo-hGGT reveal movement of amino acid residues within the active site as the substrate binds. Asn-401 and Thr-381 each form hydrogen bonds with two atoms of GSH spanning the γ-glutamyl bond. Three different atoms of hGGT1 interact with the carboxyl oxygen of the cysteine of GSH. Interactions between the enzyme and substrate change as the substrate moves deeper into the active site cleft. The substrate reorients and a new hydrogen bond is formed between the substrate and the oxyanion hole. Thr-381 is locked into a single conformation as an acyl bond forms between the substrate and the enzyme. These data provide insight on a molecular level into the substrate specificity of hGGT1 and provide an explanation for seemingly disparate observations regarding the enzymatic activity of hGGT1 mutants. This knowledge will aid in the design of clinically useful hGGT1 inhibitors.

Liposomal Nanotherapy for Treatment of Atherosclerosis.

Atherosclerosis is a chronic disease that can lead to life-threatening events such as myocardial infarction and stroke, is characterized by the build-up of lipids and immune cells within the arterial wall. It is understood that inflammation is a hallmark of atherosclerosis and can be a target for therapy. In support of this concept, an injectable nanoliposomal formulation encapsulating fluocinolone acetonide (FA), a corticosteroid, is developed that allows for drug delivery to atherosclerotic plaques while reducing the systemic exposure to off-target tissues. In this study, FA is successfully incorporated into liposomal nanocarriers of around 100 nm in size with loading efficiency of 90% and the formulation exhibits sustained release up to 25 d. The anti-inflammatory effect and cholesterol efflux capability of FA-liposomes are demonstrated in vitro. In vivo studies carried out with an apolipoprotein E-knockout (Apoe-/- ) mouse model of atherosclerosis show accumulation of liposomes in atherosclerotic plaques, colocalization with plaque macrophages and anti-atherogenic effect over 3 weeks of treatment. This FA-liposomal-based nanocarrier represents a novel potent nanotherapeutic option for atherosclerosis.

Surface engineering within a microchannel for hydrodynamic and self-assembled cell patterning.

The applications of cell patterning are widespread due to the high-throughput testing and different resolutions offered by these platforms. Cell patterning has aided in deconvoluting in vivo experiments to better characterize cellular mechanisms and increase therapeutic output. Here, we present a technique for engineering an artificial surface via surface chemistry to form large-scale arrays of cells within a microchannel by employing microstamping. By changing the approach in surface chemistry, H1568 cells were patterned hydrodynamically using immunoaffinity, and neutrophils were patterned through self-assembly via chemotaxis. The high patterning efficiencies (93% for hydrodynamic patterning and 68% for self-assembled patterning) and the lack of secondary adhesion demonstrate the reproducibility of the platform. The interaction between H1568 and neutrophils was visualized and quantified to determine the capability of the platform to encourage cell-cell interaction. With the introduction of H1568 cells into the self-assembled patterning platform, a significant hindrance in the neutrophils' ability to swarm was observed, indicating the important roles of inflammatory mediators within the nonsmall cell lung cancer tumor microenvironment.