Fenofibrate-Loaded Biodegradable Nanoparticles for the Treatment of Neovascular Age-Related Macular Degeneration

Fenofibrate-Loaded Biodegradable Nanoparticles for the Treatment of Neovascular Age-Related Macular Degeneration Russell Simmers, Depts. of Physics and Chemistry, with Dr. Qingguo Xu, VCU School of Pharmacy Background: Neovascular age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly population in the industrialized world. The current treatment for neovascular AMD is anti-vascular endothelial growth factor (anti-VEGF) therapy; however, nearly 40-50% of patients do not fully respond to anti-VEGF therapy. Therefore, non-VEGF therapeutics are required for neovascular AMD treatment. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα) agonist and has demonstrated robust therapeutic effects on neovascular AMD in animal models; however, it must be delivered frequently via intravitreal injection due to quick clearance of the drug from the eye, and may induce injection associated side effects such as retinal detachment, ocular hemorrhage and endophthalmitis. Purpose: To develop and optimize fenofibrate-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Feno-NP) with high-drug loading and long-lasting drug release profile to effectively treat neovascular AMD for 6-months with one single intravitreal injection. Methods: Feno-NPs were prepared by emulsification method and were fully characterized in terms of particle size, surface charge, morphology and in vitro drug release profiles and the ocular pharmacokinetics studies were performed in rats following intravitreal injection. Efficacy on neovascular-AMD was determined by measuring vascular leakage, vascular permeability, and the numbers of subretinal neovascular (SRNV) and intraretinal neovascular (IRNV) lesions after intravitreal injection of Feno-NPs in a laser-induced choroid neovascularization (CNV) rat model.https://scholarscompass.vcu.edu/uresposters/1387/thumbnail.jp

Differences in metabonomic profiles of abdominal subcutaneous adipose tissue in women with polycystic ovary syndrome

IntroductionPolycystic ovary syndrome (PCOS) is a complex endocrine disorder that often coexists with a metabolic disorder. Studies have demonstrated that the malfunction of adipose tissue, particularly abdominal adipose tissue, could exacerbate reproductive and metabolic problems in PCOS patients. Adipose tissue-secreted signaling mediators (e.g., lipids and metabolites) would then interact with other body organs, including the ovary, to maintain the systemic equilibrium.MethodsIn this study, we examined adipose samples from PCOS patients and unaffected individuals using a liquid chromatography–mass spectrometry-based metabonomics approach (LC–MS/MS). PCOS biomarkers were selected using multivariate statistical analysis.ResultsOur pathway analysis revealed that these differential metabolites could be engaged in inflammatory diseases and mitochondrial beta-oxidation. We further developed an in vitro PCOS cell model to examine the effects of hyperandrogenism on granulosa cells and related metabolic disorders. We noted that isoleucine recovered the promotive effect on cell apoptosis, inhibitory effect on cell proliferation, sex hormone secretion, and mitochondrial function induced by dehydroepiandrosterone. Our gas chromatography–mass spectrometry targeted analysis (GC–MS/MS) revealed that isoleucine was significantly decreased in PCOS patients.DiscussionBased on these results, we speculate that metabolome alterations are vital in ameliorating PCOS symptoms. This may be a novel therapeutic target for PCOS treatment. Our study provides preliminary evidence that these findings will enhance our ability to accurately diagnose and intervene in PCOS

Self-organized Voids Revisited: Experimental Verification of the Formation Mechanism*

In this paper, several experiments were conducted to further clarify the formation mechanism of self organized void array induced by a single laser beam, including energy-related experiments, refractive-index-contrast-related experiments, depth-related experiments and effective-numerical-aperture experiment. These experiments indicate that the interface spherical aberration is indeed responsible for the formation of void arrays

Reciprocal facilitation between annual plants and burrowing crabs:Implications for the restoration of degraded saltmarshes

Increasing evidence shows that facilitative interactions between species play an essential role in coastal wetland ecosystems. However, there is a lack of understanding of how such interactions can be used for restoration purposes in saltmarsh ecosystems. We therefore studied the mechanisms of reciprocal facilitative interactions between native annual plants, Suaeda salsa, and burrowing crabs, Helice tientsinensis, in a middle-elevation saltmarsh (with generally high plant density and moderate tides) in the Yellow River Delta of China. We investigated the relationship between the densities of the plants and crab burrows in different seasons. Then, we tested whether and how saltmarsh plants and crabs indeed facilitate each other in a series of field and laboratory experiments. Finally, we applied the results by creating a field-scale artificial approach for microtopographic modification to restore a degraded saltmarsh. We found that the density of plant seedlings in spring was positively correlated with the density of crab burrows in the previous autumn; moreover, the density of crab burrows was correlated with the density of plants in summer. The concave-convex surface microtopography created by crabs promoted seed retention and seedling establishment of saltmarsh plants in winter and spring. These plants in turn facilitated crabs by inhibiting predators, providing food and reducing physical stresses for crabs in summer and autumn. The experimental removal of saltmarsh plants decreased crab burrow density, while both transplanting and simulating plants in bare patches promoted crabs. The microtopographic modification, inspired by our new understanding of the interactions between saltmarsh plants and crabs, showed that these degraded saltmarsh ecosystems can be restored by a single ploughing intervention. Synthesis. Our results suggest a reciprocal facilitation between annual plants and burrowing crabs in a middle-elevation saltmarsh ecosystem. This knowledge yielded new restoration options for degraded coastal saltmarshes through the one-time ploughing initiation of microtopographic variation, which could promote the re-establishment of ecosystem engineers and lead to the efficient recovery of pioneer coastal vegetation and associated fauna

Artificial intelligence breast ultrasound and handheld ultrasound in the BI-RADS categorization of breast lesions: A pilot head to head comparison study in screening program

BackgroundArtificial intelligence breast ultrasound diagnostic system (AIBUS) has been introduced as an alternative approach for handheld ultrasound (HHUS), while their results in BI-RADS categorization has not been compared.MethodsThis pilot study was based on a screening program conducted from May 2020 to October 2020 in southeast China. All the participants who received both HHUS and AIBUS were included in the study (N = 344). The ultrasound videos after AIBUS scanning were independently watched by a senior radiologist and a junior radiologist. Agreement rate and weighted Kappa value were used to compare their results in BI-RADS categorization with HHUS.ResultsThe detection rate of breast nodules by HHUS was 14.83%, while the detection rates were 34.01% for AIBUS videos watched by a senior radiologist and 35.76% when watched by a junior radiologist. After AIBUS scanning, the weighted Kappa value for BI-RADS categorization between videos watched by senior radiologists and HHUS was 0.497 (p < 0.001) with an agreement rate of 78.8%, indicating its potential use in breast cancer screening. However, the Kappa value of AIBUS videos watched by junior radiologist was 0.39, when comparing to HHUS.ConclusionAIBUS breast scan can obtain relatively clear images and detect more breast nodules. The results of AIBUS scanning watched by senior radiologists are moderately consistent with HHUS and might be used in screening practice, especially in primary health care with limited numbers of radiologists

Primary renal myxoid liposarcoma with pancreatic invasion on 18F-FDG PET/CT: first case report and literature review

BackgroundMyxoid liposarcoma (MLS) is a rare malignant soft tissue sarcoma that predominantly manifests in the deep soft tissues of the extremities, particularly within the musculature of the thigh. Unlike other types of liposarcoma, MLS demonstrates a propensity for metastasis to atypical sites, including the lung parenchyma, soft tissues, retroperitoneum, mediastinum, breast, liver, thymus, lymph nodes, and bones. The definitive diagnosis primarily relies on histology with HE staining. Imaging modalities such as ultrasound, CT, MRI, and 18F-FDG PET/CT scans serve as valuable tools for tumor identification.Case reportA 57-year-old man presented with symptoms of abdominal distention and vomiting 1 month ago. Contrast-enhancement CT revealed a heterogeneous hypodense mass in the upper-middle part of the left kidney, displaying irregular morphology and protrusion towards the exterior of the kidney, with abundant blood supply and had a maximum dimension of approximately 10.7 cm × 9.0 cm. Additionally, a rounded soft tissue density was identified in the pancreatic body. Multiplanar reconstruction demonstrated a connection between the pancreatic lesion and the kidney mass. 18F-FDG PET/CT was conducted for staging, revealing significant growth of the lesion in the upper-middle part of the left kidney, extending beyond the kidney and infiltrating the pancreatic body. The lesion demonstrated remarkably high 18F-FDG uptake (SUVmax = 10.2, MTV = 136.13 cm3, TLG = 484.62). The postoperative pathological examination confirmed the diagnosis of MLS. On the 10th day post-surgery, the patient presented with tumor recurrence and underwent another surgical resection. Unfortunately, during the operation, the patient experienced a sudden cardiac arrest and died.ConclusionRenal MLS with invasion into the pancreas is very rare in clinical practice. Due to the limited research on the utilization of 18F-FDG PET/CT in this particular context, given the rarity and low incidence of MLS, its role remains largely unexplored. As PET/CT imaging becomes increasingly prevalent, thorough imaging of disease sites becomes indispensable for the development of treatment protocols and the monitoring of treatment response

Early detection of SARS-CoV-2 variants through dynamic co-mutation network surveillance

BackgroundPrecise public health and clinical interventions for the COVID-19 pandemic has spurred a global rush on SARS-CoV-2 variant tracking, but current approaches to variant tracking are challenged by the flood of viral genome sequences leading to a loss of timeliness, accuracy, and reliability. Here, we devised a new co-mutation network framework, aiming to tackle these difficulties in variant surveillance.MethodsTo avoid simultaneous input and modeling of the whole large-scale data, we dynamically investigate the nucleotide covarying pattern of weekly sequences. The community detection algorithm is applied to a co-occurring genomic alteration network constructed from mutation corpora of weekly collected data. Co-mutation communities are identified, extracted, and characterized as variant markers. They contribute to the creation and weekly updates of a community-based variant dictionary tree representing SARS-CoV-2 evolution, where highly similar ones between weeks have been merged to represent the same variants. Emerging communities imply the presence of novel viral variants or new branches of existing variants. This process was benchmarked with worldwide GISAID data and validated using national level data from six COVID-19 hotspot countries.ResultsA total of 235 co-mutation communities were identified after a 120 weeks' investigation of worldwide sequence data, from March 2020 to mid-June 2022. The dictionary tree progressively developed from these communities perfectly recorded the time course of SARS-CoV-2 branching, coinciding with GISAID clades. The time-varying prevalence of these communities in the viral population showed a good match with the emergence and circulation of the variants they represented. All these benchmark results not only exhibited the methodology features but also demonstrated high efficiency in detection of the pandemic variants. When it was applied to regional variant surveillance, our method displayed significantly earlier identification of feature communities of major WHO-named SARS-CoV-2 variants in contrast with Pangolin's monitoring.ConclusionAn efficient genomic surveillance framework built from weekly co-mutation networks and a dynamic community-based variant dictionary tree enables early detection and continuous investigation of SARS-CoV-2 variants overcoming genomic data flood, aiding in the response to the COVID-19 pandemic

The association between alteration of maternal lipid levels and birthweight at term: A within-family comparison.

CONTEXT: Maternal lipid levels affect birthweight and the long-term health of the offsprings. However, this association could be influenced by genetic and other common factors. OBJECTIVE: This work aimed to explore the relationship between maternal lipid levels and birthweight of two pregnancies in the same mother. METHODS: In this population-based cohort study, 705 women and their 1 410 offsprings were included. From an initial sample of women with more than one singleton birth in the database, we made the following exclusions: missing data for pre-pregnancy BMI, pregnancy weight gain, birthweight and lipid values; maternal age less than 19 or older than 44 years old; gestational age 41weeks, gestational diabetes mellitus/diabetic. In the second and third trimesters, serum samples were collected for the determination of fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. Then we assessed the association between maternal lipids and birthweight. RESULTS: Infants of women whose 2nd-trimester TC increased by 10th-20th percentile (-0.92~-0.56 mmol/L) from 1st to 2nd pregnancy were 239.69 (62.32~417.06) g lighter at birth than were infants of women those of 40th-50th percentile (-0.20~-0.03 mmol/L). Parity, gestational age, neonatal gender, maternal pre-pregnancy body mass index, maternal weight gain, and 3rd-trimester TC and HDL-C were all associated with higher birth weight. Every unit increase in TC in the third trimester increases birthweight by 53.13 (14.32 ~91.94) g. CONCLUSION: Maternal TC level is associated with birthweight independent of shared genes. TC may be used to guide diet and predict birthweight combined with ultrasound and other indicators