Enhancing Surgical Vision: Augmented Reality in Otolaryngology-Head and Neck Surgery.

Augmented reality (AR) technology has become widely established in otolaryngology-head and neck surgery. Over the past 20 years, numerous AR systems have been investigated and validated across the subspecialties, both in cadaveric and in live surgical studies. AR displays projected through head-mounted devices, microscopes, and endoscopes, most commonly, have demonstrated utility in preoperative planning, intraoperative guidance, and improvement of surgical decision-making. Specifically, they have demonstrated feasibility in guiding tumor margin resections, identifying critical structures intraoperatively, and displaying patient-specific virtual models derived from preoperative imaging, with millimetric accuracy. This review summarizes both established and emerging AR technologies, detailing how their systems work, what features they offer, and their clinical impact across otolaryngology subspecialties. As AR technology continues to advance, its integration holds promise for enhancing surgical precision, simulation training, and ultimately, improving patient outcomes.

Impact of sex and hypoxia on brain region-specific expression of membrane androgen receptor AR45 in rats.

Background: Sex differences in oxidative stress-associated cognitive decline are influenced by sex hormone levels. Notably, oxidative stress-associated neuronal cell death can be exacerbated through testosterone signaling via membrane androgen receptor AR45, which is complexed with G protein Gαq within plasma membrane-associated lipid rafts. The objective of this study was to elucidate the impact of sex on the expression of AR45 and Gαq in brain regions associated with cognitive function, specifically hippocampus subregions and entorhinal cortex. Additionally, we investigated whether chronic intermittent hypoxia (CIH), an oxidative stressor with sex-specific effects, would modulate AR45 and Gαq expression in these brain regions. Methods: Adult male and female Sprague-Dawley rats were exposed to CIH or normoxia (room air) during their sleep phase for 14 days. We quantified AR45 and Gαq protein expression in various cognition-associated brain regions [dorsal hippocampal CA1, CA3, dentate gyrus (DG), and entorhinal cortex (ETC)] via western blotting. For comparisons, AR45 and Gαq protein expression were also assessed in brain regions outside the hippocampal-ETC circuit [thalamus (TH) and striatum (STR)]. Results: The highest AR45 levels were expressed in the hippocampal CA1 and DG while the lowest expression was observed in the extrahippocampal STR. The highest Gαq levels were expressed in the hippocampal-associated ETC while the lowest expression was observed in the extrahippocampal TH. Females expressed higher levels of AR45 in the hippocampal DG compared to males, while no sex differences in Gαq expression were observed regardless of brain region assessed. Moreover, there was no effect of CIH on AR45 or Gαq expression in any of the brain regions examined. AR45 expression was positively correlated with Gαq expression in the CA1, DG, ETC, TH, and STR in a sex-dependent manner. Conclusion: Our findings reveal enrichment of AR45 and Gαq protein expression within the hippocampal-ETC circuit, which is vulnerable to oxidative stress and neurodegeneration during cognitive decline. Nonetheless, CIH does not modulate the expression of AR45 or Gαq. Importantly, there are sex differences in AR45 expression and its association with Gαq expression in various brain regions, which may underlie sex-specific differences in cognitive and motor function-associated declines with aging.

Apple Vision Pro Augmented Reality-Assisted Minimally Invasive Surgical Treatment of Spinal Dural Arteriovenous Fistula.

This report outlines the innovative use of augmented reality (AR) in the surgical planning and treatment of a spinal dural arteriovenous fistula (dAVF) via a minimally invasive technique. AR technology by way of an Apple Vision Pro headset was employed to enhance preoperative visualization and understanding of the pathology, leading to successful surgical ligation of the AVF. This case describes a 56-year-old male presenting with progressive weakness and thoracic myelopathy who showed marked improvement postoperatively, highlighting AR's potential to improve surgical approach and outcomes.

Structural analysis of the human C5a-C5aR1 complex using cryo-electron microscopy.

The complement system is a complex network of proteins that plays a crucial role in the innate immune response. One important component of this system is the C5a-C5aR1 complex, which is critical in the recruitment and activation of immune cells. In-depth investigation of the activation mechanism as well as biased signaling of the C5a-C5aR1 system will facilitate the elucidation of C5a-mediated pathophysiology. In this study, we determined the structure of C5a-C5aR1-Gi complex at a high resolution of 3 Šusing cryo-electron microscopy (Cryo-EM). Our results revealed the binding site of C5a, which consists of a polar recognition region on the extracellular side and an amphipathic pocket within the transmembrane domain. Furthermore, we found that C5a binding induces conformational changes of C5aR1, which subsequently leads to the activation of G protein signaling pathways. Notably, a key residue (M265) located on transmembrane helix 6 (TM6) was identified to play a crucial role in regulating the recruitment of ß-arrestin driven by C5a. This study provides more information about the structure and function of the human C5a-C5aR1 complex, which is essential for the proper functioning of the complement system. The findings of this study can also provide a foundation for the design of new pharmaceuticals targeting this receptor with bias or specificity.

The miRNAs 203a/210-3p/5001-5p regulate the androgen/androgen receptor/YAP-induced migration in prostate cancer cells.

BACKGROUND: Prostate cancer (PCa) patients with elevated level of androgen receptor (AR) correlate with higher metastatic incidence. Protein expression of AR and its target gene prostate-specific antigen (PSA) are elevated in metastatic prostate tumors as compared to organ-confined tumors. Androgen treatment or elevation of AR promotes metastasis of PCa in cell culture and murine model. However, under androgen depleted condition, AR suppressed cell mobility and invasiveness of PCa cells. Androgen deprivation therapy in PCa patients is associated with higher risk of cancer metastasis. We therefore investigated the dual roles of AR and miRNAs on PCa metastasis. METHODS: The PC-3AR (PC-3 cells re-expressing AR) and LNCaP cells were used as PCa cell model. Transwell migration and invasion assay, wound-healing assay, zebrafish xenotransplantation assay, and zebrafish vascular exit assay were used to investigate the role of AR and androgen on PCa metastasis. Micro-Western Array, co-immunoprecipitation and Immunofluorescence were applied to dissect the molecular mechanism lying underneath. The miRNA array, miRNA inhibitors or plasmid, and chromatin immunoprecipitation assay were used to study the role of miRNAs on PCa metastasis. RESULTS: In the absence of androgen, AR repressed the migration and invasion of PCa cells. When androgen was present, AR stimulated the migration and invasion of PCa cells both in vitro and in zebrafish xenotransplantation model. Androgen increased phospho-AR Ser81 and yes-associated protein 1 (YAP), decreased phospho-YAP Ser217, and altered epithelial-mesenchymal transition (EMT) proteins in PCa cells. Co-IP assay demonstrated that androgen augmented the interaction between YAP and AR in nucleus. Knockdown of YAP or treatment with YAP inhibitor abolished the androgen-induced migration and invasion of PCa cells, while overexpression of YAP showed opposite effects. The miRNA array revealed that androgen decreased hsa-miR-5001-5p but increased hsa-miR-203a and hsa-miR-210-3p in PC-3AR cells but not PC-3 cells. Treatment with inhibitors targeting hsa-miR-203a/hsa-miR-210-3p, or overexpression of hsa-miR-5001-5p decreased YAP expression as well as suppressed the androgen-induced migration and invasion of PCa cells. Chromatin immunoprecipitation (ChIP) assay demonstrated that AR binds with promoter region of has-miR-210-3p in the presence of androgen. CONCLUSIONS: Our observations indicated that miRNAs 203a/210-3p/5001-5p regulate the androgen/AR/YAP-induced PCa metastasis.

Phosphorus fertiliser is associated with reduced grass grub (Costelytra giveni) fitness in Epichloë endophyte-infected meadow fescue and perennial ryegrass.

BACKGROUND: Fertiliser applications are well-established tools in pasture-based agricultural landscapes. This study focuses on the impact of phosphorus (P) fertiliser on grass grub (Costelytra giveni), a major pasture pest. This research investigates the interplay between P, plant growth, and grass grub fitness in Epichloë endophyte-infected perennial ryegrass (Epichloë sp. LpTG-3 strain AR37) and meadow fescue infected with E. uncinata (strain MaxR; AR1017), alongside their endophyte-free counterparts. In a glasshouse trial, plants were grown in P-enriched soil with varying Olsen P levels (9, 18, 28 or 78 mg L-1), and grass grubs were introduced. Their survival and weight gain, and plant performance were measured. In a bioassay, grass grubs were placed in specimen vials with P-enriched soils (Olsen P levels 9, 18, 28 and 78 mg L-1) and provided with identical plant material to assess their diet consumption and weight gain. RESULTS: In the glasshouse trial, results highlighted a notable decrease in the survival of grass grub on plants infected with MaxR endophyte, but not with AR37, as well as increasing soil Olsen P levels in both plant species. While grass grub decreased plant performance at the low Olsen P level (9 mg L-1), this effect diminished with increasing P. Likewise, results from the bioassay showed a decrease in diet consumption with increasing soil Olsen P levels. In both trials increasing Olsen P levels correlated with diminished grass grub performance, revealing a nuanced relationship between soil fertility and pest dynamics. CONCLUSION: The study underscores the pivotal role of selected Epichloë endophyte-grass associations in mitigating grass grub damage across varying phosphorus levels. This study highlights the potential to integrate P applications for sustainable pest control against grass grub. Further field trials are required to validate these findings. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Advances in the understanding of androgen receptor structure and function and in the development of next-generation AR-targeted therapeutics.

Androgen receptor (AR) and its ligand androgens are important for development and physiology of various tissues. AR and its ligands also play critical role in the development of various diseases, making it a valuable therapeutic target. AR ligands, both agonists and antagonists, are being widely used to treat pathological conditions, including prostate cancer and hypogonadism. Despite AR being studied widely over the last five decades, the last decade has seen striking advances in the knowledge on AR and discoveries that have the potential to translate to the clinic. This review provides an overview of the advances in AR biology, AR molecular mechanisms of action, and next generation molecules that are currently in development. Several of the areas described in the review are just unraveling and the next decade will bring more clarity on these developments that will put AR at the forefront of both basic biology and drug development.

Animal Reproduction journal and International Symposium on Animal Biology of Reproduction: Historical and personal reflections on two decades of exciting amalgamation of young and old science and scientists.

In 2024, the Brazilian College of Animal Reproduction (CBRA in Portuguese) is proudly celebrating its golden 50th anniversary. Founded in 1974, CBRA has had a very productive and challenging journey of five decades, achieving many important milestones that have established it as a major society and its journal as a major reference in the field of animal reproduction, both in Brazil and internationally. Coincidentally, the Animal Reproduction journal and the International Symposium on Animal Biology (ISABR), both created and sponsored by CBRA, are also celebrating their 20th and 10th anniversary and edition, respectively, this year. These remarkable events are being celebrated in the city of Fortaleza, Brazil, during the 10th edition of ISABR. As someone who had the privilege of playing a leading role in the creation and establishment of both Animal Reproduction journal and ISABR, I am honored to describe here the favorable circumstances that led to these significant achievements. The crucial steps and combined efforts required to make these institutions successful were unconditionally supported by the CBRA. Additionally, significant global networking and scientific collaborations, both individual and collective, have been pivotal in advancing the science and connecting the scientific community, spanning both young and experienced members, for decades. Finally, I hope that this historical article will inspire future generations of scientists in the field to continue CBRA's journey and leadership, ensuring the growth of Animal Reproduction and ISABR advancement to even higher standards.

Protective role of the CD73-A2AR axis in cirrhotic cardiomyopathy through negative feedback regulation of the NF-κB pathway.

Background: Myocardial inflammation and apoptosis induced by cirrhosis are among the primary mechanisms of cirrhotic cardiomyopathy. CD73, a common extracellular nucleotidase also known as 5'-nucleotidase, is associated with the progression of inflammation and immunity in multiple organs. However, the mechanism by which CD73 contributes to myocardial inflammation and apoptosis in cirrhosis remains unclear. Methods: In this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNT-NT5E-mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured. Results: In the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A. Conclusion: Our study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway.

Augmented Reality (AR) in Surgery in Low- and Middle-Income Countries (LMICs): A Scoping Review.

Surgical disparities persist in low- and middle-income countries (LMICs). Insufficient access to surgical care places a large burden on these regions, with high mortality rates for otherwise standard procedures performed in high-income countries (HICs). Augmented Reality (AR) and Virtual Reality (VR) now provide us with a platform to improve the delivery of surgical access and training to LMICs. The use of AR technologies to provide additional training to surgeons and residents globally can help bridge the gap and reduce health disparities in LMICs. The goal of this scoping review is to evaluate whether surgical trainees and surgeons from LMICs have access to or use AR software in their training or practice. A systematic search was conducted on seven databases. Inclusion criteria included populations in LMICs with access to AR-based training. Articles using VR software, or those conducted in HICs were excluded from the review. From the 428 records screened, 58 reports were assessed for eligibility, and of these, a total of six studies were included in the review. Five of the six studies used mentors from an HIC, including the United States (US) and the United Kingdom (UK), whereas one study had mentorship from another LMIC. Three surgical specialties were explored: neurosurgery, plastic surgery, and urology. Although the integration of AR in surgical training is promising, the six studies evaluated in this review emphasize that costs and connection issues are major challenges that can set back these technologies in the operating room. Despite these revelations, with certain improvements, AR training programs are promising as they can help to reduce the global disparity in surgical proficiency.

New and emerging oral therapies for psoriasis.

Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the global population. Traditional systemic treatments, such as methotrexate, cyclosporine, acitretin and fumaric acid esters, have limited efficacy and are associated with significant adverse effects, necessitating regular monitoring and posing risks of long-term toxicity. Recent advancements have introduced biologic drugs that offer improved efficacy and safety profiles. However, their high cost and the inconvenience of parenteral administration limit their accessibility. Consequently, there is a growing interest in developing new, targeted oral therapies. Small molecules, such as phosphodiesterase 4 inhibitors (e.g. apremilast) and TYK2 inhibitor (e.g. deucravacitinib), have shown promising results with favourable safety profiles. Additionally, other novel oral agents targeting specific pathways, including IL-17, IL-23, TNF, S1PR1 and A3AR, are under investigation. These treatments aim to combine the efficacy of biologics with the convenience and accessibility of oral administration, addressing the limitations of current therapies. This narrative review synthesizes the emerging oral therapeutic agents for psoriasis, focusing on their mechanisms of action, stages of development and clinical trial results.

Proximal auditory AR rehabilitation: system integration and wellness applications-from hearing support up toward vestibular rehabilitation.

We present a new rehabilitation system based on novel principles, which consists of an auditory augmented reality (AR) headset we originated. The auditory AR headset, which does not cover both ears, allows users to hear both Real and Virtual environmental sounds at the same time. It can also be used in combination with Hearing Aids. We have studied a system to support hearing-impaired people and conducted a test evaluation. The system was able to provide convenience akin to "reading glasses for sound" to those who had mild hearing disabilities. Furthermore, by combining the system with surrounding speakers, a completely novel virtual auditory illusion was created in which the sound image jumps into the ear and runs away. We name this "proximal auditory AR (PAAR)" system. This system directly affects the unconscious level of reflexes for maintaining a standing position and can generate very subtle body motion disturbance. Using this system, we can modulate the standing posture and observe the autonomic nerve system's ability to subliminally compensate for the disturbance, using a stabilometer that measures body sways by center of pressure (COP). We observed a significant difference in the declination of COP only when using the PAAR, which is combined with array speakers and the auditory AR headphone, compared using a conventional closed-type and a bone-conduction headphone. By analyzing such big data of physical movement through machine learning, we expect to realize new systems for diagnosis, rehabilitation, function maintenance, and fall prevention.

Coffee and multiple sclerosis (MS).

Multiple Sclerosis (MS) is a long-term autoimmune disorder affecting the central nervous system, marked by inflammation, demyelination, and neurodegeneration. While the exact cause of MS remains unknown, recent research indicates that environmental factors, particularly diet, may influence the disease's risk and progression. As a result, the potential neuroprotective effects of coffee, one of the most popular beverages worldwide, have garnered significant attention due to its rich content of bioactive compounds. This chapter explores the impact of coffee consumption on patients with Multiple Sclerosis, highlighting how coffee compounds like caffeine, polyphenols, and diterpenes can reduce inflammation and oxidative stress while enhancing neural function. It highlights caffeine's effect in regulating adenosine receptors, specifically A1R and A2AR, which play important roles in neuroinflammation and neuroprotection in MS. The dual role of microglial cells, which promote inflammation while also aiding neuroprotection, is also highlighted concerning caffeine's effects. Furthermore, the potential of A2AR as a therapeutic target in MS and the non-A2AR-dependent neuroprotective benefits of coffee. In this chapter we suggest that the consumption of coffee has no harmful effect on an MS patient and to a larger extent on public health, and informs future research directions and clinical practice, ultimately improving outcomes for individuals living with MS.

Unveiling the role of astrogliosis in Alzheimer's disease Pathology: Insights into mechanisms and therapeutic approaches.

Alzheimer's disease (AD) is one of the most debilitating age-related disorders that affect people globally. It impacts social and cognitive behavior of the individual and is characterized by phosphorylated tau and Aß accumulation. Astrocytesmaintain a quiescent, anti-inflammatory state on anatomical level, expressing few cytokines and exhibit phagocytic activity to remove misfolded proteins. But in AD, in response to specific stimuli, astrocytes overstimulate their phagocytic character with overexpressing cytokine gene modules. Upon interaction with generated Aß and neurofibrillary tangle, astrocytes that are continuously activated release a large number of inflammatory cytokines. This cytokine storm leads to neuroinflammation which is also one of the recognizable features of AD. Astrogliosis eventually promotes cholinergic dysfunction, calcium imbalance, oxidative stress and excitotoxicity. Furthermore, C5aR1, Lcn2/, BDNF/TrkB and PPARα/TFEB signaling dysregulation has a major impact on the disease progression. This review clarifies numerous ways that lead to astrogliosis, which is stimulated by a variety of processes that exacerbate AD pathology and make it a suitable target for AD treatment. Drugs under clinical and preclinical investigations that target several pathways managing astrogliosis and are efficacious in ameliorating the pathology of the disease are also included in this study. D-ALA2GIP, TRAM-34, Genistein, L-serine, MW150 and XPro1595 are examples of few drugs targeting astrogliosis. Therefore, this study may aid in the development of a potent therapeutic agent for ameliorating astrogliosis mediated AD progression.

Augmented reality for chemistry education to promote the use of chemical terminology in teacher training.

Chemistry as a whole is divided into three levels. The macroscopic level describes real, observable phenomena of the material world. The submicroscopic level focuses on particles. The representative level includes pictorial and symbolic representations to visualize substance in its nature. Students often have problems separating these levels and conceptually transfer each of the three levels to the other. Therefore, teachers need to use chemical terminology correctly when teaching the substance-particle concept. Augmented Reality (AR) connects real and virtual world. The observer physically moves in a real environment that integrates virtual elements. The AR technology has great potential for learning in the subject chemistry, especially when it comes to making the "invisible" visible and illustrating scientific phenomena at particle level. The simultaneous presentation should avoid split-attention and offers new possibilities to interactively deal with (M)ER. The question arises whether AR has a positive effect on the use of technical language and the associated understanding of the concept of dealing with (M)ER at the substance and particle levels. With an AR app on the tablet and the AR glasses, the chemical processes of a real experiment are represented by AR visualizations. Therefore, the AR app was piloted. This study captured the chemistry handling with (M)ER of chemistry teachers (N = 30) using a pre-post survey. The participating preservice teachers are described below. Each test includes five tasks elaborated by thinking aloud. The thinking-aloud protocols to acquire the use of the chemical terminology are evaluated in MAXQDA.

The C5AR1/TNFSF13B axis alleviates osteoarthritis by activating the PI3K/Akt/GSK3ß/Nrf2/HO-1 pathway to inhibit ferroptosis.

Chondrocyte ferroptosis induces the occurrence of osteoarthritis (OA). As a key gene of OA, C5a receptor 1 (C5AR1) is related to ferroptosis. Here, we investigated whether C5AR1 interferes with chondrocyte ferroptosis during OA occurrence. C5AR1 was downregulated in PA-treated chondrocytes. Overexpression of C5AR1 increased the cell viability and decreased ferroptosis in chondrocytes. Moreover, Tumor necrosis factor superfamily member 13B (TNFSF13B) was downregulated in PA-treated chondrocytes, and knockdown of TNFSF13B eliminated the inhibitory effect of C5AR1 on ferroptosis in chondrocytes. More importantly, the PI3K/Akt/GSK3ß/Nrf2/HO-1 pathway inhibitor LY294002 reversed the inhibition of C5AR1 or TNFSF13B on ferroptosis in chondrocytes. Finally, we found that C5AR1 alleviated joint tissue lesions and ferroptosis in rats and inhibited the progression of OA in the rat OA model constructed by anterior cruciate ligament transection (ACLT), which was reversed by interfering with TNFSF13B. This study shows that C5AR1 reduces the progression of OA by upregulating TNFSF13B to activate the PI3K/Akt/GSK3ß/Nrf2/HO-1 pathway and thereby inhibiting chondrocyte sensitivity to ferroptosis, indicating that C5AR1 may be a potential therapeutic target for ferroptosis-related diseases.

Multi-omics analysis of overexpressed tumor-associated proteins: gene expression, immunopeptide presentation, and antibody response in oropharyngeal squamous cell carcinoma, with a focus on cancer-testis antigens.

Introduction: The human leukocyte antigen complex (HLA) is essential for inducing specific immune responses to cancer by presenting tumor-associated peptides (TAP) to T cells. Overexpressed tumor associated antigens, mainly cancer-testis antigens (CTA), are outlined as essential targets for immunotherapy in oropharyngeal squamous cell carcinoma (OPSCC). This study assessed the degree to which presentation, gene expression, and antibody response (AR) of TAP, mainly CTA, are correlated in OPSCC patients to evaluate their potential as immunotherapy targets. Materials and methods: Snap-frozen tumor (NLigand/RNA=40), healthy mucosa (NRNA=6), and healthy tonsils (NLigand=5) samples were obtained. RNA-Seq was performed using Illumina HiSeq 2500/NovaSeq 6000 and whole exome sequencing (WES) utilizing NextSeq500. HLA ligands were isolated from tumor tissue using immunoaffinity purification, UHPLC, and analyzed by tandem MS. Antibodies were measured in serum (NAb=27) utilizing the KREX™ CT262 protein array. Data analysis focused on 312 proteins (KREX™ CT262 panel + overexpressed self-proteins). Results: 183 and 94 of HLA class I and II TAP were identified by comparative profiling with healthy tonsils. Genes from 26 TAP were overexpressed in tumors compared to healthy mucosa (LFC>1; FDR<0.05). Low concordance (r=0.25; p<0.0001) was found between upregulated mRNA and class I TAP. The specific mode of correlation of TAP was found to be dependent on clinical parameters. A lack of correlation was observed both between mRNA and class II TAP, as well as between class II tumor-unique TAP (TAP-U) presentation and antibody response (AR) levels. Discussion: This study demonstrates that focusing exclusively on gene transcript levels fails to capture the full extent of TAP presentation in OPSCC. Furthermore, our findings reveal that although CTA are presented at relatively low levels, a few CTA TAP-U show potential as targets for immunotherapy.

Epoxyeicosatrienoic Acids Attenuate LPS-Induced NIH/3T3 Cell Fibrosis through the A2AR and PI3K/Akt Signaling Pathways.

Inflammation plays a crucial role in progression of fibrosis. Epoxyeicosatrienoic acids (EET) have multiple protective effects in different diseases, but their ability to inhibit the development of LPS-induced fibrosis remains unknown. The potential therapeutic effects of 11,12-EET were studied in in vitro model of LPS-induced fibrosis. Mouse embryonic fibroblast cells NIH/3T3 were pre-incubated with 1 µM 11,12-EET and/or a structural analogue and selective EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid before exposing to LPS. The effect of EET was evaluated by the protein and mRNA expression of NF-κB, collagens I and III, and α-smooth muscle actin by Western blotting and quantitative reverse transcription PCR, respectively. LPS provoked inflammation and fibrosis-like changes accompanied by elevated expression of NF-κB and collagens in NIH/3T3 cells. We also studied the effects of 11,12-EET on the A2AR and PI3K/Akt signaling pathways in intact and LPS-treated NIH/3T3 cells. 11,12-EET prevented inflammation and fibrosis-like changes through up-regulation of A2AR and PI3K/Akt signaling pathways. Our findings demonstrate the potential antifibrotic effects of 11,12-EET, which can be natural antagonists of tissue fibrosis.

High Mobility Group AT-hook 2: A Biomarker Associated with Resistance to Enzalutamide in Prostate Cancer Cells.

Metastatic prostate cancer (mPCa) is a leading cause of mortality, partly due to its resistance to anti-androgens like enzalutamide. Snail can promote this resistance by increasing full-length AR and AR-V7. High Mobility Group AT-hook 2 (HMGA2), a DNA-binding protein upstream of Snail, is crucial in proliferation and epithelial-mesenchymal transition (EMT). This study examines HMGA2's role in enzalutamide resistance. LNCaP and 22Rv1 cells overexpressing wild-type HMGA2, but not truncated HMGA2, showed EMT. Both variants led to a decreased sensitivity to enzalutamide but not alisertib compared to Neo control cells. The overexpression of HMGA2 did not alter AR expression. Enzalutamide-resistant C4-2B cells (C4-2B MDVR) had higher HMGA2 and AR/AR variant expression than enzalutamide-sensitive C4-2B cells but remained sensitive to alisertib. The HMGA2 knockdown in C4-2B MDVR cells increased sensitivity to both enzalutamide and alisertib without changing AR expression. A clinical analysis via cBioPortal revealed HMGA2 alterations in 3% and AR alterations in 59% of patients. The HMGA2 changes were linked to treatments like enzalutamide, abiraterone, or alisertib, with amplifications more prevalent in bone, lymph node, and liver metastases. Conclusively, HMGA2 is a potential biomarker for enzalutamide resistance in mPCa, independent of Snail and AR signaling, and alisertib may be an effective treatment for mPCa that expresses HMGA2.