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1.
Front Cell Dev Biol ; 12: 1421204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39011396

RESUMO

Circadian rhythm disruption is closely related to increased incidence of prostate cancer. Incorporating circadian rhythms into the study of prostate cancer pathogenesis can provide a more comprehensive understanding of the causes of cancer and offer new options for precise treatment. Therefore, this article comprehensively summarizes the epidemiology of prostate cancer, expounds the contradictory relationship between circadian rhythm disorders and prostate cancer risk, and elucidates the relationship between circadian rhythm regulators and the incidence of prostate cancer. Importantly, this article also focuses on the correlation between circadian rhythms and androgen receptor signaling pathways, as well as the applicability of time therapy in prostate cancer. This may prove significant in enhancing the clinical treatment of prostate cancer.

2.
Front Immunol ; 15: 1411315, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979410

RESUMO

Pregnancy is a fascinating immunological phenomenon because it allows allogeneic fetal and placental tissues to survive inside the mother. As a component of innate immunity with high inflammatory potential, the complement system must be tightly regulated during pregnancy. Dysregulation of the complement system plays a role in pregnancy complications including pre-eclampsia and intrauterine growth restriction. Complement components are also used as biomarkers for pregnancy complications. However, the mechanisms of detrimental role of complement in pregnancy is poorly understood. C5a is the most potent anaphylatoxin and generates multiple immune reactions via two transmembrane receptors, C5aR1 and C5aR2. C5aR1 is pro-inflammatory, but the role of C5aR2 remains largely elusive. Interestingly, murine NK cells have been shown to express C5aR2 without the usual co-expression of C5aR1. Furthermore, C5aR2 appears to regulate IFN-γ production by NK cells in vitro. As IFN-γ produced by uterine NK cells is one of the major factors for the successful development of a vital pregnancy, we investigated the role anaphylatoxin C5a and its receptors in the establishment of pregnancy and the regulation of uterine NK cells by examinations of murine C5ar2-/- pregnancies and human placental samples. C5ar2-/- mice have significantly reduced numbers of implantation sites and a maternal C5aR2 deficiency results in increased IL-12, IL-18 and IFN-γ mRNA expression as well as reduced uNK cell infiltration at the maternal-fetal interface. Human decidual leukocytes have similar C5a receptor expression patterns showing clinical relevance. In conclusion, this study identifies C5aR2 as a key contributor to dNK infiltration and pregnancy success.


Assuntos
Células Matadoras Naturais , Camundongos Knockout , Receptor da Anafilatoxina C5a , Útero , Receptor da Anafilatoxina C5a/genética , Receptor da Anafilatoxina C5a/metabolismo , Feminino , Animais , Gravidez , Camundongos , Útero/imunologia , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Placenta/imunologia , Placenta/metabolismo , Complemento C5a/imunologia , Complemento C5a/metabolismo , Camundongos Endogâmicos C57BL , Interferon gama/metabolismo , Interferon gama/imunologia
3.
Int J Mol Sci ; 25(13)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39000396

RESUMO

Latrophilins (LPHNs), a group of the G-protein-coupled receptor to which a spider venom latrotoxin (LTX) is known to bind, remain largely uncharacterized in neoplastic diseases. In the present study, we aimed to determine the role of LPHNs in the progression of prostate cancer. We assessed the actions of LPHNs, including LPHN1, LPHN2, and LPHN3, in human prostate cancer lines via their ligand (e.g., α-LTX, FLRT3) treatment or shRNA infection, as well as in surgical specimens. In androgen receptor (AR)-positive LNCaP/C4-2/22Rv1 cells, dihydrotestosterone considerably increased the expression levels of LPHNs, while chromatin immunoprecipitation assay revealed the binding of endogenous ARs, including AR-V7, to the promoter region of each LPHN. Treatment with α-LTX or FLRT3 resulted in induction in the cell viability and migration of both AR-positive and AR-negative lines. α-LTX and FLRT3 also enhanced the expression of Bcl-2 and phosphorylated forms of JAK2 and STAT3. Meanwhile, the knockdown of each LPHN showed opposite effects on all of those mediated by ligand treatment. Immunohistochemistry in radical prostatectomy specimens further showed the significantly elevated expression of each LPHN in prostate cancer, compared with adjacent normal-appearing prostate, which was associated with a significantly higher risk of postoperative biochemical recurrence in both univariate and multivariable settings. These findings indicate that LPHNs function as downstream effectors of ARs and promote the growth of androgen-sensitive, castration-resistant, or even AR-negative prostate cancer.


Assuntos
Progressão da Doença , Neoplasias da Próstata , Receptores Androgênicos , Masculino , Humanos , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Linhagem Celular Tumoral , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Movimento Celular/genética , Movimento Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Receptores de Peptídeos/metabolismo , Receptores de Peptídeos/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/genética , Transdução de Sinais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Processamento Alternativo
4.
Bioorg Med Chem Lett ; 110: 129877, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964518

RESUMO

Small cell lung cancer (SCLC) keeps on the leading cause of cancer mortality world widely, while there is lack of efficient therapeutic drugs especially for the resistant ones. In this work, a compound named penindolone (PND) with new skeleton was found to show weak inhibitory effect (IC50 = 42.5 µM) on H69AR cells (SCLC, adriamycin-resistant) proliferation by screening our in-house compound library. With the aim of improving its low potency, a series of PND derivatives were synthesized and biologically evaluated by the Sulforhodamine B (SRB) assay. Among all tested derivatives, compound 5h possessed higher antiproliferation potency (IC50 = 1.6 µM). Furthermore, preliminary mechanism investigation revealed that 5h was able to induce apoptosis and arrest the cell cycle at G0/G1 phase. These findings suggest that this novel skeleton has expanded the anti-SCLC compound reservoir and provided a new drug lead.

5.
Heliyon ; 10(12): e32852, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975124

RESUMO

Nowadays with the increase of high-rise buildings, emergency evacuation is an indispensable part of urban environment management. Due to various disaster incidents occurred in indoor environments, research has concentrated on ways to deal with the different difficulties of indoor emergency evacuation. Although global navigation satellite systems (GNSSs) such as global positioning system (GPS) come in handy in outdoor spaces, they are not of much use in enclosed places, where satellite signals cannot penetrate easily. Therefore, other approaches must be considered for pedestrian navigation to cope with the indoor positioning problem. Another problem in such environments is the information of the building indoor space. The majority of the studies has used prepared maps of the building, which limits their methodology to that specific study area. However, in this study we have proposed an end-to-end method that takes advantage of BIM model of the building, thereby applicable to every structure that has an equivalent building information model (BIM). Moreover, we have used a mixture of Wi-Fi fingerprinting and pedestrian dead reckoning (PDR) method with relatively higher accuracy compared to other similar methods for navigating the user to the exit point. For implementing PDR, we used the sensors in smartphones to calculate user steps and direction. In addition, the navigational information was superimposed on the smartphone screen using augmented reality (AR) technology, thus communicating the direction information in a user-friendly manner. Finally, the AR mobile emergency evacuation application developed was assessed with a sample audience. After an experience with the app, they filled out a questionnaire which was designed in the system usability scale test (SUS) format. The evaluation results showed that the app achieved an acceptable suitability for usage.

6.
Appl Neuropsychol Adult ; : 1-4, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976768

RESUMO

The integration of virtual, mixed, and augmented reality technologies in cognitive neuroscience and neuropsychology represents a transformative frontier. In this Commentary, we conducted a meta-analysis of studies that explored the impact of Virtual Reality (VR), Mixed Reality (MR), and Augmented Reality (AR) on cognitive neuroscience and neuropsychology. Our review highlights the versatile applications of VR, ranging from spatial cognition assessments to rehabilitation for Traumatic Brain Injury. We found that MR and AR offer innovative avenues for cognitive training, particularly in memory-related disorders. The applications extend to addressing social cognition disorders and serving as therapeutic interventions for mental health issues. Collaborative efforts between neuroscientists and technology developers are crucial, with reinforcement learning and neuroimaging studies enhancing the potential for improved outcomes. Ethical considerations, including informed consent, privacy, and accessibility, demand careful attention. Our review identified common aspects of the meta-analysis, including the potential of VR technologies in cognitive neuroscience and neuropsychology, the use of MR and AR in memory research, and the role of VR in neurorehabilitation and therapy.

7.
mSystems ; : e0043024, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953319

RESUMO

The erythromycin resistance RNA methyltransferase (erm) confers cross-resistance to all therapeutically important macrolides, lincosamides, and streptogramins (MLS phenotype). The expression of erm is often induced by the macrolide-mediated ribosome stalling in the upstream co-transcribed leader sequence, thereby triggering a conformational switch of the intergenic RNA hairpins to allow the translational initiation of erm. We investigated the evolutionary emergence of the upstream erm regulatory elements and the impact of allelic variation on erm expression and the MLS phenotype. Through systematic profiling of the upstream regulatory sequences across all known erm operons, we observed that specific erm subfamilies, such as ermB and ermC, have independently evolved distinct configurations of small upstream ORFs and palindromic repeats. A population-wide genomic analysis of the upstream ermB regions revealed substantial non-random allelic variation at numerous positions. Utilizing machine learning-based classification coupled with RNA structure modeling, we found that many alleles cooperatively influence the stability of alternative RNA hairpin structures formed by the palindromic repeats, which, in turn, affects the inducibility of ermB expression and MLS phenotypes. Subsequent experimental validation of 11 randomly selected variants demonstrated an impressive 91% accuracy in predicting MLS phenotypes. Furthermore, we uncovered a mixed distribution of MLS-sensitive and MLS-resistant ermB loci within the evolutionary tree, indicating repeated and independent evolution of MLS resistance. Taken together, this study not only elucidates the evolutionary processes driving the emergence and development of MLS resistance but also highlights the potential of using non-coding genomic allele data to predict antibiotic resistance phenotypes. IMPORTANCE: Antibiotic resistance (AR) poses a global health threat as the efficacy of available antibiotics has rapidly eroded due to the widespread transmission of AR genes. Using Erm-dependent MLS resistance as a model, this study highlights the significance of non-coding genomic allelic variations. Through a comprehensive analysis of upstream regulatory elements within the erm family, we elucidated the evolutionary emergence and development of AR mechanisms. Leveraging population-wide machine learning (ML)-based genomic analysis, we transformed substantial non-random allelic variations into discernible clusters of elements, enabling precise prediction of MLS phenotypes from non-coding regions. These findings offer deeper insight into AR evolution and demonstrate the potential of harnessing non-coding genomic allele data for accurately predicting AR phenotypes.

8.
Int J Biol Macromol ; 275(Pt 2): 133692, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38972657

RESUMO

Bombus terrestris are efficient pollinators in forestry and agriculture, with higher cold tolerance than other bees. Yet, their cold tolerance mechanism remains unclear. Aquaporins (AQPs) function as cell membrane proteins facilitating rapid water flow, aiding in osmoregulation. Recent studies highlight the importance of insect AQPs in dehydration and cold stress. Comparative transcriptome analysis of B. terrestris under cold stress revealed up-regulation of four AQPs, indicating their potential role in cold tolerance. Seven AQPs-Eglp1, Eglp2, Eglp3, DRIP, PRIP, Bib, and AQP12L-have been identified in B. terrestris. These are widely expressed in various tissues, particularly in the alimentary canal and Malpighian tubules. Functional analysis of BterAQPs in the Xenopus laevis oocytes expressing system showed distinct water and glycerol selectivity, with BterDrip exhibiting the highest water permeability. Molecular modeling of BterDrip revealed six transmembrane domains, two NPA motifs, and an ar/R constriction region (Phe131, His256, Ser265, and Arg271), likely contributing to its water selectivity. Silencing BterDRIP accelerated mortality in B. terrestris under cold stress, highlighting the crucial role of BterDRIP in their cold tolerance and providing a molecular mechanism for their cold adaptation.

9.
Fitoterapia ; 177: 106116, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38977254

RESUMO

Androgenetic alopecia (AGA) is the leading cause of hair loss in adults. Its pathogenesis remains unclear, but studies have shown that the androgen-mediated 5α-reductase-AR receptor pathway and the Wnt/ß-catenin signaling pathway play significant roles. Camellia oleifera is an oil plant, and its fruits have been documented in folklore as having a hair cleansing effect and preventing hair loss. In this study, we used UPLC-Q-TOF-MS/MS to identify the structure of the substances contained in the polyphenols of Camellia oleifera seed shell. These polyphenols are mainly used for shampooing and anti-hair loss purposes. Next, we used molecular docking technology to dock 41 polyphenols and steroidal 5 alpha reductase 2 (SRD5A2). We found that the docking scores and docking sites of 1,3,6-tri-O-galloylglucose (TGG) and finasteride were similar. We constructed a mouse model of DHT-induced AGA to evaluate the effects of Camellia oleifera seed shell polyphenols (CSSP) and TGG in vivo. Treatment with CSSP and TGG alleviated alopecia symptoms and reduced DHT levels. Additionally, CSSP and TGG were able to reduce androgen levels by inhibiting the SRD5A2-AR receptor signaling pathway. Furthermore, by regulating the secretion of growth factors and activating the Wnt/ß-catenin signaling pathway, CSSP and TGG were able to extend the duration of hair growth. In conclusion, our study showed that CSSP and TGG can improve AGA in C57BL/6 J mice and reduce the effect of androgen on hair follicle through the two signaling pathways mentioned above. This provides new insights into the material basis and mechanism of the treatment of AGA by CSSP.

10.
Clin Exp Med ; 24(1): 139, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951265

RESUMO

IgA nephropathy (IgAN) is still one of the leading causes of end-stage kidney disease (ESRD), and complement system activation is a key to the pathogenesis of IgAN. The role of complement C3a/C3aR and C5a/C5aR in late stage of IgAN remains unknown. Renal specimens of 75 IgAN patients at the stage 4 CKD were stained using immunofluorescence and immunohistochemistry. The primary outcome was a composite of end-stage renal disease (ESRD) and death. Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses. During a median follow-up of 15.0 months, 27 patients progressed to ESRD and none died. Lower eGFR [hazards ratio (HR), 0.827, 95% confidence interval (CI), 0.732-0.935; P = 0.002] and glomerular C3 deposition (HR, 3.179, 95% CI, 1.079-9.363; P = 0.036) were predictive of time to ESRD in stage 4 CKD IgAN. Higher expression of C3a (P = 0.010), C3aR (P = 0.005), C5a (P = 0.015), and C5aR (P < 0.001) was identified in ESRD group than in non-ESRD group. Glomerular C3a/C3aR and C5a/C5aR deposits were both correlated with a lower baseline eGFR, higher baseline 24 h-urinary protein (24 h-UP) and faster decline of eGFR. Besides, C3a and C5a deposits were found in patients with high S (S1) and T (T1/2) scores, respectively. Complement C3a/C3aR and C5a/C5aR in IgAN patients with stage 4 CKD may portend a faster deterioration of kidney function.

11.
Pharmacol Rep ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971919

RESUMO

BACKGROUND: The serotonin 5-HT5A receptor has attracted much more research attention, due to the therapeutic potential of its ligands being increasingly recognized, and the possibilities that lie ahead of these findings. There is a growing body of evidence indicating that these ligands have procognitive, pro-social, and anti-depressant properties, which offers new avenues for the development of treatments that could address socially important conditions related to the malfunctioning of the central nervous system. The aim of our study was to unravel the molecular determinants for 5-HT5AR ligands that govern their activity towards the receptor. METHODS: In response to the need for identification of molecular determinants for 5-HT5AR activity, we prepared a comprehensive collection of 5-HT5AR ligands, carefully gathering literature and patent data. Leveraging molecular modeling techniques, such as pharmacophore hypothesis development, docking, and molecular dynamics simulations enables to gain valuable insights into the specific interactions of 5-HT5AR ligand groups with the receptor. RESULTS: The obtained comprehensive set of 2160 compounds was divided into dozens of subsets, and a pharmacophore model was developed for each group. The results from the docking and molecular dynamics simulations have enabled the identification of crucial ligand-protein interactions that are essential for the compound's activity towards 5-HT5AR. CONCLUSIONS: The findings from the molecular modeling study provide valuable insights that can guide medicinal chemists in the development of new 5-HT5AR ligands. Considering the pharmacological significance of these compounds, they have the potential to become impactful treatments for individuals and communities in the future. Understanding how different crystal/cryo-EM structures of 5-HT5AR affect molecular modeling experiments could have major implications for future computational studies on this receptor.

12.
Behav Res Methods ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009823

RESUMO

To unravel how within-person psychological processes fluctuate in daily life, and how these processes differ between persons, intensive longitudinal (IL) designs in which participants are repeatedly measured, have become popular. Commonly used statistical models for those designs are multilevel models with autocorrelated errors. Substantive hypotheses of interest are then typically investigated via statistical hypotheses tests for model parameters of interest. An important question in the design of such IL studies concerns the determination of the number of participants and the number of measurements per person needed to achieve sufficient statistical power for those statistical tests. Recent advances in computational methods and software have enabled the computation of statistical power using Monte Carlo simulations. However, this approach is computationally intensive and therefore quite restrictive. To ease power computations, we derive simple-to-use analytical formulas for multilevel models with AR(1) within-person errors. Analytic expressions for a model family are obtained via asymptotic approximations of all sample statistics in the precision matrix of the fixed effects. To validate this analytical approach to power computation, we compare it to the simulation-based approach via a series of Monte Carlo simulations. We find comparable performances making the analytic approach a useful tool for researchers that can drastically save them time and resources.

13.
Reprod Toxicol ; 128: 108662, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38986849

RESUMO

The Adverse Outcome Pathway (AOP) framework has gained widespread acceptance in toxicological disciplines as a tool for aiding chemical hazard assessment. Despite increased activity in AOP development, progress towards a high volume of fully endorsed AOPs has been slow, partly due to the challenging task of constructing complete AOPs according to the AOP Developer's Handbook. To facilitate greater uptake of new knowledge units onto the open-source AOP-wiki platform, a pragmatic approach was recently proposed. This approach involves considering Key Event Relationships (KERs) for individual development through systematic approaches, as they represent essential units of knowledge from which causality can be inferred; from low complexity test data to adverse outcomes in intact organisms. However, more broadly adopted harmonized methodologies for KER development would be desirable. Using the AOP Developer's Handbook as a guide, a KER linking 'decreased androgen receptor (AR) activity' with 'reduced anogenital distance (AGD)' was developed to demonstrate a methodology applicable for future developments of KERs requiring systematic literature retrieval approaches.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38956972

RESUMO

BACKGROUND: Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that ß2-adrenergic receptor (ß2-AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome. OBJECTIVES: The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy. METHODS: Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours. RESULTS: The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of ß2-AR agonist formoterol (50 µg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels. CONCLUSION: Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the ß2-AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.

15.
J Neurooncol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958849

RESUMO

PURPOSE: Artificial Intelligence (AI) has become increasingly integrated clinically within neurosurgical oncology. This report reviews the cutting-edge technologies impacting tumor treatment and outcomes. METHODS: A rigorous literature search was performed with the aid of a research librarian to identify key articles referencing AI and related topics (machine learning (ML), computer vision (CV), augmented reality (AR), virtual reality (VR), etc.) for neurosurgical care of brain or spinal tumors. RESULTS: Treatment of central nervous system (CNS) tumors is being improved through advances across AI-such as AL, CV, and AR/VR. AI aided diagnostic and prognostication tools can influence pre-operative patient experience, while automated tumor segmentation and total resection predictions aid surgical planning. Novel intra-operative tools can rapidly provide histopathologic tumor classification to streamline treatment strategies. Post-operative video analysis, paired with rich surgical simulations, can enhance training feedback and regimens. CONCLUSION: While limited generalizability, bias, and patient data security are current concerns, the advent of federated learning, along with growing data consortiums, provides an avenue for increasingly safe, powerful, and effective AI platforms in the future.

16.
medRxiv ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38978661

RESUMO

Together with obesity and type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic. Activation of the complement system and infiltration of macrophages has been linked to progression of metabolic liver disease. The role of complement receptors in macrophage activation and recruitment in MASLD remains poorly understood. In human and mouse, C3AR1 in the iver is expressed primarily in Kupffer cells, but is downregulated in humans with MASLD compared to obese controls. To test the role of complement 3a receptor (C3aR1) on macrophages and liver resident macrophages in MASLD, we generated mice deficient in C3aR1 on all macrophages (C3aR1-MφKO) or specifically in liver Kupffer cells (C3aR1-KpKO) and subjected them to a model of metabolic steatotic liver disease. We show that macrophages account for the vast majority of C3ar1 expression in the liver. Overall, C3aR1-MφKO and C3aR1-KpKO mice have similar body weight gain without significant alterations in glucose homeostasis, hepatic steatosis and fibrosis, compared to controls on a MASLD-inducing diet. This study demonstrates that C3aR1 deletion in macrophages or Kupffer cells, the predominant liver cell type expressing C3aR1, has no significant effect on liver steatosis, inflammation or fibrosis in a dietary MASLD model.

17.
Clin Immunol ; 266: 110309, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002795

RESUMO

Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.

18.
J Exp Clin Cancer Res ; 43(1): 194, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39014480

RESUMO

Continued exploration of the androgen receptor (AR) is crucial, as it plays pivotal roles in diverse diseases such as prostate cancer (PCa), serving as a significant therapeutic focus. Therefore, the Department of Urology Dresden hosted an international meeting for scientists and clinical oncologists to discuss the newest advances in AR research. The 2nd International Androgen Receptor Symposium was held in Dresden, Saxony, Germany, from 26-27.04.2024, organised by Dr. Holger H.H. Erb. Following the format of the first meeting, more than 35 scientists from 8 countries attended the event to discuss recent developments, research challenges, and identification of venues in AR research. An important new feature was the involvement of PhD students and young investigators, acknowledging the high scientific quality of their work. The symposium included three covers: new advances from clinical research, basic and translational research, and novel strategies to target AR. Moreover, based on its increasing clinical relevance, a PSMA theranostic mini-symposium was added at the end of the AR symposium to allow the audience to discuss the newest advances in PSMA theranostic. This report focuses on the highlights and discussions of the meeting.


Assuntos
Neoplasias da Próstata , Receptores Androgênicos , Humanos , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/terapia , Neoplasias da Próstata/genética , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética
19.
Cureus ; 16(5): e60479, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38882985

RESUMO

BACKGROUND: We developed a 3D camera system to track motion in a surgical field. This system has the potential to introduce augmented reality (AR) systems non-invasively, eliminating the need for the invasive AR markers conventionally required. The present study was performed to verify the real-time tracking accuracy of this system, assess the feasibility of integrating this system into the surgical workflow, and establish its potential to enhance the accuracy and efficiency of orthopedic procedures. METHODS: To evaluate the accuracy of AR technology using a 3D camera, a forearm bone model was created. The forearm model was depicted using a 3D camera, and its accuracy was verified in terms of the positional relationship with a 3D bone model created from previously imaged CT data. Images of the surgical field (capturing the actual forearm) were taken and saved in nine poses by rotating the forearm from pronation to supination. The alignment of the reference points was computed at the three points of CT versus the three points of the 3D camera, yielding a 3D rotation matrix representing the positional relationship. In the original system, a stereo vision-based 3D camera, with a depth image resolution of 1280×720 pixels, 30 frames per second, and a lens field of view of 64 specifications, with a baseline of 3 cm, capable of optimally acquiring real-time 3D data at a distance of 40-60 cm from the subject was used. In the modified system, the following modifications were made to improve tracking performance: (1) color filter processing was changed from HSV to RGB, (2) positional detection accuracy was modified with supporting marker sizes of 8 mm in diameter, and (3) the detection of marker positions was stabilized by calculating the marker position for each frame. Tracking accuracy was examined with the original system and modified system for the following parameters: differences in the rotation matrix, maximum and minimum inter-reference point errors between CT-based and camera-based 3D data, and the average error for the three reference points. RESULTS: In the original system, the average difference in rotation matrices was 5.51±2.68 mm. Average minimum and maximum errors were 1.10±0.61 and 15.53±12.51 mm, respectively. The average error of reference points was 6.26±4.49 mm. In the modified system, the average difference in rotation matrices was 4.22±1.73 mm. Average minimum and maximum errors were 0.79±0.49 and 1.94±0.87 mm, respectively. The average error of reference points was 1.41±0.58 mm. In the original system, once tracking failed, it was difficult to recover tracking accuracy. This resulted in a large maximum error in supination positions. These issues were resolved by the modified system. Significant improvements were achieved in maximum errors and average errors using the modified system (P<0.05). CONCLUSION: AR technology using a 3D camera was developed. This system allows direct comparisons of 3D data from preoperative CT scans with 3D data acquired from the surgical field using a 3D camera. This method has the advantage of introducing AR into the surgical field without invasive markers.

20.
Orthop J Sports Med ; 12(6): 23259671241252649, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840792

RESUMO

Background: The Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire is a validated instrument for assessing symptoms of Achilles tendinopathy (AT). However, there is a need to validate the Arabic version of the VISA-A (VISA-A-AR) in Arabic-speaking patients with AT. Purpose: To validate the VISA-A-AR in Arabic patients with AT and evaluate its reliability and validity. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: The translation and cultural adaptation of the VISA-A questionnaire into Arabic followed international guidelines. A total of 81 participants were recruited, including 45 patients diagnosed with AT and 36 healthy individuals. The AT group comprised male and female native Arabic speakers aged ≥18 years who were diagnosed with and had symptoms of AT. The inclusion criteria for the healthy group were the same, except that they must not have had AT at the time of the study or previously. The exclusion criteria were individuals with a partial or complete Achilles tendon rupture or prior Achilles tendon surgery. The internal consistency of the VISA-A-AR was assessed using the Cronbach α coefficient. Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC[3,1]). Construct validity was assessed through correlation analysis between VISA-A-AR scores and the Arabic versions of the Short Form-36 Health Survey (SF-36-AR) and the Numeric Pain Rating Scale (ANPRS). Differences in VISA-A-AR scores between patients with AT and healthy controls were analyzed using appropriate statistical tests. Results: The VISA-A-AR demonstrated a high level of internal consistency (Cronbach α = 0.935) and excellent test-retest reliability (ICC[3,1] = 0.985). Significant positive correlations were observed between VISA-A-AR scores and SF-36-AR (r(43) = 0.838, P < .001), indicating good construct validity. In addition, VISA-A-AR scores showed a significant negative correlation with ANPRS (rS(43) = -0.835, P < .001). Furthermore, VISA-A-AR scores exhibited a significant difference between patients with AT (mean, 45.82 ± 16.65) and healthy controls (mean, 99.94 ± 0.33) (P < .001). Conclusion: The findings of this study validate the VISA-A-AR as a reliable and valid tool for assessing symptoms of AT in Arabic-speaking patients.

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