Epigallocatechin-3-gallate derived polymer coated Prussian blue for synergistic ROS elimination and antibacterial therapy.

Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core-shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm2), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In vivo therapeutic effect was evaluated using a S. aureus-infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.

Modeling of new markers for the diagnosis and prognosis of pancreatic cancer based on the transition from inflammation to cancer.

Background: Pancreatic adenocarcinoma (PAAD) is a lethal disease with a poor prognosis. Genes involved in acute pancreatitis (AP) or chronic pancreatitis (CP) might be important for PAAD development. This study sought to identify potential PAAD diagnosis markers and to establish a PAAD prognosis prediction model based on AP- and CP-related genes. Methods: The significantly differentially expressed genes in both AP or CP and PAAD were obtained by a bioinformatics analysis. A risk-score model for predicting survival was constructed based on The Cancer Genome Atlas (TCGA) data and validated using an International Cancer Genome Consortium (ICGC) cohort. Protein expression and the effects of the genes in the risk models were validated by immunohistochemistry, or Cell Counting Kit-8 (CCK-8) and transwell assays. The study sample data included six AP tissue samples and five normal pancreatic tissue samples, six CP tissue samples and six normal pancreatic tissue samples from the Gene Expression Omnibus (GEO) expression profiling microarrays GSE109227 and GSE41418 data sets, respectively, and fragments per kilobase per million mapped fragments (FPKM) data from four normal controls and 150 PAAD cases from TCGA database, and 182 cancer patient samples with complete survival prognostic data from the ICGC database. Results: In total, 508 significantly differentially expressed genes were found in both AP or CP and PAAD. Trefoil factor 2 (TFF2), tubulointerstitial nephritis antigen (TINAG), trefoil factor 1 (TFF1), aquaporin 5 (AQP5), SAM pointed domain containing ETS transcription factor (SPDEF), anterior gradient protein 2 (AGR2), apolipoprotein B messenger RNA editing enzyme catalytic subunit 1 (APOBEC1), kallikrein-related peptidase 6 (KLK6), dopa decarboxylase (DDC), mucin 13 (MUC13), claudin 18 (CLDN18), annexin A10 (ANXA10), and tetraspanin 1 (TSPAN1) were found to be present in PAAD and had the largest fold change. A risk-score model, comprising 19 genes, was constructed for prognostic prediction. A high-risk score indicated a poor prognosis. TINAG, DDC, SPDEF, and APOBEC1 proteins were increased in PAAD, while TINAG and DDC were correlated with the pathologic grade. Decreased TINAG, APOBEC1, transmembrane protein 94 (TMEM94), and kelch like family member 36 (KLHL36) expression inhibited PAAD cell proliferation, while decreased SPDEF, TMEM94, and KLHL36 expression significantly inhibited PAAD cell migration. Conclusions: The AP and CP co-related genes were significantly correlated with PAAD. TINAG, DDC, SPDEF, and APOBEC1 could serve as new PAAD predictors. The risk model developed in this study could be used to predict the prognosis of PAAD patients.

Rediscovering AMD with Swept-Source OCT Imaging: The 2022 Charles L. Schepens, MD, Lecture.

PURPOSE: Swept-source optical coherence tomography angiography (SS-OCTA) scans of eyes with age-related macular degeneration (AMD) were used to replace color, autofluorescence, infrared reflectance, and dye-based fundus angiographic imaging for the diagnosis and staging of AMD. Through the use of different algorithms with the SS-OCTA scans, both structural and angiographic information can be viewed and assessed using both cross-sectional and en face imaging strategies. DESIGN: Presented at the 2022 Charles L. Schepens, MD, Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, on September 30, 2022 PARTICIPANTS: Patients with AMD METHODS: Review of published literature and ongoing clinical research using SS-OCTA imaging in AMD. MAIN OUTCOME MEASURES: SS-OCTA imaging of AMD at different stages of disease progression. RESULTS: Volumetric SS-OCTA dense raster scans were used to diagnose and stage both exudative and nonexudative AMD. In eyes with nonexudative AMD, a single SS-OCTA scan was used to detect and measure structural features in the macula such as the area and volume of both typical soft drusen and calcified drusen, the presence and location of hyperreflective foci, the presence of reticular pseudodrusen, also known as subretinal drusenoid deposits, the thickness of the outer retinal layer, the presence and thickness of basal laminar deposits, the presence and area of persistent choroidal hypertransmission defects, and the presence of treatment-naïve nonexudative macular neovascularization. In eyes with exudative AMD, the same SS-OCTA scan pattern was used to detect and measure the presence of macular fluid, the presence and type of macular neovascularization, and the response of exudation to treatment with vascular endothelial growth factor inhibitors. In addition, the same scan pattern was used to quantitate choriocapillaris (CC) perfusion, CC thickness, choroidal thickness, and the vascularity of the choroid. CONCLUSIONS: Compared with using several different instruments to perform multimodal imaging, a single SS-OCTA scan provides a convenient, comfortable, and comprehensive approach for obtaining qualitative and quantitative anatomic and angiographic information to monitor the onset, progression, and response to therapies in both nonexudative and exudative AMD.

Use of ultra-high performance liquid chromatography-high-resolution mass spectroscopy to profile the metabolites from the serum of patients with breast cancer.

Breast cancer (BC) is the most common type of malignancy and the leading cause of cancer-associated mortality in women worldwide. As such, assessing the metabolic changes during human breast carcinogenesis is key for developing disease prevention methods and treatment. In the present study, non-targeted metabolomics with chemometrics based on ultra-high performance liquid chromatography-high-resolution mass spectrometry were performed to assess differences in serum metabolite patterns between patients with BC and healthy individuals. A total of 3,246 metabolites in the sera of healthy controls and patients with BC were found. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that arginine, proline, nicotinate, nicotinamide, caffeine and arachidonic acid metabolism, as well as fatty acid biosynthesis were significantly altered in patients with BC in comparison with controls. These results suggested that serum metabolic profiling has potential for discovering molecular biomarkers for the detection of BC. It may also further the understanding of the underlying mechanisms associated with this disease.

Genome-wide identification and comparative analysis of YABBY transcription factors in oil tea and tea tree.

The plant-specific transcription factor gene family, YABBY, plays an important role in plant development and stress response. Although YABBY genes have been identified in numerous species, a comprehensive characterization of YABBYs in tea tree and oil tea has been lacking. In this study, ten and three YABBY genes were identified in Camellia sinensis and C. oleifera, respectively. YABBY proteins could be divided into five subfamilies. Most YABBY genes in the same clade had similar structures and conserved motifs. Protein evolutionary analysis revealed that FIL/YAB3 displayed high conservation in all positions, followed by INO, YAB2, YAB5, and CRC. Specific site analysis suggested that the YABBY family was polyphyletic during the evolution. Compared to C. oleifera, two segmentally duplicated gene pairs were formed in C. sinensis during recent WGD events generated 30.69 and 45.08 Mya, respectively. Cis-acting element indicated that most YABBY genes contain box4, ARE, and MYB elements. A total of 120 SSR loci were found within CsYABBYs, consisting of six types, while 48 SSR loci were identified within CoYABBY, consisting of three types. Transcriptome results revealed that CRC and INO clades were specifically expressed in floral organs. The expression of CsYABBY10 and CsYABBY5 was significantly up-regulated under drought and salt treatments, respectively, as confirmed by qRT-PCR. CoYABBY genes were more susceptible to salt stress, as CoYABBY3 increased by about 15-fold. Furthermore, functional differentiation may have occurred in duplicated genes. These discoveries provide important information for further research on YABBYs in tea tree and oil tea. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03940-9.

The blockade of neuropeptide FF receptor 1 and 2 differentially contributed to the modulating effects on fentanyl-induced analgesia and hyperalgesia in mice.

Neuropeptide FF (NPFF) plays a critical role in various physiological processes through the activation of neuropeptide FF receptor 1 and 2 (NPFFR1 and NPFFR2). Numerous evidence has indicated that NPFF exhibits opposite opioid-modulating effects on opioid-induced analgesia after supraspinal and spinal administrations, while the detailed role of NPFFR1 and NPFFR2 remains unclear. In this study, we employed pharmacological and genetic inhibition of NPFFR to investigate the modulating roles of central NPFFR1 and NPFFR2 in opioid-induced analgesia and hyperalgesia, using a male mouse model of acute fentanyl-induced analgesia and secondary hyperalgesia. Our findings revealed that intrathecal (i.t.) injection of the nonselective NPFFR antagonist RF9 significantly enhanced fentanyl-induced analgesia, whereas intracerebroventricular (i.c.v.) injection did not show the same effect. Moreover, NPFFR2 deficient (npffr2-/-) mice exhibited stronger analgesic responses to fentanyl compared to wild type (WT) or NPFFR1 knockout (npffr1-/-) mice. Intrathecal injection of RF9 in npffr1-/- mice also significantly enhanced fentanyl-induced analgesia. These results indicate a crucial role of spinal NPFFR2 in the enhancement of opioid analgesia. Contrastingly, hyperalgesia induced by fentanyl was markedly reversed in npffr1-/- mice but remained unaffected in npffr2-/- mice. Similarly, i.c.v. injection of the selective NPFFR1 antagonist RF3286 effectively prevented fentanyl-induced hyperalgesia in WT or npffr2-/- mice. Notably, co-administration of i.c.v. RF3286 and i.t. RF9 augmented fentanyl-induced analgesia while reducing hyperalgesia. Collectively, these findings highlight the modulating effects of blocking spinal NPFFR2 and supraspinal NPFFR1 on fentanyl-induced analgesia and hyperalgesia, respectively, which shed a light on understanding the pharmacological function of NPFF system in future studies.

Salvia miltiorrhiza Bunge extract and Przewalskin ameliorate Bleomycin-induced pulmonary fibrosis by inhibition of apoptosis, oxidative stress and collagen deposition via the TGF-ß1 pathway.

BACKGROUND: Salvia miltiorrhiza Bunge (Labiatae) (DS) is a key part of the traditional Chinese medicine, whose roots are used to remove blood stasis, relieve pain, eliminate carbuncle and calm the nerves. Our research team found that the DS extract could significantly reverse LPS-induced lung injury, and five new diterpenoid quinones in DS extract with excellent lung protective activity for the first time. However, the material basis and mechanism of DS on pulmonary fibrosis (PF) needs to be explored in depth. OBJECTIVE: Bleomycin (BLM) was employed to establish the PF model, and Transcriptome and Surface plasmon resonance (SPR) ligand fishing technology were used to explore the material basis and mechanism of DS on PF, and provided theoretical research for clinical treatment of PF. METHODS: DS extract (24.58 or 49.16 mg/kg, i.g.) was administered daily from Day 8 to Day 28, followed by intratracheal BLM drip (5 mg/kg) to induce PF. Data about the influences of DS on PF were collected by transcriptome sequencing technology. Pulmonary ultrasound, airway responsiveness, lung damage, collagen deposition, and the levels of TNF-α, IL-1ß, apoptosis, oxidative stress (OS), immune cells, TGF-ß1, α-SMA, E-Cadherin and Collage Ⅰ were examined. The affinity component (Przewalskin) in DS extract targeted by TGF-ß1 was fished by SPR ligand fishing technology. Furthermore, an in vivo PF mouse model and an in vitro TGF-ß1 induced BEAS-2B cell model were established, to explore the mechanism of Przewalskin on PF from the apoptosis, OS and epithelial mesenchymal transformation pathway. RESULTS: DS extract improved pulmonary ultrasound, reduced lung damage and collagen deposition, downregulated TNF-α, IL-1ß, apoptosis, OS, TGF-ß1, α-SMA, E-Cadherin and Collage Ⅰ, transformed immune cells following Bleomycin challenge. Furthermore, affinity component (Przewalskin) also improved pulmonary ultrasound and airway responsiveness, reduced lung damage and collagen deposition, downregulated TNF-α, IL-1ß, apoptosis, OS in vivo and in vitro. CONCLUSION: Analysis using a mouse model revealed that DS extract and Przewalskin can relieve clinical symptoms of PF, reduce lung injury and improve lung function. Meanwhile, DS extract and Przewalskin can improve BLM-induced PF by inhibition of, OS, apoptosis and collagen deposition might via the TGF-ß1 pathway. This study provides references to identification of novel therapeutic targets, thereby facilitating drug development for PF.

Deep learning-based algorithm for the detection of idiopathic full thickness macular holes in spectral domain optical coherence tomography.

BACKGROUND: Automated identification of spectral domain optical coherence tomography (SD-OCT) features can improve retina clinic workflow efficiency as they are able to detect pathologic findings. The purpose of this study was to test a deep learning (DL)-based algorithm for the identification of Idiopathic Full Thickness Macular Hole (IFTMH) features and stages of severity in SD-OCT B-scans. METHODS: In this cross-sectional study, subjects solely diagnosed with either IFTMH or Posterior Vitreous Detachment (PVD) were identified excluding secondary causes of macular holes, any concurrent maculopathies, or incomplete records. SD-OCT scans (512 × 128) from all subjects were acquired with CIRRUS™ HD-OCT (ZEISS, Dublin, CA) and reviewed for quality. In order to establish a ground truth classification, each SD-OCT B-scan was labeled by two trained graders and adjudicated by a retina specialist when applicable. Two test sets were built based on different gold-standard classification methods. The sensitivity, specificity and accuracy of the algorithm to identify IFTMH features in SD-OCT B-scans were determined. Spearman's correlation was run to examine if the algorithm's probability score was associated with the severity stages of IFTMH. RESULTS: Six hundred and one SD-OCT cube scans from 601 subjects (299 with IFTMH and 302 with PVD) were used. A total of 76,928 individual SD-OCT B-scans were labeled gradable by the algorithm and yielded an accuracy of 88.5% (test set 1, 33,024 B-scans) and 91.4% (test set 2, 43,904 B-scans) in identifying SD-OCT features of IFTMHs. A Spearman's correlation coefficient of 0.15 was achieved between the algorithm's probability score and the stages of the 299 (47 [15.7%] stage 2, 56 [18.7%] stage 3 and 196 [65.6%] stage 4) IFTMHs cubes studied. CONCLUSIONS: The DL-based algorithm was able to accurately detect IFTMHs features on individual SD-OCT B-scans in both test sets. However, there was a low correlation between the algorithm's probability score and IFTMH severity stages. The algorithm may serve as a clinical decision support tool that assists with the identification of IFTMHs. Further training is necessary for the algorithm to identify stages of IFTMHs.

Deep-learning-based automated measurement of outer retinal layer thickness for use in the assessment of age-related macular degeneration, applicable to both swept-source and spectral-domain OCT imaging.

Effective biomarkers are required for assessing the progression of age-related macular degeneration (AMD), a prevalent and progressive eye disease. This paper presents a deep learning-based automated algorithm, applicable to both swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT) scans, for measuring outer retinal layer (ORL) thickness as a surrogate biomarker for outer retinal degeneration, e.g., photoreceptor disruption, to assess AMD progression. The algorithm was developed based on a modified TransUNet model with clinically annotated retinal features manifested in the progression of AMD. The algorithm demonstrates a high accuracy with an intersection of union (IoU) of 0.9698 in the testing dataset for segmenting ORL using both SS-OCT and SD-OCT datasets. The robustness and applicability of the algorithm are indicated by strong correlation (r = 0.9551, P < 0.0001 in the central-fovea 3 mm-circle, and r = 0.9442, P < 0.0001 in the 5 mm-circle) and agreement (the mean bias = 0.5440 um in the 3-mm circle, and 1.392 um in the 5-mm circle) of the ORL thickness measurements between SS-OCT and SD-OCT scans. Comparative analysis reveals significant differences (P < 0.0001) in ORL thickness among 80 normal eyes, 30 intermediate AMD eyes with reticular pseudodrusen, 49 intermediate AMD eyes with drusen, and 40 late AMD eyes with geographic atrophy, highlighting its potential as an independent biomarker for predicting AMD progression. The findings provide valuable insights into the ORL alterations associated with different stages of AMD and emphasize the potential of ORL thickness as a sensitive indicator of AMD severity and progression.

Spectral-Domain and Swept-Source OCT Angiographic Scans Yield Similar Drusen Measurements When Processed with the Same Algorithm.

Purpose: An algorithm developed to obtain drusen area and volume measurements using swept-source OCT angiography (SS-OCTA) scans was tested on spectral-domain OCT angiography (SD-OCTA) scans. Design: Retrospective study. Participants: Forty pairs of scans from 27 eyes with intermediate age-related macular degeneration and drusen. Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 mm × 6 mm OCTA scan patterns. Using the same algorithm, we obtained drusen area and volume measurements within both 3 mm and 5 mm fovea-centered circles. Paired 2-sample t-tests were performed along with Pearson's correlation tests. Main Outcome Measures: Mean square root (sqrt) drusen area and cube root (cbrt) drusen volume within the 3 mm and 5 mm fovea-centered circles. Results: Mean sqrt drusen area values from SD-OCTA and SS-OCTA scans were 1.57 (standard deviation [SD] 0.57) mm and 1.49 (SD 0.58) mm in the 3 mm circle and 1.88 (SD 0.59) mm and 1.76 (SD 0.58) mm in the 5 mm circle, respectively. Mean cbrt drusen volume measurements were 0.54 (SD 0.19) mm and 0.51 (SD 0.20) mm in the 3 mm circle, and 0.60 (SD 0.17) mm and 0.57 (SD 0.17) mm in the 5 mm circle. Small differences in area and volume measurements were found (all P < 0.001); however, the correlations between the instruments were strong (all coefficients > 0.97; all P < 0.001). Conclusions: An algorithm originally developed for SS-OCTA scans performs well when used to obtain drusen volume and area measurements from SD-OCTA scans; thus, a separate SD-OCT structural scan is unnecessary to obtain measurements of drusen. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Structure-Activity Relationships of a Novel Cyclic Hexapeptide That Exhibits Multifunctional Opioid Agonism and Produces Potent Antinociceptive Activity.

The cyclic peptide c[d-Lys2, Asp5]-DN-9 has recently been identified as a multifunctional opioid/neuropeptide FF receptor agonist, displaying potent analgesic activity with reduced side effects. This study utilized Tyr-c[d-Lys-Gly-Phe-Asp]-d-Pro-NH2 (0), a cyclic hexapeptide derived from the opioid pharmacophore of c[d-Lys2, Asp5]-DN-9, as a chemical template. We designed, synthesized, and characterized 22 analogs of 0 with a single amino acid substitution to investigate its structure-activity relationship. Most of these cyclic hexapeptide analogs exhibited multifunctional activity at µ and δ opioid receptors (MOR and DOR, respectively) and produced antinociceptive effects following subcutaneous administration. The lead compound analog 15 showed potent agonistic activities at the MOR, κ opioid receptor (KOR), and DOR in vitro and produced a strong and long-lasting analgesic effect through peripheral MOR and KOR in the tail-flick test. Further biological evaluation identified that analog 15 did not cause significant side effects such as tolerance, withdrawal, or reward liability.

All-Hydrocarbon Stapled Peptide Multifunctional Agonists at Opioid and Neuropeptide FF Receptors: Highly Potent, Long-Lasting Brain Permeant Analgesics with Diminished Side Effects.

Our previous study reported the multifunctional agonist for opioid and neuropeptide FF receptors DN-9, along with its cyclic peptide analogues c[D-Cys2, Cys5]-DN-9 and c[D-Lys2, Asp5]-DN-9. These analogues demonstrated potent antinociceptive effects with reduced opioid-related side effects. To develop more stable and effective analgesics, we designed, synthesized, and evaluated seven hydrocarbon-stapled cyclic peptides based on DN-9. In vitro calcium mobilization assays revealed that most of the stapled peptides, except 3, displayed multifunctional agonistic activities at opioid and neuropeptide FF receptors. Subcutaneous administration of all stapled peptides resulted in effective and long-lasting antinociceptive activities lasting up to 360 min. Among these stapled peptides, 1a and 1b emerged as the optimized compounds, producing potent central antinociception following subcutaneous, intracerebroventricular, and oral administrations. Additionally, subcutaneous administration of 1a and 1b caused nontolerance antinociception, with limited occurrence of constipation and addiction. Furthermore, 1a was selected as the final optimized compound due to its wider safety window compared to 1b.

[Aqueous extract of Epimedium sagittatum mitigates pulmonary fibrosis in mice].

This study aims to investigate the intervention effect of the aqueous extract of Epimedium sagittatum Maxim on the mouse model of bleomycin(BLM)-induced pulmonary fibrosis, so as to provide data support for the clinical treatment of pulmonary fibrosis. Ninety male C57BL/6N mice were randomized into normal(n=10), model(BLM, n=20), pirfenidone(PFD, 270 mg·kg~(-1), n=15), and low-, medium-, and high-dose E. sagittatum extract(1.67 g·kg~(-1), n=15; 3.33 g·kg~(-1), n=15; 6.67 g·kg~(-1), n=15) groups. The model of pulmonary fibrosis was established by intratracheal instillation of BLM(5 mg·kg~(-1)) in the other five groups except the normal group, which was treated with an equal amount of normal saline. On the day following the modeling, each group was treated with the corresponding drug by gavage for 21 days. During this period, the survival rate of the mice was counted. After gavage, the lung index was calculated, and the morphology and collagen deposition of the lung tissue were observed by hematoxylin-eosin(HE) and Masson staining, respectively. The levels of reactive oxygen species(ROS) in lung cell suspensions were measured by flow cytometry. The levels of glutathione peroxidase(GSH-Px), total superoxide dismutase(T-SOD), and malondialdehyde(MDA) the in lung tissue were measured. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling(TUNEL) was employed to examine the apoptosis of lung tissue cells. The content of interleukin-6(IL-6), chemokine C-C motif ligand 2(CCL-2), matrix metalloproteinase-8(MMP-8), transforming growth factor-beta 1(TGF-ß1), alpha-smooth muscle actin(α-SMA), E-cadherin, collagen Ⅰ, and fibronectin in the lung tissue was measured by enzyme-linked immunosorbent assay(ELISA). The expression levels of F4/80, Ly-6G, TGF-ß1, and collagen Ⅰ in the lung tissue were determined by immunohistochemistry. The mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue were determined by qRT-PCR. The content of hydroxyproline(HYP) in the lung tissue was determined by alkaline hydrolysation. The expression of α-SMA and E-cadherin was detected by immunofluorescence, and the protein levels of α-SMA, vimentin, E-cadherin in the lung tissue were determined by Western blot. The results showed the aqueous extract of E. sagittatum increased the survival rate, decreased the lung index, alleviated the pathological injury, collagen deposition, and oxidative stress in the lung tissue, and reduced the apoptotic cells. Furthermore, the aqueous extract of E. sagittatum down-regulated the protein levels of F4/80 and Ly-6G and the mRNA levels of CCL-2, IL-6, and MMP-7 in the lung tissue, reduced the content of IL-6, CCL-2, and MMP-8 in the alveolar lavage fluid. In addition, it lowered the levels of HYP, TGF-ß1, α-SMA, collagen Ⅰ, fibronectin, and vimentin, and elevated the levels of E-cadherin in the lung tissue. The aqueous extract of E. sagittatum can inhibit collagen deposition, alleviate oxidative stress, and reduce inflammatory response by regulating the expression of the molecules associated with epithelial-mesenchymal transition, thus alleviating the symptoms of bleomycin-induced pulmonary fibrosis in mice.

Construction of clinical research nurse training program based on position competence.

BACKGROUND: As one of the most important members in clinical trials, the number of clinical research nurses (CRN) can't keep up with the growth of experimental projects, so it is urgent to build clinical research training and strengthen the background knowledge of nurses. AIM: To construct CRN training program based on position competence, accelerate the construction of CRN talent pool, and provide scientific guidance significance for CRN training. METHODS: Based on the position competence model, combined with literature research and qualitative interview results, the first draft was prepared of the CRN training program. Two rounds of correspondence with 16 experts were conducted using the Delphi method to determine the training program. RESULTS: The effective recovery rate of the expert correspondence questionnaire was 100% and the authority coefficients of the 2 rounds of experts were 0.826 and 0.895. Finally, 4 first-level indicators and determine 15 s-level indicators of training objectives. The training program included 4 first-level indicators, training requirements, content, methods, assessment and evaluation, 15 s-level indicators, and 74 third-level indicators. CONCLUSION: The CRN training program based on position competence is scientific and extendable, providing a basis for participation in CRN training.

Down Regulation of EGF and AZGP1 Were Associated with Clinical Characteristics in Chronic Rhinosinusitis with Nasal Polyps: An Observation Study.

Objective: The mechanisms underlying the chronic rhinosinusitis with nasal polyps (CRSwNP) remained unclear. This study aimed to identify differentially expressed genes (DEGs) in nasal polyps from CRSwNP patients compared to healthy controls and explore key genes and pathways associated with CRSwNP pathophysiology and prognosis. Methods: Three datasets were obtained from the Gene Expression Omnibus database and the intersecting DEGs were identified in CRSwNP patients. Gene Ontology (GO) and protein-protein interaction (PPI) network analysis were applied to investigate the function of DEGs. Nasal specimens from 90 CRSwNP and 45 controls were further collected and qRT-PCR was applied to verify the mRNA expression of hub genes, and moreover, their association with tissue eosinophilia and clinical characteristics in CRSwNP were analyzed. Results: Sixty-eight co-DEGs including 8 upregulated and 60 downregulated genes were identified and GO analyses identified the terms including positive regulation of ERK1 and ERK2 cascade, transforming growth factor beta receptor signaling pathway. PPI networks identified hub genes including EGF, ERBB4, AZGP1, CRISP3 and PIP which were validated to be significantly down-regulated in CRSwNP and showed well diagnostic prediction quality. In addition, lower mRNA expressions level of EGF and AZGP1 in eosinophilic CRSwNP compared with non-eosinophilic CRSwNP were found. Aberrant low expressions of EGF and AZGP1 protein in CRSwNP were identified, and there was good consistency between their mRNA expression level and protein relative expression level. Furthermore, the expressions of EGF and AZGP1 mRNA were significantly correlated with clinical severity parameters. Conclusion: Integrated analysis revealed 68 co-DEGs between nasal polyps and controls and identified hub genes, of which EGF and AZGP1 expression was significantly downregulated in eosinophilic CRSwNP and correlated with disease severity. Downregulation of EGF and AZGP1 may contribute to epithelial barrier dysfunction and type 2 inflammation in CRSwNP, suggesting them as potential diagnostic biomarkers and therapeutic targets.

Tripartite motif containing 26 prevents steatohepatitis progression by suppressing C/EBPδ signalling activation.

Currently potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) and NASH-related pathopoiesis have failed to achieve expected therapeutic efficacy due to the complexity of the pathogenic mechanisms. Here we show Tripartite motif containing 26 (TRIM26) as a critical endogenous suppressor of CCAAT/enhancer binding protein delta (C/EBPδ), and we also confirm that TRIM26 is an C/EBPδ-interacting partner protein that catalyses the ubiquitination degradation of C/EBPδ in hepatocytes. Hepatocyte-specific loss of Trim26 disrupts liver metabolic homeostasis, followed by glucose metabolic disorder, lipid accumulation, increased hepatic inflammation, and fibrosis, and dramatically facilitates NASH-related phenotype progression. Inversely, transgenic Trim26 overexpression attenuates the NASH-associated phenotype in a rodent or rabbit model. We provide mechanistic evidence that, in response to metabolic insults, TRIM26 directly interacts with C/EBPδ and promotes its ubiquitin proteasome degradation. Taken together, our present findings identify TRIM26 as a key suppressor over the course of NASH development.

Choroidal Changes After Anti-VEGF Therapy in AMD Eyes With Different Types of Macular Neovascularization Using Swept-Source OCT Angiography.

Purpose: Choroidal changes before and after anti-VEGF therapy were investigated in eyes with exudative AMD to determine if there was a difference between eyes with macular neovascularization (MNV) that arises from the choroid (type 1 or 2) versus the retinal circulation (type 3). Methods: Patients with treatment-naïve AMD were imaged with swept-source optical coherence tomography angiography using a 12 × 12-mm scan pattern. The mean choroidal thickness and choroidal vascularity index (CVI) were measured within 5-mm and 11-mm fovea-centered circles before, at the onset of, and after anti-VEGF therapy. Results: Forty-one eyes of 37 patients were included; 24 eyes with type 1 MNV, 4 eyes with type 2 MNV, and 13 eyes with type 3 MNV. Within the 5-mm and 11-mm circles, the mean choroidal thickness and CVI measurements increased from pretreatment to the onset of exudation (P ≤ 0.03). The mean choroidal thickness and CVI measurements decreased from the onset of exudation to after treatment (P < 0.001). No significant changes in mean choroidal thickness or CVI were observed when comparing measurements before or after treatment (P ≥ 0.38). No significant differences in mean choroidal thickness or CVI measurements were observed between eyes with type 1 or 2 MNV and type 3 MNV. Conclusions: In treatment-naïve AMD eyes with MNV, the choroidal thickness and vascularity increased at the onset of exudation and then decreased after anti-VEGF therapy. This finding suggests that these choroidal changes develop in response to the proangiogenic milieu before treatment and in response to treatment, regardless of the site of origin for the MNV.

Salviamilthone A-O, diterpenoid quinones from Salvia miltiorrhiza.

Fifteen undescribed diterpenoid quinones salviamilthone A-O (1-15), together with three known diterpenoid quinones (16-18), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by NOESY correlations and comparison between experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthone J (10), salviamone (18) (10 µM) significantly increased cell viability and decreased the expression of IL-1ß in lipopolysaccharide-induced BEAS-2B cells. These data provide the molecular justification for the usage of Salvia miltiorrhiza in treating acute lung injury.

Apically extruded debris, canal transportation, and shaping ability of nickel-titanium instruments on contracted endodontic cavities in molar teeth.

PURPOSE: Apically extruded debris, canal transportation and shaping ability were compared between contracted endodontic cavities (CECs) and traditional endodontic cavities (TECs) after instrumentation with XP-endo Shaper (XPS), ProTaper Gold (PTG), ProTaper for hand-use (HPT) and Hero Shaper. METHODS: The CECs or TECs groups were sub-divided into 24 groups according to root canal morphology and nickel-titanium (Ni-Ti) instruments. The weight of apically extruded debris was calculated using the Myers and Montgomery model. Pre- and postoperative images of teeth were scanned using micro-CT and the three-dimensional models were constructed and compared. RESULTS: Under CECs or TECs, XPS and PTG produced less apical debris and formed less canal transportation than HPT and Hero Shaper (P < 0.05). XPS group under CECs extruded less apical debris than that under TCEs for round canals with curvature of 20°-35° (P < 0.05). The centering ratios of four tested instruments were higher under TECs than those under CECs (P < 0.05). The HPT and Hero Shaper had more transportation under CECs than that under TCEs (P < 0.05). No statistical difference was found regarding shaping ability among all the groups. CONCLUSION: Under CECs, XPS preserves the original root canal anatomy, meanwhile it produces less apical debris than the other instruments.