Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 189
Filter
1.
RSC Adv ; 14(31): 22086-22090, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39005247

ABSTRACT

Cold rolling has been used as a real-time surface oxidation control method to create colored strips on flexible substrates. By controlling the extrusion rate in real time, a variety of colored strips have been fabricated on Ga-based liquid metal (LM) strips. X-ray photoelectron spectroscopy (XPS) analysis shows that the surfaces of the colored strips, which were obtained through extrusion rate control of LM-Al, consist primarily of metal oxide composites, including Ga2O3, Ga2O, Al2O3, SnO2, and In2O3. The colors of the strip surfaces are directly correlated with the oxide film thickness. Additionally, these cold-rolled colored thin strips demonstrate high conductivity and have significant potential for use as conductive flexible components with indicator functions in the flexible electronics realm.

2.
Neural Netw ; 178: 106458, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38901093

ABSTRACT

The detection of therapeutic peptides is a topic of immense interest in the biomedical field. Conventional biochemical experiment-based detection techniques are tedious and time-consuming. Computational biology has become a useful tool for improving the detection efficiency of therapeutic peptides. Most computational methods do not consider the deviation caused by noise. To improve the generalization performance of therapeutic peptide prediction methods, this work presents a sequence homology score-based deep fuzzy echo-state network with maximizing mixture correntropy (SHS-DFESN-MMC) model. Our method is compared with the existing methods on eight types of therapeutic peptide datasets. The model parameters are determined by 10 fold cross-validation on their training sets and verified by independent test sets. Across the 8 datasets, the average area under the receiver operating characteristic curve (AUC) values of SHS-DFESN-MMC are the highest on both the training (0.926) and independent sets (0.923).

3.
Kidney Res Clin Pract ; 43(4): 548-558, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38934027

ABSTRACT

BACKGROUND: The Acute Disease Quality Initiative advocates multidisciplinary care for the survivors of acute kidney injury (AKI). The bundled care strategy recognizes the role of pharmacists. However, their specific contributions in this context remain underexplored. METHODS: This retrospective study examined the efficacy of pharmacist-led post-AKI pharmaceutical care in outpatient settings at a single center. Adults with recent AKI during hospitalization, maintaining an estimated glomerular filtration rate <45 mL/min/1.73 m2 postdischarge, were enrolled in a multidisciplinary team care program from March 2022 to January 2023, with a 6-month follow-up period. Pharmacist-delivered care adhered to international multidisciplinary consensus guidelines. Efficacy was evaluated by analyzing medication-related recommendations, medication adherence, nephrotoxic drug utilization, and renoprotective medication usage before and after the intervention. RESULTS: A total of 40 patients were referred to the pharmacist-managed clinic. Of these, 33 patients (mean age, 63 ± 15 years; 60.6% male) attended the clinic. Nineteen patients completed follow-up visits. The pharmacist provided 14 medication-related recommendations to relevant physicians, with 10 of these recommendations (71.4%) being accepted. There was a significant decrease in the use of modifiable nephrotoxic drugs (p = 0.03). However, no significant improvements were noted in medication adherence or the utilization of renoprotective medications. CONCLUSION: Our study underscores the potential benefits of pharmacist-led post-AKI bundled care strategy in outpatient settings. We observed a significant reduction in the utilization of modifiable nephrotoxic drugs, indicating the effectiveness of pharmacist interventions in optimizing medication regimens to mitigate renal harm.

4.
Adv Biol (Weinh) ; 8(7): e2300678, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38837283

ABSTRACT

This study focuses on the role of topoisomerases (TOPs) in sarcomas (SARCs), highlighting TOPs' influence on sarcoma prognosis through mRNA expression, genetic mutations, immune infiltration, and DNA methylation analysis using transcriptase sequencing and other techniques. The findings indicate that TOP gene mutations correlate with increased inflammation, immune cell infiltration, DNA repair abnormalities, and mitochondrial fusion genes alterations, all of which negatively affect sarcoma prognosis. Abnormal TOP expression may independently affect sarcoma patients' survival. Cutting-edge genomic tools such as Oncomine, gene expression profiling interactive analysis (GEPIA), and cBio Cancer Genomics Portal (cBioPortal) are utilized to explore the TOP gene family (TOP1/1MT/2A/2B/3A/3B) in soft-tissue sarcomas (STSs). This in-depth analysis reveals a notable upregulation of TOP mRNA in STS patients arcoss various SARC subtypes, French Federation Nationale des Centres de Lutte Contre le Cancer classification (FNCLCC) grades, and specific molecular profiles correlating with poorer clinical outcomes. Furthermore, this investigation identifies distinct patterns of immune cell infiltration, genetic mutations, and somatic copy number variations linked to TOP genes that inversely affect patient survival rates. These findings underscore the diagnostic and therapeutic relevance of the TOP gene suite in STSs.


Subject(s)
Sarcoma , Humans , Sarcoma/genetics , Sarcoma/therapy , Prognosis , DNA Topoisomerases/genetics , DNA Topoisomerases/metabolism , Mutation , Genomics , Gene Expression Regulation, Neoplastic , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/therapy , Soft Tissue Neoplasms/mortality , Gene Expression Profiling
5.
Angew Chem Int Ed Engl ; : e202408321, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926096

ABSTRACT

exo-6b2-Methyl-substituted pentabenzocorannulene (exoPBC-Me) was synthesized by the palladium-catalyzed cyclization of 1,2,3-triaryl-1H-cyclopenta[l]phenanthrene. Its bowl-shaped geometry with an sp3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X-ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen-doped analogs with intact π-conjugated backbones (see the main text), exo-PBC-Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250-620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO-LUMO gap (2.01 eV). exo-PBC-Me formed polar crystals where all bowl-in-bowl stacking with close π···π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp3 carbon atom in the backbone.

6.
Int Immunopharmacol ; 133: 112101, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38640717

ABSTRACT

Intervertebral disc degeneration (IVDD) is a progressive degenerative disease influenced by various factors. Genkwanin, a known anti-inflammatory flavonoid, has not been explored for its potential in IVDD management. This study aims to investigate the effects and mechanisms of genkwanin on IVDD. In vitro, cell experiments revealed that genkwanin dose-dependently inhibited Interleukin-1ß-induced expression levels of inflammatory factors (Interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2) and degradation metabolic protein (matrix metalloproteinase-13). Concurrently, genkwanin upregulated the expression of synthetic metabolism genes (type II collagen, aggrecan). Moreover, genkwanin effectively reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) pathways. Transcriptome sequencing analysis identified integrin α2 (ITGA2) as a potential target of genkwanin, and silencing ITGA2 reversed the activation of PI3K/AKT pathway induced by Interleukin-1ß. Furthermore, genkwanin alleviated Interleukin-1ß-induced senescence and apoptosis in nucleus pulposus cells. In vivo animal experiments demonstrated that genkwanin mitigated the progression of IVDD in the rat model through imaging and histological examinations. In conclusion, This study suggest that genkwanin inhibits inflammation in nucleus pulposus cells, promotes extracellular matrix remodeling, suppresses cellular senescence and apoptosis, through the ITGA2/PI3K/AKT, NF-κB and MAPK signaling pathways. These findings indicate that genkwanin may be a promising therapeutic candidate for IVDD.


Subject(s)
Apoptosis , Cellular Senescence , Flavonoids , Intervertebral Disc Degeneration , Signal Transduction , Animals , Humans , Male , Rats , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Apoptosis/drug effects , Cellular Senescence/drug effects , Disease Models, Animal , Flavonoids/pharmacology , Flavonoids/therapeutic use , Integrin alpha2/metabolism , Integrin alpha2/genetics , Interleukin-1beta/metabolism , Intervertebral Disc Degeneration/drug therapy , Intervertebral Disc Degeneration/pathology , Intervertebral Disc Degeneration/metabolism , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 13/genetics , Nucleus Pulposus/drug effects , Nucleus Pulposus/pathology , Nucleus Pulposus/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats, Sprague-Dawley , Signal Transduction/drug effects
7.
Biomedicines ; 12(4)2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38672277

ABSTRACT

This review critically evaluates advancements in multifunctional hydrogels, particularly focusing on their applications in osteoarthritis (OA) therapy. As research evolves from traditional natural materials, there is a significant shift towards synthetic and composite hydrogels, known for their superior mechanical properties and enhanced biodegradability. This review spotlights novel applications such as injectable hydrogels, microneedle technology, and responsive hydrogels, which have revolutionized OA treatment through targeted and efficient therapeutic delivery. Moreover, it discusses innovative hydrogel materials, including protein-based and superlubricating hydrogels, for their potential to reduce joint friction and inflammation. The integration of bioactive compounds within hydrogels to augment therapeutic efficacy is also examined. Furthermore, the review anticipates continued technological advancements and a deeper understanding of hydrogel-based OA therapies. It emphasizes the potential of hydrogels to provide tailored, minimally invasive treatments, thus highlighting their critical role in advancing the dynamic field of biomaterial science for OA management.

8.
DNA Res ; 31(3)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38590243

ABSTRACT

Calophaca sinica is a rare plant endemic to northern China which belongs to the Fabaceae family and possesses rich nutritional value. To support the preservation of the genetic resources of this plant, we have successfully generated a high-quality genome of C. sinica (1.06 Gb). Notably, transposable elements (TEs) constituted ~73% of the genome, with long terminal repeat retrotransposons (LTR-RTs) dominating this group of elements (~54% of the genome). The average intron length of the C. sinica genome was noticeably longer than what has been observed for closely related species. The expansion of LTR-RTs and elongated introns emerged had the largest influence on the enlarged genome size of C. sinica in comparison to other Fabaceae species. The proliferation of TEs could be explained by certain modes of gene duplication, namely, whole genome duplication (WGD) and dispersed duplication (DSD). Gene family expansion, which was found to enhance genes associated with metabolism, genetic maintenance, and environmental stress resistance, was a result of transposed duplicated genes (TRD) and WGD. The presented genomic analysis sheds light on the genetic architecture of C. sinica, as well as provides a starting point for future evolutionary biology, ecology, and functional genomics studies centred around C. sinica and closely related species.


Subject(s)
Genome, Plant , Retroelements , Fabaceae/genetics , Chromosomes, Plant , Gene Duplication , Genome Size , DNA Transposable Elements , Evolution, Molecular , Terminal Repeat Sequences , Genomics , Introns , Phylogeny
10.
Anal Chim Acta ; 1297: 342303, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38438223

ABSTRACT

Nitric oxide (NO) plays critical roles in both physiology and pathology, serving as a significant signaling molecule. Recent investigations have uncovered the pivotal role of lysosome as a critical organelle where intracellular NO exists and takes function. In this study, we developed a novel ratiometric fluorescent probe called XL-NO and modified it with a morpholine unit, which followed the intramolecular charge transfer (ICT) mechanism. The probe could detect lysosomal nitric oxide with high selectivity and sensitivity. The probe XL-NO contained a secondary amine moiety that could readily react with NO in lysosomes, leading to the formation of the N-nitrosation product. The N-nitroso structure enhanced the capability in push-pull electron, which obviously led to the change of fluorescence from 621 nm to 521 nm. In addition, XL-NO was discovered to have some evident advantages, such as significant ratiometric signal (I521/I621) change, strong anti-interference ability, good biocompatibility, and a low detection limit (LOD = 44.3 nM), which were crucial for the detection of lysosomal NO. To evaluate the practical application of XL-NO, NO imaging experiments were performed in both living cells and zebrafish. The results from these experiments confirmed the feasibility and reliability of XL-NO for exogenous/endogenous NO imaging and lysosome targeting.


Subject(s)
Fluorescent Dyes , Nitric Oxide , Animals , Reproducibility of Results , Zebrafish , Lysosomes
11.
Phys Rev E ; 109(1-1): 014218, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38366533

ABSTRACT

The eigenvalue statistics are an important tool to capture localization to delocalization transition in physical systems. Recently, a ß-Gaussian ensemble is being proposed as a single parameter to describe the intermediate eigenvalue statistics of many physical systems. It is critical to explore the universality of a ß-Gaussian ensemble in complex networks. In this work, we study the eigenvalue statistics of various network models, such as small-world, Erdos-Rényi random, and scale-free networks, as well as in comparing the intermediate level statistics of the model networks with that of a ß-Gaussian ensemble. It is found that the nearest-neighbor eigenvalue statistics of all the model networks are in excellent agreement with the ß-Gaussian ensemble. However, the ß-Gaussian ensemble fails to describe the intermediate level statistics of higher order eigenvalue statistics, though there is qualitative agreement till n<4. Additionally, we show that the nearest-neighbor eigenvalue statistics of the ß-Gaussian ensemble is in excellent agreement with the intermediate higher order eigenvalue statistics of model networks.

12.
Biomedicines ; 12(2)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38397931

ABSTRACT

Cancer-associated muscle wasting is a widespread syndrome in people with cancer and is characterized by weight loss and muscle atrophy, leading to increased morbidity and mortality. However, the tumor-derived factors that affect the development of muscle wasting and the mechanism by which they act remain unknown. To address this knowledge gap, we aimed to delineate differences in tumor molecular characteristics (especially secretion characteristics) between patients with and without sarcopenia across 10 tumor types from The Cancer Genome Atlas (TCGA). We integrated radiological characteristics from CT scans of TCGA cancer patients, which allowed us to calculate skeletal muscle area (SMA) to confirm sarcopenia. We combined TCGA and GTEx (The Genotype-Tissue Expression) data to analyze upregulated secretory genes in 10 tumor types compared with normal tissues. Upregulated secretory genes in the tumor microenvironment and their relation to SMA were analyzed to identify potential muscle wasting biomarkers (560 samples). Meanwhile, their predictive values for patient survival was validated in 3530 samples in 10 tumor types. A total of 560 participants with transcriptomic data and SMA were included. Among those, 136 participants (24.28%) were defined as having sarcopenia based on SMA. Enrichment analysis for upregulated secretory genes in cancers revealed that pathways associated with muscle wasting were strongly enriched in tumor types with a higher prevalence of sarcopenia. A series of SMA-associated secretory protein-coding genes were identified in cancers, which showed distinct gene expression profiles according to tumor type, and could be used to predict prognosis in cancers (p value ≤ 0.002). Unfortunately, those genes were different and rarely overlapped across tumor types. Tumor secretome characteristics were closely related to sarcopenia. Highly expressed secretory mediators in the tumor microenvironment were associated with SMA and could affect the overall survival of cancer patients, which may provide a valuable starting point for the further understanding of the molecular basis of muscle wasting in cancers. More importantly, tumor-derived pro-sarcopenic factors differ across tumor types and genders, which implies that mechanisms of cancer-associated muscle wasting are complex and diverse across tumors, and may require individualized treatment approaches.

13.
Patient Prefer Adherence ; 18: 267-274, 2024.
Article in English | MEDLINE | ID: mdl-38327729

ABSTRACT

Purpose: Patients with chronic kidney disease (CKD) are particularly vulnerable to the risks of polypharmacy, largely owing to various comorbid conditions. This vulnerability is further compounded by an escalated risk of renal function deterioration when exposed to nephrotoxic medications. As part of the national health insurance program in Taiwan, the pre-end-stage kidney disease patient care and education plan has included pharmaceutical care since October 2021. This study aims to explore the effect of pharmacist involvement in a multidisciplinary care team for patients with kidney disease in outpatient settings. Patients and Methods: This retrospective observational study was conducted at a single center. It analyzed data from May 2022 to May 2023, focusing on patients who received medication therapy management in the kidney disease pharmacist-managed clinic. The study assessed changes in patient medication adherence, non-steroidal anti-inflammatory drugs (NSAIDs) usage, CKD stage, and urine protein-to-creatinine ratio (UPCR) after pharmacist intervention. It also documented pharmacists' medication recommendations and the rate of acceptance by physicians. Results: A total of 202 patients who had at least two clinic visits were included in the study. After pharmacist intervention, the proportion of poor medication adherence reduced significantly from 67.8% to 43.1% (p<0.001). The proportion of NSAID users also decreased significantly from 19.8% to 8.4% (p=0.001). CKD stage showed a significant reduction (p=0.007), and the average UPCR improved from 2828.4 to 2111.0 mg/g (p<0.001). The pharmacists provided a total of 56 medication recommendations, with an acceptance rate of 86%. Conclusion: The involvement of pharmacists in the multidisciplinary care team can effectively provide medication-related recommendations, ensuring the effectiveness and safety of patients' medication use, and lead to better kidney function and lower proteinuria.

15.
J Infect Dis ; 229(1): 252-261, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-37882788

ABSTRACT

BACKGROUND: Delayed diagnosis and improper therapy for intraocular infections usually result in poor prognosis. Due to limitations of conventional culture and polymerase chain reaction methods, most causative pathogens cannot be identified from vitreous humor (VH) or aqueous humor (AH) samples with limited volume. METHODS: Patients with suspected intraocular infections were enrolled from January 2019 to August 2021. Metagenomic next-generation sequencing (mNGS) was used to detected causative pathogens. RESULTS: This multicenter prospective study enrolled 488 patients, from whom VH (152) and AH (336) samples were respectively collected and analyzed using mNGS of cell-free DNA (cfDNA). Taking final comprehensive clinical diagnosis as the gold standard, there were 39 patients with indefinite final diagnoses, whereas 288 and 161 patients were diagnosed as definite infectious and noninfectious diseases, respectively. Based on clinical adjudication, the sensitivity (92.2%) and total coincidence rate (81.3%) of mNGS using VH samples were slightly higher than those of mNGS using AH samples (85.4% and 75.4%, respectively). CONCLUSIONS: Using mNGS of cfDNA, an era with clinical experience for more rapid, independent, and impartial diagnosis of bacterial and other intraocular infections can be expected.


Subject(s)
Cell-Free Nucleic Acids , Eye Infections , Humans , Aqueous Humor , Cell-Free Nucleic Acids/genetics , Prospective Studies , High-Throughput Nucleotide Sequencing , Metagenomics , Sensitivity and Specificity
16.
Sci Rep ; 13(1): 20303, 2023 11 20.
Article in English | MEDLINE | ID: mdl-37985702

ABSTRACT

Endothelial dysfunction is a critical initiating factor contributing to cardiovascular diseases, involving the gut microbiome-derived metabolite trimethylamine N-oxide (TMAO). This study aims to clarify the time-dependent molecular pathways by which TMAO mediates endothelial dysfunction through transcriptomics and metabolomics analyses in human microvascular endothelial cells (HMEC-1). Cell viability and reactive oxygen species (ROS) generation were also evaluated. TMAO treatment for either 24H or 48H induces reduced cell viability and enhanced oxidative stress. Interestingly, the molecular signatures were distinct between the two time-points. Specifically, few Gene Ontology biological processes (BPs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were modulated after a short (24H) compared to a long (48H) treatment. However, the KEGG signalling pathways namely "tumour necrosis factor (TNF)" and "cytokine-cytokine receptor interaction" were downregulated at 24H but activated at 48H. In addition, at 48H, BPs linked to inflammatory phenotypes were activated (confirming KEGG results), while BPs linked to extracellular matrix (ECM) structural organisation, endothelial cell proliferation, and collagen metabolism were repressed. Lastly, metabolic profiling showed that arachidonic acid, prostaglandins, and palmitic acid were enriched at 48H. This study demonstrates that TMAO induces distinct time-dependent molecular signatures involving inflammation and remodelling pathways, while pathways such as oxidative stress are also modulated, but in a non-time-dependent manner.


Subject(s)
Endothelial Cells , Vascular Diseases , Humans , Endothelial Cells/metabolism , Methylamines/metabolism , Inflammation/chemically induced , Inflammation/genetics , Inflammation/metabolism , Oxides
17.
Biomedicines ; 11(10)2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37893139

ABSTRACT

The Neural Calcium Sensor1 (NCS1) is a crucial protein that binds to Ca2+ and is believed to play a role in regulating tumor invasion and cell proliferation. However, the role of NCS1 in immune infiltration and cancer prognosis is still unknown. Our study aimed to explore the expression profile, immune infiltration pattern, prognostic value, biological function, and potential compounds targeting NCS1 using public databases. High expression of NCS1 was detected by immune histochemical staining in LIHC (Liver hepatocellular carcinoma), BRCA (Breast invasive carcinoma), KIRC (Kidney renal clear cell carcinoma), and SKCM (Skin Cutaneous Melanoma). The expression of NCS1 in cancer was determined by TCGA (The Cancer Genome Atlas Program), GTEx (The Genotype-Tissue Expression), the Kaplan-Meier plotter, GEO (Gene Expression Omnibus), GEPIA2.0 (Gene Expression Profiling Interactive Analysis 2.0), HPA (The Human Protein Atlas), UALCAN, TIMER2.0, TISIDB, Metascape, Drugbank, chEMBL, and ICSDB databases. NCS1 has genomic mutations as well as aberrant DNA methylation in multiple cancers compared to normal tissues. Also, NCS1 was significantly different in the immune microenvironment, tumor mutational burden (TMB), microsatellite instability (MSI), and immune infiltrate-associated cells in different cancers, which could be used for the typing of immune and molecular subtypes of cancer and the presence of immune checkpoint resistance in several cancers. Univariate regression analysis, multivariate regression analysis, and gene enrichment analysis to construct prognostic models revealed that NCS1 is involved in immune regulation and can be used as a prognostic biomarker for SKCM, LIHC, BRCA, COAD, and KIRC. These results provide clues from a bioinformatic perspective and highlight the importance of NCS1 in a variety of cancers.

18.
Int J Mol Med ; 52(4)2023 10.
Article in English | MEDLINE | ID: mdl-37654229

ABSTRACT

Osteoarthritis (OA) is a chronic progressive articular illness which commonly affects older­aged adults, presenting with cartilage inflammation and degradation. Rutaecarpine (RUT) has been shown to exert promising anti­inflammatory effects; however, the efficacy of RUT in the treatment of OA is debatable. The present study investigated the potential of RUT in alleviating OA in a mouse model. Treatment with RUT inhibited the inflammatory response and extracellular matrix degradation by suppressing process regulators in interleukin (IL)­1ß­stimulated chondrocytes. Moreover, treatment with RUT in vitro upregulated the gene expression of anabolic agents, such as collagen type II, aggrecan and SRY­box transcription factor 9, indicating that RUT contributed to cartilage repair. Additionally, flow cytometric assays, and the measurement of ß­galactosidase levels, autophagic flux and related protein expression revealed that RUT effectively attenuated IL­1ß­induced chondrocyte apoptosis, senescence and autophagy impairment. In addition, bioinformatics analysis and in vitro experiments demonstrated that RUT protected cartilage by mediating the phosphoinositide­3­kinase (PI3K)/Akt/nuclear factor­κB (NF­κB) and mitogen­activated protein kinase (MAPK) pathways. The ameliorative effects of RUT on IL­1ß­stimulated chondrocytes were abrogated when siRNA was used to knock down integrin αVß3. Furthermore, the results of immunohistochemical analysis and microcomputed tomography confirmed the in vivo therapeutic effects of RUT in mice with OA. On the whole, the present study demonstrates that RUT attenuates the inflammatory response and cartilage degradation in mice with OA by suppressing the activation of the PI3K/AKT/NF­κB and MAPK pathways. Integrin αVß3 may play a pivotal role in these effects.


Subject(s)
NF-kappa B , Osteoarthritis , Animals , Mice , Mitogen-Activated Protein Kinases , Integrin alphaVbeta3 , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , X-Ray Microtomography , Osteoarthritis/drug therapy
19.
Clin Transl Immunology ; 12(9): e1461, 2023.
Article in English | MEDLINE | ID: mdl-37720629

ABSTRACT

Objectives: Non-infectious uveitis is often secondary to systemic autoimmune diseases, with Behçet's disease (BD) and Vogt-Koyanagi-Harada disease (VKHD) as the two most common causes. Uveitis in BD and VKHD can show similar clinical manifestations, but the underlying immunopathogenesis remains unclear. Methods: To understand immune landscapes in inflammatory eye tissues, we performed single-cell RNA paired with T cell receptor (TCR) sequencing of immune cell infiltrates in aqueous humour from six patients with BD (N = 3) and VKHD (N = 3) uveitis patients. Results: Although T cells strongly infiltrated in both types of autoimmune uveitis, myeloid cells only significantly presented in BD uveitis but not in VKHD uveitis. Conversely, VKHD uveitis but not BD uveitis showed an overwhelming dominance by CD4+ T cells (> 80%) within the T cell population due to expansion of CD4+ T cell clusters with effector memory (Tem) phenotypes. Correspondingly, VKHD uveitis demonstrated a selective expansion of CD4+ T cell clones which were enriched in pro-inflammatory Granzyme H+ CD4+ Tem cluster and showed TCR and Th1 pathway activation. In contrast, BD uveitis showed a preferential expansion of CD8+ T cell clones in pro-inflammatory Granzyme H+ CD8+ Tem cluster, and pathway activation for cytoskeleton remodelling, cellular adhesion and cytotoxicity. Conclusion: Single-cell analyses of ocular tissues reveal distinct landscapes of immune cell infiltration and T-cell clonal expansions between VKHD and BD uveitis. Preferential involvements of pro-inflammatory CD4+ Th1 cells in VKHD and cytotoxic CD8+ T cells in BD suggest a difference in disease immunopathogenesis and can guide precision disease management.

20.
Angew Chem Int Ed Engl ; 62(42): e202309619, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37610742

ABSTRACT

In this work, a facile and versatile strategy for the synthesis of contorted polycyclic aromatic hydrocarbons (PAHs) starting from the functionalized pentacene was established. A series of novel PAHs 1-4 and their derivatives were synthesized through a simple two-step synthesis procedure involving an intramolecular reductive Friedel-Crafts cyclization of four newly synthesized pentacene aldehydes 5-8 as a key step. All the molecules were confirmed by single-crystal X-ray diffraction and their photophysical and electrochemical properties were studied in detail. Interestingly, the most striking feature of 1-4 is their highly contorted carbon structures and the accompanying helical chirality. In particular, the optical resolution of 2 was successfully achieved by chiral-phase HPLC, and the enantiomers were characterized by circular dichroism and circularly polarized luminescence spectroscopy. Despite the highly nonplanar conformations, these contorted PAHs exhibited emissive properties with moderate-to-good fluorescence quantum yields, implying the potential utility of this series PAHs as high-quality organic laser dyes. By using a self-assembly method with the help of epoxy resin, a bottle microlaser based on 3 a was successfully illustrated with a lasing wavelength of 567.8 nm at a threshold of 0.3 mJ/cm2 . We believe that this work will shed light on the chemical versatility of pentacene and its derivatives in the construction of novel functionalized PAHs.

SELECTION OF CITATIONS
SEARCH DETAIL
...