Objective
To elucidate the role of decorin, a small leucine‐rich proteoglycan, in the degradation of cartilage matrix during the progression of post‐traumatic osteoarthritis (OA).
Methods
...Three‐month–old decorin‐null (Dcn−/−) and inducible decorin‐knockout (DcniKO) mice were subjected to surgical destabilization of the medial meniscus (DMM) to induce post‐traumatic OA. The OA phenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan (sGAG) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy–nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro–computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild‐type and Dcn−/− mice were stimulated with the inflammatory cytokine interleukin‐1β (IL‐1β) in vitro (n = 6 mice per group). The resulting chondrocyte response to IL‐1β and release of sGAGs were quantified.
Results
In both Dcn−/− and DcniKO mice, the absence of decorin resulted in accelerated sGAG loss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control (P < 0.05). Also, Dcn−/− mice developed more salient osteophytes, illustrating more severe OA. In cartilage explants treated with IL‐1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion of sGAGs was released to the media from Dcn−/− mouse explants, in both live and devitalized conditions (P < 0.05).
Conclusion
In post‐traumatic OA, decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration.
Acute lung injury (ALI) is a high mortality disease with acute inflammation. Corylin is a compound isolated from the whole plant of Psoralea corylifolia L. and has been reported to have ...anti-inflammatory activities. Herein, we investigated the therapeutic potential of corylin on lipopolysaccharides (LPS)-induced ALI, both in vitro and in vivo. The levels of proinflammatory cytokine secretions were analyzed by ELISA; the expressions of inflammation-associated proteins were detected using Western blot; and the number of immune cell infiltrations in the bronchial alveolar lavage fluid (BALF) were detected by multicolor flow cytometry and lung tissues by hematoxylin and eosin (HE) staining, respectively. Experimental results indicated that corylin attenuated LPS-induced IL-6 production in human bronchial epithelial cells (HBEC3-KT cells). In intratracheal LPS-induced ALI mice, corylin attenuated tissue damage, suppressed inflammatory cell infiltration, and decreased IL-6 and TNF-α secretions in the BALF and serum. Moreover, it further inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including p-JNK, p-ERK, p-p38, and repressed the activation of signal transducer and activator of transcription 3 (STAT3) in lungs. Collectively, our results are the first to demonstrate the anti-inflammatory effects of corylin on LPS-induced ALI and suggest corylin has significant potential as a novel therapeutic agent for ALI.
The air-conditioning systems have become an indispensable part of our daily life for keeping the quality of life. However, to improve the thermal comfort and reduce energy consumption is crucial to ...use the air conditioners effectively with rapid development of artificial intelligence technology. This study explored the correlation between the response of human physiological parameters and thermal sensation voting (TSV) to evaluate the comfort level among various cold and hot stimulations. The variations of the three physiological parameters, which were body surface temperature, skin blood flow (SBF), and sweat area on the skin surface, and TSV values were all positively correlated with the stimulation amount under the stimulation of cold wind, hot wind, and heat radiation, but the relationship was not completely linear. Among the three physiological parameters, the forehead skin temperature has the closest relationship with TSV, followed by the SBF and sweat. Among three stimulations, the cold wind stimulation causes the closest relationship between TSV and forehead temperature, followed by the radiation and hot wind stimulations. Through three different machine learning models, namely, random forest (RF) model, support vector machine (SVM) model, and neural network (NN) model, the stimulation of cold wind, hot wind, and heat radiation was applied to investigate the variation of the three physiological parameters as the input of the models. Moreover, the models were evaluated and verified by TSV. The results revealed that among the three different machine learning methods, RF had the best accuracy. The established thermal comfort models can predict the real-time user’s thermal comfort feeling, so that air-conditioning equipment’s performance can be optimized to create a healthy and energy-saving comfortable environment.
The clinical success of dental titanium implants is profoundly linked to implant stability and osseointegration, which comprises pre-osteoblast proliferation, osteogenic differentiation, and ...extracellular mineralization. Because of the bio-inert nature of titanium, surface processing using subtractive or additive methods enhances osseointegration ability but limits the benefit due to accompanying surface contamination. By contrast, laser processing methods increase the roughness of the implant surface without contamination. However, the effects of laser-mediated distinct surface structures on the osteointegration level of osteoblasts are controversial. The role of a titanium surface with a laser-mediated microchannel structure in pre-osteoblast maturation remains unclear. This study aimed to elucidate the effect of laser-produced microchannels on pre-osteoblast maturation. Pre-osteoblast human embryonic palatal mesenchymal cells were seeded on a titanium plate treated with grinding (G), sandblasting with large grit and acid etching (SLA), or laser irradiation (L) for 3-18 days. The proliferation and morphology of pre-osteoblasts were evaluated using a Trypan Blue dye exclusion test and fluorescence microscopy. The mRNA expression, protein expression, and protein secretion of osteogenic differentiation markers in pre-osteoblasts were evaluated using reverse transcriptase quantitative polymerase chain reaction, a Western blot assay, and a multiplex assay, respectively. The extracellular calcium precipitation of pre-osteoblast was measured using Alizarin red S staining. Compared to G- and SLA-treated titanium surfaces, the laser-produced microchannel surfaces enhanced pre-osteoblast proliferation, the expression/secretion of osteogenic differentiation markers, and extracellular calcium precipitation. Laser-treated titanium implants may enhance the pre-osteoblast maturation process and provide extra benefits in clinical application.
Di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, is a ubiquitous environmental pollutant that can disrupt endocrine function. Epidemiological studies suggest that chronic exposure to DEHP in ...the environment is associated with the prevalence of childhood allergic diseases; however, the underlying causal relationship and immunological mechanism remain unclear. This study explored the immunomodulatory effect of DEHP on allergic lung inflammation, while particularly focusing on the impact of DEHP and its metabolite on dendritic cell differentiation and activity of peroxisome proliferator-activated receptor gamma (PPARγ). The results showed that exposure to DEHP at a human tolerable daily intake dose exacerbated allergic lung inflammation in mice.
flow cytometric analysis revealed that DEHP-exposed mice displayed a significantly decreased number of CD8α
dendritic cells (DCs) in spleens and DC progenitors in the bone marrow, as well as, less interleukin-12 production in splenic DCs and increased T helper 2 polarization. Pharmacological experiments showed that mono-(2-ethylhexyl) phthalate (MEHP), the main metabolite of DEHP, significantly hampered the differentiation of CD8α
DCs from Fms-like tyrosine kinase 3 ligand-differentiated bone marrow culture, by modulating PPARγ activity. These results suggested that chronic exposure to DEHP at environmentally relevant levels, promotes allergic lung inflammation, at least in part, by altering DC differentiation through the MEHP-PPARγ axis. This study has crucial implications for the interaction(s) between environmental pollutants and innate immunity, with respect to the development of allergic asthma.
Abstract
Obtaining sufficient genetic material from a limited biological source is currently the primary operational bottleneck in studies investigating biodiversity and genome evolution. In this ...study, we employed multiple displacement amplification (MDA) and Smartseq2 to amplify nanograms of genomic DNA and mRNA, respectively, from individual Caenorhabditis elegans. Although reduced genome coverage was observed in repetitive regions, we produced assemblies covering 98% of the reference genome using long-read sequences generated with Oxford Nanopore Technologies (ONT). Annotation with the sequenced transcriptome coupled with the available assembly revealed that gene predictions were more accurate, complete and contained far fewer false positives than de novo transcriptome assembly approaches. We sampled and sequenced the genomes and transcriptomes of 13 nematodes from early-branching species in Chromadoria, Dorylaimia and Enoplia. The basal Chromadoria and Enoplia species had larger genome sizes, ranging from 136.6 to 738.8 Mb, compared with those in the other clades. Nine mitogenomes were fully assembled, and displayed a complete lack of synteny to other species. Phylogenomic analyses based on the new annotations revealed strong support for Enoplia as sister to the rest of Nematoda. Our result demonstrates the robustness of MDA in combination with ONT, paving the way for the study of genome diversity in the phylum Nematoda and beyond.
Graphical Abstract
Graphical Abstract
Background
Periodontal disease is a chronic inflammatory disease. Given its high prevalence, especially in aging population, the detailed mechanisms about pathogenesis of periodontal disease are ...important issues for study. Neutrophil firstly infiltrates to periodontal disease‐associated pathogen loci and amplifies the inflammatory response for host defense. However, excessive neutrophil‐secreted neutrophil elastase (NE) damages the affected gingival. In lung and esophageal epithelium, NE had been proved to upregulate several growth factors including placenta growth factor (PGF). PGF is an angiogenic factor with proinflammatory properties, which mediates the progression of inflammatory disease. Therefore, we hypothesize excessive NE upregulates PGF and participates in the pathogenesis and progression of periodontal disease.
Methods
In gingival epithelial cells (GEC), growth factors array demonstrated NE‐increased growth factors and further be corroborated by Western blot assay and ELISA. The GEC inflammation was evaluated by ELISA. In mice, the immunohistochemistry results demonstrated ligature implantation‐induced neutrophil infiltration and growth factor upregulation. By multiplex assay, the ligature‐induced proinflammatory cytokines level in gingival crevicular fluid (GCF) were evaluated. Finally, alveolar bone absorption was analyzed by micro‐CT images and H & E staining.
Results
NE upregulated PGF expression and secretion in GEC. PGF promoted GEC to secret IL‐1β, IL‐6, and TNF‐α in GCF In periodontal disease animal model, ligature implantation triggered NE infiltration and PGF expression. Blockade of PGF attenuated the ligature implantation‐induced IL‐1β, IL‐6, TNF‐α and MIP‐2 secretion and ameliorated the alveolar bone loss in mice.
Conclusion
In conclusion, the NE‐induced PGF triggers gingival epithelium inflammation and promotes the pathogenesis and progression of periodontal disease.
The techniques, protocols, and advancements revolving around printed circuit boards (PCBs) have been gaining sustained attention in the realm of micro-total analysis systems (μTAS) as more and more ...efforts are devoted to searching for standardized, highly reliable, and industry-friendly solutions for point-of-care diagnostics. In this Perspective, we set out to identify the current state in which the field of μTAS finds itself, the challenges encountered by researchers in the implementation of these technologies, and the potential improvements that can be targeted to meet the current demands. We also line up some trending innovations, such as 3D printing and wearable devices, along with the development of lab-on-PCB to increase the possibility of multifunctional biosensing activities propelled by integrated microfluidic networks for a wider range of applications, anticipating to catalyze the full potential of μTAS.
Periodic mammography and/or sonography examinations are conducted across numerous hospitals nationalwidely, especially for antedees with a positive mammography screening. Despite the regular ...practice, clinical efficacy of hospital-based breast cancer surveillance remains unclear. Specifically, the impact of surveillance interval upon survival and prognostic surrogates stratified by menopausal status, as well as malignant transition rate should be deciphered. We retrieved cancer registry to ascertain 841 breast cancers with surveillance history through administration data. Healthy controls underwent breast surveillance and were concurrently free of cancer. More benign diseases rather than cancers were identified from premenopausal women (age ≤50 years) with sonography alone within one year, as well as older women (age >50) with both mammography and sonography one to two years before a cancer or benign diagnosis. Among breast cancers, mammography alone during the antecedent one to two years had a protective effect for diagnosing carcinoma in situ rather than invasive cancer (age-adjusted odds ratio: 0.048, P = 0.016). Three-state time homogeneous Markov model showed that hospital-based breast surveillance within 2 years of disease onset reduced the malignant transition rate by 65.16% (59.79–76.74%). The clinical efficacy of breast cancer surveillance was evidenced.
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