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BACKGROUND: Maedi-visna virus (MVV) is a lentivirus that infects monocyte/macrophage lineage cells in sheep, goats, and wild ruminants and causes pneumonia, mastitis, arthritis, and encephalitis. The immune response to MVV infection is complex, and a complete understanding of its infection and pathogenesis is lacking. This study investigated the in vivo transcriptomic patterns of lung tissues in sheep exposed to MVV using the RNA sequencing technology. RESULT: The results indicated that 2,739 genes were significantly differentially expressed, with 1,643 downregulated genes and 1,096 upregulated genes. Many variables that could be unique to MVV infections were discovered. Gene Ontology analysis revealed that a significant proportion of genes was enriched in terms directly related to the immune system and biological responses to viral infections. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the most enriched pathways were related to virus-host cell interactions and inflammatory responses. Numerous immune-related genes, including those encoding several cytokines and interferon regulatory factors, were identified in the protein-protein interaction network of differentially expressed genes (DEGs). The expression of DEGs was evaluated using real-time polymerase chain reaction and western blot analysis. CXCL13, CXCL6, CXCL11, CCR1, CXCL8, CXCL9, CXCL10, TNFSF8, TNFRSF8, IL7R, IFN-γ, CCL2, and MMP9 were upregulated. Immunohistochemical analysis was performed to identify the types of immune cells that infiltrated MVV-infected tissues. B cells, CD4+ and CD8+ T cells, and macrophages were the most prevalent immune cells correlated with MVV infection in the lungs. CONCLUSION: Overall, the findings of this study provide a comprehensive understanding of the in vivo host response to MVV infection and offer new perspectives on the gene regulatory networks that underlie pathogenesis in natural hosts.
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Pulmão , Vírus Visna-Maedi , Animais , Vírus Visna-Maedi/genética , Pulmão/virologia , Pulmão/imunologia , Pulmão/patologia , Ovinos , Perfilação da Expressão Gênica , Transcriptoma , Pneumonia Intersticial Progressiva dos Ovinos/genética , Pneumonia Intersticial Progressiva dos Ovinos/virologia , Pneumonia Intersticial Progressiva dos Ovinos/imunologia , Mapas de Interação de Proteínas , Regulação da Expressão Gênica , Ontologia GenéticaRESUMO
Abdominal aortic aneurysm (AAA) is a dangerous vascular disease without any effective drug therapies so far. Emerging evidence suggests the phenotypic differences in perivascular adipose tissue (PVAT) between regions of the aorta are implicated in the development of atherosclerosis evidenced by the abdominal aorta more vulnerable to atherosclerosis than the thoracic aorta in large animals and humans. The prevalence of thoracic aortic aneurysms (TAA) is much less than that of abdominal aortic aneurysms (AAA). In this study we investigated the effect of thoracic PVAT (T-PVAT) transplantation on aortic aneurysm formation and the impact of T-PVAT on vascular smooth muscle cells. Calcium phosphate-induced mouse AAA model was established. T-PVAT (20 mg) was implanted around the abdominal aorta of recipient mice after removal of endogenous abdominal PVAT (A-PVAT) and calcium phosphate treatment. Mice were sacrificed two weeks after the surgery and the maximum external diameter of infrarenal aorta was measured. We found that T-PVAT displayed a more BAT-like phenotype than A-PVAT; transplantation of T-PVAT significantly attenuated calcium phosphate-induced abdominal aortic dilation and elastic degradation as compared to sham control or A-PVAT transplantation. In addition, T-PVAT transplantation largely preserved smooth muscle cell content in the abdominal aortic wall. Co-culture of T-PVAT with vascular smooth muscle cells (VSMCs) significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. RNA sequencing analysis showed that T-PVAT was enriched by browning adipocytes and anti-apoptotic secretory proteins. We further verified that the secretome of mature adipocytes isolated from T-PVAT significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. Using proteomic and bioinformatic analyses we identified cartilage oligomeric matrix protein (COMP) as a secreted protein significantly increased in T-PVAT. Recombinant COMP protein significantly inhibited VSMC apoptosis. We conclude that T-PVAT exerts anti-apoptosis effect on VSMCs and attenuates AAA formation, which is possibly attributed to the secretome of browning adipocytes.
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Aneurisma da Aorta Abdominal , Aneurisma Aórtico , Aterosclerose , Humanos , Camundongos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Peróxido de Hidrogênio/metabolismo , Secretoma , Músculo Liso Vascular/metabolismo , Cicloeximida/metabolismo , Proteômica , Tecido Adiposo/metabolismo , Aneurisma Aórtico/metabolismo , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/metabolismo , Aorta Abdominal/cirurgia , Aterosclerose/metabolismo , Adipócitos Marrons , Camundongos Endogâmicos C57BLRESUMO
PURPOSE: Colchicine, a multipotent anti-inflammatory drug, has been reported to alleviate cardiac remodeling and improve cardiac function after acute myocardial infarction (AMI). However, the underlying mechanism remains incompletely understood. Because neutrophils extracellular traps (NETs) enhance inflammation and participate in myocardial ischemia injury, and colchicine can inhibit NETosis, we thus aimed to determine whether colchicine exerts cardioprotective effects on AMI via suppressing NETs. METHODS: Adult C57BL/6 mice were subjected to permanent ligation of the left anterior descending coronary artery and treated with colchicine (0.1 mg/kg/day) or Cl-amidine (10 mg/kg/day) for 7 or 28 days after AMI. Cardiac function was evaluated by echocardiography, and NETs detected by immunofluorescence. ROS production was detected using 2',7'-dichlorodihydrofluorescein diacetates (DCFH-DA) fluorometry. Intracellular Ca2+ concentration was assessed by a fluorometric ratio technique. RESULTS: We found that colchicine treatment significantly increased mice survival (89.8% in the colchicine group versus 67.9% in control, n = 32 per group; log-rank test, p < 0.05) and improved cardiac function at day 7 (left ventricular ejection fraction (LVEF): 28.0 ± 9.2% versus 12.6 ± 3.9%, n = 8 per group; p < 0.001) and at day 28 (LVEF: 26.2 ± 7.2% versus 14.8 ± 6.7%, n = 8 per group; p < 0.001) post-AMI. In addition, the administration of colchicine inhibited NETs formation and inflammation. Furthermore, colchicine inhibited NETs formation by reducing NOX2/ROS production and Ca2+ influx. Moreover, prevention of NETs formation with Cl-amidine significantly alleviated AMI-induced cardiac remodeling. CONCLUSIONS: Colchicine inhibited NETs and cardiac inflammation, and alleviated cardiac remodeling after acute myocardial infarction.
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Type 1 diabetes (T1D) is correlated with osteopenia primarily due to low bone formation. Parathyroid hormone (PTH) is a known anabolic agent for bone, the anabolic effects of which are partially mediated through the Wnt/ß-catenin signaling pathway. In the present study, we first determined the utility of intermittent PTH treatment in a streptozotocin-induced T1D mouse model. It was shown that the PTH-induced anabolic effects on bone mass and bone formation were attenuated in T1D mice compared with nondiabetic mice. Further, PTH treatment failed to activate ß-catenin signaling in osteoblasts of T1D mice and was unable to improve osteoblast proliferation and differentiation. Next, the Col1-3.2 kb-CreERTM; ß-cateninfx(ex3) mice were used to conditionally activate ß-catenin in osteoblasts by injecting tamoxifen, and we addressed whether or not preactivation of ß-catenin boosted the anabolic action of PTH on T1D-related bone loss. The results demonstrated that pretreatment with activation of osteoblastic ß-catenin followed by PTH treatment outperformed PTH or ß-catenin activation monotherapy and led to greatly improved bone structure, bone mass, and bone strength in this preclinical model of T1DM. Further analysis demonstrated that osteoblast proliferation and differentiation, as well as osteoprogenitors in the marrow, were all improved in the combination treatment group. These findings indicated a clear advantage of developing ß-catenin as a target to improve the efficacy of PTH in the treatment of T1D-related osteopenia.
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Anabolizantes/farmacologia , Osso e Ossos/efeitos dos fármacos , Diabetes Mellitus Tipo 1/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Hormônio Paratireóideo/farmacologia , beta Catenina/metabolismo , Animais , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/patologia , CamundongosRESUMO
Bone marrow adipose tissue (BMAT) has recently been found to induce osteoclastogenesis by secreting RANKL. Although Type 1 diabetes mellitus (T1DM) has been reported to be associated with increased BMAT and bone loss, little is known about the relationship between BMAT and osteoclasts in T1DM. We studied the role of BMAT in the alterations of osteoclast activities in early-stage T1DM, by using a streptozotocin-induced T1DM mouse model. Our results showed that osteoclast activity was enhanced in the long bones of T1DM mice, accompanied by increased protein expression of RANKL. However, RANKL mRNA levels in bone tissues of T1DM mice remained unchanged. Meanwhile, we found that BMAT was significantly increased in the long bones of T1DM mice, and both mRNA and protein levels of RANKL were elevated in the diabetic BMAT. More importantly, RANKL protein was mainly expressed on the cell membranes of the increased adipocytes, most of which were located next to the metaphyseal region. These results suggest that the enhanced bone resorption in early-stage diabetic mice is induced by RANKL derived from BMAT rather than the bone tissue itself.
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Adipócitos/patologia , Reabsorção Óssea/patologia , Diabetes Mellitus Tipo 1/patologia , Ligante RANK/metabolismo , Adipócitos/metabolismo , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Reabsorção Óssea/etiologia , Reabsorção Óssea/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ligante RANK/análiseRESUMO
BACKGROUND: Fractures in older men are not uncommon and need to be healed as soon as possible to avoid related complications. Anti-osteoporotic drugs targeting Wnt/ß-catenin and PTH (parathyroid hormone) to promote fracture healing have become an important direction in recent years. The study is to observe whether there is a difference in adult and aged situations by activating two signal paths. METHODS: A single cortical hole with a diameter of 0.6 mm was made in the femoral metaphysis of Catnblox(ex3) mice and wild-type mice. The fracture healing effects of CA (Wnt/ß-catenin activation) and PTH (activated by PTH (1-34) injections) were assessed by X-ray and CT imaging on days 7, 14, and 21 after fracture. The mRNA levels of ß-catenin, PTH1R(Parathyroid hormone 1 receptor), and RUNX2(Runt-related transcription factor 2) in the fracture defect area were detected using RT-PCR. Angiogenesis and osteoblasts were observed by immunohistochemistry and osteoclasts were observed by TRAP (Tartrate-resistant Acid Phosphatase). RESULT: Adult CA mice and adult PTH mice showed slightly better fracture healing than adult wild-type (WT) mice, but there was no statistical difference. Aged CA mice showed better promotion of angiogenesis and osteoblasts and better fracture healing than aged PTH mice. CONCLUSION: The application of Wnt/ß-catenin signaling pathway drugs for fracture healing in elderly patients may bring better early effects than PTH signaling pathway drugs, but the long-term effects need to be observed.
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Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/metabolismo , Consolidação da Fratura/fisiologia , Hormônio Paratireóideo/metabolismo , Via de Sinalização Wnt/fisiologia , Fatores Etários , Animais , Masculino , Camundongos , Camundongos TransgênicosRESUMO
Parathyroid hormone (PTH) and agents related to the manipulation of Wnt/ß-catenin signalling are two promising anabolic anti-osteoporotic therapies that have been shown to promote the healing of bone fractures. Now, it is widely accepted that cortical bone and trabecular bone are two different compartments, and should be treated as separate compartments in pathological processes, such as fracture healing. It is currently unknown whether PTH and the activation of ß-catenin signalling would demonstrate different effects on cortical bone and trabecular bone healing. In the current study, single 0.6-mm cortex holes were made in the femur metaphysis and diaphysis of mice, and then, PTH application and ß-catenin activation were used to observe the promoting effect on bone healing. The effects of ß-catenin and PTH signalling on fracture healing were observed by X-ray and CT at 3, 6, and 14 days after fracture, and the levels of ß-catenin were detected by RT-PCR assay, and the number of specific antigen-positive cells of BRDU, OCN, RUNX2 was counted by immunohistochemical staining. While ß-catenin activation and PTH were found to demonstrate similar effects on accelerating metaphyseal bone healing, activation of ß-catenin showed a more striking effect than PTH on promoting diaphyseal bone healing. These findings might be helpful for selecting proper medication to accelerate fracture healing of different bone compartments.
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Fêmur/fisiopatologia , Hormônio Paratireóideo/metabolismo , Proteínas Wnt/metabolismo , Cicatrização , beta Catenina/metabolismo , Animais , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/metabolismo , Fraturas do Fêmur/fisiopatologia , Fêmur/diagnóstico por imagem , Masculino , Camundongos , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
In recent years, several studies have found that the disruption of type IA receptor of bone morphogenetic proteins (BMPR1A) could increase bone mass. However, whether disruption of BMPR1A could have an effect on bone quality and bone strength is currently unknown. Osteoblast-targeted conditional knockout (cKO) of BMPRIA by crossing 3.2-kb Col1-CreER™ mice with BMPR1A fx +/+ mice was conducted. Then, in vitro and in vivo studies were employed to examine the effect of BMPR1A knockout on bone quality and bone strength. It was found that the ultimate force and stiffness of the femora decreased significantly in cKO mice when compared to control mice. The content of collagen and mineralization level decreased as the structure of the collagen became disorganized. The morphology of osteocytes in cKO mice was abnormal as well. The expression level of osteocalcin, a marker for the terminal differentiation of osteoblasts, decreased in cKO mice. This data indicated that the differentiation of osteoblasts in cKO mice was impaired. Immunohistochemistry examination revealed deregulated expression of dickkopf 1(DKK1) in osteocytes in cKO mice. Adding DKK1 to the culture medium reversed these effects. In conclusion, even though disruption of BMPR1A could increase bone mass, it also impairs bone quality and bone strength.
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Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Osso e Ossos/fisiologia , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Animais , Biomarcadores/metabolismo , Fenômenos Biomecânicos , Contagem de Células , Diferenciação Celular , Colágeno/metabolismo , Masculino , Camundongos Knockout , Osteoblastos/citologia , Osteoblastos/ultraestrutura , Osteócitos/metabolismo , Osteócitos/ultraestrutura , Tíbia/fisiologiaRESUMO
Accumulating evidence suggests that Wnt/ß-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of ß-catenin (CA-ß-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-ß-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-ß-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-ß-catenin mice. Then the effect of CA-ß-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-ß-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-ß-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-ß-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-ß-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-ß-catenin mice. In summary, osteoblastic CA-ß-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength.
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Osso e Ossos/metabolismo , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Osteoblastos/metabolismo , beta Catenina/metabolismo , Animais , Desenvolvimento Ósseo , Osso e Ossos/citologia , Diferenciação Celular/genética , Linhagem Celular , Camundongos , Osteoblastos/citologia , Proteínas Wnt/metabolismo , Via de Sinalização Wnt/fisiologiaRESUMO
Introduction: Optical coherence tomography (OCT) is a pivotal imaging modality in ophthalmology for real-time, in vivo visualization of retinal structures. To enhance the capability and safety of OCT, this study focuses on the development of a micro intraocular OCT probe. The demand for minimal invasiveness and precise imaging drives the need for advanced probe designs that can access tight and sensitive areas, such as the ocular sclera. Methods: A novel OCT probe was engineered using a piezoelectric tube with quartered electrodes to drive Lissajous scanning movements at the end of a single-mode fiber. This design allows the probe to enter the eyeball through a scleral opening. Structural innovation enables the outer diameter of the endoscopic OCT probe to be adjusted from 13G (2.41 mm) to 25G (0.51 mm), accommodating various imaging field sizes and ensuring compatibility with different scleral incisions. Results: The fabricated micro intraocular OCT probe successfully performed preliminary imaging experiments on in vivo fingers. The Lissajous scanning facilitated comprehensive coverage of the target area, enhancing the imaging capabilities. Discussion: The integration of a piezoelectric tube with quartered outside electrodes into the OCT probe design proved effective for achieving precise control over scanning movements and adaptability to different surgical needs. The design characteristics and practical applications demonstrated the probe's potential in clinical settings.
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Lithium-sulfur (Li-S) batteries, recognized as one of the most promising next-generation energy storage systems, are still limited by the "shuttle effect" of soluble polysulfides (LiPSs) on the cathode and the uncontrolled growth of lithium dendrites on the anode. These issues are critical obstacles to their practical application. Currently, many researchers have addressed these challenges from a unilateral perspective. Herein, we propose bifunctional hosts based on high-entropy selenides (HE-Se) to simultaneously tackle the persistent problems on both the positive and negative electrodes of Li-S batteries. On the one hand, HE-Se interacts with polysulfides to promote their conversion, effectively mitigating the shuttle effect. On the other hand, HE-Se provides multiple lithophilic sites during the initial nucleation of Li+, which reduces overpotential and exhibits excellent lithophilicity and cyclic stability. As a result, Li-S batteries incorporating the HE-Se host demonstrate outstanding performance in terms of rate capability and cycling stability. Additionally, the porous lithophilic HE-Se structure offers sufficient nucleation sites, inhibits the growth of dendritic lithium, and accommodates volume changes during charging and discharging cycles. This study highlights the potential of sulphophilic/lithophilic high-entropy materials in designing advanced Li-S batteries and encourages further exploration in this area.
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The original version of this article (Liu et al., 2021) unfortunately contained a mistake: statement of equal contribution is missing. This correction article shows that Chiyu LIU and Sixu CHEN contributed equally to this work. The original article has been corrected.
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To effectively utilize the photodynamic antibacterial ability of vitamin K3 (VK3), by solving the photothermal instability of VK3, it was combined with natural polymers to apply the preservation of chilled mutton. We encapsulated VK3 in the (2-Hydroxypropyl)-ß-cyclodextrin (HP-ß-CD) to construct VK3-HP-ß-CD complex and then introduced the complex to chitosan (CS) and polyvinyl alcohol (PVA) to fabricate an antibacterial film (CS/PVA-VK3-HP-ß-CD film). Through the packaging performance test of the film, the content of VK3-HP-ß-CD was an important factor determining the properties of film including tensile strength, elongation at break, water vapor permeability, water content and water contact angle. Meanwhile, CS/PVA-VK3-HP-ß-CD films could continuously release ROS under light and suspended in dark, thus realizing >99 % antibacterial rate for Escherichia coli and Staphylococcus aureus. In the application experiment of chilled mutton, CS/PVA-VK3-1-HP-ß-CD film could significantly inhibit the increase of total viable count (TVC), pH value (pH) and total volatile base nitrogen (TVB-N) of chilled mutton, and extended its shelf life for at least 12 days. These results indicated that the CS/PVA film with the VK3-HP-ß-CD complex might have promising potential as an antibacterial material for packaging and preserving food.
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Antibacterianos , Quitosana , Escherichia coli , Embalagem de Alimentos , Quitosana/química , Quitosana/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Embalagem de Alimentos/métodos , Escherichia coli/efeitos dos fármacos , Álcool de Polivinil/química , Staphylococcus aureus/efeitos dos fármacos , Conservação de Alimentos/métodos , Permeabilidade , Animais , 2-Hidroxipropil-beta-Ciclodextrina/química , 2-Hidroxipropil-beta-Ciclodextrina/farmacologiaRESUMO
Objective: Osteoarthritis (OA), which involves total joint damage and dysfunction, is a leading cause of disability worldwide. However, its exact pathogenesis remains unclear. Here, we identified TCF12 as an important regulator of the progression of OA. Methods: qRT-PCR, immunoblotting and immunohistochemistry (IHC) were used to detect the expression level of TCF12. The interaction of TCF12 with its downstream factor CXCR4 was assessed by Western blotting, immunofluorescence, qRT-PCR and luciferase assays. A mouse model was generated to examine the functions and mechanism of TCF12 in vivo. Result: TCF12 expression was upregulated in chondrocytes stimulated with IL-1ß and osteoarthritic chondrocytes. TCF12 upregulates the expression of CXCR4 and leads to dysfunction of the TGF-ß signaling pathway. Furthermore, knockdown of TCF12 alleviated cartilage damage in a mouse model generated by destabilization of the medial meniscus (DMM). Conclusion: TCF12 aggravates the progression of OA by targeting CXCR4 and then activating the TGF-ß signaling pathway, suggesting that TCF12 may be a new target for the treatment of OA. The translational potential of this article: Transcription Factor 12(TCF12), is known to regulate cell development and differentiation, It has been widely studied in various organs and diseases, but its role in OA remains unclear. Here, we identified Transcription Factor 12(TCF12) as an important regulator mediating chondrocyte senescence and cartilage extracellular matrix degradation indicating its role in OA. We found that TCF12 expression was upregulated both locally and systemically as OA advanced in patients with OA, and in mice after DMM surgery to induce OA. TCF12 expression caused striking progressive articular cartilage damage, synovial hyperplasia in OA mice, and remarkably, it was relieved by intra-articular administration of mutant mouse TCF12 lentiviral vector (shTCF12). Furthermore, TCF12 upregulated the expression of CXCR4, leading to exacerbation of experimental OA partially through activation of TGF-ß signaling in chondrocytes. TCF12 expression was upregulated in chondrocytes treated with IL-1ß and osteoarthritic chondrocytes. Our findings established an essential role of TCF12 in chondrocyte senescence and cartilage extracellular matrix degradation during OA, and identified intra-articular injection of TCF12 as a potential therapeutic strategy for OA prevention and treatment.
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IMPORTANCE: Ovine pulmonary adenomatosis (OPA) and maedi-visna disease (MVD) are chronic and progressive infectious diseases in sheep caused by Jaagsiekte sheep retrovirus (JSRV) and maedi-visna virus (MVV), respectively. OBJECTIVE: To investigate the pathological changes and conduct viral gene analysis of OPA and MVD co-occurrence in Inner Mongolia, China. METHODS: Using gross pathology, histopathology, immunohistochemistry, ultrastructural pathology, PCR, and sequence analysis, we investigated the concurrent infection of JSRV and MVV in 319 Dorper rams slaughtered in a private slaughterhouse in Inner Mongolia, in 2022. RESULTS: Of the 319 rams included, 3 showed concurrent JSRV and MVV infection. Gross lung pathology showed diffuse enlargement, consolidation, and greyish-white miliary nodules on the lung surface; the trachea was filled with a white foamy fluid; hilar and mediastinal lymph nodes were significantly enlarged. Histopathology results revealed typical OPA and MVD lesions in the lung tissue. Immunohistochemical results were positive for JSRV envelope protein (Env) in the tumor cells and MVV CA in alveolar macrophages. Transmission electron microscopy showed several virions and autophagosomes in the lung tissue, severely damaged mitochondria, and the induced mitophagy. Nucleotide sequences obtained for JSRV env and MVV gag showed the highest homology with the Inner Mongolian strains of JSRV env (JQ837489) and MVV gag (MW248464). CONCLUSIONS AND RELEVANCE: Our study confirmed that OPA and MVD co-occurrence and identified the pathological changes in Inner Mongolia, China, thereby providing references for the identification of concurrent JSRV and MVV infections.
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The spontaneous healing of critical-sized bone defects is often limited, posing an increased risk of complications and suboptimal outcomes. Osteogenesis, a complex process central to bone formation, relies significantly on the pivotal role of osteoblasts. Despite the well-established osteogenic properties of vitamin D3 (VD3), its lipophilic nature confines administration to oral or muscle injection routes. Therefore, a strategic therapeutic approach involves designing a multifunctional carrier to enhance efficacy, potentially incorporating it into the delivery system. Here, we introduce an innovative sterosome-based delivery system, utilizing palmitic acid (PA) and VD3, aimed at promoting osteogenic differentiation and facilitating post-defect bone regeneration. The delivery system exhibited robust physical characteristics, including excellent stability, loading efficiency, sustained drug release and high cellular uptake efficiency. Furthermore, comprehensive investigations demonstrated outstanding biocompatibility and osteogenic potential in both 2D and 3D in vitro settings. A critical-sized calvarial defect model in mice recapitulated the notable osteogenic effects of the sterosomes in vivo. Collectively, our research proposes a clinically applicable strategy for bone healing, leveraging PA/VD3 sterosomes as an efficient carrier to deliver VD3 and enhance bone regenerative effects.
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Regeneração Óssea , Colecalciferol , Osteogênese , Animais , Regeneração Óssea/efeitos dos fármacos , Colecalciferol/administração & dosagem , Osteogênese/efeitos dos fármacos , Liberação Controlada de Fármacos , Ácido Palmítico/química , Crânio/efeitos dos fármacos , Camundongos , Sistemas de Liberação de Medicamentos , Masculino , Humanos , Diferenciação Celular/efeitos dos fármacos , Portadores de Fármacos/química , Camundongos Endogâmicos C57BL , Osteoblastos/efeitos dos fármacosRESUMO
AIMS: The prognostic significance of N-terminal pro B-type natriuretic peptide (NT-proBNP) in heart failure with preserved ejection fraction (HFpEF) has been well established. HFpEF and atrial fibrillation (AF) commonly coexist, and each contributes to poor outcomes independently. Nevertheless, the ability of NT-proBNP to predict AF in HFpEF patients remains uncertain. METHODS AND RESULTS: A total of 367 HFpEF patients without baseline AF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were included. The Cox proportional hazard model was used to assess the association of NT-proBNP with the risk of AF. The C-statistic, categorical net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate the ability of NT-proBNP in new-onset AF prediction. During a median follow-up of 2.91 years, 17 (4.63%) new-onset AF cases occurred. Every 1000 pg/mL increase in NT-proBNP was associated with a 16% increase in the risk of AF occurrence after adjustments (hazard ratio, 1.16 [95% CI, 1.02-1.32]). NT-proBNP showed a moderate performance for new-onset AF at 3 years (C-statistic, 0.67). Adding NT-proBNP to CHADS2/R2CHADS2/CHA2DS2-VASc/C2HSET scores improved their predictive performance for AF risk (CHADS2: C-statistic, 0.63, CHADS2+NT: C-statistic, 0.69, NRI, 47.46%, IDI, 1.18%; R2CHADS2: C-statistic, 0.65, R2CHADS2+NT: C-statistic, 0.70, NRI, 48.03%, IDI, 0.51%; CHA2DS2-VASc: C-statistic, 0.67, CHA2DS2-VASc+NT: C-statistic, 0.72, NRI, 49.41%, IDI, 0.86%; C2HSET: C-statistic, 0.77, C2HSET+NT: C-statistic, 0.80, NRI, 50.32%, IDI, 1.58%). CONCLUSIONS: Among patients with HFpEF, the NT-proBNP level was positively associated with the incidence of new-onset AF and may be a promising predictor.
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Introduction: Green building (GB) technologies have been introduced to reduce the negative effect of the building and construction industry on the economy, the ecosystem, and society. A more thorough and accurate knowledge of the factors for implementation is required to stimulate the wider adoption of GB technologies. The theoretical framework for this study is developed using psychological capital (PC), self-determination theory (SDT), and green theory. The study addresses gaps in the research in this field. The effect of PC on psychological health (PH), green innovation ambidexterity (GIA), and subjective health (SH), and the impact of GIA on green performance (GP) are determined. The effect of PH and SH on organizational performance (OP) is also determined. Methods: The information for this study is collected from a variety of sources in the Chinese GB industry. The subjects for this study are Chinese employees of GB-based companies. Using a convenience sampling method, a total of 504 employees were selected. The employees' answers to a restricted, self-administered survey are used to generate the data. Results: Data from this study shows that PC has a significant effect on GIA, SH, and PH and that GIA has a substantial impact on GP. Both SH and PH significantly affect OP. Discussion: This study encourages managers in the green building industry to support fresh concepts in order to gain a competitive edge by implementing and promoting innovative cultures, especially in terms of service delivery and customer understanding, because innovation plays a critical role in these industries.
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Indústria da Construção , Humanos , Autoavaliação Diagnóstica , Ecossistema , Povo Asiático , Pesquisa EmpíricaRESUMO
To investigate whether activating the Wnt/ß-catenin signalling pathway differentially promotes fracture healing in aged and adult individuals. CatnbTM2Kem, Catnblox(ex3) and wild-type adult and aged mice were used in this study. The femur was electroporated through a hole with a diameter of 0.6 mm. On the 7th, 14th and 21st days after fracture establishment, repair of the femoral diaphyseal bone was examined using X-ray and CT, the levels of mRNAs related to Wnt/ß-catenin signalling were detected using real-time polymerase chain reaction (RT-PCR), and angiogenesis and cell differentiation were observed using immunohistochemistry. The numbers of osteoclasts were determined by TRAP staining. Wnt/ß-catenin activation accelerated fracture healing in adult mice, with more pronounced effects on aged mice. Compared with wild-type mice at the corresponding ages, Wnt/ß-catenin signalling activation induced higher levels of angiogenesis and cell differentiation in aged mice than in adult mice and promoted fracture healing. The administration of medications targeting Wnt/ß-catenin signalling to aged patients may accelerate fracture healing to a greater extent.
Assuntos
Consolidação da Fratura , Fraturas Ósseas , Animais , Diferenciação Celular , Consolidação da Fratura/fisiologia , Humanos , Camundongos , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismoRESUMO
BACKGROUND: Fibular support for the lateral tibial plateau through the proximal tibiofibular joint (PTFJ) results in nonuniform settlement of the tibial plateau in middle-aged and elderly persons and may lead to medial compartment knee osteoarthritis. However, the inclination angle of the PTFJ surface varies widely and may affect nonuniform settlement. The purpose of this case-control study was to assess the association between the inclination angle of the PTFJ surface and medial compartment knee osteoarthritis. METHODS: The fibular inclination angle (FIA) and tibial inclination angle (TIA) of the PTFJ surface were measured using radiographs. Differences of FIA and TIA among groups were assessed with t tests and the odds ratios (ORs) for risk factors of medial compartment knee osteoarthritis were calculated with binary logistic regression analysis. RESULTS: Forty patients and 40 control participants were included in this case-control study. Patients had both a lower FIA (P=0.005) and TIA (P=0.000) than the controls, and logistic regression analysis showed that FIA (OR =7.000) and TIA (OR =17.000) were risk factors for medial compartment knee osteoarthritis. CONCLUSIONS: A lower inclination angle of the PTFJ surface is associated with a risk of medial compartment knee osteoarthritis. Clinically, early prevention of medial compartment knee osteoarthritis should be considered for middle-aged and elderly persons with low PTFJ inclination angles.