Flavokawain A alleviates the progression of mouse osteoarthritis: An in vitro and in vivo study

Osteoarthritis (OA) is one of the most prevalent chronic degenerative joint diseases affecting adults in their middle or later years. It is characterized by symptoms such as joint pain, difficulty in movement, disability, and even loss of motion. Moreover, the onset and progression of inflammation are directly associated with OA. In this research, we evaluated the impact of Flavokawain A (FKA) on osteoarthritis. In-vitro effects of FKA on murine chondrocytes have been examined using cell counting kit-8 (CCK-8), safranin o staining, western blot, immunofluorescence staining, senescence β-galactosidase staining, flow cytometry analysis, and mRFP-GFP-LC3 adenovirus infection. An in-vivo model of destabilization of the medial meniscus (DMM) was employed to investigate FKA’s effect on OA mouse. An analysis of bioinformatics was performed on FKA and its potential role in OA. It was observed that FKA blocked interleukin (IL)-1β-induced expression of inflammatory factors, i.e., cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) in chondrocytes. In addition, FKA also downregulated the catabolic enzyme expression, i.e., aggrecanase-2 (ADAMTS5) and matrix metalloproteinases (MMPs), and helped in the upregulation of the anabolic protein expression, i.e., type II collagen (Col2), Aggrecan, and sry-box transcription factor 9 (SOX9). Moreover, FKA ameliorated IL-1β-triggered autophagy in chondrocytes, and it was observed that the FKA causes anti-inflammatory effects by the mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathways inhibition. The results of immunohistochemical analysis and microcomputed tomography from the in vivo OA mouse model confirmed the therapeutic effect of FKA. Finally, we assessed the anti-arthritic impacts of FKA by conducting in vivo and in vitro analyses. We concluded that FKA can be employed as a useful therapeutic agent for OA therapy, but the findings require needs further clinical investigation

High-efficient crystal particle manufacture by microscale process intensification technology

High-end crystal manufacture has drawn a permanent concern on the high-efficient manufacture of crystal particles, especially in fine chemical, pharmaceutical, electronics, biological and relative engineering fields. In recent years, a series of microscale process intensification (MPI) technologies have been widely used in crystal particles preparation via addressing the control of nucleation and growth process. Herein, we review the research progresses of microscale process intensification technology from three aspects, microfluidics devices, microscale force field technology and membrane-based microchannels and interface transfer process. Firstly, the principle of microfluidic and relative microscale device on improving micro-mixing and mass transfer are briefly described. The advantage of microfluidic in continuous nano particle preparation is outlined. Microscale external force field (ultrasonic, high-gravity, electric and magnetic fields) is then introduced as another novel approach for ultrafine nanoparticles and continuous drug crystallization process. Further, in view of the micro-scale intensified mass transfer and microscale interfacial force field established on membrane technology, the basic mechanism of membrane crystallization (microscale 2D supersaturation degree control, auto seed detachment, microporous membrane dispersion, etc.) is reviewed. The process coupling and design strategy aiming for enhancing the manufacture capacity is also illustrated. Finally, the developing tendency and key challenges of high-efficient crystal particle preparation technology via microscale processes are overviewed

Better approach for autoimmune pulmonary alveolar proteinosis treatment: inhaled or subcutaneous granulocyte-macrophage colony-stimulating factor: a meta-analyses

Abstract Background Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare pulmonary disease caused by functional deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF therapy in aPAP has been reported effective in some studies. This meta-analyses aimed to evaluate whether GM-CSF therapy, including inhaled and subcutaneous GM-CSF have therapeutic effect in aPAP patients. Methods We analyzed 10 studies searched from PubMed, EmBase, Web of Science, Wiley Online Library and Cochrane Collaboration databases to evaluate the pooled effects of GM-CSF treatment in aPAP patients. Results Ten observational studies involving 115 aPAP patients were included. The pooled analyses of response rate (81%, p < 0.001), relapse rate (22%, p = 0.009), PaO2 (13.76 mmHg, p < 0.001) and P(A-a)O2 (19.44 mmHg, p < 0.001) showed that GM-CSF treatment was effective on aPAP patients. Further analyses showed that inhaled GM-CSF treatment was more effective than subcutaneous GM-CSF therapy, including a higher response rate (89% vs. 71%, p = 0.023), more improvements in PaO2 (21.02 mmHg vs. 8.28 mmHg, p < 0.001) and P(A-a)O2 (19.63 mmHg vs. 9.15 mmHg, p < 0.001). Conclusions As two routes of exogenous GM-CSF treatment, inhaled and subcutaneous were both proven to have effect on aPAP patients. Furthermore, inhaled GM-CSF therapy showed a higher response rate, more improvements on PaO2 and P(A-a)O2 than subcutaneous GM-CSF treatment in aPAP patients, suggesting inhaled GM-CSF therapy could have more benefits on aPAP patients. Therefore, GM-CSF therapy, especially inhaled GM-CSF, might be a promising therapeutic option in treating aPAP

Viral infection increases the risk of idiopathic pulmonary fibrosis: A meta-analysis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic lung disease with a poor prognosis. Although many factors have been identified that possibly trigger or aggravate IPF, such as viral infection, the exact cause of IPF remains unclear. Until now, there has been no systematic review to assess the role of viral infection in IPF quantitatively.ObjectiveThis meta-analysis aims to present a collective view on the relationship between viral infection and IPF.MethodsWe searched studies reporting the effect of viral infection on IPF in the PubMed, Embase, Cochrane Library, Web of Science, and Wiley Online Library databases. We calculated ORs with 95% CIs to assess the risk of virus in IPF. We also estimated statistical heterogeneity by using I2 and Cochran Q tests and publication bias by using the funnel plot, Begg test, Egger test, and trim-and-fill methods. Regression, sensitivity, and subgroup analyses were performed to assess the effects of confounding factors, such as sex and age.ResultsWe analyzed 20 case-control studies from 10 countries with 1,287 participants. The pooled OR of all viruses indicated that viral infection could increase the risk of IPF significantly (OR, 3.48; 95% CI, 1.61-7.52; P = .001), but not that of exacerbation of IPF (OR, 0.99; 95% CI, 0.47-2.12; P = .988). All analyzed viruses, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 7 (HHV-7), and human herpesvirus 8 (HHV-8), were associated with a significant elevation in the risk of IPF, except human herpesvirus 6 (HHV-6).ConclusionsThe presence of persistent or chronic, but not acute, viral infections, including EBV, CMV, HHV-7, and HHV-8, significantly increases the risk of developing IPF, but not exacerbation of IPF. These findings imply that viral infection could be a potential risk factor for IPF