NASH is a chronic liver disease that affects 3%–6% of individuals and requires urgent therapeutic developments. Isolating the key cell types in the liver is a necessary step towards understanding their function and roles in disease pathogenesis. However, traditional isolation methods through gradient centrifugation can only collect one or a few cell types simultaneously and pose technical difficulties when applied to NASH livers. Taking advantage of identified cell surface markers from liver single-cell RNAseq, here we established the combination of gradient centrifugation and antibody-based cell sorting techniques to isolate five key liver cell types (hepatocytes, endothelial cells, stellate cells, macrophages and other immune cells) from a single mouse liver. This method yielded high purity of each cell type from healthy and NASH livers. Our five-in-one protocol simultaneously isolates key liver cell types with high purity under normal and NASH conditions, enabling for systematic and accurate exploratory experiments such as RNA sequencing. 相似文献
It has been demonstrated that neural precursor cell expressed developmentally downregulated protein (NEDD) plays crucial roles in tumorigenesis and may serve as potential biomarkers in cancer diagnosis and prognosis. However, few studies systematically investigated the expression of NEDD family members in acute myeloid leukaemia (AML). We systemically determined the expression of NEDD family members in AML and determined their clinical significance. We identified that NEDD9 expression was the only member among NEDD family which was significantly increased in AML. NEDD9 overexpression was more frequently classified as FAB-M4/M5 (p = 0.008 and 0.013, respectively), hardly as FAB-M2/M3. Moreover, NEDD9 overexpression was significantly associated with complex karyotype and TP53 mutation. The significant association between NEDD9 overexpression and survival was also observed in whole-cohort AML and non-M3 AML patients. Notably, AML patients with NEDD9 overexpression may benefit from hematopoietic stem cell transplantation (HSCT), whereas those cases without NEDD9 overexpression did not. Finally, a total of 822 mRNAs and 31 microRNAs were found to be differentially expressed between two groups. Among the microRNAs, miR-381 was also identified as a microRNA that could direct target NEDD9. Taken together, our findings demonstrated that NEDD9 overexpression is associated with genetic abnormalities as well as prognosis and might act as a potential biomarker guiding the choice between HSCT and chemotherapy in patients with AML after achieving complete remission. 相似文献
Alzheimer's disease (AD), a severe age‐related neurodegenerative disorder, lacks effective therapeutic methods at present. Physical approaches such as gamma frequency light flicker that can effectively reduce amyloid load have been reported recently. Our previous research showed that a physical method named photobiomodulation (PBM) therapy rescues Aβ‐induced dendritic atrophy in vitro. However, it remains to be further investigated the mechanism by which PBM affects AD‐related multiple pathological features to improve learning and memory deficits. Here, we found that PBM attenuated Aβ‐induced synaptic dysfunction and neuronal death through MKP7‐dependent suppression of JNK3, a brain‐specific JNK isoform related to neurodegeneration. The results showed PBM‐attenuated amyloid load, AMPA receptor endocytosis, dendrite injury, and inflammatory responses, thereby rescuing memory deficits in APP/PS1 mice. We noted JNK3 phosphorylation was dramatically decreased after PBM treatment in vivo and in vitro. Mechanistically, PBM activated ERK, which subsequently phosphorylated and stabilized MKP7, resulting in JNK3 inactivation. Furthermore, activation of ERK/MKP7 signaling by PBM increased the level of AMPA receptor subunit GluR 1 phosphorylation and attenuated AMPA receptor endocytosis in an AD pathological model. Collectively, these data demonstrated that PBM has potential therapeutic value in reducing multiple pathological features associated with AD, which is achieved by regulating JNK3, thus providing a noninvasive, and drug‐free therapeutic strategy to impede AD progression. 相似文献
International Journal of Peptide Research and Therapeutics - Pidotimod has been shown to exhibit immunomodulatory activities and exert protective effects against bacterial infections. This study... 相似文献
Alternative polarization of macrophages regulates multiple biological processes. While M1-polarized macrophages generally mediate rapid immune responses, M2-polarized macrophages induce chronic and mild immune responses. In either case, polyunsaturated fatty acid (PUFA)-derived lipid mediators act as both products and regulators of macrophages. Prostaglandin E3 (PGE3) is an eicosanoid derived from eicosapentaenoic acid, which is converted by cyclooxygenase, followed by prostaglandin E synthase successively. We found that PGE3 played an anti-inflammatory role by inhibiting LPS and interferon-γ-induced M1 polarization and promoting interleukin-4-mediated M2 polarization (M2a). Further, we found that although PGE3 had no direct effect on the growth of prostate cancer cells in vitro, PGE3 could inhibit prostate cancer in vivo in a nude mouse model of neoplasia. Notably, we found that PGE3 significantly inhibited prostate cancer cell growth in a cancer cell-macrophage co-culture system. Experimental results showed that PGE3 inhibited the polarization of tumour-associated M2 macrophages (TAM), consequently producing indirect anti-tumour activity. Mechanistically, we identified that PGE3 regulated the expression and activation of protein kinase A, which is critical for macrophage polarization. In summary, this study indicates that PGE3 can selectively promote M2a polarization, while inhibiting M1 and TAM polarization, thus exerting an anti-inflammatory effect and anti-tumour effect in prostate cancer. 相似文献
Osteoarthritis (OA) is one of the most frequent chronic joint diseases with the increasing life expectancy. The main characteristics of the disease are loss of articular cartilage, subchondral bone sclerosis and synovium inflammation. Physical measures, drug therapy and surgery are the mainstay of treatments for OA, whereas drug therapies are mainly limited to analgesics, glucocorticoids, hyaluronic acids and some alternative therapies because of single therapeutic target of OA joints. Baicalein, a traditional Chinese medicine extracted from Scutellaria baicalensis Georgi, has been widely used in anti-inflammatory therapies. Previous studies revealed that baicalein could alleviate cartilage degeneration effectively by acting on articular chondrocytes. However, the mechanisms involved in baicalein-mediated protection of the OA are not completely understood in consideration of integrality of arthrosis. In this study, we found that intra-articular injection of baicalein ameliorated subchondral bone remodelling. Further studies showed that baicalein could decrease the number of differentiated osteoblasts by inhibiting pre-osteoblasts proliferation and promoting pre-osteoblasts apoptosis. In addition, baicalein impaired angiogenesis of endothelial cells and inhibited proliferation of synovial cells. Taken together, these results implicated that baicalein might be an effective medicine for treating OA by regulating multiple targets. 相似文献
Marine Biotechnology - The widely recognized color polymorphisms of molluscan shell have been appreciated for hundreds of years by collectors and scientists, while molecular mechanisms underlying... 相似文献
The organic non-crystalline medium of 5,6-dichloro-2-[[5,6-dichloro-1-ethyl-3-(4-sulfobutyl)-benzimidazol-2-ylidene]-propenyl]-1-ethyl-3-(4-sulfobutyl)-benzimidazolium hydroxide (TDBC) is emerging as possible alternative plasmonic material for noble metal in visible region. In this paper, a novel long-range surface exciton-polariton (LRSEP) sensor based on TDBC film covered with graphene is reported. To enhance the imaging sensitivity, the thickness of TDBC film and the number of graphene layers are optimized. The result shows that the optimized imaging sensitivity is enhanced to 3243 RIU−1 when ns = 1.34. Compared with the traditional noble metal film-based sensor, the proposed LRSEP sensor demonstrates that the imaging sensitivity has been greatly improved. This is the first study of the TDBC film-based LRSEP sensor, which we hope to support the potential development of chemical sensing and bio-sensing.