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简介：AbstractObjective:This study was performed to investigate the relationship between the human melanogenesis and antioxidant systems and to further confirm the synergistic effect of oxyresveratrol (OXYR) and resveratrol (RES) in human epidermal melanocyte cell line.Methods:The human epidermal melanocyte line PIG1 cells were divided into the UV groups and control group, treated with different doses of UVB and without UVB, respectively. MTT assay and flow cytometry were used to detect cell viability and apoptosis. The expression of Nrf2/HO-1 and melanogenesis-associated proteins/genes was measured by Western blotting and real-time qPCR (RT-qPCR). pCMV6-XL5-Nrf2 was used to upregulate the expression of Nrf2. Subsequently, the proteins/genes levels of Nrf2/HO-1 and tyrosinase (TYR), melanin/eumelanin content, and reactive oxygen species (ROS) were analyzed. Isobologram analysis and cell experiment were used to analyze whether OXYR and RES inhibit TYR synergistically. Western blotting, RT-qPCR, and NaOH splitting method were used to determine the Nrf2/HO-1 and melanogenesis-associated proteins/genes expression and melanin content to evaluate the efficacy of OXYR and RES.Results:The activated Nrf2 and HO-1 eliminated ROS produced by UVB irradiation. The melanogenesis-associated proteins/genes of melanocyte-inducing transcription factor (MITF, P < 0.01 on protein expression), TYR (both P < 0.01), TYR-related protein (TRP)-1 (both P < 0.05), and TRP2 (P < 0.05 on mRNA expression) were activated in PIG1 cells by UVB irradiation. Simultaneously, the upregulation of Nrf2 significantly reduced melanogenesis formation (P < 0.001) and TYR level (P < 0.01 on protein expression). Moreover, OXYR and RES synergistically inhibited TYR activity (P < 0.001) and reduced melanin content (P < 0.001).Conclusions:A microbalance exists between Nrf2/HO-1 signaling and melanogenesis production in the UVB-induced responses of melanocytes. Simultaneously, OXYR enhances the ability of RES to inhibit melanin production.

简介：AbstractThe immune system has the function of immune surveillance to resist the occurrence and development of tumors, and is essential for inhibition of tumor metastasis. Nevertheless, tumor cells can still suppress immune responses through multiple mechanisms to escape recognition and elimination. Photodynamic and sonodynamic therapy involve systemic or local use of sensitizers followed by light or ultrasound treatment of the affected area, leading to tumor cell death by various mechanisms. The capability of the immune system is essentially affected by photodynamic and sonodynamic therapy. To understand the tumor therapeutic mechanisms of photodynamic and sonodynamic therapy and to explore the use of these modalities for improvement of the antitumor immune effect, extensive preclinical and clinical studies have been carried out. Besides direct killing of tumors, photodynamic and sonodynamic therapy also cause inflammatory reactions, achieve antitumor immune responses, and potentially prevent tumor recurrence, thereby treating both primary and metastatic tumors. In this review, we summarize the antitumor immune responses induced by photodynamic and sonodynamic therapy, describe the processes of the antitumor immune responses in detail, and discuss the clinical applications of the resulting antitumor immunity.

简介：AbstractThe field of drug-induced sleep endoscopy (DISE) has grown considerably over the last 10~15 years, to now include its use in pediatric patients. In this review article, we outline our approach to the use of this technology in Children with Airway Obstruction, most specifically in the management of children with airway obstruction and known or suspected adenotonsillar enlargement.

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简介：AbstractBackground:Although osteopontin (OPN) is expressed in the liver and pigment gallstones of patients with hepatolithiasis, its role in pigment gallstone formation remains unclear. This study aimed to explore the function of OPN in pigment gallstone formation.Methods:Rats were fed a chow diet (CD) or lithogenic diet (LD) for 10 consecutive weeks; blocking tests were then performed using an OPN antibody (OPN-Ab). Incidence of gallstones and levels of several bile components, OPN, tumor necrosis factor alpha (TNF-α), and cholesterol 7 alpha-hydroxylase (CYP7A1) were analyzed. To determine TNF-α expression in hepatic macrophages and both CYP7A1 and bile acid (BA) expression in liver cells, recombinant rat OPN and recombinant rat TNF-α were used to treat rat hepatic macrophages and rat liver cells, respectively. Chi-square or Fisher exact tests were used to analyze qualitative data, Student t-test or one-way analysis of variance were used to analyze qualitative data.Results:Incidence of gallstones was higher in LD-fed rats than in CD-fed rats (80% vs. 10%, P < 0.05). BA content significantly decreased in bile (t= -36.08, P < 0.01) and liver tissue (t= -16.16, P < 0.01) of LD-fed rats. Both hepatic OPN protein expression (t= 9.78, P < 0.01) and TNF-α level (t= 8.83, P < 0.01) distinctly increased in the LD group; what’s more, CYP7A1 mRNA and protein levels (t= -12.35, P < 0.01) were markedly down-regulated in the LD group. Following OPN-Ab pretreatment, gallstone formation decreased (85% vs. 25%, χ2 = 14.55, P < 0.01), liver TNF-α expression (F = 20.36, P < 0.01) was down-regulated in the LD group, and CYP7A1 expression (F = 17.51, P < 0.01) was up-regulated. Through CD44 and integrin receptors, OPN promoted TNF-α production in macrophage (F= 1041, P < 0.01), which suppressed CYP7A1 expression (F = 48.08, P < 0.01) and reduced liver BA synthesis (F= 119.4, P < 0.01).Conclusions:We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.

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简介：AbstractBackground:Obesity is a fundamental factor in metabolic disorders such as hyperlipidemia, insulin resistance, fatty liver, and atherosclerosis. However, effective preventive measures are still lacking. This study aimed to investigate different surgical protocols for removing partial adipose tissue before the onset of obesity and determine whether, and by which protocol, preliminary adipose removal could exert potent preventive effects against diet-induced metabolic disorders.Methods:Male low-density lipoprotein receptor (LDL-R) knockout (KO) mice were randomly divided into four groups and subjected to epididymal fat removal (Epi-FR) surgery, subcutaneous fat removal (suQ-FR) surgery, both subcutaneous and epididymal fat removal (Epi + suQ-FR) surgery, or sham-operation. After 1 week of recovery, all mice were given a high-fat diet (HFD) for 10 weeks to induce metabolic disorders.Results:In the Epi-FR group and the sham-operated group, the mean numbers of the residual subcutaneous fat were 28.59 mg/g and 18.56 mg/g, respectively. The expression of relative genes such as Pparg, Cebpa, Dgat2, Fabp4 and Cd36 in the residual subcutaneous fat increased 2.62, 3.90, 3.11, 2.06, 1.78 times in the Epi-FR group compared with that in the sham-operated group. Whereas in the other fat-removal groups, the residual fat depots had no significant change in either size or gene expression, as compared with those of the sham-operated group. Plasma lipid and glucose levels and insulin sensitivity, as detected by the glucose tolerance test, were not significantly alleviated in the three fat removal groups. Liver mass or lipid content was not attenuated in any of the three fat removal groups. The atherosclerosis burdens in the entire inner aorta and aortic root did not decrease in any of the three fat removal groups.Conclusions:Our data suggest that removal of epididymal adipose or subcutaneous adipose alone or in combination before the onset of obesity did not protect against hyperlipidemia, insulin resistance, fatty liver, or atherosclerosis in LDL-R KO mice fed with a HFD. Hence, adipose removal possibly does not represent a potential approach in preventing obesity-related metabolic disorders in the obesity-susceptible population.

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简介：AbstractBackground:Estrogen is involved in the pathophysiological process of benign prostatic hyperplasia (BPH), in which epithelial-mesenchymal transition (EMT) plays an important role. Upregulation of aquaporin (AQP) 5, which is directly activated by estrogen, has been reported to promote EMT in multiple cells. This study aimed to examine the effects of AQP5 on estrogen-induced EMT in the prostate.Methods:Normal prostate (NP) tissue samples without any histopathological changes and BPH tissue samples with pathologically confirmed hyperplasia were obtained. An EMT cell model was subsequently established by adding estradiol (E2) to RWPE-1 cells, after which AQP5 knockdown was performed. Tissue morphological and immunohistochemical features were examined using hematoxylin-eosin and immunohistochemical staining. Western blot analysis was performed to determine the expression of AQPs, estrogen receptors, and EMT-related proteins. Cell proliferation was assessed and supernatants were collected for enzyme-linked immunosorbent assay to determine transforming growth factor-β1 (TGF-β1) concentrations. Immunofluorescence staining was performed to assess protein expressions in RWPE-1 cells.Results:BPH tissues exhibited greater EMT (TGF-β1: 1.362 ± 0.196 vs. 0.107 ± 0.067, P = 0.003; vimentin: 1.581 ± 0.508 vs. 0.221 ± 0.047, P < 0.001; E-cadherin: 0.197 ± 0.188 vs. 1.344 ± 0.088, P < 0.001), higher AQP5 (1.268 ± 0.136 vs. 0.227 ± 0.055, P < 0.001) and estrogen receptor (ER) α (1.250 ± 0.117 vs. 0.329 ± 0.134, P < 0.001) expression but lower ERβ (0.271 ± 0.184 vs. 1.564 ± 0.130, P < 0.001) expression than NP tissues. E2-stimulated cells had higher AQP5 expression (1.298 ± 0.058 vs. 1.085 ± 0.104, P = 0.049), increased cell proliferation (1.510 ± 0.089 vs.1.000 ± 0.038, P < 0.001), and EMT (TGF-β1 concentration: 0.352 ± 0.021 ng/mL vs. 0.125 ± 0.014 ng/mL, P < 0.001; vimentin: 1.641 ± 0.120 vs. 0.188 ± 0.020, P = 0.002; E-cadherin: 0.075 ± 0.030 vs. 0.843 ± 0.046, P < 0.001) than controls. E2-stimulated cells with AQP5 knockdown exhibited decreased EMT (TGF-β1 concentration: 0.223 ± 0.041 ng/mL vs. 0.352 ± 0.021 ng/mL, P= 0.016; vimentin: 0.675 ± 0.056 vs. 1.641 ± 0.120, P = 0.001; E-cadherin: 0.159 ± 0.037 vs. 0.075 ± 0.030, P = 0.040) than E2-stimulated cells with non-related small interfering RNA (siRNA).Conclusion:Our findings suggest that estrogen induces BPH possibly by promoting AQP5 expression. Hence, AQP5 might be a novel target for modulating EMT in prostate epithelial cells.

简介：AbstractBackground:Accumulating evidence suggests that lithium influences mesenchymal stem cell (MSC) proliferation and osteogenic differentiation. As decreased bone formation in femoral heads is induced by glucocorticoids (GCs), we hypothesized that lithium has a protective effect on GC-induced osteonecrosis of femoral heads (ONFH).Methods:A rat ONFH model was induced by methylprednisolone (MP) and the effect of lithium chloride on the models was evaluated. Micro-computed tomography (CT)-based angiography and bone scanning were performed to analyze the vessels and bone structure in the femoral heads. Hematoxylin and eosin and immunohistochemical staining were performed to evaluate the trabecular structure and osteocalcin (OCN) expression, respectively. Bone marrow-derived MSCs were isolated from the models, and their proliferative and osteogenic ability was evaluated. Western blotting and quantitative real-time polymerase chain reaction were performed to detect osteogenic-related proteins including Runx2, alkaline phosphatase, and Collagen I.Results:Micro-CT analysis showed a high degree of osteonecrotic changes in the rats that received only MP injection. Treatment with lithium reduced this significantly in rats that received lithium (MP + Li group); while 18/20 of the femoral heads in the MP showed severe osteonecrosis, only 5/20 in the MP + Li showed mild osteonecrotic changes. The MP + Li group also displayed a higher vessel volume than the MP group (0.2193 mm3vs. 0.0811 mm3, P < 0.05), shown by micro-CT-based angiography. Furthermore, histological analysis showed better trabecular structures and more OCN expression in the femoral heads of the MP + Li group compared with the MP group. The ex vivo investigation indicated higher proliferative and osteogenic ability and upregulated osteogenic-related proteins in MSCs extracted from rats in the MP + Li group than that in the MP group.Conclusions:We concluded that lithium chloride has a significant protective effect on GC-induced ONFH in rats and that lithium also enhances MSC proliferation and osteogenic differentiation in rats after GC administration.

简介：AbstractBackground:Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis, partially by activating lung fibroblasts. However, how macrophages communicate with lung fibroblasts is largely unexplored. Exosomes can mediate intercellular communication, whereas its role in lung fibrogenesis is unclear. Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis.Methods:In vivo, bleomycin (BLM)-induced lung fibrosis model was established and macrophages infiltration was examined. The effects of GW4869, an exosomes inhibitor, on lung fibrosis were assessed. Moreover, macrophage exosomes were injected into mice to observe its pro-fibrotic effects. In vitro, exosomes derived from angiotensin II (Ang II)-stimulated macrophages were collected. Then, lung fibroblasts were treated with the exosomes. Twenty-four hours later, protein levels of α-collagen I, angiotensin II type 1 receptor (AT1R), transforming growth factor-β (TGF-β), and phospho-Smad2/3 (p-Smad2/3) in lung fibroblasts were examined. The Student’s t test or analysis of variance were used for statistical analysis.Results:In vivo, BLM-treated mice showed enhanced infiltration of macrophages, increased fibrotic alterations, and higher levels of Ang II and AT1R. GW4869 attenuated BLM-induced pulmonary fibrosis. Mice with exosomes injection showed fibrotic features with higher levels of Ang II and AT1R, which was reversed by irbesartan. In vitro, we found that macrophages secreted a great number of exosomes. The exosomes were taken by fibroblasts and resulted in higher levels of AT1R (0.22 ± 0.02 vs. 0.07 ± 0.02, t = 8.66, P = 0.001), TGF-β (0.54 ± 0.05 vs. 0.09 ± 0.06, t= 10.00, P < 0.001), p-Smad2/3 (0.58 ± 0.06 vs. 0.07 ± 0.03, t= 12.86, P < 0.001) and α-collagen I (0.27 ± 0.02 vs. 0.16 ± 0.01, t = 7.01, P = 0.002), and increased Ang II secretion (62.27 ± 7.32 vs. 9.56 ± 1.68, t= 12.16, P < 0.001). Interestingly, Ang II increased the number of macrophage exosomes, and the protein levels of Alix (1.45 ± 0.15 vs. 1.00 ± 0.10, t = 4.32, P = 0.012), AT1R (4.05 ± 0.64 vs. 1.00 ± 0.09, t = 8.17, P = 0.001), and glyceraldehyde-3-phosphate dehydrogenase (2.13 ± 0.36 vs. 1.00 ± 0.10, t = 5.28, P = 0.006) were increased in exosomes secreted by the same number of macrophages, indicating a positive loop between Ang II and exosomes production.Conclusions:Exosomes mediate intercellular communication between macrophages and fibroblasts plays an important role in BLM-induced pulmonary fibrosis.

简介：AbstractObjective:Metabolic disorders are markedly common in women with polycystic ovary syndrome (PCOS), and nonalcoholic fatty liver disease (NAFLD) is observed in 30%-55% of all PCOS patients. Many studies have reported that autophagy and apoptosis, which are closely related to mitochondrial function, play important roles in the development of NAFLD. Therefore, in this study, we aimed to explore the role of mitochondrial dysfunction caused by liver apoptosis and autophagy imbalance in the development of NAFLD in a PCOS mouse model.Methods:We used a dihydrotestosterone (DHT)-induced PCOS model to mimic the pathological process of hyperandrogenism. Hematoxylin and eosin and Oil Red O staining assays were used to observe the pathological changes in the liver. Western blotting and quantitative real-time polymerase chain reaction were used to perform mitochondrion-related assays.Results:Hepatic steatosis and different degrees of inflammation were observed in the DHT-treated mice. The expression of molecules involved in the respiratory chain and aerobic respiration process was altered. The levels of the key molecules associated with apoptosis and autophagy were abnormal.Conclusions:Androgens may play a role in the process of hepatic steatosis development by affecting mitochondrial function and subsequently inducing apoptosis and autophagy. Such phenomena might be involved in the pathogenesis of NAFLD in women with PCOS.

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