Functional Analysis and Tissue-Specific Expression of Calcitonin and CGRP with RAMP-Modulated Receptors CTR and CLR in Chickens.

Calcitonin (CT) and calcitonin gene-related peptide (CGRP) are critical regulators of calcium balance and have extensive implications for vertebrate physiological processes. This study explores the CT and CGRP signaling systems in chickens through cloning and characterization of the chicken calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR), together with three receptor activity-modifying proteins (RAMPs). We illuminated the functional roles for chickens between the receptors examined alone and in RAMP-associated complexes using luciferase reporter assays. Chicken CTRs and CLRs stimulated the cAMP/PKA and MAPK/ERK signaling pathways, signifying their functional receptor status, with CT showing appreciable ligand activity at nanomolar concentrations across receptor combinations. Notably, it is revealed that chicken CLR can act as a functional receptor for CT without or with RAMPs. Furthermore, we uncovered a tissue-specific expression profile for CT, CGRP, CTR, CLR, and RAMPs in chickens, indicating the different physiological roles across various tissues. In conclusion, our data establish a clear molecular basis to reveal information on CT, CGRP, CTR, CLR, and RAMPs in chickens and contribute to understanding the conserved or divergent functions of this family in vertebrates.

SSTR2 Mediates the Inhibitory Effect of SST/CST on Lipolysis in Chicken Adipose Tissue.

Somatostatin shows an anti-lipolytic effect in both chickens and ducks. However, its molecular mediator remains to be identified. Here, we report that somatostatin type 2 receptor (SSTR2) is expressed at a high level in chicken adipose tissue. In cultured chicken adipose tissue, the inhibition of glucagon-stimulated lipolysis by somatostatin was blocked by an SSTR2 antagonist (CYN-154086), supporting an SSTR2-mediated anti-lipolytic effect. Furthermore, a significant pro-proliferative effect was detected in SST28-treated immortalized chicken preadipocytes (ICP-1), and this cell proliferative effect may be mediated through the MAPK/ERK signaling pathway activated by SSTR2. In summary, our results demonstrate that SSTR2 may regulate adipose tissue development by affecting the number and volume of adipocytes in chickens.

The effect of warming ropivacaine on ultrasound-guided subgluteal sciatic nerve block: a randomized controlled trial.

BACKGROUND: There is a long latent period for the sciatic nerve block before a satisfactory block is attained. Changes in the temperature of local anesthetics may influence the characters of the peripheral nerve block. This study was designed to evaluate the effect of warming ropivacaine on the ultrasound-guided subgluteal sciatic nerve block. METHODS: Fifty-four patients for distal lower limbs surgery were randomly allocated into warming group (group W, n = 27) or room tempeture group (group R, n = 27) with the ultrasound-guided subgluteal sciatic nerve block. The group W received 30 ml of ropivacaine 0.5% at 30℃ and the group R received 30 ml of ropivacaine 0.5% at 23℃. The sensory and motor blockade were assessed every 2 min for 30 min after injection. The primary outcome was the onset time of limb sensory blockade. RESULTS: The onset time of sensory blockade was shorter in group W than in group R (16 (16,18) min vs 22 (20,23) min, p < 0.001), and the onset time of motor blockade was also shorter in group W than in group R (22 (20,24) min vs 26 (24,28) min, p < 0.001). The onset time of sensory blockade for each nerve was shorter in group W than in group R (p < 0.001). No obvious differences for the duration of sensory and motor blockade and the patient satisfaction were discovered between both groups. No complications associated with nerve block were observed 2 days after surgery. CONCLUSIONS: Warming ropivacaine 0.5% to 30℃ accelerates the onset time of sensory and motor blockade in the ultrasound-guided subgluteal sciatic nerve block and it has no influence on the duration of sensory and motor blockade. TRIAL REGISTRATION: The trial was registered on October 3, 2022 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/bin/project/edit?pid=181104 ), registration number ChiCTR2200064350 (03/10/2022).

Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells.

Congenital cataracts are the leading cause of childhood blindness. To date, surgical removal of cataracts is the only established treatment, but surgery is associated with multiple complications, which often lead to visual impairment. Therefore, mechanistic studies and drug-candidate screening have been intrigued by the aims of developing novel therapeutic strategies. However, these studies have been hampered by a lack of an appropriate human-disease model of congenital cataracts. Herein, we report the establishment of a human congenital cataract in vitro model through differentiation of patient-specific induced pluripotent stem cells (iPSCs) into regenerated lenses. The regenerated lenses derived from patient-specific iPSCs with known causative mutations of congenital cataracts (CRYBB2 [p. P24T] and CRYGD [p. Q155X]) showed obvious opacification that closely resembled that seen in patients' cataracts in terms of opacification severity and disease course accordingly, as compared with lentoid bodies (LBs) derived from healthy individuals. Increased protein aggregation and decreased protein solubility corresponding to the patients' cataract severity were observed in the patient-specific LBs and were attenuated by lanosterol treatment. Taken together, the in vitro model described herein, which recapitulates patient-specific clinical manifestations of congenital cataracts and protein aggregation in patient-specific LBs, provides a robust system for research on the pathological mechanisms of cataracts and screening of drug candidates for cataract treatment.

Macrophage Inflammatory Protein-2 in High Mobility Group Box 1 Secretion of Macrophage Cells Exposed to Lipopolysaccharide.

BACKGROUND/AIMS: Macrophage inflammatory protein-2 (MIP-2), a type of leukocyte chemokine, is primarily produced by macrophages, and levels increase significantly in early inflammation. However, the precise biological functions and mechanisms of MIP-2 in the development of inflammation remain unclear. The purposes of the present study were to investigate the role of MIP-2 in inflammation induced by lipopolysaccharide (LPS) in vitro and to determine the possibility of blocking the high mobility group box 1 (HMGB1) signalling pathway via MIP-2 inhibition. METHODS: Macrophage cells (RAW264.7, U937 and THP-1 cells) were divided into control and treatments groups. Expression levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α), HMGB1, chemokine (C-C motif) ligand-2 (Ccl-2), Toll-like receptor-4 (TLR-4), inducible nitric oxide synthase (iNOS), phosphorylated MAPKs (p38, ERKs, JNKs), PI3K/Akts, JAKs/STAT3, IκB, and cytoplasmic and nuclear NF-κB p65 in RAW264.7 cells were detected by qRT-PCR, enzyme-linked immunosorbent assay (ELISA) or western blot assays. RESULTS: mip-2 siRNA and an anti-MIP-2 antibody significantly reduced the expression levels of Ccl-2, TLR-4, iNOS, IL-6, IL-1ß, HMGB1, and TNF-α in RAW264.7 cells exposed to LPS (P<0.01). Additionally, mRNA expression levels of HMGB1 and TLR-4 in cells treated with LPS+mip-2 siRNA were significantly lower than those in cells treated with LPS alone (P<0.01 or P<0.05). The MIP-2 antibody significantly suppressed activation of p38-MAPK, p-STAT3, and p-Akts and translocation of NF-κB p65 from the cytoplasm to the nucleus in RAW264.7 exposed to LPS (P<0.01 or P<0.05). CONCLUSION: mip-2 siRNA and the MIP-2 antibody can reduce the inflammatory effects induced by LPS in macrophage cells. The mechanisms may occur through down-regulation of p38-MAPK, STAT3 and Akts phosphorylation and translocation of NF-κB p65. MIP-2 plays an important role in inflammation induced by LPS.

Generation of Functional Lentoid Bodies From Human Induced Pluripotent Stem Cells Derived From Urinary Cells.

Purpose: The pathological mechanisms underlying cataract formation remain largely unknown on account of the lack of appropriate in vitro cellular models. The aim of this study is to develop a stable in vitro system for human lens regeneration using pluripotent stem cells. Methods: Isolated human urinary cells were infected with four Yamanaka factors to generate urinary human induced pluripotent stem cells (UiPSCs), which were induced to differentiate into lens progenitor cells and lentoid bodies (LBs). The expression of lens-specific markers was examined by real-time PCR, immunostaining, and Western blotting. The structure and magnifying ability of LBs were investigated using transmission electron microscopy and observing the magnification of the letter "X," respectively. Results: We developed a "fried egg" differentiation method to generate functional LBs from UiPSCs. The UiPSC-derived LBs exhibited crystalline lens-like morphology and a transparent structure and expressed lens-specific markers αA-, αB-, ß-, and γ-crystallin and MIP. During LB differentiation, the placodal markers SIX1, EYA1, DLX3, PAX6, and the specific early lens markers SOX1, PROX1, FOXE3, αA-, and αB-crystallin were observed at certain time points. Microscopic examination revealed the presence of lens epithelial cells adjacent to the lens capsule as well as both immature and mature fiber-like cells. Optical analysis further demonstrated the magnifying ability (1.7×) of the LBs generated from UiPSCs. Conclusions: Our study provides the first evidence toward generating functional LBs from UiPSCs, thereby establishing an in vitro system that can be used to study human lens development and cataractogenesis and perhaps even be useful for drug screening.

Temporary Balloon Occlusion of the Abdominal Aorta in Treatment of Complex Acetabular Fracture.

BACKGROUND The aim of this study was to explore the efficacy of temporary balloon occlusion of the abdominal aorta assisting open reduction and internal fixation (ORIF) in the treatment of complex acetabular fracture. MATERIAL AND METHODS From August 2000 to October 2011, a total of 48 patients with complex acetabular fracture were enrolled in this study. Average operative time, intraoperative blood loss volume, blood transfusion volume, satisfactory reduction, and postoperative functional recovery rate were recorded and compared between the 2 groups. RESULTS A significant difference was observed between the 2 groups in operative time (P=0.003). For intraoperative blood loss and blood transfusion, ORIF combined with temporary balloon occlusion of abdominal aorta techniques appeared to be superior to normal ORIF (blood loss: P=0.007; and blood transfusion: P=0.019, respectively). However, no differences were observed in postoperative blood loss or transfusion (P>0.05). Patients in group A showed better hip function than those in group B (group A: a good-to-excellent rate of 77.8%; group B: a good-to-excellent rate of 78.3%; P>0.05). With regard to the incidence of postoperative complications, there were no significant differences between the 2 groups (group A: 9/18; group B: 11/23; P=0.890). CONCLUSIONS In the treatment of complex acetabular fracture, temporary balloon occlusion of the abdominal aorta is a reliable technique to assist ORIF surgery to staunch the flow of blood.

Regulation of angiogenin expression and epithelial-mesenchymal transition by HIF-1α signaling in hypoxic retinal pigment epithelial cells.

Choroidal neovascularization (CNV) is a major cause of vision loss in many retinal diseases. Hypoxia is determined to be a key inducer of CNV and hypoxia-inducible factor-1 (HIF-1) is an important transcription factor. Epithelial-mesenchymal transition (EMT) and the synthesis of proangiogenic cytokines make great contributions to the development of CNV. In the present study, the role of HIF-1α signaling in the regulation of angiogenin (ANG) expression and EMT in hypoxic retinal pigment epithelial cells was investigated. A significant elevation expression of ANG expression level in a mouse model of laser-induced CNV was demonstrated. In a hypoxic model of ARPE-19, an increased expression level of ANG and induction of EMT accompanied with stabilization and nucleus translocation of HIF-1α. Blockage of HIF-1α signaling resulted in inhibition of high expression of ANG and EMT features. The direct interaction between HIF-1α and ANG promoter region was identified by ChIP-qPCR. The association of RNase 4 mRNA level with HIF-1α signaling was also clarified in APRE-19. Moreover, the exogenous ANG translocated into the nucleus, enhanced 45S rRNA transcription, promoted cell proliferation and tube formation in human retinal microvascular endothelial cells. In conclusion, the hypoxic conditions regulate the expression of ANG and EMT via an activation of HIF-1α signaling. It provides molecular evidence for potential therapy strategies of treating CNV.

Effects of Granulocyte Colony-Stimulating Factor on Patients with Liver Failure: a Meta-Analysis.

BACKGROUND AND AIMS: It remains controversial whether granulocyte colony-stimulating factor (G-CSF) prolongs survival in liver failure (LF) patients. This meta-analysis was performed to evaluate the effect of G-CSF on patients with LF. METHODS: PubMed, EMBASE, and Web of Science databases were searched to identify English language randomized controlled trials comparing G-CSF with control therapy published before14 February 2015. A meta-analysis was performed to examine changes in liver function and patient survival. The association was tested using odds ratio (OR) or risk ratio (RR) with 95% confidence intervals (CI). RESULTS: Five randomized controlled trials were eligible for the meta-analysis. Significant amelioration of prothrombin time and total bilirubin in LF patients was attributed to G-CSF therapy (OR, -0.064; 95% CI,-0.481 to 0.353; p< 0.001; and OR, -0.803; 95% CI, -1.177 to -0.430; p = 0.000, respectively). Treatment with G-CSF resulted in improved Model for End-Stage Liver Disease and Child-Turcotte-Pugh scores (OR, -1.741; 95% CI, -2.234 to -1.250; p = 0.000; and OR, -0.830, 95% CI, -1.194 to -0.465; p = 0.000, respectively). A lower incidence of sepsis was found in patients treated with G-CSF (RR, 0.367; 95% CI, 0.158 to 0.854; p = 0.020). G-CSF therapy significantly increased survival rate in LF patients (RR, 2.25; 95% CI, 1.517 to 3.338; p = 0.000). CONCLUSIONS: The results of this meta-analysis indicate that G-CSF treatment in patients with LF significantly improved liver function, reduced the incidence of sepsis, and prolonged short-term survival.

Comparing the Curative Effects between Femtosecond Laser-Assisted Cataract Surgery and Conventional Phacoemulsification Surgery: A Meta-Analysis.

PURPOSE: To compare the outcomes of femtosecond laser-assisted cataract surgery (FLACS) with those of conventional phacoemulsification surgery (CPS) for age-related cataracts. METHODS: A comprehensive literature search of PubMed, EMBASE, and the Cochrane Controlled Trials Register was conducted to identify randomized controlled trials (RCT) and comparative cohort studies comparing FLACS with CPS. Endothelial cell loss percentage (ECL%), central corneal thickness (CCT), corrected and uncorrected distant visual acuity (CDVA and UDVA), and mean absolute error (MAE) of refraction were used as primary outcomes. Secondary outcomes included surgically induced astigmatism (SIA), mean effective phacoemulsification time (EPT), phacoemulsification power and circularity of the capsulorhexis. RESULTS: Nine RCTs and fifteen cohort studies including 4,903 eyes (2,861 in the FLACS group and 2,072 in the CPS group) were identified. There were significant differences between the two groups in ECL% at one week, about one month and three months postoperatively, in CCT at one day, about one month postoperatively and at the final follow-up, in CDVA at one week postoperatively, and in UDVA at the final follow-up. Significant differences were also observed in MAE, EPT, phacoemulsification power, and the circularity of capsulorhexis. However, no significant differences were observed in CDVA at one week postoperatively or in surgically induced astigmatism. CONCLUSIONS: Compared to CPS, FLACS is a safer and more effective method for reducing endothelial cell loss and postoperative central corneal thickening as well as achieving better and faster visual rehabilitation and refractive outcomes. However, there is no difference in final CDVA and surgically induced astigmatism between the two groups.

Expression of high mobility group box 1 protein predicts a poorer prognosis for patients with osteosarcoma.

The high mobility group box 1 (HMGB1) protein functions as an extracellular signaling molecule that is critical in inflammation and carcinogenesis. The HMGB1 protein is actively secreted by natural killer cells, monocytes and macrophages, and acts as an inflammatory cytokine. The present study enrolled 174 patients that underwent a tumorectomy between 2006 and 2013 in Shandong Provincial Hospital. The age of the patients ranged between 13 and 74 years, with a median age of 27 years. The tumors of the patients were staged according to the Union for International Cancer Control 2009 tumor-node-metastasis tumor staging system. Nuclear grading was based on the Fuhrman grading system. In the osteosarcoma tissue samples, HMGB1 expression was detected in 84 samples (48.3%) with a low immunoreactivity and in 90 samples (51.7%) with a high immunoreactivity. The association between clinicopathological characteristics and tumor cell HMGB1 expression (low vs. high) was summarized. The association between HMGB1 expression and tumor size, tumor stage and nuclear grade was statistically significant (P=0.034, 0.008 and 0.019, respectively). There was no significant association between HMGB1 expression and the age of the patients (P=0.335; Table I). The current study demonstrated that patients with a high HMGB1 expression (>50% cells expressing HMGB1) had poorer survival rates, and therefore a poorer prognosis, compared with patients with low HMGB1 immunostaining (10-50% cells expressing HMGB1). The results of the present study suggest that higher expression levels of HMGB1 are significantly associated with a poorer prognosis and may act as a marker for prognosis in osteosarcoma, particularly osteosarcoma recurrence. Additional studies investigating the biological features of HMGB1 may confirm the potential role of HMGB1 as a novel target for anticancer therapy in osteosarcoma.

Comparison of Isocentric C-Arm 3-Dimensional Navigation and Conventional Fluoroscopy for Percutaneous Retrograde Screwing for Anterior Column Fracture of Acetabulum: An Observational Study.

Percutaneous screw insertion for minimally displaced or reducible acetabular fracture using x-ray fluoroscopy and computer-assisted navigation system has been advocated by some authors. The purpose of this study was to compare intraoperative conditions and clinical results between isocentric C-arm 3-dimensional (Iso-C 3D) fluoroscopy and conventional fluoroscopy for percutaneous retrograde screwing of acetabular anterior column fracture.A prospective cohort study was conducted. A total of 22 patients were assigned to 2 different groups: 10 patients in the Iso-C 3D navigation group and 12 patients in the conventional group. The operative time, fluoroscopic time, time of screw insertion, blood loss, and accuracy were analyzed between the 2 groups.There were significant differences in operative time, screw insertion time, fluoroscopy time, and mean blood loss between the 2 groups. Totally 2 of 12 (16.7%) screws were misplaced in the conventional fluoroscopy group, and all 10 screws were in safe zones in the navigation group. Percutaneous screw fixation using the Iso-C 3D computer-assisted navigation system significantly reduced the intraoperative fluoroscopy time and blood loss in percutaneous screwing for acetabular anterior column fracture.The Iso-C 3D computer-assisted navigation system provided a reliable and effective method for percutaneous screw insertion in acetabular anterior column fractures compared to conventional fluoroscopy.

Application of Additional Medial Plate in Treatment of Proximal Humeral Fractures With Unstable Medial Column: A Finite Element Study and Clinical Practice.

The purpose of this study was to use finite element analysis to compare the biomechanical characteristics after lateral locking plate (LLP) or LLP with a medial anatomical locking plate (LLP-MLP) fixation of proximal humeral fractures with an unstable medial column.First, a 3-dimensional, finite element analysis model was developed. Next, LLP and LLP-MLP implants were instrumented into the proximal humeral fracture models. Compressive and rotational loads were then applied to the humerus model to determine the biomechanical characteristics. Both normal and osteoporotic proximal humerus fractures were simulated using 2 internal fixation methods each under 7 loading conditions. To assess the biomechanical characteristics, the construct stiffness, fracture micromotion, and stress distribution on the implants were recorded and compared.The LLP-MLP method provided both lateral and medial support that reduced the stress on the LLP and the amount of displacement in the fracture region. In contrast, the LLP method resulted in more instability in the medial column and larger magnitudes of stress. In osteoporotic bone, the LLP was more inclined to fail than LLP-MLP.The LLP-MLP method provides a strong support for the medial column and increases the stability of the region surrounding the fracture.

Comparison of 3D C-arm fluoroscopy and 3D image-guided navigation for minimally invasive pelvic surgery.

PURPOSE: This study aims to compare the efficacy and accuracy of percutaneous screw fixation using three-dimensional [Formula: see text] navigation and conventional C-arm fluoroscopy in pelvic fracture surgery. METHODS: This was a retrospective study of 81 patients with pelvic fractures treated using percutaneous screw fixation between June 2005 and January 2011. All pelvic fractures were treated with closed reduction, small open reduction, or medium open reduction. Intraoperative radiation exposure, fixation, surgical outcome, and functional recovery were compared based on the fluoroscopy navigation method used during screw fixation. Radiographic follow-up was assessed at 1, 3, 6, and 9 months postoperatively, and a CT scan was completed at 9 months postoperatively. RESULTS: A total of 130 cannulated screws were placed. Average screw fixation time and fluoroscopy exposure time in [Formula: see text] group were lower than the C-arm fluoroscopy group ([Formula: see text] vs [Formula: see text]) [Formula: see text]. Seventy-four of the 81 patients made a full recovery. Successful outcome was confirmed with radiological imaging and postoperative follow-up at 6-24 months. No delayed union or nonunion was detected. No significant difference in functional recovery at 6 months postoperative was found due to the fluoroscopy imaging technique. CONCLUSIONS: Percutaneous screw fixation using the [Formula: see text] navigational system minimizes the fluoroscope exposure and screw insertion time, while improving screw insertion accuracy. Moreover, the [Formula: see text] navigational system provided a reliable method for fluoroscopy imaging in pelvic fractures.

Emodin protects against concanavalin A-induced hepatitis in mice through inhibiting activation of the p38 MAPK-NF-κB signaling pathway.

BACKGROUND/AIMS: To investigate the effects of emodin on concanavalin A (Con A)-induced hepatitis in mice and to elucidate its underlying molecular mechanisms. METHODS: A fulminant hepatitis model was established successfully by the intravenous administration of Con A (20 mg/kg) to male Balb/c mice. Emodin was administered to the mice by gavage before and after Con A injection. The levels of pro-inflammatory cytokines and chemokines, numbers of CD4(+) and F4/80(+) cells infiltrated into the liver, and amounts of phosphorylated p38 MAPK and NF-κB in mouse livers and RAW264.7 and EL4 cells were measured. RESULTS: Pretreatment with emodin significantly protected the animals from T cell-mediated hepatitis, as shown by the decreased elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as reduced hepatic necrosis. In addition, emodin pretreatment markedly reduced the intrahepatic expression of pro-inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1ß, IL-6, IL-12, inducible nitric oxide synthase (iNOS), integrin alpha M (ITGAM), chemokine (C-C motif) ligand 2 (CCL2), macrophage inflammatory protein 2 (MIP-2) and chemokine (CXC motif) receptor 2 (CXCR2). Furthermore, emodin pretreatment dramatically suppressed the numbers of CD4(+) and F4/80(+) cells infiltrating into the liver as well as the activation of p38 MAPK and NF-κB in Con A-treated mouse livers and RAW264.7 and EL4 cells. CONCLUSION: The results indicate that emodin pretreatment protects against Con A-induced liver injury in mice; these beneficial effects may occur partially through inhibition of both the infiltration of CD4(+) and F4/80(+) cells and the activation of the p38 MAPK-NF-κB pathway in CD4(+) T cells and macrophages.

Association of osteopontin expression with the prognosis of glioma patient: a meta-analysis.

So far, several studies on the association between osteopontin (OPN) expression and glioma have been performed, but the conclusion still was not clear. The aim of the present meta-analysis was to determine the relationship between OPN expression and prognosis of patients with glioma. The electronic database was searched for articles on the association between OPN expression and glioma until 31 January 2014. Odds ratios (OR) and the relative risks with 95 % CI were utilized to analyze the qualitative data in retrospective studies and prospective studies, respectively. The standardized mean difference and the corresponding 95 % CI were used for analyzing the studies with quantitative data. Heterogeneity of all included studies was assessed using Cochrane's Q test and I (2) measurement. The publication bias was examined by the Egger test. Sixteen cohort studies (854 patients) on OPN expression and gliomas prognosis were included in the present meta-analysis. It was found that OPN expression was significantly higher in patients with high-grade glioma than in patients with low-grade glioma (χ (2) = 8.38, I (2) = 16.6 %, P = 0.300), and the expression of OPN increased with glioma grade. The combined data showed the correlation between high OPN expression and tumor reoccurrence (OR = 18.61, 95 % CI = 6.34-54.67, P = 0.405). In addition, the results of the pooled analysis indicated that OPN expression was significantly related to overall survival (HR = 1.83; 95 % CI = 1.36-2.46). In conclusion, OPN may be a biomarker for predicting the prognosis of gliomas.

Hypertension and risk of cataract: a meta-analysis.

BACKGROUND: Cataract is the major cause of blindness across the world. Many epidemiologic studies indicated that hypertension might play an important role in the development of cataract, while others not. We therefore conducted this meta-analysis to determine the relationship between risk of cataract and hypertension. METHODS: Retrieved studies on the association of hypertension with cataract risk were collected from PubMed, Web of Science and the Cochrane Library during June 2014 and were included into the final analysis according to the definite inclusion criteria. Odds ratio (OR) or risk ratio (RR) were pooled with 95% confidence interval (CI) to evaluate the relationship between hypertension and cataract risk. Subgroup analyses were carried out on the basis of cataract type, race and whether studies were adjusted for main components of metabolic syndrome (MS). RESULTS: The final meta-analysis included 25 studies (9 cohort, 5 case-control and 11 cross-sectional) from 23 articles. The pooled results showed that cataract risk in populations with hypertension significantly increased among cohort studies (RR 1.08; 95% CI: 1.05-1.12) and case-control or cross-sectional studies (OR 1.28; 95% CI: 1.12-1.45). This association was proved to be true among both Mongolians and Caucasians, and the significance was not altered by the adjustment of main components of MS. Subgroup analysis on cataract types indicated that an increased incidence of posterior subcapsular cataract (PSC) resulted among cohort studies (RR 1.22; 95% CI: 1.03-1.46) and cross-sectional/case-control studies (OR 1.23; 95% CI: 1.09-1.39). No association of hypertension with risk of nuclear cataract was found. CONCLUSIONS: The present meta-analysis suggests that hypertension increases the risk of cataract, especially PSC. Further efforts should be made to explore the potential biological mechanisms.

Resveratrol reduces the proinflammatory effects and lipopolysaccharide- induced expression of HMGB1 and TLR4 in RAW264.7 cells.

BACKGROUND: Resveratrol (Res) is a polyphenol anti-inflammatory agent. We have studied the link between the anti-inflammatory effects of Res and the high mobility group box 1(HMGB1) signaling pathway. METHODS: Murine macrophage-like RAW264.7 cells (RAW264.7 cells) were either untreated (control) or treated with Res, LPS, or LPS + Res. Levels of IL-6, NO, and TNF-α were measured by ELISA and colorimetric assays. Expression of HMGB1 was detected by qRT-PCR, western blot, and immunofluorescence assays. Protein and mRNA expression levels of TLR4 were also examined. RESULTS: Res significantly reduced the levels of IL-6, NO, and TNF-α in RAW264.7 cells exposed to LPS. Expression levels of HMGB1 (mRNA and protein) and of TLR4 in the LPS + Res-treated cells were lower than in cells treated with LPS alone. CONCLUSIONS: Res can block the inflammatory effects induced by LPS in RAW264.7 cells. Down-regulation of HMGB expression may be one of the mechanisms of action of Res. Res may also influence TLR4 expression in the HMGB1-TLR4 signaling pathway.

Shikonin inhibits the lipopolysaccharide-induced release of HMGB1 in RAW264.7 cells via IFN and NF-κB signaling pathways.

To study the anti-inflammation effect of Shikonin (Shik) and its mechanism, murine macrophage-like RAW264.7 cells (RAW264.7 cells) were divided into control group, LPS group (0.125, 0.25 and 0.5µg/ml), LPS (0.125, 0.25 and 0.5µg/ml) plus Shik (0.5, 1 and 2µM) group, and Shik (2µM) group. After exposure for 24h, the levels of Interleukin-6 (IL-6), nitric oxide (NO) and Tumor Necrosis Factor-α (TNF-α) in supernatant were measured with ELISA, the expression of high mobility group box 1(HMGB1) in supernatant and cytoplasm was assayed using qRT-PCR, western blot and immunofluorescence assays, the expression of IFN-ß in cellular and supernatant was assayed by qRT-PCR and ELISA, and the ratio of nuclear to cytoplasm for NF-κB protein expression was assayed using western blot. The results of our investigation demonstrated that Shik could reduce significantly the levels of IL-6, NO and TNF-α in RAW264.7 cells exposed to LPS (P<0.05 or P<0.01). The expression of HMGB1, IFN-ß and the ratio of nuclear to cytoplasm for NF-κB protein expression in LPS plus Shik group declined significantly as compared with LPS group (P<0.05 or P<0.01). The inhibitors of IFN-ß signaling molecule JAK and NF-κB could attenuate significantly the expression of HMGB1 in supernatant. It was found in the present study that Shik could have the anti-inflammatory effects in RAW264.7 cells exposed to LPS, and one of the mechanisms may be the down-regulation of HMGB expression, which was associated with the IFN-ß and NF-κB signaling pathways.

MicroRNA-223 acts as an important regulator to Kupffer cells activation at the early stage of Con A-induced acute liver failure via AIM2 signaling pathway.

BACKGROUND: Acute liver failure (ALF), known as a rapid and severe clinical syndrome, can induce multiple organ dysfunction and failure. It was noticed that Kupffer cells activation at the initial phase was involved in some intense inflammatory responses in the pathogenesis of ALF. However, detailed regulation mechanism of Kupffer cells activation during ALF is still obscured. Present study aimed to discover the potential regulator and explore deeper information of Kupffer cells activation at the early stage of ALF. METHODS: The mouse model of ALF was established by Concanavalin A injection. Dynamic immunological statuses of Kupffer cells at the early stage of ALF were exhibited by detecting typical cytokines. The expression of inflammasome AIM2 was measured in both RNA and protein level. Its role of affecting Kupffer cells activation during ALF by inducing IL-1ß production was identified by RNA interference in vitro. Moreover, the expression of miR-223 in vivo was measured by q-PCR and its role in regulating Kupffer cells activation during Con A induced ALF was determined by RNAs transfection. RESULTS: Present study showed that mass production of IL-1ß from isolated Kupffer cells in Con A treated mice might be the main driving force of Kupffer cells pro-inflammatory activation during ALF. The role of AIM2 in affecting pro-inflammatory activation of Kupffer cells by inducing IL-1ß production was crucial to ALF. Further study found that miR-223 acted as a regulator in Kupffer cells activation at the early stage of ALF by influencing IL-1ß production via AIM2 pathway. CONCLUSION: For the first time, this paper demonstrated that miR-223 acted to inhibit IL-1ß production via AIM2 pathway, suppressing Kupffer cells pro-inflammatory activation at the early stage of ALF. Thus, it played an important role in the pathogenesis of ALF.