Dynamic communication within adipose tissue depends on highly vascularized structural characteristics to maintain systemic metabolic homoeostasis. Recently, it has been noted that adipose endothelial ...cells (AdECs) act as essential bridges for biological information transmission between adipose-resident cells. Hence, paracrine regulators that mediate crosstalk between AdECs and adipose stromal cells were summarized. We also highlight the importance of AdECs to maintain adipocytes metabolic homoeostasis by regulating insulin sensitivity, lipid turnover and plasticity. The differential regulation of AdECs in adipose plasticity often depends on vascular density and metabolic states. Although choosing pro-angiogenic or anti-angiogenic therapies for obesity is still a matter of debate in clinical settings, the growing numbers of drugs have been confirmed to play an anti-obesity effect by affecting vascularization. Pharmacologic angiogenesis intervention has great potential as therapeutic strategies for obesity.
A tetrabutylammonium decatungstate (TBADT)-photocatalyzed direct coupling of inert alkanes and quinoxalin-2(1H)-ones with H2 evolution was developed at room temperature. The present transformation ...achieved direct C(sp3)–H/C(sp2)–H coupling under noble metal-free, acid-free and oxidant-free conditions. With this method, a series of 3-alkylated quinoxalin-2(1H)-ones bearing various functional groups were synthesized in good to excellent yields.
AIM： To detect the expression of miR-211 in age-related cataract tissue, explore the effects of miR-211 on lens epithelial cell proliferation and apoptosis, and identify its target gene.METHODS： This ...study used real-time quantitative polymerase chain reaction（RT-q PCR） to measure the expression of miR-211 and its predicted target gene silent matingtype information regulation 2 homolog 1（SIRT1） in 46 anterior lens capsules collected from age-related cataract patients. Human lens epithelial cell line（SRA01/04） cells were transfected with either miR-211 mimics, mimic controls, miR-211 inhibitors or inhibitor controls, 72 h after transfection, miR NA and protein expression of SIRT1 were measured using RT-qP CR and Western blotting; then cells were exposed to 200 μmol/L H2O2 for 1h, whereupon cell viability was measured by MTS assay, caspase-3 assay was performed. Dual luciferase reporter assay was performed to verify the relationship between miR-211 of SIRT1.RESULTS： Compared to the control group, expression of miR-211 was significantly increased（P〈0.001）, the miR NA and protein expression of SIRT1 were significantly decreased（P〈0.001） in the anterior lens capsules of patients with age-related cataracts. Relative to the control group, SIRT1 miR NA and protein levels in the miR-211 mimic group were significantly reduced, cell proliferation activity significantly decreased, and caspase-3 activity was significantly increased（P〈0.001）. In the miR-211 inhibitor group, SIRT1 miRNA and protein expression were significantly increased, cell proliferation activity significantly increased, and caspase-3 activity was significantly decreased（P〈0.001）. A dual luciferase reporter assay confirmed that SIRT1 is a direct target of miR-211.CONCLUSION： miR-211 is highly expressed in the anterior lens capsules of patients with age-related cataracts. By negatively regulating the expression of SIRT1, miR-211 promotes lens epithelial cell apoptosis and inhibits lens epithelial cell proliferation.
K-Ras is a well-studied oncogene, and its mutation is frequently found in epithelial cancers like pancreas, lung, and colorectal cancers. Cancer cells harboring K-Ras mutations are difficult to treat ...due to the drug resistance and metastasis properties. Cancer stem cells (CSCs) are believed the major cause of chemotherapeutic resistance and responsible for tumor recurrence and metastasis. But how K-Ras mutation affects CSCs and inflammation is not clear. Here, we compared two colon cancer cell lines, HCT-116 and HT-29, with the former being K-Ras
G13D
mutant and the latter being wildtype. We found that HCT-116 cells treated with a K-Ras mutation inhibitor S7333 formed significantly more tumor spheroids than the untreated control, while the wild type of HT-29 cells remained unchanged. However, the size of tumor spheroids was smaller than the untreated controls, indicating their proliferation was suppressed after S7333 treatment. Consistent with this, the expressions of stem genes Lgr5 and CD133 significantly increased and the expression of self-renewal gene TGF-β1 also increased. The flow cytometry analysis indicated that the expression of stem surface marker CD133 increased in the treated HCT-116 cells. To understand the pathway through which the G13D mutation induced the effects, we studied both RAS/ERK and PI3K/Akt pathways using specific inhibitors SCH772984 and BEZ235. The results indicated that RAS/ERK rather than PI3K/Akt pathway was involved. As CSCs play the initial role in cancer development and the inflammation is a vital step during tumor initiation, we analyzed the correlation between increased stemness and inflammation. We found a close correlation of increased Lgr5 and CD133 with proinflammatory factors like IL-17, IL-22, and IL-23. Together, our findings suggest that K-Ras
G13D
mutation promotes cancer cell growth but decreases cancer stemness and inflammation thus tumorigenesis and metastasis potential in colon cancer. Inhibition of this mutation reverses the process. Therefore, care needs be taken when employing targeted therapies to K-Ras
G13D
mutations in clinics.
Oral lichen planus (OLP) is a chronic inflammatory lesion involving the oral mucosa, which has a high likelihood of progressing to cancer. The present study investigated the periostin expression in ...the mucosa and serum of patients with OLP and its correlation with serum cytokines. A total of 117 patients with OLP and 110 healthy controls were included in the study. The protein expression of periostin were measured in the OLP and normal oral mucosa by immunohistochemistry. ELISA was performed to measure the serum levels of periostin, tumour necrosis factor-α (TNF-α), interleukin (IL)-6, interferon-γ (IFN-γ), IL-4 and thymic stromal lymphopoietin (TSLP). Compared with the control group the OLP group had a significantly increased number of cases with high periostin expression in the oral mucosa and a significantly increased serum periostin level (P<0.05). Among all 117 OLP subjects, high periostin expression was associated with higher serum IL-6, TNF-α, TSLP and tissue mast cell density. High periostin expression was also significantly associated with a lower IFN-γ/IL-4 ratio (P<0.05). The present study concluded that periostin expression was increased in the oral mucosa and serum of patients with OLP and was associated with inflammatory response, T helper 2 cytokine-predominant immune imbalance, increased mast cell count and TSLP. The modulation of periostin may represent an attractive novel therapeutic target.
This study aimed to investigate the effect of LAMA5 on palatal development in mice.
The palatine process of C57BL/6 J fetal mice on the embryonic day 13.5 (E13.5) was cultured in vitro via the ...rotating culture method. The LAMA5-shRNA adenovirus vector was constructed, then transfected into the palatal process of E13.5 for 48 h in vitro. A fluorescence microscope was used to visualize the fusion of palates. The expression of LAMA5 was also detected. The expression of ki67, cyclin D1, caspase 3, E-cadherin, vimentin and SHH signaling pathway-related signaling factors in the blank control group, the negative control group, and the LAMA5 interference group were detected after virus transfection.
The bilateral palates in the LAMA5 interference group were not fused after virus transfection. PCR and WB showed that the mRNA and protein expressions of LAMA5 were decreased in the LAMA5 interference group. Furthermore, the mRNA and protein expressions of ki67, cyclin D1 and gli1 were decreased in the LAMA5 interference group, while the mRNA and protein expressions of caspase 3 were increased. However, the mRNA and protein expression of E-cadherin, vimentin, Shh and ptch1 did not significantly change in the LAMA5 interference group.
LAMA5 silencing causes cleft palate by inhibiting the proliferation of mouse palatal cells and promoting apoptosis, which may not be involved in EMT. LAMA5 silencing can also cause cleft palate by interfering with the SHH signaling pathway.
Lateral meniscal posterior root (LMPR) is an important stabilizer for knee joint, providing the stability during tibia forward shifting and internal rotating. It is still controversial that whether ...the LMPR tear (LMPRT) should be repaired together with ACL reconstruction. This study aims to investigate the effects of LMPR on knee stability with intact ACL.
Eight cadaver knees were used and performed the biomechanical kinematics tests in orders of: Group A: the LMPR was intact; Group B: the LMPR was cut off from its tibial end; Group C: the LMPRT has been repaired. 1) An internal rotation moment (5 Nm) was given to the tibia, then the internal rotation angle of the tibia was measured; 2) An forward shifting force (134 N) was given to the tibia, then the anterior displacement of the tibia was measured; 3) An internal rotation moment (5 Nm) and a valgus moment (10 Nm) were given to the tibia, then the internal rotation angle and the anterior displacement was measured. The stability was inferred from smaller rotation angle and displacement, and all of the angles and displacements were measured at knee flexion of 0°, 30°, 60° and 90°, respectively.
Comparing to Group A, the internal rotation angle in Group B was increased significantly at knee flexion of 30° (
= 0.025), 60° (
= 0.041), 90° (
= 0.002); the anterior tibia displacement in Group B was increased significantly at knee flexion of 30° (
= 0.015), 60° (
= 0.024); at knee valgus, the internal rotation angle was also increased significantly at knee flexion of 60° (
= 0.011), 90° (
= 0.037). Comparing to Group B, the internal rotation angle in Group C was decreased significantly at knee flexion of 30° (
= 0.030), 60° (
= 0.019), 90° (
= 0.021); the anterior displacement in Group C was decreased significantly at knee flexion of 30° (
= 0.042), 60° (
= 0.037); at valgus, the internal rotation angle was also decreased significantly at knee flexion of 60° (
= 0.013), 90° (
= 0.045). Comparing to Group A, only the internal rotation angle (
= 0.047) and anterior displacement (
= 0.033) in Group C were increased at knee flexion of 30°.
In simulated knee with intact ACL, LMPRT can still lead to the notable internal rotational instability at knee flexion from 30° to 90°, as well as the anterior shift instability at knee flexion from 30° to 60°. LMPRT repair help to improve the internal rotation stability at 30° and restore it at 60° to 90°, and improve the anterior shift stability at 30° and restore it at 60°.
•Monitoring of distributioncharacteristicsofrailheaveanddeformation.•Study on the link betweenexpansibilityandmoistureofmudstoneandfiller.•Numericalsimulationofrailheavecausedbyfoundationandfiller ...swelling.
The ballastless track has been a widely-used track form in high-speed railway (HSR), however, its application is seriously hampered by the railway heave, which is mainly caused by subgrade swelling. In order to identify the mechanism of HSR subgrade swelling and the rules of swelling-induced railway heave response, long-term longitudinal-continuous deformation monitoring and layered deformation monitoring over a heaving-affected site have been carried out. Furthermore, a coarse-grained soil oedometer was applied to explore the correlations between swelling pressure and swelling ratio of the subgrade filler and mudstone foundation to the on-site water content. With the aid of FLAC3D-PFC3D coupled numerical simulation, the influence of different swelling ratios for subgrade filler and mudstone foundation on the railway heave response of a double-block ballastless track under was analyzed. According to the field monitoring results, swelling deformation occurred in both the filler layer and subgrade layer of the heave section, and this combined action within the two layers resulted in railway heave displacement. Laboratory tests indicated that the swelling ratios of the subgrade filler and mudstone foundation under in-situ water content reached 0.205% and 3.325%, respectively. The swelling pressure and swelling ratio in the subgrade filler and mudstone foundation both followed a logistic function relationship with the water content. Numerical results showed that the railway heave amount followed Expassoc and Nelder distribution relationships with the swelling ratios of the subgrade filler and mudstone foundation, respectively. The research results could provide some reference value for the study on the swelling potential of expansive soils and the prediction of railway deformation in railway engineering.
Perfluoroalkyl acids (PFAAs) are widespread environmental contaminants which have been detected in humans and linked to adverse health effects. Previous toxicological studies mostly focused on ...nuclear receptor-mediated pathways and did not support the observed toxic effects. In this study, we aimed to investigate the molecular mechanisms of PFAA toxicities by identifying their biological targets in cells. Using a novel electrochemical biosensor, 16 PFAAs were evaluated for inhibition of protein tyrosine phosphatase SHP-2 activity. Their potency increased with PFAA chain length, with perfluorooctadecanoic acid (PFODA) showing the strongest inhibition. Three selected PFAAs, 25 μM perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid, and PFODA, also inhibited SHP-2 activity in HepG2 cells and increased paxillin phosphorylation level. PFOA was detected in the immunoprecipitated SHP-2 from the cells exposed to 250 μM PFOA, providing unequivocal evidence for the direct binding of PFOA with SHP-2 in the cell. Molecular docking rationalized the formation of PFAA/SHP-2 complex and chain length-dependent inhibition potency. Our results have established SHP-2 as a new cellular target of PFAAs.
Background
The triglyceride glucose (TyG) index is closely associated with subclinical atherosclerosis. However, the association remains inconclusive among obese and nonobese individuals.
Methods
...This prospective study was conducted in 5751 adults with normal carotid intima‐media thickness (CIMT) at baseline. We divided the population into four groups based on the TyG index, which was calculated by the following formula: Ln (fasting triglycerides mg/dL × fasting glucose mg/dL/2). Information on CIMT was acquired by ultrasonography. Incident elevated CIMT was defined as IMT values greater than 0.9 mm at follow‐up. Odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between TyG index and elevated CIMT were estimated using multivariable logistic regression models.
Results
After a median follow‐up of 4.3 years, 722 (12.6%) individuals had progressed to elevated CIMT. Compared with the second quartile of the TyG index, the first and fourth quartile both conferred higher risks of elevated CIMT after adjusting for potential confounders. In the total population, the ORs for the first and fourth quartile were 1.29 (95% CI, 1.00‐1.66) and 1.42 (95% CI, 1.11‐1.83), respectively. Restricted cubic splines demonstrated an approximately U‐shaped association between TyG index and elevated CIMT among the total and nonobese adults (P for nonlinearity <.05), but not in those with general or abdominal obesity.
Conclusions
A U‐shaped association was observed between TyG index and elevated CIMT only among nonobese Chinese adults.
摘要
背景
甘油三酯血糖(TyG)指数与亚临床动脉粥样硬化密切相关。然而，肥胖者和非肥胖者之间的联系仍然没有定论。
方法
这项前瞻性研究在5751名基线颈动脉内膜中层厚度(CIMT)正常的成年人中进行。根据TyG指数将人群分为四组，计算公式为:Ln(空腹甘油三酯mg/dL×空腹血糖mg/dL/2)。超声检查获得CIMT的相关信息。升高的CIMT定义为随访时IMT值大于0.9 mm。用多变量Logistic回归模型估计TyG指数与CIMT升高之间关联的优势比(OR)和95%置信区间(CI)。
结果
经过平均4.3年 的随访，有722例(12.6%)患者进展为CIMT升高。与TyG指数的第二个四分位数相比，在校正了潜在的混杂因素后，第一和第四个四分位数都具有更高的CIMT升高风险。在总人口中，第一和第四个四分位数的OR值分别为1.29(95%CI，1.00~1.66)和1.42(95%CI，1.11~1.83)。限制立方样条法显示TyG指数与非肥胖者和非肥胖者的CIMT升高呈近似的U型相关(P<0.05)，但在一般肥胖者或腹型肥胖者中不存在。
结论
仅在非肥胖的中国成年人中，TyG指数与CIMT升高呈U型相关。
Highlights
Many studies have reported that the triglyceride glucose (TyG) index is an inexpensive biochemical marker to assess metabolic and cardiovascular diseases.
Our findings indicate that the TyG index is nonlinearly associated with the risk of new‐onset elevated carotid intima‐media thickness (CIMT) during a follow‐up of 4.3 years. We further evaluated such relationship in participants by body size phenotypes. A U‐shaped association between TyG index and elevated CIMT only existed among those without general or abdominal obesity.
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