The mechanisms underlying the two‐way relationship between diabetes mellitus (DM) and periodontitis are unclear. We examined a possible effect of galectin‐3 (Gal‐3), a factor in DM and bone ...metabolism, on periodontitis with or without DM. Using enzyme‐linked immunosorbent assay, we detected saliva Gal‐3 in patients with periodontitis, with or without type 2 diabetes mellitus (T2DM). In animal models, we measured periodontal bone microarchitecture via micro computed tomography, and detected Gal‐3, Runt‐related transcription factor 2 (Runx2), and interleukin‐6 (IL‐6) expression in alveolar bone. Applying dual luciferase reporter assay, we explored the target binding of miR‐124‐3p and Gal‐3. We examined osteocyte‐derived exosomes with transmission electron microscopy and detected miR‐124‐3p, Gal‐3, and IL‐6 expression in exosomes. Saliva Gal‐3 was increased in DM compared with controls but decreased in patients with moderate periodontitis and DM compared with those who had moderate periodontitis only. Alveolar bone mass was increased in DM and exacerbated in DM with periodontitis. Gal‐3 and Runx2 were both increased in periodontitis and DM compared with controls, but decreased in DM with periodontitis compared with DM alone. MiR‐124‐3p targeted and inhibited Gal‐3 expression in vitro. Osteocytes secreted exosomes carrying miR‐124‐3p, Gal‐3, and IL‐6, which were influenced by high glucose. These findings indicate that osteocyte‐derived exosomes carrying miR‐124‐3p may regulate Gal‐3 expression of osteoblasts, especially under high‐glucose conditions, suggesting a possible mechanism for DM‐related alveolar bone pathologies.
Neuropeptides, as pervasive intercellular signaling molecules in the CNS, modulate a variety of behavioral systems in both protostomes and deuterostomes. Allatostatins are neuropeptides in arthropods ...that inhibit the biosynthesis of juvenile hormones. Based on amino acid sequences, they are divided into three different types in arthropods: allatostatin A, allatostatin B, allatostatin C. Allatostatin C (AstC) was first isolated from Manduca sexta, and it has an important conserved feature of a disulfide bridge formed by two cysteine residues. Moreover, AstC appears to be the ortholog of mammalian somatostatin, and it has functions in common with somatostatin, such as modulating feeding behaviors. The AstC signaling system has been widely studied in arthropods, but minimally studied in molluscs. In this study, we seek to identify the AstC signaling system in the marine mollusc Aplysia californica. We cloned the AstC precursor from the cDNA of Aplysia. We predicted a 15-amino acid peptide with a disulfide bridge, i.e., AstC, using NeuroPred. We then cloned two putative allatostatin C-like receptors and through NCBI Conserved Domain Search we found that they belonged to the G protein-coupled receptor (GPCR) family. In addition, using an inositol monophosphate 1 (IP1) accumulation assay, we showed that Aplysia AstC could activate one of the putative receptors, i.e., the AstC-R, at the lowest EC
, and AstC without the disulfide bridge (AstC') activated AstC-R with the highest EC
. Moreover, four molluscan AstCs with variations of sequences from Aplysia AstC but with the disulfide bridge activated AstC-R at intermediate EC
. In summary, our successful identification of the Aplysia AstC precursor and its receptor (AstC-R) represents the first example in molluscs, and provides an important basis for further studies of the AstC signaling system in Aplysia and other molluscs.
We investigate the
B
+
→
J
/
ψ
ϕ
K
+
decay via various rescattering diagrams. Without introducing genuine exotic resonances, it is shown that the
Z
cs
(
4000
)
,
Z
cs
(
4220
)
and
X
(4700) reported ...by the LHCb collaboration can be simulated by the
J
/
ψ
K
∗
+
,
ψ
′
K
+
and
ψ
′
ϕ
threshold cusps, respectively. These cusps are enhanced by some nearby triangle singularities. The
X
(4685) with
J
P
=
1
+
cannot be well simulated by the threshold effects in our model, which implies that it may be a genuine resonance.
Colorectal cancer (CRC) is the third‐leading cause of cancer mortality worldwide. HACE1 function as a tumor‐suppressor gene and is downregulated in several kinds of cancers. However, the distribution ...and clinical significance of HACE1 in CRC is still not clarified. In this study, we found that the HACE1 expression is greatly downregulated in CRC tissues and cell lines. Moreover, the HACE1 expression was significantly associated with inhibition of CRC cell proliferation, metastasis, and invasion. HACE1 inhibited epithelial–mesenchymal transition in CRC cells. Furthermore, we found that
HACE1 altered the protein expression of the Hippo pathway by downregulation of YAP1. HACE1 suppresses the invasive ability of CRC cells by negatively regulating the YAP1 pathway. Our data indicates that HACE1 directly targets YAP1 and induces downregulation of YAP1, thereby increasing the activity of the Hippo pathway. In summary, these findings demonstrated that HACE1–YAP1 axis had an important part in the CRC development and progression.
Loss of HACE1 promoted epithelial–mesenchymal transition (EMT), migration and invasion in CRC cells. Loss of HACE1 upregulated YAP1 expression in CRC cells. Knockdown of HACE1, via YAP1‐mediated EMT, is involved in cancer cell migration in CRC cells
Gastric cancer(GC) is the fifth most common malignancy in the world. The major cause of GC is chronic infection with Helicobacter pylori(H. pylori). Infection with H. pylori leads to an active ...inflammatory microenvironment that is maintained by immune cells such as T cells, macrophages, natural killer cells, among other cells. Immune cell dysfunction allows the initiation and accumulation of mutations in GC cells, inducing aberrant proliferation and protection from apoptosis. Meanwhile, immune cells can secrete certain signals, including cytokines, and chemokines, to alter intracellular signaling pathways in GC cells. Thus, GC cells obtain the ability to metastasize to lymph nodes by undergoing the epithelial-mesenchymal transition(EMT), whereby epithelial cells lose their epithelial attributes and acquire a mesenchymal cell phenotype. Metastasis is a leading cause of death for GC patients, and the involved mechanisms are still under investigation. In this review, we summarize the current research on how the inflammatory environment affects GC initiation and metastasis via EMT.
Background and Aims
Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. Clinical trials use the NASH Clinical Research Network (CRN) system for semiquantitative ...histological assessment of disease severity. Interobserver variability may hamper histological assessment, and diagnostic consensus is not always achieved. We evaluate a second harmonic generation/two‐photon excitation fluorescence (SHG/TPEF) imaging‐based tool to provide an automated quantitative assessment of histological features pertinent to NASH.
Approach and Results
Images were acquired by SHG/TPEF from 219 nonalcoholic fatty liver disease (NAFLD)/NASH liver biopsy samples from seven centers in Asia and Europe. These were used to develop and validate qFIBS, a computational algorithm that quantifies key histological features of NASH. qFIBS was developed based on in silico analysis of selected signature parameters for four cardinal histopathological features, that is, fibrosis (qFibrosis), inflammation (qInflammation), hepatocyte ballooning (qBallooning), and steatosis (qSteatosis), treating each as a continuous rather than categorical variable. Automated qFIBS analysis outputs showed strong correlation with each respective component of the NASH CRN scoring (P < 0.001; qFibrosis r = 0.776, qInflammation r = 0.557, qBallooning r = 0.533, and qSteatosis r = 0.802) and high area under the receiver operating characteristic curve values (qFibrosis 0.870‐0.951; 95% confidence interval {CI}, 0.787‐1.000; P < 0.001, qInflammation 0.820‐0.838; 95% CI, 0.726‐0.933; P < 0.001), qBallooning 0.813‐0.844; 95% CI, 0.708‐0.957; P < 0.001, and qSteatosis 0.939‐0.986; 95% CI, 0.867‐1.000; P < 0.001) and was able to distinguish differing grades/stages of histological disease. Performance of qFIBS was best when assessing degree of steatosis and fibrosis, but performed less well when distinguishing severe inflammation and higher ballooning grades.
Conclusions
qFIBS is an automated tool that accurately quantifies the critical components of NASH histological assessment. It offers a tool that could potentially aid reproducibility and standardization of liver biopsy assessments required for NASH therapeutic clinical trials.
Maintenance of normal lipid homeostasis is crucial to heart function. On the other hand, the heart is now recognized to serve an important role in regulating systemic lipid metabolism; however, the ...molecular basis remains unclear. In this study, we identify the Drosophila Snail family of transcription factors (herein termed Sna TFs) as new mediators of the heart control of systemic lipid metabolism. Overexpression of Sna TF genes specifically in the heart promotes whole-body leanness whereas their knockdown in the heart promotes obesity. In addition, flies that are heterozygous for a snail deficiency chromosome also exhibit systemic obesity, and that cardiac-specific overexpression of Sna substantially reverses systemic obesity in these flies. We further show that genetically manipulating Sna TF levels in the fat body and intestine do not affect systemic lipid levels. Mechanistically, we find that flies bearing the overexpression or inhibition of Sna TFs in the postnatal heart only exhibit systemic lipid metabolic defects but not heart abnormalities. Cardiac-specific alterations of Sna TF levels also do not perturb cardiac morphology, viability, lipid metabolism or fly food intake. On the other hand, cardiac-specific manipulations of Sna TF levels alter lipogenesis and lipolysis gene expression, mitochondrial biogenesis and respiration, and lipid storage droplet 1 and 2 (Lsd-1 and Lsd-2) levels in the fat body. Together, our results reveal a novel and specific role of Sna TFs in the heart on systemic lipid homeostasis maintenance that is independent of cardiac development and function and involves the governance of triglyceride synthesis and breakdown, energy utilization, and lipid droplet dynamics in the fat body.
To review the effects of core stability exercise or general exercise for patients with chronic low back pain (LBP).
Exercise therapy appears to be effective at decreasing pain and improving function ...for patients with chronic LBP in practice guidelines. Core stability exercise is becoming increasingly popular for LBP. However, it is currently unknown whether core stability exercise produces more beneficial effects than general exercise in patients with chronic LBP.
Published articles from 1970 to October 2011 were identified using electronic searches. For this meta-analysis, two reviewers independently selected relevant randomized controlled trials (RCTs) investigating core stability exercise versus general exercise for the treatment of patients with chronic LBP. Data were extracted independently by the same two individuals who selected the studies.
From the 28 potentially relevant trials, a total of 5 trials involving 414 participants were included in the current analysis. The pooling revealed that core stability exercise was better than general exercise for reducing pain mean difference (-1.29); 95% confidence interval (-2.47, -0.11); P = 0.003 and disability mean difference (-7.14); 95% confidence interval (-11.64, -2.65); P = 0.002 at the time of the short-term follow-up. However, no significant differences were observed between core stability exercise and general exercise in reducing pain at 6 months mean difference (-0.50); 95% confidence interval (-1.36, 0.36); P = 0.26 and 12 months mean difference (-0.32); 95% confidence interval (-0.87, 0.23); P = 0.25.
Compared to general exercise, core stability exercise is more effective in decreasing pain and may improve physical function in patients with chronic LBP in the short term. However, no significant long-term differences in pain severity were observed between patients who engaged in core stability exercise versus those who engaged in general exercise.
http://www.crd.york.ac.uk/PROSPERO PROSPERO registration number: CRD42011001717.
Breast cancer is among the most common malignant cancers in women. B‐cell‐specific Moloney murine leukemia virus integration site 1 (BMI‐1) is a transcriptional repressor that has been shown to be ...involved in tumorigenesis, the cell cycle, and stem cell maintenance. In our study, increased expression of BMI‐1 was found in both human triple negative breast cancer and luminal A‐type breast cancer tissues compared with adjacent tissues. We also found that knockdown of BMI‐1 significantly suppressed cell proliferation and migration in vitro and in vivo. Further mechanistic research demonstrated that BMI‐1 directly bound to the promoter region of CDKN2D/BRCA1 and inhibited its transcription in MCF‐7/MDA‐MB‐231. More importantly, we discovered that knockdown of CDKN2D/BRCA1 could promote cell proliferation and migration after repression by PTC‐209. Our results reveal that BMI‐1 transcriptionally suppressed BRCA1 in TNBC cell lines whereas, in luminal A cell lines, CDKN2D was the target gene. This provides a reference for the precise treatment of different types of breast cancer in clinical practice.
BMI‐1 promotes proliferation and migration via transcriptional inhibition of cyclin‐dependent kinase inhibitor 2D (CDKN2D) in luminal A‐type breast cancer but via transcriptional inhibition of breast cancer susceptibility gene 1 (BRCA1) in TNBC.
Promoting the reconstruction of electrocatalysts during the oxygen evolution reaction (OER) is generally regarded as a promising strategy for enhanced activity. F anions with strong electronegativity ...are predicted to enhance this transformation. Herein, a fluorine-anion doping route is proposed to convert the well-latticed NiMoO4@MNF to amorphous F-NiMoO4@MNF by a facile and versatile molten salt strategy. The well-defined nanorod arrays guarantee abundant exposed active sites, rapid mass transfer, and fast gas bubble release. Moreover, the emerged loose amorphous structure is conducive to the dynamic migration of F species and effective penetration of the electrolyte; therefore, the resulting exchange between F and hydroxide anions induces the formation of an active oxy(hydroxide) layer, thus finally optimizing the electronic structure and absorption/desorption energy on the surface of F-NiMoO4@MNF. The boosted OER performance of reconstructed F-NiMoO4@MNF is reliably confirmed by a low overpotential of 188 mV at 50 mA cm–2, a small Tafel slope of 33.8 mV dec–1, and favorable long-term stability. In addition, accelerated hydrogen evolution is observed, which is ascribed to the finely tuned electron distribution. This work would provide a new reconstruction route assisted by F-anion doping to the development of high-performance catalysts.
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