Background/ObjectiveIn mice, a high fat diet (HFD) induces obesity, insulin resistance and myostatin production. We tested whether inhibition of myostatin in mice can reverse these HFD-induced abnormalities.Subjects/MethodsC57BL/6 mice were fed a HFD for 16 weeks including the final 4 weeks some mice were treated with an anti-myostatin peptibody. Body composition, the respiratory exchange ratio plus glucose and insulin tolerance tests were examined. Myostatin knock down in C2C12 cells was performed using ShRNA lentivirus. Adipose tissue-derived stem cells were cultured to measure their reponses to conditioned media from C2C12 cells lacking myostatin, or to recombinant myostatin or Irisin. Isolated peritoneal macrophages were treated with myostatin or Irisin to determine if myostatin or Irisin induce inflammatory mechanisms.ResultsIn HFD-fed mice, peptibody treatment stimulated muscle growth and improved insulin resistance. The improved glucose and insulin tolerances were confirmed when we found increased muscle expression of p-Akt and the glucose transporter, Glut4. In mice fed the HFD, the peptibody suppressed macrophage infiltration and the expression of proinflammatory cytokines in both muscle and adipocytes. Inhibition of myostatin caused the conversion of white (WAT) to brown adipose tissue (BAT) while stimulating fatty acid oxidation and increasing energy expenditure. The related mechanism is a muscle-to-fat cross talk mediated by Irisin. Myostatin inhibition increased PGC-1α expression and Irisin production in muscle. Irisin then stimulated WAT browning. Irisin also suppresses inflammation and stimulates macrophage polarization from M1 to M2 types.Concusionthese results uncover a metabolic pathway from an increase in myostatin that suppresses Irisin leading to activation of inflammatory cytokines and insulin resistance. Thus, myostatin is a potential therapeutic target to treat insulin resistance of type II diabetes as well as the shortage of brown/beige fat in obesity.

Eleven weedy or wild species or subspecies of the genus Secale L. were compared with a set of cultivated rye accessions, based on inter-simple sequence repeat (ISSR) markers to analyze their phylogenetic relationships. A total of 846 bands were amplified from reactions using 12 screening primers, including 79 loci with a mean of 10.1 alleles per locus. The number of amplified bands for each primer ranged from 12 to 134, with a mean of 70.5 amplified bands per primer. The presence and distribution of amplified bands in different accessions demonstrate that a rapid evolutionary trend of microsatellite repeats occurred during the speciation process from the perennial wild form to annual cultivated rye. In addition, variation, amplification, and deletion of microsatellites in genomes revealed phylogenetic relationships in the genus Secale. Analysis of the presence, number, and distribution of amplified bands in genomes, as well as the comparison with genetic similarity (GS) indices based on ISSR, indicate that Secale strictum subsp. africanum (Stapf) Hammer, Secale strictum anatolicum (Boiss.) Hammer, Secale sylvestre Host, and Secale strictum subsp. strictum (C. Presl) Hammer emerged in succession from a common ancestor of Secale following geographic separation and genetic differentiation. The annual weedy rye evolved from S. strictum subsp. strictum, which was domesticated as present-day cultivated rye. Data from ISSR analyses separated all investigated accessions of the genus Secale into three distinct groups. These results support the division of the genus Secale into three species: the annual wild species S. sylvestre; the perennial wild species S. strictum, including several differential subspecies forms such as strictum, africanum, and anatolicum; and S. cereale, including cultivated and weedy rye as subspecies forms.

The effects of treatment with 50 and 100 mM NaCl on cotyledon growth, nitrogen assimilation, and the activities of key nitrogen metabolism enzymes were investigated in developing Jatropha curcas cotyledons. Growth inhibition was observed, and relative water content in the developing cotyledons significantly decreased in the 100 mM NaCl treatment. Lower levels of NO 3 -, NO 2 -, and NH 4 + in the cotyledons were recorded when they were supplied with 50 and 100 mM NaCl. Nitrate reductase activities decline by 9.5% to 31.8% with respect to the control groups. Salt treatment also led to a marked decrease in nitrite reductase activity compared with the controls. Glutamine synthase, glutamate synthetase and dehydrogenase, alanine aminotransferase (AlaAT) and aspartate aminotransferase (AspAT) were markedly induced by the addition of NaCl. These findings will be useful for elucidating the roles key enzymes involved in nitrogen assimilation pathway of J. curcas plant.

Oral submucous fibrosis (OSMF), a potentially malignant oral cavity disorder that causes speech and mastication problems, lacks an established treatment regimen; moreover, no treatment can effectively reverse the course of OSMF. A meta-analysis was conducted to investigate the efficacy of the peripheral vasodilator, pentoxifylline, in the treatment of OSMF. We searched five different databases for studies meeting our eligibility criteria (up to June 30, 2017). Statistical analyses were performed using RevMan 5.3 software. Three randomized controlled trials (247 OSMF patients) were selected. Pentoxifylline increased the objective sign maximal mouth opening (MMO; WMD: -4.59, 95% CI: -8.65, -0.53; p < 0.05) following short-term (under 1 month; WMD: -1.94, 95% CI: -3.12, -0.77; p < 0.05) and long-term (over 1 month; WMD: -5.44, 95% CI: -6.81, -4.07; p < 0.05) application. Pentoxifylline improved the subjective symptom burning sensation (WMD: -0.11, 95% CI: -0.17, -0.05; p < 0.05) only following long-term application (WMD: 0.42, 95% CI: 0.18, 0.96; p < 0.05). The efficacy on MMO and burning sensation increased with time. Although OSMF lacks definitive treatment modalities, our meta-analysis shows that pentoxifylline effectively improves the objective signs and subjective symptoms of OSMF and its therapeutic efficacy increases with time.

Metastasis, a powerful prognostic indicator of oral squamous cell carcinoma (OSCC), is chiefly responsible for poor cancer outcomes. Despite an increasing number of studies examining the mechanisms underlying poor outcomes, the development of potent strategies is hindered by insufficient characterization of the crucial regulators. Long noncoding RNAs (lncRNAs) have recently been gaining interest as significant modulators of OSCC metastasis; however, the detailed mechanisms underlying lncRNA-mediated OSCC metastasis remain relatively uncharacterized. Here, we identified a novel alternative splice variant of oral cancer overexpressed 1 ( ORAOV1), named as ORAOV1-B, which was subsequently validated as an lncRNA and correlated with OSCC lymph node metastasis; significantly increased invasion and migration were observed in ORAOV1-B–overexpressing OSCC cells. RNA pulldown and mass spectrometry identified Hsp90 as a direct target of ORAOV1-B, and cDNA microarrays suggested TNFα as a potential downstream target of ORAOV1-B. ORAOV1-B was shown to directly bind to and stabilize Hsp90, which maintains the function of client proteins, receptor-interaction protein, and IκB kinase beta, thus activating the NF-κB pathway and inducing TNFα. Additionally, TNFα reciprocally enhanced p-NF-κB-p65 and the downstream epithelial-mesenchymal transition. ORAOV1-B effects were reversed by a TNFα inhibitor, demonstrating that TNFα is essential for ORAOV1-B–regulated metastatic ability. Consistent epithelial-mesenchymal transition in the ORAOV1-B group was demonstrated via an orthotopic model. In the metastatic model, ORAOV1-B significantly contributed to OSCC-related lung metastasis. In summary, the novel splice variant ORAOV1-B is an lncRNA, which significantly potentiates OSCC invasion and metastasis by binding to Hsp90 and activating the NF-κB-TNFα loop. These findings demonstrate the versatile role of ORAOV1 family members and the significance of genes located within 11q13 in promoting OSCC. ORAOV1-B might serve as an attractive OSCC metastasis intervention target.