Potential regulatory mechanisms of lncRNA in diabetes and its complications.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides without protein-coding potential. Although these molecules were initially considered as "junk products" of transcription without biological relevance, recent advances in research have shown that lncRNA plays an important role, not only in cellular processes such as proliferation, differentiation, and metabolism, but also in the pathological processes of cancers, diabetes, and neurodegenerative diseases. In this review, we focus on the potential regulatory roles of lncRNA in diabetes and the complications associated with diabetes.

The Physiological Role of Tumor Necrosis Factor in Human Immunity and Its Potential Implications in Spinal Manipulative Therapy: A Narrative Literature Review.

OBJECTIVE: Although tumor necrosis factor (TNF) is a well-known inflammatory cytokine in the pathological development of various human diseases, its physiological roles are not widely understood nor appreciated. The molecular mechanisms underlying spinal manipulation therapy (SMT) remain elusive. The relationship between TNF and SMT is unclear. Thus, we performed this literature review to better understand TNF physiology and its potential relationship with SMT, and we propose a novel mechanism by which SMT may achieve clinical benefits by using certain beneficial features of TNF. METHODS: We searched several databases for relevant articles published between 1975 and 2015 and then reexamined the studies from current immunophysiological perspectives. RESULTS: The history and recent progresses in TNF physiology research were explored. Conflicting reports on the relationship between TNF and SMT were identified. Based on the newly discovered interaction between TNF and regulatory T cells, we proposed a putative biphasic TNF response to SMT, which may resolve the conflicts in the reported observations and interpretations. CONCLUSION: The current literature about TNF informed our discussion of new physiological roles for TNF, which may help to better understand the physiological effects of SMT.

The Impacts of Obesity and Metabolic Abnormality on Carotid Intima-Media Thickness and Non-Alcoholic Fatty Liver Disease in Children from an Inland Chinese City.

The Chinese inland, where low child obesity and overweight rates were reported in earlier studies, has recently experienced rapid economy changes. This may impact children's health. In the present study, we investigated the obesity rate, metabolic health status, and their impacts on carotid intima-media thickness (IMT) and non-alcoholic fatty liver disease (NAFLD) among children from Yueyang, an inland city of China. We found that the obesity rate was about 5% for both 7- and 11-year olds. Overweightness rates were 9.5% and 11.5% for the 7- and 11-year olds, respectively. Clinical and laboratory examinations revealed significant differences among different weight groups in the 11-year old volunteers, which were absent in the 7-year olds. Further statistical analysis showed that: age, BMI, blood pressure, triglyceride level, and metabolic abnormality were positively correlated to carotid IMT; triglyceride level, obesity, male, and the number of metabolic abnormalities were independent risk factors for NAFLD in these children. Our study suggests that: childhood overweightness and obesity are now epidemic in Yueyang, which have contributed to increased carotid IMT and may also increased NAFLD incidents; and serum triglyceride level is a critical factor in the development of childhood NAFLD. Thus, childhood metabolic health warrants further vigorous research in the inland of China.

The role of caveolae in regulating calcitonin receptor-like receptor subcellular distribution in vascular smooth muscle cells.

To determine whether caveolae and caveolin-1 affect the distribution of calcitonin receptor-like receptors (CLR) in vascular smooth muscle cell (VSMC) membranes, we have used VSMCs cell line A10. We found that calcitonin gene-related peptide (CGRP) reduced CLR protein in the VSMC membrane in a time-dependent manner, which was dramatically decreased after 4 h CGRP treatment, and remained at a low level after 16 h. CGRP8-37 or ß-cyclodextrin (ß-CD) blocked this effect, without changing the total levels of CLR protein and mRNA in the cells. Co-immunoprecipitation experiments showed that CLR bound to caveolin-1 in cell membrane fractions. Confocal laser microscopic studies confirmed this co-localization relationship at the cell plasma membrane. Thus, our data indicate that the structural integrity of caveolae plays an important role in regulating subcellular distribution of CLR.

The physiological and pathophysiological roles of adipocyte miRNAs.

MicroRNAs (miRNAs) are highly conserved, small, noncoding RNAs that regulate gene expression at the posttranscriptional level. Their actions affect numerous important biological processes, including adipocyte differentiation and function, sugar and lipid metabolism, and insulin production and secretion. Recent reports suggest miRNAs may also be involved in the pathogenic processes of obesity, diabetes, and insulin resistance. In this review, we summarize research progresses on adipocyte miRNAs and their physiological and pathological implications.

Differential protein and mRNA expression of CaMKs during osteoclastogenesis and its functional implications.

The calmodulin-dependent kinase (CaMK) family has been recently recognized to participate in the regulation of osteoclastogenesis. However, there are some controversial reports regarding the mRNA expression patterns of CaMKs during osteoclastogenesis, although the protein expression pattern of most CaMKs during osteoclastogenesis have not been studied. In the present study, we attempted to address this issue by using a mouse bone marrow monocyte model and parallel Western blotting and quantitative real-time PCR. Our results revealed some interesting expression patterns of CaMKs during the process. Among all CaMKs examined, only CaMKIIδ exhibited consistent expression patterns between its mRNA and protein with both rising remarkably during osteoclastogenesis. CaMKIV protein was not detectable during the first three days of cell culture, but it rose on Day 5. The CaMK inhibitor, KN93, subdued osteoclastogenesis during the first three days of cell culture, a time when CaMKIV was absent while other KN93-sensitive CaMKs presented. In addition, KN93 was found to inhibit the expression of some early receptor activator of NF-κB (RANK) signaling intermediates (extracellular signal-regulated kinase (ERK) and Akt) in the non-differentiated mouse bone marrow monocytes. Collectively, these data reveal differential expression patterns of KN93-sensitive CaMK proteins and their mRNAs during osteoclastogenesis, supporting a CaMKII-RANK signaling interaction in the regulation of early osteoclastogenesis.

MicroRNA-375 promotes 3T3-L1 adipocyte differentiation through modulation of extracellular signal-regulated kinase signalling.

1. Adipocyte hypertrophy and hyperplasia are important processes in the development of obesity. To understand obesity and its associated diseases, it is important to elucidate the molecular mechanisms governing adipogenesis. MicroRNA-375 has been shown to inhibit differentiation of neurites, and participate in the regulation of insulin secretion and blood homeostasis. However, it is unknown whether miR-375 plays a role in adipocyte differentiation. 2. To investigate the role of miR-375 in adipocyte differentiation, we compared the miR-375 expression level between 3T3-L1 pre-adipocytes and adipocytes using miRNA microarray and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis. Furthermore, we evaluated the effects of overexpression or inhibition of miR-375 on 3T3-L1 adipocyte differentiation. 3. In the present study, we found that miR-375 expression was increased after induction of adipogenic differentiation. Overexpression of miR-375 enhanced 3T3-L1 adipocyte differentiation, as evidenced by its ability to increase mRNA levels of both CCAAT/enhancer binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor-γ (PPARγ2), and induction of adipocyte fatty acid-binding protein (aP2) and triglyceride (TG) accumulation. Furthermore, we found overexpression of miR-375 suppressed phosphorylation levels of extracellular signal-regulated kinases 1/2 (ERK1/2). In contrast, anti-miR-375 increased ERK1/2 phosphorylation levels and inhibited mRNA expression of C/EBPα, PPARγ2 and aP2 in 3T3-L1 adipocyte, accompanied by decreased adipocyte differentiation. 4. Taken together, these data suggest that miR-375 promotes 3T3-L1 adipocyte differentiation, possibly through modulating the ERK-PPARγ2-aP2 pathway.