MicroRNAs in type 1 diabetes: new research progress and potential directions.

MicroRNAs (miRNAs) are a class of noncoding single-stranded RNA molecules encoded by endogenous genes of about 22 nucleotides, which are involved in post-transcriptional gene expression regulation in animals and plants. Type 1 diabetes (T1D) is an autoimmune disease that is clinically silent until the majority of ß cells are destroyed, and a large number of studies have shown that miRNAs are involved in the pathological mechanism of T1D. In this review, we searched the related research in recent years and summarized the important roles of miRNAs in T1D diagnosis and treatment. Furthermore, we summarized the current understanding of miRNA-mediated regulation mechanisms of gene expression in the T1D pathogenesis as well as related signaling pathways with a focus on the important roles of miRNAs and their antagonists in T1D pathogenesis, and brought insight into the potential therapeutic value of miRNAs for T1D patients. In view of the important roles of miRNAs in T1D pathology, disordered miRNAs may be important diagnostic markers and therapeutic targets for patients with T1D.

Recent research progress of microRNAs in hypertension pathogenesis, with a focus on the roles of miRNAs in pulmonary arterial hypertension.

Hypertension is the most widespread disease in the world affecting humans and imparts a significant cardiovascular and renal risk to patients, and extensive research over the past few decades has enhanced our understanding of the underlying pathogenesis of hypertension. A growing number of studies have shown that miRNAs are involved in the pathological mechanisms of hypertension. This review summarizes the current understanding of miRNA-mediated modulation of gene expression in the hypertension pathogenesis in the past few years. A systematic review of PUBMED, EMBASE and SCOPUS was conducted for studies published in the past few years. The review covers three topics: miRNAs in pulmonary arterial hypertension (PAH), miRNAs and systemic arterial hypertension (SAH), miRNAs and application in hypertension. This review summarizes the current understanding of miRNA-mediated modulation in the hypertension pathogenesis in the past few years, with especially emphasis on miRNAs in PAH. We also discussed the roles of miRNAs in SAH, and the therapeutic applications of these miRNAs will be detailed discussed in this review. Evidence suggests that miRNAs are involved in the pathological mechanisms of hypertension, and the roles of miRNAs in the hypertension pathogenesis are confirmed. We need to further investigate the regulated roles of miRNAs in the pathogenesis of hypertension and the application of miRNAs in the diagnosis and treatment of this disease in the future.

MicroRNAs in idiopathic pulmonary fibrosis, new research progress and their pathophysiological implication.

Many studies have shown that microRNAs (miRNAs) play important roles in the development of idiopathic pulmonary fibrosis (IPF). The purpose of this review is to systematically summarize the recent advance of miRNAs in the pathology of IPF, highlighting the new research progress and their pathophysiological implication. Recent studies have shown that miRNAs differentially expressed in blood and lung tissue from IPF patients are closely related to the occurrence of IPF disease, which may be IPF diagnostic markers and prognostic indicators. Furthermore, studies have shown that miRNAs are involved in the pathological mechanisms of IPF, including the lung epithelial repair, epithelial-mesenchymal transition (EMT), fibroblast activation, myofibroblast differentiation, macrophage polarization, alveolar epithelial cells (AEC) senescence and collagen production. In this review, the regulation mechanisms of miRNAs in IPF pathology, such as the long noncoding RNAs (lncRNAs) in miRNA expression, the cross-talk among miRNAs, and the mutual effect of miRNA and DNA methylation, are also systematically reviewed. According to the recent studies of miRNAs in the pathology of IPF, miRNAs play important roles in the pathogenesis of IPF, and miRNAs involved in IPF pathology are helpful to elucidate the pathogenesis of IPF and the treatment of this disease.

MicroRNAs in the pathogenesis of type 2 diabetes: new research progress and future direction.

miRNA is a short non-coding RNA that can influence mRNA processing at the post-transcriptional level. A large number of miRNAs have been found in virtually all species so far, and these small molecules play an important role in many different physiological processes and various pathologic conditions, such as cell metabolism, cancer, autoimmune disease, and diabetes mellitus. T2D arises from a dysregulated response to the elevated glucose level in the circulation. The prevalence of T2D has increased dramatically in all age groups, and T2D in older adults is associated with more T2D complications and higher mortality. Despite the existing findings describing the pathological mechanism, T2D pathology is more complex and the pathophysiology of the disease is still not fully elucidated. In this review, we summarize the current understanding of miRNA-mediated modulation of gene expression in T2D pathogenesis, as well as related signaling pathways, and insight into the important role of miRNA in various T2D complications. Furthermore, the potential therapeutic value of miRNA for T2D patients is also discussed in detail.

miR-148b-3p affects the pathogenesis of adjuvant-induced arthritis rats through the direct target DNMT1.

Our previous study showed that up-regulated DNA methyltransferase-1 (DNMT1) played an important role in the hypermethylation modification of SFRP4 in adjuvant-induced arthritis (AIA) rats. This work focused on the role of disordered miR-148b-3p in RA pathology and its corresponding regulatory targets. The expression of miR-148b-3p and DNMT1, and the effect of miR-148b-3p on the DNMT1 expression were determined by real-time qPCR, western blotting and double luciferase reporter genes. The role of miR-148b-3p on the SFRP4 expression, the canonical Wnt signaling and the pathology of AIA rats was investigated using real-time qPCR, western blotting and methylation-specific PCR (MSP). The results showed that the expression of miR-148b-3p was significantly decreased, the expression of DNMT1 was significantly increased and the DNMT1 was the direct target of miR-148b-3p in AIA rats compared with normal group. Transfection of miR-148b-3p mimics up-regulated the SFRP4 expression, inhibited the canonical Wnt signaling and the pathogenesis of AIA rats by targeting the DNMT1. The role of miR-148b-3p knockdown was opposite to that of miR-148b-3p overexpression. These results suggest that miR-148b-3p may influence the pathogenesis of RA with the DNMT1 as a direct target and miR-148b-3p may be a potential diagnostic and therapeutic target for RA patients.

CUL4B promotes the pathology of adjuvant-induced arthritis in rats through the canonical Wnt signaling.

This work aims to discuss the possibility that disordered CUL4B was involved in the pathogenesis of adjuvant-induced arthritis (AIA) in rats. Synovium and FLS from AIA rats both showed increased CUL4B and ß-catenin, and up-regulated CUL4B enhanced the canonical Wnt signaling by targeting the GSK3ß. Increased CUL4B promoted the FLS abnormal proliferation, activated the secretion of IL-1ß and IL-8, and promoted the production of AIA pathology gene MMP3 and fibronectin. Furthermore, miR-101-3p was significantly down-regulated in AIA rats compared with controls, and transfection of AIA FLS with miR-101-3p mimics significantly down-regulated the CUL4B expression, whereas transfection with miR-101-3p inhibitors resulted in an opposite observation. The dual-luciferase reporter assay confirmed that the CUL4B was a direct target of miR-101-3p, and further analysis suggested that lowly expressed miR-101-3p contributed to disordered CUL4B activating the canonical Wnt signaling pathway and further promoting the development of AIA rats. Thus clarification of the CUL4B roles in the pathogenesis of AIA rats and corresponding mechanisms will contribute to the disease diagnosis and treatment for rheumatoid arthritis (RA) patients. KEY MESSAGES: CUL4B expression is up-regulated in synovium and FLS from AIA rats. Increased CUL4B promotes the canonical Wnt signaling. Increased CUL4B promotes the pathogenesis of AIA rats. Decreased miR-101-3p contributes to disordered CUL4B.

Acupuncture Treatment of Lateral Elbow Pain: A Nonrandomized Pilot Study.

In planning for a large-scale multicenter trial to evaluate the effect of acupuncture for the treatment of lateral elbow pain, a pilot study was conducted. This was a prospective, investigator- and patient-blinded, nonrandomized, placebo controlled trial. Subjects were evaluated at baseline, before fourth, seventh, and ninth treatment, and at a two-week posttreatment follow-up. The treatment group received unilateral acupuncture at LI 10 and LI 11 at the affected side with manual needle manipulation; the control group received sham-laser acupuncture at the same acupoints. Measures included (i) disabilities of the arm, shoulder, and hand (DASH) questionnaire, (ii) pain-free grip strength (PFGS), and (iii) a visual analogue scale (VAS) for pain. Significant differences in DASH score, PFGS, and VAS between treatment and control group were found at the ninth treatment (n = 20 for each group, P < 0.05). Only DASH showed significant differences compared to the control for all the measurement time points after treatment commenced and appears to be a sensitive and appropriate primary outcome measure for the future multisite trial. Results from this pilot study provided relevant information about treatment efficacy, credibility of control treatment, and sensitivity of different outcome measures for the planning of the future trial.

[Acupoint combination and acupuncture-moxibustion prescription].

The modern physicians have different views on acupoint combination and acupuncture-moxibustion prescription and confuse them in clinical practice. It is significant to clarify the conception, connotation and relationship between them so as to normalize the therapeutic program of acupuncture and moxibustion and promote the standardization of acupuncture and moxibustion. Through the collection of relevant literature and analysis on the differences in the understandings among physicians, the conception, connotation and relationship between acupoint combination and acupuncture-moxibustion prescription are summarized. It is viewed that the acupoint combination is based on TCM theory. Under the guide of acupoint selection, in combination of the characters of clinical practice and acupoint indications, two or more than two acupoints of the same function are combined to enhance the collaborative effects of acupoints so as to achieve specific efficacy and improve clinical efficacy. Regarding acupuncture-moxibustion prescription, on the basis of disorder and syndrome differentiation of patients, the concrete therapeutic program is put forward, including acupoint composition and therapeutic method. Acupoint combination is the basic element of acupuncture-moxibustion prescription. Acupuncture-moxibustion prescription is the specific application of acupoint combination.

A time course-dependent metastatic gene expression signature predicts outcome in human metastatic melanomas.

BACKGROUND: The prognosis of patients with metastatic melanomas is extremely heterogeneous. Therefore, identifying high-risk subgroups by using innovative prediction models would help to improve selection of appropriate management options. METHODS: In this study, two datasets (GSE7929 and GSE7956) of mRNA expression microarray in an animal melanoma model were normalized by frozen Robust Multi-Array Analysis and then combined by the distance-weighted discrimination method to identify time course-dependent metastasis-related gene signatures by Biometric Research Branch-ArrayTools (BRB)-ArrayTools. Then two datasets (GSE8401 and GSE19234) of clinical melanoma samples with relevant clinical and survival data were used to validate the prognosis signature. RESULTS: A novel 192-gene set that varies significantly in parallel with the increasing of metastatic potentials was identified in the animal melanoma model. Further, this gene signature was validated to correlate with poor prognosis of human metastatic melanomas but not of primary melanomas in two independent datasets. Furthermore, multivariate Cox proportional hazards regression analyses demonstrated that the prognostic value of the 192-gene set is independent of the TNM stage and has higher areas under the receiver operating characteristic curve than stage information in both validation datasets. CONCLUSION: Our findings suggest that a time course-dependent metastasis-related gene expression signature is useful in predicting survival of malignant melanomas and might be useful in informing treatment decisions for these patients.

Pseudomonas aeruginosa ecthyma gangrenosum in a woman with recurrent Graves' disease.

A 35-year-old woman with postoperative recurrent Graves' disease presented with a 5-day history of a red swelling on the right cheek associated with 4 days of remittent hyperpyrexia. Investigations revealed fever, a gangrenous ulcer on the right cheek, submandibular lymphadenopathy, and thyroid gland enlargement. Her white blood cell count, immunoglobulins, and lymphocyte subsets were unremarkable. Thyroid function tests showed low thyroid-stimulating hormone, high free thyroxine, and elevated radioactive iodine uptake. Repeated pus cultures grew Pseudomonas aeruginosa, but blood cultures were negative. An ill-demarcated erythematous plaque occurred on the right leg on hospital day 3. She was treated with intravenous antibiotics with topical gentamicin, recombinant bovine basic fibroblast growth factor, and radioiodine therapy with anti-thyroid drugs. The ulcer healed leaving a depressed scar at 35 days after discharge. This patient may represent the first case of P. aeruginosa ecthyma gangrenosum and cellulitis in postoperative recurrent Graves' disease.

Rac1 regulates skin tumors by regulation of keratin 17 through recruitment and interaction with CD11b+Gr1+ cells.

Rac1 is a member of the Rho family of small GTPases that control cells proliferation, differentiation, migration, and inflammation. Rac1 is crucial in tumorigenesis and development. Keratin17 and CD11b+Gr1+ cells are considered to regulate skin inflmmation. Here we discuss the regulation of Rac1 on skin tumor formation and its relationship. In samples from human skin squamous cell carcinoma (SCC), Rac1 activity was higher in cancer tissues than in normal skin and activity correlated with keratin 17 overexpression. In a DMBA/TPA-induced mouse skin tumor model, inhibition of Rac1 activity and depletion of CD11b+Gr1+ cells resulted in significant tumor formation. TPA induced recruitment of CD11b+Gr1+ cells into dermis; however, Rac1 inhibitor abolished this recruitment. In vitro, Rac1 induced interferon (IFN) and interlukin (IL6) production in keratinocytes, repression of keratin 17 inhibited IFN and IL6 production induced by Rac1. Moreover, both inhibition of Rac1 activity and repression of keratin 17 restricted proliferation and induction of differentiation in keratinocytes. Coculture of CD11b+Gr1+ cells with keratinocytes activated Wnt pathway in keratinocytes, resulting in enhanced Rac1 activity, overexpression of keratin 17, and hyperproliferation of keratinocytes. Our results suggested that hyperactive Rac1 recruited and interacted with CD11b+Gr1+ cells, inducing keratin 17-regulated inflammation and promoting skin tumor formation.

STEP wastewater treatment: a solar thermal electrochemical process for pollutant oxidation.

A solar thermal electrochemical production (STEP) pathway was established to utilize solar energy to drive useful chemical processes. In this paper, we use experimental chemistry for efficient STEP wastewater treatment, and suggest a theory based on the decreasing stability of organic pollutants (hydrocarbon oxidation potentials) with increasing temperature. Exemplified by the solar thermal electrochemical oxidation of phenol, the fundamental model and experimental system components of this process outline a general method for the oxidation of environmentally stable organic pollutants into carbon dioxide, which is easily removed. Using thermodynamic calculations we show a sharply decreasing phenol oxidation potential with increasing temperature. The experimental results demonstrate that this increased temperature can be supplied by solar thermal heating. In combination this drives electrochemical phenol removal with enhanced oxidation efficiency through (i) a thermodynamically driven decrease in the energy needed to fuel the process and (ii) improved kinetics to sustain high rates of phenol oxidation at low electrochemical overpotential. The STEP wastewater treatment process is synergistic in that it is performed with higher efficiency than either electrochemical or photovoltaic conversion process acting alone. STEP is a green, efficient, safe, and sustainable process for organic wastewater treatment driven solely by solar energy.