Biomechanical response of lower limb joints to lateral wedge insoles.

Lateral wedge insole (LWI) is a frequently recommended treatment option for early and midterm stages of medial knee osteoarthritis. However, studies of its effects on the lower limb joints are incomplete and imperfect. The main purpose of this study was to quantitatively analyze the response of intervention of LWI on lower-limb joint kinematics, ground reaction forces (GRFs), and centre of pressure (COP). Gait analysis of 16 healthy subjects was conducted. Three-dimensional motion data and force plate measurements were collected in the control (barefoot) and experimental conditions (wearing a pair of assigned shoes with 0, 7, and 10 mm LWIs). Results showed that the peak knee flexion angle was increased by 3.43°, 3.09°, and 3.27° with 0, 7, and 10 mm LWIs, respectively (p < 0.01). The ankle peak dorsiflexion angle was significantly decreased by 3.79°, 2.19°, and 1.66° with 0, 7, and 10 mm LWIs, respectively (p = 0.02). The internal rotation angle was increased by 2.78°, 3.76°, and 4.58° with 0, 7, and 10 mm LWIs, respectively (p < 0.01). The forefoot with LWIs showed highly significantly smaller inversion, eversion, and adduction angles (all p < 0.01). The 1st peak of the vertical GRF (p = 0.016) also increased significantly by a maximum of 0.06 body weight (BW) with LWIs. These results indicated that biomechanical changes and limitations of lateral wedges insole should be analyzed in more detail, possibly leading to new guidelines for the design and application.

Comprehensive gene and microRNA expression profiling reveals a role for miRNAs in the oncogenic roles of SphK1 in papillary thyroid cancer.

PURPOSE: The oncogenic roles of sphingosine kinase 1 (SphK1) in various cancers, including thyroid cancer, have been well demonstrated. However, the microRNAs (miRNAs) associated with the oncogenic roles of SphK1 remain largely unknown. METHODS: Global gene and miRNA expression in TPC1-Vector and TPC1-SphK1 cells was analyzed using digital gene expression (DGE) analysis and small RNA-seq, respectively. miRNA-mRNA interactions were explored by microT-CDS, and the predicted networks were visualized using CytoScape®. Cell invasion and migration were assessed by performing Transwell invasion and wound-healing assays. Luciferase reporter and immunoblot assays were used to evaluate the targeting of fibronectin 1 (FN1) by miR-144-3p. RESULTS: In this study, we found that overexpression of SphK1 differentially regulates the expression of 46 miRNAs and 506 mRNAs in papillary thyroid cancer (PTC) TPC1 cells. Combining bioinformatics predictions of mRNA targets with DGE data on mRNA expression allowed us to identify the mRNA targets of deregulated miRNAs. The direct interaction between miR-144-3p and FN1, which mediates the pro-invasive role of SphK1 in PTC cells, was experimentally validated. CONCLUSIONS: Our results demonstrated that SphK1 overexpression drives a regulatory network governing miRNA and mRNA expression in PTC cells. We also demonstrated the roles played by miR-144-3p and FN1 in mediating the oncogenic function of SphK1, which enhanced the understanding of the etiology of PTC.

Cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.

Vascularization of acellular nerves has been shown to contribute to nerve bridging. In this study, we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves. The rat nerve defects were treated with acellular nerve grafting (control group) alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein (experimental group). As shown through two-dimensional imaging, the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation, and gradually covered the entire graft at day 21. The vascular density, vascular area, and the velocity of revascularization in the experimental group were all higher than those in the control group. These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.

Effect of fosinopril on chemerin and VEGF expression in diabetic nephropathy rats.

As the most common and severe complication of diabetes, diabetic nephropathy (DN) has been known to be related with angiotensin converting enzyme inhibitor (ACEI), which can reduce proteinuria and protect renal function. This study analyzed the effect of ACEI analog-fosinopril-on the expression of chemerin and vascular epithelial growth factor (VEGF), in an attempt to reveal the mechanism of ACEI analog on renal protection. A total of 45 SD rats were induced by sreptozotocin for diabetes and were given fosinopril via intragastric cannulation for 12 weeks. After sacrifice, serum and renal chemerin and VEGF contents were quantified by enzyme linked immunosorbent assay (ELISA) and Western blot method, in addition to biochemical laboratory examinations. In diabetic model rats, blood glucose, creatinine, urea nitrogen, 24-hour urinary protein, chemerin and VEGF protein contents were all significantly elevated when compared to those in control group (P<0.05). After fosinopril treatment, blood creatinine, urea nitrogen, 24-hour urinary protein, Chemerin and VEGF protein concentrations were significantly depressed (P<0.05 compared to model group). Positive relationships existed between renal chemerin, VEGF and urea protein levels. Fosinopril may protect renal tissues in diabetes by suppressing chemerin and VEGF protein expression.

Response of maize serine/arginine-rich protein gene family in seedlings to drought stress.

Alternative splicing (AS) in eukaryotic organisms is closely related to the gene regulation in plant abiotic stress responses, in which serine/arginine-rich proteins (SR proteins) act as key regulators. The genome sequence of maize inbred line B73 was analyzed, showing that the promoter regions of SR genes possess about three to eight kinds of cis-acting regulatory elements. Twenty-seven SR genes encode alkaline proteins, and 23 of which are divided into five subgroups in terms of the first RNA recognition motif (RRM) at the amino terminal. The expression of SR genes showed tissue-specific and genotype-dependent features under drought stress in the hybrid Zhengdan-958 and its parents, Zheng-58 and Chang-7-2 via bidirectional hierarchical clustering. SR genes were down-regulated in roots while they were up-regulated in shoots under drought stress. However, SR genes were down-regulated in both roots and shoots in three different rehydration stages after severe drought stress. Additionally, a widespread alternative splicing exists in all SR genes although SR genes showed differential expression tendency under drought stress and/or during rehydration stages. Results above will deepen our understanding of the molecular mechanisms of plant response to abiotic stress from the perspective of AS-network.

Interleukin-12 and interleukin-2 alone or in combination against the infection in invasive pulmonary aspergillosis mouse model.

Aspergillus fumigatus is an intracellular opportunistic fungus causing invasive pulmonary mycosis, characterised by hyphal invasion and destruction of pulmonary tissue. Th1 cytokines could enhance fungicidal activity. The effects from the combination of interleukin-12 (IL-12) and IL-2 are rarely known in invasive pulmonary aspergillosis infection. To assess the cleaning of A. fumigatus infection in the pulmonary tissues by IL-12 and IL-2, interferon-γ (IFN-γ) was detected in the sera using ELISA, quantification of IFN-γ mRNA using real-time RT-PCR and lung Colony-forming unit was assayed by cultivation. Morphology was analysed by histopathological examination. Our results showed that IL-12 and/or IL-2 could enhance the IFN-γ expression in the pulmonary tissue, reduce the colony load in the pulmonary tissue and increase the survival rate of mouse. The combination of IL-12 and IL-2 could assist in increasing the IFN-γ expression in the pulmonary tissue, but neither reduce colony load in the pulmonary tissue nor increase the survival rate of mouse significantly. It was demonstrated that IL-12 and IL-2 were strong immunomodulatory cytokines as a prerequisite for protecting the host from infectious agents.