The regulatory process and practical significance of non-coding RNA in the dissemination of prostate cancer to the skeletal system.

Prostate cancer is a major contributor to male cancer-related mortality globally. It has a particular affinity for the skeletal system with metastasis to bones seriously impacting prognosis. The identification of prostate cancer biomarkers can significantly enhance diagnosis and patient monitoring. Research has found that cancer and metastases exhibit abnormal expression of numerous non-coding RNA. Some of these RNA facilitate prostate cancer bone metastasis by activating downstream signaling pathways, while others inhibit this process. Elucidating the functional processes of non-coding RNA in prostate cancer bone metastasis will likely lead to innovative treatment strategies for this malignant condition. In this review, the mechanistic role of the various RNA in prostate cancer is examined. Our goal is to provide a new avenue of approach to the diagnosis and treatment of bone metastasis in this cancer.

Recent Progress of Spectroscopic Probes for Peroxynitrite and Their Potential Medical Diagnostic Applications.

Peroxynitrite (ONOO-) is a crucial reactive oxygen species that plays a vital role in cellular signal transduction and homeostatic regulation. Determining and visualizing peroxynitrite accurately in biological systems is important for understanding its roles in physiological and pathological activity. Among the various detection methods, fluorescent probe-based spectroscopic detection offers real-time and minimally invasive detection, high sensitivity and selectivity, and easy structural and property modification. This review categorizes fluorescent probes by their fluorophore structures, highlighting their chemical structures, recognition mechanisms, and response behaviors in detail. We hope that this review could help trigger novel ideas for potential medical diagnostic applications of peroxynitrite-related molecular diseases.

Synthesis of Heptamethine Cyanines from Furfural Derivatives.

Despite the widespread theranostic utilization of cyanine dyes (Cy7), their synthetic method is still limited with pyridine or cyclohexanone derivatives as starting materials. Herein, we report the synthesis of Cy7 from furfural derivatives. First, a one-pot reaction strategy is developed to solve the unstable problem of the Stenhouse salts. Second, a stepwise condensation strategy is exploited to regioselectively synthesize asymmetrical Cy7. The methodology possesses advantages, such as easy handling, high yield, wide substrate scopes, and good functional group tolerance.

lncRNA NEAT1/miR-495-3p regulates angiogenesis in burn sepsis through the TGF-ß1 and SMAD signaling pathways.

INTRODUCTION: To investigate the role of the long-chain noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in the process of angiogenesis in human umbilical vein endothelial cells (HUVECs) and illustrate its potential role in burn sepsis (BS) pathogenesis. METHODS: HUVECs were treated with BS patient serum or healthy control serum. NEAT1 shRNA, miR-495-3p mimics, and miR-495-3p inhibitor were transfected into HUVECs. NEAT1 and miR-495-3 levels in serum or HUVECs were detected using quantitative reverse transcription-polymerase chain reaction. Cell counting kit-8 and flow cytometry assays were used to explore the proliferation and apoptosis of HUVECs. The expression of vascular endothelial growth factor (VEGF) in the supernatant was detected using enzyme-linked immunosorbent assay. Tube formation of HUVECs was also analyzed. Western blot analysis was used to analyze signaling pathway proteins. RESULTS: In HUVECs stimulated with BS patient serum, NEAT1 expression was increased, while miR-495-3p expression was decreased. In addition, NEAT1 silencing by specific shRNA inhibited cell proliferation, VEGF production, and tube formation under burn patient serum treatment, which decreased the TGFß1/SMAD signaling pathway activation. Moreover, miR-495-3p minics inhibited angiogenesis and the activation of signaling pathways induced by NEAT1 shRNA. Furthermore, miR-495-3p inhobitor promoted angiogenesis in HUVECs and activated the TGFß1/SMAD signaling pathway. In patients with BS, NEAT1 expression was significantly increased and miR-495-3p expression was decreased compared to healthy controls, and NEAT1 and miR-495-3p expression was associated with the clinical features of patients. CONCLUSIONS: Our results indicate that lncRNA NEAT1 regulates angiogenesis and activates the TGFß1/SMAD signaling pathway during the occurrence of BS.

Identification of Key Genes in Severe Burns by Using Weighted Gene Coexpression Network Analysis.

The aims of this work were to explore the use of weighted gene coexpression network analysis (WGCNA) for identifying the key genes in severe burns and to provide a reference for finding therapeutic targets for burn wounds. The GSE8056 dataset was selected from the gene expression database of the US National Center for Biotechnology Information for analysis, and a WGCNA network was constructed to screen differentially expressed genes (DEGs). Gene Ontology and pathway enrichment of DGEs were analyzed, and protein interaction network was constructed. A burn mouse model was constructed, and the burn tissue was taken to identify the expression levels of differentially expressed genes. The results showed that the optimal soft threshold for constructing the WGCNA network was 9. 10 coexpressed gene modules were identified, among which the green, brown, and gray modules had the largest number of burn-related genes. The DEGs were mainly related to immune cell activation, inflammatory response, and immune response, and they were enriched in PD-1/PD-L1, Toll-like receptor, p53, and nuclear factor-kappa B (NF-κB) signaling pathways. 5 DEGs were screened and identified, namely, Jun protooncogene (JUN), signal transducer and activator of transcription 1 (STAT1), BCL2 apoptosis regulator (Bcl2), matrix metallopeptidase 9 (MMP9), and Toll-like receptor 2 (TLR2). Compared with skin tissue of normal mouse, the messenger ribose nucleic acid (mRNA) and protein expression levels (PEL) of STAT1 and Bcl2 in burn tissue were greatly decreased, while those of JUN, MMP9, and TLR2 were increased obviously (p < 0.05). In conclusion, STAT1, Bcl2, JUN, MMP9, and TLR2 can be potential biological targets for the treatment of severe burn wounds.

Clnical observation, of the effects of lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine on the treatment of hyperplastic scar / 中华烧伤杂志

<p><b>OBJECTIVE</b>To explore the clinical effects of lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine ( Fuchunsan ) on the treatment of postburn hyperplastic scar.</p><p><b>METHODS</b>Sixty-three patients with hyperplastic scar after burn injury hospitalized from February 2012 to June 2014 in our department were treated with lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine (Fuchunsan). Patients were divided into early stage group (E, n = 35), middle stage group (M, n = 25), and late stage group ( L, n = 3) according to the formation time of scar, which was respectively 3 weeks to 3 months, longer than 3 months and less than or equal to 6 months, and 3 to 15 years in groups E, M, and L. The number of times of laser treatment of patients in each group was recorded. The degree of scar pain in patients of the three groups was assessed by the Numerical Rating Scale (NRS) before treatment and after treatment for 1, 2, and 3 times. The scar condition of patients in groups E and M was assessed by the Vancouver Scar Scale (VSS) before treatment and after treatment for 1, 3, and 5 times. Patients in group L did not receive VSS assessment but were evaluated by clinical observation only. Photos of scar in treating area were taken before treatment and after treatment for 3 and 5 times to evaluate the clinical effect. Data were processed with t test.</p><p><b>RESULTS</b>Patients in groups E and M were treated with laser for (4.8 ± 1.1) and (7.7 ± 2.1) times respectively. In group L, the treatment was stopped in 2 patients after laser treatment for 5 times, and 1 patient received laser treatment for 12 times. The degree of pain in patients of groups E and M was alleviated significantly after treatment for one time, and the number of patients scoring 1-4 point(s) in NRS increased from 5 cases to 38 cases. After treatment for 2 and 3 times, the increase in the number of patients scoring 1-4 point (s) in NRS was on a small scale. Before treatment and after treatment for 1 time, VSS scores of patients in groups E and M were similar (with values respectively 0.641 and 0. 082, P values above 0. 05). After treatment for 3 and 5 times, VSS scores of patients in group E were respectively (9.2 ± 0.8) and (7.0 ± 1.1) points, which were significantly lower than those in group M [ (9.7 ± 1.0) and (8.2 ± 1.0) points, with values respectively -1.993 and -4.433 , P < 0.05 or P < 0.01]. After treatment for 3 times, the rate of improvement in appearance was respectively 88.6% (31/35) and 72.0% (18/25) in groups E and M, and it was respectively 100.0% (35/35) and 96.0% (24/25) after treatment for 5 times. No significant effect in appearance was found in the 3 patients in group L.</p><p><b>CONCLUSIONS</b>Early application of lattice ultra pulse carbon dioxide laser combined with traditional Chinese medicine (Fuchunsan) for the treatment of postburn hyperplastic scar is effective.</p>

[Correction of claw hand deformity after burns by elastic traction].

OBJECTIVE: To investigate a new method for correction of claw hand deformity after burns. METHODS: From May 2006 to Jul. 2010, 12 patients with claw hands deformities after burns were treated with skin grafts (11 hands) and skin flap (1 hand) with unsatisfactory results. Then elastic traction (skin traction or skeletal traction) were performed with individual functional brace. RESULTS: All patients were followed up for 0.5 to 2 years. Elastic traction was effective in the correction of metacarpophalangeal joint deformity, buttonhole deformity, thumb-in-palm deformity, scar contracture, and palmar arch deformity. CONCLUSIONS: Elastic traction is a simple and effective way for the correction of claw hand deformity after burns with less morbidity and stable results.

[Mode of debridement, negative-pressure therapy combined with tissue transplantation for treatment of complicated and refractory wounds].

OBJECTIVE: To observe therapeutic effect of negative-pressure treatment combined with tissue transplantation on complicated and refractory wounds after debridement. METHODS: After debridement, 20 patients with 20 complicated and refractory wounds hospitalized in our burn wards from May 2008 to June 2010 were randomly divided into treatment group (T, treated with negative-pressure from -19 kPa to -8 kPa, n = 10) and control group (C, covered with petrolatum gauze overlaid with saline gauze and dry gauze, n = 10) according to alternating method. On post treatment day (PTD) 4, 7, and 14, granulation tissues of wound surface in size of 4 mm × 3 mm × 2 mm were harvested for histopathological observation (including capillary growth, inflammatory cells, and collagen arrangement) with HE staining, and the numbers of vascular endothelial cells (VEC, with addition of rabbit anti-human coagulation factor VIII related antigen polyclonal antibody) and proliferation period cells (with addition of mouse anti-human Ki-67 monoclonal antibody) were counted by immunohistochemical staining. Data were processed with t test. Another 59 patients harboring 62 complicated and refractory wounds admitted to our burn ward at the same period were treated with the same mode of debridement, negative-pressure therapy, followed by timely skin or skin flap grafting. RESULTS: (1) Granulation tissue in T group grew more rapidly than that in C group. More capillaries and less inflammatory cells were observed in T group on PTD 7 as compared with those in C group. Collagen in T group on PTD 14 was more regular in arrangement than that in C group. The number of VEC per 400 times visual field in T group on PTD 4, 7, and 14 was respectively higher than that in C group (108.7 ± 11.2 vs. 31.0 ± 3.6, 138.0 ± 14.7 vs. 34.6 ± 4.5, 68.7 ± 6.9 vs. 55.1 ± 6.5, with t values from 4.62 to 30.28, P values all equal to 0.01). The number of proliferation period cell per 400 times visual field in T group on PTD 4 and 7 was respectively higher than that in C group (88.9 ± 5.9 vs. 16.6 ± 3.3, 128.1 ± 13.0 vs. 110.1 ± 8.9, with t value respectively 19.89, 3.33, P values all below 0.05). The number of proliferation period cell per 400 times visual field in T group on PTD 14 was obviously lower than that in C group (26.7 ± 5.1 vs. 59.7 ± 4.5, t = -12.43, P = 0.01). (2) After being treated with above therapeutic mode, necrotic tissues were removed completely and granulation tissue grew rapidly in 62 complicated and refractory wounds with high survival rate of skin grafts or skin flaps with good repair effect. CONCLUSIONS: Negative-pressure therapy can accelerate VEC formation and stimulate cell proliferation after debridement. Debridement, negative-pressure therapy, and timely skins/skin flaps grafting can effectively increase healing rate of complicated and refractory wounds.

[Influence of rhubarb on gastrointestinal motility and intestinal mucosal barrier in patients with severe burn].

OBJECTIVE: To observe the influence of rhubarb on gastrointestinal motility and intestinal mucosal barrier in patients with severe burn. METHODS: Thirty patients with severe burn admitted to our burn wards within 48 hours after burn injury from December 2009 to December 2010 were divided into therapeutic group (T, treated with 10 g rhubarb by nasal feeding and 5 g L-glutamine by oral administration beginning from 6 hours after admission, three times per day, and also given enteral nutrition beginning from 24 hours after admission, n = 16) and control group (C, received the same treatment as used in T group but without rhubarb, n = 14) according to the random number table. Gastrointestinal function indexes including restoration of bowel sound within 24 hours, abdominal distension, tolerance to enteral nutrition, and defecation were observed after treatment. The serum samples were harvested on post burn day (PBD) 3, 7, 14 for determination of the levels of gastrin (GAS) by radioimmunoassay, motilin (MTL) by enzyme-linked immunosorbent assay, diamine oxidase (DAO) by enzyme spectrophotometry, and endotoxin (ET) by kinetic turbidimetric assay with TAL. Data were processed with t test and chi-square test. RESULTS: Compared with those in C group, the numbers of patients with restoration of bowel sound within 24 hours and tolerance to enteral nutrition in T group were increased (with chi2 value respectively 5.01, 4.84, P values all below 0.05), the number of patients with abdominal distension was decreased (chi2 = 4.84, P = 0.025). Compared with those of C group, defecation time was earlier, number of bowel movement was increased with soft feces in patients of T group. The serum levels of GAS in T group on PBD 3, 7, 14 [ (92 +/- 26), (95 +/- 16), (98 +/- 18) ng/L] were significantly higher than those in C group [(80 +/- 15), (75 +/- 17), (79 +/- 13) ng/L, with t value respectively 15.352, 22.951, 19.263, P values all below 0.01]. The serum levels of MTL in T group on PBD 3, 7, 14 [(246 +/- 80), (299 +/- 76), (300 +/- 100) ng/L] were significantly higher than those in C group [(189 +/- 44), (203 +/- 64), (200 +/- 67) ng/L, with t value respectively 14.173, 19.294, 26.298, P values all below 0.01]. The serum levels of ET in T group on PBD 3, 7, 14 [(0.398 +/- 0.035), (0.373 +/- 0.005), (0.238 +/- 0.019) EU/mL] were significantly lower than those in C group [(0.493 +/- 0.043), (0.501 +/- 0.045), (0.423 +/- 0.099) EU/mL, with t value respectively 6.213, 9.153, 15.134, P < 0.05 or P < 0.01]. The serum levels of DAO in T group on PBD 3, 7 [ (3.0 +/- 0.4), (2.9 +/- 0.5) U/mL] were significantly lower than those in C group [(3.9 +/- 0.5), (3.6 +/- 0.6) U/mL, with t value respectively 3.982, 4.236, P values all below 0.05], and there was no obvious difference between T and C groups on PBD 14 (t = 1.762, P > 0.05). CONCLUSIONS: Rhubarb can protect intestinal mucosal barrier in patients with severe burn through increasing secretion of gastrointestinal hormones and promoting restoration of gastrointestinal motility.

[Analysis of the proteomic changes of the serum of the Smad3 targeted deficient mice].

We have studied the proteomic changes of the serum of the Smad3 targeted deficient mice using 2-DE and PMF approaches. 7 proteins expressed at different level in wild type mice and the Smad3 deficient mice were identified. These results would benefit the research on diagnosis and therapy of osteoarthritis and provided clues to studying the important function of Smad3 mediated TGF-beta signals during the skeletal development.

[Generation and characterization of chondrocyte specific Cre transgenic mice].

A chondrocyte specific transgenic construct (pcol2A1-Cre) containing the cartilage specific type II collagen A1 promoter, the Cre recombinase gene and the polyA of human growth factor gene was generated. The 9.3 kb DNA fragments were recovered from Not I digested fragments and microinjected into 323 fertilized eggs. The injected eggs were implanted into the oviduct of 14 female mice. In the 52 offsprings, there were 10 mice carring the transgene identified by PCR, and the efficiency was 19.2%. The col2A1-Cre transgenic mice were crossed with a conditional gene targeting mice to check the Cre mediated recombination in multiple tissues. The results of the PCR analysis suggested that the Cre recombinase was expressed only in cartilaginous tissue and could mediate the recombination between the LoxP sites in vivo. The result was further confirmed by Southern-blot.