Identification of FAM107A as a potential biomarker and therapeutic target for prostate carcinoma.

FAM107A may have a dual role in regulating the biological functions of tumors; however, its role in prostate adenocarcinoma (PRAD) remains unknown. We analyzed FAM107A expression by employing databases to clarify its potential prognostic value for PRAD, as well as its role in the pathogenesis of PRAD. We observed that the FAM107A expression level is decreased in PRAD, and the reduced expression is considerably associated with poor overall survival and progression-free survival (PFS). To explore the mechanism of FAN107A in PRAD, we performed an immune cell infiltration analysis and a gene set enrichment analysis. The results showed that FAM107A expression is positively related to mast cells and natural killer cells. The Wnt signaling pathway, the MAPK signaling pathway, and the immune responses are differentially enriched in the FAM107A high-expression phenotype. The FAM107A low-expression phenotype is linked to apoptosis-induced DNA fragmentation and DNA methylation in PRAD. To assess the relationship between the clinical features and the FAM107A expression, we performed a logistic regression analysis and observed that a decreased FAM107A expression is associated with poor prognostic features, including the T stage, the N stage, the Gleason score, residual tumors, and the TP53 status. Our multivariate Cox regression results showed that the Gleason score, the primary therapy outcome, and the FAM107A expression are independent prognostic factors in PFS. In summary, we consider FAM107A an independent risk factor for PFS in PRAD. Moreover, several pathways may reveal the role of FAM107A in triggering carcinogenesis. These discoveries provide novel perspectives for future research to elucidate the pathogenic mechanism underlying PRAD.

[Effect of electroacupuncture on neurovascular unit and Wnt/ß-catenin signaling in rats with cerebral ischemia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Baihui" (GV20), "Shuigou" (GV26), etc. on the expressions of vascular endothelial growth factor (VEGF), collagen fibrillary acidic protein (GFAP), neuronal nucleus antigen(NeuN), ß-catenin and Axin2 protein and mRNA in rats with cerebral ischemia (CI), so as to explore its mechanism underlying improvement of ischemic stroke. METHODS: A total of 108 male SD rats were randomly divided into control, model and EA groups, which were further divided into 7 d, 14 d and 21 d subgroups, with 12 rats in each group. The CI model was established by occlusion of the middle cerebral artery. EA (2 Hz/100 Hz, 2-4 V) was applied to GV20, GV26, bilateral "Sanyinjiao" (SP6) and bilateral "Neiguan" (PC6) for 30 min, once daily (except Sundays) for 21 days at most. The neurological deficit score was evaluated according to Longa's methods. The cerebral infarction state was assessed by using a magnetic resonance T2 imaging system. The expression levels of neurovascular markers as VEGF,GFAP and NeuN, and ß-catenin and Axin2 protein and mRNA in the ischemic brain tissue were detected by using immunohistochemistry and quantitative real-time PCR, respectively. RESULTS: After modeling, the neurological deficit score and cerebral infarction size were significantly increased (P<0.01), and the expression of NeuN and Axin2 proteins and mRNAs were significantly and gradually decreased with time (day 7, 14 and 21) (P<0.01), whereas the expression levels of VEGF, GFAP, ß-catenin proteins and mRNAs were significantly increased on day 7, 14 and 21 in the model group relevant to the control group (P<0.01). Compared with the model group, the neurological deficit score, cerebral infarction size and the expressions of Axin2 protein and mRNA were significantly decreased on day 7, 14 and 21 (P<0.01), whereas the expression levels of VEGF, GFAP and NeuN and ß-catenin proteins and mRNAs were considerably up-regulated in the EA group on day 7, 14 and 21 (P<0.01). CONCLUSION: EA can protect the neurovascular units from injury, reduce the volume of cerebral infarction and improve the symptoms of neurological deficit in cerebral ischemic rats, which may be related to its effects in up-regulating ß-catenin expression and in down-regulating Axin2 expression to further activate classical Wnt/ ß-catenin signal pathway.

[Advances in the experimental mechanism of acupuncture in the treatment of Alzheimer's disease based on Wnt/ß-catenin pathway].

Alzheimer's disease is a neurodegenerative disease closely related to age, which is characterized by cognitive and memory impairment. Extensive studies have confirmed that Wnt/ß-catenin signal pathway is involved in the occurrence and development of Alzheimer's disease. With the characteristics of holistic concept and syndrome differentiation, acupuncture is widely used in clinic. Acupuncture plays a role in the treatment of Alzheimer's disease through the regulation of each target and the whole of the pathway. The author reviewed and combed the research on acupuncture treatment of Alzheimer's disease in recent years, and reviewed the regulatory effects of acupuncture on the important components of Wnt/ß-catenin signal pathway (Wnt protein, ß-catenin, glycogen synthase kinase-3ß) and whole, ATP-binding cassette subfamily B member 1 (ABCB1), low density lipoprotein receptor associated protein-1 (LRP-1)．.

[Research advances in neurovascular unit mechanism in acupuncture treatment of ischemic stroke].

Ischemic stroke is a type of clinical syndrome caused by brain blood supply disorders due to various cerebrovascular diseases, which lead to local cerebral ischemia, hypoxic necrosis, and corresponding neurological defects. In recent years, the neurovascular unit mechanism of ischemic stroke has been proposed in modern medicine. With the principles of syndrome differentiation-based treatment and holistic view in traditional Chinese medicine, acupuncture has the advantage of multi-target and multi-link effect and good clinical efficacy on this disease, and current studies have shown that acupuncture has a marked effect on each component and the whole of neurovascular unit. This article reviews the effect of acupuncture on the regulation of blood-brain barrier, astrocytes, microglial cells, neurons, and neurovascular units.

Preparation and Evaluation of Upconversion Nanoparticles Based miRNA Delivery Carrier in Colon Cancer Mice Model.

Therapeutic efficacy of solid tumor is often severely hampered by poor penetration of therapeutics into diseased tissues and lack of tumor targeting. In this study, the functionalized upconversion nanoparticles (UCNP)-based delivery vector targeting cancer cells was developed. Firstly, NaYF4:Yb/Tm (UCNP) was prepared with the solvothermal method for the uniform nanoparticle size and brilliant lattice structure. The SiO2 coated UCNP was demonstrated a high upconversion emission and good monodispersity, which was coupled with polyetherimide (PEI) and miR-145 vector. Then, it was further functionalized via hyaluronic acid (HA) (UCNP/PEI/HA Nanocomplex, UCNPs) coating for the targeted delivery and improved biocompatibility. The UCNPs/miR-145 displays an excellent biocompatibility, a high level of cellular uptake and miR-145 expression, which results in a significant cell cycle arrest in G1, and induces CCND1, CDK6 and CCNE2 proteins downregulation. In vivo, the HA-coated UCNPs were enriched at the tumor site by targeting and retention effects, which resulted in a significant inhibition of tumor growth. Histological experiments demonstrated that UCNPs did not show significant toxicity in mice colon cancer model. Taken together, a UCNPs-based delivery platform was successfully constructed and used for miRNA target delivery, which provided a new method and idea for bioengineering and nanotechnology-based tumor therapy.

Downregulation of microRNA­182 inhibits cell viability, invasion and angiogenesis in retinoblastoma through inhibition of the PI3K/AKT pathway and CADM2 upregulation.

Retinoblastoma (RB) is a well­vascularized tumor dependent on angiogenesis. The present study aimed to explore whether microRNA (miR)­182 regulates cell viability, invasion and angiogenesis in RB via the phosphatidylinositol­3­OH kinase (PI3K)/protein kinase B (AKT) signaling pathway and by targeting cell adhesion molecule 2 (CADM2). The expression levels of miR­182 and CADM2 were initially detected in RB tissues from patients with RB who underwent ophthalmectomy, and normal retinal tissues collected from other trauma patients who underwent eye enucleation. To determine whether CADM2 was targeted by miR­182, a dual luciferase reporter assay was conducted. Subsequently, Y79 and WERI­Rb­1 RB cells were transfected with a miR­182 mimic or miR­182 inhibitor, or small interfering RNA against CADM2, in order to investigate the effects of miR­182 on viability and invasion, which were detected using MTT and Transwell assays, respectively. In addition, to determine whether the regulatory mechanism underlying the effects of miR­182 was associated with the PI3K/AKT signaling pathway, the expression levels of associated genes were detected by reverse transcription­quantitative polymerase chain reaction and western blot analysis. A xenograft tumor model in nude mice was also established, in order to evaluate the effects of miR­182 on tumor growth and angiogenesis. The results indicated that miR­182 expression was increased and CADM2 expression was reduced in RB tissues; CADM2 was confirmed to be targeted and negatively regulated by miR­182. When the expression of miR­182 was downregulated, cell viability, invasion, tumor volume and angiogenesis were significantly decreased. Furthermore, the expression levels of PI3K/AKT signaling pathway­associated genes were increased in response to miR­182 overexpression or CADM2 silencing. Taken together, these results suggested that inhibition of miR­182 may suppress cell viability, invasion and angiogenesis in RB through inactivation of the PI3K/AKT pathway and CADM2 upregulation. This mechanism may reveal a novel potential therapeutic target.

Synergistic effects of polymer adsorbents on the performance of bilirubin hemoperfusion.

Neonatal hyperbilirubinemia (jaundice) is a common disease with high incidence. Currently, the clinical inefficiency of adult bilirubin hemoperfusion medical adsorbent is a major technical barrier for the application of hemoperfusion treatment to rescue the severe neonatal jaundice. Based on the well-known principle of synergistic effects, a series of customized bilirubin polymeric compounds, comprised of one or more of the following components (glycidyl methacrylate, sodium acrylate, methacrylic acid isooctyl, hexamethylene diamine, albumin), were designed and fabricated based on molecular design. Their adsorption performances upon bilirubin were investigated and compared under the same conditions, and the compound with the highest adsorption performance was then subject to preliliminary safety assessments and compared with a commercial one (BS330). The results showed that positive synergistic effects appeared on the adsorption performance to adsorb bilirubin based on this study, and the one comprised of glycidyl methacrylate+sodium acrylate+methacrylic acid isoocty+hexamethylene diamine+albumin possesses the highest adsorption performance as well as outome clinical acceptable medical safety assessments, and its adsorption efficiency was up to 46% while the commerical one's was about 26% under the same conditions. This study sheds a new light on how to design and develop hemoperfusion bilirubin adsorbents with good overall clinical performance, as well as providing a novel idea and experimental referrences for future related topics.

[Effects of Gelatin on Performance of α-tricalcium Phosphate Bone Cement].

OBJECTIVE: To determine the effects of gelatin on the performance of calcium phosphate cement (CPC). METHODS: α-tricalcium phosphate (α-TCP) bone cement was mixed with different concentrations of gelatin solutions. The CPC samples were soaked into simulated body fluid for one day before their compressive and bending strengths were measured. We also compared their waterproof performance, solidification time and surface topography. RESULTS: Gelatin solutions changed the performance of CPC. Optimal performance of CPC was achieved when the volume ratio of gelatin solution to CPC (Vgelatin solution:V(CPC liquid)) was set at 25:100, which increased compressive strength from (7.874 54 ± 0.660 97) MPa to (9.936 52 ± 0.433 17) MPa and bending strength from (5.157 06 ± 0.298 30) MPa to (7.959 71 ± 0.281 63) MPa. Gelatin solution also prolonged setting time of CPC, improved its waterproof performance, and promoted formulation of more dense and uniform hydroxyapatite crystals. CONCLUSION: Gelatin can improve the compressive and bending strengths of CPC, and make CPC more suitable for clinic use through improvements in setting time and waterproof performance.

Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells.

AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis (EAU) and investigate of role of rapamycin on T cell subsets in the disease. METHODS: EAU was induced in rats using peptides 1169 to 1191 of the interphotoreceptor binding protein (IRBP). Rapamycin (0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-ß1, and IL-6 produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4+CD25+ regulatory T cells (Tregs) from rat spleen were detected by flow cytometry. RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro. Rapamycin also significantly increased TGF-ß1 production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore, rapamycin decreased the ratio of Th17 cells/CD4+T cells and upregulated Tregs in EAU, as detected by flow cytometry. CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU. Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.

Spirochensilides A and B, Two New Rearranged Triterpenoids from Abies chensiensis.

Two new triterpenoids, spirochensilides A (1) and B (2) were isolated from Abies chensiensis. Comprehensive spectroscopic analysis revealed that 1 and 2 are the first example of triterpenoids possessing a unique 8,10-cyclo-9,10-seco and methyl-rearranged carbon skeleton. The single crystal X-ray diffraction analyses and computational methods allowed the absolute configuration assignments of the two compounds. A plausible biogenetic pathway of spirochensilide A (1) is also proposed.

New lignans from the roots of Schisandra sphenanthera.

Nine new lignans (1-8, 13) and five known ones (9-12, 14) have been isolated from the roots of Schisandra sphenanthera and were tested for their capacity to scavenge 2,2-diphenyl-1-Picryl-hydrazyl (DPPH). Of these lignans tested, compounds 1, 7, 8 and 13 exhibited noteworthy antioxidant activity with IC50 values of 92, 115, 35 and 48 µg/mL, respectively. The anti-oxidative haemolysis of human red blood cells (RBCs) activity of the most active compound 8, which is similar to that of vitamin C, was evaluated.