Bidirectional regulation of angiogenesis and miR-18a expression by PNS in the mouse model of tumor complicated by myocardial ischemia

BACKGROUND: Panax Notoginseng Saponins (PNS) is the major class of active constituents of notoginseng, a natural product extensively used as a therapeutic agent in China. Tumor when accompanied by cardiovascular disorders poses a greater challenge for clinical management given the paradoxical involvement of angiogenesis, therefore gaining increased research attention. This study aim to investigate effects of PNS and its activity components in the mouse model of tumor complicated with myocardial ischemia. METHODS: Tumor complexed with myocardial ischemia mouse model was first established, which was followed by histological and immunohistochemistry examination to assess the effect of indicated treatments on tumor, myocardial ischemia and tissue specific angiogenesis. MicroRNA (miRNA) profiling was further carried out to identify potential miRNA regulators that might mechanistically underline the therapeutic effects of PNS in this complex model. RESULTS: PNS and its major activity components Rg1, Rb1 and R1 suppressed tumor growth and simultaneously attenuated myocardial ischemia. PNS treatment led to decreased expression of CD34 and vWF in tumor and increased expression of these vascular markers in heart. PNS treatment resulted in reduced expression of miR-18a in tumor and upregulated expression of miR-18a in heart. CONCLUSIONS: Our data demonstrated for the first time that PNS exerts tissue specific regulatory effects on angiogenesis in part through modulating the expression of miR-18a, which could be responsible for its bidirectional effect on complex disease conditions where paradoxical angiogenesis is implicated. Therefore, our study provides experimental evidence warranting evaluation of PNS and related bioactive component as a rational therapy for complex disease conditions including co-manifestation of cancer and ischemic cardiovascular disease

Upconversion Plasmonic Lasing from an Organolead Trihalide Perovskite Nanocrystal with Low Threshold

The understanding of nonlinear light–matter interactions at the nanoscale has fueled worldwide interest in upconversion emission for imaging, lasing, and sensing. Upconversion lasers with anti-Stokes-type emission with various designs have been reported. However, reducing the volume and lasing threshold of such lasers to the nanoscale level is a fundamental photonics challenge. Here, we demonstrate that the upconversion efficiency can be improved by exploiting single-mode upconversion lasing from a single organo-lead halide perovskite nanocrystal in a resonance-adjustable plasmonic nanocavity. This upconversion plasmonic nanolaser has a very low lasing threshold (10 μJ cm⁻²) and a calculated ultrasmall mode volume (∼0.06 λ³) at 6 K. To provide the unique feature for lasing action, a temporal coherence signature of the upconversion plasmonic nanolasing was determined by measuring the second-order correlation function. The localized-electromagnetic-field confinement can be tailored in titanium nitride resonance-adjustable nanocavities, enhancing the pump-photon absorption and upconverted photon emission rate to achieve lasing. The proof-of-concept results significantly expand the performance of upconversion nanolasers, which are useful in applications such as on-chip, coherent, nonlinear optics, information processing, data storage, and sensing

Remission of symptoms is not equal to functional recovery: Psychosocial functioning impairment in major depression

The ultimate goal of depression treatment is to achieve functional recovery. Psychosocial functioning is the main component of functional impairment in depressed patients. The concept of psychosocial functioning has an early origin; however, its concept and connotation are still ambiguous, which is the basic and key problem faced by the relevant research and clinical application. In this study, we start from the paradox of symptoms remission and functional recovery, describe the concept, connotation, and characteristics of psychosocial functioning impairment in depressed patients, and re-emphasize its importance in depression treatment to promote research and clinical applications related to psychosocial functioning impairment in depressed patients to achieve functional recovery

Protective role for collectin‐11 in rheumatoid arthritis in mice

OBJECTIVE. Collectin-11 (CL-11) is a soluble C-type lectin, a mediator of innate immunity. Its role in autoimmune disorders is unknown. The goal of this study was to determine the role of CL-11 in a mouse model of rheumatoid arthritis (RA). METHODS. A murine collagen-induced arthritis (CIA) model, combining both gene deletion of Colec11 and recombinant (rCL-11) treatment approaches were employed. Joint inflammation and tissue destruction, circulating levels of inflammatory cytokines and adaptive immune responses were assessed in CIA mice. Splenic CD11c(+) cells were used to examine the influence of CL-11 on antigen presenting cell (APC) function. Serum levels of CL-11 in RA patients were also examined. RESULTS. Colec11(−/−) mice developed more severe arthritis than WT mice (as determined by disease incidence, clinical arthritis scores and histopathology; P<0.05). Disease severity is associated with significantly enhanced APC activation, Th1/Th17 responses, pathogenic IgG2a production and joint inflammation, as well as elevated circulating levels of inflammatory cytokines. In vitro analysis of CD11c(+) cells revealed that CL-11 is critical for suppression of APC activation and function. Pharmacological treatment of mice with rCL-11 reduced the severity of CIA in mice. Analysis of human blood samples revealed that serum levels of CL-11 was lower in RA patients (n=51) compared to healthy controls (n=53), a serum CL-11 reduction also displays a negative relationship with DAS28, ESR and CRP (P<0.05). CONCLUSION. Our findings demonstrate a novel role for CL-11 in protection against RA, suggesting the underlying mechanism involved suppression of APC activation and subsequent T cell responses