Orrella daihaiensis sp. nov., a bacterium isolated from Daihai Lake in Inner Mongolia.

A novel aerobic, Gram-staining-negative, non-motile, short-rod-shaped strain, designated f23, was obtained from Daihai Lake, Inner Mongolia, Republic of China. 16S rRNA gene sequences analysis showed that f23 belongs to the genus Orrella and is most closely related to Orrella marina H-Z20 with 98.35% sequence similarity.

Targeting DNA Damage Response and Immune Checkpoint for Anticancer Therapy.

Deficiency in DNA damage response (DDR) genes leads to impaired DNA repair functions that will induce genomic instability and facilitate cancer development. However, alterations of DDR genes can serve as biomarkers for the selection of suitable patients to receive specific therapeutics, such as immune checkpoint blockade (ICB) therapy. In addition, certain altered DDR genes can be ideal therapeutic targets through adapting the mechanism of synthetic lethality.

TLR4 activity is required in the resolution of pulmonary inflammation and fibrosis after acute and chronic lung injury.

Pulmonary fibrosis is an inflammation-driven lung disease with a poor prognosis and no cure. Here we report that basal toll-like receptor 4 (TLR4) activity is critical for the resolution of acute and chronic inflammation and pulmonary fibrosis in mouse models of lung injury. We found that genetic or pharmacologic inhibition of TLR4 exacerbates bleomycin-induced pulmonary inflammation, fibrosis, dysfunction, and animal death through promoting formation of an immunosuppressive tissue microenvironment and attenuating autophagy-associated degradation of collagen and cell death in the fibrotic lung tissues.

Timing is critical for an effective anti-metastatic immunotherapy: the decisive role of IFNγ/STAT1-mediated activation of autophagy.

Background: Immunotherapy is often recommended as an adjuvant treatment to reduce the chance of cancer recurrence or metastasis. Interestingly, timing is very important for a successful immunotherapy against metastasis, although the precise mechanism is still unknown.

Methods And Findings: Using a mouse model of melanoma metastasis induced by intravenous injection of B16-F10 cells, we investigated the mechanism responsible for the diverse efficacy of the prophylactic or therapeutic TLR4 and TLR9 agonist complex against metastasis.

Blocking IL-17A promotes the resolution of pulmonary inflammation and fibrosis via TGF-beta1-dependent and -independent mechanisms.

Pulmonary fibrosis is the pathologic basis for a variety of incurable human chronic lung diseases. IL-17A, a glycoprotein secreted from IL-17-producing cells, has recently been shown to be a proinflammatory cytokine involved in chronic inflammation and autoimmune disease. In this study, we report that IL-17A increased the synthesis and secretion of collagen and promoted the epithelial-mesenchymal transition in alveolar epithelial cells in a TGF-β1-dependent manner.

Interleukin-17A is involved in development of spontaneous pulmonary emphysema caused by Toll-like receptor 4 mutation.

Aim: To explore the pathogenic role of Th17 cells and interleukin-17A (IL-17A)-associated signaling pathways in spontaneous pulmonary emphysema induced by a Toll-like receptor 4 mutant (TLR4(mut)).

Methods: Lungs were obtained from wild-type (WT) or TLR4mut mice that were treated with or without recombinant mouse IL-17A (1 μg·kg(-1)·d(-1), ip) from the age of 3 weeks to 3 months. Pulmonary emphysema was determined using histology, immunochemistry, and biochemical analysis.

[The pattern recognition receptor-mediated immune tolerance is involved in tumor metastasis].

The interaction of tumor cells with host cells undergoes a progress of immunoediting, including surveillance, equilibrium and escape. The capability of escape from immune-surveillance is a hall marker of tumor cells, which greatly contributes to the tumor growth out of control and the therapy failure in tumor metastasis. It is indicated that tumor cells can recruit amounts of immune cells to tumor site and establish a suppressive immune microenvironment leading to tumor escape.

Toll like receptor 2 mediates bleomycin-induced acute lung injury, inflammation and fibrosis in mice.

Anti-cancer drug bleomycin (BLM) can cause acute lung injury (ALI) which often results in pulmonary fibrosis due to a failure of resolving acute inflammatory response. The aim of this study is to investigate whether toll-like receptor (TLR) 2 mediates BLM-induced ALI, inflammation and fibrosis. BLM-induced dendritic cells (DCs) maturation was analyzed by flow cytometry and cytokine secretion was detected by the ELISA method.

Activation of Toll-like receptor 9 attenuates unilateral ureteral obstruction-induced renal fibrosis.

Aim: to study whether activation of TLR9 by CpG-ODN would protect against and/or reverse renal fibrosis.

Methods: animals were treated with CpG-ODN before or after undergoing a unilateral ureteral obstruction (UUO) procedure. The interstitial fibrotic lesions of obstructed kidneys were evaluated using histology and immunohistostaining.

DEDD negatively regulates transforming growth factor-beta1 signaling by interacting with Smad3.

Transforming growth factor-beta1 (TGF-beta1) regulates a wide variety of cellular responses, such as proliferation, differentiation, migration and apoptosis. Here we report that death effector domain-containing DNA-binding protein (DEDD) physically interacts with Smad3. The inhibition of Smad3 by DEDD resulted in a reduction in TGF-beta1/Smad3-mediated transcription.

Intracellular or extracellular heat shock protein 70 differentially regulates cardiac remodelling in pressure overload mice.

Aims: Innate and adaptive immune responses are associated with the development of hypertension-induced myocardial hypertrophy and fibrosis. As a result, we investigated whether heat shock protein (HSP) 70, which is a molecule of damage-associated molecular patterns, could induce inflammation in the myocardium and promote the development of hypertension-induced cardiac hypertrophy and fibrosis.

Methods And Results: We found that HSP70 serum levels, as well as the amount of HSP70 translocation to the cardiomyocyte membranes and the interstitial space, were elevated in the hypertensive mice caused by abdominal aortic constriction (AAC).

Efficacy of topical aminolevulinic acid photodynamic therapy for the treatment of verruca planae.

Objective: To evaluate the safety and efficacy of topical aminolevulinic acid (ALA) photodynamic therapy (PDT) in the treatment of verruca planae.

Methods: A total of 18 patients with facial verruca planae was treated with ALA-PDT. A 10% ALA emulsion was applied on facial lesions for a 4-h incubation period after azone infiltrating for 30 min.

[Damage-associated molecular patterns and chronic diseases].

Molecules of damage-associated molecular patterns (DAMPs) are a class of substances released to intercellular space or peripheral blood by tissues or cells which are stimulated by insults, ischemia or stress. DAMP molecules can be recognized by Toll like receptors, Nod1-like receptors, or Rig-I like receptors and induce autoimmunity or immune tolerance, which play critical roles in various chronic diseases such as arthritis, atherosclerosis, cancer and systemic lupus erythematosus. DAMP molecules include high-mobility group B protein 1, heat shock proteins and S100 proteins etc.

[The identification and advances of regulatory B cells].

B cells are typically characterized by their ability to regulate the immune responses through presenting antigens and producing antibodies. However, a novel B cell subset, named regulatory B cells (Bregs), has been identified. As Tregs, the Bregs are capable of performing both pathogenic and regulatory functions by production of suppressive cytokines, such as IL-10 or TGF-beta1, or by interaction with pathogen T cells or other immune cells.

Photodynamic therapy of port-wine stains.

Objectives: The purpose of this study was to observe the improvements of port-wine stains (PWSs) under photodynamic therapy (PDT) and to further evaluate the safety and efficacy of PDT in the dermatology clinic for the treatment of PWSs.

Methods: Total of 75 PWS patients were treated with PDT. The PWS lesions were exposed to the copper vapor laser after intravenous injection of photosensitizer (Photocarcinorin, PsD-007).

Blocking TLR2 activity attenuates pulmonary metastases of tumor.

Background: Metastasis is the most pivotal cause of mortality in cancer patients. Immune tolerance plays a crucial role in tumor progression and metastasis.

Methods And Findings: In this study, we investigated the potential roles and mechanisms of TLR2 signaling on tumor metastasis in a mouse model of intravenously injected B16 melanoma cells.

Targeting TLR2 attenuates pulmonary inflammation and fibrosis by reversion of suppressive immune microenvironment.

Pulmonary fibrosis is a consequence of chronic lung injury and is associated with a high mortality. Despite the pathogenesis of pulmonary fibrosis remaining as an enigma, immune responses play a critical role in the deregulation of wound healing process after lung injury, which leads to fibrosis. Accumulating evidence argues the rationales for current treatments of pulmonary fibrosis using immunosuppressive agents such as corticosteroids.

[Expression and function of toll-like receptors in B lymphocytes].

Toll-like receptors (TLRs) are widely expressed in the innate and adaptive immune system. They initiate host defense against endogenous and exogenous pathogens containing conserved pathogen associated molecular patterns. TLRs are critical bridges between the innate and adaptive immunity, especially the cellular immunity mediated by T cells.

[Advances in the study of molecular mechanisms, applications and screening for altered peptide ligand].

Altered peptide ligand (APL), a short peptide with immune regulatory activity and substitutions of a single or multiple amino acids in an antigenic peptide, has shown potential therapeutic effect on autoimmune disease, tumor and virus infection. APL regulates immune responses by interfering the interaction between the major histocompatibility complex (MHC), antigenic peptide and T cell receptor (TCR), or by regulating the intracellular signaling of antigen presenting cells, bystander suppression and inducing heterogenous immune responses. High-specific and high-affinity APL screened from peptide laboratory by phage display, has a potential to be a new resource for drug with antigen specificity.

Bacillus Calmette-Guérin and TLR4 agonist prevent cardiovascular hypertrophy and fibrosis by regulating immune microenvironment.

Hypertension-induced cardiovascular hypertrophy and fibrosis are critical in the development of heart failure. The activity of TLRs has been found to be involved in the development of pressure overload-induced myocardial hypertrophy and cardiac fibrosis. We wondered whether vaccine bacillus Calmette-Guérin (BCG), which activated TLR4 to elicit immune responses, modulated the pressure overload-stimulated cardiovascular hypertrophy and cardiac fibrosis in the murine models of abdominal aortic constriction (AAC)-induced hypertension.

A novel immunostimulator, N-[alpha-O-benzyl-N-(acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N6-trans-(m-nitrocinnamoyl)-L-lysine, and its adjuvancy on the hepatitis B surface antigen.

N(2)-[alpha-O-benzyl-N-(acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N(6)-trans-(m-nitrocinnamoyl)-L-lysine (muramyl dipeptide C, or MDP-C) has been synthesized as a novel, nonspecific immunomodulator. The present study shows that MDP-C induces strong cytolytic activity by macrophages on P388 leukemia cells and cytotoxic activity by cytotoxic T lymphocytes (CTLs) on P815 mastocytoma cells. Our results also indicate that MDP-C is an effective stimulator for production of interleukin-2 and interleukin-12 by murine bone marrow derived dendritic cells (BMDCs) and production of interferon-gamma by CTLs.

Ginsenoside-Ro enhances cell proliferation and modulates Th1/Th2 cytokines production in murine splenocytes.

Aim: To study the effects of ginsenoside-Ro on cell proliferation and cytokine production in murine splenocytes.

Methods: The effect of ginsenoside-Ro on murine splenocytes proliferation was studied using [3H] thymidine incorporation assay. Effects of ginsenoside-Ro on the production of cytokines interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) from murine splenocytes were detected by ELISA method.

Protopanaxatriol-type ginsenosides differentially modulate type 1 and type 2 cytokines production from murine splenocytes.

Seven protopanaxatriol-type ginsenosides and their aglycones including PPT, PT, -Re, -Rg (1), -F (1), -Rh (1), 20(R)-Rh (1) which are closely related in structure were studied for their effects on type 1 and type 2 cytokines production from murine splenocytes and their related mechanisms were examined. The results indicate that PPT, PT and ginsenoside-Re show hardly any or weak effects on concanavalin A (Con A)-induced production of IFN-gamma and IL-4. Ginsenoside-Rh (1) and 20(R)-Rh (1) induce a Con A-induced type 1 cytokine pattern by increasing the production of interleukin-12 (IL-12), the expression of IFN-gamma, T-bet and enhancing NF-kappaB DNA binding activity.

Immunoenhancing activity of protopanaxatriol-type ginsenoside-F3 in murine spleen cells.

Aim: To investigate the immunoenhancing activity of ginsenoside-F3 in murine spleen cells and explore its mechanism.

Methods: The enhancing effect of ginsenoside-F3 on murine spleen cell proliferation was studied using [3H]thymidine incorporation assay. Effects of ginsenoside-F3 on the production of type 1 cytokines IL-2, IFN-gamma, and type 2 cytokines IL-4 and IL-10 from murine spleen cells were detected by ELISA method.

Parallel approach for solution-phase synthesis of 2-quinoxalinol analogues and their inhibition of LPS-induced TNF-alpha release on mouse macrophages in vitro.

A parallel solution-phase synthesis of 2-quinoxalinol analogues is described. The key step-simultaneous reductions of m-Ar(NO2)2 to m-Ar(NH2)2 was investigated extensively. We obtained preliminary pharmacological activity of those analogues for the inhibition of LPS-induced TNF-alpha release on mouse macrophage in vitro.