LC-MS-based quantitation of proteomic changes induced by Norcantharidin in MTB-Treated macrophages.

Tuberculosis drug resistance contributes to the spread of tuberculosis. Immunotherapy is an effective strategy for treating tuberculosis, with the regulation of macrophage-mediated anti-tuberculosis immunity being crucial. Norcantharidin (NCTD), a drug used in tumor immunotherapy, has significant immunomodulatory effects.

Serum cytokine biosignatures for identification of tuberculosis among HIV-positive inpatients.

Background: Serum cytokines correlate with tuberculosis (TB) progression and are predictors of TB recurrence in people living with HIV. We investigated whether serum cytokine biosignatures could diagnose TB among HIV-positive inpatients.

Methods: We recruited HIV-positive inpatients with symptoms of TB and measured serum levels of inflammation biomarkers including IL-2, IL-4, IL-6, IL-10, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ).

Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors.

Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma.

Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to delineate the methylome landscape and characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome.

MxA suppresses TAK1-IKKα/β-NF-κB mediated inflammatory cytokine production to facilitate Mycobacterium tuberculosis infection.

Objectives: Interferons (IFNs) play multifunctional roles in host defense against infectious diseases by inducing IFN-stimulated genes (ISGs). However, little is known about how ISGs regulate host immune response to Mycobacterium tuberculosis (Mtb) infection, the major cause of tuberculosis (TB).

Methods: We thus profiled the potential effects and mechanisms of eight Mtb-induced ISGs on Mtb infection by RNA interference in human macrophages (Mφs) derived from peripheral blood monocytes (hMDMs) and THP-1 cell line derived Mφs (THP-1-Mφs).

Construction of a human cell landscape at single-cell level.

Single-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex systems. However, a comprehensive single-cell atlas has not been achieved for humans. Here we use single-cell mRNA sequencing to determine the cell-type composition of all major human organs and construct a scheme for the human cell landscape (HCL).

IL-36γ Promotes Killing of by Macrophages via WNT5A-Induced Noncanonical WNT Signaling.

, which primarily infects mononuclear phagocytes, remains the leading bacterial cause of enormous morbidity and mortality because of bacterial infections in humans throughout the world. The IL-1 family of cytokines is critical for host resistance to As a newly discovered subgroup of the IL-1 family, although IL-36 cytokines have been proven to play roles in protection against infection, the antibacterial mechanisms are poorly understood. In this study, we demonstrated that IL-36γ conferred to human monocyte-derived macrophages bacterial resistance through activation of autophagy as well as induction of WNT5A, a reported downstream effector of IL-1 involved in several inflammatory diseases.

Interferon regulatory factor 1 eliminates mycobacteria by suppressing p70 S6 kinase via mechanistic target of rapamycin signaling.

Objectives: Although it has been reported that Interferon regulatory factor 1 (IRF1) inhibits Mycobacterium tuberculosis (Mtb) infection via inducible nitric oxide synthase (iNOS) in mice, how it counteracts with mycobacterial infection in human remains largely obscure. This study was conducted to investigated the effect of IRF1 on Mtb infection in human macrophages (Mϕs).

Methods: We thus investigated the IRF1 expression by using PBMC and monocytes of pulmonary tuberculosis (TB) patients and human monocyte-derived macrophages (hMDMs) and THP-1-derived macrophages (THP-1-Mϕ).

NLRC3 negatively regulates CD4+ T cells and impacts protective immunity during Mycobacterium tuberculosis infection.

NLRC3, a member of the NLR family, has been reported as a negative regulator of inflammatory signaling pathways in innate immune cells. However, the direct role of NLRC3 in modulation of CD4+ T-cell responses in infectious diseases has not been studied. In the present study, we showed that NLRC3 plays an intrinsic role by suppressing the CD4+ T cell phenotype in lung and spleen, including differentiation, activation, and proliferation.

Vitamin B5 Reduces Bacterial Growth Regulating Innate Immunity and Adaptive Immunity in Mice Infected with .

The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5) can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with (MTB) strain H37Rv and the therapeutic potential of VB5 with tuberculosis.

Novel Function of Cyclooxygenase-2: Suppressing Mycobacteria by Promoting Autophagy via the Protein Kinase B/Mammalian Target of Rapamycin Pathway.

In Mycobacterium tuberculosis-infected macrophages, cyclooxygenase-2 (COX-2) expression considerably increases to defend the body against mycobacteria by regulating adaptive immunity and restoring the mitochondrial inner membrane. Moreover, in cancer cells, COX-2 enhances the autophagy machinery, an important bactericidal mechanism. However, the association between M.

Profiling dendritic cell subsets in the patients with active pulmonary tuberculosis.

Dendritic cell (DC) plays an important role in the immune response against pulmonary tuberculosis. However, the phenotypic profile of DC subsets in peripheral blood in individuals with active pulmonary tuberculosis (APT) is still inconclusive. Here, we demonstrated that the absolute numbers of total DC (tDC), myeloid DC (mDC) and plasmacytoid DC (pDC) in individuals with APT were decreased compared to healthy controls (HCs).

Development and characterization of monoclonal antibody against human IL-37b.

IL-37 has been described as a natural inhibitor of immune responses. Monoclonal antibody (mAb) against human IL-37b with high affinity and specificity can serve as a molecular probe to detect IL-37 and study IL-37 functions, mechanisms and related signal pathways in inflammatory diseases. However, there are very few such mAbs against human IL-37 commercially available so far.

Characterization of Dof Transcription Factors and Their Responses to Osmotic Stress in Poplar (Populus trichocarpa).

The DNA-binding One Zinc Finger (Dof) genes are ubiquitous in many plant species and are especial transcription regulators that participate in plant growth, development and various procedures, including biotic and abiotic stress reactions. In this study, we identified 41 PtrDof members from Populus trichocarpa genomes and classified them into four groups. The conserved motifs and gene structures of some PtrDof genes belonging to the same subgroup were almost the same.

BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell proliferation.

Despite past extensive studies on B and T lymphocyte attenuator (BTLA)-mediated negative regulation of T cell activation, the role of BTLA in antigen presenting cells (APCs) in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here, we demonstrate that BTLA expression on CD11c APCs increased in patients with ATB. Particularly, BTLA expression in CD11c APCs was likely associated with the attenuated stimulatory capacity on T cells (especially CD8+ T cell) proliferation.

Elevated serum IL-35 and increased expression of IL-35-p35 or -EBI3 in CD4(+)CD25(+) T cells in patients with active tuberculosis.

Despite the recent appreciation of interleukin 35 (IL-35) function in inflammatory diseases, little is known for IL-35 response in patients with active tuberculosis (ATB). In the current study, we demonstrated that ATB patients exhibited increases in serum IL-35 and in mRNA expression of both subunits of IL-35 (p35 and EBI3) in white blood cells and peripheral blood mononuclear cells. Consistently, anti-TB drug treatment led to reduction in serum IL-35 level and p35 or EBI3 expression.

IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin.

Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth.

[Preparation and characterization of polyclonal antibody against 5-fluorouracil].

Objective: To prepare 5-fluorouracil (5-FU) immunogen and develop polyclonal antibodies against 5-FU.

Methods: The derivant of 5-FU (5-fluorouracil-1-yl-aceto amino acid, 5-FUAA) was synthesized, and then conjugated with bovine serum albumin (BSA) or ovalbumin (OVA) by carbodiimide (CDI) method. 5-FUAA conjugating BSA (5-FUAA-BSA) was used to immunize BALB/c mice to produce antiserum, and 5-FUAA conjugating OVA (5-FUAA-OVA) was used as coating antigen to detect the titer of the antiserum by indirect ELISA.

[The number of peripheral blood CD11c+ antigen presenting cells increases and their function strengthens in the patients with active pulmonary tuberculosis].

Objective: To detect the percentage of CD11c positive antigen presenting cells (CD11c(+) APCs) in peripheral blood from patients with active pulmonary tuberculosis (APT) and the levels of HLA-DR and CD86. Methods Fifty-two APT patients were enrolled in the study and 15 healthy volunteers served as controls. The frequencies of CD11c(+) APCs and the expressions of HLA-DR and CD86 in CD11c(+) APCs in the peripheral blood were determined by flow cytometry.