To investigate long noncoding RNA PVT1 expression in the serum of cervical cancer patients, and to evaluate serum PVT1 level as a diagnostic biomarker for cervical cancer.
Eighty-eight cervical ...cancer patients, 64 cervical intraepithelial neoplasia patients, 25 breast cancer patients, 25 ovarian cancer patients, and 111 healthy control subjects were enrolled into this study. PVT1 serum level in these participants and PVT1 expression in 20 pairs of cervical cancer tissues and adjacent paired normal tissues was measured by quantitative reverse transcription-polymerase chain reaction. The diagnostic values of serum PVT1 were evaluated by receiver operating characteristic curves analysis.
Serum PVT1 level is significantly increased in cervical cancer patients and correlated with tumor size, clinical stage, and lymph node metastasis of cervical cancer. Serum PVT1 could accurately discriminate cervical cancer patients from cervical intraepithelial neoplasia patients and healthy control subjects, and also discriminate early stage cervical cancer patients from healthy control subjects. But serum PVT1 level is not changed in breast cancer and ovarian cancer patients. Furthermore, serum PVT1 level is positively correlated with tissue PVT1 expression, and could indicate cervical cancer dynamics.
Long noncoding RNA PVT1 may be a novel noninvasive biomarker for early diagnosis of cervical cancer.
The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem ...cells) can be isolated prospectively as a highly enriched CD271+ MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2−/− c−/− mice. The CD271+ subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271+ melanoma cells into engrafted human skin or bone in Rag2−/− c−/− mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271− cells. We also show that in mice, tumours derived from transplanted human CD271+ melanoma cells were capable of metastatsis in vivo. CD271+ melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.
Summary
Background
Symmetrical acrokeratoderma (SAK) is characterized by brown to black hyperkeratotic patches on acral regions. Although epidermal hyperkeratosis and acanthosis are consistent ...pathological changes, the nature of epidermal hyperplasia is unknown.
Aim
To evaluate epidermal proliferation and differentiation and melanocytic density in skin lesions of SAK.
Methods
Expression of keratin 10 (K10), K14, K16, involucrin, filaggrin, Ki‐67, and Melan‐A was detected by immunohistochemistry in eight patients with SAK, seven patients with ichthyosis vulgaris (IV) and six healthy controls (HCs).
Results
Expression of K14, K16, involucrin and filaggrin was upregulated in patients with SAK compared with patients with IV and the HCs (P < 0.01–0.05), but K10 expression was similar for the three groups (P > 0.05). Numbers of Ki‐67+ and Melan‐A+ cells were higher in patients with SAK than in patients with IV and the HCs (P < 0.05).
Conclusions
These results demonstrate that excessive keratinocyte proliferation and abnormal differentiation contribute to epidermal hyperplasia, while melanocytic proliferation is responsible for the pigmented lesions in SAK.
Summary
Vitamin D receptor (VDR) mediates various biochemical activities between the cytoplasm and the nucleus in the cell. The nucleotide‐binding, oligomerization domain (NOD)‐like receptor family, ...pyrin domain containing 3 (NLRP3) protein is involved in the T helper type 2 (Th2) response. This study tests a hypothesis that VDR interacts with NLRP3 to restrict the Th2‐biased response. In this study, VDR–/– mice and WT (WT) mice were used. Th2 cell differentiation between VDR–/– mice and WT mice was observed. We observed that CD4+ T cell activation was higher in VDR–/– mice. The VDR–/–CD4+ T cells were prone to Th2 polarization. VDR–/– mice produced more immunoglobulin (Ig)E. VDR bound NLRP3 to prevent Th2 differentiation by restricting IL4 gene transcription. Th2 biased inflammation spontaneously developed in the intestine of VDR–/– mice. In conclusion, VDR binds NLRP3 to restrict IL4 gene transcription and prevent biased Th2 polarization.
VDR expression is lower in CD4+ T cells of FA patients; VDR is negatively correlated with Th2 cytokines in CD4+ T cells of FA patients
Peptidoglycan is the major bacterial component recognized by the insect immune system. Peptidoglycan recognition proteins (PGRPs) are a family of pattern‐recognition receptors that recognize ...peptidoglycans and modulate innate immune responses. Some PGRPs retain N‐acetylmuramoyl‐L‐alanine amidase (Enzyme Commission number: 3.5.1.28) activity to hydrolyse bacterial peptidoglycans. Others have lost the enzymatic activity and work only as immune receptors. They are all important modulators for innate immunity. Here, we report the cloning and functional analysis of PGRP‐S4, a short‐form PGRP from the domesticated silkworm, Bombyx mori. The PGRP‐S4 gene encodes a protein of 199 amino acids with a signal peptide and a PGRP domain. PGRP‐S4 was expressed in the fat body, haemocytes and midgut. Its expression level was significantly induced by bacterial challenges in the midgut. The recombinant PGRP‐S4 bound bacteria and different peptidoglycans. In addition, it inhibited bacterial growth and hydrolysed an Escherichia coli peptidoglycan in the presence of Zn2+. Scanning electron microscopy showed that PGRP‐S4 disrupted the bacterial cell surface. PGRP‐S4 further increased prophenoloxidase activation caused by peptidoglycans. Taken together, our data suggest that B. mori PGRP‐S4 has multiple functions in immunity.
Recent evidence suggests that certain vaccines, including Bacillus-Calmette Guérin (BCG), can induce changes in the innate immune system with non-specific memory characteristics, termed 'trained ...immunity'. Here we present the results of a randomised, controlled phase 1 clinical trial in 20 healthy male and female volunteers to evaluate the induction of immunity and protective efficacy of the anti-tuberculosis BCG vaccine against a controlled human malaria infection. After malaria challenge infection, BCG vaccinated volunteers present with earlier and more severe clinical adverse events, and have significantly earlier expression of NK cell activation markers and a trend towards earlier phenotypic monocyte activation. Furthermore, parasitemia in BCG vaccinated volunteers is inversely correlated with increased phenotypic NK cell and monocyte activation. The combined data demonstrate that BCG vaccination alters the clinical and immunological response to malaria, and form an impetus to further explore its potential in strategies for clinical malaria vaccine development.
Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is a secreted glycoprotein that is overexpressed in lung cancer tumor tissues and is correlated with the invasive ability in a lung ...cancer cell line model. These observations suggest that SCUBE3 may have a role in lung cancer progression. By exogenous SCUBE3 treatment or knockdown of SCUBE3 expression, we found that SCUBE3 could promote lung cancer cell mobility and invasiveness. Knockdown of SCUBE3 expression also suppressed tumorigenesis and cancer metastasis in vivo. The secreted SCUBE3 proteins were cleaved by gelatinases (matrix metalloprotease-2 (MMP-2) and MMP-9) in media to release two major fragments: the N-terminal epidermal growth factor-like repeats and the C-terminal complement proteins C1r/C1s, Uegf and Bmp1 (CUB) domain. Both the purified SCUBE3 protein and the C-terminal CUB domain fragment, bound to transforming growth factor-β (TGF-β) type II receptor through the C-terminal CUB domain, activated TGF-β signaling and triggered the epithelial-mesenchymal transition (EMT). This process includes the induction of Smad2/3 phosphorylation, the increase of Smad2/3 transcriptional activity and the upregulation of the expression of target genes involved in EMT and cancer progression (such as TGF-β1, MMP-2, MMP-9, plasminogen activator inhibitor type-1, vascular endothelial growth factor, Snail and Slug), thus promoting cancer cell mobility and invasion. In conclusion, in lung cancer cells, SCUBE3 could serve as an endogenous autocrine and paracrine ligand of TGF-β type II receptor, which could regulate TGF-β receptor signaling and modulate EMT and cancer progression.
Introduction
Adverse childhood experiences (ACEs) constitute a significant global mental health burden. Prior studies typically investigated the impact of ACEs on mental health using a cumulative ...risk approach; most ACEs studies were also conducted in Western settings.
Purpose
This study aimed to examine ACEs using a pattern-based approach and assess their associations with mental health outcomes by early adulthood in East Asia.
Methods
The present study included measures of exposure to 13 categories of ACEs, depression, anxiety, maladjustment, and posttraumatic stress in a sample of 1346 university students from Hong Kong, China, Taiwan, and Japan.
Results
Latent class analysis indicated three distinct patterns of ACE exposure: Class 1: Low ACEs (76.0%); Class 2: Household Violence (20.6%); and Class 3: Household Dysfunction (3.4%). Those representing Class 3 had significantly more ACEs compared with those in Classes 1 or 2. Controlling for age and sex, those in Class 2 reported significantly higher depression and maladjustment symptoms compared with those in Class 1; both Classes 2 and 3 had significantly higher anxiety symptoms and odds for meeting diagnostic criteria for posttraumatic stress disorders compared with those in Class 1.
Conclusions
Study findings suggest that young adults’ mental health, at least under certain contexts, is more closely linked with the nature and pattern of ACE co-occurrence, rather than the number of ACEs.
The Y-stent technique, including crossing-Y and kissing-Y, is a promising therapeutic option for some complex bifurcation aneurysms. Here, its efficacy and safety are evaluated on the basis of 11 ...bifurcation aneurysms.
A retrospective review was conducted for all patients who underwent endovascular treatment of aneurysms in our department between January 2009 and June 2011 to identify and analyze cases with bifurcation aneurysms reconstructed by using Y-stents.
Eleven patients (4 ruptured and 7 unruptured aneurysms) were identified (4 men, 7 women) with a mean age of 60.4 years. Nine aneurysms (2 AcomAs, 3 MCA-Bifs, 1 PcomA, 3 BA apexes) were treated by using the crossing-Y technique, and 2 (both BA apexes) were treated with the kissing-Y technique, achieving complete occlusion in 6 aneurysms, residual neck in 4, and partial occlusion in 1. Perioperatively, a single thromboembolic event occurred in 1 case without neurologic deficit, which required a salvaging second stent implantation. Means of 9.9 months of angiographic and 13.7 months of clinical follow-up were available. As a result, 9 (81.8) aneurysms were completely occluded, 1 with a residual neck remained stable, and 1 residual aneurysm sac was recanalized, which was retreated and achieved a complete occlusion. All patients were independent with an mRS score of 0-1 at discharge and follow-up.
In selected patients, the reconstruction of bifurcation aneurysms by using the Y-stent can be successfully achieved with satisfactory midterm results.
Summary
Malignant lymphoma (ML) is a common hematological malignancy with many subtypes. Patients with ML usually undergo traditional treatment failure and become relapsed or refractory (R/R) cases. ...Recently, immunotherapy, such as immune checkpoint inhibitors (ICIs) and cellular treatment, has gradually emerged and used in clinical trials with encouraging achievements for ML treatment, which exerts anti‐tumor activity by blocking the immune evasion of tumor cells and enhancing the attack ability of immune cells. Targets of immune checkpoints include programmed cell death‐1 (PD‐1), programmed cell death‐ligand 1 (PD‐L1), cytotoxic T lymphocyte‐associated protein 4 (CTLA‐4), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin‐3 (TIM‐3) and lymphocyte activation gene 3 (LAG‐3). Examples of cellular treatment are chimeric antigen receptor (CAR) T cells, cytokine‐induced killer (CIK) cells and natural killer (NK) cells. This review aimed to present the current progress and future prospects of immunotherapy in lymphoma, with the focus upon ICIs and cellular treatment.
Most patients with malignant lymphoma inevitably develop into relapsed or refractory (R/R) cases after traditional treatment failure. Immunotherapy, such as immune checkpoint inhibitors (ICIs) and cellular treatment has played roles in ML treatment by blocking the immune evasion of tumor cells and enhancing the attack ability of immune cells. This review was aimed to present the current progress and future prospects of immunotherapy in lymphoma, with the focus on ICIs and cellular treatment.
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