Hepatitis D virus (HDV) is a defective virus that completes its life cycle only with hepatitis B virus (HBV). The HBV with HDV super-infection has been considered as one of the most severe forms of ...the chronic viral hepatitis. However, there is a scarcity of data on the global burden of HDV infection.
We searched PubMed, Embase, Cochrane Library and China Knowledge Resource Integrated databases from 1 January 1977 to 31 December 2016. We included studies with a minimum sample size of 50 patients. Our study analysed data from a total of 40 million individuals to estimate the prevalence of HDV by using Der-Simonian Laird random-effects model. The data were further categorised according to risk factors.
From a total of 2717 initially identified studies, only 182 articles from 61 countries and regions met the final inclusion criteria. The overall prevalence of HDV was 0.98% (95% CI 0.61 to 1.42). In HBsAg-positive population, HDV pooled prevalence was 14.57% (95% CI 12.93 to 16.27): Seroprevalence was 10.58% (95% CI 9.14 to 12.11) in mixed population without risk factors of intravenous drug use (IVDU) and high-risk sexual behaviour (HRSB). It was 37.57% (95% CI 29.30 to 46.20) in the IVDU population and 17.01% (95% CI 10.69 to 24.34) in HRSB population.
We found that approximately 10.58% HBsAg carriers (without IVDU and HRSB) were coinfected with HDV, which is twofold of what has been estimated before. We also noted a substantially higher HDV prevalence in the IVDU and HRSB population. Our study highlights the need for increased focus on the routine HDV screening and rigorous implementation of HBV vaccine programme.
Abstract Context MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate the gene expressions at the posttranscriptional level, subsequently control crucial physiological ...processes. Recent evidence demonstrates that some miRNAs have the functions similar to oncogene or tumor suppressors, it may play important roles in tumorigenesis. MiRNA expression profiles may become useful biomarkers for cancer diagnostics, prognosis and prediction of response to treatment, and it could be a powerful tool for cancer prevention and therapeutics. Objective To explore the global expression profile of miRNAs in non small cell lung cancer (NSCLC) and its potential relevance to clinicopathological characteristics and prognosis. Methods LNA microRNA microarrays were utilized to detect miRNA expression levels in eight surgically removed lung carcinoma tissues (LCT) and their corresponding normal lung tissues (NT). After initial microarray validation by quantitative real-time reverse transcription polymerase chain reaction assays (qRT-PCR), miR-21, miR-143 and miR-181a were selected for further study in another 47 paired LCTs and matched NTs by qRT-PCR using Taqman microRNA assay. Results Twenty-seven microRNAs were observed to be deregulated greater than two-fold in LCT compared with NT by microarray. Consistenting with the microarray, the expression level of miR-21 by qRT-PCR was significantly higher in tumor tissues than in adjacent normal tissues ( P = 0.026); while miR-143 ( P = 0.000) and miR-181a ( P = 0.000) were downregulated in LCT. Interestingly, among the 47 NSCLC cases, low level expression of miR-143 was significantly correlated with smoking status ( P = 0.026), high miR-21 expression (hazard ratio, 5.993; 95% confidence interval, 2.518–14.264; P = 0.000) and low miR-181a expression (hazard ratio, 0.328; 95% confidence interval 0.142–0.756; P = 0.009) were associated with poor survival, independent of clinical covariates, including TNM staging, lymph note status. Conclusion Our data thus indicating the potential of miR-21, miR-143 and miR-181a as a novel diagnostic or prognostic biomarker for NSCLC. Besides, these data will guide further studies of specific microRNAs might become potential targets for therapeutic intervention.
Gestational diabetes mellitus (GDM) is one type of diabetes that presents during pregnancy and significantly increases the risk of a number of adverse consequences for the fetus and mother. The ...microRNAs (miRNA) have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. However, no reported study investigates the associations between serum miRNA and GDM.
We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to screen miRNAs in serum collected at 16-19 gestational weeks. The expression levels of three miRNAs (miR-132, miR-29a and miR-222) were significantly decreased in GDM women with respect to the controls in similar gestational weeks in our discovery evaluation and internal validation, and two miRNAs (miR-29a and miR-222) were also consistently validated in two-centric external validation sample sets. In addition, the knockdown of miR-29a could increase Insulin-induced gene 1 (Insig1) expression level and subsequently the level of Phosphoenolpyruvate Carboxy Kinase2 (PCK2) in HepG2 cell lines.
Serum miRNAs are differentially expressed between GDM women and controls and could be candidate biomarkers for predicting GDM. The utility of miR-29a, miR-222 and miR-132 as serum-based non-invasive biomarkers warrants further evaluation and optimization.
Interleukin-37 (IL-37) is a newly discovered member of IL-1 family. The cytokine was proved to have extensive protective effects in infectious diseases, allergic diseases, metabolic diseases, ...autoimmune diseases and tumors since its discovery. IL-37 was mainly produced by immune and some non-immune cells in response to inflammatory stimulus. The IL-37 precursors can convert into the mature forms after caspase-1 cleavage and activation intracellularly, and then bind to Smad-3 and transfer to the nucleus to inhibit the production and functions of proinflammatory cytokines; extracellularly, IL-37 binds to cell surface receptors to form IL-37/IL-18Rα/IL-1R8 complex to exert immunosuppressive function via inhibiting/activating multiple signal pathways. In addition, IL-37 can attenuate the pro-inflammatory effect of IL-18 through directly or forming an IL-37/IL-18BP/IL-18Rβ complex. Therefore, IL-37 has the ability to suppress innate and acquired immunity of the host, and effectively control inflammatory stimulation, which was considered as a new hallmark of cancer. Specifically, it is concluded that IL-37 can inhibit the growth and migration of tumor cells, prohibit angiogenesis and mediate the immunoregulation in tumor microenvironment, so as to exert effective anti-tumor effects. Importantly, latest studies also showed that IL-37 may be a novel therapeutic target for cancer monitoring. In this review, we summarize the immunoregulation roles and mechanisms of IL-37 in anti-tumor process, and discuss its progress so far and potential as tumor immunotherapy.
The role of γδ T cells, innate-like lymphocytes with unrestrained MHC, in various malignancies has recently been extensively studied. However, there is limited research regarding γδ T cells in ...ovarian cancer (OC) patients.
Here, we investigated the distribution patterns of γδ T cells and their main subsets in peripheral blood and tumor tissues among OC patients, benign ovarian tumor (BOT) patients, and age-matched healthy controls (HC) by flow cytometry, as well as the expression levels of IFN-γ and IL-17A secreted from γδ T cells. Immunohistochemical staining was utilized to detect the numbers of γδ T cells and their main subsets in different types of ovarian tumor tissues. Additionally, we also investigated chemotaxis effects on γδ T cells, as well as their cytotoxic activity and proliferation.
We found that the percentages of γδ T cells and Vδ1 T cells were significantly higher in OC tissues than BOT tissues and normal (N) ovarian tissues, while there were no obvious differences in peripheral blood. Meanwhile, higher numbers of γδ T cells and Vδ1 T cells were observed in OC tissues, and were positively related to advanced clinicopathological features of OC patients. Further, the levels of IFN-γ secreted by γδ T cells were relatively lower, while IL-17A was expressed at a high level in both the peripheral blood and tissues of OC patients. Chemotaxis assay revealed that supernatants derived from OC tissues possessed a stronger capacity to attract and recruit γδ T cells. However, γδ T cells sorted from OC tissues showed weakened cytotoxic activity against ovarian cancer cells, and γδ T cells cocultured with OC tissue supernatants could effectively inhibit the proliferative activity of naïve CD4
T cells.
These data suggested that γδ T cells might have critical roles in OC progression and potential utilization in treatment approaches or prognosis prediction.
Treatment with programmed cell death protein-1 (PD-1) antibodies has minimal response rates in patients with non-small cell lung cancer (NSCLC), and, actually, they are treated with chemotherapy ...combined with anti-PD-1 therapy clinically. Reliable markers based on circulating immune cell subsets to predict curative effect are still scarce.
We included 30 patients with NSCLC treated with nivolumab or atezolizumab plus platinum drugs between 2021 and 2022. Whole blood was collected at baseline (before treatment with nivolumab or atezolizumab). The percentage of circulating PD-1
Interferon-γ (IFN-γ
) subset of CD8
T cell was determined by flow cytometry. The proportion of PD-1
IFN-γ
was calculated after gating on CD8
T cells. Neutrophil/lymphocyte ratio (NLR), relative eosinophil count (%), and Lactate dehydrogenase (LDH) concentration at baseline of included patients were extracted from electronic medical records.
The percentage of circulating PD-1
IFN-γ
subset of CD8
T cell at baseline in responders was significantly higher than those in non-responders (P < 0.05). Relative eosinophil count (%) and LDH concentration in responders showed no significance between non-responders and responders. NLR in responders was significantly lower than those in non-responders (
< 0.05). Receiver operation characteristic (ROC) analysis found that the areas under the ROC curve for PD-1
IFN-γ
subset of CD8
T cell and NLR were 0.7781 (95% CI, 0.5937-0.9526) and 0.7315 (95% CI, 0.5169-0.9461). Moreover, high percentage of PD-1
IFN-γ
subset in CD8
T cells was relevant to long progression-free survival in patients with NSCLC treated with chemotherapy combined with anti-PD-1 therapy.
The percentage of circulating PD-1
IFN-γ
subset of CD8
T cell could be a potential marker at baseline to predict early response or progression in patients with NSCLC receiving chemotherapy combined with anti-PD-1 therapy.
Regulatory T （Treg） cells may participate in mediating a suppressive microenvironment that blunts successful anti-tumor immunotherapy. Recent studies show that CD8＋ Treg cells might impede effective ...immune responses to established tumors. However, there is limited research regarding CD8＋ Treg cells in ovarian cancer （OC） patients. Here, we investigated CD8＋ Treg cells in OC patients and their in vitro induction. The immunohistochemistry of tumor-infiltrating lymphocytes revealed a significant correlation between the intratumoral CD8＋ T cells and the forkhead box p3 （Foxp3）＋ cells in the intraepithelial and stromal areas of advanced OC tissues. We examined the expression of Treg markers in CD8＋ T cells from the peripheral blood and fresh tumor tissues of OC patients using flow cytometry. Our results indicated an increase in the CD8＋ Treg cell subsets of OC patients compared with those in patients with benign ovarian tumors and healthy controls, including a n increased expression of CD25, cytotoxic T-lymphocyte-associated protein 4 （CTLA-4）, and Foxp3 and decreased CD28 expression. To demonstrate whether the tumor microenvironment could convert CD8＋ effector T cells into suppressor cells, we used an in vitro transwell culturing system. Compared with the CD8＋ T cells cultured alone, the CD8＋ Treg cells induced in vitro by coculture with SK-OV-3/A2780 showed increased CTLA-4 and Foxp3 expression and decreased CD28 expression. In addition, the in vitro-induced CD8＋ Treg cells inhibited naive CD4＋ T-cell proliferation, which was partially mediated through TGF-β1 and IFN-γ. Our study suggests that CD8＋ Treg cells were increased in OC patients and could be induced in vitro, which may be the way that tumors limit antitumor immunity and evade immune surveillance.
Introduction:
Non-small cell lung cancer (NSCLC) exhibits heterogeneity with diverse immune cell infiltration patterns that can influence tumor cell behavior and immunotherapy. A comprehensive ...characterization of the tumor microenvironment can guide precision medicine.
Methods:
Here, we generated a single-cell atlas of 398170 cells from 52 NSCLC patients, and investigated the imprinted genes and cellular crosstalk for macrophages. Subsequently, we evaluated the effect of tumor cells on macrophages and verified the expression of marker genes using co-culture experiments, flow cytometry and RT-qPCR assays.
Results:
Remarkable macrophage adaptability to NSCLC environment was observed, which contributed to generating tumor-associated macrophages (TAMs). We identified 5 distinct functional TAM subtypes, of which the majority were SELENOP-positive macrophages, with high levels of
SLC40A1
and
CCL13
. The TAMs were also involved in mediating CD8
+
T cell activity and form intercellular interaction with cancer cells, as indicated by receptor-ligand binding. Indirect coculture of tumor cells SPC-A1 and THP-1 monocytes, produced M2-like TAMs that highly expressed several markers of SELENOP-positive macrophages. The abundance of this type TAMs seemed to be associated with poorer overall survival rates hazard ratio (HR) = 1.34, 95% confidence interval (CI) = 0.98-1.83,
p
= 0.068 based on deconvolution of TCGA-LUAD dataset.
Discussion:
In summary, we provided a high-resolution molecular resource of TAMs, and displayed the acquired properties in the tumor microenvironment. Dynamic crosstalk between TAMs and tumor cells via multiple ligand-receptor pairs were revealed, emphasizing its role in sustaining the pro-tumoral microenvironment and its implications for cancer therapy.
Auranofin, a gold complex that has been used to treat rheumatoid arthritis in clinics and has documented pharmacokinetic and safety profiles in humans, has recently been investigated for its ...anticancer activity in leukemia and some solid cancers. However, auranofin's single agent activity in lung cancer is not well characterized. To determine whether auranofin has single agent activity in lung cancer, we evaluated auranofin's activity in a panel of 10 non-small cell lung cancer (NSCLC) cell lines. Cell viability analysis revealed that auranofin induced growth inhibition in a subset of NSCLC cell lines with a half maximal inhibitory concentration (IC50) below 1.0 μM. Treatment with auranofin elicited apoptosis and necroptosis in auranofin-sensitive cell lines. Moreover, the susceptibility of NSCLC cells to auranofin was inversely correlated with TXNRD1 expression in the cells. Transient transfection of the TXNRD1-expressing plasmid in auranofin-sensitive Calu3 cells resulted in partial resistance, indicating that high TXNRD level is one of causal factors for resistance to auranofin. Further mechanistic characterization with proteomic analysis revealed that auranofin inhibits expression and/or phosphorylation of multiple key nodes in the PI3K/AKT/mTOR pathway, including S6, 4EBP1, Rictor, p70S6K, mTOR, TSC2, AKT and GSK3. Ectopic expression of TXNRD1 partially reversed auranofin-mediated PI3K/AKT/mTOR inhibition, suggesting that TXNRD1 may participate in the regulation of PI3K/AKT/mTOR pathway. Administration of auranofin to mice with xenograft tumors derived from NSCLC cells significantly suppressed tumor growth without inducing obvious toxic effects. Our results demonstrated feasibility of repurposing auranofin for treatment of lung cancer.
Shigella is becoming an increasing public health problem due to development of multiple antimicrobial resistance, frequently resulting in treatment failure. A systematic review was conducted based on ...a literature search of computerised databases. Random or fixed-effects models were used, based on the P-value considering the possibility of heterogeneity between studies, for meta-analysis. Statistical analyses were performed using STATA 10.0. In the area of Asia–Africa, resistance rates to nalidixic acid and ciprofloxacin were 33.6% 95% confidence interval (CI) 21.8–46.6% and 5.0% (95% CI 2.8–7.8%), respectively, 10.5 and 16.7 times those of Europe–America. Moreover, resistance to nalidixic acid and ciprofloxacin in Asia–Africa progressively increased each year, reaching 64.5% (95% CI 13.8–99.3%) and 29.1% (95% CI 0.9–74.8%), respectively, in 2007–2009, whilst isolates in Europe–America remained at low levels of resistance (<5.0% and <1.0%, respectively). All Shigella flexneri strains showed higher resistance than Shigella sonnei in Europe–America: overall, 3.5% (95% CI 1.4–6.4%) vs. 2.6% (95% CI 1.0–5.0%) resistant to nalidixic acid and 1.0% (95% CI 0.3–2.2%) vs. 0.1% (95% CI 0.0–0.3%) resistant to ciprofloxacin. In Asia–Africa, a similar trend was found for ciprofloxacin 3.0% (95% CI 1.4–5.3%) vs. 0.5% (95% CI 0.2–0.8%), whereas the trend was reversed for nalidixic acid 32.6% (95% CI 14.5–53.9%) vs. 44.3% (95% CI 26.9–62.5%). In conclusion, quinolone resistance in Shigella has increased at an alarming speed, reinforcing the importance of continuous monitoring of antimicrobial resistance in Shigella.
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