Pyroptosis and the tumor immune microenvironment: A new battlefield in ovarian cancer treatment.

Ovarian cancer is a less common tumor in women compared to cervical or breast cancer, however it is more malignant and has worse outcomes. Ovarian cancer patients still have a five-year survival rate < 50% despite advances in therapy. Due to recent developments in immune checkpoint inhibitors (ICIs), cancer immunotherapy has attracted increased interest. Pyroptosis is a highly inflammatory form of cell death, which is essential for bridging innate and adaptive immunity, and is involved in immune regulation within the tumor microenvironment (TME). Recent research has shown that pyroptosis can promote immunotherapy of ovarian cancer, including treatment with chimeric antigen receptor T-cells (CAR-T) or ICIs. Moreover, inflammasomes, various signaling pathways and lncRNAs can all affect pyroptosis in ovarian cancer. Here we discuss how pyroptosis affects the development and progression of ovarian cancer as well as the TME. We also provide a summary of small molecule drugs that could target pyroptotic cell death processes and may be useful in ovarian cancer therapy.

Effects of a death education based on narrative pedagogy in a palliative care course among Chinese nursing students.

Background: Death education has been confirmed to be an effective method to enhance nursing students' attitudes and coping abilities toward death. However, integrated Narrative Pedagogy into the death education to explore educational effectiveness is still limited. The study aimed to evaluate the effects of a death education based on Narrative Pedagogy in a palliative care course on the attitude toward death, coping with death, and attitude toward caring for the dying among undergraduate nursing students in China. Methods: The study was designed as a pre-post intervention study with a quasi-experimental design. All the participants received 6 class hours of death education which was designed in a palliative care course. The death education includes preparation, presentation, discussion, reflection, and practice of the narrative materials. Death Attitude Profile-Revised (DAP-R), Coping with Death Scale (CDS), and Frommelt Attitude Toward Care of the Dying-Form B (FATCOD-Form B) were used to measure outcomes. Results: Sixty undergraduate nursing students who consented. There were statistically significant increases in the mean score of neutral acceptance and approach acceptance in the DAP-R, CDS, and FATCOD-Form B before and after the intervention. Conclusion: This death education integrated Narrative Pedagogy which indicated to improve attitude toward death, competence to cope with death, and attitude toward the care of dying patients. The findings assist teachers in understanding the importance and urgency of death education, as well as providing a favorable approach to death education. However, the long-term effectiveness still needs to study in further.

FTO promotes the progression of cervical cancer by regulating the N6-methyladenosine modification of ZEB1 and Myc.

Cervical cancer is a malignant tumor of the cervix in women. However, the pathogenesis of cervical cancer has not been fully understood. N6-methyladenosine (m6A) is a kind of RNA modification that plays a critical role in cancer development. We aim to find out the possible m6A regulatory mechanism of the fat mass and obesity-associated protein (FTO) on the development of cervical cancer. The proliferative capacity of cervical cancer cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), colony formation and 5-ethynyl-20-deoxyuridine (EdU) staining. The migration and invasion of cervical cancer cells were determined by transwell assay. The function of FTO on tumor growth was evaluated by a xenograft model. We found that FTO was highly expressed in cervical cancer tissues and cell lines. FTO silencing suppressed the proliferation, migration, and invasion of cervical cancer cells. Mechanistically, FTO modulated the m6A modification of Zinc finger E-box binding homeobox 1 (ZEB1) and Myelocytomatosis oncogene (Myc). Furthermore, ZEB1 and Myc overexpression reverse the effect of FTO knockdown on the malignant behaviors of cervical cancer cells. FTO may be a novel therapeutic target for cervical cancer.

Rational targeting of autophagy in colorectal cancer therapy: From molecular interactions to pharmacological compounds.

The abnormal progression of tumors has been a problem for treatment of cancer and therapeutic should be directed towards targeting main mechanisms involved in tumorigenesis in tumors. The genomic mutations can result in changes in biological mechanisms in human cancers. Colorectal cancer is one of the most malignant tumors of gastrointestinal tract and its treatment has been faced some difficulties due to development of resistance in tumor cells and also, their malignant behavior. Hence, new therapeutic modalities for colorectal cancer are being investigated. Autophagy is a "self-digestion" mechanism that is responsible for homeostasis preserving in cells and its aberrant activation/inhibition can lead to tumorigenesis. The current review focuses on the role of autophagy mechanism in colorectal cancer. Autophagy may be associated with increase/decrease in progression of colorectal cancer due to mutual function of this molecular mechanism. Pro-survival autophagy inhibits apoptosis to increase proliferation and survival rate of colorectal tumor cells and it is also involved in cancer metastasis maybe due to EMT induction. In contrast, pro-death autophagy decreases growth and invasion of colorectal tumor cells. The status of autophagy (upregulation and down-regulation) is a determining factor for therapy response in colorectal tumor cells. Therefore, targeting autophagy can increase sensitivity of colorectal tumor cells to chemotherapy and radiotherapy. Interestingly, nanoparticles can be employed for targeting autophagy in cancer therapy and they can both induce/suppress autophagy in tumor cells. Furthermore, autophagy modulators can be embedded in nanostructures in improving tumor suppression and providing cancer immunotherapy.

Characteristics and occupational risk assessment of occupational silica-dust and noise exposure in ferrous metal foundries in Ningbo, China.

Introduction: To investigate the major existing occupational hazards and to assess the occupational health risks for ferrous metal foundries (FMFs) in Ningbo, China. Methods: Unified questionnaires were formulated to investigate the information on the basic situations, occupational hazards, and occupational health management for 193 FMFs in Ningbo. Furthermore, we used the semi-quantitative risk assessment model, which was developed by the International Council on Mining and Metals (ICMM), to assess occupational health risks for 59 of 193 the FMFs. Results: The casting process of FMFs in Ningbo was mainly divided into sand casting and investment casting, and silica-dust and noise were the major occupational hazards in both sand casting and investment casting foundries. Silica-dust mainly occurred in industries with such work as sand handling, modeling, falling sand, and sand cleaning, with the median of the permissible concentration-time weighted average (PC-TWA) was 0.80, 1.15, 3.52, 0.83 mg/m3, respectively. The noise mainly existed in industries with such work as sand handling, core making, falling sand, sand cleaning, cutting and grinding, and smelting with median of PC-TWA was 81.72 dB(A), 82.93 dB(A), 90.75 dB(A), 80.18 dB(A), 90.05 dB(A), 82.70 dB(A), respectively. In addition, the results of the ICMM assessment model indicated that 100 and 98.7% of the jobs exposed to silica-dust and noise in 59 FMFs have an "intolerable risk" level of risks of causing pneumoconiosis and noise deaf, respectively. Discussion: The hazard risk of silica-dust and noise is serious for FMFs in Ningbo. It is necessary to supervise enterprises to improve operating environmental conditions, accelerate the reduction of silica-dust and noise exposure risks, and promote the healthy and sustainable development of the foundry industry.

The Prognosis of Diabetic Foot Ulcer is Independent of age? A Comparative Analysis of the Characteristics of Patients with Diabetic Foot Ulcer in Different age Groups: A Cross-Sectional Study from China.

Background: With younger onset age of type 2 diabetes mellitus (T2DM), the incidence of diabetic foot ulcer (DFU) in young and middle-aged adults is also increasing. Elucidating the distinctive characteristics of DFU in different ages and exploring the influence of age on the prognosis of DFU are crucial to the improvement of DFU treatments. Methods: 684 patients hospitalized for DFU in the department of endocrinology were recruited and assigned into the young and middle-aged group (age <65 years old) and the elderly group (age ≥65 years old). Demographic data and clinical features were compared between two groups. Results: Compared with the elderly group, the young and middle-aged group had higher proportion of males (72.3% vs 49.6%, P < .01) and smokers (52.5% vs 35.8%, P < .01), shorter duration of diabetes mellitus (155 months vs 196 months, P < .01), higher levels of glycosylated hemoglobin (9.3% vs 8.7%, P < .01), lower ratio of ankle-brachial index <0.9 (25.8% vs 51.1%, P < .01) and higher levels of c-reactive protein and erythrocyte sedimentation rate (14 mg/L vs 10 mg/L, P < .05; 36 mm/h vs 30 mm/h, P < .05). The prevalence of diabetic peripheral neuropathy and Wagner Grade were similar in two groups. Of note, the prognosis was similar in different age groups, as there were no significant differences in the healing rate (59.7% vs 60.1%, P > .05), healing time (30 days vs 22 days, P > .05) and minor amputation rate (11.9% vs 8.7%, P > .05). Conclusions: We found that no evidence to suggest a better prognosis with younger DFU patients. Compared with elderly ones, young and middle-aged patients were characterized by a higher proportion of smoking, worse glycemic control, higher inflammatory biomarkers but less severe lower limb ischemia, indicating that smoking cessation, strict blood glucose control and early detection of infection were crucial for improving the prognosis of young and middle-aged diabetic DFU patients.

Blocking TIGIT/CD155 signalling reverses CD8+ T cell exhaustion and enhances the antitumor activity in cervical cancer.

OBJECTIVE: TIGIT/CD155 has attracted widespread attention as a new immune checkpoint and a potential target for cancer immunotherapy. In our study, we evaluated the role of TIGIT/CD155 checkpoints in the progression of cervical cancer. METHODS: The expression of CD155 and TIGIT in cervical cancer tissues was detected using flow cytometry, immunohistochemistry (IHC) and gene expression profiling. In vivo and in vitro experiments have proven that blocking TIGIT/CD155 restores the ability of CD8+ T cells to produce cytokines. Changes in the NF-κB and ERK pathways were detected using western blotting (WB) after blocking TIGIT/CD155 signalling. RESULTS: TIGIT expression was elevated in patients with cervical cancer. High TIGIT expression in CD8+ T lymphocytes from patients with cervical cancer promotes the exhaustion of CD8+ T lymphocytes. In addition, CD155 is expressed at high levels in cervical cancer tissues and is negatively correlated with the level of infiltrating CD8+ T cells. We found that TIGIT, upon binding to CD155 and being phosphorylated, inhibited NF-κB and ERK activation by recruiting SHIP-1, resulting in the downregulation of cytokine production. Blocking TIGIT in activated CD8+ T cells attenuates the inhibitory effect of SHIP-1 on CD8+ T cells and enhances the activation of NF-κB and ERK. In vivo and in vitro experiments have proven that blocking TIGIT/CD155 restores the ability of CD8+ T cells to produce cytokines. Injecting the blocking antibody TIGIT in vivo inhibits tumour growth and enhances CD8+ T lymphocyte function. Treatment with a combination of TIGIT and PD-1 inhibitors further increases the efficacy of the TIGIT blocking antibody. CONCLUSIONS: Our research shows that TIGIT/CD155 is a potential therapeutic target for cervical cancer.

Human umbilical cord-derived mesenchymal stem cells alleviate insulin resistance in diet-induced obese mice via an interaction with splenocytes.

BACKGROUND: Previous research has demonstrated that the spleen plays an important role in mesenchymal stem cell (MSC)-mediated alleviation of acute inflammation, as MSC infusion increases the spleen-derived anti-inflammatory cytokine interleukin 10 (IL-10) levels. However, studies on splenic involvement in MSC-induced protection against chronic inflammatory diseases are limited. Obesity is characterized by chronic low-grade inflammation, a key driver of insulin resistance. This study aims to evaluate the effects of MSCs on obesity-related insulin resistance and explore the underlying mechanism, particularly regarding splenic involvement. METHODS: We induced obesity in mice by feeding them high-fat diets for 20 weeks. Human umbilical cord-derived MSCs (UC-MSCs) were systemically infused into the obese mice once per week for 6 weeks. Systemic glucose metabolic homeostasis and insulin sensitivity in epididymal adipose tissue (EAT) were evaluated. Then, we conducted in vivo blockade of IL-10 during UC-MSC infusion by intraperitoneally administrating an IL-10-neutralizing antibody twice per week. We also investigated the therapeutic effects of UC-MSCs on obese mice after removal of the spleen by splenectomy. RESULTS: UC-MSC infusions improved systemic metabolic homeostasis and alleviated insulin resistance in EAT but elicited no change in weight. Despite rare engraftment of UC-MSCs in EAT, UC-MSC infusions attenuated insulin resistance in EAT by polarizing macrophages into the M2 phenotype, coupled with elevated serum IL-10 levels. In vivo blockade of IL-10 blunted the effects of UC-MSCs on obese mice. Furthermore, UC-MSCs overwhelmingly homed to the spleen, and the ability of UC-MSCs to elevate serum IL-10 levels and alleviate insulin resistance was impaired in the absence of the spleen. Further in vivo and in vitro studies revealed that UC-MSCs promoted the capacity of regulatory T cells (Treg cells) to produce IL-10 in the spleen. CONCLUSIONS: Our results demonstrated that UC-MSCs elevated serum IL-10 levels and subsequently promoted macrophage polarization, leading to alleviation of insulin resistance in EAT. The underlying mechanism was that UC-MSCs improved the capacity of Treg cells to produce IL-10 in the spleen. Our findings indicated that the spleen played a critical role in amplifying MSC-mediated immunomodulatory effects, which may contribute to maximizing MSC efficacy in clinical applications in the future.

Cervical cancer-derived exosomal miR-663b promotes angiogenesis by inhibiting vinculin expression in vascular endothelial cells.

BACKGROUND: Angiogenesis provides essential nutrients and oxygen for tumor growth and has become the main mechanism of tumor invasion and metastasis. Exosomes are nanoscale membrane vesicles containing proteins, lipids, mRNA and microRNA (miRNA), which mediate intercellular communication and play an important role in tumor progression. Accumulated evidence indicates that tumor-derived exosomal miRNAs participate in the tumor microenvironment and promote angiogenesis. METHODS: Bioinformatic target prediction and dual luciferase reporter assays were performed to identify the binding site between miR-663b and the 3'-UTR of vinculin (VCL). VCL overexpression lentivirus and miR-663b overexpression/inhibition lentivirus were used to create a VCL overexpression model and miR-663b overexpression/inhibition model in-vitro. Immunohistochemistry (IHC) assays and western blot assays were used to detect protein expression. Exosome-cell cocultures, wound healing assays, tube formation assays and transwell assays were used to measure the migration and tube formation ability of vascular endothelial cells [human umbilical vein endothelial cells (HUVECs)]. siRNA targeted VCL was used to knockdown VCL. RESULTS: In the present study, we found that miR-663b was elevated in cervical cancer tissue and exosomes. miR-663b could bind the 3'-UTR of VCL and inhibit its expression. VCL is downregulated in cervical cancer, and decreased VCL has a negative correlation with a high level of miR-663b. Further studies demonstrated that exosomes secreted by cervical cancer cells can deliver miR-663b to HUVECs and inhibit the expression of VCL, thereby promoting angiogenesis and tumor growth. CONCLUSIONS: miR-663b derived from cancer cell exosomes acts as a driving factor for angiogenesis and a potential target of antiangiogenic therapy in cervical cancer. Our findings illustrated a new signaling pathway, including exosomes, miRNAs and target genes, which provides potential targets for antiangiogenic therapy.

CD155 Promotes the Progression of Cervical Cancer Cells Through AKT/mTOR and NF-κB Pathways.

Expression of the immunoglobulin superfamily member CD155 was increased in a variety of human malignancies, but the role of CD155 in tumorigenesis and tumor development in cervical cancer has not been elucidated. In this study, immunohistochemistry and enzyme-linked immunosorbent assay analyses showed that CD155 expression gradually increases with the degree of cervical lesions. In vitro and in vivo, reducing the expression of CD155 inhibited cell proliferation, cell viability and tumor formation and arrested the cell cycle in G0/G1 phase. Antibody array-based profiling of protein phosphorylation revealed that CD155 knockdown can inhibited the AKT/mTOR/NF-κB pathway and activated autophagy and apoptosis; the opposite effects were observed upon CD155 has overexpression. We proved that there is an interaction between CD155 and AKT by immunoprecipitation. We further confirmed the mechanism between CD155 and AKT/mTOR/NF-κB through rescue experiments. AKT knockdown reversed the anti-apoptotic effects and activation of the AKT/mTOR/NF-κB pathway induced by CD155 overexpression. Our research demonstrated that CD155 can interact with AKT to form a complex, activates the AKT/mTOR/NF-κB pathway and inhibit autophagy and apoptosis. Thus, CD155 is a potential screening and therapeutic biomarker for cervical cancer.

KDM2A Targets PFKFB3 for Ubiquitylation to Inhibit the Proliferation and Angiogenesis of Multiple Myeloma Cells.

The lysine demethylase KDM2A (also known as JHDM1A or FBXL11) demethylates histone H3 at lysine K36 which lead to epigenetic regulation of cell proliferation and tumorigenesis. However, many biological processes are mediated by KDM2A independently by its histone demethylation activity. In the present study, we aimed to characterize the functional significance of KDM2A in multiple myeloma (MM) disease progression. Specifically, we defined that one of the key enzymes of glycolysis PFKFB3 (6-phosphofructo-2-kinase) is ubiquitylated by KDM2A which suppresses MM cell proliferation. Previous study showed that KDM2A and PFKFB3 promoted angiogenesis in various tumor cells. We further reveal that KDM2A targets PFKFB3 for ubiquitination and degradation to inhibit angiogenesis. Several angiogenic cytokines are also downregulated in MM. Clinically, MM patients with low KDM2A and high PFKFB3 levels have shown worse prognosis. These results reveal a novel function of KDM2A through ubiquitin ligase activity by targeting PFKFB3 to induce proliferation, glycolysis and angiogenesis in MM cells. The data provides a new potential mechanism and strategy for MM treatment.

Personal exposure to PM2.5-bound heavy metals associated with cardiopulmonary function in general population.

To better understand the cardiopulmonary alterations associated with personal exposed PM2.5-bound heavy meals, we conducted a cross-sectional study in 2018 on 54 general residents. For each subject, PM2.5 exposure filter was collected by a low-volume sampler for 24 h; blood and urine samples were collected subsequently. Heavy metals in PM2.5, blood, and urine samples were determined by inductively coupled plasma mass spectrometry method. PM2.5-bound Mn, Cd, Sb, Pb, and Ni levels were 20.5, 9.27, 9.59, 28.3, and 16.9 ng/m3, respectively. The distribution of these metals followed the order: Pb (33.47%) > Mn (24.24%) > Ni (19.99%) > Sb (11.34%) > Cd (10.96%). The distribution of heavy meals in PM2.5, blood, and urine differed from each other. PM2.5-bound Cd, Pb levels were positively correlated with blood Cd, Pb levels (r = 0.323, r = 0.334, p < 0.05), respectively. PM2.5-bound Cd level was significantly higher in smoking group than non-smoking group (28.8 vs. 7.27 ng/m3, p < 0.01), same as Sb level (12.0 vs. 9.34 ng/m3, p < 0.01). Cd and Pb exposure might interact with cardiovascular function through autonomic regulation. No significant correlation was observed between metal exposure and pulmonary function. In conclusion, our data suggested that personal exposure to specific PM2.5-bound heavy metals might interact with profound cardiovascular alterations.

Role and mechanism of FLNa and UCP2 in the development of cervical cancer.

Recent studies have reported that filamin A (FLNa) and uncoupling protein 2 (UCP2) are highly expressed in various types of cancer, but little is currently known about their roles in cervical cancer (CC). In the present study, immunohistochemical staining of paraffin sections of cervical tissues was performed in order to compare the differential expression of FLNa, UCP2, p16 and Ki67 between CC and high­grade intraepithelial neoplasia (HSIL). UCP2 and FLNa were knocked down in CC cell lines to investigate the effects on cell proliferation, cell cycle arrest, apoptosis, migration and invasion. In addition, the present study investigated the expression of cell­associated proteins [extracellular signal­regulated kinase (ERK), phosphorylated (p) ERK, protein kinase B (AKT), p­AKT and B­cell lymphoma­2 (Bcl­2)] and the mRNA levels of cellular proteins such as Ras, matrix metalloproteinase (MMP)­2 and MMP­9. FLNa and UCP2 expression levels were significantly higher in CC tissues than in HSIL tissues, with no significant differential expression of p16 or Ki67. UCP2 expression was significantly different in patients with clinical stage II or higher or lymph node metastasis compared with in other patients with cervical cancer. FLNa or UCP2 knockdown slowed or decreased SiHa and HeLa cell proliferation, migration and invasion, with no significant change in apoptosis, and downregulated the protein levels of p­ERK1/2, and the mRNA levels of Ras, MMP­2 and MMP­9. UCP2 knockdown arrested the cell cycle at the G2 phase in SiHa and HeLa cells, while FLNa knockdown arrested the cell cycle at the G2 phase in HeLa cells. The results of the present study revealed that FLNa and UCP2 play roles in the development and progression of CC via the Ras/MAPK/ERK signalling pathway. FLNa and UCP2 are superior to p16 and Ki67 for early prediction of CC, indicating that FLNa and UCP2 may be used for the early diagnosis of CC. UCP2 may be used to predict the prognosis of CC.

A Small Molecule Inhibitor, OGP46, Is Effective against Imatinib-Resistant BCR-ABL Mutations via the BCR-ABL/JAK-STAT Pathway.

Chronic myeloid leukemia (CML) is caused by the Philadelphia (Ph+) chromosome carrying the BCR-ABL oncogene, a constitutively active tyrosine kinase. The discovery of imatinib represents a major success story in the treatment against CML. However, mutations in the BCR-ABL kinase domain are a major cause of resistance to imatinib, demonstrating that BCR-ABL remains a critical drug target. Here, we investigate a novel small molecule inhibitor, OGP46, for its inhibitory activity against K562, a panel of murine BaF3 cell lines stably expressing either wild-type BCR-ABL or its mutant forms, including T315I. OGP46 exhibits potent activity against imatinib-resistant BCR-ABL mutations, including T315I. OGP46 induced cell differentiation accompanied by G0/G1 cell-cycle arrest and suppressed the colony formation capacity of cells. Treatment with OGP46 significantly decreased the mRNA and protein expression of BCR-ABL in K562 and BaF3-p210-T315I cells. Mechanistically, the anti-cancer activity of OGP46 induced by cell differentiation is likely through the BCR-ABL/JAK-STAT pathway in native BCR-ABL and mutant BCR-ABL, including T315I, of CML cells. Our findings highlight that OGP46 is active against not only native BCR-ABL but also 11 clinically relevant BCR-ABL mutations, including T315I mutation, which are resistant to imatinib. Thus, OGP46 may be a novel strategy for overcoming imatinib-resistance BCR-ABL mutations, including T315I.

MIR210HG promotes cell proliferation and invasion by regulating miR-503-5p/TRAF4 axis in cervical cancer.

Long non-coding RNAs (lncRNAs) play important roles in the progression of cervical cancer (CC). However, the roles and underlying molecular mechanisms of lncRNAs in CC remain unclear. In the current study, we discovered a new lncRNA MIR210HG which was upregulated in CC tissues through microarray. The upregulation of MIR210HG was associated with advanced FIGO stage, metastasis, and poor prognosis in CC patients. Function assays showed that MIR210HG inhibition significantly suppressed the proliferation, invasion, and epithelial-mesenchymal transition (EMT) processes in CC and reduced tumor growth in vivo. Mechanistically, we identified that MIR210HG might serve as a competing endogenous RNA (ceRNA) of miR-503-5p to relieve the repressive effect of miR-503-5p on TRAF4 expression in CC cells. In conclusion, we demonstrated that MIR210HG promoted CC progression through regulating the MIR210HG/miR-503-5p/TRAF4 axis, indicating that MIR210HG might act as a novel insight into CC treatment.

Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway.

Human epididymis protein 4 (HE4) is well known to be a predictor of ovarian cancer clinically. HE4 is reported to play crucial roles in ovarian cancer progression and metastasis. The purpose of the present study was to explore its biological role and molecular mechanism in ovarian cancer. In our study, we found that expression levels of HE4 in tissues, serum and urine in ovarian cancer were upregulated compared to healthy and benign groups. HE4 expression was elevated in ovarian cancer cells. Knockdown of HE4 dampened cell proliferation and Ki67 expression, as well as enhanced apoptosis, caspase-3 activity and cleaved-caspase-3 expression. In addition, HE4 downregulation repressed invasion and migration capabilities of ovarian cancer cells. Western blot analyses showed that knockdown of HE4 reduced the levels of matrix metalloproteinases (MMP-2 and MMP-9) and inhibited epithelial to mesenchymal transition (EMT) in ovarian cancer cells. In vivo animal experiments revealed that HE4 downregulation constrained the growth of xenograft tumor. Mechanism research showed that knockdown HE4 inhibited the activity of JAK/STAT3 pathway in vitro and in vivo In conclusion, our findings reported that knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway, which provides valuable insights to contribute to develop novel HE4-targeted therapies.

Forkhead box P3 gene silencing inhibits the expression of chemokines and chemokine receptors associated with cell growth, migration, and apoptosis in hepatocellular carcinoma cells.

The aberrant expression of forkhead box P3 (FOXP3) leads to the formation of malignant tumors. FOXP3 expression levels are also elevated in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the effects of FOXP3 silencing on cell proliferation, migration, apoptosis and chemokine/chemokine receptor expression in the MHCC-97H HCC cell line. Three FOXP3 short hairpin (sh)RNA constructs were designed: Sh-FOXP3-1-pGreenPuro, sh-FOXP3-2-pGreenPuro, and sh-FOXP3-3-pGreenPuro. MHCC-97H cells were transfected with shRNA-FOXP3, and the mRNA and protein expression levels of C-X-C motif chemokine (CXC) ligand 12 (CXCL12), CXCL11, CXC receptor 4 (CXCR4) and CXCR7 were measured. Cell Counting Kit-8, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling and Transwell assays were used to evaluate cell proliferation, apoptosis and migration, respectively. Of the three FOXP3 lentivirus carriers constructed, sh-FOXP3-1 significantly reduced FOXP3 expression levels and was chosen for further experiments. sh-FOXP3-1 inhibited cell proliferation, promoted apoptosis and inhibited cell migration compared with the negative control. The mRNA and protein expression levels of CXCL12, CXCL11, CXCR4 and CXCR7 were decreased significantly in response to FOXP3 silencing. FOXP3 silencing may therefore inhibit cell growth, induce apoptosis and inhibit migration in HCC cells, possibly by impairing the chemokine/chemokine receptor axes.

Characterization and health risk assessment of PM2.5-bound polycyclic aromatic hydrocarbons in 5 urban cities of Zhejiang Province, China.

In 2015, we measured polycyclic aromatic hydrocarbons (PAHs) in atmospheric fine particulate matter (PM2.5) collected from 5 cities in Zhejiang Province. The mean toxic equivalent quotient (TEQ) values of benzo(a)pyrene (BaP) ranged between 1.2-3.1 ng/m3. The BaP-TEQ displayed seasonal trends, such that winter > spring and autumn > summer. During the winter, the most abundant individual PAHs were 4-6ring PAHs (84.04-91.65%). The median daily intake of atmospheric PAHs ranged between 2.0-7.4 ng/day for all populations, with seasonal trends identical to that of BaP-TEQ. The 95th incremental lifetime cancer risk (ILCR) values induced by PM2.5-bound PAHs were far lower than 10-6 for all populations. The data suggested that the pollution levels in the 5 Zhejiang Province cities were higher than the Chinese National Ambient Air Quality Standard (NAAQS). In the future, relevant measures should be taken to control atmospheric PAHs, especially 4-6 ring PAHs. The data also revealed no obvious cancer risk for populations residing in these 5 cities of Zhejiang Province.