Ambient fine particulate matter and allergic symptoms in the middle-aged and elderly population: results from the PIFCOPD study.

BACKGROUND: The associations between short- and long-term exposure to ambient fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) and allergic symptoms in middle-aged and elderly populations remain unclear, particularly in China, where most cities have severe air pollution. METHODS: Participants (n = 10,142; age = 40-75 years) were recruited from ten regions in China from 2018 to 2021 for the Predictive Value of Inflammatory Biomarkers and Forced Expiratory Volume in 1 s (FEV1) for Chronic Obstructive Pulmonary Disease (PIFCOPD) study. Short-term (lag0 and lag0-7 day) and long-term (1-, 3- and 5-year) PM2.5 concentrations at residences were extracted from the air pollutant database known as Tracking Air Pollution (TAP) in China. Multivariate logistic regression models were used to estimate associations for short- and long-term PM2.5 exposure concentrations and long-term exposure models were additionally adjusted for short-term deviations. RESULTS: A 10 µg/m3 increase in PM2.5 on the day the allergic symptoms questionnaire was administered (lag0 day) was associated with higher odds of allergic nasal (1.09, 95% CI 1.05, 1.12) and eye symptoms (1.08, 95% CI 1.05, 1.11), worsening dyspnea caused by allergens (1.06, 95% CI 1.02, 1.10), and ≥ 2 allergic symptoms (1.07, 95% CI 1.03, 1.11), which was similar in the lag0-7 day concentrations. A 10 µg/m3 increase in the 1-year average PM2.5 concentration was associated with an increase of 23% for allergic nasal symptoms, 22% for eye symptoms, 20% for worsening dyspnea caused by allergens, and 21% for ≥ 2 allergic symptoms, similar to the 3- and 5-year average PM2.5 concentrations. These associations between long-term PM2.5 concentration and allergic symptoms were generally unchanged after adjustment for short-term deviations. CONCLUSIONS: Short- and long-term exposure to ambient PM2.5 was associated with an increased risk of allergic nasal and eye symptoms, worsening dyspnea caused by allergens, and ≥ 2 allergic symptoms. TRIAL REGISTRATION: Clinical trial ID: NCT03532893 (29 Mar 2018).

PLK3 promotes the proneural-mesenchymal transition in glioblastoma via transcriptional regulation of C5AR1.

BACKGROUND: Accumulating evidence suggests that polo-like kinase 3 (PLK3) plays an essential role in tumor cells and induces cell proliferation and may have implications for the prognosis of various cancers. We sought to define the role of PLK3-dependent proneural-mesenchymal transition (PMT) in the glioblastoma (GBM) therapy. METHODS AND RESULTS: We analyzed the expression data for PLK3 by using the TCGA database. PLK3 expression in GBM cell lines was determined by qRT-PCR and Western blotting. PLK3 levels were modulated using Lentivirus infection, and the effects on symptoms, tumor volume, and survival in mice intracranial xenograft models were determined. Irradiation (IR) was performed to induce PMT. PLK3 expression was significantly elevated in mesenchymal subtype GBM and promoted tumor proliferation in GBM. Additionally enriched PLK3 expression could be associated with poor prognosis in GBM patients compared with those who have lower PLK3 expression. Mechanically, PLK3-dependent PMT induced radioresistance in GBM cells via transcriptional regulation of complement C5a receptor 1 (C5AR1). In therapeutic experiments conducted in vitro, targeting PLK3 by using small molecule inhibitor decreased tumor growth and radioresistance of GBM cells both in vitro and in vivo. CONCLUSIONS: PLK3-C5AR1 axis induced PMT thus enhanced radioresistance in GBM and could become a novel potential therapeutic target for GBM.

Bioaccumulation, biomagnification, and ecological risk of trace metals in the ecosystem around oilfield production area: A case study in Shengli Oilfield.

The production for crude oil usually leads to contamination of the soil with trace metals and organic contaminants from spilled petroleum. Organic contaminants were generally paid more attention than trace metals in the oilfield pollution. Many studies have investigated the impacts of some petroleum hydrocarbon pollutants, however, the impacts and risk assessment of trace metals remain largely unexplored. Moreover, under some circumstances, the risks associated with trace metals are not necessarily lower than those associated with organic contaminants. This study aimed to investigate methods to evaluate the possible risks associated with 11 trace metals (Ti, Ba, Sr, Rb, V, Li, Mo, Co, Cs, Bi, and Tl) in soil and biota samples from the Shengli Oilfield using ICP-MS. The results showed that 11 trace metals in the surface soils exceeded the local background levels. The geo-accumulation index (Igeo) indicated that the soils had light-moderate to moderate contamination levels, with higher Igeo value of Ba, V, Li, Mo, Co, and Cs. The individual potential ecological risk indices ([Formula: see text]) demonstrated moderate Bi and Tl pollution in soils. Comparatively, the [Formula: see text] is recommended for the risk assessment of trace metals on the ecosystem around the oilfield area. Mo, Bi, and Sr easily accumulate in plants, as reflected by their bioaccumulation factor. Ti, Ba, V, Li, Co, Cs, Bi, and Tl exhibited considerable biomagnification, particularly in birds. In this study, trace metals showed considerable bioaccumulation and biomagnification, and the risks of these trace metals on the ecosystem around oilfield production area need more attention.

The formation mechanism and homeostasis of extrachromosomal DNA.

Extrachromosomal DNA, referred to as extrachromosomal DNA (ecDNA), was found in most cancers and nearly absent in normal cells. The properties of ecDNA enable tumor cells to be more responsive to various environments. The non-Mendelian genetic mechanism of ecDNA could arouse increasing tumor heterogeneity. Besides, ecDNA would promote tumor invasiveness and provide resistance mechanisms associated with poorer survival consequences. Furthermore, ecDNA could profoundly impact oncogene activation, genome instability, tumor heterogeneity, etc. Consequently, they may offer potential possibilities for tumor diagnosis and therapeutics. We primarily reviewed the classification, several primary formation mechanisms, homeostasis maintenance and frontier progress of ecDNA and late emphasized its fundamental roles in tumorigenesis and put forward some new insights.

A yes-associated protein 1- Notch1 receptor positive feedback loop promotes breast cancer lung metastasis by attenuating the bone morphogenetic protein 4-SMAD family member 1/5 signaling.

The Notch1 (Notch1 receptor) and yes-associated protein 1 (YAP1) signaling can regulate breast cancer metastasis. This study aimed at investigating whether and how these two signal pathways crosstalk to promote breast cancer lung metastasis. Here, we show that YAP1 expression was positively correlated with Notch1 in breast cancer according to bioinformatics and experimental validation. Mechanistically, YAP1 with TEA domain transcription factors (TEADs) enhanced Jagged1(JAG1)-Notch1 signaling. Meanwhile, Notch1 promoted YAP1 stability in breast cancer cells by inhibiting the ß-TrCP-mediated degradation, thereby, forming a YAP1- JAG1/Notch1 positive feedback loop in breast cancer. Furthermore, YAP1 enhanced the mammosphere formation and stemness of MDA-MB-231 cells by attenuating the inhibition of the BMP4-SMAD1/5 signaling. In vivo, the YAP1- JAG1/Notch1 positive feedback loop promoted the lung colonization of MDA-MB-231 cells. Our data for the first time indicate that the YAP1-Notch1 positive feedback loop promotes lung metastasis of breast cancer by modulating self-renewal and inhibiting the BMP4-SMAD1/5 signaling.

Transmembrane protein 88 inhibits transforming growth factor-ß1-induced-extracellular matrix accumulation and epithelial-mesenchymal transition program in human pleural mesothelial cells through modulating TGF-ß1/Smad pathway.

Pleural fibrosis is an irreversible pathological process occurred in the development of several lung diseases. TMEM88 is a member of transmembrane (TMEM) family and has been found to be involved in the regulation of fibrogenesis. However, the role of TMEM88 in pleural fibrosis remains unknown. In this study, we aimed to explore the role of TMEM88 in pleural fibrosis in vitro using transforming growth factor-ß1 (TGF-ß1)-induced human pleural mesothelial cell line MeT-5A cells. Our results showed that the expression levels of TMEM88 were downregulated in pleural fibrosis tissues and TGF-ß1-treated Met-5A cells. Overexpression of TMEM88 inhibited the proliferation of Met-5A cells under TGF-ß1 stimulation. In addition, TMEM88 overexpression prevented TGF-ß1-induced extracellular matrix (ECM) accumulation and epithelial-mesenchymal transition (EMT) in Met-5A cells with decreased expression levels of Col I and fibronectin, increased levels of cytokeratin-8 and E-cadherin, as well as decreased levels of vimentin and α-SMA. Furthermore, overexpression of TMEM88 inhibited the expression of TGF-ß receptor I (TßRI) and TßRII and suppressed the phosphorylation of Smad2 and Smad3 in Met-5A cells. In conclusion, these results indicated that TMEM88 exhibited an anti-fibrotic activity in pleural fibrosis via inhibiting the activation of TGF-ß1/Smad signaling pathway.

MiR-26a-5p regulates proliferation, apoptosis, migration and invasion via inhibiting hydroxysteroid dehydrogenase like-2 in cervical cancer cell.

BACKGROUND: Evidences have indicated that miR-26a-5p regulates the malignant properties of various tumor cells. However, the influences of miR-26a-5p on proliferation, apoptosis and invasion are still vague in the cervical cancer (CC) cells. METHODS: The miRNA microarray and real-time quantitative PCR (RT-qPCR) analysis were utilized to detect the expression of miR-26a-5p in the patients with CC. Kaplan-Meier plotter was performed to evaluate the overall survival (OS) of the patients with CC. The CCK-8, flow cytometry, transwell and wound healing analyses were respectively used to analyze proliferation, migration and invasion in the CC cells. RT-qPCR, western blot and IHC analysis were executed to measure the expression of hydroxysteroid dehydrogenase like-2 (HSDL2) in the patients with CC. Bioinformatics and luciferase reporter assay were carried out to verify the relationship of miR-26a-5p and HSDL2. RESULTS: The expression of miR-26a-5p was downregulated and low expression of miR-26a-5p indicated a poor OS in patients with CC. Overexpression of miR-26a-5p significantly inhibited proliferation, migration and invasion, accelerated apoptosis in the Hela and C33A cells. The expression of HSDL2 was upregulated, and negatively correlated with miR-26a-5p in the patients with CC. HSDL2 was directly targeted by miR-26a-5p and rescue experiments displayed that HSDL2 partially abolished proliferation, apoptosis, migration, and invasion induced by miR-26a-5p in CC cells. CONCLUSIONS: MiR-26a-5p alleviated progression of CC by suppressing proliferation, migration and invasion, promoting apoptosis through downregulating HSDL2.

Progress on the role of extrachromosomal DNA in tumor pathogenesis and evolution.

The amplification of oncogenes on extrachromosomal DNA (ecDNA) provides a new mechanism for cancer cells to adapt to the changes in the tumor microenvironment and accelerate tumor evolution. These extrachromosomal elements contain oncogenes, and their chromatin structures are more open than linear chromosomes and therefore have stronger oncogene transcriptional activity. ecDNA always contains enhancer elements, and genes on ecDNA can be reintegrated into the linear genome to regulate the selective expression of genes. ecDNA lacks centromeres, and the inheritance from the parent cell to the daughter cell is uneven. This non-Mendelian genetic mechanism results in the increase of tumor heterogeneity with daughter cells that can gain a competitive advantage through a large number of copies of oncogenes. ecDNA promotes tumor invasiveness and provides a mechanism for drug resistance associated with poorer survival outcomes. Recent studies have demonstrated that the overall proportion of ecDNA in tumors is approximately 40%. In this review, we summarize the current knowledge of ecDNA in the field of tumorigenesis and development.

Rh-Catalyzed Decarbonylative Cross-Coupling between o-Carboranes and Twisted Amides: A Regioselective, Additive-Free, and Concise Late-Stage Carboranylation.

The convenient cross-coupling of sp2 or sp3 carbons with a specific boron vertex on carborane cage represents significant synthetic values and insurmountable challenges. In this work, we report an Rh-catalyzed reaction between o-carborane and N-acyl-glutarimides to construct various Bcage -C bonds. Under the optimized condition, the removable imine directing group (DG) leads to B(3)- or B(3,6)-C couplings, while the pyridyl DG leads to B(3,5)-Ar coupling. In particular, an unexpected rearrangement of amide reagent is observed in pyridyl directed B(4)-C(sp3 ) formation. This scalable protocol has many advantages, including easy access, the use of cheap and widely available coupling agents, no requirement of an external ligand, base or oxidant, high efficiency, and a broad substrate scope. Leveraging the RhI dimer and twisted amides, this method enables straightforward access to diversely substituted and therapeutically important carborane derivatives at boron site, and provides a highly valuable vista for carborane-based drug screening.

Metformin suppresses HIF-1α expression in cancer-associated fibroblasts to prevent tumor-stromal cross talk in breast cancer.

The tumor microenvironment (TME) is a crucial factor in cancer progression. In breast cancer, cancer-associated fibroblasts (CAFs) and the derived stromal components have been recognized as comprising the majority of the pathological structure of the TME. In this study, we show that metformin (Met), a diabetes drug, transforms CAFs in the TME. Met disrupts tumor-stromal cross talk by preventing breast cancer cell transforming growth factor-ß (TGF-ß) signaling and the production of stromal-derived factor-1 (SDF-1) and interleukin-8 (IL-8) by CAFs. The suppression of bidirectional signaling between tumor cells and CAFs by Met is attributed to increased phospho-AMP kinase (p-AMPK) levels. By upregulating p-AMPK in CAFs, Met induces prolyl hydroxylases (PHDs), leading to the degradation of hypoxia-inducible factor-1α (HIF-1α) in CAFs. Moreover, interruption of HIF-1α-driven SDF-1 signaling in CAFs by Met leads to decreased breast cancer cell invasion. These findings suggest that Met may be used to target tumor-promoting signaling between CAFs and breast cancer cells in the TME.

The interplay between ATF2 and NEAT1 contributes to lung adenocarcinoma progression.

BACKGROUND: Activating transcription factor 2 (ATF2), a member of the activator protein 1 (AP-1) transcription factor family, has been shown to be involved in the pathobiology of numerous cancers. However, the biological role and mechanism of ATF2 in lung adenocarcinoma (LUAD) remains to be elucidated. METHODS: The expression of ATF2, NEAT1 and miR-26a-5p in LUAD tissues and cell lines was detected by qRT-PCR and western blotting. The interaction between ATF2, NEAT1, and miR-26a-5p was validated by chromatin immunoprecipitation, luciferase reporter assay and RNA immunoprecipitation. Cell proliferation, invasion and tumorigenesis of LUAD cells were analyzed by using CCK8, transwell invasion assay and xenograft tumor model. RESULTS: We confirmed that ATF2 expression was increased in LUAD tissues compared with normal adjacent lung tissues. Functional experiments showed that ATF2 positively regulated cell proliferation and invasion in LUAD cells. Moreover, we identified that NEAT1 expression was increased in LUAD tissues and positively correlated with ATF2 expression. Mechanistically, ATF2 could bind to the promoter of NEAT1 to promote its transcription. Rescue experiments showed that ATF2 exerted its oncogenic function in LUAD, at least, partly through NEAT1 upregulation. In turn, NEAT1 could positively regulate ATF2 expression and form a positive feedback loop in LUAD cells. Furthermore, we demonstrated that NEAT1 positively regulated ATF2 expression via sponging miR-26a-5p. CONCLUSION: ATF2 and NEAT1 form a positive feedback loop mediated by miR-26a-5p and coordinately contribute to LUAD progression.

Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways.

BACKGROUND: It is well established that airway remodeling and inflammation are characteristics for chronic obstructive pulmonary disease (COPD). Moreover, cigarette smoke extract (CSE) promots inflammation, apoptosis and oxidative stress in COPD. And, there is evidence suggested that alantolactone (ALT), a sesquiterpene lactone isolated from Inula helenium, plays an adverse role in inflammation, apoptosis and oxidative stress. However, few studies have investigated the function and mechanism of ALT treatment on the COPD pathological process. METHODS: The levels of IL-1 ß, TNF-α, IL-6 and IFN-γ were examined by ELISA. Cells' apoptosis and caspase-3 activity were detected by Cell Death Detection PLUS enzyme-linked immunosorbent assay and caspase-Glo 3/7 Assay, respectively. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by using MDA and SOD assay kits. Reactive oxygen species (ROS) generation was measured by DCFH-DA assay. Protein expression was assayed by Western blot. RESULTS: In the present study, we aimed to observe the protective effects of ALT against inflammation, apoptosis and oxidative stress in human bronchial epithelial Beas-2B and NHBE cells. Our results showed that different doses of CSE exposure induced Beas-2B and NHBE cell inflammatory cytokines IL-1 ß, TNF-α, IL-6 and IFN-γ expression, cell apoptosis, caspase-3 activity and mediated oxidative stress markers MDA, ROS and SOD levels, while ALT treatment counteracted the effects of CSE. Further studies suggested that ALT attenuated NF-κB pathway activation. ALT also activated the Nrf2/HO-1 signal pathway through promoting Nrf2 nuclear aggregation and downstream HO-1 protein expression. HO-1 inhibitor tin protoporphyrin IX (SnPP IX) reversed the effects of ALT on Beas-2B and NHBE cell inflammation, apoptosis and oxidative stress. CONCLUSIONS: The above results collectively suggested that ALT suppressed CSE-induced inflammation, apoptosis and oxidative stress by modulating the NF-ĸB and Nrf2/ HO-1 axis.

MicroRNA-147b suppresses the proliferation and invasion of non-small-cell lung cancer cells through downregulation of Wnt/ß-catenin signalling via targeting of RPS15A.

Deregulation of microRNAs (miRNAs) leads to malignant growth and aggressive invasion during cancer occurrence and progression. miR-147b has emerged as one of the cancer-related miRNAs that are dysregulated in multiple cancers. Yet, the relevance of miR-147b in non-small-cell lung cancer (NSCLC) remains unclear. In the present study, we aimed to report the biological function and signalling pathways mediated by miR-147b in NSCLC. Our results demonstrate that miR-147b expression is significantly downregulated in NSCLC tissues and cell lines. Overexpression of miR-147b decreased the proliferative ability, colony-forming capability, and invasive potential of NSCLC cells. Notably, our study identified ribosomal protein S15A (RPS15A), an oncogene in NSCLC, as a target gene of miR-147b. Our results showed that miR-147b negatively modulates RPS15A expression in NSCLC cells. An inverse correlation between miR-147b and RPS15A was evidenced in NSCLC specimens. Moreover, miR-147b overexpression downregulated the activation of Wnt/ß-catenin signalling via targeting of RPS15A. Overexpression of RPS15A partially reversed the miR-147b-mediated antitumour effect in NSCLC cells. Collectively, these findings reveal that miR-147b restricts the proliferation and invasion of NSCLC cells by inhibiting RPS15A-induced Wnt/ß-catenin signalling and suggest that the miR-147b/RPS15A/Wnt/ß-catenin axis is an important regulatory mechanism for malignant progression of NSCLC.

Brønsted Basicity in Metal-Organic Framework-808 and Its Application in Base-Free Catalysis.

The Brønsted basicity in activated metal-organic framework-808 (hereinafter denoted as MOF-808a) was confirmed by the analyses of CO2-TPD-MS, in situ DRIFTS, and acid-base titration. MOF-808a exhibited efficient recyclable catalytic activities for Heck coupling and oxidation of alcohol as a one-pot tandem reaction in base-free catalysis. It is the first evidence of the Brønsted basicity in zirconium metal-organic frameworks (Zr-MOFs) and gave rise to a new opportunity to extend the catalytic application of Zr-MOFs.

TLR4 Overexpression Inhibits Endothelial PAS Domain-Containing Protein 1 Expression in the Lower Respiratory Tract of Patients with Chronic COPD.

BACKGROUND/AIMS: The study was designed to explore the potential relationship of TLR4 and endothelial PAS domain-containing protein 1 (EPAS1) in vivo and vitro experiments. METHODS: Bronchoalveolar lavage fluid (BALF) samples were collected from 55 chronic obstructive pulmonary disease (COPD) patients and 25 healthy subjects. The differential cell count was performed using Wright-Giemsa staining. The expression levels of TLR4 and TLR5 were detected by RT-qPCR. The levels of methylation and mRNA expression of EPAS1 were assayed by bisulfite sequencing PCR and real-time PCR. The correlation of TLR4 and EPAS1 was also analyzed in TLR 4-overexpressing endothelial cells. RESULTS: The results showed that the number of neutrophils, lymphocytes and macrophages and expression of TLR 4 were significantly increased in lower respiratory tract of COPD patients. Moreover, decreased EPAS1 mRNA and increased EPAS1 promoter methylation were detected in COPD, which were closely associated with increased TLR4 expression. According to in vitro experiments, TLR 4 inhibited EPAS1 mRNA expression and promoted promoter methylation in endothelial cells. CONCLUSION: These findings suggest that TLR4 over-expression decreased EPAS1expression which contributes to the progress of COPD.

Cigarette smoke extract-treated mast cells promote alveolar macrophage infiltration and polarization in experimental chronic obstructive pulmonary disease.

OBJECTIVE: Cigarette smoking is the main cause of chronic obstructive pulmonary disease (COPD) and may modulate the immune response of exposed individuals. Mast cell function can be altered by cigarette smoking, but the role of smoking in COPD remains poorly understood. The current study aimed to explore the role of cigarette smoke extract (CSE)-treated mast cells in COPD pathogenesis. METHODS: Cytokine and chemokine expression as well as degranulation of bone marrow-derived mast cells (BMMCs) were detected in cells exposed to immunoglobulin E (IgE) and various doses of CSE. Adoptive transfer of CSE-treated BMMCs into C57BL/6J mice was performed, and macrophage infiltration and polarization were evaluated by fluorescence-activated cell sorting (FACS). Furthermore, a coculture system of BMMCs and macrophages was established to examine macrophage phenotype transition. The role of protease serine member S31 (Prss31) was also investigated in the co-culture system and in COPD mice. RESULTS: CSE exposure suppressed cytokine expression and degranulation in BMMCs, but promoted the expressions of chemokines and Prss31. Adoptive transfer of CSE-treated BMMCs induced macrophage infiltration and M2 polarization in the mouse lung. Moreover, CSE-treated BMMCs triggered macrophage M2 polarization via Prss31 secretion. Recombinant Prss31 was shown to activate interleukin (IL)-13/IL-13Rα/Signal transducers and activators of transcription (Stat) 6 signaling in macrophages. Additionally, a positive correlation was found between Prss31 expression and the number of M2 macrophages in COPD mice. CONCLUSION: In conclusion, CSE-treated mast cells may induce macrophage infiltration and M2 polarization via Prss31 expression, and potentially contribute to COPD progression.

Targeting ENPP1 for cancer immunotherapy: Killing two birds with one stone.

Cancer immunotherapy, particularly with immune checkpoint inhibitors, has revolutionized the paradigm of cancer treatment. Nevertheless, the efficacy of cancer immunotherapy remains limited in most clinical settings due to the lack of a preexisting antitumor T-cell response in tumors. Therefore, the clinical outcomes of cancer immunotherapy must be improved crucially. With increased awareness of the importance of the innate immune response in the recruitment of T cells, as well as the onset and maintenance of the T cell response, great interest has been shown in activating the cGAS-STING signaling pathway to awaken the innate immune response, thereby orchestrating both innate and adaptive immune responses to induce tumor clearance. However, tumor cells have evolved to overexpress ectonucleotide pyrophosphate phosphodiesterase 1 (ENPP1), which degrades the immunotransmitter 2',3'-cGAMP and promotes the production of immune-suppressing adenosine, resulting in inhibition of the anticancer immune response in the tumor microenvironment. Clinically, ENPP1 overexpression is closely associated with poor prognosis in patients with cancer. Conversely, depleting or inhibiting ENPP1 has been verified to elevate extracellular 2',3'-cGAMP levels and inhibit the generation of adenosine, thereby reinvigorating the anticancer immune response for tumor elimination. A variety of ENPP1 inhibitors have recently been developed and have demonstrated significant promise for cancer immunotherapy. In this review, we provide an overview of ENPP1, dissect its immunosuppressive mechanisms, and discuss the development of ENPP1 inhibitors with the potential to further improve the efficacy of cancer immunotherapy.

Factors affecting patient activation among patients with systemic lupus erythematosus.

There are limited published studies on patient activation among patients with systemic lupus erythematosus (SLE) in China. Disease activity can significantly influence a patient's perception of their condition, subsequently impacting patient activation. However, the mechanisms through which disease activity influences patient activation remain poorly understood. This study aimed to investigate patient activation among patients with SLE in China and explore the influencing factors. We conducted a cross-sectional study from June to December 2021 at a rheumatology and immunology department of a tertiary hospital in Chengdu, China. Data were collected by questionnaire, including general information, disease activity, quality of chronic illness care, health literacy, self-efficacy, motivation, social support, and patient activation. A patient activation model was constructed based on the conceptual framework derived from the individual and family self-management theory. To evaluate the moderating effect of disease activity on patient activation model, participants were divided into two subgroups (low disease activity group and high disease activity group). 426 SLE patients were included. The mean score of patient activation among SLE patients was 63.28 ± 11.82, indicating that most SLE patients lacked skills and confidence to stick with health-promoting behaviors. Health literacy, social support, and self-efficacy had the greatest effect on patient activation. In the multi-group analysis, social support and health literacy contributed more to patient activation in SLE patients with high and low disease activity, respectively. Patient activation among SLE patients in China was at the third level. Healthcare professionals should help them adhere to health-promoting behaviors. Health literacy, social support, and self-efficacy are vital factors for patient activation. These factors should be prioritized based on disease activity when developing individually tailored interventions for patient activation.

VEGFA/NRP-1/GAPVD1 axis promotes progression and cancer stemness of triple-negative breast cancer by enhancing tumor cell-macrophage crosstalk.

Triple-negative breast cancer (TNBC) has long been considered a major clinical challenge due to its aggressive behavior and poor prognosis. Cancer stem cells (CSCs) are known as the main cells responsible for tumor origination, progression, recurrence and metastasis. Here, we report that M2-type tumor-associated macrophages (TAMs) contribute to cancer stemness in TNBC cells via the secretion of VEGFA. Reciprocally, elevated VEGFA expression by TAM-educated TNBC cells acts as a regulator of macrophage polarization, therefore constitute a feed-back loop between TNBC cells and TAMs. Mechanistically, VEGFA facilitates the CSC phenotype via the NRP-1 receptor and downstream GAPVD1/Wnt/ß-catenin signaling pathway in TNBC cells. Our study underscores the crosstalk between TNBC cells and TAMs mediated by VEGFA and further clarifies the role and underlying mechanisms of the VEGFA/NRP-1/GAPVD1 axis in regulating cancer stemness. We also document an immunosuppressive function of VEGFA in the tumor microenvironment (TME). Therefore, the present study indicates crosstalk between TNBC cells and TAMs induced by VEGFA and provides a potential implication for the combination of immunotherapy and VEGFA-targeted agents in TNBC therapy.

Metformin suppresses NFE2L1 pathway activation to inhibit gap junction beta protein expression in NSCLC.

OBJECTIVE: Non-small-cell lung cancer (NSCLC) is a deadly form of cancer that exhibits extensive intercellular communication which contributed to chemoradiotherapy resistance. Recent evidence suggests that arrange of key proteins are involved in lung cancer progression, including gap junction proteins (GJPs). METHODS AND RESULTS: In this study, we examined the expression patterns of GJPs in NSCLC, uncovering that both gap junction protein, beta 2 (GJB2) and gap junction protein, beta 2 (GJB3) are increased in LUAD and LUSC. We observed a correlation between the upregulation of GJB2, GJB3 in clinical samples and a worse prognosis in patients with NSCLC. By examining the mechanics, we additionally discovered that nuclear factor erythroid-2-related factor 1 (NFE2L1) had the capability to enhance the expression of connexin26 and connexin 31 in the NSCLC cell line A549. In addition, the use of metformin was discovered to cause significant downregulation of gap junction protein, betas (GJBs) by limiting the presence of NFE2L1 in the cytoplasm. CONCLUSION: This emphasizes the potential of targeting GJBs as a viable treatment approach for NSCLC patients receiving metformin.