Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

Nurse-to-patient ratios and readiness for hospital discharge: A moderated mediation model.

AIM: To explore whether and to what extent, nurse-patient assessment differences mediate the association between nurse-to-patient ratios and readiness for hospital discharge, and examine whether nurse-patient characteristics moderate the indirect and/or direct effect of mediation model. DESIGN: A cross-sectional study was carried out from March 2021 to December 2022. METHODS: A total of 523 pairs of gastrointestinal cancer patients with PICC and their nurses were recruited. All the participants were invited to complete the general information questionnaire and the Readiness for Hospital Discharge Scale. Outcome measure was patient-reported readiness for hospital discharge. This study was reported according to the STROBE checklist. RESULTS: The patients reported a low level of readiness for hospital discharge. Nurse-patient assessment differences were positively associated with nurse-to-patient ratios but negatively associated with readiness for hospital discharge. Furthermore, nurse-patient assessment differences fully mediated the effect of nurse-to-patient ratios on readiness for hospital discharge, and age and gender of patients only moderated the indirect path of mediation model.

Boerechalasins A-G, cytochalasans from the fungus Boeremia exigua with anti-inflammatory and cytotoxic activities.

Seven previously undescribed cytochalasans, namely, boerechalasins A-G, together with one analogue, were characterized from the solid culture of the fungus Boeremia exigua. Their structures and absolute configurations were elucidated on the basis of extensive spectroscopic analysis as well as electronic circular dichroism calculations. Remarkably, boerechalasin F possessed an unusual sulfoxide moiety that might be derived from methionine, while boerechalasin G had an unusual 5-methylcyclohexane-1,2,3-triol substituent at N-2 position. Boerechalasins A and E exhibited inhibitory activities against nitric oxide production in LPS-induced RAW264.7 macrophages with IC50 values of 21.9 and 5.7 µM, respectively. Boerechalasin F displayed cytotoxicity against human MCF‒7 cells with an IC50 value of 22.8 µM.

AGR2 and FOXA1 as prognostic markers in ER-positive breast cancer.

BACKGROUND: The prognostic role of either forkhead box A1 (FOXA1) or anterior gradient 2 (AGR2) in breast cancer has been found separately. Considering that there were interplays between them depending on ER status, we aimed to assess the statistical interaction between AGR2 and FOXA1 on breast cancer prognosis and examine the prognostic role of the combination of them by ER status. METHODS: AGR2 and FOXA1 expression in tumor tissues were evaluated with tissue microarrays by immunohistochemistry in 915 breast cancer patients with follow up data. The expression levels of these two markers were treated as binary variables, and many different cutoff values were tried for each marker. Survival and Cox proportional hazard analyses were used to evaluate the relationship between AGR2, FOXA1 and prognosis, and the statistical interaction between them on the prognosis was assessed on multiplicative scale. RESULTS: Statistical interaction between AGR2 and FOXA1 on the PFS was significant with all the cutoff points in ER-positive breast cancer patients but not ER-negative ones. Among ER-positive patients, the poor prognostic role of the high level of FOXA1 was significant only in patients with the low level of AGR2, and vice versa. When AGR2 and FOXA1 were considered together, patients with low levels of both markers had significantly longer PFS compared with all other groups. CONCLUSIONS: There was a statistical interaction between AGR2 and FOXA1 on the prognosis of ER-positive breast cancer. The combination of AGR2 and FOXA1 was a more useful marker for the prognosis of ER-positive breast cancer patients.

Combined low levels of H4K16ac and H4K20me3 predicts poor prognosis in breast cancer.

BACKGROUND: Results of previous studies about the prognostic roles of histone H4 lysine 16 acetylation (H4K16ac) and histone H4 lysine 20 trimethylation (H4K20me3) in breast cancer were inconsistent. Cellular experiments revealed the interplays between H4K16ac and H4K20me3, but no population study explored the interaction between them on the prognosis. METHODS: H4K16ac and H4K20me3 levels in tumors were evaluated by immunohistochemistry for 958 breast cancer patients. Hazard ratios for overall survival (OS) and progression-free survival (PFS) were estimated using Cox regression models. Interaction was assessed on multiplicative scale. Concordance index (C-index) was calculated to verify the predictive performance. RESULTS: The prognostic roles of the low level of H4K16ac or H4K20me3 were significant only in patients with the low level of another marker and their interactions were significant. Moreover, compared with joint high levels of both them, only the combined low levels of both them was associated with a poor prognosis but not the low level of single one. The C-index of the clinicopathological model combined the joint expression of H4K16ac and H4K20me3 [0.739 for OS; 0.672 for PFS] was significantly larger than that of the single clinicopathological model [0.699 for OS, P < 0.001; 0.642 for PFS, P = 0.003] or the model combined with the single H4K16ac [0.712 for OS, P < 0.001; 0.646 for PFS, P < 0.001] or H4K20me3 [0.724 for OS, P = 0.031; 0.662 for PFS, P = 0.006]. CONCLUSIONS: There was an interaction between H4K16ac and H4K20me3 on the prognosis of breast cancer and the combination of them was a superior prognostic marker compared to the single one.

Clinicopathologic features, tumor immune microenvironment and genomic landscape of EBV-related and EBV-unrelated poorly differentiated nonkeratinizing squamous cell carcinoma of the thymus.

OBJECTIVES: Knowledge regarding thymic EBV-related poorly differentiated nonkeratinizing squamous cell carcinoma (PDNKSCC), also known as lymphoepithelial carcinoma (LEC), is extremely limited due to its rarity. MATERIALS AND METHODS: This multi-institutional study enrolled 85 patients with thymic PDNKSCC. DNA in situ hybridization was performed to evaluate the EBV status of all 85 cases. Immunohistochemistry and next generation sequencing were performed to compare the differences in the clinicopathological and molecular features between EBV-related and EBV-unrelated PDNKSCC. Tumor-infiltrating lymphocytes (TILs) were also analyzed by these methods. RESULTS: The 85 cases were classified into 27 EBV-related PDNKSCCs (31.8 %) and 58 EBV-unrelated PDNKSCCs (68.2 %) according to the EBV status, and 35 Lymphoepithelioma pattern (LP) (41.2 %) and 50 desmoplastic pattern (DP) (58.8 %) according to the histological characteristics. Compared to the EBV-unrelated PDNKSCC, EBV-related PDNKSCC showed a younger patient predominance and more commonly displayed a LP subtype. Additionally, LP-type cases were divided into two groups: Group 1 (EBV-related, 20/85) and Group 2 (EBV-unrelated, 15/85); the DP-type cases were divided into Group 3 (EBV-unrelated, 43/85) and Group 4 (EBV-related, 7/85). The four Groups showed a significant association with patients' OS and PFS. EBV-related PDNKSCC had significantly higher PD-L1 + tumor cells (TCs) and PD-L1 + and CD8 + immune cells (ICs) than EBV-unrelated PDNKSCC. The tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was more common in EBV-related PDNKSCC, especially in Group 1(LP and EBV related) with more than 90 % cases belonged to TMIT I. Molecular analysis demonstrated that EBV-related PDNKSCC had a significantly higher tumour mutational burden and frequency of somatic mutations than EBV-unrelated cases. CONCLUSIONS: EBV-related PDNKSCC, especially the Group 1, could be a candidate for immunotherapy and EBV positivity may provide an indication for the selection of targeted therapy due to their high tumour mutational burden.

Diagnostic performance of CA125, HE4, ROMA, and CPH-I in identifying primary ovarian cancer.

AIMS: To evaluate the ability of carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), and Copenhagen Index (CPH-I) to identify primary ovarian cancer (OC) from borderline and benign ovarian tumors (OTs) and explore ideal cutoff points. METHODS: A total of 684 OTs containing 276 OC patients, 116 ovarian borderline OTs and 292 benign OTs patients who underwent surgery in our hospital were included. We retrospectively searched the results of CA125 and HE4 before patients' surgery from the hospital's electronic medical records system. ROMA and CPH-I were calculated according to their menopausal status and age, respectively. Diagnostic performance of these four were assessed by drawing receiver operating characteristic (ROC) curves. RESULTS: CA125, HE4, ROMA, and CPH-I were all significantly higher in OC women compared with borderline OTs (p < 0.001), followed by benign OTs (p < 0.001). Area under the curves (AUCs) for distinguishing OC were 0.850 (0.818-0.882), 0.891 (0.865-0.916), 0.910 (0.888-0.933) and 0.906 (0.882-0.930), respectively, and the corresponding ideal cutoff values for CA125, HE4, ROMA, and CPH-I were 132.5, 68.6, 23.8, and 6.4, respectively. The difference between ROMA and CPH-I was not significant (p = 0.97), but both were higher than CA125 and HE4 (p < 0.05). HE4 showed a significantly higher AUC than CA125 (p < 0.05). For postmenopausal women, CA125 performed equivalently to ROMA (p = 0.73) and CPH-I (p = 0.91). CONCLUSIONS: In identifying patients with OC, ROMA and CPH-I outperformed single tumor marker. The diagnostic performance of HE4 was significantly higher than that of CA125. CA125 was more suitable for postmenopausal women.

GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization.

Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.

Thorax radiotherapy using 18F-positron emission tomography/computed tomography-guided precision radiotherapy is a prognostic factor for survival in patients with extracranial oligometastatic non-small cell lung cancer:A two-center propensity score-matched analysis.

Background: This retrospective study compared positron emission tomography (PET)/computed tomography (CT) and CT in the treatment of extracranial oligometastatic non-small-cell lung cancer (NSCLC) and explored the impact of thorax radiotherapy (TRT) on patient survival. Methods: We reviewed the medical records of Chinese patients with stage IV extracranial oligometastatic NSCLC who underwent PET/CT or CT at two centers. Propensity score matching (PSM) was used to control differences in patient characteristics between the maintenance chemotherapy alone and TRT plus maintenance chemotherapy groups. Results: We analyzed 192 eligible patients. The median survival time was better in patients who received PET/CT than in those who only received CT (n = 192, 16 months vs. 6 months, p<0.001). Subgroup analysis showed the median survival time was significantly longer in the TRT plus maintenance group than in the chemotherapy alone group in patients who underwent PET/CT examinations (n = 94, 25 months vs. 11 months, p<0.001). However, there was no statistical difference in survival between both groups in patients who underwent CT examinations (n = 98, 8 months vs. 5 months, p = 0.180). A multifactorial analysis revealed a more favorable prognosis in patients who underwent PET/CT evaluation (HR: 0.343, 95% CI: 0.250-0.471, p <0.001) and TRT (HR: 0.624, 95% CI: 0.464-0.840, p = 0.002), than in those who did not. PSM was consistent with these results. Conclusions: PET/CT-guided TRT is associated with improved clinical outcomes in patients with stage IV extracranial oligometastatic NSCLC.

Association of H3K9me3 with breast cancer prognosis by estrogen receptor status.

BACKGROUND: Cellular experiments revealed that a decreased histone H3 lysine 9 trimethylation (H3K9me3) level was associated with the upregulation of oncogenes in breast cancer cells. Moreover, the role of H3K9me3 in breast cancer was closely associated with estrogen receptor (ER) status. Therefore, we aimed to examine the prognostic value of H3K9me3 on breast cancer by ER status. The level of H3K9me3 in tumors were evaluated with tissue microarrays by immunohistochemistry for 917 women diagnosed with primary invasive breast cancer. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) were estimated using Cox regression models. Interaction between H3K9me3 and ER on the prognosis was assessed on multiplicative scale. RESULTS: The level of H3K9me3 in tumor tissues was lower than that in adjacent tissues. The high level of H3K9me3 was associated with a better OS (HR = 0.43, 95% CI: 0.21-0.86) and PFS (HR = 0.49, 95% CI: 0.29-0.81) among only ER-positive but not ER-negative tumors. Moreover, the interaction between the level of H3K9me3 and ER status (negative and positive) on the prognosis was significant (Pinteraction = 0.011 for OS; Pinteraction = 0.022 for PFS). Furthermore, the ER-positive tumors were stratified by ER-low and ER-high positive tumors, and the prognostic role of H3K9me3 was significant among only ER-high positive patients (HR = 0.34, 95% CI: 0.13-0.85 for OS; HR = 0.47, 95% CI: 0.26-0.86 for PFS). CONCLUSIONS: Our study showed that the prognostic value of H3K9me3 on breast cancer was related to ER status and expression level, and the high level of H3K9me3 was associated with a better prognosis among ER-positive tumors, particularly ER-high positive tumors.

Vascular toxicity of multi-walled carbon nanotubes targeting vascular endothelial growth factor.

Multiwalled carbon nanotubes (MWCNTs) are currently widely used and are expected to be used as drug carriers and contrast agents in clinical practice. Previous studies mainly focused on their lung toxicity; therefore, their effects on the vascular endothelium are unclear. In this study, a human angiogenesis array was used to determine the effect of MWCNTs on the expression profile of angiogenic factors in endothelial cells and to clarify the role of vascular endothelial growth factor (VEGF) in MWCNT-induced endothelial cell injury at the cellular and animal levels. The results indicated that MWCNTs (20-30 nm and 30-50 nm) could enter endothelial cells and disrupt human umbilical vein endothelial cell (HUVECs) activity in a concentration-dependent manner. MWCNTs disrupted the tube formation ability and cell migration function of HUVECs. The results from a Matrigel Plug experiment in mice showed that angiogenesis in the MWCNT experimental group was significantly reduced. The results of a protein chip analysis indicated that VEGF expression in the MWCNT treatment group was decreased, a finding that was validated by ELISA results. The protein expression levels of AKT and eNOS in the MWCNT treatment group were significantly decreased; the administration of recombinant VEGF significantly alleviated the migration ability and tube formation ability of endothelial cells injured by MWCNTs, upregulated the protein expression of AKT and eNOS, and increased the number of neovascularization in mice in the MWCNT treatment group. This study demonstrated that MWCNTs affect angiogenesis via the VEGF-Akt-eNOS axis which can be rescued by VEGF endothelial treatment.

Prognostic value of glutaminase 1 in breast cancer depends on H3K27me3 expression and menopausal status.

Glutaminase 1 (GLS) is a therapeutic target for breast cancer; although GLS inhibitors have been developed, only a few subjects responded well to the therapy. Considering that the expression of histone H3 lysine 27 trimethylation (H3K27me3) and menopausal status was closely linked to GLS, we examined the effects of H3K27me3 and menopausal status on GLS to breast cancer prognosis. Data for 962 women diagnosed with primary invasive breast cancer were analyzed. H3K27me3 and GLS expression in tumors were evaluated with tissue microarrays by immunohistochemistry. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival and progression-free survival were estimated using Cox regression models. Statistical interaction was assessed on multiplicative scale. There was a beneficial prognostic effect of GLS expression on overall survival for those with low H3K27me3 level (HR = 0.50, 95% CI: 0.20-1.28) but an adverse prognostic effect for those with high H3K27me3 level (HR = 3.90, 95% CI: 1.29-11.78) among premenopausal women, and the statistical interaction was significant (Pinteraction = 0.003). Similar pattern was further observed for progression-free survival (HR = 0.44, 95% CI: 0.20-0.95 for low H3K27me3 level, HR = 1.35, 95% CI: 0.74-2.48 for high H3K27me3 level, Pinteraction = 0.024). The statistical interaction did not occur among postmenopausal women. Our study showed that the prognostic effects of GLS on breast cancer correlated to the expression level of H3K27me3 and menopausal status, which would help optimize the medication strategies of GLS inhibitors.

Time-varying effects of FOXA1 on breast cancer prognosis.

PURPOSE: Results of previous studies on the associations between Forkhead box A1 (FOXA1) expression in breast cancer tissues and the prognosis varied depending on the follow-up durations. The present study would investigate whether there is a time-varying effect of FOXA1 in breast cancer tissues on the prognosis. METHODS: FOXA1 expressions were evaluated in 1041 primary invasive breast tumors with tissue microarrays by immunohistochemistry. Cox models with restricted cubic splines and Kaplan-Meier survival analysis were used to examine the associations between FOXA1 and the prognosis. Flexible parametric models were applied to explore the time-varying effect of FOXA1. RESULTS: Overall, the association between FOXA1 expression and the prognosis was not significant but varied on the time of follow-up. Compared to FOXA1 ≤ 270 of H-score, the hazard ratios (HRs) of death for those with 271-285 of FOXA1 expression increased from 0.35 (95% CI 0.14-0.86) at 6 months after diagnosis to 2.88 (95% CI 1.35-6.15) at 120 months with a crossover at around 36 months. Similar patterns were also observed for FOXA1 > 285 of H-score and for progression free survival (PFS). Moreover, when allowed both FOXA1 and estrogen receptor (ER) to change over time in the model (considering that ER had a similar time-varying effect), these time-varying effects remained for FOXA1 on both overall survival (OS) (P < 0.01) and PFS (P = 0.01) but were attenuated for ER (P = 0.13 for OS). CONCLUSIONS: This study revealed an independent time-varying effect of FOXA1 on breast cancer prognosis, which would provide an insight into the roles of FOXA1 as a marker of breast cancer prognosis and may help optimize the medication strategies.

Adenovirus Infection-associated Central Nervous System Disease in Children.

BACKGROUND: Adenovirus (Adv) is a frequent etiology of acute respiratory tract infections. Although rare, neurologic manifestations are known to occur during Adv infection. METHODS: We retrospectively analyzed clinical, laboratory, outcome and the relationship between clinical characteristics and viral detection results in the cerebrospinal fluid (CSF) in children with Adv-associated central nervous system (CNS) dysfunction. RESULTS TWENTYONE: (1.5%) cases had Adv-associated CNS manifestations. The median age was 1.4 years and 20 (95%) were less than 5 years of age. Six (28%) were male. The most frequently cited CNS symptoms were altered consciousness (100%) and seizure (14.3%). Fourteen cases (73.7%) had abnormal electroencephalogram examination and 6 cases (37.5%) had abnormal imaging. None of the patients had received cidofovir administration. Twenty children recovered without sequelae and 1 patient died of respiratory failure. Patients with positive Adv polymerase chain reaction (n = 11) presented lower onset age compared with that of patients with negative Adv polymerase chain reaction (n = 10) in the CSF. Clinical manifestation, laboratory findings, imaging studies and electroencephalogram showed no significant difference between the 2 groups. CONCLUSION: Adv is a rare cause of CNS disease in children, mainly causing altered consciousness. Adv was detected in more cases in the respiratory tract than the CSF, but the majority of patients had the virus detected in both. The lack of Adv in the CSF does not exclude CNS involvement. Furthermore, the viral detection results in the CSF do not seem useful as an indicator of the severity of CNS disease.

EBV-miR-BART10-3p and EBV-miR-BART22 promote metastasis of EBV-associated gastric carcinoma by activating the canonical Wnt signaling pathway.

PURPOSE: Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) constitutes the largest subpopulation in EBV-associated tumors worldwide. To date, 44 mature EBV-encoded microRNAs (EBV miRNAs) have been identified, but their roles in EBVaGC development are still poorly understood. In this study, we aimed to investigate the roles and targets of ebv-miR-BART10-3p (BART10-3p) and ebv-miR-BART22 (BART22) in EBVaGC. METHODS: EBV miRNA expression in EBVaGCs was evaluated by deep sequencing and qRT-PCR, and relationships between BART10-3p or BART22 expression and clinicolpathological characteristics and survival rates of patients with EBVaGC were analyzed. The roles of BART10-3p and BART22 and their underlying mechanisms were further investigated through exogenous overexpression or silencing in EBVaGC cells, and validated in clinical EBVaGC tissue samples. RESULTS: BART10-3p and BART22 were found to be highly expressed in the EBVaGC cell lines SNU719 and YCCEL1. Higher expression of BART10-3p or BART22 in primary EBVaGC samples was significantly associated with lymph node metastasis and a worse 5-year overall survival. BART10-3p and BART22 promoted cell migration and invasion by targeting adenomatous polyposis coli (APC) and Dickkopf 1 (DKK1), thereby activating the Wnt signaling pathway and, consequently, upregulating downstream Twist and downregulating downstream E-cadherin. In 874 primary gastric carcinoma samples, APC and DKK1 were found to be lower expressed in EBVaGC than in EBV-negative samples, and their expression levels were inversely correlated with those of BART10-3p and BART22 in 71 EBVaGC samples. CONCLUSIONS: From our data we conclude that BART10-3p and BART22 play vital roles in promoting EBVaGC metastasis by targeting APC and DKK1 and, subsequently, activating the Wnt signaling pathway, thereby providing novel prognostic biomarkers and potential therapeutic targets for EBVaGC.

Treatment patterns and survival after 18F-fluorodeoxyglucose positron emission tomography/computed tomography-guided local consolidation therapy for oligometastatic non-small cell lung cancer: a two-center propensity score-matched analysis.

PURPOSE: In this retrospective study, we evaluated the treatment patterns and survival after positron emission tomography-computed tomography (PET/CT)-guided local consolidation therapy (LCT) for oligometastatic non-small cell lung cancer (NSCLC). METHODS: We reviewed the medical records of Chinese patients with oligometastatic stage IV non-small cell lung cancer (≤ 5 metastases) who had undergone PET/CT and were eligible for systemic therapy at two centers between May 2005 and August 2019. Propensity score matching (1:1) was used to reduce selection bias and imbalanced distribution of confounding factors. RESULTS: We identified 84 eligible patients and used propensity scores to create well-matched groups of 35 patients who did or did not undergo LCT. Among all patients, the 1-year overall survival (OS) rate was 47.6% and the 2-year OS rate was 22.6%. Relative to the group that did not receive LCT, the LCT group had a significantly higher OS rate (13 months vs. 7 months, p = 0.002). The two groups had similar incidences and classifications of LCT-related side effects. In multivariable analysis, LCT was found to be strongly associated with a favorable OS (hazard ratio: 0.508, 95% confidence interval: 0.311-0.828, p = 0.001). CONCLUSION: We concluded that LCT was significantly associated with improved clinical outcomes among the Chinese patients with oligometastatic NSCLC who were eligible for systemic treatment and could undergo PET/CT evaluation.

Influence of rutin on the effects of neonatal cigarette smoke exposure-induced exacerbated MMP-9 expression, Th17 cytokines and NF-κB/iNOS-mediated inflammatory responses in asthmatic mice model.

Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects. We investigated the ability of rutin to modulate T-cells and inhibit inflammation in experimentally-induced asthma in cigarette smoke exposed mice. Separate groups of neonatal mice were exposed to CS for 10 days from post-natal days 2 to 11. After 2 weeks, the mice were sensitized and challenged with ovalbumin (OVA). Treatment group were given rutin (37.5 or 75 mg/kg body weight) during OVA sensitization and challenge. Rutin treatment was found to significantly inhibit cellular infiltration in the airways and Th2 and Th17 cytokine levels as well. Flow cytometry revealed effectively raised CD4+CD25+Fox3+ Treg cells and supressed Th17 cell population on rutin treatment. Airway hyper-responsiveness observed following CS and OVA challenge were inhibited by rutin. NF-κB and iNOS, chief regulators of inflammatory responses robustly activated by CS and OVA were down-regulated by rutin. Rutin also inhibited the expression of matrix metalloproteinase 9, thereby aiding in prevention of airway remodelling in asthma thereby revealing to be a potent candidate in asthma therapy.

A novel "signal-on" photoelectrochemical sensor for ultrasensitive detection of alkaline phosphatase activity based on a TiO2/g-C3N4 heterojunction.

The use of alkaline phosphatase (ALP) as a biomarker in some diseases including hepatitis, obstructive jaundice, osteoblastic bone cancer, and osteomalacia is important in clinical diagnosis. Furthermore, ALP activity detection is an essential hot topic in environmental monitoring, biomedical research, and other research fields. In this study, a novel "signal-on" photoelectrochemical (PEC) biosensor based on the ALP-catalyzed phosphorylation reaction was designed to sensitively detect ALP activity. In this design, ascorbic acid-an electron donor-was catalytically produced by ALP from l-ascorbic acid 2-phosphate trisodium salt in situ, which results in an increased photocurrent response signal. For immobilizing the ALP on the electrode surface, poly diallyl dimethyl ammonium chloride was used for the conjugation of ALP, and titanium dioxide (TiO2)-a photoactive material-and graphite-like carbon nitride (g-C3N4) nanocomposites were prepared and characterized. TiO2 attached on g-C3N4 plays an important role for the biosensing purpose due to their good biocompatibility and chemical/thermal stability, while g-C3N4 provides the PEC response signal. Furthermore, the prepared TiO2/g-C3N4 nanocomposites can effectively suppress electron-hole recombinations, improve the excitation conversion efficiency, and make the best use of solar energy. The PEC biosensor for ALP activity detection displays a detection limit of 0.03 U L-1 (S/N = 3), which offers a new route for the ALP activity assay in human serum samples.

FOXM1 promotes proliferation in human hepatocellular carcinoma cells by transcriptional activation of CCNB1.

The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression, including human hepatocellular carcinoma (HCC). However, the regulatory role and underlying mechanisms of FOXM1 is still limited. Here, we found that the high level expression of FOXM1 and CCNB1 is closely associated with poor prognosis in HCC patients. And FOXM1 and CCNB1 were overexpressed concomitantly in liver tumor tissues. Knockdown of FOXM1 significantly inhibited the expression levels of CCNB1 in HCC cell lines at both the mRNA and protein levels. Mechanistic studies revealed that FOXM1 binds directly to the promoter region of CCNB1 and regulates the expression levels of the CCNB1 gene in the transcriptional level. Furthermore, the loss of functional and rescue experiments showed that CCNB1 is essential for FOXM1-driven proliferation in HCC cells. In the present study, our results partially explained the dysregulated expression of FOXM1 play an important role in proliferation of human hepatocellular carcinoma cells via transcriptional activation of CCNB1 expression. And it also highlights a FOXM1/CCNB1 axis could be a potential target for the treatment of HCCs.

LncRNA Gas5 acts as a ceRNA to regulate PTEN expression by sponging miR-222-3p in papillary thyroid carcinoma.

Accumulating evidence demonstrates that the long non-coding RNA Growth Arrest-Specific 5 (Gas5) has practical significance in cancer progression and metastasis. However, its role and function in papillary thyroid carcinoma (PTC) remains unknown. In this study, we aimed to explore the potential involvement of Gas5 in papillary thyroid carcinogenesis and to highlight the emerging roles of ceRNAs in the biological regulation of PTC cells. The results suggested that Gas5 was markedly downregulated in both PTC tissues and PTC cell lines. Over-expression of Gas5 remarkably suppressed PTC cells proliferation in vitro and inhibited the growth of tumor cells in vivo likewise. Furthermore, Gas5 was identified as a target of miR-222-3p which was aberrantly high in PTC cells. Enhanced expression of miR-222-3p promoted the proliferation of PTC cells while knocking down miR-222-3p could inhibit it. The advanced effects of miR-222-3p on the proliferation of PTC cells could be partly reversed by the upregulation of Gas5 expression. Furthermore, we validated that Gas5 increased the protein level of the PTEN, one of miR-222-3p's targets, which further activated PTEN/AKT pathway. Taken together, our study identified a tumor suppressive role of Gas5 in PTC cells acting as a ceRNA, effectively becoming a sink for miR-222-3p, modulating the expression of PTEN, which lead to PTEN/AKT pathway activation and proliferation suppression. This finding may offer a new potential therapeutic strategy for PTC.