Cancer stem cells (CSCs) are associated with cancer recurrence and metastasis. Prostate cancer cells often metastasize to the bone with a complex microenvironment of cytokines favoring cell survival. In this study, the cell stemness influence of a group of interleukins including IL-3, 6, 10, 11 and 24 on human prostate cancer cell lines LNCaP and PC-3 was explored in vitro. Sulforhodamine B(SRB) and 5-ethynyl-2'-deoxyuridine (EdU) assays were applied to examine the effect on cell proliferation, and wound healing and transwell assays were used for migration and invasion studies, in addition to colony formation, Western blotting and flowcytometry for the expression of stemness factors and chemotherapy sensitivity. We observed that ILs-3, 6 and 11 stimulated while ILs-10 and 24 inhibited the growth, invasion and migration of both cell lines. Interestingly, ILs-3, 6 and 11 significantly promoted colony formation and increased the expression of SOX2, CD44 and ABCG2 in both prostate cancer cell lines. However, ILs-10 and 24 showed the opposite effect on the expression of these factors. In line with the above findings, treatment with either IL-3 or IL-6 or IL-11 decreased the chemosensitivity to docetaxel while treatment with either IL-10 or IL-24 increased the sensitivity of docetaxel chemotherapy. In conclusion, our results suggest that ILs-3, 6 and 11 function as tumor promoters while ILs-10 and 24 function as tumor suppressors in the prostate cancer cell lines PC-3 and LNCaP in vitro, and such differences may attribute to their different effect on the stemness of PCa cells.

Bone morphogenetic protein 9 (BMP9) belongs to the transforming growth factor‑β (TGF‑β) superfamily, and has been reported to promote cancer cell proliferation and epithelial‑mesenchymal transition (EMT). Cisplatin (DDP) is the first line treatment for ovarian cancer. However, initiation of EMT confers insensitivity to chemotherapy. The present study aimed to verify and examine the mechanisms underlying the effects of BMP9 on treatment with DDP for ovarian cancer. Prior to treatment with DDP, ovarian cancer cells were exposed to BMP9 for 3 days. Following this, cell viability, apoptosis rate and the extent of DNA damage were evaluated to compare the effects of DDP on BMP9‑pretreated and non‑pretreated ovarian cancer cells. In addition, EMT marker expression was evaluated by western blotting and immunofluorescence. The results demonstrated that BMP9 pretreatment inhibited the cytotoxicity of DDP on ovarian cancer cells. Additionally, BMP9‑pretreated ovarian cancer cells had downregulated expression of the epithelial marker E‑cadherin, which was accompanied by an upregulation of the mesenchymal markers N‑cadherin, Snail, Slug, and Twist. Taken together, the findings of the present study indicated that BMP9 conferred resistance to DDP in ovarian cancer cells by inducing EMT. The present study provided valuable insight into the mechanisms of chemotherapy in ovarian cancer and highlighted the potential of BMP9 as a novel therapeutic target for improving cisplatin chemosensitivity.

Spinal cord stimulation (SCS) has been shown to improve the consciousness levels of patients with disorder of consciousness (DOC). However, the underlying mechanisms of SCS remain poorly understood. This study recorded resting-state electroencephalograms (EEG) from 16 patients with minimally conscious state (MCS), before and after SCS, and investigated the mechanisms of SCS on the neuronal dynamics in MCS patients. Detrended fluctuation analysis (DFA), combined with surrogate data method, was employed to measure the long-range temporal correlations (LRTCs) of the EEG signals. A surrogate data method was utilized to acquire the genuine DFA exponents (GDFAE) reflecting the genuine LRTCs of brain activity. We analyzed the GDFAE in four brain regions (frontal, central, posterior, and occipital) at five EEG frequency bands [delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-45 Hz)]. The GDFAE values ranged from 0.5 to 1, and showed temporal and spatial variation between the pre-SCS and the post-SCS states. We found that the channels with GDFAE spread wider after SCS. This phenomenon may indicate that more cortical areas were engaged in the information integration after SCS. In addition, the GDFAE values increased significantly in the frontal area at delta, theta, and alpha bands after SCS. At the theta band, a significant increase in GDFAE was observed in the occipital area. No significant change was found at beta or gamma bands in any brain region. These findings show that the enhanced LRTCs after SCS occurred primarily at low-frequency bands in the frontal and occipital regions. As the LRTCs reflect the long-range temporal integration of EEG signals, our results indicate that information integration became more "complex" after SCS. We concluded that the brain activities at low-frequency oscillations, particularly in the frontal and occipital regions, were improved by SCS.

Silicosis is a common occupational disease, characterized by silicotic nodules and diffuse pulmonary fibrosis. We demonstrated an anti-fibrotic effect of bone marrow mesenchymal stem cells (BMSCs) in silica-induced lung fibrosis. In the present study, we sought to clarify the homing ability of BMSCs and the specific mechanisms for their effects.

Low-intensity pulsed ultrasound stimulation (LIPUS) has been proven to be a noninvasive method with high spatial resolution and deep penetration. Previous studies have qualitatively demonstrated that the electromyographic response caused by LIPUS in the mouse motor cortex is affected by the anesthetic state of the mice. However, the quantitative relationship between motor response and anesthetic dose remains unclear.

The activities of enzymes are the basis of evaluating the quality of honey. Beekeepers usually use concentrators to process natural honey into concentrated honey by concentrating it under high temperatures. Active enzymes are very sensitive to high temperatures and will lose their activity when they exceed a certain temperature. The objective of this work is to study the kinetic mechanism of the temperature effect on diastase activity and to develop a nondestructive approach for quick determination of the diastase activity of honey through a heating process based on visible and near-infrared (Vis/NIR) spectroscopy. A total of 110 samples, including three species of botanical origin, were used for this study. To explore the kinetic mechanism of diastase activity under high temperatures, the honey of three kinds of botanical origins were processed with thermal treatment to obtain a variety of diastase activity. Diastase activity represented with diastase number (DN) was measured according to the national standard method. The results showed that the diastase activity decreased with the increase of temperature and heating time, and the sensitivity of acacia and longan to temperature was higher than linen. The optimum temperature for production and processing is 60 °C. Unsupervised clustering analysis was adopted to detect spectral characteristics of these honeys, indicating that different botanical origins of honeys can be distinguished in principal component spaces. Partial least squares (PLS) and least squares-support vector machine (LS-SVM) algorithms were applied to develop quantitative relationships between Vis/NIR spectroscopy and diastase activity. The best result was obtained through Gaussian filter smoothing-standard normal variate (GF-SNV) pretreatment and the LS-SVM model, known as GF-SNV-LS-SVM, with a determination coefficient (R²) of prediction of 0.8872, and root mean square error (RMSE) of prediction of 0.2129. The overall results of this paper showed that the diastase activity of honey can be determined quickly and non-destructively with Vis/NIR spectral methods, which can be used to detect DN in the process of honey production and processing, and to maximize the nutrient content of honey.

miR-182 was revealed to be upregulated in colorectal cancer (CRC) and contributed to CRC development. However, the detailed molecular mechanism of miR-182 in the progression of CRC remains largely elusive. Herein, miR-182 was upregulated in CRC serum samples, CRC tissues and cells. miR-182 expression was evidently reduced in postoperative serum samples, compared with preoperative serum samples, whereas miR-182 expression was re-elevated in serum samples from CRC patients who developed postoperative recurrence. Exogenous miR-182 promoted the proliferation, colony formation, increased ki67 level and facilitated the invasion capability of CRC cells by enhancing the expressions of MMP-2 and MMP-9, while inhibition of miR-182 showed the opposite effects. Additionally, miR-182 was demonstrated to target DAB2IP and suppress its expression in CRC cells. Downregulation of miR-182 inhibited CRC tumor growth in vivo by upregulating DAB2IP. Moreover, restoration of DAB2IP attenuated miR-182-mediated activation of the PI3K/Akt/mTOR and Wnt/β-catenin pathways in CRC cells. Taken together, our findings showed that miR-182 exerted its oncogenic role in CRC by targeting DAB2IP, which may be involved in activating the PI3K/Akt/mTOR and Wnt/β-catenin pathways, shedding a novel light on the molecular mechanism of CRC tumorigenesis.

The lateral prefrontal cortex (LPFC) plays an important role in the neural networks involved in intertemporal choice. However, little is known about how the neural oscillation of LPFC functions during intertemporal choice, owing to the technical limitations of functional magnetic resonance imaging and event-related brain potential recordings. Electrocorticography (ECoG) is a novel neuroimaging technique that has high spatial and temporal resolution. In this study, we used ECoG and projected the ECoG data onto individual brain spaces to investigate human intracranial cortex activity and how neural oscillations of the LPFC impact intertemporal choice. We found that neural activity of theta oscillation was significantly higher during impulsive decisions, while beta oscillation activity was significantly higher during non-impulsive ones. Our findings suggest a functional dissociation between cortical theta and beta oscillations during decision-making processes involved in intertemporal choice, and that decision outcomes may be determined by LPFC modulation, which involves neural oscillations at different frequencies.

Innate immunity is the first line of defense in human beings against pathogen infection; monocytes/macrophages are the primary cells of the innate immune system. Recently, macrophages/monocytes have been discovered to participate in LPS clearance, and the clearance efficiency determines the magnitude of the inflammatory response and subsequent organ injury. Previously, we reported that artesunate (AS) protected sepsis mice against heat-killed E. coli challenge. Herein, we further confirmed that AS protected cecal ligation/puncture (CLP) sepsis mice. Its protection on sepsis mice was related to not only reduction of pro-inflammatory cytokines and serum LPS levels but also improvement of liver function. Based on the fact that AS did not directly bind and neutralize LPS, we hypothesized that the reduction of serum LPS level might be related to enhancement of LPS internalization and subsequent detoxification. Our results showed that AS increased FITC-LPS internalization by peritoneal macrophage and liver Kupffer cell, but enhancement of LPS internalization by AS was not related to the clathrin-dependent pathway. However, AS induced mRNA expression of important scavenger receptors (SRs); SR-A and MARCO mRNA expression was upregulated, suggesting that AS enhancement of LPS internalization and inhibition of pro-inflammatory cytokines was related to changes in mRNA expression of SRs.

The Yi-nao-jie-yu decoction (YNJYD) is a herbal preparation widely used in the clinics of traditional Chinese medicine and has been recently used as an important new therapeutic agent in poststroke anxiety (PSA). The neuroendocrine-immune system plays an important role in PSA mechanisms, although the modulating effects of YNJYD remain unknown. This study investigated the potential effects of YNJYD on the neuroendocrine-immune system in a rat model of PSA.

Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect. In addition, the HIF-1α expression and ROS production were also activated upon UK5099 application. It was further revealed that the UK5099-treated cells became significantly more resistant to chemotherapy and radiotherapy, and the UK5099-treated tumor cells also exhibited stronger invasive capacity compared to the parental cells. In contrast to esophageal squamous epithelium cells, decreased MPC protein expression was observed in a series of 157 human squamous cell carcinomas, and low/negative MPC1 expression predicted an unfavorable clinical outcome. All these results together revealed the potential connection of altered MPC expression/activity with the Warburg metabolic reprogramming and tumor aggressiveness in cell lines and clinical samples. Collectively, our findings highlighted a therapeutic strategy targeting Warburg reprogramming of human esophageal squamous cell carcinomas.

Transcription factors of the AP2/ERF family play important roles in plant growth, development, and responses to biotic and abiotic stresses. In this study, a physic nut AP2/ERF gene, JcDREB2, was functionally characterized. Real-time PCR analysis revealed that JcDREB2 was expressed mainly in the leaf and could be induced by abscisic acid but suppressed by gibberellin (GA) and salt. Transient expression of a JcDREB2-YFP fusion protein in Arabidopsis protoplasts cells suggested that JcDREB2 is localized in the nucleus. Rice plants overexpressing JcDREB2 exhibited dwarf and GA-deficient phenotypes with shorter shoots and roots than those of wild-type plants. The dwarfism phenotype could be rescued by the application of exogenous GA3. The expression levels of GA biosynthetic genes including OsGA20ox1, OsGA20ox2, OsGA20ox4, OsGA3ox2, OsCPS1, OsKO2, and OsKAO were significantly reduced in plants overexpressing JcDREB2. Overexpression of JcDREB2 in rice increased sensitivity to salt stress. Increases in the expression levels of several salt-tolerance-related genes in response to salt stress were impaired in JcDREB2-overexpressing plants. These results demonstrated not only that JcDREB2 influences GA metabolism, but also that it can participate in the regulation of the salt stress response in rice.

Circulating lncRNAs have been defined as a novel biomarker for non-small cell lung cancer (NSCLC), MALAT-1 was first identified lncRNA that was related to lung cancer metastasis. However, the relationship between exosomal lncRNAs and the diagnosis and prognosis of NSCLC was poorly understood. The aim of this study is to evaluate the clinical significance of serum exosomal MALAT-1 as a biomarker in the metastasis of NSCLC. In this study, we firstly isolated the exosomes from healthy subjects and NSCLC patients. Then we measured the expression levels of MALAT-1 contained in exosomes, and found that exosomal MALAT-1 was highly expressed in NSCLC patients, more importantly, the levels of exosomal MALAT-1 were positively associated with tumor stage and lymphatic metastasis. In addition, we decreased MALAT-1 expression by short hairpin RNA and conducted a series of assays including MTT, cell cycle, colony formation, wound-healing scratch and Annexin/V PI by flow cytometry in human lung cancer cell lines. These in vitro studies demonstrated that serum exosome-derived long noncoding RNA MALAT-1 promoted the tumor growth and migration, and prevented tumor cells from apoptosis in lung cancer cell lines. Taken together, this study shed a light on utilizing MALAT-1 in exosomes as a non-invasive serum-based tumor biomarker for diagnosis and prognosis of NSCLC.

Transcranial direct current stimulation (tDCS) has been reported to be a promising technique for consciousness improvement for patients with disorders of consciousness (DOC). However, there has been no direct electrophysiological evidence to demonstrate the efficacy of tDCS on patients with DOC. Therefore, we aim to measure the cortical excitability changes induced by tDCS in patients with DOC, to find electrophysiological evidence supporting the therapeutic efficacy of tDCS on patients with DOC. In this study, we enrolled sixteen patients with DOC, including nine vegetative state (VS) and seven minimally conscious state (MCS) (six females and ten males). TMS-EEG was applied to assess cortical excitability changes after twenty minutes of anodal tDCS of the left dorsolateral prefrontal cortex. Global cerebral excitability were calculated to quantify cortical excitability in the temporal domain: four time intervals (0-100, 100-200, 200-300, 300-400 ms). Then local cerebral excitability in the significantly altered time windows were investigated (frontal, left/right hemispheres, central, and posterior). Compared to baseline and sham stimulation, we found that global cerebral excitability increased in early time windows (0-100 and 100-200 ms) for patients with MCS; for the patients with VS, global cerebral excitability increased in the 0-100 ms interval but decreased in the 300-400 ms interval. The local cerebral excitability was significantly different between MCS and VS. The results indicated that tDCS can effectively modulate the cortical excitability of patients with DOC; and the changes in excitability in temporal and spatial domains are different between patients with MCS and those with VS.

The purpose of this study is to examine the effect of psychological intervention on the life quality of patients with laryngeal cancer.

BACKGROUND Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), a peptide aldehyde proteasome inhibitor, can inhibit tumor progression by inactivating nuclear factor (NF)-κB signaling. Paclitaxel (PTX) is part of a routine regimen for the treatment of breast cancer. However, activation of the NF-κB pathway after treatment with PTX confers insensitivity to this drug. This study investigated the potential effect of MG132 as a co-treatment with PTX against breast cancer, and clarifies the underlying molecular mechanisms. MATERIAL AND METHODS Breast cancer cells were treated with PTX, MG132, or PTX plus MG132, and the therapeutic effects were evaluated phenotypically. A mouse model of breast cancer was used to determine the combined effect of PTX plus MG132 in vivo. RESULTS Treatment with PTX plus MG132 suppressed aggressive phenotypes of breast cancer cells more effectively than PTX alone. Consistently, MG132 also enhanced the suppressive effect of PTX on tumor growth in C57BL/6 mice. Significantly, activation of the NF-κB pathway by PTX was attenuated by MG132. CONCLUSIONS Based on our findings, we suggest the application of MG132 in clinical practice in combination with PTX for the treatment of breast cancer.

Cancer cells exhibit an altered metabolism, which is characterized by a preference for aerobic glycolysis more than mitochondrial oxidation of pyruvate. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) play a bottleneck role by transporting pyruvate into mitochondrial through the mitochondrial inner membrane. Therefore, their protein expression in cancers may be of clinical consequences. There are studies showing low levels of MPC1 expression in colon, kidney and lung cancers, and the expression of MPC1 correlates with poor prognosis. However, the expression status of MPC1 and MPC2 in prostate cancer (PCA) is unclear.

Increased use of vancomycin has led to the emergence of vancomycin-intermediate Staphylococcus aureus (VISA). To investigate the mechanism of VISA development, 39 methicillin-susceptible strains and 3 MRSA strains were treated with vancomycin to induce non-susceptibility, and mutations in six genes were analyzed. All the strains were treated with vancomycin in vitro for 60 days. MICs were determined by the agar dilution and E-test methods. Vancomycin was then removed to assess the stability of VISA strains and mutations. Following 60 days of vancomycin treatment in vitro, 29/42 VISA strains were generated. The complete sequences of rpoB, vraS, graR, graS, walK, and walR were compared with those in the parental strains. Seven missense mutations including four novel mutations (L466S in rpoB, R232K in graS, I594M in walk, and A111T in walR) were detected frequently in strains with vancomycin MIC ≥ 12 μg/mL. Jonckheere-Terpstra trend test indicated these mutations might play an important role during VISA evolution. After the vancomycin treatment, strains were passaged to vancomycin-free medium for another 60 days, and the MICs of all strains decreased. Our results suggest that rpoB, graS, walk, and walR are more important than vraS and graR in VISA development.

Basal-like breast cancer (BLBC) is associated with high-grade, distant metastasis and poor prognosis. Elucidating the determinants of aggressiveness in BLBC may facilitate the development of novel interventions for this challenging disease. In this study, we show that aldo-keto reductase 1 member B1 (AKR1B1) overexpression highly correlates with BLBC and predicts poor prognosis in breast cancer patients. Mechanistically, Twist2 transcriptionally induces AKR1B1 expression, leading to nuclear factor κB (NF-κB) activation. In turn, NF-κB up-regulates Twist2 expression, thereby fulfilling a positive feedback loop that activates the epithelial-mesenchymal transition program and enhances cancer stem cell (CSC)-like properties in BLBC. AKR1B1 expression promotes, whereas AKR1B1 knockdown inhibits, tumorigenicity and metastasis. Importantly, epalrestat, an AKR1B1 inhibitor that has been approved for the treatment of diabetic complications, significantly suppresses CSC properties, tumorigenicity, and metastasis of BLBC cells. Together, our study identifies AKR1B1 as a key modulator of tumor aggressiveness and suggests that pharmacologic inhibition of AKR1B1 has the potential to become a valuable therapeutic strategy for BLBC.

Colorectal cancer (CRC) is a prevalent worldwide disease in which the antioxidant enzyme peroxiredoxin 2 (PRDX2) plays an important role. To investigate the molecular mechanism of PRDX2 in CRC, we performed bioinformatics analysis of The Cancer Genome Atlas (TCGA) datasets and Gene Expression Omnibus (GEO) DataSets (accession no. GSE81429). Our results suggest that PRDX2 is associated with cell-cycle progression and autophagy activated by the P38 MAPK/FOXO signaling pathway. Using a short-hairpin RNA vector, we verified that PRDX2 is essential for CRC cell proliferation and S-phase progression. Immunostaining, electron microscopy and western blotting assays verified the effect of PRDX2 knockdown on autophagy flux and p38 activation. The P38 activator dehydrocorydaline chloride partially rescued the effects of sh-PRDX2 on the expression of proteins related to cell-cycle progression and autophagy. We verified the correlation between PRDX2 expression and the expression of an array of cell-cycle and autophagy-related genes using data from an independent set of 222 CRC patient samples. A mouse xenoplast model was consistent with in vitro results. Our results suggest that PRDX2 promotes CRC cell-cycle progression via activation of the p38 MAPK pathway.