Effects of brief mindfulness meditation training on attention and dispositional mindfulness in young adult males.

This study examined the impact of brief mindfulness meditation (BMM) training on attention function and dispositional mindfulness in young males. 126 male participants aged 18-26 from the security industry were recruited, with 66 participants (M = 22.84, SD = 2.41) undergoing 4-week mindfulness meditation training and 60 participants (M = 23.07, SD = 2.29) in the active control group. The intervention was integrated into the participants' schedules. Measures included Five Facets Mindfulness Questionnaires (FFMQ), concentration and assignment attention tasks, Attention Network Test (ANT), and saliva cortisol concentration. Findings indicate that brief mindfulness meditation training led to significant improvements in participants' FFMQ scores), with marginally significant enhancements in the executive control network. However, it had no discernible effect on alertness and orientation networks. Additionally, brief mindfulness meditation training enhanced attention allocation to light stimulation and prolonged individual attention. Surprisingly, there was no observed decrease in saliva cortisol concentration among meditation training participants. However, this study did not find a decrease in saliva cortisol concentration in the brief mindfulness meditation group. In conclusion, this study highlights the potential of a 4-week brief mindfulness meditation training program to enhance dispositional mindfulness and specific aspects of attention function in young men, offering practical insights into the benefits of mindfulness meditation practices for this demographic.

Fast photocatalytic degradation of rhodamine B using indium-porphyrin based cationic MOF under visible light irradiation.

A broad light-harvesting range and efficient charge separation are two main ways to enhance the visible photocatalytic performance of semiconductors. Herein, an ionic porphyrin MOF [In(TPyP)]·(NO3) (1) (TPyP = 5,10,15,20-tetrakis(4-pyridyl)-21H,23H-porphyrin) was synthesized via in situ metalation. The orderly arranged porphyrin photosensitizer and the internal electric field between the MOF host and NO3- guests enable effective visible light response and electron-hole separation. Consequently, the as-synthesized MOF shows efficient photocatalytic degradation of rhodamine B (RhB), methyl orange (MO) and methylene blue (MB) organic pollutants. It can degrade 99.07% of RhB within only 20 minutes under visible light irradiation (λ > 420 nm) with a high chemical reaction rate constant of 0.2400 min-1. The photocatalytic activity of the title MOF is more efficient than those of other reported MOFs, COFs and even inorganic semiconductors. The reusability, energy level, band gap, charge distribution and main degradation mechanisms of the photocatalyst were well studied.

The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice.

BACKGROUND: Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). METHODS: Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aß metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. RESULTS: CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aß metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 µg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1ß in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aß metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. CONCLUSIONS: Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.

Isoalantolactone mediates the degradation of BCR-ABL protein in imatinib-resistant CML cells by down-regulating survivin.

Isoalantolactone (Iso) is a bioactive lactone isolated from the root of Inula helenium L, which has been reported to have many pharmacological effects. To investigate the role and mechanism of isoalantolactone in chronic myeloid leukemia (CML), we first investigated isoalantolactone's anti-proliferative effects on imatinib-sensitive and imatinib-resistant CML cells by CCK8. Flow cytometry was used to detect isoalantolactone-induced cell apoptosis. Survivin was overexpressed in KBM5 and KBM5T315I cells using the lentivirus vector pSIN-3×flag-PURO. In KBM5 and KBM5T315I cells, shRNA was used to knockdown survivin. Cellular Thermal Shift Assay (CETSA) was used to detect the interaction between isoalantolactone and survivin. The ubiquitin of survivin induced by isoalantolactone was detected through immunoprecipitation. Quantitative polymerase-chain reaction (Q-PCR) and western blotting were used to detect the levels of mRNA and protein. Isoalantolactone inhibits the proliferation and promotes apoptosis of imatinib-resistant CML cells. Although isoalantolactone inhibits the proteins of BCR-ABL and survivin, it cannot inhibit survivin and BCR-ABL mRNA levels. Simultaneously, it was shown that isoalantolactone can degrade survivin protein by increasing ubiquitination. It was demonstrated that isoalantolactone-induced survivin mediated downregulation of BCR-ABL protein. It was also revealed that isoalantolactone triggered BCR-ABL protein degradation via caspase-3. Altogether, isoalantolactone inhibits survivin through the ubiquitin proteasome pathway, and mediates BCR-ABL downregulation in a caspase-3 dependent manner. These data suggest that isoalantolactone is a natural compound, which can be used as a potential drug to treat TKI-resistant CML.

Red room temperature phosphorescence of lead halide based coordination polymer showing efficient angle-dependent polarized emission and photoelectric performance.

The development of organic-inorganic hybrid materials with long-lived room temperature phosphorescence (RTP) has attracted tremendous attention owing to their promising applications in the optoelectronic and anti-counterfeiting fields. In this work, by the selection of lead halide and electron-poor heteroaromatic molecule 1,10-phenanthroline (phen), a coordination polymer [Pb(phen)Cl2] has been synthesized under hydrothermal conditions. This complex shows an alternating arrangement of a long-range order of phen π-conjugated systems and lead halide inorganic chains as revealed by X-ray single-crystal structural analysis. This structural character and special chemical components endow this hybrid material with a rare example of red room temperature phosphorescence. Its electronic structure and electronic transition behavior were further examined by theoretical calculations. Meanwhile, the film of the complex features remarkable angle-dependent polarized emission and photoelectric performance.

An anthracene based metal-organic framework showing efficient angle-dependent polarized emission, luminescence thermometry, and photoelectronic response.

The development of luminescent metal-organic frameworks (MOFs) has attracted extensive attention due to their applications in photoelectric devices, organic light-emitting diodes (OLEDs), anti-counterfeiting, biological imaging and so on. In this work, a novel anthracene based metal-organic framework, [Cd(DCPA)(DMF)]·(H2O) (1) (H2DCPA = 9,10-di(p-carboxyphenyl)anthracene), has been successfully synthesized under solvothermal conditions. The highly ordered arrangement and special spatial conformation of the anthracene chromophore play a significant role in the photophysical properties of 1. The combination of theoretical calculations and experiments shows that the molecular orbitals have good separation for inhibiting the recombination of electrons and holes. Furthermore, the fluorescence emission of 1 can be instantaneously and reversibly tuned between blue and green at different polarizing angles. Temperature-dependent fluorescence measurements indicate a good linear relationship between the maximum emission intensity/wavelength and the temperature for efficient thermochromism and luminescence thermometry. Photoelectric measurements reveal that 1 shows high performance of photocurrent generation under light illumination. Therefore, our research affords a new perspective to extend the application of luminescent MOFs in the fields of polarized emission, thermometry and photoelectronic response.

Tumor microenvironment immune-related lncRNA signature for patients with melanoma.

BACKGROUND: The incidence of malignant melanoma accounts for only approximately 5% of skin malignant tumors, however, it accounts for 75% of its mortality. Long-chain non-coding RNA (lncRNA) has a wide range of functional activities. Disorders of lncRNAs may lead to the occurrence and development of melanoma, and may also be related to immunotherapy. METHODS: The transcriptomic data of primary and metastatic melanoma patients and 331 immune-related genes were downloaded from skin cutaneous melanoma (SKCM) in the The Cancer Genome Atlas (TCGA) database. On this basis, 460 immunologically relevant lncRNAs were identified by constructing a co-expression network of immunogenic genes and lncRNAs in primary and metastatic melanoma patients. Prognostic genes were screened using univariate Cox regression analysis. ROC analysis was performed to evaluate the robustness of the prognostic signature. RESULTS: Univariate correlation analysis showed that only 3 of the 23 immune-related lncRNAs were at high risk and the rest were at low risk. Signatures of 7 immune-related lncRNAs were identified by multivariate correlation analysis. The clinical correlation analysis showed that the 7 immune-related lncRNAs were associated with the clinical stage of primary and metastatic melanoma. Principal component analysis (PCA) showed that only 7 immune-related lncRNA signals divided tumor patients into high-risk and low-risk groups, while the low-risk group was enriched in the immune system process M13664 and immune response M19817 sets. PPI interaction network analysis showed that 11 G protein-coupled receptors and 6 corresponding ligands in the 2 gene sets affected the tumor microenvironment and were negatively related to the risk of the 7 immune-related lncRNAs. The tumor microenvironment immune cell infiltration analysis also supported the finding that anti-tumor immunity in the low-risk group was stronger than in the high-risk group. CONCLUSIONS: These results indicate that characteristics of the 7 immune-related lncRNAs have prognostic value for melanoma patients and can be used as potential immunotherapy targets.

PPARγ Activation-Mediated Egr-1 Inhibition Benefits Against Brain Injury in an Experimental Ischaemic Stroke Model.

BACKGROUND: Inflammatory response is a critical contributor to cerebral ischaemia injuries and blood-brain barrier (BBB) dysfunction. Early growth response-1 (Egr-1), an oxygen-sensing transcription factor which is rapidly and markedly triggered in ischaemic events, acts as a master switch coordinating the upregulation of multiple target proinflammatory genes. Here, we explored whether peroxisome proliferator-activated receptor-gamma (PPARγ) activation by telmisartan can modulate Egr-1 expression and the subsequent inflammatory responses in a rat model of cerebral ischaemia. METHODS: Cerebral ischaemia was induced in rats by middle cerebral artery occlusion (MCAO). Brain injury was evaluated by brain water content, infarct volume, and Evans blue dye extravasation. Egr-1 and claudin-5 levels were assessed by western blot and real-time polymerase chain reaction. RESULTS: MCAO-provoked Egr-1 expression was time dependent, peaking at 24 h and continuing to 72 h. The elevation in Egr-1 was coupled with a reduction in claudin-5. Telmisartan treatment significantly corrected the alterations of Egr-1 and claudin-5, alleviated the neurological deficits, and reduced brain water content, infarct volume, and Evans blue dye extravasation 24 h after MCAO. However, all the benefits of telmisartan were reversed by antagonising PPARγ with GW9662. CONCLUSION: Egr-1, a proinflammatory factor, is positively associated with post-ischaemic inflammation and the associated BBB dysfunction. PPARγ serves as an upstream transcription factor of the Egr-1 cascade. Targeting Egr-1 may emerge as a potential strategy to suppress inflammatory responses following ischaemic stroke.

A signal peptide derived from Hsp60 induces protective cytotoxic T lymphocyte immunity against lymphoid malignancies independently of TAP and classical MHC-I.

Hsp60sp, a signal peptide derived from the leader sequence of heat shock protein 60 kDa (Hsp60), is a Qa-1/HLA-E-binding peptide. We previously showed that Hsp60sp-specific CD8+ T cells are involved in the immunoregulation of autoimmune diseases by controlling the response of self-reactive lymphocytes. Here, we report that Hsp60sp-specific CD8+ T cells killed malignant lymphocytes in vitro independently of transporter associated with antigen processing (TAP) and classical MHC-I expression. Induction of this cytotoxic T lymphocyte (CTL) response in vivo, either by adoptive transfer of in vitro-amplified CTLs or peptide-loaded dendritic cell immunization, resulted in effective control of lymphoid tumors, including TAP- or classical MHC-I-deficient cells. Hsp60sp-specific immune activation combined with programmed cell death protein 1 (PD-1) blocking synergistically restrained mouse lymphoma development. Importantly, Hsp60sp-specific CD8+ T cells did not negatively affect normal tissues and cells. Our data suggest that Hsp60sp-based immunotherapy is an inviting strategy to control lymphoid malignancies.

MicroRNA-92b acts as an oncogene by targeting PTEN/AKT in NSCLC.

MicroRNAs can act as tumour suppressors or oncogenes by regulating cellular differentiation, proliferation and apoptosis, and the dysregulation of miRNA is involved in the occurrence and development of NSCLC. Here, we provided evidence that miR-92b as an oncogene in NSCLC by targeting PTEN/AKT. We found that miR-92b was up-regulated in human NSCLC tissues and cell lines. MiR-92b knockdown suppressed the NSCLC cells proliferation and migration in both in vivo and in vitro models. Conversely, miR-92b overexpression induced an aggressive phenotype. Moreover, miR-92b-mediated regulation of NSCLC cell proliferation and migration depended on binding to PTEN mRNA, which then led to the degradation of PTEN and activation of the downstream AKT signalling pathway. Overall, this study revealed the oncogenic roles of miR-92b in NSCLC by targeting PTEN/AKT, and provided novel insights for future treatments of NSCLC patients. SIGNIFICANCE OF THE STUDY: MiR-92b was up-regulated in human NSCLC tissues and cell lines. Our study demonstrated that miR-92b as an oncogene in NSCLC by targeting PTEN/AKT in both in vivo and in vitro models and provided novel insights for future treatments of NSCLC patients.

Oridonin induces Mdm2-p60 to promote p53-mediated apoptosis and cell cycle arrest in neuroblastoma.

Oridonin could induce NB (neuroblastoma) cells growth inhibition by inducing apoptosis and cell cycle arrest, and the molecular mechanisms behind the effects deserve to be further explored. Here, oridonin was confirmed to cause the reactivation of p53 (cellular tumor antigen p53) to promote the expression of a series of apoptosis- and cell cycle arrest-related proteins for the biological effects. During the process, oridonin relied on the caspase activation to cleave p53-induced Mdm2 (E3 ubiquitin-protein ligase Mdm2) to generate Mdm2-p60. The generation of Mdm2-p60 stabilized p53, and resulted in p53 accumulation for p53 continuous activation. In our research, it was also found that the reactivation of p53 induced by oridonin was closely related with the generation of ROS (reactive oxygen species). Taken together, these findings explain that oridonin exerts its anticancer activity partially by targeting the Mdm2-p53 axis in NB cells, which lay an experimental base for future research of exploring the effects and molecular mechanisms of oridonin.

GSK3ß-dependent cyclin D1 and cyclin E1 degradation is indispensable for NVP-BEZ235 induced G0/G1 arrest in neuroblastoma cells.

Cyclin D1 and cyclin E1, as vital regulatory factors of G1-S phase cell cycle progression, are frequently constitutive expressed and associated with pathogenesis and tumorigenesis in most human cancers and they have been regarded as promising targets for cancer therapy. In this study, we established NVP-BEZ235, a potent dual kinase inhibitor, could induce neuroblastoma cells proliferation inhibition without apoptosis activation. Moreover, we showed NVP-BEZ235 could induce neuroblastoma cells arrested at G0/G1 phase accompanied with significant reduction of the cyclin D1 and E1 proteins in a dose dependent manner at nanomole concentration. Additionally we found that GSK3ß was dephosphorylated and activated by NVP-BEZ235 and then triggered cyclin D1 and cyclin E1 degradation through ubiquitination proteasome pathway, based on the evidences that NVP-BEZ235 induced downregulation of cyclin D1 and cyclin E1 were obviously recovered by proteasome inhibitor and the blockade of GSK3ß contributed to remarkable rescue of cyclin D1 and cyclin E1. Analogous results about its anti-proliferation effects and molecular mechanism were observed on neuroblastoma xenograft mouse model in vivo. Therefore, these results indicate that NVP-BEZ235-induced cyclin D1 and cyclin E1 degradation, which happened through activating GSK3ß, and GSK3ß-dependent down-regulation of cyclin D1 and cyclin E1 should be available for anticancer therapeutics.

USP7 promotes cell proliferation through the stabilization of Ki-67 protein in non-small cell lung cancer cells.

The Ki-67 antigen (Ki-67) is the most reliable immunohistochemical marker for evaluation of cell proliferation in non-small cell lung cancer. However, the mechanisms underlying the regulation of protein levels of Ki-67 in non-small cell lung cancer have remained elusive. In this study, we found that Ki-67 and ubiquitin-specific processing protease 7 (USP7) protein were highly expressed in the nucleus of non-small cell lung cancer cells. Furthermore, statistical analysis uncovered the existence of a strong correlation between Ki-67 and USP7 levels. We could also show that the protein levels of Ki-67 in non-small cell lung cancer cells significantly decreased after treatment with P22077, a selective chemical inhibitor of USP7, while the Ki-67 mRNA levels were unperturbed. Similar results were obtained by knocking down USP7 using short hairpin RNA (shRNA) in lung cancer cells. Interestingly, we noticed that ubiquitination levels of Ki-67 increased dramatically in USP7-silenced cells. The tests in vitro and vivo showed a significant delay in tumor cell growth upon knockdown of USP7. Additionally, drug sensitivity tests indicated that USP7-silenced A549 cells had enhanced sensitivity to paclitaxel and docetaxel, while there was no significant change in sensitivity toward carboplatin and cisplatin. Taken together, these data strongly suggest that the overexpression of USP7 might promote cell proliferation by deubiquitinating Ki-67 protein, thereby maintaining its high levels in the non-small cell lung cancer. Our study also hints potential for the development of deubiquitinase-based therapies, especially those targeting USP7 to improve the condition of patients diagnosed with non-small cell lung cancer.

Tiron Inhibits UVB-Induced AP-1 Binding Sites Transcriptional Activation on MMP-1 and MMP-3 Promoters by MAPK Signaling Pathway in Human Dermal Fibroblasts.

Recent research found that Tiron was an effective antioxidant that could act as the intracellular reactive oxygen species (ROS) scavenger or alleviate the acute toxic metal overload in vivo. In this study, we investigated the inhibitory effect of Tiron on matrix metalloproteinase (MMP)-1 and MMP-3 expression in human dermal fibroblast cells. Western blot and ELISA analysis revealed that Tiron inhibited ultraviolet B (UVB)-induced protein expression of MMP-1 and MMP-3. Real-time quantitative PCR confirmed that Tiron could inhibit UVB-induced mRNA expression of MMP-1 and MMP-3. Furthermore, Tiron significantly blocked UVB-induced activation of the MAPK signaling pathway and activator protein (AP)-1 in the downstream of this transduction pathway in fibroblasts. Through the AP-1 binding site mutation, it was found that Tiron could inhibit AP-1-induced upregulation of MMP-1 and MMP-3 expression through blocking AP-1 binding to the AP-1 binding sites in the MMP-1 and MMP-3 promoter region. In conclusion, Tiron may be a novel antioxidant for preventing and treating skin photoaging UV-induced.

Oridonin enhances the anticancer activity of NVP-BEZ235 against neuroblastoma cells in vitro and in vivo through autophagy.

The aberrant activation of PI3K/Akt/mTOR signaling pathway plays an important role in the oncogenesis, prognosis and chemotherapy resistance of neuroblastoma. However, NVP-BEZ235, a potent dual PI3K and mTOR inhibitor have not shown beneficial effects on neuroblastoma especially in terms of apoptosis induction as a single agent. We therefore attempted to explore an effective combination regimen to enhance the anticancer activity of NVP-BEZ235. Interestingly, we found that oridonin, a natural biologically active compound extracted from the Chinese medicinal herb Rabdosia rubescens, combined with NVP-BEZ235 markedly induced apoptosis of neuroblastoma cells. Notably, the synergistic activation of the apoptotic pathway was accompanied with enhanced autophagy as evidenced by significant decreased p62 expression as well as upregulated conversion of LC3-II. Suppression of the Beclin-1, a core component of the autophagy machinery, by means of shRNA resulted in diminished synergistic antitumor effect. Furthermore, the co-treatment with oridonin and NVP-BEZ235 was also much more effective than either agent alone in inhibiting the growth of neuroblastoma xenografts and in inducing tumor cells apoptosis. Taken together, our results suggest that the combination of NVP-BEZ235 and oridonin is a novel and potential strategy for neuroblastoma therapy.