Reliability and validity of the cancer-related dysfunctional beliefs and attitudes about sleep scale in cancer patients.

BACKGROUND: Insomnia is a common health problem among cancer patients, which is not only a physical problem but also a psychological problem. Sleep plays an important role in the mental and somatic rehabilitation of cancer patients, and the sleep beliefs and attitudes of cancer patients are key factors in improving their sleep situation and quality of life. The aim of this study was to translate the Cancer-Related Dysfunctional Beliefs and Attitudes about Sleep (C-DBAS-14) scale into Chinese and to validate its reliability and validity in cancer patients. METHOD: The C-DBAS-14 scale was translated into Chinese using the backward and forward translation procedure. The reliability of the scale was measured by internal consistency, split-half reliability and retest reliability. The validity of the scale was assessed through the content validity indicators, exploratory factor analysis and validation factor analysis. RESULT: The Cronbach's ɑ coefficient of the Chinese version of the C-DBAS-14 was 0.932 while the McDonald's omega coefficient (ω t) was 0.934. The split-half reliability coefficient was 0.908, and the test-retest reliability was 0.857. The four-factor model was obtained using exploratory factor analysis, explaining 72.7% of the variance, with each item loading greater than 0.4 on the common factor. The results of the confirmatory factor analysis revealed that all indicators of model fit were within an acceptable range, indicating a well-fitting model. CONCLUSION: The Chinese version of the C-DBAS-14 has good reliability and validity among cancer patients. It can be used to measure the sleep beliefs and attitudes of Chinese cancer patients.

Relationship between self-esteem and quality of life in middle-aged and older patients with chronic diseases: mediating effects of death anxiety.

BACKGROUND: Many studies have explored the relationship between self-esteem and quality of life. However, few studies have elucidated the mechanisms underlying the relationship between self-esteem and quality of life in middle-aged and older patients with chronic diseases. The present study aimed to explore the mediating role of death anxiety in this relationship. METHODS: Middle-old-aged patients with chronic diseases were selected as the respondents by using a multi-stage sampling method, random number table method from October 2021 to February 2022 in the Second Affiliated Hospital of Zhejiang University School of Medicine. The Cumulative Disease Rating Scale, the Self-Esteem Scale (SES), the Chinese version of the Death Anxiety Scale (CT-DAS), and the Simplified version of the Quality of Life Scale (SF-12) were used as the researching tools to conduct the survey. SPSS26.0 was used to analysis data. AMOS 23.0 software was used to construct structural equation modeling. RESULTS: 294 valid questionnaires were collected. There were significant differences in quality of life among middle-aged and elderly patients with chronic diseases who have different physical activities, socialization, and chronic pain (P < 0.01); Self-esteem was positively associated with quality of life (r = 0.330, P < 0.01), self-esteem was negatively associated with death anxiety (r = -0.222, P < 0.01), and death anxiety was negatively associated with quality of life (r = -0.263, P < 0.01); Death anxiety partially mediated the relationship between self-esteem and quality of life, with the mediating effect accounting for 18.40% of the total effect. CONCLUSION: Death anxiety partially mediates the relationship between self-esteem and quality of life. Interventions to improve self-esteem and reduce death anxiety should be used to improve the quality of life of middle-aged and senior patients with chronic diseases.

Psychological resilience and quality of life among middle-aged and older adults hospitalized with chronic diseases: multiple mediating effects through sleep quality and depression.

BACKGROUND: The present study is intended to examine the multiple mediating roles of sleep quality and depression in the relationship between psychological resilience and quality of life in middle-aged and older adults hospitalized with chronic diseases. METHODS: From October 2, 2021, to February 27, 2022, a questionnaire survey was conducted using a multistage stratified sampling method among 339 middle-aged and older adults (45 years and over) hospitalized with chronic diseases. These participants were recruited from a hospital in Zhejiang Province, China. The questionnaire included the Aged Cumulative Disease Rating Scale, the Psychological Resilience Scale, the Pittsburgh Sleep Quality Index Scale, the Depression Scale, and the Quality-of-Life Scale. A descriptive analysis was performed to characterize the sample. Linear regression was utilized to evaluate the relationship between psychological resilience and quality of life. Amos 24.0 was used to analyze the multiple mediated effects of sleep quality and depression. RESULTS: Psychological resilience exerted a remarkable direct effect on the quality of life in middle-aged and older adults hospitalized with chronic diseases (ß = 0.239, 95% CI = 0.125-0.354), which represented 52.98% of the total effect. Through three significantly mediated pathways indirectly affect the quality of life: (1) through the sleep quality pathway (ß = 0.115, 95% CI = 0.056-0.201), which represented 25.39% of the total effect; (2) through the depression pathway (ß = 0. 060, 95% CI = 0.023-0.114), which represented 13.24% of the total effect; and (3) through both the sleep quality and depression pathway (ß = 0. 038, 95% CI = 0.019-0.074), which represented 8.39% of the total effect. The total mediating effect was 47.02%. CONCLUSIONS: Sleep quality and depression mediate the relationship between psychological resilience and quality of life in middle-aged and older adults hospitalized with chronic diseases. Therefore, healthcare professionals and stakeholders should be concerned about the sleep status and mental health of middle-aged and older adults hospitalized with chronic diseases, strengthen their attention to psychological resilience, and provide interventions and treatment measures for hospitalized patients who have sleep problems and depressive tendencies.

Mediating effect of successful aging on the relationship between psychological resilience and death anxiety among middle-aged and older adults with hypertension.

Objective: The aging trend of China's population is severe and successful aging (SA) is imminent. Aging can lead to various chronic diseases, with hypertension being the most common. Due to this lifelong disease, patients suffer from many anxieties, as death anxiety (DA) can be the most prevalent. Studies have exhibited that middle-aged adults approaching the transition to an older state show more pronounced DA than the more senior. It has been suggested that psychological resilience (PR) can reduce DA. Therefore, this study aimed to analyze the mediating effect of SA between PR and DA in middle-aged and older adults with hypertension. Methods: A cross-sectional survey was designed. From August to December 2021, 298 middle-aged and older adults with hypertension were selected by multistage cluster random sampling in three districts (Ling he District, Gu ta District, and Tai He District) of Jinzhou City, Liaoning Province. They were surveyed using the demographic questionnaires, the Conner-Davidson Resilience Scale, the Successful Aging Inventory, and the Chinese version of a Likert-type Templer-Death Anxiety Scale. Descriptive analyses, independent sample T-test, and one-way analysis of variance (ANOVA) were used to describe demographic characteristics among hypertensive patients with different characteristics, respectively. Statistics were considered significant when P < 0.05. Pearson correlation coefficients describe the relationship between PR, SA, and DA. The research model was shaped through Structural Equation Modeling (SEM). SPSS PROCESS macro was used to verify the mediation model. A binary logistic regression model was used with DA as the dependent variable. Results: The scores for PR, SA, and DA in hypertensive patients are (49.52 ± 14.38) points, (51.22 ± 7.63) points, and (46.67 ± 9.03) points. PR was negatively correlated with DA (r = -0.307, P < 0.01). Moreover, incorporating SA as a mediating variable in PR and DA, SA was positively correlated with PR (r = 0.335, P < 0.01) and DA (r = 0.085, P > 0.05). The direct effect is opposite to the sign of the indirect effect. There is a suppression between PR and DA with a percentage of 20.7%. Good self-assessed health status [0.057 (0.018, 0.183)] may be a protective factor for DA. Conclusion: Healthcare providers should improve the PR of middle-aged and older adults with hypertension through interventions that reduce DA and increase the likelihood of SA.

Commensal bacteria promote azathioprine therapy failure in inflammatory bowel disease via decreasing 6-mercaptopurine bioavailability.

Azathioprine (AZA) therapy failure, though not the primary cause, contributes to disease relapse and progression in inflammatory bowel disease (IBD). However, the role of gut microbiota in AZA therapy failure remains poorly understood. We found a high prevalence of Blautia wexlerae in patients with IBD with AZA therapy failure, associated with shorter disease flare survival time. Colonization of B. wexlerae increased inflammatory macrophages and compromised AZA's therapeutic efficacy in mice with intestinal colitis. B. wexlerae colonization reduced 6-mercaptopurine (6-MP) bioavailability by enhancing selenium-dependent xanthine dehydrogenase (sd-XDH) activity. The enzyme sd-XDH converts 6-MP into its inactive metabolite, 6-thioxanthine (6-TX), thereby impairing its ability to inhibit inflammation in mice. Supplementation with Bacillus (B.) subtilis enriched in hypoxanthine phosphoribosyltransferase (HPRT) effectively mitigated B. wexlerae-induced AZA treatment failure in mice with intestinal colitis. These findings emphasize the need for tailored management strategies based on B. wexlerae levels in patients with IBD.

Psychometric evaluation of the Chinese version of the Elderly-Constipation Impact Scale: a translation and validation study.

OBJECTIVE: The objective of this study was to translate the Elderly-Constipation Impact Scale into Chinese and to examine its reliability and validity in a population of older people suffering from chronic constipation. METHODS: In this study, the scale was paraphrased, back-translated, cross-culturally adapted and pre-experimented using the Brislin double translation-back-translation method to create the initial Chinese version of the Elderly-Constipation Impact Scale. A convenience sampling method was used to select 564 study participants who met the inclusion and exclusion criteria in Liaoning and Shanxi, China, to evaluate the reliability and validity of the scale. General information about the study population was using descriptive statistics; item analysis was used to screen the items of the scale. Content validity, exploratory factor analysis, and validation factor analysis were chosen to validate the scales; internal consistency, spilt-half reliability and retest reliability were used determine the reliability of the measurement scales. RESULTS: The Chinese version of the Elderly-Constipation Impact Scale contains 7 dimensions and 21 items. The Cronbach's alpha coefficient for the total scale was 0.901 and the range of Cronbach's alpha values for each dimension was 0.707 to 0.918. The split-half reliability of the scale was 0.736 and the retest reliability was 0.763. The exploratory factor analysis showed a KMO value of 0.873 and a Bartlett's spherical test X2 value of 3499.978 (p < 0.001). A total of seven common factors were extracted, namely daily activities, treatment satisfaction, lack of control of bodily function, diet restriction, symptom intensity, anxiety and preventive actions, with a cumulative variance contribution of 77.813%. Each item had a loading value > 0.4 on its common factor. In the validation factor analysis, the model fit results were X2 / df = 1.886, GFI = 0.910, AGFI = 0.874, PGFI = 0.654, IFI = 0.955, TLI = 0.942, CFI = 0.954, RMSEA = 0.056 and PNFI = 0.718. The model fit indicators were all within acceptable limits. CONCLUSION: The Chinese version of the E-CIS has good reliability and validity in the chronic constipation population of elderly individuals. The results of the questionnaire can effectively and comprehensively reflect the impact of chronic constipation on the quality of life of elderly individuals. It provides a meaningful reference for identifying targets for intervention.

Carbon dots electrochemically prepared from dopamine and epigallocatechin gallate for hypochlorite detection with high selectivity via a dynamic quenching mechanism.

Monitoring hypochlorite levels in water is of great importance because of its high toxicity and wide applications as water disinfectants. In this manuscript, carbon dot (CD) was electrochemically prepared by using dopamine and epigallocatechin gallate (molar ratio 1:1) as the carbon source for efficient hypochlorite determination. By electrolyzing the solution at 10 V for 12 min with PBS as an electrolyte, dopamine would react with epigallocatechin at the anode, and through polymerization, dehydration, and carbonization, strong blue-fluorescent CDs were obtained. CDs were characterized by UV-Vis spectroscopy, fluorescence spectroscopy, high-resolution transmission electron microscopy, FT-IR, etc. These CDs have an excitation wavelength at 372 nm and an emission wavelength at 462 nm, owing an average particle size of 5.5 nm. The presence of hypochlorites can quench the fluorescence of CDs, and its reduction in intensity is linear with hypochlorite concentration over the range of 0.5-50 µM, ΔF/F0 = 0.0056 + 0.0194CClO-, R2=0.997. The detection limit achieved 0.23 µM (S/N = 3). The mechanism for fluorescence quenching is via a dynamic process. Different from many other fluorescence methods based on the strong oxidizing ability of hypochlorites, our method shows strong selectivity toward hypochlorites over other oxidizing agents such as H2O2. The assay was validated by the detection of hypochlorites in water samples, with recoveries between 98.2% and 104.3%.

Identification and investigation of depression-related molecular subtypes in inflammatory bowel disease and the anti-inflammatory mechanisms of paroxetine.

Background: Up to 40 per cent of people with active inflammatory bowel disease (IBD) also suffer from mood disorders such as anxiety and depression. Notwithstanding, the fundamental biological pathways driving depression in IBD remain unknown. Methods: We identified 33 core genes that drive depression in IBD patients and performed consensus molecular subtyping with the NMF algorithm in IBD. The CIBERSORT were employed to quantify the immune cells. Metabolic signature was characterized using the "IOBR" R package. The scoring system (D. score) based on PCA. Pre-clinical models are constructed using DSS. Results: Using transcriptome data from the GEO database of 630 IBD patients, we performed a thorough analysis of the correlation between IBD and depression in this research. Firstly, the samples were separated into two different molecular subtypes (D. cluster1 and D. cluster2) based on their biological signatures. Moreover, the immunological and metabolic differences between them were evaluated, and we discovered that D. cluster2 most closely resembled IBD patients concomitant with depression. We also developed a scoring system to assess the IBD-related depression and predict clinical response to anti-TNF- therapy, with a higher D. score suggesting more inflammation and worse reaction to biological therapies. Ultimately, we also identified through animal experiments an antidepressant, paroxetine, has the added benefit of lowering intestinal inflammation by controlling microorganisms in the digestive tract. Conclusions: This study highlights that IBD patients with or without depression show significant variations and antidepressant paroxetine may help reduce intestinal inflammation.

LncRNA CACClnc promotes chemoresistance of colorectal cancer by modulating alternative splicing of RAD51.

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis. However, the effect of lncRNA on chemoresistance and RNA alternative splicing remains largely unknown. In this study, we identified a novel lncRNA, CACClnc, which was upregulated and associated with chemoresistance and poor prognosis in colorectal cancer (CRC). CACClnc promoted CRC resistance to chemotherapy via promoting DNA repair and enhancing homologous recombination in vitro and in vivo. Mechanistically, CACClnc specifically bound to Y-box binding protein 1 (YB1, a splicing factor) and U2AF65 (a subunit of U2AF splicing factor), promoting the interaction between YB1 and U2AF65, and then modulated alternative splicing (AS) of RAD51 mRNA, and consequently altered CRC cell biology. In addition, expression of exosomal CACClnc in peripheral plasma of CRC patients can effectively predict the chemotherapy effect of patients before treatment. Thus, measuring and targeting CACClnc and its associated pathway could yield valuable insight into clinical management and might ameliorate CRC patients' outcomes.

Reliability and validity of the Chinese version of the self-directed learning instrument in Chinese nursing students.

BACKGROUND: In a rapidly changing healthcare environment, Self-directed learning (SDL) ability is recognized as a crucial condition for nursing students and nurse to deal with severe challenges positively. Developing SDL ability is becoming more and more important among nursing students. SDL is related to nursing students enhancing their own knowledge, skills and maintaining lifelong learning. This study is aim at translating the Self-directed Learning Instrument (SDLI) into Chinese and verify its reliability and validity among nursing students. METHODS: The study adopted a cross-sectional design and the multistage sampling design. The SDLI was translated into Chinese, and the reliability and validity of the scale were tested among 975 nursing students. RESULTS: The Cronbach's α value of the Chinese version of SDLI was 0.916. The split-half reliability coefficient was 0.829, and the retest coefficient was 0.884. The content validity index of the scale was 0.95. Furthermore, the four-factors model was obtained by using exploratory factor analysis, explaining 55.418% variance, and the communalities of the items ranged from 0.401 to 0.664. With modified confirmatory factor analysis, the fit indices were chi-square/degree of freedom (CMIN/DF) = 2.285, the comparative fit index (CFI) = 0.947, and the tucker lewis index (TLI) was 0.938. And, the model fitting indexes were all in the acceptable range and confirmatory factor analysis indicated that the model fit the SDLI well. CONCLUSION: The Chinese version of SDLI has good validity and reliability among nursing students. It can be used to measure the SDL ability of nursing students in China.

CUX2 prevents the malignant progression of gliomas by enhancing ADCY1 transcription.

Gliomas are one of the most prevalent brain tumors. This study sought to elucidate the mechanism of CUX2 in glioma development via ADCY1. CUX2 and ADCY1 expression in glioma predicted by bioinformatics analysis. Subsequent to gain- and loss-of-function experiments in glioma cells, cell proliferation was tested by CCK8 and plate clone formation assays, and cell migration and invasion by Transwell assay. The binding between CUX2 and ADCY1 was examined with dual-luciferase gene reporter and ChIP assays. The xenograft mouse model was established to verify the effect of the CUX2/ADCY1 axis on glioma cell growth in vivo. CUX2 and ADCY1 expression was low in glioma. The overexpression of CUX2 repressed the proliferative, migrating, and invasive abilities of glioma cells. Moreover, CUX2 was enriched in the ADCY1 promoter to enhance ADCY1 expression. ADCY1 upregulation diminished glioma cell proliferative, migrating, and invasive properties. Silencing of ADCY1 abrogated and upregulation of ADCY1 promoted the inhibitory influence of CUX2 upregulation on the malignant behaviors of glioma cells in vitro and gliomas cell growth in vivo. Collectively, CUX2 promoted ADCY1 transcription to delay glioma cell migration, proliferation, and invasion.

Health-related quality of life among Chinese patients with Crohn's disease: a cross-sectional survey using the EQ-5D-5L.

BACKGROUND: Crohn's disease (CD) is a chronic disease that may have an adverse impact on health-related quality of life (HRQoL). This study aimed to describe the HRQoL of CD patients and assess correlating factors using the EQ-5D-5L in China. METHODS: We recruited CD patients at Shanghai Renji Hospital from October 2018 to May 2019. The data collected included demographic and clinical information, medical expenditures, and EQ-5D-5L questionnaire responses. The chi-square test or Fisher's exact test was applied to analyse the proportion of patients in subgroups at each level. After the selection of correlating variables by univariate analysis, multivariate regression analyses were used to explore the correlating factors of HRQoL in CD patients. RESULTS: A total of 202 CD inpatients with a mean disease duration of 3.3 years were enrolled in the study. A total of 71.8% of patients were males, and 49.5% of patients were aged between 30 and 49 years. The average EQ-5D-5L utility score was 0.85, with a standard deviation (SD) of 0.12. Males, ileum lesions, remission status, and lower expenditure predicted higher EQ-5D-5L scores. In each EQ-5D-5L dimension, the proportion of patients differed significantly by gender, disease activity and location subgroup. In the multivariate regression models, being in an active CD state and using antibiotics had significantly adverse impacts on HRQoL (p < 0.05). CONCLUSIONS: CD may have a significant negative impact on HRQoL in Chinese CD patients. Being in an active phase of the disease and using antibiotics were identified as affecting HRQoL.

Microbe-based management for colorectal cancer.

ABSTRACT: Colorectal cancer (CRC) is one of the most prevalent, most lethal cancers in the world. Increasing evidence suggests that the intestinal microbiota is closely related to the pathogenesis and prognosis of CRC. The normal microbiota plays an essential role in maintaining gut barrier function and the immune microenvironment. Recent studies have identified carcinogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) and Streptococcus gallolyticus (S. gallolyticus), as well as protective bacterial such as Akkermansia muciniphila (A. muciniphila), as potential targets of CRC treatment. Gut microbiota modulation aims to restore gut dysbiosis, regulate the intestinal immune system and prevent from pathogen invasion, all of which are beneficial for CRC prevention and prognosis. The utility of probiotics, prebiotics, postbiotics, fecal microbiota transplantation and dietary inventions to treat CRC makes them novel microbe-based management tools. In this review, we describe the mechanisms involved in bacteria-derived colorectal carcinogenesis and summarized novel bacteria-related therapies for CRC. In summary, we hope to facilitate clinical applications of intestinal bacteria for preventing and treating CRC.

Enterotoxigenic Bacteroidesfragilis Promotes Intestinal Inflammation and Malignancy by Inhibiting Exosome-Packaged miR-149-3p.

BACKGROUND & AIMS: Enterotoxigenic Bacteroides fragilis (ETBF) is strongly associated with the occurrence of inflammatory bowel disease (IBD), colitis-associated colorectal cancer, and colorectal cancer (CRC). However, the mechanism of ETBF-induced intestinal inflammation and tumorigenesis remains unclear. METHODS: microRNA sequencing was used to detect the differentially expressed microRNAs in both ETBF-treated cells and exosomes derived from ETBF-inoculated cells. Cell Counting Kit 8 assays were used to evaluate the effect of ETBF and exosomes on CRC cell proliferation. The biological role and mechanism of ETBF-mediated miR-149-3p in colitis and colon carcinogenesis were determined both in vitro and in vivo. RESULTS: ETBF promoted CRC cell proliferation by down-regulating miR-149-3p both in vitro and in vivo. ETBF-down-regulated miR-149-3p depended on METTL14-mediated N6-methyladenosine methylation. As the target gene of miR-149-3p, PHF5A transactivated SOD2 through regulating KAT2A messenger RNA alternative splicing after ETBF treatment in CRC cells. miR-149-3p could be released in exosomes and mediated intercellular communication by modulating T-helper type 17 cell differentiation. The level of plasma exosomal miR-149-3p was gradually decreased from healthy control individuals to patients with IBD and CRC. miR-149-3p, existing in plasma exosomes, negatively correlated with the abundance of ETBF in patients with IBD and CRC. CONCLUSIONS: Exosomal miR-149-3p derived from ETBF-treated cells facilitated T-helper type 17 cell differentiation. ETBF-induced colorectal carcinogenesis depended on down-regulating miR-149-3p and further promoting PHF5A-mediated RNA alternative splicing of KAT2A in CRC cells. Targeting the ETBF/miR-149-3p pathway presents a promising approach to treat patients with intestinal inflammation and CRC with a high amount of ETBF.

BMSCs Regulate Astrocytes through TSG-6 to Protect the Blood-Brain Barrier after Subarachnoid Hemorrhage.

BACKGROUND: In patients with subarachnoid hemorrhage (SAH), the damage of the blood-brain barrier (BBB) can be life-threatening. Mesenchymal stem cells are widely used in clinical research due to their pleiotropic properties. This study is aimed at exploring the effect of BMSCs regulating astrocytes on the BBB after SAH. METHODS: The SAH model was established by perforating the blood vessels. BMSCs were transfected with TSG-6 inhibitor plasmid and cocultured with astrocytes. Intravenous transplantation of BMSCs was utilized to treat SAH rats. We performed ELISA, neurological scoring, Evans blue staining, NO measurement, immunofluorescence, BBB permeability, Western blot, HE staining, Nissl staining, and immunohistochemistry to evaluate the effect of BMSCs on astrocytes and BBB. RESULTS: SAH rats showed BBB injury, increased BBB permeability, and brain histological damage. BMSCs will secrete TSG-6 after being activated by TNF-α. Under the influence of TSG-6, the NF-κB and MAPK signaling pathways of astrocytes were inhibited. The expression of iNOS was reduced, while occludin, claudin 3, and ZO-1 expression was increased. The production of harmful substances NO and ONOO- decreased. The level of inflammatory factors decreased. The apoptosis of astrocytes was weakened. TSG-6 secreted by BMSCs can relieve inflammation caused by SAH injury. The increase in BBB permeability of SAH rats was further reduced and the risk of rebleeding was reduced. CONCLUSION: BMSCs can regulate the activation of astrocytes through secreting TSG-6 in vivo and in vitro to protect BBB.

Memantine protects blood-brain barrier integrity and attenuates neurological deficits through inhibiting nitric oxide synthase ser1412 phosphorylation in intracerebral hemorrhage rats: involvement of peroxynitrite-related matrix metalloproteinase-9/NLRP3 inflammasome activation.

Memantine has demonstrated beneficial effects on several types of brain insults via therapeutic mechanisms mainly related to its activity as a receptor antagonist of N-methyl-d-aspartate. However, the influences of memantine on intracerebral hemorrhage (ICH) remain obscure. This research probed into the neurovascular protective mechanisms of memantine after ICH and its impacts on neuronal nitric oxide synthase (nNOS) ser1412 phosphorylation. ICH model was established by employing intrastriatal collagenase injection in rats. After modeling, rats were then allocated randomly into sham-operated (sham), vehicle-treated (ICH+V), and memantine-administrated (ICH+M) groups. Memantine (20 mg/kg/day) was intraperitoneally administered 30 min after ICH and thenceforth once daily. Rats were dedicated at 0.25, 6, 12, 24 h, 3 and 7 d post-ICH for measurement of corresponding indexes. Behavioral changes, brain edema, levels of nNOS ser1412 phosphorylation, peroxynitrite, matrix metalloproteinase (MMP)-9, NLRP3, IL-1ß and numbers of dying neurons, as well as the cellular localization of gelatinolytic activity, were detected among the groups. Memantine improved the neurologic deficits and mitigated brain water content, levels of MMP-9, NLRP3, IL-1ß and dying neurons. Additionally, treatment with memantine also reduced nNOS ser1412 phosphorylation and peroxynitrite formation compared with the ICH+V group at 24 h after ICH. In situ zymography simultaneously revealed that gelatinase activity was primarily colocalized with vessel walls and neurons. We concluded that memantine ameliorated blood-brain barrier disruption and neurologic dysfunction in an ICH rat model. The underlying mechanism might involve repression of nNOS ser1412 phosphorylation, as well as peroxynitrite-related MMP-9 and NLRP3 inflammasome activation.

The Interval Anchoring Effect.

The anchoring effect refers to a decision bias that initial irrelevant information can influence late judgment. So far, most (if not all) studies on the anchoring effect adopted only point anchors (e.g., "Do you want to buy a computer with a price higher or lower than $1,000?"). In reality, people also use interval anchors (e.g., "Do you want to buy a computer with a price within $800-1,200?"). Can interval anchors also produce anchoring effect? Which kind of anchors have stronger anchoring effect? To answer these questions, we conducted four experiments involving quite different content. In each experiment, we found extremely significant anchoring effects for point anchors and interval anchors, respectively, but no significant difference between them. The results suggest that rarely researched interval anchors can be as powerful as intensively investigated point anchors and thus deserve more research and applications henceforth.

Intravenous administration of human amniotic mesenchymal stem cells improves outcomes in rats with acute traumatic spinal cord injury.

We previously reported that intraspinal transplantation of human amniotic mesenchymal stem cells (hAMSCs) promotes functional recovery in a rat model of acute traumatic spinal cord injury (SCI). However, whether intravenous transplantation of hAMSCs also has therapeutic benefit remains uncertain. In this study, we assessed whether intravenous transplantation of hAMSCs improves outcomes in rats with acute traumatic SCI. In addition, the potential mechanisms underlying the possible benefits of this therapy were investigated. Adult female Sprague-Dawley rats were subjected to SCI using a weight drop device, and then hAMSCs or PBS were administered after 2 h via the tail vein. Our results indicated that transplanted hAMSCs could migrate to injured spinal cord lesion. Compared with the control group, hAMSCs transplantation significantly decreased the numbers of ED1 macrophages/microglia and caspase-3 cells, and reduced levels of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6 and IL-1ß. In addition, hAMSCs transplantation significantly attenuated Evans blue extravasation, promoted angiogenesis and axonal regeneration. hAMSCs transplantation also significantly improved functional recovery. These results suggest that intravenous administration of hAMSCs provides neuroprotective effects in rats after acute SCI, and could be an alternative therapeutic approach for the treatment of acute SCI.

CCMAlnc Promotes the Malignance of Colorectal Cancer by Modulating the Interaction Between miR-5001-5p and Its Target mRNA.

OBJECTIVE: Colorectal cancer (CRC) is highly malignant and cancer metastasis remains the predominant cause of CRC death. The potential molecular mechanism of long non-coding RNA (lncRNAs) in CRC malignance is still poorly elucidated. METHODS: CCMAlnc expression was analyzed by using the Sequence ReadArchive (SRA) database. Target gene expression was examined by real-time PCR and Western blotting. The biological function of CCMAlnc and miR-5001-5p was detected by cell invasion, CCK8 proliferation, and colony formation assays in loss of function and gain of function experiments in vitro. A luciferase assay was performed to validate the target site of miR-5001-5p on the 3'-UTR of HES6 mRNA. RESULTS: CCMAlnc was identified as a novel functional lncRNA in CRC. Elevated CCMAlnc was detected in CRC cells as well as in clinical CRC tissue samples, and the expression of this lncRNA positively correlated with the poor prognosis of CRC patients. Functional validation assays revealed that downregulation of CCMAlnc impaired CRC cell proliferation and invasion in vitro, but upregulation of CCMAlnc reversed this effect. Moreover, CCMAlnc was validated to act as a competing endogenous RNA (ceRNA) that stabilizes the expression of HES6 by downregulating miR-5001-5p. CONCLUSION: CCMAlnc/miR-5001-5p/HES6 signaling is strongly activated to promote CRC malignance. CCMAlnc is defined as a potential candidate biomarker for metastasis prediction in CRC patients and as a potential therapeutic target for CRC treatment.

Lactoferrin- and RGD-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers for gliomatosis cerebri combination therapy.

PURPOSE: Glioblastoma multiforme (GBM) is the most common malignant brain tumor originating in the central nervous system in adults. Based on nanotechnology such as liposomes, polymeric nanoparticles, and lipid nanoparticles, recent research efforts have been aimed to target drugs to the brain. METHODS: In this study, lactoferrin- and arginine-glycine-aspartic acid (RGD) dual- ligand-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers (L/RT/V-NLCs) were introduced for GBM combination therapy. The physicochemical properties of L/R-T/V-NLCs such as particle size, zeta potential, and encapsulated efficiency are measured. The drug release profile, cellular uptake, cytotoxicity, tissue distribution, and antitumor activity of L/R-T/V-NLCs are further investigated in vitro and in vivo. RESULTS: L/R-T/V-NLCs were stable with nanosize and high drug encapsulation efficiency. L/R-T/V-NLCs exhibited sustained-release behavior, high cellular uptake, high cytotoxicity and synergy effects, increased drug accumulation in the tumor tissue, and obvious tumor inhibition efficiency with low systemic toxicity. CONCLUSION: L/R-T/V-NLCs could be a promising drug delivery system for glioblastoma chemotherapy.