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Inflammation is a key player in the regulation of depression. Shanzhiside methylester (SM) is an iridoid glycoside with strong anti-inflammatory properties. However, the antidepressant effect of SM remains unknown. The present study aimed to investigate whether SM protects against depression by targeting inflammation. A chronic unpredictable mild stress (CUMS)-induced mouse model of depression was established to assess the antidepressant effect of SM in vivo. In addition, an LPS plus ATP-induced cellular model of inflammation was used to explore the related inflammatory mechanism. We found that both SM and miRNA-155-5p sponge markedly remedied CUMS-induced depression-like behaviors in the sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST), accompanied by decreased Iba1 expression and the production of TNF-α, IL-1β, and IL-6. Moreover, SM and miRNA-155-5p sponge upregulated the protein levels of SOCS1 and downregulated the protein expression of p-JAK2 and p-STAT3 in the hippocampus of CUMS-exposed mice. miRNA-155-5p expression was also decreased following SM and miRNA-155-5p sponge administration. Furthermore, SM repressed LPS- and ATP-induced inflammatory responses in BV2 cells by regulating the SOCS1/JAK2/STAT3 signaling pathway, which was similar to the anti-inflammatory effects induced by the miRNA-155-5p sponge. Collectively, these findings suggested that SM exerted antidepressant actions by targeting the miRNA-155-5p/SOCS1 axis. [ABSTRACT FROM AUTHOR]

Herein, we report a catalytic enantioselective addition of C-alkynyl imines with hydroperoxides catalyzed by chiral BINOL calcium phosphate, affording a broad range of enantioenriched α-peroxy propargylamines in good yields (80–99%) with high enantioselectivities (up to 94% ee). The protocol is characterized by mild conditions, easy accessibility and good practicability. [ABSTRACT FROM AUTHOR]

Thefirst method for the asymmetric synthesis of C3-monosubstitutedchiral carbazolones, structural motifs common in medicinal chemistry,has been achieved using Pd-catalyzed decarboxylative protonation ofcarbazolones. This methodology has been applied to the first catalyticenantioselective formal synthesis of (−)-aspidofractinine withstep economy and simplicity. [ABSTRACT FROM AUTHOR]

We report the first catalytic asymmetric approach to octahydroindolones and a divergent enantioselective synthesis of perhydroindole alkaloids, as exemplified by lycorine-type Amaryllidaceae alkaloids (+)-α-lycorane and (+)-lycorine, from a common intermediate by using a highly concise route. The assembly of octahydroindolones employs a catalytic enantioselective 1,4-conjugate addition of nitro dienynes, followed by a TsOH-catalyzed cascade synthesis of highly functionalized enones, and a diastereoselective intramolecular Michael addition. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the effects of low-level laser therapy (LLLT) on the homeostasis of reactive oxygen species (ROS) and expression of IGF-1 and TGF-β1 in the gastrocnemius muscles of rats following contusion. Muscle regeneration involves cell proliferation, migration, and differentiation and is regulated by growth factors. A growing body of evidence suggests that LLLT promotes skeletal muscle regeneration and accelerates tissue repair. Adult male Sprague-Dawley rats (n=96) were randomly divided into three groups: control group (no lesion, untreated, n=6), contusion group (n=48), and contusion-plus-LLLT group (n=42). Gallium aluminum arsenide (GaAlAs) laser irradiation (635 nm; beam spot, 0.4 cm(2); output power, 7 mW; power density, 17.5 mW/cm(2); 20 min) was administered to the gastrocnemius contusion for 20 min daily for 10 days. Muscle remodeling was evaluated at 0 h and 1, 2, 3, 7, 14, 21, and 28 days after injury. Hematoxylin and eosin and Van Gieson staining were used to evaluate regeneration and fibrosis; muscle superoxide dismutase (SOD) and malondialdehyde (MDA) were detected via biochemical methods; expression of transforming growth factor beta-1 (TGF-β1) and insulin-like growth factor-1 (IGF-1) were investigated via immunohistochemistry. The results showed that LLLT markedly promoted the regeneration of muscle and reduced scar formation. LLLT also significantly enhanced muscle SOD activity and significantly decreased muscle MDA levels 1, 2, and 3 days after injury. LLLT increased the expression of IGF-1 2, 3, and 7 days after injury and decreased the expression of IGF-1 21 and 28 days after injury. LLLT decreased the expression of TGF-β1 3 and 28 days after injury but increased expression at 7 and 14 days after injury. Our study showed that LLLT could modulate the homeostasis of ROS and of the growth factors IGF-1 and TGF-β1, which are known to play important roles in the repair process. This may constitute a new preventive approach to muscular fibrosis. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the effects of low-level laser therapy (LLLT) on the homeostasis of reactive oxygen species (ROS) and expression of IGF-1 and TGF-β1 in the gastrocnemius muscles of rats following contusion. Muscle regeneration involves cell proliferation, migration, and differentiation and is regulated by growth factors. A growing body of evidence suggests that LLLT promotes skeletal muscle regeneration and accelerates tissue repair. Adult male Sprague-Dawley rats ( n = 96) were randomly divided into three groups: control group (no lesion, untreated, n = 6), contusion group ( n = 48), and contusion-plus-LLLT group ( n = 42). Gallium aluminum arsenide (GaAlAs) laser irradiation (635 nm; beam spot, 0.4 cm; output power, 7 mW; power density, 17.5 mW/cm; 20 min) was administered to the gastrocnemius contusion for 20 min daily for 10 days. Muscle remodeling was evaluated at 0 h and 1, 2, 3, 7, 14, 21, and 28 days after injury. Hematoxylin and eosin and Van Gieson staining were used to evaluate regeneration and fibrosis; muscle superoxide dismutase (SOD) and malondialdehyde (MDA) were detected via biochemical methods; expression of transforming growth factor beta-1 (TGF-β1) and insulin-like growth factor-1 (IGF-1) were investigated via immunohistochemistry. The results showed that LLLT markedly promoted the regeneration of muscle and reduced scar formation. LLLT also significantly enhanced muscle SOD activity and significantly decreased muscle MDA levels 1, 2, and 3 days after injury. LLLT increased the expression of IGF-1 2, 3, and 7 days after injury and decreased the expression of IGF-1 21 and 28 days after injury. LLLT decreased the expression of TGF-β1 3 and 28 days after injury but increased expression at 7 and 14 days after injury. Our study showed that LLLT could modulate the homeostasis of ROS and of the growth factors IGF-1 and TGF-β1, which are known to play important roles in the repair process. This may constitute a new preventive approach to muscular fibrosis. [ABSTRACT FROM AUTHOR]

Ten-eleven translocation protein 1 (Tet1) is associated with the regulation of depression-like behaviour in mice. However, the mechanism by which Tet1 affects neurogenesis in mice to regulate depression-like behaviours remains unclear. In this study, the chronic social defeat stress (CSDS) paradigm was constructed by overexpressing Tet1 protein in the mouse hippocampus, and 5-ethynyl-2′-deoxyuridine (EdU, 50 mg/kg) was injected on the seventh day to explore the mechanism of the regulation of the Tet1/Delta-like protein 3 (DLL3)/Notch1 protein pathway in mice hippocampal neurogenesis and its influence on depression-like behaviour. Following CSDS, the expression level of Tet1 decreased significantly. Moreover, due to the downregulation of Tet1 protein, the maintenance of the DNA methylation and demethylation balance was affected, resulting in a significant increase in the methylation levels of Notch1 and DLL3 and a significant decrease in the protein expression levels of DLL3, Notch1, and brain-derived neurotrophic factor (BDNF). At the same time, the proliferation and differentiation of neurones were affected, which was related to a significant decrease in the number of EdU+, doublecortin (DCX)+, and Ki67+ cells in the hippocampus of the CSDS model mice. When the Tet1 protein was overexpressed in the mouse hippocampus, DLL3 and Notch1 protein expression levels were upregulated, promoting hippocampal neurogenesis and alleviating depression-like behaviour in mice. These findings suggest that regulation of the hippocampal Tet1/DLL3/Notch1 protein pathway to influence neurogenesis may be a therapeutic strategy for depression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to describe the current situation and explore overwork predictors among ICU nurses in China. BACKGROUND: Overwork is a comprehensive condition of labor where employees work for extended periods with high intensity and high pressure, which can negatively affect their health. Limited literature exists regarding the prevalence, characteristics, professional identity, and environment of overwork among ICU nurses. METHODS: A cross-sectional design study was conducted. The Professional Identification Scale for Nurses, the Practice Environment Scale of the Nursing Work Index, and the Overwork Related Fatigue Scale (ORFS) were used. To explore relationships between variables, univariate analysis or bivariate correlations were used. Multiple regression was used to identify predictors of overwork. RESULTS: Almost 85% of nurses were categorized as overworked, of which, 30% were moderately to severely overworked. Gender, form of employment, stress related to ICU nursing technology and equipment updates, nurses' professional identity, and nurse working environment accounted for 36.6% in the ORFS. CONCLUSIONS: Overwork is common among ICU nurses. Nurse managers need to develop and implement strategies to better support nurses to prevent overwork. [ABSTRACT FROM AUTHOR]

The first catalytic enantioselective formal synthesis of (-)-aspidofractinine (II) is achieved via key intermediate (I), which is synthesized in only ten steps from commercially available starting materials. [ABSTRACT FROM AUTHOR]

The article presents a chemical structure of Lycorine-Type Amaryllidaceae Alkaloids (+)-α-Lycorane and (+)-Lycorine.

The incorporation of different functional groups into organic molecules is a common method to construct soft liquid crystalline materials with multiple properties and adjust mesophases from one-dimensional to three-dimensional structures. This article reports the synthesis, characterization, self-assembly, and binding selectivity behaviors of the first isoflavone-based hexacatenar liquid crystalline materials with an isoflavone as central rigid core and two 1,2,3-triazole dendritic wings as terminal functional units. Polarized optical microscopy, differential scanning calorimetry, and small-angle X-ray scattering (SAXS) investigations indicated that all the compounds could self-assemble into rectangular columnar mesophase. The differences in temperature range of mesophase and sequence of mesophase compared with previously reported coumarin-based polycatenars were attributed to the change of position of carbonyl. The optical spectra indicated that these compounds display selectivity for Fe2+ among the different and cations. FT-IR and density functional theory calculations before and after interaction with Fe2+ were employed to demonstrate the recognition sites. The design strategy here provides a simple method to construct supramolecular self-assembly materials with wide properties and potentials. [ABSTRACT FROM AUTHOR]

It has been found that pilose antler peptide has an antidepressant effect on depression. However, the exact molecular mechanism of its antidepressant effect is still unclear. The study sought to determine the impact of monomeric pilose antler peptide (PAP; sequence LVLVEAELRE) on depression as well as investigate potential molecular mechanisms. Chronic unexpected mild stress (CUMS) was used to establish the model, and the effect of PAP on CUMS mice was detected by the behavioral test. The influence of PAP on neuronal cells and dendritic spine density was observed by immunofluorescence and Golgi staining. FGFR3 and the CaMKII-associated pathway were identified using quantitative real-time polymerase chain reaction, and Western blot analysis was utilized to measure their proteins and gene expression levels. Molecular docking and microscale thermophoresis were applied to detect the binding of PAP and FGFR3. Finally, the effect of FGFR3's overexpression on PAP treatment of depression was detected. PAP alleviated the changes in depressive behavior induced by CUMS, promoted the growth of nerve cells, and the density of dendritic spines was increased to its original state. PAP therapy successfully downregulated the expression of FGFR3 and ERK1/2 while upregulating the expression of CREB, BDNF, and CaMKII. Based on the current research, PAP has a therapeutic effect on depression brought on by CUMS by inhibiting FGFR3 expression and enhancing synaptic plasticity. [Display omitted] • PAP (sequence LVLVEAELRE) alleviates depressive behavior in CUMS mice. • PAP enhanced CUMS-induced reduction of neurogenesis and synaptic plasticity. • PAP reduces depressive behavior by affecting FGFR3 and CaMKII-related pathways. • Overexpression of FGFR3 inhibits the therapeutic effects of PAP. [ABSTRACT FROM AUTHOR]

Microglia are the static resident cells possessing the phagocytic properties in the central nervous system (CNS). In many relevant studies, the immortalized murine microglial cell line BV2 has been used as a tool in primary microglia (PM) relevant studies. Microglia participate in neuroinflammation by converting into M1‐ and M2‐like phenotypes. In this study, we established M1‐ and M2‐like phenotype response models by exposing PM and BV2 cells to lipopolysaccharides (LPS) and interlukin‐4 (IL‐4), respectively, and discovered the proteomic differences between the two types of microglia. It turned out that the BV2 cell responses to LPS and IL‐4 were narrower and weaker than that of PM. In addition, irradiation, which has been shown to activate microglia and induces neuroinflammation, was also used as a treatment in this study. The results showed that BV2 cells have stronger capacity of DNA damage repair. Besides, irradiation had a negative effect on the regulation of KEGG pathways such as proteasome, ribosome, oxidative phosphorylation and TCA cycle in both cells. Furthermore, the KEGG pathways including cell cycle and DNA replication (significantly downregulated), and antigen processing and presentation and FC γ R mediated phagocytosis (significantly up‐regulated) were only found in irradiated PM. These data demonstrate that PM is more fragile to irradiation. Results in this study indicate that BV2 cells only partially model PM, and thus, using BV2 in microglia related studies should be carefully considered. [ABSTRACT FROM AUTHOR]

Objective: Multidrug-resistant tuberculosis (MDR-TB) causes persistent infection and challenges tuberculosis control worldwide. T cell-mediated immunity plays a critical role in controlling Mycobacterium tuberculosis (Mtb) infection, and therefore, enhancing Mtb-specific T cell immune responses represents a promising therapeutic strategy against TB. Cytokine-induced killer (CIK) immunotherapy is based on autologous infusion of in vitro expanded bulk T cells, which include both pathogen-specific and nonspecific T cells from patient peripheral blood mononuclear cells (PBMC) into TB patients. Preclinical mouse studies have shown that the adoptive T cell therapy inhibited Mtb infection. However, the efficacy of CIK immunotherapy in the treatment of MDR-TB infection has not been evaluated in clinical trials.Methods: We performed a retrospective study of MDR-TB patients who received CIK immunotherapy in combination with anti-TB chemotherapy and those who had standard chemotherapy.Results: Our results showed that CIK immunotherapy in combination with anti-TB chemotherapy treatment increased the conversion rate of sputum smear and Mtb culture, alleviated symptoms, improved lesion absorption, and increased recovery. The kinetics of serology and immunology index monitoring data showed good safety profiles for the CIK treatment.Conclusion: Our study has provided strong evidence that CIK immunotherapy in combination with anti-TB chemotherapy is beneficial for MDR-TB patients. A multicenter clinical trial is warranted to evaluate CIK as a new immune therapy for MDR-TB. [ABSTRACT FROM AUTHOR]

Filamin A (FlnA) is an actin cross-linking protein. Previous studies have demonstrated its role in tumor progression in a wide range of cancer types. It has been reported that FlnA interacts with the DNA damage response protein, breast cancer gene 1 (BRCA1), which is a tumor suppressor gene. However, to the best of our knowledge, there are no studies evaluating the association of these genes in human carcinomas. In the present study, the immunohistochemistry of a tissue microarray was used to investigate the clinical significance of FlnA and BRCA1 expression in pathological specimens collected from 424 patients treated for breast cancer. In addition, FlnA and BRCA1 expression was downregulated in the breast cancer cell line, MCF-7, through FlnA RNA interference. FlnA expression was exhibited by cancer tissues collected from 137 patients with breast cancer, which also exhibited high expression of BRCA1 and were associated with a relatively long survival time. A significant association was identified between FlnA protein expression and tumor size, and between FlnA protein expression and progesterone receptor expression. These results suggest that BRCA1 expression could be regulated by FlnA in the breast cancer cell line, MCF-7. Overall, the present study demonstrates that FlnA expression was associated with BRAC1 expression and tumor size in breast cancer, which provides important implications for future study of FlnA in the progression of human breast cancer. [ABSTRACT FROM AUTHOR]

Both membrane-bound and soluble forms of costimulatory molecules play important roles in immune-regulatory networks. B7-H3, a member of the B7 family, has been found with aberrant expression in tumors and infectious disease. However, the significance of sB7-H3 expression in systemic lupus erythematosus (SLE) has not been investigated. Using the peripheral blood of 78 SLE patients, we established a comprehensive database containing clinical data and relevant laboratory tests. We found that sB7-H3 expression in SLE patients was significantly lower compared with the healthy individuals. In addition, sB7-H3 levels in the patients were positively correlated with the disease activity as indicated by SLE disease activity index score, rashes, fever, and inflammatory cytokines. Moreover, sB7-H3 was associated with the counts of red blood cells and hemoglobin. Our findings suggest that sB7-H3 might counteract the aberrant immune response and potentially serve as a monitoring indicator of disease progression and therapeutic target in SLE treatment. [ABSTRACT FROM AUTHOR]

Abstract: Stress has been reported to activate the locus coeruleus (LC)–noradrenergic system. However, the molecular link between chronic stress and noradrenergic neurons remains to be elucidated. In the present study adult Fischer 344 rats were subjected to a regimen of chronic social defeat (CSD) for 4weeks. Measurements by in situ hybridization and Western blotting showed that CSD significantly increased mRNA and protein levels of the norepinephrine transporter (NET) in the LC region and NET protein levels in the hippocampus, frontal cortex and amygdala. CSD-induced increases in NET expression were abolished by adrenalectomy or treatment with corticosteroid receptor antagonists, suggesting the involvement of corticosterone and corticosteroid receptors in this upregulation. Furthermore, protein levels of protein kinase A (PKA), protein kinase C (PKC), and phosphorylated cAMP-response element binding (pCREB) protein were significantly reduced in the LC and its terminal regions by the CSD paradigm. Similarly, these reduced protein levels caused by CSD were prevented by adrenalectomy. However, effects of corticosteroid receptor antagonists on CSD-induced down-regulation of PKA, PKC, and pCREB proteins were not consistent. While mifeprestone and spironolactone, either alone or in combination, totally abrogate CSD effects on these protein levels of PKA, PKC and pCREB in the LC and those in the hippocampus, frontal cortex and amygdala, their effects on PKA and PKC in the hippocampus, frontal cortex and amygdala were region-dependent. The present findings indicate a correlation between chronic stress and activation of the noradrenergic system. This correlation and CSD-induced alteration in signal transduction molecules may account for their critical effects on the development of symptoms of major depression. [Copyright &y& Elsevier]

Abstract: Systemic administration of mice with folic acid (FA) has been used for studying the pathogenesis of acute renal failure. However, the molecular mechanisms by which FA induces acute renal failure remain poorly understood. We found that CD-1 mice treated with FA developed acute renal failure characterized by increased blood urea nitrogen, necrosis, and apoptosis of tubular epithelial cells. Compared to control mice, tumor necrosis factor-α (TNF-α) was markedly elevated in blood and kidneys of these FA-treated mice, accompanied by markedly reduced expression of anti-apoptotic protein BclxL in their kidneys. In vivo administration of FA-treated CD-1 mice with neutralizing anti-TNF-α antibody restored the expression of BclxL in kidneys and inhibited the necrosis and apoptosis of renal tubular epithelial cells, leading to the amelioration of acute renal failure. In ex vivo cultures, we found that FA enhanced production of TNF-α, decreased expression of BclxL protein, and induced apoptosis of mouse cortical tubule (MCT) cells. Addition of neutralizing anti-TNF-α antibody, but not control IgG, in the cultures markedly blocked the apoptotic death of FA-treated MCT cells and restored expression of BclxL to the same levels as those MCT cells cultured in the absence of FA. All these results suggest that TNF-α is a critical inflammatory cytokine responsible for FA-mediated acute renal failure. Furthermore, in vivo administration of anti-TNF-α antibody may be proved as an effective approach for acute renal failure prevention and treatment. [Copyright &y& Elsevier]

Background: A wealth of published studies have been published on association between Chlamydia pneumoniae (C.pneumoniae) infection and cerebrovascular (CV) disease, but the results were inconsistent. This meta-analysis provides a systematic review of the available evidence from all serological and pathological studies of CV disease and C.pneumoniae.Methods: A comprehensive research was conducted of MEDLINE, EMBASE, CNKI, WanFang technological periodical database and reference lists of articles to identify eligible case-control and cohort studies. Odds radio (OR) was calculated for each study outcome. Random effect model was used as pooling method and publication bias was estimated for the results.Results: Fifty-two published studies that met criteria were selected. In case control studies, an association between C.pneumoniae infection and CV disease was revealed by serum specific IgG (OR, 1.61; 95% CI: 1.34 to 1.94), serum IgA (OR, 2.33; 95% CI: 1.76 to 3.08) and PCR technique of C.pneumoniae in peripheral blood cells (OR, 1.90; 95% CI: 1.17 to 3.07). No significant association was found in serum anti-C.pneumonae IgM seropositivity or in-situ-detection of C.pneumoniae in arterial biopsies with CV disease. Subgroup analysis by available studies suggested that C.pneumoniae may paly a role in atherosclerotic stroke, but be less significant in stroke of cardioembolism or other etiologies.Conclusion: Association between C.pneumoniae infection and CV disease depends on the analytical method adopted, which seems stronger with stroke due to large artery atherosclerosis. Establishing a causal relationship between C.peumoniae infection and CV disease will require more prospective studies with combination of techniques and stratified by etiological subtypes. [ABSTRACT FROM AUTHOR]