Identify GADD45G as a potential target of 4-methoxydalbergione in treatment of liver cancer: bioinformatics analysis and in vivo experiment.

BACKGROUND: The growth arrest and DNA damage-inducible gene gamma (GADD45G), an important member of GADD45 family, has been connected to the development of certain human cancers. Our previous studies have confirmed that GADD45G expression could be upregulated by 4-methoxydalbergione (4MOD) in liver cancer cells, but its potential pathological role in hepatocellular carcinoma (HCC) has not been fully understood. This study aimed to determine potential role of GADD45G in HCC, and the effects of 4-methoxydalbergione (4MOD) on the regulation of GADD45G expression in vivo were also analyzed. METHODS: Publicly available data and in-house immunohistochemistry (IHC) experiments were utilized to explore the expression profiles and clinical significance of GADD45G in HCC samples. Functional enrichment analysis based on GADD45G co-expression genes was used to excavate the molecular mechanism of GADD45G in HCC. We also conducted in vivo experiment on BALB/c nude mice to excavate the inhibitory effect of 4MOD on HCC and to evaluate the differences in the expression of GADD45G in xenograft tissues between the 4MOD-treated and untreated groups. RESULTS: GADD45G displayed significant low expression in HCC tissues. Downregulated expression of GADD45G was positively correlated with some high risk factors in HCC patients and predicted worse prognosis of HCC patients. There was a close association of GADD45G mRNA expression and immune cells, including neutrophils, NK cells, CD8 T cells, and macrophages. Co-expressed genes of GADD45G were involved in several pathways including cell cycle, carbon metabolism, and peroxisome. 4MOD could significantly suppress the growth of HCC in vivo, and this inhibitory effect was dependent on the upregulation of GADD45G expression. CONCLUSION: GADD45G expression can be used as a new clinical biomarker for HCC and GADD45G may be a potential target for the anti-cancer effect of 4MOD in liver cancer.

Empathetic nursing with mindful cognitive therapy for fatigue, depression, and negative emotions in leukemia patients undergoing long-term chemotherapy.

BACKGROUND: Leukemia is a broad term for blood cell cancer. Leukemia is divided into acute or chronic, depending on cell differentiation. Leukemia patients are prone to adverse reactions during chemotherapy, such as anxiety, depression, and even suicide, affecting prognosis. As a nursing model developed by three well-known cognitive psychologists, empathetic nursing with mindfulness cognitive therapy (ENMCT) can effectively reduce anxiety and depression and improve the quality of life in patients with chronic disease. AIM: To explore the effect of ENMCT on cancer-induced fatigue, hope level, and negative emotions in patients with long-term leukemia chemotherapy. METHODS: A total of 103 patients with long-term leukemia chemotherapy diagnosed and treated in our hospital from July 2017 to October 2019 were enrolled and randomly assigned to observation and control groups using the random number table approach. Fifty-one patients in the control group received routine nursing, while 52 patients in the observation group received empathic nursing with mindfulness cognitive therapy. After three months of nursing care, cancer-induced fatigue was measured with the Piper Fatigue Scale (PFS), hope level with the Herth Hope Index (HHI), and negative emotion with the Hamilton Anxiety Scale (HAMA)/Hamilton Depression Scale (HAMD). Self-management (Chinese Strategies Used by People to Promote Health) was also recorded. RESULTS: The observation group's total scores in behavior, cognition, emotion, feeling, and PFS were lower than the control group after the intervention (P < 0.05). Keeping close contact with others, the attitude of taking positive actions, the attitude toward reality and future, and the total HHI score were higher in the observation group than the control group (P < 0.05). The observation group's HAMA and HAMD scores were lower than the control group (P < 0.05). The observation group's positive attitude, self-decision, and self-relief scores were greater than the control group (P < 0.05). CONCLUSION: Empathetic nursing with cognitive mindfulness therapy is beneficial in improving cancer-related fatigue, negative emotions, expectation level, and self-management ability in patients with long-term leukemia chemotherapy.

Adverse effects of iron deficiency anemia on pregnancy outcome and offspring development and intervention of three iron supplements.

Iron deficiency anemia (IDA) is a common micronutrient deficiency among pregnant women with severe consequences including impaired immuno-inflammatory system, premature birth, fetal death etc. The present study aimed to investigate the effects of three iron supplements on IDA female rats and their offspring. The IDA female rat model was established with low iron diet and the rats were then mated. After pregnancy, rats were fed diets containing different iron supplements (iron polysaccharide complex, iron protein succinylate and ferrous sulfate) until their offspring were 42 days old. Pregnancy outcomes, haematological, iron metabolism, physical and neurological development indexes were determined. The results showed that all three iron supplements improved the levels of hematological parameters of both mother and offspring rats. After iron supplementation, serum iron, transferrin saturation and serum ferritin levels were increased compared with the IDA group. The level of ferritin light chain in the liver and spleen of both mother and offspring rats in iron supplemented groups was significantly higher than that of the IDA group. The average number of born alive per litter in the iron treatment groups was significantly higher than that in the IDA group. Iron supplements also improved the physical growth and neurobehavioral development of offspring rats. It was also found that iron supplementation improved the expression of ferritin light chain and the synaptic growth associated proteins in the brain and hippocampus. No significant difference was found in the efficacy of three iron supplements. These results suggest that pregnant and postpartum IDA affects pregnancy outcomes, offspring physical development and causes neural impairment. Sufficient iron supplementation can significantly improve IDA and its adverse effects on both mother and offspring.

Long Afterglow of a Nonporous Coordination Polymer with Tunable Room-Temperature Phosphorescence by the Doping of Dye Molecules.

Metal-organic frameworks (MOFs) or coordination polymers (CPs)-based phosphorescence materials may provide a powerful route for photoelectric and optical recording devices. Herein, two phosphorescence ligands, iso-phthalic acid (IPA) and 2-methylimidazole (MIM), were selected to construct an nonporous CP {Zn(IPA)(MIM)2} (1) with a long-lived phosphorescence lifetime up to 552 ms. By the doping of Eosin Y (EY) dye molecules under an in situ process, the phosphorescence emission color of 1 can be expressly tuned from green to red. The light-harvesting range can also be vastly broadened from the UV to the visible region (550 nm). Photoelectron measurements reveal that the synergistic effect of bias voltage and illumination can greatly restrain electron-hole recombination for the generation of additional free charges.

Hexanuclear Zn(II)-Induced Dense π-Stacking in a Metal-Organic Framework Featuring Long-Lasting Room Temperature Phosphorescence.

A new strategy to enhance the room temperature phosphorescence performance has been developed through hexanuclear Zn(II)-cluster-induced dense π-stacking in a metal-organic framework matrix. The synergistic effect of metal clusters and large overlap of π-conjugated dimers facilitate the phosphorescence emission, migration, and separation of charge carriers for excellent photocatalytic activity.

Fast Crystallization-Deposition of Orderly Molecule Level Heterojunction Thin Films Showing Tunable Up-Conversion and Ultrahigh Photoelectric Response.

Molecular cocrystals have received much attention for tuning physicochemical properties in pharmaceutics, luminescence, organic electronics, and so on. However, the effective methods for the formation of orderly cocrystal thin films are still rather limited, which have largely restricted their photofunctional and optoelectronic applications. In this work, a fast crystallization-deposition procedure is put forward to obtain acridine (AD)-based cocrystals, which are self-assembled with three typical isophthalic acid derivatives (IPA, IPB, and TMA). The obtained donor-acceptor cocrystal complexes exhibit an adjustable energy level, wide range of photoluminescence color, and rotational angle-dependent polarized emission. The orderly and uniform cocrystal thin films further present tunable one-/two-photon up-conversion and different semiconductor properties. Particularly, AD-TMA cocrystal thin film shows a rare example of a molecule level heterojunction with the alternating arrangement of AD electronic acceptor layers and TMA electronic donor layers, and thus, provides a way for efficient mobility and separation of electron-hole pairs. A large on-off photocurrent ratio of more than 104 can be achieved for the AD-TMA thin film, which is higher than state-of-the-art molecular semiconductor systems. Therefore, this work extends the application scopes of orderly cocrystal thin film materials for future luminescent and optoelectronic micro-/nanodevices.

Facile synthesis of a micro-scale MOF host-guest with long-lasting phosphorescence and enhanced optoelectronic performance.

Micro-scale MOFs with a persistent phosphorescence lifetime of 900 ms can be facilely synthesized by a fast precipitation process in aqueous solution. The in situ encapsulation of a dye into the MOF matrix can expressly tune the phosphorescence color from green to a rare example of red emission with a lifetime of 450 ms, highly enhancing the photoelectrocatalytic water splitting.

Genistein inhibits nasopharyngeal cancer stem cells through sonic hedgehog signaling.

Genistein, a soy derived isoflavanoid compound, exerts anticancer effects in various cancers. Nasopharyngeal cancer stem cells (NCSCs) are a small subpopulation of cancer cells which are responsible for initiation, progression, metastasis, and recurrence of nasopharyngeal cancer. The present study aimed to investigate the suppressive effects of genistein on NCSCs and its underlying mechanism. NCSCs were enriched from human nasopharyngeal cancer cell lines CNE2 and HONE1 through tumorsphere-forming assay. It was shown that genistein inhibited the tumorsphere formation capacity, decreased the number of EpCAM+ cells, downregulated the expression of NCSCs markers, suppressed cell proliferation, and induced apoptosis of NCSCs. Genistein suppressed the activity of Sonic hedgehog (SHH) signaling, which was important for the maintenance of NCSCs, while activation of SHH signaling by purmorphamine diminished the inhibitory effects of genistein on NCSCs. Our data suggested that genistein inhibited NCSCs through the suppression of SHH signaling. These findings support the use of genistein for targeting NCSCs.

Room temperature phosphorescence of Mn(ii) and Zn(ii) coordination polymers for photoelectron response applications.

Room temperature phosphorescence of Mn(ii) and Zn(ii) based coordination polymers (Mn-CP and Zn-CP) with a different mechanism was confirmed by experiments and theory calculations. The Mn-CP exhibits high photoelectron response performance while Zn-CP can generate frequency tunable alternating current when the period of on-off illumination is changed.

{Zn6} Cluster Based Metal-Organic Framework with Enhanced Room-Temperature Phosphorescence and Optoelectronic Performances.

Molecule-based solid-state materials with long lifetimes could enable longer migration distances for excitons, which are beneficial for vast applications in optoelectronic field. Herein, we report a hexanuclear zinc cluster based MOF exhibits highly enhanced phosphorescence about 2 orders of magnitude in comparison with the pristine phosphor ligand. The combination of both experimental and computational results suggest that the {Zn6} cluster is very important for adjusting molecular conformations, packing arrangement, and photophysical properties of the organic phosphor ligands within the MOF matrix. Optoelectronic measurements reveal that the MOF-modified electrode is catalytically active to hydrogen evolution under light irradiation in neutral solution. Thus, our study provide an effective way to achieve low-cost metal-based phosphorescence MOF, expanding its further optoelectronic applications.

[Effects of exogenous melatonin on nitrogen metabolism and osmotic adjustment substances of melon seedlings under sub-low temperature].

The melon cultivar 'Yangjiaosu' was subjected to the treatment of 18 °C/12 °C (day/night) in an artificial climate chamber for 6 days, and the activities of nitrogen metabolism related enzymes [nitrate reductase (NR), glutamine synthetase (GS), glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH) ] , the contents of total N, NO3(-)-N and NH4+-N as well as the osmotic adjustment substances of melon leaf were then determined. The results showed that, compared with the control, sub-low temperature treatment reduced the contents of total N, NO3(-)-N and the NR activity, but increased the content of NH4(+)-N, thereby leading to the growth inhibition of melon. Exogenous MT treatment significantly improved the activities of nitrogen metabolism related enzymes, especially the activities of GS and GOGAT, effectively reducing the content of NH4+-N. Moreover, MT treatment increased the contents of proline, soluble protein and soluble sugar, and alleviated the damage of sub-low temperature on the cell membrane by reducing the relative electrical conductivity and MDA content of melon leaves. In short, this work suggested that exogenous MT would enhance the sub-low temperature adaptability of melon by decreasing the leaf content of NH4-N, increasing the contents of osmotic adjustment substances and reducing the membrane lipid peroxidation levels.

The effect of benzodiazepines on insomnia in patients with chronic obstructive pulmonary disease: a meta-analysis of treatment efficacy and safety.

BACKGROUND: Insomnia is a common comorbidity associated with COPD. Although benzodiazepines (BZDs) can have adverse effects on respiratory response in COPD patients, these are the most common hypnotics. The aim of this study was to examine by meta-analysis the efficacy and safety of BZD to treat insomnia in COPD patients. MATERIALS AND METHODS: Electronic databases (PubMed, China National Knowledge Infrastructure, Cochrane clinical trials database) were searched. Studies were eligible if they compared the effects of BZD versus placebo on insomnia in COPD patients. Two reviewers extracted data independently. Disagreements were resolved by discussion with another reviewer until a consensus was achieved. Data that included objective and subjective sleep evaluation and respiratory function variables were extracted. Data were analyzed by the methods recommended by Review Manager 5.3 software. RESULTS: A total of 233 records were identified through the initial search; of these, five studies were included in the meta-analysis. When BZD was compared with placebo, objective sleep quality was significantly improved, including total sleep time (95% confidence interval [CI] 0.54-1.14, P<0.00001), sleep efficiency (95% CI 0.48-1.16, P<0.00001), sleep latency (95% CI -18.24 to -4.46, P=0.001), and number of arousals/hour of sleep (95% CI -0.72 to -0.07, P=0.02). Otherwise, subjective sleep quality was not improved remarkably. Apart from maximum transcutaneous carbon dioxide pressure increase during sleep (95% CI 0.05-0.28, P=0.006), BZD administration had no effect on respiratory assessment. CONCLUSION: In this meta-analysis, the results suggested BZDs might be efficient and safe hypnotics. Compared with placebo, BZD improved sleep quality partly, and significantly increased maximum transcutaneous carbon dioxide pressure during sleep. More randomized controlled trials are necessary to determine the potential effect of BZD in COPD patients with insomnia.

[Effects of brassinolide on the antioxidant system and photosynthesis of cucumber seedlings under suboptimal temperature, light and salt environment].

The effects of 24-epibrassinolide (EBR) on antioxidant system and photosynthesis of cucumber seedlings were studied under suboptimal temperature, light and salt environment. Compared with the control, the leaf H2O2 content, lipid peroxidation and cell membrane permeability significantly increased, and the leaf net photosynthetic rate (Pn), stomatal conductance (g(s)), intercellular CO2 concentration (Ci), transpiration rate (Tr) and dry matter accumulation decreased by 39.3%, 40.0%, 21.2%, 47.2% and 35.9% in the suboptimal environment, respectively. Applying EBR could further improve the antioxidant enzyme activity, reduce the H2O2 content and membrane permeability of seedlings, alleviate the drop range of Pn, g(s) and Tr, improve the growth of seedlings and increase the dry matter accumulation by 25.9%. Therefore, EBR treatment could keep higher photosynthetic performance to effectively promote cucumber seedlings growth through adjusting the protective enzyme activity and reducing membrane lipid peroxide level under suboptimal temperature, light and salt environment.

[Effects of exogenous silicon on physiological characteristics of cucumber seedlings under ammonium stress].

The present study evaluated the effects of exogenous silicon on growth and physiological characteristics of hydroponically cultured cucumber seedlings under ammonium stress. The results showed that the growth, especially the aerial part growth of cucumber seedlings cultured with ammonium were significantly inhibited than those with nitrate, especially after treatment for 10 d, the aerial part fresh mass of cucumber seedlings were reduced 6.17 g per plant. The accumulation of reactive oxygen species (ROS) was also promoted in cucumber seedlings under ammonium, and the contents of O2*- and H2O2 were significantly increased in cucumber leaves. With the exogenous silicon treatment, the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX) were significantly improved, the ability to remove reactive oxygen species was enhanced, the contents of O2*- and H2O2 were significantly reduced in cucumber leaves, decreasing the reactive oxygen damage to the cell membrane, and the ratio of electrolyte leakage and the content of MDA in cucumber leaves. Also, with exogenous silicon treatment, the plasma membrane and activity of vacuolar membrane H(+)-ATP was significantly increased, transport capacity of intracellular proton was improved, and the level of ammonium in cucumber body was significantly reduced, thereby reducing the toxicity of ammonium. In conclusion, exogenous silicon could relieve ammonium stress, by increasing the antioxidant enzyme activity, H(+)-ATP activity, and decreasing the ammonium content in cucumber seedlings.

miR-26a suppresses tumor growth and metastasis by targeting FGF9 in gastric cancer.

The role of miR-26a in cancer cells seemed controversial in previous studies. Until now, the role of miR-26a in gastric cancer remains undefined. In this study, we found that miR-26a was strongly downregulated in gastric cancer (GC) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of GC. We also found that ectopic expression of miR-26a inhibited GC cell proliferation and GC metastasis in vitro and in vivo. We further identified a novel mechanism of miR-26a to suppress GC growth and metastasis. FGF9 was proved to be a direct target of miR-26a, using luciferase assay and western blot. FGF9 overexpression in miR-26a-expressing cells could rescue invasion and growth defects of miR-26a. In addition, miR-26a expression inversely correlated with FGF9 protein levels in GC. Taken together, our data suggest that miR-26a functions as a tumor suppressor in GC development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for GC.

[Alleviation effects of brassinolide on cucumber seedlings under NaCl stress].

This paper studied the effects of 2,4-epibrassinolide (EBR) on the photosynthesis and antioxidant system of cucumber seedling leaves under NaCl stress. As compared with the control, NaCl stress increased the leaf superoxide anion production rate, hydrogen peroxide content, malondialdehyde content, and cell membrane permeability while decreased the leaf net photosynthetic rate, stomatal conductance, transpiration rate, and intercellular CO2 concentration significantly, and inhibited the seedlings growth significantly. Applying EBR could increase the activities of leaf superoxide dismutase, peroxidase, and catalase, decrease the leaf superoxide anion production rate, hydrogen peroxide content, malondialdehyde content, and cell membrane permeability, make the leaves keep a higher photosynthetic rate, and thus, promote the seedlings growth, being able to effectively alleviate the damage of NaCl stress.

Prognostic value of leptin: 6-month outcome in patients with intracerebral hemorrhage.

Leptin has recently been discussed as a novel biomarker for the clinical outcome of critical illness. This study aims to investigate the prognostic value of leptin with regard to long-term clinical outcomes in patients with intracerebral hemorrhage. In 50 healthy controls and 92 patients with acute spontaneous basal ganglia hemorrhage presenting to the emergency department of a large primary care hospital, we measured plasma leptin levels using an enzyme-linked immunosorbent assay in a blinded fashion. Plasma leptin levels on admission were considerably higher in patients than healthy controls. A significant correlation emerged between plasma leptin level and National Institutes of Health Stroke Scale score. A multivariate analysis identified plasma leptin level as an independent predictor for 6-month clinical outcomes including 6-month mortality and unfavorable outcome (Modified Rankin Scale score>2). Using receiver operating characteristic curves, we calculated areas under the curve for 6-month clinical outcomes. The predictive performance of leptin was similar to, but did not obviously improve that of National Institutes of Health Stroke Scale scores. Thus, leptin may help in the prediction of 6-month mortality and unfavorable outcome after intracerebral hemorrhage.

Activation of canonical wnt pathway promotes differentiation of mouse bone marrow-derived MSCs into type II alveolar epithelial cells, confers resistance to oxidative stress, and promotes their migration to injured lung tissue in vitro.

The differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells in vivo and in vitro, is critical for reepithelization and recovery in acute lung injury (ALI), but the mechanisms responsible for differentiation are unclear. In the present study, we investigated the role of the canonical wnt pathway in the differentiation of mouse bone marrow-derived MSCs (mMSCs) into AT II cells. Using a modified co-culture system with murine lung epithelial-12 (MLE-12) cells and small airway growth media (SAGM) to efficiently drive mMSCs differentiation, we found that GSK 3ß and ß-catenin in the canonical wnt pathway were up-regulated during differentiation. The levels of surfactant protein (SP) C, SPB, and SPD, the specific markers of AT II cells, correspondingly increased in mMSCs when Wnt3a or LiCl was added to the co-culture system to activate wnt/ß-catenin signaling. The expression of these factors was depressed to some extent by inhibiting the pathway with the addition of DKK 1. The differentiation rate of mMSCs also depends on their abilities to accumulate and survive in inflammatory tissue. Our results suggested that the activation of wnt/ß-catenin signaling promoted mMSCs migration towards ALI mouse-derived lung tissue in a Transwell assay, and ameliorated the cell death and the reduction of Bcl-2/Bax induced by H(2) O(2), which simultaneously caused reduced GSK 3ß and ß-catenin in mMSCs. These data supports a potential mechanism for the differentiation of mMSCs into AT II cells involving canonical wnt pathway activation, which may be significant to their application in ALI.

[Effects of brassinolide on the leaf mitochondria and chloroplast ultrastructure and photosynthesis of cucumber seedlings under hypoxia stress].

A hydroponic experiment was conducted to investigate the effects of 24-epibrassinolide (EBR) on the leaf mitochondria and chloroplast ultrastructure and photosynthesis of cucumber seedlings under hypoxia stress. Under the stress, the apparent quantum yield (AQY) and carboxylation efficiency (CE) decreased significantly, while the light compensation point (LCP), dark breathing rate (R(d)), and CO2 compensation point (CCP) had a significant increase. The application of EBR increased the CE significantly by 29.4%, and decreased the LCP and R(d) significantly by 15.0% and 14.4%, respectively. The light response curve (P(n)-PPFD) and CO2 response curve (P(n)-C(i)) indicated that under hypoxia stress, the increment of net photosynthetic rate (P(n)) decreased, while EBR addition enhanced the increment of the P(n). Hypoxia stress damaged the mitochondria and chloroplast ultrastructure, while EBR could alleviate the damages in chloroplast and mitochondria under hypoxia stress, and keep the leaves in a higher photosynthetic performance.

Modulation of FLT3 signaling targets conventional dendritic cells to attenuate acute lung injury.

Conventional dendritic cells (cDCs) have been reported to participate in the pathophysiology of acute lung injury (ALI). Fms-like tyrosine kinase 3 (FLT3) signaling represents a highly specific pathway for the manipulation of cDCs in vivo. The purpose of this study was to clarify the effect of FLT3 signaling on the accumulation and maturation of pulmonary cDCs, and whether inhibition of FLT3 signaling may attenuate acute lung inflammation and lung injury. C57BL/6 mice were pretreated with FLT3-ligand (FLT3L) and lestaurtinib separately for five consecutive days. A murine model of ALI was subsequently generated by intra-tracheal instillation of lipopolysaccharide (LPS) and lung specimens were harvested 24 h later. Flow cytometry was conducted to measure the accumulation and maturation of pulmonary cDCs. IL-6, IFN-γ, IL-4, MPO activity and transcription factor T-bet/GATA-3 mRNA ratio were quantified to evaluate lung inflammation. Lung injury was estimated by lung wet weight/body weight ratio (LWW/BW) and histopathological analysis. LPS challenge resulted in rapid accumulation and maturation of pulmonary cDCs. FLT3L pretreatment further stimulated the accumulation and maturation of pulmonary cDCs, leading to a markedly increased LWW/BW and aggravated lung histopathology. Meanwhile, lung MPO activity, T-bet/GATA-3 mRNA ratio and concentrations of IL-6 and IFN-γ were elevated by FLT3L administration. In contrast, lestaurtinib pretreatment inhibited the accumulation and maturation of pulmonary cDCs, leading to a significantly decreased LWW/BW and improved lung histopathology. Lestaurtinib administration also suppressed lung MPO activity, T-bet/GATA-3 mRNA ratio and production of IL-6 and IFN-γ. Our findings show that FLT3 signaling ameliorates ALI by regulating the accumulation and maturation of pulmonary cDCs, suggesting an innovative pharmacotherapy for ALI.