Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice.

Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression. Moreover, CCl4-induced apoptosis in the mouse liver was inhibited by hSAP, as measured by terminal-deoxynucleotidyl transferase mediated nick-end labeling (TUNEL) assay and cleaved caspase-3 expression. hSAP significantly restored the expression of B cell lymphoma/leukemia (Bcl)-2 and suppressed the expression of Bcl-2-associated X protein (Bax) in vivo. The number of hepatocytes in early apoptosis stained with Annexin V was significantly reduced by 28-30% in the hSAP treatment group compared with the CCl4 group, and the expression of Bcl-2 was increased, whereas the expression of Bax and cleaved caspase-3 were significantly inhibited in the hSAP pre-treatment group compared with the CCl4 group. hSAP administration also inhibited the migration and activation of hepatic stellate cells (HSCs) in CCl4-injured liver and suppressed the activation of isolated primary HSCs induced by transforming growth factor (TGF)-β1 in vitro. Collectively, these findings suggest that hSAP exerts a protective effect againts CCl4-induced hepatic injury by suppressing the inflammatory response and hepatocyte apoptosis, potentially by inhibiting HSC activation

Can agricultural protectionist policies help achieve food security in Nigeria?

This study mapped the dynamic interaction of narratives regarding Nigeria's pursuit of rice self-sufficiency and related trade policies since the 1970s to explore whether agricultural protectionist policies can help achieve food security in Nigeria. Developing agricultural trade policies that simultaneously secure imported food supplies and protect domestic agricultural development is a challenging task. Nigeria's protectionist policies have a controversial agenda. Few studies have investigated the dynamic process of rice production and trade policy from a historical viewpoint; our study fills this gap. Through mapping Nigeria's pursuit of rice self-sufficiency over the past 50 years, we found that seesawed trade policy parallels complex rice development, leaving imported rice dependence unchanged. Regardless of when policies switch to trade protection or liberalization, the procedure does not directly lead to increased rice production. Since much exploration is needed regarding how to achieve food security in Nigeria, we also identify three new dimensions for future food security research based on our findings' optimal recommendations

Enhanced thermal and electrical properties by Ag nanoparticles decorated GO-CNT nanostructures in PEEK composites

A nanostructure of graphene oxide (GO) and carbon nanotubes (CNTs) decorated with silver nanoparticles (AgGNT) has been prepared via a molecular-level-mixing (MLM) method followed by a subsequent freeze-drying and reduction process. The obtained well-dispersed AgGNT nanostructures were then applied as fillers to reinforce the poly(ether ether ketone) (PEEK) matrix. AgGNT-PEEK composites have then demonstrated excellent electrical and thermal conduction performances as well as high thermal durability compared with pure PEEK and its pure Ag or GO-CNT (GNT) enhanced composites. Owing to the unique morphology of AgGNT nanostructures, which made them uniformly dispersed in the PEEK matrix and formed a 3D network structure, the AgGNT-PEEK composites displayed 60% higher thermal conductivity and around 109 times better electrical conduction performance than pure PEEK, and superior thermal durability even above the melting temperature of pure PEEK. Thus, the AgGNT-PEEK composites have shown great potential for applications such as semiconductors, high-temperature electrical applications, aerospace, and automobile materials

Heterostructured SnO2-SnS2@C Embedded in Nitrogen-Doped Graphene as a Robust Anode Material for Lithium-Ion Batteries

Tin-based anode materials with high capacity attract wide attention of researchers and become a strong competitor for the next generation of lithium-ion battery anode materials. However, the poor electrical conductivity and severe volume expansion retard the commercialization of tin-based anode materials. Here, SnO2-SnS2@C nanoparticles with heterostructure embedded in a carbon matrix of nitrogen-doped graphene (SnO2-SnS2@C/NG) is ingeniously designed in this work. The composite was synthesized by a two-step method. Firstly, the SnO2@C/rGO with a nano-layer structure was synthesized by hydrothermal method as the precursor, and then the SnO2-SnS2@C/NG composite was obtained by further vulcanizing the above precursor. It should be noted that a carbon matrix with nitrogen-doped graphene can inhibit the volume expansion of SnO2-SnS2 nanoparticles and promote the transport of lithium ions during continuous cycling. Benefiting from the synergistic effect between nanoparticles and carbon matrix with nitrogen-doped graphene, the heterostructured SnO2-SnS2@C/NG further fundamentally confer improved structural stability and reaction kinetics for lithium storage. As expected, the SnO2-SnS2@C/NG composite exhibited high reversible capacity (1201.2 mA h g−1 at the current rate of 0.1 A g−1), superior rate capability and exceptional long-life stability (944.3 mAh g−1 after 950 cycles at the current rate of 1.0 A g−1). The results demonstrate that the SnO2-SnS2@C/NG composite is a highly competitive anode material for LIBs

TNF-α and IFN-γ synergistically inhibit the repairing ability of mesenchymal stem cells on mice colitis and colon cancer.

BACKGROUND(#br)Mesenchymal stem cells (MSCs) can be efficiently recruited to wound, inflammatory and tumor sites to repair and regenerate tissue. However, its role in colitis and colitis associated colon cancer is still controversial. This study was designed to evaluate the role and mechanisms of inflammatory cytokines-activated-MSCs in mice colitis and colon cancer.(#br)METHODS(#br)We selected two well-characterized pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), to expand the inflammatory microenvironment of MSCs. The severity of colitis and colon cancer was evaluated by measuring colon length, Myeloperoxidase (MPO) activity, Hematoxylin-eosin staining, Western Blot, Immunohistochemistry and Immunofluorescence. These techniques were also performed to analyze the mechanisms of inflammatory cytokines-activated-MSCs in mice colitis and colon cancer. Real-time PCR and Enzyme-linked Immunosorbent Assay (ELISA) were used to measure the secretion of pro-inflammatory factors.(#br)RESULTS(#br)We found that the incubation of MSCs with TNF-α and IFN-γ aggravates colitis, where high levels of pro-inflammatory factors, such as interleukin (IL)-17, IL-8, IL-12, IL-1β, transforming growth factor (TGF)-β, TNF-α and IFN-γ, were secreted. Furthermore, this phenomenon was associated with the activation of the nuclear factor-kappa-B (NF-κB)/Signal transducer and activator of transcription three (STAT3) pathway. In addition, our study demonstrated that TNF-α and IFN-γ pretreated MSCs synergistically exacerbated mice colon cancer, which was closely associated with angiogenesis.(#br)CONCLUSIONS(#br)Taken together, these results indicate that TNF-α and IFN-γ pretreatment effectively inhibited the repair ability of MSCs and accelerated inflammation and tumor progression involving NF-κB/STAT3 pathway and angiogenesis-related factors

Ubiquitin-specific peptidase 39 regulates the process of proliferation and migration of human ovarian cancer via p53/p21 pathway and EMT.

Ovarian cancer is one of the most lethal gynecological cancers; owning to its late detection and chemoresistance, understanding the pathogenesis of this malignant tumor is much critical. Previous studies have reported that ubiquitin-specific peptidase 39 (USP39) is generally overexpressed in a variety of cancers, including hepatocellular carcinoma, gastric cancer and so forth. Furthermore, USP39 is proved to be associated with the proliferation of malignant tumors. However, the function and mechanism of USP39 in ovarian cancer have not been elucidated. In the present study, we observed that USP39 was frequently overexpressed in human ovarian cancer and was highly correlated with TNM stage. Suppression of USP39 markedly inhibited the growth and migration of ovarian cancer cell lines HO-8910 and SKOV3 and induced cell cycle G2/M arrest. Moreover, knockdown of USP39 inhibited ovarian tumor growth in a xenograft model. In addition, our findings indicated that cell cycle arrest induced by USP39 knockdown might be involved in p53/p21 signaling pathway. Furthermore, we found that the depletion of USP39 inhibited the migration of ovarian cancer cells via blocking epithelial-mesenchymal transition. Taken together, these results suggest that USP39 may play vital roles in the genesis and progression and may serve as a potential biomarker for diagnosis and therapeutic target of ovarian cancer

Ubiquitin-specific peptidase 39 regulates the process of proliferation and migration of human ovarian cancer via p53/p21 pathway and EMT

Abstract(#br)Ovarian cancer is one of the most lethal gynecological cancers; owning to its late detection and chemoresistance, understanding the pathogenesis of this malignant tumor is much critical. Previous studies have reported that ubiquitin-specific peptidase 39 (USP39) is generally overexpressed in a variety of cancers, including hepatocellular carcinoma, gastric cancer and so forth. Furthermore, USP39 is proved to be associated with the proliferation of malignant tumors. However, the function and mechanism of USP39 in ovarian cancer have not been elucidated. In the present study, we observed that USP39 was frequently overexpressed in human ovarian cancer and was highly correlated with TNM stage. Suppression of USP39 markedly inhibited the growth and migration of ovarian cancer cell..

Structure-Activity Relationship Study Enables the Discovery of a Novel Berberine Analogue as RXRα Activator to Inhibit Colon Cancer

黄连素是从黄连、黄柏等传统中药中提取的单体化合物，常用于治疗痢疾及其它消化道感染。近年来，黄连素的抗心律失常、调控能量代谢、降血糖血脂和抗癌等多重功效使其成为一个“明星”中药单体化合物。尽管黄连素具有很好的安全性，但其抗癌作用在临床应用上仍具有许多局限性，包括抗癌活性低、溶解度和生物利用度低等。然而，由于黄连素的分子靶点不清楚，以往对黄连素的改造比较盲目和随机，并未取得较好的进展。胡天惠团队与张延东团队紧密合作、优势互补，针对黄连素与RXR的结合模式，运用结构生物学方法和全合成相结合，设计合成了多种黄连素衍生物，并开展了构效关系分析。发现黄连素衍生物B-12在结合并激活RXR、抗肠癌活性、溶解度和生物利用度方面均明显优于黄连素，且保留了黄连素的肿瘤选择性和低毒副作用，具有很好的临床转化前景。该研究也为结构生物学指导黄连素衍生物药物设计提供了理论基础。本论文的通讯作者为医学院占艳艳副教授、张延东教授和胡天惠教授。医学院博士生徐贝贝和化学化工学院博士生江训金为共同第一作者。We reported recently that berberine, a traditional oriental medicine to treat gastroenteritis, binds and activates Retinoid X receptor α (RXRα) to suppress the growth of colon cancer cells. Here, we extended our studies based on the binding mode of berberine with RXRα by design, synthesis and biological evaluation of a focused library of 15 novel berberine analogues. Among them, 3,9-dimethoxy-5,6-dihydroisoquinolino[3,2-a]isoquinolin-7-ium chloride (B-12) was identified as the optimal RXRα activator. More efficiently than berberine, B-12 bound and altered the conformation of RXRα/LBD, thereby suppressing Wnt/β-catenin pathway and colon cancer cell growth via RXRα mediation. In addition, B-12 not only preserved berberine’s tumor selectivity but also greatly improved its bioavailability. Remarkably, in mice, B-12 did not show obvious side effects including hypertriglyceridemia as other RXRα agonists, or induce hepatorenal toxicity. Together, our study describes an approach for the rational design of berberine-derived RXRα activators as novel effective antineoplastic agents for colon cancer.This work was supported by the National Natural Science Foundation of China (31770860, 21772164, 81572589, 81602560 and 21572187), and the Natural Science Foundation of Fujian Province (2018R1036-2, 2017J06020, 2019R1001-4, and 2019R1001-5). 项目得到了国家自然科学基金委促进海峡两岸科技合作联合基金重点项目、面上项目和福建省自然科学基金的支持

Identification of a six-gene signature to predict survival and immunotherapy effectiveness of gastric cancer

BackgroundGastric cancer (GC) ranks as the fifth most prevalent malignancy and the second leading cause of oncologic mortality globally. Despite staging guidelines and standard treatment protocols, significant heterogeneity exists in patient survival and response to therapy for GC. Thus, an increasing number of research have examined prognostic models recently for screening high-risk GC patients.MethodsWe studied DEGs between GC tissues and adjacent non-tumor tissues in GEO and TCGA datasets. Then the candidate DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of DEGs. We used the ROC curve, Kaplan-Meier curve, and risk score plot to evaluate the signature’s performance and prognostic power. ESTIMATE, xCell, and TIDE algorithm were used to explore the relationship between the risk score and immune landscape relationship. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model.ResultsThere were 3211 DEGs in TCGA, 2371 DEGs in GSE54129, 627 DEGs in GSE66229, and 329 DEGs in GSE64951 selected as candidate genes and intersected with to obtain DEGs. In total, the 208 DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of 6 DEGs. External validation showed favorable predictive efficacy. We studied interaction between risk models, immunoscores, and immune cell infiltrate based on six-gene signature. The high-risk group exhibited significantly elevated ESTIMATE score, immunescore, and stromal score relative to low-risk group. The proportions of CD4+ memory T cells, CD8+ naive T cells, common lymphoid progenitor, plasmacytoid dentritic cell, gamma delta T cell, and B cell plasma were significantly enriched in low-risk group. According to TIDE, the TIDE scores, exclusion scores and dysfunction scores for low-risk group were lower than those for high-risk group. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model.ConclusionIn conclusion, we discovered a 6 gene signature to forecast GC patients’ OS. This risk signature proves to be a valuable clinical predictive tool for guiding clinical practice