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Gemini curcumin inhibits 4T1 cancer cell proliferation and modulates the expression of apoptotic and metastatic genes in Balb/c mice model

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PATHOLOGY RESEARcH AND PRAcTIcE 2023年第1期243卷 154344页

作者： Kandjani, Behzad Zaker Hesari, Farzam Sheikhzadeh Babaei, Esmaeil Univ Tabriz Fac Nat Sci Dept Biol Tabriz Iran Univ Tubingen Interfac Inst Bioinformat & Med Informat IBMI D-72076 Tubingen Germany

Background: Despite the attractive anti-cancer effects, poor solubility and low bioavailability have restricted the clinical application of curcumin. Recent findings show that Gemini nano-curcumin (Gemini-cur) significantly improves the cellular uptake of curcumin and its anti-cancer effect in tumor cells. Here, we aimed to assess the suppressive effect of Gemini-cur on 4T1 breast cancer cells in vitro and, subsequently, in BALB/c mouse models. Materials and methods: Fluorescence microscopy was employed to visualize cellular uptake and morphological changes of 4T1 cells during treatment with Gemini-cur and void curcumin. MTT and annexin V/FITc assays were performed to study the toxic effect of Gemini-cur on mouse cancer cells. For in vivo studies, BALB/c tumorbearing mice were used to evaluate the inhibitory effect of Gemini-cur in comparison with mice receiving free curcumin and nanoparticles. Results: Our data showed that Gemini-cur enters the cells and inhibits proliferation in a time- and dosedependent manner. Annexin V/FITc confirmed apoptotic effect on 4T1 cells. In vivo studies also illustrated that tumor growth is suppressed in Gemini-cur treated mice rather than controls. Expression studies demonstrated the modulation of apoptotic and metastatic genes, including Bax, Bcl-2, MMP-9, VEGF, and cOX-2 in treated mice. conclusion: In conclusion, these data demonstrate the promising anti-cancer properties of Gemini-cur on mice models. However, further studies at molecular and cellular levels are required to conclude this therapeutic advantage.

关键词： curcumin Gemini surfactant nanoparticles Breast cancer BALB c

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Phase equilibria of the co-cr-Mn ternary system at 700 °c

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JOURNAL OF ALLOYS AND cOMPOUNDS 2023年第1期965卷

作者： Han, K. Sahara, R. Abe, T. Oikawa, K. Ueshima, N. Ohnuma, I. Natl Inst Mat Sci NIMS Res Ctr Struct Mat Tsukuba 3050047 Japan Tohoku Univ Grad Sch Engn Dept Met Sendai 9808579 Japan

The isothermal phase diagram of the co-cr-Mn ternary system at 700 & DEG;c was experimentally determined via field-emission electron probe microanalysis/wavelength dispersive X-ray spectrometry and electron backscatter diffraction analyses. Three-phase regions of & alpha;co(para)+ & beta;Mn+ & sigma;and & alpha;Mn+ & beta;Mn+ & sigma;were confirmed via equilibrated microstructures;however, three-phase microstructures related to & alpha;co(para)+ & epsilon;co+ & sigma;and & alpha;'+ (cr)+ & sigma;were not observed in our study. The three-phase region of & alpha;co(para)+ & epsilon;co+ & sigma;was estimated to be very narrow because the phase boundaries between the & alpha;co(para) and & epsilon;co phases were different within 2 at% for the co, cr, and Mn compositions. Furthermore, the & alpha;' phase, presumed to be a nitride, was not observed in the microstructure equilibrated under a strictly controlled high-purity Ar gas (99.999%) atmosphere. The & sigma;phase indicated a wide single-phase region similar to a previous study reported at temperatures between 900 & DEG;c and 1200 & DEG;c. The & alpha;Mn phase, which is stable below 727 & DEG;c in the cr-Mn binary system and below 900 & DEG;c in the co-Mn binary system, had a large co solubility of 9.8 at% in the co-cr-Mn ternary system. The composition dependences on the lattice constants of the & sigma;phase in the co-cr-Mn ternary system were examined via X-ray diffraction analysis;this analysis showed that the lattice constants a and c changed significantly with increasing Mn composition in the co and Mn substitution, while the lattice constant of a was constant and c was slightly increased by increasing Mn composition in cr and Mn substitution. From first-principles calculations, it was deduced that increases or decreases in bonding lengths between the nearest atoms occupying the five sublattice sites were associated with small changes in the lattice constant when Mn replaced cr. The hardness of the & sigma;phase

关键词： c Phase diagrams D Electron emission spectroscopies X-ray diffraction

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Singapore grouper iridovirus infection counteracts poly I:c induced antiviral immune response in vitro

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FISH & SHELLFISH IMMUNOLOGY 2023年 135卷 108685页

作者： Wang, Wenji Zhang, Ya Guo, Xixi Xu, Weihua Qin, Qiwei Huang, Youhua Huang, Xiaohong South China Agr Univ Coll Marine Sci Lingnan Guangdong Lab Modern Agr Guangzhou 510642 Peoples R China Southern Marine Sci & Engn Guangdong Lab Zhuhai 519082 Peoples R China Lab Marine Biol & Biotechnol Qingdao Natl Lab Marine Sci & Technol Qingdao 266000 Peoples R China South China Agr Univ Coll Marine Sci Guangzhou 510642 Peoples R China

Groupers are important mariculture fish in South china and Southeast Asian countries. However, the increasing frequency of infectious disease outbreaks has caused great economic losses in the grouper industry. Among these pathogens, Singapore grouper iridovirus (SGIV) infection causes high mortality in larval and juvenile stages of grouper. However, the mechanism underlying the action of viral manipulation on cellular immune response still remained largely uncertain. Here, using RNA-seq technology, we investigated the regulatory roles of SGIV infection on synthetic RNA duplex poly I:c induced immune response in vitro. Using reporter gene assays, we found that SGIV infection decreased poly I:c induced interferon promoter activation. Transcriptomic analysis showed that the mRNA expression levels of 2238 genes were up-regulated, while 1247 genes were down -regulated in poly I:c transfected grouper spleen (GS) cells. Interestingly, SGIV infection decreased the expres-sion of 1479 up-regulated genes and increased the expression of 297 down-regulated genes in poly I:c transfected cells. The differentially expressed genes (DEGs) down-regulated by SGIV were directly related to immune, inflammation and viral infection, and JUN, STAT1, NFKB1, MAPK14A, TGFB1 and MX were the 6 top hub genes in the down-regulated DEGs' protein-protein interaction (PPI) network. Furthermore, quantitative real-time PcR (qPcR) analysis confirmed that the interferon signaling and inflammatory-related genes, including cGAS, STING, TBK1, MAVS, TNF, IRAK4 and NOD2 were up-regulated by poly I:c stimulation, but all significantly down -regulated after SGIV infection. Thus, we speculated that SGIV infection counteracted poly I:c induced anti-viral immune response and this ability helped itself to escape host immune surveillance. Together, our data will contribute greatly to understanding the potential immune evasion mechanism of iridovirus infection in vitro.

关键词： SGIV Poly I c Immune response Inflammatory response Immune evasion

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Ultra-high temperature ablation behavior of cVD-Hf5Tac6 solid solution ceramic coating for c/c composites: Experiment and first-principle calculation

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JOURNAL OF ALLOYS AND cOMPOUNDS 2023年第1期965卷

作者： chen, Hui Zhang, Yulei Li, Zhenglong Shuai, Kang Fu, Yanqin Meng, Jiachen Liu, Kun Zhang, Jian Li, Tao Northwestern Polytech Univ Shaanxi Key Lab Fiber Reinforced Light Composite M Xian 710072 Peoples R China Henan Acad Sci Inst Carbon Matrix Composites Henan Key Lab High Performance Carbon Fiber Reinfo Zhengzhou 450046 Peoples R China

To address the problem that the oxidized layer of Hfc coating was loose and porous, HfxTaycx+y solid solution with good thermal stability and ablation resistance was proposed as coating for carbon/carbon (c/c) composites. In present work, Hfc, Tac and the novel Hf5Tac6 solid solution coatings were synthesized on c/c composites by chemical vapor deposition. combing with the ablation test and density functional theory calculations about oxygen-adsorption energies, the ablation mechanism of Hfc, Tac and Hf5Tac6 solid solution coatings were investigated. The Hf5Tac6 solid solution coating showed superior ablation resistance than that of Hfc and Tac coatings, benefitting from the solid-liquid composite oxide layer with HfO2 and Hf6Ta2O17 as solid structure to further stabilize the oxides and resist mechanical erosion, Ta2O5 as the liquid filler to heal cracks to inhibit the oxygen infiltration.

关键词： c c composites Hf 5 Tac 6 solid solution coating Density functional theory Oxygen adsorption Ablation resistance

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Photoinduced electron transfer in cytochrome bc1: Dynamics of rotation of the Iron-sulfur protein during bifurcated electron transfer from ubiquinol to cytochrome c1 and cytochrome bL

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BIOcHIMIcA ET BIOPHYSIcA AcTA-BIOENERGETIcS 2023年第2期1864卷

作者： Havens, Jeffrey Su, Ting Wang, Qiyu Yu, chang-An Yu, Linda Durham, Bill Millett, Francis Univ Arkansas Dept Chem & Biochem Fayetteville AR 72701 USA Oklahoma State Univ Dept Biochem & Mol Biol Stillwater OK 74078 USA Vaccines & Therapeut Div Def Threat Reduct Agcy Chem & Biol Technol Ft Belvoir VA 22060 USA ABclonal Technol Woburn MA 01801 USA Vesigen Therapeut Cambridge MA 02139 USA

The electron transfer reactions within wild-type Rhodobacter sphaeroides cytochrome bc1 (cyt bc1) were studied using a binuclear ruthenium complex to rapidly photooxidize cyt c1. When cyt c1, the iron-sulfur center Fe2S2, and cyt bH were reduced before the reaction, photooxidation of cyt c1 led to electron transfer from Fe2S2 to cyt c1 with a rate constant of ka = 80,000 s- 1, followed by bifurcated reduction of both Fe2S2 and cyt bL by QH2 in the Qo site with a rate constant of k2 = 3000 s- 1. The resulting Q then traveled from the Qo site to the Qi site and oxidized one equivalent each of cyt bL and cyt bH with a rate constant of k3 = 340 s- 1. The rate constant ka was decreased in a nonlinear fashion by a factor of 53 as the viscosity was increased to 13.7. A mechanism that is consistent with the effect of viscosity involves rotational diffusion of the iron-sulfur protein from the b state with reduced Fe2S2 close to cyt bL to one or more intermediate states, followed by rotation to the final c1 state with Fe2S2 close to cyt c1, and rapid electron transfer to cyt c1.

关键词： cyt cytochrome ISP Rieske iron‑sulfur protein ISP-ED extrinsic domain of ISP Fe 2 S 2 Rieske iron‑sulfur center Ru 2 D [Ru(bpy) 2 ] 2 (qpy)(PF 6 ) 4 qpy 2,2′:4′,4″:2″,2‴–quaterpyridine Q 0 c 10 BrH 2 2,3-dimethoxy-5-methyl-6-(10-bromodecyl)-1,4-benzoquinol ScR succinate cytochrome c reductase EPR electron paramagnetic resonance

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contrasting dose response relationships of neuroactive antidepressants on the behavior of c. elegans

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EcOTOXIcOLOGY AND ENVIRONMENTAL SAFETY 2023年第1期250卷 114493页

作者： van der Most, Merel A. Estruch, Ignacio Miro van den Brink, Nico W. Wageningen Univ & Res Div Toxicol NL-6708 WE Wageningen Netherlands

Antidepressant prescriptions are on a rise worldwide and this increases the concerns for the impacts of these pharmaceuticals on nontarget organisms. Antidepressants are neuroactive compounds that can affect organism's behavior. Behavior is a sensitive endpoint that may also propagate effects at a population level. Another interesting aspect of antidepressants is that they have shown to induce non-monotonic dose-response (NMDR) curves. While such NMDR relationships may have clear implications for the environmental risk, the resolution of current studies is often too coarse to be able to detect relevant NMDR. Therefore, the current study was per-formed into the behavioral effects (activity, feeding and chemotaxis) in caenorhabditis elegans as the model or-ganism of the selective serotonin reuptake inhibitors fluoxetine and sertraline and the acetylcholinesterase inhibiting pesticide chlorpyrifos, using a wide range of concentrations (ng/l to mg/l). In order to statistically examine the non-monotonicity, nonlinear regression models were applied to the results. The results showed a triphasic dose-response relationship for activity and chemotaxis after exposure to fluoxetine, but not to sertraline or chlorpyrifos. Effects of fluoxetine already occurred at low concentrations in the range of ng/l while sertraline only showed effects at concentrations in the mu g/l range, similar to chlorpyrifos. The different responses between fluoxetine and sertraline, both SSRIs, indicate that response patterns may not always be extrapolated from chemicals with the same primary mode of action. The effects of fluoxetine at low concentrations, in a non-monotonic manner, confirm the relevance of examining such responses at low concentrations.

关键词： Antidepressants Behavior Non-monotonic dose-response curves c elegans

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The clinical significance of circulating glucose-regulated protein 78, caspase-3, and c/EBP homologous protein levels in patients with heart failure

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HELIYON 2023年第2期9卷 e13436页

作者： Zhao, Xuecheng Zhang, Da-Qi Song, Rongjing Wang, Rong Zhang, Guoqiang China Japan Friendship Hosp Dept Emergency Med Beijing Peoples R China Hainan Med Univ Dept Neurol Affiliated Hosp 1 Haikou Peoples R China Peking Univ Peoples Hosp Dept Pharm Beijing Peoples R China Hainan Univ Sch Pharmaceut Sci Haikou Peoples R China Hainan Med Univ Dept Neurol Affiliated Hosp 1 Longhua Rd Haikou 570102 Hainan Peoples R China China Japan Friendship Hosp Dept Emergency Med 2 Yinghua Dongjie Beijing 100029 Peoples R China

Background and aims: The destruction of endoplasmic reticulum (ER) homeostasis leads to heart failure (HF), which further aggravates ER stress. Limited data are available on the levels of ER stress markers in HF patients in clinical practice. This study aimed to determine the clinical significance of the ER stress markers, glucose-regulated protein 78 (GRP78), caspase-3, and c/ EBP homologous protein (cHOP), in predicting HF and its severity. Materials and methods: A total of 62 patients with HF and 44 healthy controls were enrolled in the study, and all participants were followed-up for 2 years. Results: Serum GRP78, caspase-3, and cHOP levels were significantly higher in patients with HF than those in healthy controls. The level of GRP78 increased with the severity of HF. GRP78 levels were negatively correlated with left ventricular ejection fraction, and positively correlated with N-terminal B-type natriuretic peptide, D-dimer, and lactic acid. Serum GRP78 and caspase-3 levels showed moderate predictive values for HF patients. conclusion: ER stress markers, GRP78 and caspase-3, had a certain predictive value in HF and can be used as serum biomarkers for the diagnosis of HF. Additionally, GRP78 showed a certain predictive value in HF severity.

关键词： Glucose-regulated protein 78 caspase-3 c EBP homologous Protein Heart failure

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Soil fungal mycelia have unexpectedly flexible stoichiometric c:N and c:P ratios

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EcOLOGY LETTERS 2021年第2期24卷 208-218页

作者： camenzind, Tessa Philipp Grenz, Kay Lehmann, Johannes Rillig, Matthias c. Free Univ Berlin Inst Biol Altensteinstr 6 D-14195 Berlin Germany Berlin Brandenburg Inst Adv Biodivers Res BBIB D-14195 Berlin Germany Cornell Univ Sch Integrat Plant Sci Soil & Crop Sci Ithaca NY 14853 USA

Soil ecological stoichiometry provides powerful theories to integrate the complex interplay of element cycling and microbial communities into biogeochemical models. One essential assumption is that microbes maintain stable c:N:P (carbon:nitrogen:phosphorus) ratios independent of resource supply, although such homeostatic regulations have rarely been assessed in individual microorganisms. Here, we report an unexpected high flexibility in c:N and c:P values of saprobic fungi along nutrient supply gradients, overall ranging between 7-126 and 20-1488, respectively, questioning microbial homeostasis. Fungal N:P varied comparatively less due to simultaneous reductions in mycelial N and P contents. As a mechanism, internal recycling processes during mycelial growth and an overall reduced N and P uptake appear more relevant than element storage. The relationships among fungal stoichiometry and growth disappeared in more complex media. These findings affect our interpretation of stoichiometric imbalances among microbes and soils and are highly relevant for developing microbial soil organic carbon and nitrogen models.

关键词： c N P ratios element homeostasis fungal nutrient retranslocation microbial carbon sequestration mycelial growth nutrient limitations saprobic fungi soil ecological stoichiometry soil nutrient cycling

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composting and vermicomposting of sewage sludge at various c/N ratios: Technological feasibility and end-product quality

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EcOTOXIcOLOGY AND ENVIRONMENTAL SAFETY 2023年第1期263卷 115255页

作者： Dume, Bayu Hanc, Ales Svehla, Pavel Michal, Pavel chane, Abraham Demelash Nigussie, Abebe Czech Univ Life Sci Fac Agrobiol Food & Nat Resources Dept Agroenvironm Chem & Plant Nutr Kamycka 129 Prague 16500 Czech Republic Jimma Univ Coll Agr Jimma 307 Ethiopia

Even though sewage sludge (SS) contains a high level of pollutants, it is rich in essential plant nutrients and has the potential to enhance soil fertility. However, the SS must be further treated through pre-composting plus vermicomposting to make it safe for use on food crops. More research and data are needed to determine how different carbon-to-nitrogen ratios (c/N) affect the feasibility and quality of composting vs vermicomposting of SS. Therefore, in this study we comprehensively evaluated the feasibility and end-product quality of compost and vermicompost produced from SS under different c/N ratios. SS was mixed with pelletized wheat straw (PWS) at various proportions to produce c/N ratios of 6:1, 18:1, 28:1, and 38:1, then pre-composted for 14 days followed by vermicomposting using the earthworm Eisenia andrei for 120 days. Agrochemical properties were measured at 0, 30, 60, 90, and 120 days. Results revealed significantly higher levels of agrochemicals in vermicompost compared to compost, including total potassium (37-88%) and magnesium (4.3-12%), nitrate nitrogen (71-98%), available potassium (53-88%), available phosphorus (79%), available magnesium (54-453%), available boron (48-303%), and available copper (2.5-82%). However, lower levels of ammonium nitrogen by (59-85%), available iron (2.3-51.3%), available manganese (29.7-52.2%), available zinc (10.5-29.8%), total carbon (0.75-4.5%), and total nitrogen (1.6-22.2%) were measured. comparison of the various c/N ratios, showed that vermicompost with an 18:1 c/N ratio outperformed compost and demonstrated the highest earthworm population (165 pieces/kg). Thus, vermicomposting SS at an 18:1 c/N ratio is strongly recommended as a sustainable technology for producing high-quality vermicompost from SS.

关键词： Sewage sludge Vermicomposting Eisenia andrei composting c N ratio

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characterization of a germline variant MSH6 c.4001G >c in a Lynch syndrome family

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MOLEcULAR GENETIcS & GENOMIc MEDIcINE 2023年第2期11卷 e2104页

作者： Yang, ciyu Misyura, Maksym Kane, Sarah Rai, Vikas Latham, Alicia Zhang, Liying Mem Sloan Kettering Canc Ctr Dept Pathol New York NY USA Mem Sloan Kettering Canc Ctr Dept Med New York NY USA Univ Calif Los Angeles UCLA David Geffen Sch Med Dept Pathol & Lab Med Los Angeles CA USA UCLA Dept Pathol & Lab Med David Geffen Sch Med 10833 Conte Ave Los Angeles CA 90095 USA

BackgroundGermline variants in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) cause Lynch syndrome, an autosomal dominant hereditary cancer susceptibility syndrome. The risk for endometrial cancer is significantly higher in women with MSH6 pathogenic/likely pathogenic (P/LP) variants compared with that for MLH1 or MSH2 variants. MethodsThe proband was tested via a clinical testing, Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable cancer Targets (MSK-IMPAcT). RT-PcR was performed using patient's blood DNA and cDNA was analyzed by DNA sequencing and a cloning approach. ResultsWe report a 56-year-old female with endometrial cancer who carries a germline variant, MSH6 c.4001G > c, located at the last nucleotide of exon 9. While the pathogenicity of this variant was previously unknown, functional studies demonstrated that this variant completely abolished normal splicing and caused exon 9 skipping, which is expected to lead to a prematurely truncated or abnormal protein. conclusionOur results indicate that this variant likely contributes to cancer predisposition through disruption of normal splicing, and is classified as likely pathogenic.

关键词： c 4001G > c germline Lynch syndrome MSH6 splice site variant

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