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- ArticleWongsomboon P, Rattanajak R, Kamchonwongpaisan S, Pyne SG, Limtharakul T.Phytochemistry. 2021 Mar;183:112615.The phytochemical investigation of the methanol extracts of the leaves and twigs of Mitrephora tomentosa Hook. f. & Thomson resulted in the isolation and identification of undescribed polyacetylenic ester-neolignan derivatives, along with six known compounds. These six undescribed natural products were named as mitrephentosins A-F. The structures of these compounds were determined by spectroscopic techniques including UV, IR, NMR, and mass spectrometric analyses. The absolute configurations of mitrephentosins A-F were determined based on specific rotations values and ECD spectral data by comparisons made with the known parent neoligan compound mitredrusin. Mitrephentosins C, E, and F showed moderate antimalarial activities (IC50 values of 13.3-24.6 μM) against the Plasmodium falciparum strains TM4/8.2 and K1CB1 and were not toxic to Vero cells, while the other isolated compounds were not active against these P. falciparum strains.
- ArticlePelligra A, Mrugala J, Griess K, Kirschner P, Nortmann O, Bartosinska B, Köster A, Krupenko NI, Gebel D, Westhoff P, Steckel B, Eberhard D, Herebian D, Belgardt BF, Schrader J, Weber APM, Krupenko SA, Lammert E.Cell Rep. 2023 06 27;42(6):112615.Type 2 diabetes is characterized by insulin hypersecretion followed by reduced glucose-stimulated insulin secretion (GSIS). Here we show that acute stimulation of pancreatic islets with the insulin secretagogue dextrorphan (DXO) or glibenclamide enhances GSIS, whereas chronic treatment with high concentrations of these drugs reduce GSIS but protect islets from cell death. Bulk RNA sequencing of islets shows increased expression of genes for serine-linked mitochondrial one-carbon metabolism (OCM) after chronic, but not acute, stimulation. In chronically stimulated islets, more glucose is metabolized to serine than to citrate, and the mitochondrial ATP/ADP ratio decreases, whereas the NADPH/NADP+ ratio increases. Activating transcription factor-4 (Atf4) is required and sufficient to activate serine-linked mitochondrial OCM genes in islets, with gain- and loss-of-function experiments showing that Atf4 reduces GSIS and is required, but not sufficient, for full DXO-mediated islet protection. In sum, we identify a reversible metabolic pathway that provides islet protection at the expense of secretory function.
- ArticleMa G, Huang X, Xu F, Ren D, Bi Y, Guo Z, Yuan F, Sun Q, Zhang N, An L, Chen Z, Wu X, Wang L, Yang F, Li X, He L, Sun X, Yu T, He G.Psychiatry Res. 2020 02;284:112615.
- ArticleKuo YC, Lee YJ, Rajesh R.Biomater Adv. 2022 Feb;133:112615.Upregulated proliferation of neoplastic cells from suppressing apoptotic signals associated with the inhibitors of apoptosis proteins (IAP) makes difficult the achievement of therapeutic efficiency against glioblastoma multiforme. Studies in the last few years have witnessed a paradigm focusing on targeting IAP using its antagonists, such as Smac mimetics, to restrain tumor malignancy. A Smac mimetic compound needs to penetrate the blood-brain barrier (BBB), and must be internalized into cerebral tumor for improved chemotherapy. Rabies virus glycoprotein (RVG) and lactoferrin (Lf)-grafted liposomes were developed in this study to carry two IAP antagonists, AZD5582 and SM-164, across the BBB and to induce apoptosis in U87 MG and human brain cancer stem cells (HBCSCs). Liposomes modified with RVG slightly reduced BBB tightness and enhanced capability of AZD5582 and SM-164 for traversing the barrier because of their brain-targeting ability. Immunofluorescence and western-blot results revealed that AZD5582- and SM-164-encapsulated liposomes facilitated mutual curative intensity, effectively triggered apoptosis of U87 MG and HBCSCs, reduced the expression of cellular IAP 1 (cIAP1) and X-linked IAP (XIAP), and enhanced the expression of caspase-3. Hence, RGV-Lf-liposomes carrying AZD5582 and SM-164 can be promising formulations to activate apoptosis of U87 MG and HBCSCs, and this functionalized drug delivery system targeting cIAP and XIAP is a potential strategy to cure glioblastoma in clinical cancer management.
- ArticleSun CC, Li YJ, Zhu DT, Chen ZL, Xiao JL, Chen XT, Zheng L, Peng XY, Tang CF.Exp Gerontol. 2024 Dec;198:112615.BACKGROUND: Skeletal muscle atrophy is one of the main side effects of high-dose or continuous use of glucocorticoids (such as dexamethasone). However, there are limited studies on dexamethasone-induced skeletal muscle atrophy in zebrafish and even fewer explorations of the underlying molecular mechanisms. This study aimed to construct a model of dexamethasone-induced skeletal muscle atrophy in zebrafish and to investigate the molecular mechanisms.
METHODS: Zebrafish soaked in 0.01 % dexamethasone solution for 10 days. Loli Track (Denmark) and Loligo Swimming Respirometer were used to observe the effect of dexamethasone on swimming ability. The effects of dexamethasone on zebrafish skeletal muscle were observed by Transmission electron microscopy, H&E, and wheat germ agglutinin techniques. Enriched genes and signaling pathways were analyzed using Transcriptome sequencing. Further, the levels of mitochondrial and endoplasmic reticulum-related proteins were examined to investigate possible mechanisms.
RESULTS: 0.01 % dexamethasone reduced zebrafish skeletal muscle mass (p < 0.05), myofibre size and cross-sectional area (p < 0.001), and increased protein degradation (ubiquitination and autophagy) (p < 0.05). In addition, 0.01 % dexamethasone reduced the swimming ability of zebrafish, as evidenced by the reluctance to move, fewer movement trajectories, decreased total distance traveled (p < 0.001), average velocity of movement (p < 0.001), oxygen consumption (p < 0.001), critical swimming speed (p < 0.01) and increased exhaustive swimming time (p < 0.001). Further, 0.01 % dexamethasone-induced mitochondrial dysfunction (decreased mitochondrial biogenesis, disturbs kinetic homeostasis, increased autophagy) and endoplasmic reticulum stress.
CONCLUSIONS: 0.01 % dexamethasone induces skeletal muscle atrophy and impairs the swimming ability of zebrafish through mitochondrial dysfunction and endoplasmic reticulum stress. - ArticleDi T, Luo QY, Song JT, Yan XL, Zhang L, Pan WT, Guo Y, Lu FT, Sun YT, Xia ZF, Yang LQ, Qiu MZ, Yang DJ, Sun J.Int Immunopharmacol. 2024 Sep 30;139:112615.BACKGROUND AND PURPOSE: Liver cancer is the fourth leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) being the most common type of primary liver cancer. APG-1252 is a small molecule inhibitor targeting Bcl-2 and Bcl-xl. However, its anti-tumor effects in HCC, alone or in combination with Cabozantinib, have not been extensively studied.
EXPERIMENTAL: Approach: TCGA database analysis was used to analysis the gene expression levels of Bcl-2 and Bcl-xl in HCC tissues. Western blot was employed to detect the protein expression levels. And the inhibitory effects of APG-1252 and Cabozantinib on the proliferation of HCC cell lines was detected by CCK-8. The effect on the migration and invasion of HCC cells was verified by transwell assay. Huh7 xenograft model in nude mice was used to investigate the combination antitumor effect in vivo.
KEY RESULTS: Our study demonstrated that APG-1252 monotherapy inhibited the proliferation and migration ability of HCC cells, and induced HCC cells apoptosis. The combination of APG-1252 and Cabozantinib showed significant synergistic antitumor effects. Furthermore, the in vivo experiment demonstrated that the combination therapy exerted a synergistic effect in delaying tumor growth, notably downregulating MEK/ERK phosphorylation levels. In terms of mechanism, Cabozantinib treatment caused an increase in the phosphorylation levels of CREB and Bcl-xl proteins, while the combination with APG-1252 mitigated this effect, thereby enhanced the antitumor effect of Cabozantinib.
CONCLUSION AND IMPLICATIONS: Our findings suggest that APG-1252 in combination with Cabozantinib offers a more effective treatment strategy for HCC patients, warranting further clinical investigation. - ArticleRuan F, Zhang J, Liu J, Sun X, Li Y, Xu S, Xia W.Environ Res. 2022 04 15;206:112615.The association between prenatal exposure to the metal mixture and allergic diseases is poorly understood. We aimed to explore the individual effect and the combined effect of prenatal exposure to vanadium (V), chromium (Cr), nickel (Ni), arsenic (As), cadmium (Cd), thallium (Tl), and lead (Pb) on early childhood allergic diseases based on a birth cohort study that included 628 mother-infant pairs. Metals were measured in maternal urine samples collected in the first, second, and third trimesters. Children were prospectively followed up at age 4 years to collect information on allergic rhinitis, wheeze, and eczema status. By applying logistic regression models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR), the different statistical analyses revealed urinary metals were only associated with early childhood allergic rhinitis. The averaged prenatal As exposure was significantly associated with an increased OR for allergic rhinitis in both single-metal (OR = 2.04, 95% CI: 1.35, 3.07) and multiple-metal logistic regression models (OR = 1.78, 95% CI: 1.15, 2.78). The WQS index of mixed metal exposure was positively associated with allergic rhinitis (OR = 1.66, 95% CI: 1.26, 2.19), and As and Tl had the largest weights in the WQS index (weighted 0.51 and 0.29, respectively). The BKMR analysis also showed the overall effect of the metal mixture was significantly associated with allergic rhinitis when all the metals were at their 55th percentile or above, compared to their 50th percentile. The effect of As and Tl on the risk of allergic rhinitis was significant when all of the other metals were fixed at the specific percentiles. Our findings suggest that prenatal co-exposure to higher levels of the seven metals increases the risk of allergic rhinitis in children, and As and Tl may contribute most to the combined risk.
- ArticleYadon N, Owen A, Cakora P, Bustamante A, Hall-South A, Smith N, Felder MR, Vrana PB, Shorter KR.Physiol Behav. 2019 10 01;209:112615.Folic acid and other dietary methyl donors are widely supplemented due to their ability to prevent neural tube defects. Dietary methyl donors are also added to other consumables such as energy drinks due to energy-promoting attributes and other perceived benefits. However, there is mounting evidence that indicates developmental exposure to high levels of dietary methyl donors may have deleterious effects. We assessed whether behavior was affected in the social North American rodent species Peromyscus polionotus exposed to a diet enriched with folic acid, Vitamin B12, choline, and betaine/trimethylglycine(TMG). P. polionotus (PO) animals are very social and exhibit little repetitive behavior, particularly compared to their sister species, P. maniculatus. We assayed the effects of dietary methyl-donor supplementation on anxiety-like repetitive and social behaviors by testing young adult animals for novel cage behavior and in social interaction tests. Animals of both sexes exposed to the diet had increased repetitive behaviors and reduced social interactions. Males exposed to the diet became more aggressive compared to their control counterparts. Since methyl-diet animals were larger than control animals, DEXA scans and hormone analyses were performed. Animals exposed to the diet had increased body fat percentages and experienced hormonal changes typically associated with excess fat storage and anxiety-like behavior changes. Therefore, these data suggest the wide use of these dietary supplements makes further investigation imperative.
- ArticlePrata JC, Venâncio C, da Costa JP, Lopes I, Duarte AC, Rocha-Santos T.Mar Pollut Bull. 2021 Sep;170:112615.The ubiquity of microplastics raises issues regarding contamination control measures and laboratory practices. The objective was to adapt the use of counting chambers and plastic microplates on the ecotoxicity evaluation of microplastics. Counting chambers, originally used to quantify cells, can also be used to count high concentrations of microplastics (<100 μm) used in laboratory assays. By decontaminating the chamber and mixing the test solution with Nile Red (1:1), fluorescent particles can be easily counted under optical microscopy. Microplate wells, due to their composition, can be contaminated or release microplastics to the test medium, which can interfere with the results of ecotoxicity assays or spectroscopy readings. A cleaning method based on ethanol was developed, which effectively removed particles by 91% without interfering with microalgae yield. Besides providing practical applications that can improve ecotoxicity assays, this work intends to raise awareness on the need to adapt laboratory practices when working with microplastics.
- ArticleAndrade C, Pereira DM, G M Gomes N, Ferreres F, Gil-Izquierdo A, Andrade PB, Duangsrisai S, Valentão P.Food Res Int. 2023 05;167:112615.Kitul (Caryota urens L.) inflorescences are broadly used for sweet sap production in Asian countries and Kitul food products are known as being suitable for diabetic patients. Considering the strong ability to inhibit α-glucosidase, we hypothesize that kitul antidiabetic properties might also involve the modulation of inflammatory pathways and hyperglycaemia-induced oxidative damage. Hence, the effects of an inflorescence's methanol extract were investigated in glucose-stimulated pancreatic cells (RIN-5F) and LPS-stimulated RAW 264.7 macrophages. The extract reduced the overproduction of intracellular reactive species in pancreatic cells and also NO, L-citrulline and IL-6 levels in LPS-stimulated RAW 264.7 macrophages. Inhibition of 5-lipoxygenase (IC50 = 166.1 µg/mL) through an uncompetitive manner was also recorded upon treatment with C. urens inflorescences extract. The phenolic profile of the inflorescences was characterized by HPLC-DAD, six hydroxycinnamic acids being identified and quantified. Overall, our data provide additional evidence on the pleiotropic mechanisms of Kitul inflorescences as an antidiabetic agent.
- ArticlePrajapati AK, Mondal MK.J Environ Manage. 2021 Jul 15;290:112615.The CuO-ZnO-Carbon (CZC) nanocomposites (NCs) were synthesized via a green method at 300 and 400 °C calcinated temperatures, using waste marigold (Tagetes spp.) flower petal extract as a reducing agent and carbon source. A novel green strategy for the synthesis of highly effective CZC NCs was developed which showed better adsorption of toxic Cr(VI) and Congo red (CR) dye compared to unsupported carbon NCs. In this strategy, fine powder of petals as carbon source were passed with the flower liquid extract during the filtration process, which supported the metal oxides nanorods(NRs)/nanoparticles(NPs) on the surface. Furthermore, the surface of the synthesized NCs was modified by Cetyl Trimethyl Ammonium Bromide (CTAB) cationic surfactant to increase surface functionality, surface area, and positive charge density of NCs. Additionally, the adsorption performance of Cr(VI) and CR dye improved from acidic pH to neutral pH after surfactant modification of NCs compared to unmodified NCs. The characterization techniques such as Powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET) surface area analysis, Point of zero charge (pHpzc), Field Emission Scanning Electron Microscopy (FE-SEM), Transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) were performed to examine physio-chemical properties of NCs and CTAB modified NCs. The FTIR and BET analysis confirmed that CTAB modified NCs showed excellent functionality and more than 49% and ~67% greater surface area than CZC-300 and CZC-400, respectively, which prepared at 300 and 400 °C temperature. XRD analysis confirmed that NCs were highly crystalline and no phase change after surfactant modification. The FE-SEM and TEM analysis confirmed the pentagonal NRs and spherical NPs of ZnO and CuO, respectively, were formed on the carbon surface. After CTAB modification, no change in the surface morphology of NCs was observed. Thus, comparative study of NCs and CTAB modified NCs was done for Cr(VI) and CR dye adsorption by varying batch conditions, such as initial pH, contact time, temperature, and initial concentration of Cr(VI)/CR dye. The equilibrium time and concentration data were fitted with non-linear forms of kinetic and isotherm models, respectively. CTAB modified CZC-300 NCs showed excellent adsorption capacity for both pollutants up to pH 6 compared to CZC-300 and CZC-400 NCs. Additionally, the maximum adsorption capacity of CTAB modified NCs for Cr(VI) and CR dye were 201.56 and 331.36 mg/g, respectively, at pH 2 and 30 °C and increased with increasing temperature. The effect of co-existing anions on adsorption capacity of both NCs for Cr(VI) and CR dye adsorption was investigated. The regeneration and reusability experiments of both NCs were also performed.
- ArticleZhou X, Wang J, Lu Y, Chen C, Hu Y, Liu P, Dong X.J Ethnopharmacol. 2020 Apr 24;252:112615.ETHNOPHARMACOLOGICAL RELEVANCE: In this study, in order to explore potential depressive biomarkers and potential regulatory targets of KXS on depression, we assessed the effects of Kai-Xin-San (KXS) on lipid metabolism in depressed patients (DPs) and rats exposed to chronic and unpredictable mild stress (CUMS).
MATERIALS AND METHODS: Serum samples were collected from DPs, DPs with 8 weeks of KXS treatment (KXS) and healthy controls (HCs), and non-targeted lipidomics was used to analyze the effect of KXS on serum lipid metabolites in DPs. Based on UPLC-Q-TOF/MS technology, differential metabolites were validated in a large sample size. The potential regulatory network of KXS was analyzed by bioinformatic analysis, and the expressions of proteins in serum were verified using western boltting analysis. Moreover, effects of KXS on serum lipid and lipid metabolism-related hormone levels in CUMS rats were detected by enzyme-linked immunosorbent assay and enzymatic method.
RESULTS: We validated that the levels of six serum lipid metabolites (N-Desmethylcitalopram (HMDB14021), PC(14:1(9Z)/24:0) (HMDB07926), PC(P-18:1(11Z)/20:0) (HMDB11281), PC(O-18:0/20:4(8Z,11Z,14Z,17Z)) (HMDB13420), PC(16:0/P-18:0) (HMDB07995) and PC(16:0/P-18:1(11Z)) (HMDB07996)) between HC/DP groups and between DP/KXS groups were significantly different. Among these six metabolites, HMDB07995, HMDB07996, HMDB13420 and HMDB11281 were highly sensitive and specific for depression and KXS treatment by receiver operating characteristic (ROC) curve analysis. matrix metalloproteinases (MMPs) including MMP2 and MMP9, apolipoproteins (Apo) including APOA1 and APOC1 were up-regulated and apolipoproteins (Apo) including APOB, APOD and APOE, phospholipid transfer protein (PLTP), Paraoxonase 1 (PON1) were down-regulated in DPs, and KXS treatment could reverse these changes. In CUMS rats, KXS could increase the open-field score, sucrose preference and body weight, and reduce immobility time. Furthermore, KXS increased the serum levels of the above-mentioned six metabolites, reduced serum total cholesterol (TCH), triglyceride (TG) and free fatty acid (FFA) levels and increased the serum high-density lipoprotein cholesterol (HDL-C) level in CUMS rats. In addition, leptin and ghrelin were down-regulated by KXS.
CONCLUSIONS: The results suggested that KXS exerted antidepressant effects by regulating the signaling pathways involved in lipid metabolism disorders. The lipid metabolites might be potential biomarkers of depression and possible targets for KXS-based treatment of depression. - ArticleYu YY, Li XQ, Hu WP, Cu SC, Dai JJ, Gao YN, Zhang YT, Bai XY, Shi DY.Biomed Pharmacother. 2022 Mar;147:112615.Sepsis-induced acute kidney injury (AKI) and acute lung injury (ALI) have high morbidity and mortality, with no effective clinically available drugs. Anti-inflammation is effective strategy in the therapy of AKI and ALI. NF-κB is a target for the development of anti‑inflammatory agents. The purpose of the study is to evaluate the effect of 270, self-developed NF-κB inhibitor, in LPS-induced AKI and ALI. LPS-induced macrophages were used to examine the anti-inflammation activity of 270 in vitro. Sepsis-induced AKI and ALI mice models were established by intraperitoneal injection of LPS (10 mg/kg) for 24 h. Oral administration 270 for 14 days before LPS stimulation. Plasma, kidney and lung tissues were collected and used for histopathology, biochemical assay, ELISA, RT-PCR, and western blot analyses. In vitro, we showed that 270 suppressed the inflammation response in LPS-induced RAW 264.7 macrophages and bone marrow derived macrophages. In vivo, we found that 270 ameliorated LPS-induced AKI and ALI, as evidenced by improving various pathological changes, reducing the expression of pro-inflammation genes, blocking the activation of NF-κB and JNK pathways, attenuating the elevated myeloperoxidase (MPO) activity and malondialdehyde (MDA) content, ameliorating the activated ER stress, reversing the inhibition effect on autophagy in kidney and lung tissues, and alleviating the enhanced plasma level of creatinine (Crea), blood urea nitrogen (BUN) and pro-inflammation cytokines. Our investigations provides evidence that NF-κB inhibitor 270 is a potential drug that against LPS-induced AKI and ALI in the future.
- ArticleBolotsky A, Muralidharan R, Butler D, Root K, Murray W, Liu Z, Ebrahimi A.Biosens Bioelectron. 2021 Jan 15;172:112615.Rapid antibiotic susceptibility testing (AST) is critical in determining bacterial resistance or susceptibility to a particular antibiotic. Simple-to-use phenotype-based AST platforms can assist care-givers in timely prescription of the right antibiotic. Monitoring the change of bacterial viability by measuring electrochemical Faradaic current is a promising approach for rapid AST. However, the existing works require mixing redox-active reagents in the solution which can interfere with the antibiotics. In this paper, we developed a facile electrodeposition process for creating a redox-active crystalline layer (denoted as RZx) on pyrolytic graphite sheets (PGS), which was then utilized as the sensing layer for reagent-free electrochemical AST. To demonstrate the proof-of-principle, we tested the sensors with Escherichia coli (E. coli) K-12 treated with two antibiotics, ampicillin and kanamycin. While the sensors enable detection of bacterial metabolism mainly due to pH-sensitivity of RZx (∼ 53 mV/pH), secreted redox-active metabolites/compounds from whole cells are likely contributing to the signal as well. By monitoring the differential voltammetric signals, the sensors enable accurate prediction of the minimum inhibitory concentration (MIC) in 60 min (p < 0.03). The sensors are stable after 60 days storage in ambient conditions and enable analysis of microbial viability in complex solutions, as demonstrated in spiked milk and human whole blood.
- ArticleShi Q, Lu Y, Zhang G, Yang X, Li R, Zhang G, Guo X, Song J, Ding Q.Colloids Surf B Biointerfaces. 2022 Sep;217:112615.The recurrence and bone defect of malignant osteosarcoma postsurgical treatment have gained remarkable attention. Therefore, the development of multifunctional treatment platform is urgently desirable to achieve efficient tumor treatment and bone regeneration. In this paper, a multifunctional nanomaterial using mesoporous silica (MSN) as platform modified with quercetin (Qr), collagen (Col) and dopamine (PDA) was developed. Our findings demonstrated that the nanoparticles designed in this work had excellent photothermal properties and pH responsiveness. In addition, the nanoparticles had outstanding anti-tumor ability and could killed Saos-2 cells within 10 min under 808 nm laser irradiation owing to the synergistic effect of hyperthermia and Qr. Besides, the modification of PDA and Col endows the nanoparticles with excellent osteogenic activity.
- ArticleDeng YR, Li YF, Yang H, Fan YR, Huang Y.J Inorg Biochem. 2024 Aug;257:112615.A series of bis-naphthyl ferrocene derivatives were synthesized and characterized. Based on the results obtained from UV-visible absorption titration and ethidium bromide (EB) displacement experiments, it was observed that the synthesized compounds exhibited a strong binding ability to dsDNA. In comparison to the viscosity curve of EB, the tested compounds demonstrated a bisintercalation binding mode when interacting with CT-DNA. Differential pulse voltammetry (DPV) was employed to assess the binding specificity of these indicators towards ssDNA and dsDNA. All tested indicators displayed more pronounced signal differences before and after hybridization between probe nucleic acids and target nucleic acids compared to Methylene Blue (MB). Among the evaluated compounds, compound 3j containing an ether chain showed superior performance as an indicator, making it suitable for constructing DNA-based biosensors. Under optimized conditions including probe ssDNA concentration and indicator concentration, this biosensor exhibited good sensitivity, reproducibility, stability, and selectivity. The limit of detection was calculated as 4.53 × 10-11 mol/L. Furthermore, when utilizing 3j as the indicator in serum samples, the biosensor achieved satisfactory recovery rates for detecting the BRCA1 gene.
- ArticleSun Z, Meng H, Li J, Wang J, Li Q, Wang Y, Zhang Y.PLoS One. 2014;9(11):e112615.Many terpenoids have important pharmacological activity and commercial value; however, application of these terpenoids is often limited by problems associated with the production of sufficient amounts of these molecules. The use of Saccharomyces cerevisiae (S. cerevisiae) for the production of heterologous terpenoids has achieved some success. The objective of this study was to identify S. cerevisiae knockout targets for improving the synthesis of heterologous terpeniods. On the basis of computational analysis of the S. cerevisiae metabolic network, we identified the knockout sites with the potential to promote terpenoid production and the corresponding single mutant was constructed by molecular manipulations. The growth rates of these strains were measured and the results indicated that the gene deletion had no adverse effects. Using the expression of amorphadiene biosynthesis as a testing model, the gene deletion was assessed for its effect on the production of exogenous terpenoids. The results showed that the dysfunction of most genes led to increased production of amorphadiene. The yield of amorphadiene produced by most single mutants was 8-10-fold greater compared to the wild type, indicating that the knockout sites can be engineered to promote the synthesis of exogenous terpenoids.
- ArticleGillies NA, Lovell AL, Waldie KE, Wall CR.Nutrition. 2025 Feb;130:112615.OBJECTIVES: To synthesize evidence from fruit and vegetable intervention studies investigating mental or cognitive health outcomes (or both) in children ≤10 y. Our aim was to understand the efficacy of such interventions in improving measures of cognitive performance or mental health and to identify successful intervention elements to inform future research.
METHODS: We conducted a systematic search of the Cochrane, Embase, PubMed, and CINAHL databases for articles published before August 2022 (PROSPERO registration no. CRD42022356571). A narrative synthesis was conducted according to the Synthesis Without Meta-Analysis guidelines.
RESULTS: Of the 4686 articles identified, only 7 of the 17 full texts screened were included in the final review. No studies investigated the efficacy of interventions using "whole" fruits or vegetables. Six studies examined the effects of blueberries using drinks made from fresh (1 cup) or freeze-dried (30 g) blueberries and one study evaluated a mulberry powder-based drink. Sample sizes ranged from 14 to 54, and most studies were acute interventions with outcomes measured in a 2- to 3-h window (n = 6). Through a narrative synthesis of direction of responses, measures of executive function appeared sensitive to intervention effects in both acute and longer-term settings. Some concerns of risk of bias were evident, according to the RoB 2 tool, related to incomplete reporting of methodological aspects.
CONCLUSIONS: The studies identified through this systematic review could not directly address the planned research question, resulting in poor certainty of evidence. Future research with whole fruit and vegetable interventions could better inform population health strategies for improved mental and cognitive health outcomes in children. - ArticleHao P, Huang Y, Peng J, Yu J, Guo X, Bao F, Dian Z, An S, Xu TR.Exp Cell Res. 2021 06 15;403(2):112615.IRS4 is a member of the insulin receptor substrate (IRS) protein family. It acts as a cytoplasmic adaptor protein, integrating and transmitting signals from receptor protein tyrosine kinases to the intracellular environment. IRS4 can induce mammary tumorigenesis and is usually overexpressed in non-small cell lung cancer (NSCLC). However, little is known about the role of IRS4 in the development and progression of lung cancer. In this study, we show that IRS4 knockout suppresses the proliferation, colony formation, migration, and invasion of A549 lung cancer cells, as well as tumor growth in a nude mouse xenograft model. In contrast, stable expression of IRS4 showed the opposite effects. As expected, IRS4 was found to activate the PI3K/Akt and Ras-MAPK pathways, and we also showed that IRS4 depletion significantly enhanced the sensitivity of EGFR tyrosine kinase inhibitor (EGFR-TKI)-resistant cells to gefitinib. Taken together, these results show that IRS4 promotes NSCLC progression and may represent a potential therapeutic target for EGFR-TKI-resistant NSCLC.
- ArticleYaralı Çevik ZB, Karaman O, Topaloğlu N.J Photochem Photobiol B. 2023 Jan;238:112615.One of the novel strategies for bone tissue regeneration is photobiomodulation (PBM) which depends on the red and near-infrared light absorption by mitochondria and may trigger bone tissue regeneration via the production of intracellular ROS and ATP, NO release, etc. It is also important to identify the changes in those signal molecule levels in an in vivo mimicking platform such as 3-Dimensional (3D) Scaffold Free Microtissues (SFMs) that may serve more natural osteogenic differentiation responses to PBM. Herein, we aimed to increase the osteogenic differentiation capability of the co-culture of Human Bone Marrow Stem Cells (hBMSC) and Human Umbilical Vein Endothelial Cells (HUVECs) on 3D SFMs by triple light treatment at 655 and 808-nm of wavelengths with the energy densities of 1, 3, and 5 J/cm2. We performed the analysis of cell viability, diameter measurements of SFMs, intracellular ROS production, NO release, ATP activity, temperature measurements, DNA content, ALPase activity, calcium content, and relative gene expressions of ALP, Collagen, and Osteopontin by qRT-PCR. It was found that both wavelengths were effective in terms of the viability of SFMs. 1 and 5 J/cm2 energy densities of both wavelengths increased the SFM diameter with significant changes in intracellular ROS, ATP, and NO levels compared to the control group. We concluded that PBM therapy was successful to induce osteogenesis. 1 J/cm2 at 655 nm of wavelength and 5 J/cm2 at 808 nm of wavelength were the most effective energy densities for osteogenic differentiation on SFMs with triple light treatment.