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  • Article
    Lin CY, Chang YM, Tseng HY, Shih YL, Yeh HH, Liao YR, Tang HH, Hsu CL, Chen CC, Yan YT, Kao CF.
    Cell Rep. 2023 11 28;42(11):113416.
    Differentiated cardiomyocytes (CMs) must undergo diverse morphological and functional changes during postnatal development. However, the mechanisms underlying initiation and coordination of these changes remain unclear. Here, we delineate an integrated, time-ordered transcriptional network that begins with expression of genes for cell-cell connections and leads to a sequence of structural, cell-cycle, functional, and metabolic transitions in mouse postnatal hearts. Depletion of histone H2B ubiquitin ligase RNF20 disrupts this gene network and impairs CM polarization. Subsequently, assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis confirmed that RNF20 contributes to chromatin accessibility in this context. As such, RNF20 is likely to facilitate binding of transcription factors at the promoters of genes involved in cell-cell connections and actin organization, which are crucial for CM polarization and functional integration. These results suggest that CM polarization is one of the earliest events during postnatal heart development and provide insights into how RNF20 regulates CM polarity and the postnatal gene program.
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  • Article
    Khalafi M, Symonds ME.
    Physiol Behav. 2021 07 01;236:113416.
    Liver fat is a marker of the metabolic derangements associated with obesity for which exercise training is a potential therapy. We therefore performed a systematic meta-analysis to investigate the effect of high intensity interval training (HIIT) on liver fat content in overweight or obese adults with metabolic disorders. PubMed, Scopus, Web of Science and the Cochrane were searched up to October 2020 for HIIT vs. Control (CON) or HIIT vs. moderate intensity interval training (MICT) studies on liver fat content in overweight and obese individuals with metabolic disorders. Standardized mean differences (SMD) and 95% confidence intervals (95% CIs) were calculated. Ten studies involving 333 participants were included in the meta-analysis. Based on studies that directly compared HIIT and CON (6 studies), HIIT was beneficial for promoting a reduction in liver fat [-0.51 (95% CI: -0.85 to -0.17), p = 0.003]. However, there were no significant evidence for an effect of HIIT on liver fat [-0.07 (95% CI: -0.33 to 0.19), p = 0.59], when compared with MICT (7 studies). These results suggest that a HIIT could induce improvements in liver fat of overweight and obese adults with metabolic disorders despite no weight loss.
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  • Article
    Nordli DR, Nordli DR, Galan FN.
    J Pediatr. 2023 07;258:113416.
    An 11-month-old girl with febrile seizures and first unprovoked seizures was evaluated in the hospital. Relevant history included developmental delay and strong family history of febrile seizures and migraines. A routine electroencephalogram was performed and was abnormal due to the presence of a slowed posterior dominant rhythm, generalized spike-wave discharges, and multifocal sharp waves. The findings were concerning for a developmental and epileptic encephalopathy. Given the concern for a developmental and epileptic encephalopathy, a next generation sequence epilepsy gene panel was ordered which identified a pathogenic variant in SCN1A. The clinical history, electroencephalogram, and pathogenic variant were compatible with a diagnosis of Dravet syndrome. This Grand Rounds manuscript highlights the thought process, evaluation, differential diagnosis, treatment, and prognosis in Dravet syndrome.
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  • Article
    Gao LH, Ning J, Bao WL, Yan A, Yin QR.
    Mar Pollut Bull. 2022 Mar;176:113416.
    The construction of world-class Bay makes the marine ecology in Guangdong-Hong Kong-Macao Great Bay Area in risk. Based on the DPSIR index framework, Lotka-Volterra symbiosis model is applied to calculate symbiosis degree between coastal socio-economic system and marine ecosystem in 9 coastal cities. It is found that the marine ecological pressure in this area have not been reversed in recent 20 years. Most cities are in the stage that socio-economic development and marine ecological damage coexist. In Shenzhen, Guangzhou, Dongguan and Zhongshan, the damaged marine ecology has begun to restrain the further expansion of economy and society. The massive population agglomeration in Hong Kong, Macao and other places has caused serious marine ecological stress. It is urgent to improve the marine ecological security by cultivating ecological industrial system and industrial clusters, establishing a land-sea ecological restoration, promoting joint-protection and co-governance across different administrative regions.
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  • Article
    Rafiei A, Schriemer DC.
    Anal Biochem. 2019 12 01;586:113416.
    Microtubules (MTs) are key components in the cytoskeleton of the eukaryotic cell, and play roles in processes such as intracellular transport and cell division. An improved understanding MT regulation requires structural analysis of the extensive interactions between the MT lattice and its regulatory proteins, but MT interactions are challenging for even the most advanced structural methods to characterize. Integrative methods involving crosslinking mass spectrometry (XL-MS) can extend structural analysis to many interaction classes, but the representation of MTs in crosslinking data-sets has been surprisingly low. Here, we explore the basis for the underrepresentation of the MT lattice and present an enhanced method for mapping MT structural features using an optimized set of reagents, together with fluorescence detection to ensure MT structural integrity. Through the application of stringent identification criteria, 91 unique crosslinks were identified, 78 of which were uniquely matched to 7 distinct structural features of the MT lattice. Of note, 4 crosslinks were detected for the lattice-A protofilament organization. The lattice-A structure defines a "seam" or discontinuity in MTs and is an emerging site of interest for MT regulation. Our methodology should be broadly applicable to integrative structural studies involving any MT-protein interaction.
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  • Article
    Zhang Z, He Y, Liu H, Liu Y, Wu T, Li R, Wang Y, Ma W.
    Int Immunopharmacol. 2024 Oct 18;143(Pt 2):113416.
    BACKGROUND: Ferroptosis, an iron-dependent form of cell death, plays a pivotal role in the pathologic progression of asthma. Electroacupuncture (EA) has demonstrated considerable efficacy in mitigating asthma airway inflammation, although its underlying mechanisms remain partially elucidated.
    METHODS: We investigated the regulatory effect of NLRP3 on ferroptosis using a lipopolysaccharide (LPS)-induced inflammation model in BEAS-2B cells, where NLRP3 expression was modulated with si-RNA and overexpression plasmids. The levels of inflammatory cytokines TNF-α, IL-1β, and IL-6 were quantified. We also assessed NLRP3 and JAK2/STAT3 pathway-related proteins, and evaluated lipid peroxidation, mitochondrial membrane potential (ΔΨm), and antioxidant system functionality. In vivo, we examined the impact of EA on ferroptosis and airway inflammation by modulating NLRP3 activation. Asthma inflammation severity was evaluated using H&E, Masson, and PAS staining, alongside ELISA. NLRP3 and JAK2/STAT3 pathway-related proteins, as well as ferroptosis indicators, were also analyzed. The mechanism by which NLRP3 activates ferroptosis was investigated through in vitro assays.
    RESULTS: LPS exposure resulted in increased intracellular inflammatory cytokines, and activation of the NLRP3 and JAK2/STAT3 pathways, leading to enhanced lipid peroxidation, decreased ΔΨm, and disruption of antioxidant system balance, ultimately inducing ferroptosis. Si-NLRP3 countered the effects of LPS, whereas oe-NLRP3 exacerbated symptoms. In vivo studies revealed that EA reduced airway inflammation, inhibited NLRP3 activation, and decreased phosphorylation of JAK2/STAT3, effectively lowering ferroptosis-related indicators. Utilizing JAK2/STAT3 activators and inhibitors, we confirmed that NLRP3 mediates ferroptosis via the JAK2/STAT3 pathway.
    CONCLUSIONS: EA alleviates HDM-induced asthma, primarily through the inhibition of NLRP3 activation, which modulates the JAK2/STAT3 pathway and mediates ferroptosis.
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  • Article
    Rizza V, Torre M, Tratzi P, Fazzini P, Tomassetti L, Cozza V, Naso F, Marcozzi D, Petracchini F.
    J Environ Manage. 2021 Nov 01;297:113416.
    This study aims to evaluate and quantify the environmental, health, and economic benefits due to the penetration of electric vehicles in the fleet composition by replacing conventional vehicles in an urban area. This study has been performed for the city of Turin, where road transport represents one of the main primary emission sources. Air pollution data were evaluated by ADMS-Roads, the flow traffic data used for simulation come from a real-time monitoring. Instead, statistics on mortality and hospitalizations due to cardiovascular and respiratory diseases were collected from the regional health information system and the National Health Institute and implemented in the BenMap software to evaluate the health and economic impacts. In both cases, two scenarios to evaluate the annual benefits of reducing PM10, PM2.5 and NO2 were used: reduction to the levels gained by the assumptions of 2025 and 2030 Scenario and the PM10, PM2.5 and NO2 concentrations were considered for evaluating short-term and long-term effects. The analysis performed doesn't include background pollution levels, i.e. the concentrations percentage reductions are only related to the local contribution, therefore derived from the contribution only of traffic source. The results show that fleet electrification has a potential benefit for concentrations reduction in comparison to the base Scenario, especially related to NO2, less for PM10 and PM2.5. Regarding 2025 Scenario (4 % (passenger car) and 5 % (light-duty vehicles) electric vehicles), reductions of 52 % of NO2, 35 % of PM10 and 49 % of PM2.5 are observed. Meanwhile, as regards 2030 Scenario reductions of 87 % of NO2, 36 % of PM10 and 50 % of PM2.5 are reached. Also, in terms of social costs a decrease of 47 % for the 2025 Scenario and 66 % for the 2030 Scenario in comparison to the base Scenario is arise.
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  • Article
    Hellman M.
    Behav Brain Res. 2021 08 27;412:113416.
    This essay contrasts a late modernist epistemological paradigm with an ontology-oriented Anthropocene-conscious Approach (ACA) as frameworks for understanding the coming into being and the making of addiction. Operationalizable theories and concepts of addiction have been crucial in an era with a great demand for compartmentalizing and systemically defining psychological struggles and social problems. In the modernistic progress story, the addiction phenomenon materializes through the conceptual division between capacity and non-capacity, with those capable of mastering their urges on one side and those incapable of doing so on the other. The ACA strives actively to move beyond artificial divides between agency/structure, culture/nature, mind/matter and instead explore phenomena ecologically across these continuums. This entails a conscious re-focus away from authoritative human-made assumptions towards new types of knowledge and knowing. In the ACA assemblage-like ontology, different elements are brought together in their capacities to affect each other into entities. Due to its claims of practical uses, I predict that the ACA will become as influential as Foucauldian genealogy in the field of addiction studies.
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  • Article
    Huang YJ, Lee PH, Chen LC, Lin BC, Lin C, Chan TC.
    Environ Res. 2022 09;212(Pt C):113416.
    INTRODUCTION: Green space and air pollution have been recognized as vital health determinants. There is a paucity of studies examining the interplay between green space, fine particulate matter (PM2.5), and the incidence of specific cancers.
    OBJECTIVE: We aimed to explore the contributions of green space and ambient PM2.5 to the risk of specific cancers in terms of the most common cancers based on incidence or mortality rate in Taiwan and to ascertain the interaction between green space and PM2.5 and their role in cancer risk.
    MATERIALS AND METHODS: This retrospective longitudinal cohort study included 407,415 participants. Data were obtained from the 2000-2015 Mei Jau Health Examination Database linked to the Taiwan Cancer Registry and Causes of Death datasets. All participants were aged ≥20 years and had no history of cancer. The environmental exposure were the normalized difference vegetation index (NDVI) and the 2-year average PM2.5 at baseline. Multivariate adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. We adjusted for covariates including demographics, anthropometrics, comorbidities, health behaviors, biochemical data, and environmental factors.
    RESULTS: During a median follow-up of 10.37 years, 11,576 cancer cases were reported. PM2.5 exposure increased the risk of all cancers (HR: 1.11, [95% CI: 1.06-1.15]), stomach cancer (HR: 1.27, [1.02-1.58]), endocrine gland cancer (HR: 2.13, [1.39-3.26]), breast cancer (HR: 1.12, [1.03-1.22]), and lung cancer (HR: 1.12, [1.01-1.24]). An increase in NDVI reduced the risk of prostate cancer (HR: 0.93, [0.88-0.99]) and lung cancer (HR: 0.95, [0.91-0.99]). NDVI influenced the incidence of prostate and all cancers by reducing PM2.5 concentrations.
    CONCLUSION: Long-term PM2.5 exposure is associated with an increased risk of some types of cancers. In contrast, an increase in environmental green space exposure is associated with lowering of the risk of prostate and lung cancer.
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  • Article
    Dey A, Hazra AK, Mukherjee A, Nandy S, Pandey DK.
    J Ethnopharmacol. 2021 Feb 10;266:113416.
    ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochia indica L. (Aristolochiaceae) is a common medicinal plant described in many traditional medicine as well as in Ayurveda used against snakebites. Besides, the plant has also been reported traditionally against fever, rheumatic arthritis, madness, liver ailments, dyspepsia, oedema, leishmaniasis, leprosy, dysmenorrhoea, sexual diseases etc. The plant is known to contain its major bioactive constituent aristolochic acid (AA) known for its anti-snake venom, abortifacient, antimicrobial and antioxidant properties.
    MATERIALS AND METHODS: This present work describes a validated, fast and reproducible high performance thin layer chromatography (HPTLC) method to estimate AA from the roots of 20 chemotypes of A. indica procured from 20 diverse geographical locations from the state of West Bengal, India. Further, an evidence-based approach was adopted to investigate the reported anti-venom activity of the aqueous extracts of the A. indica roots by assessing its phospholipase A2 (PLA2) inhibitory properties since PLA2 is a major component of many snake-venoms. Finally, the cytotoxicity and genotoxicity of the aqueous root extract of the Purulia (AI 1) chemotype were assessed at various concentrations using Allium cepa root meristematic cells.
    RESULTS: The highest amount of AA (7643.67 μg/g) was determined in the roots of A. indica chemotype collected from Purulia district followed by the chemotypes collected from Murshidabad, Jalpaiguri and Birbhum districts (7398.34, 7345.09 and 6809.97 μg/g respectively). This study not only determines AA in the plants to select pharmacologically elite chemotypes of A. indica, but it also identifies high AA producing A. indica for further domestication and propagation of the plants for pharmacological and industrial applications. The method was validated via analyzing inter-day and intra-day precision, repeatability, reproducibility, instrumental precision, limit of detection (LOD) and limit of quantification (LOQ) and specificity. Chemotypes with high AA content exhibited superior anti-PLA2 activity by selectively inhibiting human-group PLA2. Moreover, A. indica root extract significantly inhibited mitosis in Allium cepa root tips as a potent clastogen.
    CONCLUSIONS: The present quick, reproducible and validated HPTLC method provides an easy tool to determine AA in natural A. indica plant populations as well as in food and dietary supplements, a potential antivenin at one hand and a possible cause of aristolochic acid nephropathy (AAN) at another. Besides, the cytotoxic and mitotoxic properties of the root extracts should be used with caution especially for oral administration.
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  • Article
    Ji H, Xie W, Liu W, Liu X, Zhao D.
    Environ Pollut. 2020 Jan;256:113416.
    Marine oil spill often causes contamination of drinking water sources in coastal areas. As the use of oil dispersants has become one of the main practices in remediation of oil spill, the effect of oil dispersants on the treatment effectiveness remains unexplored. Specifically, little is known on the removal of dispersed oil from contaminated water using conventional adsorbents. This study investigated sorption behavior of three prototype activated charcoals (ACs) of different particle sizes (4-12, 12-20 and 100 mesh) for removal of dispersed oil hydrocarbons, and effects of two model oil dispersants (Corexit EC9500A and Corexit EC9527A). The oil content was measured as n-alkanes, polycyclic aromatic hydrocarbons (PAHs), and total petroleum hydrocarbons (TPHs). Characterization results showed that the smallest AC (PAC100) offered the highest BET surface area of 889 m2/g and pore volume of 0.95 cm3/g (pHPZC = 6.1). Sorption kinetic data revealed that all three ACs can efficiently adsorb Corexit EC9500A and oil dispersed by the two dispersants (DWAO-I and DWAO-II), and the adsorption capacity followed the trend: PAC100 > GAC12 × 20 > GAC4 × 12. Sorption isotherms confirmed PAC100 showed the highest adsorption capacity for dispersed oil in DWAO-I with a Freundlich KF value of 10.90 mg/g∙(L/mg)1/n (n = 1.38). Furthermore, the presence of Corexit EC9500A showed two contrasting effects on the oil sorption, i.e., adsolubilization and solubilization depending on the dispersant concentration. Increasing solution pH from 6.0 to 9.0 and salinity from 2 to 8 wt% showed only modest effect on the sorption. The results are useful for effective treatment of dispersed oil in contaminated water and for understanding roles of oil dispersants.
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  • Article
    Shi J, Sun S, Xing S, Huang C, Huang Y, Wang Q, Xue X, Chen Z, Wang Y, Huang Z.
    Biomed Pharmacother. 2022 Sep;153:113416.
    Glioblastoma (GBM) is the most prevalent type of adult primary brain tumor and chemotherapy of GBM was limited by drug-resistance. Fraxinellone is a tetrahydro-benzofuranone derivative with various pharmacological activities. However, the pharmacological effects of fraxinellone on GBM remains largely unknown. Here, we found that fraxinellone inhibited the proliferation and growth of GBM cells in a dose-dependent manner in vitro. Subsequently, we found that fraxinellone suppressed the migration and induced apoptosis of GBM cells in vitro. Using western blot and immunostaining, we further found that fraxinellone downregulated the expressions of sirtuin 3 (SIRT3), and superoxide dismutase 2 (SOD2), a downstream of SIRT3 in GBM cells. Meanwhile, reactive oxygen species (ROS) were increased in these fraxinellone-treated GBM cells. Interestingly, overexpression of SIRT3 (SIRT3-OE) indeed partially restored the inhibition of both cell proliferation and migration of GBM cells induced by fraxinellone. Finally, we found that fraxinellone could inhibit the growth of GBM in xenograft model through the inactivation of SIRT3 signaling pathway. Taken together, these results suggest that fraxinellone suppressed the growth and migration of GBM cells by downregulating SIRT3 signaling in vitro, and inhibited the tumorigenesis of GBMs in vivo.
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  • Article
    Xuan H, Zhang Z, Jiang W, Li N, Sun L, Xue Y, Guan H, Yuan H.
    Colloids Surf B Biointerfaces. 2023 Aug;228:113416.
    Development of a controlled delivery ultrafine fibrous system with two bioactive molecules is required to stimulate tendon healing in different phase. In this study, we used emulsion stable jet electrospinning to fabricate aligned poly(L-lactic acid) (PLLA) based ultrafine fibers with two small bioactive molecules of L-Arginine (Arg) and low molecular weight hyaluronic acid (HA). The results demonstrated that the aligned Arg/HA/PLLA microfibrous scaffold showed core-shell structure and allowed sequential release of Arg and HA due to their different electric charge. The scaffold also showed enhanced hydrophilicity, cell migration, spread and proliferation. Using an Achilles tendon repair model in rats, we demonstrated that this novel fibrous scaffold can prevent adhesion and promote tendon regeneration. Additionally, two p53 and ER-α-mediated signalling pathways were described as the probable main path of synergistic effects of the novel scaffold on tendon generation. Thus, this study may provide an important strategy for developing biofunctional and biomimetic tendon scaffolds.
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  • Article
    Huang J, Hu Z, Li G, Chin Y, Pei Z, Yao Q, Li D, Hu Y.
    Food Res Int. 2023 11;173(Pt 2):113416.
    A novel stable PVA/HPMC/roselle anthocyanin (RAE) indicator film co-pigmented with oxalic acid (OA) was prepared, its properties, application effects and stability enhancement mechanism were investigated correspondingly. The structural characterization revealed that more stable network was formed due to the co-pigmentation facilitated generation of molecular interactions. Meanwhile, the co-pigmentation improved film mechanical and hydrophobic properties compared to both PVA/HPMC/RAE newly prepared (PHRN) or stored (PHRS) film, expressing as higher tensile strength values (12.25% and 14.44% higher than PHRN and PHRS), lower water solubility (7.22% and 10.09% lower than PHRN and PHRS) and water vapor permeability values (33.20% and 21.05% lower than PHRN and PHRS) of PVA/HPMC/RAE/OA newly prepared (PHON) or stored (PHOS) film. Compared with the PHRS film, the PHOS film still presented more distinguishable color variations when being applied to monitor shrimp freshness, owing to the stabilization behaviors of co-pigmentation in anthocyanin conformation. Hence, the co-pigmentation was an effective strategy to enhance film stability, physical and pH-responsive properties after long term storage, leading to better film monitoring effects when applied in real-time freshness monitoring.
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  • Article
    Genevini P, Papiani G, Ruggiano A, Cantoni L, Navone F, Borgese N.
    PLoS One. 2014;9(11):e113416.
    VAPB is a ubiquitously expressed, ER-resident adaptor protein involved in interorganellar lipid exchange, membrane contact site formation, and membrane trafficking. Its mutant form, P56S-VAPB, which has been linked to a dominantly inherited form of Amyotrophic Lateral Sclerosis (ALS8), generates intracellular inclusions consisting in restructured ER domains whose role in ALS pathogenesis has not been elucidated. P56S-VAPB is less stable than the wild-type protein and, at variance with most pathological aggregates, its inclusions are cleared by the proteasome. Based on studies with cultured cells overexpressing the mutant protein, it has been suggested that VAPB inclusions may exert a pathogenic effect either by sequestering the wild-type protein and other interactors (loss-of-function by a dominant negative effect) or by a more general proteotoxic action (gain-of-function). To investigate P56S-VAPB degradation and the effect of the inclusions on proteostasis and on ER-to-plasma membrane protein transport in a more physiological setting, we used stable HeLa and NSC34 Tet-Off cell lines inducibly expressing moderate levels of P56S-VAPB. Under basal conditions, P56S-VAPB degradation was mediated exclusively by the proteasome in both cell lines, however, it could be targeted also by starvation-stimulated autophagy. To assess possible proteasome impairment, the HeLa cell line was transiently transfected with the ERAD (ER Associated Degradation) substrate CD3δ, while autophagic flow was investigated in cells either starved or treated with an autophagy-stimulating drug. Secretory pathway functionality was evaluated by analyzing the transport of transfected Vesicular Stomatitis Virus Glycoprotein (VSVG). P56S-VAPB expression had no effect either on the degradation of CD3δ or on the levels of autophagic markers, or on the rate of transport of VSVG to the cell surface. We conclude that P56S-VAPB inclusions expressed at moderate levels do not interfere with protein degradation pathways or protein transport, suggesting that the dominant inheritance of the mutant gene may be due mainly to haploinsufficiency.
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  • Article
    Lind CM, Moore IT, Vernasco BJ, Latney LV, DiGeronimo PM, Farrell TM.
    Gen Comp Endocrinol. 2020 05 01;290:113416.
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  • Article
    Chen L, Liu Y, Xu Y, Afify SM, Gao A, Du J, Liu B, Fu X, Liu Y, Yan T, Zhu Z, Seno M.
    Exp Cell Res. 2023 01 01;422(1):113416.
    In the previous study, we originally developed cancer stem cells (CSCs) models from mouse induced pluripotent stem cells (miPSCs) by culturing miPSCs in the conditioned medium of cancer cell lines, which mimiced as carcinoma microenvironment. However, the molecular mechanism of conversion in detail remains to be uncovered. Microarray analysis of the CSCs models in this study revealed Dsg2, one of the members of the desmosomal cadherin family, was up-regulated when compared with the original miPSCs. Moreover, the expression of key factors in Wnt/β-catenin signaling pathway were also found up-regulated in one of the CSCs models, named miPS-LLCcm. An autocrine loop was implied between Dsg2 and Wnt/β-catenin signaling pathway when miPSCs were treated with Wnt/β-catenin signaling pathway activators, Wnt3a and CHIR99021, and when the CSCs model were treated with inhibitors, IWR-1 and IWP-2. Furthermore, the ability of proliferation and self-renewal in the CSCs model was markedly decreased in vitro and in vivo when Dsg2 gene was knocked down by shRNA. Our results showed that the Wnt/β-catenin signaling pathway is activated by the up-regulation of Dsg2 expresssion during the conversion of miPSCs into CSCs implying a potential mechanism of the tranformation of stem cells into malignant phenotype.
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  • Article
    Phipps E, Butt T, Desjardins N, Schonauer M, Schlonies R, Masuda JR.
    Soc Sci Med. 2021 02;270:113416.
    Local communities are struggling with persistent health inequities driven by income disparity, housing inadequacy, and other intersecting factors that constrain individual and community well-being. Increasingly, intersectoral approaches are recognized as essential to tackle such challenges, given their intersecting nature. This paper describes Equity-focused Intersectoral Practice (EquIP), a novel methodology that merges participatory research principles with the purposeful positioning of grounded expertise (lived experience) to shift the gaze of intersectoral actors towards the contextual factors that contribute to health inequities. The EquIP methodology creates uncommon spaces for intersectoral encounter that support critical reflexivity and relationship-building among institutional and community-based intersectoral actors. A case example of the EquIP methodology, implemented in a small, rural Canadian city in the context of a regional housing crisis, illustrates how investment in reflexivity and relational praxis among diverse intersectoral actors supports the identification of existing structures, beliefs, and practices within institutional settings that constrain effective intersectoral response to health inequities.
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  • Article
    Frydrych J, Keough DT, Chavchich M, Travis J, Dračínský M, Edstein MD, Guddat LW, Hocková D, Janeba Z.
    Eur J Med Chem. 2021 Jul 05;219:113416.
    Parasites of the Plasmodium genus are unable to produce purine nucleotides de novo and depend completely on the salvage pathway. This fact makes plasmodial hypoxanthine-guanine-(xanthine) phosphoribosyltransferase [HG(X)PRT] a valuable target for development of antimalarial agents. A series of nucleotide analogues was designed, synthesized and evaluated as potential inhibitors of Plasmodium falciparum HGXPRT, P. vivax HGPRT and human HGPRT. These novel nucleoside phosphonates have a pyrrolidine, piperidine or piperazine ring incorporated into the linker connecting the purine base to a phosphonate group(s) and exhibited a broad range of Ki values between 0.15 and 72 μM. The corresponding phosphoramidate prodrugs, able to cross cell membranes, have been synthesized and evaluated in a P. falciparum infected human erythrocyte assay. Of the eight prodrugs evaluated seven exhibited in vitro antimalarial activity with IC50 values within the range of 2.5-12.1 μM. The bis-phosphoramidate prodrug 13a with a mean (SD) IC50 of 2.5 ± 0.7 μM against the chloroquine-resistant P. falciparum W2 strain exhibited low cytotoxicity in the human hepatocellular liver carcinoma (HepG2) and normal human dermal fibroblasts (NHDF) cell lines at a concentration of 100 μM suggesting good selectivity for further structure-activity relationship investigations.
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  • Article
    Liu Y, Ma S, Cai Q.
    J Pharm Biomed Anal. 2020 Sep 10;189:113416.
    Processing herbal medicine is a classic characters of traditional Chinese medicine (TCM) clinic. Stir-frying with bran is a common method of processing Atractylodis Rhizoma (AR), which is considered to enhance the therapeutic effect in TCM theory. However, the processing mechanism remains unclear. In our previous study, we found that bran-fried AR was better than raw AR in regulating gut flora. To further compare the effect of raw and bran-fried AR on the symbiotic metabolism of gut flora and host, we established a fecal metabonomics method of ARs intervention on spleen-deficiency rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. 22 potential biomarkers of spleen-deficiency were identified under the positive and negative ion mode. Through the analysis of metabolic pathway, 6 significant changes of metabolic pathway were found, 5 of which were both improved by raw and bran-fried AR. Especially bran-fried AR was better than raw AR in the improvement of tyrosine metabolism and purine metabolism. Correlation analysis between the metabolic potential biomarkers and the microbiological biomarkers published in our previous study revealed that one of the spleen-strengthening mechanisms of ARs could be associated with the improvement of the symbiotic metabolism of gut flora and host by regulating gut-flora. The results can help us to understand the mechanism of AR intervention on spleen deficiency and the enhanced-efficacy mechanism of bran-fried AR.
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