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1.
Nanotechnology ; 32(1): 015301, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33078716

RESUMO

Clinical data shows that antitumor treatments are often ineffective if tumor cells have metastasized. To gain an effective antitumor therapeutic effect, in this report, the tumor cell was limited to the primary site and simultaneously ablated by chemotherapy. Considering the extremely complicated process of cancer metastasis, we seek to comprehensively suppress tumor metastases at both micro and macro levels, which closely link to migration and interact with each other. At the micro level, the motility of the tumor cell was decreased via accelerating mitochondria fusion. At the macro level, the unfavorable hypoxia environment was improved. A liposome-based multifunctional nanomedicine was designed by coloading latrunculin B (LAT-B), an inhibitor of actin polymerization, and doxorubicin (DOX) into the hydrophobic bilayers and aqueous cavity, respectively. Meanwhile, an oxygen reservoir named perfluoropentane (PFP) was encapsulated into the liposome core to fulfill synergistic treatment of metastatic tumors. In this paper, we demonstrated that the metastasis of the tumor cell could be effectively inhibited by LAT-B through promoting mitochondria fusion without affecting its function, making it as an encouraging candidate for effective anti-metastasis therapy. Meanwhile, we found that the combination of LAT-B and DOX shows a synergistic effect against tumors because the combined effect of these two drugs cover the entire cell proliferation process. In a word, this report presents a potential improvement in the treatment of metastatic cancer.

2.
Protein Expr Purif ; 177: 105765, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32987120

RESUMO

The SaeRS two-component system in Staphylococcus aureus controls the expression of a series of virulence factors, such as hemolysins, proteases, and coagulase. The response regulator, SaeR, belongs to the OmpR family with an N-terminal regulatory domain and a C-terminal DNA binding domain. To improve the production and stability of the recombinant protein SaeR, l-arginine (L-Arg) was added to the purification buffers. L-Arg enhanced the solubility and stability of the recombinant protein SaeR. The thermal denaturation temperature of SaeR in 10 mM L-Arg buffer was significantly increased compared to the buffer without L-Arg. Microscale Thermophoresis (MST) analysis results showed that the SaeR protein could bind to the P1 promoter under both phosphorylated and non-phosphorylated status in buffer containing 10 mM L-Arg. These results illustrate an effective method to purify SaeR and other proteins.

3.
Apoptosis ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068199

RESUMO

Blockade of hypoxia-caused nonmyocytes apoptosis helps improve survival and mitigate ventricular remodeling and dysfunction during the chronic stage of myocardial infarction. But tools affecting nonmyocyte apoptosis are very rare. Sphingosylphosphorylcholine (SPC), a naturally occurring bioactive sphingolipid in plasma, was proved to protect cardiomyocyte against apoptosis in an ischemic model in our previous study. Here, we showed that SPC also inhibited hypoxia-induced apoptosis in myofibroblasts, an important type of nonmyocytes in the heart. Calmodulin (CaM) is an identified receptor of SPC. We clarified that SPC inhibited myofibroblast apoptosis through CaM as evidenced by decreased cleaved caspase 3, PARP1 and condensed nucleus. Furthermore, the employment of inhibitor and agonist of p38 and STAT3 suggests that SPC inhibits myofibroblast apoptosis by regulating the phosphorylation of p38 and STAT3, and they act as downstream of CaM. The present work may provide new evidence on the regulation of myofibroblasts apoptosis by SPC and a novel target for heart remodeling after hypoxia.

4.
Stem Cells ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038290

RESUMO

Loss of tissue attachment as a consequence of bacterial infection and inflammation represents the main therapeutic target for the treatment of periodontitis. Cementoblasts, the cells that produce the mineralized tissue, cementum, that is responsible for connecting the soft periodontal tissue to the tooth, are a key cell type for maintaining/restoring tissue attachment following disease. Here, we identify two distinct stem cell populations that contribute to cementoblast differentiation at different times. During postnatal development, cementoblasts are formed from perivascular-derived cells expressing CD90 and perivascular-associated cells that express Axin2. During adult homeostasis, only Wnt-responsive Axin2+ cells form cementoblasts but following experimental induction of periodontal disease, CD90+ cells become the main source of cementoblasts. We thus show that different populations of resident stem cells are mobilized at different times and during disease to generate precursors for cementoblast differentiation and thus provide an insight into the targeting cells resident cells for novel therapeutic approaches. The differentiation of these stem cells into cementoblasts is however inhibited by bacterial products such as lipopolysaccharides, emphasizing that regeneration of periodontal ligament soft tissue and restoration of attachment will require a multipronged approach.

5.
CNS Neurosci Ther ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058536

RESUMO

BACKGROUND: In this brief report, we investigated the impact of COVID-19 on outpatient stroke clinics and inpatient services and their recovery process. METHODS: We sent a survey to physicians worldwide through the network of the World Stroke Organization to investigate the impact of COVID-19 on stroke clinics. To farther along in recovering from the outbreak, we reviewed stroke and other neurology outpatient clinic visits (approximately 50% were stroke related) and the number of inpatient services from December 2019 to July 2020 in a large neurology department in Shanghai, China, where there was no official city lockdown. RESULTS: We received 112 valid survey responses from 46 countries, representing all continents except for Antarctica. Only seven of the survey responders (7/112, 6.3%) reported that they have kept their outpatient clinics open as usual, but they did exercise increased precautions for COVID-19 by following recent guidelines regarding use of personal protective equipment and isolation techniques. The remainder of the respondents have either reduced outpatient clinic services or suspended outpatient clinics completely. Telephone consultation or telemedicine with video capability was used for new patients or follow-ups, with limited in-person evaluations when necessary. Outpatient clinic visits and inpatient services from a large tertiary hospital in China decreased dramatically during the peak period of the outbreak, but then rebounded back quickly following the partial or full recovery from the outbreak. Compared with the recovery process of inpatient services, outpatient clinic visits decreased faster and recovered much slower. This is consistent with our global survey data which indicates that some outpatient clinics have rescheduled their outpatient visits for 3 to 6 months. CONCLUSIONS: The COVID-19 pandemic caused a significant drop of in-person outpatient visits and inpatient services. Clinic visits recovered slower than inpatient services in stroke and other neurological diseases after the pandemic.

6.
Ann Hum Biol ; : 1-16, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33059477

RESUMO

BACKGROUND: Mongolian populations are widely distributed geographically, showing abundant ethnic diversity with geographic and tribal differences. AIM: To infer the genetic substructure, admixture and ancient genetic sources of Mongolians together with Kazakhs. SUBJECTS AND METHODS: We genotyped more than 690,000 genome-wide SNPs from 33 Mongolian and Chinese Kazakh individuals s and compared these with both ancient and present-day Eurasian populations using Principal Component Analysis (PCA), ADMIXTURE, Refine-IBD, f statistics, qpWave and qpAdm. RESULTS: We found genetic substructures within Mongolians corresponding to Ölöd, Chahar, and Inner Mongolian clusters, which was consistent with tribe classifications. Mongolian and Kazakh groups derived about 6% to 40% of West Eurasian related ancestry, most likely from Bronze Age Steppe populations. The East Asian related ancestry in Mongolian and Kazakh groups was well represented by the Neolithic DevilsCave related nomadic lineage, comprising 42% to 64% of studied groups. We also detected 10% to 51% of Han Chinese related ancestry in Mongolian and Kazakh groups, especially in Inner Mongolians. The average admixture times for Inner Mongolian, Mongolian_Chahar, Mongolian_Ölöd and Chinese Kazakh were about 1381, 626, 635 and 632 years ago, respectively, with Han and French as the sources. CONCLUSIONS: The DevilsCave related ancestry was once widespread westwards covering a wide geographical range from Far East Russia to the Mongolia Plateau. The formation of present-day Mongolic and Turkic-speaking populations has also received genetic influence from agricultural expansion.

7.
Int J Biol Macromol ; 165(Pt A): 530-541, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33002533

RESUMO

In this report, we present the strategy for the revelation of synergistic effect and elucidation of active fractions from an immunomodulatory complex polysaccharide derived from seven herbs (Lentinula edodes, Ganodorma lucidum, Tremella fuciformis, Chrysanthemum, Lycium barbarum, Codonopsis pilosula and Poria cocos), a formula used as health product in China market, using the combination of HPSEC-MALLS, immunological bioassay and saccharide mapping analysis. The effects of complex polysaccharide and their fractions on RAW 246.7 macrophages demonstrated that the fractions (CD1, CD2, CD3) with molecular weight above 10 kDa exhibited immune activity by directly stimulated NO release and phagocytosis, and induced macrophages to secrete cytokines. Especially, fraction CD2 with molecular weight of 100-1000 kDa showed the strongest bioactivity (EC50 = 0.19 µg/mL) compared with their individual corresponding herbal polysaccharides fractions due to synergistic effect, which supported the scientific use of Chinese herbal mixture. Moreover, their chemical characters were analyzed by HPSEC-MALLS and saccharide mapping, and the original herbs, including L. edodes, G. lucidum, T. fuciformis and Chrysanthemum, responsible for the immunomodulatory activity were tentatively revealed. Results are beneficial for the quality analysis and formula optimization of complex polysaccharides in both biomedical and functional food field.

8.
Genome Biol Evol ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045048

RESUMO

Dendrobium huoshanense is used to treat various diseases in traditional Chinese medicine. Recent studies have identified active components. However, the lack of genomic data limits research on the biosynthesis and application of these therapeutic ingredients. To address this issue, we generated the first chromosome-level genome assembly and annotation of D. huoshanense. We integrated PacBio sequencing data, Illumina paired-end sequencing data, and Hi-C sequencing data to assemble a 1.285 Gb genome, with contig and scaffold N50 lengths of 598 kb and 71.79Mb, respectively. We annotated 21,070 protein-coding genes and 0.96 Gb transposable elements, constituting 74.92% of the whole assembly. In addition, we identified 252 genes responsible for polysaccharide biosynthesis by Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation. Our data provide a basis for further functional studies, particularly those focused on genes related to glycan biosynthesis and metabolism, and have implications for both conservation and medicine.

9.
J Mol Cell Cardiol ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33045251

RESUMO

AIMS: Calcific aortic valve disease (CAVD) is a primary cause of cardiovascular mortality; however, its mechanisms are unknown. Currently, no effective pharmacotherapy is available for CAVD. Aldo-keto reductase family 1 member B (Akr1B1) has been identified as a potential therapeutic target for valve interstitial cell calcification. Herein, we hypothesized that inhibition of Akr1B1 can attenuate aortic valve calcification. METHODS AND RESULTS: Normal and degenerative tricuspid calcific valves from human samples were analyzed by immunoblotting and immunohistochemistry. The results showed significant upregulation of Akr1B1 in CAVD leaflets. Akr1B1 inhibition attenuated calcification of aortic valve interstitial cells in osteogenic medium. In contrast, overexpression of Akr1B1 aggravated calcification in osteogenic medium. Mechanistically, using RNA sequencing (RNAseq), we revealed that Hippo-YAP signaling functions downstream of Akr1B1. Furthermore, we established that the protein level of the Hippo-YAP signaling effector active-YAP had a positive correlation with Akr1B1. Suppression of YAP reversed Akr1B1 overexpression-induced Runx2 upregulation. Moreover, YAP activated the Runx2 promoter through TEAD1 in a manner mediated by ChIP and luciferase reporter systems. Animal experiments showed that the Akr1B1 inhibitor epalrestat attenuated aortic valve calcification induced by a Western diet in LDLR-/- mice. CONCLUSION: This study demonstrates that inhibition of Akr1B1 can attenuate the degree of calcification both in vitro and in vivo. The Akr1B1 inhibitor epalrestat may be a potential treatment option for CAVD.

10.
Breast Cancer ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047272

RESUMO

BACKGROUND: Triple negative breast cancer (TNBC) is the most aggressive subtype with the worst prognosis. The role of profilin 2 (PFN2) in TNBC is very controversial. The current study is to explore the role of PFN2 in TNBC. METHODS: PFN2 expression in TNBC and normal breast tissues were evaluated by immunohistochemical analysis. The association between PFN2 expression and prognosis in TNBC patients was analyzed from the TCGA database. A cell counting kit-8 (CCK8) assay was employed to investigate the effects of PFN2 in TNBC cell proliferations. The migration and invasion capability of TNBC cells was evaluated by transwell assays. Western blot was performed to assess the related protein expression of TGF-ß/Smad signaling and epithelial to mesenchymal transition. Finally, TNBC xenografts were established to determine the tumorigenicity in vivo using female Nod/Scid mice. RESULTS: PFN2 is upregulated in TNBC and the higher expression was associated with worse survival. CCK8 assays and Transwell assays demonstrated that PFN2 promoted the proliferation, migration and invasion of TNBC cells. Smad2 and Smad3 were upregulated in PFN2 overexpressing TNBC cells, which further induced the process of epithelial­to­mesenchymal transition. Similarly, the overexpressing PFN2 TNBC cells exhibited stronger tumorigenicity in vivo. CONCLUSIONS: Higher PFN2 expression is associated with a worse 10-year overall survival and relapse-free survival in breast cancer patients, as well as worse 10-year relapse-free survival in TNBC patients. PFN2 promotes the proliferation, migration and invasion of TNBC cells by regulating epithelial-to-mesenchymal transition.

11.
Eur J Pediatr ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048238

RESUMO

This study reports on vocal cord paralysis caused by esophageal button battery (BB) ingestion in children. Medical records of children with vocal cord paralysis and esophageal BB ingestion treated at a tertiary referral institute between January 2016 and March 2020 were reviewed. Five patients aged 9-58 months were identified; three were male. Each patient had accidentally swallowed a 20-mm-diameter lithium battery (3 CR2032 type and 2 CR2025 type). One battery was removed within 4 h after ingestion, and three batteries were removed within 12 h. Removal of the battery was achieved with rigid esophagoscopy in four patients and direct laryngoscopy in one patient. Four patients had bilateral, and one had unilateral vocal cord paralysis. Three patients underwent tracheotomy; two were tracheotomy-dependent until follow-up, while the third patient died of multiple organ dysfunction syndrome a month after surgery. The two cases without tracheotomy remain under close follow-up.Conclusion: Accidentally ingested button batteries should be removed promptly to avoid severe complications. Respiratory support and neurotrophic treatment in the early stage of vocal cord paralysis may be beneficial for recovery of vocal cord movement. What is Known: • Button battery ingestion in children is extremely harmful, especially when the diameter of the button battery exceeds 20 mm. • Esophageal button battery impaction can cause serious complications such as esophageal perforation, mediastinal infection, tracheoesophageal fistula, vocal cord paralysis, and life-threatening bleeding. What is New: • Vocal cord paralysis in children with button battery ingestion plays an early warning role for identifying the severity of the disease. • Early neurotrophic drugs and glucocorticoid therapy may be helpful for the recovery of vocal cord movement, thereby avoiding tracheotomy.

13.
Acta Pharmacol Sin ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024239

RESUMO

Cannabinoids have long been used for their psychotropic and possible medical properties of symptom relief. In the past few years, a vast literature shows that cannabinoids are neuroprotective under different pathological situations. Most of the effects of cannabinoids are mediated by the well-characterized cannabinoid receptors, the cannabinoid type 1 receptor (CB1R) and cannabinoid type 2 receptor (CB2R). Even though CB1Rs are highly expressed in the central nervous system (CNS), the adverse central side effects and the development of tolerance resulting from CB1R activation may ultimately limit the clinical utility of CB1R agonists. In contrast to the ubiquitous presence of CB1Rs, CB2Rs are less commonly expressed in the healthy CNS but highly upregulated in glial cells under neuropathological conditions. Experimental studies have provided robust evidence that CB2Rs seem to be involved in the modulation of different neurological disorders. In this paper, we summarize the current knowledge regarding the protective effects of CB2R activation against the development of neurological diseases and provide a perspective on the future of this field. A better understanding of the fundamental pharmacology of CB2R activation is essential for the development of clinical applications and the design of novel therapeutic strategies.

14.
Oncol Rep ; 44(5): 1885-1894, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000216

RESUMO

The aim of the study was to investigate the effects of lactic acid on the phenotypic polarization and immune function of macrophages. The human monocyte/macrophage cell line, THP­1, was selected and treated with lactic acid. Immunofluorescence staining, laser confocal microscopy, reverse­transcription polymerase chain reaction (RT­PCR), western blot, siRNA, and ELISA analyses were used to observe changes in the levels of cluster of differentiation (CD)68, CD163, hypoxia inducible factor (HIF)­1α, and programmed death ligand­1 (PD­L1) as well as those of cytokines, tumor necrosis factor (TNF)­α, interferon (IFN)­Î³, interleukin (IL)­12, and IL­10. THP­1 macrophages and T cells were co­cultured in vitro to observe the changes in proliferation and apoptosis of T cells. The results showed that, lactic acid (15 mmol/l) significantly upregulated the expression of the macrophage M2 marker CD163 (P<0.05), cytokines, IFN­Î³ and IL­10, secreted by M2­tumor­associated macrophages (TAM, P<0.05), and HIF­1α and PD­L1 (P<0.05), and downregulated the expression of cytokines, TNF­α and IL­12, secreted by M1­TAM (P<0.05). Redistribution of M2­TAM subsets and PD­L1 expression was reversed after further transfection of THP­1 cells with HIF­1α siRNA (P<0.05). After co­culturing, T­cell proliferation was inhibited and apoptosis was promoted. In summary, modulation of lactic acid level can redistribute M2­TAM subsets and upregulate PD­L1 to assist tumor immune escape. The HIF­1α signaling pathway may participate in this process, revealing that macrophages, as 'checkpoints' in organisms, are links that connect the immune status and tumor evolution, and can be used as a target in tumor treatment.

15.
Brain Imaging Behav ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052506

RESUMO

Wilson's disease (WD) is an inherited autosomal recessive disorder of copper metabolism, and its neurological and neuropsychiatric manifestations are associated with copper accumulation in brain. A few neuroimaging studies have shown that gray matter atrophy in WD affects both subcortical structures and cortex. This study aims to quantitatively evaluate the morphometric brain abnormalities in patients with WD in terms of whole brain volume and cortical thickness and their associations with clinical severity of WD. Thirty patients clinically diagnosed as WD with neurological manifestations and 25 healthy controls (HC) were recruited. 3D T1-weighted images were segmented into 276 whole-brain regions of interest (ROIs) and 68 cortical ROIs. WD-vs-HC group comparisons were then conducted for each ROI. The associations between those morphometric measurements and the Global Assessment Scale (GAS) score for WD were analyzed. Compared with HC, significant WD-related volumetric decreases were found in the bilateral subcortical nuclei (putamen, globus pallidus, caudate nucleus, substantia nigra, red nucleus and thalamus), diffuse white matter and several gray matter regions. WD patients showed reduced cortical thickness in the left precentral gyrus and the left insula. Further, the volumes of the right globus pallidus, bilateral putamen, right external capsule and left superior longitudinal fasciculus were negatively correlated with GAS. Our results indicated that significant WD-related morphometric abnormalities were quantified in terms of whole-brain volumes and cortical thicknesses, some of which correlated significantly to the clinical severity of WD. Those morphometrics may provide a potentially effective biomarker of WD.

16.
New Phytol ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089895

RESUMO

Rice (Oryza sativa) is a short-day (SD) plant originally having strong photoperiod sensitivity (PS), with SDs promoting and long days (LDs) suppressing flowering. Although the evolution of PS in rice has been extensively studied, there are few studies that combine the genetic effects and underlying mechanism of different PS gene combinations with variations in PS. We created a set of isogenic lines among the core PS-flowering genes Hd1, Ghd7 and DTH8 using CRISPR mutagenesis, to systematically dissect their genetic relationships under different day-lengths. We investigated their monogenic, digenic, and trigenic effects on target gene regulation and PS variation. We found that Hd1 and Ghd7 have the primary functions for promoting and repressing flowering, respectively, regardless of day-length. However, under LD conditions, Hd1 promotes Ghd7 expression and is recruited by Ghd7 and/or DTH8 to form repressive complexes that collaboratively suppress the Ehd1-Hd3a/RFT1 pathway to block heading, but under SD conditions Hd1 competes with the complexes to promote Hd3a/RFT1 expression, playing a tradeoff relationship with PS flowering. Natural allelic variations of Hd1, Ghd7 and DTH8 in rice populations have resulted in various PS performances. Our findings reveal that rice PS flowering is controlled by crosstalk of two modules - Hd1-Hd3a/RFT1 in SD conditions and (Hd1/Ghd7/DTH8)-Ehd1-Hd3a/RFT1 in LD conditions - and the divergences of these genes provide the basis for rice adaptation to broad regions.

17.
Water Res ; 188: 116482, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33039829

RESUMO

Solar energy is considered one of the most promising energy sources for the degradation of pollutants in the water treatments. An innovative solar photo-thermochemical system involving peroxydisulfate (PDS) as an oxidant and xenon lamp as a solar irradiation light source was applied with hopes to degrade organic matters and alleviate the ultrafiltration (UF) membrane fouling when treating the real surface water. Moreover, heat-activated PDS pretreatment was used as a comparison to explore the respective proportions of solar light and heating effects, finding that solar light effect dominated the activation of PDS to degrade natural organic matters (NOMs) when the reaction temperature was below 50 °C and they both contributed to the production of free radicals at the temperature of >50 °C. The results indicated that solar-activated PDS pretreatment significantly alleviated membrane fouling caused by Songhua River water with the highest transmembrane pressure (TMP) reduction of approximately 69.6% at 70 °C. Organic substances (characterized by DOC, UV254 and the maximum florescent intensity) and micropollutant (atrazine) in the feed water were better degraded in the presence of solar light. Both total fouling index (TFI) and hydraulic irreversible fouling index (HIFI) were moderate correlated with the UV254 and DOC, whereas remarkably correlated with the Fmax of component 2 (C2) and component 3 (C3). In addition, no significant correlation was observed between fouling indexes (TFI and HIFI) and the Fmax of component 1 (C1). The membrane irreversible fouling was attributed to the accumulation of cake layers mainly composed of protein-like substances on the membrane surface. Solar-activated PDS pretreatment would efficiently degrade the protein-like substances and terrestrially derived humic-like matters to control UF membrane fouling. The findings are beneficial to develop new strategies for membrane fouling alleviation based on the solar irradiation and PDS oxidation.

18.
J Pharm Biomed Anal ; 192: 113675, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33099113

RESUMO

Sample preparation such as isolation and pre-concentration is a crucial step for the phytochemical analysis. Magnetic solid-phase extraction (MSPE) has received considerable attention, mainly due to its phase separation more conveniently by facile magnetic decantation as compared to traditional SPE. This review focused on the recent applications of MSPE in sample preparation for the analysis of phytochemical compounds in plants, biological samples and Chinese herbal preparations. In addition, the enzymes immobilized on the magnetic materials and used for the biospecific extraction of enzyme inhibitors were also discussed. The information summarized in this article may provide a reference to the further applications of MSPE in phytochemical analysis.

19.
Anal Biochem ; 610: 113992, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33075315

RESUMO

Gushudan (GSD), a traditional Chinese medicine with a history of more than 15 years, has been shown to have anti-osteoporosis effects, but the specific therapeutic mechanism behind it is still unclear. To further elucidate the pathogenesis of osteoporosis and the preventive mechanism of GSD on glucocorticoid-induced osteoporosis (GIOP) rats, a rapid and comprehensive 1H NMR metabolomics method was established to detect urinary metabolic profiles in the control group, model group and GSD treatment group in this study. The orthogonal partial least squares discriminant analysis (OPLS-DA) was performed to investigate changes in the metabolites, and related metabolic pathways were discovered using MetaboAnalyst platform. As a result, a total of 27 differential metabolites were identified. Of these, 17 metabolites such as formate, allantoin and l-threonate were newly discovered as GIOP potential biomarkers. Energy metabolism, intestinal flora metabolism, amino acid metabolism and oxidative stress response were significantly changed in the urinary profiles of GIOP rats, and GSD could play an anti-osteoporosis role by regulating these metabolic pathways. This study compliments the earlier LC-MS based urine metabolomics research, and helps further understand the pathogenesis of osteoporosis and the potential preventive effects of GSD on GIOP rats.

20.
Lung Cancer ; 150: 76-82, 2020 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-33080551

RESUMO

OBJECTIVES: Immune checkpoint inhibitors (ICIs) have revolutionized the oncologic treatment landscape, but have been accompanied by immune-related adverse events (irAEs). ICI-related pneumonitis (ICI-pneumonitis) is a potentially fatal irAE. However, the risk factors associated with ICI-pneumonitis remain unclear. There is an urgent need to identify risk factors for ICI-pneumonitis using reliable and accessible parameters. Here, we aimed to identify baseline peripheral-blood biomarkers correlated with ICI-pneumonitis and clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) who were treated with ICIs. MATERIALS AND METHODS: We conducted a retrospective analysis of eligible patients with advanced NSCLC who were treated with ICIs at our center. Receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value for analyzing risk of ICI-pneumonitis. Multivariate logistic analysis was performed to identify risk factors of ICI-pneumonitis. Clinical characteristics and treatment outcomes were collected and compared according to the optimal cutoff value. RESULTS: A total of 300 patients were included, in which 54 patients (18 %) experienced ICI-pneumonitis. Patients with ICI-pneumonitis had a high level of baseline peripheral-blood absolute eosinophil count (AEC) than those without ICI-pneumonitis (P = 0.013). The optimal threshold of baseline peripheral-blood AEC to predict ICI-pneumonitis was 0.125 × 109 cells/L. The incidence of ICI-pneumonitis was higher in the high-AEC group (AEC ≥ 0.125 × 109 cells/L; 27.7 %) than in the low-AEC group (AEC < 0.125 × 109 cells/L; 9.8 %, P < 0.001). Moreover, patients with high AEC (compared with those with low AEC) had a higher objective response rate (ORR) (40.9 % versus 28.8 %, P = 0.029) and longer median progression-free survival (PFS) (8.93 months versus 5.87 months, P = 0.038). CONCLUSIONS: Among patients treated with ICIs, a baseline feature of high AEC (≥0.125 × 109 cells/L) was associated with an increasing risk of ICI-pneumonitis, and with a better clinical outcome.

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