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1.
J Agric Food Chem ; 72(19): 10970-10980, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38708787

ABSTRACT

Eleven alkaloids (1-11) including seven new ones, 1-7, were isolated from the solid fermentation of Aspergillus fumigatus VDL36, an endophytic fungus isolated from the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub distributed across the Southwest regions of China, Myanmar, and Vietnam. Their structures were elucidated on the basis of extensive spectroscopic methods. The isolates were evaluated for in vitro antifungal activities against five phytopathogenic fungi (Fusarium oxysporum, Coriolus versicolor, Fusarium solani, Botrytis cinerea, Fusarium graminearum). As a result, the new compounds fumigaclavine I (1), 13-ethoxycyclotryprostatin A (5), 13-dehydroxycyclotryprostatin A (6), and 12ß-hydroxy-13-oxofumitremorgin C (7) exhibited antifungal activities with MIC values of 7.8-62.5 µg/mL which were comparable to the two positive controls ketoconazole (MIC = 7.8-31.25 µg/mL) and carbendazim (MIC = 1.95-7.8 µg/mL). Furthermore, compounds 1 and 5 demonstrated potent protective and curative effects against the tomato gray mold in vivo. Preliminary structure-activity relationships of the tested indole diketopiperazine alkaloids indicate that the introduction of a substituent group at position C-13 enhances their biological activities.


Subject(s)
Alkaloids , Aspergillus fumigatus , Endophytes , Alkaloids/pharmacology , Alkaloids/chemistry , Aspergillus fumigatus/drug effects , Endophytes/chemistry , Molecular Structure , Fusarium/drug effects , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Plant Leaves/microbiology , Plant Leaves/chemistry , Microbial Sensitivity Tests , China , Plant Diseases/microbiology
2.
Fitoterapia ; 175: 105938, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38565379

ABSTRACT

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.


Subject(s)
Antineoplastic Agents, Phytogenic , Limonins , Phytochemicals , Plant Leaves , Toona , Humans , Molecular Structure , Cell Line, Tumor , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Plant Leaves/chemistry , Limonins/isolation & purification , Limonins/pharmacology , Limonins/chemistry , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , China , Toona/chemistry , Plant Stems/chemistry
3.
Anal Chim Acta ; 1294: 342293, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38336414

ABSTRACT

BACKGROUND: The practical application of moisture sensitive metal organic frameworks (MOFs) in extraction technology faces challenges related to competitive adsorption and water stability. The target analytes cannot be effectively extracted under humid conditions due to the competitive moisture adsorption and/or framework structure collapse of MOFs. In this study, the microporous organic networks (MONs) were synthesized through Sonogashira coupling reaction to use for hydrophobic modification on the surface of MOF-199. RESULTS: The MOF-199@MON as coating was deposited on stainless steel wires for solid-phase microextraction (SPME) of benzene series (BTEX) in aqueous environments. Under the optimal extraction conditions, the MOF-199@MON coated fiber for SPME coupled with GC-MS for the determination of BTEX gave the linear range of 0.5-500 µg L-1, the limit of detections (LODs, S/N = 3) of 0.01-0.04 µg L-1, the limit of quantifications (LOQs, S/N = 10) of 0.04-0.12 µg L-1, the enhancement factors of 3567-4878, and the intra-day, inter-day and fiber-to-fiber precisions (relative standard deviations, RSDs) of 1.0-9.8, 1.9-7.9 and 4.5-9.5 %, respectively. The developed method was successfully applied to the analysis of BTEX in water samples with the recoveries of 71.0 %-113 %. SIGNIFICANCE: This work reveals the home-made SPME fibers have a long service life (the extraction efficiency of fiber decreased by only 7.26 %-13.14 % after 100 cycles). The potential of MON functionalized MOFs as effective adsorbents for the SPME of pollutants in the water environment.

4.
ACS Omega ; 9(6): 6924-6931, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38371847

ABSTRACT

Blockage is often generated in the air nozzle guide duct in a circulating fluidized-bed coal gasifier (CFBG), especially with Zhundong sub-bituminous coal (ZSBC) as the raw material. A typical example is found in one CFBG sample from Xinjiang Yihua Chemical Industry Co, Ltd. The serious blockage can be observed obviously. As so far, it is not clear for the characteristics and generation mechanism of the blockage. For analysis, the blockage can be classified into two parts, wall-layer blockage (WLB) and center-layer blockage (CLB). To inhibit its formation, it is of significance to analyze the composition, surface morphology, and formation mechanism of the two blockages. In our experiments, WLB and CLB were tested by XRF, XRD, FTIR, SEM-EDS, and SEM-mapping methods. Results showed that WLB presents high content of Fe, Cr, and Ni, and Fe mainly existed in the form of metal oxides. CLB is dominated by Si (43.04%), derived from silica and alkali and alkaline-earth metals silicates, and the migration of Fe, Cr, and Ni elements from the duct material was observed. Compared with WLB, from FTIR analysis, CLB contains more inorganic minerals, and the absorption peak of inorganic minerals is mainly attributed to asymmetric Si-O-Si. Many fine particles are attached to the surface of the WLB, while the surface of the CLB is smooth, and there is noticeable raised texture, which is presumed to be the result of particle melting and agglomerating as the bottom ash enters the duct in the gasification process. For the formation of the blockage, this paper speculates that it is mainly due to the difference in flow resistance near the air nozzle outlet, resulting in the formation of a flow dead zone at the bottom of the gasifier, which leads to large amounts of ash overcoming the outlet resistance and leaking into the air nozzle, and next, the ash corrodes in the tube, resulting in wall deposition and ultimately blocking the air guide duct. Two methods can be tried to avoid or inhibit the formation of blockage in the duct, including optimizing air nozzle with more wear-resistant and heat-resistant materials and adjusting the distance between air nozzles to avoid mutual interference from ash particles.

5.
Mol Psychiatry ; 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38233469

ABSTRACT

Previous studies have shown that excessive alcohol consumption is associated with poor sleep. However, the health risks of light-to-moderate alcohol consumption in relation to sleep traits (e.g., insomnia, snoring, sleep duration and chronotype) remain undefined, and their causality is still unclear in the general population. To identify the association between alcohol consumption and multiple sleep traits using an observational and Mendelian randomization (MR) design. Observational analyses and one-sample MR (linear and nonlinear) were performed using clinical and individual-level genetic data from the UK Biobank (UKB). Two-sample MR was assessed using summary data from genome-wide association studies from the UKB and other external consortia. Phenotype analyses were externally validated using data from the National Health and Nutrition Examination Survey (2017-2018). Data analysis was conducted from January 2022 to October 2022. The association between alcohol consumption and six self-reported sleep traits (short sleep duration, long sleep duration, chronotype, snoring, waking up in the morning, and insomnia) were analysed. This study included 383,357 UKB participants (mean [SD] age, 57.0 [8.0] years; 46% male) who consumed a mean (SD) of 9.0 (10.0) standard drinks (one standard drink equivalent to 14 g of alcohol) per week. In the observational analyses, alcohol consumption was significantly associated with all sleep traits. Light-moderate-heavy alcohol consumption was linearly linked to snoring and the evening chronotype but nonlinearly associated with insomnia, sleep duration, and napping. In linear MR analyses, a 1-SD (14 g) increase in genetically predicted alcohol consumption was associated with a 1.14-fold (95% CI, 1.07-1.22) higher risk of snoring (P < 0.001), a 1.28-fold (95% CI, 1.20-1.37) higher risk of evening chronotype (P < 0.001) and a 1.24-fold (95% CI, 1.13-1.36) higher risk of difficulty waking up in the morning (P < 0.001). Nonlinear MR analyses did not reveal significant results after Bonferroni adjustment. The results of the two-sample MR analyses were consistent with those of the one-sample MR analyses, but with a slightly attenuated overall estimate. Our findings suggest that even low levels of alcohol consumption may affect sleep health, particularly by increasing the risk of snoring and evening chronotypes. The negative effects of alcohol consumption on sleep should be made clear to the public in order to promote public health.

6.
Cell Rep ; 43(2): 113688, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38245869

ABSTRACT

Macrophages are phenotypically and functionally diverse in the tumor microenvironment (TME). However, how to remodel macrophages with a protumor phenotype and how to manipulate them for therapeutic purposes remain to be explored. Here, we show that in the TME, RARγ is downregulated in macrophages, and its expression correlates with poor prognosis in patients with colorectal cancer (CRC). In macrophages, RARγ interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), which prevents TRAF6 oligomerization and autoubiquitination, leading to inhibition of nuclear factor κB signaling. However, tumor-derived lactate fuels H3K18 lactylation to prohibit RARγ gene transcription in macrophages, consequently enhancing interleukin-6 (IL-6) levels in the TME and endowing macrophages with tumor-promoting functions via activation of signal transducer and activator of transcription 3 (STAT3) signaling in CRC cells. We identified that nordihydroguaiaretic acid (NDGA) exerts effective antitumor action by directly binding to RARγ to inhibit TRAF6-IL-6-STAT3 signaling. This study unravels lactate-driven macrophage function remodeling by inhibition of RARγ expression and highlights NDGA as a candidate compound for treating CRC.


Subject(s)
Colorectal Neoplasms , Interleukin-6 , Humans , Carcinogenesis/metabolism , Cell Transformation, Neoplastic/metabolism , Colorectal Neoplasms/pathology , Histones/metabolism , Interleukin-6/metabolism , Lactates/metabolism , Macrophages/metabolism , STAT3 Transcription Factor/metabolism , TNF Receptor-Associated Factor 6/metabolism , Tumor Microenvironment
7.
Zhongguo Zhong Yao Za Zhi ; 48(18): 4993-5002, 2023 Sep.
Article in Chinese | MEDLINE | ID: mdl-37802841

ABSTRACT

The resin ethanol extract of Gegen Qinlian Decoction(GGQLD) has been found to significantly alleviate the intestinal toxicity caused by Irinotecan, but further research is needed to establish its overall quality and clinical medication standards. This study aimed to establish an HPLC characteristic fingerprint of the resin ethanol extract of GGQLD, predicted the targets and signaling pathways of its pharmacological effects based on network pharmacology, identified core compounds with pharmacological relevance, and analyzed potential quality markers(Q-markers) of the resin eluate of GGQLD for relieving Irinotecan-induced toxicity. By considering the uniqueness, measurability, and traceability of Q-markers based on the "five principles" of Q-markers and combining them with network pharmacology techniques, the overall efficacy of the resin ethanol extract of GGQLD can be characterized. Preliminary predictions suggested that the four components of puerarin, berberine, baicalin, and baicalein might serve as potential Q-markers for the resin etha-nol extract of GGQLD. This study provides a basis and references for the quality control and clinical mechanism of the resin ethanol extract of GGQLD.


Subject(s)
Drugs, Chinese Herbal , Network Pharmacology , Irinotecan , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use
8.
Zhongguo Zhong Yao Za Zhi ; 48(11): 2968-2980, 2023 Jun.
Article in Chinese | MEDLINE | ID: mdl-37381957

ABSTRACT

This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.


Subject(s)
Antineoplastic Agents , Biological Products , Animals , Mice , Chromatography, High Pressure Liquid , Cyclooxygenase 2 , Diarrhea/chemically induced , Diarrhea/drug therapy
9.
Cell Chem Biol ; 30(7): 709-725.e6, 2023 07 20.
Article in English | MEDLINE | ID: mdl-37354905

ABSTRACT

Metastatic colorectal cancer (mCRC) is characterized by poorer prognosis of patients and limited therapeutic approach, partly due to the lack of effective target. Using mouse models and tumor organoids, this study reported a tripartite motif 21 (TRIM21) protein, exerting potential inhibitory effects on the invasion and metastasis of CRC. Mechanistically, TRIM21 directly interacted with and ubiquitinated MST2 at lysine 473 (K473) via K63-linkage. This ubiquitination enabled the formation of MST2 homodimer and enhanced its kinase activity, ultimately resulting in the functional inactivation of yes-associated protein (YAP) and inhibition of an epithelial-mesenchymal transition (EMT) feature. We identified that vilazodone, an antidepressant, directly bound to TRIM21 to exert effective anti-metastatic action both in vitro and in vivo. Collectively, these findings revealed a previously unrecognized interplay between TRIM21 and the Hippo-YAP signaling. These results suggested that vilazodone could be repositioned as an anti-tumor drug to inhibit CRC metastasis by targeting TRIM21.


Subject(s)
Colorectal Neoplasms , Signal Transduction , Animals , Mice , Cell Line, Tumor , Colorectal Neoplasms/metabolism , Phosphorylation , Ubiquitination , Vilazodone Hydrochloride/pharmacology
10.
ACS Appl Mater Interfaces ; 15(4): 5990-5997, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36689469

ABSTRACT

Here, two-dimensional (2D) nitrogen-doped carbon nanosheets (CNSs) were prepared through carbonizing MOFs (ZIF-8) in-situ grown using graphitic carbon nitride (g-C3N4) as a template. The developed ZIF-8 CNS was then used as solid-phase microextraction (SPME) fiber coating for beneficiation of five biomarkers in exhalation of patients with esophageal cancer and in gas chromatography-mass spectrometry (GC-MS) for determination. The ZIF-8 CNS fiber exhibits satisfactory enrichment factors (3490-5631), wide linearity (5-1000 µg L-1), and low detection limits (0.26-0.96 µg L-1). The relative standard deviations (RSDs) for six replicate extractions of the same ZIF-8 CNS fiber were between 2.0-3.9% (intra-day) and 2.8-5.2% (inter-day). The reproducibility of three fibers prepared by the same approach was in the range 6.8-12.3% (RSD). The developed ZIF-8 CNS fiber can persist in 120 SPME cycles with no prominent loss of extraction efficiency and precision. The high enrichment factors of the 2D ZIF-8 CNS coatings are attributed to the high specific surface area, ultrathin thickness, and nano-pore or interlayer channels; moreover, nitrogen doping also endows the π system with a strong electron absorption ability, which will enhance the π-π interaction between the ZIF-8 CNS and the aromatic ring. Ultimately, the self-made ZIF-8 CNS-coated SPME fiber was applied to the analysis of exhaled breath samples. The recoveries of spiked analytes are between 84 and 105%.


Subject(s)
Carbon , Esophageal Neoplasms , Humans , Carbon/chemistry , Nitrogen , Solid Phase Microextraction/methods , Exhalation , Reproducibility of Results
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 287(Pt 1): 122069, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36371877

ABSTRACT

A novel fluorescent probe L consisting of ß-Cyclodextrin (ß-CD) and thiosemicarbazide moieties was designed for copper ions detection. Apparent fluorescence quenching of probe L in Tris-HCl(pH = 7.4)solution was observed only in the presence of Cu2+, among other interfering ions. The present probe L was 1:1 complexed with Cu2+ and the detection limit of probe L was calculated to be 1.37 µM. The results demonstrate that the probe L may provide a convenient method for visual detection of Cu2+ in the environmental and biological systems.


Subject(s)
Cyclodextrins , Fluorescent Dyes , Copper , Spectrometry, Fluorescence/methods , Ions , Water
12.
Gland Surg ; 11(9): 1538-1545, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36221278

ABSTRACT

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign, but locally aggressive breast disease. Steroids are widely used as a breast-conserving option, however, the response rate of steroids varies in reported studies, as well as its different reported usage. This prospective observational cohort study aimed to report the outcomes of methylprednisolone for IGM treatment. Methods: From Aug 2019 to Dec 2021, the clinicopathological information of 156 IGM patients who sought treatment at West China Hospital was prospectively collected. A total of 88 patients treated with methylprednisolone were included in the study. The clinical features, treatment response, and follow-up data were analyzed. Results: The median age at diagnosis was 32 years, and 90.9% of patients were multipara. The predominant symptom at presentation was painful breast mass, with a median size of 4.7 cm. For steroid usage, an initial 20 mg methylprednisolone daily was given until disease stable. The median duration of 20 mg methylprednisolone treatment was 45 (range, 14-376) days. The median duration of whole steroid therapy was 105 (range, 28-381) days. A total of 80.7% of patients (71/88) responded well to steroid treatment. In 63 patients, steroid treatment was successfully withdrawn, and treatment was completed. With an average of 283 days follow-up (range, 0-770 days), relapse was observed in 21 (33.33%) patients. Compared with patients with residual disease as shown by physical examination (PE), those with complete clinical remission (CCR) at the end of treatment had longer relapse-free intervals. Conclusions: Steroids are the preferable breast-conserving option for IGM. Treatment with 20 mg methylprednisolone for an average of 1.5 months is usually required, and full steroid treatment might last for 3 months.

13.
ACS Omega ; 7(25): 21397-21406, 2022 Jun 28.
Article in English | MEDLINE | ID: mdl-35785316

ABSTRACT

Sequential extract residues (R i , i = 1, 2, 3, 4, and 5) were obtained from Hefeng acid-washing coal (HFAC) by petroleum ether, carbon disulfide, methanol, acetone, and isometric carbon disulfide/acetone mixture, sequentially. Pyrolysis behavior of the residues was determined using thermogravimetry analysis. The Coats-Redfern method with different reaction orders was used to analyze the pyrolysis kinetic of each sample, and the kinetic parameters, including correlation coefficient (R 2), activation energy (E), and pre-exponential factor (A), were calculated. Results showed that the weight loss of extract residues was higher than HFAC, and pyrolysis behavior varies greatly for residues, which is related to the unstable structure after extraction. From conversion-temperature (α-T) curves, the pyrolysis process was divided into three stages: low-temperature stage (150-350 °C), medium-temperature stage (350-550 °C), and high-temperature stage (550-950 °C). The medium-temperature stage made great contribution to the process of pyrolysis, which was dominated by depolymerization and decomposition reaction. The relationship between kinetic parameters and reaction order showed that the swelling effect is an important reason for the discrepancy of E for each sample in the process of pyrolysis.

14.
HLA ; 100(5): 534-536, 2022 11.
Article in English | MEDLINE | ID: mdl-35766332

ABSTRACT

HLA-C*03:597 differs from HLA-C*03:03:01:01 by a single non-synonymous nucleotide substitution in exon 5 (922 A>G).


Subject(s)
HLA-C Antigens , Nucleotides , Alleles , China , HLA-C Antigens/genetics , Humans , Sequence Analysis, DNA
15.
Clin Psychol Rev ; 92: 102128, 2022 03.
Article in English | MEDLINE | ID: mdl-35150965

ABSTRACT

The present meta-analytic review aimed to synthesize the global prevalence characteristics of digital addiction in the general population. We searched PubMed, Embase, Cochrane Library, and PsycINFO for studies reporting prevalence of various subtypes of digital addiction published before October 31, 2021. Studies were eligible if they were published in peer-reviewed journals, used a validated tool to assess digital addiction, and passed the qualify assessment. In total, 498 articles with 507 studies were included in systematic review, and the meta-analysis included 495 articles with 504 studies covering 2,123,762 individuals from 64 countries. Global pooled prevalence estimates were 26.99% (95% CI, 22.73-31.73) for smartphone addiction, 17.42% (95% CI, 12.42-23.89) for social media addiction, 14.22% (95% CI, 12.90-15.65) for Internet addiction, 8.23% (95% CI, 5.75-11.66) for cybersex addiction, and 6.04% (95% CI, 4.80-7.57) for game addiction. Higher prevalence of digital addiction was found in Eastern Mediterranean region and low/lower-middle income countries. Males had higher risk for Internet and game addiction. An increasing trend of digital addiction during the past two decades was found, which dramatically worsened during COVID-19 pandemic. This study provides the first and comprehensive estimation for the global prevalence of multiple subtypes of digital addiction, which varied between regions, economic levels, time periods of publication, genders, and assessment scales. PROSPERO ID: CRD42020171117.


Subject(s)
Behavior, Addictive , COVID-19 , Behavior, Addictive/epidemiology , Female , Humans , Male , Pandemics , Prevalence , SARS-CoV-2
16.
Oncogene ; 41(8): 1166-1177, 2022 02.
Article in English | MEDLINE | ID: mdl-35058597

ABSTRACT

BEST4 is a member of the bestrophin protein family that plays a critical role in human intestinal epithelial cells. However, its role and mechanism in colorectal cancer (CRC) remain largely elusive. Here, we investigated the role and clinical significance of BEST4 in CRC. Our results demonstrate that BEST4 expression is upregulated in clinical CRC samples and its high-level expression correlates with advanced TNM (tumor, lymph nodes, distant metastasis) stage, LNM (lymph node metastasis), and poor survival. Functional studies revealed that ectopic expression of BEST4 promoted CRC cell proliferation and metastasis, whereas the depletion of BEST4 had the opposite effect both in vitro and in vivo. Mechanistically, BEST4 binds to the p85α regulatory subunit of phosphatidylinositol-3-kinase (PI3K) and promotes p110 kinase activity; this leads to activation of Akt signaling and expression of MYC and CCND1, which are critical regulators of cell proliferation and metastasis. In clinical samples, the expression of BEST4 is positively associated with the expression of phosphorylated Akt, MYC and CCND1. Pharmacological inhibition of Akt activity markedly repressed BEST4-mediated Akt signaling and proliferation and metastasis of CRC cells. Importantly, the interaction between BEST4 and p85α was also enhanced by epidermal growth factor (EGF) in CRC cells. Therapeutically, BEST4 suppression effectively sensitized CRC cells to gefitinib treatment in vivo. Taken together, our findings indicate the oncogenic potential of BEST4 in colorectal carcinogenesis and metastasis by modulating BEST4/PI3K/Akt signaling, highlighting a potential strategy for CRC therapy.


Subject(s)
Proto-Oncogene Proteins c-akt
17.
Front Mol Biosci ; 8: 763652, 2021.
Article in English | MEDLINE | ID: mdl-34722636

ABSTRACT

Objective: 5-fluorouracil- and oxaliplatin-based FOLFOX regimens are mainstay chemotherapeutics for colorectal cancer (CRC) but drug resistance represents a major therapeutic challenge. To improve patient survival, there is a need to identify resistance genes to better understand the mechanisms underlying chemotherapy resistance. Methods: Transcriptomic datasets were retrieved from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and combined with our own microarray data. Weighted gene co-expression network analysis (WGCNA) was used to dissect the functional networks and hub genes associated with FOLFOX resistance and cancer recurrence. We then conducted analysis of prognosis, profiling of tumor infiltrating immune cells, and pathway overrepresentation analysis to comprehensively elucidate the biological impact of the identified hub gene in CRC. Results: WGCNA analysis identified the complement component 3 (C3) gene as the only hub gene associated with both FOLFOX chemotherapy resistance and CRC recurrence after FOLFOX chemotherapy. Subsequent survival analysis confirmed that high C3 expression confers poor progression-free survival, disease-free survival, and recurrence-free survival. Further correlational analysis revealed significant negative association of C3 expression with sensitivity to oxaliplatin, but not 5-fluorouracil. Moreover, in silico analysis of tumor immune cell infiltration suggested the change of C3 expression could affect tumor microenvironment. Finally, gene set enrichment analysis (GSEA) revealed a hyperactivation of pathways contributing to invasion, metastasis, lymph node spread, and oxaliplatin resistance in CRC samples with C3 overexpression. Conclusion: Our results suggest that high C3 expression is a debilitating factor for FOLFOX chemotherapy, especially for oxaliplatin sensitivity, and C3 may represent a novel biomarker for treatment decision of CRC.

18.
Steroids ; 172: 108874, 2021 08.
Article in English | MEDLINE | ID: mdl-34102197

ABSTRACT

A preliminary chemical investigation on 70% MeOH extract of the roots of Asparagus cochinchinensis resulted in the isolation of nine steroids. These isolates comprised of four new C21 (1-4) and one new pregnane (5) glycosides, and four known C27 (6-9) spirostanol steroids. Their structures were identified via analysis of the spectroscopic data and the results of hydrolytic cleavage. The cytotoxic activities of the compounds were tested toward the human tumor cell line Hela (cervical cancer), and compounds 7 and 8 displayed moderate activity with IC50 values of 35.5 and 39.6 µM, respectively.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apocynaceae/chemistry , Glycosides/pharmacology , Plant Extracts/pharmacology , Pregnanes/pharmacology , Steroids/pharmacology , Uterine Cervical Neoplasms/drug therapy , Cell Proliferation , Female , Humans , Molecular Structure , Plant Roots/chemistry , Uterine Cervical Neoplasms/pathology
19.
Clin Chim Acta ; 508: 154-160, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32417215

ABSTRACT

BACKGROUND: Netrin-1 is an axon guidance protein, which can inhibit inflammatory reaction and stabilize the blood-brain barrier to protect against experimental brain injury. We evaluated the concentration of netrin-1 in acute intracerebral hemorrhage (ICH) patients and explored whether netrin-1 is a potential prognostic biomarker for ICH. METHODS: This study recruited a total of 126 ICH patients and 126 healthy controls. Netrin-1 concentration was determined using a commercially available human enzyme-linked immune sorbent assay kit. National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used to assess hemorrhagic severity. An unfavorable outcome was defined as modified Rankin Scale >2 at 90 days. RESULTS: ICH patients showed significantly lower serum netrin-1 concentrations than controls. Serum netrin-1 concentrations were strongly and inversely correlated with serum C-reactive protein concentrations, NIHSS score and hematoma volume. Multivariate analyses revealed that low netrin-1 concentration was associated with 90-day death, unfavorable outcome and overall survival after adjustment for other confounding variables. Under the receiver operating characteristic curve, serum netrin-1 remarkably discriminated patients at risk of 90-day death and unfavorable outcome. CONCLUSIONS: Serum netrin-1 concentrations are decreased in patients with ICH, and the concentrations of netrin-1 were intimately associated with inflammation, hemorrhagic severity and clinical outcome of ICH.


Subject(s)
Cerebral Hemorrhage , Hematoma , Cerebral Hemorrhage/diagnosis , Humans , Netrin-1 , Prognosis , ROC Curve
20.
Ying Yong Sheng Tai Xue Bao ; 30(11): 3971-3979, 2019 Nov.
Article in Chinese | MEDLINE | ID: mdl-31833711

ABSTRACT

Arbuscular mycorrhizal fungi (AMF) are ancient and ubiquitous soil microorganisms, which can form mutually beneficial association with most terrestrial plants. Within the symbiotic relationship, AMF helps their host plants to absorb nutrients such as nitrogen and phosphorus while obtains carbon from the hosts. AMF plays an important role in agricultural ecosystem, including promoting plant growth, improving crop quality, increasing plant stress resistance, stabilizing soil structure, keeping ecological balance, and maintaining a sustainable agricultural development. We summarized the research advances of AMF in terrestrial agro-ecosystem in recent years, by focusing on AMF species diversity, spatial and temporal distribution, and influence factors of AMF biodiversity in terrestrial agro-ecosystem of China. Further research works were also prospected.


Subject(s)
Mycorrhizae , Biodiversity , China , Ecosystem , Fungi , Plant Roots , Soil Microbiology , Symbiosis
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