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  • MDPI AG  (55)
  • Pharmacy  (55)
  • 1
    In: Marine Drugs, MDPI AG, Vol. 21, No. 10 ( 2023-09-23), p. 504-
    Abstract: A systematic chemical investigation of the deep-sea-derived fungus Aspergillus versicolor 170217 resulted in the isolation of six new (1–6) and 45 known (7–51) compounds. The structures of the new compounds were established on the basis of exhaustive analysis of their spectroscopic data and theoretical–statistical approaches including GIAO-NMR, TDDFT-ECD/ORD calculations, DP4+ probability analysis, and biogenetic consideration. Citriquinolinones A (1) and B (2) feature a unique isoquinolinone-embedded citrinin scaffold, representing the first exemplars of a citrinin–isoquinolinone hybrid. Dicitrinones K–L (3–4) are two new dimeric citrinin analogues with a rare CH-CH3 bridge. Biologically, frangula-emodin (32) and diorcinol (17) displayed remarkable anti-food allergic activity with IC50 values of 7.9 ± 3.0 μM and 13.4 ± 1.2 μM, respectively, while diorcinol (17) and penicitrinol A (20) exhibited weak inhibitory activity against Vibrio parahemolyticus, with MIC values ranging from 128 to 256 μM.
    Type of Medium: Online Resource
    ISSN: 1660-3397
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 2
    In: Pharmaceuticals, MDPI AG, Vol. 15, No. 11 ( 2022-10-28), p. 1336-
    Abstract: Pancreatic adenocarcinoma (PAAD), one of the most malignant tumors, not only has abundant mesenchymal components, but is also characterized by an extremely high metastatic risk. The purpose of this study was to construct a model of stroma- and metastasis-associated prognostic signature, aiming to benefit the existing clinical staging system and predict the prognosis of patients. First, stroma-associated genes were screened from the TCGA database with the ESTIMATE algorithm. Subsequently, transcriptomic data from clinical tissues in the RenJi cohort were screened for metastasis-associated genes. Integrating the two sets of genes, we constructed a risk prognostic signature by Cox and LASSO regression analysis. We then obtained a risk score by a quantitative formula and divided all samples into high- and low-risk groups based on the scores. The results demonstrated that patients with high-risk scores have a worse prognosis than those with low-risk scores, both in the TCGA database and in the RenJi cohort. In addition, tumor mutation burden, chemotherapeutic drug sensitivity and immune infiltration analysis also exhibited significant differences between the two groups. In exploring the potential mechanisms of how stromal components affect tumor metastasis, we simulated different matrix stiffness in vitro to explore its effect on EMT key genes in PAAD cells. We found that cancer cells stimulated by high matrix stiffness may trigger EMT and promote PAAD metastasis.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2193542-7
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  • 3
    Online Resource
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    MDPI AG ; 2021
    In:  Marine Drugs Vol. 19, No. 10 ( 2021-10-17), p. 580-
    In: Marine Drugs, MDPI AG, Vol. 19, No. 10 ( 2021-10-17), p. 580-
    Abstract: A systematic chemical investigation of the deep-sea-derived fungus Penicillium solitum MCCC 3A00215 resulted in the isolation of one novel polyketide (1), two new alkaloids (2 and 3), and 22 known (4–25) compounds. The structures of the new compounds were established mainly on the basis of exhaustive analysis of 1D and 2D NMR data. Viridicatol (13) displayed moderate anti-tumor activities against PANC-1, Hela, and A549 cells with IC50 values of around 20 μM. Moreover, 13 displayed potent in vitro anti-food allergic activity with an IC50 value of 13 μM, compared to that of 92 μM for the positive control, loratadine, while indole-3-acetic acid methyl ester (9) and penicopeptide A (10) showed moderate effects (IC50 = 50 and 58 μM, respectively).
    Type of Medium: Online Resource
    ISSN: 1660-3397
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2175190-0
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  • 4
    In: Antibiotics, MDPI AG, Vol. 10, No. 4 ( 2021-04-03), p. 377-
    Abstract: Four new secondary metabolites, including one spiro[anthracenone-xanthene] derivative aspergiloxathene A (1), one penicillide analogue, Δ2′-1′-dehydropenicillide (2), and two new phthalide derivatives, 5-methyl-3-methoxyepicoccone (3) and 7-carboxy-4-hydroxy-6-methoxy-5-methylphthalide (4), together with four known compounds, yicathin C (5), dehydropenicillide (6), 3-methoxyepicoccone (7), 4-hydroxy-6-methoxy-5-methylphthalide (8), were identified from the marine-derived fungus Aspergillus sp. IMCASMF180035. Their structures were determined by spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D nuclear magnetic resonance (NMR) techniques. Compound 1 was identified as the first jointed molecule by xanthene and anthracenone moieties possessing an unprecedented carbon skeleton with spiro-ring system. All compounds were evaluated activities against Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Escherichia coli, Escherichia faecium, Pseudomonas aeruginosa, and Helicobacter pylori. Compound 1 showed significant inhibitory effects against S. aureus and MRSA, with minimum inhibitory concentration (MIC) values of 5.60 and 22.40 µM. Compounds 2 and 6 exhibited potent antibacterial activities against H. pylori, with MIC values of 21.73 and 21.61 µM, respectively.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 5
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 6 ( 2022-06-13), p. 1257-
    Abstract: Metastatic osteosarcoma often results in poor prognosis despite the application of surgical en bloc excision along with chemotherapy. HO-3867 is a curcumin analog that induces cell apoptosis in several cancers, but the apoptotic effect and its mechanisms on osteosarcoma cells are still unknown. After observing the decrease in cellular viability of three human osteosarcoma U2OS, HOS, and MG-63 cell lines, and the induction of cellular apoptosis and arrest in sub-G1 phase in U2OS and HOS cells by HO-3867, the human apoptosis array showed that heme oxygenase (HO)-1 and cleaved caspase-3 expressions had significant increases after HO-3867 treatment in U2OS cells and vice versa for cellular inhibitors of apoptosis (cIAP)1 and X-chromosome-linked IAP (XIAP). Western blot analysis verified the results and showed that HO-3867 activated the initiators of both extrinsic caspase 8 and intrinsic caspase 9, and significantly increased cleaved PARP expression in U2OS and HOS cells. Moreover, with the addition of HO-3867, ERK1/2, and JNK1/2 phosphorylation were increased in U2OS and HOS cells. Using the inhibitor of JNK (JNK in 8), HO-3867’s increases in cleaved caspases 3, 8, and 9 could be expectedly suppressed, indicating that JNK signaling is responsible for both apoptotic pathways, including extrinsic and intrinsic, in U2OS and HOS cells caused by HO-3867. Through JNK signaling, HO-3867 has proven to be effective in causing both extrinsic and intrinsic apoptotic pathways of human osteosarcoma cells.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527217-2
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  • 6
    In: Antioxidants, MDPI AG, Vol. 12, No. 9 ( 2023-09-20), p. 1782-
    Abstract: The degeneration of dopamine (DA) neurons is known to be associated with defects in mitochondrial biogenesis caused by aging, environmental factors, or mutations in genes, leading to Parkinson’s disease (PD). As PD has not yet been successfully cured, the strategy of using small molecule drugs to protect and restore mitochondrial biogenesis is a promising direction. This study evaluated the efficacy of synthetic chiisanoside (CSS) identified in the leaves of Acanthopanax sessiliflorus to prevent PD symptoms. The results show that in the 6-hydroxydopamine (6-OHDA) model, CSS pretreatment can effectively alleviate the reactive oxygen species generation and apoptosis of SH-SY5Y cells, thereby lessening the defects in the C. elegans model including DA neuron degeneration, dopamine-mediated food sensitivity behavioral disorders, and shortened lifespan. Mechanistically, we found that CSS could restore the expression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α), a key molecule in mitochondrial biogenesis, and its downstream related genes inhibited by 6-OHDA. We further confirmed that this is due to the enhanced activity of parkin leading to the ubiquitination and degradation of PGC-1α inhibitor protein Zinc finger protein 746 (ZNF746). Parkin siRNA treatment abolished this effect of CSS. Furthermore, we found that CSS inhibited 6-OHDA-induced expression of miR-181a, which targets parkin. The CSS’s ability to reverse the 6-OHDA-induced reduction in mitochondrial biogenesis and activation of apoptosis was abolished after the transfection of anti-miR-181a and miR-181a mimics. Therefore, the neuroprotective effect of CSS mainly promotes mitochondrial biogenesis by regulating the miR-181a/Parkin/ZNF746/PGC-1α axis. CSS potentially has the opportunity to be developed into PD prevention agents.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704216-9
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  • 7
    In: Antioxidants, MDPI AG, Vol. 11, No. 10 ( 2022-10-04), p. 1981-
    Abstract: The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity, MnSOD Ala-9Val polymorphism and cognitive dysfunction in unmedicated first-episode (UMFE) SZ patients, which has not been examined. We recruited 234 UMFE SZ patients and 232 healthy controls (HC) and evaluated them with Repeated Battery for the Assessment of Neuropsychological Status (RBANS), plasma MnSOD activity and MnSOD Ala-9Val (rs4880) polymorphism. In addition, we used the Positive and Negative Syndrome Scale (PANSS) to assess the severity of patients’ psychopathological symptoms. Compared with HC, UMFE patients showed extensive cognitive impairment on RBANS, and had higher MnSOD activity. MnSOD Ala-9Val polymorphism was not associated with SZ susceptibility and cognitive impairment, but only affected MnSOD activity in patients. Moreover, only in SZ patients with Val homozygotes, MnSOD activity was significantly correlated with cognitive impairment, especially in RBANS total score, visuospatial/constructional and attention index scores. Our results suggest that cognitive impairment is associated with MnSOD activity in patients with first-episode SZ, which may be regulated by MnSOD Ala-9Val polymorphism.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704216-9
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  • 8
    In: Antioxidants, MDPI AG, Vol. 11, No. 11 ( 2022-11-15), p. 2252-
    Abstract: The intake of antioxidant vitamins can scavenge free radicals and reduce oxidative stress, which may be beneficial for stroke. However, the relationship between total antioxidant capacity (TAC) of antioxidant vitamins and stroke is controversial. This study aims to investigate the association between dietary TAC and the risk of stroke in US adults. This study included participants over 20 years old from the 2001–2018 National Health and Nutrition Examination Survey (NHANES). Data from two 24 h dietary recalls were used to estimate the usual intake of antioxidant vitamins. TAC was calculated by the vitamin C equivalent antioxidant capacity reference values of individual antioxidant vitamins. Survey-weighted generalized linear models were performed to evaluate the relationship between TAC and the risk of stroke. A restricted cubic spline regression model was used to investigate the dose–response association. A total of 37,045 participants was involved, of whom 1391 suffered a stroke. Compared with the first tertile, the participants in the second tertile of TAC showed a lower risk of stroke (OR = 0.788, 95% CI: 0.662, 0.936) after adjusting for potential risk factors. The dose–response analysis showed a gradual increase in the risk of stroke as TAC decreases. Subgroups analyses indicated that this association was primarily in the population of those aged over 60 years old, who were female, consumed alcohol, were a former smoker and inactive. The sensitivity analysis presented consistent results. These results suggest that deficiency of dietary TAC was associated with an increased risk of stroke, particularly in populations with underlying oxidative stress injury.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704216-9
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  • 9
    In: Antibiotics, MDPI AG, Vol. 12, No. 3 ( 2023-02-22), p. 431-
    Abstract: Background: To investigate the epidemiological characteristics and resistance changes of carbapenem-resistant organisms (CROs) under the COVID-19 outbreak to provide evidence for precise prevention and control measures against hospital-acquired infections during the pandemic. Methods: The distribution characteristics of CROs (i.e., carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii) were analyzed by collecting the results of the antibiotic susceptibility tests of diagnostic isolates from all patients. Using interrupted time series analysis, we applied Poisson and linear segmented regression models to evaluate the effects of COVID-19 on the numbers and drug resistance of CROs. We also conducted a stratified analysis using the Cochran–Mantel–Haenszel test. Results: The resistance rate of carbapenem-resistant Acinetobacter baumannii (CRAB) was 38.73% higher after the COVID-19 outbreak compared with before (p 〈 0.05). In addition, the long-term effect indicated that the prevalence of CRAB had a decreasing trend (p 〈 0.05). However, the overall resistance rate of Klebsiella pneumoniae did not significantly change after the COVID-19 outbreak. Stratified analysis revealed that the carbapenem-resistant Klebsiella pneumoniae (CRKP) rate increased in females (OR = 1.98, p 〈 0.05), those over 65 years old (OR = 1.49, p 〈 0.05), those with sputum samples (OR = 1.40, p 〈 0.05), and those in the neurology group (OR = 2.14, p 〈 0.05). Conclusion: The COVID-19 pandemic has affected the change in nosocomial infections and resistance rates in CROs, highlighting the need for hospitals to closely monitor CROs, especially in high-risk populations and clinical departments. It is possible that lower adherence to infection control in crowded wards and staffing shortages may have contributed to this trend during the COVID-19 pandemic, which warrants further research.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2681345-2
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  • 10
    In: Pharmaceutics, MDPI AG, Vol. 15, No. 3 ( 2023-03-06), p. 854-
    Abstract: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths in the world. It is urgent to search for safe and effective therapies to address the CRC crisis. The siRNA-based RNA interference targeted silencing of PD-L1 has extensive potential in CRC treatment but is limited by the lack of efficient delivery vectors. In this work, the novel cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs)/siPD-L1 co-delivery vectors AuNRs@MS/CpG ODN@PEG-bPEI (ASCP) were successfully prepared by two-step surface modification of CpG ODNs-loading and polyethylene glycol-branched polyethyleneimine-coating around mesoporous silica-coated gold nanorods. ASCP promoted dendritic cells (DCs) maturation by delivering CpG ODNs, exhibiting excellent biosafety. Next, mild photothermal therapy (MPTT) mediated by ASCP killed tumor cells and released tumor-associated antigens, further promoting DC maturation. Furthermore, ASCP exhibited mild photothermal heating-enhanced performance as gene vectors, resulting in an increased PD-L1 gene silencing effect. Enhanced DCs maturity and enhanced PD-L1 gene silencing significantly promoted the anti-tumor immune response. Finally, the combination of MPTT and mild photothermal heating-enhanced gene/immunotherapy effectively killed MC38 cells, leading to strong inhibition of CRC. Overall, this work provided new insights into the design of mild photothermal/gene/immune synergies for tumor therapy and may contribute to translational nanomedicine for CRC treatment.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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