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  • MDPI AG  (12)
  • Pharmacy  (12)
  • 1
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Antibiotics Vol. 10, No. 12 ( 2021-12-19), p. 1555-
    In: Antibiotics, MDPI AG, Vol. 10, No. 12 ( 2021-12-19), p. 1555-
    Abstract: Antibiotic resistance is a serious global health concern that may have significant social and financial consequences. Methicillin-resistant Staphylococcus aureus (MRSA) infection is responsible for substantial morbidity and leads to the death of 21.8% of infected patients annually. A lack of novel antibiotics has prompted the exploration of therapies targeting bacterial virulence mechanisms. The two-component signal transduction system (TCS) enables microbial cells to regulate gene expression and the subsequent metabolic processes that occur due to environmental changes. The YycFG TCS in S. aureus is essential for bacterial viability, the regulation of cell membrane metabolism, cell wall synthesis and biofilm formation. However, the role of YycFG-associated biofilm organization in S. aureus antimicrobial drug resistance and gene regulation has not been discussed in detail. We reviewed the main molecules involved in YycFG-associated cell wall biosynthesis, biofilm development and polysaccharide intercellular adhesin (PIA) accumulation. Two YycFG-associated regulatory mechanisms, accessory gene regulator (agr) and staphylococcal accessory regulator (SarA), were also discussed. We highlighted the importance of biofilm formation in the development of antimicrobial drug resistance in S. aureus infections. Data revealed that inhibition of the YycFG pathway reduced PIA production, biofilm formation and bacterial pathogenicity, which provides a potential target for the management of MRSA-induced infections.
    Type of Medium: Online Resource
    ISSN: 2079-6382
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2681345-2
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  • 2
    In: Antioxidants, MDPI AG, Vol. 11, No. 2 ( 2022-01-18), p. 178-
    Abstract: Vulvovaginal candidiasis (VVC) is one of the most frequent diseases induced by Candida albicans (C. albicans) during pregnancy, which results in enormous pain to women and their partners in daily life. Perillaldehyde (PAE), a natural monoterpenoid, has significant anti-microbial, anti-inflammatory and anti-oxidation effects. Reactive oxygen species (ROS) are key factors for the host to resist the invasion of fungi. However, excess ROS can cause additional damage independent of the pathogen itself, and the mechanism of ROS in VVC has not been investigated. In this murine study, we revealed that C. albicans infection increased the expression of NADPH oxidase 2 (NOX2) and the content of malonaldehyde (MDA). C. albicans inhibited the activity of antioxidant enzymes in the vagina, including superoxide dismutase (SOD), Catalase (CAT), glutathione peroxidase (GSH-PX) and heme oxygenase (HO-1), which were returned to normal levels after treatment with PAE. Furthermore, PAE inhibited the activities of Keap1 and promoted Nrf2 transfer from cytoplasm to nucleus, which were mediated by excessive accumulation of ROS in the VVC mice. In this study, we also indicated that PAE inhibited the apoptosis of vagina cells via Caspase 9- Caspase 7-PARP pathway and prevented the release of IL-1ꞵ in VVC mice. In summary, this study revealed that the treatment of VVC in mice with PAE might be mediated by inhibition of ROS, and established the therapeutic potential of PAE as an antifungal agent for the treatment of VVC.
    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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  • 3
    In: Antioxidants, MDPI AG, Vol. 11, No. 10 ( 2022-09-21), p. 1859-
    Abstract: Esophageal adenocarcinoma (EAC), the predominant type of esophageal cancer in the United States, develops through Barrett’s esophagus (BE)-dysplasia-carcinoma cascade. Gastroesophageal reflux disease, where acidic bile salts refluxate into the esophagus, is the main risk factor for the development of BE and its progression to EAC. The NFE2-related factor 2 (NRF2) is the master cellular antioxidant regulator. We detected high NRF2 protein levels in the EAC cell lines and primary tissues. Knockdown of NRF2 significantly enhanced acidic bile salt-induced oxidative stress, DNA damage, and inhibited EAC cell growth. Brusatol, an NRF2 inhibitor, significantly inhibited NRF2 transcriptional activity and downregulated the NRF2 target genes. We discovered that in addition to inducing apoptosis, Brusatol alone or in combination with cisplatin (CDDP) induced significant lipid peroxidation and ferroptosis, as evidenced by reduced xCT and GPX4 expression, two known ferroptosis markers. The combination of Brusatol and CDDP significantly inhibited EAC tumor xenograft growth in vivo and confirmed the in vitro data showing ferroptosis as an important mechanism in the tumors treated with Brusatol or Brusatol and CDDP combination. Our data support the role of NRF2 in protecting against stress-induced apoptosis and ferroptosis in EACs. Targeting NRF2 in combination with platinum therapy can be an effective strategy for eliminating cancer cells in EAC.
    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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  • 4
    In: Marine Drugs, MDPI AG, Vol. 20, No. 11 ( 2022-11-13), p. 711-
    Abstract: Five undescribed polyketide derivatives, pestaloketides A–E (1–5), along with eleven known analogues (6–16), were isolated from the sponge-derived fungus Pestalotiopsis sp. Their structures, including absolute configurations, were elucidated by analyses of NMR spectroscopic HRESIMS data and electronic circular dichroism (ECD) calculations. Compounds 5, 6, 9, and 14 exhibited weak cytotoxicities against four human cancer cell lines, with IC50 values ranging from 22.1 to 100 μM. Pestaloketide A (1) is an unusual polyketide, featuring a rare 5/10/5-fused ring system. Pestaloketides A (1) and B (2) exhibited moderately inhibited LPS-induced NO production activity, with IC50 values of 23.6 and 14.5 μM, respectively, without cytotoxicity observed. Preliminary bioactivity evaluations and molecular docking analysis indicated that pestaloketides A (1) and B (2) had the potential to be developed into anti-inflammatory activity drug leads.
    Type of Medium: Online Resource
    ISSN: 1660-3397
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175190-0
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  • 5
    In: Marine Drugs, MDPI AG, Vol. 17, No. 1 ( 2019-01-03), p. 24-
    Abstract: Increasing evidence indicates that environmental tobacco smoke (ETS) impairs cognitive function and induces oxidative stress in the brain. Recently, astaxanthin (ATX), a marine bioactive compound, has been reported to ameliorate cognitive deficits. However, the underlying pathogenesis remains unclear. In this study, ATX administration (40 mg/kg and 80 mg/kg, oral gavage) and cigarette smoking were carried out once a day for 10 weeks to investigate whether the p38 MAPK is involved in cognitive function in response to ATX treatment in the cortex and hippocampus of ETS mice. Results indicated that ATX administration improved spatial learning and memory of ETS mice (p 〈 0.05 or p 〈 0.01). Furthermore, exposure to ATX prevented the increases in the protein levels of the p38mitogen-activated protein kinase (p38 MAPK; p 〈 0.05 or p 〈 0.01) and nuclear factor-kappa B (NF-κB p65; p 〈 0.05 or p 〈 0.01), reversed the decreases in the mRNA and protein levels of synapsin I (SYN) and postsynaptic density protein 95 (PSD-95) (all p 〈 0.05 or p 〈 0.01). Moreover, ATX significantly down-regulated the increased levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) (all p 〈 0.05 or p 〈 0.01). Meanwhile, the increased level of malondialdehyde (MDA) and the decreased activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were suppressed after exposure to ATX (all p 〈 0.05 or p 〈 0.01). Also, the results of the molecular docking study of ATX into the p38 MAPK binding site revealed that its mechanism was possibly similar to that of PH797804, a p38 MAPK inhibitor. Therefore, our results indicated that the ATX might be a critical agent in protecting the brain against neuroinflammation, synaptic plasticity impairment, and oxidative stress in the cortex and hippocampus of ETS mice.
    Type of Medium: Online Resource
    ISSN: 1660-3397
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2175190-0
    SSG: 15,3
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  • 6
    Online Resource
    Online Resource
    MDPI AG ; 2018
    In:  Marine Drugs Vol. 16, No. 2 ( 2018-02-02), p. 48-
    In: Marine Drugs, MDPI AG, Vol. 16, No. 2 ( 2018-02-02), p. 48-
    Type of Medium: Online Resource
    ISSN: 1660-3397
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2175190-0
    SSG: 15,3
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  • 7
    In: Pharmaceuticals, MDPI AG, Vol. 15, No. 6 ( 2022-06-13), p. 740-
    Abstract: Glucagon-like peptide-1 (GLP-1) is easily degraded by dipeptidyl peptidase-4 (DPP-4) in the human body, limiting its therapeutic effect on type II diabetes. Therefore, improving GLP-1 receptor agonist (GLP-1RA) stability is a major obstacle for drug development. We analyzed human GLP-1, DPP-4, and GLP-1 receptor structures and designed three GLP-1RAs, which were introduced into fusion protein fragments and changed in the overall conformation. This modification effectively prevented GLP-1RAs from entering the DPP-4 active center without affecting GLP-1RAs’ ability to bind to GLP-1R, the new GLP-1RA hypoglycemic effect lasting for 〉 24 h. Through molecular modeling, molecular dynamics calculation, and simulation, possible tertiary structure models of GLP-1RAs were obtained; molecular docking with DPP-4 and GLP-1R showed access to the fusion protein. The overall conformational change of GLP-1RAs prevented DPP-4 binding, without affecting GLP-1RAs’ affinity to GLP-1R. This study provides important drug design ideas for GLP-1RA development and a new example for application of structural biology-based protein design in drug development.
    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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  • 8
    In: Pharmaceutics, MDPI AG, Vol. 13, No. 9 ( 2021-08-25), p. 1327-
    Abstract: Gastric cancer (GC) is a fatal malignant tumor, and effective therapies to attenuate its progression are lacking. Nanoparticle (NP)-based solutions may enable the design of novel treatments to eliminate GC. Refined, receptor-targetable NPs can selectively target cancer cells and improve the cellular uptake of drugs. To overcome the current limitations and enhance the therapeutic effects, epigallocatechin-3-gallate (EGCG) and low-concentration doxorubicin (DX) were encapsulated in fucoidan and d-alpha-tocopherylpoly (ethylene glycol) succinate-conjugated hyaluronic acid-based NPs for targeting P-selectin-and cluster of differentiation (CD)44-expressing gastric tumors. The EGCG/DX-loaded NPs bound to GC cells and released bioactive combination drugs, demonstrating better anti-cancer effects than the EGCG/DX combination solution. In vivo assays in an orthotopic gastric tumor mouse model showed that the EGCG/DX-loaded NPs significantly increased the activity of gastric tumors without inducing organ injury. Overall, our EGCG/DX-NP system exerted a beneficial effect on GC treatment and may facilitate the development of nanomedicine-based combination chemotherapy against GC in the future.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527217-2
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  • 9
    In: Pharmaceuticals, MDPI AG, Vol. 16, No. 3 ( 2023-03-20), p. 462-
    Abstract: Fucoidan and deep-sea water (DSW) are attractive marine resources for treating type 2 diabetes (T2DM). In this study, the regulation and mechanism associated with the co-administration of the two were first studied using T2DM rats, induced by a high fat diet (HFD) and streptozocin (STZ) injection. Results demonstrate that, compared to those with DSW or FPS alone, the orally administered combination of DSW and FPS (CDF), especially the high dose (H-CDF), could preferably inhibit weight loss, decrease levels of fasting blood glucose (FBG) and lipids, and improve hepatopancreatic pathology and the abnormal Akt/GSK-3β signaling pathway. The fecal metabolomics data show that H-CDF could regulate the abnormal levels of metabolites mainly through the regulation of linoleic acid (LA) metabolism, bile acid (BA) metabolism, and other related pathways. Moreover, H-CDF could adjust the diversity and richness of bacterial flora and enrich bacterial groups, such as Lactobacillaceae and Ruminococcaceae UCG-014. In addition, Spearman correlation analysis illustrated that the interaction between the gut microbiota and BAs plays an essential role in the action of H-CDF. In the ileum, H-CDF was verified to inhibit activation of the farnesoid X receptor (FXR)–fibroblast growth factor 15 (FGF15) pathway, which is regulated by the microbiota–BA–axis. In conclusion, H-CDF enriched Lactobacillaceae and Ruminococcaceae UCG-014, thereby changing BA metabolism, linoleic acid metabolism, and other related pathways, as well as enhancing insulin sensitivity and improving glucose and lipid metabolism.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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  • 10
    Online Resource
    Online Resource
    MDPI AG ; 2023
    In:  Antioxidants Vol. 12, No. 4 ( 2023-04-20), p. 967-
    In: Antioxidants, MDPI AG, Vol. 12, No. 4 ( 2023-04-20), p. 967-
    Abstract: Inflammatory bowel disease (IBD) is a long-term, progressive, and recurrent intestinal inflammatory disorder. The pathogenic mechanisms of IBD are multifaceted and associated with oxidative stress, unbalanced gut microbiota, and aberrant immune response. Indeed, oxidative stress can affect the progression and development of IBD by regulating the homeostasis of the gut microbiota and immune response. Therefore, redox-targeted therapy is a promising treatment option for IBD. Recent evidence has verified that Chinese herbal medicine (CHM)-derived polyphenols, natural antioxidants, are able to maintain redox equilibrium in the intestinal tract to prevent abnormal gut microbiota and radical inflammatory responses. Here, we provide a comprehensive perspective for implementing natural antioxidants as potential IBD candidate medications. In addition, we demonstrate novel technologies and stratagems for promoting the antioxidative properties of CHM-derived polyphenols, including novel delivery systems, chemical modifications, and combination strategies.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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