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  • 1
    Online Resource
    Online Resource
    Temozolomide hexadecyl ester targeted plga nanoparticles for drug-resistant glioblastoma therapy via intranasal administration
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-8-17)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-8-17)
    Abstract: Introduction: Temozolomide (TMZ) is the first-line drug for glioblastoma (GBM), but it is limited in clinical use due to the drug resistance, poor brain targeting, and side effects. Temozolomide hexadecyl ester (TMZ16e), a TMZ derivative with high lipophilicity, membrane permeability, and high anti-glioma properties, has the potential to reverse drug resistance. In this study, anti-ephrin type-A receptor 3 (EphA3) modified TMZ16e loaded nanoparticles (NPs) were prepared for targeted GBM therapy via intranasal administration to deliver TMZ16e to the brain, treat drug-resistant glioma effectively, and reduce peripheral toxicity. Methods: TMZ16e loaded NPs were prepared by emulsion solvent evaporation method followed by modified with anti-EphA3 (anti-EphA3-TMZ16e-NPs). In vitro evaluations were performed by an MTT assay and flow cytometry analysis. The orthotopic nude mice models were used to evaluate the anti-glioma effect in vivo . Additionally, we investigated the anti-drug resistant mechanism by western blot analysis. Results: The particle size of the prepared NPs was less than 200 nm, and the zeta potential of TMZ16e-NPs and anti-EphA3-TMZ16e-NPs were -23.05 ± 1.48 mV and -28.65 ± 1.20mV, respectively, which is suitable for nasal delivery. In vitro studies have shown that anti-EphA3 modification increased the cellular uptake of nanoparticles in T98G cells. The cytotoxicity in the anti-EphA3-TMZ16e-NPs treated group was significantly higher than that of the TMZ16e-NPs, TMZ16e, and TMZ groups ( p & lt; 0.01), and the cell cycle was blocked. Western blotting analysis showed that the TMZ16e-loaded NPs were able to effectively downregulate the expression level of O6-methylguanine-deoxyribonucleic acid-methyltransferase (MGMT) protein in T98G cells and reverse drug resistance. In vivo studies showed that the median survival time of tumor-bearing nude mice in the anti-EphA3-TMZ16e-NPs group was extended to 41 days, which was 1.71-fold higher than that of the saline group and the TUNEL staining results of the brain tissue section indicated that the TMZ16e-loaded NPs could elevate apoptosis in T98G cells. Conclusion: In conclusion, the TMZ16e-loaded NPs can be effectively delivered to the brain and targeted to gliomas, exhibiting better anti-glioma activity, indicating they possess great potential in the treatment of drug-resistant glioma.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.965789
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 2
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    Online Resource
    DataSheet_1.docx
    Frontiers Media SA ; 2020
    In:  Frontiers in Pharmacology Vol. 11 ( 2020-5-13)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 11 ( 2020-5-13)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2020.00669
    DOI: 10.3389/fphar.2020.00669.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587355-6
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  • 3
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    Online Resource
    Comparison of Pancreatic Damage in Rats for Two Methods of Paraquat Administration
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-4-20)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-4-20)
    Abstract: It is noted that elevated serum amylase levels suggesting pancreatic damage has an association with prognosis in PQ patients. This study aimed to determine whether PQ can cause pancreatic damage. The two conventional models (intragastric infusion (iG) and intraperitoneal injection (iP)) may exhibit different effects on the pancreas depending on whether or not they pass through the digestive tract. In this study, the rats were divided into four groups: the intragastric infusion group (PQ-iG, n = 45), intraperitoneal injection group (PQ-iP, n = 53), normal control group 1 (NC-iG, n = 6) and normal control group 2 (NC-iP, n = 6). Pancreatic damage was compared between groups using serum amylase activity assay, hematoxylin and eosin (H & amp;E) staining, TUNEL assay, and transmission electron microscopy (TEM). Serum amylase levels in group PQ-iG were significantly higher than in group PQ-iP ( p & lt; 0.05). Examination of the H & amp;E sections showed damage to the pancreas. Both experimental groups were displayed inflammatory infiltration within 9 h of PQ treatment. After 9 h, patchy necrosis was observed in group PQ-iP, when inflammatory infiltration was still the dominant pathology. Necrosis appeared and gradually worsened in group PQ-iG, in which necrosis was the dominant pathology. The TUNEL assay showed significantly higher numbers of apoptotic cells in the pancreas of PQ-groups than in the control NC- groups ( p & lt; 0.05). TEM showed expansive endoplasmic reticulum lumens and mitochondria swelling in the pancreas of the PQ-groups. It is concluded that both methods of modeling could cause pancreatic damage and the type and degree of damage would change over time. Note that pancreatic damage in group PQ-iG was more severe than that in group PQ-iP. Therefore, clinical practitioners should pay close attention to pancreatic damage caused by PQ, especially when the route of PQ administration was oral.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.611433
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
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  • 4
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    Online Resource
    Adenosine monophosphate activated protein kinase contributes to skeletal muscle health through the control of mitochondrial function
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-10-20)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-10-20)
    Abstract: Skeletal muscle is one of the largest organs in the body and the largest protein repository. Mitochondria are the main energy-producing organelles in cells and play an important role in skeletal muscle health and function. They participate in several biological processes related to skeletal muscle metabolism, growth, and regeneration. Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor and regulator of systemic energy balance. AMPK is involved in the control of energy metabolism by regulating many downstream targets. In this review, we propose that AMPK directly controls several facets of mitochondrial function, which in turn controls skeletal muscle metabolism and health. This review is divided into four parts. First, we summarize the properties of AMPK signal transduction and its upstream activators. Second, we discuss the role of mitochondria in myogenesis, muscle atrophy, regeneration post-injury of skeletal muscle cells. Third, we elaborate the effects of AMPK on mitochondrial biogenesis, fusion, fission and mitochondrial autophagy, and discuss how AMPK regulates the metabolism of skeletal muscle by regulating mitochondrial function. Finally, we discuss the effects of AMPK activators on muscle disease status. This review thus represents a foundation for understanding this biological process of mitochondrial dynamics regulated by AMPK in the metabolism of skeletal muscle. A better understanding of the role of AMPK on mitochondrial dynamic is essential to improve mitochondrial function, and hence promote skeletal muscle health and function.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.947387
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 5
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    Online Resource
    Engineering of Stimulus-Responsive Pirfenidone Liposomes for Pulmonary Delivery During Treatment of Idiopathic Pulmonary Fibrosis
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-4-25)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-4-25)
    Abstract: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive and irreversible loss of lung function. Clinically safe and efficacious drug treatments for IPF are lacking. Pirfenidone (an anti-inflammatory, antioxidant and anti-fibrotic small-molecule drug) is considered a promising treatment for IPF. Unfortunately, several disadvantages of pirfenidone caused by traditional administration (e.g., gastrointestinal reactions, short elimination half-life) hinder its implementation. We designed pirfenidone pH-sensitive liposomes (PSLs) to target the acidic microenvironment of IPF and act directly at the disease site through pulmonary administration. Pirfenidone was encapsulated in liposomes to extend its half-life, and modified with polyethylene glycol on the surface of liposomes to improve the permeability of the mucus layer in airways. In vitro , the cytotoxicity of pirfenidone PSLs to pulmonary fibroblasts was increased significantly at 48 h compared with that using pirfenidone. In a murine and rat model of bleomycin-induced pulmonary fibrosis, pirfenidone PSLs inhibited IPF development and increased PSL accumulation in the lungs compared with that using pirfenidone solution or phosphate-buffered saline. Pirfenidone PSLs had potentially fewer side effects and stronger lung targeting. These results suggest that pirfenidone PSLs are promising preparations for IPF treatment.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.882678
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 6
    Online Resource
    Online Resource
    Anti-hyperplasia Effects of Total Saponins From Phytolaccae Radix in Rats With Mammary Gland Hyperplasia via Inhibition of Proliferation and Induction of Apoptosis
    Frontiers Media SA ; 2018
    In:  Frontiers in Pharmacology Vol. 9 ( 2018-5-23)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 9 ( 2018-5-23)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2018.00467
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2587355-6
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  • 7
    Online Resource
    Online Resource
    Table1.XLSX
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-7-10)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-7-10)
    Abstract: Objective: Colonoscopy plays an important role in the diagnosis, prognosis prediction, assessment of disease activity and severity, and treatment of inflammatory bowel disease (IBD)-related complications. However, some patients refuse to undergo colonoscopy due to perceived pain and other discomfort, their diagnosis and treatment are affected. Therefore, we conducted a prospective study to explore the efficacy and safety of midazolam combined with dezocine for sedation in IBD patients undergoing colonoscopy. Methods: 224 patients were divided into sedative-colonoscopy-group (SCG, n = 93), anesthesia-colonoscopy-group (ACG, n = 90) and ordinary-colonoscopy-group (OCG, n = 41). The vital signs (blood pressure, pulse, respiration and blood oxygen saturation), pain degree during colonoscopy, satisfaction and complication rates of the three groups were compared. Results: Before colonoscopy, there was no significant difference among the vital signs of the three groups. The vital signs of the ACG were significantly lower than those of the SEG and the OCG ( p & lt; 0.05), and the difference was not significant between the SCG and OCG during colonoscopy. The colonoscopy pain score in the SCG was lower than that in the OCG (0.79 ± 1.09 vs. 2.98 ± 1.27, p & lt; 0.001). The satisfaction score of the SCG (9.26 ± 1.16) was not significantly different from that of the ACG (9.42 ± 1.41) but was higher than that of the OCG (6.63 ± 1.13) ( p & lt; 0.001). The total complication rate of the ACG was 45.56% (41/90), which was significantly higher than that of the SCG [20.43% (19/93)] and the OCG [19.51% (8/41)] . Colon perforation, abnormal blood pressure fluctuation and hypoxemia were significantly more common in the ACG than in the SCG and the OCG ( p & lt; 0.05). However, there was no significant difference in the incidence of complications between the SCG and OCG. Conclusion: Compared with ordinary-colonoscopy, colonoscopy performed under midazolam and dezocine sedation is more comfortable for patients, thereby increasing satisfaction and compliance. Colonoscopy that is performed under midazolam and dezocine is similar to colonoscopy that is anesthesia with propofol in terms of comfort, satisfaction and compliance and similar to ordinary-colonoscopy in terms of safety. Considering the shortage of anesthesiologists, the application of midazolam combined with dezocine for digestive endoscopy is worthy of clinical promotion.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2023.1150045
    DOI: 10.3389/fphar.2023.1150045.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 8
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    Online Resource
    Table1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-5-13)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-5-13)
    Abstract: This study explored the role of metformin (MET) in regulating the polarization of alveolar macrophages to protect against acute lung injury (ALI) in rats caused by paraquat (PQ) poisoning. The in vivo studies showed that the 35 mg/kg dose of MET increased the survival rate of rats, alleviated pathological damages to the lungs and their systemic inflammation, promoted the reduction of the pro-inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and increased the anti-inflammatory factor IL-10 levels in the rat serum. At the same time, the MET intervention decreased the expression of M1 macrophage marker iNOS in the lungs of the PQ-poisoned rats while increasing the M2 macrophage marker, Arg1, expression. In vitro , the concentration of MET & gt; 10 mmol/L affected NR8383 viability adversely and was concentration-dependent; however, no adverse impact on NR8383 viability was observed at MET ≤ 10 mmol/L concentration, resisting the reducing effect of PQ on NR8383 vitality. The PQ-induced NR8383 model with MET intervention showed significantly reduced secretions of IL-6 and TNF-α in NR8383, and lowered expressions of M1 macrophage markers iNOS and CD86. Additionally, MET increased IL-10 secretion and the M2 macrophage markers, Arg1 and Mrcl, expressions. Therefore, we speculate that MET could regulate alveolar macrophage polarization to protect against PQ-poisoning caused ALI.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.811372
    DOI: 10.3389/fphar.2022.811372.s001
    DOI: 10.3389/fphar.2022.811372.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 9
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    Online Resource
    Efficacy and safety of midazolam combined with dezocine for sedation and analgesia in digestive endoscopy: A prospective open single-center study
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-11-3)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-11-3)
    Abstract: Objective: Digestive endoscopy is an important means of diagnosing and treating gastrointestinal diseases and a tool for screening and monitoring early gastrointestinal tumors. Digestive endoscopy can be performed using midazolam combined with dezocine for sedation and analgesia. This study explored the efficacy and safety of midazolam combined with dezocine. Methods: A total of 135 patients undergoing digestive endoscopy in the Department of Gastrointestinal Endoscopy of the Sixth Affiliated Hospital, Sun Yat-sen University, from June 2021 to September 2021, were enrolled and non-blindly and non-randomly divided into a sedation-endoscopy-group (SEG, n = 45), anesthesia-endoscopy-group (AEG, n = 44), and ordinary-endoscopy-group (OEG, n = 46). Vital signs, levels of sedation and analgesia, the degree of pain during colonoscopy, satisfaction, and the incidence of complications were compared among the three groups. Results: There were no statistically significant differences in vital signs (blood pressure, pulse, respiration, and blood oxygen saturation) among the three groups before endoscopy ( p & gt; 0.05). The AEG reported no pain during colonoscopy, and the pain score during colonoscopy for the SEG was lower than that for the OEG (1.11 ± 1.21 vs . 3.00 ± 1.16, p & lt; 0.001). The scores for satisfaction were 8.84 ± 1.30 points in the SEG, 8.95 ± 1.10 points in the AEG, and 6.37 ± 0.90 points in the OEG; the differences were statistically significant ( p & lt; 0.001). The total incidence of complications in the AEG was 38.64% (17/44), which was significantly higher than that in the SEG [13.33% (6/45)] and OEG [13.04% (6/46)] ( p & lt; 0.001). In the SEG, the overall incidence of complications in women was significantly higher than that in men ( p = 0.027). Conclusion: Digestive endoscopy using midazolam combined with dezocine for sedation makes patients more comfortable, more satisfied and more compliant than the ordinary endoscopy. Additionally, it is comparable to endoscopy under general anesthesia with propofol with regard to comfort, satisfaction, and patient compliance and comparable to the ordinary endoscopy with regard to safety. Considering the shortage of anesthesiologists, the application of midazolam combined with dezocine in digestive endoscopy is worthy of clinical popularization. This study has been registered in the Hospital Ethics Committee of the Sun Yat-sen University Sixth Affiliated Hospital (Ethical Number: 2021ZSLYEC-182).
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.945597
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 10
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    Online Resource
    The emerging role of long non-coding RNAs in renal cell carcinoma progression and clinical therapy via targeting metabolic regulation
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-3-9)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-3-9)
    Abstract: Renal cell carcinoma (RCC) is the most frequent renal malignancy in the world, and its incidence is increasing year by year. RCC is a well-known drug resistant tumor, and the treatment methods are limited. Most patients with RCC are discovered at the advanced stage, and thus have poor prognosis even after treatment. Therefore, it is very urgent to find new markers for the diagnosis and treatment of RCC. Accumulating evidence shows that lncRNAs participate in the occurrence and progression of RCC, which is achieved by the lncRNA-miRNA-mRNA axis. It is widely known that metabolic defect is an essential pathogenesis in RCC. As is the case with other tumors, RCC can satisfy the demands of cancerous cells for uncontrolled proliferation through aerobic glycolysis. However, whether lncRNAs can modulate RCC progression through metabolic pathway is still not clarified. Taken together, this review mainly summarized the metabolic regulatory mechanisms of lncRNAs in RCC progression, especially their roles in glucose metabolism, lipid metabolism, amino acid metabolism and mitochondrial dynamics, as well as the clinical applications of lncRNAs via targeting metabolism in RCC therapy. It will provide the new targets and approaches for early clinical diagnosis, treatment and prognosis of RCC.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2023.1122065
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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