Pub Date : 2023-01-01Epub Date: 2023-08-03DOI: 10.1159/000531321
Robert Krysiak, Karolina Kowalcze, Bogusław Okopień
Introduction: Polycystic ovary syndrome (PCOS) is a frequent endocrinopathy in young women with significantly increased cardiometabolic risk. Siblings of women with this disorder are at increased risk of insulin resistance and androgen excess. The current study was aimed at investigating cardiometabolic effects of atorvastatin in sisters of women with PCOS.
Methods: This prospective observational study compared two age-, body mass index-, blood pressure-, and plasma lipid-matched groups of women with hypercholesterolemia: sisters of PCOS probands (group A) and unrelated control subjects (group B), receiving atorvastatin (40 mg daily). Plasma lipids, glucose homeostasis markers, concentrations of sex hormones, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen and uric acid, and the urinary albumin-to-creatinine ratio (UACR) were measured before entering the study and 6 months later.
Results: Both groups differed in the degree of insulin resistance, testosterone, free androgen index (FAI), circulating levels of hsCRP and homocysteine, and UACR. There were no between-group differences in the impact of atorvastatin on plasma lipids. Despite reducing hsCRP and homocysteine in both groups of women, the effect on these biomarkers was stronger in group B than in group A. Only in group B, atorvastatin did reduce fibrinogen, uric acid, and UACR. Only in group A, atorvastatin did worsen insulin sensitivity and tended to reduce testosterone and FAI. The impact of atorvastatin on hsCRP, homocysteine, fibrinogen, uric acid, and UACR inversely correlated with testosterone and FAI.
Conclusion: The obtained results suggest that sisters of women with PCOS may benefit to a lesser degree from atorvastatin treatment than other women.
{"title":"The Impact of Atorvastatin on Cardiometabolic Risk Factors in Sisters of Women with Polycystic Ovary Syndrome.","authors":"Robert Krysiak, Karolina Kowalcze, Bogusław Okopień","doi":"10.1159/000531321","DOIUrl":"10.1159/000531321","url":null,"abstract":"<p><strong>Introduction: </strong>Polycystic ovary syndrome (PCOS) is a frequent endocrinopathy in young women with significantly increased cardiometabolic risk. Siblings of women with this disorder are at increased risk of insulin resistance and androgen excess. The current study was aimed at investigating cardiometabolic effects of atorvastatin in sisters of women with PCOS.</p><p><strong>Methods: </strong>This prospective observational study compared two age-, body mass index-, blood pressure-, and plasma lipid-matched groups of women with hypercholesterolemia: sisters of PCOS probands (group A) and unrelated control subjects (group B), receiving atorvastatin (40 mg daily). Plasma lipids, glucose homeostasis markers, concentrations of sex hormones, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen and uric acid, and the urinary albumin-to-creatinine ratio (UACR) were measured before entering the study and 6 months later.</p><p><strong>Results: </strong>Both groups differed in the degree of insulin resistance, testosterone, free androgen index (FAI), circulating levels of hsCRP and homocysteine, and UACR. There were no between-group differences in the impact of atorvastatin on plasma lipids. Despite reducing hsCRP and homocysteine in both groups of women, the effect on these biomarkers was stronger in group B than in group A. Only in group B, atorvastatin did reduce fibrinogen, uric acid, and UACR. Only in group A, atorvastatin did worsen insulin sensitivity and tended to reduce testosterone and FAI. The impact of atorvastatin on hsCRP, homocysteine, fibrinogen, uric acid, and UACR inversely correlated with testosterone and FAI.</p><p><strong>Conclusion: </strong>The obtained results suggest that sisters of women with PCOS may benefit to a lesser degree from atorvastatin treatment than other women.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiqi Zhu, Jian Jiang, Jian Wang, Zhiyin Zhou, Xiaoming Ge
Introduction and objective: Endothelial progenitor cells (EPCs) have been proven to exhibit a therapeutic effect in deep vein thrombosis, but are susceptible to microenvironment. Besides, Matrine has promotive effects on EPCs, but its effects on microRNA (miR)-126 remain obscure, which are therefore discussed in the study.
Methods: The cultured EPCs were extracted from Sprague-Dawley rats and identified by immunofluorescence assay. After being treated with Matrine or transfected with miR-126b inhibitor and small interfering RNA targeting forkhead box (FOXO) 4, the viability and apoptosis of EPCs were determined by cell counting kit-8 assay and flow cytometry. The migration, invasion, and tube formation abilities were detected by scratch, Transwell, and tube formation assays. The target genes of miR-126b were predicted by TargetScan, and verified by dual-luciferase reporter assay. The expressions of miR-126b, FOXO4, matrix metalloproteinase (MMP) 2, MMP9, and vascular endothelial growth factor (VEGF) A were determined by quantitative real-time polymerase chain reaction and Western blot.
Results: The EPCs were successfully extracted and cultured, as evidenced by positive reaction cluster of differentiation (CD) 34 and CD133. Matrine promoted the viability, migration, invasion, and tube formation while inhibiting the apoptosis of EPCs, and upregulated the expression of miR-126b. Besides, miR-126b inhibitor reversed the effects of Matrine on EPCs and downregulated the expression levels of MMP2, MMP9, and VEGFA. MiR-126b targeted the FOXO4, and siFOXO4 reversed the abovementioned effects of miR-126b inhibitor on EPCs.
Conclusion: Matrine protects EPCs from apoptosis and promotes their migration, invasion, and tube formation abilities via regulating miR-126b/FOXO4 axis.
{"title":"Matrine Protects Endothelial Progenitor Cells against Apoptosis and Promotes Their Migration, Invasion, and Tube Formation Abilities via Modulating miR-126b/FOXO4 Axis.","authors":"Xiqi Zhu, Jian Jiang, Jian Wang, Zhiyin Zhou, Xiaoming Ge","doi":"10.1159/000527812","DOIUrl":"https://doi.org/10.1159/000527812","url":null,"abstract":"<p><strong>Introduction and objective: </strong>Endothelial progenitor cells (EPCs) have been proven to exhibit a therapeutic effect in deep vein thrombosis, but are susceptible to microenvironment. Besides, Matrine has promotive effects on EPCs, but its effects on microRNA (miR)-126 remain obscure, which are therefore discussed in the study.</p><p><strong>Methods: </strong>The cultured EPCs were extracted from Sprague-Dawley rats and identified by immunofluorescence assay. After being treated with Matrine or transfected with miR-126b inhibitor and small interfering RNA targeting forkhead box (FOXO) 4, the viability and apoptosis of EPCs were determined by cell counting kit-8 assay and flow cytometry. The migration, invasion, and tube formation abilities were detected by scratch, Transwell, and tube formation assays. The target genes of miR-126b were predicted by TargetScan, and verified by dual-luciferase reporter assay. The expressions of miR-126b, FOXO4, matrix metalloproteinase (MMP) 2, MMP9, and vascular endothelial growth factor (VEGF) A were determined by quantitative real-time polymerase chain reaction and Western blot.</p><p><strong>Results: </strong>The EPCs were successfully extracted and cultured, as evidenced by positive reaction cluster of differentiation (CD) 34 and CD133. Matrine promoted the viability, migration, invasion, and tube formation while inhibiting the apoptosis of EPCs, and upregulated the expression of miR-126b. Besides, miR-126b inhibitor reversed the effects of Matrine on EPCs and downregulated the expression levels of MMP2, MMP9, and VEGFA. MiR-126b targeted the FOXO4, and siFOXO4 reversed the abovementioned effects of miR-126b inhibitor on EPCs.</p><p><strong>Conclusion: </strong>Matrine protects EPCs from apoptosis and promotes their migration, invasion, and tube formation abilities via regulating miR-126b/FOXO4 axis.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Cholestasis is the stoppage of bile flow, leading to the accumulation of potentially cytotoxic bile components in the liver. These cytotoxic molecules affect many organs. Cholestasis-induced lung injury is a severe complication that could lead to tissue fibrosis and respiratory distress. Substantial evidence indicates the role of oxidative stress and inflammatory response in the pathogenesis of cholestasis-associated pulmonary damage. Agmatine (AGM; 1-amino-4-guanidinobutane) is a biogenic amine endogenously synthesized in the human body. This amine provides potent anti-inflammatory and antioxidant properties.
Methods: In the current study, a series (six C57BL/6J male mice/group) of bile duct-ligated (BDL) animals were monitored at scheduled intervals (7, 14, and 28 days after the BDL operation) to ensure inflammatory response in their lung tissue (by analyzing their bronchoalveolar lavage fluid [BALF]). It was found that the level of inflammatory cells, pro-inflammatory cytokines, and IgG in the BALF reached their maximum level on day 28 after the BDL surgery. Therefore, other research groups were selected as follows: 1) Sham-operated (2.5 mL/kg normal saline, i.p., for 28 consecutive days), 2) BDL, 3) BDL + AGM (1 mg/kg/day, i.p., for 28 consecutive days), and 4) BDL + AGM (10 mg/kg/day, i.p., for 28 consecutive days). Then, the BALF was monitored at scheduled time intervals (7, 14, and 28 days post-BDL).
Results: It was found that pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), bile acids, bilirubin, and inflammatory cells (monocytes, neutrophils, and lymphocytes) were significantly increased in the BALF of BDL mice. Moreover, biomarkers of oxidative stress were significantly increased in the pulmonary tissue of cholestatic animals. Lung tissue histopathological changes, tissue collagen deposition, and increased TGF-β were also detected. It was found that AGM significantly ameliorated cholestasis-induced lung injury.
Conclusion: The effects of AGM on inflammatory indicators, oxidative stress biomarkers, and tissue fibrosis seem to play a pivotal role in its protective properties.
{"title":"Cholestasis-Associated Pulmonary Inflammation, Oxidative Stress, and Tissue Fibrosis: The Protective Role of the Biogenic Amine Agmatine.","authors":"Mohammad Mehdi Ommati, Hossein Niknahad, Asma Najibi, Abdollah Arjmand, Sepideh Alidaee, Sahra Mazloomi, Parinaz Ahmadi, Alireza Ghiasvand, Maral Javadi, Jamal Yazdani, Samira Sabouri, Heresh Rezaei, Negar Azarpira, Reza Heidari","doi":"10.1159/000530307","DOIUrl":"https://doi.org/10.1159/000530307","url":null,"abstract":"<p><strong>Introduction: </strong>Cholestasis is the stoppage of bile flow, leading to the accumulation of potentially cytotoxic bile components in the liver. These cytotoxic molecules affect many organs. Cholestasis-induced lung injury is a severe complication that could lead to tissue fibrosis and respiratory distress. Substantial evidence indicates the role of oxidative stress and inflammatory response in the pathogenesis of cholestasis-associated pulmonary damage. Agmatine (AGM; 1-amino-4-guanidinobutane) is a biogenic amine endogenously synthesized in the human body. This amine provides potent anti-inflammatory and antioxidant properties.</p><p><strong>Methods: </strong>In the current study, a series (six C57BL/6J male mice/group) of bile duct-ligated (BDL) animals were monitored at scheduled intervals (7, 14, and 28 days after the BDL operation) to ensure inflammatory response in their lung tissue (by analyzing their bronchoalveolar lavage fluid [BALF]). It was found that the level of inflammatory cells, pro-inflammatory cytokines, and IgG in the BALF reached their maximum level on day 28 after the BDL surgery. Therefore, other research groups were selected as follows: 1) Sham-operated (2.5 mL/kg normal saline, i.p., for 28 consecutive days), 2) BDL, 3) BDL + AGM (1 mg/kg/day, i.p., for 28 consecutive days), and 4) BDL + AGM (10 mg/kg/day, i.p., for 28 consecutive days). Then, the BALF was monitored at scheduled time intervals (7, 14, and 28 days post-BDL).</p><p><strong>Results: </strong>It was found that pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), bile acids, bilirubin, and inflammatory cells (monocytes, neutrophils, and lymphocytes) were significantly increased in the BALF of BDL mice. Moreover, biomarkers of oxidative stress were significantly increased in the pulmonary tissue of cholestatic animals. Lung tissue histopathological changes, tissue collagen deposition, and increased TGF-β were also detected. It was found that AGM significantly ameliorated cholestasis-induced lung injury.</p><p><strong>Conclusion: </strong>The effects of AGM on inflammatory indicators, oxidative stress biomarkers, and tissue fibrosis seem to play a pivotal role in its protective properties.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9749422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: The aim of the study was to investigate the role of D-cycloserine (DCS) in the adaptation process and maintenance of motion sickness (MS).
Methods: In experiment 1, 120 SD rats were used to study the promoting effect of DCS on the adaptation process of MS in rats. They were randomly divided into four groups, DCS-rotation (DCS-Rot), DCS-static, saline-rotation (Sal-Rot), and saline-static, and further divided into three subgroups according to the adaptation time (4 days, 7 days, and 10 days) in each group. After being given DCS (0.5 mg/kg) or 0.9% saline, they were rotated or kept static according to the group. Their fecal granules, total distance, and total activity of spontaneous activity were recorded and analyzed. In experiment 2, other 120 rats were used. The experimental grouping and specific experimental method were the same as experiment 1. According to the grouping of the adaptive maintenance duration, the animals of 14 days, 17 days, and 21 days groups were measured on the corresponding date of the changes in the animals' exploratory behavior.
Results: In experiment 1, the fecal granules, total distance, and total activity of spontaneous activity of Sal-Rot returned to the control level on 9 days, and the DCS-Rot group returned to the control level on 6 days, indicating that DCS could shorten the adaptation time of MS rats from 9 days to 6 days. In experiment 2, the Sal-Rot could not maintain the adaptive state after 14 days' absence from the seasickness environment. The fecal granules of DCS-Rot increased significantly, and total distance and total activity of spontaneous activity of DCS-Rot decreased significantly from 17 days. These illustrate that DCS can prolong the adaptive maintenance time from within 14 days to 17 days in MS rats.
Conclusion: 0.5 mg/kg DCS injected intraperitoneally can shorten the MS adaptation process and extend the maintenance time of adaptation of SD rats.
{"title":"New Role of D-Cycloserine: Shorten Adaptation Process and Extend Maintenance Time of Motion Sickness.","authors":"Yilin Lu, Zehua Chen, Leilei Pan, Ling Zhang, Shuifeng Xiao, Ruirui Qi, Yiling Cai, Junqin Wang","doi":"10.1159/000530575","DOIUrl":"https://doi.org/10.1159/000530575","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to investigate the role of D-cycloserine (DCS) in the adaptation process and maintenance of motion sickness (MS).</p><p><strong>Methods: </strong>In experiment 1, 120 SD rats were used to study the promoting effect of DCS on the adaptation process of MS in rats. They were randomly divided into four groups, DCS-rotation (DCS-Rot), DCS-static, saline-rotation (Sal-Rot), and saline-static, and further divided into three subgroups according to the adaptation time (4 days, 7 days, and 10 days) in each group. After being given DCS (0.5 mg/kg) or 0.9% saline, they were rotated or kept static according to the group. Their fecal granules, total distance, and total activity of spontaneous activity were recorded and analyzed. In experiment 2, other 120 rats were used. The experimental grouping and specific experimental method were the same as experiment 1. According to the grouping of the adaptive maintenance duration, the animals of 14 days, 17 days, and 21 days groups were measured on the corresponding date of the changes in the animals' exploratory behavior.</p><p><strong>Results: </strong>In experiment 1, the fecal granules, total distance, and total activity of spontaneous activity of Sal-Rot returned to the control level on 9 days, and the DCS-Rot group returned to the control level on 6 days, indicating that DCS could shorten the adaptation time of MS rats from 9 days to 6 days. In experiment 2, the Sal-Rot could not maintain the adaptive state after 14 days' absence from the seasickness environment. The fecal granules of DCS-Rot increased significantly, and total distance and total activity of spontaneous activity of DCS-Rot decreased significantly from 17 days. These illustrate that DCS can prolong the adaptive maintenance time from within 14 days to 17 days in MS rats.</p><p><strong>Conclusion: </strong>0.5 mg/kg DCS injected intraperitoneally can shorten the MS adaptation process and extend the maintenance time of adaptation of SD rats.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9805589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Milorad Stojadinovic, Radica Zivkovic Zaric, Mirjana Lausevic, Tamara Jemcov, Ljiljana Komadina, Dejan Petrovic, Petar Djuric, Ana Bulatovic, Slobodan Jankovic
Introduction: Inappropriate prescribing is common in patients with end-stage kidney disease, especially in those over 65 years of age. Our study aimed to reveal potentially inappropriate drug prescribing in patients on peritoneal dialysis (PD) and explore factors associated with this phenomenon.
Methods: The research was designed as an observational, cross-sectional study on a convenient sample of 145 consecutive patients with PD who attended the four tertiary-care hospitals in Serbia. The main outcome was the extent of inappropriate prescribing, as assessed by the medication appropriateness index, and potential predictors were tested by multiple linear regression.
Results: Inappropriate prescribing was a widespread phenomenon among patients on PD. The main factors that promote inappropriate prescribing in this subgroup of patients on kidney replacement therapy are comorbidities (p = 0.000), increased body weight (p = 0.022), a number of prescribed drugs (p = 0.000), and arterial hypertension on examination (p = 0.030). On the other hand, drinking alcohol and higher systolic blood pressure were associated with a lower inappropriate prescribing.
Conclusion: In order to prevent the occurrence of inappropriate prescribing and its severe health or economic consequences, clinicians should pay special attention when prescribing new drugs to high-risk patients.
{"title":"Factors Associated with Potentially Inappropriate Prescribing in Patients on Peritoneal Dialysis.","authors":"Milorad Stojadinovic, Radica Zivkovic Zaric, Mirjana Lausevic, Tamara Jemcov, Ljiljana Komadina, Dejan Petrovic, Petar Djuric, Ana Bulatovic, Slobodan Jankovic","doi":"10.1159/000527263","DOIUrl":"https://doi.org/10.1159/000527263","url":null,"abstract":"<p><strong>Introduction: </strong>Inappropriate prescribing is common in patients with end-stage kidney disease, especially in those over 65 years of age. Our study aimed to reveal potentially inappropriate drug prescribing in patients on peritoneal dialysis (PD) and explore factors associated with this phenomenon.</p><p><strong>Methods: </strong>The research was designed as an observational, cross-sectional study on a convenient sample of 145 consecutive patients with PD who attended the four tertiary-care hospitals in Serbia. The main outcome was the extent of inappropriate prescribing, as assessed by the medication appropriateness index, and potential predictors were tested by multiple linear regression.</p><p><strong>Results: </strong>Inappropriate prescribing was a widespread phenomenon among patients on PD. The main factors that promote inappropriate prescribing in this subgroup of patients on kidney replacement therapy are comorbidities (p = 0.000), increased body weight (p = 0.022), a number of prescribed drugs (p = 0.000), and arterial hypertension on examination (p = 0.030). On the other hand, drinking alcohol and higher systolic blood pressure were associated with a lower inappropriate prescribing.</p><p><strong>Conclusion: </strong>In order to prevent the occurrence of inappropriate prescribing and its severe health or economic consequences, clinicians should pay special attention when prescribing new drugs to high-risk patients.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10479605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2023-06-21DOI: 10.1159/000530703
Yanni Fang, Wenwen Jin, Zhen Guo, Jumei Hao
Introduction: The aim of the study was to discuss whether the anti-asthmatic effect of quercetin is related to periostin and the downstream molecular pathway of quercetin's anti-asthmatic effect.
Methods: We constructed asthmatic mice, sensitized by ovalbumin, and administrated different treatments into mice according to the experimental design. In this study, we mainly observed the inflammatory response, airway fibrosis, and airway hyperresponsiveness in asthmatic mice. Pathological stains (H&E, PAS, and Masson) were performed. We also detected the inflammation factors and fibrosis-related cytokines by enzyme-linked immunosorbent serologic assay. In addition, we also explored the level of periostin by enzyme-linked immunosorbent serologic assay and Western blot. At the same time, TGF-β1/Smad pathway was also determined by Western blot.
Results: A high expression of periostin was found in asthmatic mice, and quercetin decreases periostin content in bronchoalveolar lavage fluid. Quercetin and OC-20 inhibit airway inflammation response, airway fibrosis, and airway hyperreactivity. Quercetin downregulated TGF-β1/Smad pathway in the lung tissues of asthmatic mice. Anti-asthma role of quercetin is related to periostin. Then deeper mechanical study revealed that inhibiting TGF-β1 could improve asthmatic symptoms, and quercetin exerted the protective effect on asthmatic mice through inhibition of TGF-β1/Smad pathway.
Conclusion: Quercetin provided a protective role against asthma via periostin, manifested by mild inflammatory infiltration, reduced goblet cell proliferation, and reduced airway fibrosis. TGF-β1/Smad pathway is an important transduction system, participating in the protective effect of quercetin on asthma.
{"title":"Quercetin Alleviates Asthma-Induced Airway Inflammation and Remodeling through Downregulating Periostin via Blocking TGF-β1/Smad Pathway.","authors":"Yanni Fang, Wenwen Jin, Zhen Guo, Jumei Hao","doi":"10.1159/000530703","DOIUrl":"10.1159/000530703","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study was to discuss whether the anti-asthmatic effect of quercetin is related to periostin and the downstream molecular pathway of quercetin's anti-asthmatic effect.</p><p><strong>Methods: </strong>We constructed asthmatic mice, sensitized by ovalbumin, and administrated different treatments into mice according to the experimental design. In this study, we mainly observed the inflammatory response, airway fibrosis, and airway hyperresponsiveness in asthmatic mice. Pathological stains (H&E, PAS, and Masson) were performed. We also detected the inflammation factors and fibrosis-related cytokines by enzyme-linked immunosorbent serologic assay. In addition, we also explored the level of periostin by enzyme-linked immunosorbent serologic assay and Western blot. At the same time, TGF-β1/Smad pathway was also determined by Western blot.</p><p><strong>Results: </strong>A high expression of periostin was found in asthmatic mice, and quercetin decreases periostin content in bronchoalveolar lavage fluid. Quercetin and OC-20 inhibit airway inflammation response, airway fibrosis, and airway hyperreactivity. Quercetin downregulated TGF-β1/Smad pathway in the lung tissues of asthmatic mice. Anti-asthma role of quercetin is related to periostin. Then deeper mechanical study revealed that inhibiting TGF-β1 could improve asthmatic symptoms, and quercetin exerted the protective effect on asthmatic mice through inhibition of TGF-β1/Smad pathway.</p><p><strong>Conclusion: </strong>Quercetin provided a protective role against asthma via periostin, manifested by mild inflammatory infiltration, reduced goblet cell proliferation, and reduced airway fibrosis. TGF-β1/Smad pathway is an important transduction system, participating in the protective effect of quercetin on asthma.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9673612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2023-07-17DOI: 10.1159/000531319
Agata Czarnywojtek, Magdalena Borowska, Kamil Dyrka, Stefaan Van Gool, Nadia Sawicka-Gutaj, Jakub Moskal, Jeremi Kościński, Patryk Graczyk, Tomasz Hałas, Agnieszka Marta Lewandowska, Rafał Czepczyński, Marek Ruchała
Background: Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in the treatment of GBM. In addition to the newest form of GBM removal using fluorescence, three-dimensional (3D) imaging, tomoradiotherapy, moderate electro-hyperthermia, and adjuvant temozolomide (post-operative chemotherapy), new developments have been made in the fields of immunology, molecular biology, and virotherapy. An unusual and modern treatment has been created, especially for stage 4 GBM, using the latest therapeutic techniques, including immunotherapy and virotherapy. Modern oncological medicine is producing extraordinary and progressive therapeutic methods. Oncological therapy includes individual analysis of the properties of a tumour and targeted therapy using small-molecule inhibitors. Individualised medicine covers the entire patient (tumour and host) in the context of immunotherapy. An example is individualised multimodal immunotherapy (IMI), which relies on individual immunological tumour-host interactions. In addition, IMI is based on the concept of oncolytic virus-induced immunogenic tumour cell death.
Summary: In this review, we outline current knowledge of the various available treatment options used in the therapy of GBM including both traditional therapeutic strategy and modern therapies, such as tomotherapy, electro-hyperthermia, and oncolytic virotherapy, which are promising treatment strategies with the potential to improve prognosis in patients with GBM.
Key messages: This newest therapy, immunotherapy combined with virotherapy (oncolytic viruses and cancer vaccines), is displaying encouraging signs for combating GBM. Additionally, the latest 3D imaging is compared to conventional two-dimensional imaging.
{"title":"Glioblastoma Multiforme: The Latest Diagnostics and Treatment Techniques.","authors":"Agata Czarnywojtek, Magdalena Borowska, Kamil Dyrka, Stefaan Van Gool, Nadia Sawicka-Gutaj, Jakub Moskal, Jeremi Kościński, Patryk Graczyk, Tomasz Hałas, Agnieszka Marta Lewandowska, Rafał Czepczyński, Marek Ruchała","doi":"10.1159/000531319","DOIUrl":"10.1159/000531319","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in the treatment of GBM. In addition to the newest form of GBM removal using fluorescence, three-dimensional (3D) imaging, tomoradiotherapy, moderate electro-hyperthermia, and adjuvant temozolomide (post-operative chemotherapy), new developments have been made in the fields of immunology, molecular biology, and virotherapy. An unusual and modern treatment has been created, especially for stage 4 GBM, using the latest therapeutic techniques, including immunotherapy and virotherapy. Modern oncological medicine is producing extraordinary and progressive therapeutic methods. Oncological therapy includes individual analysis of the properties of a tumour and targeted therapy using small-molecule inhibitors. Individualised medicine covers the entire patient (tumour and host) in the context of immunotherapy. An example is individualised multimodal immunotherapy (IMI), which relies on individual immunological tumour-host interactions. In addition, IMI is based on the concept of oncolytic virus-induced immunogenic tumour cell death.</p><p><strong>Summary: </strong>In this review, we outline current knowledge of the various available treatment options used in the therapy of GBM including both traditional therapeutic strategy and modern therapies, such as tomotherapy, electro-hyperthermia, and oncolytic virotherapy, which are promising treatment strategies with the potential to improve prognosis in patients with GBM.</p><p><strong>Key messages: </strong>This newest therapy, immunotherapy combined with virotherapy (oncolytic viruses and cancer vaccines), is displaying encouraging signs for combating GBM. Additionally, the latest 3D imaging is compared to conventional two-dimensional imaging.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10203477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2023-10-11DOI: 10.1159/000532078
Peiyu Guo, Hua Li, Xuming Wang, Xingguo Li, Xi Li
Introduction: Osteoarthritis (OA) is a degenerative disease common in the elderly and is characterized by joint pain, swelling, and restricted movement. In recent years, heparanase has been reported to play an important role in the development of osteoarthritic cartilage. PG545 is a heparan sulfate mimetic with heparanase inhibitory activity. In this study, the therapeutic effects and possible mechanisms of PG545 were investigated in a chondrocyte injury model induced by interleukin-1β (IL -1β).
Methods: Following treatment with PG545 or the autophagy inhibitor 3-methyladenine (3-MA), chondrocyte viability was detected using Cell Counting Kit-8 and fluorescein diacetate/propidium iodide double staining. The apoptosis rate of chondrocytes was determined by flow cytometry. Expression of light chain 3 and P62 was monitored by immunofluorescence labeling. Western blot, lentivirus infection with red fluorescent protein and green fluorescent protein, and quantitative real-time polymerase chain reaction were used to determine the expression levels of chondrocyte markers, apoptosis-related factors, autophagy proteins, and key proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. The expression and activity of stress-specific enzymes such as malondialdehyde, superoxide dismutase, and catalase (CAT) were investigated. Chondrocytes with ATG5 knockdown were used to investigate the relationship between the therapeutic effect of PG545 and autophagy. The therapeutic effect of PG545 was verified in vivo.
Results: PG545 had a significant protective effect on chondrocytes by reducing oxidative stress, apoptosis, and degradation of chondrocytes and increasing chondrocyte proliferation. PG545 was effective in inducing autophagy in IL-1β-treated cells, while 3-MA attenuated the effect. The PI3K/Akt/mTOR pathway may be involved in the promotion of autophagy and OA treatment by PG545.
Conclusion: PG545 was able to restore impaired autophagy and autophagic flux via the PI3K/Akt/mTOR pathway, thereby delaying the progression of OA, suggesting that PG545 may be a novel therapeutic approach for OA.
{"title":"PG545 Prevents Osteoarthritis Development by Regulating PI3K/AKT/mTOR Signaling and Activating Chondrocyte Autophagy.","authors":"Peiyu Guo, Hua Li, Xuming Wang, Xingguo Li, Xi Li","doi":"10.1159/000532078","DOIUrl":"10.1159/000532078","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoarthritis (OA) is a degenerative disease common in the elderly and is characterized by joint pain, swelling, and restricted movement. In recent years, heparanase has been reported to play an important role in the development of osteoarthritic cartilage. PG545 is a heparan sulfate mimetic with heparanase inhibitory activity. In this study, the therapeutic effects and possible mechanisms of PG545 were investigated in a chondrocyte injury model induced by interleukin-1β (IL -1β).</p><p><strong>Methods: </strong>Following treatment with PG545 or the autophagy inhibitor 3-methyladenine (3-MA), chondrocyte viability was detected using Cell Counting Kit-8 and fluorescein diacetate/propidium iodide double staining. The apoptosis rate of chondrocytes was determined by flow cytometry. Expression of light chain 3 and P62 was monitored by immunofluorescence labeling. Western blot, lentivirus infection with red fluorescent protein and green fluorescent protein, and quantitative real-time polymerase chain reaction were used to determine the expression levels of chondrocyte markers, apoptosis-related factors, autophagy proteins, and key proteins of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. The expression and activity of stress-specific enzymes such as malondialdehyde, superoxide dismutase, and catalase (CAT) were investigated. Chondrocytes with ATG5 knockdown were used to investigate the relationship between the therapeutic effect of PG545 and autophagy. The therapeutic effect of PG545 was verified in vivo.</p><p><strong>Results: </strong>PG545 had a significant protective effect on chondrocytes by reducing oxidative stress, apoptosis, and degradation of chondrocytes and increasing chondrocyte proliferation. PG545 was effective in inducing autophagy in IL-1β-treated cells, while 3-MA attenuated the effect. The PI3K/Akt/mTOR pathway may be involved in the promotion of autophagy and OA treatment by PG545.</p><p><strong>Conclusion: </strong>PG545 was able to restore impaired autophagy and autophagic flux via the PI3K/Akt/mTOR pathway, thereby delaying the progression of OA, suggesting that PG545 may be a novel therapeutic approach for OA.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41210011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2023-07-27DOI: 10.1159/000531604
Shehroze Tabassum, Aroma Naeem, Uzzam Ahmed Khawaja, Abdulqadir J Nashwan
Dear Editor, Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed drugs; however, they can lead to potential adverse effects [1]. The detrimental association between NSAIDs (apart from aspirin) usage and the peril to cardiac health has been documented profoundly in the literature [2–7]. The possible mechanism behind this adverse relationship can be due to an imbalance in the levels of prostaglandin E2 and vasodilatory prostacyclin compared to those of vasoconstrictive thromboxane A2, established due to NSAID usage targeting the endothelium and eventually leading to thrombus formation [8, 9]. Unlike other NSAIDs, aspirin irreversibly inhibits COX-1, leading to a reduction in thromboxane A2 and clot formation, while not significantly impacting vasodilatory prostaglandins and at low doses, this provides a cardioprotective effect [2]. NSAIDs are further known to exacerbate heart failure (HF) through increased salt and water retention [10–12]. A study conducted by Page and Henry [13] evaluated the hospitalization risk of HF for patients on NSAIDs. A relative risk of 2.1 was found in patients taking NSAIDs compared to nonusers. According to this study, NSAIDs use might contribute to 19% of newly diagnosed congestive HF cases. A study by Mamdani et al. [14] compared the hospitalization risk for congestive HF for patients being managed with nonselective NSAIDs, coxibs, and controls. Patients taking rofecoxib showed the most significant risk (RR = 1.8, 95% confidence interval [CI] = 1.5–2.2). While those taking nonselective NSAIDs showed a relative risk of 1.4 (95% CI = 1.0–1.9). These studies demonstrate that NSAIDs can cause as well as exacerbate preexisting HF. However, there is very limited data available that can relate to patients with first-time cardiac failure prescribed NSAIDs having T2DM. A study recently presented at the 2022 Congress of the European Society of Cardiology (ESC) revealed that short-term NSAID use could potentially augment the chance of first-time HF in patients having T2DM [15]. A greater than 40% increase in the likelihood of hospitalization for first-time HF in patients who took NSAIDs, including ibuprofen, the most widely used drug, was observed. According to the statement from ESC, lead investigator Anders Holt, MD, stated that almost 1 in 6 patients with T2DM in their study had usage of at least one NSAID for 1 year. Holt and a team of colleagues from institutions in Denmark and the United Kingdom designed this study as an observational one using data from Danish registers to find patients suffering with DM from 1998 to 2018. Investigators used a case-crossover method where the
{"title":"Can Nonsteroidal Anti-Inflammatory Drugs Lead to First-Time Heart Failure in Patients with Diabetes Mellitus Type-2: Is There a Link?","authors":"Shehroze Tabassum, Aroma Naeem, Uzzam Ahmed Khawaja, Abdulqadir J Nashwan","doi":"10.1159/000531604","DOIUrl":"10.1159/000531604","url":null,"abstract":"Dear Editor, Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed drugs; however, they can lead to potential adverse effects [1]. The detrimental association between NSAIDs (apart from aspirin) usage and the peril to cardiac health has been documented profoundly in the literature [2–7]. The possible mechanism behind this adverse relationship can be due to an imbalance in the levels of prostaglandin E2 and vasodilatory prostacyclin compared to those of vasoconstrictive thromboxane A2, established due to NSAID usage targeting the endothelium and eventually leading to thrombus formation [8, 9]. Unlike other NSAIDs, aspirin irreversibly inhibits COX-1, leading to a reduction in thromboxane A2 and clot formation, while not significantly impacting vasodilatory prostaglandins and at low doses, this provides a cardioprotective effect [2]. NSAIDs are further known to exacerbate heart failure (HF) through increased salt and water retention [10–12]. A study conducted by Page and Henry [13] evaluated the hospitalization risk of HF for patients on NSAIDs. A relative risk of 2.1 was found in patients taking NSAIDs compared to nonusers. According to this study, NSAIDs use might contribute to 19% of newly diagnosed congestive HF cases. A study by Mamdani et al. [14] compared the hospitalization risk for congestive HF for patients being managed with nonselective NSAIDs, coxibs, and controls. Patients taking rofecoxib showed the most significant risk (RR = 1.8, 95% confidence interval [CI] = 1.5–2.2). While those taking nonselective NSAIDs showed a relative risk of 1.4 (95% CI = 1.0–1.9). These studies demonstrate that NSAIDs can cause as well as exacerbate preexisting HF. However, there is very limited data available that can relate to patients with first-time cardiac failure prescribed NSAIDs having T2DM. A study recently presented at the 2022 Congress of the European Society of Cardiology (ESC) revealed that short-term NSAID use could potentially augment the chance of first-time HF in patients having T2DM [15]. A greater than 40% increase in the likelihood of hospitalization for first-time HF in patients who took NSAIDs, including ibuprofen, the most widely used drug, was observed. According to the statement from ESC, lead investigator Anders Holt, MD, stated that almost 1 in 6 patients with T2DM in their study had usage of at least one NSAID for 1 year. Holt and a team of colleagues from institutions in Denmark and the United Kingdom designed this study as an observational one using data from Danish registers to find patients suffering with DM from 1998 to 2018. Investigators used a case-crossover method where the","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9885634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Lenvatinib mesylate (LEN) is an orally administered tyrosine kinase inhibitor used for the treatment of various cancers, including hepatocellular carcinoma (HCC). HCC treatment with LEN is associated with a very high incidence of adverse events, especially hypothyroidism. This study investigated the incidence of hypothyroidism due to LEN and the relationships between hypothyroidism incidence and patient demographics by analyzing clinical laboratory data from HCC patients treated with LEN.
Methods: This was a single-center, retrospective study of HCC patients who received LEN between April 19, 2018, and September 30, 2020. The observation period was from 1 week before the start of LEN administration to 1 month after the end of administration.
Results: In total, 61 patients with HCC were enrolled. High-grade hypothyroidism (CTCAE Grade 2-3) was found in 36.1% (22/61 patients). In high-grade hypothyroidism, eosinophil (EOSINO) count was significantly low (p = 0.029). The cutoff value of EOSINO count was estimated to be approximately 150/µL. The adjusted odds ratios of high-grade hypothyroidism for current smoking and EOSINO count <150/µL were 0.237 (95% confidence interval: 0.063-0.893) and 4.219 (95% confidence interval: 1.119-15.92), respectively.
Conclusion: The results showed that noncurrent smoking and EOSINO count <150/µL are risk factors for LEN-induced high-grade hypothyroidism.
{"title":"Risk Factors for Lenvatinib-Induced High-Grade Hypothyroidism in Patients with Hepatocellular Carcinoma: A Retrospective Study.","authors":"Shusuke Uekusa, Maho Nemoto, Yuki Hanai, Misaki Nakashin, Arisu Miyagawa, Sachiko Yanagino, Yoshiki Arita, Takahiro Matsumoto, Kenji Nishizawa, Hidenari Nagai, Koji Higai, Kazuhiro Matsuo","doi":"10.1159/000531881","DOIUrl":"10.1159/000531881","url":null,"abstract":"<p><strong>Introduction: </strong>Lenvatinib mesylate (LEN) is an orally administered tyrosine kinase inhibitor used for the treatment of various cancers, including hepatocellular carcinoma (HCC). HCC treatment with LEN is associated with a very high incidence of adverse events, especially hypothyroidism. This study investigated the incidence of hypothyroidism due to LEN and the relationships between hypothyroidism incidence and patient demographics by analyzing clinical laboratory data from HCC patients treated with LEN.</p><p><strong>Methods: </strong>This was a single-center, retrospective study of HCC patients who received LEN between April 19, 2018, and September 30, 2020. The observation period was from 1 week before the start of LEN administration to 1 month after the end of administration.</p><p><strong>Results: </strong>In total, 61 patients with HCC were enrolled. High-grade hypothyroidism (CTCAE Grade 2-3) was found in 36.1% (22/61 patients). In high-grade hypothyroidism, eosinophil (EOSINO) count was significantly low (p = 0.029). The cutoff value of EOSINO count was estimated to be approximately 150/µL. The adjusted odds ratios of high-grade hypothyroidism for current smoking and EOSINO count <150/µL were 0.237 (95% confidence interval: 0.063-0.893) and 4.219 (95% confidence interval: 1.119-15.92), respectively.</p><p><strong>Conclusion: </strong>The results showed that noncurrent smoking and EOSINO count <150/µL are risk factors for LEN-induced high-grade hypothyroidism.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10396136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}