Frontiers in Pharmacology最新文献

{"title":"Revealing the secrets of Blue Zones.","authors":"N Nuray Ulusu","doi":"10.3389/fphar.2024.1428111","DOIUrl":"10.3389/fphar.2024.1428111","url":null,"abstract":"<p><p>Aging is influenced by cellular senescence mechanisms that are associated with oxidative stress. Oxidative stress is the imbalance between antioxidants and free radicals. This imbalance affects enzyme activities and causes mitochondrial dysfunction. It also slows down cellular energy production and disrupts cellular homeostasis. Additionally, oxidative stress stimulates inflammation, increases the number of point mutations, and alters intercellular communication. It can lead to epigenetic alterations, genomic instability, telomere attrition, and loss of proteostasis. Ultimately, these factors contribute to aging and the development of chronic diseases. Glucose-6-phosphate dehydrogenase (G6PD) is an antioxidant enzyme that protects cells from oxidative and nitrosative damage. It helps restore redox balance, preserve macromolecule function, and rescue cells from cellular senescence, autophagy, and stress-induced apoptosis. G6PD is considered an anti-senescence enzyme. The World Health Organization classifies G6PD variants into five groups based on the enzyme's residual activity. The first four classes are categorized according to the degree of G6PD deficiency, while the fifth class includes variants with enzyme activities greater than normal. Increased G6PD activity does not exhibit clinical manifestations. Consequently, the full spectrum of mutations and the prevalence of increased G6PD activity in the population remain unknown. The world's oldest and healthiest people live in Blue Zones. These comprise isolated populations, and there may be a geographic prevalence of high-activity G6PD variants that protect against oxidative stress-induced senescence. To uncover the secret of centenarians' longevity, additional research is needed to determine whether the hidden factor is the increased activity of the G6PD enzyme.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1428111"},"PeriodicalIF":4.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between anthropometric indices and hypertension: identifying optimal cutoff points for U.S. adults across different populations.","authors":"Xueliang Zhang, Yan Nie, Dan Li, Chunhua Zhou","doi":"10.3389/fphar.2024.1503059","DOIUrl":"10.3389/fphar.2024.1503059","url":null,"abstract":"<p><strong>Objective: </strong>This study compares the relationships between five anthropometric indices, a body shape index (ABSI), body roundness index (BRI), waist circumference (WC), body mass index (BMI) and waist-to-height ratio (WHtR), and hypertension, assessing their predictive capacities. The aim is to determine the specific numerical changes in hypertension incidence, systolic blood pressure (SBP) and diastolic blood pressure (DBP) for each increase in standard deviation of these indices, and to identify the optimal predictive indicators for different populations, including the calculation of cutoff values.</p><p><strong>Methods: </strong>This study used data from the NHANES datasets spanning 2007 to 2018. Logistic regression analysis was used to quantify the associations between these anthropometric indices and hypertension, calculating β coefficients and odds ratios (ORs). Receiver operating characteristic (ROC) analysis was used to evaluate the predictive ability of each index for hypertension.</p><p><strong>Results: </strong>For each increase in standard deviation in WC, BMI, WHtR, ABSI and BRI, the prevalence of hypertension increased by 33% (95% CI: 27%-40%), 32% (95% CI: 26%-38%), 35% (95% CI: 28%-42%), 9% (95% CI: 4%-16%) and 32% (95% CI: 26%-38%), respectively. The SBP correspondingly increased by 2.36 mmHg (95% CI: 2.16-2.56), 2.41 mmHg (95% CI: 2.21-2.60), 2.48 mmHg (95% CI: 2.28-2.68), 0.42 mmHg (95% CI: 0.19-0.66) and 2.46 mmHg (95% CI: 2.26-2.66), respectively. Similarly, DBP increased by 1.83 mmHg (95% CI: 1.68-1.98), 1.72 mmHg (95% CI: 1.58-1.87), 1.72 mmHg (95% CI: 1.57-1.88), 0.44 mmHg (95% CI: 0.27-0.62) and 1.64 mmHg (95% CI: 1.48-1.79). In the youth and middle-aged groups, WC had the best predictive ability, with AUCs of 0.749 and 0.603, respectively. Among the elderly group, the AUCs for all five indices ranged between 0.5 and 0.52.</p><p><strong>Conclusion: </strong>Increases in WC, BMI, WHtR and BRI are significantly associated with higher incidences of hypertension and increases in SBP and DBP, while the impact of ABSI on blood pressure is relatively weak. Stratified analysis indicates significant age-related differences in the predictive value of these indices, with the strongest associations observed in the youth group, followed by the middle age group, and the weakest in the elderly. WC demonstrates excellent predictive ability across youth populations.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1503059"},"PeriodicalIF":4.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Which fluoroquinolone is safer when combined with bedaquiline for tuberculosis treatment: evidence from FDA Adverse Event Reporting System database from 2013 to 2024.","authors":"Sheng Wei, Changping He, Xiangping Xie, Anping Zhang, Simin Tang, Sha Li, Yanlang He","doi":"10.3389/fphar.2024.1491921","DOIUrl":"10.3389/fphar.2024.1491921","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate which fluoroquinolone is safer when combined with bedaquiline for tuberculosis treatment by using the FDA Adverse Event Reporting System (FAERS) database.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We selected data from the first quarter (Q1) of 2013 to the second quarter (Q4) of 2024 from the FDA FAERS database for disproportionality analysis. Signal detection was conducted using the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;This study analyzed 12, 303, 879 reports from the FAERS database, including 722 reports related to the combination of bedaquiline and levofloxacin (with 2,723 adverse events) and 573 reports related to the combination of bedaquiline and moxifloxacin (with 2,233 adverse events). For the bedaquiline-levofloxacin regimen, these reports were categorized into 100 preferred terms (PTs) and 24 System Organ Classification (SOCs). The three most common SOCs were hepatobiliary disorders (n = 128, ROR 5.79, PRR 5.56, IC 2.48, EBGM 5.56), blood and lymphatic system disorders (n = 217, ROR 5.04, PRR 4.72, IC 2.24, EBGM 4.71), and metabolism and nutrition disorders (n = 185, ROR 3.44, PRR 3.27, IC 1.71, EBGM 3.27). In terms of PTs, the three strongest signals were portal fibrosis (ROR 330.64), hepatitis C RNA increased (ROR 301.24), and toxic optic neuropathy (ROR 238.11). Reports of prolonged QT interval on ECG (125 cases) and anemia (130 cases) were significantly more frequent than other PTs. For the bedaquiline-moxifloxacin regimen, these reports were categorized into 85 preferred terms (PTs) and 24 System Organ Classification (SOCs). The three most common SOCs were hepatobiliary disorders (n = 141, ROR 7.9, PRR 7.47, IC 2.9, EBGM 7.46), ear and labyrinth disorders (n = 40, ROR 4.03, PRR 3.97, IC 1.99, EBGM 3.97), and cardiac disorders (n = 141, ROR 3.08, PRR 2.95, IC 1.56, EBGM 2.95). The three strongest PT signals were chronic pyelonephritis (ROR 563.29), bronchopleural fistula (ROR 314.86), and toxic neuropathy (ROR 187.11). Prolonged QT interval on ECG (152 cases) remained the most frequently reported PT. In both treatment regimens, individuals under 45 years of age experienced a higher frequency and variety of AEs, indicating the need for enhanced monitoring. For those over 45, particular attention should be given to ECG changes, especially in men. Finally, some PTs with extremely high signal strength, such as chronic pyelonephritis (ROR 563.29), hepatitis C RNA increased (ROR 301.24), and bronchopleural fistula (ROR 301.24), may represent rare adverse events associated with the combination of bedaquiline-fluoroquinolone.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our study suggests that the safety profile of bedaquiline combined with moxifloxacin does not appear superior to that of bedaquiline combined with levofloxacin in terms of cardiac, hepatic, ","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1491921"},"PeriodicalIF":4.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors influencing vancomycin trough concentration in burn patients: a single center retrospective study.","authors":"Yan Shi, Zongqi Yin, Qin Zhang, Lei Yi, Yi Dou","doi":"10.3389/fphar.2024.1377930","DOIUrl":"10.3389/fphar.2024.1377930","url":null,"abstract":"<p><strong>Objective: </strong>To analyze factors influencing the vancomycin trough concentration in burn patients to provide a basis for the more rational use of vancomycin in these patients.</p><p><strong>Materials and methods: </strong>We collected the clinical data of adult burn patients treated with vancomycin in a Chinese hospital. Vancomycin was administered at a dosing regimen of 1.0 g q12 h. Patients were divided into a therapeutic group with vancomycin trough concentration in the target therapeutic range (10-20 μg/mL) and a subtherapeutic group with vancomycin trough concentration in the subtherapeutic range (<10 μg/mL).</p><p><strong>Results: </strong>The therapeutic group included 14 patients (17.5%), with an average trough concentration of 14.36 ± 2.82 μg/mL; the subtherapeutic group included 66 patients (82.5%), with an average trough concentration of 5.18 ± 2.77 μg/mL. The serum creatinine level was significantly higher in the therapeutic group (84.93 ± 47.26 μmol/L) than that in the subtherapeutic group (62.44 ± 14.49 μmol/L) (<i>p</i> < 0.01). Serum albumin levels were significantly lower in the therapeutic group (30.50 ± 2.28 g/L) than those in the subtherapeutic group (34.00 ± 6.22 g/L) (<i>p</i> < 0.05). Using receiver operating characteristic (ROC) curve analysis, for serum albumin, the area under the ROC curve (AUC) (95% confidence interval [CI]) was 0.67 (0.553, 0.788); the optimal cut-off point was 34.50 g/L (<i>p</i> = 0.046), the sensitivity was 0.379, and the specificity was 1.0. For creatinine clearance, the AUC (95% CI) was 0.72 (0.537, 0.902); the optimal cut-off point was 76.64 mL/min (<i>p</i> = 0.01), the sensitivity was 0.985, and the specificity was 0.5. The linear stepwise regression equation was as follows: trough concentration = 0.14 × age + 0.071 × serum creatinine -4.196.</p><p><strong>Conclusion: </strong>In this study, a high proportion of burn patients had a vancomycin trough concentration below the standard range. Serum creatinine clearance and albumin levels are important indicators for predicting whether the vancomycin trough concentration is within the standard range. Using a linear stepwise regression equation, the vancomycin trough concentration can be estimated using the patient's age and serum creatinine level.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1377930"},"PeriodicalIF":4.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tomatidine relieves neuronal damage in spinal cord injury by inhibiting the inflammatory responses and apoptosis through blocking the NF-κB/CXCL10 pathway activation.","authors":"Xu Wang, Wei Huang, Hao Sun, Hua Wang, Dongxu Wang, Yongxiang Wang","doi":"10.3389/fphar.2024.1503925","DOIUrl":"10.3389/fphar.2024.1503925","url":null,"abstract":"<p><strong>Background: </strong>Spinal cord injury (SCI) is a neurological disease characterized by high disability and mortality rates. Tomatidine, a natural steroid alkaloid, has been evidenced to have neuroprotective properties. However, the underlying mechanisms of tomatidine in treating SCI remain ambiguous. This study aimed to illustrate the molecular mechanisms of tomatidine in modulating the inflammatory response and promoting functional rehabilitation after SCI.</p><p><strong>Methods: </strong>Sprague-Dawley (SD) rats were used to construct an <i>in vivo</i> SCI model and were intraperitoneally injected with tomatidine (5, 10, or 20 mg/kg) for 7 days, followed by treatment with the nuclear factor-κB (NF-κB) pathway agonist (PMA). In addition, lipopolysaccharide (LPS)-induced PC-12 cells were used to establish an SCI cell model and were stimulated with tomatidine, PMA, or a CXCL10 inhibitor. The pathophysiological changes and neurological function were evaluated using blood-brain barrier (BBB) scoring, water content determination, hematoxylin and eosin (H&E) staining, and TUNEL assay. Levels of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, were measured. Cell proliferation, apoptosis, and the expression of C-X-C motif chemokine ligand 10 (CXCL10) were determined. Moreover, the expression of cleaved-caspase 3, caspase 3, CXCL10, p-p65, and p65 were analyzed.</p><p><strong>Results: </strong>Our data revealed that tomatidine promoted neuronal damage recovery, reduced histopathological changes, elevated cell proliferation, and inhibited the apoptosis and inflammatory factor levels in spinal cord tissues and LPS-induced PC-12 cells. Moreover, tomatidine decreased the expression of CXCL10 <i>in vitro</i> and <i>in vivo</i>, which was accompanied by the regulation of the NF-κB pathway. However, the NF-κB pathway agonist PMA reversed the protective effect of tomatidine <i>in vitro</i>. PMA also enhanced the CXCL10 expression and stimulated the activation of the NF-κB pathway, as demonstrated by the upregulation of phosphorylated p65. The CXCL10 inhibitor had effects similar to tomatidine on cleaved-caspase 3 expression, CXCL10 expression, and the NF-κB pathway.</p><p><strong>Conclusion: </strong>Tomatidine can alleviate neuronal damage in SCI by inhibiting apoptosis and inflammation through the NF-κB/CXCL10 pathway. Our findings provide a novel therapeutic target and candidate for the treatment of SCI.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1503925"},"PeriodicalIF":4.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of danshen class injections in the treatment of coronary heart disease: a network meta-analysis.","authors":"Shuang Dai, Yukun Ding, Jianbo Guo, Xian Wang","doi":"10.3389/fphar.2024.1487119","DOIUrl":"10.3389/fphar.2024.1487119","url":null,"abstract":"<p><strong>Background: </strong>Danshen [Salvia miltiorrhiza Bunge (Lamiaceae; Salviae miltiorrhizae radix et rhizoma)] class injections (DSCIs) are widely used in the treatment of coronary heart disease (CHD). However, there are various types of DSCIs available on the market, and it remains uncertain which DSCI has the best clinical efficacy, as well as which one is most effective in regulating inflammatory markers and oxidative stress indicators. The aim of this network meta-analysis (NMA) is to compare the therapeutic effects of different DSCIs to identify the optimal DSCI for the treatment of CHD.</p><p><strong>Methods: </strong>The databases searched to identify randomized controlled trials (RCTs) of DSCIs for CHD included the China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (CBM), PubMed, Web of Science, and Cochrane Library. The search period spanned from the inception of each database up to June 2024. NMA was conducted using RevMan 5.3 and Stata 16.0 software.</p><p><strong>Results: </strong>A total of 106 studies including 14,979 patients, involving 10,931 patients, with 5,640 in the experimental group and 5,291 in the control group. And ten DSCIs were extracted, namely: Danhong injection (DH), Danshen injection (DS), Danshenchuanxiongqin injection (DSCXQ), Dansenduofensuanyan injection (DSDFSY), Danshenfen injection (DSFZ), Fufang Danshen injection (FFDS), Guanxinning injection (GXN), Sodium Tanshinone IIA Sulfonate injection (STS), Xiangdan injection (XD), Shenxiongputaotang injection (SXPTT). The results of NMA showed that, XD injection significantly enhances clinical efficacy; STS is more effective in reducing hs-CRP levels; DSDFSY shows better efficacy in decreasing IL-1 and increasing NO levels; DSCXQ has a greater advantage in reducing IL-6 levels; GXN is more effective in regulating SOD levels; and DH is better at reducing MDA levels.</p><p><strong>Conclusion: </strong>The combined treatment of DSCIs and WM more significant efficacy in patients with CHD compared to WM treatment alone, including clinical efficacy evaluation, inflammatory markers, and oxidative stress markers. Overall, DSDFSY and DSCXQ show better performance in clinical efficacy evaluation and regulation of inflammatory markers, while DH exhibits a more stable effect in regulating oxidative stress. However, larger sample sizes and high-quality RCTs are still necessary to further compare the various DSCIs.</p><p><strong>Systematic review registration: </strong>[PROSPERO], identifier [CRD42024548928].</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1487119"},"PeriodicalIF":4.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11669530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attenuation of neutrophil adhesion and formation of neutrophil extracellular traps by pooled human immune globulins.","authors":"Vidhya R Rao, Sana Iqbal, Bradford A Young, Christine Mun, Sandeep Jain, Simon Kaja","doi":"10.3389/fphar.2024.1465776","DOIUrl":"10.3389/fphar.2024.1465776","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated the efficacy of pooled human immune globulins (Flebogamma^® DIF) to combat the formation of neutrophil extracellular traps (NETs) and NETosis, along with neutrophil adhesion to corneal epithelial cells in response to dry eye disease relevant stimuli.</p><p><strong>Methods: </strong>Human neutrophils were isolated by bead-based immunomagnetic depletion of non-target cells from human whole blood. NETosis was induced using phorbol 12-myristate 13-acetate (PMA) or anti-citrullinated histone 4 R3 antibody (H4R3 ACPA). Extracellular DNA was used as a surrogate biomarker of NETosis, and it was quantified using a 96-well, plate reader-based fluorescent assay and by confocal microscopy in 8-well chambers using the DNA dye, SYTOX^TM Green. Neutrophils were labeled with calcein-AM and adhesion to human corneal epithelial cells was measured. The efficacy of a dose-range of pooled human immune globulin (Flebogamma^® DIF, 0.01%-5%) was tested in all assays.</p><p><strong>Results: </strong>Pooled human immune globulins (Flebogamma^® DIF) dose-dependently inhibited both PMA and H4R3 ACPA induced NETosis, with concentrations ≥2.5% fully preventing release of extracellular DNA over a 2-16 h time period. Similarly, Flebogamma^® 5% DIF prevented NETosis against PMA (20 nM) and a dose range (0.1-10 μg/mL) of H4R3 ACPA. Both PMA and H4R3 ACPA increased adhesion of neutrophils to corneal epithelial cells by 20% and 5%, respectively. Flebogamma^® DIF treatment resulted in a dose-dependent reduction of neutrophil adhesion, with Flebogamma^® 5% DIF reducing adhesion to baseline levels.</p><p><strong>Discussion: </strong>These findings show the dose-dependent efficacy of pooled human immune globulins, specifically Flebogamma^® DIF against experimentally and pathologically induced NETosis and neutrophil adhesion to corneal epithelial cells, <i>in vitro</i>. The results from this study support the continued clinical development of Flebogamma^® 5% DIF as a novel and efficacious treatment for the signs and symptoms of dry eye disease.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1465776"},"PeriodicalIF":4.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ailanthone blocks mitophagy to promote mtDNA leakage through BAX-BAK1 pores and suppress hepatocellular carcinoma cell proliferation.","authors":"Yan Qin, Ying Gao, Dan Wu, Qing-Qing Liu, Chang Su, Guan Liu, Le Yang, Ming-Gao Zhao, Jing-Yue Yao","doi":"10.3389/fphar.2024.1509482","DOIUrl":"10.3389/fphar.2024.1509482","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC), the third leading cancer mortality worldwide, shows rising incidence. The mitochondria in HCC cells are prone to damage from metabolic stress and oxidative stress, necessitating heightened mitophagy for mitochondrial homeostasis and cell survival. Thus, mitophagy inhibition is a promising HCC therapy. The traditional Chinese medicinal herb ailanthone have proved promote mitochondrial dysfunction and inhibits HCC. However, the underlying mechanism remains unclear.</p><p><strong>Methods: </strong>CCK8 assay was applied to detect the proliferation. JC-1, MitoTracker Red/Green and MitoSOX staining were applied to detect the mitochondrial homeostasis. Inflammatory factors were analysed via ELISA and WB assay. Mitochondria and cytoplasm separation, genome extraction and qPCR were used to detect mitochondrial DNA (mtDNA) leakage. Mitochondria ultrastructure was detected by transmission electron microscopy. WB and IHC experiments were applied to detect protein expression. Protein-protein interactions detected by immunoprecipitation and immunofluorescence imaging. The <i>in vivo</i> antitumor effect was validated by the xenograft mouse model.</p><p><strong>Results: </strong>In this study, we demonstrated the potent anti-HCC properties of ailanthone and revealed its molecular mechanism. <i>In vitro</i> studies demonstrated that ailanthone effectively inhibited PINK1-PRKN mediated mitophagy and promoted BAX-BAK1 mitochondrial pores formation through PRKN inhibition. This process led to the mitochondrial mtDNA leakage into the cytoplasm, which subsequently triggered the induction of inflammatory factors. The inhibition of mitophagy and the activation of inflammatory response ultimately led to HCC proliferation inhibition. In vivo studies demonstrated that ailanthone exhibited stronger anti-HCC activity than 5-Fluorouracil (5-FU), with no significant adverse effects on animal body weight or the physiological functions of vital organs.</p><p><strong>Conclusion: </strong>This study highlighted the efficacy of ailanthone against HCC and elucidated its underlying molecular mechanisms, suggesting the promising therapeutic potential of ailanthone for HCC.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1509482"},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Peptides against infectious diseases: from antimicrobial peptides to vaccines.","authors":"Joanna Bojarska, Xiumin Wang, Mariusz Skwarczynski","doi":"10.3389/fphar.2024.1522148","DOIUrl":"10.3389/fphar.2024.1522148","url":null,"abstract":"","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1522148"},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of inhaled nitric oxide on bronchopulmonary dysplasia in preterm infants with PPHN or HRF at birth: a propensity score matched study.","authors":"Xue-Rong Huang, Lian Wang, Guo-Bao Liang, Sheng-Qian Huang, Bao-Ying Feng, Lu Zhu, Xu-Fang Fan, Mu-Lin Yao, Jing Zhang, Meng-Jiao Wang, Zhi Zheng, Yao Zhu, Wen-Li Duan, Zhan-Kui Li, Jian Mao, Li Ma, Fa-Lin Xu, Fan Wu, Qiu-Fen Wei, Ling Liu, Xin-Zhu Lin","doi":"10.3389/fphar.2024.1515030","DOIUrl":"10.3389/fphar.2024.1515030","url":null,"abstract":"<p><strong>Background: </strong>Bronchopulmonary Dysplasia (BPD) is a chronic lung disease affecting preterm infants, with limited prevention and treatment options. Inhaled Nitric Oxide (iNO) is sometimes used to treat Persistent Pulmonary Hypertension of the Newborn (PPHN) and Hypoxemic Respiratory Failure (HRF), and its impact on BPD development remains debated.</p><p><strong>Objective: </strong>To assess whether iNO-related factors are potential contributors to the development of BPD Grade Ⅱ-Ⅲ in very premature infants (VPI) diagnosed with PPHN or HRF at birth using Propensity Score Matching (PSM).</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of infants born at 22-32 weeks gestation with PPHN or HRF, treated with iNO for over 3 h. PSM matched groups by gestational age, birth weight, and gender, etc. Multivariate logistic regression evaluated the association between iNO treatment and BPD outcomes to identify influencing factors, while Restricted Cubic Spline (RCS) and mediation analysis examined iNO dose effects and potential mediators like mechanical ventilation time and oxygenation index (OI).</p><p><strong>Results: </strong>A higher initial iNO dose was significantly associated with a reduced risk of BPD Grade Ⅱ-Ⅲ (<i>adjusted OR = 0.68, 95% CI: 0.52-0.89, p < 0.01</i>). Additionally, administration of iNO within the first 7 days of life was identified as an important influencing factor No significant mediation effects were observed for factors such as mechanical ventilation time and OI.</p><p><strong>Conclusion: </strong>A higher initial iNO dose within the first 7 days was associated with a reduced risk of BPD Grade Ⅱ-Ⅲ in VPI with PPHN or HRF.</p>","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"15 ","pages":"1515030"},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}