Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Targeting Nrf2/HO-1, NF-κB, and Apoptotic Pathways: Mechanistic Evaluation of Phlorizin Nanoparticles in Diabetic Renal Injury.","authors":"Ahmed M S Hegazy, Nasser S Alqahtani, Ayat B Al-Ghafari, Huda A Al Doghaither, Ekramy M Elmorsy, Noha Osama El-Shaer, Dania Abdelhady","doi":"10.1111/1440-1681.70129","DOIUrl":"https://doi.org/10.1111/1440-1681.70129","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a chronic metabolic disorder associated with hyperglycemia, dyslipidemia, oxidative stress, inflammation, apoptosis, and renal dysfunction. Although phlorizin (PHL) possesses well-documented antidiabetic properties, its clinical applicability is limited by poor bioavailability and rapid metabolism, which may restrict its therapeutic efficacy. This study evaluated the therapeutic potential of phlorizin (PHL) and its chitosan nanoparticle formulation (PHL-CSNPs) in streptozotocin (STZ)-induced type 1 diabetic rats. Ninety adult male albino rats were randomly divided into six groups (n = 15 each): non-diabetic control, non-diabetic treated with crude PHL, non-diabetic treated with PHL-CSNPs, diabetic untreated (STZ-induced T1DM), diabetic treated with crude PHL, and diabetic treated with PHL-CSNPs. STZ-induced T1DM caused significant reductions in serum insulin, body weight gain, renal antioxidant defences, and mitochondrial function, accompanied by marked elevations in fasting blood glucose, dyslipidemia, oxidative stress markers, pro-inflammatory cytokines, apoptotic markers, and renal fibrotic mediators, as well as pronounced histopathological and ultrastructural kidney damage. In diabetic rats, treatment with PHL-CSNPs significantly improved insulin levels, glucose homeostasis, and body weight, restored lipid profiles and antioxidant enzyme activities, enhanced mitochondrial respiratory complex activities and ATP production, suppressed NF-κB-mediated inflammation, upregulated Nrf2/HO-1 signalling, decreased Bax and caspase-3 levels, increased Bcl-2 levels, and reduced TGF-β1-mediated fibrosis. Crude PHL provided moderate protective effects but was consistently less effective than the nanoparticle formulation. Importantly, the chitosan nanoparticle formulation markedly enhanced the therapeutic efficacy of PHL, likely by improving its stability, bioavailability, and renal tissue delivery, thereby producing stronger antioxidant, anti-inflammatory, and anti-apoptotic effects than crude PHL. Non-diabetic rats treated with either PHL or PHL-CSNPs maintained normal metabolic and renal parameters, confirming the safety of the treatments. Histopathological and ultrastructural analyses further confirmed the preservation of renal architecture in PHL-CSNP-treated diabetic rats. Collectively, this study demonstrates that nanoencapsulation significantly potentiates the biological activity of PHL, providing a clear therapeutic advantage over the crude compound. Overall, these findings demonstrate that PHL-CSNPs provide superior nephroprotective, antioxidant, anti-inflammatory, and metabolic benefits, highlighting their potential as a promising therapeutic strategy for managing type 1 diabetes-induced metabolic and renal complications.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":"e70129"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834410","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}

{"title":"Ginsenoside Rg1 Improves Cardiac Function and Ventricular Remodelling by Down-Regulating SH2B Adaptor Protein 1 Expression in Rats With Myocardial Infarction.","authors":"Na Xiang, Jiayun Hu, Xueting Luo","doi":"10.1111/1440-1681.70121","DOIUrl":"https://doi.org/10.1111/1440-1681.70121","url":null,"abstract":"<p><strong>Objective: </strong>Acute myocardial infarction (AMI) remains the leading global cause of mortality. This study explored the mechanism by which ginsenoside Rg1 (Rg1) ameliorates cardiac function and ventricular remodelling (VR) in rats with AMI by regulating SH2 domain-containing adapter protein B1 (SH2B1).</p><p><strong>Methods: </strong>An AMI rat model was established by ligating the left anterior descending coronary artery. Gain- and loss-of-function experiments were conducted to explore the role of SH2B1 in mediating cardioprotective effects of Rg1. Cardiac function and VR were evaluated using echocardiography, enzyme-linked immunosorbent assay (ELISA) and histological staining. RT-qPCR and western blot were employed to analyse SH2B1 expression and molecular docking to predict the binding affinity between Rg1 and SH2B1.</p><p><strong>Results: </strong>Rg1 improved echocardiographic parameters, decreased levels of pro-inflammatory cytokines, reduced infarct size, weakened myocardial tissue cell apoptosis, diminished blue collagen fibre deposition and reduced the proportion of α-smooth muscle actin-positive cells in myocardial tissues of rats with AMI in a dose-dependent manner within a certain range. Additionally, SH2B1 mRNA and protein expression was elevated in the myocardial tissue of AMI rats and Rg1 dose-dependently reduced SH2B1 expression. A binding energy of -2.14 kcal/mol was observed between Rg1 and SH2B1, indicating a potential interaction. SH2B1 knockdown improved cardiac function and VR in rats with AMI, and SH2B1 overexpression partially counteracted the beneficial effects of Rg1 in AMI rats.</p><p><strong>Conclusion: </strong>Rg1 improves cardiac function and VR in rats with AMI by down-regulating SH2B1; these effects are partially nullified by SH2B1 overexpression.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":"e70121"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764143","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}

{"title":"Ciliatoside A Improves Klebsiella pneumoniae-Induced Pneumonia by Modulating Mitochondrial Autophagy via the SIRT1/PINK1/Parkin Pathway.","authors":"Jingxuan Zhu, Lingling Zhou, Xiaoqin Li","doi":"10.1111/1440-1681.70125","DOIUrl":"https://doi.org/10.1111/1440-1681.70125","url":null,"abstract":"<p><strong>Background: </strong>Klebsiella pneumoniae (KP)-induced pneumonia has a high incidence rate, and current treatment options remain limited. The efficacy and mechanism of the novel natural compound Ciliatoside A (CA) against KP-induced pneumonia remain unclear.</p><p><strong>Aims: </strong>Investigating whether CA improves KP-induced pneumonia through the sirtuin 1 (SIRT1)/PTEN-induced putative kinase 1 (PINK1)/Parkin axis.</p><p><strong>Methods: </strong>KP was used to infect A549 cells, and resistance genes expression was detected using qRT-PCR. To evaluate CA's effect on cell viability, the Cell Counting Kit-8 assay was utilised. Different kits were employed to measure mitochondrial membrane potential, mitochondrial reactive oxygen species (mtROS), and ATP production. Transmission electron microscopy was used to observe autophagosome formation, and cellular autophagy was assessed via Western blot and LC3 fluorescence analysis. Flow cytometry, PI/Hoechst staining, and ELISA were employed to investigate the impacts of CA on A549 cell death and cytokine secretion. A KP mouse pneumonia model was established. Pathological staining was used to observe lung tissue damage and inflammatory infiltration, and Western blot was employed to validate protein expression in vivo. To verify whether CA alleviates KP-induced pneumonia through the SIRT1/PINK1/Parkin axis, intervention with SIRT1 agonists/inhibitors was conducted.</p><p><strong>Results: </strong>CA treatment downregulated drug resistance genes in KP and A549 cells, enhanced the viability of A549 cells following KP infection, and inhibited apoptosis. CA reduced mtROS accumulation, increased mitochondrial membrane potential and ATP production, promoted mitochondrial autophagy, and inhibited NLRP3-mediated inflammasome-mediated cell death. Additionally, CA alleviated pulmonary edema and pathological damage in mice following KP infection, while inhibiting apoptosis and pulmonary inflammation. Following KP infection, the SIRT1/PINK1/Parkin axis was blocked in A549 cells and mouse lung tissue; CA treatment activated this pathway. SIRT1 agonists enhanced the protective impact of CA against KP infection in A549 cells and mouse lung tissue, while SIRT1 inhibitors reduced the protective effect of CA.</p><p><strong>Conclusion: </strong>CA improves KP-induced pneumonia through activating the SIRT1/PINK1/Parkin axis to regulate mitochondrial autophagy.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":"e70125"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764111","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}

{"title":"Epigallocatechin gallate for Parkinson's disease.","authors":"Consolato M Sergi","doi":"10.1111/1440-1681.13691","DOIUrl":"https://doi.org/10.1111/1440-1681.13691","url":null,"abstract":"<p><p>In the last couple of decades, we have experienced increased use of nutraceuticals worldwide with a demand for organic foods, which has been elevated to an extent probably unmatched with other periods of our civilization. One of the nutraceuticals that gained attention is epigallocatechin gallate (EGCG), a polyphenol in green tea. It has been suggested that diseases of the central nervous system can benefit from consuming some antioxidants, despite current results showing little evidence for their use in preventing and treating these diseases. ECGC may be beneficial in delaying the neurodegeneration of the substantia nigra regardless of the origin of Parkinson's disease (PD). This review covers the effect of EGCG on vitro and animal models of PD, the potential mechanisms of neuroprotection involved and summaries recent clinical trials in human PD. This review also aims to provide an investigative analysis of the current knowledge in this field and to identify putative crucial issues. Environmental factors such as dietary habits, drug use and social interaction are all factors that influence the evolution of neurodegenerative diseases. Therefore, the use of nutraceuticals requires further investigation.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":" ","pages":"1029-1041"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40393605","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}

{"title":"Potential role of cellular senescence in pulmonary arterial hypertension.","authors":"Lumei Liu,&nbsp;Yaqin Wei,&nbsp;Sergio Giunta,&nbsp;Qinghu He,&nbsp;Shijin Xia","doi":"10.1111/1440-1681.13696","DOIUrl":"https://doi.org/10.1111/1440-1681.13696","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a rare and chronic lung vasculature disease characterised by pulmonary vasculature remodelling, including abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional endothelial cells (ECs). Remodelling of the pulmonary vasculature occurs from maturity to senescence, and it has become apparent that cellular senescence plays a central role in the pathogenesis of various degenerative vascular diseases and pulmonary pathologies. Cellular senescence represents a state of stable proliferative arrest accompanied by the senescence-associated secretory phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment. Evidence shows that in PAH patients, higher levels of cytokines, chemokines and inflammatory mediators can be detected and correlate with clinical outcome. Moreover, senescent cells accrue with age in epithelial, endothelial, fibroblastic and immunological compartments within human lungs, and evidence has shown that ECs and PASMCs in lungs from patients with chronic obstructive pulmonary disease were characterised by a higher number of senescent cells. However, there is little evidence uncovering the molecular pulmonary vasculature senescence in PAH. Herein, we review the cellular senescence in pulmonary vascular remodelling, and emphasise its importance in PAH. We further introduce some signalling pathways which might be involved in vasculature senescence and PAH, with the intent to discuss the possibility of the PAH therapy via targeting cellular senescence and reduce PAH progression and mortality.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":" ","pages":"1042-1049"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40395182","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}

{"title":"Erythema induratum of Bazin after intravesical Bacillus Calmette-Guérin immunotherapy.","authors":"Lamiaa Hamie,&nbsp;Ossama Abbas,&nbsp;Souha Kanj-Sharara,&nbsp;Jihane Abou Rahal","doi":"10.1111/1440-1681.13619","DOIUrl":"https://doi.org/10.1111/1440-1681.13619","url":null,"abstract":"Bacillus CalmetteGuérin (BCG) is a liveattenuated strain of Mycobacterium bovis. It is recognised as an effective agent for the treatment of superficial bladder cancer and has been used in the form of a vaccine primarily against tuberculosis infections. Both applications are not devoid of complications.1 Intravesical BCG can be associated with local and systemic infectious complications which are usually selflimited, but in about 5% of patients serious side effects can occur.1 BCG vaccination on the other hand is notoriously known for its cutaneous side effects. Overall, localised abscesses, ulcers or regional suppurative lymphadenitis are the most common complications.2 Disseminated disease is much rarer and is usually associated with cellmediated immune deficiencies.2 Nonetheless, when dissemination occurs it often results in mortality.2 Here we present a unique cutaneous complication due to intravesical BCG: erythema induratum (EI) of Bazin. A 69yearold woman with bladder cancer presented to us for recurrent, disseminated, tender lesions over the trunk and extremities associated with highgrade fever. The lesions appeared 1 month after the last dose of intravesical Bacillus CalmetteGuérin (BCG). The patient was referred to us for persistent lesions and fever, not responding to levofloxacin and systemic corticosteroids. On exam, erythematoviolaceous subcutaneous nodules on the legs were appreciated (Figure 1). Similar smaller papules on the lower back, trunk, and upper extremities were noted as well. Initial blood workup was nonrevealing. A computed tomography of the chest and abdomen revealed scattered lymphadenopathy. Three sets of blood cultures, bacterial identification by 16s DNA sequencing, acidfast bacilli (AFB) smear and mycobacterial culture were nonrevealing. PPD and urine Mycobacterium tuberculosis PCR and AFB smear were negative as well. Histological examination of the nodules revealed a predominantly lobular panniculitis with mixed inflammatory cell infiltrate composed of lymphocytes, neutrophils, eosinophils, and histiocytes with focal granuloma formation (Figure 2A). Focal necrosis and vasculitic changes of small vessels were also noted (Figure 2B). Bacterial, fungal, mycobacterial cultures, AFB smear, special stains and TB PCR failed to identify any organisms. These findings were highly suggestive of EI. The patient showed significant improvement 6 months after starting prednisone and antituberculosis therapy with rifampin, isoniazid and ethambutol. Followed by a mild relapse after treatment discontinuation which eventually selfresolved. Erythema induratum is primarily regarded as a tuberculid since it occurs more frequently in populations with a high prevalence of tuberculosis, with frequent detection of mycobacterial DNA in the cutaneous lesions. Tuberculids are a cutaneous hypersensitivity towards the presence of the bacilli elsewhere in the body.3 They usually appear in patients who can mount a strong immunity against the Myc","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"49 4","pages":"544-545"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39750952","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}

{"title":"The effect of the protective face mask on cardiorespiratory response during aerobic exercise.","authors":"Danilo Marcelo Leite do Prado,&nbsp;Valmir Oliveira Silvino,&nbsp;Daisy Motta-Santos,&nbsp;Marcos Antônio Pereira Dos Santos","doi":"10.1111/1440-1681.13624","DOIUrl":"https://doi.org/10.1111/1440-1681.13624","url":null,"abstract":"<p><p>The protective face mask (PFM) has been widely used for safety purposes and, after the advent of the COVID-19 pandemic, its use is growing steadily, not only among healthcare personnel but also the general population. While the PFM is important to preserve the wearer from contaminating agents present in the airflow, they are well known to increase the subjective perception of breathing difficulty. Although some studies have demonstrated that PFM use worsens exercise tolerance, several studies state that there is no such limitation with the use of PFM. Moreover, no serious adverse effects during physical exercise have been found in the literature. Physical exercise represents a significant challenge to the human body through a series of integrated changes in function that involve most of its physiologic systems. In this respect, cardiovascular and respiratory systems provide the capacity to sustain physical tasks over extended periods. Within this scenario, both convective oxygen (O₂ ) transport (product of arterial O₂ content × blood flow) to the working locomotor muscles and O₂ diffusive transport from muscle capillaries to mitochondria are of paramount importance to endurance performance. Interestingly, the effects of PFM on cardiorespiratory response during aerobic exercise depends on the type of mask and exercise (i.e., walking, running, or cycling), the ventilatory demands, arterial oxygen levels, maximal oxygen consumption and endurance performance. The purpose of this review is to elucidate the effect of protective face mask-wearing on (1) cardiorespiratory responses during aerobic exercise and (2) endurance performance.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"49 4","pages":"453-461"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39729792","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}

{"title":"Necrostatin-1 mitigates renal ischaemia-reperfusion injury - time dependent - via aborting the interacting protein kinase (RIPK-1)-induced inflammatory immune response.","authors":"Hend Ashour,&nbsp;Heba A Hashem,&nbsp;Akef A Khowailed,&nbsp;Laila A Rashed,&nbsp;Randa M Hassan,&nbsp;Ayman S Soliman","doi":"10.1111/1440-1681.13625","DOIUrl":"https://doi.org/10.1111/1440-1681.13625","url":null,"abstract":"<p><p>The recently defined necroptosis process participates in the pathophysiology of several tissue injuries. Targeting the necroptosis mediator receptor-interacting protein kinase (RIPK1) by necrostatin-1 in different phases of ischaemia-reperfusion injury (IRI) may provide new insight into the protection against renal IRI. The rat groups included (n = 8 in each group): 1) Sham; 2) Renal IRI; 3) Necrostatin-1 treatment 20 min before ischaemia induction in a dose of 1.65 mg/kg/intravenous; 4) Necrostatin-1 injection just before reperfusion; 5) Necrostatin-1 injection 20 min after reperfusion establishment; and 6) drug injection at both the pre-ischaemia and at reperfusion time in the same dose. Timing dependent, necrostatin-1 diminished RIPK1 (p < 0.001), and aborted the necroptosis-induced renal cell injury. Necrostatin-1 decreased the renal chemokine (CXCL1), interleukin-6, intercellular adhesion molecule (ICAM-1), myeloperoxidase, and the nuclear factor (NFκB), concomitant with reduced inducible nitric oxide synthase (iNOS), inflammatory cell infiltration, and diminished cell death represented by apoptotic cell count and the BAX/Bcl2 protein ratio. In group 6, the cell injury was minimal and the renal functions (creatinine, BUN and creatinine clearance) were almost normalised. The inflammatory markers were diminished (p < 0.001) compared to the IRI group. The results were confirmed by histopathological examination. In conclusion, RIPK1 inhibition ameliorates the inflammatory immune response induced by renal IRI. The use of two doses was more beneficial as the pathophysiology of cell injury is characterised.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"49 4","pages":"501-514"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39729789","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}

{"title":"Pretreatment with nicotinamide mononucleotide increases the effect of ischaemic postconditioning on cardioprotection and mitochondrial function following ex vivo myocardial reperfusion injury in aged rats.","authors":"Mojgan Rajabi,&nbsp;Manouchehr S Vafaee,&nbsp;Leila Hosseini,&nbsp;Reza Badalzadeh","doi":"10.1111/1440-1681.13616","DOIUrl":"https://doi.org/10.1111/1440-1681.13616","url":null,"abstract":"<p><p>The present study aims to evaluate the combined effect of ischaemic postconditioning (IPostC) and nicotinamide mononucleotide (NMN) on cardioprotection and mitochondrial function in aged rats subjected to myocardial ischaemia-reperfusion (IR) injury. Sixty aged Wistar rats were randomly divided into five groups (n = 12), including sham, control, NMN, IPostC, and NMN + IPostC. Regional ischaemia was induced by 30-min occlusion of the left anterior descending coronary artery (LAD) followed by 60-min reperfusion. IPostC was applied at the onset of reperfusion, by six cycles of 10-s reperfusion/ischaemia. NMN (100 mg/kg) was intraperitoneally injected every other day for 28 days before IR. Myocardial haemodynamics and infarct size (IS) were measured, and the left ventricles samples were harvested to assess cardiac mitochondrial function. The results showed that all treatments reduced lactate dehydrogenase release compared to those of the control group. IPostC alone failed to reduce IS and myocardial function. However, NMN and combined therapy could significantly improve myocardial function and decrease the IS compared to the control animals. Moreover, the effects of combined therapy on the decrease of IS, mitochondrial reactive oxygen species (ROS), and improvement of mitochondrial membrane potential (MMP) were greater than those of stand-alone treatments. These results demonstrated that cardioprotection by combined therapy with NMN + IPostC was superior to individual treatments, and pretreatment of aged rats with NMN was able to correct the failure of IPostC in protecting the hearts of aged rats against IR injury.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"49 4","pages":"474-482"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39796622","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}

{"title":"High expression of NPM1 via the Wnt/β-catenin signalling pathway might predict poor prognosis for patients with prostate adenocarcinoma.","authors":"Yong Ruan,&nbsp;Houqiang Xu,&nbsp;Xinqin Ji","doi":"10.1111/1440-1681.13628","DOIUrl":"https://doi.org/10.1111/1440-1681.13628","url":null,"abstract":"<p><p>Prostate adenocarcinoma (PRAD) occurs only in males and has a higher incidence rate than other cancers. NPM1 is a nucleocytoplasmic shuttling protein that participates in the development of multiple tumours. The aim of this research was to explore the effect of the upregulation or downregulation of the NPM1 protein on the malignancy of prostate cancer and its possible signalling pathway. Prostate adenocarcinoma cell lines were used in this study, including RWPE-1, PC3, LNCap, and 22RV1 cells. Our research revealed that NPM1 was widely expressed in the PRAD cell lines, as determined by western blotting, and that the levels of NPM1 protein were positively correlated with the degree of malignancy of the PRAD cell lines. Through interference and overexpression experiments, we found that PC3 cell growth was inhibited after NPM1 knockdown and that this inhibition was partly reversed by CTNNB1 overexpression; in contrast, PC3 cells growth was promoted after NPM1 overexpression, and this promotion was partly reversed by CTNNB1 knockdown, suggesting that NPM1 and CTNNB1 play important roles in the progression of prostate cancer cells via the Wnt/β-catenin signalling pathway. NPM1 may serve as an important biomarker and candidate therapeutic for patients with prostate cancer.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"49 4","pages":"525-535"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39881022","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}