Clinical and Experimental Pharmacology and Physiology最新文献

{"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}

{"title":"A single bout of exhaustive treadmill exercise increased AMPK activation associated with enhanced autophagy in mice skeletal muscle.","authors":"Ping Wang,&nbsp;Chun Guang Li,&nbsp;Xian Zhou,&nbsp;Di Cui,&nbsp;Ting Ouyang,&nbsp;Weikai Chen,&nbsp;Shuzhe Ding","doi":"10.1111/1440-1681.13632","DOIUrl":"https://doi.org/10.1111/1440-1681.13632","url":null,"abstract":"<p><p>Previous studies reported inconsistent findings on autophagy activation in skeletal muscles after acute exercise. In this study, we investigated the effect of a single bout of exhaustive treadmill exercise on AMPK and autophagy activations in mice gastrocnemius muscle in vivo. Male ICR/CD-1 mice were randomly divided into the control and exercise groups. The later was subjected to a single bout of exhaustive treadmill exercise. Changes of AMPK, phosphorylation of AMPK^Thr172 (pAMPK^Thr172 ), and autophagy markers including Beclin1, LC3II/LC3I and p62 mRNA and protein expressions in gastrocnemius muscle at different times (0, 6, 12, 24 h) after the exercise were analysed by quantitative real-time PCR and western blot. Our results demonstrated that a single bout of exhaustive treadmill exercise significantly induced AMPK content and AMPK activity at 0, 6 and 12 h after the exercise, and changed the expressions of autophagy markers at different time points in the recovery period, respectively. Moreover, we observed positive correlations between expressions of LC3II/LC3I ratio and pAMPK^Thr172 or AMPK, and a negative correlation between expressions of p62 and AMPK or pAMPK^Thr172 . In conclusion, a single bout of exhaustive treadmill exercise in mice caused a prolonged activation of AMPK and improved autophagy in the gastrocnemius muscle. The regulation of autophagic markers were related to enhanced AMPK activity. The findings indicate that acute exercise enhanced AMPK-related autophagy activation may be the underlying molecular mechanism that regulates cellular energy metabolism during exercise.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"49 4","pages":"536-543"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39880890","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":"Lipopolysaccharide induces acute lung injury and alveolar haemorrhage in association with the cytokine storm, coagulopathy and AT1R/JAK/STAT augmentation in a rat model that mimics moderate and severe Covid-19 pathology.","authors":"Bahjat Al-Ani,&nbsp;Asmaa M ShamsEldeen,&nbsp;Samaa S Kamar,&nbsp;Mohamed A Haidara,&nbsp;Fahaid Al-Hashem,&nbsp;Mohammad Y Alshahrani,&nbsp;Ahmed M Al-Hakami,&nbsp;Dina H Abdel Kader,&nbsp;Amro Maarouf","doi":"10.1111/1440-1681.13620","DOIUrl":"https://doi.org/10.1111/1440-1681.13620","url":null,"abstract":"<p><p>Progress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin-converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell signalling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being killed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a \"cytokine storm\" (>2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p < 0.0001). In addition, LPS increased the expression of lung angiotensin II type I receptor (AT1R)-JAK-STAT axis (>4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and haemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the interalveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"49 4","pages":"483-491"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39712029","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":"Cross-talk of cholinergic and β-adrenergic receptor signalling in chronic myeloid leukemia K562 cells.","authors":"Banu Aydın,&nbsp;Mehmet Zafer Gören,&nbsp;Zehra Kanlı,&nbsp;Hülya Cabadak","doi":"10.1111/1440-1681.13627","DOIUrl":"https://doi.org/10.1111/1440-1681.13627","url":null,"abstract":"<p><p>In many studies on breast, skin and intestinal cancers, β-adrenergic receptor antagonists have been shown to inhibit cell proliferation and angiogenesis and increase apoptosis in cancers. Carbachol inhibits chronic myeloid leukaemia K562 cell proliferation. Beta-blockers are known to inhibit cell progression. The aim of this study is to explain the mechanism of action of β-adrenergic receptors agonists and antagonists on apoptosis in chronic myeloid leukaemia cells. We tried to determine the effect of combined treatment of β-adrenergic and cholinergic drugs on adrenergic β₁ and β₂ gene expression, cell proliferation and apoptosis in chronic myeloid leukaemia K562 cells. Cell proliferation was evaluated by the 5-bromo-2-deoxy-uridine (BrdU) incorporation kit. Caspase 3, 8, 9 activities were measured by the caspase assay kit. Protein expression level was detected by western blotting. We found that exposure to propranolol either by combination with carbachol facilitates additive effects on inhibition of caspase 3 and 8 expression in chronic myeloid leukaemia K562 cells. However, caspase 9 expression level was increased by propranolol alone or with propranolol and carbachol combination. The combined therapy of cholinergic and adrenergic receptor drugs will decrease cell proliferation in K562 cells. This decrease in cell proliferation may be mediated by the mitochondrial-dependent intrinsic apoptosis pathway.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"49 4","pages":"515-524"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39728788","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}