Advances in Clinical and Experimental Medicine最新文献

{"title":"An analysis of the clinical significance of the TKI-resistant gene ZNF687 for hepatocellular carcinoma patients.","authors":"Guan-Lan Zhang, Jian-Di Li, Ji-Feng He, Kun-Jun Wu, Ying-Yu Mo, Song-Yang Zhong, Xuan-Fei Wang, Fei-Fei Wu, Yi-Si Qin, Hong Zhao, Zhi-Guang Huang, Gang Chen, Rong-Quan He","doi":"10.17219/acem/188425","DOIUrl":"https://doi.org/10.17219/acem/188425","url":null,"abstract":"<p><strong>Background: </strong>Novel treatments such as monotherapy and combined immunotherapy significantly extend overall survival (OS) for hepatocellular carcinoma (HCC) patients, but HCC is susceptible to treatment resistance during long-term therapy. The resistance mechanism to targeted drugs in HCC remains ambiguous, making research on HCC drug resistance targets crucial for the development of precision medicine.</p><p><strong>Objectives: </strong>To investigate the transcriptional features, biological functions and potential clinical value of the tyrosine kinase inhibitor (TKI)-resistant gene ZNF687 in HCC.</p><p><strong>Material and methods: </strong>The TKI-resistant genes of HCC were identified using clustered regularly interspaced short palindromic repeats (CRISPR) in vitro screening. Then, the dependence of HCC cell lines on ZNF687 was investigated in silico. We collected global mRNA datasets of HCC tissue, integrated the mRNA expression characteristics of ZNF687 in HCC and explored the impact of ZNF687 on HCC patient prognoses using the Kaplan-Meier method (in silico). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were then conducted, and a connectivity map and molecular docking technology were applied to find the underlying agent opposing ZNF687.</p><p><strong>Results: </strong>In vitro, the guide RNA corresponding to ZNF687 was weakly detected in HCC cells, and ZNF687 deficiency was found to inhibit growth in HCC cell lines. ZNF687 mRNA was overexpressed and had a high discriminatory ability for HCC in 2,975 HCC samples, contrasting with 2,340 non-HCC samples. Moreover, an excessive ZNF687 transcript level was related to a worse overall survival (OS) prognosis. Histone modification, spliceosome, transcription coregulator activity, and nucleocytoplasmic transport were the most significant pathways for ZNF687 differential-related gene enrichment. Chaetocin was found to be a candidate compound and presented a strong affinity to ZNF687.</p><p><strong>Conclusions: </strong>ZNF687 represents a TKI-resistant and growth-dependent gene for HCC, the overexpression of which indicates poor OS for HCC patients. Additionally, ZNF687 is expected to be a druggable target for overcoming TKI resistance, and chaetocin may be a candidate therapeutic compound for ZNF687.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387159","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":"Comparative study of quality of life after aortic valve replacement through partial upper ministernotomy versus full median sternotomy.","authors":"Michał Bociański, Mateusz Puślecki, Martyna Ratajczak, Sebastian Stefaniak, Piotr Buczkowski, Bartłomiej Perek, Marek Jemielity","doi":"10.17219/acem/190454","DOIUrl":"https://doi.org/10.17219/acem/190454","url":null,"abstract":"<p><strong>Background: </strong>Upper ministernotomy for sutureless aortic prosthesis implantation provides an attractive opportunity compared to conventional access. Although in the last decade, the former has gained popularity, data comparing quality of life (QoL) following these procedures are scarce.</p><p><strong>Objectives: </strong>The purpose of this study was to assess the patient's QoL after aortic valve replacement (AVR) using a ministernotomy approach compared to a full sternotomy.</p><p><strong>Material and methods: </strong>One hundred fifteen AVR patients were operated on using either minimally invasive access with sutureless valve implantation through an upper median ministernotomy (group I; n = 58) or through a full sternotomy (group II; n = 57) with either biological Edwards Perimount Magna™ (Edwards Lifescience, Irvine, USA) (n = 30) or mechanical On-X™ (Carbomedics, Austin, USA) (n = 27) aortic valve prostheses implantation by 1 experienced surgeon. At the end of the follow-up period, QoL was assessed using the EQ-5D-5L scale telephone survey.</p><p><strong>Results: </strong>In group I, there were significantly fewer problems with mobility, pain and usual activities than in group II (p < 0.05). Moreover, the visual analogue scale (VAS) and Health Index (HI) scores were more favorable for patients treated with ministernotomy. Additionally, group II participants provided comments beyond the survey questions, such as tiredness, dyspnea or pain. These kinds of remarks were not reported in group I. Ultimately, the EQ-5D-5L Index Score (IS) was consistent with the variables and more beneficial for group I subjects. Each group was compatible with the benefits for patients in group I.</p><p><strong>Conclusions: </strong>Cardiac surgical procedures for severe aortic stenosis through minimally invasive access are associated with improved QoL parameters.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387160","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":"Prognostic factors associated with worse outcomes in patients with GBS: A systematic review.","authors":"Marta Grelowska, Katarzyna Logoń, Edyta Dziadkowiak","doi":"10.17219/acem/186949","DOIUrl":"https://doi.org/10.17219/acem/186949","url":null,"abstract":"<p><p>Guillain-Barré syndrome (GBS) is an autoimmune polyradiculoneuropathy with diverse clinical subtypes, characterized by rapidly evolving motor weakness, sensory disturbances and areflexia. The global prevalence of GBS has been steadily increasing, with regional disparities. Mortality rates vary but remain elevated in patients requiring mechanical ventilation. This systematic review aimed to evaluate the predictive risk factors for the severity of the disease and poor shortand long-term outcomes of GBS. The literature search was conducted using the PubMed database by 2 independently working researchers. After a screening process of studies published before November 2023, a total of 109 articles were selected. Original articles, systematic and narrative reviews, meta-analyses, and editorials were selected based on their clinical relevance. The exclusion criteria included patients under 18 years of age, pregnant women and articles in languages other than English and Polish. Long-lasting GBS complications included pain, fatigue and persistent neurological deficits, affecting patients for years after recovery. Identifying the appropriate therapeutic methods, risk factors and prognoses of GBS at an early stage is crucial. Various risk factors for death and poor functional outcomes were found, regarding patient characteristics, the clinical course of GBS, laboratory and neurographic results, as well as treatment methods.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387162","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":"Chronic acid sphingomyelinase deficiency diagnosed in infancy/childhood in Polish patients: 2024 update.","authors":"Patryk Lipiński, Agnieszka Ługowska, Anna Tylki-Szymańska","doi":"10.17219/acem/193696","DOIUrl":"https://doi.org/10.17219/acem/193696","url":null,"abstract":"<p><strong>Background: </strong>Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive lysosomal storage disease (LSD) associated with biallelic pathogenic variants in the sphingomyelin phosphodiesterase 1 (SMPD1) gene.</p><p><strong>Objectives: </strong>The aim of this study was to provide the 2024 update on chronic visceral and neurovisceral ASMD diagnosed in the infancy/childhood in Polish patients.</p><p><strong>Material and methods: </strong>All the patients diagnosed in the pediatric age (0-18 years) with ASMD, both chronic neurovisceral and visceral type, and then systematically followed up, were enrolled into the study.</p><p><strong>Results: </strong>A total number of 7 patients were enrolled into the study. Four patients were previously reported. Two patients were newly recognized with ASMD - 1 with chronic visceral and 1 with chronic neurovisceral ASMD. Splenomegaly was noted in all the patients while a mild liver enlargement was observed in 4 of 7 patients. All patients presented with decreased high-density lipoprotein cholesterol (HDL-C) and decreased serum 25-hydroxy-vitamin D concentration while almost all (6 of 7) with hypercholesterolemia. Cherry-red spot was observed in 5 of 7 patients, including 1 patient with neurovisceral type. Seven various SMPD1 gene variants were identified and missense variants were the most common types of genetic lesions, comprising 71% of all alleles. In all the screened patients, lyso-sphingomyelin (lyso-SM) in dried blood spot (DBS) was found elevated; however, the greater values were observed for patients with chronic neurovisceral type.</p><p><strong>Conclusion: </strong>Chronic acid sphingomyelinase deficiency (ASMD) is a slowly progressive disease. Pediatric ASMD is characterized by spleno-hepatomegaly, dyslipidemia (with decreased HDL-C as the most characteristic) and infiltrative (interstitial) lung disease. Both visceral and neurovisceral chronic ASMD patients could present with cherry-red spot. Both acid spingomyelinase activity and lyso-spingomyelin concentration in DBS should be regarded as a first-tier screening method into ASMD.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":"33 10","pages":"1163-1168"},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492800","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 clinical impact of plasma estrogen receptor-1 mutation in patients with metastatic breast cancer: A meta-analysis.","authors":"Xiaoli Zhang, Ye Tian, Dan Mo, Wenli Chen, Yi Ding, Yanjiang Yang, Xinning Li","doi":"10.17219/acem/175816","DOIUrl":"10.17219/acem/175816","url":null,"abstract":"<p><strong>Background: </strong>The relevance of the discovered plasma ESR1 mutations in positive metastatic breast cancer (BC) patients who had progressing disease after aromatase inhibitor (AI)-based therapy is still being debated.</p><p><strong>Objectives: </strong>We conducted this meta-analysis to explore the prognostic and predictive role of plasma ESR1 mutations in patients with progressive BC who have previously received AI therapy.</p><p><strong>Material and methods: </strong>We searched for relevant studies in the PubMed, Embase and Cochrane Library databases to be included in the meta-analysis. This study was performed to compute combined hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the progression-free survival (PFS) rate and overall survival (OS) rate. Subgroup and sensitivity analyses were also performed. The heterogeneity between studies was evaluated using the I2 statistic.</p><p><strong>Results: </strong>In this meta-analysis, a total of 1,844 patients with metastatic BC and positive for estrogen receptors (ERs) were enrolled from 8 articles. The analysis revealed that patients with circulating ESR1 mutations had significantly worse PFS (HR: 1.34; 95% CI: 1.17-1.55; p < 0.001) and OS (HR: 1.59; 95% CI: 1.31-1.92; p < 0.001) compared to wild-type ESR1 patients. Subgroup analysis showed that the types of plasma ESR1 mutations were associated with differences in the prognosis of metastatic BC. The D538G mutation showed a statistically significant lower PFS (p = 0.03), while the Y537S mutation was not significantly correlated with PFS (p = 0.354).</p><p><strong>Conclusion: </strong>According to the findings of this meta-analysis, the assessment for plasma ESR1 mutations may provide prognostic and clinical guidance regarding subsequent endocrine therapy decisions for ER-positive, metastatic BC patients who had received prior therapy with AIs.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"1069-1076"},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139728764","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":"Survival time in Alzheimer's disease: An overlooked measure of safety and efficacy of disease-modifying therapies.","authors":"Markku Kurkinen, Timothy Daly","doi":"10.17219/acem/194003","DOIUrl":"10.17219/acem/194003","url":null,"abstract":"<p><p>It is of vital importance to patients and physicians, as well as administrators and drug regulators, that the treatment for a disease has been shown to be safe and clinically meaningful in long-term use. Recent literature has highlighted 3 major categories of arguments for and against modification of the underlying disease process in Alzheimer's disease (AD): pathophysiology, biomarkers and data from clinical trials. We argue that the Alzheimer's arena is over-reliant on theories of disease modification based solely on brain positron emission tomography (PET) imaging and blood biomarkers of tau and Aβ peptides. Here, we instead focus on a historically-grounded empirical criterion from other fields of medicine to overcome the weak interpretations of short Alzheimer's trials: survival time (ST). Our analysis has identified 3 key points. First, if anti-amyloid therapies are AD-modifying treatments, then we argue that they should increase ST more than the standard \"symptomatic\" care with memantine and acetylcholinesterase inhibitors. Second, we question memantine and cholinesterase inhibitors being labeled simply as \"symptomatic\" Alzheimer's drugs since long-term use of them can produce disease modification, that is, increase ST. Third, we make a case for memantine or cholinesterase inhibitors being used as controls in clinical trials with amyloid-lowering and other drugs, and argue against their current under-use in care of Alzheimer's patients.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"1039-1043"},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455724","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":"Autoimmune cytopenias in patients with malignant lymphoma: A multicenter report by the Polish Lymphoma Research Group.","authors":"Magdalena Witkowska, Joanna Drozd-Sokołowska, Anna Waszczuk-Gajda, Agnieszka Giza, Barbara Lewicka, Joanna Zdziarska, Damian Mikulski, Piotr Smolewski","doi":"10.17219/acem/174502","DOIUrl":"10.17219/acem/174502","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune cytopenias (ACs), including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA) and autoimmune granulocytopenia, are rare complications observed in lymphoma patients. They may appear before, during or after lymphoma diagnosis, whether the patients had disease progression or not.</p><p><strong>Objectives: </strong>This study aims to correlate ACs with lymphoma type, disease course and prognosis. We performed a multicenter retrospective analysis of adult patients with malignant lymphoma and ACs coexistence diagnosed and treated in centers aligned with the Polish Lymphoma Research Group (PLRG).</p><p><strong>Material and methods: </strong>The analysis covers the years 2016-2022 and included 51 patients comprised of 23 women and 28 men. Of these, 35 patients were diagnosed with AIHA, 15 patients with ITP and 1 patient with both AIHA and ITP.</p><p><strong>Results: </strong>The most common type of lymphoma was Hodgkin lymphoma (HL) (12 patients) and diffuse large B-cell lymphoma (DLBCL) (14 patients). At the time of diagnosis, 31 (61%) of patients had stage 4 of HL or DLBCL, according to Ann Arbor classification. In total, the response to treatment was evaluated in 50 patients, with 25 being in complete remission and 6 in partial remission. We observed that B cell symptoms (p = 0.036), bone marrow involvement (p = 0.073), splenomegaly (p = 0.025), and more than 2 lines of treatment were more common in AIHA compared to ITP patients. Conversely, eucopenia (p = 0.056) and ACs without lymphoma progression (p = 0.002) were more often diagnosed in ITP patients.</p><p><strong>Conclusions: </strong>In the study group, relapsed and refractory disease was observed more often, and shorter overall survival (OS) was noted in patients with DLBCL. We found that AC is associated with a worse prognosis in comparison to the general population of lymphoma patients. There were no differences in response to AC therapy. To have more accurate data, a larger group, as part of a multicenter study, should be evaluated.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"1097-1104"},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443549","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":"Analysis of aerosol generation during Er:YAG laser-assisted caries treatment: A randomized clinical trial.","authors":"Jacek Matys, Tomasz Gedrange, Marzena Dominiak, Kinga Grzech-Leśniak","doi":"10.17219/acem/174536","DOIUrl":"10.17219/acem/174536","url":null,"abstract":"<p><strong>Background: </strong>Maintaining biosafety in dental practice involves the effective elimination of aerosols produced during dental treatment.</p><p><strong>Objectives: </strong>To assess the quantity of aerosols and aerobic bacteria in the air during the treatment of caries.</p><p><strong>Material and methods: </strong>The study involved 60 patients with a total of 60 molar teeth (n = 60) in the mandible who were divided into 2 groups based on caries treatment method. Group 1 (G1, n = 30) received treatment with a conventional dental turbine (W&H Synea TA-98LC; W&H, Burmoos, Austria), while group 2 (G2, n = 30) underwent treatment with an Er:YAG (erbium-doped yttrium aluminium garnet) laser (LightWalker, Fotona, Slovenia). Measurements of aerosol particles between 0.3 Ęm and 10.0 Ęm near the operatorfs mouth were taken using the PC200 laser particle counter (Trotec GmbH, Schwerin, Germany). The number of aerobic bacteria in the air was determined using 60 Petri plates with a microbiological medium (Columbia agar with 5% sheep blood) and the sedimentation method. A control group (G3) was established to measure initial aerosol levels and initial total number of bacteria colony-forming units (CFUs) before each treatment.</p><p><strong>Results: </strong>In G1 (dental turbine), the median value of aerosol particles was 57,021 (42,564.67,568), while in G2 (Er:YAG laser), it was significantly lower at 33,318 (28,463.35,484) (p < 0.001). The median total bacteria count per cubic meter of air in G1 (conventional dental turbine + high volume evacuator (HVE)), G2 (Er:YAG laser + HVE) and G3 (control group before caries treatment) were 734 (420.988), 158 (96.288) and 48 (32.74), respectively, with a statistically significant difference between the groups (p < 0.001).</p><p><strong>Conclusions: </strong>The use of Er:YAG laser during caries treatment resulted in a 41.6% reduction in aerosol amounts and a 78.5% decrease in the total bacterial count (TBC) compared to treatment with a dental turbine.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"1087-1095"},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097111","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":"Fixed appliances orthodontic therapy as a risk factor for caries development: Systematic review.","authors":"Irena Duś-Ilnicka, Maciej Jedliński, Simone Padella, Denise Corridore, Marta Mazur","doi":"10.17219/acem/174444","DOIUrl":"10.17219/acem/174444","url":null,"abstract":"<p><p>Orthodontic treatment is often mandatory to improve the patient's health condition. However, the fixed appliance can create additional plaque retention areas, which can increase the risk of caries development. Clinically, one can observe various effects of fixed appliance treatment on caries prevalence. This study aims to analyze to what extent orthodontic therapy with fixed appliances is a risk factor for developing caries in pediatric and adult patients. The keywords used in the search strategy were as follows: (\"caries\" AND \"caries risk\" AND \"caries experience\" AND\" \"orthodontic treatment\" OR \"fixed appliance\" \") and (\"caries experience\" AND \"orthodontic treatment\").From 808 potential articles, 15 were included in the review. In individuals undergoing fixed orthodontic therapy, several factors can increase the risk of car-ies during fixed orthodontic treatment, such as salivary composition, oral dysbiosis and plaque accumulation. On the other hand, factors that reduce caries risk are, i.e., oral hygiene self-awareness and previous orthodontic treatment. In most studies which used the Decayed, Missing, and Filled Teeth (DMFT) index, there were no significant differences between the values obtained before orthodontic treatment and after the treatment. Moreover, it is easier for a patient with aligned teeth to remove plaque.In the young population, fixed orthodontic treatment appears to reduce the incidence of caries. In the adult population, fixed orthodontic treatment increases the risk of dental caries. However, education on proper oral hygiene during orthodontic treatment can reduce the risk of dental caries. The study protocol was registered in the PROSPERO database [PROSPERO CRD42022356628].</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"1153-1161"},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097113","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":"Unraveling the therapeutic potential of ginsenoside compound Mc1 in Alzheimer's disease: Exploring the role of AMPK/SIRT1/NF-κB signaling pathway and mitochondrial function.","authors":"Qi Yuan, Zhaokun Yang","doi":"10.17219/acem/175049","DOIUrl":"10.17219/acem/175049","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a disabling neurodegenerating disorder characterized by chronic neuroinflammation, cognitive impairment and memory loss. Current treatment options for AD offer limited benefits, underscoring the urgent need for alternative therapeutics. Despite the promising effects of ginsenosides in neurodegenerative diseases, the therapeutic potential of ginsenoside compound Mc1 (GCMc1) in AD remains to be thoroughly investigated.</p><p><strong>Objectives: </strong>This study aimed to investigate the therapeutic potential of GCMc1 in rats with AD and to elucidate the molecular mechanisms responsible for its effects.</p><p><strong>Material and methods: </strong>Alzheimer's disease was induced in Sprague Dawley rats through a single intra-cerebro-ventricular injection of amyloid-beta (Aβ)1-42 peptide. The animals were divided into 5 groups: a control group and 4 AD subgroups, with or without receiving 10 mg/kg of GCMc1 and/or 100 μg/kg of compound C intraperitoneally (ip.). Behavioral tests, mitochondrial function, inflammatory cytokines, and proteins expression were evaluated using the Morris water maze (MWM) test, fluorometry, enzyme-linked immunosorbent assay (ELISA), and immunoblotting techniques, respectively.</p><p><strong>Results: </strong>Treatment with GCMc1 improved cognitive function, reduced hippocampal Aβ accumulation, and suppressed interleukin (IL)-1β, IL-10 and tumor necrosis factor alpha (TNF-α) levels. Ginsenoside compound Mc1 reduced mitochondrial reactive oxygen species (ROS) levels and membrane depolarization, increased adenosine triphosphate (ATP) levels, upregulated the expression of AMPK, PGC-1α and SIRT1 proteins, and downregulated the nuclear factor-kappa-B (NF-κB) expression. Importantly, co-administration of compound C, an AMPK inhibitor, attenuated the beneficial effects of GCMc1, suggesting the involvement of AMPK pathway in mediating GCMc1's neuroprotective effects.</p><p><strong>Conclusions: </strong>We showed that GCMc1 confers substantial neuroprotection in rats with AD by modulating the AMPK/SIRT1/NF-κB signaling pathway. These findings highlight the potential of GCMc1 as a promising therapeutic agent for AD treatment.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"1105-1114"},"PeriodicalIF":2.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477422","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}