David Fisman, Maarten Postma, Myron J Levin, Joaquin Mould-Quevedo
{"title":"Absenteeism and Productivity Loss Due to Influenza or Influenza-like Illness in Adults in Europe and North America.","authors":"David Fisman, Maarten Postma, Myron J Levin, Joaquin Mould-Quevedo","doi":"10.3390/diseases12120331","DOIUrl":"10.3390/diseases12120331","url":null,"abstract":"<p><p>Healthy working-age adults are susceptible to illness or caregiving requirements resulting from annual seasonal influenza, leading to considerable societal and economic impacts. The objective of this targeted narrative review is to understand the societal burden of influenza in terms of absenteeism and productivity loss, based on the current literature. This review includes 48 studies on the impact of influenza and influenza-like illness (ILI) and reports on the effect of influenza vaccination, age, disease severity, caring for others, comorbidities, and antiviral prophylaxis on absenteeism and productivity loss due to influenza/ILI, focusing on publications originating from Canada, Europe, and the United States. Influenza/ILI results in substantial work time and productivity loss among working adults and students in Canada, Europe, and the United States, particularly those who are unvaccinated, are <65 years of age, or who have severe disease. Considerable work time and productivity loss is attributable to illness and caregiver burden related to influenza. Further research is required on the impact of influenza on absenteeism and productivity loss in adults with comorbidities to support the development of effective employer policies for working adults with underlying health conditions.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"12 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Milan Smiesko, Ester Jenigarova, Peter Stanko, Zsolt Kasa, Ivan Cavarga, Stefan Lassan
{"title":"Tongue Ultrasonography in the Screening of Severe Obstructive Sleep Apnea Syndrome-Promising Potential for Overloaded Sleep Centers.","authors":"Milan Smiesko, Ester Jenigarova, Peter Stanko, Zsolt Kasa, Ivan Cavarga, Stefan Lassan","doi":"10.3390/diseases12120330","DOIUrl":"10.3390/diseases12120330","url":null,"abstract":"<p><p>Obstructive sleep apnea syndrome (OSAS) is a frequently underdiagnosed sleep disorder marked by recurrent episodes of apnea and/or hypopnea during sleep, primarily resulting from the partial or complete collapse of the upper airway. OSAS significantly affects patients' health and quality of life. Additionally, it is a recognized risk factor for inducing microsleep episodes during daily activities, particularly in occupations such as professional driving, where sustained attention is critical. The aim of our study was to identify an effective screening test for use in outpatient settings, capable of distinguishing patients with a severe form of OSAS. Patients who test positive with this screening tool would subsequently be prioritized for polysomnographic evaluation in a sleep laboratory. A total of 64 patients who underwent polysomnography (PSG) or polygraphy (PG) examination at our clinic were subsequently examined by USG of the tongue with measurements of tongue base thickness (TBT) and the distance between lingual arteries (DLA) during wakefulness and in a relaxed tongue position. The measurements of TBT and DLA were subsequently correlated with the apnea-hypopnea index (AHI) obtained from PSG or PG. In our cohort of patients diagnosed with severe OSAS, a TBT threshold of ≥65 mm served as an effective cutoff value. A TBT value of ≥65 mm reached an AUC value of 78.1%, sensitivity of 74.4%, specificity of 61.9%, positive predictive value of 80%, negative predictive value of 54.2% and overall accuracy of 70.3%. A DLA value of ≥30 mm in our sample of patients with severe OSAS showed an AUC of 76.5%, sensitivity of 69.8%, specificity of 71.1%, positive predictive value of 83.3%, negative predictive value of 53.6%, and overall accuracy of 70.3%. Tongue USG markers, particularly TBT and DLA measurements during wakefulness and in a relaxed tongue position, show potential as effective screening tools for identifying severe OSAS in European populations. These markers demonstrate improved accuracy over traditional screening questionnaires by reducing the likelihood of false-negative results. Patients with a positive screening should preferably be referred for polysomnography. In this way, patients with a serious illness could receive adequate therapy sooner.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"12 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11675877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manuela Chiavarini, Jacopo Dolcini, Giorgio Firmani, Elisa Ponzio, Pamela Barbadoro
{"title":"Prevalence of Diabetes, Hypertension, and Associated of Cardiovascular Diseases: A Comparative Pre- and Post-COVID Study.","authors":"Manuela Chiavarini, Jacopo Dolcini, Giorgio Firmani, Elisa Ponzio, Pamela Barbadoro","doi":"10.3390/diseases12120329","DOIUrl":"10.3390/diseases12120329","url":null,"abstract":"<p><p><b>Background</b>: Diabetes and hypertension are major global health challenges aggravated by COVID-19's impact on healthcare and lifestyle factors. This study aims to compare the prevalence and associated socio-demographic factors of these conditions before and after the pandemic (2019 vs. 2022). <b>Materials and Methods</b>: We used data from Italy's \"Aspects of Daily Life\" survey; 74,294 adults were included. <b>Results</b>: Results show a rise in diabetes prevalence from 7.76% in 2019 to 8.49% in 2022 (<i>p</i> < 0.05), while hypertension did not show this. Logistic regression analysis for the years 2019 and 2022 revealed a statistically significant association between the year 2022 and increased odds of diabetes (OR = 1.08, <i>p</i> = 0.008). BMI's role as a risk factor intensified, with higher odds ratios (ORs) for both conditions in overweight and obese individuals in 2022. For example, obesity-related ORs for diabetes increased from 2.45 (95%CI 1.73-3.47) in 2019 to 3.02 (95%CI 2.09-4.35) in 2022, and for hypertension from 2.86 (95%CI 2.28-3.58) to 3.64 (95%CI 2.87-4.61). Lower education levels also showed a greater association with hypertension risk in 2022; subjects with only middle or high school diplomas had significantly higher ORs than individuals with higher education; there was a non-significant trend in 2019. However, diabetes risk associated with lower education remained stable and significant in both years. <b>Conclusions</b>: These findings suggest that the pandemic may have increased risk factors for diabetes and hypertension, particularly BMI and educational level, compared with the literature on the increased burden of chronic diseases during COVID-19.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"12 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Relationship Between Serum Myostatin and Endothelial Function in Non-Dialysis Patients with Chronic Kidney Disease.","authors":"Ho-Hsiang Chang, Chih-Hsien Wang, Yu-Li Lin, Chiu-Huang Kuo, Hung-Hsiang Liou, Bang-Gee Hsu","doi":"10.3390/diseases12120328","DOIUrl":"10.3390/diseases12120328","url":null,"abstract":"<p><strong>Background/objectives: </strong>Myostatin, primarily produced by skeletal muscle, inhibits muscle growth and promotes protein degradation. It has been implicated in conditions such as obesity, insulin resistance, and cardiovascular disease. However, its association with endothelial function in chronic kidney disease (CKD) patients remains unclear. This study aimed to investigate the relationship between serum myostatin levels and endothelial function in 136 non-dialysis CKD patients at stages 3-5.</p><p><strong>Methods: </strong>Fasting blood samples were collected to measure serum myostatin levels using enzyme-linked immunosorbent assay kits. Endothelial function was evaluated non-invasively by measuring the vascular reactivity index (VRI) with a digital thermal monitoring test.</p><p><strong>Results: </strong>VRI values were classified as poor (<1.0, <i>n</i> = 25, 18.4%), intermediate (1.0 to <2.0, <i>n</i> = 63, 46.3%), or good (≥2.0, <i>n</i> = 48, 35.3%). Factors associated with poor vascular reactivity included older age (<i>p</i> = 0.026), elevated serum blood urea nitrogen (<i>p</i> = 0.020), serum creatinine (<i>p</i> = 0.021), urine protein-to-creatinine ratio (UPCR, <i>p</i> = 0.013), and myostatin levels (<i>p</i> = 0.003), along with reduced estimated glomerular filtration rate (<i>p</i> = 0.015). Multivariate regression analysis identified older age, higher serum creatinine, and log-transformed myostatin levels as significant independent predictors of lower VRI.</p><p><strong>Conclusions: </strong>These findings suggest that myostatin may serve as a potential biomarker for endothelial dysfunction in CKD patients. Future large-scale, longitudinal studies are warranted to confirm and extend our preliminary findings.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"12 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Challenges in the Management of a Calvarial Defect in an NF1-Patient.","authors":"Imane Abbas, Jinan Behnan, Abhishek Dubey, Genesis Liriano, Oren Tepper, Andrew J Kobets","doi":"10.3390/diseases12120325","DOIUrl":"10.3390/diseases12120325","url":null,"abstract":"<p><strong>Background: </strong>Calvarial defects in NF1 are rare and lack standardized management guidelines. This study seeks to shed light on calvarial defects in NF1 patients with extensive skull erosion.</p><p><strong>Methods: </strong>This case report focuses on clinical and radiological presentations and surgical interventions during six years of follow-up, comparing the results with those in the literature.</p><p><strong>Results: </strong>A five-year-old female with NF1 disease was diagnosed with a spontaneous calvarial defect in the occipital region and an arachnoid cyst underneath. The lesion enlarged progressively over the years and at the age of nine, she underwent her first surgery. Our surgery team performed a cranioplasty using a split-thickness bone graft harvested from the parietal bone after cyst decompression. Two years later, she underwent revision surgery with a titanium mesh plate due to total resorption of the initial bone graft and unsuccessful closure of the large defect.</p><p><strong>Conclusions: </strong>Calvaria defects are a relatively unknown aspect of NF1, and no standard treatment exists. Their management requires a personalized approach, considering factors like lesion size, and the potential for multiple interventions throughout the patient's lifetime. Due to their progressive nature and the possibility of additional lesions, long-term follow-up is crucial for effective monitoring and intervention planning.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"12 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142899868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Boris Kos, Dinko Martinovic, Danko Muller, Iva Markota, Zoran Karlovic, Josko Bozic, Emil Dediol
{"title":"Secondary Primary Carcinoma Arising on the Flap Skin in the Oral Cavity-Case Series.","authors":"Boris Kos, Dinko Martinovic, Danko Muller, Iva Markota, Zoran Karlovic, Josko Bozic, Emil Dediol","doi":"10.3390/diseases12120324","DOIUrl":"10.3390/diseases12120324","url":null,"abstract":"<p><p><b>Background:</b> Oral squamous cell carcinoma (OSCC) causes considerable morbidity and mortality rates, posing a major global health burden. The management of the OSCC is multidisciplinary, but still the gold standard is surgical resection and reconstruction of the postablative defect. The appearance of secondary primary OSCC is not uncommon; however, it is quite rare that it appears on the skin of the flap that was used for reconstruction during the previous surgical therapy. <b>Methods:</b> We present three cases in which a secondary primary OSCC appeared on the skin of two radial forearm free flaps and two on regional pectoralis major flaps. <b>Results:</b> Our case series show that, although relatively rare, there is a chance of a secondary primary tumor on the flap used for intraoral reconstruction after the first oncological reconstruction. According to the latest and available literature, there is still no explanation of the underlying mechanism that leads to this occurrence. <b>Conclusions:</b> The learning point of this case series should be that, aside from the neck metastasis or recurrence of the primary oral cancer, the clinicians should also bear in mind that the flap itself should be physically examined in detail.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"12 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ovidiu Alexandru Mederle, Laurentiu Sima, Daian Ionel Popa, Carmen Gabriela Williams, Diana Mitu, Dumitru Șutoi, Cosmin Iosif Trebuian, Mircea Selaru, Dan Lolos, Ana-Maria Pah, Florina Buleu
{"title":"Primary Iliopsoas Abscess and Drug-Induced Liver Injury in the Emergency Department: A Case Report.","authors":"Ovidiu Alexandru Mederle, Laurentiu Sima, Daian Ionel Popa, Carmen Gabriela Williams, Diana Mitu, Dumitru Șutoi, Cosmin Iosif Trebuian, Mircea Selaru, Dan Lolos, Ana-Maria Pah, Florina Buleu","doi":"10.3390/diseases12120326","DOIUrl":"10.3390/diseases12120326","url":null,"abstract":"<p><strong>Background and objective: </strong>Iliopsoas abscess (IPA) is a rare condition with varied symptomology and etiology. Less than one-third of patients with IPA present in the emergency department (ED) with the traditional triad of fever, back pain, and restricted hip motion (or limp), leading to delays in diagnosis and management. Acute liver failure is also a rare clinical presentation in the ED, being associated with high morbidity and mortality. It occurs most often in young patients without pre-existing liver disease, presenting unique challenges in clinical management. Most cases currently happen because of drug-induced liver injury (DILI), mainly from acetaminophen or idiosyncratic drug reactions. This case report aims to raise awareness among healthcare professionals regarding the two atypical presentations in ED and introduce a potential differential diagnosis when evaluating patients with fever and back pain or liver enzyme elevations with or without nonspecific symptoms associated with the development of jaundice. The intention is to provide insights into the signs and symptoms that may indicate the presence of an iliopsoas abscess and prompt additional investigations.</p><p><strong>Case report: </strong>Here, we describe a case of primary iliopsoas abscess associated with drug-induced liver injury in our ED. The patient complained of pain in the left lumbar region and fatigue that started two weeks before this presentation, claiming that, during the previous night, the pain suddenly worsened. At the first clinical examination in the ED, the patient presented pain at palpation in the right hypochondriac and left lumbar regions, accompanied by fever, vomiting, and jaundice. On abdominal ultrasonography, the diagnosis of acute cholangitis was suspected. The laboratory test shows leukocytosis with neutrophilia, thrombocytosis, elevated liver enzymes, and hyperbilirubinemia with the predominance of indirect bilirubin. After analyzing the laboratory test results, we repeated and performed a more detailed anamnesis and medical history of the patient. Because of her increasing pain and persistent fever, she recognized excessive consumption in the last five days of drug-induced hepatotoxicity. We performed abdominal and pelvic computed tomography, which confirmed the diagnosis of cholelithiasis observed with the diameter of the bile duct within normal limits but also showed an abscess collection fused to the interfibrillar level of the left iliopsoas muscle, a diagnosis we most likely would have missed. The patient was hospitalized in the General Surgery Department, and surgical abscess drainage was performed. The patient's evolution was excellent; she was discharged after 11 days.</p><p><strong>Conclusions: </strong>The case presented here exemplifies how iliopsoas abscess, a rare cause of back pain, can quickly go unrecognized, especially in the emergency department. Our experiences will raise awareness among doctors in emergency de","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"12 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trigeminal Pontine Sign: From Imaging to Diseases Beyond Trigeminal Neuralgia.","authors":"Marialuisa Zedde, Rosario Pascarella","doi":"10.3390/diseases12120327","DOIUrl":"10.3390/diseases12120327","url":null,"abstract":"<p><p>The so-called trigeminal pontine sign has been described as a marker of different diseases, from multiple sclerosis to herpetic infections. First, it has been proposed as linear hyperintensity in the pons on the Magnetic Resonance Imaging (MRI) of patients with multiple sclerosis and trigeminal neuralgia. After these descriptions, it has been reported as incidental findings in the same patients and in patients with HSV or VZV infections. In addition, patients with neuromyelitis optica spectrum disorders (NMOSD) have been more rarely described with this neuroradiological sign. In this review, the main anatomical and neuroradiological issues underlying the trigeminal pontine sign are described, together with the limitations of the published studies from the clinical and neuroimaging point of view. Finally, the association with different diseases is detailed.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"12 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chest X-Ray Features in 130 Patients with Bronchiectasis.","authors":"Hikaru Sawada, Ryohei Kudoh, Atsushi Yokoyama, Akihiko Hagiwara, Kazufumi Hiramatsu, Jun-Ichi Kadota, Kosaku Komiya","doi":"10.3390/diseases12120323","DOIUrl":"10.3390/diseases12120323","url":null,"abstract":"<p><p><i>Background/Objectives:</i> The prevalence of bronchiectasis is increasing globally, and early detection using chest imaging has been encouraged to improve its prognosis. However, the sensitivity of a chest X-ray as a screening tool remains unclear. This study examined the chest X-ray features predictive of bronchiectasis. <i>Methods:</i> We retrospectively reviewed the chest X-rays of patients with bronchiectasis diagnosed using high-resolution computed tomography who visited our institute from January 2013 to March 2020. Patients with cardiac pacemakers, lung cancer, and interstitial pneumonia, which might bias the detection of bronchiectasis, were excluded. Two respiratory physicians independently determined the presence or absence of potential features reflecting bronchiectasis, including a vague cardiac silhouette on chest X-rays. <i>Results:</i> The study enrolled 130 patients, including 72 women (55.4%), with a mean age of 72 years. The features observed on chest X-rays included granular shadows (88.5%, n = 115), vague cardiac silhouettes (48.5%, n = 64), nodular shadows (45.4%, n = 59), a tram-track appearance (35.4%, n = 46), pleural thickening (26.9%, n = 35), vague diaphragm silhouettes (25.4%, n = 33), and a ring sign (24.6%, n = 32). The kappa values for these features were 0.271, 0.344, 0.646, 0.256, 0.312, 0.514, and 0.376, respectively. <i>Conclusions:</i> Although traditional chest X-ray features believed to reflect bronchiectasis, such as the tram-track appearance or ring sign, were not frequently seen, vague cardiac silhouettes and granular shadows had high positivity rates, indicating their potential utility for bronchiectasis screening. However, the interobserver concordance rates were unsatisfactory.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"12 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cyclosporine A Causes Gingival Overgrowth by Promoting Entry into the S Phase at the G1/S Cell Cycle Checkpoint in Gingival Fibroblasts Exposed to Lipopolysaccharide.","authors":"Reiri Takeuchi, Noriko Kuwahara, Yuta Amino, Sachiyo Hayashi, Chieko Taguchi, Itaru Suzuki, Haruka Suzuki, Teruaki Nagashima, Kazumune Arikawa, Yuichiro Okada, Takato Nomoto, Koichi Hiratsuka","doi":"10.3390/diseases12120322","DOIUrl":"10.3390/diseases12120322","url":null,"abstract":"<p><strong>Objectives: </strong>Cyclosporine A promotes gingival fibrosis by enhancing the proliferation of gingival fibroblasts, leading to gingival overgrowth. The population of gingival fibroblasts is regulated by cell cycle machinery, which balances cell growth and inhibition. Cells that detect DNA damage pause at the G1/S checkpoint to repair the damage instead of progressing to the S phase. Previous studies have linked drug-induced gingival overgrowth to the response of fibroblasts to lipopolysaccharide (LPS) and cyclosporine A. This research investigates the effects of cyclosporine A on the G1/S checkpoint and its mediators in LPS-treated gingival fibroblasts to clarify the mechanisms behind cyclosporine-A-induced gingival overgrowth.</p><p><strong>Methods: </strong>Semi-confluent human gingival fibroblasts were treated with LPS or cyclosporine A in DMEM. Cell proliferation was evaluated by counting the total number of cells. The distribution of the cell cycle phases was analyzed using flow cytometry. Additionally, the expression levels of mRNAs and proteins related to cell cycle regulators were quantified by reverse-transcription quantitative PCR and Western blotting, respectively.</p><p><strong>Results: </strong>Cyclosporine A treatment significantly enhanced cell proliferation and the G1-S cell cycle transition. It increased the mRNA levels of <i>CDC25A</i> and <i>CYCLIN D</i> while decreasing those of <i>RB1</i>, <i>SMAD3</i>, and <i>SMAD4</i>. Additionally, it upregulated the protein levels of CDC25A, CYCLIN D, CDK4, CDK6, and pRB and downregulated the protein levels of SMAD3 and SMAD4.</p><p><strong>Conclusions: </strong>Gingival overgrowth induced by cyclosporine A could be attributed to these alterations.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"12 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}