Ava G Stechschulte, Andrea C Bakker, Jasmine Steele, Sara O Vargas
Objective: We hypothesized that reticence to address a groin mass may result in late presentation of testicular/paratesticular malignancy in early puberty through adolescence.
Methods: Malignant testicular and paratesticular tumors (malignant germ cell tumors and rhabdomyosarcomas) diagnosed at our institution from 1994-2023 for patients aged 11-20 were included. Clinicopathologic features were recorded, and statistically analyzed.
Results: Eighty-five cases were identified. Patient ages ranged from 11 to 20 years (mean 17 years, median 16 years). The greatest tumor dimension ranged from 0.8 to 18.0 cm (mean 4.4 cm, median 3.5 cm). Ten tumors (11.8% of cases) were ≥10.0 cm. In the 11-13-year-old age group, 100% of tumors (3/3) were ≥10 cm. The proportion of tumors ≥10 cm was significantly higher in the 11-13-year-old age group than in either the 14-16-year-old (P<0.001) or 17-20-year-old (P<0.001) age groups.
Conclusion: This adolescent cohort with malignant testicular and paratesticular tumors showed a high proportion (11.8%) of very large (≥10 cm) tumors. Although the reasons are unknown and likely multifactorial, this study suggests that adolescents, particularly the 11-13 year age group, are a vulnerable population.
{"title":"Large Malignant Testicular/Paratesticular Tumors in Adolescence: Assessment of Gross Tumor Size in a Vulnerable Age Group.","authors":"Ava G Stechschulte, Andrea C Bakker, Jasmine Steele, Sara O Vargas","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>We hypothesized that reticence to address a groin mass may result in late presentation of testicular/paratesticular malignancy in early puberty through adolescence.</p><p><strong>Methods: </strong>Malignant testicular and paratesticular tumors (malignant germ cell tumors and rhabdomyosarcomas) diagnosed at our institution from 1994-2023 for patients aged 11-20 were included. Clinicopathologic features were recorded, and statistically analyzed.</p><p><strong>Results: </strong>Eighty-five cases were identified. Patient ages ranged from 11 to 20 years (mean 17 years, median 16 years). The greatest tumor dimension ranged from 0.8 to 18.0 cm (mean 4.4 cm, median 3.5 cm). Ten tumors (11.8% of cases) were ≥10.0 cm. In the 11-13-year-old age group, 100% of tumors (3/3) were ≥10 cm. The proportion of tumors ≥10 cm was significantly higher in the 11-13-year-old age group than in either the 14-16-year-old (<i>P</i><0.001) or 17-20-year-old (<i>P</i><0.001) age groups.</p><p><strong>Conclusion: </strong>This adolescent cohort with malignant testicular and paratesticular tumors showed a high proportion (11.8%) of very large (≥10 cm) tumors. Although the reasons are unknown and likely multifactorial, this study suggests that adolescents, particularly the 11-13 year age group, are a vulnerable population.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140183577","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}
Objective: Polydopamine nanoparticles (PDA NPs) are a promising topic in the fields of drug delivery, tissue engineering, bioimaging, etc. The present study aims to explore the impact of PDA NPs carrying ferroptosis inhibitor ferstatin-1 (Fer-1) on myocardial ischemia-reperfusion injury (MIRI).
Methods: After establishment of a rat model of MIRI and PDA NPs, the rats were divided into 4 groups: model group, sham operation group, Fer-1 group, and nano+Fer-1 group (n=8). To detect the effect of PDA NPs encapsulating Fer-1 on ferroptosis in MIRI rats, we further set up NOX4 overexpression group (pc-NOX4 group), NOX4 inhibitor group (Fulvene-5 group), nano+Fer-1+pc-NOX4 group, and nano+Fer-1+Fulvene-5 group (n=8). A CCK-8 assay was conducted to assess cell viability and staining to detect cardiomyocyte apoptosis and observe myocardial infraction.
Results: PDA NPs loaded with Fer-1 were successfully prepared with good safety and biocompatibility. Administration of PDA NPs carrying Fer-1 notably alleviated myocardial injury and hindered the process of ferroptosis in MIRI rats when inducing downregulation of NOX4 expression. Additionally, overexpression of GPX4 significantly attenuated myocardial injury in MIRI rats. While Fer-1 was shown to inhibit the expression of NOX4, the NOX4 inhibitor Fulvene-5 greatly elevated GPX4 and FTH1 expression in cardiomyocytes, and down-regulated the content of Fe2+, especially in the nanometer+Fer-1+Fulvene-5 group.
Conclusion: With promising safety and biocompatibility, PDA NPs encapsulated Fer-1 decrease GPX4 and FTH1 expression by inhibiting the level of NOX4 in myocardial cells of MIRI rats, thereby suppressing ferroptosis of cardiomyocytes and alleviating myocardial injury.
{"title":"Polydopamine Nanoparticles-Encapsulated Ferroptosis Inhibitor Ferstatin-1 Promotes GPX4 Expression by Down-Regulating NOX4 to Alleviate Myocardial Ischemia-Reperfusion Injury.","authors":"Zhibo Hong, Jing Cui, Yu Chen","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Polydopamine nanoparticles (PDA NPs) are a promising topic in the fields of drug delivery, tissue engineering, bioimaging, etc. The present study aims to explore the impact of PDA NPs carrying ferroptosis inhibitor ferstatin-1 (Fer-1) on myocardial ischemia-reperfusion injury (MIRI).</p><p><strong>Methods: </strong>After establishment of a rat model of MIRI and PDA NPs, the rats were divided into 4 groups: model group, sham operation group, Fer-1 group, and nano+Fer-1 group (n=8). To detect the effect of PDA NPs encapsulating Fer-1 on ferroptosis in MIRI rats, we further set up NOX4 overexpression group (pc-NOX4 group), NOX4 inhibitor group (Fulvene-5 group), nano+Fer-1+pc-NOX4 group, and nano+Fer-1+Fulvene-5 group (n=8). A CCK-8 assay was conducted to assess cell viability and staining to detect cardiomyocyte apoptosis and observe myocardial infraction.</p><p><strong>Results: </strong>PDA NPs loaded with Fer-1 were successfully prepared with good safety and biocompatibility. Administration of PDA NPs carrying Fer-1 notably alleviated myocardial injury and hindered the process of ferroptosis in MIRI rats when inducing downregulation of NOX4 expression. Additionally, overexpression of GPX4 significantly attenuated myocardial injury in MIRI rats. While Fer-1 was shown to inhibit the expression of NOX4, the NOX4 inhibitor Fulvene-5 greatly elevated GPX4 and FTH1 expression in cardiomyocytes, and down-regulated the content of Fe<sup>2+</sup>, especially in the nanometer+Fer-1+Fulvene-5 group.</p><p><strong>Conclusion: </strong>With promising safety and biocompatibility, PDA NPs encapsulated Fer-1 decrease GPX4 and FTH1 expression by inhibiting the level of NOX4 in myocardial cells of MIRI rats, thereby suppressing ferroptosis of cardiomyocytes and alleviating myocardial injury.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156874","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}
Amitava Dasgupta, Kelsey Woodard, Bheemraj Ramoo, Clinton Frazee, Uttam Garg
Objective: Testosterone is the principal male sex hormone and is secreted primarily by the testes. In most clinical laboratories testosterone is routinely measured for diagnosis of male hypogonadism or androgen excess in females using FDA approved immunoassays. We compared testosterone values measured by Beckman access immunoassay with those measured by a reference LC-MS/MS method.
Methods: Testosterone was measured in 36 patients using left over serum or plasma specimens by both Beckman immunoassay on the DXI 800 analyzer and a reference LC-MS/MS method.
Results: We observed overall significant negative bias of approximately 31.9 % when testosterone values obtained by the reference LC-MS/MS method were plotted in the x-axis and the corresponding testosterone values using the immunoassay in the y-axis, as regression equation was y=0.6887x+38.81 (n=36). The corresponding Deming regression was y=0.6639x+34.7163. However, in eight specimens with low testosterone concentrations, immunoassays significantly overestimated testosterone concentrations.
Conclusions: Immunoassays may underestimate the true testosterone concentration in males but overestimate in females with low testosterone concentration. Therefore, for diagnosis of hypogonadism in males and androgen excess in females, testosterone values obtained by Beckman Access immunoassay on the DXI 800 analyzer should be interpreted with caution.
{"title":"<i>Technical Note:</i> Significant Positive Bias in Lower Concentrations but Negative Bias in Higher Concentrations in Testosterone Measurement Using Beckman Access Immunoassay Compared to a Liquid Chromatography-Tandem Mass Spectrometry Reference Method.","authors":"Amitava Dasgupta, Kelsey Woodard, Bheemraj Ramoo, Clinton Frazee, Uttam Garg","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Testosterone is the principal male sex hormone and is secreted primarily by the testes. In most clinical laboratories testosterone is routinely measured for diagnosis of male hypogonadism or androgen excess in females using FDA approved immunoassays. We compared testosterone values measured by Beckman access immunoassay with those measured by a reference LC-MS/MS method.</p><p><strong>Methods: </strong>Testosterone was measured in 36 patients using left over serum or plasma specimens by both Beckman immunoassay on the DXI 800 analyzer and a reference LC-MS/MS method.</p><p><strong>Results: </strong>We observed overall significant negative bias of approximately 31.9 % when testosterone values obtained by the reference LC-MS/MS method were plotted in the x-axis and the corresponding testosterone values using the immunoassay in the y-axis, as regression equation was y=0.6887x+38.81 (n=36). The corresponding Deming regression was y=0.6639x+34.7163. However, in eight specimens with low testosterone concentrations, immunoassays significantly overestimated testosterone concentrations.</p><p><strong>Conclusions: </strong>Immunoassays may underestimate the true testosterone concentration in males but overestimate in females with low testosterone concentration. Therefore, for diagnosis of hypogonadism in males and androgen excess in females, testosterone values obtained by Beckman Access immunoassay on the DXI 800 analyzer should be interpreted with caution.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157958","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}
Rita W J Hayes, Lance Van Truong, Nina Tatevian, Alexander Chirkov
Foreign body ingestion of sharp objects can be a striking feature of psychological dysfunction with high morbidity and mortality. While the phenomenon has been reported on, primarily from a psychiatric perspective, this report will present the effects of this behavior on the intestinal system from a pathology perspective. The report is of a 43-year-old female with a past medical history of foreign object ingestion, borderline personality disorder, depression, anxiety, and prior suicidality who passed away due to bowel obstruction. Review of her history revealed an eighteen-year history of repeated foreign body ingestion with multiple surgical interventions. A particularly remarkable aspect revealed through the surgical history is the nature of the complications. They begin in 2008 with bowel perforation due to a blunt object and continue to present with perforation in the early years but show a gradual change to adhesions and obstruction as the primary concern. Her final presentation to the hospital and cause of death was due to obstruction, not perforation, even though the foreign bodies were six knives. While this case is not the only known report of foreign body ingestion, the extensive timeline and frequency allow for an examination of the gradual progression of fibrosis and adhesions within the intestines and abdominal wall, which led to the obstruction and death despite being a protective factor against further perforation.This case was presented at the annual Association of Clinical Scientists meeting (April 2-4, Jacksonville, FL).
{"title":"Fibrosis of the Intestines in Response to Foreign Objects: A Case Report.","authors":"Rita W J Hayes, Lance Van Truong, Nina Tatevian, Alexander Chirkov","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Foreign body ingestion of sharp objects can be a striking feature of psychological dysfunction with high morbidity and mortality. While the phenomenon has been reported on, primarily from a psychiatric perspective, this report will present the effects of this behavior on the intestinal system from a pathology perspective. The report is of a 43-year-old female with a past medical history of foreign object ingestion, borderline personality disorder, depression, anxiety, and prior suicidality who passed away due to bowel obstruction. Review of her history revealed an eighteen-year history of repeated foreign body ingestion with multiple surgical interventions. A particularly remarkable aspect revealed through the surgical history is the nature of the complications. They begin in 2008 with bowel perforation due to a blunt object and continue to present with perforation in the early years but show a gradual change to adhesions and obstruction as the primary concern. Her final presentation to the hospital and cause of death was due to obstruction, not perforation, even though the foreign bodies were six knives. While this case is not the only known report of foreign body ingestion, the extensive timeline and frequency allow for an examination of the gradual progression of fibrosis and adhesions within the intestines and abdominal wall, which led to the obstruction and death despite being a protective factor against further perforation.This case was presented at the annual Association of Clinical Scientists meeting (April 2-4, Jacksonville, FL).</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158072","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}
Mengying Gao, Xixia Pang, Suna Ni, Zhixia Wei, Dandan Li
Objective: The study investigated the association between FLG-AS1 and cervical cancer prognosis and the interaction mechanism between FLG-AS1 and miR-147b in order to identify potential therapeutic targets for cervical cancer.
Methods: In this study, tissue samples and clinicopathological characteristics were obtained from 125 cervical cancer patients. FLG-AS1 expression levels in the samples were detected by polymerase chain reaction assay. CCK-8 and Transwell assays were used to evaluate FLG-AS1's impact on cervical cancer cell proliferation and metastasis. The mechanism of action of FLG-AS1 and miR-147b was probed by a dual luciferase reporter gene assay. The prognostic nature of FLG-AS1 in cervical cancer was explored by a series of statistical approaches.
Results: In cervical cancer cells and tissues, FLG-AS1 expression is markedly downregulated. FLG-AS1 inhibits the activities of cervical cancer cells by negatively regulating miR-147b expression. Patients with cervical cancer have a poor prognosis when FLG-AS1 expression is low.
Conclusion: FLG-AS1 may be considered as a novel cervical cancer prognostic biomarker candidate, which affects cancer cell progression by negatively regulating miR-147b.
{"title":"Long Non-Coding RNA FLG-AS1 Inhibits Cervical Cancer Progression through Negatively Modulating miR-147b.","authors":"Mengying Gao, Xixia Pang, Suna Ni, Zhixia Wei, Dandan Li","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>The study investigated the association between FLG-AS1 and cervical cancer prognosis and the interaction mechanism between FLG-AS1 and miR-147b in order to identify potential therapeutic targets for cervical cancer.</p><p><strong>Methods: </strong>In this study, tissue samples and clinicopathological characteristics were obtained from 125 cervical cancer patients. FLG-AS1 expression levels in the samples were detected by polymerase chain reaction assay. CCK-8 and Transwell assays were used to evaluate FLG-AS1's impact on cervical cancer cell proliferation and metastasis. The mechanism of action of FLG-AS1 and miR-147b was probed by a dual luciferase reporter gene assay. The prognostic nature of FLG-AS1 in cervical cancer was explored by a series of statistical approaches.</p><p><strong>Results: </strong>In cervical cancer cells and tissues, FLG-AS1 expression is markedly downregulated. FLG-AS1 inhibits the activities of cervical cancer cells by negatively regulating miR-147b expression. Patients with cervical cancer have a poor prognosis when FLG-AS1 expression is low.</p><p><strong>Conclusion: </strong>FLG-AS1 may be considered as a novel cervical cancer prognostic biomarker candidate, which affects cancer cell progression by negatively regulating miR-147b.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156797","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}
Objective: Blood donation is critical in Saudi Arabia due to high rates of sickle cell disease and thalassemia. Recent trends show a decline in the number of blood donors, threatening blood supplies for medical treatments. This study aims to identify factors that influence blood donation decisions and behaviors among young Saudi Arabian adults to develop strategies to enhance donation rates.
Methods: A cross-sectional study was conducted with 407 university students in Riyadh Province (Shaqra, Riyadh City, Al-Majmaah and Al-Duwadimi) and occurred from December 2022 to May 2023, using convenience sampling. Data were collected via online questionnaires and analyzed using logistic regression.
Results: Findings revealed a significant gender disparity in donation rates with males more likely to donate. Knowledge gaps were prevalent, especially regarding eligibility criteria. Support for organ donation, prior experience of receiving blood, and high levels of self-determined motivation positively associated with donation likelihood. Conversely, amotivation was a strong negative predictor of donation.
Conclusion: This study highlights the importance of educational interventions to address misconceptions about blood donation and tailor campaigns to enhance donor motivation. Strategies focusing on these aspects could improve the donor pool and ensure a stable blood supply for patients with blood disorders in Saudi Arabia.
{"title":"Factors Influencing Blood Donation among Young Saudi Arabian Adults: A Cross-Sectional Study to Inform Donor Recruitment and Retention Programs.","authors":"Fahd A Kuriri","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Blood donation is critical in Saudi Arabia due to high rates of sickle cell disease and thalassemia. Recent trends show a decline in the number of blood donors, threatening blood supplies for medical treatments. This study aims to identify factors that influence blood donation decisions and behaviors among young Saudi Arabian adults to develop strategies to enhance donation rates.</p><p><strong>Methods: </strong>A cross-sectional study was conducted with 407 university students in Riyadh Province (Shaqra, Riyadh City, Al-Majmaah and Al-Duwadimi) and occurred from December 2022 to May 2023, using convenience sampling. Data were collected via online questionnaires and analyzed using logistic regression.</p><p><strong>Results: </strong>Findings revealed a significant gender disparity in donation rates with males more likely to donate. Knowledge gaps were prevalent, especially regarding eligibility criteria. Support for organ donation, prior experience of receiving blood, and high levels of self-determined motivation positively associated with donation likelihood. Conversely, amotivation was a strong negative predictor of donation.</p><p><strong>Conclusion: </strong>This study highlights the importance of educational interventions to address misconceptions about blood donation and tailor campaigns to enhance donor motivation. Strategies focusing on these aspects could improve the donor pool and ensure a stable blood supply for patients with blood disorders in Saudi Arabia.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158070","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}
Tamar A Smith-Norowitz, Esther M Norowitz, Haram Abdelmajid, Stephan Kohlhoff
{"title":"<i>Letter to the Editor:</i> Effect of Guanosine Triphosphate on B Cell Characterization in U266 Cells.","authors":"Tamar A Smith-Norowitz, Esther M Norowitz, Haram Abdelmajid, Stephan Kohlhoff","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157955","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}
Dan Ma, Yongting Lu, Hong Ye, Chunyan Li, Jie Zhang, Tian Hao Bao, Jianhong Han
Objective: Cerebral microbleeds (CMBs) are punctate hemorrhagic lesions within the brain parenchyma and are a classic manifestation of cerebral small vessel disease (CSVD). The primary objective of this study is to investigate the potential role of miR-4685-3p and underlying mechanisms by which miR-4685-3p modulates matrix metalloproteinase-9 (MMP9) in cerebral microvascular endothelial cell injury.
Methods: We employed high-throughput sequencing to screen for differentially expressed miRNAs in the peripheral blood of patients with CMBs and healthy controls. Employing lipopolysaccharide (LPS) to induce cellular damage, we aim to establish a model of human brain microvascular endothelial cells (hCMEC/D3) injury. We also had cells transfected with miR-4685-3p mimic and MMP9 overexpression plasmid. We utilized quantitative polymerase chain reaction (qPCR) to assess the expression levels of miR-4685-3p and performed Western blot analysis to examine MMP9 expression levels in the cells. We employed the CCK-8 assay, TUNEL assay, and tube formation assay to evaluate cellular viability, apoptotic rates, and angiogenic capabilities. Furthermore, dual-luciferase reporter assay analysis was conducted to confirm the relationship between miR-4685-3p and MMP9.
Results: The sequencing results indicated a downregulation of miR-4685-3p in the peripheral blood of patients with CMBs. Within the context of LPS-induced injury to hCMEC/D3 cells, miR-4685-3p exhibits reduced expression, whereas MMP9 expression levels are elevated. The elevation of miR-4685-3p expression levels attenuates LPS-induced cellular apoptosis and enhances the viability and tube-forming capacity of hCMEC/D3 cells. Concomitant transfection with MMP9 overexpression constructs effectively reversed the detrimental effects of LPS on hCMEC/D3 cell integrity. We further confirmed that miR-4685-3p overexpression directly targets MMP9, leading to negative regulation of MMP9 expression.
Conclusion: Upregulating miR-4685-3p, which targets the MMP9 axis, mitigated LPS-induced cerebral microvascular endothelial cell injury, potentially playing a protective role in the progression of CMBs.
{"title":"miR-4685-3p Alleviates Human Brain Microvascular Endothelial Cells Injury by Regulating MMP9.","authors":"Dan Ma, Yongting Lu, Hong Ye, Chunyan Li, Jie Zhang, Tian Hao Bao, Jianhong Han","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Cerebral microbleeds (CMBs) are punctate hemorrhagic lesions within the brain parenchyma and are a classic manifestation of cerebral small vessel disease (CSVD). The primary objective of this study is to investigate the potential role of miR-4685-3p and underlying mechanisms by which miR-4685-3p modulates matrix metalloproteinase-9 (MMP9) in cerebral microvascular endothelial cell injury.</p><p><strong>Methods: </strong>We employed high-throughput sequencing to screen for differentially expressed miRNAs in the peripheral blood of patients with CMBs and healthy controls. Employing lipopolysaccharide (LPS) to induce cellular damage, we aim to establish a model of human brain microvascular endothelial cells (hCMEC/D3) injury. We also had cells transfected with miR-4685-3p mimic and MMP9 overexpression plasmid. We utilized quantitative polymerase chain reaction (qPCR) to assess the expression levels of miR-4685-3p and performed Western blot analysis to examine MMP9 expression levels in the cells. We employed the CCK-8 assay, TUNEL assay, and tube formation assay to evaluate cellular viability, apoptotic rates, and angiogenic capabilities. Furthermore, dual-luciferase reporter assay analysis was conducted to confirm the relationship between miR-4685-3p and MMP9.</p><p><strong>Results: </strong>The sequencing results indicated a downregulation of miR-4685-3p in the peripheral blood of patients with CMBs. Within the context of LPS-induced injury to hCMEC/D3 cells, miR-4685-3p exhibits reduced expression, whereas MMP9 expression levels are elevated. The elevation of miR-4685-3p expression levels attenuates LPS-induced cellular apoptosis and enhances the viability and tube-forming capacity of hCMEC/D3 cells. Concomitant transfection with MMP9 overexpression constructs effectively reversed the detrimental effects of LPS on hCMEC/D3 cell integrity. We further confirmed that miR-4685-3p overexpression directly targets MMP9, leading to negative regulation of MMP9 expression.</p><p><strong>Conclusion: </strong>Upregulating miR-4685-3p, which targets the MMP9 axis, mitigated LPS-induced cerebral microvascular endothelial cell injury, potentially playing a protective role in the progression of CMBs.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156842","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}
Objective: Interferon-α (IFNα) therapy has been an integral part of the current treatment for hepatitis B virus (HBV) infection. However, the exact effect of IFNα antiviral therapy on liver function and iron metabolism in patients with chronic hepatitis B (CHB) remains unclear. Here, we investigated the characteristics of changes in liver function and iron metabolism indexes in patients with chronic hepatitis B before and after IFNα treatment. Additionally, we determined their predictive value for the therapeutic response of IFNα treatment.
Methods: In this study, 34 patients with CHB before and after IFNα treatment were enrolled. Serum levels of virological indicators, liver function, and iron metabolism markers were detected and analyzed in each patient. ROC curve analysis was performed to compare the predictive value of serum liver function and iron metabolism markers for the therapeutic response of IFN α treatment.
Results: A significant decrease in serum HBV DNA (P<0.001) and HBsAg (P<0.001) was observed before and after IFNα treatment. Compared to the patients before IFNα treatment, patients after IFNα treatment showed a significant increase in serum albumin (ALB) (P<0.05) and a significant decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P=0.003 and P=0.034). These findings suggested that the synthetic function of the liver was improved, and liver inflammation was alleviated. Serum HEPC and serum ferritin (SF) levels in patients after IFNα treatment were significantly higher (P<0.001, P<0.001); however, serum iron (SI) levels were significantly lower (P=0.005) than those in patients before IFNα treatment. These findings indicate that IFNα treatment regulated iron metabolism homeostasis in CHB patients. Combined liver function and iron metabolism markers, including ALB, SI, SF, and HEPC, had the highest predictive value for the therapeutic response of IFNα treatment for CHB.
Conclusion: IFNα treatment improved liver function and iron metabolism homeostasis in patients with CHB. Regular monitoring of serum ALB, SI, SF, and HEPC can help predict the therapeutic response of IFNα treatment for CHB.
{"title":"Predictive Value of Serum Albumin, Iron, Ferritin, and Hepcidin for Antiviral Efficacy of IFNα Treatment in Patients with Chronic Hepatitis B.","authors":"Qian Liu, Futing Liu, Wanlu Duan, Yu Wei, Tingdong Zhou, Hao Zhang, Zhi Duan, Qiang Zhou, Qin Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Interferon-α (IFNα) therapy has been an integral part of the current treatment for hepatitis B virus (HBV) infection. However, the exact effect of IFNα antiviral therapy on liver function and iron metabolism in patients with chronic hepatitis B (CHB) remains unclear. Here, we investigated the characteristics of changes in liver function and iron metabolism indexes in patients with chronic hepatitis B before and after IFNα treatment. Additionally, we determined their predictive value for the therapeutic response of IFNα treatment.</p><p><strong>Methods: </strong>In this study, 34 patients with CHB before and after IFNα treatment were enrolled. Serum levels of virological indicators, liver function, and iron metabolism markers were detected and analyzed in each patient. ROC curve analysis was performed to compare the predictive value of serum liver function and iron metabolism markers for the therapeutic response of IFN α treatment.</p><p><strong>Results: </strong>A significant decrease in serum HBV DNA (<i>P</i><0.001) and HBsAg (<i>P</i><0.001) was observed before and after IFNα treatment. Compared to the patients before IFNα treatment, patients after IFNα treatment showed a significant increase in serum albumin (ALB) (<i>P</i><0.05) and a significant decrease in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (<i>P</i>=0.003 and <i>P</i>=0.034). These findings suggested that the synthetic function of the liver was improved, and liver inflammation was alleviated. Serum HEPC and serum ferritin (SF) levels in patients after IFNα treatment were significantly higher (<i>P</i><0.001, <i>P</i><0.001); however, serum iron (SI) levels were significantly lower (<i>P</i>=0.005) than those in patients before IFNα treatment. These findings indicate that IFNα treatment regulated iron metabolism homeostasis in CHB patients. Combined liver function and iron metabolism markers, including ALB, SI, SF, and HEPC, had the highest predictive value for the therapeutic response of IFNα treatment for CHB.</p><p><strong>Conclusion: </strong>IFNα treatment improved liver function and iron metabolism homeostasis in patients with CHB. Regular monitoring of serum ALB, SI, SF, and HEPC can help predict the therapeutic response of IFNα treatment for CHB.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156847","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}
Objective: Glutathione peroxidase-4 (GPX4) is a member of Ferroptosis and lipid circulation. This study aims to investigate the expression of GPX4 in esophageal squamous cell carcinoma and its impact on radiosensitivity.
Method: Immunohistochemistry staining was used to detect GPX4 expression in 180 samples of ESCC tissues and adjacent tissues. We analyzed the relationship between GPX4 expression and ESCC clinical parameters. In vitro experiments were conducted using apoptosis assays and colony formation assays to investigate the effect of GPX4 on the radiosensitivity of ESCC cells. In vivo experiments were carried out using a nude mouse xenograft model to evaluate the impact of GPX4 on the radiosensitivity of ESCC.
Results: GPX4 expression was lower in adjacent tissues than tumor tissues. The expression of GPX4 was significantly associated with the pathological grade of ESCC. The overall survival time (OS) of ESCC patients with low GPX4 expression was significantly longer than that of patients with high GPX4 expression. GPX4 could be used as independent prognostic factors in patients with ESCC. In vivo experiments, silencing of GPX4 or using GPX4 inhibitors significantly inhibits the viability and colony formation of ESCC cells after radiation exposure while increasing intracellular reactive oxygen species (ROS) levels, and significantly suppresses the tumorigenic ability of ESCC cells in subcutaneous xenografts after radiation exposure.
Conclusion: GPX4 is highly expressed in ESCC, which has the potential value for prognostic assessment of ESCC. Silencing or inhibiting GPX4 can enhance the radiosensitivity of ESCC.
{"title":"Expression of Glutathione Peroxidase4 in Patients with Esophageal Squamous Carcinoma and Its Impact on the Radiosensitivity of Esophageal Squamous Carcinoma.","authors":"Chen Chen, Wendong Gu, Yingjie Shao, Panpan Zheng, Jingting Jiang","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Glutathione peroxidase-4 (GPX4) is a member of Ferroptosis and lipid circulation. This study aims to investigate the expression of GPX4 in esophageal squamous cell carcinoma and its impact on radiosensitivity.</p><p><strong>Method: </strong>Immunohistochemistry staining was used to detect GPX4 expression in 180 samples of ESCC tissues and adjacent tissues. We analyzed the relationship between GPX4 expression and ESCC clinical parameters. In vitro experiments were conducted using apoptosis assays and colony formation assays to investigate the effect of GPX4 on the radiosensitivity of ESCC cells. <i>In vivo</i> experiments were carried out using a nude mouse xenograft model to evaluate the impact of GPX4 on the radiosensitivity of ESCC.</p><p><strong>Results: </strong>GPX4 expression was lower in adjacent tissues than tumor tissues. The expression of GPX4 was significantly associated with the pathological grade of ESCC. The overall survival time (OS) of ESCC patients with low GPX4 expression was significantly longer than that of patients with high GPX4 expression. GPX4 could be used as independent prognostic factors in patients with ESCC. <i>In vivo</i> experiments, silencing of GPX4 or using GPX4 inhibitors significantly inhibits the viability and colony formation of ESCC cells after radiation exposure while increasing intracellular reactive oxygen species (ROS) levels, and significantly suppresses the tumorigenic ability of ESCC cells in subcutaneous xenografts after radiation exposure.</p><p><strong>Conclusion: </strong>GPX4 is highly expressed in ESCC, which has the potential value for prognostic assessment of ESCC. Silencing or inhibiting GPX4 can enhance the radiosensitivity of ESCC.</p>","PeriodicalId":8228,"journal":{"name":"Annals of clinical and laboratory science","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158066","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}