Analytical Cellular Pathology最新文献

{"title":"Diagnostic Accuracy of p16^INK4a/Ki-67 Dual Immunostaining for Detection of High-Grade Cervical Intraepithelial Neoplasia in Women Involved in Cervical Cancer Screening in Georgia.","authors":"Sopio Kakaliashvili-Dzagnidze,&nbsp;Omar Khardzeishvili,&nbsp;Sergo Tabagari","doi":"10.1155/2023/7988323","DOIUrl":"https://doi.org/10.1155/2023/7988323","url":null,"abstract":"<p><strong>Background: </strong>Despite the widespread introduction of primary and secondary preventative measures, death rates for cervical cancer are still significantly high among females, especially in developing countries. Pap cytology and human papillomavirus-based screening often lead to unnecessary additional testing. The aim of this study is to analyze diagnostic accuracy of p16^INK4a/Ki-67 dual immunostaining (DS) in cervical smear for identifying high-grade cervical intraepithelial neoplasia (CIN2+).</p><p><strong>Materials and methods: </strong>We studied the diagnostic performance of p16^INK4a/Ki-67 DS in cervical smear of those women, who enrolled in cervical cancer screening due to abnormal previous screening results and compared it with Pap test results in identifying CIN2+. The reference standard was histopathology results. p16^INK4a/Ki-67 DS and Pap test results for 162 women and histopathology results for 29 women were available, respectively.</p><p><strong>Results: </strong>In our study, sensitivity, specificity, positive predictive value, and negative predictive value of p16^INK4a/Ki-67 DS, irrespective of the morphology of stained cells to detect CIN2+ were 100%, 89%, 85%, and 100% (<i>p</i> < 0.01), respectively. The diagnostic accuracy of p16^INK4a/Ki-67 DS is superior to that of existing cervical screening tests in the detection of CIN2+.</p><p><strong>Conclusion: </strong>The findings of cervical cancer screening based on Pap cytology highlight the importance of assessing the cost-effectiveness of integrating p16^INK4a/Ki-67 biomarkers in cervical cancer cytology. Furthermore, these findings emphasize the need to enhance support for preventive programs for cervical cancer in Georgia.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2023 ","pages":"7988323"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9666251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenium Donor Inhibited Hepatitis B Virus Associated Hepatotoxicity via the Apoptosis and Ferroptosis Pathways.","authors":"Jingdong Shi,&nbsp;Zhen Liu,&nbsp;Weina Li,&nbsp;Di Wang","doi":"10.1155/2023/6681065","DOIUrl":"https://doi.org/10.1155/2023/6681065","url":null,"abstract":"<p><strong>Methods: </strong>The serum selenium level was determined in 45 patients with HBV-positive HCC (HBV⁺-HCC group), 45 patients with chronic hepatitis B virus infection (CHB group), and 45 healthy cases (HC group). The sodium selenite (Na₂SeO₃)-treated HepG2.2.15 cells were used to observe the regulatory role of selenium on HBV replication. D-GalN/erastin-added HL7702 was used to determine the regulatory roles of Na₂SeO₃ on hepatotoxicity or hepatocyte ferroptosis. The wild-type (WT) C57BL/6 mice and HBx-Tg mice were received lipopolysaccharide (LPS)/D-GalN, together with or without Na₂SeO₃ administration for indicated period. Following euthanasia, the blood and liver tissue samples were collected, and specific markers were evaluated subsequently.</p><p><strong>Results: </strong>The serum selenium level was downregulated in patients with HBV-positive HCC (HBV⁺-HCC group) (57.2 ± 22.5 <i>μ</i>g/L vs. 91.8 ± 43.9 <i>μ</i>g/L, <i>P</i> < 0.001), and its higher level could provide a better prognosis in these patients. The treatment using Na₂SeO₃, a selenium donor, at high concentration (5 <i>μ</i>M), suppressed the HBV replication by about 50% in HepG2.2.15 cells (<i>P</i> < 0.001), through promoting apoptotic cell death and inhibiting cellular inhibitor of apoptosis proteins (cIAPs). In addition, low-dose (500 nM) Na₂SeO₃ could almost totally reversed the hepatotoxicity induced by hepatitis B virus X protein (HBx) (<i>P</i> < 0.001), which were the main causes of HCC in patients. Studies at the cellular levels showed that low-dose Na₂SeO₃ inhibited the HBx-related hepatotoxicity by blocking ferroptosis, and glutathione peroxidase 4 (GPX4) mediated this regulatory role. Mice model results confirmed that the treatment with Na₂SeO₃ could mitigated LPS/D-GalN-induced hepatic injury through ferroptosis pathways.</p><p><strong>Conclusion: </strong>Selenium regulated the dual cell death in different HCC stages via different signaling pathways, which could partly explain the anti-HBV and anti-HCC properties of selenium.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2023 ","pages":"6681065"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10567286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>PCSK9-</i>D374Y Suppresses Hepatocyte Migration through Downregulating Free Cholesterol Efflux Rate and Activity of Extracellular Signal-Regulated Kinase.","authors":"Lei Huang,&nbsp;Ying Cheng,&nbsp;Yulian Mu,&nbsp;Kui Li","doi":"10.1155/2023/6985808","DOIUrl":"https://doi.org/10.1155/2023/6985808","url":null,"abstract":"<p><p>Proprotein convertase subtilisin/kexin type 9 can mediate the intracellular lysosomal degradation of the low-density lipoprotein receptor protein in hepatocytes and decrease the liver's ability to scavenge low-density lipoprotein cholesterol from circulation, resulting in high levels of cholesterol in the circulatory system. Current studies have primarily focused on the relationship between <i>PCSK9</i> and blood lipid metabolism; however, the biological function of <i>PCSK9</i> in hepatocytes is rarely addressed. In this study, we evaluate its effects in the human hepatoma carcinoma cell line HepG2, including proliferation, migration, and free cholesterol transport. <i>PCSK9-</i>D374Y is a gain-of-function mutation that does not affect proliferation but significantly suppresses the migration and cholesterol efflux capacity of these cells. The suppression of the transmembrane outflow of intracellular-free cholesterol regulates small G proteins and the suppression of extracellular signal-regulated kinase. In summary, <i>PCSK9-</i>D374Y affects hepatocyte features, including their migration and free cholesterol transport capabilities.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2023 ","pages":"6985808"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10567304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotine Suppresses Phagocytic Ability of Macrophages by Regulating the miR-296-3p-SIRP<i>α</i> Axis.","authors":"Zhen Liu,&nbsp;Fang Wang,&nbsp;Xiaowu Huang,&nbsp;Zhi Chen,&nbsp;Yicheng Zhao,&nbsp;Yawei Wang,&nbsp;Xiaobo Luo,&nbsp;Guanren Zhao","doi":"10.1155/2023/6306358","DOIUrl":"https://doi.org/10.1155/2023/6306358","url":null,"abstract":"<p><p>Phagocytic ability of macrophage is responsible for tuberculosis infection. Nicotine has been shown to attenuate the phagocytic ability of macrophage; however, the underlying mechanism remains unclear. Here, we demonstrated that nicotine increased the message RNA (mRNA) and protein expression of signal regulatory protein alpha (SIRP<i>α</i>) and enhanced the stability of SIRP<i>α</i> mRNA in macrophage. Nicotine decreased the expression of microRNA (miR)-296-3p, which directly targeted the 3'-untranslated region (3'-UTR) of SIRP<i>α</i> mRNA in macrophage. Furthermore, nicotine inhibited the phagocytic ability of macrophage by regulating the miR-296-3p-SIRP<i>α</i> axis. Moreover, nicotine decreased miR-296-3p expression via increasing c-Myc expression in macrophage. Together, we found that nicotine attenuate the phagocytic ability of macrophage by regulating the c-Myc-miR-296-3p-SIRP<i>α</i> signal.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2023 ","pages":"6306358"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9946743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10813394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Action of Decitabine in the Treatment of Acute Myeloid Leukemia by Regulating LINC00599.","authors":"Fan Du,&nbsp;Ting Jin,&nbsp;Li Wang","doi":"10.1155/2023/2951519","DOIUrl":"https://doi.org/10.1155/2023/2951519","url":null,"abstract":"<p><strong>Objective: </strong>Acute myeloid leukemia (AML) is a heterogeneous malignancy with a low long-term survival rate. The aim of this study was to investigate the effects of decitabine (DAC) treatment cell proliferation and apoptosis in AML and role of the expression of LINC00599 and, consequently, miR-135a-5p.</p><p><strong>Materials and methods: </strong>Human promyelocytic leukemia cells (HL-60) and human acute lymphatic leukemia (CCRF-CEM) cells were treated with various concentrations of DAC. Cell proliferation in each group was detected using the cell counting kit 8. For each group, apoptosis and reactive oxygen species (ROS) levels were detected using flow cytometry. Reverse transcription polymerase chain reaction (RT-PCR) was performed to examine the expression of lncRNA LINC00599. The expression of apoptosis-related proteins was analyzed using western blotting. The regulatory relationship between miR-135a-5p and LINC00599 was verified by constructing miR-135a-5p mimics, miR-135a-5p inhibit, wild type LINC00599 3'-untranslated region (UTR), and mutant LINC00599 3'-UTR. Ki-67 expression in the tumor tissues of nude mice was detected using immunofluorescent assays.</p><p><strong>Results: </strong>Both DAC and LINC00599 Inhibit groups were able to significantly reduce the proliferation of HL60 and CCRF-CEM cells, increase apoptosis, upregulate the expression of Bad, cleaved caspase-3, and miR-135a-5p, downregulate the expression of Bcl-2, and elevate ROS levels in cells, with these effects being more pronounced after combined treatment with DAC and LINC00599 Inhibit. In comparison to mimic NC, the miR-135a-5p mimic group significantly decreased the relative fluorescence activity ratio of LINC00599 3'-UTR wild-type CCRF-CEM cells. The LINC00599 Inhibit and miR-135a-5p mimic groups exhibited substantially reduced proliferation of HL60 and CCRF-CEM cells, increased apoptosis, upregulated Bad, cleaved caspase-3, and miR-135a-5p expression, along with downregulated Bcl-2 and LINC00599 expression and increased ROS levels in cells; these effects were more pronounced after LINC00599 Inhibit was combined with miR-135a-5p mimics. In vivo experiments revealed that both DAC and LINC00599 Inhibit were able to considerably reduce the long diameter, short meridian, volume, and mass of tumors, increase miR-135a-5p expression, and decrease LINC00599 and ki-67 expression in tumor tissues of nude mice. This effect was more pronounced when the DAC and LINC00599 Inhibit were used in combination.</p><p><strong>Conclusion: </strong>DAC regulates the expression of miR-135a-5p by regulating the expression of LINC00599, which in turn affects cell proliferation, apoptosis, and tumor proliferation. Our findings provide a theoretical basis for improving the clinical outcome of AML.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2023 ","pages":"2951519"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10854216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of miR-182-5p Targets FGF9 to Alleviate Osteoarthritis.","authors":"Yang Sun,&nbsp;Sanmao Su,&nbsp;Mengjun Li,&nbsp;Ang Deng","doi":"10.1155/2023/5911546","DOIUrl":"https://doi.org/10.1155/2023/5911546","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of osteoarthritis (OA) is complex and there is no specific drug for treatment. The aim of this study was to identify the molecular targets of OA therapy, focusing on the expression and biological functions of miR-182-5p and its target genes in OA.</p><p><strong>Methods: </strong>miR-182-5p and fibroblast growth factor 9 (FGF9) were overexpressed or knocked down in IL-1<i>β</i>-induced chondrocytes. An OA knee model was performed by surgically destroying the medial meniscus. The gene expression of miR-182-5p and FGF9 was calculated. The protein FGF9 was tested by western blotting. Cell counting kit-8 (CCK8), plate cloning assay, and flow cytometry were conducted to evaluate cell proliferation and apoptosis. The expression of inflammatory factors, tumor necrosis factor-alpha (TNF-<i>α</i>), interleukin (IL)-6, and interleukin (IL)-8, was evaluated using enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assays validated the targeting relationship between miR-182-5p and FGF9. Hematoxylin-eosin (HE) and safranin O-fast Green (S-O) staining were utilized to access cartilage damage. Ki67 expression in cartilage was detected using immunohistochemistry (IHC). TdT-mediated dUTP nick-end labeling (TUNEL) assays were used to calculate the apoptosis rate of cartilage.</p><p><strong>Results: </strong>The expression of miR-182-5p was upregulated, and FGF9 was downregulated in the IL-1<i>β</i>-induced chondrocytes. OA chondrocytes proliferation ability in the miR-182-5p mimics group was decreased, and the apoptosis rate and inflammatory factor were increased. Transfection with miR-182-5p inhibitor increased the proliferative ability and decreased the apoptosis rate in the IL-1<i>β</i>-induced chondrocytes. Transfection with miR-182-5p inhibitor reversed IL-1<i>β</i>-induced inflammatory factor release in chondrocytes. Targeted binding sites existed between miR-182-5p and FGF9. After overexpression of FGF9, the miR-182-5p effect on OA chondrocytes was reversed. The hyaline cartilage thickness and proteoglycan content decreased in OA rats, and this was reversed by miR-182-5p inhibitor treatment.</p><p><strong>Conclusions: </strong>miR-182-5p expression levels were increased in OA chondrocytes and regulated chondrocyte proliferation, apoptosis, and inflammation by targeting FGF9. miR-182-5p is a potential gene for OA treatment.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2023 ","pages":"5911546"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9266676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Accurate Interpretation and Clinical Significance of Morphological Features of Fine Needle Aspiration Cells in Papillary Thyroid Carcinoma.","authors":"Xue-Jiao Xiong,&nbsp;Ming-Ming Xiao,&nbsp;Yi-Xia Zhang,&nbsp;Dong-Ge Liu,&nbsp;Mu-Lan Jin,&nbsp;Jian Wang,&nbsp;Hong-Tao Xu,&nbsp;Qing-Chang Li,&nbsp;Guang-Ping Wu","doi":"10.1155/2023/9397755","DOIUrl":"https://doi.org/10.1155/2023/9397755","url":null,"abstract":"<p><p>Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid gland; fine needle aspiration cytology is the most basic and reliable diagnostic method before PTC operation. However, it is not clear which cell morphological changes can be used as a reliable standard for the diagnosis of PTC. A retrospective analysis was performed on 337 patients with PTC confirmed by postoperative histology. An additional 197 randomly selected patients with benign thyroid lesions were included in the study and used as a control group. True papillary arrangements, swirl arrangements, and escape arrangements had high specificity, all of which were 100%, but only swirl arrangements had ideal sensitivity (77.61%). The nuclear volume characteristics had a high sensitivity of more than 90%, but the specificities of both nuclear crowding and nuclear overlap were too low, only 16.34% and 23.35%. The sensitivities of five nuclear structural characteristics were more than 90%, but only the specificity of intranuclear cytoplasmic pseudoinclusions (INCIs) reached 100%, nuclear contour irregularity and pale nuclei with powdery chromatin also had ideal interpretation value except for grooves and marginally placed micronucleoli. Although the sensitivity of psammoma bodies (PBs) was low, the specificity was 100%. In terms of preparation methods, the method of liquid-based preparation (LBP) is obviously better than that of conventional smears. The diagnostic efficiency by the combined detection method of parallel tests showed that without reducing the specificity, the sensitivity increased with the increase of the number of morphological characteristics and finally reached 98.81%. The INCIs and swirl arrangements are the most common and important indicators for the diagnosis of PTC, whereas papillary-like arrangements, the crowding and overlap of nuclear, grooves, marginally placed micronucleoli, and multinucleated giant cells are of little significance for the diagnosis of PTC.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2023 ","pages":"9397755"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9469593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Use of Cell Block and Smear Improves the Cytological Diagnosis of Malignancy in Non-Palpable Breast Lesions Screened by Imaging.","authors":"Rieko Nishimura,&nbsp;Mikinao Oiwa","doi":"10.1155/2023/1869858","DOIUrl":"https://doi.org/10.1155/2023/1869858","url":null,"abstract":"<p><strong>Background: </strong>Currently, core needle biopsy is replacing fine needle aspiration biopsy (FNAB) for pathological diagnosis of breast lesions. However, FNAB is extensively used for diagnosing breast lesions, including screened lesions, at our hospital. Furthermore, direct smears as well as cell blocks (CBs) from the FNAB specimens have been used. To prepare the CBs, hematoxylin and eosin (HE) staining as well as immunostaining with a mixture of p63 and cytokeratin 5/6 antibodies are routinely used. Therefore, in the current study, we sought to assess the efficacy of diagnosing breast lesions using conventional smears and CB immunostaining.</p><p><strong>Methods: </strong>Breast FNAB reports of direct smears and CBs from The Nagoya Medical Center between December 2014 and March 2020, were reviewed. The efficiency of diagnoses made with direct smears and CBs were compared using histology-based diagnoses.</p><p><strong>Results: </strong>Among the 169 histologically confirmed malignant lesions, 12 lesions that were reported as unsatisfactory, benign, or atypia probably benign, using direct smears were diagnosed as malignant using CB. Histologically, these lesions were diagnosed as carcinomas with mild atypia or papillary structures. Ten (83.3%) of the twelve lesions were non-palpable and only detected upon imaging.</p><p><strong>Conclusion: </strong>Combined use of CB and conventional smear leads to the detection of more malignant lesions in breast FNAB specimens, particularly in lesions detected by imaging alone. Immunostaining of CB sections using a mixture of p63 and cytokeratin 5/6 antibodies provides more information than HE staining alone. Breast FNAB with CB preparation can be successfully applied for evaluation of breast lesions in developed countries.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2023 ","pages":"1869858"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9469594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cartilage Damage Pathological Characteristics of Diabetic Neuropathic Osteoarthropathy.","authors":"Pei-Long Liu,&nbsp;Jia-Yu Diao,&nbsp;Qiong Wang,&nbsp;Huan Liu,&nbsp;Yan Zhang,&nbsp;Jing-Qi Liang,&nbsp;Feng Zhang,&nbsp;Xiao-Jun Liang,&nbsp;Hong-Mou Zhao","doi":"10.1155/2023/7573165","DOIUrl":"https://doi.org/10.1155/2023/7573165","url":null,"abstract":"<p><strong>Background: </strong>Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients.</p><p><strong>Methods: </strong>The articular cartilages of eight patients with DNOAP and eight normal controls were included. Masson staining and safranine O/fixed green staining (S-O) were used to observe the histopathological characteristics of cartilage. The ultrastructure and morphology of chondrocytes were detected by electron microscopy and toluidine blue staining. Chondrocytes were isolated from DNOAP group and control group. The expression of receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-1 beta (IL-1<i>β</i>), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-<i>α</i>), and Aggrecan protein was evaluated by western blot. Reactive oxygen species (ROS) levels were measured using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) probe. The percentage of apoptotic cells was determined by flow cytometry (FCM). The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG.</p><p><strong>Results: </strong>Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia, and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swellings were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 vs. 11.9 ± 0.7; <i>P</i> < 0.05). The expression of RANKL, TNF-<i>α</i>, IL-1<i>β</i>, and IL-6 protein in DNOAP group was higher than that in normal control group, whereas OPG and Aggrecan protein were lower than that in normal control group (both <i>P</i> < 0.05). FCM showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group (<i>P</i> < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15 mM.</p><p><strong>Conclusions: </strong>DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL and OPG) and inflammatory cytokines (IL-1<i>β</i>, IL-6, and TNF-<i>α</i>) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15 mM made the RANKL/OPG ratio change rapidly.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2023 ","pages":"7573165"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10185426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain Renin-Angiotensin System: From Physiology to Pathology in Neuronal Complications Induced by SARS-CoV-2.","authors":"Shamseddin Ahmadi,&nbsp;Shiler Khaledi","doi":"10.1155/2023/8883492","DOIUrl":"https://doi.org/10.1155/2023/8883492","url":null,"abstract":"<p><p>Angiotensin-converting enzyme 2 (ACE2), a key enzyme in the renin-angiotensin system (RAS), is expressed in various tissues and organs, including the central nervous system (CNS). The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease-2019 (COVID-19), binds to ACE2, which raises concerns about the potential for viral infection in the CNS. There are numerous reports suggesting a link between SARS-CoV-2 infection and neurological manifestations. This study aimed to present an updated review of the role of brain RAS components, especially ACE2, in neurological complications induced by SARS-CoV-2 infection. Several routes of SARS-CoV-2 entry into the brain have been proposed. Because an anosmia condition appeared broadly in COVID-19 patients, the olfactory nerve route was suggested as an early pathway for SARS-CoV-2 entry into the brain. In addition, a hematogenous route via disintegrations in the blood-brain barrier following an increase in systemic cytokine and chemokine levels and retrograde axonal transport, especially via the vagus nerve innervating lungs, have been described. Common nonspecific neurological symptoms in COVID-19 patients are myalgia, headache, anosmia, and dysgeusia. However, more severe outcomes include cerebrovascular diseases, cognitive impairment, anxiety, encephalopathy, and stroke. Alterations in brain RAS components such as angiotensin II (Ang II) and ACE2 mediate neurological manifestations of SARS-CoV-2 infection, at least in part. Downregulation of ACE2 due to SARS-CoV-2 infection, followed by an increase in Ang II levels, leads to hyperinflammation and oxidative stress, which in turn accelerates neurodegeneration in the brain. Furthermore, ACE2 downregulation in the hypothalamus induces stress and anxiety responses by increasing corticotropin-releasing hormone. SARS-CoV-2 infection may also dysregulate the CNS neurotransmission, leading to neurological complications observed in severe cases of COVID-19. It can be concluded that the neurological manifestations of COVID-19 may be partially associated with changes in brain RAS components.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":"2023 ","pages":"8883492"},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}