The activation of activin receptor-like kinase 4 (ALK4) signaling plays a pivotal role in the pressure-overloaded heart, and haplodeficiency of ALK4 can alleviate cardiac fibrosis secondary to myocardial infarction and preserve cardiac function through partially inactivating the Smad3/4 pathway. However, whether transforming growth factor (TGF) β signaling is involved in the beneficial effects of ALK4 knockdown on the ischemic heart is still unclear. This study was undertaken to investigate the change in the TGFβ signaling after ALK4 knockdown in vivo and in vitro. Forty C57BL/6J mice were randomized into ALK4+/- ischemia/reperfusion (I/R) group (ALK4+/-+I/R, n = 10), ALK4+/- sham group (ALK4+/-+sham, n = 10), wild-type sham group (WT+sham, n = 10), and WT I/R group (WT+I/R, n = 10). Heart histology and the levels of cytokines related to antioxidant and inflammation, as well as protein and mRNA expressions of molecules associated with TGFβ pathway, were examined in different groups. Our results showed that the reduction of ALK4 expression ameliorated myocardial I/R injury through inhibiting TGFβ signaling pathway. Our findings indicate that ALK4 may become a novel target for the therapy of myocardial I/R injury.
激活素受体样激酶4 (activin receptor-like kinase 4, ALK4)信号的激活在压力过载的心脏中起着关键作用，ALK4单倍体缺失可以通过部分失活Smad3/4通路，减轻心肌梗死继发的心肌纤维化，维持心功能。然而，转化生长因子(TGF) β信号是否参与了ALK4敲低对缺血心脏的有益作用尚不清楚。本研究旨在探讨体内和体外敲除ALK4后tgf - β信号通路的变化。将40只C57BL/6J小鼠随机分为ALK4+/-缺血/再灌注(I/R)组(ALK4+/-+I/R, n = 10)、ALK4+/-假手术组(ALK4+/-+sham, n = 10)、野生型假手术组(WT+sham, n = 10)和WT I/R组(WT+I/R, n = 10)。检测各组心脏组织学、抗氧化和炎症相关细胞因子水平以及TGFβ通路相关分子蛋白和mRNA表达。结果表明，降低ALK4表达可通过抑制tgf - β信号通路改善心肌I/R损伤。我们的研究结果表明，ALK4可能成为心肌I/R损伤治疗的新靶点。
{"title":"Reduction of Activin Receptor-Like Kinase 4 Expression Ameliorates Myocardial Ischemia/Reperfusion Injury through Inhibiting TGFβ Signaling Pathway","authors":"Mantian Chen, Yinggang Sun, Qian Wang, Yigang Li","doi":"10.1155/2022/5242323","DOIUrl":"https://doi.org/10.1155/2022/5242323","url":null,"abstract":"The activation of activin receptor-like kinase 4 (ALK4) signaling plays a pivotal role in the pressure-overloaded heart, and haplodeficiency of ALK4 can alleviate cardiac fibrosis secondary to myocardial infarction and preserve cardiac function through partially inactivating the Smad3/4 pathway. However, whether transforming growth factor (TGF) β signaling is involved in the beneficial effects of ALK4 knockdown on the ischemic heart is still unclear. This study was undertaken to investigate the change in the TGFβ signaling after ALK4 knockdown in vivo and in vitro. Forty C57BL/6J mice were randomized into ALK4+/- ischemia/reperfusion (I/R) group (ALK4+/-+I/R, n = 10), ALK4+/- sham group (ALK4+/-+sham, n = 10), wild-type sham group (WT+sham, n = 10), and WT I/R group (WT+I/R, n = 10). Heart histology and the levels of cytokines related to antioxidant and inflammation, as well as protein and mRNA expressions of molecules associated with TGFβ pathway, were examined in different groups. Our results showed that the reduction of ALK4 expression ameliorated myocardial I/R injury through inhibiting TGFβ signaling pathway. Our findings indicate that ALK4 may become a novel target for the therapy of myocardial I/R injury.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"215 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122843222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spinal cord injury (SCI) is an extreme neurological impairment with few effective drug treatments. Pyroptosis is a recently found and proven type of programmed cell death that is characterized by a reliance on inflammatory caspases and the release of a large number of proinflammatory chemicals. Pyroptosis differs from other cell death mechanisms such as apoptosis and necrosis in terms of morphological traits, incidence, and regulatory mechanism. Pyroptosis is widely involved in the occurrence and development of SCI. In-depth research on pyroptosis will help researchers better understand its involvement in the onset, progression, and prognosis of SCI, as well as provide new therapeutic prevention and treatment options. Herein, we investigated the role of AMPK-mediated activation of the NLRP3 inflammasome in the neuroprotection of MET-regulated pyroptosis. We found that MET treatment reduced NLRP3 inflammasome activation by activating phosphorylated AMPK and reduced proinflammatory cytokine (IL-1β, IL-6, and TNF-α) release. At the same time, MET improved motor function recovery in rats after SCI by reducing motor neuron loss in the anterior horn of the spinal cord. Taken together, our study confirmed that MET inhibits neuronal pyroptosis after SCI via the AMPK/NLRP3 signaling pathway, which is mostly dependent on the AMPK pathway increase, hence decreasing NLRP3 inflammasome activation.
{"title":"Metformin Protects against Spinal Cord Injury and Cell Pyroptosis via AMPK/NLRP3 Inflammasome Pathway","authors":"Yajiang Yuan, Xiangyi Fan, Zhanpeng Guo, Zipeng Zhou, Weiran Gao","doi":"10.1155/2022/3634908","DOIUrl":"https://doi.org/10.1155/2022/3634908","url":null,"abstract":"Spinal cord injury (SCI) is an extreme neurological impairment with few effective drug treatments. Pyroptosis is a recently found and proven type of programmed cell death that is characterized by a reliance on inflammatory caspases and the release of a large number of proinflammatory chemicals. Pyroptosis differs from other cell death mechanisms such as apoptosis and necrosis in terms of morphological traits, incidence, and regulatory mechanism. Pyroptosis is widely involved in the occurrence and development of SCI. In-depth research on pyroptosis will help researchers better understand its involvement in the onset, progression, and prognosis of SCI, as well as provide new therapeutic prevention and treatment options. Herein, we investigated the role of AMPK-mediated activation of the NLRP3 inflammasome in the neuroprotection of MET-regulated pyroptosis. We found that MET treatment reduced NLRP3 inflammasome activation by activating phosphorylated AMPK and reduced proinflammatory cytokine (IL-1β, IL-6, and TNF-α) release. At the same time, MET improved motor function recovery in rats after SCI by reducing motor neuron loss in the anterior horn of the spinal cord. Taken together, our study confirmed that MET inhibits neuronal pyroptosis after SCI via the AMPK/NLRP3 signaling pathway, which is mostly dependent on the AMPK pathway increase, hence decreasing NLRP3 inflammasome activation.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"230 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130517478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Currently, the Thinprep cytologic test (TCT) is the most popular cervical cancer cytology test technique. It can detect precancerous conditions and microbial infections. However, this technique entirely relies on manual operation and doctors' naked eye observation, resulting in a heavy workload and low accuracy rate. Recently, automatic pathological diagnosis has been developed to solve this problem. Cervical cell classification is a key technology in the intelligent cervical cancer diagnosis system. Training a deep neural network-based classification model requires a large amount of data. However, cervical cell labeling requires specialized physicians and the cost of labeling is high, resulting in a lack of sufficient labeling data in this field. To address this problem, we propose a method to ensure high accuracy in cervical cell classification with a small amount of labeled data by introducing manual features and a voting mechanism to achieve data expansion in semi-supervised learning. The method consists of three main steps, using a clarity function to filter out high-quality cervical cell images, annotating a small amount of them, and balancing the training data using a voting mechanism. With a small amount of labeled data, the accuracy of the proposed method in this paper can reach to 91.94%.
{"title":"A Semi-supervised Deep Learning Method for Cervical Cell Classification","authors":"Siqi Zhao, Yongjun He, Jian Qin, Zixuan Wang","doi":"10.1155/2022/4376178","DOIUrl":"https://doi.org/10.1155/2022/4376178","url":null,"abstract":"Currently, the Thinprep cytologic test (TCT) is the most popular cervical cancer cytology test technique. It can detect precancerous conditions and microbial infections. However, this technique entirely relies on manual operation and doctors' naked eye observation, resulting in a heavy workload and low accuracy rate. Recently, automatic pathological diagnosis has been developed to solve this problem. Cervical cell classification is a key technology in the intelligent cervical cancer diagnosis system. Training a deep neural network-based classification model requires a large amount of data. However, cervical cell labeling requires specialized physicians and the cost of labeling is high, resulting in a lack of sufficient labeling data in this field. To address this problem, we propose a method to ensure high accuracy in cervical cell classification with a small amount of labeled data by introducing manual features and a voting mechanism to achieve data expansion in semi-supervised learning. The method consists of three main steps, using a clarity function to filter out high-quality cervical cell images, annotating a small amount of them, and balancing the training data using a voting mechanism. With a small amount of labeled data, the accuracy of the proposed method in this paper can reach to 91.94%.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124511850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingying Sun, Qiuying Cao, Xiaoyu Zhao, Chunyan Liu, Z. Shao
Introduction Lymphocyte activation gene 3 (LAG3) is an inhibitory checkpoint protein expressed on activated T effector, T regulatory, and natural killer cells. The main function of LAG3 is the regulation of immune homeostasis. Several studies have suggested its role in malignant and autoimmune diseases. The objective of this study was to explore the association between LAG3 single-nucleotide polymorphisms (SNPs) and bone marrow failure diseases. Methods Sixty-two patients newly diagnosed with bone marrow failure diseases in the Hematology Department of Tianjin Medical University General Hospital between January 2019 and December 2020 and 16 healthy controls were enrolled in this study. SNPs in LAG3 were investigated by performing Sanger sequencing, and the association of the detected SNPs with bone marrow failure diseases was analyzed. Results Eleven SNPs were identified. Among them, the frequency of LAG3 rs1941928301 (C>T) was statistically different among the groups (P = 0.013). It was higher in the myelodysplastic syndrome (MDS) group than that in the severe aplastic anemia (SAA) group (P = 0.004) and that in the healthy control group (P = 0.009). Conclusions LAG3 rs1941928301 (C>T) might be associated with a higher risk of MDS. The detected LAG3 SNPs have no apparent effect on susceptibility to SAA and immune-related pancytopenia (IRP).
{"title":"Lymphocyte Activation Gene 3 Single-Nucleotide Polymorphisms in Bone Marrow Failure Diseases","authors":"Yingying Sun, Qiuying Cao, Xiaoyu Zhao, Chunyan Liu, Z. Shao","doi":"10.1155/2022/3528598","DOIUrl":"https://doi.org/10.1155/2022/3528598","url":null,"abstract":"Introduction Lymphocyte activation gene 3 (LAG3) is an inhibitory checkpoint protein expressed on activated T effector, T regulatory, and natural killer cells. The main function of LAG3 is the regulation of immune homeostasis. Several studies have suggested its role in malignant and autoimmune diseases. The objective of this study was to explore the association between LAG3 single-nucleotide polymorphisms (SNPs) and bone marrow failure diseases. Methods Sixty-two patients newly diagnosed with bone marrow failure diseases in the Hematology Department of Tianjin Medical University General Hospital between January 2019 and December 2020 and 16 healthy controls were enrolled in this study. SNPs in LAG3 were investigated by performing Sanger sequencing, and the association of the detected SNPs with bone marrow failure diseases was analyzed. Results Eleven SNPs were identified. Among them, the frequency of LAG3 rs1941928301 (C>T) was statistically different among the groups (P = 0.013). It was higher in the myelodysplastic syndrome (MDS) group than that in the severe aplastic anemia (SAA) group (P = 0.004) and that in the healthy control group (P = 0.009). Conclusions LAG3 rs1941928301 (C>T) might be associated with a higher risk of MDS. The detected LAG3 SNPs have no apparent effect on susceptibility to SAA and immune-related pancytopenia (IRP).","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132701576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Papillary thyroid cancer (PTC) is a type of epithelial-derived differentiated TC that reportedly accounts for a majority of TCs. Curcumin, a polyphenolic compound and a member of the Zingiberaceae (ginger) family derived from turmeric plants, can exhibit anticancer effects. Herein, we aimed to investigate the effect of curcumin on PTC and elucidate underlying mechanisms. Accordingly, PTC B-CPAP cells were treated with curcumin, in combination with/without long noncoding RNA LINC00691 inhibition, to determine the effect of curcumin and its relationship with LINC00691 in PTC cells. We observed that curcumin treatment decreased B-CPAP cell proliferation and promoted apoptosis. Curcumin inhibited LINC00691 expression in B-CPAP cells. Curcumin administration or si-LINC00691 transfection alone promoted ATP levels, inhibited glucose uptake and lactic acid levels, and inhibited lactate dehydrogenase A and hexokinase 2 protein expression in B-CPAP cells, which were further enhanced by combination treatment. Moreover, curcumin administration or si-LINC00691 transfection alone inhibited p-Akt activity, further suppressed by combination treatment. Akt inhibition promoted apoptosis and suppressed the Warburg effect in B-CPAP cells. In conclusion, our findings indicate that curcumin promotes apoptosis and suppresses proliferation and the Warburg effect by inhibiting LINC00691 in B-CPAP cells. The precise molecular mechanism might be mediated through the Akt signaling pathway, providing a theoretical basis for the treatment of PTC with curcumin.
{"title":"Curcumin Inhibits Papillary Thyroid Cancer Cell Proliferation by Regulating lncRNA LINC00691","authors":"Zhihua Li, Youbing Gao, Lijun Li, Shanshan Xie","doi":"10.1155/2022/5946670","DOIUrl":"https://doi.org/10.1155/2022/5946670","url":null,"abstract":"Papillary thyroid cancer (PTC) is a type of epithelial-derived differentiated TC that reportedly accounts for a majority of TCs. Curcumin, a polyphenolic compound and a member of the Zingiberaceae (ginger) family derived from turmeric plants, can exhibit anticancer effects. Herein, we aimed to investigate the effect of curcumin on PTC and elucidate underlying mechanisms. Accordingly, PTC B-CPAP cells were treated with curcumin, in combination with/without long noncoding RNA LINC00691 inhibition, to determine the effect of curcumin and its relationship with LINC00691 in PTC cells. We observed that curcumin treatment decreased B-CPAP cell proliferation and promoted apoptosis. Curcumin inhibited LINC00691 expression in B-CPAP cells. Curcumin administration or si-LINC00691 transfection alone promoted ATP levels, inhibited glucose uptake and lactic acid levels, and inhibited lactate dehydrogenase A and hexokinase 2 protein expression in B-CPAP cells, which were further enhanced by combination treatment. Moreover, curcumin administration or si-LINC00691 transfection alone inhibited p-Akt activity, further suppressed by combination treatment. Akt inhibition promoted apoptosis and suppressed the Warburg effect in B-CPAP cells. In conclusion, our findings indicate that curcumin promotes apoptosis and suppresses proliferation and the Warburg effect by inhibiting LINC00691 in B-CPAP cells. The precise molecular mechanism might be mediated through the Akt signaling pathway, providing a theoretical basis for the treatment of PTC with curcumin.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"234 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121481914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanfei Li, Dafa Shi, Haoran Zhang, Xiang Yao, Ke Ren
Background The definitive mechanisms of CI-AKI include contrast medium (CM) nephrotoxicity and CM disturbances in renal blood flow, but how the immune system responds to CM has rarely been mentioned in previous studies, and different cell death pathways have not been clearly distinguished. Aim To confirm whether MRI detect early CI-AKI and to investigate whether immunity-related responses, pyroptosis, and mitophagy participate in contrast-induced acute renal injury (CI-AKI). Methods C57BL/6 mice with CI-AKI were established by tail vein injection of iodixanol 320. Magnetic resonance imaging of 9.4 T scanner and microscopic appearance of renal H&E staining were tools to test the occurrence of CI-AKI at different times. Immunohistochemistry and NGAL were used to examine the immune responses in the kidneys with CI-AKI. Transmission electron microscopy and western blot methods were used to distinguish various cell death pathways in CI-AKI. Key Results. The densitometry of T2WI, DTI, and BOLD presents CI-AKI in a regular way. The microscopic appearance presents the strongest renal damage in CI-AKI mice that existed between 12 h (P < 0.0001) and 24 h (P < 0.05) after contrast medium (CM) injection. Strong correlation may exist between MRI densitometry (T2WI, DTI, and BOLD) and pathology. Neutrophil and macrophage chemotaxis occurred in CI-AKI, and we observed that Ly6G was the strongest at 48 h (P < 0.0001). Pyroptosis (Nlrp3/caspase-1, P < 0.05), mitophagy (BNIP/Nix, P < 0.05), and apoptosis (Bax, P < 0.05) occurred in CI-AKI. Conclusions fMRI can detect early CI-AKI immediately after CM injection. NLRP3 inflammasomes are involved in CI-AKI, and mitophagy may play a role in mitigating kidney injury. The mitochondrion is one of the key organelles in the tubular epithelium implicated in CI-AKI.
CI-AKI的明确机制包括造影剂(CM)肾毒性和造影剂对肾血流的干扰，但在以往的研究中很少提到免疫系统对CM的反应，不同的细胞死亡途径也没有明确区分。目的探讨MRI是否能早期检测到造影剂诱导的急性肾损伤(CI-AKI)，探讨免疫相关反应、焦亡和线粒体自噬是否参与造影剂诱导的急性肾损伤(CI-AKI)。方法采用尾静脉注射碘沙醇320建立CI-AKI小鼠C57BL/6模型。mri 9.4 T扫描和肾H&E染色镜检是检测不同时间CI-AKI发生的工具。采用免疫组织化学和NGAL检测CI-AKI肾脏的免疫反应。采用透射电镜和western blot方法区分CI-AKI细胞的各种死亡途径。关键的结果。T2WI、DTI、BOLD的密度测定显示CI-AKI具有规律性。造影剂(CM)注射后12 h ~ 24 h (P < 0.05)， CI-AKI小鼠肾损伤在显微镜下表现为最强。MRI密度测量(T2WI, DTI和BOLD)与病理之间可能存在很强的相关性。CI-AKI发生中性粒细胞和巨噬细胞趋化，我们观察到Ly6G在48 h时最强(P < 0.0001)。CI-AKI发生焦亡(Nlrp3/caspase-1, P < 0.05)、线粒体自噬(BNIP/Nix, P < 0.05)和细胞凋亡(Bax, P < 0.05)。结论fMRI可在CM注射后立即发现早期CI-AKI。NLRP3炎性小体参与CI-AKI，线粒体自噬可能在减轻肾损伤中发挥作用。线粒体是参与CI-AKI的小管上皮的关键细胞器之一。
{"title":"Magnetic Resonance Imaging of Contrast-Induced Acute Renal Injury and Related Pathological Alterations In Vivo","authors":"Yanfei Li, Dafa Shi, Haoran Zhang, Xiang Yao, Ke Ren","doi":"10.1155/2022/6984200","DOIUrl":"https://doi.org/10.1155/2022/6984200","url":null,"abstract":"Background The definitive mechanisms of CI-AKI include contrast medium (CM) nephrotoxicity and CM disturbances in renal blood flow, but how the immune system responds to CM has rarely been mentioned in previous studies, and different cell death pathways have not been clearly distinguished. Aim To confirm whether MRI detect early CI-AKI and to investigate whether immunity-related responses, pyroptosis, and mitophagy participate in contrast-induced acute renal injury (CI-AKI). Methods C57BL/6 mice with CI-AKI were established by tail vein injection of iodixanol 320. Magnetic resonance imaging of 9.4 T scanner and microscopic appearance of renal H&E staining were tools to test the occurrence of CI-AKI at different times. Immunohistochemistry and NGAL were used to examine the immune responses in the kidneys with CI-AKI. Transmission electron microscopy and western blot methods were used to distinguish various cell death pathways in CI-AKI. Key Results. The densitometry of T2WI, DTI, and BOLD presents CI-AKI in a regular way. The microscopic appearance presents the strongest renal damage in CI-AKI mice that existed between 12 h (P < 0.0001) and 24 h (P < 0.05) after contrast medium (CM) injection. Strong correlation may exist between MRI densitometry (T2WI, DTI, and BOLD) and pathology. Neutrophil and macrophage chemotaxis occurred in CI-AKI, and we observed that Ly6G was the strongest at 48 h (P < 0.0001). Pyroptosis (Nlrp3/caspase-1, P < 0.05), mitophagy (BNIP/Nix, P < 0.05), and apoptosis (Bax, P < 0.05) occurred in CI-AKI. Conclusions fMRI can detect early CI-AKI immediately after CM injection. NLRP3 inflammasomes are involved in CI-AKI, and mitophagy may play a role in mitigating kidney injury. The mitochondrion is one of the key organelles in the tubular epithelium implicated in CI-AKI.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121655799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Y. Lee, Hyunchul Kim, I. Kwak, Young-Gyu Jang, Y. Choi
Background Post-burn hypertrophic scars commonly occur after burns. Studies that compare dermal substitutes with other treatment methods are insufficient. The purpose was to analyze the histopathological differences in hypertrophic burn scars after Matriderm®+split-thickness skin graft (STSG) and compare with AlloDerm®+STSG, STSG, full-thickness skin graft (FTSG), and normal skin. Methods Samples of unburned, normal skin and deep 2nd or 3rd degree burns were obtained from patients who experienced a burn injury in the past to at least 6 months before biopsy, which was performed between 2011 and 2012. All subjects received >6 months of treatment before the biopsy. Intervention groups were normal (63), STSG (28), FTSG (6), Matriderm® (11), and AlloDerm® (18). Immunohistochemical analyses of elastin, collagen I, collagen III, cluster of differentiation 31 (CD31), smooth muscle actin (α-SMA), and laminin from scar and control tissues were performed and compared. Results α-SMA vascular quantity and vessel width, stromal CD31, and basement membrane laminin expression were not significantly different between normal and intervention groups. Matriderm® group showed no significant difference in elastin, collagen III, stromal CD31 and α-SMA, CD31 vessel width, stromal α-SMA, vessel quantity and width, and laminin length compared to the normal group, meaning they were not significantly different from the normal skin traits. Conclusion Dermal substitutes may be an optimal alternative to address the cosmetic and functional limitations posed by other treatment methods.
{"title":"Immunohistochemical Analysis of Postburn Scars following Treatment Using Dermal Substitutes","authors":"M. Y. Lee, Hyunchul Kim, I. Kwak, Young-Gyu Jang, Y. Choi","doi":"10.1155/2022/3686863","DOIUrl":"https://doi.org/10.1155/2022/3686863","url":null,"abstract":"Background Post-burn hypertrophic scars commonly occur after burns. Studies that compare dermal substitutes with other treatment methods are insufficient. The purpose was to analyze the histopathological differences in hypertrophic burn scars after Matriderm®+split-thickness skin graft (STSG) and compare with AlloDerm®+STSG, STSG, full-thickness skin graft (FTSG), and normal skin. Methods Samples of unburned, normal skin and deep 2nd or 3rd degree burns were obtained from patients who experienced a burn injury in the past to at least 6 months before biopsy, which was performed between 2011 and 2012. All subjects received >6 months of treatment before the biopsy. Intervention groups were normal (63), STSG (28), FTSG (6), Matriderm® (11), and AlloDerm® (18). Immunohistochemical analyses of elastin, collagen I, collagen III, cluster of differentiation 31 (CD31), smooth muscle actin (α-SMA), and laminin from scar and control tissues were performed and compared. Results α-SMA vascular quantity and vessel width, stromal CD31, and basement membrane laminin expression were not significantly different between normal and intervention groups. Matriderm® group showed no significant difference in elastin, collagen III, stromal CD31 and α-SMA, CD31 vessel width, stromal α-SMA, vessel quantity and width, and laminin length compared to the normal group, meaning they were not significantly different from the normal skin traits. Conclusion Dermal substitutes may be an optimal alternative to address the cosmetic and functional limitations posed by other treatment methods.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124294312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gang Yu, Wanjing Chen, Xianghua Li, Liang Yu, Yanyan Xu, Q. Ruan, Yawei He, Yong Wang
The association between collagen type I alpha (COL1A) and chemoresistance has been verified in cancers. However, the specific role of COL1A2 in gastric cancer (GC) cell resistance to apatinib, a highly selective small-molecule inhibitor of vascular endothelial growth factor receptor 2, has not been investigated before. The purpose of this study was to explore the potential factors associated with COL1A2 regulation on GC cell apatinib resistance in vitro. With the aid of the Oncomine database and integrated bioinformatics methods, we identified COL1A2 overexpression in GC and its prognostic value. Mechanistically, the COL1A2 promoter has a distinct H3K27ac modification site and that E1A binding protein p300 (EP300) and twist family bHLH transcription factor 1 (TWIST1) can bind to the COL1A2 promoter, which in turn transcriptionally activated COL1A2 expression. In addition, overexpression of COL1A2 significantly promoted resistance to apatinib in GC cells, but knockdown of EP300 or TWIST1 remarkably inhibited COL1A2 expression and promoted sensitivity of GC cells to apatinib. Our findings demonstrated that the combination of EP300 and TWIST1 has a synergistically regulatory effect on COL1A2 expression, thus contributing to apatinib resistance in GC cells.
{"title":"TWIST1-EP300 Expedites Gastric Cancer Cell Resistance to Apatinib by Activating the Expression of COL1A2","authors":"Gang Yu, Wanjing Chen, Xianghua Li, Liang Yu, Yanyan Xu, Q. Ruan, Yawei He, Yong Wang","doi":"10.1155/2022/5374262","DOIUrl":"https://doi.org/10.1155/2022/5374262","url":null,"abstract":"The association between collagen type I alpha (COL1A) and chemoresistance has been verified in cancers. However, the specific role of COL1A2 in gastric cancer (GC) cell resistance to apatinib, a highly selective small-molecule inhibitor of vascular endothelial growth factor receptor 2, has not been investigated before. The purpose of this study was to explore the potential factors associated with COL1A2 regulation on GC cell apatinib resistance in vitro. With the aid of the Oncomine database and integrated bioinformatics methods, we identified COL1A2 overexpression in GC and its prognostic value. Mechanistically, the COL1A2 promoter has a distinct H3K27ac modification site and that E1A binding protein p300 (EP300) and twist family bHLH transcription factor 1 (TWIST1) can bind to the COL1A2 promoter, which in turn transcriptionally activated COL1A2 expression. In addition, overexpression of COL1A2 significantly promoted resistance to apatinib in GC cells, but knockdown of EP300 or TWIST1 remarkably inhibited COL1A2 expression and promoted sensitivity of GC cells to apatinib. Our findings demonstrated that the combination of EP300 and TWIST1 has a synergistically regulatory effect on COL1A2 expression, thus contributing to apatinib resistance in GC cells.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129610270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Shi, Meng Li, Hui Wang, Chao Li, Wencong Liu, Yongxiang Gao, Bowei Wang, Jiajun Song, Yuqing Ma
Background Esophageal cancer is one of the most common malignant tumors of the digestive system, with high incidence and mortality. Methods Immunohistochemical method was used to detect the expression of MACC1, c-Met, and cyclin D1 in ESCC and its adjacent tissues. Statistical analysis was done by SPSS 23.0. Results The high expression of MACC1 and cyclin D1 was significantly correlated with tumor size. High c-Met expression was associated with patient ethnicity. MACC1 expression was positively correlated with both c-Met and cyclin D1. c-Met expression was also positively correlated with cyclin D1. Patients with high expression of MACC1 and c-Met had worse OS; patients with high c-Met expression also had worse PFS. Conclusion MACC1, c-Met, and cyclin D1 proteins are closely related to the occurrence and development of esophageal squamous cell carcinoma. MACC1 may affect the prognosis of ESCC by regulating the expression of the c-Met/cyclin D1 axis.
{"title":"The Relationship between MACC1/c-Met/Cyclin D1 Axis Expression and Prognosis in ESCC","authors":"Yan Shi, Meng Li, Hui Wang, Chao Li, Wencong Liu, Yongxiang Gao, Bowei Wang, Jiajun Song, Yuqing Ma","doi":"10.1155/2022/9651503","DOIUrl":"https://doi.org/10.1155/2022/9651503","url":null,"abstract":"Background Esophageal cancer is one of the most common malignant tumors of the digestive system, with high incidence and mortality. Methods Immunohistochemical method was used to detect the expression of MACC1, c-Met, and cyclin D1 in ESCC and its adjacent tissues. Statistical analysis was done by SPSS 23.0. Results The high expression of MACC1 and cyclin D1 was significantly correlated with tumor size. High c-Met expression was associated with patient ethnicity. MACC1 expression was positively correlated with both c-Met and cyclin D1. c-Met expression was also positively correlated with cyclin D1. Patients with high expression of MACC1 and c-Met had worse OS; patients with high c-Met expression also had worse PFS. Conclusion MACC1, c-Met, and cyclin D1 proteins are closely related to the occurrence and development of esophageal squamous cell carcinoma. MACC1 may affect the prognosis of ESCC by regulating the expression of the c-Met/cyclin D1 axis.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121735296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Zhao, Xiulong Niu, S. Huang, Jing Yang, Yiying Wei, X. Wang, Junhong Wang, Yue Wang, Xiaoqin Guo
Inflammation and hypoxia are involved in numerous cancer progressions. Reportedly, the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway and hypoxia-inducible factor-1α (HIF-1α) are activated and closely related to the chemoresistance and poor prognosis of epithelial ovarian cancer (EOC). However, the potential correlation between TLR4/NF-κB and HIF-1α remains largely unknown in EOC. In our study, the possible positive correlation among TLR4, NF-κB, and HIF-1α proteins was investigated in the EOC tissues. Our in vitro results demonstrated that LPS can induce and activate HIF-1α through the TLR4/NF-κB signaling in A2780 and SKOV3 cells. Moreover, hypoxia-induced TLR4 expression and the downstream transcriptional activity of NF-κB were HIF-1α-dependent. The cross talk between the TLR4/NF-κB signaling pathway and HIF-1α was also confirmed in the nude mice xenograft model. Therefore, we first proposed the formation of a TLR4/NF-κB/HIF-1α loop in EOC. The positive feedback loop enhanced the susceptibility and responsiveness to inflammation and hypoxia, which synergistically promote the initiation and progression of EOC. The novel mechanism may act as a future therapeutic candidate for the treatment of EOC.
{"title":"TLR4 Agonist and Hypoxia Synergistically Promote the Formation of TLR4/NF-κB/HIF-1α Loop in Human Epithelial Ovarian Cancer","authors":"Bin Zhao, Xiulong Niu, S. Huang, Jing Yang, Yiying Wei, X. Wang, Junhong Wang, Yue Wang, Xiaoqin Guo","doi":"10.1155/2022/4201262","DOIUrl":"https://doi.org/10.1155/2022/4201262","url":null,"abstract":"Inflammation and hypoxia are involved in numerous cancer progressions. Reportedly, the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway and hypoxia-inducible factor-1α (HIF-1α) are activated and closely related to the chemoresistance and poor prognosis of epithelial ovarian cancer (EOC). However, the potential correlation between TLR4/NF-κB and HIF-1α remains largely unknown in EOC. In our study, the possible positive correlation among TLR4, NF-κB, and HIF-1α proteins was investigated in the EOC tissues. Our in vitro results demonstrated that LPS can induce and activate HIF-1α through the TLR4/NF-κB signaling in A2780 and SKOV3 cells. Moreover, hypoxia-induced TLR4 expression and the downstream transcriptional activity of NF-κB were HIF-1α-dependent. The cross talk between the TLR4/NF-κB signaling pathway and HIF-1α was also confirmed in the nude mice xenograft model. Therefore, we first proposed the formation of a TLR4/NF-κB/HIF-1α loop in EOC. The positive feedback loop enhanced the susceptibility and responsiveness to inflammation and hypoxia, which synergistically promote the initiation and progression of EOC. The novel mechanism may act as a future therapeutic candidate for the treatment of EOC.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128504190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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