Katarzyna Blachnio, Beata Grygalewicz, Renata Woroniecka, Jolanta Rygier, Barbara Pienkowska-Grela, Grzegorz Rymkiewicz, Jerzy Kawiak
{"title":"Predictive role of NKCD56bright cells in monitoring the progression of chronic lymphocytic leukemia during treatment.","authors":"Katarzyna Blachnio, Beata Grygalewicz, Renata Woroniecka, Jolanta Rygier, Barbara Pienkowska-Grela, Grzegorz Rymkiewicz, Jerzy Kawiak","doi":"10.5603/FHC.a2022.0023","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0023","url":null,"abstract":"<p><strong>Introduction: </strong>Standard treatment for chronic lymphocytic leukemia (CLL) has experienced a dramatic change over the last few years. Until recently, CLL was treated using chemoimmunotherapy (CIT) with anti-CD20 monoclonal antibodies. Even though novel agents such as BTKi (Bruton Tyrosine Kinase inhibitor) and BCL2 inhibitors are the standard of care in most therapeutic settings, CIT still has its place in CLL treatment. Interestingly, little is known about its effects on the immune system of patients with CLL. Contrary to the reduction of the number of CLL cells during CIT administration, little attention has been paid to the cellular microenvironment, the evaluation of which during treatment may provide additional information about the course of the disease and prognosis and therefore was set as the aim of this study.</p><p><strong>Material and methods: </strong>Flow cytometry was used to evaluate the phenotypes of different populations and subpopulations of lymphocytes in the peripheral blood (PB) of 20 patients with CLL before, during, and after CIT.</p><p><strong>Results: </strong>During the CIT with R-FC (Rituximab, Fludarabine, and Cyclophosphamide) and R-B (Rituximab, Bendamustine) regimens, the sizes of the assessed populations and subpopulations of lymphocytes were dramatically reduced. Twenty-eight days after the first course of treatment, the exponential decrease of CLL cells was observed, and their number had declined to the median level of 10% of the numbers observed before the treatment. T cells, NK cells, NKCD56dim, NKT-like, and NKT-like CD56dim also decreased exponentially. After the second treatment course, a decline in the numbers of T, NK, NKCD56dim, NKT-like, and NKT-like CD56dim cells was observed, which were stable until the sixth treatment course. However, the number of NKT-like CD56bright cells decreased to the third course of treatment and then increased. The number of CLL cells in peripheral blood correlated with the number of NKCD56bright cells, influencing the treatment response.</p><p><strong>Conclusions: </strong>Upon CIT, the reduction of CLL cells is accompanied by shifts in immune cell populations, T, NK, and NKT-like cells. Monitoring changes of those cell populations in the peripheral blood may serve as an important predictive and prognostic indicator.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40334428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Lin, Linjing Li, Gui Ma, Yaqiong Kang, Xingdong Wang, Jianxin He
{"title":"Overexpression of IL-8 and Wnt2 is associated with prognosis of gastric cancer.","authors":"Li Lin, Linjing Li, Gui Ma, Yaqiong Kang, Xingdong Wang, Jianxin He","doi":"10.5603/FHC.a2022.0002","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0002","url":null,"abstract":"<p><strong>Introduction: </strong>This study is to detect the expression of inflammatory factor or neutrophil-activating factor IL-8 and Wnt2 in gastric cancer (GC) and investigate the involvement of IL-8 and Wnt2 expressions in the clinicopathological indexes and prognosis.</p><p><strong>Material and methods: </strong>We detected the expression of IL-8 and Wnt2 in 100 GC tissues and 40 normal gastric mucosae using immunohistochemistry. The relationships between the IL-8 and Wnt2 expression and the clinicopathological characteristics were explored. The relationship between IL-8 expression, Wnt2 expression, and prognosis of GC was analyzed by survival curve and survival regression.</p><p><strong>Results: </strong>The expression of IL-8 and Wnt2 in GC tissue was 64% and 75% respectively, which was significantly higher than that in adjacent normal gastric mucosa tissues, moreover, expressions of IL-8 and Wnt2 were positively correlated. The positive rate of IL-8 and Wnt2 expressions were correlated with lymph node metastasis and TNM staging (P < 0.01, and Wnt2 was also correlated with infiltration depth (P = 0.021), but there was no difference with age, sex, and differentiation (P > 0.05). The 3-year survival analysis showed that the survival rates of IL-8- and Wnt2-positive patients were 20% and 24%, respectively, which were significantly lower than those of negative patients. Cox regression analysis showed that IL-8 and Wnt2 may be independent factors affecting the prognosis of GC.</p><p><strong>Conclusions: </strong>Our data demonstrated that the overexpression of IL-8 and Wnt2 could be isolated prognostic factors in patients with GC and, possibly, may present new targets for the treatment of GC.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39827109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"EID1 plays a protective role in early-onset pre-eclampsia via promoting proliferation and invasion in trophoblast cells.","authors":"Ying Li, Jiuxiang Feng, Yue Bian, Wei Cheng, Chong Qiao","doi":"10.5603/FHC.a2022.0001","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0001","url":null,"abstract":"<p><strong>Introduction: </strong>Pre-eclampsia is a pregnancy-specific syndrome, which is partly due to abnormal proliferation and invasion of trophoblast cells. EP300 interacting inhibitor of differentiation 1 (EID1) participates in cell proliferation and invasion. This study aims to investigate the roles of EID1 in trophoblast cells and pre-eclampsia.</p><p><strong>Material and methods: </strong>The expression of EID1 in placental tissues from 60 women with pre-eclampsia and 60 health pregnancies was detected by real-time PCR and immunohistochemical staining. EID1 was overexpressed or silenced by transfection of plasmid or siRNA in HTR-8/SVneo trophoblast cells, and then cell proliferation, cell cycle transition, migration, and invasion were determined by CCK-8 assay, flow cytometry, immunofluorescent staining, immunoblotting, and transwell assays. In addition, the activity of Akt/b-catenin signaling was measured by immunofluorescent staining and Western blot.</p><p><strong>Results: </strong>EID1 mRNA level was decreased in placental tissues of pre-eclampsia patients, especially early-onset pre-eclampsia, accompanied by more severe clinical manifestation and a higher rate of fetal growth restriction (FGR). Gain- and loss-of-function experiments demonstrated that EID1 promoted proliferation and cell cycle transition, migration, and invasion in HTR-8/SVneo cells and its knockdown played opposite roles, suggesting that EID1 may be required for normal gestation. Akt/b-catenin signaling was activated after EID1 forced expression and deactivated after its silencing.</p><p><strong>Conclusions: </strong>EID1 promoted proliferation and invasion of cultured trophoblast cells with possible involvement of Akt/b-catenin signaling. These findings may provide novel insights for the diagnosis and treatment of early-onset pre-eclampsia in a clinic.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39828848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xingnuan Li, Shan He, Ping Wu, Yichun Zhou, Kai Long, Tao Wang
{"title":"MiR-328-5p inhibits the adipogenic differentiation of hMSCs by targeting fatty acid synthase.","authors":"Xingnuan Li, Shan He, Ping Wu, Yichun Zhou, Kai Long, Tao Wang","doi":"10.5603/FHC.a2022.0028","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0028","url":null,"abstract":"<p><strong>Introduction: </strong>Adipogenesis, a highly coordinated process regulated by numerous effectors, is largely responsible for the quantity and size of adipocytes. Attenuation of adipocyte differentiation has been proposed as a viable technique for reducing obesity and its associated diseases. MicroRNAs play an important role in human bone marrow mesenchymal stem cells (hMSCs) adipogenic differentiation. However, there is a lack of clarity regarding the role of miR-328-5p in adipogenesis.</p><p><strong>Material and methods: </strong>Using the lentiviral vectors to overexpress fatty acid synthase (FASN) and miR-328-5p, RT-qPCR and Western blotting were carried out to assess RNA expression and protein levels of FASN and adipogenic marker factors. Meanwhile, Oil red O staining and lipid quantification was performed to evaluate the accumulation of intracellular lipid droplets. Additionally, the validity of FASN as a potential target gene for miR-328-5p was carried out using a luciferase reporter assay.</p><p><strong>Results: </strong>Our data showed that hMSCs adipogenic differentiation was associaed with the reduced miR-328-5p expression, while an elevated expression of the underlined miRNA attenuated adipogenesis and the expression of adipogenic marker genes. Luciferase reporter assay validated FASN as a target gene of miR-328-5p, and an elevated FASN expression reversed the anti-adipogenic effects of miR-328-5p.</p><p><strong>Conclusions: </strong>The results revealed that miR-328-5p inhibits hMSCs adipogenic differentiation by targeting FASN. These findings contribute to our understanding of obesity-related disease development.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10451054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dexmedetomidine alleviates intestinal barrier dysfunction and inflammatory response in mice via suppressing TLR4/MyD88/NF-κB signaling in an experimental model of ulcerative colitis.","authors":"Xiaojin Ye, Huailiang Xu, Yuan Xu","doi":"10.5603/FHC.a2022.0029","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0029","url":null,"abstract":"<p><strong>Introduction: </strong>Ulcerative colitis (UC) is a nonspecific intestinal inflammatory disease. Dexmedetomidine (DEX) is a selective alpha 2-adrenergic receptor agonist commonly used for analgesia and sedation in intensive care units. Herein, the role and mechanism of DEX in dextran sulfate sodium (DSS)-induced colitis was explored.</p><p><strong>Materials and methods: </strong>A murine model of DSS-induced colitis was established by adding 3.5% (w/v) DSS in drinking water to C57BL/6J female mice. The severity of colitis was measured by the disease activity index (DAI) score, colon length and body weight of mice. The serum concentration and mRNA levels of inflammatory cytokines in colon tissues were assessed by ELISA and RT-qPCR, respectively. Protein levels of apoptotic markers, tight junction proteins and genes involved in the TLR4/MyD88/NF-κB signaling were quantified utilizing Western blotting. The pathological changes of colon tissues were evaluated by hematoxylin-eosin (HE) staining and histological score. Intestinal permeability in vivo was assessed by fluorescein isothiocyanate (FITC)-dextran (FITC-D) administration. TUNEL assay was used to determine cell apoptosis in the intestinal epithelium.</p><p><strong>Results: </strong>DSS administration resulted in weight loss, shortening of the colon, increased DAI score, histological abnormalities, and increased serum FITC-D levels in mice, all of which were reversed by DEX injection. Moreover, DEX attenuated DSS-triggered inflammatory response, intestinal barrier injury and intestinal epithelial cell apoptosis. Mechanically, DEX inactivated the TLR4/MyD88/NF-κB signaling in the colon tissues.</p><p><strong>Conclusions: </strong>DEX exerts beneficial effects against the intestinal barrier dysfunction, inflammatory response, and apoptosis of intestinal epithelial cells via inactivation of the TLR4/MyD88/NF-κB signaling in mice with DSS-induced colitis.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10841287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Wedelolactone ameliorates synovial inflammation and cardiac complications in a murine model of collagen-induced arthritis by inhibiting NF-κB/NLRP3 inflammasome activation.","authors":"Jingjing Cao, Yanhui Ni, Xiaoran Ning, Huaxing Zhang","doi":"10.5603/FHC.a2022.0025","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0025","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid arthritis (RA) is an autoimmune disorder associated with joint damage and attendant cardiovascular complications. Wedelolactone (Wed), derived from Eclipta alba, possesses anti-inflammatory activity. Whether Wed regulates RA inflammation and related heart damage remains unknown.</p><p><strong>Material and methods: </strong>A murine model of collagen-induced arthritis (CIA) was well-established by two subcutaneous injections of type II collagen (days 0 and 21). Wed was then administered via intraperitoneal injection every other day from day 28 to day 48. Joint swelling was monitored and paw thickness was calculated. Histopathological changes in synovial tissues or ankle cartilage were evaluated by hematoxylin and eosin (H&E) and Safranin O-Fast Green staining. The concentrations of inflammatory factors in serum and synovial tissues were detected by ELISA. The qRT-PCR, Western blotting, immunohistochemistry (IHC), and immunofluorescence (IF) were performed to assess receptor activator of nuclear factor kappa ligand (RANKL), matrix metalloprotease (MMP)-3, NLRP3, caspase-1 (pro- and cleaved forms), p-p65, IκBα, p-IκBα, p65, αsmooth-actin 2 (ACTA2), collagen type I and E-cadherin expression. H&E and Masson staining were used to assess the pathological alterations in the heart.</p><p><strong>Results: </strong>Treatment with Wed ameliorated ankle joint swelling and cartilage degradation. Wed decreased the infiltration of inflammatory cells, the release of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-18), and the expression of RANKL and MMP-3 in serum and synovial tissues of CIA mice. Moreover, Wed increased the expression of NLRP3 and cleaved-caspase-1 in the synovium, leading to IL-1β and IL-18 secretion. Nuclear factor-kappaB (NF-κB) activation in synovial tissues was suppressed by Wed, as manifested by reduced phosphorylation of p65 and IκBα and nuclear translocation of p65. Furthermore, Wed reduced in CIA mice heart weight/body weight ratio and dampened cardiac inflammation and fibrosis that was accompanied at the mRNA level by down-regulation of ACTA2 and collagen I and up-regulation of E-cadherin.</p><p><strong>Conclusions: </strong>These findings suggested that Wed attenuated synovial inflammation and joint damage in a mouse model of RA via inhibiting NF-κB/NLRP3 inflammasome activation, and ameliorated RA-induced cardiac complications.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10474218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Insulin-like growth factor-1 inhibits apoptosis of rat gastric smooth muscle cells under high glucose condition via adenosine monophosphate-activated protein kinase (AMPK) pathway.","authors":"Xiang-Zi Zhang, Yan Sun, Mo-Han Zhang, Zheng Jin","doi":"10.5603/FHC.a2022.0005","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0005","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic gastroparesis (DGP) is a common chronic complication of diabetes characterized by decreased gastric motility, and an effective number of gastric smooth muscle cells (GSMCs) ensures gastric motility. A previous study documented that apoptosis was present in gastric smooth muscles in rats with DGP and adenosine monophosphate-activated protein kinase (AMPK) was an important factor of apoptosis of rat GSMCs cultured under high glucose conditions. This study aimed to explore the effect of insulin-like growth factor-1 (IGF-1) on apoptosis of high glucose cultured rat GSMCs after silencing of AMPK and elucidate the underlying mechanism.</p><p><strong>Material and methods: </strong>A total of 120 rats were divided into normal control (NC, n = 20), diabetic gastroparesis (DGP, n = 50) and DGP + IGF-1 (n = 50) groups. After establishing the rat model of DGP, rats in the DGP+IGF-1 group received an intraperitoneal injection of IGF-1 at a dose of 1.5 μg/kg/d for 10 weeks. The level of AMPK activity, liver kinase B1 (LKB1) activity, and calcium/calmodulin-dependent protein kinase b (CaMKKb) expression in rat gastric smooth muscle tissues was detected by Western blot analysis. Apoptosis in rat gastric smooth muscle tissues was detected by TUNEL assay. We also cultured rat GSMCs in vitro under high glucose (HG) condition (35 mM), incubated cells with IGF-1, and silenced AMPK with siRNA. The cells were divided into HG, HG + IGF-1, HG + siRNA, and HG + siRNA + IGF-1 groups. The apoptosis rates of rat GSMCs after silencing AMPK were detected by TUNEL assay and flow cytometry, and apoptosis-related protein expression in rat GSMCs was detected by Western blot.</p><p><strong>Results: </strong>IGF-1 decreased LKB1 activity, CaMKKb expression, AMPK activity, and inhibited apoptosis in rat gastric smooth muscle tissues. Compared with rat GSMCs cultured in vitro under HG conditions, apoptosis rates were reduced after treatment with IGF-1 and AMPK silencing (both p < 0.01). Apoptosis rates were higher in the HG + siRNA group compared with the HG + IGF-1 group (p < 0.05). IGF-1 down-regulated the expression of calcium/calmodulin-dependent kinase II (CaMKII) and p53, up-regulated the expression of p21, PLC-b3, PI3K p110 Ser1070, and the activities of Akt, p70S6K, mTORC1, and mTORC2. IGF-1 also up-regulated Bcl-2 expression and down-regulated the expression of BAX and Caspase-3.</p><p><strong>Conclusions: </strong>IGF-1 can inhibit the apoptosis of rat GSMCs under high glucose conditions, its mechanism may be related to the regulation of expression and activity of p53, PI3K, TSC-2, Akt, mTOR, 4E-BP1, p70S6K, p21, CaMKII, and PLC-b3 in rat GSMCs acting through AMPK pathway.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39792772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Celastrol alleviates murine lupus nephritis via inducting CD4+Foxp3+ regulatory T cells.","authors":"Guangbo Xiang, Kai Shi, Jinjun Wang","doi":"10.5603/FHC.a2022.0020","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0020","url":null,"abstract":"<p><strong>Introduction: </strong>Lupus nephritis (LN) is an autoimmune glomerulonephritis secondary to systemic lupus erythematosus. Commonly, immunosuppressive agents are required for treating LN. However, frequent use of conventional immunosuppressants may produce a variety of side effects. Hence, seeking alternative drugs for treating LN is very important. This report aims to figure out the immunoregulatory efficacy of celastrol (CLT) in LN.</p><p><strong>Material and methods: </strong>A spontaneous in vivo model of LN was established in FasL-deficient B6/gld mice. ELISA was used for analyzing serum creatinine (Scr) and anti-dsDNA levels in mice. IHC staining, immunofluorescence and hematoxylin-eosin and PAS staining were applied to determine renal immunopathology and histology. Cytokine gene levels were assessed using RT qPCR. CD4+Foxp3+ Treg frequency in murine kidneys, lymph nodes and spleens was determined using flow cytometry analysis.</p><p><strong>Results: </strong>CLT treatment alleviated renal dysfunction and renal injury in LN-prone B6/gld mice. Moreover, CLT reduced CD3+ T cell infiltration and inhibited proinflammatory cytokine expression in renal tissues of B6/gld mice. Importantly, CLT enhanced CD4+FoxP3+ Treg frequency in kidneys, lymph nodes and spleens of B6/gld mice.</p><p><strong>Conclusions: </strong>CLT exerts therapeutic effects on murine LN by improving renal function and immunopathology and inducing CD4+FoxP3+ Tregs.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40475114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kamila Bujko, Mateusz Adamiak, Ahmed Abdelbaset-Ismail, Arjun Thapa, Nicoletta Ilowska, Janina Ratajczak, Magdalena Kucia, Mariusz Z Ratajczak
{"title":"Novel evidence that the P2X1 purinergic receptor-Nlrp3 inflammasome axis orchestrates optimal trafficking of hematopoietic stem progenitors cells.","authors":"Kamila Bujko, Mateusz Adamiak, Ahmed Abdelbaset-Ismail, Arjun Thapa, Nicoletta Ilowska, Janina Ratajczak, Magdalena Kucia, Mariusz Z Ratajczak","doi":"10.5603/FHC.a2022.0027","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0027","url":null,"abstract":"<p><strong>Introduction: </strong>Our previous research demonstrated P2X purinergic receptors as important extracellular adenosine triphosphate (eATP) sensing receptors promoting the trafficking of hematopoietic stem progenitor cells (HSPCs). Accordingly, mice deficient in expression of P2X4 and P2X7 receptors turned out to mobilize poorly HSPCs. Similarly, defective expression of these receptors on transplanted HSPCs or in the bone marrow (BM) microenvironment of graft recipient mice led to defective homing, engraftment, and delayed hematopoietic reconstitution. This correlated with decreased activation of intracellular pattern recognition receptor Nlrp3 inflammasome. The P2X receptor family consists of seven purinergic receptors (P2X1-7) and we noticed that in addition to P2X4 and P2X7, HSPCs also highly express rapidly signaling the P2X1 receptor. Therefore, we asked if P2X1 receptor is also involved in HSPCs trafficking.</p><p><strong>Material and methods: </strong>We employed in vitro and in vivo murine models to study the role of P2X1 receptor blocked on HSPCs or bone marrow microenvironment cells by specific small molecular inhibitor NF499. First, we performed in vitro cell migration assays of bone marrow mononuclear cells (BMMNCs) isolated from normal mice that were exposed to NF499 and compared them to unexposed control cells. Next, in experiments in vivo we mobilized mice exposed to NF499 with G-CSF or AMD3100 and compared mobilization to control unexposed animals. Flow cytometry was employed to identify cell populations and clonogenic assays to enumerate the number of mobilized clonogenic progenitors. Similarly, in homing and engraftment experiments BMMNCs or recipient mice were exposed to NF499 and we evaluated homing and engraftment of transplanted cells by enumerating the number of cells labeled with fluorochromes in recipient mice BM and by evaluating the number of clonogenic progenitors in BM and spleen 24 hours and 12 days after transplantation. We also evaluated the potential involvement of Nlrp3 inflammasome in P2X1 receptor-mediated HSPCs trafficking.</p><p><strong>Results: </strong>We report that the functional P2X1 receptor is highly expressed on murine and human HSPCs. We could demonstrate that the P2X1 receptor promotes the trafficking of murine cells in Nlrp3 inflammasome-dependent manner. Mice after exposure to P2X1 receptor inhibitor poorly mobilized HSPCs from the bone marrow into the peripheral blood. Mice transplanted with BMNNCs exposed to NF499 or recipient mice pretreated with this inhibitor demonstrated defective homing and engraftment as compared to control animals transplanted with cells not exposed to P2X1 inhibitor. Similar effects were noticed for control recipient mice that were not exposed to NF499.</p><p><strong>Conclusions: </strong>This study demonstrates for the first time the novel role of the P2X1 receptor in HSPCs trafficking in the mouse. Furthermore, it supports an important role of purinergic sig","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40386127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Theodora-Eleftheria Deftereou, Avgi Tsolou, Anastasios Liberis, Kyriaki Georgiadi, Triantafyllos Alexiadis, Olga Pagonopoulou, Christina-Angelika Alexiadi, Maria Simopoulou, Grigorios Tripsianis, Maria Lambropoulou
{"title":"Differential apoptotic activity in trophoblast of spontaneous abortions and normal pregnancies.","authors":"Theodora-Eleftheria Deftereou, Avgi Tsolou, Anastasios Liberis, Kyriaki Georgiadi, Triantafyllos Alexiadis, Olga Pagonopoulou, Christina-Angelika Alexiadi, Maria Simopoulou, Grigorios Tripsianis, Maria Lambropoulou","doi":"10.5603/FHC.a2022.0003","DOIUrl":"https://doi.org/10.5603/FHC.a2022.0003","url":null,"abstract":"<p><strong>Introduction: </strong>Apoptosis is a key process during normal trophoblastic development and, consequently, the whole gestation. However, in trophoblastic differentiation in spontaneous abortions apoptosis has been hardly investigated. Therefore, the aim of the study was to investigate the correlation between apoptotic frequency in trophoblast and spontaneous abortion incidences.</p><p><strong>Material and methods: </strong>A total of 72 trophoblastic tissue samples were immunohistochemically examined. 42 of 72 derived from first-trimester spontaneous abortions and the remaining 30 from elective terminations during the same trimester of pregnancy. TUNEL assay and M30 marker were used for apoptosis evaluation by immunohistochemistry.</p><p><strong>Results: </strong>Comparative study of tissues from spontaneous abortions and elective pregnancy terminations demonstrated increased expression of both apoptotic markers in tissues derived from spontaneous abortions compared to normal pregnancies. In addition, statistical analysis correlated maternal age and gravidity with increased spontaneous abortion incidences. Moreover, both M30 and TUNEL staining were significantly correlated with maternal age and primigravidity in spontaneous abortion cases.</p><p><strong>Conclusions: </strong>Our data proved that elevated apoptotic activity during the first pregnancy trimester is clearly involved in spontaneous abortions. Moreover, two well-established apoptotic markers revealed high statistical significance in the evaluation of post-abortive tissues.</p>","PeriodicalId":12322,"journal":{"name":"Folia histochemica et cytobiologica","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39826986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}