European Journal Of Histochemistry[JOURNAL]
Sun
200 papers
Polydatin reverses oxidation low lipoprotein (oxLDL)-induced apoptosis of human umbilical vein endothelial cells <em>via</em> regulating the miR-26a-5p/BID axis.
Wang D, Zhou Z, Yuan L
Eur J Histochem · 2022 Sep · PMID 36128773 · Full text
Atherosclerosis is a disease in which lipids and inflammatory factors accumulate on the walls of arteries, forming plaques that eventually block the flow of blood. Polydatin was derived from plant knotweed, which could p...
Atherosclerosis is a disease in which lipids and inflammatory factors accumulate on the walls of arteries, forming plaques that eventually block the flow of blood. Polydatin was derived from plant knotweed, which could play an important role in inhibiting the progression of atherosclerosis. However, the mechanism by which polydatin regulates the genesis and development of atherosclerosis remains unclear. To detect the function of polydatin in atherosclerosis, the proliferation, apoptosis and migration of human umbilical vein endothelial cells (HUVECs) was detected using 5-ethynyl-2'-deoxyuridine staining, flow cytometry and transwell assays, respectively. In addition, the branch points and capillary length of HUVECs were observed using a tube formation assay, and the lipid accumulation was tested by Oil-red O staining assay. Dual luciferase reporter assays were performed to confirm the association between microRNA (miR)-26a-5p and BH3 interacting domain death agonist (BID) in HUVECs. The data suggested oxidized low-density lipoprotein (oxLDL) notably inhibited the viability of HUVECs in a dose-dependent manner, and polydatin reversed the oxLDL-induced inhibition of HUVECs viability and proliferation. In addition, polydatin inhibited the apoptosis, migration and epithelial mesenchymal transition (EMT) process in oxLDL-treated HUVECs. Polydatin reversed oxLDL-induced lipid accumulation and angiogenesis inhibition in HUVECs. Furthermore, BID was targeted by miR-26a-5p, and polydatin reversed the oxLDL-induced apoptosis of HUVECs via regulating the miR-26a-5p/BID axis. In summary, polydatin reversed the oxLDL-induced apoptosis of HUVECs via regulating the miR-26a-5p/BID axis. Therefore, polydatin could act as a new agent for atherosclerosis treatment.
Imaging and spectral analysis of autofluorescence patterns in larval head structures of mosquito vectors.
Scolari F, Girella A, Croce AC
Eur J Histochem · 2022 Sep · PMID 36128772 · Full text
Autofluorescence (AF) in mosquitoes is currently poorly explored, despite its great potential as a marker of body structures and biological functions. Here, for the first time AF in larval heads of two mosquitoes of key...
Autofluorescence (AF) in mosquitoes is currently poorly explored, despite its great potential as a marker of body structures and biological functions. Here, for the first time AF in larval heads of two mosquitoes of key public health importance, Aedes albopictus and Culex pipiens, is studied using fluorescence imaging and spectrofluorometry, similarly to a label-free histochemical approach. In generally conserved distribution patterns, AF shows differences between mouth brushes and antennae of the two species. The blue AF ascribable to resilin at the antennal bases, more extended in Cx. pipiens, suggests a potential need to support different antennal movements. The AF spectra larger in Cx. pipiens indicate a variability in material composition and properties likely relatable to mosquito biology, including diverse feeding and locomotion behaviours with implications for vector control.
Long non-coding RNA WAC antisense RNA 1 mediates hepatitis B virus replication <em>in vitro</em> by reinforcing miR-192-5p/ATG7-induced autophagy.
Cao M, Yuan D, Jiang H … +3 more , Zhou G, Chen C, Han G
Eur J Histochem · 2022 Sep · PMID 36053263 · Full text
Long non-coding RNA WAC antisense RNA 1 (lncRNA WAC-AS1) is involved in the replication of the hepatitis B virus (HBV). The purpose of this study was to determine its functions and specific mechanism. The levels of lncRN...
Long non-coding RNA WAC antisense RNA 1 (lncRNA WAC-AS1) is involved in the replication of the hepatitis B virus (HBV). The purpose of this study was to determine its functions and specific mechanism. The levels of lncRNA WAC-AS1, RNA (miR)-192-5p and were examined in serum of HBV-infected patients and in HepG2.2.15 cells using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. Using the database starBase, the target binding sites of lncRNA WAC-AS1 and miR-192-5p were predicted and confirmed by dual-luciferase reporter assay and RNA pull-down assay. The expression of pgRNA and HBV DNA was determined by qRT-PCR, while the levels of HBeAg and HBsAg were measured by enzyme-linked immunosorbent assay (ELISA). Using laser scanning confocal microscopy, the light chain 3 (LC3) expression was analyzed. qRT-PCR and Western blotting were used to assess the expression of beclin-1, p62, and LC3I/II. Overexpression of lncRNA WAC-AS1, upregulation of ATG7. and downregulation of miR-192-5p were observed in the serum of HBV-infected patients and the in vitro model. miR-192-5p directly targets lncRNA WAC-AS1. LncRNA WAC-AS1 was downregulated in lncRNA WAC-AS1-shRNA‒transfected cells. miR-192-5p was upregulated in lncRNA WAC-AS1-shRNA-transfected cells and downregulated in cells transfected with a miR-192-5p inhibitor. In HepG2 2.15 cells, the downregulation of lncRNA WAC-AS1 inhibited HBV replication and autophagy. In contrast, the miR-192-5p inhibitor-transfected group exhibited the opposite results, and ATG7 overexpression reversed the effects of miR-192-5p mimic or lncRNA WAC-AS1-shRNA on HBV replication and cell autophagy. Our findings indicate that lncRNA WAC-AS1 regulates HBV replication by reinforcing the autophagy induced by miR-192-5p/ATG7. Consequently, lncRNA WAC-AS1 may serve as a therapeutically-promising target in HBV patients.
Immunofluorescence signal intensity measurements as a semi-quantitative tool to assess sarcoglycan complex expression in muscle biopsy.
Zanotti S, Magri F, Poggetti F … +8 more , Ripolone M, Velardo D, Fortunato F, Ciscato P, Moggio M, Corti S, Comi GP, Sciacco M
Eur J Histochem · 2022 Sep · PMID 36047345 · Full text
Sarcoglycanopathies are highly heterogeneous in terms of disease progression, muscular weakness, loss of ambulation and cardiac/respiratory involvement. Their clinical severity usually correlates with the residual protei...
Sarcoglycanopathies are highly heterogeneous in terms of disease progression, muscular weakness, loss of ambulation and cardiac/respiratory involvement. Their clinical severity usually correlates with the residual protein amount, which makes protein quantification extremely relevant. Sarcoglycanopathy diagnosis is genetic, but skeletal muscle analysis - by both immunohistochemistry and Western blot (WB) - is still mandatory to establish the correct diagnostic process. Unfortunately, however, WB analysis cannot be performed if the bioptic specimen is scarce. This study provides a sensitive tool for semi-quantification of residual amount of sarcoglycans in patients affected by sarcoglycanopathies, based on immunofluorescence staining on skeletal muscle sections, image acquisition and software elaboration. We applied this method to eleven sarcoglycanopathies, seven Becker muscular dystrophies and four age-matched controls. Fluorescence data analysed in patients and compared to age-matched controls showed a significant reduction of the mutated sarcoglycan expression and a variable reduction of the other sarcoglycans. Fluorescence normalized data analysed in relation to the age of onset of the disease, showed a negative correlation of α-sarcoglycan fluorescent signal versus fibrosis in patients with an early age of onset and a negative correlation between δ-sarcoglycan signal and fibrosis in both intermediate and late age of onset groups. The availability of a method that allows objective quantification of the sarcolemmal proteins, faster and less consuming than WB analysis and able to detect low residual sarcoglycan expression with great sensitivity, proves useful to better define both patient prognosis and expected disease evolution. The proposed method could be employed also to monitor the efficacy of therapeutic interventions and during clinical trials.
Inhibition of APLN suppresses cell proliferation and migration and promotes cell apoptosis in esophageal cancer cells <em>in vitro</em>, through activating PI3K/mTOR signaling pathway.
Wang Y, Wang G, Liu X … +6 more , Yun D, Cui Q, Wu X, Lu W, Yang X, Zhang M
Eur J Histochem · 2022 Aug · PMID 35920446 · Full text
Esophageal cancer is the sixth leading cause of cancer mortalities globally with a high incidence rate. Apelin (APLN) plays regulatory roles in different organs. However, its role in esophageal cancer remains unknown. Th...
Esophageal cancer is the sixth leading cause of cancer mortalities globally with a high incidence rate. Apelin (APLN) plays regulatory roles in different organs. However, its role in esophageal cancer remains unknown. Therefore, our study aims to explore the effect of APLN on esophageal cancer. One hundred and eighty-four (184) esophageal tumor tissues samples from patients with esophageal cancer, and 11 esophageal tissues samples from healthy volunteers were analyzed for the expression of APLN. APLN was highly expressed in the tumor of patients with esophageal cancer and esophageal cancer cells. Patients with high expressions of APLN had a lower survival rate than the ones with low to medium expressions of APLN. Human esophageal carcinoma cell lines, TE-1 and ECA-109 cells were transfected with APLN siRNA to knockdown APLN, or transfected with pcDNA-APLN to overexpress APLN. Inhibition of APLN by siRNA-APLN reduced proliferative, migrative, and invasive abilities of esophageal cancer cells and promoted cell apoptosis, which could be all restored by pcDNA-APLN. Moreover, knocking down APLN by siRNA-APLN suppressed the PI3K/mTOR signaling pathway. These findings identify that APLN inhibition might ameliorate esophageal cancer through activating the PI3K/mTOR signaling pathway, thus APLN could be a potential target for esophageal cancer.
MiR-550a-3p restores damaged vascular smooth muscle cells by inhibiting thrombomodulin in an <em>in vitro</em> atherosclerosis model.
Chen S, Zhang L, Feng B … +6 more , Wang W, Liu D, Zhao X, Yu C, Wang X, Gao Y
Eur J Histochem · 2022 Jul · PMID 35855629 · Full text
Thrombomodulin (TM) is involved in the pathological process of atherosclerosis; however, the underlying mechanism remains unclear. Oxidised low-density lipoprotein (Ox-LDL; 100 μg/mL) was used to induce human vascular sm...
Thrombomodulin (TM) is involved in the pathological process of atherosclerosis; however, the underlying mechanism remains unclear. Oxidised low-density lipoprotein (Ox-LDL; 100 μg/mL) was used to induce human vascular smooth muscle cells (HVSMCs) into a stable atherosclerotic cell model. The expression levels of miR-550a-3p and TM were detected by real-time reverse transcription-polymerase chain reaction. Cell proliferation was estimated using CCK8 and EDU assays. Wound scratch and transwell assays were used to measure the ability of cells to invade and migrate. Propidium iodide fluorescence-activated cell sorting was used to detect apoptosis and cell cycle changes. A dual-luciferase reporter assay was performed to determine the binding of miR-550a-3p to TM. Our results suggested the successful development of a cellular atherosclerosis model. Our data revealed that TM overexpression significantly promoted the proliferation, invasion, migration, and apoptosis of HVSMCs as well as cell cycle changes. Upregulation of miR-550a-3p inhibited the growth and metastasis of HVSMCs. Furthermore, miR-550a-3p was confirmed to be a direct target of TM. Restoration of miR-550a-3p expression rescued the effects of TM overexpression. Thus, miR-550a-3p might play a role in atherosclerosis and, for the first time, normalised the function of injured vascular endothelial cells by simultaneous transfection of TM and miR-550a-3p. These results suggest that the miR-550a-3p/TM axis is a potential therapeutic target for atherosclerosis.
Lobetyolin suppressed lung cancer in a mouse model by inhibiting epithelial-mesenchymal transition.
Liu L, Liu Z, Yang L … +4 more , Wu X, Zhu J, Liu L, Liu Y
Eur J Histochem · 2022 Jul · PMID 35785916 · Full text
Traditional Chinese medicines are gaining more attention as promising adjuvant agents for conventional chemotherapy. Recent studies have shown that lobetyolin (LBT) is one of the main bioactive compounds of traditional C...
Traditional Chinese medicines are gaining more attention as promising adjuvant agents for conventional chemotherapy. Recent studies have shown that lobetyolin (LBT) is one of the main bioactive compounds of traditional Chinese medicines and it exhibits anticancer activity in several types of cancer. Therefore, this study aimed to investigate the mechanism by which LBT inhibits lung cancer. A549 human lung cancer cells were treated with LBT. In addition, A549 cells were injected into Balc/b nude mice to establish model of lung cancer. The mice were treated with cisplatin (DDP) or LBT alone or in combination, and tumor growth was monitored. Protein levels of E-cadherin, vimentin and matrix metalloproteinase 9 (MMP9) were detected. We found that the combination of LBT and DDP showed stronger effect to inhibit the proliferation of A549 cells compared to LBT or DDP treatment alone. Wound healing assay showed that the ratio of wound healing was significantly lower in LBT group and DDP group and was the lowest in LBT+DDP group. Transwell invasion assay showed that the invasion ability of A549 cells was the weakest in LBT+DDP group. Protein levels of E-cadherin were the highest while those of vimentin and MMP9 were the lowest in A549 cells treated with LBT+DDP. Nude mouse xenograft tumor model showed that the combination of LBT with DDP had the highest efficacy to inhibit the growth of lung cancer, and tumor tissues of mice treated with LBT+DDP had the lowest expression of vimentin and MMP9 and the highest expression of E-cadherin. In conclusion, LBT significantly enhances the efficacy of chemotherapy on lung cancer, and the mechanism may be related to the inhibition of epithelial-mesenchymal transition.
Clinicopathological assessment of cancer/testis antigens NY‑ESO‑1 and MAGE‑A4 in osteosarcoma.
Hashimoto K, Nishimura S, Ito T … +3 more , Oka N, Kakinoki R, Akagi M
Eur J Histochem · 2022 Jun · PMID 35736245 · Full text
The cancer/testis antigens (CTAs), New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen gene (MAGE)-A4 are normally restricted to male germ cells but are aberrantly expressed in several cancers....
The cancer/testis antigens (CTAs), New York esophageal squamous cell carcinoma-1 (NY-ESO-1) and melanoma antigen gene (MAGE)-A4 are normally restricted to male germ cells but are aberrantly expressed in several cancers. Considering the limited information regarding their significance in osteosarcoma (OS), the purpose of this study was to determine the clinical significance of NY-ESO-1 and MAGE-A4 expression in OS. Nine patients with OS treated at Kindai University Hospital were included in the study. The median age was 27 years, and median follow-up period was 40 months. The specimens obtained at the time of biopsy were used to perform immunostaining for NY-ESO, MAGE-A4, p53, and Ki-67. The positive cell rates and positive case rates of NY-ESO, MAGE-A4, p53, and Ki-67 were calculated. The correlation between the positive cell rate of immunohistochemical markers was also calculated. The correlation between the positive cell rate of NY-ESO-1 or MAGE-A4 and tumor size or maximum standardized uptake (SUV-max) was also determined. The positive cell rates of NY-ESO-1 or MAGE-A4 in continuous disease-free (CDF) cases were also compared with those in alive with disease (AWD) or dead of disease (DOD) cases. The average positive cell rates of NY-ESO, MAGEA4, p53, and Ki-67 were 71.7%, 85.1%, 16.2%, and 14.7%, and their positive case rates were 33.3%, 100%, 44.4%, and 100%, respectively. The positivity rates of NY-ESO-1 and p53 were strongly correlated, whereas those of NY-ESO-1 and Ki-67 were moderately correlated. The MAGE-A4 and p53 positivity rates and the MAGE-A4 and Ki-67 positive cell rates were both strongly correlated. The NY-ESO-1 and MAGE-A4 positivity rates were moderately correlated. The positive correlation between the NY-ESO-1 positive cell rate and tumor size was medium, and that between the MAGE-A4 positivity rate and SUV-max was very strong. There was no significant difference in the positive cell rates of NY-ESO-1 or MAGE-A4 between CDF cases and AWD or DOD cases. Overall, our results suggest that NY-ESO-1 and MAGE-A4 may be involved in the aggressiveness of OS.
Extracellular vesicles from bone mesenchymal stem cells transport microRNA-206 into osteosarcoma cells and target NRSN2 to block the ERK1/2-Bcl-xL signaling pathway.
Keremu A, Aila P, Tusun A … +2 more , Abulikemu M, Zou X
Eur J Histochem · 2022 Jun · PMID 35730574 · Full text
Osteosarcoma (OS) is a kind of malignant tumor originating from mesenchymal tissue Bone mesenchymal stem cells-derived extracellular vesicles (BMSCs-EVs) can play important roles in OS. This study investigated the mechan...
Osteosarcoma (OS) is a kind of malignant tumor originating from mesenchymal tissue Bone mesenchymal stem cells-derived extracellular vesicles (BMSCs-EVs) can play important roles in OS. This study investigated the mechanism of BMSCs-EVs on OS. BMSC surface antigens and adipogenic and osteogenic differentiation were detected by flow cytometry, and oil red O and alizarin red staining. EVs were isolated from BMSCs by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot (WB). miR-206 and neurensin-2 (NRSN2) levels in human osteoblast hFOB 1.19 or OS cells (143B, MG-63, Saos2, HOS) were detected by RT-qPCR. Human OS cells with lower miR-206 levels were selected and treated with BMSCs-EVs or pSUPER-NRSN2. The uptake of EVs by 143B cells, cell proliferation, apoptosis, invasion, and migration were detected by immunofluorescence, 5-ethynyl-2'-deoxyuridine (EdU) and colony formation assays, flow cytometry, scratch test, and transwell assays. The binding sites between miR-206 and NRSN2 were predicted by Starbase database and verified by dual-luciferase assay. The OS xenograft model was established and treated by BMSCs-EVs. Tumor growth rate and volume, cell proliferation, and p-ERK1/2, ERK1/2, and Bcl-xL levels were detected by vernier caliper, immunohistochemistry, and WB. BMSCs-EVs were successfully extracted. miR-206 was diminished and NRSN2 was promoted in OS cells. BMSCs-EVs inhibited proliferation, migration, and invasion, and promoted apoptosis of OS cells. BMSCs-EVs carried miR-206 into OS cells. Inhibition of miR-206 in EVs partially reversed the inhibitory effect of EVs on malignant behaviors of OS cells. miR-206 targeted NRSN2. Overexpression of NRSN2 reversed the inhibitory effect of EVs on OS cells. NRSN2 activated the ERK1/2-Bcl-xL pathway. BMSC-EVs inhibited OS growth in vivo. In summary, BMSC-EVs targeted NRSN2 and inhibited the ERK1/2-Bcl-xL pathway by carrying miR-206 into OS cells, thus inhibiting OS progression.
Transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) ameliorates sepsis-associated acute kidney injury by maintaining mitochondrial homeostasis and improving the mitochondrial function.
Chen Z, Wang H, Hu B … +5 more , Chen X, Zheng M, Liang L, Lyu J, Zeng Q
Eur J Histochem · 2022 Jun · PMID 35726572 · Full text
Mitochondrial dysfunction has a role in sepsis-associated acute kidney injury (S-AKI), so the restoration of normal mitochondrial homeostasis may be an effective treatment strategy. Transcription factor nuclear factor er...
Mitochondrial dysfunction has a role in sepsis-associated acute kidney injury (S-AKI), so the restoration of normal mitochondrial homeostasis may be an effective treatment strategy. Transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) is a main regulator of cell-redox homeostasis, and recent studies reported that NRF2 activation helped to preserve mitochondrial morphology and function under conditions of stress. However, the role of NRF2 in the process of S-AKI is still not well understood. The present study investigated whether NRF2 regulates mitochondrial homeostasis and influences mitochondrial function in S-AKI. We demonstrated activation of NRF2 in an in vitro model: lipopolysaccharide (LPS) challenge of ductal epithelial cells of rat renal tubules (NRK-52e cells), and an in vivo model: cecal ligation and puncture (CLP) of rats. Over-expression of NRF2 attenuated oxidative stress, apoptosis, and the inflammatory response; enhanced mitophagy and mitochondrial biogenesis; and mitigated mitochondrial damage in the in vitro model. In vivo experiments showed that rats treated with an NRF2 agonist had higher adenosine triphosphate (ATP) levels, lower blood urea nitrogen and creatinine levels, fewer renal histopathological changes, and higher expression of mitophagy-related proteins [PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PRKN), microtubule-associated protein 1 light chain 3 II (LC3 II)] and mitochondrial biogenesis-related proteins [peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α) and mitochondrial transcription factor A (TFAM)]. Electron microscopy of kidney tissues showed that mitochondrial damage was alleviated by treatment with an NRF2 agonist, and the opposite response occurred upon treatment with an NRF2 antagonist. Overall, our findings suggest that mitochondria have an important role in the pathogenesis of S-AKI, and that NRF2 activation restored mitochondrial homeostasis and function in the presence of this disease. This mitochondrial pathway has the potential to be a novel therapeutic target for the treatment of S-AKI.
Inhibition of HMGB1 suppresses inflammation and catabolism in temporomandibular joint osteoarthritis <em>via</em> NF-κB signaling pathway.
Li YY, Feng YP, Liu L … +2 more , Ke J, Long X
Eur J Histochem · 2022 Jun · PMID 35726537 · Full text
HMGB1 is a highly conserved nuclear protein that is rapidly released into the extracellular environment during infection or tissue damage. In osteoarthritis, HMGB1 acts as a pro-inflammatory cytokine inducing a positive...
HMGB1 is a highly conserved nuclear protein that is rapidly released into the extracellular environment during infection or tissue damage. In osteoarthritis, HMGB1 acts as a pro-inflammatory cytokine inducing a positive feedback loop for synovial inflammation and cartilage degradation. The aim of this study was to explore the role of HMGB1 in inflammation and catabolism of temporomandibular joint osteoarthritis (TMJOA) and whether inhibition of HMGB1 affects TMJOA. Human synovial fibroblasts were incubated with HMGB1, the expression of pro-inflammatory cytokines and catabolic mediators were measured by Western blot and ELISA. NF-κB signaling pathway involvement was studied by the NF-κB inhibitor and detected by Western blotting and immunofluorescence staining. TMJOA was induced by an injection of Complete Freund's adjuvant (CFA) into anterosuperior compartment of rat's joint. An anti-HMGB1 antibody was used to assess the effect to HMGB1 in the synovium and cartilage of the CFA-induced TMJOA rats by H&E, Safranin O, Masson trichrome staining, immunohistochemistry and immunofluorescence. HMGB1 markedly increased the production of MMP13, ADAMTS5, IL-1β and IL-6 through activating NF-κB signaling pathway in human synovial fibroblasts. In vivo, application of the HMGB1 neutralizing antibody effectively ameliorated the detrimental extent of TMJOA. Furthermore, the HMGB1 neutralizing antibody reduced the expression of NF-κB, pro-inflammatory cytokines and catabolic mediators in the synovium and cartilage of CFA-induced TMJOA rats. HMGB1 inhibition alleviates TMJOA by reducing synovial inflammation and cartilage catabolism possibly through suppressing the NF-κB signaling pathway and may become a therapeutic method against TMJOA.
Ferroptosis resistance cooperates with cellular senescence in the overt stage of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.
Vetuschi A, Cappariello A, Onori P … +4 more , Gaudio E, Latella G, Pompili S, Sferra R
Eur J Histochem · 2022 Jun · PMID 35726536 · Full text
Cellular senescence and ferroptosis are the two main, fine-tuned processes in tissue damage restraint; however, they can be overactivated in pathologies such as nonalcoholic fatty liver disease/nonalcoholic steatohepatit...
Cellular senescence and ferroptosis are the two main, fine-tuned processes in tissue damage restraint; however, they can be overactivated in pathologies such as nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH), becoming dangerous stimuli. Senescence is characterized by a decline in cell division and an abnormal release of reactive oxygen species (ROS), and ferroptosis is represented by iron deposition associated with an excessive accumulation of ROS. ROS and cellular stress pathways are also drivers of NAFLD/NASH development. The etiology of NAFLD/NASH lies in poor diets enriched in fat and sugar. This food regimen leads to liver steatosis, resulting in progressive degeneration of the organ, with a late onset of irreversible fibrosis and cirrhosis. Few studies have investigated the possible connection between senescence and ferroptosis in NAFLD/NASH progression, despite the two events sharing some molecular players. We hypothesized a possible link between senescence and ferroptosis in a NAFLD background. To thoroughly investigate this in the context of "Western-style" diet (WSD) abuse, we used an amylin-modified liver NASH mouse model. The main NASH hallmarks have been confirmed in this model, as well as an increase in apoptosis, and Ki67 and p53 expression in the liver. Senescent beta-galactosidase-positive cells were elevated, as well as the expression of the related secretory molecules Il-6 and MMP-1. Features of DNA damage and iron-overload were found in the livers of NASH mice. Gpx4 (glutathione peroxidase 4) expression, counteracting ferroptotic cell death, was increased. Notably, an increased number of senescent cells showing overexpression of gpx4 was also found. Our data seem to suggest that senescent cells acquire a gpx4-mediated mechanism of ferroptosis resistance and thus remain in the liver, fostering the deterioration of liver fitness.
MALAT1 regulates hypertrophy of cardiomyocytes by modulating the miR-181a/HMGB2 pathway.
Chen F, Li W, Zhang D … +5 more , Fu Y, Yuan W, Luo G, Liu F, Luo J
Eur J Histochem · 2022 Jun · PMID 35726535 · Full text
Noncoding RNAs are important for regulation of cardiac hypertrophy. The function of MALAT1 (a long noncoding mRNA), miR-181a, and HMGB2; their contribution to cardiac hypertrophy; and the regulatory relationship between...
Noncoding RNAs are important for regulation of cardiac hypertrophy. The function of MALAT1 (a long noncoding mRNA), miR-181a, and HMGB2; their contribution to cardiac hypertrophy; and the regulatory relationship between them during this process remain unknown. In the present study, we treated primary cardiomyocytes with angiotensin II (Ang II) to mimic cardiac hypertrophy. MALAT1 expression was significantly downregulated in Ang II-treated cardiomyocytes compared with control cardiomyocytes. Ang II-induced cardiac hypertrophy was suppressed by overexpression of MALAT1 and promoted by genetic knockdown of MALAT1. A dual-luciferase reporter assay demonstrated that MALAT1 acted as a sponge for miR-181a and inhibited its expression during cardiac hypertrophy. Cardiac hypertrophy was suppressed by overexpression of a miR-181a inhibitor and enhanced by overexpression of a miR-181a mimic. HMGB2 was downregulated during cardiac hypertrophy and was identified as a target of miR-181a by bioinformatics analysis and a dual-luciferase reporter assay. miR-181a overexpression decreased the mRNA and protein levels of HMGB2. Rescue experiments indicated that MALAT1 overexpression reversed the effect of miR-181a on HMGB2 expression. In summary, the results of the present study show that MALAT1 acts as a sponge for miR-181a and thereby regulates expression of HMGB2 and development of cardiac hypertrophy. The novel MALAT1/miR-181a/HMGB2 axis might play a crucial role in cardiac hypertrophy and serve as a new therapeutic target.
MiR-130a-5p contributed to the progression of endothelial cell injury by regulating FAS.
Wang W, Tang W, Shan E … +4 more , Zhang L, Chen S, Yu C, Gao Y
Eur J Histochem · 2022 May · PMID 35638591 · Full text
MicroRNAs (miRNAs) play critical roles in the development of vascular diseases. However, the effects of miR-130a-5p and its functional targets on atherosclerosis (AS) are still largely unknown. In this regard, our aim is...
MicroRNAs (miRNAs) play critical roles in the development of vascular diseases. However, the effects of miR-130a-5p and its functional targets on atherosclerosis (AS) are still largely unknown. In this regard, our aim is to explore the potentially important role of miR-130a-5p and its target gene during the progression of endothelial cell injury. We first found oxidized low-density lipoprotein (ox-LDL) induced FAS and cell apoptosis in HUVECs. Subsequently, miR-130a-5p expression was verified to be downregulated after ox-LDL treatment and negatively correlated with FAS, and FAS was identified as substantially upregulated in the ox-LDL-treated HUVEC cells. After that, the knockdown of FAS and overexpression of miR-130a-5p together were observed to aggregate ox-LDL-induced reduction of cell viability and apoptosis, cell cycle progression, cell proliferation, cell migration and invasion. In conclusion, we detected that miR-130a-5p contributed to the progression of endothelial cell injury by regulating of FAS, which may provide a new and promising therapeutic target for AS.
Endoplasmic reticulum stress contributed to inflammatory bowel disease by activating p38 MAPK pathway.
Long Y, Zhao Y, Ma X … +6 more , Zeng Y, Hu T, Wu W, Deng C, Hu J, Shen Y
Eur J Histochem · 2022 May · PMID 35603939 · Full text
Recent evidence suggests that endoplasmic reticulum (ER) stress plays a vital role in inflammatory bowel disease (IBD). Therefore, the aim of this study was to investigate the mechanism by which ER stress promotes inflam...
Recent evidence suggests that endoplasmic reticulum (ER) stress plays a vital role in inflammatory bowel disease (IBD). Therefore, the aim of this study was to investigate the mechanism by which ER stress promotes inflammatory response in IBD. The expression of Gro-α, IL-8 and ER stress indicator Grp78 in colon tissues from patients with Crohn's disease (CD) and colonic carcinoma was analyzed by immunohistochemistry staining. Colitis mouse model was established by the induction of trinitrobenzene sulphonic acid (TNBS), and the mice were treated with ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Then the body weight, colon length and colon inflammation were evaluated, and Grp78 and Gro-α in colon tissues were detected by immunohistochemistry. Epithelial cells of colon cancer HCT116 cells were treated with tunicamycin to induce ER stress. Grp78 was detected by Western blot, and chemokines were measured by PCR and ELISA. The expression levels of Grp78, Gro-α and IL-8 were significantly upregulated in intestinal tissues of CD patients. Mice with TNBS induced colitis had increased expression of Grp78 and Gro-α in colonic epithelia. TUDCA reduced the severity of TNBS-induced colitis. In HCT116 cells, tunicamycin increased the expression of Grp78, Gro-α and IL-8 in a concentration-dependent manner. Furthermore, p38 MAPK inhibitor significantly inhibited the upregulation of Gro-α and IL-8 induced by tunicamycin. In conclusion, ER stress promotes inflammatory response in IBD, and the effects may be mediated by the activation of p38 MAPK signaling pathway.
microRNA-16-5p suppresses cell proliferation and angiogenesis in colorectal cancer by negatively regulating forkhead box K1 to block the PI3K/Akt/mTOR pathway.
Huang X, Xu X, Ke H … +6 more , Pan X, Ai J, Xie R, Lan G, Hu Y, Wu Y
Eur J Histochem · 2022 May · PMID 35536149 · Full text
MicroRNAs (miRNAs/miRs) have aroused increasing attention in colorectal cancer (CRC) therapy. This study is designed for a detailed analysis of the roles of miR-16-5p and forkhead box K1 (FOXK1) in cell angiogenesis and...
MicroRNAs (miRNAs/miRs) have aroused increasing attention in colorectal cancer (CRC) therapy. This study is designed for a detailed analysis of the roles of miR-16-5p and forkhead box K1 (FOXK1) in cell angiogenesis and proliferation during CRC in addition to their underlying mechanisms. CRC tissues and colon cancer cell lines (SW620 and HCT8) were investigated. qRT-PCR and Western blot were utilized to evaluate miR-16-5p and FOXK1 expression. Following gain- and loss-of-function assays on miR-16-5p or FOXK1, the effects of miR-16-5p and FOXK1 were assessed on cell angiogenesis and proliferation in CRC cells. A dual-luciferase reporter assay was employed to evaluate the binding relationship of miR-16-5p and FOXK1. Western blot was used to determine the effects of miR-16-5p and FOXK1 on key molecules of the PI3K/Akt/mTOR pathway. Highly expressed FOXK1 and lowly expressed miR-16-5p were observed in CRC cells and tissues. miR-16-5p overexpression or FOXK1 knockdown reduced CRC cell proliferation and angiogenesis of human umbilical vein endothelial cells co-cultured with the supernatant of CRC cells, whereas miR-16-5p silencing or FOXK1 upregulation caused opposite trends. Additionally, miR-16-5p negatively modulated FOXK1 expression. The blockade of the PI3K/Akt/mTOR pathway was triggered by miR-16-5p overexpression or FOXK1 silencing. In conclusion, miR-16-5p hampers cell angiogenesis and proliferation during CRC by targeting FOXK1 to block the PI3K/Akt/mTOR pathway.
Seasonal changes in the expression of PACAP, VPAC1, VPAC2, PAC1 and testicular activity in the testis of the muskrat (<em>Ondatra zibethicus</em>).
Tang Z, Yuan X, Bai Y … +5 more , Guo Y, Zhang H, Han Y, Yuan Z, Weng Q
Eur J Histochem · 2022 May · PMID 35502591 · Full text
Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the steroidogenesis and spermatogenesis in the testis through its receptors PAC1, VPAC1, and VPAC2. In this study, we investigated the...
Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in the steroidogenesis and spermatogenesis in the testis through its receptors PAC1, VPAC1, and VPAC2. In this study, we investigated the seasonal expressions of PACAP, PAC1, VPAC1, VPAC2, luteinizing hormone receptor (LHR), follicle stimulating hormone receptor (FSHR), steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), and CYP17A1 in the testis of the male muskrat during the breeding season and the non-breeding season. Histologically, we found the presence of Leydig cells, Sertoli cells and all kinds of germ cells in the testis during the breeding season but only Leydig cells, Sertoli cells, spermatogonia and primary spermatocyte during the non-breeding season. The immunohistochemical localizations of PACAP and VPAC1 were identified in the Leydig cells, spermatogonia and spermatozoa during the breeding season while only in Leydig cells and spermatogonia during the non-breeding season, and PAC1 and VPAC2 were localized in the Leydig cells in both seasons, in which LHR, StAR, 3β-HSD and CYP17A1 were also expressed. Meanwhile, protein and mRNA expression levels of PACAP, PAC1, VPAC1, VPAC2, LHR, FSHR, StAR, 3β-HSD and CYP17A1 in the testis during the breeding season were significantly higher than those during the non-breeding season. These results suggested that PACAP may involve in the regulation of, steroidogenesis and spermatogenesis via an endocrine, autocrine or paracrine manner in the testis of the muskrat.
Secreted key regulators (Fgf1, Bmp4, Gdf3) are expressed by PAC1-immunopositive retinal ganglion cells in the postnatal rat retina.
Dénes V, Kovacs K, Lukáts Á … +4 more , Mester A, Berta G, Szabó A, Gabriel R
Eur J Histochem · 2022 Apr · PMID 35477223 · Full text
Identified as a member of the secretin/glucagon/VIP superfamily, pituitary adenylate cyclase-activating polypeptide (PACAP1-38) has been recognized as a hormone, neurohormone, transmitter, trophic factor, and known to be...
Identified as a member of the secretin/glucagon/VIP superfamily, pituitary adenylate cyclase-activating polypeptide (PACAP1-38) has been recognized as a hormone, neurohormone, transmitter, trophic factor, and known to be involved in diverse and multiple developmental processes. PACAP1-38 was reported to regulate the production of important morphogens (Fgf1, Bmp4, Gdf3) through PAC1-receptor in the newborn rat retina. To follow up, we aimed to reveal the identity of retinal cells responsible for the production and secretion of Fgf1, Bmp4, and Gdf3 in response to PACAP1-38 treatment. Newborn (P1) rats were treated with 100 pmol PACAP1-38 intravitreally. After 24 h, retinas were dissected and processed for immunohistochemistry performed either on flat-mounted retinas or cryosections. Brn3a and PAC1-R double labeling revealed that 90% of retinal ganglion cells (RGCs) expressed PAC1-receptor. We showed that RGCs were Fgf1, Bmp4, and Gdf3-immunopositive and PAC1-R was co-expressed with each protein. To elucidate if RGCs release these secreted regulators, the key components for vesicle release were examined. No labeling was detected for synaptophysin, Exo70, or NESP55 in RGCs but an intense Rab3a-immunoreactivity was detected in their cell bodies. We found that the vast majority of RGCs are responsive to PACAP, which in turn could have a significant impact on their development or/and physiology. Although Fgf1, Bmp4, and Gdf3 were abundantly expressed in PAC1-positive RGCs, the cells lack synaptophysin and Exo70 in the newborn retina, thus unable to release these proteins. These proteins could regulate postnatal RGC development acting through intracrine pathways.
Immunohistochemical expression and clinicopathological assessment of PD-1, PD-L1, NY-ESO-1, and MAGE-A4 expression in highly aggressive soft tissue sarcomas.
Hashimoto K, Nishimura S, Ito T … +2 more , Kakinoki R, Akagi M
Eur J Histochem · 2022 Apr · PMID 35448937 · Full text
Immunotherapy has altered the treatment paradigm for soft tissue sarcomas (STSs). Considering the limited information regarding the clinical significance of immunohistochemical markers in STS, the purpose of this study w...
Immunotherapy has altered the treatment paradigm for soft tissue sarcomas (STSs). Considering the limited information regarding the clinical significance of immunohistochemical markers in STS, the purpose of this study was to determine the clinical significance of programmed cell death-1 (PD-1), PD ligand-1 (PD-L1), New York esophageal squamous cell carcinoma-1 (NY-ESO-1), and melanoma-associated antigen-A4 (MAGE-A4) expression in STSs. Twenty-two patients (median age, 72.5 years) with STSs treated at our hospital were included in this study. The specimens obtained at the time of biopsy were used to perform immunostaining for PD-1, PD-L1, NY-ESO, and MAGE-A4. The rates of PD-1-, PD-L1-, NY-ESO-, and MAGE-A4-positive cells and cases were calculated. The correlations among the positive cell rates of the immunohistochemical markers as well as their correlations with the histological grade, tumor size, or maximum standardized uptake (SUVmax) value were also determined. The average rates of PD-1-, PD-L1-, NY-ESO-, and MAGE-A4-positive cells were 4.39%, 28.0%, 18.2%, and 39.4%, respectively. Although the PD-1-positive cell rate showed no correlation with the rates of NY-ESO-1- and MAGE-A4-positive cells, the PD-L1-positive cell rates showed strong positive correlations with the rates of NY-ESO-1- and MAGE-A4-positive cells. PD-1-, PD-L1-, NY-ESO-1-, and MAGE-A4-positive cell rates showed weak to moderate correlations with histological grade or tumor size, while the PD-1-, PD-L1-, and MAGE-A4-positive cell rates showed strong to very strong positive correlations with the SUVmax value. Thus, PD-1, PD-L1, NY-ESO, and MAGE-A4 expressions are correlated and may be involved in the aggressive elements of STSs.
Histochemistry for nucleic acid research: 60 years in the European Journal of Histochemistry.
Casali C, Siciliani S, Zannino L … +1 more , Biggiogera M
Eur J Histochem · 2022 Apr · PMID 35441834 · Full text
Since the discovery of DNA structure in 1953, the deoxyribonucleic acid has always been playing a central role in biological research. As physical and ordered nucleotides sequence, it stands at the base of genes existenc...
Since the discovery of DNA structure in 1953, the deoxyribonucleic acid has always been playing a central role in biological research. As physical and ordered nucleotides sequence, it stands at the base of genes existence. Furthermore, beside this 2-dimensional sequence, DNA is characterized by a 3D structural and functional organization, which is of interest for the scientific community due to multiple levels of expression regulation, of interaction with other biomolecules, and much more. Analogously, the nucleic acid counterpart of DNA, RNA, represents a central issue in research, because of its fundamental role in gene expression and regulation, and for the DNA-RNA interplay. Because of their importance, DNA and RNA have always been mentioned and studied in several publications, and the European Journal of Histochemistry is no exception. Here, we review and discuss the papers published in the last 60 years of this Journal, focusing on its contribution in deepening the knowledge about this topic and analysing papers that reflect the interest this Journal always granted to the world of DNA and RNA.
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