International Journal Of Experimental Pathology[JOURNAL]
Sun
200 papers
The role of thromboxane prostanoid receptor signaling in gastric ulcer healing.
Yamane S, Amano H, Ito Y … +5 more , Betto T, Matsui Y, Koizumi W, Narumiya S, Majima M
Int J Exp Pathol · 2022 Feb · PMID 34655121 · Full text
The process of gastric ulcer healing includes cell migration, proliferation, angiogenesis and re-epithelialization. Platelets contain angiogenesis stimulating factors that induce angiogenesis. Thromboxane A (TXA ) not on...
The process of gastric ulcer healing includes cell migration, proliferation, angiogenesis and re-epithelialization. Platelets contain angiogenesis stimulating factors that induce angiogenesis. Thromboxane A (TXA ) not only induces platelet activity but also angiogenesis. This study investigated the role of TXA in gastric ulcer healing using TXA receptor knockout (TPKO) mice. Gastric ulcer healing was suppressed by treatment with the TXA synthase inhibitor OKY-046 and the TXA receptor antagonist S-1452 compared with vehicle-treated mice. TPKO showed delayed gastric ulcer healing compared with wild-type mice (WT). The number of microvessels and CD31 expression were lower in TPKO than in WT mice, and TPKO suppressed the expression of transforming growth factor beta (TGF-β) and vascular endothelial growth factor A (VEGF-A) in areas around gastric ulcers. Immunofluorescence assays showed that TGF-β and VEGF-A co-localized with platelets. Gastric ulcer healing was significantly reduced in WT mice transplanted with TPKO compared with WT bone marrow. These results suggested that TP signalling on platelets facilitates gastric ulcer healing through TGF-β and VEGF-A.
A simple optical tissue clearing pipeline for 3D vasculature imaging of the mediastinal organs in mice.
Sun Q, Tiziana P, Khan AUM … +2 more , Heuveline V, Gretz N
Int J Exp Pathol · 2021 Aug · PMID 34613652 · Full text
Optical tissue clearing (OTC) methods render tissue transparent by matching the refractive index within a sample to enable three-dimensional (3D) imaging with advanced microscopes. The application of OTC method in medias...
Optical tissue clearing (OTC) methods render tissue transparent by matching the refractive index within a sample to enable three-dimensional (3D) imaging with advanced microscopes. The application of OTC method in mediastinal organs in mice remains poorly understand. Our aim was to establish a simple protocol pipeline for 3D imaging of the mediastinal organs in mice. Trachea, oesophagus, thymus and heart were harvested from mice after retrograde perfusion via the abdominal aorta. We combined and optimized antibody labelling of thick tissue samples, OTC with cheap and non-toxic solvent ethyl cinnamate (ECi), and light-sheet fluorescence microscopy (LSFM) or laser confocal fluorescence microscopy (LCFM) to visualize the vasculature of those tissues. A high degree of optical transparency of trachea, oesophagus, thymus and heart was achieved after ECi-based OTC. With anti-CD31 antibody immunofluorescence labelling before ECi-based OTC, the vasculature of these tissues with their natural morphology, location and organizational network was imaged using LSFM or LCFM. This simple protocol pipeline provides an easy-to-setup and comprehensive way to study the vasculature of mediastinal organs in 3D without any special equipment. We anticipate that it will facilitate diverse applications in biomedical research of thoracic diseases and even other organs.
Xeroderma Pigmentosum group D suppresses proliferation and promotes apoptosis of HepG2 cells by downregulating ERG expression via the PPARγ pathway.
He Y, Tao W, Shang C … +4 more , Qi C, Ji D, Lu W, Chen G
Int J Exp Pathol · 2021 Jun · PMID 33993564 · Full text
Xeroderma Pigmentosum group D (XPD) gene has been shown to suppress hepatocellular carcinoma (HCC) progression, but its mechanism remains not fully understood. ETS-related gene (ERG) is generally known as an oncogenic ge...
Xeroderma Pigmentosum group D (XPD) gene has been shown to suppress hepatocellular carcinoma (HCC) progression, but its mechanism remains not fully understood. ETS-related gene (ERG) is generally known as an oncogenic gene. This study aimed to explore whether XPD regulated HCC cell proliferation, apoptosis and cell cycle by inhibiting ERG expression via the PPARγ pathway. The human hepatoma cells (HepG2) were transfected with the XPD overexpression vector (pEGFP-N2/XPD) or empty vector (pEGFP-N2). The PPARγ inhibitor GW9662 was used to determine whether XPD effects were mediated by activation of PPARγ pathway. Cell cycle and apoptosis were ascertained by flow cytometry, and cell viability was measured by MTT assay. Reverse transcription-polymerase chain reaction and Western blot were performed to determine the mRNA and protein levels. Overexpression of XPD significantly enhanced the expression of PPARγ and p-PPARγ, whereas it downregulated that of ERG and cdk7. Furthermore, XPD overexpression notably inhibited proliferation, promoted apoptosis and decreased the percentage of cells in the S + G2 phase of HepG2 cells. However, these effects of XPD overexpression were abrogated by GW9662. Collectively, XPD suppresses proliferation and promotes apoptosis of HepG2 cells by downregulating ERG expression via activation of the PPARγ pathway.
Aberrant expression of LncRNA CASC2 mediated the cell viability, apoptosis and autophagy of colon cancer cells by sponging miR-19a via NF-κB signaling pathway.
Zhang P, Pan Y, Sun J … +1 more , Pan G
Int J Exp Pathol · 2021 Jun · PMID 33983643 · Full text
Abnormal and rapid proliferation of colon cancer cells is a severe problem that can be regulated by non-coding RNAs. Thus, our study focused on effects of lncRNA CASC2 and miR-19a on colon cancer cells. Expressions of ln...
Abnormal and rapid proliferation of colon cancer cells is a severe problem that can be regulated by non-coding RNAs. Thus, our study focused on effects of lncRNA CASC2 and miR-19a on colon cancer cells. Expressions of lncRNA CASC2, miR-19a, Bcl-2, Bax and NF-κB/p65 were examined by RT-qPCR. Cell viabilities were detected by CCK-8. A luciferase report assay was used for measuring binding conditions between lncRNA CASC2 and miR-19a. Western blotting was used to evaluate expression of LC3-I, LC3-II and p62 related to autophagy. Expression of lncRNA CASC2 lower in cancer cell lines and the overexpression reduced the cell viability of HT29 and SW480. Furthermore, Bcl-2 was suppressed by overexpressed lncRNA CASC2, while Bax was upregulated. LC3-Ⅰ and p62 were both inhibited, but LC3-Ⅱ was promoted. MiR-19a was predicted to bind lncRNA CASC2 and expressed higher in cancer cell lines. Overexpressed miR-19a reduced expression of lncRNA CASC2 and increased cell viability. This was repressed by upregulated lncRNA CASC2. Bcl-2 and Bax expression and proteins implicated in autophagy that are regulated by lncRNA CASC2 upregulation were reversed by miR-19a overexpression. NF-κB was upregulated in colon cancer cell lines, while inhibition of NF-κB reversed functions of lncRNA CASC2 and magnified roles of miR-19a. Our findings showed that lncRNA CASC2 inhibited cell viability in colon cancer cell lines and miR-19a reversed its functions through the NF-κB signalling pathway, suggesting that these could be factors in treating colon cancer in the future.
Identification of growth differentiation factor 15 as a pro-fibrotic factor in mouse liver fibrosis progression.
Qi P, Ma MZ, Kuai JH
Int J Exp Pathol · 2021 Jun · PMID 33983642 · Full text
The aim of this study was elucidate the inhibitory role of growth differentiation factor 15 (GDF15) in liver fibrosis and its possible activation mechanism in hepatic stellate cells (HSCs) of mice. We generated a GDF15-n...
The aim of this study was elucidate the inhibitory role of growth differentiation factor 15 (GDF15) in liver fibrosis and its possible activation mechanism in hepatic stellate cells (HSCs) of mice. We generated a GDF15-neutralizing antibody that can inhibit TGF-β1-induced activation of the TGF-β/Smad2/3 pathway in LX-2 cells. All the mice in this study were induced by carbon tetrachloride and thioacetamide. In addition, primary HSCs from mice were isolated from fresh livers using Nycodenz density gradient separation. The severity and extent of liver fibrosis were evaluated by Sirius Red and Masson staining. The effect of GDF15 on the activation of the TGF-β pathway was detected using dual-luciferase reporter and Western blotting assays. The expression of GDF15 in cirrhotic liver tissue was higher than that in normal liver tissue. Blocking GDF15 with a neutralizing antibody resulted in a delay in primary hepatic stellate cell activation and remission of liver fibrosis induced by carbon tetrachloride or thioacetamide. Meanwhile, TGF-β pathway activation was partly inhibited by a GDF15-neutralizing antibody in primary HSCs. These results indicated that GDF15 plays an important role in regulating HSC activation and liver fibrosis progression. The inhibition of GDF15 attenuates chemical-inducible liver fibrosis and delays hepatic stellate cell activation, and this effect is probably mainly attributed to its regulatory role in TGF-β signalling.
The role of caveolin-1 and endothelial nitric oxide synthase polymorphisms in susceptibility to prostate cancer.
Aliyari M, Elieh Ali Komi D, Kiani A … +8 more , Moradi M, Tanhapour M, Rahimi Z, Mozafari H, Mohammadi-Noori E, Pourmotabbed T, Vaisi-Raygani A, Bahrehmand F
Int J Exp Pathol · 2021 Dec · PMID 33964050 · Full text
Caveolin-1(cav-1) is overexpressed in prostate cancer (PC) and is associated with progression of the disease. We investigated the effects of CAV1-T29107A and endothelial nitric oxide synthase (eNOS) G894T polymorphisms o...
Caveolin-1(cav-1) is overexpressed in prostate cancer (PC) and is associated with progression of the disease. We investigated the effects of CAV1-T29107A and endothelial nitric oxide synthase (eNOS) G894T polymorphisms on the serum levels of testosterone, NO and prostate-specific antigen (PSA) in patients with PC. We genotyped cav-1 and eNOS genes in 112 PC patients and 150 healthy controls by PCR-RFLP. Serum levels of and were measured using spectrophotometry, and serum levels of testosterone and PSA were measured by ELISA. The frequencies of CAV1 genotypes A/T vs. A/A according to the dominant model AT + TT vs. AA genotype and T allele were significantly higher in PC patients in comparison with the control group and considerably increased the risk of disease by 2.19-, 1.44- and 1.6-fold, respectively. AT + TT genotypes were associated significantly with the increased risk of PC in those with smoking or diabetes by 3.08-fold (P = .004). Individuals carrying concurrently the T allele of CAV1 A29107T and the T allele of eNOS G894T genes had a significantly increased risk of PC by 2.52-fold (P = .009). We did not find any significant relationship between eNOS G894T genotypes and alleles with susceptibility to PC. Our results highlighted the significance of CAV1-T29107A SNP but not (eNOS) G894T in the susceptibility to PC in our the population that we have studied.
The utility of c-Met as a diagnostic tissue biomarker in primary colorectal cancer.
Armstrong GR, Khot MI, Tiernan JP … +5 more , West NP, Perry SL, Maisey TI, Hughes TA, Jayne DG
Int J Exp Pathol · 2021 Jun · PMID 33951261 · Full text
The transmembrane protein, c-Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection...
The transmembrane protein, c-Met, is thought to be overexpressed and activated in colorectal cancer (CRC). This study explored its potential as a diagnostic tissue biomarker for CRC in a large human CRC tissue collection obtained from a randomized clinical trial. Tissue microarrays of matched normal colorectal epithelium and primary cancer were prepared from specimens obtained from 280 patients recruited to the MRC CLASICC trial (ISRCTN 74883561) and interrogated using immunohistochemistry for c-Met expression. The distribution and intensity of immunopositivity was graded using a validated, semi-quantifiable score, and differences in median scores analysed using the Wilcoxon signed-rank test. A receiver operating characteristic (ROC) curve was plotted to measure the diagnostic accuracy of c-Met as a biomarker in CRC. Epithelial cell membrane expression of c-Met differed significantly between CRC and normal colorectal tissue: median 12.00 (Interquartile range (IQR) 6-15) versus median 6.00 (IQR 2.70-12.00) respectively (P = <.0001). ROC-AUC analysis of c-Met expression yielded a CRC diagnostic probability of 0.66 (95% CI: 0.61 to 0.70; P < .0001). A score of ≥14.50 showed high specificity at 85.32% (95% CI 80.33%-89.45%) but sensitivity of only 30.92% (CI 25.37%-36.90%). Thus c-Met is consistently overexpressed in human CRC as compared to normal colorectal epithelium tissue. c-Met expression may have a role in diagnosis and prognostication if combined with other biomarkers.
The effects of cell surface CD47 downregulation on ischaemia-reperfusion injury during pig liver transplantation.
Wang Z, Guo H, Xu R … +2 more , Zhao CN, Xia Y
Int J Exp Pathol · 2021 Jun · PMID 33881787 · Full text
This study aimed to investigate the effect of cell surface CD47 downregulation on ischaemia-reperfusion injury (IRI) during pig liver transplantation. Blood samples were collected from healthy miniature Bama pigs randoml...
This study aimed to investigate the effect of cell surface CD47 downregulation on ischaemia-reperfusion injury (IRI) during pig liver transplantation. Blood samples were collected from healthy miniature Bama pigs randomly and equally divided into CD47 antagonism (group A), without CD47 antagonism (group B) and a sham group (group C). Blood samples were collected from groups A and B at 0, 8 and 48 hours after establishment of the new liver through an indwelling tube in the right internal jugular vein. Blood samples were collected at the same time points after liver dissociation from group C. The expression of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA); CD47 expression was detected by Western blot; and liver function indices, including alanine aminotransferase (ALT) and aspartic transaminase (AST), were directly read by an automatic biochemical analyzer. The concentrations of both receptors in group A were significantly lower than groups B and C, at 8 and 48 hours after establishment of blood flow. At 8 and 48 hours in the new liver stage, the values of CD47 levels, ALT and AST in group A were significantly reduced compared to groups B and C (P < 0.05). The levels of CD47 in the three groups were consistent with the trends of the aforementioned observation indicators. The liver functions of the recipients were significantly improved by reducing the release of the inflammatory mediators. This study provides new ideas and intervention approaches for the treatment of IRI in liver transplantation.
British Society for Matrix Biology Autumn 2020 Meeting: "Basement Membranes in Health and Disease".
Int J Exp Pathol · 2021 Apr · PMID 33745160 · Full text
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Protein restriction during puberty alters nutritional parameters and affects ovarian and uterine histomorphometry in adulthood in rats.
de Morais Oliveira DA, Lupi LA, Silveira HS … +1 more , de Almeida Chuffa LG
Int J Exp Pathol · 2021 Apr · PMID 33729619 · Full text
In a large part of the population inefficient ingestion of proteins, whether for cultural, aesthetic or economic reasons, is a global concern. Low-protein diets can cause severe functional complications, mainly during th...
In a large part of the population inefficient ingestion of proteins, whether for cultural, aesthetic or economic reasons, is a global concern. Low-protein diets can cause severe functional complications, mainly during the development and maturation of organs and systems, including the female reproductive system. The present study investigated the effect of nutritional protein restriction during puberty on the oestrous cycle and expression of sex steroid receptors (AR, ERα e ERβ) in ovarian and uterine tissues of adult rats. Protein restriction promoted lower body weight gain, feed efficiency and higher caloric intake. There was an increase in the oestrus phase arrest without changing the total length of the oestrous cycle. The consumption of low-protein diet also reduced the thickness of the uterine endometrium (uterine epithelium and endometrial stroma) in addition to increasing the number of primary and atretic follicles in the ovaries. Furthermore, the low-protein diet reduced the levels of androgen receptor (AR) and increased the oestrogen receptor β (ERβ) in the ovary, while no significant changes were observed in the uterus. Our study reinforces the importance of adequate protein intake during puberty, since physiological changes in this developmental period interfere with the histomorphometry of the ovaries and uteri, possibly resulting in impaired folliculogenesis and fertility in the reproductive period.
Modelling hypercholesterolaemia in rats using high cholesterol diet.
Cunha LF, Ongaratto MA, Endres M … +1 more , Barschak AG
Int J Exp Pathol · 2021 Apr · PMID 33710712 · Full text
Hypercholesterolaemia is a complex condition with multiple causes, including both lifestyle and genetic aspects. It is also a risk factor for cardiovascular diseases (CVDs), which are responsible for 172 million deaths/y...
Hypercholesterolaemia is a complex condition with multiple causes, including both lifestyle and genetic aspects. It is also a risk factor for cardiovascular diseases (CVDs), which are responsible for 172 million deaths/year. Although the reasons for hypercholesterolaemia are known, there are many critical questions that remain to be answered so that new therapeutics can be developed. In order to elucidate the pathobiology of this condition, animal models can mimic the pathology of human hypercholesterolaemia. One example of an animal model is induced by the hypercholesterolaemic diet in Wistar rats. The present review first summarizes the current understanding of the metabolic profile involved in hypercholesterolaemia in humans. Next it comments about the lack of consensus as to which hypercholesterolaemia induction protocol should be used. The present work aimed to review experimental studies that induced hypercholesterolaemia in Wistar rats it was not intended to judge the "best" model, since they all achieved the goal of inducing an increase in serum cholesterol.
Establishment of a long-term hypertrophic scar model by injection of anhydrous alcohol: A rabbit model.
Zu W, Jiang B, Liu H
Int J Exp Pathol · 2021 Apr · PMID 33710702 · Full text
The processes of hypertrophic scar formation are extremely complex, and current animal models have limitations in terms of the complete characterization of lesions. An ideal animal model is indispensable for exploring th...
The processes of hypertrophic scar formation are extremely complex, and current animal models have limitations in terms of the complete characterization of lesions. An ideal animal model is indispensable for exploring the complex progression of scar formation to elucidate its pathophysiology and to perform therapeutic testing. This study aimed to establish a long-term, consistent and easily testable animal model by injecting anhydrous alcohol into the dorsal trunk dermis of rabbits. The rabbits were injected with different amounts of anhydrous alcohol. Anhydrous alcohol was infiltrated into the subcutaneous and superficial fascia. The optimal amount of anhydrous alcohol was determined by measuring the area and thickness of the scar. The typical model was established by determining the optimum dosage, and then we analysed the histological characteristics and fibrosis-associated protein expression. The dermal scar was generated by treating with 2 ml/kg anhydrous alcohol and displayed histopathologic features that characterize human hypertrophic scarring, including a parallel collagen fibre orientation, dermal and epidermal thickening, broad collagen deposition and the loss of dermal adnexal structures. The expression of fibrotic pan-markers was also enhanced. Moreover, the scar features and duration were compared between the anhydrous alcohol model and the rabbit ear model. Our results show that injecting anhydrous alcohol in the rabbit model thickened the dermal tissue, stimulated dermal fibroproliferation and resulted in hypertrophic scars with protein and histologic features similar to those seen in humans. Taken together, the findings from this study show that our model could be a feasible and useful tool for further research on the pathogenesis of hypertrophic scars.
Exposure to chewing tobacco promotes primary oral squamous cell carcinoma and regional lymph node metastasis by alterations of SDF1α/CXCR4 axis.
Ray S, Saha D, Alam N … +5 more , Mitra Mustafi S, Mandal S, Sarkar A, Majumder B, Murmu N
Int J Exp Pathol · 2021 Apr · PMID 33655604 · Full text
A high incidence of oral squamous cell carcinoma (OSCC) is observed in South-East Asian countries due to addictions such as chewing tobacco. Local invasion and distant metastases are primary causes of poor prognosis in O...
A high incidence of oral squamous cell carcinoma (OSCC) is observed in South-East Asian countries due to addictions such as chewing tobacco. Local invasion and distant metastases are primary causes of poor prognosis in OSCC. This study aimed to understand the alterations in metastasis biomarkers, such as stromal cell-derived factor-1α (SDF-1 or SDF1α) and its receptor C-X-C chemokine receptor type 4 (CXCR4), in OSCC patient samples that were stratified based on the history of addiction to chewing tobacco. Targeted immunohistochemical staining and Western blotting were performed on primary tumour and metastatic lymph node (LN) tissues in parallel. Overexpression of hepatocyte growth factor (HGF), activated form of its cognate receptor tyrosine kinase, c-Met (p-Met), GRB2-associated-binding protein 1 (Gab1), phospho-protein kinase B (pAkt), nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2) were observed in primary tumour and metastatic lymph nodes in both chewer and non-chewer cohorts. Variance analysis showed significant positive correlation between them (P < .0001) indicating upregulation of these biomarkers upon ligand-induced activation of c-Met in both tobacco chewers and non-chewers. Significantly higher expressions of SDF1α and CXCR4 were observed in both primary tumours and metastatic lymph nodes of tobacco chewers (P < .0001) and coincided with overexpressed HGF. In contrast, no significant correlation was observed between expression of HGF and that of SDF1α and CXCR4 in non-chewers. Together, our findings provide important insights into the association of HGF/c-Met and the SDF1α/CXCR4 axis in lymph node metastasis and to an aetiological link with the habit of chewing tobacco.
Time response of rat testicular alterations induced by cryptorchidism and orchiopexy.
Ferragut Cardoso AP, Gomide LMM, Souza NP … +5 more , de Jesus CMN, Arnold LL, Cohen SM, de Camargo JLV, Nascimento E Pontes MG
Int J Exp Pathol · 2021 Feb · PMID 33502821 · Full text
Cryptorchidism is one of the main risk factors for infertility and testicular cancer. Orchiopexy surgery corrects cryptorchidism effects. Different models of cryptorchidism developed in the rat include surgery. We assess...
Cryptorchidism is one of the main risk factors for infertility and testicular cancer. Orchiopexy surgery corrects cryptorchidism effects. Different models of cryptorchidism developed in the rat include surgery. We assessed testicular alterations in rats submitted to surgical cryptorchidism and examined their potential for reversibility at different time points in order to verify time dependency effect(s) on the recovery of the undescended testes. Cryptorchidism was induced in 3-week-old rats. Animals were euthanized 3, 6 or 11 weeks after surgery to evaluate the morphological progression of cryptorchidism-induced germinative epithelial alterations. Other groups underwent orchiopexy 3, 5 or 9 weeks after surgical cryptorchidism, before or after puberty. Animals were euthanized 3 or 8 weeks after orchiopexy. Controls underwent sham surgery at the same time points as the surgical groups. Cryptorchid testes showed decreased weight, germinative epithelial degeneration, apoptosis and vacuolation, corresponding to impairment of spermatogenesis and of Sertoli cells. Some tubules has a Sertoli cell-only pattern and atrophy. The intensity of damage was related to the duration of cryptorchidism. After orchiopexy, spermatogenesis completely recovered only when testicular relocation occurred before puberty and the interval for recovery was extended. These results indicate that age, sexual maturity and extension of germ cell damage were relevant for producing germ cell restoration and normal spermatogenesis. We provide original observations on the time dependency of testicular alterations induced by cryptorchidism and their restoration using morphologic, morphometric and immunohistochemical approaches. It may be useful to study germ cell impairment, progression and recovery in different experimental settings, including exposure to exogenous chemicals.
Different anaesthesia methods affect the development of hepatoblastoma after platelet activation.
Fei G, Cao M, Ge C … +1 more , Xie Y
Int J Exp Pathol · 2021 Feb · PMID 33410572 · Full text
This study aims to compare the influence of different anaesthesia methods on the mechanisms involved in the development of hepatoblastoma (HB). HB rabbit models were constructed and divided into three groups: disoprofol,...
This study aims to compare the influence of different anaesthesia methods on the mechanisms involved in the development of hepatoblastoma (HB). HB rabbit models were constructed and divided into three groups: disoprofol, pentobarbital sodium and HB groups. After anaesthesia, rabbit blood was collected from the tail vein. Haematological analysis (platelets) and an ELISA was used to measure the thrombopoietin (TPO) and 5-hydroxytryptamine (5-HT). Flow cytometry was used to determine expression of P-selectin and PAF. The expression of 5-HTR2B, PCNA, vWF, P70s6k, 4E-BP1, mTOR and FRAP was determined in the tumour itself or in vascular tissues obtained from the rabbits. The platelet content in the disoprofol group. The content or expression of TPO, 5-HT, P-selectin, PAF, 5-HTR2B, PCNA, vWF, P70s6k, 4E-BP1, mTOR and FRAP was significantly higher in the disoprofol group compared to pentobarbital sodium and HB groups. Expression of these molecules was much higher in the pentobarbital sodium group compared with the HB group. These findings suggest that disoprofol anaesthesia can promote HB development via the mTOR/p70S6K1 and FRAP signalling pathway.
Mucosal IL-10 and IL-10 receptor expression patterns in paediatric patients with ulcerative colitis.
Wittmann Dayagi T, Werner L, Pinsker M … +4 more , Salamon N, Barschak I, Weiss B, Shouval DS
Int J Exp Pathol · 2021 Feb · PMID 33405352 · Full text
Interleukin-10 (IL-10) is a key anti-inflammatory cytokine. We aimed to assess IL-10 and IL-10 receptor (IL-10R) expression in the gut, and determine whether these patterns are altered in patients with ulcerative colitis...
Interleukin-10 (IL-10) is a key anti-inflammatory cytokine. We aimed to assess IL-10 and IL-10 receptor (IL-10R) expression in the gut, and determine whether these patterns are altered in patients with ulcerative colitis (UC). Formalin-fixed paraffin-embedded rectal and transverse colon sections were collected from three groups of patients: (a) control subjects with normal colonoscopy and without history of inflammatory bowel disease; (b) UC patients with extensive colitis or pancolitis (E3/E4 phenotype); and (c) UC patients with limited distal disease (E1/E2 phenotype; n = 8-10 subjects per group). Immunohistochemistry (IHC) was performed to assess expression patterns of IL-10, IL-10R1 and IL-10R2, and was correlated with clinical, endoscopic and histologic severity indices among patients. A trend towards increased IL-10 expression was noted in rectal biopsies of patients with active UC, compared with controls. Moreover, IL-10 levels were significantly increased in transverse colon biopsies of patients with extensive/pancolitis, compared with control subjects and patients with limited distal disease. Rectal IL-10R1 and IL-10R2 levels were comparable between control subject and patients with active UC. However, transverse colon IL-10R1 levels were significantly higher in patients with E3/E4 colitis, compared with controls. Finally, we found no correlation between clinical, endoscopic and histologic severity of inflammation among UC patients and IL-10, IL-10R1 or IL-10R2 expression in rectal sections. Mucosal expression patterns of IL-10 and IL-10R, evaluated by IHC, were overall similar between control subjects and patients with active UC. Given IL-10's anti-inflammatory properties, additional studies are required to determine whether signalling through the IL-10R is altered among these patients.
Biological evaluation of hesperidin for direct pulp capping in dogs' teeth.
Abo El-Mal EO, Abu-Seida AM, El Ashry SH
Int J Exp Pathol · 2021 Feb · PMID 33405328 · Full text
This study compared the biological effect of Hesperidin, Mineral Trioxide Aggregate (MTA)-Angelus and calcium hydroxide for direct pulp capping. A total of 126 dogs teeth were divided according to the post-treatment eval...
This study compared the biological effect of Hesperidin, Mineral Trioxide Aggregate (MTA)-Angelus and calcium hydroxide for direct pulp capping. A total of 126 dogs teeth were divided according to the post-treatment evaluation period into three groups (42 teeth each), group I: 2 weeks, group II: 4 weeks and group III: 8 weeks. Each group was further subdivided according to the pulp capping material into three subgroups (14 teeth each), subgroup A (Hesperidin), subgroup B (MTA-Angelus) and subgroup C (Dycal). Both inflammatory response and dentine bridge formation were assessed by histopathology. All data were statistically analysed. Resolution of the inflammation was recorded by the time with a significant difference between subgroups within the same group (P<.05). Hesperidin, MTA-Angelus and Dycal showed either mild or moderate inflammation at 2 weeks with significant differences between subgroups (P < .05). At 4 and 8 weeks, there were no significant differences between subgroups (P > .05). Absence of complete or partial calcified bridge with no odontoblastic layer was reported in all subgroups at 2 weeks while at 4 weeks, the majority of samples in Hesperidin and MTA subgroups showed amorphous calcified deposit. At 8 weeks, there was no significant difference (P > .05) between subgroups except that 78.5% and 92.9% of Hesperidin and MTA-Angelus samples, respectively, showed moderate dentine bridge. Also, 78.5% of Hesperidin and Dycal samples revealed moderately thick dentine bridge while 78.7% of MTA-Angelus showed a thin dentine bridge with a significant difference between them (P < .05). In conclusion, Hesperidin is a promising pulp capping material inducing mild inflammation and good dentine bridge formation.
Circular RNA ITCH mediates HO-induced myocardial cell apoptosis by targeting miR-17-5p via wnt/β-catenin signalling pathway.
Zhang N, Wang X
Int J Exp Pathol · 2021 Feb · PMID 33350543 · Full text
Cardiovascular disease is a severe threat health worldwide, and circRNAs have been shown to be correlated with the development of cardiovascular disease. Expression of circ-ITCH and miR-17a-5p was evaluated by RT-qPCR. C...
Cardiovascular disease is a severe threat health worldwide, and circRNAs have been shown to be correlated with the development of cardiovascular disease. Expression of circ-ITCH and miR-17a-5p was evaluated by RT-qPCR. Cell viability was measured using CCK-8. Flow cytometry was applied to measure apoptosis rate. Binding between miR-17-5p and circ-ITCH was detected via luciferase reporter assays. Levels of ATP in cells were examined with ATP testing. Western blot was used to evaluate apoptosis-related proteins and proteins in Wnt/β-catenin signalling pathway. HO induced apoptosis of H9c2 cells and lowered cell viability as well as ATP levels and circ-ITCH expression. After overexpression, circ-ITCH enhanced cell viability and ATP concentration. Meanwhile, apoptosis was inhibited. MiR-17-5p was the target of circ-ITCH as evidenced by luciferase report assays, with higher expression in HO-induced H9c2 cells. Knockdown of miR-17-5p could promote cell viability and level of ATP and curb apoptosis and p53 and PARP expression. Moreover, overexpressed miR-17-5p could reverse the function of upregulated circ-ITCH. Wnt3a, Wnt5a and β-catenin in Wnt/β-catenin signalling pathway were increased after HO induction. Suppression of Wnt/β-catenin signalling pathway could initiate the process of injury in H9c2 cells. Circ-ITCH could protect myocardial cells from injuries caused by HO by suppressing apoptosis while miR-17-5p played a reverse role, which could upregulate apoptosis and inhibit cell viability via Wnt/β-catenin signalling pathway.
Ixazomib, an oral proteasome inhibitor, exhibits potential effect in dystrophin-deficient mdx mice.
Micheletto MLJ, Hermes TA, Bertassoli BM … +5 more , Petri G, Perez MM, Fonseca FLA, Carvalho AAS, Feder D
Int J Exp Pathol · 2021 Feb · PMID 33296126 · Full text
Dystrophin deficiency makes the sarcolemma fragile and susceptible to degeneration in Duchenne muscular dystrophy. The proteasome is a multimeric protease complex and is central to the regulation of cellular proteins. Pr...
Dystrophin deficiency makes the sarcolemma fragile and susceptible to degeneration in Duchenne muscular dystrophy. The proteasome is a multimeric protease complex and is central to the regulation of cellular proteins. Previous studies have shown that proteasome inhibition improved pathological changes in mdx mice. Ixazomib is the first oral proteasome inhibitor used as a therapy in multiple myeloma. This study investigated the effects of ixazomib on the dystrophic muscle of mdx mice. MDX mice were treated with ixazomib (7.5 mg/kg/wk by gavage) or 0.2 mL of saline for 12 weeks. The Kondziela test was performed to measure muscle strength. The tibialis anterior (TA) and diaphragm (DIA) muscles were used for morphological analysis, and blood samples were collected for biochemical measurement. We observed maintenance of the muscle strength in the animals treated with ixazomib. Treatment with ixazomib had no toxic effect on the mdx mouse. The morphological analysis showed a reduction in the inflammatory area and fibres with central nuclei in the TA and DIA muscles and an increase in the number of fibres with a diameter of 20 µm in the DIA muscle after treatment with ixazomib. There was an increase in the expression of dystrophin and utrophin in the TA and DIA muscles and a reduction in the expression of osteopontin and TGF-β in the DIA muscle of mdx mice treated with ixazomib. Ixazomib was thus shown to increase the expression of dystrophin and utrophin associated with improved pathological and functional changes in the dystrophic muscles of mdx mice.
Green tea extract rich in epigallocatechin gallate impairs alveolar bone loss in ovariectomized rats with experimental periodontal disease.
Vargas-Sanchez PK, Pitol DL, de Sousa LG … +5 more , Beloti MM, Rosa AL, Rossi AC, Siéssere S, Bombonato-Prado KF
Int J Exp Pathol · 2020 Dec · PMID 33174663 · Full text
Periodontal disease and osteoporosis are characterized by bone resorption, and researchers have shown an association between these two diseases through increasing loss of systemic bone mass and triggering alveolar bone l...
Periodontal disease and osteoporosis are characterized by bone resorption, and researchers have shown an association between these two diseases through increasing loss of systemic bone mass and triggering alveolar bone loss. Green tea is a common and easily accessible beverage, and evidences show that flavonoid epigallocatechin gallate (EGCG) could decrease bone loss in pathologies such as osteoporosis and periodontal disease. In order to verify its possible effects and apply them in the treatment and prevention of these diseases, this investigation aimed to evaluate the influence of green tea extract (GTE) on bone metabolism of ovariectomized rats after experimental periodontal disease (EPD) by histological, morphological and microtomographic parameters. Wistar female rats were divided into Sham, Sham + EPD, Sham + EPD + GTE, OVX, OVX + EPD and OVX + EPD + GTE groups. Immediately after surgery, gavage administration of 50 mg/kg of green tea extract (GTE) was performed for 60 days, with subsequent induction of periodontal disease by ligature 15 days before euthanasia. Mandible and femur samples were collected for histological, morphometric and microtomographic analysis. The results were analysed by means of statistical software with significance set at 5%. Histological and morphometric analysis showed a significant decrease in alveolar and femoral trabecular bone loss in groups that received GTE. Microtomographic results showed that trabecular thickness and bone surface density values in alveolar bone interradicular septum of the OVX + EPD + GTE groups were similar to the Sham group. The results obtained suggest that green tea extract may improve bone metabolism in osteoporotic rats with periodontal disease.
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