Effect of Gestational and Lactational Exposure to DEHP, DINP, and DEP on Intestinal Morphology, Disaccharidases, and Alkaline Phosphatase in Rats during Postnatal Development

2018 ◽  
Vol 35 (13) ◽  
pp. 1251-1259 ◽  
Author(s):  
O. Kharoubi ◽  
A. Aoues ◽  
M. Bouchekara ◽  
B. Khaladi ◽  
M. Taleb ◽  
...  
Keyword(s):  
Corn Oil ◽  
Villous Atrophy ◽  
Wistar Rat ◽  
Treated Group ◽  
The Body ◽  
Intestinal Morphology ◽  
Proliferation Index ◽  
Postnatal Exposure ◽  
Ki 67 ◽  
The Impact

Introduction The diesters of 1,2-benzenedicarboxylic acid (phthalic acid), commonly known as phthalates, are used primarily as plasticizers of polyvinyl chloride and as additives in consumer and personal care products. Objective This study was designed to evaluate the impact of in utero and postnatal exposure to diisononyl phthalate (DINP), diethylhexyl phthalate (DEHP), and diethyl phthalate (DEP) on gut maturation in a Wistar rat model. Materials and Methods Pregnant females were gavaged from day 8 of gestation through postnatal day (pd) 30 with 0 (vehicle control), DEHP (380 mg/kg/d), DINP (380 mg/kg/d), or DEP (800 mg/kg/d) dissolved in corn oil. Intestinal samples have been collected at 0, 7, 14, 21, and 30 pd for histological and biochemical analysis. The mitotic index has been evaluated based on the expression of Ki-67 antigen. Results All tested phthalate treatments have significantly decreased the body as well as the organ's weight (p < 0.001). DINP exposure resulted in severe villous atrophy, while DEHP treated group was characterized by lymphoepithelial lesions. In addition, a significant decrease of the Ki-67 proliferation index was observed in the youngest rats (0 and 7 days) upon the various treatments (p < 0.0001), whereas at day 30, an increased numbers of Ki-67 positive cells were observed in DEHP and DEP but bot DINP group. Lactase and sucrase activities were inhibited by DEP in contrast to DINP and DEHP which increased enzymes activity (p < 0.05). Conclusion Our results suggest that exposure to phthalates during gestational and lactational phases negatively impacts the development of the small intestine.

Psoralidin exerts anti-tumor, anti-angiogenic, and immunostimulatory activities in 4T1 tumor‐bearing balb/c mice

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Davar Amani ◽  
Elham Shakiba ◽  
Ehsan Motaghi ◽  
Hiva Alipanah ◽  
Mahshad Jalalpourroodsari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Serum Level ◽  
Tumor Volume ◽  
Treated Group ◽  
The Body ◽  
Ki 67 ◽  
Tumor Bearing ◽  
Anti Cancer ◽  
Ifn Γ

Abstract Background Psoralidin as a compound of the Psoralea corylifolia seeds exhibited several anti-cancer potentials in various cancers. Materials and methods In this study, 4T1 tumor‐bearing Balb/c mice were treated by intraperitoneal administration of Psoralidin, and Paraffin, as a control group to investigate anti-tumor, anti-angiogenic, and immunostimulatory activities in breast cancer. Body weight and tumor volume measurement were performed. Hematoxylin and Eosin (H&E) staining as well as immunohistochemistry for Ki-67, CD31 and VEGF markers were conducted. In addition, ELISA assay was performed for evaluating the serum level of IFN-γ and IL-4. Moreover, real time assay was performed to evaluate the expression of angiogenesis and immunostimulatory related genes. Results There were no significant changes in the body weight of all animal groups. The anti-cancer effects of Psoralidin were significantly observed after 24 days of the last treatment, confirmed by smaller tumor volume and also H&E staining. The expression level of Ki‐67, CD31 and VEGF were significantly decreased in tumor tissues of the Psoralidin-treated group in comparison with Paraffin-treated group. Moreover, there was a significant reduction in the serum level of IL-4 in tumor-bearing mice after Psoralidin treatment while the serum level of IFN-γ was significantly augmented in all groups. Moreover, the reduction in expression of VEGF-a and IL-1β was observed. Interestingly Psoralidin treatment led to expression increase of FOXp3. Conclusions Psoralidin shows the anti-cancer potential in an animal model of breast cancer; however, further studies are recommended to elucidate its mechanisms of action.

scholarly journals Case Report: Genetic Alterations Associated with the Progression of Carotid Paraganglioma

2021 ◽  
Vol 43 (3) ◽  
pp. 2266-2275
Author(s):  
Vladislav Pavlov ◽  
Anastasiya Snezhkina ◽  
Dmitry Kalinin ◽  
Alexander Golovyuk ◽  
Anastasiya Kobelyatskaya ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Neck Region ◽  
Genetic Alterations ◽  
The Body ◽  
Proliferation Index ◽  
Recurrent Tumor ◽  
Sdhb Mutation ◽  
Ki 67 ◽  
Whole Exome ◽  
Tert Gene

Paragangliomas (PGLs) are rare neuroendocrine tumors that can develop from any paraganglion across the body. The carotid body is the most often location of PGLs in the head and neck region. Carotid PGLs (CPGLs) are characterized by predominantly non-aggressive behavior; however, all tumors have the potential to metastasize. To date, molecular mechanisms of paraganglioma progression remain elusive. We report a case of a 38-year-old woman with metastatic CPGL manifesting as a recurrent tumor with lymph node metastasis. The tumor was fast-growing and had a high Ki-67 proliferation index. Immunohistochemical (IHC) examination and whole-exome sequencing were performed for both recurrent tumor and metastasis. A germline pathogenic splice acceptor variant in the SDHB gene was found in the patient. Immunoreactivity of the SDHB subunit was weak diffuse in both samples, indicating deficiency of the succinate dehydrogenase. Moreover, the recurrent tumor exhibited loss of heterozygosity (LOH) at the SDHB locus, that is according to Knudson’s "two-hit" hypothesis of cancer causation. We also identified a rare somatic promotor mutation in the TERT gene associated with the tumor progression. Obtained results confirmed the indicative role of the germline SDHB mutation for metastatic CPGLs, as well as the potential prognostic value of the TERT promoter mutation.

Mechanism of Villous Atrophy in Celiac Disease: Role of Apoptosis and Epithelial Regeneration

2013 ◽  
Vol 137 (9) ◽  
pp. 1262-1269 ◽  
Author(s):  
DM Shalimar ◽  
Prasenjit Das ◽  
Vishnubhatla Sreenivas ◽  
Siddhartha Datta Gupta ◽  
Subrat K. Panda ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Epithelial Cell ◽  
Villous Atrophy ◽  
Proliferation Index ◽  
Cell Regeneration ◽  
Ki 67 ◽  
Epithelial Regeneration ◽  
Treatment Naïve ◽  
Apoptotic Pathways

Context.—The data on status of apoptosis in patients with celiac disease are conflicting. Furthermore, complex interaction between intrinsic and common apoptotic pathways, apoptotic inhibitors, and epithelial cell proliferation is largely unclear for patients with celiac disease. Objectives.—To determine the role of apoptosis and epithelial cell regeneration in celiac disease. Design.—Twenty-five treatment-naïve patients with celiac disease and 6 patients with functional dyspepsia, as controls, were included and duodenal biopsy specimens from all were subjected to immunohistochemistry with markers of intrinsic apoptotic pathway (AIF, H2AX, p53), common pathway (CC3, M30), apoptotic inhibitors (XIAP, Bcl2), and epithelial proliferation (Ki-67). Apoptotic and proliferation indices were calculated. Results.—Expression of end-apoptotic products, that is, H2AX in the cell nuclei (P = .01) and M30 in the cell cytoplasm (P &lt; .01), was significantly upregulated in celiac disease in comparison to controls. Cleaved caspase-3 was also upregulated in villous cytoplasm in celiac disease. Apoptotic inhibitor Bcl2 was significantly down-regulated in celiac disease in comparison to controls. In addition, Ki-67 proliferation index was upregulated both in the crypts and villous mucosal epithelium in comparison to the crypts of the controls. Conclusions.—Treatment-naïve patients with celiac disease have significantly higher level of apoptosis that involves both the common and intrinsic apoptotic pathways. Increased apoptosis and unequaled cell regeneration in crypts probably results in villous atrophy. Down-regulation of apoptotic inhibitors in treatment-naïve celiac disease imparts an additional pro-apoptotic effect.

scholarly journals Profile Of Oxidative Stress Genes In Response To Obesity Treatment

2021 ◽  
Author(s):  
Amira Ahmed ◽  
Huda Farah ◽  
Omnia Ahmed ◽  
Dina Elsayegh ◽  
Abdelrahman Elgamal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Skeletal Muscles ◽  
Bioactive Compound ◽  
Treated Group ◽  
The Body ◽  
Tissue Samples ◽  
Increased Risk ◽  
The Impact

Background: Oxidative stress (OS) is an imbalance between free radical production and the antioxidants defense in the body. Previous studies demonstrated the correlation of OS to the increased risk of developing metabolic disorders such as obesity. Sulforaphane (SFN), a bioactive compound, can protect against inflammation and OS, thus an effective anti-obesity supplement. Aim: This study explores the impact of SNF on OS in diet induced obese (DIO) mice via profiling of OS genes and pathways in skeletal muscles related to the anti-obesity effect. Methods: Wild-type CD1 male mice and the knockout of nuclear factor (erythroid-derived 2) like 2 (NrF2) mice were fed a high-fat diet (HFD) for 16 weeks; to induce obesity. Subsequently, each group was subdivided into two subgroups and received either Vehicle (25μl) or SFN (5 mg/kg BW) for four weeks. Body weight was measured daily, and a glucose tolerance test (GTT) was performed after 21 days of treatment. Afterward, mice were decapitated, blood and tissue samples were collected and snap-frozen immediately. Total RNA was extracted from Skeletal muscle and epididymal white adipose tissue (eWAT), leptin expression was measured in (eWAT), and 84 OS genes in skeletal muscle were examined using RT-PCR. Results: Significant reduction in body weight in SFN treated WT mice, while no change in KO mice. Plasma glucose, leptin, and leptin gene expression (eWAT) were significantly reduced in the WT-DIO SFN treated group, while no changes were detected in KO mice. SFN decreases OS damage in skeletal muscles, such as lipid peroxidation and production of reactive oxygen species (ROS). Conclusion: This study demonstrated that SFN had lowered body weight in WT-DIO mice by decreasing OS damage in skeletal muscles through the NrF2 pathway and can be a potential anti-obesity drug.

scholarly journals Lactose Glycation of the Maillard-Type Impairs the Benefits of Caseinate Digest to the Weaned Rats for Intestinal Morphology and Serum Biochemistry

Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2104
Author(s):  
Xiao-Peng Wang ◽  
Xin-Huai Zhao
Keyword(s):  
Body Weight ◽  
Maillard Reaction ◽  
Brush Border ◽  
Enzyme Activities ◽  
Milk Proteins ◽  
The Body ◽  
Intestinal Morphology ◽  
Villus Height ◽  
Brush Border Enzyme ◽  
The Impact

The Maillard reaction between the lactose and milk proteins unavoidably occurs during the thermal treatment of milk. Although the impact of this reaction on protein nutrition and safety has been well-studied, whether a lactose glycation of milk proteins of the Maillard-type might affect the rats in their growth and intestinal morphology needs an investigation. In this study, caseinate and lactose-glycated caseinate were digested using pepsin and trypsin. Afterward, the resultant caseinate digest and glycated caseinate digest (lactose content of 13.5 g/kg of protein) at 100, 200, and 400 mg/kg body weight (BW)/d were assessed for their effects on the female weaned Wistar rats in terms of daily body weight gain, intestinal morphology, digestive and brush-border enzyme activities, as well as serum chemical indices. The results showed that glycated caseinate digest always showed a weaker effect on rat than caseinate digest either at the 0–7 or 0–28 d feeding stage, and more importantly, at the highest dose of 400 mg/kg BW/d, it caused obvious adverse effect on the rats, reflected by lower values of these indices. Compared with caseinate digest, glycated caseinate digest in the rats caused 0.9–15.4% and 10.6–49.7% decreases in average daily gain of BW and small intestinal length, 1.1–21.5% and 2.3–33.3% decreases in villus height and the ratio of villus height to crypt depth of the small intestine, or 0.3–57.6% and 0.2–55.7% decreases in digestive and critical brush-border enzyme activities, respectively. In addition, when the rats were fed with glycated caseinate digest, some serum indices related to oxidative stress status were enhanced dose-dependently. Lactose glycation of the Maillard-type is thus considered as a negative event of the Maillard reaction on milk proteins because this reaction might impair protein benefits to the body.

scholarly journals Neuroprotective Effects of Berberine Hydrochloride on Cognitive Dysfunction-Induced by Methamphetamine: Immunohistochemical and Behavioral Studies in Rats

2021 ◽  
Author(s):  
Leila Rezaeian ◽  
◽  
Mehdi Khaksari ◽  
Raheleh Rafaiee ◽  
Hamid Kalalian Moghaddam ◽  
...  
Keyword(s):  
Treated Group ◽  
Control Group ◽  
Self Administration ◽  
Neuroprotective Effects ◽  
Ki 67 ◽  
Berberine Hydrochloride ◽  
Behavioral Studies ◽  
Gfap Expression ◽  
Male Wistar Rats ◽  
The Impact

Introduction: Methamphetamine (MA) as an addictive psychostimulant drug affects the central nervous system. The present research aimed at evaluating the impact of Berberine-hydrochloride on cognitive function Improvement and neuroprotective effects in MA Addicted Rats. Methods: In this study, 27 Male Wistar rats were randomly assigned to three groups, including Control, MA addiction and MA addiction with Berberine Hydrochloride (100 mg/kg/day) per oral during the three-week period of withdrawal. Two groups received inhaled MA self-administration for two weeks (up to 10 mg/kg). Following the experimental procedures, Morris Water Maze (MWM) and shuttle box were used to assess memory and hippocampal sections from the animals were examined for caspase-3, ki-67 and GFAP expression. Results: The obtained results from MWM showed that Berberine Hydrochloride decreases (p<0.01) the distance moved and spent time to reach the hidden platform in four-day learning trails phase and there were significant differences in the distance moved, spent time and frequency of motion in target quadrant on probe test day between groups. Berberine Hydrochloride reduced also the latency to enter animals into the dark chamber in the treated group in comparison with the control group (p<0.05). A significant decrease in activation of caspases-3, higher percentages of Ki67 expression and increase in GFAP expression of cells in Addicted group was found to compare with Berberine-treated and control groups (p<0.05). Conclusions: Berberine Hydrochloride administration for 3 weeks improves cognition function in MA addiction and it has a potential for neuroprotective efficacy.

scholarly journals Correlation of Ki-67 Expression as Tumor cell Proliferation Activity Marker with Cutaneous Squamous Cell Carcinoma Grading

2019 ◽  
Vol 7 (20) ◽  
pp. 3384-3386
Author(s):  
Ibnu T. Alferally ◽  
D. Munir ◽  
I. B. Putra ◽  
R. J. Sembiring
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
The Body ◽  
Proliferation Index ◽  
Ki 67 ◽  
Skin Malignancy ◽  
Anatomical Pathology

Cutaneous Squamous Cell Carcinoma (cSCC) is a malignant keratinocyte tumour that develops through the suprabasal epidermis. This malignant tumour is the second most common skin malignancy after Basal Cell Carcinoma (BCC). The increased incidence of cSCC is directly proportional to increasing age. Generally, the predisposing factor of cSCC is exposure to recurrent sunlight for a long time, so localisation of cSCC is a part of the body that often exposed to direct sunlight, such as the forehead, face, ears, scalp, neck, and back of the hand. The carcinogenesis process of cSCC is a cumulation of a series of events, one of which plays an important role is the proliferation index assessed by Ki-67. Forty-eight tissue paraffin blocks were diagnosed histopathologically as cutaneous squamous cell carcinoma from the Anatomical Pathology Laboratory of the Faculty of Medicine, Universitas Sumatera Utara and the Anatomical Pathology Unit of Haji Adam Malik General Hospital Medan, as the research sample. The results of protein expression from Ki-67 were assessed based on area. There was no significant correlation between cSCC grading and Ki-67 expression (p > 0.05). Ki-67 antigen tumour marker, widely used to determine the level of tumour cell proliferation.

scholarly journals Assessment of Ki-67 proliferation index with deep learning in DCIS (ductal carcinoma in situ)

2021 ◽  
Author(s):  
Lukasz Fulawka ◽  
Jakub Błaszczyk ◽  
Martin Tabakov ◽  
Agnieszka Halon
Keyword(s):  
Deep Learning ◽  
Surface Area ◽  
Ductal Carcinoma ◽  
Region Of Interest ◽  
Absolute Error ◽  
Visual Assessment ◽  
Total Surface Area ◽  
Proliferation Index ◽  
Ki 67 ◽  
The Impact

Abstract The proliferation index (PI) is crucial in histopathologic diagnostics, in particular tumors. It is calculated based on Ki-67 protein expression by immunohistochemistry. PI is routinely evaluated by a visual assessment of the sample by a pathologist. However, this approach is far from ideal due to its poor intra- and interobserver variability and time-consuming. These factors force the community to seek out more precise solutions. Virtual pathology as being increasingly popular in diagnostics, armed with artificial intelligence, may potentially address this issue. The proposed solution calculates the Ki-67 proliferation index by utilizing a deep learning model and fuzzy-set interpretations for hot-spots detection. The obtained region-of-interest is then used to segment relevant cells via classical methods of image processing. The index value is approximated by relating the total surface area occupied by immunopositive cells to the total surface area of relevant cells. The achieved results are compared to the manual calculation of the Ki-67 index made by a domain expert. To increase results reliability, we trained several models in a 3-fold manner and compared the impact of different hyper-parameters. Our best-proposed method estimates PI with 0,026 mean absolute error, which gives a significant advantage over the current state-of-the-art solution.

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