Epithelial Cell Hyperplasia Research Articles

Effects of long-term exposure to high temperature on growth performance, chemical composition, hematological and histological changes, and physiological responses in hybrid catfish [♂Clarias gariepinus (Burchell, 1822) ×♀C. macrocephalus (Günther, 1864)

The anthropogenic and climate-driven rise in water temperature is expected to have an effect on the physiological functions of ectothermic species. In the present study, hybrid catfish were subjected to three different temperatures (27, 32, and 37 °C) for 50 days to examine the effect of long-term exposure to high temperatures on growth and physiological parameters. The results showed that acclimation temperature improves growth and feed utilization with a quadratic effect (P < 0.05). The highest performance was observed at 32 °C, but fish acclimated at 37 °C decreased growth and feed utilization. In addition, skin darkening was observed in fish acclimated with increasing temperatures. Fat content of whole-body, liver, and dorsal muscle of fish was decreased by increasing temperatures (P < 0.05). Higher temperature levels significantly increased in all blood parameters (P < 0.05), except for high-density lipoprotein cholesterol, which was quadratically decreased (P = 0.004). Fish acclimated with increasing temperature also altered gill and liver histology such as gill shortening, hyperplasia and edema in the connective tissue, severe hyperplasia of epithelial cells, and desquamation, hepatocyte vacuolization, nuclei displacement, and pyknotic hepatic cells. While mucus cells were periphery distributed in the subcutaneous skin. In addition, cuboidal shape-like of club cells and melanophores were also observed in fish acclimated at 37 °C resulting in increased epithelial layer thickness. After fish subjected to increasing temperature exhibited an increase in the number of operculum movement and number of gasping for air (P < 0.05) in all acclimated groups. While fish challenged at 37 °C showed higher critical thermal maximum (CTmax, 41.33 °C) than those of the other groups. Overall, the maximum temperature (37 °C) may rick to hybrid catfish. To prevent physiological damage to the fish, as well as reduction of growth and productivity, the temperature in the aquaculture setting should be kept below 37 °C.

Cystic Endometrial Hyperplasia in a Domestic Rabbit (Oryctolagus cuniculus domesticus)

Background: Cystic endometrial hyperplasia is a hormone-dependent disease induced by systemic increase in progesterone that can occur in several domestic species, such as the rabbit. This disease may be associated with sex steroid hormones, especially progesterone, and may be asymptomatic, and it is diagnosed using complementary imaging tests such as total abdominal ultrasound. However, surgical excisional biopsy with histopathological tissue analysis is the gold standard. This study reports a case of asymptomatic cystic endometrial hyperplasia in a female Miniature Lion Lop rabbit (Oryctolagus cuniculus domesticus) treated with therapeutic ovariohysterectomy.Case: A domestic, adult, female Miniature Lion Lop rabbit (Oryctolagus cuniculus domesticus), aged approximately 5 years and weighing 3.2 kg, was referred to specialized care to undergo ovariohysterectomy, an elective procedure. The tutor only reported the occurrence of a single episode of vulvar secretion more than 2 years ago, treated with antibiotics, with remission of clinical signs. In the intraoperative period after celiotomy, the uterine horn and uterine body showed a significant increase in volume, with abnormal color changes and tissue consistency; however, both changes were clinically asymptomatic. Subsequently, biopsy was performed during the ovariohysterectomy procedure. The excised uterus and ovaries were placed in 10% formalin and histopathologically analyzed. The macroscopic histopathological examination of the sectioned tissue revealed a slight amount of brownish fluid inside the uterine horns, in addition to multiple cystic areas in the uterine mucosa. Microscopic examination revealed marked hyperplasia of well-differentiated endometrial epithelial cells, occasionally forming cystic structures of different sizes. Moderate congestion, mild multifocal hemorrhage, and mild multifocal inflammatory infiltrate in the lamina comprising lymphocytes and plasma cells were also observed. Therefore, a diagnosis of cystic endometrial hyperplasia with mild lymphoplasmacytic endometritis was made. Observation of the patient was recommended without therapeutic indication.Discussion: Although the pathogenesis of cystic endometrial hyperplasia remains unknown, it is suggested that it is associated with the presence of sex steroids. Hence, this is a common disease in female rabbits, as they have non-seasonal polyestrous cycles and induced ovulation. Cystic endometrial hyperplasia may be asymptomatic or subclinical, without any significant clinical signs. Conversely, when associated with an infection such as pyometritis, the clinical signs include intermittent hematuria, anemia, lethargy, anorexia, and tenderness in the uterus on palpation. Although diagnosis can be made using total abdominal ultrasound and radiography, it can only be confirmed by the histopathological evaluation of the biopsied uterine tissue. Histopathological features of this disease include endometrial thickening with irregular glandular cystic elevations and hyperplasia of the pseudostratified cylindrical ciliated cells of the uterine glands. Furthermore, lymphoplasmacytic infiltrate is found in the uterine tissue, demonstrating an inflammatory reaction or bacterial infection concomitant with endometrial hyperplasia. In this case, the treatment of choice was therapeutic ovariohysterectomy, which is considered curative in this disease. Thus, ovariohysterectomy can resolve cystic endometrial hyperplasia in a domestic female Miniature Lion Lop rabbit.Keywords: surgery, ovariohysterectomy, rabbits, wildlife.Título: Hiperplasia endometrial cística em coelho-doméstico (Oryctolagus cuniculus domesticus)Descritores: cirurgia, ovariosalpingohisterectomia, coelhos, animais selvagens.

Bioactive Materials Promote Wound Healing through Modulation of Cell Behaviors.

Skin wound repair is a multistage process involving multiple cellular and molecular interactions, which modulate the cell behaviors and dynamic remodeling of extracellular matrices to maximize regeneration and repair. Consequently, abnormalities in cell functions or pathways inevitably give rise to side effects, such as dysregulated inflammation, hyperplasia of nonmigratory epithelial cells, and lack of response to growth factors, which impedes angiogenesis and fibrosis. These issues may cause delayed wound healing or even non‐healing states. Current clinical therapeutic approaches are predominantly dedicated to preventing infections and alleviating topical symptoms rather than addressing the modulation of wound microenvironments to achieve targeted outcomes. Bioactive materials, relying on their chemical, physical, and biological properties or as carriers of bioactive substances, can affect wound microenvironments and promote wound healing at the molecular level. By addressing the mechanisms of wound healing from the perspective of cell behaviors, this review discusses how bioactive materials modulate the microenvironments and cell behaviors within the wounds during the stages of hemostasis, anti‐inflammation, tissue regeneration and deposition, and matrix remodeling. A deeper understanding of cell behaviors during wound healing is bound to promote the development of more targeted and efficient bioactive materials for clinical applications.

Analysis of diagnostic cases of turkey viral enteritis in commercial turkey poults in California

Poult enteritis complex is a multifactorial intestinal disease of young turkeys, which results in considerable economic losses for commercial turkey producers. The objectives of this study were to determine the current prevalence of viral enteritis in California turkeys, assess the methods of detection and the gross and histological presentations of laboratory case submissions. The electronic database at the California Animal Health and Food Safety ( CAHFS ) system was searched for necropsy cases in which intestinal content from commercial turkey poults was submitted for transmission electron microscopy ( TEM ) and/or quantitative reverse transcriptase ( qRT )-PCR for enteric viruses for the period February 1, 2020 to February 1, 2021. Based on these search parameters, the study identified and analyzed a total of 66 poult necropsy cases originating from 22 commercial turkey premises. A diagnosis of viral enteritis was made in 43 of the 66 cases (65.1%) screened for enteric viruses by TEM and/or qRT-PCR. The viruses detected in this study included turkey astroviruses, avian rotavirus, avian reovirus, avian enteric picornavirus, and avian parvovirus. Turkey astroviruses species (32/43, 74.4%) were the most frequently detected viruses, with turkey astrovirus-2 (24/43, 55.8%) being the most common species detected amongst all enteric viruses. A single enteric virus was detected in 44.2% (19/43) of cases submissions, while 2 or more enteric viruses were detected in 55.8% (24/43) of submissions. The age at which enteric viruses were detected ranged from one to 7 wk of age, with the highest frequency of detection occurring in the first 3 wk of life (38/43, 88.4%, 95% CI: 1.2–13.3, odds ratio [ OR ] = 4.1). Within the first 3 wk, the majority (24/43, 55.8%) of poults positive for enteric viruses ranged between 1 and 7 d of age. Our assessment of the different diagnostic methods used at CAHFS indicates that the use of TEM in conjunction with qRT-PCR improved our ability to detect viruses in cases where 2 or more enteric viruses were present. The most common macroscopic findings included pale, thin-walled, fluid-filled small intestines (76.7%); thin, dilated, fluid-filled ceca (69.7%), and primarily litter in the gizzard (60.4%). The most common microscopic findings included villi changes (atrophy, fusion, blunting) (72%), infiltration of the lamina propria with mixed inflammatory cells (51%), hyperplasia of crypt epithelial cells (16%), and increase in the number of goblet cells (16%). This study provides an update on the prevalence of turkey viral enteritis in California commercial turkeys operations and discussed production practices which impact the occurrence of the disease complex. It also identified the current presentation of this disease condition in California and discussed the best approach for diagnosing turkey viral enteritis.

High-fat Western diet consumption exacerbates silica-induced pulmonary inflammation and fibrosis

Consumption of a high-fat Western diet (HFWD) contributes to obesity, disrupted adipose endocrine function, and development of metabolic dysfunction (MetDys). Impaired lung function, pulmonary hypertension, and asthma are all associated with MetDys. Over 35% of adults in the U.S. have MetDys, yet interactions between MetDys and hazardous occupational inhalation exposures are largely unknown. Occupational silica-inhalation leads to chronic lung inflammation, progressive fibrosis, and significant respiratory morbidity and mortality. In this study, we aim to determine the potential of HFWD-consumption to alter silica-induced inflammatory responses in the lung. Six-wk old male F344 rats fed a high fat Western diet (HFWD; 45 kcal % fat, sucrose 22.2% by weight) to induce MetDys, or standard rat chow (STD, controls) for 16 wk were subsequently exposed to silica (6 h/d, 5 d/wk, 39 d; Min-U-Sil 5®, 15 mg/m3) or filtered air; animals remained on their assigned diet for the study duration. Indices of lung inflammation and histopathologic assessment of lung tissue were quantified at 0, 4, and 8 wk after cessation of exposure. Combined HFWD+silica exposure increased bronchoalveolar lavage (BAL) total cells, leukocytes, and BAL lactate dehydrogenase compared to STD+silica exposure controls at all timepoints. HFWD+silica exposure increased BAL proinflammatory cytokines at 4 and 8 wk compared to STD+silica exposure. At 8 wk, histopathological analysis confirmed that alveolitis, epithelial cell hypertrophy and hyperplasia, lipoproteinosis, fibrosis, bronchoalveolar lymphoid hyperplasia and granulomas were exacerbated in the HFWD+silica-exposed group compared to STD+silica-exposed controls. Our results suggest an increased susceptibility to silica-induced lung disease caused by HFWD consumption.

Effect of subabul (Leucaena leucocephala) based complete rations on carcass characteristics and serum thyroxine profile of kids

A study was conducted to evaluate the effect of feeding complete rations containing untreated Leucaena leucocepahala leaf meal (ULLLM) (Subabul) and treated (moist heat) L. leucocepahala leaf meal (TLLLM) at 30 and 40 parts on plane of nutrition and nitrogen balance in kids. Mimosine content of LLLM after moist heat treatment for single-treated and double-treated material was 1.91 and 1.17%, respectively. A feeding trial was conducted with 30 non-descript kids (8.42±0.15 kg, 3 to 4 month-old) by allocating to five complete rations as CR1 (control), CR2 (30% ULLLM), CR3 (30% TLLLM), CR4 (40% ULLLM) and CR5 (40% TLLLM). Average daily gain was significantly (p<0.05) higher in CR1 (55.90±2.25 g/d) and CR3 (56.30±0.92 g/d) followed by CR2 (37.90±3.95 g/d) and CR5 (38.70±5.60 g/d) and lowest in CR4 (23.90±3.65 g/d) group. Dressing yield (39.53 to 44.99%) did not indicate significant changes among the groups. The edible, non-edible, organ weights and wholesale cuts did not indicate significant difference among the groups. Serum T3 (|jg/ml) and T4 (ng/ml) hormone profile showed significant reduction (p<0.05) at 90 days in CR2 (1.80±0.10 and 49.43±2.50) and CR4 (1.10±0.10 and 40.11±2.10) as compared to other groups CR1 (3.61±0.70 and 87.14±8.20), CR3 (2.42±0.20 and 83.14±7.20) and CR5 (2.81±0.30 and 78.11±5.10). Histopathological examination of thyroid gland showed hyperplasia of epithelial cells and follicular vacuolation with cuboidal epithelium in CR2 and CR4 groups. However, normal pattern was observed in CR1 and very mild changes in CR3 and CR5 groups. It was concluded that hot water treatment of L. leucocepahala leaf meal is partially effective in ameliorating mimosine toxicity and can be included at 30% level in complete rations of kids.

Mice Uterine Stem Cells are Affected by Neonatal Endocrine Disruption & Initiate Uteropathies in Adult Life Independent of Circulatory Ovarian Hormones.

It is generally believed that ovarian hormones regulate uterine functions and their altered levels result in various uteropathies like non-receptive uterus, endometrial hyperplasia, adenomyosis, endometriosis, leiomyomas and cancer. Uterus harbors two populations of stem cells including pluripotent, very small embryonic-like stem cells (VSELs) and tissue-specific progenitors (endometrial stem cells, EnSCs). Unlike endometrial mesenchymal stem/ stromal cells, VSELs/EnSCs express ERα, ERβ and PR which makes them directly vulnerable to perinatalendocrine insults. Present study was undertaken to evaluate whether uteropathies occur due to altered hormones and/or intrinsic changes in stem/progenitor cells. Mice pups, exposed to estradiol (20µg/pup/day) on postnatal days 3-7 or vehicle, were subjected to bilateral ovariectomy on day 30 and later exposed sequentially to estradiol and progesterone resulting in receptive uterus in control mice. Despite similar hormonal exposure, endocrine disruption resulted in non-receptive uterus with noticeable endometrial and myometrial hyperplasia and up-regulation of stem cell markers (Oct-4A, Oct-4, Sox2, Nanog). Glands were poorly formed and 'defective' epithelial progenitors were found disseminated into myometrium and blood vessels revealing how adenomyosis and endometriosis possibly initiate. Progesterone resistance and estradiol dominance due to downregulation of Erα & Pr and upregulation of Erβ transcripts was observed in both intact uterus and stem cells enriched from uterus. Transcripts specific for DNA mismatch repair axis (Pcna, NP95 and Dnmt1), repair enzymes (Brca-1, Rad51 and Mlh1) were dysregulated whereas Ki67 was ten-folds increased suggestive of genomic instability. Study reveals role of stem cells in initiating uteropathies during adult life independent of circulatory ovarian hormones. Endocrine disruption affects tissue resident stem/progenitor cells (VSELs/EnSCs) in both endometrium and myometrium, result in epithelial cells hyperplasia, non-receptive endometrium, adenomyosis and defective stem cells and epithelial progenitors were detected in the perimetrium from where they can mobilize to ectopic sites to initiate endometriosis. Study shows stem cell basis for various uteropathies. VSEL: Very small embryonic like stem cell; EnSC: Endometrial stem cell; E + P: Estradiol + Progesterone; E: Endometrium; P: Perimetrium; M: Myometrium; ACD: Asymmetrical cell division; SCD: Symmetrical cell division; CE: Clonal expansion; G: Gland; S: Stromal cell; US: Undifferentiated stromal cell; LE: Luminal epithelium; GE: Glandular epithelium; EP: Epithelial progenitors; SMC: Spindle-shaped myometrial cell; OMC: Oval-shaped myometrial cell.

Casein kinase II activates Bik to induce death of hyperplastic mucous cells in a cell cycle-dependent manner.

Extensive inflammation causes epithelial cell hyperplasia in the airways and Bcl-2-interacting killer (Bik) reduces epithelial cell and mucous cell hyperplasia without affecting resting cells to restore homeostasis. These observations suggest that Bik induces apoptosis in a cell cycle-specific manner, but the mechanisms are not understood. Mice were exposed to an allergen for 3, 14, or 30 days and Bik expression was induced in airway epithelia of transgenic mice. Bik reduced epithelial and mucous cell hyperplasia when mice were exposed to an allergen for 3 or 14 days, but not when exposure lasted for 30 days, and Ki67-positivity was reduced. In culture, Bik expression killed proliferating cells but not quiescent cells. To capture the stage of the cell cycle when Bik induces cell death, airway cells that express fluorescent ubiquitin cell cycle indicators were generated that fluoresce red or green during the G0/G1 and S/G2/M phases of the cells cycle, respectively. Regardless of the cell cycle stage, Bik expression eliminated green-fluorescent cells. Also, Bik, when tagged with a blue-fluorescent protein, was only detected in green cells. Bik phosphorylation mutants at threonine 33 or serine 35 demonstrated that phosphorylation activated Bik to induce death even in quiescent cells. Immunoprecipitation and proteomic approaches identified casein kinase IIα to be responsible for phosphorylating and activating Bik to kill cells in S/G2/M. Ascasein kinase 2 alpha (CKIIα) is expressed only during the G2/M phase, we conclude that Bik activation in airway epithelial cells selectively targets hyperplastic epithelial cells, while leaving resting airway cells unaffected.

Detection and characterization of Hepatitis E virus from commercial rabbit livers in Hebei, China

Rabbit hepatitis E virus (HEV) has been reported for years and is thought to have the potential for zoonotic transmission from rabbits to humans. As reported, HEV genotype 3 (gt3) is the most prevalent form of HEV in rabbits. To determine the prevalence of HEV in commercial rabbit livers, 176 liver samples were collected from an abattoir in Hebei Province, China. Three (1.7%) samples tested positive for RNA of HEV-ORF2 (open reading frames-2). Sequence analysis showed that the three isolates shared high identities with each other (94.08–98.85%). Further analysis showed that all the rabbit strains clustered together in the branch of HEV gt3. Further study by immunohistochemistry (IHC) assays showed that 131 (74.4%) liver samples were positive for HEV ORF2 protein. Pathological changes including cell degeneration, inflammatory cell infiltration and bile duct epithelial cell hyperplasia were observed under microscopy. These findings indicated the presence of HEV in commercial livers of rabbits. Additional studies should be conducted to investigate the infectivity of rabbit HEV (rHEV) and the potential risks of zoonotic transmission of rHEV from rabbits to human beings.

Effects of larval extracts from identified Protaetia brevitarsis seulensis against benign prostatic hyperplasia induced by testosterone in rats.

Protaetia brevitarsis seulensis is an animal‐based medicine used traditionally in China, Japan, and Korea to treat hepatic disorders; it has been shown to possess various pharmacological effects such as antibacterial and antioxidant activities. In this study, we investigated the effects of P. brevitarsis on a testosterone‐induced benign prostatic hyperplasia (BPH) rat model. To establish the BPH model, the animals were administered a subcutaneous injection of testosterone daily for 28 days. P. brevitarsis was administered by oral gavage at doses of 12.5, 25, and 50 mg/kg for 28 days, along with testosterone injection. P. brevitarsis treatment markedly decreased the absolute and relative prostate weight of BPH animals. The levels of dihydrotestosterone was reduced in P. brevitarsis‐treated animals compared to those in the BPH animals. Histological analysis of the prostate showed that P. brevitarsis treatment effectively suppressed the testosterone‐induced hyperplasia of prostatic epithelial cells, which was accompanied by reductions in the PCNA and Ki‐67 expressions in prostatic tissues. These results indicate that P. brevitarsis effectively suppresses testosterone‐induced development of BPH, and thus, is a potential therapeutic agent for BPH.

Lethal dose and histopathological alterations induced by Aeromonas salmonicida in experimentally challenged common carp, Cyprinus carpio

Aeromonas salmonicida is the obligate pathogen of fishes having zoonotic potential. It is reported to cause considerable losses in world aquaculture. The current study has successfully demonstrated the induction of histopathological lesions in experimentally infected common carp. In the current study, the lethal concentration (LD50-96 h) of typical A. Salmonicida for common carp was found to be 1.5 × 107CFU mL−1. About 40% and 60% fish mortalities occurred after 72 h in the groups inoculated with 107 and 108 CFU mL−1 bacterial suspension, respectively. The fish challenged with A. salmonicida showed symptoms like abnormal swimming behaviour, lethargy, intra-abdominal fluid, haemorrhages on the ventral side of the body, vent and fins. The signs proceeded with the death of fish. In the histological sections, severe pathological alterations were reported in the tissue sections of internal organs. The microscopic observation showed sinusoidal and large blood vessel congestion in the liver, profuse haemorrhage, necrosis and infiltration of blood cells in the internal organs. The tubular architecture was lost with the infiltration of leucocytes in the kidney. In gills, more intense and prominent lamellar fusion was observed with leucocytic infiltration, telangiectasia and hyperplasia of lamellar epithelial cells. In summary, we have experimentally induced the typical A. salmonicida infection in common carp. The study will provide a research foundation for further studies on the host-pathogen interaction, therapeutics and epidemiology of A. salmonicida.

Histologic lesions of experimental infection with Lymantria dispar multicapsid nucleopolyhedrovirus and Lymantria dispar cytoplasmic polyhedrosis virus in European gypsy moth caterpillars (Lymantria dispar dispar).

European gypsy moths (Lymantria dispar dispar) are an invasive species in North America, and are listed by the International Union for the Conservation of Nature as one of the 100 most destructive invasive species worldwide. They have several known viruses, some of which are used as biological control agents. However, there are no detailed descriptions of many entomopathogenic viral infections, including in European gypsy moths, using bright-field microscopy. In this study, 11 European gypsy moth caterpillars were evaluated histologically: 4 were experimentally infected with Lymantria dispar multicapsid nucleopolyhedrovirus (LdMNPV; Baculoviridae); 4 were experimentally infected with Lymantria dispar cytoplasmic polyhedrosis virus (LdCPV; Reoviridae); 3 control animals were uninfected. A complete tissue set was evaluated in all animals from all groups using bright-field microscopy, including epidermis, cuticle, striated muscle, tracheae, foregut, midgut, hindgut, Malpighian tubules, hemocytes, fat body, and nervous system. LdMNPV-infected caterpillars had marked karyomegaly and intranuclear viral inclusions in cells of the epidermis, tracheae, fat body, and hemocytes. LdMNPV-infected caterpillars also had hyperplasia and hypertrophy of epidermal and tracheal epithelial cells. LdCPV-infected caterpillars had numerous granular eosinophilic intracytoplasmic viral inclusions in midgut epithelial cells. Both LdMNPV-infected and LdCPV-infected caterpillars had atrophy of fat body adipocytes; this change was more pronounced in LdCPV-infected caterpillars. This work provides the first detailed descriptions of these viral infections in European gypsy moth caterpillars using bright-field light microscopy and provides images of normal histology from control caterpillars.

Alteration of Histopathology in Recurrent Nasal Polyps

Objective: The objective of this study was to analyze the histopathologic changes in recurrent nasal polyps (NPs) in terms of tissue inflammatory cells infiltration and mucosal remodeling. Methods: Thirty-five patients with primary NPs requiring a revision surgery during follow-up and a matched control group of 35 primary NP patients without recurrence were retrospectively enrolled. Histopathologic examination was performed of tissue inflammatory cells, subepithelial edema, epithelial cell hyperplasia, basement membrane thickness, and fibrosis. Results: The mean eosinophil and neutrophil counts, proportions of eosinophil and neutrophil, as well as total inflammatory cell count were significantly higher in the recurrent group than those in the controls. Higher subepithelial edema was seen in the recurrent group. Within the recurrent group, the mean tissue eosinophil count and relative eosinophilia reduced from the first operation to revision surgery, whereas neutrophil count and proportion, and total inflammatory cell counts remained unchanged. Subepithelial edema and epithelial cell hyperplasia were significantly reduced after the first surgical procedure. Conclusion: NP recurrence is associated with higher inflammatory grade (especially in eosinophilia and neutrophilia). Surgical and corticoid treatments may have an impact on mucosal histopathologic changes but need further certification.

The Effect of Prepared Therapeutic Food Mixtures on the Intestinal Tissues of Malnourished Rats

The current study was conducted in the laboratories of the College of Agriculture and Animal House of the College of Veterinary Medicine at Tikrit University for the period from 5/5/2020 to 29/10/2020. And it aimed to produce therapeutic food mixtures to treat people with malnutrition and to know their impact on the health of the small intestine and large intestine. Where three ready-to-use therapeutic food mixtures have been prepared (do not need to be prepared or cooked before eating) consisting of milk, sprouted oats, non-sprouted oats, Sesame, Rice, chickpeas, Dates, bananas, apples, potatoes and oil, provided that the moisture and fat content does not exceed 2.5% and 32%, the percentage of protein and carbohydrates is not less than 14% and 40% respectively, and they were given to Thirty healthy rats and divided into six groups equally, a control group (+) natural, control group (-) (malnourished for a period of time 48 days), 1st, 2nd, 3d and 4th. The studied groups were affected with malnutrition for a period of 24 days, then the first food mixture was given to the 1st, the second food mixture for the 2nd, the third food mixture for 3d, the standard food mixture F-100 for the 4th. After 24 days of consuming the prepared nutritional mixtures, the tissues of the small and large intestine were examined under a microscope. The histological analysis of the small intestine showed that the 1st and the 2nd gave completely healthy tissues to the small intestine similar to the control group (+) and the 4th, while the 3d showed congestion in the blood vessels with hyperplasia of intestinal epithelial cells compared to the control group (-) which showed High-intensity cellular degeneration in the lining cells of the intestine with chronic and acute inflammations. As for the large intestine, the 1st gave a complete recovery of colon tissue, similar to the control group (+) and the 4th, while the 2nd and 3d showed pathological changes that included infiltration and local grouping of inflammatory cells in the submucosal layer of the colon and flattening of the villi and their union with acute inflammation compared to a control group (- ), Which showed pathological changes represented by infiltration of inflammatory cells with an overgrowth of mesenteric lymph tissue and multiple lymph sacs. It was found that the first nutritional mixture prepared on which the 1st of rats fed give similar results to the results of the control group (+) and the 4th

Attenuation of hyperplasia in lung parenchymal and colonic epithelial cells in DMBA-induced cancer by administering Andrographis paniculata Nees extract using animal model.

This study was designed to evaluate the potential of Andrographis paniculata ethanolic extract to inhibit the increase in proliferation and induction of abnormal cell death. The hyperplasia stage as an early stage of cancer development was induced by oral administration of 20mg/Kg BW DMBA to SD rats twice a week for 5weeks. There were five groups in this study include negative control, positive control, and treatment groups of DMBA induction followed by administration of A.paniculata ethanolic extract in doses equivalent to 10, 30 or 100mg/Kg BW andrographolide once per day for 6 consecutive weeks. On the last day, rats were sacrificed, lung and colon tissues were collected. Histological examination by HE staining and immunohistochemistry using p53, telomerase, and caspase-3 antibodies were aimed at observing hyperplasia state in these tissues. DMBA induction to SD rats was able to produce hyperplasia in lung parenchymal and colon epithelial tissue. This can be showed by the increasing number of proliferated cells and as indicated by the number of brown-colored nuclei with sharper intensity. As well telomerase appears to be overexpressed strongly, while p53 and caspase-3 show low intensity. The administration of A.paniculata extract for 6weeks showed a decrease in the number of cells that actively proliferate, a decrease in telomerase activity, and an increase in caspase-3 levels which indicate cellular death activity. A.paniculata ethanolic extract can inhibit the development of cancer at the hyperplasia stage by reducing telomerase activity and increasing apoptosis, marked by an increase of caspase-3 expressions.

FC 038CRESCENTS DERIVE FROM SINGLE PODOCYTE PROGENITORS AND A DRUG ENHANCING THEIR DIFFERENTIATION ATTENUATES RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

Abstract Background and Aims Rapidly progressive glomerulonephritis (RPGN) encompasses a group of diverse disorders characterized by the presence of massive hyperplasia of parietal epithelial cells (PEC) as the main histopathological lesion at kidney biopsy. It is associated with a rapid decline in kidney function referred to altogether as rapidly progressive glomerulonephritis. Typically, crescent formation is the consequence of diverse upstream pathomechanisms involving the specific activation of PEC. PEC normally reside peacefully along Bowman capsule and represent in part renal progenitor cells (RPC). Previous studies observed RPC markers in crescents from patients with different types of glomerulonephritis. Similarities between stem cell niches of bone marrow and kidney, prompted us to hypothesized that crescents result from monoclonal expansion of a single RPC clone conceptually similar to monoclonal diseases originating from hematopoietic stem cells. According to this analogy, we further hypothesized that drugs known to cure monoclonal disease of the hematopoietic stem cells by enforcing their terminal differentiation could also attenuate crescentic glomerulonephritis. Method To address this hypothesis, we established a RPGN disease model in a conditional transgenic mouse based on the mT/mG and the Confetti reporter that allows lineage tracing and clonal analysis of RPCs. Animals were treated with known pharmacological inhibitors of clonal stem cell proliferation in myeloproliferative disorders. Crescentic lesions were characterized by super-resolution STED microscopy. Finally, we employed single cell RNA sequencing of human renal progenitor cultures to identify the immature progenitor subset-generating crescent in human to identify putative new biomarker(s) of RPNG to validate in biopsy of patients. Results We observed that the crescentic lesions originated from the clonal expansion of single RPC, thus suggesting a clonal stem cell disorder. Therefore, we administrated a series of drugs known to ameliorates myeloproliferative neoplasms to our RPGN mouse model as potential therapeutic agents. In particular, treatment with one of the compounds induced a reduction in both proteinuria and crescent formation. 3D confocal microscopy and STED super-resolution imaging of glomeruli showed that this compound turned the uncontrolled hyperplasia of a specific immature PEC subset into a controlled differentiation into new podocytes thereby restoring the injured glomerular filtration barrier. Single cell RNA sequencing of human renal progenitor cultures identified a new marker of the crescent-generating progenitor cells. Expression of this marker in biopsies of patients with rapidly progressive glomerulonephritis associated with progression toward end stage kidney disease. Treatment of human PEC with the drug that in in vivo experiments showed a therapeutic effect on RPGN reduced proliferation of the immature progenitor subset promoting their differentiation into podocytes. Conclusion These results demonstrate that glomerular hyperplastic lesions derive from clonal amplification of a RPC subset and that shifting proliferation to podocyte differentiation reverses crescent formation and improves clinical outcome.

Histopathological alterations caused by monogenean parasites the gills of tambaqui Colossoma macropomum (Serrasalmidae)

Monogeneans are ectoparasites of fish with a global distribution. In farmed fish, high infestations may result in morbidity and mortality. This study investigated the histopathological effects of three species of monogeneans Anacanthorus spathulatus, Notozothecium janauachensis and Mymarothecium boegeri on the gills of farmed Colossoma macropomum. Parasitological indices revealed a prevalence of 100%, and a mean abundance of 81.3 ± 11.8. This infection caused displacement of the gill epithelium, focal hyperplasia of epithelial cells, lamellar fusion, congestion and shortening of the secondary lamellae of gills, in addition a complete fusion of the secondary lamellae. However, these tissue alterations were reversible and punctually located lesions, which may not compromise the normal functioning of gills. Lastly, this study showed the potential damages caused by parasite monogeneans to gills of infested fish, thus sanitary management is essential for the growth of fish farm of C. macropomum.

Diseases Caused by Amoebae in Fish: An Overview.

Simple SummaryAmoebae can be found in many different aquatic environments and are also an emerging risk for fish health. Amoebae can display different types of relationships with fish, some of them (amoeba acting as commensals) do not harm fish. However, in many cases they can act as parasites and can be the cause of severe diseases affecting mainly the gills and also causing relevant systemic infections.Parasitic and amphizoic amoebae are ubiquitous and can affect a huge variety of hosts, from invertebrates to humans, and fish are not an exception. Most of the relationships between amoebae and fish are based on four different types: ectocommensals, ectoparasites, endocommensals and endoparasites, although the lines between them are not always clear. As ectocommensals, they are located specially on the gills and particularly the amphizoic Neoparamoeba perurans is the most relevant species, being a real pathogenic parasite in farmed salmon. It causes amoebic gill disease, which causes a progressive hyperplasia of epithelial cells in the gill filaments and lamellae. Nodular gill disease is its analogue in freshwater fish but the causative agent is still not clear, although several amoebae have been identified associated to the lesions. Other species have been described in different fish species, affecting not only gills but also other organs, even internal ones. In some cases, species of the genera Naegleria or Acanthamoeba, which also contain pathogenic species affecting humans, are usually described affecting freshwater fish species. As endocommensals, Entamoebae species have been described in the digestive tract of freshwater and marine fish species, but Endolimax nana can reach other organs and cause systemic infections in farmed Solea senegalensis. Other systemic infections caused by amoebae are usually described in wild fish, although in most cases these are isolated cases without clinical signs or significance.

Prenatal polycyclic aromatic hydrocarbons, altered ERα pathway-related methylation and expression, and mammary epithelial cell proliferation in offspring and grandoffspring adult mice

BackgroundAirborne polycyclic aromatic hydrocarbons (PAH) possess carcinogenic and endocrine disrupting properties linked to mammary tumorigenesis. These effects may be initiated during a prenatal period of susceptibility to PAH activation of the aryl hydrocarbon receptor (Ahr) and through downstream effects on estrogen receptor (Er) α. PurposeWe hypothesized prenatal airborne PAH exposure induces sustained effects in female adult wild type BALB/cByj mice detected in the offspring (F1) and grandoffspring (F2) generation. We hypothesized these effects would include altered expression and epigenetic regulation of Erα and altered expression of aryl hydrocarbon receptor repressor (Ahrr, Ahrr/aryl hydrocarbon receptor nuclear translocator (Arnt), and breast cancer type 1 susceptibility (Brca1). Further, we hypothesized that PAH would induce precancerous outcomes such as epithelial cell proliferation and epithelial cell hyperplasia in mammary glands of adult female offspring and grandoffspring. ResultsPrenatal ambient PAH exposure lowered Erα mRNA expression (F1 and F2: p<0.001 for each) and induced methylation in the Erα promoter in mammary tissue in offspring and grandoffspring mice on postnatal day (PND) 60. Prenatal PAH lowered Brca1 mRNA (F1: p=0.002, F2: p=0.02); Erα mRNA was correlated with Brca1 (F1: r=0.42, p=0.02; F2: r=0.53, p=0.005). Prenatal PAH lowered Ahrr (F1: p=0.03, F2: p=0.009) and raised Arnt mRNA expression (F1: p=0.01, F2: p=0.03). Alterations in Erα mRNA (F2: p<0.0001) and Ahrr (F2: p=0.02) in the grandoffspring mice also occured by PND 28, and similarly occurred in the dam on postpartum day (PPD) 28. Finally, prenatal PAH was associated with higher mammary epithelial cell proliferation in the offspring (p=0.02), but not grandoffspring mice, without differences in the frequency of mammary cell hyperplasia. These results did not differ after adjustment by each candidate gene expression level. ConclusionsPrenatal PAH exposure induces DNA methylation and alters gene expression in the Erα-mediated pathway across generations, and suggests that functional outcomes such as mammary cell proliferation also may occur in offspring as a result.

Rapamycin alleviates renal damage in mice with systemic lupus erythematosus through improving immune response and function

This study aimed to explore the therapeutic effect and mechanism of rapamycin (RAPA) on systemic lupus erythematosus (SLE) in BALB/C mice induced by pristane. The mice were randomly divided into 5 groups (n = 6): control, model, saline, RAPA (1 mg/kg) and RAPA (2 mg/kg). All groups were injected with pristane except control. HE staining revealed 1 mg/kg and 2 mg/kg RAPA treatments obviously alleviated pathological changes in the kidney of SLE mice such as glomeruli enlargement, hyperplasia of mesangial cells, epithelial and endothelial cells, infiltration of inflammatory cells, and edema-like degeneration of renal tubules. Compared with control group, body weights and anti-ribosomal P-protein antibody (ARPA) level of the mice in model group and saline group decreased (P < 0.05), while immune complex deposition and levels of anti-dsDNA antibody, anti-smRNP antibody and urine protein in model group and saline group increased (P < 0.05). However, compared with model group and saline group, body weights of the mice in RAPA (1 mg/kg) group and RAPA (2 mg/kg) group increased (P < 0.05), while immune complex deposition and levels of anti-dsDNA antibody, anti-smRNP antibody, ARPA, and urine protein in RAPA (1 mg/kg) group and RAPA (2 mg/kg) group decreased (P < 0.05). Compared with control group, the proportion of dentritic cells (DC) in the kidney and peripheral blood decreased while the proportion of Th1, Th2 and Th17 cells in the spleen, kidney and peripheral blood increased in model group and saline group (P < 0.05). Compared with model group and saline group, 1 mg/kg and 2 mg/kg RAPA treatments boosted the proportion of DC in the kidney and peripheral blood, reduced the proportion of Th1 and Th17 cells in the spleen, kidney and peripheral blood, and lessened the proportion of Th2 cells in the kidney and peripheral blood (P < 0.05). In conclusion, RAPA alleviated renal damage in SLE mice through improving immune response and function.