Epigenetically regulated gene expression profiles reveal four molecular subtypes with prognostic and therapeutic implications in colorectal cancer

Transcriptomic deregulation by epigenetic mechanisms plays a crucial role in the heterogeneous progression of colorectal cancer (CRC). Herein, we first demonstrated that the frequencies of the aberrancies of DNA methylation-correlated (METcor) and microRNA (miRNA)-correlated (MIRcor) genes were significantly co-regulated. Next, through integrative clustering of the expression profiles of METcor and MIRcor genes, four molecular subtypes were identified in CRC patients from The Cancer Genome Atlas and then validated in four independent datasets. More importantly, the four subtypes were well characterized and showed distinct clinical and molecular features: (i) S-I: high metabolic activity, sensitive to 5-fluorouracil-based chemotherapy and good prognosis; (ii) S-II: moderate metabolic activity, marked proliferation, frequent KRAS mutation and intermediate prognosis; (iii) S-III: moderate metabolic activity, marked proliferation, promoter DNA hypermethylation, high mutation burden, frequent BRAF and EGFR mutations, moderate levels of epithelial-mesenchymal transition (EMT) and transforming growth factor β (TGFβ) signals, immune-inflamed phenotype, sensitive to cetuximab and death protein-1 inhibitor treatment and relatively poor prognosis and (iv) S-IV: miRNA overexpression, stem/serrated/mesenchymal-like properties, hypoxia, high levels of EMT and TGFβ signals, immune-excluded phenotype and poor prognosis. Overall, this study established a molecular classification based on epigenetically regulated gene expression profiles, thereby providing a better understanding of the epigenetic mechanisms underlying CRC heterogeneity.

Proliferative enteropathy caused by Lawsonia intracellularis in rabbits in Southern Brazil

Proliferative enteropathy (PE), also known as ileitis, is a disease caused by the bacterium Lawsonia intracellularis. This disease is characterized by diarrhea and ill-thrift. The aim of this study is to describe a PE outbreak in rabbits that occurred in Southern Brazil. The farm had 700 rabbits at the time the outbreak occurred. The clinical signs were severe diarrhea, dehydration, and apathy. Necropsy was performed in 33 rabbits, and the most evident macroscopic findings were thickening of the intestinal wall, intestinal loops distended by large amounts of gas, and liquid feces. Histopathological examination demonstrated a marked proliferation of enterocytes in intestinal crypts, decrease number of goblet cells, and crypts microabscesses. Silver impregnation technique (Warthin-Starry) demonstrated in intestinal crypts inside of enterocytes cytoplasm, curved vibrioid bacteria compatible with L. intracellularis. Immunohistochemical staining with anti-L. intracellularis confirmed the agent presence. PCR was performed and L. intracellularis was confirmed as the etiological agent.

Cutaneous vascular hamartoma in a lamb

A male Polwarth lamb with a good body score was born with a pendulous, oval, red mass adhering to the skin in the left ventrolateral thoracic area. The nodule was removed when the lamb was five days old and sent for a gross and histopathological evaluation. Macroscopically, the mass was reddish, slightly oval and flat, well delineated, and contained a central ulcerated area. Microscopically, it showed a marked proliferation of well-differentiated endothelial cells with the formation of new blood vessels. An immunohistochemical analysis showed mild cytoplasmic immunostaining for the von Willebrand Factor in the endothelial cells. To the best of our knowledge, this is the first report of a cutaneous vascular hamartoma in a sheep.

Nanofat 2.0: Experimental Evidence for a Fat Grafting Rich in Mesenchymal Stem Cells

Different strategies have been developed in the last decade to obtain fat grafts as rich as possible of mesenchymal stem cells, so exploiting their regenerative potential. Recently, a new kind of fat grafting, called “nanofat”, has been obtained after several steps of fat emulsification and filtration. The final liquid suspension, virtually devoid of mature adipocytes, would improve tissue repair because of the presence of adipose mesenchymal stem cells (ASCs). However, since it is probable that many ASCs may be lost in the numerous phases of this procedure, we describe here a novel version of fat grafting, which we call “nanofat 2.0”, likely richer in ASCs, obtained avoiding the final phases of the nanofat protocol. The viability, the density and proliferation rate of ASCs in nanofat 2.0 sample were compared with samples of nanofat and simple lipoaspirate. Although the density of ASCs was initially higher in lipoaspirate sample, the higher proliferation rate of cells in nanofat 2.0 virtually filled the gap within 8 days. By contrast, the density of ASCs in nanofat sample was the poorest at any time. Results show that nanofat 2.0 emulsion is considerably rich in stem cells, featuring a marked proliferation capability.

Gastric Intussusceptions in a Red Corn Snake (Pantherophis guttatus) Associated with Cryptosporidiosis

A 3-year-old female red corn snake (Pantherophis guttatus) was presented for a three-week history of anorexia and decreased defecations. On physical examination, a soft midbody intracoelomic swelling was palpated. Transcutaneous coelomic ultrasound revealed a target-like mass on a transverse section of the stomach, suggesting the presence of a gastrointestinal intussusception. On exploratory coeliotomy, a double compounded esophagogastric and gastroduodenal intussusception was diagnosed and reduced surgically. A gastropexy was also performed to prevent recurrence. On histopathology, the gastric glandular mucosa showed moderate to marked proliferation. Diffusely lining the luminal surface of glandular epithelium and free within the lumen were a myriad of protozoa consistent with Cryptosporidium sp. A diagnosis of chronic proliferative gastritis due to Cryptosporidium sp. was made based on these findings. Intussusceptions are rare in reptiles and are infrequently reported in snakes. This is the first report of a double compounded intussusception in a nonmammalian species and the first report of an intussusception involving the stomach in a snake with gastritis due to Cryptosporidium sp.

First description of hypospadias and inguinal bilateral cryptorchidism in mouflon (Ovis Gmelini Musimon) — short communication

A mouflon showing severe weight loss and cachexia was examined. The animal had horns and a male-like body frame but the preputial fur was missing. The scrotum was completely absent. Both testicles were located next to the inguinal canal under the skin, and appeared only slightly smaller than normal. The prepuce was located in a perianal position under the anus and it resembled a vulva. The penis was underdeveloped and curled up inside the prepuce like an enlarged clitoris. The bulbourethral region and the urinary bladder looked normal. The orifice of the urethra was located in its normal position, but the glans penis appeared deformed. Microscopic examination of the testicles revealed mild degeneration of the seminiferous tubules and a marked proliferation of the interstitial connective tissue with Leydig cells still present. There were no marked changes in the bulbar part of the penis but the apical part exhibited marked interstitial fibrosis. This is the first description of hypospadias and cryptorchidism in mouflon.

The Mitigating Effect ofCitrullus colocynthis(L.) Fruit Extract against Genotoxicity Induced by Cyclophosphamide in Mice Bone Marrow Cells

Possible genoprotective effect ofCitrullus colocynthis(L.) (CCT) fruits extract against cyclophosphamide- (CP-)induced DNA damage in mice bone marrow cells was evaluated using micronucleus assay, as an index of induced chromosomal damage. Mice were preadministered with different doses of CCT via intraperitoneal injection for 7 consecutive days followed by injection with CP (70 mg/kg b.w.) 1 hr after the last injection of CCT. After 24 hr, mice were scarified to evaluate the frequency of micronucleated polychromatic erythrocytes (MnPCEs). In addition, the number of polychromatic erythrocytes (PCEs) among 1000 normochromatic erythrocytes (NCEs) per animal was recorded to evaluate bone marrow. Pretreatment with CCT significantly reduced the number of MnPCEs induced by CP in bone marrow cells (P<0.0001). At 200 mg/kg, CCT had a maximum chemoprotective effect and reduced the number of MnPCEs by 6.37-fold and completely normalized the mitotic activity. CCT also led to marked proliferation and hypercellularity of immature myeloid elements after mice were treated with CP and mitigated the bone marrow suppression. Our study revealed that CCT has an antigenotoxic effect against CP-induced oxidative DNA damage in mice. Therefore, it could be used concomitantly as a supplement to protect people undergoing chemotherapy.

Immunosuppressive Action of Deoxynivalenol of Thymus in Chickens

Deoxynivalenol (DON, vomitoxin) is a type B-trichothecene, naturally occurring contaminants of animal feed, being implicated in several mycotoxicoses in farm livestock. This mycotoxin occurs predominantly in grains such as wheat, barley, oats, rye, and maize, and less often in rice, sorghum, and triticale. Deoxynivalenol is potent nefrotoxic, hepatotoxic and immunosuppressant. High doses of trichothecenes promote rapid onset of leukocyte apoptosis (programmed cell death), which is manifested as immunosuppression. The study aimed to prove the immunosuppressant action of deoxynivalenol in chickens experimentally treated each day, from the 7th day of life, using 5,4 mg/kg b.w in E group for 28 days (since 35 days of life). Histopathology studies of thymus were made on 7th, 14th, 21st and 28th days of experiment. In E group small lesions of thymus were observed even after 7th day of poisoning but intense lesions, hydropic degeneration, necrotic foci and moderate lymphoid depletion was observed after the 14th and 21st day of poisoning. After 28th day a marked proliferation of stromal cells in the reticulum network, in medulla zone, presence of mucous cells, small mucous cysts and haemorages were observed.