Voltage-gated potassium (Kv) channels are known to be involved in cancer development and cancer cell proliferation. KV9.3, an electronically silent subunit, forms heterotetramers with KV2.1 in excitable cells and modulates its electrophysiological properties. However, the role of KV9.3 alone in non-excitable cancer cells has not been studied. Here, we evaluated the effect of silencing KV9.3 on cancer cell proliferation in HCT15 colon carcinoma cells and A549 lung adenocarcinoma cells. We confirmed the expression of KV9.3 mRNA in HCT15 and A549 cells and showed that silencing KV9.3 using small interfering RNA caused G0/G1 cell cycle arrest and alterations in cell cycle regulatory proteins in both HCT15 and A549 cells without affecting apoptosis. Also, stable knockdown of KV9.3 expression using short-hairpin RNA inhibited tumor growth in SCID mouse xenograft model. Using a bioinformatics approach, we identified Sp1 binding sites in the promoter region of the gene encoding KV9.3. We further found that Sp1 bound to this region and showed that the Sp1 inhibitor, mithramycin A, induced a concentration-dependent decrease in KV9.3 expression. Taken together, these data suggest that knockdown of KV9.3 inhibits proliferation in colon carcinoma and lung adenocarcinoma cell lines and may be regulated by Sp1.
Feline infectious peritonitis (FIP) virus is the most common infectious cause of uveitis in cats. Confirmatory diagnosis is usually only reached at postmortem examination. The relationship between the histologic inflammatory pattern, which depends on the stage of the disease, and the likelihood of detection of the viral antigen and/or RNA has not been investigated. We hypothesized that viral detection rate by either immunohistochemistry, in situ hybridization or RT-qPCR is dependent upon the predominant type of uveal inflammatory response (i.e., pyogranulomatous vs. plasmacytic). Thus, the aims of this study were to evaluate cases of FIP-induced uveitis, localize the viral antigen and RNA, and assess the relationship between the inflammatory pattern (macrophage- vs. plasma cell-rich) and the likelihood of detecting the FIP antigen and/or RNA. We evaluated 30 cats with FIP-induced uveitis. The viral antigen and/or RNA were detected within uveal macrophages in 11/30 cases, of which 8 tested positive by RT-qPCR. Correlation analysis determined a weak to moderate but significant negative correlation between the degree of plasmacytic uveal inflammation and the likelihood of detecting the FIP antigen and RNA. This study suggests that predominance of plasmacytic inflammation in cases of FIP uveitis reduces the odds of a confirmatory diagnosis through the viral detection methods available.
Reptiles are highly susceptible to anthropogenic activities as a result of their narrow geographical ranges and habitat specialization, making them a conservation concern. Geckos represent one of the mega-diverse reptile lineages under pressure; however, limited assisted reproductive technologies currently exist for these animals. Exogenous pregnant mare serum gonadotropin (PMSG) has been found to exhibit follicle stimulating hormone-like action and has been routinely used to alter reproductive hormones of vertebrates in assisted reproductive protocols. The purpose of this study was to determine the effects of serial injections of 20 IU and 50 IU PMSG on circulating testosterone concentrations, testicular dynamics, and semen production in a model species of gecko. Twenty-four captive-bred, adult, male leopard geckos (Eublepharis macularius) were divided into three treatment groups and administered a once-weekly injection of either PMSG or saline for a total of nine weeks. Ultrasonographic testicular measurements, electrostimulation for semen collection, and venipuncture were performed on days 0, 21, 42, and 63. Right unilateral orchidectomies and epididymectomies were performed in all animals on day 63; tissues were submitted for histopathology. PMSG treated geckos had significantly higher testicular volumes and weights, spermatozoa motility, and spermatozoa concentrations compared with controls. However, there were no significant differences in testosterone concentrations by treatment or time. Under the conditions outlined, PMSG is effective at stimulating spermatogenesis and increasing testicular size, but not effective at increasing testosterone concentrations in the leopard gecko between October–December in the Northern hemisphere.
20 August 2024 in Journal of Veterinary Diagnostic Investigation
Here we describe a case of fatal amebic gastritis associated with Naegleria australiensis infection in an 11-mo-old Linnaeus’s two-toed sloth ( Choloepus didactylus). The sloth had a history of weight loss and intermittent diarrhea for 18 d, and subsequently died despite empirical treatment. Postmortem findings included emaciation, gastric dilation with fluid content, and fibrinonecrotic gastritis with intralesional amebic trophozoites and cysts in the glandular region of the fundus. Transmission electron microscopy ruled out Amoebozoa of the family Entamoebidae based on the presence of mitochondria in the amoeboid organisms. PCR for pan–free-living amebae followed by next-generation sequencing of the PCR product revealed 99% identity with Naegleria australiensis. Gastric amebiasis has been reported sporadically in macropods and in leaf-eating monkeys with a sacculated stomach. To our knowledge, gastric amebiasis has not been reported previously in a sloth, which also has a sacculated and multi-chambered stomach.
1 November 2024 in Journal of the American Veterinary Medical Association
"Persistently elevated liver enzymes and bile acids, icterus, and weight loss in a 1.5-year-old Thoroughbred colt" published on 14 Aug 2024 by American Veterinary Medical Association.
4 September 2024 in Journal of Veterinary Diagnostic Investigation
An 18-y-old American Saddlebred mare was admitted with fever and acute onset of neurologic signs including grade 3 of 5 ataxia, difficulty in prehension, and dull mentation. Because of financial restraints, desired testing could not be performed; the horse’s condition declined despite supportive treatment, and euthanasia was elected. Postmortem examination revealed petechiae and ecchymoses in the meninges and neuroparenchyma of the encephalon. Blast-like neoplastic round cells were identified within the vasculature and areas of hemorrhage in the neuroparenchyma, the intestinal submucosa, and other organs, including the liver, kidney, lung, and mesenteric lymph node. Necrotizing enterocolitis and acute fibrinonecrotizing bacterial pneumonia were also noted. Of the atypical round cells in the encephalon, >70% expressed ionized calcium–binding adapter molecule 1 (Iba1), 10–20% expressed myeloperoxidase (MPO), and <10% expressed PAX5, CD3, CD20, CD79a, or MUM1. The bone marrow was diffusely effaced by neoplastic round cells expressing Iba1, and ~70% of these cells expressed MPO with no expression of CD3 or CD20. CD172a also immunolabeled a portion of the neoplastic cells. These findings were consistent with the diagnosis of acute myeloid leukemia-M1 with an unusual neurologic presentation.