Viridian Therapeutics, Inc.’s Post

#Cover: KLF15 deficiency promotes white-to-beige adipocyte conversion: https://buff.ly/4eGCHWD Li et al. report that KLF15 is required for maintenance of white adipocyte properties in subcutaneous fat depots and is a potential therapeutic target for obesity and associated diseases. #Image: multilocular beige adipocytes in a subcutaneous depot of a Klf15-deficient mouse; #Credit: Liang Li. Authors: Liang Li and Brian J. Feldman #CellBiology #Endocrinology

vtx:think This is the cytology from the pleural fluid of a 14 year old male neutered domestic shorthaired cat (presented for dyspnoea). A mediastinal mass was detected on CT scan. There are moderate to high numbers of intermediate to large lymphocytes present (when compared to neutrophils) (Image 1). These cells have a small amount of blue cytoplasm which often contains small round discrete clear vacuoles. Nuclei are eccentric, round to circumferentially convoluted with coarse to coarsely stippled chromatin and often one to two central or peripheral small to intermediate round to oval prominent nucleoli (Image 2). Moderate to high numbers of mitotic figures are seen, with frequent asymmetrical and multipolar examples (Image 3). These preparations are most consistent with lymphoma which is most likely high grade given the mitotic index. If you wanted to confirm this diagnosis, what other tests could you ask the lab to run on this fluid? ⁠ Our latest online tutored course will take an in depth look into feline medicine with Steph Sorrel (Feline Medicine Specialist). The course starts Monday 21st August 2023. BOOK YOUR PLACE /https://lnkd.in/eh3zcUxe We look forward to seeing you there! ⁠ ⁠ #vtx #vtx_cpd #veterinarycpd #veterinarycourses

Today is Rare Disease Day 📅 To mark this important occasion, we’re highlighting key aspects of clinical care for Cushing's syndrome. Tune in to examine the diagnostic delay associated with this rare condition and explore the critical role of screening in cases of suspected hypercortisolemia. Join Drs. Martin Reincke and Maria Fleseriu as they discuss practical diagnostic tools and key considerations for specialist referrals: https://ow.ly/7msW50QJnlt #CushingsDisease #RareDiseaseDay #Endocrinology #MedEd #Endocrinologist

Indian Journal of Animal Research Published Volume 58 Issue 3 (MARCH 2024) Effects of Concomitant Use of N-acetylcysteine and Cyclosporine A on Acetaminophen-induced Acute Kidney Injury in Mice Gonca Ozan Kocamüftüoğlu, Nalan Kaya Tektemur, Elif Erdem Güzel, Ahmet Tektemur, İbrahim Enver Ozan doi: 10.18805/IJAR.BF-1736 Cite article:- Kocamüftüoğlu Ozan Gonca, Tektemur Kaya Nalan, Güzel Erdem Elif, Tektemur Ahmet, Ozan Enver İbrahim (2024). Effects of Concomitant Use of N-acetylcysteine and Cyclosporine A on Acetaminophen-induced Acute Kidney Injury in Mice . Indian Journal of Animal Research. 58(3): 459-469. doi: 10.18805/IJAR.BF-1736. ABSTRACT Background: Acetaminophen (APAP), a commonly used analgesic, causes acute kidney injury (AKI) in overdose although it is rare. Mitochondrial dysfunction plays a major role in the pathophysiology of renal damage, although the exact molecular mechanism is unknown. This study aimed to evaluate the potential therapeutic effect of cyclosporin A (CsA), a mitochondrial membrane permeability transition pore (MPTP) inhibitor, with N-acetylcysteine (NAC) in APAP-induced AKI. Methods: Male BALB/c mice were divided into control, APAP, APAP+NAC, APAP+CsA and APAP+NAC+CsA groups (n=6). A single dose of APAP (400 mg/kg) was administered intraperitoneally. All other treatments (1200 mg/kg NAC, 50 mg/kg CsA) were performed intraperitoneally 3 h after APAP administration. All animals were decapitated and blood samples and kidney tissue samples were collected for evaluation. Serum creatinine (Cr) and blood urea nitrogen (BUN) levels were measured. The kidney tissue 8-hydroxy-deoxyguanosine (8-OHdG), cytochrome c (Cytc) and 3-nitrotyrosine (3-NT) levels and cytochrome c (Cytc) expressions were determined. Result: Increased Cr and BUN levels, histopathological examinations and expressions of 8-OHdG, 3-NT and Cytc were detected in the APAP group. Combined NAC+CsA treatment sufficiently reversed oxidative stress, serum Cr and BUN levels and histopathological alterations induced by APAP. Moreover, cytc levels and renal tubular injury were remarkably reduced by combined drug treatment compared to the APAP+NAC group. These data suggest that the therapeutic effect of combined NAC+CsA treatment in mice with APAP-induced nephrotoxicity can be related to the combination of the antioxidant effect of NAC and the mitochondrial MPTP inhibitor effect of CsA. KEYWORDS 3-Nitrotyrosine, 8-Hydroxy-Deoxyguanosine, Combined Drug Treatment, Cytochrome C, Mitochondrial Dysfunction, Nephrotoxicity https://lnkd.in/gUteEBe2

This company plans to transplant gene-edited pig hearts into babies next year: eGenesis has started transplanting gene-edited pigs’ hearts into infant baboons—and humans may be next. The baby baboon is wearing a mesh gown and appears to be sitting upright. “This little lady … looks pretty philosophical, I would say,” says Eli Katz, who is showing me the image over a Zoom call. This baboon is the first to receive a heart transplant from a young gene-edited pig as part of a study that should pave the way for similar transplants in human babies, says Katz, chief medical officer at the biotech company eGenesis. The company, based in Cambridge, Massachusetts, has developed a technique that uses the gene-editing tool #crisprcas9 to make around 70 edits to a pig’s genome. These edits should allow the organs to be successfully transplanted into people, the team says. As soon as next year, eGenesis hopes to transplant pig hearts into babies with serious heart defects. The goal is to buy them more time to wait for a human heart. Before that happens, the team at eGenesis will practice on 12 infant baboons. Two such surgeries have been performed so far. Neither animal survived beyond a matter of days. Editing risk: Over 100,000 people in the US alone are waiting for an organ transplant. Every day, around 17 of them die. Researchers are exploring multiple options, including the possibility of bioprinting organs or growing new ones inside people’s bodies. Transplanting animal organs is another potential alternative to help meet the need. https://lnkd.in/ddsAvspZ #pig #transplant #animal #organs

Japanese squirrels develop human hereditary diseases with ageing: Research - https://lnkd.in/g9xHV-7K , August 18 (ANI): A team led by Dr Tomoaki Murakami of the Tokyo University of Agriculture and Technology discovered that fibrinogen A-chain amyloidosis, a previously unknown disease in animals other than humans, is common in Japanese squirrels (Sciurus lis). They compared the pathology of Japanese squirrels to that of humans in this work, and they emphasised the importance of Japanese squirrels in the comparative pathological investigation of fibrinogen A-chain amyloidosis. The researchers published their results on August 8th in the Journal of Pathology. Amyloidosis is a disease group in which amyloid, generated by misfolding of host proteins, deposits in several organs. Fibrinogen Aalpha;-chain amyloidosis is an inherited disorder in which fibrinogen Aalpha;-chain, a protein involved in blood coagulation, becomes amyloid and deposits in the renal glomeruli, resulting in renal failure. The disease was first reported in 1993, but a definitive treatment has not been established due to the small number of patients and many unknowns about the pathogenesis. In this study, they found that fibrinogen Aalpha;-chain amyloidosis occurs extremely frequently in Japanese squirrels, and compared the pathogenesis of this disease with that in humans. The research team first conducted histopathological analysis on the whole body organs of a total of 38 captive Japanese squirrels that died at five zoos in Japan between 2018 and 2022, and found that 29 cases (76.3%) had suffered systemic amyloidosis characterized by severe glomerular amyloid deposition. "I was amazed because it is rare to see such a high incidence of amyloidosis in one animal species," said Susumu Iwaide, the first author and a graduate student in Laboratory of Veterinary Toxicology at TUAT. They performed mass spectrometry-based proteomic analysis and immunohistochemistry, and identified fibrinogen Aalpha;-chain as a precursor protein. "Interestingly, amyloid exclusively deposited in the glomeruli but not in the tubulointerstitium in the affected kidney, which is same as the human condition," said Iwaide. Further analysis using mass spectrometry found that approximately 100 amino acids in the C-terminal region of the fibrinogen Aalpha;-chain accumulate in amyloid deposits, which coincides with human disease. Gene analysis revealed no mutations in the amyloid-forming region between amyloidosis-affected and non-affected squirrels. Statistically, there was a significant association between the development of amyloidosis and aging. In addition, some affected individuals were close descendants of wild-protected squirrels. "We concluded that the reduced genetic diversity due to breeding in the zoo does not cause fibrinogen Aalpha;-chain amyloidosis in Japanese squirrels, but an age-related disease inherent to th

🔬At Connected-Pathology, we frequently evaluate high volumes of samples from preclinical efficacy studies in various animal models of diseases. In this post, we share an example of histopathology analyses performed in a mouse model of kidney disease. 🔬 #AutosomalDominantPolycysticKidneyDisease (ADPKD) is the most common single-gene disorder and the most prevalent progressive kidney disorder. The kidneys of PKD patients are affected by fluid-filled cyst formation and growth, ultimately resulting in kidney failure. The efficacy of novel therapies to slow down cyst growth is typically investigated in mouse models. 🔬 On the tissue level, growth of fluid-filled cysts in the diseased kidneys can be confirmed by simple H&E staining. As seen in the images below, compared to healthy mice (first image), kidneys of ADPKD mice (second image) are marked by kidney parenchyma severely occupied by cysts. Following treatment (third image), cysts (marked by arrows) are significantly smaller and have lower distribution throughout the kidney. 🔬 Based on the H&E stainings, quantitative measurements, such as the #CysticIndex, allow our veterinary pathologists to evaluate the efficacy of novel treatments in preclinical models of PKD. 👉 Send your samples to obtain histopathology assessments in industry-competitive times now: https://lnkd.in/gg2NXym

Andrea Dunaif, MD discusses the promising results of a study on artemether's efficacy in treating polycystic ovarian syndrome (PCOS), highlighting its potential to reduce ovarian androgen production. "Artemether presents a novel approach to managing PCOS by targeting the androgen excess at its source, offering new hope for patients." #PCOS #Artemether #WomensHealth #Endocrinology #MedicalResearch Andrea Dunaif https://lnkd.in/gshj7GEr

Want to challenge those little grey cells? Then check out Nicolas Granger and Abi Clarke’s spotlight on treating non-infectious meningoencephalomyelitis. Online now! https://lnkd.in/e2kJ7EAA #VeterinaryPractice #Veterinary #Neurology

Scientific progress often arises from unanswered questions that drive further inquiry. In the field of feline alimentary lymphoma, one long-standing question has been whether mesenteric lymph nodes analysis could serve as a surrogate for intestinal biopsy. Taking advantage of the extensive histopathological database of MYLAV laboratorio di analisi veterinarie, we sought to address this question. The findings from our investigation are presented here: https://lnkd.in/dJSFuGt5. Enjoy your reading!