OrganOx’s Post

In the publication “A living organoid biobank of patients with Crohn’s disease reveals molecular subtypes for personalized therapeutics,” researchers aim to discover ways to improve current therapy by creating a living biobank of Crohn’s disease (CD) patient-derived organoid cultures (PDOs). These cultures focused on human colon epithelium cells, since the colon is involved in over half of patients diagnosed with CD. This image depicts a CD PDO cell section which was revealed to have irregular morphology when compared to healthy PDOs. Highlighted in green are adherens junctions, while tight junctions are in red. Desmosomes are highlighted in blue. CD PDOs tend to have cells that exhibit more junctions and desmosomes compared to that of healthy human PDOs. In bright pink are various interdigitations (loops) and cell membranes, and microvilli actin filament sections are in dull pink, colorized for visual effect. This sample was from an organoid pellet fixed with 2% glutaraldehyde in 0.10 M cacodylate buffer and postfixed with 1% osmium. The pellet was stained with 2% uranyl acetate and dehydrated with ethanol, then washed with ethanol and acetone. It was sectioned at 60 nm and post-stained with 2% uranyl acetate. The image was taken by Ayden G. Fonseca using the JEOL 1400 Plus, operated at 80 KeV at the EM Core. Link to publication: https://lnkd.in/g_aeQKeQ

✔ Targeting Apolipoprotein to alleviate liver fibrosis: #Liver fibrosis, a pathological hallmark of chronic #liver diseases, has long posed a challenge in therapeutic management. In a recent study, researchers have identified a natural small molecule, 12-deoxy phorbol 13-palmitate that significantly mitigates #liver_fibrosis by targeting #apolipoprotein L2 (APOL2), a protein newly implicated in fibrosis progression. #APOL2 is activated by transforming the growth factor-β1 (#TGF_β1) pathway. This activation leads to the binding of APOL2 to sarcoplasmic/ER calcium ATPase 2 (SERCA2), which induces endoplasmic reticulum (ER) stress and enhances the PERK–HES1 signaling pathway activity, contributing to the progression of liver fibrosis. The study demonstrated that 12-deoxy phorbol 13-palmitate effectively downregulates APOL2 expression, inhibiting the activation of #hepatic_stellate_cells (#HSCs)—a key driver of fibrotic scarring.  In both in vitro and in vivo models, treatment with this molecule resulted in a marked reduction in #collagen deposition and liver stiffness, two critical indicators of fibrosis severity. In preclinical animal models, this compound improved liver function and halted disease progression, showcasing its potential as a therapeutic candidate. Its safety profile is especially noteworthy; as a naturally occurring compound, it exhibited minimal toxicity, making it a promising alternative to current antifibrotic therapies, which often have significant side effects. Further clinical studies are now anticipated to assess the molecule’s efficacy and long-term safety in humans. This represents a critical step forward in developing safer, more effective treatments for #liver_fibrosis. REF: https://lnkd.in/dYgWnC6Z #HCC_Awareness_Campaign #LiverFibrosis #ApolipoproteinL2 #RegenerativeMedicine #FibrosisResearch #Biotechnology

Low metabolic turnover can make in vitro clearance difficult to evaluate. Hepatocyte #spheroids can extend culture time to achieve higher drug turnover but face limitations on cell number per well. A newly published study from researchers at AbbVie uses BioIVT cells and subcellular fractions to assesses microcavity spheroid properties for clearance assays compared to #microsomes, hepatocyte suspensions, 2D plated #hepatocytes, and macrowell spheroids. View the results: https://hubs.ly/Q02B51-R0 #ADME #DrugMetabolism #ScientificResearch

We're thrilled to unveil our latest protocol with Cell Press for the RASTRUM Platform: a cutting-edge approach to creating 3D primary human hepatocyte (PHH) cell models. This breakthrough enables more accurate prediction of hepatotoxicity and enhances drug testing precision. 🔬 Key Highlights: - Develop 3D human hepatocyte models within a liver-relevant matrix using the RASTRUM Platform. - Maintain viable primary hepatocytes for up to 2 weeks for chronic drug exposure. - Assess vital metrics including albumin production, CYP450 activity, and drug response. - Utilize a 384-well plate format for efficient drug screening applications. Our new protocol empowers researchers to better simulate liver function and drug interactions, driving forward the future of hepatotoxicity studies. Dive into the details and elevate your research capabilities with RASTRUM: https://lnkd.in/gujMi78C #DrugDiscovery #DrugResearch #InventiaLifeScience

Exciting new protocol for developing 3D human hepatocyte models to moniutor drug response. In addition, the primary cell line mainatined viability for the experiment's 2 week run time! #cells #3Dmodeling #drugdevelopment #viability #outgrowth #drugdiscovery

I'm excited to share my latest review article on the effects of Tacrolimus on the gut microbiota! This paper explores the critical role of the gut microbiome in clinical treatment and pharmacology. You can read and download it for free until January 24, 2025. https://lnkd.in/gy5_hP_S

#PMC403 Our data support a key role of the endothelium in the development of IR-AKI, introduce Hepta-ANG1 as a putative new therapeutic biologic, and report a model to explain how IRI reduces Tie2 signaling and how Tie2 activation protects the kidney.

“PolySia-NPs represent a potential breakthrough in addressing conditions such as GA/AMD caused by immune overactivation,” according to Anitha Krishnan, Ph.D, Sr. Director/Head of Biology at Aviceda Therapeutics. "Their systemic and ocular safety has been rigorously evaluated, making them a promising candidate for clinical trials. As the first therapeutic sialic acid-coated nanoparticle to enter human trials, PolySia-NPs may pave the way for effective treatments in retinal degenerative diseases.” You can read the piece Dr. Krishnan and colleagues published in the journal Pharmaceuticals here: https://lnkd.in/eq-wSDgr

On this Word Lupus Awareness Day, Biomedcode is proud to contribute in the preclinical development of novel lupus-targeting human therapeutics with our recently published humanized IL23A driven mouse model of #SLE (https://lnkd.in/dH_S2PSG), a valuable disease model for studying the aetiopathogenic role of human IL23A in SLE and for validating the #preclinical in vivo #efficacy of novel disease-related therapeutics. Let’s all help raise global awareness of the physical, emotional and economic impact that lupus can have and bring greater attention and resources to efforts to end lupus. #makelupusvisible, #worldlupusday, #CRO, #mousediseasemodel, #IL23, #SLE, #drugtesting, #autoimmunity, #guselkumab, #tremfya, #TghIL23A, #humanized

Source: SLAS discovery : advancing life sciences R & D The study used the Cellular Thermal Shift Assay (CETSA) coupled with Mass Spectrometry (CETSA-MS) to investigate the mode of action of sorafenib, a multikinase inhibitor used to treat hepatocellular carcinoma. The study identified aldehyde dehydrogenase 2 (ALDH2) as a novel target of sorafenib. The interaction between sorafenib and ALDH2 was validated using pure recombinant protein, and it was found that sorafenib inhibits ALDH2 activity. Additionally, the study showed that ALDH2 protein expression and activity were reduced in sorafenib-resistant cells compared to the parental cell line. Overall, the findings suggest that ALDH2 may play a role in both hepatocellular carcinoma and sorafenib resistance.