Enhancing the wound healing potential using earthworm clitellum factors and elucidating its molecular mechanism in an in-vitro and earthworm model.

Earthworm, Eudrilus eugeniae cannot survive and regenerate without clitellum segments. In regenerating worms, the clitellum's epithelial and circular muscular layers are reduced to one-third, and longitudinal cell layers to half. In C2C12 cells, Clitellum Factors (CF - 5, 25 and 50%) and Regenerative Clitellum Factors (RCF - 5, 25, 50, 75%) ameliorate the cell viability up to 20-28% and 30-38% respectively than the control.

SNRK regulates TGFβ levels in atria to control cardiac fibrosis.

Atrial fibrosis is central to the pathology of heart failure (HF) and atrial fibrillation (AF). Identifying precise mechanisms underlying atrial fibrosis will provide effective strategies for clinical intervention. This study investigates a metabolic serine threonine kinase gene, that we previously reported to control cardiac metabolism and function.

Functional significance of earthworm clitellum in regulating the various biological aspects of cell survival and regeneration.

Earthworms are a highly abundant species in nature, with nearly 7000 different species being discovered. Despite the similarities in morphology among earthworm species, their regeneration capabilities vary based on the clitellum. The clitellum plays a crucial role in the clitellum-dependent worms, as it is involved in the processes of regeneration and reproduction in earthworms.

Effects of gene replacement therapy with resamirigene bilparvovec (AT132) on skeletal muscle pathology in X-linked myotubular myopathy: results from a substudy of the ASPIRO open-label clinical trial.

Background: X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital muscle disease caused by mutations in the MTM1 gene that result in profound muscle weakness, significant respiratory insufficiency, and high infant mortality. There is no approved disease-modifying therapy for XLMTM. Resamirigene bilparvovec (AT132; rAAV8-Des-hMTM1) is an investigational adeno-associated virus (AAV8)-mediated gene replacement therapy designed to deliver MTM1 to skeletal muscle cells and achieve long-term correction of XLMTM-related muscle pathology.

Mesenchymal Stromal Cells Facilitate Tip Cell Fusion Downstream of BMP-Mediated Venous Angiogenesis-Brief Report.

Background: The goal of this study was to identify and characterize cell-cell interactions that facilitate endothelial tip cell fusion downstream of BMP (bone morphogenic protein)-mediated venous plexus formation.

Methods: High resolution and time-lapse imaging of transgenic reporter lines and loss-of-function studies were carried out to study the involvement of mesenchymal stromal cells during venous angiogenesis.

Results: BMP-responsive stromal cells facilitate timely and precise fusion of venous tip cells during developmental angiogenesis.

Fluorescein clearance kinetics in blood and bile indicates hepatic ischemia-reperfusion injury in rats.

Quantitative measurement of the degree of hepatic ischemia-reperfusion injury (IRI) is crucial for developing therapeutic strategies for its treatment. We hypothesized that clearance of fluorescent dye through bile metabolism may reflect the degree of hepatic IRI. In this study, we investigated sodium fluorescein clearance kinetics in blood and bile for quantifying the degree of hepatic IRI.

Inverse co-expression of EZH2 and acetylated H3K27 in prostatic tissue.

Context: Enhancer of Zeste 2 (EZH2), a methyltransferase and an upregulated gene is an adverse prognosticator in prostate cancer. It catalyzes histone H3 lysine 27 trimethylation (H3K27me3) leading to repressive chromatin status (heterochromatin). Following demethylation and acetylation of H3 protein (H3K27ac) the result is transcriptionally activated status (euchromatin), a key metastasis facilitator being targeted by ongoing clinical trials, as with palbociclib.

Erratum: Voluntary wheel running complements microdystrophin gene therapy to improve muscle function in mdx mice.

[This corrects the article DOI: 10.1016/j.omtm.

Optical Metabolic Imaging of Mitochondrial Dysfunction on HADH Mutant Newborn Rat Hearts.

Background: Mitochondrial [Formula: see text]-oxidation of fatty acids is the primary energy source for the heart and carried out by Hydroxy Acyl-CoA Dehydrogenase (HADH) encoded trifunctional protein. Mutations in the genes encoding mitochondrial proteins result in functionally defective protein complexes that contribute to energy deficiencies, excessive reactive oxygen species (ROS) production, and accumulation of damaged mitochondria. We hypothesize that a dramatic alternation in redox state and associated mitochondrial dysfunction is the underlying cause of Fatty Acid Oxidation (FAO) deficiency mutant, resulting in heart failure.

Voluntary wheel running complements microdystrophin gene therapy to improve muscle function in mdx mice.

We tested the hypothesis that voluntary wheel running would complement microdystrophin gene therapy to improve muscle function in young mdx mice, a model of Duchenne muscular dystrophy. mdx mice injected with a single dose of AAV9-CK8-microdystrophin or vehicle at age 7 weeks were assigned to three groups: mdxRGT (run, gene therapy), mdxGT (no run, gene therapy), or mdx (no run, no gene therapy). Wild-type (WT) mice were assigned to WTR (run) and WT (no run) groups.

NOGOB receptor-mediated RAS signaling pathway is a target for suppressing proliferating hemangioma.

Infantile hemangioma is a vascular tumor characterized by the rapid growth of disorganized blood vessels followed by slow spontaneous involution. The underlying molecular mechanisms that regulate hemangioma proliferation and involution still are not well elucidated. Our previous studies reported that NOGOB receptor (NGBR), a transmembrane protein, is required for the translocation of prenylated RAS from the cytosol to the plasma membrane and promotes RAS activation.

Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids.

Maternal alcohol exposure during pregnancy can substantially impact the development of the fetus, causing a range of symptoms, known as fetal alcohol spectrum disorders (FASDs), such as cognitive dysfunction and psychiatric disorders, with the pathophysiology and mechanisms largely unknown. Recently developed human cerebral organoids from induced pluripotent stem cells are similar to fetal brains in the aspects of development and structure. These models allow more relevant in vitro systems to be developed for studying FASDs than animal models.

Anticholestatic Effect of Bardoxolone Methyl on Hepatic Ischemia-reperfusion Injury in Rats.

Background: Cholestasis is a sign of hepatic ischemia-reperfusion injury (IRI), which is caused by the dysfunction of hepatocyte membrane transporters (HMTs). As transcriptional regulation of HMTs during oxidative stress is mediated by nuclear factor erythroid 2-related factor 2, we hypothesized that bardoxolone methyl (BARD), a nuclear factor erythroid 2-related factor 2 activator, can mitigate cholestasis associated with hepatic IRI.

Methods: BARD (2 mg/kg) or the vehicle was intravenously administered into rats immediately before sham surgery, 60 min of ischemia (IR60), or 90 min of ischemia (IR90); tissue and blood samples were collected after 24 h to determine the effect on key surrogate markers of bile metabolism and expression of HMT genes (Mrp (multidrug resistance-associated protein) 2, bile salt export pump, , sodium-taurocholate cotransporter, and organic anion-transporting polypeptide 1).

Cardiomyocyte-Specific Prevents Inflammation in the Heart.

Background The SNRK (sucrose-nonfermenting-related kinase) enzyme is critical for cardiac function. However, the underlying cause for heart failure observed in cardiac conditional knockout mouse is unknown. Methods and Results Previously, 6-month adult mice knocked out for in cardiomyocytes (CMs) displayed left ventricular dysfunction.

Confocal Microscopy Confirmed that in Phosphatidylcholine Giant Unilamellar Vesicles with very High Cholesterol Content Pure Cholesterol Bilayer Domains Form.

The cholesterol (Chol) content in the fiber cell plasma membranes of the eye lens is extremely high, exceeding the solubility threshold in the lenses of old humans. This high Chol content forms pure Chol bilayer domains (CBDs) and Chol crystals in model membranes and membranes formed from the total lipid extracts from human lenses. CBDs have been detected using electron paramagnetic resonance (EPR) spin-labeling approaches.

Decreased OLA1 (Obg-Like ATPase-1) Expression Drives Ubiquitin-Proteasome Pathways to Downregulate Mitochondrial SOD2 (Superoxide Dismutase) in Persistent Pulmonary Hypertension of the Newborn.

Persistent pulmonary hypertension of the newborn (PPHN) is a failure of pulmonary vascular resistance to decline at birth rapidly. One principal mechanism implicated in PPHN development is mitochondrial oxidative stress. Expression and activity of mitochondrial SOD2 (superoxide dismutase) are decreased in PPHN; however, the mechanism remains unknown.

Detection of mitochondria-generated reactive oxygen species in cells using multiple probes and methods: Potentials, pitfalls, and the future.

Reactive oxygen and nitrogen species (ROS/RNS) such as superoxide (O), hydrogen peroxide, lipid hydroperoxides, peroxynitrite, and hypochlorous and hypobromous acids play a key role in many pathophysiological processes. Recent studies have focused on mitochondrial ROS as redox signaling species responsible for promoting cell division, modulating and regulating kinases and phosphatases, and activating transcription factors. Many ROS also stimulate cell death and senescence.

A model of TH17-associated ileal hyperplasia that requires both IL-17A and IFNγ to generate self-tolerance and prevent colitis.

Homeostasis in the ileum, which is commonly disrupted in patients with Crohn's disease, involves ongoing immune responses. To study how homeostatic processes of the ileum impact CD4T cell responses, we used TCR transgenic tools to breed mice that spontaneously produced CD4T cells reactive to an antigen expressed in the ileum. At an early age, the ilea of these mice exhibit crypt hyperplasia and accumulate increased numbers of T17 cells bearing non-transgenic clonotypes.

Temporal and Spatial Post-Transcriptional Regulation of Zebrafish mRNA by Long Noncoding RNA During Brain Vascular Assembly.

Objective: Tie1 (tyrosine kinase containing immunoglobulin and epidermal growth factor homology 1), an endothelial and hematopoietic cell-specific receptor tyrosine kinase, is an important regulator of angiogenesis and critical for maintaining vascular integrity. The post-transcriptional regulation of mRNA expression is not understood, but it might partly explain Tie1's differential expression pattern in endothelium. Following up on our previous work that identified natural antisense transcripts from the locus- (), which regulates mRNA levels in zebrafish-we attempted to identify the mechanism of this regulation.

Nogo-B receptor increases the resistance of estrogen receptor positive breast cancer to paclitaxel.

Intrinsic or acquired chemoresistance is a hurdle in oncology. Only 7%-16% of estrogen receptor α (ERα) positive breast cancer cases achieve a pathological complete response (pCR) after neo-adjuvant chemotherapy. Nogo-B receptor (NgBR) is a cell surface receptor that binds farnesylated Ras and promotes Ras translocation to the plasma membrane.

Sucrose Non-Fermenting Related Kinase Expression in Ovarian Cancer and Correlation with Clinical Features.

Sucrose non-fermenting related kinase (SNRK) is a serine/threonine kinase known to regulate cellular metabolism and adipocyte inflammation. Since alterations in adipocyte metabolism play a role in ovarian cancer metastasis, we investigated the expression of SNRK in benign and malignant human ovarian tissue using immunohistochemistry and qPCR. The number of SNRK positive (+) nuclei is increased in malignant tissue compared to benign tissue (21.

Sucrose Nonfermenting-Related Kinase Enzyme-Mediated Rho-Associated Kinase Signaling is Responsible for Cardiac Function.

Background: Cardiac metabolism is critical for the functioning of the heart, and disturbance in this homeostasis is likely to influence cardiac disorders or cardiomyopathy. Our laboratory has previously shown that SNRK (sucrose nonfermenting related kinase) enzyme, which belongs to the AMPK (adenosine monophosphate-activated kinase) family, was essential for cardiac metabolism in mammals. Snrk global homozygous knockout (KO) mice die at postnatal day 0, and conditional deletion of Snrk in cardiomyocytes (Snrk cmcKO) leads to cardiac failure and death by 8 to 10 months.

Nogo-B receptor deficiency causes cerebral vasculature defects during embryonic development in mice.

Nogo-B receptor (NgBR) was identified as a receptor specific for Nogo-B. Our previous work has shown that Nogo-B and its receptor (NgBR) are essential for chemotaxis and morphogenesis of endothelial cells in vitro and intersomitic vessel formation via Akt pathway in zebrafish. Here, we further demonstrated the roles of NgBR in regulating vasculature development in mouse embryo and primitive blood vessel formation in embryoid body culture systems, respectively.

Tumor Suppressor Interferon-Regulatory Factor 1 Counteracts the Germinal Center Reaction Driven by a Cancer-Associated Gammaherpesvirus.

Unlabelled: Gammaherpesviruses are ubiquitous pathogens that are associated with the development of B cell lymphomas. Gammaherpesviruses employ multiple mechanisms to transiently stimulate a broad, polyclonal germinal center reaction, an inherently mutagenic stage of B cell differentiation that is thought to be the primary target of malignant transformation in virus-driven lymphomagenesis. We found that this gammaherpesvirus-driven germinal center expansion was exaggerated and lost its transient nature in the absence of interferon-regulatory factor 1 (IRF-1), a transcription factor with antiviral and tumor suppressor functions.