New genetic tools to define the pathophysiology of inborn errors of cobalamin metabolism impacting mammalian development.

The congenital, autosomal recessive disorder combined methylmalonic acidemia and homocystinuria - cblC type, is the most common inborn error of cobalamin (vitamin B) metabolism. In its early onset form, cblC profoundly impacts fetal development of the central nervous system, hematopoietic system, and other tissues. Previously, mutations in the MMACHC gene, which encodes a protein required for the intracellular trafficking and enzymatic processing of free cobalamin into active coenzyme forms, were found to cause cblC.

Efficacy of Risperidone Orally Disintegrating Tablets Combined with Oxazepam in the Treatment of Schizophrenia.

Objective: To explore the efficacy of risperidone orally disintegrating tablets combined with oxazepam in the treatment of schizophrenia.

Methods: From May 2019 to May 2021, 60 patients with schizophrenia treated in our hospital were recruited and assigned into an observation group (risperidone orally disintegrating tablets combined with oxazepam treatment) and a control group (alprazolam combined with chlorpromazine treatment) according to the random number table method. The positive and negative symptom score (PANSS), quality of life score (QOL-75), ability of daily living score (ADL), clinical efficacy, incidence of adverse reactions, and disease recurrence were compared between the two groups before and after treatment.

Clinical efficacy of clonazepam in the treatment of status epilepticus.

To explore the clinical efficacy of clonazepam in the treatment of status epilepticus. Totally 60 patients with status epilepticus were identified as research subjects and assigned (1:1) via the randomized double-blind method to receive either diazepam (Valium) comparison group) or clonazepam (observation group). After treatment and follow-up visits, the treatment efficacy, incidence of adverse reactions, quality of life, and recurrence were evaluated and compared between the two groups.

Mutations in Hcfc1 and Ronin result in an inborn error of cobalamin metabolism and ribosomopathy.

Combined methylmalonic acidemia and homocystinuria (cblC) is the most common inborn error of intracellular cobalamin metabolism and due to mutations in Methylmalonic Aciduria type C and Homocystinuria (MMACHC). Recently, mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) were shown to result in cellular phenocopies of cblC. Since HCFC1/RONIN jointly regulate MMACHC, patients with mutations in these factors suffer from reduced MMACHC expression and exhibit a cblC-like disease.

Mouse models to study the pathophysiology of combined methylmalonic acidemia and homocystinuria, cblC type.

Combined methylmalonic acidemia and homocystinuria, cblC type, is the most common inherited disorder of cobalamin metabolism and is characterized by severe fetal developmental defects primarily impacting the central nervous system, hematopoietic system, and heart. CblC was previously shown to be due to mutations in the MMACHC gene, which encodes a protein thought to function in intracellular cobalamin trafficking and biosynthesis of adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). These coenzymes are required for the production of succinyl-CoA and methionine, respectively.

The Hippo Pathway Blocks Mammalian Retinal Müller Glial Cell Reprogramming.

In response to retinal damage, the Müller glial cells (MGs) of the zebrafish retina have the ability to undergo a cellular reprogramming event in which they enter the cell cycle and divide asymmetrically, thereby producing multipotent retinal progenitors capable of regenerating lost retinal neurons. However, mammalian MGs do not exhibit such a proliferative and regenerative ability. Here, we identify Hippo pathway-mediated repression of the transcription cofactor YAP as a core regulatory mechanism that normally blocks mammalian MG proliferation and cellular reprogramming.

Live imaging of developing mouse retinal slices.

Background: Ex vivo, whole-mount explant culture of the rodent retina has proved to be a valuable approach for studying retinal development. In a limited number of recent studies, this method has been coupled to live fluorescent microscopy with the goal of directly observing dynamic cellular events. However, retinal tissue thickness imposes significant technical limitations.

The mito::mKate2 mouse: A far-red fluorescent reporter mouse line for tracking mitochondrial dynamics in vivo.

Mitochondria are incredibly dynamic organelles that undergo continuous fission and fusion events to control morphology, which profoundly impacts cell physiology including cell cycle progression. This is highlighted by the fact that most major human neurodegenerative diseases are due to specific disruptions in mitochondrial fission or fusion machinery and null alleles of these genes result in embryonic lethality. To gain a better understanding of the pathophysiology of such disorders, tools for the in vivo assessment of mitochondrial dynamics are required.

HNF1B Loss Exacerbates the Development of Chromophobe Renal Cell Carcinomas.

Chromophobe renal cell carcinoma (ChRCC) is characterized by major changes in chromosomal copy number (CN). No model is available to precisely elucidate the molecular drivers of this tumor type. HNF1B is a master regulator of gene expression.

Lipoxin A4 exerts protective effects against experimental acute liver failure by inhibiting the NF-κB pathway.

Although rare, acute liver failure (ALF) is associated with high levels of mortality, warranting the development of novel therapies. Nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) play roles in ALF. Lipoxin A4 (LXA4) has been shown to alleviate inflammation in non-hepatic tissues.