Indole-3-acetic acid improves the hepatic mitochondrial respiration defects by PGC1a up-regulation.

Recent evidences have linked indole-3-acetic acid (I3A), a gut microbiota-derived metabolite from dietary tryptophan, with the protection against non-alcoholic fatty liver disease (NAFLD). However, the values of I3A on mitochondrial homeostasis in NAFLD have yet to be analyzed. In this study, we verified that I3A alleviated dietary-induced metabolic impairments, particularly glucose dysmetabolism and liver steatosis.

Effect of low-dose rituximab treatment on autoimmune nodopathy with anti-contactin 1 antibody.

Background: Autoimmune nodopathy with anti-contactin-1 (CNTN1) responds well to rituximab instead of traditional therapies. Although a low-dose rituximab regimen was administered to patients with other autoimmune diseases, such as myasthenia gravis and neuromyelitis optica spectrum disorders, and satisfactory outcomes were obtained, this low-dose rituximab regimen has not been trialed in anti-CNTN1-positive patients.

Methods: Anti-CNTN1 nodopathy patients were enrolled in this prospective, open-label, self-controlled pilot study.

Reversible cerebral artery constriction accompanied with stroke-like episode in MELAS: A case series.

Objective: The pathophysiology of stroke-like episode (SLE) in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was uncertain, though mitochondrial metabolic crisis of cortical neurons and mitochondrial proliferation in small vessels of brain have been considered. However, the involvement of major cerebral vessels was debated. We aimed to investigate whether major cerebral vessels participate in SLE.

Leber's hereditary optic neuropathy plus dystonia caused by the mitochondrial ND1 gene m.4160 T > C mutation.

Background: Leber's hereditary optic neuropathy (LHON) is a common mitochondrial disease. More than 30 variants in the mitochondrial DNA (mtDNA) have been previously described in LHON. However, the pathogenicity of some variants remains unclear.

Establishment of an induced pluripotent stem cell (iPSC) line (INNDSUi001-A) from a healthy female Chinese Han.

We have established the human induced pluripotent stem cell (hiPSC) line (INNDSUi001-A) from skin fibroblasts of a healthy 24-year-old female individual by using non-integrating reprogramming method. The resulted cells had typical features of embryonic stem cell as indicated by expression of specific pluripotency markers and had the capability of in vitro differentiation into the three germ layers. This iPSC line can be used as a healthy control for disease study.

Clinicopathologic Profiles of Sporadic Late-Onset Nemaline Myopathy: Practical Importance of Anti-α-Actinin Immunostaining.

Background And Objectives: Sporadic late-onset nemaline myopathy (SLONM) is a treatable or otherwise fatal myopathy. Diagnosis of SLONM is still challenging, and no therapeutic consensus has been achieved. Here, we reported the clinicopathologic features and long-term follow-up data of SLONM in a Chinese cohort.

Generation of a human induced pluripotent stem cell line (INNDSUi003-A) derived from patient with Becker muscular dystrophy (BMD).

Becker muscular dystrophy (BMD), an X-linked recessive disorder caused of mutation in the dystrophin gene, is characterized by progressive muscle degeneration and proximal muscle weakness. We generated a human induced pluripotent stem cell (hiPSC) line from the fibroblasts isolated from patient with BMD by non-integrating reprogramming methods. The iPSC line highly expresses pluripotency markers, displays the normal karyotype and is able to differentiate into the three germ layers in vitro.

Empirical dynamic modeling of the association between ambient PM and under-five mortality across 2851 counties in Mainland China, 1999-2012.

Background: Ambient fine particulate matter (PM) pollution has been associated with mortality from various diseases, however, its association with under-five mortality rate (U5MR) has remained largely unknown.

Methods: Based on the U5MR data across 2851 counties in Mainland China from 1999 to 2012, we employed approximate Bayesian latent Gaussian models to assess the association between ambient PM and U5MR at the county level for the whole nation and sub-regions. GDP growth rate, normalized difference vegetation index (NDVI), temperature, and night-time light were included as covariates using a smoothing function.

Deficiency in Zebrafish Leads to ROS Production and Mitophagy, and Idebenone Improves its Phenotypes.

Limb-girdle muscular dystrophy 2G (LGMD2G) is a subtype of limb-girdle muscular dystrophy. However, the disease's mechanisms are still not fully understood, and no established therapeutic targets have been found. Using a morpholino-based knockdown approach, we established an LGMD2G zebrafish model.

Bezafibrate Rescues Mitochondrial Encephalopathy in Mice via Induction of Daily Torpor and Hypometabolic State.

Leigh syndrome (LS) is one of the most common mitochondrial encephalopathy diseases in infants. To date, there is still an absence of effective therapy. Bezafibrate (BEZ), a pan-peroxisome proliferator-activated receptor (PPAR) agonist, ameliorates the phenotype of the mouse model of mitochondrial disease via an unclear mechanism.

Clinical and diagnostic features of anti-neurofascin-155 antibody-positive neuropathy in Han Chinese.

Objective: To investigate the clinical features of Han Chinese patients with anti-neurofascin-155 (NF155) antibody-positive neuropathy.

Methods: We screened 194 patients with peripheral neuropathy for NF155 antibodies using a cell-based assay (CBA) and teased-fiber immunofluorescence assay. We summarized the clinical findings of seropositive patients.

Novel compound heterozygous mutations in the TTN gene: elongation and truncation variants causing limb-girdle muscular dystrophy type 2J in a Han Chinese family.

Introduction: Limb-girdle muscular dystrophy (LGMD) is a group of clinically heterogeneous muscle disorders commonly manifesting proximal limb girdle muscle weakness. There have been more than 30 subtypes of LGMD associated with causative genes and limb-girdle muscular dystrophy type 2J (LGMD2J) is caused by mutations in the TTN gene.

Methods: We report a Han Chinese family with LGMD2J.

Cleavage of Kv2.1 by BACE1 decreases potassium current and reduces neuronal apoptosis.

As an aspartic protease, β-site APP cleaving enzyme 1 (BACE1) can efficiently cleave amyloid precursor protein (APP) to produce amyloid beta (Aβ), a chief constituent of senile plaques in Alzheimer's disease. Thus, BACE1 inhibitor is identified as a therapeutic candidate for AD. However, recent failures of clinical trials using BACE1 inhibitors emphasized that comprehensively understanding of BACE1 function is particularly important.

The CGG repeat expansion in RILPL1 is associated with oculopharyngodistal myopathy type 4.

Recent studies indicate that CGG repeat expansions in LRP12, GIPC1, and NOTCH2NLC are associated with oculopharyngodistal myopathy (OPDM) types 1, 2, and 3, respectively. However, some clinicopathologically confirmed OPDM cases continue to have unknown genetic causes. Here, through a combination of long-read whole-genome sequencing (LRS), repeat-primed polymerase chain reaction (RP-PCR), and fluorescence amplicon length analysis PCR (AL-PCR), we found that a CGG repeat expansion in the 5' UTR of RILPL1 is associated with familial and simplex OPDM type 4 (OPDM4).

Clinical, genetic, and pathological characterization of GNE myopathy in China.

Background: GNE myopathy is the most common distal myopathy in China. We summarized the clinical, genetic, and pathological characteristics of 125 Chinese patients with GNE myopathy.

Methods: We collected clinical data of 21 patients diagnosed at our hospital and 104 patients from previous reports.

TGM2 positively regulates myoblast differentiation via enhancing the mTOR signaling.

Myoblast differentiation is an essential process for the control of muscle regeneration. However, the intrinsic mechanisms underlying this dynamic process are still not well clarified. Herein, we identified transglutaminase type 2 (TGM2) as a novel regulator of muscle differentiation and regeneration in vitro and in vivo.

Clinical, pathological, and molecular genetic analysis of 7 Chinese patients with hereditary myopathy with early respiratory failure.

Hereditary myopathy with early respiratory failure (HMERF) is a subtype of myofibrillar myopathy. Mutations located on exon 344 of the titin-A band, the 119th fibronectin-3 domain (FN 119), are responsible for HMERF. In this article, we retrospectively analyzed the clinical features, findings of muscle imaging, muscle pathology, immunohistochemistry, and ultrastructural characteristics of seven patients diagnosed with HMERF at a single center in China.

A heterozygous deletion of PDGFB gene causes paroxysmal kinesigenic dyskinesia with primary familial brain calcification.

Background: Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized with calcium deposition in multiple brain regions. Mutations in PDGFB have been discovered in sporadic and familial PFBC cases. While several known variants displayed loss-of function, no complete deletion of platelet-derived growth factor B (PDGFB) has been reported.

Clinical, pathological and genetic features and follow-up of 110 patients with late-onset MADD: a single-center retrospective study.

To observe a long-term prognosis in late-onset multiple acyl-coenzyme-A dehydrogenation deficiency (MADD) patients and to determine whether riboflavin should be administrated in the long-term and high-dosage manner, we studied the clinical, pathological and genetic features of 110 patients with late-onset MADD in a single neuromuscular center. The plasma riboflavin levels and a long-term follow-up study were performed. We showed that fluctuating proximal muscle weakness, exercise intolerance and dramatic responsiveness to riboflavin treatment were essential clinical features for all 110 MADD patients.

Novel biallelic mutations in POLG gene: large deletion and missense variant associated with PEO.

Background: Mitochondrial disorders are clinically heterogeneous diseases associated with impaired oxidative phosphorylation (OXPHOS) activity. POLG, which encodes the DNA polymerase-γ (Polγ) catalytic subunit, is the most commonly mutated nuclear gene associated with mitochondrial disorders.

Methods: We carried out whole-exome sequencing (WES) to identify the gene associated with progressive external ophthalmoplegia (PEO).

Anti-HMGCR myopathy overlaps with dermatomyositis-like rash: a distinct subtype of idiopathic inflammatory myopathy.

Objective: To characterize the clinical and pathological features of anti-HMGCR myopathy.

Methods: The presence of anti-HMGCR antibody in the serum of 227 patients with idiopathic inflammatory myopathy (IIM) and 100 healthy control individuals was assessed by ELISA. All ELISA positive samples were retested by indirect immunofluorescence assay (IIFA) on HEK293 cells.

Late-Onset Leukodystrophy Mimicking Hereditary Spastic Paraplegia without Diffuse Leukodystrophy on Neuroimaging.

Purpose: Leukodystrophies are frequently regarded as childhood disorders, but they can occur at any age, and the clinical and imaging patterns of the adult-onset form are usually different from the better-known childhood variants. Several reports have shown that various late-onset leukodystrophies, such as X-linked adrenoleukodystrophy and Krabbe disease, may present as spastic paraplegia with the absence of the characteristic white matter lesions on neuroimaging; this can be easily misdiagnosed as hereditary spastic paraplegia. The objective of this study was to investigate the frequency of late-onset leukodystrophies in patients with spastic paraplegia.