RESUMO
A boy was admitted at the age of 17 months. He had psychomotor retardation in early infancy. Physical examination revealed microcephalus, unusual facies, and a single palmar crease on his right hand, as well as muscle hypotonia in the extremities and hyperextension of the bilateral shoulder and hip joints. Genetic detection identified two pathogenic compound heterozygous mutations, c.8868-1G>A (splicing) and c.11624_11625del (p.V3875Afs*10), in the VPS13B gene, and thus the boy was diagnosed with Cohen syndrome. Cohen syndrome is a rare autosomal recessive disorder caused by the VPS13B gene mutations and has complex clinical manifestations. Its clinical features include microcephalus, unusual facies, neutropenia, and joint hyperextension. VPS13B gene detection helps to make a confirmed diagnosis.
Assuntos
Neutropenia/complicações , Sequência de Bases , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Dedos/anormalidades , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Masculino , Microcefalia/diagnóstico , Microcefalia/genética , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/genética , Mutação , Miopia/diagnóstico , Miopia/genética , Neutropenia/genética , Neutropenia/psicologia , Obesidade/diagnóstico , Obesidade/genética , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/etiologia , Transtornos Psicomotores/genética , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/genética , Proteínas de Transporte Vesicular/genéticaRESUMO
Circular RNAs (circRNAs) play a vital role in diabetic peripheral neuropathy. However, their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood. Here, we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls. Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group. Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation. A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs. circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy. Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin (PLLP) expression. Moreover, overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function. The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p, while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration. These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients, improving myelin sheath structure and nerve function. Thus, this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.
Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Humanos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Hematoma Subdural/diagnóstico por imagem , Hematoma Subdural/etiologia , Hematoma Subdural/cirurgiaRESUMO
Multidrug resistance protein 4 (MRP4) is capable of transporting acyclic nucleotide phosphonates, but little is known about its role in lamivudine (LAM) and entecavir (ETV) transport. In the present study, the involvement of MRP4 in the transport of LAM and ETV was investigated through in vitro experiments. The cytotoxicity of three antiviral drugs and their activities against HBV as characterized in HepG2.4D14 [wildtype hepatitis B virus (HBV)] and HepG2.A64 (ETVresistant HBV) cells. LAM, ETV and tenofovir (TFV) demonstrated a 50% effective concentration against HBV of 4.14±0.03, 0.13±0.02 and 3.24±0.01 µM in HepG2.4D14 cells and of 5.94±0.20, 6.28±0.07 and 11.43±0.09 µM in HepG2.A64 cells, respectively. After administering 3-([(3-(2-[7-chloro-2-quinolinyl]ethyl)phenyl]-[(3-dimethylamino-3-oxoporphyl)-thio)-methyl]-thio) propanoic acid (MK571), the intracellular concentrations of all three drugs were much lower than the extracellular drug concentrations in these two cell types, whereas the intracellular drug concentrations in wildtype cells were higher than those in ETVresistant cells. Furthermore, the intracellular levels of LAM, ETV and TFV were enhanced and the extracellular concentrations were reduced by addition of MK571. Thus, MRP4 is mainly responsible for the efflux of LAM and ETV in hepatocyte cultures. These results may contribute to enhancing antiviral efficacy.
Assuntos
Antivirais/farmacocinética , Guanina/análogos & derivados , Hepatócitos/metabolismo , Lamivudina/farmacocinética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Antivirais/farmacologia , Transporte Biológico , Guanina/farmacocinética , Guanina/farmacologia , Células Hep G2 , Hepatite B/tratamento farmacológico , Vírus da Hepatite B/efeitos dos fármacos , Hepatócitos/virologia , Humanos , Lamivudina/farmacologiaRESUMO
This study aimed to investigate the reconstruction of the thumb and finger extension function in patients with middle and lower trunk root avulsion injuries of the brachial plexus. From April 2010 to January 2015, we enrolled in this study 4 patients diagnosed with middle and lower trunk root avulsion injuries of the brachial plexus via imaging tests, electrophysiological examinations, and clinical confirmation. Muscular branches of the radial nerve, which innervate the supinator in the forearm, were transposed to the posterior interosseous nerve to reconstruct the thumb and finger extension function. Electrophysiological findings and muscle strength of the extensor pollicis longus and extensor digitorum communis, as well as the distance between the thumb tip and index finger tip, were monitored. All patients were followed up for 24 to 30 months, with an average of 27.5 months. Motor unit potentials (MUP) of the extensor digitorum communis appeared at an average of 3.8 months, while MUP of the extensor pollicis longus appeared at an average of 7 months. Compound muscle action potential (CMAP) appeared at an average of 9 months in the extensor digitorum communis, and 12 months in the extensor pollicis longus. Furthermore, the muscle strength of the extensor pollicis longus and extensor digitorum communis both reached grade III at 21 months. Lastly, the average distance between the thumb tip and index finger tip was 8.8 cm at 21 months. In conclusion, for patients with middle and lower trunk injuries of the brachial plexus, transposition of the muscular branches of the radial nerve innervating the supinator to the posterior interosseous nerve for the reconstruction of thumb and finger extension function is practicable and feasible.
Assuntos
Dedos/cirurgia , Traumatismos dos Nervos Periféricos/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Nervo Radial/cirurgia , Polegar/cirurgia , Potenciais de Ação/fisiologia , Adulto , Dedos/inervação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Músculo Esquelético/inervação , Traumatismos dos Nervos Periféricos/patologia , Traumatismos dos Nervos Periféricos/reabilitação , Nervo Radial/lesões , Recuperação de Função Fisiológica/fisiologia , Recrutamento Neurofisiológico/fisiologia , Polegar/inervaçãoRESUMO
Maternal hyperglycemia in gestational diabetes mellitus (GDM), especially hyperglycemic excursions, is associated with increased risks of adverse pregnancy outcomes. Continuous glucose monitoring (CGM) system (CGMS) is better than intermittent self-measurements in detecting detailed glucose profiles on the magnitude and duration of glucose fluctuations. Hyperglycemia resulted from impaired ß cell function. This study analyzed the characteristics of glycemic variability in GDM with 24-28 gestational weeks and its association with ß cell function. Thirty GDM with 24-28 gestational weeks (GDM group) were included in this study, and 20 normal gestational women (NGW group) and 20 normal glucose regulation non-pregnant women (NGRW group) were set as controls. The three groups were monitored using the CGMS for consecutive 72 h. The parameters of glycemic variability included the standard deviation of blood glucose (SDBG), mean of continuous 24-h blood glucose (MBG), mean amplitude of glycemic excursions (MAGEs), and mean of daily differences (MODDs). Homeostasis model assessments were applied to access the insulin resistance (HOMA-IR). The early insulinogenic index (ΔI30/ΔG30) and the area under the curve of insulin (AUCI180) derived from 75-g oral glucose tolerance test were applied to evaluate the early-phase insulin secretion and second-phase insulin secretion, respectively. After CGM, MAGE and MBG value increased progressively from NGRW, NGW to GDM group (p < 0.05); MODD and SDBG values of GDM group were all higher than those of NGRW and NGW groups (p < 0.05), but there are no differences in MODD and SDBG between NGRW and NGW groups (p > 0.05). After comparison of ß cell function, ΔI30/ΔG30 decreased progressively from NGRW, NGW to GDM group (p < 0.05); HOMA-IR and AUCI180 increased progressively from NGRW, NGW to GDM group (p < 0.05). MAGE value was correlated with ΔI30/ΔG30 and HOMA-IR in GDM group (r = -0.78 and 0.65, respectively, p < 0.05). Multiple linear stepwise regression analysis showed that ΔI30/ΔG30 and HOMA-IR were the independent factors of MAGE (ß = -0.61, 0.34, respectively, p < 0.05). Glycemic variability in GDM was higher than in normal pregnant women, and glycemic variability evaluated by MAGE correlates well with impaired early-phase insulin secretion in GDM. Further large-scale studies are needed to formulate treatment strategies to make up for the impaired early-phase insulin secretion and flat glycemic variability, and analyze the association between pregnancy outcomes improvement and glycemic variability remission in GDM.
Assuntos
Glicemia/metabolismo , Diabetes Gestacional/sangue , Hiperglicemia/sangue , Células Secretoras de Insulina/fisiologia , Segundo Trimestre da Gravidez/sangue , Adulto , Estudos de Casos e Controles , Diabetes Gestacional/fisiopatologia , Feminino , Teste de Tolerância a Glucose , Homeostase/fisiologia , Humanos , Hiperglicemia/fisiopatologia , Insulina/sangue , Resistência à Insulina/fisiologia , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez/fisiologia , Análise de RegressãoAssuntos
Epilepsia , Esclerose Tuberosa , Criança , Humanos , Sirolimo , Serina-Treonina Quinases TORRESUMO
This study aimed to investigate the reconstruction of the thumb and finger extension function in patients with middle and lower trunk root avulsion injuries of the brachial plexus.From April 2010 to January 2015,we enrolled in this study 4 patients diagnosed with middle and lower trunk root avulsion injuries of the brachial plexus via imaging tests,electrophysiological examinations,and clinical confirmation.Muscular branches of the radial nerve,which innervate the supinator in the forearm,were transposed to the posterior interosseous nerve to reconstruct the thumb and finger extension function.Electrophysiological findings and muscle strength of the extensor pollicis longus and extensor digitorum communis,as well as the distance between the thumb tip and index finger tip,were monitored.All patients were followed up for 24 to 30 months,with an average of 27.5 months.Motor unit potentials (MUP) of the extensor digitorum communis appeared at an average of 3.8 months,while MUP of the extensor pollicis longus appeared at an average of 7 months.Compound muscle action potential (CMAP) appeared at an average of 9 months in the extensor digitorum communis,and 12 months in the extensor pollicis longus.Furthermore,the muscle strength of the extensor pollicis longus and extensor digitorum communis both reached grade Ⅲ at 21 months.Lastly,the average distance between the thumb tip and index finger tip was 8.8 cm at 21 months.In conclusion,for patients with middle and lower trunk injuries of the brachial plexus,transposition of the muscular branches of the radial nerve innervating the supinator to the posterior interosseous nerve for the reconstruction of thumb and finger extension function is practicable and feasible.
RESUMO
The nucleotide sequences of P gene from a field strain of peste des petits ruminants virus (PPRV) ("China/Tib/Gej/07-30") was firstly determined. The P gene is 1,655 nucleotides long with two overlapping open reading frames (ORFs). The first ORF is 1530 nucleotides long and would produce P protein of 509 amino acid residues. The second ORF is 534 nucleotides long and would produce C protein of 177 amino acid residues. The first ORF produces a second mRNA transcript of 897 nucleotides long with an extra G nucleotide at position 751. Translation from this mRNA would produce V protein of 298 amino acid residues. The nucleotide and deduced amino acid sequence were compared with the homologous region of other PPRV isolates. At the amino acid level, the "China/Tib/Gej/07-30" shares homology of 86.10%-97.3%, 84.3%-94.9%, and 82.9%-96.3% for P, C, and V proteins respectively. Several sequence motifs in the P genes were identified on the basis of conservation in the PPRVs and the morbilliviruses.
Assuntos
Doenças das Cabras/virologia , Peste dos Pequenos Ruminantes/veterinária , Vírus da Peste dos Pequenos Ruminantes/genética , Fosfoproteínas/genética , Proteínas Virais/genética , Sequência de Aminoácidos , Animais , China , Feminino , Cabras , Dados de Sequência Molecular , Peste dos Pequenos Ruminantes/virologia , Vírus da Peste dos Pequenos Ruminantes/química , Vírus da Peste dos Pequenos Ruminantes/isolamento & purificação , Vírus da Peste dos Pequenos Ruminantes/metabolismo , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Análise de Sequência , Homologia de Sequência de Aminoácidos , Proteínas Virais/química , Proteínas Virais/metabolismoRESUMO
The nucleotide sequences of M and F genes from a field strain of peste des petits ruminants virus (PPRV) ("China/Tib/Gej/07-30") was firstly determined. The M gene was 1 483 nucleotides in length with a single open reading frame (ORF), encoding a protein of 335 amino acids. The F gene was 2411 nucleotides in length, encoding a protein of 546 amino acids. The resulting nucleotide sequence and the deduced amino acid sequences were compared with the homologous regions of other PPRV isolates. The nucleotide sequences of M and F genes of the "China/Tib/Gej/07-30" was 92.4%-97.7% and 85.5%-96.1% identical to other PPRV isolates, respectively, while a homology of 97.0%-98.2% and 94.3%-98.2% could be observed at the amino acids level respectively. Several sequence motifs in the M and F genes had been identified on the basis of conservation in the PPRVs and the morbilliviruses. The 3' untranslated region of M gene was 443 nucleotides in length with 82.4%-93.5% identical to other PPRV isolates. The 5' untranslated region of F gene was 634 nucleotides in length with 76.2%-91.7% identical to other PPRV isolates.
Assuntos
Peste dos Pequenos Ruminantes/veterinária , Vírus da Peste dos Pequenos Ruminantes/genética , Vírus da Peste dos Pequenos Ruminantes/isolamento & purificação , Doenças dos Ovinos/virologia , Proteínas Virais de Fusão/genética , Proteínas da Matriz Viral/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Dados de Sequência Molecular , Peste dos Pequenos Ruminantes/virologia , Vírus da Peste dos Pequenos Ruminantes/química , Vírus da Peste dos Pequenos Ruminantes/classificação , Filogenia , Homologia de Sequência de Aminoácidos , Ovinos , Tibet , Proteínas Virais de Fusão/química , Proteínas da Matriz Viral/químicaRESUMO
The N gene and genome promoter nucleotide sequence of a Chinese Peste des petits rumiants virus (PPRV) ("China/Tib/Gej/07-30") was firstly determined. The length of N gene was 1689 nucleotides with a single open reading frame (ORF). The nucleotide and deduced amino acid sequence was compared with the homologous region of other PPRV isolates. The nucleotide sequence of the "China/Tib/Gej/07-30" was 91.7%-97.6% identical to other PPRV isolates, while a homology of 94.9%-98.5% could be observed at the amino acids level. The N gene encoded a protein of 525 amino acids. Several sequence motifs were identified on the basis of conservation in the PPRVs and the morbilliviruses. The genome length of promoter region was 107 nucleotides with 91.8%-98.2% identity to other PPRV isolates. Phylogenetic analysis showed that the "China/Tib/Gej/07-30" belonged to the Asian lineage.