CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.
CapZ Actin Capping Protein , Developmental Disabilities , Epilepsy , Heterozygote , Muscle Hypotonia , Mutation , Child, Preschool , Female , Humans , Male , Developmental Disabilities/genetics , Developmental Disabilities/pathology , Epilepsy/genetics , Exome Sequencing , Intellectual Disability/genetics , Intellectual Disability/pathology , Muscle Hypotonia/genetics , Muscle Hypotonia/pathology , Phenotype , RNA Splicing/genetics , CapZ Actin Capping Protein/genetics
BACKGROUND: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, numerous studies have been published on SARS-CoV-2-related encephalitis/meningitis, but it has not been established if there are specific clinical characteristics of encephalitis/meningitis associated with SARS-CoV-2 infection. AIM: To identify the specific clinical features of cases of encephalitis/meningitis associated with SARS-CoV-2 infection in the context of this virus infection pandemic and investigate their relationship with SARS-CoV-2 infection. METHODS: We searched PubMed, and included single case reports and case series with full text in English, reporting original data of coronavirus disease-19 (COVID-19) patients with encephalitis/meningitis and a confirmed recent SARS-CoV-2 infection. Clinical data were extracted. RESULTS: We identified 22 articles (18 single case reports and 4 case series) reporting on a total of 32 encephalitis/meningitis patients with confirmed SARS-CoV-2 infection. SARS-CoV-2 infection was confirmed through reverse transcriptase-polymerase-chain-reaction (RT-PCR) in 96.88% of cases. A total of 22 (68.75%) patients had symptoms of SARS-CoV-2 infection in about 1 wk (7.91 d) preceding the onset of neurologic symptoms. The most common neurological symptoms were consciousness disturbance (59.38%), seizure (21.88%), delirium (18.75%), and headache (18.75%). Four cases were confirmed by positive RT-PCR results in cerebrospinal fluid (CSF), one was confirmed by positive RT-PCR results in postoperative brain tissue, and one by the presence of SARS-CoV-2 antibodies in CSF. The mainly damaged targets identified by neuroimaging included the temporal lobe (15.63%), white matter (12.5%), frontal lobe (9.38%), corpus callosum (9.38%), and cervical spinal cord (9.38%). Eighty percent of patients had electroencephalograms that showed a diffuse slow wave. Twenty-eight (87.5%) patients were administered with specific treatment. The majority (65.63%) of patients improved following systemic therapy. CONCLUSION: Encephalitis/meningitis is the common neurological complication in patients with COVID-19. The appropriate use of definitions and exclusion of potential similar diseases are important to reduce over-diagnosis of SARS-CoV-2 associated encephalitis or meningitis.
In spite of no homology in sequences‚ Vip3A and Cry1Ia toxins of Bacillus thuringiensis (Bt) share common characteristics‚ such as translocation across cell membranes after synthesis at the early stage of sporulation. The aim of the present study was to compare the regulation patterns and activities of the promoters of vip3A (P
RATIONALE: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) has been reported almost exclusively in the Japanese population. PATIENT CONCERNS: A 17-month-old male patient presented with fever and seizures, and subsequently fell into a coma. On the second day, he recovered consciousness. On the fourth day, he developed complex partial seizures and fell into a coma again. On day 10, the fever and seizures subsided. Head computed tomography on the first day showed no abnormalities. Brain diffusion-weighted images on the fourth day revealed reduced diffusion in the bilateral subcortical white matter. DIAGNOSIS: A diagnosis of AESD was made. INTERVENTIONS: The patient was treated with corticosteroids and intravenous immunoglobulin. OUTCOMES: At the 4-month follow-up, the patient was able to walk independently, and the epileptic seizures were well controlled. LESSONS: AESD is a rare entity, and treatment with corticosteroids and intravenous immunoglobulin can lead to a favorable prognosis. Clinicians should be aware of this condition, and clinicoradiological features can suggest the diagnosis.
Brain Diseases/complications , Diffusion Magnetic Resonance Imaging/methods , Seizures/etiology , Acute Disease , Adrenal Cortex Hormones/therapeutic use , Brain Diseases/diagnosis , Brain Diseases/drug therapy , Coma/diagnosis , Coma/etiology , Drug Therapy, Combination , Fever/diagnosis , Fever/etiology , Humans , Immunoglobulins, Intravenous/therapeutic use , Infant , Male , Seizures/diagnosis , Seizures/physiopathology , Tomography, X-Ray Computed/methods , Treatment Outcome , White Matter/diagnostic imaging , White Matter/pathology
In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24â¯months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6â¯months, while its disintegration occurred after 9â¯months of implantation. After 24â¯months of implantation, approximately 28⯱â¯13â¯vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24â¯months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24â¯months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. STATEMENT OF SIGNIFICANCE: Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.
Absorbable Implants , Coronary Vessels , Materials Testing , Stents , Tomography, Optical Coherence , Animals , Copper/chemistry , Copper/metabolism , Coronary Vessels/diagnostic imaging , Coronary Vessels/surgery , Swine , Time Factors , Zinc/chemistry , Zinc/metabolism
This study investigated the structure, antioxidant activity, antityrosinase activity and mechanism of proanthocyanidins from mung bean seed [Vigna radiata (L.) Wilczek]. The structural composition were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), electrospray ionization-full-mass spectrometry (ESI-Full-MS), and high-pressure liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) techniques. The mung bean seed proanthocyanidins were composed of procyanidins, prodelphinidins, and their rhamnosides. According to enzyme kinetic analysis, these compounds were potent, reversible, and mixed-type inhibitors of tyrosinase. They inhibited the enzyme activity by interacting with enzyme as well as substrates. The results of molecular docking showed that the interaction between mung bean seed proanthocyanidins and tyrosinase was driven by hydrogen bond, hydrophobic and electrostatic interactions. In addition, mung bean seed proanthocyanidins were demonstrated as powerful antioxidants. Therefore, this study confirmed a novel tyrosinase inhibitor and would lay a scientific foundation for their utilization in pharmaceutical and food industries.
Antioxidants/pharmacology , Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Proanthocyanidins/pharmacology , Vigna/chemistry , Antioxidants/chemistry , Chromatography, High Pressure Liquid/methods , Enzyme Inhibitors/chemistry , Kinetics , Molecular Docking Simulation , Molecular Structure , Monophenol Monooxygenase/chemistry , Monophenol Monooxygenase/metabolism , Proanthocyanidins/chemistry , Seeds/chemistry , Seeds/metabolism , Spectrometry, Mass, Electrospray Ionization , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
In this study, the content, structure, antityrosinase activity, and mechanism of longan bark condensed tannins were evaluated. The findings obtained from mass spectrometry demonstrated that longan bark condensed tannins were mixtures of procyanidins, propelargonidins, prodelphinidins, and their acyl derivatives (galloyl and p-hydroxybenzoate). The enzyme analysis indicated that these mixtures were efficient, reversible, and mixed (competitive is dominant) inhibitor of tyrosinase. What's more, the mixtures showed good inhibitions on proliferation, intracellular enzyme activity and melanogenesis of mouse melanoma cells (B16). From molecular docking, the results showed the interactions between inhibitors and tyrosinase were driven by hydrogen bond, electrostatic, and hydrophobic interactions. In addition, high levels of total phenolic and extractable condensed tannins suggested that longan bark might be a good source of tyrosinase inhibitor. This study would offer theoretical basis for the development of longan bark condensed tannins as novel food preservatives and medicines of skin diseases.
Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Plant Bark/chemistry , Sapindaceae/chemistry , Tannins/chemistry , Tannins/pharmacology , Animals , Anthocyanins/pharmacology , Biflavonoids/pharmacology , Catechin/pharmacology , Cell Proliferation/drug effects , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Mass Spectrometry , Melanins/analysis , Melanins/antagonists & inhibitors , Melanins/biosynthesis , Melanoma, Experimental , Mice , Models, Molecular , Molecular Docking Simulation , Oxidoreductases , Parabens/pharmacology , Proanthocyanidins/pharmacology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Static Electricity , Structure-Activity Relationship
In this study, the structure of proanthocyanidins purified from cherimoya (Annona squamosa) pericarp was analyzed by ESI-QTOF-MS and HPLC analyses. The result indicated that these compounds were procyanidin-type proanthocyanidins, consisting mainly of (epi)catechin units linked b y B-type interflavan bonds. The analyses of enzymology showed that the activities of monophenolase and diphenolase of tyrosinase could be powerfully inhibited by the proanthocyanidins. Further researches on the inhibition mechanism demonstrated that they were reversible and competitive inhibitors with the KI value of 27.1±3.1µg/mL. These inhibitors quenched the fluorescence of tyrosinase through a static quenching mechanism and spontaneously formed proanthocyanidins-enzyme complex. Fluorescence changes of proanthocyanidins in the presence of copper ion suggested that the interactions could reduce the fluorescence intensity of these polymers and the molecular docking analysis revealed that copper irons of the enzyme could be chelated by adjacent hydroxyl groups on the B ring of proanthocyanidins. Moreover, proanthocyanidins were proved to be efficient quencher of substrates. These results would lay scientific foundation for their farther application in food and medicine industry.
Annonaceae/chemistry , Enzyme Inhibitors/chemistry , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/chemistry , Proanthocyanidins/chemistry , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Fruit/chemistry , Molecular Docking Simulation , Monophenol Monooxygenase/metabolism , Proanthocyanidins/metabolism , Proanthocyanidins/pharmacology , Spectrometry, Fluorescence , Spectrometry, Mass, Electrospray Ionization
In this study, the inhibitory effect and mechanism of rifampicin on the activity of tyrosinase were investigated for developing a novel tyrosinase inhibitor. It was found to have a significant inhibition on the activity of tyrosinase (IC50=90±0.6µM). From the kinetics analysis, it was proved to be a reversible and noncompetitive type inhibitor of the enzyme with the KI value of 94±3.5µM. The results obtained from intrinsic fluorescence quenching indicated that rifampicin could interact with tyrosinase. In particular, the drastic decrease of fluorescence intensity was due to the formation of a rifampicin-enzyme complex in a static procedure which was mainly driven by hydrophobic forces and hydrogen bonding. Moreover, the ANS-binding fluorescence analysis suggested that rifampicin binding to tyrosinase changed the polarity of the hydrophobic regions. Molecular docking analysis further revealed that the hydrogen bonds were generated between rifampicin and amino residues Leu7, Ser52, and Glu107 in the B chain of the enzyme. And the hydrophobic forces produced through the interaction of rifampicin with B chain residues Pro9, Pro14, and Trp106. This work identified a novel tyrosinase inhibitor and potentially contributed to the usage of rifampicin as a potential hyperpigmentation drug.
Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Rifampin/pharmacology , Agaricales/enzymology , Enzyme Inhibitors/metabolism , Kinetics , Molecular Docking Simulation , Monophenol Monooxygenase/chemistry , Monophenol Monooxygenase/metabolism , Protein Conformation , Rifampin/metabolism
This study aimed to analyze the clinical characteristics, classification and treatment of childhood myasthenia gravis (MG) and address the prognosis through follow-up. The clinical data of 135 children with MG were grouped according to clinical type and therapeutic drugs, retrospectively analyzed and prospectively monitored. Of the 135 MG patients, 85.2% had type I (ocular type), with only 4.2% progressing to systemic MG; 13.4% had type II (general type); and 1.5% had type III (fulminating type). Relapse occurred in 46.1% of the 102 patients that were followed up. The positive rate for the primary acetylcholine receptor antibody was 40.19%, without significant differences among clinical subtypes. The positive rate of the repetitive nerve stimulation frequency test by electromyography was 37.97%. Decreased expression of CD4+, CD8+, or CD3+ was present in 71% of the patients. Thymic hyperplasia was present in 5.93% of the patients, while 1.48% had thymoma. Steroid treatment was effective in the majority of the patients. Ocular type MG was common in this cohort of patients. The incidence and mortality of myasthenia crisis were low, the presence of concurrent thymoma was rare and only a limited number of children developed neurological sequelae.
