Compound Heterozygous CHAT Gene Mutations of a Large Deletion and a Missense Variant in a Chinese Patient With Severe Congenital Myasthenic Syndrome With Episodic Apnea

Congenital myasthenic syndromes (CMSs) are a group of inherited disorders caused by genetic defects in neuromuscular junctions. Mutations in CHAT, encoding choline acetyltransferase, cause congenital myasthenic syndrome with episodic apnea (CMS-EA), a rare autosomal recessive disease characterized by respiratory insufficiency with cyanosis and apnea after infections, fever, vomiting, or excitement. To date, no studies have reported deletions comprised of multiple exons. Here, using next generation sequencing, we identified compound heterozygous mutations, namely a large maternally inherited deletion, including exons 4, 5, and 6, and a paternally inherited missense variant (c.914T>C [p.Ile305Thr]) in CHAT in a Chinese patient with a severe phenotype of CMS-EA. Furthermore, the large deletion was also validated by real-time fluorescence quantitative polymerase chain reaction. The patient was a 10-month-old boy, who presented with a weak cry and feeding difficulties soon after birth, ptosis at 4 months old, episodic apnea after fever at 9 months old, and respiratory insufficiency with cyanosis and apnea that required intubation after a respiratory tract infection at 10 months old. Unfortunately, he died in the Pediatric Intensive Care Unit soon after hospitalization. The patient’s elder sister had similar clinical manifestations, and she died prior to the age of 2 months old without a diagnosis. Genotype-phenotype correlation analysis revealed that loss-of-function mutations in exons 4–6 of CHAT might cause more severe CMS-EA. To our knowledge, this is the first study to show compound heterozygous CHAT mutations consisting of a large deletion and missense mutation in a patient with CMS-EA

The Structural Characteristics of an Acidic Water-Soluble Polysaccharide from Bupleurum chinense DC and Its In Vivo Anti-Tumor Activity on H22 Tumor-Bearing Mice

This study explored the preliminary structural characteristics and in vivo anti-tumor activity of an acidic water-soluble polysaccharide (BCP) separated purified from Bupleurum chinense DC root. The preliminary structural characterization of BCP was established using UV, HPGPC, FT-IR, IC, NMR, SEM, and Congo red. The results showed BCP as an acidic polysaccharide with an average molecular weight of 2.01 × 103 kDa. Furthermore, we showed that BCP consists of rhamnose, arabinose, galactose, glucose, and galacturonic acid (with a molar ratio of 0.063:0.788:0.841:1:0.196) in both α- and β-type configurations. Using the H22 tumor-bearing mouse model, we assessed the anti-tumor activity of BCP in vivo. The results revealed the inhibitory effects of BCP on H22 tumor growth and the protective actions against tissue damage of thymus and spleen in mice. In addition, the JC-1 FITC-AnnexinV/PI staining and cell cycle analysis have collectively shown that BCP is sufficient to induce apoptosis and of H22 hepatocarcinoma cells in a dose-dependent manner. The inhibitory effect of BCP on tumor growth was likely attributable to the S phase arrest. Overall, our study presented significant anti-liver cancer profiles of BCP and its promising therapeutic potential as a safe and effective anti-tumor natural agent

Structural Characteristic and In-Vitro Anticancer Activities of Dandelion Leaf Polysaccharides from Pressurized Hot Water Extraction

Dandelion (Taraxacum mongolicum Hand.-Mazz.) is a medicinal and edible plant. Dandelion has great development value for its health promoting benefits; additionally, Dandelion grows almost anywhere in the world. In this study, we report the structural characteristics and anti-cancer activity of novel dandelion leaf polysaccharides extracted by pressurized hot water extraction at 120 °C (DLP120) with Mw relative to dextran of 1.64 × 106 Da. Structural analysis indicated that DLP120 is a complex polysaccharide composed of pectin and arabinogalactan. It was mainly composed of arabinose (32.35 mol%) and galactose (44.91 mol%). The main glycosidic linkages of DLP120 were 4-β-D-Galp, 4-α-D-GalpA, T-β-D-Galp, 5-α-L-Araf, 3,5-α-L-Araf, and T-α-L-Araf. In vitro, DLP120 inhibited HepG2 cell proliferation in a dose-dependent manner by inducing cell apoptosis. Cell cycle detection results revealed that DLP120 mainly arrests the cell cycle in S phase. Cells treated with DLP120 displayed obvious apoptotic morphology, including cell volume shrinks and cytoskeleton breaks down. In short, DLP120 has potential as an anti-cancer agent

TRPV4 Promotes Metastasis in Melanoma by Regulating Cell Motility through Cytoskeletal Rearrangement

The abnormal expression of Transient Receptor Potential cation channel subfamily V member 4 (TRPV4) is closely related to the progression of multiple tumors. In addition, TRPV4 is increasingly being considered a potential target for cancer therapy, especially in tumor metastasis prevention. However, the biological correlation between TRPV4 and tumor metastasis, as well as the specific role of TRPV4 in malignant melanoma metastasis, is poorly understood. In this study, we aimed to examine the role of TRPV4 in melanoma metastasis through experiments and clinical data analysis, and the underlying anticancer mechanism of Baicalin, a natural compound, and its inhibitory effect on TRPV4 with in vivo and in vitro experiments. Our findings suggested that TRPV4 promotes metastasis in melanoma by regulating cell motility via rearranging the cytoskeletal, and Baicalin can inhibit cancer metastasis, whose mechanisms reverse the recruitment of activated cofilin to leading-edge protrusion and the increasing phosphorylation level of cortactin, which is provoked by TRPV4 activation

Electrochemical Fabrication of High Quality Graphene in Mixed Electrolyte for Ultrafast Electrothermal Heater

High quality graphene sheets have been considered as a promising candidate in several industrial applications due to their excellent electronic and thermal conductivity. However, the mass production of high quality graphene sheets from graphite bulk is still facing great challenges. Here we demonstrated a new approach to prepare high quality graphene by mixing a solution of oxalic acid and hydrogen peroxide as the electrolyte. The reaction did not involve the oxidation of graphite and thus exfoliated graphene possesses a uniform lateral size (2–6 μm, 78.1%), low oxygen content (2.41 at. %), few structure defects, and high conductivity of 26 692 S m^–1. The optimized mixed electrolyte is environmental friendly, cheap and safe, and most importantly it is easy to be removed through low temperature heating, which facilitates graphene purification. An electrothermal heater, made from highly concentrated graphene ink (8.5 mg mL^–1) on A4-size paper or polyester, exhibits excellent performance: a rapid rise of temperature (up to 75.2 °C) in a short time (30 s) under a low voltage of 10 V. The as-made graphene is considered as a promising material for future application of printable electronics and wearable devices

Relieving Sore Throat Formula Exerts a Therapeutic Effect on Pharyngitis through Immunoregulation and NF-κB Pathway

Relieving Sore Throat Formula (RSTF) is a formula approved by the China Food and Drug Administration and has been used for the treatment of pharyngitis in clinic for many years. However, the potential pharmacological mechanism still remains unknown. We combined multiple methods including bioinformatics data digging, network pharmacology analysis, and pathway analysis to predict the potential target of RSTF. We verified our in silico prediction results with an in vivo/vitro antibacterial effect test, mouse phagocytic index test, proliferation, transformation, and migration of mouse spleen lymphocytes. Alteration of NF-κB pathway was determined by Western blotting, immunofluorescence, and PCR. The in vivo experiments demonstrated that the RSTF could significantly relieve the symptoms of pharyngitis. A rat saliva secretion test showed that RSTF can effectively relieve the xerostomia symptom. A phenol red excretion test showed that RSTF has an eliminating phlegm effect. A hot plate method and granuloma experiment proved that RSTF also have analgesic and anti-inflammatory effects. In silico prediction demonstrates that 70 active compounds of RSTF were filtered out through ADME screening and 84 putative targets correlated with different diseases. Pathway enrichment analysis showed that the candidate targets were mostly related to the response to bacteria and immunity signalling pathways, which are known contributors to pharyngitis. Experimental results confirmed that RSTF exerted therapeutic effects on pharyngitis mainly by antibacterial effect and downregulation of NF-κB activities. It is demonstrated both in silico and in vivo/vitro that RSTF exerted therapeutic effects on pharyngitis mainly through an antibiotic effect and downregulation of NF-κB signalling pathway

Association between Serum Vitamin A, Blood Lipid Level and Dyslipidemia among Chinese Children and Adolescents

Background: To study the relationship between serum vitamin A (VA) level and blood lipid profiles in children and adolescents aged 6–18 years, as well as the effect of VA on dyslipidemia. Methods: The project adopted a multistage stratified cluster sampling method. The Food Frequency Questionnaire (FFQ) was used to obtain dietary factors data. Blood samples of subjects were taken via venipuncture. Generalized linear models were used to explore the correlation be-tween VA and biochemical indicators, as well as stratified and inter-actions analysis to explore the influence of confounders on these relationships. Generalized linear models were constructed to explore the association between VA and blood lipids. Restricted cubic splines were used to characterize dose–response associations between serum VA and dyslipidemia based on logistic regression. Results: Serum VA was positively correlated with TC, TG and HDL-C (p p p p < 0.01). Conclusion: Serum VA was positively correlated with blood lipids, but these associations were influenced by age. VA was a risk factor for dyslipidemias, such as hypercholesterolemia, hypertriglyceridemia and mixed hyperlipidemia, but was a protective factor for low high-density lipoprotein cholesterolemia