Successful treatment of thrombotic thrombocytopenic purpura with plasmapheresis and anti-CD20 antibodies in a patient with immune thrombocytopenia and systemic lupus erythematosus: Case report

Rationale:Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology with diverse clinical and laboratory manifestations, including thrombocytopenia. About 25% of patients with SLE may be affected by thrombocytopenia, many of whom are asymptomatic. Some patients, however, experience platelet counts that drop quite low and predispose them to bleeding. Thrombotic thrombocytopenic purpura (TTP) is defined with a classic pentad of clinical features, such as thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms and signs, renal symptoms and signs, and fever. The association of TTP and SLE has been sporadically reported in the literature.Patient concerns and diagnosis:We describe a 16-year-old girl with SLE and immune thrombocytopenia, in whom TTP was diagnosed.Interventions and outcomes:She was treated with pulse methylprednisolone, whose platelet counts normalized after therapy with plasmapheresis and an anti-CD20 monoclonal antibody (rituximab).Conclusion:A pediatric patient with SLE and immune thrombocytopenia in whom TTP developed was treated with plasmapheresis and rituximab therapy successfully, though the patient experienced a disease relapsed after 18 months, which was controlled by the same management.     

Integrative treatment of herbal medicine with western medicine on coronary artery lesions in children with Kawasaki disease

Background:Kawasaki disease (KD) is a major cause of coronary artery lesions (CALs) in children. Approximately 10% to 20% of children treated with intravenous immunoglobulin are intravenous immunoglobulin-resistant. This study evaluated the efficacy and safety of adding herbal medicine to conventional western medicines versus conventional western medicines alone for CALs in children with KD.Methods:This study searched 9 electronic databases until August 31, 2021. The inclusion criteria were the randomized controlled trials (RCTs) that assessed the CALs in children with KD and compared integrative treatment with conventional western treatments. Two authors searched independently for RCTs, including eligible articles that fulfilled the inclusion criteria, extracted data, and assessed the methodological quality using the Cochrane risk of bias tool. Meta-analysis was conducted using Cochrane Collaboration''s Review Manager 5.4 software. The effect size was presented as the risk ratio (RR), and the fixed-effect models were used to pool the results.Results:The finally selected 12 studies included a total of 1030 KD patients. According to a meta-analysis, the integrative treatment showed better results than the conventional treatment in the CAL prevalence rate (RR = 2.00; 95% confidence interval [CI], 1.49–2.71; P < .00001), CAL recovery rate (RR = 1.27; 95% CI, 1.05–1.54; P = .02), and total effective rate (RR = 1.17; 95% CI, 1.11–1.23; P < .00001). Only 2 studies referred to the safety of the treatment. The asymmetrical funnel plot of the CAL prevalence rate indicated the possibility of potential publication bias.Conclusions:This review found the integrative treatment to be more effective in reducing the CAL prevalence rate and increasing the CAL recovery rate and total effective rate in KD patients than conventional western treatment. However, additional well-designed RCTs will be needed further to compensate restrictions of insufficient trials on safety, methodological quality, and publication bias.     

β-Sitosterol Attenuates Dexamethasone-Induced Muscle Atrophy via Regulating FoxO1-Dependent Signaling in C2C12 Cell and Mice Model

Sarcopenia refers to a decline in muscle mass and strength with age, causing significant impairment in the ability to carry out normal daily functions and increased risk of falls and fractures, eventually leading to loss of independence. Maintaining protein homeostasis is an important factor in preventing muscle loss, and the decrease in muscle mass is caused by an imbalance between anabolism and catabolism of muscle proteins. Although β-sitosterol has various effects such as anti-inflammatory, protective effect against nonalcoholic fatty liver disease (NAFLD), antioxidant, and antidiabetic activity, the mechanism of β-sitosterol effect on the catabolic pathway was not well known. β-sitosterol was assessed in vitro and in vivo using a dexamethasone-induced muscle atrophy mice model and C2C12 myoblasts. β-sitosterol protected mice from dexamethasone-induced muscle mass loss. The thickness of gastrocnemius muscle myofibers was increased in dexamethasone with the β-sitosterol treatment group (DS). Grip strength and creatine kinase (CK) activity were also recovered when β-sitosterol was treated. The muscle loss inhibitory efficacy of β-sitosterol in dexamethasone-induced muscle atrophy in C2C12 myotube was also verified in C2C12 myoblast. β-sitosterol also recovered the width of myotubes. The protein expression of muscle atrophy F-box (MAFbx) was increased in dexamethasone-treated animal models and C2C12 myoblast, but it was reduced when β-sitosterol was treated. MuRF1 also showed similar results to MAFbx in the mRNA level of C2C12 myotubes. In addition, in the gastrocnemius and tibialis anterior muscles of mouse models, Forkhead Box O1 (FoxO1) protein was increased in the dexamethasone-treated group (Dexa) compared with the control group and reduced in the DS group. Therefore, β-sitosterol would be a potential treatment agent for aging sarcopenia.     

Stretchable and Conductive Cellulose/Conductive Polymer Composite Films for On-Skin Strain Sensors

Conductive composite materials have attracted considerable interest of researchers for application in stretchable sensors for wearable health monitoring. In this study, highly stretchable and conductive composite films based on carboxymethyl cellulose (CMC)-poly (3,4-ethylenedioxythiopehe):poly (styrenesulfonate) (PEDOT:PSS) (CMC-PEDOT:PSS) were fabricated. The composite films achieved excellent electrical and mechanical properties by optimizing the lab-synthesized PEDOT:PSS, dimethyl sulfoxide, and glycerol content in the CMC matrix. The optimized composite film exhibited a small increase of only 1.25-fold in relative resistance under 100% strain. The CMC-PEDOT:PSS composite film exhibited outstanding mechanical properties under cyclic tape attachment/detachment, bending, and stretching/releasing tests. The small changes in the relative resistance of the films under mechanical deformation indicated excellent electrical contacts between the conductive PEDOT:PSS in the CMC matrix, and strong bonding strength between CMC and PEDOT:PSS. We fabricated highly stretchable and conformable on-skin sensors based on conductive and stretchable CMC-PEDOT:PSS composite films, which can sensitively monitor subtle bio-signals and human motions such as respiratory humidity, drinking water, speaking, skin touching, skin wrinkling, and finger bending. Because of the outstanding electrical properties of the films, the on-skin sensors can operate with a low power consumption of only a few microwatts. Our approach paves the way for the realization of low-power-consumption stretchable electronics using highly stretchable CMC-PEDOT:PSS composite films.     

Identification and characterization of antioxidants from Sophora flavescens

The objectives of this study were to investigate the radical-scavenging activity and protective potential of Sophora flavescens from oxidative damage by the radical generator 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) in renal epithelial LLC-PK(1) cells and to identify the active components using the bioassay-linked fractionation method. The MeOH extract and fractions of CH(2)Cl(2), BuOH, and H(2)O from S. flavescens showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging effects in a dose-dependent manner (p<0.01),whereas only the BuOH and CH(2)Cl(2) fractions showed protective effects against LLC-PK(1) cellular damage induced by AAPH in a dose-dependent manner (p<0.01). In particular, the BuOH fraction had the most effective (p<0.05) antioxidative capacity. Employing a bioassay-linked HPLC/MS method, the active constituents from the BuOH fraction of S. flavescens were isolated and characterized as sophoraflavanone G and kurarinone with potent antioxidant effects against the DPPH radical, with IC(50) values of 5.26 and 7.73 microg/ml, respectively. Moreover, the compounds dose dependently recovered cell viability decreased by AAPH treatment (p<0.01), suggesting their protective roles against cellular oxidative damage. The results of this study suggest that S. flavescens has excellent antioxidative and kidney-protective potential and that flavonoids from S. flavescens, i.e., sophoraflavanone G and kurarinone, are the active constituents.     

Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-α-stimulated monocytes to endothelial cells and suppressed the TNF-α induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the TNF-α-induced nuclear factor-κB activation, which was attenuated by pretreatment with N^G-nitro-l-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease.     

Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development,hepatic mRNA expression,thyroid hormone levels,and circulating bile acid concentrations in chicken embryos

The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highest doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism.     

Cyslabdan, a new potentiator of imipenem activity against methicillin-resistant Staphylococcus aureus, produced by Streptomyces sp. K04-0144. I. Taxonomy, fermentation, isolation and structural elucidation

Cyslabdan, a new potentiator of imipenem activity against methicillin-resistant Staphylococcus aureus, was isolated from the culture broth of Streptomyces sp. K04-0144 by Diaion HP-20 and ODS column chromatographies and preparative HPLC. The structure of cyslabdan was elucidated by spectroscopic analyses including NMR. The compound has a labdane-type diterpene skeleton connecting with an N-acetylcysteine via thioether linkage.     

Pharmacokinetics and pharmacodynamics of intravenous trasemide in mutant Nagase analbuminemic rats

The importance of plasma protein binding of intravenous furosemide in circulating blood for its urinary excretion and hence its diuretic effects in mutant Nagase analbuminemic rats (NARs, an animal model for human familial analbuminemia) was reported. Based on the furosemide report, the diuretic effects of another loop diuretic, torasemide, could be expected in NARs if plasma protein binding of torasemide is considerable in the rats. This was proven by this study. After intravenous administration of torasemide, 10 mg/kg, to NARs, the plasma protein binding of torasemide was 23.3% in the rats due to binding to alpha- and beta-globulins (this value, 23.3%, was greater than only 12% for furosemide), and hence the percentages of intravenous dose of torasemide excreted in 8-h urine as unchanged drug was 14.9% in the rat (this value was considerably greater than only 7% for furosemide). After intravenous administration of torasemide to NARs, the AUC (301 versus 2680 microg/min/ml) was significantly smaller [due to significantly faster both Cl(r) (4.81 versus 0.386 ml/min/kg) and Cl(nr) (28.3 versus 3.33 ml/min/kg)], terminal half-life (18.3 versus 73.5 min) and mean residence time (6.97 versus 61.8 min) were significantly shorter (due to faster Cl, 33.2 versus 3.74 ml/min/kg), and amount of 8-h urinary excretion of unchanged torasemide (446 versus 323 microg, due to increase in intrinsic renal excretion) was significantly greater than those in control rats. The 8-h urine output and 8-h urinary excretions of sodium and chloride were comparable between two groups of rats although the 8-h urinary excretion of torasemide was significantly greater in NARs. This could be explained by the following. The amount of urinary excretion of torasemide was significantly greater in NARs than that in control rats only between 0 and 30 min urine collection. In both groups of rats, the urinary excretion rate of torasemide during 0-30 min reached an upper plateau with respect to urine flow rate as well urinary excretion rates of sodium and chloride. Therefore, the diuretic effects (8-h urine output and 8-h urinary excretions of sodium and chloride) were not significantly different between the two groups of rats.