Etanercept treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe cutaneous adverse reaction to drugs with considerable morbidity and mortality. Immunomodulators for SJS/TEN including systemic corticosteroids and intravenous immunoglobulin (IVIG) have been widely used in clinical practice. Emerging evidence suggested the therapeutic effects of tumor necrosis factor-α antagonists on SJS/TEN. OBJECTIVE: To compare the efficacy and safety of IVIG and systemic steroids in conjunction with or without etanercept, a tumor necrosis factor-α inhibitor, for patients with SJS/TEN. METHODS: We undertook a retrospective review of 41 patients with SJS/TEN admitted to our institution from 2015 to February 2021. A total of 25 patients with integrated data were involved in this study, of which 14 patients were treated with IVIG and corticosteroids and 11 were in addition given etanercept. The clinical characteristics, duration of hospitalization, exposure time to high-dose steroids, and the total amount of systemic steroids were analyzed. RESULTS: In comparison to conventional therapy, conjunction with etanercept reduced the duration of hospitalization (13.5 vs 19.0 days; P = .01), the exposure time of high-dose steroids (7.1 vs 14.9 days; P = .01), and the overall amount of systemic steroid (925 mg vs 1412.5 mg; P = .03) in patients with SJS/TEN. No pronounced adverse effects were observed within 6 months of follow-up after the treatment. CONCLUSION: The add-in of etanercept at the time of initiating conventional therapy could be a superior option to accelerate disease recovery and reduce the high dose and total amount of systemic steroids without pronounced adverse events in patients with SJS/TEN.

Aetiology of superficial fungal infections of the foot in urban outpatients in mainland China: A multicentre, prospective case study.

BACKGROUND: In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large-scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking. OBJECTIVES: To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent. METHODS: The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory. RESULTS: Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus. CONCLUSION: This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.

Effect of Gpx3 gene silencing by siRNA on apoptosis and autophagy in chicken cardiomyocytes.

Glutathione peroxidase 3 (Gpx3), as an important selenoprotein, is the most crucial antioxidant defense in cardiomyocytes. However, the role of Gpx3 in Se-deficient cardiomyocyte damage still less reported. Here, we developed Gpx3 silence cardiomyocytes culture model (small interfering RNA; siRNA) for research the crosstalk between autophagy and apoptosis. Quantitative real-time PCR and western blot analysis are performed to detect the expression of apoptosis and autophagy-related genes. MDC stain, flow cytometry, AO/EB stain, and electron microscope were performed to observe the changes of cell morphology. Our results reveal that Gpx3 suppression can significant increases in ROS (p < 0.05) levels, which further induced apoptosis through upregulated the expression of Caspase-3 in cardiomyocytes. Meanwhile, we also found that the whole process is accompanied by the occurrence of autophagy, which are promoted by inhibiting the mTOR, and increasing the expression of ATG-7, ATG-10, and ATG-12. Altogether, we conclude that the apoptotic and autophagic response machineries share antagonistic function in Gpx3 knockdown cardiomyocytes.

Edible plant extracellular vesicles: An emerging tool for bioactives delivery.

The extracellular vesicles (EVs) in edible food have a typical saucer-like structure and are nanoparticles released by numerous cells. They have different components and interact with other biological samples in diverse ways. Therefore, these nanoparticles could be used to develop bioactives delivery nanoplatforms and anti-inflammatory treatments to meet the stringent demands of current clinical challenges. This review aims to summarize current researches into EVs from edible plants, particularly those that can protect siRNAs or facilitate drug transportation. We will discuss their isolation, characterization and functions, their regulatory effects under various physiological and pathological conditions, and their immune regulation, anti-tumor, regeneration, and anti-inflammatory effects. We also review advances in their potential application as bioactives carriers, and medicinal and edible plants that change their EVs compositions during disease to achieve a therapy propose. It is expected that future research on plant-derived EVs will considerably expand their application.

Study of Ag precipitation and mechanical properties of Ti-Ta-Ag ternary alloy.

Ti-25Ta-xAg alloy samples with different content of Ag were prepared by spark plasma sintering method. X-ray diffraction, microscopic metallographic, scanning electron microscopy, and transmission electron microscopy were used to analyze the phase structure and morphology of the alloy samples. Ti-Ta-Ag can form a stable ternary alloy system. Furthermore, with the increase of Ag content and sintering temperature, Ag will be precipitated at the grain boundary. In order to explore the precipitation mechanism of Ag in the alloy and its influence on the mechanical properties, the crystal structure, electronic structure, and elastic constant under different Ag solid solubility were calculated systematically by using first-principles calculations. The results show that the critical temperature of Ag in Ti-Ta-Ag ternary alloy is about 2200 K, and the high temperature is favorable for the aging precipitation of Ag. The lattice constants and mechanical properties of (Ti1-x Ag x )3Ta solid solution suddenly change when the Ag solid solubility x value is equal to 0.8, and their changes will follow different rules. The internal mechanism of this phenomenon is that the 4d10 electronic states of Ag have changed from obvious local electronic states to mixed local and non-local electronic states. These results provide theoretical guidance for the application of Ti-Ta-Ag ternary alloys in biomedicine.

Effect of Ag alloying and trace precipitation on corrosion resistance of Ti-Ta-Ag ternary alloy.

This work systematically analysed the electrochemical and corrosion behaviour of Ti-Ta-Ag ternary alloy samples in Hank's solution. For the samples with 1.5% and 3% Ag content, the sintering temperature increased from 750 to 950°C, and the corresponding corrosion resistance increased by 100 times due to the increased alloying of Ag; meanwhile for the sample with 4.5% Ag content, the sintering temperature increased from 750 to 950°C, and the corresponding corrosion resistance decreased by six times due to the increased precipitation of Ag. These tests prove that the Ag alloying is beneficial to the enhancement of the corrosion resistance of Ti-Ta-Ag ternary alloy, but the Ag trace precipitation has the opposite effect. A series of electrochemical characterizations and density functional theory calculations explain the mechanism of the above phenomenon. Ag alloying can promote the formation of uniform, complete, dense, stable and thick passivation layer on the surface of Ti-Ta-Ag ternary alloy, which makes Ti-Ta-Ag ternary alloy uniformly corroded without pitting. In addition, Ag alloying can effectively reduce the contact resistance of the solid-liquid interface. However, the trace precipitation of Ag plays the opposite role to the above effect.

[Relationships of three microsatellite loci with GSH-Px, SOD and Na+/K+-ATP enzyme activities and daily milk yield in different seasons in Holstein cows].

Genetic variation of three microsatellite loci BMS2258, SOD1, and BM723, which were closely correlated with GSH-Px, SOD, and Na+/K+-ATPase genes, was analyzed in 130 Holstein cows by PCR and nondenaturing polyacrylamide gel-electrophoresis. Polymorphic information content, effective number of alleles and heterozygosity of these microsatellite loci were determined. Relationships of the three microsatellite loci with enzyme activities and daily milk yields in Holstein cows were analyzed by least squares linear model. The results showed significant correlations of the three microsatellite loci with their corresponding enzyme activities and daily milk yield in summer and fall (Plt;0.05). The least square means of GSH-Px activities and daily milk yields for BMS2258 (182 bp/164 bp), SOD activities for SOD1 (148 bp/148 bp), and daily milk yields for SOD1 (148 bp/146 bp), Na+/K+-ATPase activities and daily milk yields for BM723 (161 bp/111 bp) were relatively higher. These genotypes were the most favorable genotypes for enzyme activity and daily milk yields in summer and fall, which could be references for marker assisted selection in heat resistance traits in dairy cattle.

[Study on the chemical constituents from pine needles of Cedrus deodara].

OBJECTIVE: To study the chemical constituents from pine needles of Cedrus deodara. METHODS: Chemical constituents were isolated by silica gel and Sephadex LH-20 column chromatography. The structures of the isolated compounds were elucidated through spectroscopic analysis. RESULTS: The compounds were identified as 9-hydroxy-dodecanoic acid (I), ethyl laurate (II), ethyl stearate (III), 3beta-hydroxy-oleanolic acid methyl ester (IV), beta-sitosterol (V), shikimic acid (VI), methylconiferin (VII), ferulic acid beta-glucoside (VIII). CONCLUSION: Compounds I-IV, VI-VIII are isolated and identified from this genus for the first time, compound V is isolated from pine needles of this genus for the first time.

[Studies on the chemical constituents from pine needles of Cedrus deodara (II)].

OBJECTIVE: To study the chemical constituents from pine needles of Cedrus deodara. METHODS: Chemical constituents were isolated from 95% ethanol extract by silica gel and Sephadex LH-20 column chromatography. The structures were elucidated through spectroscopic analysis. RESULTS: The compounds were identified as 10-nonacosanol (1), dibutyl phthalate (2), protocatechuic acid (3), phthalic acid bis-(2-ethylhexyl) ester (4), (E)-1-O-p-coumaroyl-beta-D-glucopyranoside (5), 5-p-trans-coumaroylguinic acid (6). CONCLUSIONS: Compounds 1- 6 are obtained from this genus for the first time.

Synergistic effects of terbinafine and itraconazole on clinical isolates of Fonsecaea monophora.

Our objective was to develop new approaches to the chemotherapy of invasive infections caused by Fonsecaea monophora. The in vitro effects of a combination of terbinafine with itraconazole on 18 clinical isolates were evaluated using a checkerboard microdilution method. The mode of interaction between the two drugs on the 18 isolates was analyzed using fractional inhibitory concentration index (FICI) analysis. FICI analysis demonstrated that 12 (67%) were synergistic, 4 (22%) were additive, and 2 (11%) were indifferent, with no antagonism being observed. The minimal inhibitory concentrations (MICs) obtained with the terbinafine-itraconazole combination were within levels that can be achieved in plasma at clinically relevant doses. Our results indicate the terbinafine-itraconazole combination may be an effective therapy for Fonsecaea monophora infection, which should be tested in clinical setting with patients with this disease.

Pseudomembranous-like tinea of the scrotum: report of six cases.

Six cases of tinea of the scrotum with atypical clinical features were observed in the dermatology department of our hospital between 2001 and 2007. The age of onset ranged from 14 to 26 years. Unusual clinical presentations of pseudomembranous-like disease were observed in every patient. Causative agents were Microsporum gypseum in five patients and Trichophyton rubrum in one patient. Three of the M. gypseum isolates had atypical morphologies. All six isolates were identified by cultural morphologies and DNA sequence analysis of the internal transcribed spacer region of the ribosomal DNA.

Botulinum Toxin A Injection for Treatment of Chronic Skin Ulcer: A Case Series and Literature Review.

Chronic skin ulcer (CSU) often combines with a variety of refractory factors that respond poorly to routine treatments. Botulinum toxin A (BTX-A) can be injected subcutaneously to improve the local blood supply, to reduce pain, and to promote wound healing. At present, few reports have mentioned BTX-A injection for chronic skin ulcer treatment. We observed the effect of four cases that used BTX-A to treat CSU and provided a brief review of the literature. Four cases of CSUs with 4 different causes were treated with BTX-A injection (4 U/cm2). The specific operation is as follows: local, multipoint, cyclic, equidistant, and subcutaneous injections with a depth of 6 to 8 mm. The ulcer area was significantly reduced. Subsequently, the ulcer healed within 20 to 48 days. Botulinum toxin A is recommended as an important treatment for chronic skin ulcer that can improve healing of skin ulcers with various etiologies.

Isolation, Identification, and Activity Evaluation of Chemical Constituents from Soil Fungus Fusarium avenaceum SF-1502 and Endophytic Fungus Fusarium proliferatum AF-04.

Fusarium, a large genus of filamentous fungi, is widely distributed in soil and plants. Fusarium is a prolific source of novel chemical constituents with various bioactivities. In search for antibiotics from soil and endophytic fungi, the secondary metabolites of Fusarium avenaceum SF-1502 and Fusarium proliferatum AF-04 were investigated. An alkaloid (1), a depsipeptide (6), and five sesquiterpenoids (7-11) were isolated from the extracts of the soil fungus F. avenaceum SF-1502. Three alkaloids (2-4), a depsipeptide (5), three sesquiterpenoids (9, 11, and 12), a sesterterpene (13), and four 1,4-naphthoquinones (14-17) were also separated from the extract of the green Chinese onion derived fungus F. proliferatum AF-04. Fusaravenin (1) represents the first example of a natural naphthoisoxazole-type zwitter-ionic alkaloid, a naphthoisoxazole formic acid connected with a morpholino carbon skeleton. Cyclonerotriol B (7) is a new cyclonerane sesquiterpene. Another new sesquiterpene, 3ß-hydroxy-ß-acorenol (12), possesses an acorane framework. The known compounds 9 and 11 were found from both fungi. The structures of the new compounds were determined via extensive HR-ESI-MS and comparison between experimental and calculated NMR results. The biological properties of 1-5 and 7-17 were evaluated against eight anthropogenic bacteria, while 1 and 7-11 were also screened for inhibitory effects against four plant pathogen bacteria. The known compounds 8, 9, and 14-17 showed potent antibacterial activities toward some of the tested anthropogenic bacteria.

Asymmetric organocatalytic double-conjugate addition of malononitrile to dienones: efficient synthesis of optically active cyclohexanones.

9-Amino-9-deoxyepiquinine efficiently catalyzed the double-conjugate addition of malononitrile to dienones. A number of 1,1,2,6-tetrasubstituted cyclohexanones were prepared in good yields, diastereoselectivities, and excellent enantioselectivities.

Rapid identification and characterization of Penicillium marneffei using multiplex ligation-dependent probe amplification (MLPA) in paraffin-embedded tissue samples.

Penicillium marneffei infection is a deadly disease and early diagnosis leads to prompt and appropriate antifungal therapy. To develop a sensitive method to diagnose P. marneffei infection, a multiplex ligation-dependent probe amplification (MLPA) assay was adapted. This method can rapidly and specifically detect P. marneffei DNA in cultured cells and paraffin-embedded tissue samples. Three pairs of probes were designed for amplifying the internally (intergenic) transcribed spacer (ITS) region of P. marneffei rRNA using a systematic phylogenetic analysis. These three probe sets produced three amplicons of 198, 166, and 152 bp, respectively, specific for P. marneffei. In contrast, there was only one 198 bp amplicon produced for Talaromyces stipitatus, and one 152 bp amplicon for P. funiculosum, T. intermedius and T. derxii. The probes did not amplify any other reference strains. An array of 40 P. marneffei strains isolated from human patients, bamboo rat, and the local environment was tested by using MLPA, and all were positively identified. Most importantly, P. marneffei in paraffin-embedded tissue specimens from infected human patients was positively amplified by MLPA. The sensitivity and specificity of the MLPA assay could be a useful tool for prompt diagnosis, pathogen characterization, and epidemiological studies of fungal infections.

A high-power versatile wireless power transfer for biomedical implants.

Implantable biomedical actuators are highly desired in modern medicine. However, how to power up these biomedical implants remains a challenge since most of them need more than several hundreds mW of power. The air-core based radio-frequency transformer (two face-to-face inductive coils) has been the only non-toxic and non-invasive power source for implants for the last three decades [1]. For various technical constraints, the maximum delivered power is limited by this approach. The highest delivered power reported is 275 mW over 1 cm distance [2]. Also, the delivered power is highly vulnerable to the coils' geometrical arrangement and the electrical property of the medium around them. In this paper, a novel rotating-magnets based wireless power transfer that can deliver ∼10 W over 1 cm is demonstrated. The delivered power is significantly higher than the existing start-of-art. Further, the new method is versatile since there is no need to have the impedance matching networks that are highly susceptible to the operating frequency, the coil arrangement and the environment.

[Inhibitory effect of dexamethasone on myeloid differentiation factor 88 and tumor necrosis factor-alpha expressions in mouse peritoneal macrophages].

OBJECTIVE: To study the inhibitory effect of dexamethasone (DEX) on myeloid differentiation factor 88 (MyD88) and tumor necrosis factor-alpha (TNF-alpha) expression in mouse peritoneal macrophages in innate immune response to Penicillium marneffei (PM). METHODS: Mouse peritoneal macrophages were cultured in the presence of heat-inactivated yeast-phase PM with or without DEX, and the protein and mRNA expressions of MyD88 in the macrophages were detected using Western blotting and real-time PCR, respectively. TNF-alpha in the cell culture supernatant was measured with enzyme-linked immunosorbent assay. RESULTS: DEX suppressed TNF-alpha production by the macrophages co-cultured with PM. The expressions of MyD88 were up-regulated by PM stimulation, whose effect was inhibited by the application of DEX. CONCLUSION: The inhibitory effect of DEX on PM-induced proinflammatory responses of the macrophage is directly associated with the inhibition of MyD88 expression.

Highly enantioselective synthesis of nitrocyclopropanes via organocatalytic conjugate addition of bromomalonate to alpha,beta-unsaturated nitroalkenes.

Highly enantioselective synthesis of nitrocyclopropanes was achieved via the organocatalytic conjugate addition of dimethyl bromomalonate to nitroalkenes and the consequent intramolecular cyclopropanation. 6'-Demethyl quinine was found to be the efficient catalyst. Excellent enantioselectivities, diastereoselectivities, and good yields were obtained for a variety of aryl or heteroaryl nitroethylenes.

[Differential expression of isocitrate lyase in P. marneffei phagocytized by nonstimulated and stimulated murine macrophages].

OBJECTIVE: To investigate the differential expression of isocitrate lyase in Penicillium marneffei phagocytized by nonstimulated and stimulated murine macrophages, and explore the role of glyoxylate pathway in pathogenesis of Penicilliosis marneffei. METHODS: Penicillium marneffei conidia and Raw264.7 cells were incubated in 16 cultures, which were divided to 4 groups for treatment with N-monomethyl-L-arginine (LNMMA, CI group), murine interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS) (T group), IFN-gamma plus LPS and LNMMA (TI group), or the same volume of culture medium (C group). The transcriptional levels of isocitrate lyase were detected using real-time RT-PCR, and its expression levels detected biochemically. RESULTS: The transcriptional levels of isocitrate lyase in C, CI, T, TI groups were 1.00, 1.42, 33.09, and 74.88 (P<0.05), while the expression levels were 0.06, 0.07, 0.18, and 0.93, respectively (P<0.05). The content of nitric oxide in T group was significantly higher than that in the other groups (P<0.01), but the CFU of T group was the lowest (P<0.01). CONCLUSION: Reactive nitrogen intermediates induced by stimulated murine macrophages restrain the expression of isocitrate lyase of Penicillium marneffei and development of Penicillium marneffei, in which process the glyoxylate pathway may play an important role.