ABSTRACT
Polytetrafluoroethylene (PTFE) is prized for its unique properties in electrical applications, but its natural hydrophobicity poses challenges as it repels water and can cause electrical short circuits, shortening equipment lifespan. In this work, the mentioned issue has been tackled by using two different fluorinated compounds, such as perfluorooctanoic acid (PFOA)/perfluorooctanol (PFOL), along with plasma processing to enhance the surface hydrophilicity (water attraction) of PTFE. This method, demonstrated on Teflon membrane, quickly transformed their surfaces from hydrophobic to hydrophilic in less than 30 s. The treated films achieved a water contact angle saturation of around 80°, indicating a significant increase in water affinity. High-resolution C 1s X-ray photoelectron spectroscopy (XPS) confirmed the formation of new bonds, such as -COOH and -OH, on the surface, responsible for enhanced hydrophilicity. Extended plasma treatment led to further structural changes, evidenced by increased intensity in infrared (IR) and Raman spectra, particularly sensitive to vibrations associated with the C-F bond. Moreover, Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR) showed the formation of surface-linked functional groups, which contributed to the improved water attraction. These findings decisively show that treatment with fluoro-compound along with plasma processing can be considered as a highly effective and rapid method for converting PTFE surfaces from hydrophobic to hydrophilic, facilitating its broader use in various electrical applications.
ABSTRACT
A cultural change in medicine has placed a renewed focus on the importance of a diverse and inclusive healthcare workforce. The methods employed by anesthesiology departments in pursuit of diversity and inclusion needs to be examined. OBJECTIVE: This study's objective was to assess the frequency of established leadership infrastructures and initiatives that promote diversity and inclusion within academic anesthesiology departments. DESIGN: This was a cross-sectional survey study. The authors emailed an electronic survey to 98 academic anesthesiology departments to assess leadership roles, dissemination platforms and initiatives used to support diversity and inclusion. SETTING: Academic anesthesiology department in the United States with at least 60 residents. MAIN OUTCOME AND MEASURES: The measure tested was the existence and quantification of leadership roles and initiatives directed at diversity and inclusion efforts at academic anesthesiology departments. RESULTS: The survey response rate was 49.4% (95% CI 39.3-59.6%). While 62.5% (95% CI 47.0-75.8%) of respondents reported having faculty members with a diversity and inclusion role, only 27.5% (95% CI 16.1-42.8%) reported a clearly defined leadership role such as vice-chair or committee chair. Seventy percent of respondents reported initiatives geared towards diversity using multiple platforms to showcase these initiatives. CONCLUSIONS: Based on these survey results, many anesthesia departments have developed initiatives to promote their departmental diversity. However, only a minority have established clearly defined leadership roles, which may be critical to enhance departmental success in promoting diversity and inclusion.
Subject(s)
Anesthesiology , Leadership , Cross-Sectional Studies , Cultural Diversity , Faculty , Humans , United StatesABSTRACT
Cellular heterogeneity is a major cause of treatment resistance in cancer. Despite recent advances in single-cell genomic and transcriptomic sequencing, it remains difficult to relate measured molecular profiles to the cellular activities underlying cancer. Here, we present an integrated experimental system that connects single cell gene expression to heterogeneous cancer cell growth, metastasis, and treatment response. Our system integrates single cell transcriptome profiling with DNA barcode based clonal tracking in patient-derived xenograft models. We show that leukemia cells exhibiting unique gene expression respond to different chemotherapies in distinct but consistent manners across multiple mice. In addition, we uncover a form of leukemia expansion that is spatially confined to the bone marrow of single anatomical sites and driven by cells with distinct gene expression. Our integrated experimental system can interrogate the molecular and cellular basis of the intratumoral heterogeneity underlying disease progression and treatment resistance.
Subject(s)
Single-Cell Analysis/methods , Transcriptome/genetics , Animals , Cell Adhesion/genetics , Cell Adhesion/physiology , Cells, Cultured , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , DNA Barcoding, Taxonomic , Humans , Mice , Sequence Analysis, RNAABSTRACT
BACKGROUND: Recently, monoclonal-antibody-conjugated immunomagnetic separation (IMS) procedure combined with quantitative reverse transcription-polymerase chain reaction (qRT-PCR) has been used for quantifying non-cultivated human noroviruses (HuNoVs). METHODS: We examined the efficacy of 27 commercially available disinfectants and a prototype against GII.4 strain HuNoV through the IMS/qRT-PCR assay. RESULTS: The average log reduction in viral titer in vitro varied among the disinfectants. The prototype was the most effective with an average log reduction of 6.86 log. CONCLUSIONS: The IMS/RT-qPCR assay is an effective method to evaluate the activities of disinfectants against GII.4 HuNoV in vitro. Further work is needed to enhance the virucidal activity of the prototype disinfectant against more resistant HuNoV strains.
Subject(s)
Disinfectants/pharmacology , Immunomagnetic Separation/methods , Norovirus/drug effects , Real-Time Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , Humans , Norovirus/genetics , Norovirus/isolation & purification , Viral Load , Virus InactivationABSTRACT
Tibial nerve stimulation (TNS) is one of the neuromodulation methods used to treat an overactive bladder (OAB). However, the treatment mechanism is not accurately understood owing to significant differences in the results obtained from animal and clinical studies. Thus, this study was aimed to confirm the response of bladder activity to the different stimulation frequencies and to observe the duration of prolonged post-stimulation inhibitory effects following TNS. This study used unanesthetized rats to provide a closer approximation of the clinical setting and evaluated the changes in bladder activity in response to 30 min of TNS at different frequencies. Moreover, we observed the long-term changes of post-stimulation inhibitory effects. Our results showed that bladder response was immediately inhibited after 30 min of 10 Hz TNS, whereas it was excited at 50 Hz TNS. We also used the implantable stimulator to observe a change in duration of the prolonged post-stimulation inhibitory effects of the TNS and found large discrepancies in the time that the inhibitory effect lasted after stimulation between individual animals. This study provides important evidence that can be used to understand the neurophysiological mechanisms underlying the bladder inhibitory response induced by TNS as well as the long-lasting prolonged post-stimulation effect.
Subject(s)
Electric Stimulation Therapy/methods , Tibial Nerve/physiology , Urinary Bladder, Overactive/therapy , Urinary Bladder/innervation , Urination/physiology , Animals , Female , Muscle Contraction , Rats , Rats, Sprague-Dawley , Reflex , Urinary Bladder, Overactive/physiopathologyABSTRACT
Gut microbes play diverse roles in modulating host fitness, including longevity; however, the molecular mechanisms underlying their mediation of longevity remain poorly understood. We performed genome-wide screens using 3,792 Escherichia coli mutants and identified 44 E. coli mutants that modulated Caenorhabditis elegans longevity. Three of these mutants modulated C. elegans longevity via the bacterial metabolite methylglyoxal (MG). Importantly, we found that low MG-producing E. coli mutants, Δhns E. coli, extended the lifespan of C. elegans through activation of the DAF-16/FOXO family transcription factor and the mitochondrial unfolded protein response (UPRmt). Interestingly, the lifespan modulation by Δhns did not require insulin/insulin-like growth factor 1 signaling (IIS) but did require TORC2/SGK-1 signaling. Transcriptome analysis revealed that Δhns E. coli activated novel class 3 DAF-16 target genes that were distinct from those regulated by IIS. Taken together, our data suggest that bacteria-derived MG modulates host longevity through regulation of the host signaling pathways rather than through nonspecific damage on biomolecules known as advanced glycation end products. Finally, we demonstrate that MG enhances the phosphorylation of hSGK1 and accelerates cellular senescence in human dermal fibroblasts, suggesting the conserved role of MG in controlling longevity across species. Together, our studies demonstrate that bacteria-derived MG is a novel therapeutic target for aging and aging-associated pathophysiology.
Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans , Forkhead Transcription Factors/metabolism , Longevity/drug effects , Protein Serine-Threonine Kinases/metabolism , Pyruvaldehyde , Animals , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/microbiology , Escherichia coli/metabolism , Gastrointestinal Microbiome/physiology , Mechanistic Target of Rapamycin Complex 2/metabolism , Models, Biological , Pyruvaldehyde/metabolism , Pyruvaldehyde/pharmacology , Signal Transduction/drug effects , Transcriptome/geneticsABSTRACT
Severe fever with thrombocytopenia syndrome (SFTS) is being reported annually in South Korea since its first detection there in 2010. The causal agent is a negative-strand RNA virus 80-100 nm in diameter. It causes fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and neural symptoms. The mortality rate of SFTS was 32.6% among 172 cases reported from 2012 to 2015 in South Korea. Thus, is necessary to develop an effective diagnostic method that selectively identifies the isolates circulating in South Korea. The real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay is a simple, rapid, and sensitive approach for molecular diagnosis. Here, we designed novel primers for this assay and found that the technique had very high specificity, sensitivity, and efficiency. This real-time RT-LAMP approach using the novel primers developed herein can be applied for early diagnosis of SFTSV strains in South Korea to reduce the mortality rate of SFTS.
Subject(s)
Gastrointestinal Diseases/diagnosis , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Phlebovirus/genetics , Severe Fever with Thrombocytopenia Syndrome/diagnosis , DNA Primers/genetics , Gastrointestinal Diseases/virology , Humans , Phlebovirus/isolation & purification , RNA, Viral/genetics , Republic of Korea , Sensitivity and Specificity , Severe Fever with Thrombocytopenia Syndrome/virologyABSTRACT
BACKGROUND: The data on the seasonality of respiratory viruses helps to ensure the optimal vaccination period and to monitor the possible outbreaks of variant type. OBJECTIVES: This study was designed to describe the molecular epidemiology and seasonality of acute respiratory infection (ARI)-related respiratory viruses in the United Arab Emirates (UAE). METHODS: Both upper and lower respiratory specimens were collected for the analysis from all the patients who visited the Sheikh Khalifa Specialty Hospital (SKSH) with ARI for over 2 years. The multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) test was used to detect respiratory viruses, which include human adenovirus, influenza virus (FLU) A and B, respiratory syncytial virus, parainfluenza viruses, human rhinovirus (HRV), human metapneumovirus, human enterovirus, human coronavirus, and human bocavirus. RESULTS: A total of 1,362 respiratory samples were collected from 733 (53.8%) male and 629 (46.2%) female patients with ARI who visited the SKSH between November 2015 and February 2018. The rRT-PCR test revealed an overall positivity rate of 37.2% (507/1362). The positive rate increased during winter; it was highest in December and lowest in September. FLU was the most frequently detected virus (273/1362 [20.0%]), followed by human rhinovirus (146/1362 [10.7%]). The FLU positivity rate showed two peaks, which occurred in August and December. The peak-to-low ratio for FLU was 2.26 (95% confidence interval: 1.52-3.35). CONCLUSIONS: The pattern of FLU in the UAE parallels to that of temperate countries. The trend of the small peak of FLU in the summer suggests a possibility of semi-seasonal pattern in the UAE.
Subject(s)
Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Viruses/classification , Viruses/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Hospitals , Humans , Incidence , Infant , Male , Middle Aged , Molecular Epidemiology , Multiplex Polymerase Chain Reaction , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Seasons , United Arab Emirates/epidemiology , Viruses/genetics , Young AdultABSTRACT
MicroRNAs were discovered more than 2 decades ago and have profound impact on diverse biological processes. Specific microRNAs have important roles in modulating the innate immune response and their dysregulation has been demonstrated to contribute to inflammatory diseases. MiR-223 in particular, is very highly expressed and tightly regulated in hematopoietic cells. It functions as key modulator for the differentiation and activation of myeloid cells. The central role of miR-223 in myeloid cells, especially neutrophil and macrophage differentiation and activation has been studied extensively. MiR-223 contributes to myeloid differentiation by enhancing granulopoiesis while inhibiting macrophage differentiation. Uncontrolled myeloid activation has detrimental consequences in inflammatory disease. MiR-223 serves as a negative feedback mechanism controlling excessive innate immune responses in the maintenance of myeloid cell homeostasis. This review summarizes several topics covering the function of miR-223 in myeloid differentiation, neutrophil and macrophage functions, as well as in inflammatory diseases including acute respiratory distress syndrome and inflammatory bowel disease. In addition, nonmyeloid functions of miR-223 are also discussed in this review. Therapeutic enhancement of miR-223 to dampen inflammatory targets is also highlighted as potential treatment to control excessive innate immune responses during mucosal inflammation.
Subject(s)
Immunity, Innate/genetics , Immunity, Innate/immunology , MicroRNAs/immunology , Animals , Cell Differentiation/genetics , Cell Differentiation/immunology , HumansABSTRACT
We investigated the temperature distribution induced by laser irradiation of ultrathin magnetic films by applying a finite element method (FEM) to the finite difference time domain (FDTD) representation for the analysis of thermal induced spin currents. The dependency of the thermal gradient (∇T) of ultrathin magnetic films on material parameters, including the reflectivity and absorption coefficient were evaluated by examining optical effects, which indicates that reflectance (R) and the apparent absorption coefficient (α*) play important roles in the calculation of ∇T for ultrathin layers. The experimental and calculated values of R and α* for the ultrathin magnetic layers irradiated by laser-driven heat sources estimated using the combined FDTD and FEM method are in good agreement for the amorphous CoFeB and crystalline Co layers of thicknesses ranging from 3~20 nm. Our results demonstrate that the optical parameters are crucial for the estimation of the temperature gradient induced by laser illumination for the study of thermally generated spin currents and related phenomena.
ABSTRACT
In Fig. 3c of this Letter, the the effects of CRISPR-Cas9-mediated deletion of NR3C1, TXNIP and CNR2 in patient-derived B-lineage leukaemia cells were shown. For curves depicting NR3C1 (left graph), data s for TXNIP (middle graph) were inadvertently plotted. This figure has been corrected online, and the original Fig. 3c is shown as Supplementary Information to this Amendment for transparency. The error does not affect the conclusions of the Letter. In addition, Source Data files have been added for the Figs. 1-4 and Extended Data Figs. 1-10 of the original Letter.
ABSTRACT
Recently developed electronic packaging materials based on low dimensional materials such as carbon nanotubes, graphene, and hexagonal boron nitride (h-BN) exhibit advantageous electrical, thermal, and mechanical properties for protecting electronic devices as well as dissipating heat flux from highly integrated circuits or high power electronic devices. Their thermal transport is mainly achieved by precise control of the nanostructure for nano-fillers to form the thermally conductive pathway. However, due to the viscoelastic behaviors of host polymeric materials, their phase or structural stability is significantly reduced by enhanced molecular motion at high temperature, resulting in poor thermal transport and mechanical strength. Here, we introduce flexible and robust h-BN foam sheets with a three-dimensional network structure, which exhibit much enhanced thermostability at high temperature. Furthermore, the additional infiltration of Fe3O4 nanoparticles into those structures results in relatively high electromagnetic absorbing performance. The combination of thermostability and mechanical strength based on the h-BN foam sheets provides novel opportunities for multifunctional thermally conductive materials in coatings and films without severely compromising auxiliary characteristics such as mechanical strength and thermal stability.
ABSTRACT
Neuromodulation was introduced for patients with poor outcomes from the existing traditional treatment approaches. It is well-established as an alternative, novel treatment option for voiding dysfunction. The current system of neuromodulation uses an open-loop system that only delivers continuous stimulation without considering the patient's state changes. Though the conventional open-loop system has shown positive clinical results, it can cause problems such as decreased efficacy over time due to neural habituation, higher risk of tissue damage, and lower battery life. Therefore, there is a need for a closed-loop system to overcome the disadvantages of existing systems. The closed-loop neuromodulation includes a system to monitor and stimulate micturition reflex pathways from the lower urinary tract, as well as the central nervous system. In this paper, we reviewed the current technological status to measure biomarker for closed-loop neuromodulation systems for voiding dysfunction.
ABSTRACT
We synthesized oligomeric anthocyanins from grape skin-derived monomeric anthocyanins such as anthocyanidin and proanthocyanidin by a fermentation technique using Aspergillus niger, crude enzymes and glucosidase. The biosyntheses of the oligomeric anthocyanins carried out by the conventional method using Aspergillus niger and crude enzymes were confirmed by ESI-MS. The molecular weight of the synthesized anthocyanin oligomers was determined using MALDI-MS. The yield of anthocyanin oligomers using crude enzymes was higher than that of the synthesis using Aspergillus fermentation. Several studies have been demonstrated that oligomeric anthocyanins have higher antioxidant activity than monomeric anthocyanins. Fermentation-based synthesis of oligomeric anthocyanins is an alternative way of producing useful anthocyanins that could support the food industry.
Subject(s)
Anthocyanins/biosynthesis , Aspergillus niger/growth & development , Vitis/chemistry , Complex Mixtures/metabolism , Fermentation , Molecular Structure , Plant Extracts/chemistryABSTRACT
B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation.
Subject(s)
B-Lymphocytes/metabolism , Energy Metabolism/genetics , Gene Expression Regulation, Neoplastic , Glucose/metabolism , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Transcription Factors/metabolism , AMP-Activated Protein Kinase Kinases , AMP-Activated Protein Kinases/antagonists & inhibitors , Adenosine Triphosphate/metabolism , Animals , B-Lymphocytes/drug effects , Carcinogenesis/genetics , Carrier Proteins/agonists , Carrier Proteins/metabolism , Cell Death , Chromatin Immunoprecipitation , Citric Acid Cycle , Disease Models, Animal , Female , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , Humans , Ikaros Transcription Factor/metabolism , Mice , Mice, Transgenic , PAX5 Transcription Factor/deficiency , PAX5 Transcription Factor/genetics , PAX5 Transcription Factor/metabolism , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Protein Serine-Threonine Kinases/metabolism , Pyruvic Acid/metabolism , Receptor, Cannabinoid, CB2/agonists , Receptor, Cannabinoid, CB2/metabolism , Receptors, Glucocorticoid/metabolism , Sequence Analysis, RNAABSTRACT
Escherichia coli (E. coli) was used to activate hydrolysis reaction along with biodegradation in natural and synthetic fibers to identify possibilities as alternative substitutes for textile wastes using chemical solutions and enzymes. To confirm the reaction between the bacterial infections of E. coli and the excessively abundant interstitial spaces of the fibers, various types of natural and synthetic fibers such as cotton, wool, polyethylene terephalate (PET), polyadmide (PA), polyethylene (PE), and polypropylene (PP) were used to confirm the physico-chemical reactions. Tensile strength analysis, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle analysis were used to determine the physico-chemical property changes of the fiber by the bacteria. When biofilm was formed on the fiber surface, various physical changes such as the following were observed: (i) in the analysis of tensile strength, all except PA and PP were decreased and a decrease in cotton fibers was noticeable (ii) depending on the type of fibers, the degree of roughness was different, but generally the surface became rough. In this study, the change of roughness was the most severe on the cotton fiber surface and the change of PET and PA fiber was relatively small. It was found that the intensity peak of oxygen was increased, except for the in cases of PA and PP, through the change of chemical properties by XPS analysis. Changes in topographical properties on the surface through contact angle analysis were stronger in hydrophilic properties, and in the case of cotton, completely hydrophilic surfaces were formed. Through this study, PA and PP fibers, which are Olefin fibers, were theoretically free of physicochemical and topographical changes since there were no functional groups that could trigger the hydrolysis reaction.
ABSTRACT
BACKGROUND: Bee venom (BV), a type of toxin extracted from honeybees (Apis mellifera), has been empirically and widely used to treat inflammatory diseases throughout Asia. Essential BV (eBV) was developed by removing phospholipase A2 (PLA2) and histamine to lower occurrence of allergic reaction. This study investigated the anti-allergic and anti-inflammatory activities of eBV in vitro and in vivo and its underlying mechanism of action. METHODS: The anti-inflammatory potential of eBV was assessed in vivo using a carrageenan-induced paw edema model. To further investigate the mechanism by which eBV exerts anti-allergic and anti-inflammatory effects, compound 48/80-stimulated RBL-2H3 cells and lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells were studied in vitro. RESULTS: Release of ß-hexosaminidase and histamine was increased by eBV in a dose-dependent manner, but these levels were lower in eBV compared to original BV at the same concentration. In addition, eBV suppressed compound 48/80-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in RBL-2H3 cells. eBV was also shown to suppress nitric oxide (NO) production by down-regulating mRNA expression and subsequent protein expression of inflammatory mediators in LPS-induced RAW 264.7 cells. Phosphorylation of activators and signal transducers of transcription 1/interferon regulatory factor 3 (STAT1/IRF3) was attenuated by eBV treatment. eBV significantly inhibited carrageenan-induced acute edema in vivo. Serum levels of prostaglandin E2 (PGE2), TNF-α, and IL-1ß were also down-regulated by eBV. CONCLUSIONS: These results demonstrate that eBV inhibits allergic and inflammatory response by reducing inflammatory mediator production via regulation of the STAT1/IRF3 signaling pathway, suggesting that eBV is a feasible candidate for regulation of allergic-inflammatory response in complementary and alternative medicine.
Subject(s)
Bee Venoms/therapeutic use , Edema/drug therapy , Hypersensitivity/drug therapy , Inflammation/drug therapy , Interferon Regulatory Factor-3/antagonists & inhibitors , Signal Transduction/drug effects , Animals , Blotting, Western , Carrageenan/pharmacology , Chromatography, High Pressure Liquid , Dinoprostone/metabolism , Disease Models, Animal , Edema/chemically induced , Histamine/metabolism , Interleukin-4/metabolism , Male , Mice , RAW 264.7 Cells/drug effects , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , STAT1 Transcription Factor/drug effects , Tumor Necrosis Factor-alpha/metabolismABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: While bee venom (BV) pharmacopuncture use is common in Asia, frequent occurrence of allergic reactions during the treatment process is burdensome for both practitioner and patient. AIM OF THE STUDY: This study compared efficacy and safety in isolated and purified essential BV (eBV) pharmacopuncture filtered for phospholipase A2 (PLA2) and histamine sections, and original BV to the aim of promoting safe BV pharmacopuncture use. MATERIALS AND METHODS: In in vitro, we examined the effect of BV and eBV on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and clinically, 20 healthy adults aged 20-40 years were randomly allocated and administered eBV 0.2mL and BV pharmacopuncture 0.2mL on left and right forearm, respectively, and physician, participant, and outcome assessor were blinded to treatment allocation. Local pain, swelling, itching, redness, wheals, and adverse reactions were recorded by timepoint. RESULTS: eBV and BV exhibited similar inhibitory effects on NO production. Also, in comparison between eBV and BV pharmacopuncture administration areas on each forearm, eBV displayed significantly lower local pain at 24h post-administration (P=0.0062), and less swelling at 30min (P=0.0198), 2 (P=0.0028), 24 (P=0.0068), and 48h post-administration (P=0.0253). eBV also showed significantly less itching at 24 (P=0.0119), 48 (P=0.0082), and 96h (P=0.0141), while redness was significantly less at 30min (P=0.0090), 6 (P=0.0005), and 24h (P<0.0001). Time-by-treatment interactions were statistically significant for itching and redness (P<0.001, and P<0.001, respectively), and all original BV pharmacopuncture administered regions showed a tendency toward more severe itching and redness in later measurements. CONCLUSIONS: eBV and BV displayed comparable anti-inflammatory effects, and eBV pharmacopuncture presented less local allergic reactions.
Subject(s)
Bee Venoms/administration & dosage , Bee Venoms/immunology , Hypersensitivity/diet therapy , Insect Bites and Stings/drug therapy , Insect Bites and Stings/immunology , Acupuncture/methods , Adult , Animals , Cell Line , Double-Blind Method , Female , Forearm , Humans , Hypersensitivity/immunology , Lipopolysaccharides/immunology , Macrophages/immunology , Male , Mice , Nitric Oxide/immunology , Phospholipases A2/immunologyABSTRACT
Gliomas are the most common and aggressive primary tumors in adults. The current approaches, such as histological classification and molecular genetics, have limitation in prediction of individual therapeutic outcomes due to heterogeneity within the tumor groups. Recent studies have proposed several gene signatures to predict glioma's prognosis. However, most of the gene expression profiling studies have been performed on relatively small number of patients and combined probes from diverse microarray chips. Here, we identified prognostic 89 common genes from diverse microarray chips. The 89-gene signature classified patients into good and bad prognostic groups which differed in the overall survival significantly, reflecting the biological characteristics and heterogeneity. The robustness and accuracy of the gene signature as an independent prognostic factor was validated in three microarray and one RNA-seq data sets independently. By incorporating into histological classification and molecular marker, the 89-gene signature could further stratify patients with 1p/19q co-deletion and IDH1 mutation. Additionally, subset analyses suggested that the 89-gene signature could predict patients who would benefit from adjuvant chemotherapy. Conclusively, we propose that the 89-gene signature would have an independent and accurate prognostic value for clinical use. This study also offers opportunities for novel targeted treatment of individual patients.