Multimodal Characterization of Cardiac Organoids Using Integrations of Pressure-Sensitive Transistor Arrays with Three-Dimensional Liquid Metal Electrodes.

Herein, we present an unconventional method for multimodal characterization of three-dimensional cardiac organoids. This method can monitor and control the mechanophysiological parameters of organoids within a single device. In this method, local pressure distributions of human-induced pluripotent stem-cell-derived cardiac organoids are visualized spatiotemporally by an active-matrix array of pressure-sensitive transistors. This array is integrated with three-dimensional electrodes formed by the high-resolution printing of liquid metal. These liquid-metal electrodes are inserted inside an organoid to form the intraorganoid interface for simultaneous electrophysiological recording and stimulation. The low mechanical modulus and low impedance of the liquid-metal electrodes are compatible with organoids' soft biological tissue, which enables stable electric pacing at low thresholds. In contrast to conventional electrophysiological methods, this measurement of a cardiac organoid's beating pressures enabled simultaneous treatment of electrical therapeutics using a single device without any interference between the pressure signals and electrical pulses from pacing electrodes, even in wet organoid conditions.

Thermoregulation of Pseudomonas aeruginosa Biofilm Formation.

We investigated the effect of temperature on the biofilm formation of Pseudomonas aeruginosa and revealed that the biofilm formation increased rapidly at temperatures lower than 25°C. P. aeruginosa formed the most robust biofilm of a conspicuous mushroom-like structure at 20°C. However, when the temperature increased to 25°C, the biofilm formation rapidly decreased. Above 25°C, as the temperature rose, the biofilm formation increased again little by little despite its less-structured form, indicating that 25°C is the low point of biofilm formation. The intracellular 3',5'-cyclic diguanylate (c-di-GMP) levels also decreased rapidly as the temperature rose from 20 to 25°C. The expression levels of pelA, algD, and pslA encoding Pel, alginate, and Psl, respectively, were also dramatically affected by temperature, with pelA being regulated in a pattern similar to that of the intracellular c-di-GMP levels, and the pattern seen for algD regulation was the most similar to the actual biofilm formation pattern. Total exopolysaccharide production was thermoregulated and followed the regulation pattern of c-di-GMP. Interestingly, the thermoregulation patterns in biofilm formation were different depending on the strain of P. aeruginosa Unlike PAO1, another strain, PA14, showed a gradual decrease in biofilm formation and c-di-GMP in the range of 20 to 37°C, and P. aeruginosa clinical isolates also showed slightly different patterns in biofilm formation in conjunction with temperature change, suggesting that different strains may sense different temperature ranges for biofilm formation. However, it is obvious that P. aeruginosa forms more biofilms at lower temperatures and that temperature is an important factor in determining the biofilm formation.IMPORTANCE Biofilm formation is an important protection mechanism used by most microorganisms and provides cells with many advantages, like high infectivity, antibiotic resistance, and strong survivability. Since most persistent bacterial infections are believed to be associated with biofilms, biofilm control is an important issue in medicine, environmental engineering, and industry. Biofilm formation is influenced by various environmental factors. Temperature is the most direct environmental cue encountered by microorganisms. Here, we investigated the effect of temperature on the biofilm formation of P. aeruginosa, a notorious pathogen, and found that temperature is an important factor determining the amount and structure of biofilms. Low temperatures greatly increase biofilm formation and give biofilms a highly conspicuous structure. Although thermoregulation of biofilm formation is mainly mediated by c-di-GMP, some c-di-GMP-independent regulations were also observed. This study shows how biofilms are formed at various temperatures and provides new insights to control biofilms using temperature.

Role of acid responsive genes in the susceptibility of Escherichia coli to ciclopirox.

Antibiotic resistance poses a huge threat to the effective treatment of bacterial infections. To circumvent the limitations in developing new antibiotics, researchers are attempting to repurpose pre-developed drugs that are known to be safe. Ciclopirox, an off-patent antifungal agent, inhibits the growth of Gram-negative bacteria, and genes involved in galactose metabolism and lipopolysaccharide (LPS) biosynthesis are plausible antibacterial targets for ciclopirox, since their expression levels partially increase susceptibility at restrictive concentrations. In the present study, to identify new target genes involved in the susceptibility of Escherichia coli to ciclopirox, genome-wide mRNA profiling was performed following ciclopirox addition at sublethal concentrations, and glutamate-dependent acid resistance (GDAR) genes were differentially regulated. Additional susceptibility testing, growth analyses and viability assays of GDAR regulatory genes revealed that down-regulation of evgS or hns strongly enhanced susceptibility to ciclopirox. Further microscopy and phenotypic analyses revealed that down-regulation of these genes increased cell size and decreased motility. Our findings could help to maximise the efficacy of ciclopirox against hard-to-treat Gram-negative pathogens.

Antimicrobial susceptibility and characterization of extended-spectrum ß-lactamases in Escherichia coli isolated from bovine mastitic milk in South Korea from 2012 to 2015.

In this study, we aimed to assess trends in antimicrobial resistance and to investigate the characteristics of extended-spectrum ß-lactamase (ESBL)-producing isolates from bovine mastitic milk from 2012 to 2015. A total of 374 Escherichia coli isolates were analyzed (154 in 2012, 113 in 2013, 76 in 2014, and 31 in 2015). No consistent trends in antimicrobial resistance of E. coli isolates occurred during the 4-yr period. The most frequently observed resistance was tetracycline (23.3%), followed by streptomycin (17.1%), ampicillin (16.6%), neomycin (11.8%), and trimethoprim/sulfamethoxazole (11.2%). Multidrug resistance was observed in 15.5% of isolates. Among these isolates, 15 (4.0%) carried one or more blaCTX-M and AmpC ESBL genes from 11 different farms, including blaCTX-M-15 at 4 farms, blaCTX-M-3 at 2 farms, blaCTX-M-1 at 3 farms, and blaCMY-2 at 3 farms. This study is the first report of blaCTX-M-3-producing E. coli in dairy milk. Transfer of ESBL was observed in 3 blaCTX-M-3-producing isolates, 1 blaCTX-M-1-producing isolate, and all 3 blaCMY-2-producing isolates. Almost all blaCTX-M-15 and blaCTX-M-1 genes possessed an insertion sequence, ISECP1, upstream of the blaCTX-M gene. Identical pulsed-field gel electrophoresis profiles were also observed in blaCTX-M-producing E. coli from the same farm. These results suggested that ESBL might spread by both clonal and horizontal spread in dairy farms in South Korea. Although no significant changes occurred in the antimicrobial resistance of E. coli during the 4-yr study period, the resistance rates and presence of ESBL were high compared with those in other countries. Thus, these findings suggest the importance of control measures for E. coli, particularly ESBL-producing bacteria, on dairy farms to reduce treatment failure and transmission to humans.

Molecular Basis of Resistance to Selected Antimicrobial Agents in the Emerging Zoonotic Pathogen Streptococcus suis.

Characterization of 227 Streptococcus suis strains isolated from pigs during 2010 to 2013 showed high levels of resistance to clindamycin (95.6%), tilmicosin (94.7%), tylosin (93.8%), oxytetracycline (89.4%), chlortetracycline (86.8%), tiamulin (72.7%), neomycin (70.0%), enrofloxacin (56.4%), penicillin (56.4%), ceftiofur (55.9%), and gentamicin (55.1%). Resistance to tetracyclines, macrolides, aminoglycosides, and fluoroquinolone was attributed to the tet gene, erm(B), erm(C), mph(C), and mef(A) and/or mef(E) genes, aph(3')-IIIa and aac(6')-Ie-aph(2″)-Ia genes, and single point mutations in the quinolone resistance-determining region of ParC and GyrA, respectively.

Guidelines for Manufacturing and Application of Organoids: Liver.

Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable of accurately replicating liver functions for drug efficacy and toxicity predictions. Liver organoids, derived from human cell sources, offer promise as a reliable platform for drug evaluation. However, there is a lack of standardized quality evaluation methods, which hinders their regulatory acceptance. This paper proposes comprehensive quality standards tailored for liver organoids, addressing cell source validation, organoid generation, and functional assessment. These guidelines aim to enhance reproducibility and accuracy in toxicity testing, thereby accelerating the adoption of organoids as a reliable alternative or complementary tool to animal testing in drug development. The quality standards include criteria for size, cellular composition, gene expression, and functional assays, thus ensuring a robust hepatotoxicity testing platform.

Versatile human cardiac tissues engineered with perfusable heart extracellular microenvironment for biomedical applications.

Engineered human cardiac tissues have been utilized for various biomedical applications, including drug testing, disease modeling, and regenerative medicine. However, the applications of cardiac tissues derived from human pluripotent stem cells are often limited due to their immaturity and lack of functionality. Therefore, in this study, we establish a perfusable culture system based on in vivo-like heart microenvironments to improve human cardiac tissue fabrication. The integrated culture platform of a microfluidic chip and a three-dimensional heart extracellular matrix enhances human cardiac tissue development and their structural and functional maturation. These tissues are comprised of cardiovascular lineage cells, including cardiomyocytes and cardiac fibroblasts derived from human induced pluripotent stem cells, as well as vascular endothelial cells. The resultant macroscale human cardiac tissues exhibit improved efficacy in drug testing (small molecules with various levels of arrhythmia risk), disease modeling (Long QT Syndrome and cardiac fibrosis), and regenerative therapy (myocardial infarction treatment). Therefore, our culture system can serve as a highly effective tissue-engineering platform to provide human cardiac tissues for versatile biomedical applications.

Molecular characterization of CTX-M ß-lactamase and associated addiction systems in Escherichia coli circulating among cattle, farm workers, and the farm environment.

A total of 84 extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli isolates from cattle, farm workers, and the farm environment isolated from February to September 2008 in the Republic of Korea were investigated. All 84 ESBL-producing isolates carried blaCTX-M genes that belonged to the CTX-M-1 (n = 35) or CTX-M-9 (n = 49) family. The most predominant CTX-M type identified was CTX-M-14 (n = 49), followed by CTX-M-32 (n = 26). The blaCTX-M genes were identified most commonly in E. coli isolates from feces (n = 29), teats (n = 25), and milk (n = 14). A blaCTX-M-14 gene was also detected in an E. coli isolate from a farmer's hand. Transfer of the blaCTX-M gene from 60 blaCTX-M-positive E. coli isolates to the recipient E. coli J53 strain by conjugation was demonstrated. Plasmid isolation from blaCTX-M-positive transconjugants revealed a large (95- to 140-kb) conjugative plasmid. Almost all (82/84) blaCTX-M genes possessed an insertion sequence, ISEcp1, upstream of the blaCTX-M gene. Only in the case of the CTX-M-14 genes was IS903 downstream of the gene. The blaCTX-M genes were associated with seven kinds of addiction systems. Among them, pndAC, hok-sok, and srnBC were the most frequently identified addiction systems in both wild strains and transconjugants. The spread of blaCTX-M genes was attributed to both clonal expansion and horizontal dissemination. Our data suggest that a combination of multiple addiction systems in plasmids carrying blaCTX-M genes could contribute to their maintenance in the host cells. To our knowledge, the blaCTX-M-32 gene has not previously been reported in animal isolates from the Republic of Korea.

Prevalence and molecular characterization of CTX-M ß-lactamase-producing Escherichia coli isolated from healthy swine and cattle.

The purpose of this study was to determine the prevalence and characteristics of CTX-M ß-lactamases in Escherichia coli among healthy swine and cattle in Korea. A total of 1212 fecal samples obtained from healthy pigs (n=558) and cattle (n=654) were screened for CTX-M-type extended spectrum ß-lactamase (ESBL)-producing E. coli isolates. One hundred and twenty-one E. coli that produced ESBL were subjected to phenotypic and genotypic characterization. A high number (120/558, 21.5%) of swine fecal samples showed the presence of CTX-M ß-lactamase-producing E. coli compared to cattle samples (1/654, 0.2%). The most predominant CTX-M-type identified was CTX-M-14 (n=82), followed by CTX-M-15 (n=16). Isolates producing CTX-M-3, CTX-M-27, CTX-M-55, and CTX-M-65 were also identified. Overall, the bla(TEM-1) gene was associated with CTX-M ß-lactamase in 55 E. coli isolates. Transfer of bla(CTX-M) gene was demonstrated from 76 out of 121 bla(CTX-M)-positive E. coli isolates to the recipient E. coli J53 by conjugation. Plasmid DNA isolation from the transconjugants revealed a large (90-120 Kb) conjugative plasmid. ISEcp1 and IS903 were detected upstream and downstream of bla(CTX-M) genes in 117 and 91 E. coli isolates, respectively. Our results demonstrated that a combination of clonal expansion and horizontal transmission is spreading bla(CTX-M) genes among swine E. coli. The horizontal dissemination of bla(CTX-M) genes among E. coli was mostly mediated by IncF or IncI1-Iγ plasmids. To the best of our knowledge, this study represents the first report of CTX-M-3, CTX-M-27, CTX-M-55, and CTX-M-65 ß-lactamases in bacterial isolates from food animals in Korea. This study revealed that the CTX-M ß-lactamase-producing E. coli are widely disseminated among healthy pigs but very rare in cattle in Korea. Increasing prevalence of bla(CTX-M) genes in intestinal E. coli of food animals is a matter of concern and should be carefully monitored.

Development of clinical practice guidelines for Korean medicine: Towards evidence-based complementary and alternative medicine.

Background: Since evidence-based medicine has been pursued in complementary and alternative medicine, the clinical practice guideline (CPG) has become a key factor in providing standardized and validated practices in Korean Medicine (KM). We aimed to review the current status and characteristics of the development, dissemination, and implementation of KM-CPGs. Methods: We searched KM-CPGs and relevant publication via web-based databases. We organized the searching results focused on the year of publications and the development programs to show which and how KM-CPGs have been development. We also reviewed the manuals for KM-CPG development to introduce concise characteristics of the KM-CPGs published in Korea. Results: The KM-CPGs have been developed according to manuals and standard templates for developing evidence-based KM-CPGs. First, CPG developers reviews the previously published CPGs for a clinical condition of interest and plans the CPG development. After finalizing the key clinical questions, the evidence is searched, selected, appraised, and analyzed following the internationally standardized methods. The quality of the KM-CPGs is controlled by a tri-step appraisal process. Second, the CPGs were submitted for the appraisal of the KM-CPG Review and Evaluation Committee. The committee evaluates the CPGs according to the AGREE II tool. Finally, the Steering Committee of the KoMIT project reviews the entire process of developing the CPGs and confirms it for public disclosure and dissemination. Conclusion: Evidence-based KM from research to practice can be achieved with the attention and effort of multidisciplinary entities such as clinicians, practitioners, researchers, and policymakers for the CPGs.

Molecular characterization of extended-spectrum-ß-lactamase-producing and plasmid-mediated AmpC ß-lactamase-producing Escherichia coli isolated from stray dogs in South Korea.

A total of 47 extended-spectrum-cephalosporin-resistant Escherichia coli strains isolated from stray dogs in 2006 and 2007 in the Republic of Korea were investigated using molecular methods. Extended-spectrum ß-lactamase (ESBL) and AmpC ß-lactamase phenotypes were identified in 12 and 23 E. coli isolates, respectively. All 12 ESBL-producing isolates carried bla(CTX-M) genes. The most common CTX-M types were CTX-M-14 (n = 5) and CTX-M-24 (n = 3). Isolates producing CTX-M-3, CTX-M-55, CTX-M-27, and CTX-M-65 were also identified. Twenty-one of 23 AmpC ß-lactamase-producing isolates were found to carry bla(CMY-2) genes. TEM-1 was associated with CTX-M and CMY-2 ß-lactamases in 4 and 15 isolates, respectively. In addition to bla(TEM-1), two isolates carried bla(DHA-1), and one of them cocarried bla(CMY-2). Both CTX-M and CMY-2 genes were located on large (40 to 170 kb) conjugative plasmids that contained the insertion sequence ISEcp1 upstream of the bla genes. Only in the case of CTX-M genes was there an IS903 sequence downstream of the gene. The spread of ESBLs and AmpC ß-lactamases occurred via both horizontal gene transfer, accounting for much of the CTX-M gene dissemination, and clonal spread, accounting for CMY-2 gene dissemination. The horizontal dissemination of bla(CTX-M) and bla(CMY-2) genes was mediated by IncF and IncI1-Iγ plasmids, respectively. The clonal spread of bla(CMY-2) was driven mainly by E. coli strains of virulent phylogroup D lineage ST648. To our knowledge, this is the first report of bla(DHA-1) in E. coli strains isolated from companion animals. This study also represents the first report of CMY-2 ß-lactamase-producing E. coli isolates from dogs in the Republic of Korea.

Prevalence of plasmid-mediated quinolone resistance determinants among Escherichia coli isolated from food animals in Korea.

The aim of this study was to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR) determinants in Escherichia coli isolated from food-producing animals and to characterize the PMQR-positive isolates. A total of 365 E. coli isolates which were either nalidixic acid resistant and ciprofloxacin susceptible (NAL(R)-CIP(S); n=185), or nalidixic acid and ciprofloxacin resistant (NAL(R)-CIP(R); n=180) were assessed for the presence of PMQR determinants by polymerase chain reaction. PMQR-positive isolates were further characterized by mutation analysis within the quinolone resistance-determining region (QRDR) of gyrA, gyrB, parC, and parE, phylogenetic group analysis, and pulsed-field gel electrophoresis (PFGE). Fourteen NAL(R)-CIP(S) (n=8) and NAL(R)-CIP(R) (n=6) E. coli isolates were positive for PMQR genes. Among them, qnrB4, qnrS1, and aac(6')-Ib-cr genes were detected in two (0.5%), eight (2.2%), and four (1.1%) isolates, respectively. None of the isolates harbored qnrA, qnrC, qnrD, and qepA genes. All but one PMQR-positive isolates harbored one or more point mutations in the QRDR of gyrA, and five of these isolates had additional mutations in the parC gene. Furthermore, one isolate each had additional substitutions in gyrB and parE genes, respectively. The most prevalent mutation was Ser83-Leu within the QRDR of gyrA. Phylogenetic analysis identified three major phylogenetic lineages, with phylogroups A (n=7) and D (n=4) being the most common phylogroups. None of the isolates belonged to virulent phylogroup B2. PFGE demonstrated that a combination of clonal and horizontal gene transmission is disseminating PMQR genes among the veterinary E. coli isolates in Korea. To our knowledge, this is the first report of occurrence of qnrB, qnrS, and aac(6')-Ib-cr genes in E. coli isolated from food-producing animals in Korea. Isolation of PMQR genes from food animals is a matter of concern since they could be transmitted to humans via food animals.

Intranasal low-level laser therapy versus acupuncture treatment for allergic rhinitis: A randomized, noninferiority trial.

INTRODUCTION: Intranasal low-level laser therapy (LLLT) has already proven its immunosuppressive effects on allergic rhinitis (AR) in experimental studies; however, there is a dearth of clinical evidence supporting its effects in treating AR. The aim of this study was to assess the safety and effectiveness of intranasal LLLT in the treatment of AR compared with acupuncture. METHODS: A total of 80 patients with AR participated and were randomly assigned to the intranasal LLLT or acupuncture treatment (AT) group. They were given each treatment for 20 min 3 times a week for 4 weeks. RESULTS: Both groups improved the total nasal symptom score (TNSS), rhinoconjunctivitis quality of life questionnaire (RQLQ) score, and nasal endoscopy index in patients with AR after 4 weeks of treatment, and these effects extended 4 weeks after the end of treatment. Intranasal LLLT was noninferior to AT in regard to the TNSS. The estimated outcome difference between baseline and the 5th week was -0.38 points (upper 97.5% confidence limit 1.06 points), which was within the noninferiority margin of 2 points. The effect size of the TNSS at the 5th week was 0.19, which was close to Cohen's small effect size. There were no significant differences between two groups regarding the RQLQ, nasal endoscopy index, total serum immunoglobulin E level or absolute eosinophil count. CONCLUSION: This study showed that intranasal LLLT is noninferior compared to AT in terms of the TNSS; thus, it may be used as an alternative or adjunctive treatment option for relieving symptoms of AR. TRIAL REGISTRATION: This study was registered at the Korean National Clinical Trial Registry, Clinical Research Information Service (KCT0004079).

Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids.

Matrigel, a mouse tumor extracellular matrix protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to-batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal tissue-derived extracellular matrix hydrogels are suitable substitutes for Matrigel in gastrointestinal organoid culture. We found that the development and function of gastric or intestinal organoids grown in tissue extracellular matrix hydrogels are comparable or often superior to those in Matrigel. In addition, gastrointestinal extracellular matrix hydrogels enabled long-term subculture and transplantation of organoids by providing gastrointestinal tissue-mimetic microenvironments. Tissue-specific and age-related extracellular matrix profiles that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that extracellular matrix hydrogels derived from decellularized gastrointestinal tissues are effective alternatives to the current gold standard, Matrigel, and produce organoids suitable for gastrointestinal disease modeling, drug development, and tissue regeneration.

Enhanced Large-Scale Production of Hahella chejuensis-Derived Prodigiosin and Evaluation of Its Bioactivity.

Prodigiosin as a high-valued compound, which is a microbial secondary metabolite, has the potential for antioxidant and anticancer effects. However, the large-scale production of functionally active Hahella chejuensis-derived prodigiosin by fermentation in a cost-effective manner has yet to be achieved. In the present study, we established carbon source-optimized medium conditions, as well as a procedure for producing prodigiosin by fermentation by culturing H. chejuensis using 10 L and 200 L bioreactors. Our results showed that prodigiosin productivity using 250 ml flasks was higher in the presence of glucose than other carbon sources, including mannose, sucrose, galactose, and fructose, and could be scaled up to 10 L and 200 L batches. Productivity in the glucose (2.5 g/l) culture while maintaining the medium at pH 6.89 during 10 days of cultivation in the 200 L bioreactor was measured and increased more than productivity in the basal culture medium in the absence of glucose. Prodigiosin production from 10 L and 200 L fermentation cultures of H. chejuensis was confirmed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) analyses for more accurate identification. Finally, the anticancer activity of crude extracted prodigiosin against human cancerous leukemia THP-1 cells was evaluated and confirmed at various concentrations. Conclusively, we demonstrate that culture conditions for H. chejuensis using a bioreactor with various parameters and ethanol-based extraction procedures were optimized to mass-produce the marine bacterium-derived high purity prodigiosin associated with anti-cancer activity.

Gastrointestinal tract modeling using organoids engineered with cellular and microbiota niches.

The recent emergence of organoid technology has attracted great attention in gastroenterology because the gastrointestinal (GI) tract can be recapitulated in vitro using organoids, enabling disease modeling and mechanistic studies. However, to more precisely emulate the GI microenvironment in vivo, several neighboring cell types and types of microbiota need to be integrated into GI organoids. This article reviews the recent progress made in elucidating the crosstalk between GI organoids and components of their microenvironment. We outline the effects of stromal cells (such as fibroblasts, neural cells, immune cells, and vascular cells) on the gastric and intestinal epithelia of organoids. Because of the important roles that microbiota play in the physiology and function of the GI tract, we also highlight interactions between organoids and commensal, symbiotic, and pathogenic microorganisms and viruses. GI organoid models that contain niche components will provide new insight into gastroenterological pathophysiology and disease mechanisms.

Effectiveness and Safety of Herbal Medicine for Atopic Dermatitis: An Overview of Systematic Reviews.

OBJECTIVES: Herbal medicine (HM) is attracting attention for treating atopic dermatitis (AD). This overview was conducted to summarize and critically evaluate the current systematic reviews (SRs) on HM for the treatment of AD. METHODS: Through comprehensive searches, all relevant SRs on HM for AD published until May 2020 were included. The quality of included SRs was assessed using the AMSTAR-2 tool. Moreover, original randomized controlled trials (RCTs) included in the SRs were resynthesized to investigate the efficacy and safety of oral HM for AD. The quality of evidence for the main findings was evaluated using the GRADE approach. RESULTS: Nine SRs were included in this overview. HM showed significantly better efficacy in terms of total effective rate (TER), itching and sleep symptom scores, quality of life, and the dose of topical treatment used compared with placebo. HM as a monotherapy and/or an adjunctive therapy to conventional medication (CM) showed significantly better results on the efficacy, symptom relief, and some laboratory parameters related to the inflammatory response. The methodological quality was generally low. When 58 original RCTs were reanalyzed, HM showed significantly lower SCORing Atopic Dermatitis (SCORAD) score and higher TER than the placebo or CM. In terms of the safety profile, HM was not significantly different from the placebo and was better than CM. The quality of evidence ranged from "moderate" to "very low." CONCLUSION: The results suggested that HM as a monotherapy or an adjunctive therapy is promising for the treatment of AD. However, due to low methodological quality and low quality of evidence, further rigorous, well-designed, high-quality SRs, and RCTs are needed to make clinical recommendations on HM use.

Aligned Brain Extracellular Matrix Promotes Differentiation and Myelination of Human-Induced Pluripotent Stem Cell-Derived Oligodendrocytes.

Myelination by oligodendrocytes (OLs) is a key developmental milestone in terms of the functions of the central nervous system (CNS). Demyelination caused by defects in OLs is a hallmark of several CNS disorders. Although a potential therapeutic strategy involves treatment with the myelin-forming cells, there is no readily available source of these cells. OLs can be differentiated from pluripotent stem cells; however, there is a lack of efficient culture systems that generate functional OLs. Here, we demonstrate biomimetic approaches to promote OL differentiation from human-induced pluripotent stem cells (iPSCs) and to enhance the maturation and myelination capabilities of iPSC-derived OL (iPSC-OL). Functionalization of culture substrates using the brain extracellular matrix (BEM) derived from decellularized human brain tissue enhanced the differentiation of iPSCs into myelin-expressing OLs. Co-culture of iPSC-OL with induced neuronal (iN) cells on BEM substrates, which closely mimics the in vivo brain microenvironment for myelinated neurons, not only enhanced myelination of iPSC-OL but also improved electrophysiological function of iN cells. BEM-functionalized aligned electrospun nanofibrous scaffolds further promoted the maturation of iPSC-OLs, enhanced the production of myelin sheath-like structures by the iPSC-OL, and enhanced the neurogenesis of iN cells. Thus, the biomimetic strategy presented here can generate functional OLs from stem cells and facilitate myelination by providing brain-specific biochemical, biophysical, and structural signals. Our system comprising stem cells and brain tissue from human sources could help in the establishment of human demyelination disease models and the development of regenerative cell therapy for myelin disorders.

Effects of membrane thickness on the performance of ionic polymer-metal composite actuators.

In this study, we report the effects of Nafion thickness on the performance of ionic polymer-metal composite (IPMC) actuators. We analyzed the actuation properties of the IPMC actuators, such as displacement and tip force, under external voltage, as a function of their thickness. In order to understand the relationship between thickness and actuation properties, we developed a semi-quantitative model of voltage induced ionic diffusion and its contribution to bending of the Nafion cantilever. Furthermore, we investigated the mechanical properties of the Nafion membranes at sub-micro scale as well as bulk scale, using atomic force microscopy (AFM) and tensile test. The results of the two methods indicated opposite trends of elastic modulus and crystallinity as a function of thickness. We hypothesized that the hot-pressed Nafion was composed of three layers with different crystallinity. Our results suggest that for a high performance IPMC actuator, we need better control of the annealing temperature gradient.

Bio-artificial tongue with tongue extracellular matrix and primary taste cells.

Artificial taste devices for tastant sensing and taste information standardization are attracting increasing attention with the exponential growth of the food and beverage industries. Despite recent developments in artificial taste sensors incorporating polymers, lipid membranes, and synthetic vesicles, current devices have limited functionality and sensitivity, and are complex to manufacture. Moreover, such synthetic systems cannot simulate the taste signal transmissions that are critical for complicated taste perception. The current document describes a primary taste cell-based artificial tongue that can mimic taste sensing. To maintain viable and functional taste cells required for in vitro tastant sensing, a tongue extracellular matrix (TEM) prepared by decellularization of tongue tissue was applied to two- and three-dimensional taste cell cultures. The TEM-based system recreates the tongue's microenvironment and significantly improves the functionality of taste cells for sensing tastant molecules by enhancing cellular adhesion and gustatory gene expression compared with conventional collagen-based systems. The TEM-based platform simulates signal transmission from tastant-treated taste cells to adjacent neuronal cells, which was impossible with previous artificial taste sensors. The artificial tongue device may provide highly efficient, functional sensors for tastant detection and in vitro organ models that mimic the tongue allowing elucidation of the mechanisms of taste.