Effectiveness of dupilumab in pediatric patients with a nummular phenotype of atopic dermatitis.

The nummular phenotype of atopic dermatitis is clinically characterized by pruritic, coin-shaped plaques that are frequently recalcitrant to treatment. In this study, a retrospective chart review was conducted to evaluate the effectiveness and safety of dupilumab in children with nummular lesions of dermatitis. Twelve out of 14 patients demonstrated significant clinical improvement at a median time of 2.5 months (interquartile range, 1-4) after dupilumab initiation. A single case of paradoxical psoriasiform eruption was the only side effect reported in our cohort.

Urticaria in infants: A single-institution retrospective study.

Urticaria in infants can cause significant anxiety in parents, especially if a trigger cannot be identified. In a retrospective study of 246 infants seen for urticaria of unknown etiology at Boston Children's Hospital, 88.2% had resolution of urticaria within 6 weeks. The etiology of urticaria was ultimately established in 62.6% (72/115) of acute urticaria and 12.5% (2/16) of chronic urticaria cases with follow-up data. Pediatric healthcare providers can counsel families that while etiology of urticaria is never determined in over 40% of infants, symptoms are most likely to resolve spontaneously.

Identification of Terpene Compositions in the Leaves and Inflorescences of Hybrid Cannabis Species Using Headspace-Gas Chromatography/Mass Spectrometry.

Although cannabidiol and tetrahydrocannabinol in Cannabis species exert their pharmacological effects via the endocannabinoid system, it is believed that other phytochemicals, particularly terpenes, can modulate therapeutic outcomes through the entourage effect. Therefore, to gain a better understanding of the pharmacological effects of Cannabis, obtaining information on phytochemical compositions, including mono-, di-, and sesqui-terpenes in Cannabis species is essential. Applying a sophisticated analytical method is indispensable. In this study, headspace-gas chromatography/mass spectrometry (HS-GC/MS) was employed to identify major terpenes in the leaves and inflorescences of hybrid Cannabis species. The incubation time and temperature conditions for HS-GC/MS were optimized. This method was successfully applied to the leaves (n = 9) and inflorescences (n = 7) of hybrid Cannabis species. A total of 26 terpenes in Cannabis species were detected, and six major components, such as α-pinene (9.8-2270 µg/g), ß-pinene (2.6-930 µg/g), myrcene (0.7-17,400 µg/g), limonene (1.3-300 µg/g), ß-caryophyllene (60-3300 µg/g), and α-humulene (40-870 µg/g), were quantified. Each sample showed different terpene compositions, but six major terpenes among all the terpenes detected were consistently found in both the leaves and inflorescences of hybrid Cannabis species. In this study, the six major terpenes' potential in hybrid Cannabis species was evaluated as biomarkers to distinguish hybrid Cannabis species samples. This study contributes to a better understanding of the entourage effect of Cannabis-based botanical drugs.

Arctic Sea Ice Microalga Chlamydomonas latifrons KNF0041: Identification and Statistical Optimization of Medium for Enhanced Biomass and Omega-3/Omega-6.

Polar microorganisms produce biologically active compounds that enable them to survive in harsh environments. These compounds have potential biomedical applications. The green microalga Chlamydomonas latifrons KNF0041, isolated from Arctic sea ice, has been found to produce polyunsaturated fatty acids (PUFAs), including omega-3 and omega-6, which have antioxidant properties. To improve the biomass production of strain KNF0041, statistical methods such as the Plackett-Burman design, Box-Behnken design, and response surface methodology (RSM) were utilized for medium optimization. The optimized medium was designed with increased potassium phosphate content and reduced acetic acid (AcOH) content. The use of the optimized medium resulted in an increase in the cell number as biomass of strain KNF0041 by 34.18% and the omega-3 and omega-6 fatty acid (FA) content by 10.04% and 58.29%, respectively, compared to that in normal TAP medium, which is known as the growth medium for Chlamydomonas culture. In this study, Chlamydomonas latifrons was discovered for the first time in the polar region and identified using morphology and molecular phylogenetic analyses, the secondary structures of the internal transcribed spacers, and optimized culture conditions. The results of this study provide an efficient method for the application of polar microalgae for the production of bioactive compounds.

Polar microalgae extracts protect human HaCaT keratinocytes from damaging stimuli and ameliorate psoriatic skin inflammation in mice.

BACKGROUND: Polar microalgae contain unique compounds that enable them to adapt to extreme environments. As the skin barrier is our first line of defense against external threats, polar microalgae extracts may possess restorative properties for damaged skin, but the potential of microalgae extracts as skin protective agents remains unknown. PURPOSE: This study aimed to analyze compound profiles from polar microalgae extracts, evaluate their potential as skin epithelial protective agents, and examine the underlying mechanisms. METHODS: Six different polar microalgae, Micractinium sp. (KSF0015 and KSF0041), Chlamydomonas sp. (KNM0029C, KSF0037, and KSF0134), and Chlorococcum sp. (KSF0003), were collected from the Antarctic or Arctic regions. Compound profiles of polar and non-polar microalgae extracts were analyzed using gas chromatography-mass spectrometry (GC-MS). The protective activities of polar microalgae extracts on human keratinocyte cell lines against oxidative stress, radiation, and psoriatic cytokine exposure were assessed. The potential anti-inflammatory mechanisms mediated by KSF0041, a polar microalga with protective properties against oxidative stress, ultraviolet (UV) B, and an inflammatory cytokine cocktail, were investigated using RNA-sequencing analysis. To evaluate the therapeutic activity of KSF0041, an imiquimod-induced murine model of psoriatic dermatitis was used. RESULTS: Polar microalgae contain components comparable to those of their non-polar counterparts, but also showed distinct differences, particularly in fatty acid composition. Polar microalgae extracts had a greater ability to scavenge free radicals than did non-polar microalgae and enhanced the viability of HaCaT cells, a human keratinocyte cell line, following exposure to UVB radiation or psoriatic cytokines. These extracts also reduced barrier integrity damage and decreased mRNA levels of inflammatory cytokines in psoriatic HaCaT cells. Treatment with KSF0041 extract altered the transcriptome of psoriatic HaCaT cells toward a more normal state. Furthermore, KSF0041 extract had a therapeutic effect in a mouse model of psoriasis. CONCLUSIONS: Bioactive compounds from polar microalgae extracts could provide novel therapeutics for damaged and/or inflamed skin.

Trends of genital wart in Korea according to treatment method classification: Big data analysis of health care in 2010-2019.

PURPOSE: The purpose of this study is to investigate disease trend of genital wart through changes in each treatment method over the past 10 years in Korea. MATERIALS AND METHODS: From 2010 to 2019, surgical treatment including cauterization, excision, cryotherapy, and laser therapy, non-surgical treatment such as podophyllin, and surgical treatment for anorectal lesion were extracted and analyzed from 2010 to 2019. For each treatment method, characteristics such as sex, age, region, medical cost and average number of procedures were analyzed. RESULTS: The number of patients following all treatment modalities increased every year. Surgical treatment of genital wart and anorectal wart showed a significant increase in male patients. Number of non-surgical treatment decreased in males but increased in females. Surgical removal of the anorectal wart increased more than 250% in over 10 years, and males underwent surgery 4 times more than females. In both surgery and non-surgery, the mean session was higher in males. Most of them were carried out in primary medical institutions. In Seoul and Gyeonggi-do, the largest number of patients received treatment regardless of treatment method. CONCLUSIONS: Treatment for genital warts has increased rapidly over the past 10 years, and the increase in males is remarkable. The main treatment was surgery, and males mainly received surgical treatment, and females mainly received drug treatment. The primary medical institution was in charge of the most treatment. As the number of patients and related medical expenses are increasing rapidly, more attention and response to diseases are needed.

Flow Characteristics of the Conjugate of Anti-CD3 Monoclonal Antibodies and Magnetic Nanoparticle in PBS and Blood Vessels.

Previously, anti-CD3 antibodies delivered intravenously have been known for their negative side effects. The experimental conditions for optimal liquid production are derived from the Fc-directed conjugation of anti-CD3 foralumab antibodies and magnetic nanoparticles (Ab-MNPs). The anti-CD3 antibodies are prepared for conjugation with MNPs using SiteClick antibody labelling kits. The successful conjugation of the Ab-MNPs is confirmed using a transmission electron microscopy (TEM) image and an energy dispersive spectroscopy (EDS) analysis. The average values ​​of the moving speed of MNPs and Ab-MNPs in phosphate buffer saline (PBS) were + 3.16 pix/frame and + 6.70 pix/frame in the x-axis, respectively. This implies that MNPs with CD3 antibodies attached to the surface through biocompatible ligand functional groups has better fluidity in PBS. Afterwards, a non-clinical animal testing for the flow characteristics of Ab-MNPs inside a blood vessel is carried out to observe the effects of Ab-MNP delivery through intravenous injection.

Antarctic Marine Algae Extracts as a Potential Natural Resource to Protect Epithelial Barrier Integrity.

The intestine and skin provide crucial protection against the external environment. Strengthening the epithelial barrier function of these organs is critical for maintaining homeostasis against inflammatory stimuli. Recent studies suggest that polar marine algae are a promising bioactive resource because of their adaptation to extreme environments. To investigate the bioactive properties of polar marine algae on epithelial cells of the intestine and skin, we created extracts of the Antarctic macroalgae Himantothallus grandifolius, Plocamium cartilagineum, Phaeurus antarcticus, and Kallymenia antarctica, analyzed the compound profiles of the extracts using gas chromatography-mass spectrometry, and tested the protective activities of the extracts on human intestinal and keratinocyte cell lines by measuring cell viability and reactive oxygen species scavenging. In addition, we assessed immune responses modulated by the extracts by real-time polymerase chain reaction, and we monitored the barrier-protective activities of the extracts on intestinal and keratinocyte cell lines by measuring transepithelial electrical resistance and fluorescence-labeled dextran flux, respectively. We identified bioactive compounds, including several fatty acids and lipid compounds, in the extracts, and found that the extracts perform antioxidant activities that remove intracellular reactive oxygen species and scavenge specific radicals. Furthermore, the Antarctic marine algae extracts increased cell viability, protected cells against inflammatory stimulation, and increased the barrier integrity of cells damaged by lipopolysaccharide or ultraviolet radiation. These results suggest that Antarctic marine algae have optimized their composition for polar environments, and furthermore, that the bioactive properties of compounds produced by Antarctic marine algae can potentially be used to develop therapeutics to promote the protective barrier function of the intestine and skin.

Freezing-enhanced oxidation of iodide by hydrogen peroxide in the presence of antifreeze proteins from the Arctic yeast Leucosporidium sp.AY30.

Ice-binding proteins (IBPs), originating from Arctic or Antarctic microorganisms, have freeze-inhibiting characteristics, allowing these organisms to survive in polar regions. Despite their significance in polar environments, the mechanism through which IBPs affect the chemical reactions in ice by controlling ice crystal formation has not yet been reported. In this study, a new mechanism for iodide (I-) activation into triiodide (I3-), which is the abundant iodine species in seawater, by using hydrogen peroxide (H2O2) in a frozen solution with IBPs was developed. A significant enhancement of I- activation into I3- was observed in the presence of Arctic-yeast-originating extracellular ice-binding glycoprotein (LeIBP) isolated from Leucosporidium sp. AY30, and a further increase in the I3- concentration was observed with the introduction of H2O2 to the frozen solution (25 times higher than in the aqueous solution after 24 h of reaction). The reaction in the ice increased with an increase in LeIBP concentration. The in-situ pH measurement in ice using cresol red (CR) revealed protons accumulated in the ice grain boundaries by LeIBP. However, the presence of LeIBP did not influence the acidity of the ice. The enhanced freeze concentration effect of H2O2 by LeIBP indicated that larger ice granules were formed in the presence of LeIBP. The results suggest that LeIBP affects the formation and morphology of ice granules, which reduces the total volume of ice boundaries throughout the ice. This leads to an increased local concentration of I- and H2O2 within the ice grain boundaries. IBP-assisted production of gaseous iodine in a frozen environment provides a previously unrecognized formation mechanism of active iodine species in the polar regions.

Importance of rigidity of ice-binding protein (FfIBP) for hyperthermal hysteresis activity and microbial survival.

Ice-binding proteins (IBPs) are well-characterized proteins responsible for the cold-adaptation mechanisms. Despite extensive structural and biological investigation of IBPs and antifreeze proteins, only a few studies have considered the relationship between protein stabilization and thermal hysteresis (TH) activity as well as the implication of hyperactivity. Here, we investigated the important role of the head capping region in stabilization and the hyper-TH activity of FfIBP using molecular dynamics simulation. Data comparison revealed that residues on the ice-binding site of the hyperactive FfIBP are immobilized, which could be correlated with TH activity. Further comparison analysis indicated the disulfide bond in the head region is mainly involved in protein stabilization and is crucial for hyper-TH activity. This finding could also be generalized to known hyperactive IBPs. Furthermore, in mimicking the physiological conditions, bacteria with membrane-anchored FfIBP formed brine pockets in a TH activity-dependent manner. Cells with a higher number of TH-active IBPs showed an increased number of brine pockets, which may be beneficial for short- and long-term survival in cold environments by reducing the salt concentration. The newly identified conditions for hyper-TH activity and their implications on bacterial survival provide insights into novel mechanistic aspects of cold adaptation in polar microorganisms.

Association between thyroid hormone and components of metabolic syndrome in euthyroid Korean adults: A population-based study.

ABSTRACT: Thyroid dysfunction increases the prevalence of metabolic syndrome. However, the link between thyroid hormones and metabolic syndrome remains debatable, and the effect of sex on their relationship is not completely understood. To elucidate the relationship of thyroid hormones with metabolic syndrome and its components according to sex in euthyroid individuals in South Korea. Adult participants who underwent thyroid tests at our institution between January 2015 and December 2018 and had thyroid-stimulating hormone (TSH; 0.270-4.200 µIU/mL) and free thyroxine (FT4; 0.93-1.70 ng/dL) levels in the normal range were included. After correcting for age and body mass index, multiple linear regression was performed to assess the association of TSH and FT4 with metabolic syndrome and its components, and logistic regression was performed to estimate the risk of developing metabolic syndrome and its components according to different thyroid hormone quartiles. We included 12,478 men and 7,575 women in this study. The prevalence of metabolic syndrome was 9.68%. In men, TSH was positively associated with blood pressure and triglycerides, and the odds ratio for high blood pressure and hypertriglyceridemia was approximately 1.3 times higher in the fourth quartile than in the first quartile. FT4 associated positively with waist circumference, and a high odds ratio for abdominal obesity in the fourth quartile was observed in both men (odds ratio [OR], 1.239; 95% confidence interval [CI], 1.045-1.470) and women (OR, 1.302; 95% CI, 1.029-1.649). A negative association was found between FT4 and triglycerides, and concurrently, the odds ratios for hypertriglyceridemia were lower in the fourth quartile in both men (OR, 0.692; 95% CI, 0.619-0.774) and women (OR: 0.641; 95% CI: 0.512-0.803). In addition, a higher odds ratio for high blood pressure was observed in the fourth quartiles of FT4 and TSH in women. However, there was no association between TSH and FT4 levels and the onset of metabolic syndrome in either of the sexes. Serum TSH and FT4 levels were associated with different metabolic syndrome components in men and women, but there was no association with the onset of metabolic syndrome.

Bacterially Delivered miRNA-Mediated Toll-like Receptor 8 Gene Silencing for Combined Therapy in a Murine Model of Atopic Dermatitis: Therapeutic Effect of miRTLR8 in AD.

In atopic dermatitis (AD), skin inflammation is caused by complex interactions between genetic disposition and aberrant innate/adaptive immune responses. Toll-like receptors (TLRs) are key molecules in the innate/adaptive immune response as they recognize various molecular motifs associated with pathogens. Among them, TLR8 is implicated in eczematous skin reactions. We investigated the combined therapeutic effects of TLR8 gene silencing by the bacterial delivery of miRNA. We used Salmonella as a vector to deliver TLR8 miRNA. The recombinant strain of Salmonella enterica subsp. enterica serovar Typhimurium (ST) expressing TLR8 miRNA (ST-miRTLR8) was prepared for knockdown of TLR8. After oral administration of ST-miRTLR8 into mice, we observed the cytokine levels, skin pathology and scratching behaviors in an AD-like mouse model. TLR8 down-regulation decreased macrophage-derived chemokine concentrations in activated human mast cells. Serum IgE and interleukin-4 production were suppressed whereas IFN-γ was induced after oral administration of ST-miRTLR8. Scratching behaviors and skin inflammation were also improved. In addition, attenuated S. typhimurium safely accumulated in mouse macrophages and showed adjuvant effects. This study shows that the recombinant miRNA that expresses the TLR8 miRNA has therapeutic effects by suppressing Th2 inflammation. TLR gene modulation using miRNA via Salmonella vectors will thus have a double-protective effect in the treatment of AD.

Continuing patient care to underserved communities and medical education during the COVID-19 pandemic through a teledermatology student-run clinic.

A virtual pediatric dermatology student-run clinic was initiated during the COVID-19 pandemic, when in-person educational opportunities were limited. The clinic's aim is to provide high-quality dermatologic care to a diverse, underserved pediatric patient population while teaching trainees how to diagnose and manage common skin conditions. In our initial eight sessions, we served 37 patients, predominantly those with skin of color, and had a low no-show rate of 9.8%. This report describes the general structure of the clinic, goals, and the patient population to provide an overview of our educational model for those interested in similar efforts.

Mitochondrial genome of the Antarctic microalga Micractinium simplicissimum KSF0127 (Chlorellaceae, Trebouxiophyceae).

We report the first mitochondrial genome of the Antarctic microalga Micractinium simplicissimum KSF0127. The circular mitochondrial genome was 67,923 bp in length and contained 45 protein-coding genes, one ribosomal RNA gene, and 60 transfer RNA genes. The phylogenetic tree was constructed with eight previously reported mitogenome sequences and showed the phylogenetic position of M. simplicissimum KSF0127 within the Chlorellaceae family.

Co-production of biodiesel and bioethanol using psychrophilic microalga Chlamydomonas sp. KNM0029C isolated from Arctic sea ice.

BACKGROUND: Biofuels, generated using microalgae as sustainable energy, have received a lot of attention. Microalgae can be cultivated at low cost with CO2 and solar energy without competition from edible crops. Psychrophilic microalgae can be a suitable feedstock to produce biofuels without the environmental constraints of low temperatures, because they can grow below 10 °C. However, there is a lack of efficient strategies using psychrophilic microalgae to produce biodiesel and bioethanol. Therefore, the current study aimed to optimize the production of biodiesel and bioethanol from Arctic Chlamydomonas sp. KNM0029C at low temperatures. RESULTS: After incubation in a 20-L photobioreactor, fatty acid methyl ester (FAME) was extracted using modified FAME extraction methods, producing a maximum yield of 0.16-g FAME/g KNM0029C. Residual biomass was pretreated for bioethanol production, and the yields from different methods were compared. The highest bioethanol yield (0.22-g/g residual biomass) was obtained by pretreatment with enzyme (amyloglucosidase) after sonication. Approximately 300-mg biofuel was obtained, including 156-mg FAME biodiesel and 144-mg bioethanol per g dried cells, representing the highest recorded yield from psychrophilic microalgae. CONCLUSIONS: This is the first to attempt at utilizing biomass from psychrophilic Arctic microalga Chlamydomonas sp. KNM0029C for the co-production of bioethanol and biodiesel, and it yielded the highest values among reported studies using psychrophilic organisms. These results can be used as a source for the efficient biofuel production using polar microalgae.

Antarctic freshwater microalga, Chloromonas reticulata, suppresses inflammation and carcinogenesis.

Inflammation triggered by the innate immune system is a strategy to protect organisms from the risk of environmental infection. However, it has recently become clear that inflammation can cause a variety of human diseases, including cancer. In this study, we investigated the effects of an ethanol extract of the Antarctic freshwater microalgae, Chloromonas reticulata (ETCH), on inflammation and carcinogenesis in RAW 264.7 macrophages and HCT116 human colon cancer cells, respectively. ETCH exhibited significant anti-inflammatory activity through the dose-dependent modulation of major inflammatory markers such as COX-2, IL-6, iNOS, TNF-α, and NO production. For example, ETCH reduced LPS-induced upregulation of COX-2, IL-6, iNOS, and TNF- alpha mRNA levels, leading to a significant decrease in the levels of LPS-stimulated NO and IL-6 as well as TNF-alpha products. In contract, ETCH exhibited dose-dependent cytotoxic activity against HCT116 cells, yielding a profound reduction in the proliferation of the cancer cells. Furthermore, ETCH induced G2 phase cell cycle arrest by transcriptionally regulating of genes involved in G2 / M transition including p21 (CDKN1A), cyclin B1 (CCNB1), and CDK1; CDKN1A mRNA levels were upregulated in response to ETCH, whereas CCNB1 and CDK1 were downregulated. This study reports for the first time anti-inflammatory and anti-cancer effects of, C. reticulata and provides new insights into the molecular mechanisms of the linkage between inflammation and cancer.

Lipid Production by Arctic Microalga Chlamydomonas sp. KNF0008 at Low Temperatures.

A lipid-producing microalga, Chlamydomonas sp. KNF0008, collected from the Arctic was capable of growing at temperatures ranging from 4 to 20 °C, and the highest cell density was measured at 15 °C and 100 µmol photons m-2 s-1 light intensity under continuous shaking and external aeration. KNF0008 showed the elevated accumulation of lipid bodies under nitrogen-deficient conditions, rather than under nitrogen-sufficient conditions. Fatty acid production of KNF0008 was 4.2-fold (104 mg L-1) higher than that of C. reinhardtii CC-125 at 15 °C in Bold's Basal Medium. The dominant fatty acids were C16:0, C16:4, C18:1, and C18:3, and unsaturated fatty acids (65.69%) were higher than saturated fatty acids (13.65%) at 15 °C. These results suggested that Arctic Chlamydomonas sp. KNF0008 could possibly be utilized for production of biodiesel during periods of cold weather because of its psychrophilic characteristics.

Anti-inflammation and Anti-Cancer Activity of Ethanol Extract of Antarctic Freshwater Microalga, Micractinium sp.

Inflammation mediated by the innate immune system is an organism's protective mechanism against infectious environmental risk factors. It is also a driver of the pathogeneses of various human diseases, including cancer development and progression. Microalgae are increasingly being focused on as sources of bioactive molecules with therapeutic potential against various diseases. Furthermore, the antioxidant, anti-inflammatory, and anticancer potentials of microalgae and their secondary metabolites have been widely reported. However, the underlying mechanisms remain to be elucidated. Therefore, in this study, we investigated the molecular mechanisms underlying the anti-inflammatory and anticancer activities of the ethanol extract of the Antarctic freshwater microalga Micractinium sp. (ETMI) by several in vitro assays using RAW 264.7 macrophages and HCT116 human colon cancer cells. ETMI exerted its anti-inflammatory activity by modulating the main inflammatory indicators such as cyclooxygenase (COX)-2, interleukin (IL)-6, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and nitric oxide (NO) in a dose-dependent manner. In addition, ETMI exerted cytotoxic activity against HCT116 cells in a dose-dependent manner, leading to significantly reduced cancer cell proliferation. Further, it induced cell cycle arrest in the G1 phase through the regulation of hallmark genes of the G1/S phase transition, including CDKN1A, and cyclin-dependent kinase 4 and 6 (CDK4 and CDK6, respectively). At the transcriptional level, the expression of CDKN1A gradually increased in response to ETMI treatment while that of CDK4 and CDK6 decreased. Taken together, our findings suggest that the anti-inflammatory and anticancer activities of the Antarctic freshwater microalga, Micractinium sp., and ETMI may provide a new clue for understanding the molecular link between inflammation and cancer and that ETMI may be a potential anticancer agent for targeted therapy of colorectal cancer.