Linear IgA Bullous Dermatosis in Korea Using the Nationwide Health Insurance Database.

(1) Background: Linear immunoglobulin A bullous dermatosis (LABD) is a rare autoimmune, subepidermal blistering disease, characterized by linear IgA deposits along the epidermal basement membrane. LABD is idiopathic and is associated with medication and systemic autoimmune diseases. (2) Methods: We investigated the demographic characteristics, disease course, causative agents, and associated diseases in Korean patients with LABD. The Korean Health Insurance Review and Assessment Service database was used to obtain data. We identified 670 LABD cases between 2010 and 2022. (3) Results: The annual incidence of LABD was 1.3 per 100,000 persons, with a higher prevalence in individuals ≥60 years old. The patients were treated with dapsone for 30.7 ± 56.7 days, had 1.3 ± 0.7 hospital visits, and were hospitalized for 19.8 ± 19.7 days. Risk factors, including malignancy, commonly preceded LABD. Antibiotic use, specifically vancomycin and third-generation cephalosporins, was a risk factor. The mean age of LABD diagnosis was 55.9 ± 21.7 years. (4) Conclusion: This is the first published study to assess a nationwide cohort for LABD. The incidence of LABD was higher than that in other studies. Most case reports have linked LABD with the administration of specific antibiotics; however, this study shows there were more associations with other conditions.

Masculinity, Rather Than Biological Sex, Is Associated With Psychological Comorbidities in Patients With Irritable Bowel Syndrome.

Background/Aims: Irritable bowel syndrome (IBS) generally shows sex differences, and psychiatric comorbidities play an important role in its pathogenesis. We aim to measure the levels of gender roles and investigate their relationship with psychiatric factors in patients with IBS versus healthy controls. Methods: Patients diagnosed with IBS by Rome III and whose colonoscopy findings were normal were enrolled at multiple sites in Korea. The participants completed the Korean Sex Role Inventory-Short Form (KSRI-SF) to assess masculinity and femininity, the stress questionnaire, the Hospital Anxiety Depression Scale (HADS), and the 36-item Short Form Health Survey questionnaire to assess the quality of life (QOL). Results: In total, 102 patients with IBS (male:female = 35:67; mean age 42.6 ± 16.7 years) and 55 controls (male:female = 20:35; mean age 42.4 ± 11.1 years) were recruited. IBS patients had higher stress (9.69 ± 8.23 vs 4.56 ± 8.31, P < 0.001) and HADS scores (16.12 ± 7.17 vs 10.22 ± 5.74, P < 0.001) than the control group, but showed no significant difference in KSRI-SF scores. No significant differences in HADS and KSRI-SF scores were found between males and females. However, IBS patients whose symptoms worsened due to stress and patients with anxiety or depression had significantly lower masculinity. QOL was poorer in IBS patients than in controls. In stepwise multivariate analyses, the anxiety score, depression score, and the degree of daily life disturbance, not masculinity, were associated with the QOL of IBS patients. Conclusions: IBS patients had higher stress, more psychiatric comorbidities, and lower QOL than controls. Low masculinity, rather than sex, was associated with stress and psychological comorbidities, which deteriorated the QOL in IBS patients.

Gramicidin, a Bactericidal Antibiotic, Is an Antiproliferative Agent for Ovarian Cancer Cells.

Background and Objectives: Gramicidin, a bactericidal antibiotic used in dermatology and ophthalmology, has recently garnered attention for its inhibitory actions against cancer cell growth. However, the effects of gramicidin on ovarian cancer cells and the underlying mechanisms are still poorly understood. We aimed to elucidate the anticancer efficacy of gramicidin against ovarian cancer cells. Materials and Methods: The anticancer effect of gramicidin was investigated through an in vitro experiment. We analyzed cell proliferation, DNA fragmentation, cell cycle arrest and apoptosis in ovarian cancer cells using WST-1 assay, terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL), DNA agarose gel electrophoresis, flow cytometry and western blot. Results: Gramicidin treatment induces dose- and time-dependent decreases in OVCAR8, SKOV3, and A2780 ovarian cancer cell proliferation. TUNEL assay and DNA agarose gel electrophoresis showed that gramicidin caused DNA fragmentation in ovarian cancer cells. Flow cytometry demonstrated that gramicidin induced cell cycle arrest. Furthermore, we confirmed via Western blot that gramicidin triggered apoptosis in ovarian cancer cells. Conclusions: Our results strongly suggest that gramicidin exerts its inhibitory effect on cancer cell growth by triggering apoptosis. Conclusively, this study provides new insights into the previously unexplored anticancer properties of gramicidin against ovarian cancer cells.

Gentian Violet Inhibits Cell Proliferation through Induction of Apoptosis in Ovarian Cancer Cells.

Gentian violet (GV) is known to have antibacterial and antifungal effects, but recent studies have demonstrated its inhibitory effects on the growth of several types of cancer cells. Here, we investigated the anticancer efficacy of GV in ovarian cancer cells. GV significantly reduced the proliferation of OVCAR8, SKOV3, and A2780 cells. Results of transferase dUTP nick and labeling (TUNEL) assay and Western blot assay indicated that the inhibitory effect of GV on ovarian cancer cells was due to the induction of apoptosis. Moreover, GV significantly increased reactive oxygen species (ROS) and upregulated the expression of p53, PUMA, BAX, and p21, critical components for apoptosis induction, in ovarian cancer cells. Our results suggest that GV is a novel antiproliferative agent and is worthy of exploration as a potential therapeutic agent for ovarian cancer.

Assessment of Biomechanical Advantages in Combined Anterior-Posterior Cervical Spine Surgery by Radiological Outcomes: Pedicle Screws over Lateral Mass Screws.

BACKGROUND: The combined anterior-posterior approach has shown good clinical outcomes for multilevel cervical diseases. This work describes the biomechanical advantage of cervical-pedicle-screw fixation over lateral-mass-screw fixation in combined anterior-posterior cases. METHOD: Seventy-six patients who received combined cervical surgery from June 2013 to December 2020 were included. The patients were divided into two groups: the lateral-mass-screw group (LMS) and the pedicle-screw group (PPS). Radiological outcomes were assessed with lateral cervical spine X-rays for evaluating sagittal alignment, subsidence, and bone remodeling. RESULTS: At 1 year postoperatively, the numbers of patients whose C2-C7 cervical lordosis was less than 20 degrees decreased by more in the PPS group (p-value = 0.001). The amount of vertical-length change from immediately to 1 year postsurgery was less in the PPS group than in the LMS group (p-value = 0.030). The mean vertebral-body-width change was larger in the PPS group than in the LMS group during 3 months to 1 year postsurgery (p-value = 0.000). CONCLUSIONS: In combined anterior-posterior cervical surgery cases, maintenance of cervical lordosis and protection of the vertebral body from subsidence were better with the pedicle-screw fixation. More bone remodeling occurred when using the pedicle-screw fixation method.

A dual-action niclosamide-based prodrug that targets cancer stem cells and inhibits TNBC metastasis.

Chemotherapy typically destroys the tumor mass but rarely eradicates the cancer stem cells (CSCs) that can drive metastatic recurrence. A key current challenge is finding ways to eradicate CSCs and suppress their characteristics. Here, we report a prodrug, Nic-A, created by combining a carbonic anhydrase IX (CAIX) inhibitor, acetazolamide, with a signal transducer and transcriptional activator 3 (STAT3) inhibitor, niclosamide. Nic-A was designed to target triple-negative breast cancer (TNBC) CSCs and was found to inhibit both proliferating TNBC cells and CSCs via STAT3 dysregulation and suppression of CSC-like properties. Its use leads to a decrease in aldehyde dehydrogenase 1 activity, CD44high/CD24low stem-like subpopulations, and tumor spheroid-forming ability. TNBC xenograft tumors treated with Nic-A exhibited decreased angiogenesis and tumor growth, as well as decreased Ki-67 expression and increased apoptosis. In addition, distant metastases were suppressed in TNBC allografts derived from a CSC-enriched population. This study thus highlights a potential strategy for addressing CSC-based cancer recurrence.

Cancer Cell-Specific Fluorescent Prodrug Delivery Platforms.

Targeting cancer cells with high specificity is one of the most essential yet challenging goals of tumor therapy. Because different surface receptors, transporters, and integrins are overexpressed specifically on tumor cells, using these tumor cell-specific properties to improve drug targeting efficacy holds particular promise. Targeted fluorescent prodrugs not only improve intracellular accumulation and bioavailability but also report their own localization and activation through real-time changes in fluorescence. In this review, efforts are highlighted to develop innovative targeted fluorescent prodrugs that efficiently accumulate in tumor cells in different organs, including lung cancer, liver cancer, cervical cancer, breast cancer, glioma, and colorectal cancer. The latest progress and advances in chemical design and synthetic considerations in fluorescence prodrug conjugates and how their therapeutic efficacy and fluorescence can be activated by tumor-specific stimuli are reviewed. Additionally, novel perspectives are provided on strategies behind engineered nanoparticle platforms self-assembled from targeted fluorescence prodrugs, and how fluorescence readouts can be used to monitor the position and action of the nanoparticle-mediated delivery of therapeutic agents in preclinical models. Finally, future opportunities for fluorescent prodrug-based strategies and solutions to the challenges of accelerating clinical translation for the treatment of organ-specific tumors are proposed.

Wavelength engineerable porous organic polymer photosensitizers with protonation triggered ROS generation.

Engineering excitation wavelength of photosensitizers (PSs) for enhanced reactive oxygen species (ROS) generation has inspired new windows for opportunities, enabling investigation of previously impracticable biomedical and photocatalytic applications. However, controlling the wavelength corresponding to operating conditions remains challenging while maintaining high ROS generation. To address this challenge, we implement a wavelength-engineerable imidazolium-based porous organic photocatalytic ROS generation system (KUP system) via a cost-effective one-pot reaction. Remarkably, the optimal wavelength for maximum performance can be tuned by modifying the linker, generating ROS despite the absence of metal ions and covalently attached heavy atoms. We demonstrate that protonated polymerization exclusively enables photosensitization and closely interacts with oxygen related to the efficiency of photosensitizing. Furthermore, superior tumor eradication and biocompatibility of the KUP system were confirmed through bioassays. Overall, the results document an unprecedented polymerization method capable of engineering wavelength, providing a potential basis for designing nanoscale photosensitizers in various ROS-utilizing applications.

Low-Molecular-Weight ß-1,3-1,6-Glucan Derived from Aureobasidium pullulans Exhibits Anticancer Activity by Inducing Apoptosis in Colorectal Cancer Cells.

ß-glucan, a plant polysaccharide, mainly exists in plant cell walls of oats, barley, and wheat. It is attracting attention due to its high potential for use as functional foods and pharmaceuticals. We have previously reported that low-molecular-weight Aureobasidium pullulans-fermented ß-D-glucan (LMW-AP-FBG) could inhibit inflammatory responses by inhibiting mitogen-activated protein kinases and nuclear factor-κB signaling pathways. Bases on previous results, the objective of the present study was to investigate the therapeutic potential of LMW-AP-FBG in BALB/c mice intracutaneously transplanted with CT-26 colon cancer cells onto their backs. Daily intraperitoneal injections of LMW-AP-FBG (5 mg/kg) for two weeks significantly suppressed tumor growth in mice bearing CT-26 tumors by reducing tumor proliferation and inducing apoptosis as compared to phosphate buffer-treated control mice. In addition, LMW-AP-FBG treatment reduced the viability of CT-26 cells in a dose-dependent manner by inducing apoptosis with loss of mitochondrial transmembrane potential and increased activated caspases. Taken together, LMW-AP-FBG exhibits anticancer properties both in vivo and in vitro.

TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis.

BACKGROUND: The osteochondrogenic switch of vascular smooth muscle cells (VSMCs) is a pivotal cellular process in atherosclerotic calcification. However, the exact molecular mechanism of the osteochondrogenic transition of VSMCs remains to be elucidated. Here, we explore the regulatory role of TXNIP (thioredoxin-interacting protein) in the phenotypical transitioning of VSMCs toward osteochondrogenic cells responsible for atherosclerotic calcification. METHODS: The atherosclerotic phenotypes of Txnip-/- mice were analyzed in combination with single-cell RNA-sequencing. The atherosclerotic phenotypes of Tagln-Cre; Txnipflox/flox mice (smooth muscle cell-specific Txnip ablation model), and the mice transplanted with the bone marrow of Txnip-/- mice were analyzed. Public single-cell RNA-sequencing dataset (GSE159677) was reanalyzed to define the gene expression of TXNIP in human calcified atherosclerotic plaques. The effect of TXNIP suppression on the osteochondrogenic phenotypic changes in primary aortic VSMCs was analyzed. RESULTS: Atherosclerotic lesions of Txnip-/- mice presented significantly increased calcification and deposition of collagen content. Subsequent single-cell RNA-sequencing analysis identified the modulated VSMC and osteochondrogenic clusters, which were VSMC-derived populations. The osteochondrogenic cluster was markedly expanded in Txnip-/- mice. The pathway analysis of the VSMC-derived cells revealed enrichment of bone- and cartilage-formation-related pathways and bone morphogenetic protein signaling in Txnip-/- mice. Reanalyzing public single-cell RNA-sequencing dataset revealed that TXNIP was downregulated in the modulated VSMC and osteochondrogenic clusters of human calcified atherosclerotic lesions. Tagln-Cre; Txnipflox/flox mice recapitulated the calcification and collagen-rich atherosclerotic phenotypes of Txnip-/- mice, whereas the hematopoietic deficiency of TXNIP did not affect the lesion phenotype. Suppression of TXNIP in cultured VSMCs accelerates osteodifferentiation and upregulates bone morphogenetic protein signaling. Treatment with the bone morphogenetic protein signaling inhibitor K02288 abrogated the effect of TXNIP suppression on osteodifferentiation. CONCLUSIONS: Our results suggest that TXNIP is a novel regulator of atherosclerotic calcification by suppressing bone morphogenetic protein signaling to inhibit the transition of VSMCs toward an osteochondrogenic phenotype.

A synchronized dual drug delivery molecule targeting cancer stem cells in tumor heterogeneity and metastasis.

Cancer stem-like cells (CSCs) represent a key barrier to successful therapy for triple-negative breast cancer (TNBC). CSCs promote the emergence of chemoresistance, triggering relapse and resulting in a poor prognosis. We herein present CDF-TM, a new small molecule-based binary prodrug conjugated with SN-38 and 3,4-difluorobenzylidene curcumin (CDF) that is specifically activated in hypoxic conditions. CDF-TM treatment significantly induced apoptosis in TNBC-derived 3D spheroids, accompanied with caspase-3 activation as well as the attenuation of tumor stemness with evidence of reduction in aldehyde dehydrogenase 1 (ALDH1) activity and the CD44high/CD24low phenotype. An in vivo orthotopic allograft model was used to investigate its effects on tumor growth and metastasis. The dissemination of CSCs from primary allografts was impaired by CDF-TM, along with inhibition of tumor growth via eradication of CSCs and downregulation of multidrug resistance 1 (MDR1). This new small molecule-based binary prodrug offers a novel therapeutic option for metastatic TNBC.

Incremental Prognostic Value of Left Ventricular Longitudinal Strain Over Ejection Fraction in Coronary Artery Bypass Grafting.

OBJECTIVES: To evaluate the incremental prognostic value of longitudinal strain over left ventricular ejection fraction (LVEF) after coronary artery bypass grafting (CABG). DESIGN: Retrospective cohort study. SETTING: Single tertiary-care center. PARTICIPANTS: Patients underwent isolated CABG between January 2014 and December 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 999 patients (median age, 65 years, 23.5% female) categorized into 3 groups according to their left ventricular (LV) systolic function status: pEF/pS (preserved LVEF and preserved longitudinal strain, n = 490), pEF/iS (preserved LVEF and impaired longitudinal strain, n = 186), and rEF (reduced LVEF, n = 323). During a median follow-up of 2.7 years, 86 (8.6%) patients had died. The 5-year survival significantly differed in patients with preserved LVEF according to the strain status (pEF/pS v pEF/iS, 90.0% v 84.6%; p = 0.002). After adjusting for potential confounders, the pEF/iS group (adjusted hazard ratio [HR], 2.17; 95% CI, 1.10-4.28; p = 0.03) and the rEF group (adjusted HR, 2.96; 95% CI, 1.46-6.00; p = 0.003) had significantly higher risks for all-cause death compared with the pEF/pS group. The addition of longitudinal strain to LVEF in the prediction model significantly improved its performance (global chi-squared, 105.2 v 110.2; p = 0.03). CONCLUSIONS: Left ventricular longitudinal strain could differentiate the prognosis after CABG in patients with preserved LVEF and provide significant incremental prognostic value to LVEF.

Immunosonodynamic Therapy Designed with Activatable Sonosensitizer and Immune Stimulant Imiquimod.

Sonodynamic therapy (SDT) has garnered extensive attention as a noninvasive treatment for deep tumors. Furthermore, imiquimod (R837), an FDA-approved toll-like receptor 7 agonist, is commonly used in clinical settings as an immune adjuvant. We prepared an activatable sonodynamic sensitizer platform (MR) based on glutathione-sensitive disulfide bonds linking Leu-MB, the reduced form of methylene blue (MB), and R837 to achieve efficient combinatory SDT and immunotherapy for tumors without harming normal tissues. We also used the amphiphilic polymer C18PMH-PEG to create self-assembled MB-R837-PEG (MRP) nanoparticles for immunosonodynamic therapy (iSDT). iSDT is a cancer treatment that combines activatable SDT and immunotherapy. Our iSDT demonstrated an excellent sonodynamic effect only at the tumor site, demonstrating high specificity in killing tumor cells when compared to SDT reported in the literature. The iSDT improves its tumor-killing effect by inducing an immune response, which is accomplished by secreted immune adjuvants in the tumor site. MRP was selectively activated by glutathione in the tumor microenvironment to release MB and R837, exhibiting excellent antitumor sonodynamic and immune responses. In addition, when combined with an α-PD-L1 antibody for immune checkpoint blockade, this therapy effectively inhibited tumor metastasis. Furthermore, mice treated with iSDT and α-PD-L1 antibody did not develop tumors even after tumor reinoculation, indicating that long-term immune memory was achieved. The concept of sonodynamic sensitizer preparation as a next-generation iSDT based on a noninvasive synergistic therapeutic modality applicable in the near future is presented in this study.

DNA-Damage-Response-Targeting Mitochondria-Activated Multifunctional Prodrug Strategy for Self-Defensive Tumor Therapy.

We report a novel multifunctional construct, M1, designed explicitly to target the DNA damage response in cancer cells. M1 contains both a floxuridine (FUDR) and protein phosphatase 2A (PP2A) inhibitor combined with a GSH-sensitive linker. Further conjugation of the triphenylphosphonium moiety allows M1 to undergo specific activation in the mitochondria, where mitochondria-mediated apoptosis is observed. Moreover, M1 has enormous effects on genomic DNA ascribed to FUDR's primary function of impeding DNA/RNA synthesis combined with diminishing PP2A-activated DNA repair pathways. Importantly, mechanistic studies highlight the PP2A obtrusion in FUDR/5-fluorouracil (5-FU) therapy and underscore the importance of its inhibition to harbor therapeutic potential. HCT116 cell xenograft-bearing mice that have a low response rate to 5-FU show a prominent effect with M1, emphasizing the importance of DNA damage response targeting strategies using tumor-specific microenvironment-activatable systems.

Facile nanostructured zinc oxide coating technique for antibacterial and antifouling air filters with low pressure drop.

Air filters effectively filtrate external contaminants including pathogenic bioaerosols; however, they also act as culture sites for the pathogenic bacteria captured in nutrient organic pollutants. Although many researchers have applied various antibacterial coatings to filters, the coating application inevitably increased the pressure drop, leading to the low efficiency and high energy consumption of the purification system. Herein, we report a simple nanostructured zinc oxide (ZnO) coating technique to confer a polypropylene nonwoven filter with superior antibacterial, antifouling and anti-biofilm properties without an additional pressure drop. For aerodynamic coating designs, filters were directly immersed into low concentration precursor solutions to enable the sedimentation of the ZnO sol-gel particles on the filter fibers according to fluid dynamic. The precursor concentration affected the surface topology and so properties of the as-fabricated coating. 0.07 M precursor solution produced a rose-like nanostructured coating exhibiting no pressure-drop increase. The large specific surface area and hydrophobic surface killed and then repelled the attached bacteria effectively. As a result, the bare filter promoted the growth and consequent biofilm formation of the surface bacteria in a favorable environment for the growth of microorganisms, while the coated filter successfully suppressed biofilm development.

Post-synthetic modifications in porous organic polymers for biomedical and related applications.

Porous organic polymers (POPs) are prepared by crosslinked polymerization of multidimensional rigid aromatic building blocks. Generally, POPs can be classified into crystalline covalent organic frameworks (COFs) and other poorly crystalline or amorphous porous polymers. Due to their remarkable intrinsic properties, such as high porosity, stability, tunability, and presence of numerous building blocks, several new POPs are being developed for application across various scientific fields. The essential sensitive functional groups needed for specific applications are not sustained under harsh POP preparation conditions. The recently developed post-synthetic modification (PSM) strategies for POPs have enabled their advanced applications that are otherwise restricted. Owing to the advanced PSM strategies POPs have experienced a blossoming resurgence with diverse functions, particularly in biomedical applications, such as bioimaging tools, drugs, enzymes, gene or protein delivery systems, phototherapy, and cancer therapy. This tutorial review focuses on the recently developed PSM strategies for POPs, especially for biomedical applications, and their future perspectives as promising bioapplicable materials.

ROS activated prodrug for ALDH overexpressed cancer stem cells.

Aldehyde dehydrogenase (ALDH), a cancer stem cell biomarker, is related to drug resistance. Co-treatment of anti-cancer drug (CPT) and ALDH inhibitor (DEAB) can overcome the drug resistance of cancer stem cells (CSCs) and finally cure cancers without relapse. We herein introduce a prodrug (DE-CPT) - consisting of 1,3-oxathiolane as an ROS responsive scaffold, and an aldehyde protecting group of DEAB - to deliver the CPT and DEAB upon reaction with ROS. From tests of the sphere-forming ability and CSC marker subpopulation, we found that DE-CPT efficiently decreases the CSCs population and kills the cancer cells.

Anti-inflammatory effects of ß-1,3-1,6-glucan derived from black yeast Aureobasidium pullulans in RAW264.7 cells.

ß-glucan derived from the black yeast Aureobasidium pullulans (A. pullulans) is one of the natural products attracting attention due to its high potential for application as a functional food and pharmaceutical. Our team of researchers obtained a highly soluble, low-molecular-weight ß-glucan from the fermentation culture medium of A. pullulans via mechanochemical ball milling method, that is, the low-molecular-weight A. pullulans-fermented ß-D-glucan (LMW-AP-FBG). We investigated the anti-inflammatory effect of LMW-AP-FBG using lipopolysaccharide (LPS)-stimulated murine macrophages (RAW264.7 cells) in the current study. LMW-AP-FBG altered LPS-stimulated inflammatory responses by reducing the release of inflammatory mediators such as nitric oxide (NO), interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α. As well, the mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) signaling pathways were downregulated by LMW-AP-FBG. Furthermore, LMW-AP-FBG markedly reduced LPS-induced expression of cell surface molecules, CD14, CD86, and MHC class II, which mediate macrophage activation. These findings suggest that LMW-AP-FBG can be used as an effective immune modulator to attenuate the progression of inflammatory disease.

A Small Molecule Strategy for Targeting Cancer Stem Cells in Hypoxic Microenvironments and Preventing Tumorigenesis.

Breast cancer consists of heterogenic subpopulations, which determine the prognosis and response to chemotherapy. Among these subpopulations, a very limited number of cancer cells are particularly problematic. These cells, known as breast cancer stem cells (BCSCs), are thought responsible for metastasis and recurrence. They are thus major contributor to the unfavorable outcomes seen for many breast cancer patients. BCSCs are more prevalent in the hypoxic niche. This is an oxygen-deprived environment that is considered crucial to their proliferation, stemness, and self-renewal but also one that makes BCSCs highly refractory to traditional chemotherapeutic regimens. Here we report a small molecule construct, AzCDF, that allows the therapeutic targeting of BCSCs and which is effective in normally refractory hypoxic tumor environments. A related system, AzNap, has been developed that permits CSC imaging. Several design elements are incorporated into AzCDF, including the CAIX inhibitor acetazolamide (Az) to promote localization in MDA-MB-231 CSCs, a dimethylnitrothiophene subunit as a hypoxia trigger, and a 3,4-difluorobenzylidene curcumin (CDF) as a readily released therapeutic payload. This allows AzCDF to serve as a hypoxia-liable molecular platform that targets BCSCs selectively which decreases CSC migration, retards tumor growth, and lowers tumorigenesis rates as evidenced by a combination of in vitro and in vivo studies. To the best of our knowledge, this is the first time a CSC-targeting small molecule has been shown to prevent tumorigenesis in an animal model.

The Potential Role of Korean Mistletoe Extract as an Anti-Inflammatory Supplementation.

Korean mistletoe has anti-inflammatory and antioxidant functions and may be a useful training supplement. We investigated the effect of Korean mistletoe extract (KME) on inflammatory markers after high-intensity exercise by 20 university male rowers (KME group vs. CON group) consuming 110 mL KME/dose (2 times a day over 8 weeks). Blood samples were collected for measurement of serum cytokine levels at baseline, immediately after exercise, and following 30 minutes of recovery. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were used as markers for inflammation. After supplementation, IL-6 and TNF-α levels were significantly lowered in the KME group than in the CON group at baseline, immediately after exercise, and following 30 minutes of recovery. KME can reduce high-strength exercise-induced increases in the levels of serum inflammatory cytokines in active individuals and improve anti-inflammatory functions.