Recent advances in extracellular vesicle engineering and its applications to regenerative medicine.

Extracellular vesicles (EVs) are nanosized particles that are released from cells and reflect the characteristics of the mother cell. Recently, the EVs have been used in several types of studies across many different fields. In the field of EV research, multiple cell culture and EV isolation techniques have been highlighted in importance. Various strategies, including exclusive component culture media, three-dimensional (3D) cultures, and hypoxic conditions, have been proposed for the cell culture to control function of the EVs. Ultracentrifugation, ultrafiltration, precipitation, and tangential flow filtration (TFF) have been utilized for EV isolation. Although isolated EVs have their own functionalities, several researchers are trying to functionalize EVs by applying various engineering approaches. Gene editing, exogenous, endogenous, and hybridization methods are the four well-known types of EV functionalization strategies. EV engineered through these processes has been applied in the field of regenerative medicine, including kidney diseases, osteoarthritis, rheumatoid arthritis, nervous system-related diseases, and others. In this review, it was focused on engineering approaches for EV functionalization and their applications in regenerative medicine.

Low-Grade Myofibroblastic Sarcoma on Back with Repeated Localized Recurrence and Regional Metastasis.

Low-grade myofibroblastic sarcoma (LGMS) is a rare spindle cell tumor with indolent course. Due to rarity and low-grade histologic features of LGMS, accurate diagnosis is challenging. We report a 63-year-old female patient with a three-month history of a 3.1 cm×2.5 cm sized, firm, skin-colored, painless, protruding left back mass. Initial excisional biopsy was performed and the mass was diagnosed as nodular fasciitis. After 18 months after excision, the mass recurred with pain and grew larger. Considering the clinical manifestations, diagnostic impression was changed as dermatofibrosarcoma protuberans not nodular fasciitis. Second wide excision was performed and the histopathology revealed proliferative atypical spindle cells with moderate nuclear atypia and a distinctive whorling pattern, which is suggestive of low-grade sarcoma. Additional computed tomography and positron emission tomography revealed no metastasis and suspicious residual viable malignant tissue. To remove suspicious residual tumor, third wide excision were performed and the diagnosis confirmed as LGMS. A microscopically clear resection was achieved with deep and lateral safety margin 0.6 cm each. Despite of postoperative radiotherapy with 35 times, recurrence of the tumor and lung metastasis was found after 7 months later. LGMS rarely metastasizes and occurs most commonly in the head and neck region. Thus, we report a rare case of LGMS on back which repeated localized recurrence and regional lung metastasis occurred despite wide excision and adjuvant radiotherapy.

Fixed Drug Eruption in a Patient Taking Valacyclovir without Cross-Reactivity to Acyclovir.

Fixed drug eruption (FDE) is a well-defined hyperpigmented patch that recurs in a fixed location each time a particular drug is taken. Common causative agents of FDE are non-steroidal anti-inflammatory drugs, non-narcotic analgesics, sedatives, anticonvulsants, sulfonamides, and tetracycline. We report a 33-year-old male who presented with a recurrent, localized, brownish-to-erythematous macule and papules on the peri-philtrum area two hours after taking valacyclovir. Three episodes of valacyclovir ingestion for treatment of Herpes simplex virus infection provoked a similar skin rash at the same site. Histopathology results showed vacuolar degeneration in the basal layer of the epidermis, pigmentary incontinence, and perivascular inflammatory cell infiltration in the papillary dermis. Although patch test and skin prick test showed negative responses to acyclovir and valacyclovir, an intradermal test showed a positive reaction only to valacyclovir. The oral provocation test to acyclovir and valacyclovir showed a positive reaction only to valacyclovir. Through drug history, histopathological examination, patch test, intradermal test, and oral provocation test, we established a final diagnosis of FDE due to valacyclovir without cross-reactivity to acyclovir. To find alternative therapeutic drugs, we suggest diagnostic tests with not only the suspected drugs, but also other drugs in the same class.

Insulin-Derived Cutaneous Amyloidosis: A Possible Complication of Repeated Insulin Injections.

Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of pathological fibril aggregation of proteins in the skin without systemic involvement. Macular amyloidosis, lichen (papular) amyloidosis, and nodular amyloidosis are three different subtypes of PLCA. Although the pathological mechanism of PLCA has not yet been clarified, it is assumed that a nucleus formation of amyloid fibril is formed due to repeated external stimulation, such as subcutaneous injection, which often poses diagnostic challenges. Herein, we present a 54-year-old Korean male patient with cutaneous localized amyloidosis which occurred after repeated local insulin injections, and discuss the relationship between insulin therapy in patients with diabetes mellitus and dermal amyloid deposition.

Comparison between internal jugular vein access using midline catheter and peripheral intravenous access during cardiopulmonary resuscitation in adults.

Objectives: Vascular access is an important procedure for drug administration during the resuscitation of a patient with cardiac arrest; however, it can be challenging under emergent conditions. This study aimed to investigate the efficiency of ultrasound-guided internal jugular venous access using a midline catheter versus peripheral intravenous access during cardiopulmonary resuscitation. Methods: This was a prospective single-center observational study among patients who received cardiopulmonary resuscitation. The primary outcomes were the success rate of first attempt and the time taken for vascular access via the internal jugular and peripheral veins. We also measured the diameter of the internal jugular and peripheral veins at the access point and the distance from the access point to the heart. Results: In all, 20 patients were included in the study. Internal jugular and peripheral venous access had a first-attempt success rate of 85% and 65%, respectively (p = 0.152). The time to access the internal jugular and peripheral veins was 46.4 ± 40.5 s and 28.8 ± 14.7 s, respectively (p = 0.081). The diameter of the internal jugular and peripheral veins was 10.8 ± 2.6 mm and 2.8 ± 0.8 mm, respectively (p < 0.001). The distance from the vascular access point to the heart was 20.3 ± 4.7 cm and 48.8 ± 13.1 cm for the internal jugular and peripheral veins, respectively (p < 0.001). Conclusions: There was a trend toward higher success rates in the internal jugular vein rather than the peripheral intravenous approach, which was not statistically significant.

Pharmacokinetic and Pharmacodynamic Characteristics of Pelubiprofen Tromethamine vs. Pelubiprofen in Healthy Subjects.

Compared to pelubiprofen, a cyclooxygenase-2-selective inhibitor, pelubiprofen tromethamine has been reported to exhibit improved solubility and absorption. Pelubiprofen tromethamine combines the anti-inflammatory effect of pelubiprofen with the gastric protective function of tromethamine salt, making it a relatively safe class of non-steroidal anti-inflammatory drugs with low levels of gastrointestinal side effects in addition to its original analgesic, anti-inflammatory, and antipyretic effects. This study assessed the pharmacokinetic and pharmacodynamic characteristics of pelubiprofen and pelubiprofen tromethamine in healthy subjects. Two independent clinical trials were performed in healthy subjects using a randomized, open-label, oral, single-dose, two-sequence, four-period, crossover design. In Study I and Study II, subjects received 25 mg of pelubiprofen tromethamine and 30 mg of pelubiprofen tromethamine, respectively, with 30 mg of pelubiprofen being the reference. Study I fell within the bioequivalence study criteria. A trend of increased absorption and exposure for 30 mg of pelubiprofen tromethamine vs. the reference in Study II was observed. The maximum cyclooxygenase-2 inhibitory effect of 25 mg of pelubiprofen tromethamine was approximately 98% compared to the reference, showing no significant pharmacodynamic variation. It is thus predicted that 25 mg of pelubiprofen tromethamine would show no clinically significant discrepancies in clinical analgesic and antipyretic effects from 30 mg of pelubiprofen.

Effect of 2,6-xylidine (DMA) on secretion of biomarkers for inflammation and neurodevelopment by the placenta.

Cigarette smoke enhances placental inflammation and interferes with steroidogenesis. However, the chemicals in the smoke responsible for these biological activities are unclear. 2,6 xylidine (also called 2,6 Dimethylaniline, DMA) is a component of cigarette smoke that has carcinogenic properties but its effects on the placenta are unknown. Therefore, we hypothesized that DMA may interfere with placental steroidogenesis or enhance placental inflammation. Placental explant cultures were treated with 0-50,000 nM DMA and concentrations of progesterone (P4), estradiol (E2), testosterone (T), IL-1ß, TNF-α, IL-6, sgp130, HO-1, IL-10, 8-Isoprostane (8-IsoP), and BDNF in the conditioned medium were quantified. Since many environmental toxins enhance the proinflammatory host response to infection, we also performed experiments on placental cultures co-stimulated with 107 heat-killed E. coli. DMA alone significantly reduced P4 and T secretion but enhanced E2 secretion. The toxin also reduced placental secretion of IL-6, sgp130, and BDNF. For bacteria-stimulated cultures, DMA increased secretion of P4 and T, and proinflammatory cytokines (IL-1ß, TNF-α) but had mixed effects on anti-inflammatory markers, increasing some (sgp130, IL-10) and reducing others (HO-1). However, DMA enhanced 8-IsoP levels by bacteria-stimulated placental cultures, suggesting that it increases oxidative stress by the tissues. These studies suggest that DMA affects secretion of biomarkers by the placenta and may promote inflammation. Further studies are needed to determine if these observed changes occur in vivo and the extent to which DMA exposure increases the risk of adverse pregnancy outcomes associated with smoking in pregnancy.

Morphological and Chemical Analysis of Various Disposable Acupuncture Needles Used in South Korea.

Objectives: The Korean Industrial Standard (KS) for sterile acupuncture needles was established in 2009 based on research on the quality control of acupuncture needles. We aimed to determine the quality of acupuncture needles available in South Korea in 2021 by examining their surface condition and chemical composition using field-emission scanning electron microscopy (FE-SEM) and energy-dispersive X-ray spectroscopy (EDS). Methods: In South Korea, there are 23 brands of acupuncture needles, and we examined 10-15 needles from each brand, resulting in a total of 285 needles. The microstructures of the needles were assessed by SEM. Using SEM images, we evaluated the acupuncture needle tips for the following defects/aspects scratches, lumps, detached coating, bent tip, and tip sharpness. EDS was used to determine the chemical composition of the selected acupuncture needles. Results: Overall, 88.4% of 285 needles were found to have at least one type of abnormality. The most frequently observed abnormalities were scratches and dents on the surface (68.1%), followed by detached coating (63.2%), and lumps (61.8%); blunt tips were observed in about 24% of them. Of 252 needles with at least one defect, 86.9% had two or more types of defects. The ratio of the number of needles with any defect to that of needles without any defect varied among brands, ranging from 50% to 100%. Regarding foreign materials, higher proportions of Si and O were observed on the needles, indicating incomplete or detached silicone coating. Conclusion: The quality of acupuncture needles varied among brands, suggesting that further improvements can be made through various inspection methods.

Effect of Tranexamic Acid Administration on Postoperative Ecchymosis and Edema in Excision of Lipomas.

BACKGROUND: Previous studies have shown that systemic tranexamic acid reduces bleeding during soft tissue surgeries and reduces postoperative ecchymosis and edema experienced by surgical patients. OBJECTIVE: To evaluate the effect of postoperative tranexamic acid administration on the reduction of ecchymosis and edema after lipoma surgery. MATERIALS AND METHODS: A total of 40 patients who underwent lipoma excision were included in the comparative analysis. In the tranexamic acid group (n = 20), 1 g of tranexamic acid was administered daily for 5 consecutive postoperative days. Tranexamic acid was not administered to the control group (n = 20). The severity of ecchymosis and edema at the first visit after surgery was rated on a 4-point scale by 2 blinded dermatologists. RESULTS: The mean interval of the initial visit after surgery was 1.1 ± 0.5 (range: 1-4) days. Mean ecchymosis scores were significantly lower in the tranexamic acid group (0.5 ± 0.8) than in the control group (1.2 ± 1.0) (p < .05). No statistical difference was seen in mean edema scores between groups (0.5 ± 0.6 in tranexamic acid vs 0.7 ± 0.8 in control). CONCLUSION: We observed that postoperative administration of tranexamic acid significantly decreased ecchymosis in lipoma excision.

Effect of bisphenol-A (BPA) on placental biomarkers for inflammation, neurodevelopment and oxidative stress.

Background Bisphenol-A (BPA) is a widespread pollutant whose effects on pregnant women are poorly understood. Therefore, we investigated the effects of BPA on basal and bacteria-stimulated production of proinflammatory cytokines [interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α) and IL-6], anti-inflammatory mediators [soluble glycoprotein 130 (sgp) 130, heme oxidase-1 (HO-1) and IL-10] and biomarkers for neurodevelopment [brain-derived neurotrophic factor (BDNF)], and oxidative stress [8-isoprostane (8-IsoP)] by the placenta. Methods Placental explant cultures were treated with BPA (0-10,000 nM) in the presence or absence of 107 colony-forming unit (CFU)/mL heat-killed Escherichia coli for 24 h. Biomarker concentrations in conditioned medium were quantified by the enzyme-linked immunosorbent assay (ELISA). Results Under basal conditions, IL-1ß and IL-6 production was enhanced by BPA in a dose-dependent manner. Sgp130, a soluble receptor that reduces IL-6 bioactivity, was suppressed by BPA at 1000-10,000 nM. BPA also enhanced BDNF production at 1000 and 10,000 nM, and 8-IsoP expression at 10 and 100 nM. For bacteria-treated cultures, BPA increased IL-6 production at 100 nM and reduced sgp130 at 1000 nM but had no effect on IL-1ß, TNF-α, BDNF, HO-1, 8-IsoP or IL-10 production. Conclusion BPA may increase placental inflammation by promoting IL-1ß and IL-6 but inhibiting sgp130. It may also disrupt oxidative balance and neurodevelopment by increasing 8-IsoP and BDNF production.