Recent Progress and Advances in Stimuli-Responsive Polymers for Cancer Therapy

The conventional chemotherapeutic agents, used for cancer chemotherapy, have major limitations including non-specificity, ubiquitous biodistribution, low concentration in tumor tissue, and systemic toxicity. In recent years, owing to their unique features, polymeric nanoparticles have been widely used for the target-specific delivery of drugs in the body. Although polymeric nanoparticles have addressed a number of important issues, the bioavailability of drugs at the disease site, and especially upon cellular internalization, remains a challenge. A polymer nanocarrier system with a stimuli-responsive property (e.g., pH, temperature, or redox potential), for example, would be amenable to address the intracellular delivery barriers by taking advantage of pH, temperature, or redox potentials. With a greater understanding of the difference between normal and pathological tissues, there is a highly promising role of stimuli-responsive nanocarriers for drug delivery in the future. In this review, we highlighted the recent advances in different types of stimuli-responsive polymers for drug delivery

Loosely synchronized activation of anterior cingulate cortical neurons for scratching response during histamine-induced itch

Itch is a distinctive sensation that causes a specific affection and scratching reaction. The anterior cingulate cortex (ACC) has been linked to itch sensation in numerous studies; however, its precise function in processing pruritic inputs remains unknown. Distinguishing the precise role of the ACC in itch sensation can be challenging because of its capacity to conduct heterologous neurophysiological activities. Here, we used in vivo calcium imaging to examine how ACC neurons in free-moving mice react to pruritogenic histamine. In particular, we focused on how the activity of the ACC neurons varied before and after the scratching response. We discovered that although the change in neuronal activity was not synchronized with the scratching reaction, the overall activity of itch-responsive neurons promptly decreased after the scratching response. These findings suggest that the ACC does not directly elicit the feeling of itchiness.This work was supported by grants from the National Research Foundation (NRF) of Korea funded by the Korean government (MSIP) (NRF-2012R1A3A1050385 (B-KK), 2021R1A2C1013092 (H-GK), and 2022R1F1A1071248 (J-HL

Effects of a Herbal Medicine, Yukgunja-Tang, on Functional Dyspepsia Patients Classified by 3-Dimensional Facial Measurement: A Study Protocol for Placebo-Controlled, Double-Blind, Randomized Trial

Introduction. Functional dyspepsia (FD), a common upper gastrointestinal disease, is difficult to manage because of the limitations of current conventional treatments. Yukgunja-tang (YGJT) is widely used to treat FD in clinical practice in Korea, Japan, and China. However, YGJT significantly improves few symptoms of FD. In Korean medicine, FD is a well-known functional gastric disease that shows difference in the effect of herbal medicine depending on constitution or type of Korean medicine diagnosis. This study aims to investigate the efficacy of YGJT on FD patients classified by 3-dimensional facial measurement using a 3-dimensional facial shape diagnostic system (3-FSDS). Methods. A placebo-controlled, double-blind, randomized, two-center trial will be performed to evaluate the efficacy of YGJT on FD patients. Eligible subjects will be initially classified as two types by 3-dimensional facial measurement using the 3-FSDS. Ninety-six subjects (48 subjects per each type) will be enrolled. These subjects will be randomly allocated into treatment or control groups in a 2 : 1 ratio. YGJT or placebo will be administered to each group during the 8-week treatment period. The primary outcome is total dyspepsia symptom scale, and the secondary outcomes include single dyspepsia symptom scale, proportion of responders with adequate symptom relief, visual analog scale, Nepean dyspepsia index-Korean version, functional dyspepsia-related quality of life, and spleen qi deficiency questionnaire. Discussion. This is the first randomized controlled trial to assess the efficacy of the YGJT on FD patients classified by 3-dimensional facial measurement. We will compare the treatment effect of the YGJT on FD patients classified as two types using the 3-FSDS. The results of this trial will help the FD patients improve the symptoms and quality of life effectively and provide objective evidence for prescribing the YGJT to FD patients in clinical practice. Trial Registration. This trial is registered with Clinical Research Information Service Identifier: KCT0001920, 15 May, 2016

Clinical Implications of Residual Urine in Korean Benign Prostatic Hyperplasia (BPH) Patients: A Prognostic Factor for BPH-Related Clinical Events

Purpose Although post-void residual urine (PVR) is frequently utilized clinically in patients with benign prostatic hyperplasia (BPH), mainly because of its procedural simplicity, its role as a clinical prognostic factor, predictive of treatment goals, is still under much dispute. We investigated the predictive value of PVR for BPH-related clinical events including surgery, acute urinary retention (AUR), and admission following urinary tract infection (UTI). Methods From January to June of 2006, patients over 50 years of age who were diagnosed with BPH for the first time at the outpatient clinic and were then treated for at least 3 years with medications were enrolled in this study. The variables of patients who underwent surgical intervention for BPH, had occurrences of AUR, or required admission due to UTI (Group 1, n=43) were compared with those of patients who were maintained with medications only (Group 2, n=266). Results Group 1 had a significantly higher PVR, more severe symptoms, and a larger prostate at the time of the initial diagnosis in both the univariate and the multivariate analysis. In the 39 patients who underwent BPH-related surgery, although there was a significant change in Qmax at the time of surgery (mean, 13.1 months), PVR and the symptom score remained unchanged compared with the initial evaluation. In the receiver-operating characteristic curve analysis, the area under the curve of Group 1 was in the order of prostate volume (0.834), PVR (0.712), and symptom score (0.621). When redivided by arbitrarily selected PVR cutoffs of 50 mL, 100 mL, and 150 mL, the relative risk of clinical BPH progression was measured as 3.93, 2.61, and 2.11. Conclusions These data indicate that, in the symptomatic Korean population, increased PVR at baseline is a significant indicator of BPH-related clinical events along with increased symptom score or prostate volume

Solitary Fibrous Tumor of the Trachea: CT Findings with a Pathological Correlation

We present the multidetector CT findings with a pathologic correlation for the case of a solitary fibrous tumor located in the trachea. The MDCT revealed a well-circumscribed intraluminal mass arising from the trachea, with strong nodular enhancement in the periphery of the mass. The enhancement pattern of the mass corresponded histopathologically to a focal hypocellular area in the center and prominent blood vessels along the periphery of the mass. We also present volume-rendered and virtual bronchoscopic images of this rare submucosal tracheal tumor

Appropriateness of rabies post-exposure prophylaxis in pediatric patients visiting the emergency department due to animal bite

Purpose To study the appropriateness of rabies post-exposure prophylaxis (rPEP) for children with animal bite who visited the emergency department (ED). Methods The study enrolled children younger than 18 years with animal bite who visited the National Medical Center ED between January 2014 and October 2017. The children’s electronic medical records were retrospectively reviewed. Data for analysis included age, sex, body parts bitten by animals, species of animals, regions where animal bites occurred, history of recent antibiotics therapy and tetanus vaccination, and justification by the 2017 Guidelines for Rabies Control in Korea and implementation of rPEP. In children who underwent unjustified rPEP or did not undergo justified one, we recorded their guardians’ opinion for or against rPEP. Results Of the 63 enrolled children, rPEP was justified for 38 children by the Korean guidelines. Of the 38 children, 35 actually underwent rPEP. Among the remaining 3 children, 2 did not undergo the prophylaxis as per the guardians’ requests. Among the 25 children whose rPEP was not justified, 8 underwent the prophylaxis. Of these 8 children, 7 did based on the guardians’ requests. Conclusion In this study, inappropriate rPEP was usually affected by the guardians’ requests, regardless of the criteria for such prophylaxis. Thus, their requests for or against rPEP should be discussed with emergency physicians who are aware of the relevant criteria to prevent occurrence of rabies or unnecessary use of medical resources

Pulmonary hypertension due to obstructive sleep apnea in a child with Rubinstein-Taybi syndrome

Rubinstein-Taybi syndrome (RTS) is characterized by peculiar facies, mental retardation, broad thumbs, and great toes. Approximately one-third of the affected individuals have a variety of congenital heart diseases. They can also have upper airway obstruction during sleep, due to hypotonia and the anatomy of the oropharynx and airway, which make these patients susceptible to obstructive sleep apnea (OSA). In our case, pulmonary hypertension was caused, successively, by congenital heart defects (a large patent ductus arteriosus and arch hypoplasia) and obstructive sleep apnea during early infancy. The congenital heart defects were surgically corrected, but persistent pulmonary hypertension was identified 2 months after the operation. This pulmonary hypertension was due to OSA, and it was relieved by nasal continuous positive airway pressure. This case is the first report of pulmonary hypertension from OSA in a young infant with RTS

The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

Objective: The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. Materials and Methods: This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. Results: The tumor necrosis rate was significantly higher in the high dose group (93% +/- 7.6 [mean +/- SD]) than that in the control group (48% +/- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +/- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +/- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Conclusion: Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.Vali M, 2008, J PHARMACOL EXP THER, V327, P32, DOI 10.1124/jpet.108.141093Park HS, 2007, KOREAN J RADIOL, V8, P216Vali M, 2007, J VASC INTERV RADIOL, V18, P95, DOI 10.1016/j.jvir.2006.10.019Shin SW, 2006, ACTA RADIOL, V47, P1036, DOI 10.1080/02841850600977752Gwak GY, 2005, J HEPATOL, V42, P358, DOI 10.1016/j.jhep.2004.11.020Ko YH, 2004, BIOCHEM BIOPH RES CO, V324, P269, DOI 10.1016/j.bbrc.2004.09.047Llovet JM, 2003, LANCET, V362, P1907Yoon CJ, 2003, RADIOLOGY, V229, P126, DOI 10.1148/radio.2291021029Pedersen PL, 2002, BBA-BIOENERGETICS, V1555, P14Geschwind JFH, 2002, CANCER RES, V62, P3909Ko YH, 2001, CANCER LETT, V173, P83Smith TAD, 2000, BRIT J BIOMED SCI, V57, P170Pedersen PL, 1999, J BIOENERG BIOMEMBR, V31, P291Dang CV, 1999, TRENDS BIOCHEM SCI, V24, P68Bosch FX, 1999, SEMIN LIVER DIS, V19, P271Bruix J, 1997, HEPATOLOGY, V25, P259Rempel A, 1996, CANCER RES, V56, P2468Stuart KE, 1996, CANCER, V77, P2217MATHUPALA SP, 1995, J BIOL CHEM, V270, P16918OKADA M, 1995, BRIT J CANCER, V71, P518WATANABE D, 1995, ONCOLOGY, V52, P76REMPEL A, 1994, BBA-GENE STRUCT EXPR, V1219, P660BRUIX J, 1992, J HEPATOL, V15, P350OKUDA K, 1992, HEPATOLOGY, V15, P948SHINOHARA Y, 1991, FEBS LETT, V291, P55KO YH, 1990, ARCH BIOCHEM BIOPHYS, V278, P373BISMUTH H, 1986, WORLD J SURG, V10, P311JOHANSSON T, 1985, BIOCHEM BIOPH RES CO, V133, P608VIITANEN PV, 1984, J BIOL CHEM, V259, P9679BUSTAMANTE E, 1981, J BIOL CHEM, V256, P8699PEDERSEN PL, 1978, PROGR EXPT TUMOR RES, V22, P190WEINHOUS.S, 1972, CANCER RES, V32, P2007

Compositional assessment of carotenoid-biofortified rice using substantial equivalence

One important aspect in assessing the safety of genetically modified (GM) crops for human consumption is characterizing their nutrient composition. A β-carotene-biofortified rice was generated by inserting phytoene synthase (Psy) and carotene desaturase (Crtl) genes isolated from Capsicum and Pantoea into the genome of a conventional variety of rice (Nakdongbyeo). Nutrients (proximates, amino acids, fatty acids, minerals, and vitamins), anti-nutritive components (trypsin inhibitors and phytic acid), and ferulic acid in GM rice were compared with those in the parent line Nakdongbyeo. Statistical comparisons to test for equivalence showed that all of the analyzed components in the GM plants were equivalent to those in its non-transgenic counterpart, and most nutritional components fell within the range of values reported for other commercial lines, indicating the safety of the GM plant.Key words: Genetically modified crop, β-Carotene, Transgenic rice, Nutrient, Substantial equivalence