Pain accompanied by depressive symptoms is a common reason for seeking medical assistance, and many chronic pain patients experience comorbid depression. The brain-derived neurotrophic factor (BDNF) is a well-known neurotrophin expressed throughout the nervous system, playing a crucial role in neuronal growth and neuroplasticity. This study aimed to examine the effects of exercise on BDNF expression in the nervous system and reserpine (RSP)-induced pain-depression dyad. RSP (1 mg/kg) was subcutaneously administered once daily for three days in mice.The exercise was performed using a rota-rod tester for seven consecutive days following RSP administration. Pain responses were evaluated using von Frey filaments, and depression-like behaviors were assessed through forced swimming and open field tests. Immunofluorescence staining was performed to examine the changes in BDNF expression in the dorsal root ganglion (DRG), spinal cord, and hippocampus. Administration of RSP reduced mechanical paw withdrawal threshold, increased immobility time in the forced swimming test, and decreased movement in the open field test. The immunoreactivity of BDNF was increased in the DRG and spinal dorsal regions, and decreased in the hippocampus after RSP administration. Physical exercise significantly reduced the RSP-induced mechanical hypersensitivity and depression-like behaviors. In addition, exercise suppressed not only the increased expression of BDNF in the DRG and spinal dorsal regions but also the decreased expression of BDNF in the hippocampus induced by RSP administration. These findings suggest that repetitive exercise could serve as an effective and non-invasive treatment option for individuals experiencing both pain and depression by modulating BDNF expression.

The healing potential of the meniscus is limited because of the complex morphological features and insufficient blood supply. Various surgical procedures are used to treat meniscal lesions, such as partial meniscectomy, repair, and allograft transplantation. On the other hand, such strategies cannot fully regenerate and restore the morphology and functional aspects of the meniscus. This paper reviews the key aspects concerning meniscus regeneration, biological augmentation strategies, meniscus replacement scaffolds, cell therapies, and emerging tissue engineering technologies.

The healing potential of the meniscus is limited because of the complex morphological features and insufficient blood supply. Various surgical procedures are used to treat meniscal lesions, such as partial meniscectomy, repair, and allograft transplantation. On the other hand, such strategies cannot fully regenerate and restore the morphology and functional aspects of the meniscus. This paper reviews the key aspects concerning meniscus regeneration, biological augmentation strategies, meniscus replacement scaffolds, cell therapies, and emerging tissue engineering technologies.

The healing potential of the meniscus is limited because of the complex morphological features and insufficient blood supply. Various surgical procedures are used to treat meniscal lesions, such as partial meniscectomy, repair, and allograft transplantation. On the other hand, such strategies cannot fully regenerate and restore the morphology and functional aspects of the meniscus. This paper reviews the key aspects concerning meniscus regeneration, biological augmentation strategies, meniscus replacement scaffolds, cell therapies, and emerging tissue engineering technologies.

Background: Need for regulatory science is emerging with the development of pharmaceutical industry. It is essential to train regulatory science experts to meet the needs of technology and regulations to evaluate advanced products. Major regulatory science countries are conducting the regulatory science activities and fostering the experts. Methods: Published literature and the relevant website of European Union (EU) were reviewed and criteria were developed. In particular, we focused on in depth descriptions of the Innovative Medicines Initiative program, which was conducted twice. Results: EU is striving to provide funding and training experts for the development of the regulatory science by horizon 2020 and regulatory science to 2025. Innovative medicines initiative (IMI) is a public-private partnership aimed at the development of the pharmaceutical industry, including the regulatory science. IMI education and training projects have provided various education and training course including short-term curriculum and master and doctoral course. The difference between South Korea’s regulatory science expert training project in 2021 and the EU’s IMI education and training projects is participation of pharmaceutical companies. While the pharmaceutical companies participate in the IMI project to select project topics and form a community, South Korea’s project is focused on the Ministry of Food and Drug Safety and universities. Conclusion Through successful active networks with regulatory party, pharmaceutical companies, and universities, a great innovative advance of regulatory science in South Korea is expected.

Purpose: Indocyanine green (ICG) is a promising agent for intraoperative visualization of tumor tissues and sentinel lymph nodes in early-stage gynecological cancer. However, it has some limitations, including a short half-life and poor solubility in aqueous solutions. This study aimed to enhance the efficacy of near-infrared (NIR) fluorescence imaging by overcoming the shortcomings of ICG using a nano-drug delivery system and improve target specificity in cervical cancer. Materials and Methods: ICG and poly(lactic-co-glycolic acid) (PLGA) conjugated with polyethylenimine (PEI) were assembled to enhance stability. Hyaluronic acid (HA) was coated on PEI-PLGA-ICG nanoparticles to target CD44-positive cancer cells. The manufactured HA-ICG-PLGA nanoparticles (HINPs) were evaluated in vitro and in vivo on cervical cancer cells (SiHa; CD44+) and human dermal cells (ccd986sk; CD44-), respectively, using NIR imaging to compare intracellular uptake and to quantify the fluorescence intensities of cells and tumors. Results: HINPs were confirmed to have a mean size of 200 nm and a zeta-potential of 33 mV using dynamic light scattering. The stability of the HINPs was confirmed at pH 5.0–8.0. Cytotoxicity assays, intracellular uptake assays, and cervical cancer xenograft models revealed that, compared to free ICG, the HINPs had significantly higher internalization by cervical cancer cells than normal cells (p<0.001) and significantly higher accumulation in tumors (p<0.001) via CD44 receptor-mediated endocytosis. Conclusion This study demonstrated the successful application of HINPs as nanocarriers for delivering ICG to CD44-positive cervical cancer, with improved efficacy in NIR fluorescence imaging.

Background: The need for regulatory science development to evaluate advanced regulatory products is gradually increasing without hindering the technological development. Creating a research environment and fostering experts through the establishment of regulatory agency-led policies are essential for the development of regulatory science. Method: This is a comparative study of the United States, Japan, Singapore, and Korea. The literature and websites of each regulatory agency were reviewed, and the focus was on advantages and comparing advantages based on definition, development trends, and expert training projects. Results: The United States is striving to develop regulatory science in response to changes in the new pharmaceutical industry through the regulatory science report, and to foster expert both inside and outside the Food and Drug Administration (FDA). Japan is promoting regulatory science centered on regulatory science centers, and is focusing on researching work-related regulatory science within the Pharmaceuticals and Medical Devices Agency (PMDA) and improving employees’ ability to make regulatory decisions. Singapore was aiming to improve Southeast Asia’s regulatory capabilities under the leadership of Centre of Regulatory Excellence (CoRE) within Duke-NUS University. In 2021, Korea is in its early stages, starting to run a university's degree program related to regulatory science this year. Conclusion Regulatory science should be developed with the aim of improving the regulatory ability of the Ministry of Food and Drug Safety with Korea’s independent concept of regulatory science.

Background: Need for regulatory science is emerging with the development of pharmaceutical industry. It is essential to train regulatory science experts to meet the needs of technology and regulations to evaluate advanced products. Major regulatory science countries are conducting the regulatory science activities and fostering the experts. Methods: Published literature and the relevant website of European Union (EU) were reviewed and criteria were developed. In particular, we focused on in depth descriptions of the Innovative Medicines Initiative program, which was conducted twice. Results: EU is striving to provide funding and training experts for the development of the regulatory science by horizon 2020 and regulatory science to 2025. Innovative medicines initiative (IMI) is a public-private partnership aimed at the development of the pharmaceutical industry, including the regulatory science. IMI education and training projects have provided various education and training course including short-term curriculum and master and doctoral course. The difference between South Korea’s regulatory science expert training project in 2021 and the EU’s IMI education and training projects is participation of pharmaceutical companies. While the pharmaceutical companies participate in the IMI project to select project topics and form a community, South Korea’s project is focused on the Ministry of Food and Drug Safety and universities. Conclusion Through successful active networks with regulatory party, pharmaceutical companies, and universities, a great innovative advance of regulatory science in South Korea is expected.

Purpose: Indocyanine green (ICG) is a promising agent for intraoperative visualization of tumor tissues and sentinel lymph nodes in early-stage gynecological cancer. However, it has some limitations, including a short half-life and poor solubility in aqueous solutions. This study aimed to enhance the efficacy of near-infrared (NIR) fluorescence imaging by overcoming the shortcomings of ICG using a nano-drug delivery system and improve target specificity in cervical cancer. Materials and Methods: ICG and poly(lactic-co-glycolic acid) (PLGA) conjugated with polyethylenimine (PEI) were assembled to enhance stability. Hyaluronic acid (HA) was coated on PEI-PLGA-ICG nanoparticles to target CD44-positive cancer cells. The manufactured HA-ICG-PLGA nanoparticles (HINPs) were evaluated in vitro and in vivo on cervical cancer cells (SiHa; CD44+) and human dermal cells (ccd986sk; CD44-), respectively, using NIR imaging to compare intracellular uptake and to quantify the fluorescence intensities of cells and tumors. Results: HINPs were confirmed to have a mean size of 200 nm and a zeta-potential of 33 mV using dynamic light scattering. The stability of the HINPs was confirmed at pH 5.0–8.0. Cytotoxicity assays, intracellular uptake assays, and cervical cancer xenograft models revealed that, compared to free ICG, the HINPs had significantly higher internalization by cervical cancer cells than normal cells (p<0.001) and significantly higher accumulation in tumors (p<0.001) via CD44 receptor-mediated endocytosis. Conclusion This study demonstrated the successful application of HINPs as nanocarriers for delivering ICG to CD44-positive cervical cancer, with improved efficacy in NIR fluorescence imaging.

Objectives: To investigate the prevalence of nocturia in young patients with obstructive sleep apnea syndrome (OSAS) and to find out the risk factors of nocturia in the patients. Methods: We enrolled 415 untreated male OSAS patients (apnea-hypopnea index, AHI ≥5/h on polysomnography) who were under 50 years old (mean age 37.5±8.0 years). Participants completed Korean version of Beck depression inventory II (K-BDI-II), Pittsburgh sleep quality index-Korean (PSQI-K), insomnia severity index (ISI), and Epworth sleepiness scale (ESS). Participants were classified into nocturia and non-nocturia group according to the following question “Do you find yourself waking up to urinate more than twice each night?” All information was compared between two groups. Results: 22.7% (94/415) of patients reported to have nocturia. Patients with nocturia had higher score of K-BDI-II, PSQI-K, ISI, and ESS although their age and the proportion of consumption of alcohol or caffeine and metabolic diseases were not different from patients without nocturia. AHI was not significantly higher in nocturia group (38.0±29.2/h) than non-nocturia group (32.8±25.7/h, p=0.118), however, parameters indicating sleep quality were worse in nocturia group, i.e. lesser non-rapid eye movement sleep stage 3 (N3) sleep % and higher arousal index, total apnea index, and 90% oxygen desaturation index (ODI). 90% ODI and N3 sleep % were revealed to be independent factors associated with nocturia. Conclusions Considerable numbers of male OSAS patients who are under 50 years suffer from nocturia and they have worse sleep quality compared to non-nocturia patients. Higher oxygen desaturation and lesser N3 sleep % are highly predictive factors for nocturia rather than AHI in these patients.