ABSTRACT
Background@#Botulinum toxin type A is widely used to improve facial wrinkles associated with aging, and various types are available. However, the efficacy, particularly the duration of effect, varies among these types, and research on this subject is limited. This study aimed to compare the efficacy and safety of incobotulinum toxin A and abobotulinum toxin A. @*Methods@#This prospective analysis included cases of moderate to severe glabellar lines treated with either incobotulinum toxin A or abobotulinum toxin A. After a 24-week follow-up, clinical photos were taken at each visit. The severity of the glabellar lines was evaluated by three groups: the investigator, the patients, and an independent evaluator. @*Results@#The study included a total of 42 patients. When comparing the improvement rates of glabellar lines at maximum frown for both groups at the week-4 visit, which was the primary efficacy endpoint, no statistically significant difference was observed. However, the abobotulinum toxin A group demonstrated a higher improvement at the week-24 visit, as evaluated by the investigator, and this difference was statistically significant. @*Conclusions@#Overall, the abobotulinum toxin A group exhibited a higher improvement rate in the glabellar lines at the frown state. The difference in the improvement rate at the week-24 visit was 36.86%, which was statistically significant.
ABSTRACT
Objectives@#. The recent expansion of eligibility for cochlear implantation (CI) by the U.S. Food and Drug Administration (FDA) to include infants as young as 9 months has reignited debates concerning the clinically appropriate cut-off age for pediatric CI. Our study compared the early postoperative trajectories of receptive and expressive language development in children who received CI before 9 months of age with those who received it between 9 and 12 months. This study involved a unique pediatric cohort with documented etiology, where the timing of CI was based on objective criteria and efforts were made to minimize the influence of parental socioeconomic status. @*Methods@#. A retrospective review of 98 pediatric implantees recruited at a tertiary referral center was conducted. The timing of CI was based on auditory and language criteria focused on the extent of delay corresponding to the bottom 1st percentile of language development among age-matched controls, with patients categorized into very early (CI at 9 months), in children with profound deafness who have a clear deafness etiology and language development delays (<1st percentile).
ABSTRACT
Background@#Operative management with intramedullary nail fixation remains the definitive treatment of choice for osteoporotic subtrochanteric (ST) fractures; however, there remains no consensus regarding the proper nail length. We aimed to use 3-dimensional finite element (FE) analysis to determine the optimal nail length for the safe fixation of osteoporotic ST fractures. @*Methods@#Nine modes of FE models were constructed using 9 different lengths of cephalomedullary nails (short nails: 170, 180, and 200 mm; long nails: 280, 300, 320, 340, 360, and 380 mm) from the same company. The interfragmentary motion was analyzed. Additionally, the peak von Mises stress (PVMS) in the cortical bone, cancellous bone of the femoral head, and the nail were measured, and the yielding risk for each subject was investigated. @*Results@#Long nails were associated with less interfragmentary motion. In the cortical bone, the PVMS of short nails was observed at the distal locking screw holes of the femoral medial cortex; however, in long nails, the PVMS was observed at the lag screw holes on the lateral cortex. The mean yielding risk of long nails was 40.1% lower than that of short nails. For the cancellous bone of the femoral head, the PVMS in all 9 FE models was in the same area: at the apex of the femoral head. There was no difference in the yielding risk between short and long nails. For implants, the PVMS was at the distal locking screw hole of the nail body in the short nails and the nail body at the fracture level in the long nails. The mean yielding risk was 74.9% lower for long nails than that for short nails. @*Conclusions@#Compared to short nails, long nails with a length of 320 mm or more showed less interfragmentary motion and lower yielding risk in low-level osteoporotic ST fractures. The FE analysis supports long nails as a safer option than short nails, especially for treating transverse-type low-level osteoporotic ST fractures.
ABSTRACT
Background@#Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity. @*Methods@#A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared. @*Results@#Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered. @*Conclusion@#The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.
ABSTRACT
Purpose@#This study investigated hand-washing practice among community-dwelling older adults during the coronavirus disease 2019 (COVID-19) pandemic and aimed to identify the impact of COVID-19-related concerns and depression on hand-washing practice. @*Methods@#This was a secondary analysis of data extracted from the 2020 Community Health Survey. The primary data were collected through self-reporting from August 10 to September 8, 2020 in a cross-sectional study. The subjects consisted of 1,350 adults aged 65 or older living in J Province who participated in the 2020 Community Health Survey. Results: The factors affecting hand-washing practice among older adults were male gender (β = –.18, p < .001), age (β = –.07, p = .001), no education (β = –.20, p < .001) and elementary, middle, and high school graduation (β = –.15, p < .001) compared to a college or higher education, poor health perception (β = –.13, p < .001), COVID-19-related concerns (β = .08, p = .005), and depression (β = –.07, p = .001). To summarize, the factors negatively affecting hand-washing practice included male gender, lower education level, poor health perception, and depression, while the factors positively associated with hand-washing practice included COVID-19-related concerns. @*Conclusion@#These findings show the importance of considering these multifaceted determinants when designing targeted interventions and educational programs aimed at promoting hand-washing among older adults. Additionally, based on the relationship between hand-washing practice and COVID-19-related concerns and depression, interventions that can alleviate mental problems along with providing proper education are required.
ABSTRACT
Background@#Tinnitus is a bothersome condition associated with various symptoms. However, the mechanisms of tinnitus are still uncertain, and a standardized assessment of the diagnostic criteria for tinnitus is required. We aimed to reach a consensus on diagnosing tinnitus with professional experts by conducting a Delphi study with systematic review of the literature. @*Methods@#Twenty-six experts in managing tinnitus in Korea were recruited, and a two-round modified Delphi study was performed online. The experts evaluated the level of agreement of potential criteria for tinnitus using a scale of 1–9. After the survey, a consensus meeting was held to establish agreement on the results obtained from the Delphi process. Consensus was defined when over 70% of the participants scored 7–9 (agreement) and fewer than 15% scored 1–3 (disagreement). To analyze the responses of the Delphi survey, the content validity ratio and Kendall’s coefficient of concordance were evaluated. @*Results@#Consensus was reached for 22 of the 38 statements. For the definition of tinnitus, 10 out of 17 statements reached consensus, with three statements achieving complete agreement including; 1) Tinnitus is a conscious perception of an auditory sensation in the absence of a corresponding external stimulus, 2) Tinnitus can affect one’s quality of life, and 3) Tinnitus can be associated with hearing disorders including sensorineural hearing loss, vestibular schwannoma, Meniere’s disease, otosclerosis, and others. For the classification of tinnitus, 11 out of 18 statements reached consensus. The participants highly agreed with statements such as; 1) Vascular origin is expected in pulse-synchronous tinnitus, and 2) Tinnitus can be divided into acute or chronic tinnitus. Among three statements on the diagnostic tests for tinnitus only Statement 3, “There are no reliable biomarkers for sensory or emotional factors of tinnitus.”reached consensus. All participants agreed to perform pure-tone audiometry and tinnitus questionnaires, including the Tinnitus Handicap Inventory and Tinnitus Questionnaire. @*Conclusion@#We used a modified Delphi method to establish a consensus-based definition, a classification, and diagnostic tests for tinnitus. The expert panel reached agreement for several statements, with a high level of consensus. This may provide practical information for clinicians in managing tinnitus.
ABSTRACT
Background@#During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. @*Methods@#This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. @*Results@#Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. @*Conclusion@#This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.
ABSTRACT
Background@#and Purpose The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. @*Methods@#We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3–6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3–6. @*Results@#Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3–6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P<0.001), apparent diffusion coefficient map (P<0.001), FLAIR (P<0.001), and clinical data (P=0.004). @*Conclusion@#The integration of multimodal imaging and clinical data resulted in superior prediction of the 90-day functional outcomes in AIS patients compared to the use of a single data modality.
ABSTRACT
Objectives@#Childhood maltreatment can negatively impact cognitive development, including executive function, working memory, and processing speed. This study investigated the impact of childhood maltreatment on cognitive function in young adults using various measurements, including computerized tests, and their relationship with emotional dysregulation. @*Methods@#We recruited 149 healthy individuals with and without maltreatment experiences and used the Wechsler Adult Intelligence Scale IV (WAIS-IV) and a computerized battery to analyze cognitive function. @*Results@#Both the WAIS-IV and computerized tests revealed that individuals with a history of childhood maltreatment had decreased cognitive function, especially in terms of working memory and processing speed. These individuals tended to employ maladaptive emotion regulation strategies. Among cognitive functions, working memory is negatively related to maladaptive emotion regulation strategies such as catastrophizing. @*Conclusion@#This study highlights the effects of childhood maltreatment on cognitive function in young adulthood. Moreover, the study suggests clinical implications of cognitive interventions for improving emotion regulation and cognitive function in individuals with a history of childhood maltreatment.
ABSTRACT
The prevalence of osteoporosis and incidence of osteoporotic fractures is increasing gradually as life expectancy is prolonged and the aged population increases. Osteoporotic hip fractures (femoral neck fractures and femoral intertrochanteric fractures) have high mortality because the patients with these fractures are elderly and have several comorbidities. Thorough preparation and a multidisciplinary approach in the preoperative period are critical, and early surgery is recommended. There are also several principles to treat osteoporotic hip fractures and prevent fixation failures. Many studies have suggested various treatment methods for femoral neck fractures and femoral intertrochanteric fractures. Functional recovery treatment is essential based on the patient’s health and activity levels. Finally, aggressive management of osteoporosis and the prevention of falling is needed to treat osteoporotic hip fractures successfully.
ABSTRACT
Background@#Achilles tendon is composed of dense connective tissue and is one of the largest tendons in the body. In veterinary medicine, acute ruptures are associated with impact injury or sharp trauma. Healing of the ruptured tendon is challenging because of poor blood and nerve supply as well as the residual cell population. Platelet-rich plasma (PRP) contains numerous bioactive agents and growth factors and has been utilized to promote healing in bone, soft tissue, and tendons. @*Objective@#The purpose of this study was to evaluate the healing effect of PRP injected into the surrounding fascia of the Achilles tendon after allograft in rabbits. @*Methods@#Donor rabbits (n = 8) were anesthetized and 16 lateral gastrocnemius tendons were fully transected bilaterally. Transected tendons were decellularized and stored at −80°C prior to allograft. The allograft was placed on the partially transected medial gastrocnemius tendon in the left hindlimb of 16 rabbits. The allograft PRP group (n = 8) had 0.3 mL of PRP administered in the tendon and the allograft control group (n = 8) did not receive any treatment. After 8 weeks, rabbits were euthanatized and allograft tendons were transected for macroscopic, biomechanical, and histological assessment. @*Results@#The allograft PRP group exhibited superior macroscopic assessment scores, greater tensile strength, and a histologically enhanced healing process compared to those in the allograft control group. @*Conclusions@#Our results suggest administration of PRP on an allograft tendon has a positive effect on the healing process in a ruptured Achilles tendon.
ABSTRACT
Objectives@#This study examined the association between ultra-processed food (UPF) consumption and chronic diseases in elderly Koreans. @*Methods@#Data from the 2019–2021 Korea National Health and Nutrition Examination Survey were analyzed. Dietary intake and UPF consumption were assessed using the NOVA food classification based on 24-hour recall data from 3,790 participants (aged 65+ years).Participants were divided into 4 groups based on the quartile of energy intake from UPFs.Regions were classified as urban or rural. Multivariable logistic regression was employed to estimate the adjusted odds ratios (AORs) with 95% confidence intervals (CIs) after controlling for potential confounders. @*Results@#Among the participants, 71.3% resided in urban and 28.7% in rural areas.Compared to the urban elderly, rural participants tended to be older, have lower education and income levels, be more likely to live in single-person households, and have a higher smoking rate (P < 0.05). Urban elderly consumed more UPFs daily (146.1 g) compared to rural residents (126.6 g; P < 0.05). “Sugar-sweetened beverages” were the most consumed category in both regions. “Sweetened milk and its products” and “traditional sauces” were prominent in urban areas, while rural elderly consumed more “traditional sauces” and “distilled alcoholic beverages.” Rural areas also had a higher carbohydrate-to-calorie ratio than urban areas. Compared to the lowest quartile of UPF intake, the highest quartile was significantly associated with impaired fasting glucose only in rural areas (AOR, 1.48; 95% CI, 1.00–2.19; P for trend = 0.0014). No significant associations were observed for diabetes in either urban or rural areas. @*Conclusions@#This study suggests that high intake of UPFs is associated with increased odds of impaired fasting glucose in rural elderly. Further research is needed to elucidate the specific negative health effects of UPFs in different populations, and targeted efforts should promote healthy diets in both urban and rural areas.
ABSTRACT
Objective@#The Acceptance and Action Questionnaire for Obsessions and Compulsions (AAQ-OC) is a version of the Acceptance and Action Questionnaire (AAQ) that specifically measures unwanted intrusive thoughts and responses (e.g., experiential avoidance) to them. This study aimed to investigate the reliability and validity of the Korean version of the AAQ-OC in clinical and nonclinical Korean samples. @*Methods@#In this study, 561 university students and 121 patients with obsessive–compulsive disorder (OCD) completed the AAQ-OC and several other psychological scales. Descriptive, correlation, and exploratory and confirmatory factor analyses as well as group comparisons were conducted. @*Results@#The results of the exploratory and confirmatory factor analyses indicated a two-factor structure that best fits the data in the university sample: Factors 1 and 2 matched the original Valued Action and Willingness subscales, respectively. The reliability analyses revealed that the AAQ-OC and its factors had excellent internal consistencies. As regards the concurrent validity, the AAQ-OC and its factors had a positive correlation with the AAQ-II and Cognitive Fusion Questionnaire. Compared with the university students, the OCD patients had higher AAQ-OC scores, and their obsessive–compulsive symptoms, particularly the two symptom dimensions of responsibility for harm and mistakes and unacceptable thoughts, were significantly associated with the AAQ-OC and two subscales. @*Conclusion@#The findings of this study confirm the reliability and validity of the Korean version of the AAQ-OC.
ABSTRACT
Background@#Exhaled condensates contain inflammatory biomarkers; however, their roles in the clinical field have been under-investigated. @*Methods@#We prospectively enrolled subjects admitted to pulmonology clinics. We collected exhaled breath condensates (EBC) and analysed the levels of six and 12 biomarkers using conventional and multiplex enzyme-linked immunosorbent assay, respectively. @*Results@#Among the 123 subjects, healthy controls constituted the largest group (81 participants; 65.9%), followed by the preserved ratio impaired spirometry group (21 patients; 17.1%) and the chronic obstructive pulmonary disease (COPD) group (21 patients; 17.1%). In COPD patients, platelet derived growth factor-AA exhibited strong positive correlations with COPD assessment test (ρ=0.5926, p=0.0423) and COPD-specific version of St. George’s Respiratory Questionnaire (SGRQ-C) score (total, ρ=0.6725, p=0.0166; activity, ρ=0.7176, p=0.0086; and impacts, ρ=0.6151, p=0.0333). Granzyme B showed strong positive correlations with SGRQ-C score (symptoms, ρ=0.6078, p=0.0360; and impacts, ρ=0.6007, p=0.0389). Interleukin 6 exhibited a strong positive correlation with SGRQ-C score (activity, ρ=0.4671, p=0.0378). The absolute serum eosinophil and basophil counts showed positive correlations with pro-collagen I alpha 1 (ρ=0.6735, p=0.0164 and ρ=0.6295, p=0.0283, respectively). In healthy subjects, forced expiratory volume in 1 second (FEV1)/forced vital capacity demonstrated significant correlation with CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein 1 alpha (ρ=0.3897 and p=0.0068). FEV1 exhibited significant correlation with CCL11/eotaxin (ρ=0.4445 and p=0.0017). @*Conclusion@#Inflammatory biomarkers in EBC might be useful to predict quality of life concerning respiratory symptoms and serologic markers. Further studies are needed.
ABSTRACT
Purpose@#This study aimed to assess the feasibility and safety of administering intraoperative radiotherapy (IORT) as a boost during breast-conserving surgery (BCS) following neoadjuvant chemotherapy for patients at high risk of breast cancer recurrence. @*Materials and Methods@#Patients who underwent neoadjuvant chemotherapy received a single 20-Gy dose of IORT during BCS, followed by external beam radiotherapy 4–6 weeks after surgery. @*Results@#The median follow-up duration was 31.0 months (range, 18.0–59.0 months). Initial tumor sizes had a median of 2.6 cm (range: 0.8–5.3 cm), reducing to 0.3 cm (range: 0–4.0 cm) after neoadjuvant chemotherapy. The most common neoadjuvant chemotherapy regimen was doxorubicin and cyclophosphamide, followed by paclitaxel (n=42, 73.7%). Among 57 patients who received neoadjuvant chemotherapy before BCS and IORT, 2 patients (3.5%) required secondary surgery to achieve negative resection margins due to initially positive margins. Regional lymph node irradiation was performed in 37 (64.9%) patients. There was no grade 3 or higher adverse events, with 4 patients (7.0%) experiencing grade 2 acute radiation dermatitis and 3 (5.3%) having less than grade 2 breast edema. Binary correlation analysis did not reveal statistically significant associations between applicator size or radiation therapy modality and the risk of treatment-related toxicity. Furthermore, chi-square analysis showed that the grade of treatment-related toxicity was not associated with the fractionated regimen (p=0.375). @*Conclusion@#Most patients successfully received IORT as a tumor bed boost after neoadjuvant chemotherapy. Thus, IORT may be a safe and feasible option for patients with advanced-stage breast cancer receiving neoadjuvant chemotherapy.
ABSTRACT
Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.
ABSTRACT
The current study aimed to reveal the potential effect of meclofenamate, a nonsteroidal anti-inflammatory drug, on the gene expression of airway MUC5AC mucin. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with meclofenamate for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. Thereafter, the effect of meclofenamate on the PMAinduced nuclear factor kappa B (NF-kB) signaling pathway was assessed. Meclofenamate inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA by inhibiting the degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest meclofenamate suppresses mucin gene expression by regulating NF-kB signaling pathway in human pulmonary epithelial cells.
ABSTRACT
In this study, artesunate, an antimalarial agent, was investigated for its potential effect on the gene expression of airway MUC5AC mucin. The human pulmonary epithelial NCI-H292 cells were pretreated with artesunate for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of artesunate on PMA-induced nuclear factor kappa B (NFkB) signaling pathway was also examined. Artesunate inhibited the glycoprotein production and mRNA expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation.These results suggest artesunate suppresses the gene expression of mucin through regulation of NF-kB signaling pathway, in human pulmonary epithelial cells.
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)-β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.
ABSTRACT
Purpose@#This phase I study was conducted to determine the maximum tolerated dose and the recommended phase II dose of weekly administered Genexol-PM combined with carboplatin in patients with gynecologic cancer. @*Materials and Methods@#This open-label, phase I, dose-escalation study of weekly Genexol-PM included 18 patients with gynecologic cancer, who were equally divided into three cohorts of dose levels. Cohort 1 received 100 mg/m2 Genexol-PM and 5 area under the curve (AUC) carboplatin, cohort 2 received 120 mg/m2 Genexol-PM and 5 AUC carboplatin, and cohort 3 received 120 mg/m2 Genexol-PM and 6 AUC carboplatin. The safety and efficacy of each dose were analyzed for each cohort. @*Results@#Of the 18 patients, 11 patients were newly diagnosed and seven patients were recurrent cases. No dose-limiting toxicity was observed. The maximum tolerated dose was not defined, but a dose up to 120 mg/m2 of Genexol-PM in combination with AUC 5-6 of carboplatin could be recommended for a phase II study. In this intention-to-treat population, five patients dropped out of the study (carboplatin-related hypersensitivity, n=1; refusal of consent, n=4). Most patients (88.9%) with adverse events recovered without sequelae, and no treatment-related death occurred. The overall response rate of weekly Genexol-PM in combination with carboplatin was 72.2%. @*Conclusion@#Weekly administered Genexol-PM with carboplatin demonstrated an acceptable safety profile in gynecologic cancer pati-ents. The recommended phase II dose of weekly Genexol-PM is up to 120 mg/m2 when combined with carboplatin.