Tumor necrosis factor-α-treated human adipose-derived stem cells enhance inherent radiation tolerance and alleviate in vivo radiation-induced capsular contracture.

INTRODUCTION: Post-mastectomy radiotherapy plays a crucial role in breast cancer treatment but can lead to an inflammatory response causing soft tissue damage, particularly radiation-induced capsular contracture (RICC), impacting breast reconstruction outcomes. Adipose-derived stem cells (ADSCs), known for their regenerative potential via paracrine capacity, exhibit inherent radiotolerance. The influence of tumor necrosis factor-alpha (TNF-α) on ADSCs has been reported to enhance the paracrine effect of ADSCs, promoting wound healing by modulating inflammatory responses. OBJECTIVE: This study investigates the potential of TNF-α-treated human ADSCs (T-hASCs) on silicone implants to alleviate RICC, hypothesizing to enhance suppressive effects on RICC by modulating inflammatory responses in a radiation-exposed environment. METHODS: In vitro, T-hASCs were cultured on various surfaces to assess viability after exposure to radiation up to 20 Gy. In vivo, T-hASC and non-TNF-α-treated hASC (C-hASCs)-coated membranes were implanted in mice before radiation exposure, and an evaluation of the RICC mitigation took place 4 and 8 weeks after implantation. In addition, the growth factors released from T-hASCs were assessed. RESULTS: In vitro, hASCs displayed significant radiotolerance, maintaining consistent viability after exposure to 10 Gy. TNF-α treatment further enhanced radiation tolerance, as evidenced by significantly higher viability than C-hASCs at 20 Gy. In vivo, T-hASC-coated implants effectively suppressed RICC, reducing capsule thickness. T-hASCs exhibited remarkable modulation of the inflammatory response, suppressing M1 macrophage polarization while enhancing M2 polarization. The elevated secretion of vascular endothelial growth factor from T-hASCs is believed to induce macrophage polarization, potentially reducing RICC. CONCLUSION: This study establishes T-hASCs as a promising strategy for ameliorating the adverse effects experienced by breast reconstruction patients after mastectomy and radiation therapy. The observed radiotolerance, anti-fibrotic effects, and immune modulation suggest the possibility of enhancing patient outcomes and quality of life. Further research and clinical trials are warranted for broader clinical uses.

Dynamic Changes in Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Sepsis with Respect to Antibiotic Susceptibility.

Purpose: Proper antibiotic administration is crucial for sepsis management. Given the escalating incidence of antimicrobial resistance, there is a pressing need for indicators of antimicrobial susceptibility with short turnaround times. This study aimed to investigate the potential of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as an early biomarker for in vivo antibiotic susceptibility in patients with sepsis. Patients and Methods: We conducted a retrospective analysis of plasma samples from patients enrolled in a pre-established study designed to investigate prognostic biomarkers in patients with sepsis or septic shock. Baseline and 6 h sTREM-1 levels were examined using enzyme-linked immunosorbent assays. The primary outcome of the study was the comparison of percentage changes in sTREM-1 levels at the 6 h relative to baseline with respect to antibiotic susceptibility. Results: Of the 596 patients enrolled in the pre-established study, 29 with a median age of 75.8 and a 28-day mortality rate of 17.2% were included in the present analysis. Among these patients, 24 were classified into the susceptible group, whereas the remaining five were classified into the resistant group. The trend in plasma sTREM-1 levels differed with respect to antibiotic susceptibility. Moreover, percentage change in sTREM-1 levels at the 6 h relative to baseline was significantly higher in the resistant group (P = 0.028). Conclusion: The trend in plasma sTREM-1 levels in patients with sepsis differed with respect to antibiotic susceptibility, with a higher percentage change in patients treated with inappropriate antibiotics. These findings indicate the potential utility of sTREM-1 as an early biomarker of antibiotic susceptibility.

A Rare Atypical Case of Asymptomatic and Spontaneous Intraneural Hematoma of Sural Nerve: A Case Report and Literature Review.

Intraneural hematoma is a rare disease that results in an impaired nerve function because of bleeding around the peripheral nerve, with only 20 cases reported. Trauma, neoplasm, and bleeding disorders are known factors for intraneural hematoma. However, here we report atypical features of asymptomatic and spontaneous intraneural hematoma which are difficult to diagnose. A 60-year-old woman visited our clinic with the complaint of a palpable mass on the right calf. She reported no medical history or trauma to the right calf and laboratory findings showed normal coagulopathy. Ultrasonography was performed, which indicated hematoma near saphenous vein and sural nerve or neurogenic tumor. We performed surgical exploration and intraneural hematoma was confirmed on sural nerve. Meticulous paraneuriotomy and evacuation was performed without nerve injury. Histological examination revealed intraneural hematoma with a vascular wall. No neurologic symptoms were observed. In literature review, we acknowledge that understanding anatomy of nerve, using ultrasonography as a diagnostic tool and surgical decompression is key for intraneural hematoma. Our case report may help establish the implications of diagnosis and treatment. Also, we suggested surgical treatment is necessary even in cases that do not present symptoms because neurological symptoms and associated symptoms may occur later.

The Prognostic Value of the Modified Surprise Question in Critically Ill Emergency Department Patients.

Objective: The initiation of palliative care (PC) in the emergency department (ED) is effective in improving the quality of life for seriously ill patients. This study aimed to evaluate the prognostic value of the modified surprise question (mSQ), "Would you be surprised if this patient died in the next 30 days?" as a trigger for initiating PC in critically ill ED patients. Methods: We conducted a prospective cohort study over a 6-month period in an ED, during which 22 emergency residents answered the mSQ for critically ill ED patients (Korean Triage and Acuity Scale 1 or 2). The primary outcome was the accuracy of the positive mSQ (negative response to the mSQ) in predicting 30-day mortality, and logistic regression analysis was performed to identify the prognostic factors. Results: A total of 300 patients were enrolled, and the positive mSQ group included 118 (39.3%) patients. The 30-day mortality rate of the cohort was 10.0%. The sensitivity, specificity, positive predictive value, and negative predictive value of the positive mSQ were 83.3%, 65.6%, 21.2%, and 97.3%, respectively, with a c-statistic of 0.74 and a positive likelihood ratio of 2.42. In a multivariable analysis controlling for clinically relevant variables, the odds ratio for 30-day mortality of the positive mSQ was 4.76 (95% confidence interval, 1.61-14.09; P = .005). Conclusions: The mSQ may be valuable for identifying critically ill ED patients with an increased risk of 30-day mortality. Therefore, it may be utilized as a trigger for PC consultation in the ED.

The Multidomain Metaverse Cancer Care Digital Platform: Development and Usability Study.

BACKGROUND: As cancer treatment methods have diversified and the importance of self-management, which lowers the dependence rate on direct hospital visits, has increased, effective cancer care education and management for health professionals and patients have become necessary. The metaverse is in the spotlight as a means of digital health that allows users to engage in cancer care education and management beyond physical constraints. However, it is difficult to find a multipurpose medical metaverse that can not only be used in the field but also complements current cancer care. OBJECTIVE: This study aimed to develop an integrated metaverse cancer care platform, Dr. Meta, and examine its usability. METHODS: We conducted a multicenter, cross-sectional survey between November and December 2021. A descriptive analysis was performed to examine users' experiences with Dr. Meta. In addition, a supplementary open-ended question was used to ask users for their suggestions and improvements regarding the platform. RESULTS: Responses from 70 Korean participants (male: n=19, 27% and female: n=51, 73%) were analyzed. More than half (n=37, 54%) of the participants were satisfied with Dr. Meta; they responded that it was an interesting and immersive platform (n=50, 72%). Less than half perceived no discomfort when using Dr. Meta (n=34, 49%) and no difficulty in wearing and operating the device (n=30, 43%). Furthermore, more than half (n=50, 72%) of the participants reported that Dr. Meta would help provide non-face-to-face and noncontact services. More than half also wanted to continue using this platform in the future (n=41, 59%) and recommended it to others (n=42, 60%). CONCLUSIONS: We developed a multidomain metaverse cancer care platform that can support both health professionals and patients in non-face-to-face cancer care. The platform was uniquely disseminated and implemented in multiple regional hospitals and showed the potential to perform successful cancer care.

Targeted and efficient delivery of rifampicin to macrophages involved in non-tuberculous mycobacterial infection via mannosylated solid lipid nanoparticles.

Non-tuberculous mycobacterial infections are representative difficult-to-cure lung diseases with high incidence. Conventional treatments have several limitations such as negative side effects and increased drug resistance due to long-term administration. To overcome these limitations, there is a growing need for more stable drug delivery systems. Among the various drug delivery platforms developed thus far, solid lipid nanoparticles can be effectively loaded with hydrophobic substances and their physicochemical properties can be easily manipulated through surface modification, which makes them highly suitable drug delivery materials. Recent studies have reported the successful development of nanoparticles capable of selectively delivering drugs by targeting lectin-like receptors overexpressed on the surface of immune cells. Among these lectin-like receptors, the mannose receptor is a promising target because it is expressed on the surface of macrophages and is involved in immune activity. This study sought to synthesize rifampicin-loaded mannose surface-modified solid lipid nanoparticles (Man-RIF SLNs). The Man-RIF SLN synthesis process was first optimized, after which the characteristics of the synthesized particles were analyzed using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The surface modification with mannose was confirmed through FT-IR analysis. More importantly, the synthesized Man-RIF SLNs exhibited antibacterial and anti-biofilm properties against Mycobacterium intracellulare, a causative agent of non-tuberculous lung disease. Therefore, this study demonstrated that mannose receptor-targeted rifampicin delivery through solid lipid nanoparticles can be effectively applied to the treatment of non-tuberculous lung disease. Moreover, Man-RIF SLNs could also be used for the targeted delivery of drugs to several types of carcinoma cells or immune cells, as well as to treat lung diseases.

Liquid-Metal Core-Shell Particles Coated with Folate and Phospholipids for Targeted Drug Delivery and Photothermal Treatment of Cancer Cells.

Recently, several methods have been used for cancer treatment. Among them, chemotherapy is generally used, but general anticancer drugs may affect normal cells and tissues, causing various side effects. To reduce the side effects and increase the efficacy of anticancer drugs, a folate-based liquid-metal drug nanodelivery system was used to target the folate receptor, which is highly expressed in cancer cells. A phospholipid-based surface coating was formed on the surface of liquid-metal nanoparticles to increase their stability, and doxorubicin was loaded as a drug delivery system. Folate on the lipid shell surface increased the efficiency of targeting cancer cells. The photothermal properties of liquid metal were confirmed by near-infrared (NIR) laser irradiation. After treating cancerous and normal cells with liquid-metal particles and NIR irradiation, the particles were specifically bound to cancer cells for drug uptake, confirming photothermal therapy as a drug delivery system that is expected to induce cancer cell death through comprehensive effects such as vascular embolization in addition to targeting cancer cells.

Antibacterial and biofilm-inhibiting cotton fabrics decorated with copper nanoparticles grown on graphene nanosheets.

Infectious pathogens can be transmitted through textiles. Therefore, additional efforts are needed to develop functional fabrics containing antimicrobial substances to prevent the growth of antibiotic-resistant bacteria and their biofilms. Here, we developed a cotton fabric coated with reduced graphene oxide (rGO) and copper nanoparticles (Cu NPs), which possessed hydrophobic, antimicrobial, and anti-biofilm properties. Once the graphene oxide was dip-coated on a cellulose cotton fabric, Cu NPs were synthesized using a chemical reduction method to fabricate an rGO/Cu fabric, which was analyzed through FE-SEM, EDS, and ICP-MS. The results of our colony-forming unit assays indicated that the rGO/Cu fabric possessed high antibacterial and anti-biofilm properties against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Corynebacterium xerosis, and Micrococcus luteus. Particularly, the fabric could inhibit the growth of E. coli, C. xerosis, and M. luteus with a 99% efficiency. Furthermore, our findings confirmed that the same concentrations of rGO/Cu had no cytotoxic effects against CCD-986Sk and Human Dermal Fibroblast (HDF), human skin cells, and NIH/3T3, a mouse skin cell. The developed rGO/Cu fabric thus exhibited promising applicability as a cotton material that can maintain hygienic conditions by preventing the propagation of various bacteria and sufficiently suppressing biofilm formation while also being harmless to the human body.

Brugada Syndrome Unmasked by Cellulitis of the Face.

A 35-year-old male patient with no specific history visited an emergency medical center with a chief complaint of facial swelling accompanied by fever (38.3°C). Contrast-enhanced facial computed tomography confirmed diffuse soft tissue swelling and facial infiltration of inflammation. Additional laboratory findings revealed elevated white blood cell count and C-reactive protein level. The patient also complained of chest pain; therefore, electrocardiography was performed, which confirmed a curved pattern-like ST-segment elevation (≥2 mm) of V2 without elevated cardiac enzyme levels. Based on various test results, the patient was diagnosed with Brugada syndrome. He was administered intravenous empirical antibiotics and intravenous ibuprofen as an antipyretic for the treatment of facial cellulitis and Brugada syndrome. After the resolution of the symptoms, his body temperature normalized. A subsequent electrocardiogram confirmed a normal sinus rhythm pattern. This case report shows that Brugada syndrome, a rare but life-threatening disease, can be unmasked by facial cellulitis. Because antipyretics can immediately reduce the critical rate of sudden cardiac death, Brugada syndrome should be differentially diagnosed, with an evaluation of facial cellulitis, to prevent sudden cardiac death.

Scalp metastasis from an adenocarcinoma of the lung mimicking a cystic mass: case report and literature review.

A 67-year-old man visited our plastic surgery clinic complaining of a palpable protruding mass (2.0 × 2.5 cm) in the right occipital region. To establish an appropriate treatment plan for the cystic mass, brain magnetic resonance imaging was performed. A 2.2 cm nodular lesion with peripheral enhancement in the right occipital region of the scalp was confirmed. In addition, two rim-enhancing nodular lesions up to 9 mm with marked perilesional edema in the right frontal lobe were confirmed. The findings suggested metastasis from cancer. After further evaluations, a mass in the right lower lung field was identified as adenocarcinoma of the lung. Histological examination characterized the excised lesion as a cutaneous metastasis from lung adenocarcinoma. This case report shows that a cystic mass, which commonly occurs in the scalp, may indicate lung cancer. In particular, if a cystic mass of the scalp is identified in a person at high risk for lung cancer, appropriate evaluation and urgent treatment should be performed.

Accuracy and stability of computer-aided customized lingual fixed retainer: a pilot study.

BACKGROUND: With advances in digital technology, new types of lingual fixed retainers are being developed. However, there are few studies that quantitatively evaluate the accuracy and stability of lingual fixed retainers. The aim of this study was to assess the accuracy and stability of two types of computer-aided customized lingual fixed retainers and a conventional lingual fixed retainer. METHODS: A total of 10 maxillary and 10 mandibular duplicated dental models were selected, and then, three types of retainers were fabricated on the canine-to-canine area for each model. To evaluate accuracy, wire clearance at interproximal area (WCI) was measured using superimposition analysis. Initial flatness deformation was also measured for vertical distortion of retainers. Lateral width, anteroposterior length, and flatness deformation were measured at three-time points for stability assessment. Thermocycling was used to induce 6 months of time flow. RESULTS: The custom-bent group showed significantly higher WCI than the custom-cut and manual groups in the maxillary arch (P = 0.002). The custom-cut group showed significantly less flatness deformation, which was followed by the custom-bent and manual groups in both the maxillary and mandibular arch (P < 0.001). There was no significant difference in stability between the three retainer groups during 5100 cycles of thermocycling (corresponding to 6-month period). CONCLUSIONS: Since there was no difference in stability between the three groups, it is recommended to use custom-cut type retainers in light of accuracy. However, accuracy and stability are not the only factors to consider when selecting type of retainers. Because each retainer has advantages and disadvantages, the type of retainers should be decided in consideration of the clinical environment.

Clinical Benefits of Golden-Antrodia Camphorata Containing Antroquinonol in Liver Protection and Liver Fat Reduction After Alcoholic Hepatitis.

Objective: It has been reported that antroquinonol extracted from Golden-Antrodia camphorate exerts protective effects on liver function both in vitro and in vivo. However, the protective effects of Golden-Antrodia camphorata on liver function have not been fully investigated in human clinical studies. Therefore, the present study aimed to evaluate the beneficial effects of Golden-Antrodia camphorata on hepatic function after alcohol consumption in human subjects. Methods: A total of 80 participants with increased γ-glutamyl transferase levels (60-180 U/L) were enrolled in the current study and were randomly divided into two groups. Participants in the first group were orally administrated with 300 mg/day Golden-Antrodia camphorata (tablets), while those in the second group received placebo tablets for 12 weeks. Biochemical routine blood tests were performed at 6 and 12 weeks following the first administration. Results: At 12 weeks post the first Golden-Antrodia camphorata administration, the serum levels of aspartate aminotransferase (AST; p < 0.0001), alanine aminotransferase (ALT; p = 0.0002) and triglyceride (p = 0.0158) were notably declined in the Golden-Antrodia camphorata treatment group compared with the placebo group. No clinically significant differences were observed between the Golden-Antrodia camphorata treatment and placebo groups in terms of general safety parameters. Conclusion: A statistically significant difference was obtained in the serum levels of AST, ALT and triglycerides between the Golden-Antrodia camphorata and placebo groups. However, no clinical significance was observed in any of the safety parameters examined. Overall, these findings indicated that treatment with Golden-Antrodia camphorata exerted protective effects on liver function.

Sensitive and specific capture of polystyrene and polypropylene microplastics using engineered peptide biosensors.

Owing to increased environmental pollution, active research regarding microplastics circulating in the ocean has attracted significant interest in recent times. Microplastics accumulate in the bodies of living organisms and adversely affect them. In this study, a new method for the rapid detection of microplastics using peptides was proposed. Among the various types of plastics distributed in the ocean, polystyrene and polypropylene were selected. The binding affinity of the hydrophobic peptides suitable for each type of plastic was evaluated. The binding affinities of peptides were confirmed in unoxidized plastics and plasma-oxidized plastics in deionised or 3.5% saline water. Also, the detection of microplastics in small animals' intestine extracts were possible with the reported peptide biosensors. We expect plastic-binding peptides to be used in sensors to increase the detection efficiency of microplastics and potentially help separate microplastics from seawater.

Effect of Standardized Hydrangea serrata (Thunb.) Ser. Leaves Extract on Body Weight and Body Fat Reduction in Overweight or Obese Humans: A Randomized Double-Blind Placebo-Controlled Study.

Obesity is a major health problem that is caused by body fat accumulation and that can lead to metabolic diseases. Owing to several side effects of the currently used antiobesity drugs, natural plants have risen as safe and potential candidates to alleviate obesity. We have previously reported the antiobesity effect of Hydrangea serrata (Thunb.) Ser. leaves extract (WHS) and its underlying mechanisms. As an extension of our preclinical studies, this study aimed to investigate the effect of WHS on body weight and body fat reduction in overweight or obese humans. A total of 93 healthy overweight or obese males and females, aged 19-65 years, with body mass indexes (BMIs) ≥ 25 and <32 kg/m2, were recruited and received either an oral administration of 600 mg of WHS, or placebo tablets for 12 weeks. Daily supplementation with WHS decreased body weights, body fat masses, and BMIs compared with the placebo-treated group. The hip circumferences, visceral fat areas, abdominal fat areas, and visceral-to-subcutaneous ratios decreased after WHS supplementation. No significant side effects were observed during or after the 12 weeks of WHS intake. In conclusion, WHS, which has beneficial effects on body weight and body fat reduction, could be a promising antiobesity supplement that does not produce any side effects.

An innovative method of reconstructed penis reduction: a case report.

Background: Surgery to reduce the size of the reconstructed penis is uncommon. Patients who have undergone total penis reconstruction may want to reduce the size of their reconstructed penis due to convenience issues. To reduce reconstructed penis size, surgical treatment is essential. However, no research has thus far reported on this methodology. Case Description: A 50-year-old Asian man experienced a nearly total loss of his penis due to trauma 30 years ago. He underwent nearly total penis reconstruction using a tubed abdominal flap. The patient's reconstructed penis showed hypospadias, which caused discomfort during urination. The length of the penis was 17 cm. The patient felt that the reconstructed penis was too large, and a reduction surgery was planned for corrective action. Y-shape incision lines were applied on both lateral sides of the reconstructed penis to reduce the circumference, and curved incision lines were applied on the front and back of the penis to construct the neomeatus and glans of the penis. The incision was made, and the remnant tissue was dissected, with attention paid to avoid damage to the neourethra. After the tissue resection, the neourethra was isolated and resected to fit the height of the penis to construct the neomeatus and correct the hypospadias. An approximation was performed after the reconstructed penis reduction. Conclusions: Two years after the surgery, there were no complications, such as urethral stricture or fistula, and the patient was satisfied with the shape and size of the reduced penis (9 cm). The surgical reconstructed penis reduction procedure introduced in this case report achieved satisfactory aesthetic and functional results.

Antibiotic prescription consistent with guidelines in emergency department is associated with 30-day survival in severe community-acquired pneumonia.

BACKGROUND: The selection of initial empirical antibiotics is an important issue in the treatment of severe community-acquired pneumonia (CAP). This study aimed to investigate whether empirical antibiotic prescription concordant with guidelines in the emergency department (ED) affects 30-day mortality in patients with severe CAP. METHODS: We conducted a retrospective analysis of adult patients with severe CAP who were hospitalized in the ED. Severe CAP was defined according to the criteria of the 2007 Infectious Diseases Society of America/American Thoracic Society guidelines. Patients were divided into two groups according to whether they were prescribed empirical antibiotics concordant with guidelines. Multivariable Cox proportional hazard regression analysis was performed to identify the independent association between the prescription of initial empirical antibiotics concordant with the guidelines and 30-day mortality. Propensity score matching was performed to reduce selection bias between groups and Kaplan-Meier survival analysis was performed to analyze the time-to-event of 30-day survival. RESULTS: In total, 630 patients were hospitalized in the ED for severe CAP, and 179 (28.4%) died within 30 days. Antibiotics consistent with guidelines were prescribed to 359 (57.0%) patients. The 30-day mortality was significantly higher in the guideline-discordant group (p = 0.003) and multivariable Cox proportional hazard regression analysis revealed that the prescription of antibiotics discordant with the guidelines was independently associated with 30-day mortality (hazard ratio 1.43, 95% CI 1.05-1.93). After propensity score matching, there were 255 patients in each group. The 30-day mortality was lower in the group prescribed guideline-concordant antibiotics than in the group prescribed guideline-discordant antibiotics (23.9% vs. 33.3%, p = 0.024). Kaplan-Meier survival analysis showed that antibiotic prescription concordant with the guidelines resulted in higher survival rates at 30 days (p = 0.002). CONCLUSIONS: The prevalence of antibiotic prescription consistent with guidelines for severe CAP seemed to be low in the ED, and this variable was independently associated with 30-day survival.

Development of Therapeutic Antibodies and Modulating the Characteristics of Therapeutic Antibodies to Maximize the Therapeutic Efficacy.

Monoclonal antibodies (mAb) have been used as therapeutic agents for various diseases, and immunoglobulin G (IgG) is mainly used among antibody isotypes due to its structural and functional properties. So far, regardless of the purpose of the therapeutic antibody, wildtype IgG has been mainly used, but recently, the engineered antibodies with various strategies according to the role of the therapeutic antibody have been used to maximize the therapeutic efficacy. In this review paper, first, the overall structural features and functional characteristics of antibody IgG, second, the old and new techniques for antibody discovery, and finally, several antibody engineering strategies for maximizing therapeutic efficacy according to the role of a therapeutic antibody will be introduced.

The relationship between catastrophic health expenditure and health-related quality of life.

OBJECTIVES: The objective of our study was to investigate the relationship between catastrophic health expenditure (CHE) and health-related quality of life (HRQoL) in general population. METHODS: We used Korean Health Panel Survey data from 2011 to 2013, which included data from 8850 baseline participants of 19 years of age or older. We defined CHE as total annual out-of-pocket health payment that was 40% greater than the household's capacity to pay. HRQoL was measured using the EuroQol-visual analogue scale (EQ-VAS). We used generalized estimating equations to perform a longitudinal regression analysis. RESULTS: A total of 4.5% of the participants (n = 398) experienced CHE. Those with CHE tended to have a lower EQ-VAS index score compared with those without CHE (ß: - 1.34, p = 0.013). A subgroup analysis revealed that individuals experiencing CHE had significant decreases as the number of chronic diseases increased (three or more, ß: - 1.85, p = 0.014). CONCLUSIONS: Catastrophic health expenditure influences HRQoL, which was more pronounced in patient with chronic disease. The efforts should focus on people who suffer from excessive health expenditures and chronic diseases.

Validated UPLC-MS/MS method for the determination of tadalafil in human plasma and its application to a pharmacokinetic study.

A simple, rapid, and reliable UPLC-MS/MS method was developed and validated for the determination of tadalafil in human plasma. The plasma samples were deproteinized with acetonitrile. Chromatographic separation was performed on a Shiseido C18 (100 × 2.1 mm, 2.7 µm) column with isocratic elution using 2.0 mM ammonium acetate and acetonitrile (55:45, v/v) with 0.1% formic acid at a flow rate of 0.7 mL/min. The total run time was 1 min per sample. The quantitative analysis was performed using multiple reaction monitoring at transition of m/z 390.4 → 268.3 for tadalafil and m/z 475.3 → 283.3 for sildenafil as an internal standard. The method was fully validated over a concentration range of 5-1,000 ng/mL with a lower quantification limit of 5 ng/mL. Intra- and inter-day precision (relative standard deviation, %RSD) were within 8.4% and accuracy (relative error, %RE) was lower than -3.2%. The developed and validated method was successfully applied to a pharmacokinetic study of tadalafil (20 mg) in Korean healthy male subjects (n = 12).

Afzelin positively regulates melanogenesis through the p38 MAPK pathway.

Melanogenesis refers to synthesis of the skin pigment melanin, which plays a critical role in the protection of skin against ultraviolet irradiation and oxidative stressors. We investigated the effects of afzelin on melanogenesis and its mechanisms of action in human epidermal melanocytes. In this study, we found that afzelin increased both melanin content and tyrosinase activity in a concentration-dependent manner. While the mRNA levels of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein (TRP)-1 increased following afzelin treatment, the mRNA levels of TRP-2 were not affected by afzelin. Likewise, afzelin increased the protein levels of MITF, TRP-1, and tyrosinase but not TRP-2. Mechanistically, we found that afzelin regulated melanogenesis by upregulating MITF through phosphorylation of p38 mitogen-activated protein kinase (MAPK), independent of cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling. Taken together, these findings indicate that the promotion of melanogenesis by afzelin occurs through increased MITF gene expression, which is mediated by activation of p38 MAPK, and suggest that afzelin may be useful as a protective agent against ultraviolet irradiation.