Schisandra extract ameliorates arthritis pathogenesis by suppressing the NF-κB and MAPK signalling pathways.

Schisandra chinensis is a medicinal plant used to treat various diseases. Extracts from the leaves or fruits of S. chinensis and their components are used in osteoarthritis (OA). The OA inhibitory effect of schisandrol A, one of its components, has been previously confirmed. We aimed to confirm the OA inhibitory effect of Schisandra (including components like schisandrol A) to identify why the inhibitory effect of the Schisandra extract is better. First, we investigated the effects of the Schisandra extract on OA as a potential therapeutic. Experimental OA was induced in a mouse model via destabilized medial meniscus surgery. The animals were orally administered the Schisandra extract; the inhibition of cartilage destruction was confirmed using histological analysis. In vitro analysis showed that the Schisandra extract attenuated osteoarthritic cartilage destruction by regulating IL-1ß-induced MMP3 and COX-2 levels. The Schisandra extract inhibited IL-1ß-induced degradation of IκB (NF-κB pathway) and IL-1ß-induced phosphorylation of p38 and JNK (mitogen-activated protein kinase (MAPK) pathway). RNA-sequencing analysis showed that the Schisandra extract decreased the expression of IL-1ß-induced MAPK and NF-κB signalling pathway-related genes more than schisandrol A alone. Therefore, Schisandra extract may be more effective than schisandrol A in preventing OA progression by regulating MAPK and NF-κB signalling.

Seomae mugwort and jaceosidin attenuate osteoarthritic cartilage damage by blocking IκB degradation in mice.

Seomae mugwort, a Korean native variety of Artemisia argyi, exhibits physiological effects against various diseases. However, its effects on osteoarthritis (OA) are unclear. In this study, a Seomae mugwort extract prevented cartilage destruction in an OA mouse model. In vitro and ex vivo analyses revealed that the extract suppressed MMP3, MMP13, ADAMTS4 and ADAMTS5 expression induced by IL-1ß, IL-6 and TNF-α and inhibited the loss of extracellular sulphated proteoglycans. In vivo analysis revealed that oral administration of the extract suppressed DMM-induced cartilage destruction. We identified jaceosidin in Seomae mugwort and showed that this compound decreased MMP3, MMP13, ADAMTS4 and ADAMTS5 expression levels, similar to the action of the Seomae mugwort extract in cultured chondrocytes. Interestingly, jaceosidin and eupatilin combined had similar effects to Seomae mugwort in the DMM-induced OA model. Induction of IκB degradation by IL-1ß was blocked by the extract and jaceosidin, whereas JNK phosphorylation was only suppressed by the extract. These results suggest that the Seomae mugwort extract and jaceosidin can attenuate cartilage destruction by suppressing MMPs, ADAMTS4/5 and the nuclear factor-κB signalling pathway by blocking IκB degradation. Thus, the findings support the potential application of Seomae mugwort, and particularly jaceosidin, as natural therapeutics for OA.

Cirsium japonicum var. maackii and apigenin block Hif-2α-induced osteoarthritic cartilage destruction.

Although Hif-2α is a master regulator of catabolic factor expression in osteoarthritis development, Hif-2α inhibitors remain undeveloped. The aim of this study was to determine whether Cirsium japonicum var. maackii (CJM) extract and one of its constituents, apigenin, could attenuate the Hif-2α-induced cartilage destruction implicated in osteoarthritis progression. In vitro and in vivo studies demonstrated that CJM reduced the IL-1ß-, IL-6, IL-17- and TNF-α-induced up-regulation of MMP3, MMP13, ADAMTS4, ADAMTS5 and COX-2 and blocked osteoarthritis development in a destabilization of the medial meniscus mouse model. Activation of Hif-2α, which directly up-regulates MMP3, MMP13, ADAMTS4, IL-6 and COX-2 expression, is inhibited by CJM extract. Although cirsimarin, cirsimaritin and apigenin are components of CJM and can reduce inflammation, only apigenin effectively reduced Hif-2α expression and inhibited Hif-2α-induced MMP3, MMP13, ADAMTS4, IL-6 and COX-2 expression in articular chondrocytes. IL-1ß induction of JNK phosphorylation and IκB degradation, representing a critical pathway for Hif-2α expression, was completely blocked by apigenin in a concentration-dependent manner. Collectively, these effects indicate that CJM and one of its most potent constituents, apigenin, can lead to the development of therapeutic agents for blocking osteoarthritis development as novel Hif-2α inhibitors.

HMGB1 gene polymorphism is associated with coronary artery lesions and intravenous immunoglobulin resistance in Kawasaki disease.

OBJECTIVES: Kawasaki disease (KD) is an acute systemic vasculitis of unknown aetiology that affects infants and young children. Recent reports of elevated serum high mobility group box 1 (HMGB1) level during the acute phase of KD and its relationship to poor response to IVIG treatment suggest a possible association of HMGB1 polymorphisms with KD. We investigated the association between the polymorphisms of the HMGB1 gene, KD susceptibility, coronary artery lesions, and KD response to IVIG treatment. METHODS: Whole genome sequencing of the HMGB1 gene was performed to identify causative variants. Two tagging single nucleotide polymorphisms of the HMGB1 gene were selected using linkage disequilibrium analysis. The tagging single nucleotide polymorphisms were genotyped using the TaqMan Allelic Discrimination assay in a total of 468 subjects (265 KD patients and 203 controls). RESULTS: The HMGB1 single nucleotide polymorphisms were not associated with KD susceptibility. However, in KD patients, there was a significant association of rs1412125 with coronary artery lesions formation in the recessive model (GG vs AA + GA: odds ratio = 4.98, 95% CI = 1.69-14.66, P = 0.005). In addition, rs1412125 was associated with IVIG resistance in the recessive (GG vs AA + GA: odds ratio = 4.11, 95% CI = 1.38-12.23, P = 0.017) and allelic models (G vs A: odds ratio = 1.80, 95% CI = 1.06-3.06, P = 0.027). CONCLUSION: The rs1412125 in HMGB1 might be a risk factor for the development of coronary artery lesions and IVIG resistance in KD patients.

Effect of Coenzyme Q10 on Radiation Nephropathy in Rats.

The kidney is one of the most radiosensitive organs in the abdominal cavity and is the dose-limiting structure in cancer patients receiving abdominal or total body irradiation. In the present study, the effect of coenzyme Q10 (CoQ10) on radiation nephropathy was evaluated in rats. A total of 72 rats were equally randomized into 4 groups: Control, CoQ10, irradiation with 10 Gy (RT) + placebo, or RT + CoQ10. The 2 RT groups received single 10 Gy of abdominal irradiation. The 2 CoQ10 groups were supplemented daily with 1 mL of soybean oil containing 10 mg/kg of CoQ10. The RT + placebo and control groups received same dose of soybean oil. After 24 weeks, laboratory and histopathologic findings were compared. The 2 RT groups showed significant increases in blood urea nitrogen (BUN) and creatinine levels and significant pathologic changes such as glomerulosclerosis and tubulointerstitial fibrosis. CoQ10 supplementation resulted in significant reductions of BUN and creatinine levels compared with the RT + placebo group (P < 0.001 and P = 0.038, respectively). CoQ10 treatment significantly attenuated glomerular and tubular changes of irradiated kidney in semiquantitative analysis (P < 0.001 for both). Administration of CoQ10 can alleviate the radiation-induced nephropathy.

Body composition and personality traits in so-Yang type males.

BACKGROUND: The purpose of the present study was to examine the body composition of So-Yang type males according to Sasang constitutional medicine, which is popular in Korea. Different Sasang constitutional types are associated with different muscle distributions, body shapes, and disease susceptibilities. We used the Sasang Personality Questionnaire (SPQ) as a measure of the temperament of each Sasang type. METHODS: In total, 953 subjects aged over 20 years were recruited in Korea. We collected anthropometric parameters and bioimpedence information from the subjects and administered the SPQ. A logistic regression was conducted to calculate propensity scores. RESULTS: The percentage of skeletal muscle mass in So-Yang (SY) and non-So-Yang (non-SY) males was 45.8 ± 2.7 and 44.2 ± 3.3, respectively, before matching and 45.8 ± 2.6 and 44.9 ± 3.0, respectively, after propensity score matching. The extracellular water (ECW)/intracellular water (ICW) and extracellular water (ECW)/total body water (TBW) ratios and SPQ scores were significantly different between the SY and non-SY types. CONCLUSIONS: This study suggested that the SY type may be significantly and independently associated with body composition and could be associated with personality.

Predictors of metabolic abnormalities in phenotypes that combined anthropometric indices and triglycerides.

BACKGROUND: The hypertriglyceridemic waist (HW) phenotype has been shown to be strongly associated with metabolic abnormalities; however, to date, no study has reported the prediction of metabolic abnormalities using the HW phenotype along with waist circumference (WC) and the triglyceride (TG) level or various phenotypes consisting of an individual anthropometric index combined with the TG level. The objectives of this study were to assess the association of the HW phenotype with metabolic abnormalities in Korean women and to evaluate the predictive powers of various phenotypes with regard to metabolic abnormalities. METHODS: Total cholesterol (TC), high- and low-density lipoprotein (HDL and LDL) cholesterol, and TG levels, systolic and diastolic blood pressures (SBP and DBP), and anthropometric indices were measured in 7661 women. The Naive Bayes algorithm and logistic regression were used to determine the predictive powers of the models using different phenotypes. RESULTS: The HW phenotype demonstrated the strongest association with all metabolic components. The best phenotypic predictors were the forehead-to-rib circumference ratio + TG for the HDL level, age + TG for the LDL level, age + TG for SBP, and rib circumference + TG and neck circumference + TG for DBP. The associations between TG and TC or HDL were higher compared with those between WC and TC or HDL, whereas the associations between WC and SBP or DBP were higher compared with those between TG and SBP or DBP. Age was strongly associated with hypercholesterolemia, the HDL and LDL cholesterol levels, and SBP and had good predictive power, but not with respect to DBP. CONCLUSIONS: We have determined that the HW phenotype is a useful indicator of metabolic abnormalities in Korean women; although HW had the strongest association with metabolic abnormalities, the best phenotype combination consisting of a single anthropometric index and the TG level may differ depending on the metabolic factors in question. Our findings provide insights into the detection of metabolic abnormalities in complementary and alternative medicine.

Use of a pressure sensor array for multifunctional patient monitoring in radiotherapy: A feasibility study.

BACKGROUND: Modern radiotherapeutic techniques, such as intensity-modulated radiation therapy or stereotactic body radiotherapy, require high-dose delivery precision. However, the precise localization of tumors during patient respiration remains a challenge. Therefore, it is essential to investigate effective methods for monitoring respiration to minimize potential complications. Despite several systems currently in clinical use, there are drawbacks, including the complexity of the setup, the discomfort to the patient, and the high cost. PURPOSE: This study investigated the feasibility of using a novel pressure sensor array (PSA) as a tool to monitor respiration during radiotherapy treatments. The PSA was positioned between the treatment couch and the back of the patient lying on it and was intended to overcome some limitations of current methods. The main objectives included assessing the PSA's capability in monitoring respiratory behavior and to investigate prospective applications that extend beyond respiratory monitoring. METHODS: A PSA with 31 pressure-sensing elements was used in 12 volunteers. The participants were instructed to breathe naturally while lying on a couch without any audio or visual guidance. The performance of the PSA was compared to that of a camera-based respiratory monitoring system (RPM, Varian, USA), which served as a reference. Several metrics, including pressure distribution, weight sensitivity, and correlations between PSA and RPM signals, were analyzed. The PSA's capacity to provide information on potential applications related to patient stability was also investigated. RESULTS: The linear relationship between the weight applied to the PSA and its output was demonstrated in this study, confirming its sensitivity to pressure changes. A comparison of PSA and RPM curves revealed a high correlation coefficient of 0.9391 on average, indicating consistent respiratory cycles. The PSA also effectively measured the weight distribution at the volunteer's back in real-time, which allows for monitoring the patient's movements during the radiotherapy. CONCLUSION: PSA is a promising candidate for effective respiratory monitoring during radiotherapy treatments. Its performance is comparable to the established RPM system, and its additional capabilities suggest its multifaceted utility. This paper shows the potential use of PSA for patient monitoring in radiotherapy and suggests possibilities for further research, including performance comparisons with other existing systems and real-patient applications with respiratory training.

Analysis of risk factors for disease progression after salvage radiation therapy with androgen deprivation therapy in prostate cancer patients who have prostate-specific antigen persistence after radical prostatectomy.

PURPOSE: To assess risk factors of disease progression after salvage radiation therapy (SRT) with androgen deprivation therapy (ADT) in case of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP). MATERIALS AND METHODS: We analyzed 57 patients who received SRT with ADT between 2013 and 2019 due to PSA persistence after RP. The endpoint was disease progression defined by biochemical recurrence or clinical recurrence. Age, Pre-RP PSA level, Gleason score, pathologic stage, presence of pelvic lymph node dissection, surgical margins, and PSA at 6-8 weeks after RP were analyzed as predictive factors for disease progression. Kaplan-Meier method and Cox regression models were used for data analysis. RESULTS: At a median follow-up of 38 months (interquartile range, 26-61), 17 patients had disease progression. Pathologic T stage (pT3b vs. pT3a or lower; hazard ratio [HR] = 9.20; p = 0.035) and PSA level at 6-8 weeks after RP (≥2.04 vs. <2.04 ng/mL; HR = 5.85; p = 0.002) were predictors of disease progression. The 5-year disease progression-free survival rate was 46.7% in pT3b group as compared to 92.9 % in pT3a or lower group, and 18.4% for PSA ≥2.04 ng/mL after RP as compared to 79.2% for PSA <2.04 ng/mL. CONCLUSION: Pathological T stage (pT3b) and post RP PSA ≥2.04 ng/mL are independent risk factors of disease progression after SRT with ADT in patients with PSA persistence after RP.

BRD2-specific inhibitor, BBC0403, inhibits the progression of osteoarthritis pathogenesis in osteoarthritis-induced C57BL/6 male mice.

BACKGROUND AND PURPOSE: The discovery of new bromo- and extra-terminal inhibitors presents new drugs to treat osteoarthritis (OA). EXPERIMENTAL APPROACH: The new drug, BBC0403, was identified in the DNA-encoded library screening system by searching for compounds that target BRD (bromodomain-containing) proteins. The binding force with BRD proteins was evaluated using time-resolved fluorescence energy transfer (TR-FRET) and binding kinetics assays. Subsequently, in vitro and ex vivo analyses demonstrated the effects of the BRD2 inhibitor, BBC0403, on OA. For animal experiments, medial meniscus destabilization was performed to create a 12-week-old male C57BL/6 mouse model, and intra-articular (i.a.) injections were administered. Histological and immunohistochemical analyses were then performed. The underlying mechanism was confirmed by gene set enrichment analysis (GSEA) using RNA-seq. KEY RESULTS: TR-FRET and binding kinetics assays revealed that BBC0403 exhibited higher binding specificity for BRD2 compared to BRD3 and BRD4. The anti-OA effects of BBC0403 were tested at concentrations of 5, 10 and 20 µM (no cell toxicity in the range tested). The expression of catabolic factors, prostaglandin E2 (PGE2) production and extracellular matrix (ECM) degradation was reduced. Additionally, the i.a. injection of BBC0403 prevented OA cartilage degradation in mice. Finally, BBC0403 was demonstrated to suppress NF-κB and MAPK signalling pathways. CONCLUSION AND IMPLICATIONS: This study demonstrated that BBC0403 is a novel BRD2-specific inhibitor and a potential i.a.-injectable therapeutic agent to treat OA.

Changing trends in the management of ductal carcinoma in situ in Republic of Korea: a comprehensive analysis using Health Insurance Review and Assessment data [2009-2020].

Background: Increasing rates of diagnosis of ductal carcinoma in situ (DCIS), given the widespread use of mammography, is a global trend. Various attempts have been made in the selection of surgical methods and application of radiation therapy (RT), and the prevalence of infectious diseases has also affected these attempts. This study aimed to investigate evolving treatment patterns and trends in the management of DCIS in South Korea. Methods: We conducted a comprehensive search of the Korean Health Insurance Review and Assessment Service-National Patient Sample (HIRA-NPS) database and selected patients who underwent breast surgery following a DCIS diagnosis between 2009 and 2020. Based on this sample, the analyses were weighted according to the Korean population. We examined annual variations in mastectomy types, reconstructive procedures, and RT utilization from a multidisciplinary perspective. Results: In our weighted sample, 43,780 patients with DCIS underwent surgery, with a consistent annual increase of 10%. The proportion of lumpectomy procedures increased from 56.7% to 65.4%, showing a greater growth rate than that of total mastectomies (TMs). Following the availability of reconstruction data in 2015, shifts have emerged toward a preference for implant-based autologous tissue reconstruction. As we transitioned to the latter part of our study, the trend was marked by the increasing adoption of hypofractionated RT and omission of RT. Of the patients who underwent lumpectomy in 2020, 25.6% adopted hypofractionated RT and 53.8% omitted RT. This transformation was particularly evident among older patients, individuals treated in metropolitan areas, and those treated in small-sized healthcare facilities. Conclusions: Our study sheds light on the changing landscape of DCIS treatment in South Korea incorporating perspectives from surgeons, plastic surgeons, and radiation oncologists. We observed an increase in the rates of lumpectomy and implant-based reconstruction. Adoption of hypofractionated RT and omission of RT showed increasing trends.

A practical approach to Sasang constitutional diagnosis using vocal features.

BACKGROUND: Sasang constitutional medicine (SCM) is a type of tailored medicine that divides human beings into four Sasang constitutional (SC) types. Diagnosis of SC types is crucial to proper treatment in SCM. Voice characteristics have been used as an essential clue for diagnosing SC types. In the past, many studies tried to extract quantitative vocal features to make diagnosis models; however, these studies were flawed by limited data collected from one or a few sites, long recording time, and low accuracy. We propose a practical diagnosis model having only a few variables, which decreases model complexity. This in turn, makes our model appropriate for clinical applications. METHODS: A total of 2,341 participants' voice recordings were used in making a SC classification model and to test the generalization ability of the model. Although the voice data consisted of five vowels and two repeated sentences per participant, we used only the sentence part for our study. A total of 21 features were extracted, and an advanced feature selection method-the least absolute shrinkage and selection operator (LASSO)-was applied to reduce the number of variables for classifier learning. A SC classification model was developed using multinomial logistic regression via LASSO. RESULTS: We compared the proposed classification model to the previous study, which used both sentences and five vowels from the same patient's group. The classification accuracies for the test set were 47.9% and 40.4% for male and female, respectively. Our result showed that the proposed method was superior to the previous study in that it required shorter voice recordings, is more applicable to practical use, and had better generalization performance. CONCLUSIONS: We proposed a practical SC classification method and showed that our model having fewer variables outperformed the model having many variables in the generalization test. We attempted to reduce the number of variables in two ways: 1) the initial number of candidate features was decreased by considering shorter voice recording, and 2) LASSO was introduced for reducing model complexity. The proposed method is suitable for an actual clinical environment. Moreover, we expect it to yield more stable results because of the model's simplicity.

A malignant glomus tumor in the nasal cavity responding to radiation therapy.

Malignant glomus tumors of the head and neck are extremely rare, and to our knowledge, a response to high-dose radiation has not been described previously. We report one case in an 80-year-old woman with right nasal cavity mass. Histological examination revealed sheets of atypical round glomus cells. The presence of increased mitotic activity (25 per 10 high-power fields), cellular atypism, and tumor necrosis suggested malignancy. The smooth muscle actin, vimentin, and h-caldesmon immunohistochemistry stains the tumor cells. Two cycles of doxorubicin and cyclophosphamide chemotherapy were done and the tumor size was slightly increased. Salvage radiation therapy (RT) was delivered to the primary mass over 4 weeks (50 Gy in 20 fractions) and leading to nearly complete regression of tumor. Additional investigations are warranted so that we may determine the usefulness of RT in the management of this rare tumor.

Risk factors for primary site necrosis after definitive concurrent chemoradiotherapy in head and neck cancer.

OBJECTIVE: To identify risk factors of primary site necrosis (PSN) after definitive concurrent chemoradiation therapy (CCRT) in patients with nonoral cavity head and neck cancer (HNC). METHODS: We retrospectively reviewed the records of 256 patients treated with CCRT for HNC during 2010-2018. Patient-related (age, sex, history of smoking, hypertension, diabetes mellitus, serum hemoglobin and albumin), tumor-related (tumor site, American Joint Committee on Cancer stage), and treatment-related (induction chemotherapy, maximum point dose and mean dose of planning target volume [PTV] of primary site, absolute volumes of the PTV receiving >50-75 Gy [V50-V75]) variables were analyzed. Critical dosimetric parameters of PSN were identified using receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were used to select the significant variables for PSN development. RESULTS: After median follow-up of 44 months (range, 5-127), 7 patients (2.7%) developed PSN with a median time to event of 10 months (range, 3-12). V70 ⩾79.8 mL was the most critical dosimetric parameter for PSN (area under the ROC curve 0.873, sensitivity 0.857, specificity 0.747). In univariate analyses, pretreatment serum hemoglobin <11.0 g/dL and V70 ⩾79.8 mL were significantly associated with higher risk of PSN occurrence. V70 ⩾79.8 mL (hazard ratio 5.960, 95% confidence interval 1.289-27.548; p = 0.022) remained significant predictors of PSN in multivariate analyses. CONCLUSIONS: V70 ⩾79.8 mL is significantly related to the risk of developing PSN. These findings offer valuable clues for clinicians to minimize PSN incidence in HNC treated with curative CCRT.

Low albumin-to-alkaline phosphatase ratio is associated with inferior prognosis in patients with head and neck cancer underwent concurrent chemoradiation: A propensity score-matched analysis.

Background: Low albumin-to-alkaline phosphatase ratio (AAPR) is associated with tumor progression and poor survival outcome in some malignancies. Purpose: We aimed to determine the prognostic value of AAPR in head and neck cancer (HNC) patients underwent concurrent chemoradiotherapy (CCRT). Materials and Methods: We retrospectively reviewed medical records of 342 patients with HNC treated with definitive or adjuvant CCRT from 2007 to 2017. Receiver-operator characteristic curve assessed the cut-off value and predictive accuracy of AAPR for disease progression. Propensity score-matched (PSM) method was performed to balance baseline characteristics. Multivariate Cox regression analyses screened the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Results: The median follow-up duration was 40 months. The optimal cut-off level of AAPR was 0.523. In the PSM cohort, an AAPR < 0.523 was related to worse PFS and OS (PFS: Hazard ratio [HR], 1.936; 95% confidence interval [CI], 1.212 to 3.249; P = 0.001 and OS: HR, 1.832; 95% CI, 1.117 to 3.478; P = 0.02) compared with those with an AAPR ≥ 0.523. AJCC stage IVA-B also showed poor survival outcome compared with patients with AJCC stage II--III (PFS: HR, 1.855; 95% CI, 1.173 to 2.933; P = 0.008 and OS: HR, 1.905; 95% CI, 1.131 to 3.211; P = 0.015). Conclusions: HNC patients with low AAPR independently have worse survival outcomes than do high AAPR patients. These findings might help physicians predict treatment outcome and guide treatment strategy in patients with HNC underwent CCRT.

Influence of respiratory movement during post mastectomy radiotherapy on targets and heart for breast cancer.

BACKGROUND/AIM: This study aimed to compare the dosimetric consequences of respiratory movement in volumetric-modulated arc therapy (VMAT) and three-dimensional conformal radiation therapy (3D-CRT) during postmastectomy radiation therapy, including internal mammary nodes (IMNs). MATERIALS AND METHODS: Respiratory motion was implemented to a phantom using a dynamic device. The plans were delivered during cranial-caudal and ventral-dorsal movement in 5-mm (R05) and 10-mm (R10) amplitudes. RESULTS: At the IMN, the dose errors were -2.8% (R05) and -6.2% (R10) for 3D-CRT and -4.9% (R05) and -8.5% (R10) for VMAT. The dose errors in chest wall were -.5% (R05) and -6.0% (R10) for 3D-CRT and -1.9% (R05) and -5.3% (R10) for VMAT. The left anterior descending doses showed significantly small absolute values. The gamma pass rates of VMAT were higher than those of 3D-CRT. CONCLUSIONS: The benefit of VMAT technique in dose distribution was maintained, except in occasional instances of large breathing motion.

Novel molecule BBC0901 inhibits BRD4 and acts as a catabolic regulator in the pathogenesis of osteoarthritis.

Osteoarthritis (OA) is induced by matrix degradation and inflammation mediated by bromo-domain-containing protein 4 (BRD4)-dependent catabolic factors. BRD4 acts as both a transcriptional regulator and an epigenetic reader. BBC0901 was identified as an inhibitor of BRD4 using a DNA-encoded library screening system. We aimed to demonstrate the effects of BBC0901 on OA pathogenesis by in vitro, ex vivo, and in vivo analyses. BBC0901 inhibited the expression of catabolic factors that degrade cartilage without significantly affecting the viability of mouse articular chondrocytes. Additionally, ex vivo experiments under conditions mimicking OA showed that BBC0901 suppressed extracellular matrix degradation. RNA sequencing analysis of gene expression patterns showed that BBC0901 inhibited the expression of catabolic factors, such as matrix metalloproteinases (MMPs) and cyclooxygenase (COX)2, along with reactive oxygen species (ROS) production. Furthermore, intra-articular (IA) injection of BBC0901 into the knee joint blocked osteoarthritic cartilage destruction by inhibition of MMP3, MMP13, COX2, interleukin (IL)6, and ROS production, thereby obstructing the nuclear factor kappa-light-chain-enhancer of activated B cell and mitogen activated protein kinase signaling. In conclusion, BBC0901-mediated BRD4 inhibition prevented OA development by attenuating catabolic signaling and hence, can be considered a promising IA therapeutic for OA.

Predictive Power of the Albumin-Bilirubin Score for Hepatotoxicity in Stereotactic Ablative Radiation Therapy for Hepatocellular Carcinoma.

Assessment of liver function is crucial in predicting treatment outcomes for hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic performance of the albumin-bilirubin (ALBI) score for predicting hepatotoxicity following stereotactic body radiation therapy (SBRT) in HCC patients. A retrospective analysis was conducted on 123 HCC cases treated between 2018 and 2020. ALBI and Child-Turcotte-Pugh (CTP) scores were calculated, and hepatotoxicity was defined as a post-SBRT CTP score increase ≥2. Receiver operating characteristic (ROC) curves were used for comparison. The optimal cutoff value of the ALBI score was determined. Among the 121 patients analyzed, hepatotoxicity occurred in 5%. The ALBI score showed better predictive accuracy (area under the ROC curve: 0.77) than the CTP score. The optimal cutoff value of the ALBI score was -2.47, with a sensitivity of 85.7% and a specificity of 71.1%. Multivariable analysis revealed that ALBI score and PTV were significant factors for hepatotoxicity. In conclusion, the ALBI score demonstrated prognostic value for hepatotoxicity prediction after SBRT in HCC patients. Considering the ALBI score and PTV provides valuable insights for assessing hepatotoxicity risk during SBRT treatment for HCC.

Incidence of hypothyroidism after treatment for breast cancer: A Korean population-based study.

This Korean population-based study aimed to describe the patterns of hypothyroidism after adjuvant radiation therapy (RT) in patients with breast cancer. The Korean Health Insurance Review and Assessment Service database was searched for patients with invasive breast carcinomas. We calculated the cumulative incidence and incidence rates per 1,000 person-years of subsequent hypothyroidism and compared them using the log-rank test and the Cox proportional hazards model. Between 2007 and 2018, 117,135 women diagnosed with breast cancer with a median follow-up time of 4.6 years were identified. The 8-year incidence of hypothyroidism was 9.3% in patients treated with radiation and 8.6% in those treated without radiation (p = 0.002). The incidence rates per 1,000 person-years in the corresponding treatment groups were 6.2 and 5.7 cases, respectively. The hazard ratio (HR) in patients receiving RT was 1.081 (95% confidence interval [CI], 1.013-1.134; p = 0.002). After mastectomy, RT showed a trend toward a higher risk of hypothyroidism (HR = 1.248; 95% CI, 0.977-1.595; p = 0.076). Our study provides one of the largest population-based data analyses regarding the risk of hypothyroidism among Korean patients with breast cancer. The adjusted risk for patients treated with RT exceeded that for patients with breast cancer treated without RT. The effect was evident immediately after treatment and lasted up to approximately 9 years.

Wrinkle reduction using a Sasang constitutional medicine-based topical herbal cream in So-eum subjects: A split-face randomized double-blind placebo-controlled study.

BACKGROUND: Skin aging is caused by exogenous and endogenous factors and is commonly manifested as wrinkling, sagging, and looseness of the skin. The herbal extract including Zingiber officinale Roscoe, Atractylodes chinensis (Bunge) Kodiz, Curcuma longa L., and Cinnamomum cassia (L.) J.Presl (ZACC extract), is widely used for So-eum (SE) Sasang constitutional type individuals. This study aimed to examine the protective effects of the ZACC extract against skin aging in 21 SE type subjects. METHODS: The safety and clinical efficacy of herbal cream were evaluated after application on human skin in a split-face randomized, double-blind, placebo-controlled study. The Sasang Constitution Analysis Tool (SCAT) was used to select 21 SE type subjects, who applied herbal cream and placebo cream for 12 weeks. Visual assessment, wrinkle parameters, questionnaires, and skin safety were evaluated. RESULTS: The visual assessment score was decreased by using of the herbal cream, but there were no significant differences between groups. Among the wrinkle parameters, R1 (skin roughness) and R4 (smoothness depth) values were significantly improved after the application of the herbal cream compared to those observed after application of the placebo cream for 12 weeks. No significant differences were observed in evaluation of the product efficacy and usability by questionnaires. There were no adverse dermatologic reactions in the SE type subjects during the evaluation period. CONCLUSION: The ZACC herbal cream may be used to prevent or slow skin aging, including wrinkle formation, in SE type individuals.