Unraveling Stereochemical Structure-Activity Relationships of Sesquiterpene Lactones for Inhibitory Effects on STAT3 Activation.

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

Oral consumption of Bonito fish-derived elastin peptide (VGPG Elastin® ) improves biophysical properties in aging skin: A randomized, double-blinded, placebo-controlled study.

BACKGROUND: Recent in vitro and in vivo studies have suggested that the elastin peptide improves the skin's biophysical properties, enhancing the proliferation of fibroblasts and elastin synthesis, resulting in anti-aging properties. Therefore, we conducted a randomized, double-blinded, placebo-controlled study to clinically evaluate the effect of elastin peptide intake on human skin. MATERIALS AND METHODS: Healthy adult participants (N = 100) were randomly assigned to receive a test product containing 100 mg of Bonito elastin peptide (VGPG Elastin® ) or placebo. In this study, all participants were Asian from Korea. The parameters of skin wrinkles, hydration, and brightening (melanin index) were measured at baseline and 4, 8, and 12 weeks after intervention. RESULTS: The average skin roughness, maximum peak-to-valley values, maximum peak height of the wrinkle, maximum valley depth of the wrinkle, average maximum height of the wrinkle, and eye wrinkle volume improved considerably in the test group compared with the placebo after 12 weeks of intervention. Skin hydration was enhanced, and the melanin index was significantly lower in the test group than in the placebo group. No participant experienced adverse events related to the test product. CONCLUSION: Oral consumption of Bonito elastin peptide (VGPG Elastin®) reduced fine wrinkles, enhanced skin moisture, and decreased melanin index without significant adverse effects and may be a promising anti-wrinkle, anti-dryness, and anti-pigmentation treatment.

Clinical Activity of TGF-ß Inhibitor Vactosertib in Combination with Imatinib in Desmoid Tumors: A Multicenter Phase Ib/II Study.

PURPOSE: The study was to determine the activity and safety of the TGF-ß inhibitor vactosertib in combination with imatinib in patients with desmoid tumors. PATIENTS AND METHODS: In this investigator-initiated, open-label, multicenter, phase Ib/II trial, patients with desmoid tumors not amenable to locoregional therapies (surgery and/or radiotherapy) or with disease progression following at least one treatment were enrolled. Participants were administered 400 mg imatinib daily in combination with vactosertib (5 days on and 2 days off, twice a day) every 28 days. In phase Ib, the vactosertib dose was set at 100 mg (level -1) and 200 mg (level 1) to determine the recommended phase II dose (RP2D). Phase II assessed the efficacy, with the primary endpoint being progression-free rate (PFR) at 16 weeks. RESULTS: No dose-limiting toxicities were observed during phase Ib; therefore RP2D was defined at doses of 400 mg imatinib daily in combination with 200 mg vactosertib. Of the 27 patients evaluated, 7 (25.9%) achieved a confirmed partial response and 19 (70.4%) were stable. The PFR at 16 weeks and 1 year were 96.3% and 81.0%, respectively. Most toxicities were mild to moderate myalgia (n = 10, 37%), anemia (n = 10, 37%), and nausea (n = 9, 33.3%). Common grade 3 to 4 toxicities included neutropenia (n = 6, 22.2%) and anemia (n = 5, 18.5%). CONCLUSIONS: The vactosertib and imatinib combination was well tolerated, with promising clinical activity in patients with progressive, locally advanced desmoid tumors. This is the first study investigating a novel target agent, a TGF-ß inhibitor, in this rare and difficult-to-treat desmoid tumor.

Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial.

We aimed to determine the activity of the anti-VEGF receptor tyrosine-kinase inhibitor, pazopanib, combined with the anti-PD-L1 inhibitor, durvalumab, in metastatic and/or recurrent soft tissue sarcoma (STS). In this single-arm phase 2 trial (NCT03798106), treatment consisted of pazopanib 800 mg orally once a day and durvalumab 1500 mg once every 3 weeks. Primary outcome was overall response rate (ORR) and secondary outcomes included progression-free survival (PFS), overall survival, disease control rate, immune-related response criteria, and safety. The ORR was 30.4% and the trial met the pre-specified endpoint. The median PFS was 7.7 months (95% confidence interval: 5.7-10.4). The common treatment-related adverse events of grades 3-4 included neutropenia (9 [19.1%]), elevated aspartate aminotransferase (7 [14.9%]), alanine aminotransferase (5 [10.6%]), and thrombocytopenia (4 [8.5%]). In a prespecified transcriptomic analysis, the B lineage signature was a significant key determinant of overall response (P = 0.014). In situ analysis also showed that tumours with high CD20+ B cell infiltration and vessel density had a longer PFS (P = 6.5 × 10-4) than those with low B cell infiltration and vessel density, as well as better response (50% vs 12%, P = 0.019). CD20+ B cell infiltration was identified as the only independent predictor of PFS via multivariate analysis. Durvalumab combined with pazopanib demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile.

Low-molecular-weight collagen peptides supplement promotes a healthy skin: A randomized, double-blinded, placebo-controlled study.

BACKGROUND: Oral collagen peptides supplementation was reported to improve skin integrity and counteract skin aging. AIMS: A randomized, double-blinded, placebo-controlled study was conducted to clinically evaluate the impact of low-molecular-weight collagen peptides on the human skin. PATIENTS/METHODS: Healthy adult participants (n = 100) were randomly assigned to receive a test product containing low-molecular-weight collagen peptides or a placebo. Parameters of skin wrinkles, elasticity, hydration, and whitening (melanin and erythema indexes) were measured at baseline and after 4, 8, and 12 weeks. RESULTS: Compared with the placebo group, the average skin roughness, maximum of all peak-to-valley values, maximum peak height of the wrinkle, and average maximum height of the wrinkle were significantly improved in the test group. Parameters of skin elasticity, including overall elasticity, net elasticity, and biological elasticity, were also significantly improved in the test group at Week 12 as compared with the placebo group. Moreover, skin hydration and whitening parameters changed more significantly in the test group than in the placebo group. None of the participants experienced adverse events related to the test product. CONCLUSIONS: Taken together, these findings suggest that low-molecular-weight collagen peptides supplementation can safely ehance human skin wrinkling, hydration, elasticity, and whitening properties.

Combination of Fractional Microneedling Radiofrequency and Ablative Fractional Laser versus Ablative Fractional Laser Alone for Acne and Acne Scars.

PURPOSE: Fractional microneedle radiofrequency (FMR) systems are used to treat inflammatory acne and scarring. Nonetheless, few controlled studies have combined this treatment with the traditional ablative fractional laser (AFL). We aimed to assess the safety and efficacy of the combination of FMR and AFL versus AFL alone in treating acne and acne scars. MATERIALS AND METHODS: In this 20-week, randomized, split-face study, 23 Korean patients with facial acne and acne scars underwent FMR and AFL treatments. One half of each patient's face was randomly assigned to receive FMR+AFL, whereas the other half received AFL alone. Treatments were administered in three consecutive sessions at 4-week intervals. This study investigated the severity of inflammatory acne, acne scars, individual lesion counts, depressed scar volumes, as well as patient and physician satisfaction. In addition, five patients underwent skin biopsy, and sebum output was measured. RESULTS: The FMR+AFL treatment demonstrated superior efficacy compared to AFL alone in terms of inflammatory acne and acne scar grading, lesion counts, and subjective satisfaction. The side effects were minimal and well-tolerated in both groups. Immunohistochemical findings from skin biopsy samples revealed that the application of FMR+AFL could induce an inhibitory effect on sebum secretion at the molecular level. CONCLUSION: FMR combined with AFL is a well-tolerated and effective treatment modality for inflammatory acne and acne scarring.

Direct comparison of diagnostic and clinical values between Tc-99 m DPD and Tc-99 m PYP scintigraphy in patients with cardiac amyloidosis.

BACKGROUND: Technetium-99 m 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) and technetium-99 m sodium pyrophosphate (PYP) are the two most commonly used radiotracers for cardiac amyloidosis (CA), but no studies have directly compared them. Therefore, in this study, we directly compared the diagnostic and clinical utility of DPD and PYP scintigraphy in patients with CA. METHODS: Ten patients with CA were enrolled. Eight clinical variables and 12 scintigraphic parameters were used. Clinical variables were age, sex, estimated glomerular filtration rate (eGFR), N-terminal pro brain natriuretic peptide (NT-proBNP), and the results of electromyography (EMG), a sensory test, electrocardiogram, and echocardiography (EchoCG). Four heart retention ratios (heart/whole-body profile, heart/pelvis, heart/skull, and heart/contralateral lung) were calculated from the DPD and PYP scans and two visual scoring systems (Perugini and Dorbala systems) were used. Comparative analyses were performed between radiotracers and between visual scoring systems using clinical variables and scintigraphic parameters. RESULTS: Twenty DPD parameters and nine PYP parameters had significant associations with age, eGFR, NT-proBNP, EchoCG, and EMG. DPD parameters had more frequent significant associations with clinical variables than PYP parameters. Compared to visual scores in the DPD scan, the proportion of patients with higher visual scores in the PYP scan was relatively greater than those with lower visual scores, and there were more patients with a visual score of 2 or higher in PYP scans than DPD scans. CONCLUSIONS: DPD scintigraphy may reflect the disease severity of CA better than PYP scintigraphy, whereas PYP scintigraphy may be a more sensitive imaging modality for identifying CA involvement.

Preliminary study for prediction of benign vertebral compression fracture age by quantitative water fraction using modified Dixon sequences: an imaging biomarker of fracture age.

PURPOSE: This study aimed to evaluate whether quantitative water fraction parameters could predict fracture age in patients with benign vertebral compression fractures (VCFs). METHODS: A total of 38 thoracolumbar VCFs in 27 patients imaged using modified Dixon sequences for water fraction quantification on 3-T MRI were retrospectively reviewed. To calculate quantitative parameters, a radiologist independently measured the regions of interest in the bone marrow edema (BME) of the fractures. Furthermore, five features (BME, trabecular fracture line, condensation band, cortical or end plate fracture line, and paravertebral soft-tissue change) were analyzed. The fracture age was evaluated based on clear-onset symptoms and previously available images. A correlation analysis between the fracture age and water fraction was evaluated using a linear regression model, and a multivariable analysis of the dichotomized fracture age model was performed. RESULTS: The water fraction ratio was the only significant factor and was negatively correlated with the fracture age of VCFs in multiple linear regression (p = 0.047), whereas the water fraction was not significantly correlated (p = 0.052). Water fraction and water fraction ratio were significant factors in differentiating the fracture age of 1 year in multiple logistic regression (odds ratio 0.894, p = 0.003 and odds ratio 0.986, p = 0.019, respectively). Using a cutoff of 0.524 for the water fraction, the area under the curve, sensitivity, and specificity were 0.857, 85.7%, and 87.1%, respectively. CONCLUSIONS: Water fraction is a good imaging biomarker for the fracture healing process. The water fraction ratio of the compression fractures can be used to predict the fracture age of benign VCFs.

Oral Supplementation of Low-Molecular-Weight Collagen Peptides Reduces Skin Wrinkles and Improves Biophysical Properties of Skin: A Randomized, Double-Blinded, Placebo-Controlled Study.

Orally administered collagen peptides could contribute to antiaging by replacing the degraded extracellular matrix proteins caused by photoaging. This study aimed to evaluate the efficacy and safety of low-molecular-weight collagen peptides for treating photoaged and dry skin. In this randomized, placebo-controlled, parallel-group, double-blinded trial, we randomly assigned study participants (n = 100) to either the test product group or placebo group at a 1:1 ratio for 12 weeks. The wrinkle scale score, eye wrinkle volume, roughness parameters, such as the average maximum height of the wrinkle (Rz), arithmetic average within the total measuring length of the wrinkle (Ra), maximum profile valley depth of the wrinkle (Rv), and skin hydration, transepidermal water loss (TEWL), overall elasticity (R2), and ratio of elastic recovery to total deformation (R7) were evaluated at baseline, 6 weeks, and 12 weeks. Safety assessments with serial blood tests were also conducted. Efficacy assessments of data from 84 participants were conducted as the per-protocol analysis. After 12 weeks, the 10-grade crow's feet photo scale score, eye wrinkle volume, skin roughness parameters (Rz, Ra, and Rv), skin elasticity (R2 and R7), skin hydration, and TEWL were significantly improved in the test product group compared to the placebo group. There were no adverse events or abnormalities according to laboratory analysis associated with using the test material during the study period. This study showed that the oral supplementation of low-molecular-weight collagen peptides could improve the wrinkles, elasticity, hydration, and barrier integrity of photoaged facial skin. This clinical study was registered with the Korean Clinical Research Information Service and International Clinical Trials Registry Platform (No: KCT0006500).

Therapeutic Implications of TGF-ß Pathway in Desmoid Tumor Based on Comprehensive Molecular Profiling and Clinicopathological Properties.

(1) Background: Desmoid tumors have a relatively high local failure rate after primary treatment using surgery and/or radiotherapy. Moreover, desmoid tumors recur at the primary site for many patients. An effective therapeutic strategy for the desmoid tumor is needed to maintain quality of life and prolong survival. (2) Method: First of all, we collected desmoid tumor tissues and investigated the status of protein expression for beta-catenin and alpha-SMA through immunohistochemistry. Then, we performed targeted sequencing and whole RNA sequencing. To compare the data with other cancer types, we used NGS data from sarcoma patients at Yonsei Cancer Center (YCC-sarcoma cohort, n = 48) and The Cancer Genome Atlas (TCGA, n = 9235). Secondly, we established the novel patient-derived preclinical models (n = 2) for the validation of treatment strategy. The same gene alteration of primary tissue was demonstrated. (3) Results: We discovered specific gene sets related to the TGF-ß signaling pathway. Moreover, we selected the combination treatment comprising TGF-ß inhibitor, vactosertib, and imatinib. In screening for the anti-proliferation effect, the combination treatment of TGF-ß inhibitor was more effective for tumor suppression than monotherapy. (4) Conclusion: We found preclinical indications that TGF-ß inhibitors could prove useful as a potential treatment for patients with desmoid tumors. Moreover, we could find some examples in clinical trials.

Effect of Cancer-Related Dysfunctional Beliefs About Sleep on Fear of Cancer Progression in the Coronavirus Pandemic.

BACKGROUND: This study aimed to explore clinical correlates of fear of progression (FoP) among patients with cancer during the coronavirus disease 2019 (COVID-19) pandemic and examine the mediation effect of cancer-related dysfunctional beliefs about sleep (C-DBS). METHODS: Medical charts of patients with cancer who visited a psycho-oncology clinic between July and November 2021 were reviewed. Baseline socio-demographic and cancer-related variables were collected. Patients' self-report questionnaires, regarding FoP, depression (Patient Health Questionnaire-9 items; PHQ-9), viral anxiety (Stress and Anxiety to Viral Epidemics-6 items; SAVE-6), C-DBS, and other distress, were investigated. Pearson's correlation and linear regression were performed to examine the risk factors of FoP. Mediation effect analysis with the bootstrap method with 2,000 resamples was implemented. RESULTS: A total of 231 patients were included in the analysis. Linear regression revealed that FoP was predicted by age (ß = -0.14, P = 0.003), PHQ-9 (ß = 0.48, P < 0.001), SAVE-6 (ß = 0.34, P < 0.001), and C-DBS (ß = 0.15, P = 0.005). FoP was directly influenced by SAVE-6 and mediated by C-DBS, while it was directly influenced by PHQ-9 with no mediation effect. CONCLUSION: During the COVID-19 pandemic, the FoP of patients with cancer was associated with younger age, depression, viral anxiety, and C-DBS. Depression and viral anxiety directly influenced FoP, while C-DBS mediated the association between viral anxiety and FoP. Therefore, oncology healthcare professionals are recommended to assess C-DBS of their patients when they are highly distressed from FoP.

Assessing the Sleep-wake Pattern in Cancer Patients for Predicting a Short Sleep Onset Latency.

Objective: We investigated the sleep parameters and clinical factors related to short sleep onset latency (SL) in cancer patients. Methods: We retrospectively reviewed the medical records of 235 cancer patients. Patient Health Questionnaire-9, State and Trait Anxiety Inventory (State subcategory), Insomnia Severity Index (ISI), Cancer-related Dysfunctional Beliefs about Sleep, and Fear of Progression scale scores and sleep related parameters including sleeping pill ingestion time, bedtime, sleep onset time, and wake-up time were collected. We also calculated the duration from sleeping pill ingestion to bedtime, sleep onset time, and wake-up time; duration from wake-up time to bedtime and sleep onset time; and time spent in bed over a 24 hours period. Results: Among patients not taking sleeping pills (n = 145), early wake-up time (adjusted odds ratio [OR]: 0.39, 95% confidence interval [CI] 0.19-0.78), early sleep onset time (OR: 0.50, 95% CI 0.27-0.93), and low ISI score (OR: 0.82, 95% CI 0.71-0.93) were identified as expecting variables for SL ≤ 30 minutes. Longer duration from wake-up time to bedtime (OR: 2.49, 95% CI 1.48-4.18) predicted SL ≤ 30 minutes. Among those taking sleeping pills (n = 90), early sleep onset time (OR: 0.54, 95% CI 0.39-0.76) and short duration from pill ingestion to sleep onset time (OR: 0.05, 95% CI 0.02-0.16) predicted SL ≤ 30 minutes. Conclusion: Cancer patients who fell asleep quickly spent less time in bed during the day. Thus, before cancer patients with insomnia are prescribed sleeping pills, their sleep parameters should be examined to improve their SL.

Discrepancy between desired time in bed and desired total sleep time in patients with cancer: The DBST index and its relationship with insomnia severity and sleep onset latency.

Patients with cancer can often experience insomnia or sleep disturbances. This study aimed to explore whether the discrepancy between a patient's desired time in bed and desired total sleep time (DBST index) can be used as a measurement tool for insomnia severity or sleep onset latency [SOL] in patients with cancer. This retrospective medical records review study gathered clinical information and scores from scales and indices such as the Insomnia Severity Index (ISI), Cancer-related Dysfunctional Beliefs about Sleep (C-DBS) scale, Patient Health Questionnaire-9 items (PHQ-9), State subcategory of State and Trait Anxiety Inventory, and the short form of the Fear of Progression Questionnaire. Sleep indices of time variables (bedtime, sleep onset time, and wake-up time), duration variables [SOL, time in bed (TIB), time in bed over 24 hours (TIB/d), and duration from wake-up time to bedtime (WTB)], and DBST index were calculated. ISI scores were predicted by the PHQ-9 (ß = 0.34, P < 0.001), C-DBS scale (ß = 0.17, P = 0.034), and DBST indices (ß = 0.22, P = 0.004). Long SOL value was predicted by early bedtimes (ß = -0.18, P = 0.045), short WTB durations (ß = -0.26, P = 0.004), and high DBST index values (ß = 0.19, P = 0.013). The DBST index was significantly correlated with both insomnia severity and SOL in patients with cancer.

Functional Impairments in the Mental Health, Depression and Anxiety Related to the Viral Epidemic, and Disruption in Healthcare Service Utilization among Cancer Patients in the COVID-19 Pandemic Era.

PURPOSE: Literature is scarce regarding cancer care utilization during the massive outbreak of coronavirus disease 2019 (COVID-19) in the Republic of Korea. We investigated functional impairments in mental health and their relationships with depression, anxiety regarding the viral epidemic, and disruptions in healthcare service utilization among cancer patients in the COVID-19 pandemic era. MATERIALS AND METHODS: We used an online survey with questions related to the disturbances faced by patients with cancer in utilizing healthcare services in the pandemic era. Current mental health status was assessed using the Work and Social Adjustment Scale (WSAS), Stress and Anxiety to Viral Epidemics-6 (SAVE-6) scale, Patient Health Questionnaire-9 (PHQ-9), Insomnia Severity Index (ISI), Brief Resilience Scale (BRS), Cancer-Related Dysfunctional Beliefs about Sleep Scale (C-DBS), and Fear of COVID-19 over Cancer (FCC). RESULTS: Among the 221 responders, 95 (43.0%) reported disruptions in healthcare service utilization during the COVID-19 pandemic. Logistic regression analysis revealed that functional impairment in the mental health of these patients was expected due to disruptions in healthcare service utilization, high levels of depression, anxiety regarding the viral epidemic, fear of COVID over cancer, and low resilience. Mediation analysis showed that patient resilience and cancer-related dysfunctional beliefs about sleep partially mediated the effects of viral anxiety on functional impairment. CONCLUSION: In this pandemic era, patients with cancer experience depression, anxiety regarding the viral epidemic, and disruptions in healthcare service utilization, which may influence their functional impairments in mental health.

Gender-based disparities in burn injuries, care and outcomes: A World Health Organization (WHO) Global Burn Registry cohort study.

BACKGROUND: We aimed to describe the gender-based disparities in burn injury patterns, care received, and mortality across national income levels. METHODS: In the WHO Global Burn Registry (GBR), we compared patient demographics, injury characteristics, care and outcomes by sex using Chi-square statistics. Logistic regression was used to identify the associations of patient sex with surgical treatment and in-hospital mortality. RESULTS: Among 6431 burn patients (38 % female; 62 % male), females less frequently received surgical treatment during index hospitalization (49 % vs 56 %, p < 0.001), and more frequently died in-hospital (26 % vs 16 %, p < 0.001) than males. Odds of in in-hospital death was 2.16 (95 % CI: 1.73-2.71) times higher among females compared to males in middle-income countries. CONCLUSIONS: Across national income levels, there appears to be important gender-based disparities among burn injury epidemiology, treatment received and outcomes that require redress. Multinational registries can be utilized to track and to evaluate initiatives to reduce gender disparities at national, regional and global levels.

Preischemic Treadmill Exercise Ameliorates Memory Impairment and Microvasculature Damage in Rat Model of Chronic Cerebral Hypoperfusion.

PURPOSE: Silent information regulator 1 (SIRT1) in the brain is essential for maintaining cellular homeostasis and plays a neuroprotective role in cerebral ischemia and neurodegenerative disorders. The effect of preischemic treadmill exercise on chronic cerebral hypoperfusion (CCH)-induced spatial learning memory impairment, microvascular injury, and blood-brain barrier (BBB) disruption in relation with SIRT1 expression was evaluated. METHODS: Prior to bilateral common carotid artery occlusion (BCCAO) surgery, the rats in the exercise groups performed low-intensity treadmill running for 30 minutes once daily during 8 weeks. BCCAO surgery was performed on male Wistar rats at 12 weeks of age. Spatial learning memory was measured using the Morris water maze test. Neuronal nuclear antigen, SIRT1, and rat endothelial cells antigen 1 were determined by immunohistochemistry and platelet-derived growth factor receptor beta was determined by immunofluorescence. RESULTS: Preischemic treadmill exercise ameliorated spatial learning memory impairment and enhanced SIRT1 expression in the BCCAO rats. Preischemic treadmill exercise ameliorated BCCAO-induced damage to microvasculature and pericytes that make up the BBB. The effect of preischemic treadmill exercise was lost with sirtinol treatment. CONCLUSION: These results can apply treadmill exercise prior to cerebral ischemia as a rational preventive and therapeutic intervention strategy to improve cognitive dysfunction in CCH patients.

Low-intensity treadmill exercise protects cognitive impairment by enhancing cerebellar mitochondrial calcium retention capacity in a rat model of chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) is caused by reduced blood flow to the brain representing gradually cognitive impairment. CCH induces mitochondrial dysfunction and neuronal cell death in the brain. Exercise is known to have a neuroprotective effect on brain damage and cognitive dysfunction. This study aimed to clarify the neuroprotective effect of low-intensity treadmill exercise (LITE) by enhancing cerebellar mitochondrial calcium retention capacity in an animal model of CCH. Wistar rats were divided into the sham group, the bilateral common carotid arteries occlusion (BCCAO) group, and the BCCAO and treadmill exercise (BCCAO+Ex) group. BCCAO+Ex group engaged the LITE on a treadmill for 30 min once a day for 8 weeks before the BCCAO surgery to investigate the protective effect of LITE on cognitive impairment. CCH induced by BCCAO resulted in mitochondrial dysfunction in the cerebellum, including impaired calcium homeostasis. CCH also decreased cerebellar Purkinje cells including of calbindin D28k and parvalbumin, resulting in cognitive impairment. The impairment of mitochondrial function, loss of cerebellar Purkinje cells, and cognitive dysfunction ameliorated by exercise. The present study showed that LITE hindered the deficit of spatial working memory and loss of Purkinje cell in the cerebellum induced by CCH. We confirmed that the protective effect of LITE on Purkinje cell by enhanced the mitochondrial calcium retention capacity. We suggest that LITE may protect against cognitive impairment, and further studies are needed to develop the intervention for patients who suffered from CCH.

Prognostic Significance of Metabolic Parameters by 18F-FDG PET/CT in Thymic Epithelial Tumors.

BACKGROUND: Imaging tumor FDG avidity could complement prognostic implication in thymic epithelial tumors. We thus investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT parameters in thymic epithelial tumors with other clinical prognostic factors. METHODS: This is a retrospective study that included 83 patients who were diagnosed with thymic epithelial tumors and underwent pretreatment 18F-FDG PET/CT. PET parameters, including maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured with a threshold of SUV 2.5. Univariate and multivariate analysis of PET parameters and clinicopathologic variables for time-to-progression was performed by using a Cox proportional hazard regression model. RESULTS: There were 21 low-risk thymomas (25.3%), 27 high-risk thymomas (32.5%), and 35 thymic carcinomas (42.2%). Recurrence or disease progression occurred in 24 patients (28.9%). On univariate analysis, Masaoka stage (p < 0.001); histologic types (p = 0.009); treatment modality (p = 0.001); and SUVmax, SUVavg, MTV, and TLG (all p < 0.001) were significant prognostic factors. SUVavg (p < 0.001) and Masaoka stage (p = 0.001) were independent prognostic factors on multivariate analysis. CONCLUSION: SUVavg and Masaoka stage are independent prognostic factors in thymic epithelial tumors.

Depression, Rather Than Cancer-Related Fatigue or Insomnia, Decreased the Quality of Life of Cancer Patients.

PURPOSE: Cancer-related fatigue is a common and distressing symptom that occurs during cancer treatment. This study aimed to find factors that are related to cancer-related fatigue, and its effect on patients' quality of life. MATERIALS AND METHODS: This study included 159 patients who completed questionnaires and interviews during their initial examination at the sleep clinic for cancer patients, Asan Medical Center, between December 2018 and January 2020. Their medical reports were reviewed retrospectively. Questionnaire data about depression, anxiety, insomnia, fear of disease progression, and dysfunctional beliefs about sleep, pain, and quality of life, were reviewed. Additionally, patient sleep structure data were analyzed. RESULTS: Factors such as depression (p < 0.001), anxiety (p < 0.001), fear of cancer progression (p < 0.001), fatigue (p=0.027), and time in bed during 24 hours (p=0.037) were significant expecting variables for low quality of life from logistic regression analysis. In pathway analysis, depression (p < 0.001), not cancer-related fatigue (p=0.537), act as a direct risk factor on quality of life. And also, depression was an overall risk factor for insomnia, fatigue, and daily activity of cancer patients. CONCLUSION: Cancer-related fatigue did not show significant effect on patient's quality of life in this study. However, the result of pathway analysis highlights the importance of assessing depression in the process of cancer treatment and providing appropriate interventions.

Chemerin Treatment Inhibits the Growth and Bone Invasion of Breast Cancer Cells.

Chemerin is secreted as prochemerin from various cell types and then cleaved into the bioactive isoform by specific proteases. In various cancer types, chemerin exhibits pro- or antitumor effects. In the present study, chemerin treatment significantly inhibited the viability and invasion of breast cancer cells in the absence or presence of transforming growth factor (TGF)-ß and insulin-like growth factor (IGF)-1. The expression levels of E-cadherin and vimentin were reduced in chemerin-treated breast cancer cells. However, chemerin treatment recovered the reduced E-cadherin expression level in breast cancer cells treated with TGF-ß or IGF-1. Chemerin treatment inhibited nuclear ß-catenin levels in breast cancer cells stimulated with or without TGF-ß or IGF-1. In addition, chemerin treatment blocked the increase in the receptor activator of nuclear factor kappa-Β ligand (RANKL)/osteoprotegerin (OPG) ratio in osteoblastic cells exposed to metastatic breast cancer cell-derived conditioned medium. Chemerin treatment inhibited RANKL-induced osteoclast formation and bone resorption by reducing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K. Intraperitoneal administration of chemerin inhibited tumor growth in MCF-7 breast cancer cell-injected mice and reduced the development of osteolytic lesions resulting from intratibial inoculation of MDA-MB-231 cells. Taken together, chemerin inhibits the growth and invasion of breast cancer cells and prevents bone loss resulting from breast cancer cells by inhibiting finally osteoclast formation and activity.