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Abstract Background No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment. Methods This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26). Results Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p

WHO reported that asthma was responsible for 455,000 deaths in 2019 and asthma patients was evaluated 262 million in May 2023. The incidence is expected to increase as the average life expectancy increases, highlighting asthma as a significant health challenge in an aging society. The etiology of asthma is linked to an imbalance of Th1 and Th2 cells, respiratory inflammation, and pulmonary cell proliferation. The purpose of this study is to investigate the anti-asthmatic effect and potential mechanism of oleic acid. The anti-inflammatory effect of oleic acid was evaluated in an LPS-induced RAW 264.7 cell model, and immune modulation and the anti-apoptotic effect were measured in an ovalbumin-induced BALB/c mouse model. A variety of analytical procedures, such as MTT, qPCR, ELISA, Western blotting, immunofluorescence, gene transfection, immunohistochemistry, and several staining methods (Diff Quik, H&E, PAS), were used to evaluate the effectiveness and mechanisms of these methods. The results from in vitro experiments showed that oleic acid could reduce the levels of inflammatory cytokines (TNF-α, IL-6, and IL-1β), and molecular docking studies suggested that oleic acid could interact with TLR3 and TLR4 proteins to form ligand−protein complexes, showing good binding affinity. Additionally, oleic acid attenuated the expression of MAPK pathway components (JNK, p38 MAPK) and NF-κB pathway constituents (IκB, NF-κB, COX-2, PGE2). In vivo results indicated that oleic acid reduced the levels of inflammatory cells (WBCs and eosinophils) and IgE activity, reduced the expression of the Th2 cell transcription factor GATA-3, and decreased the levels of Th2/Th17-related cytokines (IL-4, TNF-α, and IL-6). Oleic acid also alleviated OVA-induced pathological changes in the lung, such as epithelial cell proliferation, inflammatory cell infiltration, and mucus hypersecretion. OVA restored apoptosis in lung epithelial cells by modulating the expression of Bcl-2 and Bax. In summary, oleic acid has potential as a novel candidate for asthma treatment through its ability to regulate immune cells, exert anti-inflammatory effects, and promote apoptosis, thereby ameliorating asthma manifestations.

In the field of biomechanics, customizing complex strain fields according to specific requirements poses an important challenge for bioreactor technology, primarily due to the intricate coupling and nonlinear actuation of actuator arrays, which complicates the precise control of strain fields. This paper introduces a bioreactor designed with a 9 × 9 array of independently controllable dielectric elastomer actuators (DEAs), addressing this challenge. We employ image regression-based machine learning for both replicating target strain fields through inverse control and rapidly predicting feasible strain fields generated by the bioreactor in response to control inputs via forward control. To generate training data, a finite element analysis (FEA) simulation model was developed. In the FEA, the device was prestretched, followed by the random assignment of voltages to each pixel, yielding 10,000 distinct output strain field images for the training set. For inverse control, a multilayer perceptron (MLP) is utilized to predict control inputs from images, whereas, for forward control, MLP maps control inputs to low-resolution images, which are then upscaled to high-resolution outputs through a super-resolution generative adversarial network (SRGAN). Demonstrations include inputting biomechanically significant strain fields, where the method successfully replicated the intended fields. Additionally, by using various tumor–stroma interfaces as inputs, the bioreactor demonstrated its ability to customize strain fields accordingly, showcasing its potential as an advanced testbed for tumor biomechanics research.

Abstract Background This study aimed to develop and validate a clinical prediction rule to screen older patients at risk of being toxigenic Clostridioides difficile carriers at the time of hospital admission. Methods This retrospective case-control study was performed at a university-affiliated hospital. Active surveillance using a real-time polymerase chain reaction (PCR) assay for the toxin genes of C. difficile was conducted among older patients (≥ 65 years) upon admission to the Division of Infectious Diseases of our institution. This rule was drawn from a derivative cohort between October 2019 and April 2021 using a multivariable logistic regression model. Clinical predictability was evaluated in the validation cohort between May 2021 and October 2021. Results Of 628 PCR screenings for toxigenic C. difficile carriage, 101 (16.1%) yielded positive findings. To establish clinical prediction rules in the derivation cohort, the formula was derived using significant predictors for toxigenic C. difficile carriage at admission, such as septic shock, connective tissue diseases, anemia, recent use of antibiotics, and recent use of proton-pump inhibitors. In the validation cohort, the sensitivity, specificity, and positive and negative predictive values of the prediction rule, based on a cut-off value of ≥ 0.45, were 78.3%, 70.8%, 29.5%, and 95.4%, respectively. Conclusion This clinical prediction rule for identifying toxigenic C. difficile carriage at admission may facilitate the selective screening of high-risk groups. To implement it in a clinical setting, more patients from other medical institutions need to be prospectively examined.

As older adult populations rapidly increase worldwide, loneliness among older adults is emerging as a societal burden. Whether social media use can increase or decrease older adults’ loneliness remains debated in the literature. The purpose of this study is to clarify the effect of social media use on loneliness among older adults by examining the moderating role of media literacy on the relationship between social media use and loneliness. Considering that Korea is facing the most rapid population aging among Organisation for Economic Co-operation and Development (OECD) countries and that two-thirds of Korean older adults use social media, Korean data can provide international insights into the impact of social media use on older adults. Responses from 554 Korean respondents aged 60 to 79, extracted from the 2021 Korea Media Panel Survey, were analyzed using the PROCESS Macro Model 1. The results of this study showed that the effect of social media use on loneliness among older adults was moderated by their level of media literacy. As the amount of time spent using social media increased, loneliness increased for respondents with low-to-middle media literacy. This study’s findings emphasize the importance of educational interventions to increase older adults’ digital media literacy and expand scholarly understanding of the impact of social media use in non-Western countries.

The development of therapeutic interventions for diseases necessitates a crucial step known as drug screening, wherein potential substances with medicinal properties are rigorously evaluated. This process has undergone a transformative evolution, driven by the imperative need for more efficient, rapid, and high-throughput screening platforms. Among these, microfluidic systems have emerged as the epitome of efficiency, enabling the screening of drug candidates with unprecedented speed and minimal sample consumption. This review paper explores the cutting-edge landscape of microfluidic-based drug screening platforms, with a specific emphasis on two pioneering approaches: organ-on-a-chip and C. elegans-based chips. Organ-on-a-chip technology harnesses human-derived cells to recreate the physiological functions of human organs, offering an invaluable tool for assessing drug efficacy and toxicity. In parallel, C. elegans-based chips, boasting up to 60% genetic homology with humans and a remarkable affinity for microfluidic systems, have proven to be robust models for drug screening. Our comprehensive review endeavors to provide readers with a profound understanding of the fundamental principles, advantages, and challenges associated with these innovative drug screening platforms. We delve into the latest breakthroughs and practical applications in this burgeoning field, illuminating the pivotal role these platforms play in expediting drug discovery and development. Furthermore, we engage in a forward-looking discussion to delineate the future directions and untapped potential inherent in these transformative technologies. Through this review, we aim to contribute to the collective knowledge base in the realm of drug screening, providing valuable insights to researchers, clinicians, and stakeholders alike. We invite readers to embark on a journey into the realm of microfluidic-based drug screening platforms, fostering a deeper appreciation for their significance and promising avenues yet to be explored.

Background: The COVID-19 pandemic has significantly affected societies worldwide, including the medical healthcare system and trauma care. This study explores the impact of COVID-19 infection on trauma patients in South Korea, a country with effective pandemic management. Methods: A retrospective cohort study of 4206 trauma patients from June 2020 to May 2022 was conducted. Patients were categorized into COVID-19-positive and COVID-19-negative groups. Various clinical parameters, complications, and mortality rates were analyzed. Results: COVID-19-positive patients exhibited higher rates of complications, such as pressure sores (8.8% vs. 2.3%, p < 0.001), surgical site infections (2.4% vs. 0.8%, p = 0.044), and pneumonia (8.8% vs. 4.1%, p = 0.007). There was no significant difference in mortality between COVID-19-positive and -negative groups (4% vs. 5.6%, p = 0.439). Factors influencing mortality included COVID-19 status, age, Glasgow Coma Scale, Injury Severity Score, and transfusion status. Conclusion: COVID-19 positivity may have adverse clinical effects on trauma patients, but the impact varies based on public health factors. Additional studies in different contexts are crucial to elucidate these complexities.

Abstract The risk factors of mild cognitive impairment (MCI) in patients with de novo Parkinson’s disease (PD) remain unclear. Therefore, the objective of this study was to compare motor and non-motor symptoms between de novo patients with PD with and without MCI. Moreover, detailed relationships between each cognitive deficit and other clinical characteristics in de novo patients with PD were investigated. Consecutive patients with de novo PD were retrospectively enrolled in this study. Motor symptoms were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) part-III and the Hoehn and Yahr (HY) stage. Non-motor symptoms including depression, anxiety, fatigue, and autonomic dysfunction were measured using representative questionnaires. Motor symptoms, depression, and dysautonomia were associated with MCI in de novo patients with PD. Compared with the non-MCI group with PD, the MCI group with PD had higher scores of UPDRS-III, HY stage, depression, and dysautonomia, but not fatigue or anxiety. Both UPDRS-III and HY stage were significantly linked to all cognitive deficits except attention. Logistic regression analysis showed that depression was associated with memory, visuospatial, and executive impairment, and dysautonomia was related to visuospatial and executive impairment. The results of this study suggest that cognitive impairment in PD might have a different relationship pattern to the motor and some non-motor symptoms.

Acute disseminated encephalomyelitis is a rare autoimmune demyelinating disease associated with preceding infection or vaccination. Herein, we report a case of refractory fulminant acute disseminated encephalomyelitis that occurred 25 days after Gardasil vaccination (Merck).

Abstract Background In twin pregnancies, the cord prolapse of either fetus during the pre-viable period leads to fetal death but can also cause an intrauterine infection, leading to death or prematu-re birth of the remaining fetus. However, there are no validated protocols to prolong the gestational period or decrease the morbidity and mortality of the remaining fetus. Case presentation The present cases were PPROM and cord prolapse very early during the second trimester (around 17 weeks in the first case and 19 weeks in the second case). The first fetus was evacuated, and cervical cerclage was performed at 23 and 20 weeks in the two cases, respectively. After maintaining the pregnancy, the second baby was born around 27 and 39 weeks in the first and second cases, respectively. The delivery interval between the first and second fetuses was 46 days in the first case and 126 days in the second case. Conclusion If cord prolapse is identified at a pre-viable time in twin fetuses, evacuation and cerclage should be performed as soon as possible after the cord prolapse to reduce intrauterine infection and increase the survival chances of the remaining fetus.

Molecular networking drove the selection of material from V. tenuifolia organs that targeted active flavonoid glycosides. To optimize the extraction process, the flowers of V. tenuifolia were used to produce an anti-inflammatory extract. The effects of variables—organic solvent ratio; extraction time; and temperature—were investigated by the response of anti-inflammatory activity. Bioactivities-guided experiments helped identify fractions with high total phenolic and flavonoid content as well as antioxidant potential. Furthermore, one new compound (1), 19 first isolated together, and two known compounds were obtained and identified from the active fraction of this plant. Among them, compounds (15 and 22) were first reported for nuclear magnetic resonance (NMR) data from this study. All the isolates were evaluated for their anti-inflammatory capacity throughout, modulating nitric oxide (NO), interleukin (IL)-1β, and IL-8 production. Active compounds were further investigated for their regulation and binding affinity to the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins by Western blot and in silico approaches, respectively. The findings of this study suggested that the developed extract method, active fraction, and pure components should be further investigated as promising candidates for treating inflammation and oxidation.

Endometriosis, which is the presence of endometrial stroma and glands outside the uterus, is one of the most frequently diagnosed gynecologic diseases in reproductive women. Patients with endometriosis suffer from various pain symptoms such as dysmenorrhea, dyspareunia, and chronic pelvic pain. The pathophysiology for chronic pain in patients with endometriosis has not been fully understood. Altered inflammatory responses have been shown to contribute to pain symptoms. Increased secretion of cytokines, angiogenic factors, and nerve growth factors has been suggested to increase pain. Also, altered distribution of nerve fibers may also contribute to chronic pain. Aside from local contributing factors, sensitization of the nervous system is also important in understanding persistent pain in endometriosis. Peripheral sensitization as well as central sensitization have been identified in patients with endometriosis. These sensitizations of the nervous system can also explain increased incidence of comorbidities related to pain such as irritable bowel disease, bladder pain syndrome, and vulvodynia in patients with endometriosis. In conclusion, there are various possible mechanisms behind pain in patients with endometriosis, and understanding these mechanisms can help clinicians understand the nature of the pain symptoms and decide on treatments for endometriosis-related pain symptoms.

The young leaves and shoots of V. tetrasperma are consumed daily as cooked vegetables and can provide various health benefits. The antioxidant and anti-inflammatory capacities of its total extract and fractions were accessed for the first time in this study. The bioactivities guided the separation of the active fraction (EtOAc), leading to the identification of nine flavonoid glycoside compositions from this plant for the first time. In addition, the fractions and all isolates were evaluated for their inhibition against NO and IL-8 production in LPS-stimulated RAW264.7 and HT-29 cell lines, respectively. The most active ingredient was further assayed for its inhibitory abilities to iNOS and COX-2 proteins. Indeed, its mechanisms of action modes were confirmed by Western blotting assays through the reduction in their expression levels. An in silico approach revealed the substantial binding energies of docked compounds into established complexes to verify their anti-inflammatory properties. In addition, the presence of active components in the plant was validated by an established method on the UPLC-DAD system. Our research has boosted the value of this vegetable’s daily use and provided a therapeutic approach for the development of functional food products for health improvement regarding the treatment of oxidation and inflammation.

Abstract Background It has recently been emphasized that the unmet needs of cancer patients should be evaluated more holistically, for example, by exploring caregivers’ perspectives and cross cultural differences. This study explored additional domains or items of unmet needs among Korean cancer patients in reference to the Sheffield Profile for Assessment and Referral to Care (SPARC). Methods We conducted four focus group discussions (FGDs) with 15 cancer patients, following a semi-structured format to elicit participants’ health perceptions, comments on SPARC, and opinions on the roles of medical professionals to improve the health-related quality of life of cancer patients. We analyzed the verbatim transcripts using a content analysis method. Results The following themes were derived: living as a cancer patient, striving to overcome cancer, changing attitudes toward life after the cancer diagnosis, and ways to live a better life as a cancer patient. The participants asserted the significance of providing adequate treatment information that is easily understood by cancer patients during the conversation between patients and medical professionals. Besides the physical symptoms identified by SPARC, the participants struggled with numbness in their hands and feet and hair loss. Korean cancer patients prominently wished to avoid burdening their family or others in their daily life. They considered the improvement of health behaviors, such as diet and exercise, as part of the treatment, which was not limited to drugs. Furthermore, it was essential to evaluate the value of cancer patients’ lives, as they desired to be helpful members of their families and society. Conclusions This study identified additional domains and items of unmet needs of Korean cancer patients and broadened the understanding of unmet needs among cancer patients.

Abstract The association of non-motor symptoms (NMSs) with fall-related factors in patients with Parkinson’s disease (PD) remains to be further elucidated in the early stages of the disease. Eighty-six patients with less than 5 years of the onset of PD were retrospectively enrolled in the study. We assessed potential fall-related risk factors including (1) a history of falls during the past year (faller versus non-faller), (2) the fear of falling (FoF), and (3) the freezing of gait (FoG). Different types of NMSs were measured using the Montreal Cognitive Assessment (MoCA), the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), the Parkinson’s disease Fatigue Scale (PFS), and the Scales for Outcomes in Parkinson’s disease—Autonomic dysfunction (SCOPA-AUT). The faller group (37.2%) showed higher scores for BDI, BAI, PFS, and SCOPA-AUT, compared to the non-faller group. From logistic regression analyses, the prior history of falls was related to the gastrointestinal domain of SCOPA-AUT, FoF was associated with BAI, and gastrointestinal and urinary domains of SCOPA-AUT, and FoG was linked to BAI and gastrointestinal domain of SCOPA-AUT. In conclusion, we found that fall-related risk factors in patients with early PD were highly connected with gastrointestinal dysautonomia.

The COVID-19 pandemic, starting in 2020, changed the daily activities of people in the world and it might also affect patterns of major trauma. This study aimed to compare the epidemiology and outcomes of trauma patients before and after the COVID-19 outbreak. This was a retrospective study, conducted in a single regional trauma center in Korea, and patients were grouped as pre- and post-COVID-19 and compared in terms of demographics, clinical characteristics, and clinical outcomes. A total of 4585 patients were included in the study and the mean age was 57.60 ± 18.55 and 59.06 ± 18.73 years in the pre- and post-COVID-19 groups, respectively. The rate of elderly patients (age ≥ 65) significantly increased in the post-COVID-19 group. In terms of injury patterns, self-harm was significantly increased after COVID-19 (2.6% vs. 3.5%, p = 0.021). Mortality, hospital length of stay, 24 h, and transfusion volume were not significantly different. Among the major complications, acute kidney injury, surgical wound infection, pneumonia, and sepsis were significantly different between the groups. This study revealed changes in the age of patients, injury patterns and severity, and major complication rates after the COVID-19 outbreak.

Prunus mume (Maesil) is used in health foods and alternative medicine in Korea. In the present study, the anti-inflammatory and antioxidant effects of phenolics from P. mume seed extracts were examined. First, the biological activities of various P. mume extracts were evaluated, and the profiles of their chemical compounds were investigated by Global Natural Products Social (GNPS)-molecular networking. Among these extracts, fermented Maesil seed extract (FMSE) showed potent anti-inflammatory and antioxidant activity, and demonstrated the presence of phenolic clusters in GNPS-based studies. Thus, the chemical constituents of this extract were further investigated. Subsequently, the chemical composition of the active CH2Cl2 fraction of FMSE was explored using an advanced GNPS analysis tool, MolNetEnhancer. In addition, the molecular structure of compound 1 from the CH2Cl2 fraction was similarly predicted with Network Annotation Propagation (NAP). Finally, the anti-inflammatory and antioxidant effects of compound 1 were confirmed by lipopolysaccharide (LPS)-induced nitric oxide production and DPPH assay. Western blot analysis revealed that compound 1 downregulated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. The molecular docking simulation additionally confirmed significant interactions of 1 with iNOS and COX-2 proteins. Our findings suggested that an integrated GNPS-based approach could prioritize samples in the early fractionation process and improve the accuracy of target compound prediction.

The objective of this study is to describe the separation and identification of one new phenolic and 19 known compounds from Vitex rotundifolia. Their structures were determined based on spectroscopic (NMR, CD, and MS) data analysis or Mosher’s method, and were compared with those reported in the literature. These isolates were then evaluated for their anti-inflammatory and antioxidant activities based on the inhibition of nitric oxide (NO) and interleukin (IL)-8 production in lipopolysaccharide (LPS)-stimulated cells (RAW264.7 and HT-29) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging abilities, respectively. In the NO assay, compounds 12–14 showed strong inhibition with compounds 10 and 15 displaying significant inhibition. In the IL-8 assay, compounds 8, 9, 13, 14, 19, and 20 exhibited potential to inhibit IL-8 production and other compounds displayed moderate inhibition. An in silico docking approach also revealed strong binding affinities for protein–ligand complexes of these active compounds against IL-8 production. The docking results were correlated with the experimental data of the IL-8 assay. Thus, these active compounds should be considered as candidates for further in vivo studies. This study implies the potential of new and active chemicals isolated from V. rotundifolia and provides evidence to support the development of active fractions and constituents into functional products targeting inflammatory diseases the future.

Since 2003, when the European Union (E.U.) announced the restriction of hazardous substances (RoHS), multiple efforts have been made to replace lead zirconate titanate (PZT) based piezoelectric materials. However, despite these efforts, very few PZT alternatives have been found. The Lithium niobate (LN) is one such lead-free piezoelectric material often used in acoustic applications due to its high signal generation efficiency, high curie temperature, and high mechanical Q factor. However, LN is not suitable for miniaturized applications because of its low dielectric constant and high electrical impedance. In this paper, we aim to address the problem of the low-dielectric constant of LN while avoiding hazardous PZT material. We propose to utilize 1–3 composites structure with LN and barium titanate (BT), which has a high dielectric constant while controlling acoustic properties such as density, dielectric constant, sound velocity. We also developed new LN-BT modeling to design piezoelectric composite with interdigital pair bonding (IPB) technique, based on previous PZT-polymer 1–3 composite modeling. We verified that the composite components are lead-free by examining with the scanning electron microscope (SEM) with energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). This proposed lead-free composite with high-dielectric and lower electrical impedance is better suited for miniaturized applications.

Background Female Community Health Volunteers (FCHVs) are service providers and educators for maternal health at the village level (in the hill and Terai district) in Nepal. At present, there are insufficient data and little is understood about the maternal health service (MHS) of FCHVs from Nepali mothers' perspective. Methodology The research was undertaken in three hill and mountain regions where there should be at least one FCHVs per ward, Thulo sirubari, Sano sirubari and Jalkeni in Chautara Sangachowkgadi in Nepal, during five days from 5 April to 9 April 2019. The study worked with a local partner organisation, Green Tara Nepal (GTN). The study took the form of a qualitative approach with a community-based snowball approach (seed-and-recruit approach), which consisted of interviews with six key informants and 11 village mothers who have a child aged under five. Results The study found that all participated mothers recognised FCHVs and that it was easy to contact them within walking distance. They were happy with FCHV's existence and had a close relationship between them. They were all satisfied with MHS from FCHVs. In particular, accessibility of FCHVs, frequent home visits, monthly mothers' meetings, and regular ANC were the main points of satisfaction. Moreover, NGO intervention increased their satisfaction and contributed significantly to FCHV activities. However, the lack of meeting place and sustainable incentives are challenging to implement monthly mothers' meetings. Sufficient regular refresher training for FCHVs is also required to educate them better. Furthermore, the local government's unequally distributed budget for FCHVs programmes, small incentives, and benefits for FCHVs are challenges. Conclusion This study offered various views with vivid memories into the satisfaction of FCHV's MHS among village mothers in three hill and mountain regions of Nepal. FCHVs are essential assets for MHS in rural communities. The FCHVs programme should be complemented by (1) supporting suitable meeting place of mother's meeting, (2) providing sustainable and sufficient budget for mother's meeting and FCHVs, (3) distributing the budget equally in each ward, (4) offering frequent FCHVs training to improve the MHS for village mothers.

Objective This study identified the distribution of lymphocele, as well as the factors associated with lymphocele formation, in patients undergoing pelvic and/or para-aortic lymph node dissection (PLND and/or PALND) for gynecologic malignancies. Methods This study was retrospective, and data were collected from patients who underwent surgical procedures including lymphadenectomy due to gynecologic malignancies from March 2013 to May 2016. Lymphocele was defined by postoperative computer tomography within 2 weeks after surgery. Results A total of 116 patients underwent lymphadenectomy, of whom, 47 (42.0%) developed lymphocele and 14 (12.1%) had symptomatic lymphocele formation. The affecting factors of lymphocele formation were PLND concomitant with PALND and a large amount of blood loss ≥600 mL (P=0.030 and P=0.006, respectively). All clinical factors were not significantly different between patients with symptomatic and asymptomatic lymphocele. Lymphocele developed more frequently in the left side (67.1%) of the body compared to the right side (48.7%), and in the pelvic area (75.9%) compared to the para-aortic area (24.1%, P

Abstract Background Dopamine transporter (DAT) imaging may enable clinicians to discriminate idiopathic normal pressure hydrocephalus (iNPH) from other parkinsonian disorders. However, a specific pattern of dopaminergic loss in DAT imaging of iNPH patients remains to be further elucidated. Methods In this preliminary study, 11 patients with iNPH in our hospital between March 2017 and February 2019 were finally enrolled. A diagnosis of iNPH was made according to the two established criteria. For visual analysis of DAT imaging, a striatum was divided into five domains. A semi-quantitative visual assessment was performed with a consensus between a nuclear medicine specialist and an experienced neurologist who were blinded to the clinical diagnosis. Results Striatal dopaminergic deficits were abnormal in 90.9% (10/11) of patients with iNPH. The degree of dopaminergic reduction was mild and heterogeneous. However, a tendency of preferential striatal DAT loss in the caudate nucleus (90.9%, 10/11) than in the putamen (72.7%, 8/11) was observed, whereas ventral portion (9.1%, 1/11) was relatively preserved. Conclusion Striatal dopaminergic depletion might be mild and heterogeneous in patients with iNPH. These dopaminergic deficits were more common in the caudate nucleus than in the putamen, suggesting a pattern different from other degenerative parkinsonian disorders.

Objective We aimed to identify risk factors for falls in patients with de novo Parkinson’s disease (PD). Methods Forty-six patients with de novo PD were retrospectively included in the study. We assessed details on the patients’ motor symptoms as well as non-motor symptoms using several representative scales for global cognition, depression, fatigue, and dysautonomia. Fallers and non-fallers were identified according to their history of falls during the preceding year. Results Twenty-two patients (45.8%) with de novo PD had a history of falls. Compared with the non-faller group, the faller group exhibited higher scores for postural instability/gait difficulty (PIGD), anxiety, fatigue, total dysautonomia, gastrointestinal dysfunction, and thermoregulatory dysfunction. Moreover, logistic regression analysis showed that falling was positively correlated with anxiety and gastrointestinal symptoms but negatively associated with the tremor scores. Conclusion Our findings suggest that falling in patients with de novo PD is significantly associated with PIGD/non-tremor symptoms, anxiety, and gastrointestinal dysfunction.

In this present study, we examined the anti-inflammatory and anti-oxidative properties of alcoholic lemon myrtle extract (LME). The total polyphenol and flavonoid content of LME were determined as 118.77 and 14.53 mg/g extract, respectively. LME showed anti-oxidative properties, such as 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2′-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) radical scavenging activity. The anti-inflammatory activities of LME were investigated using the lipopolysaccharide-stimulated murine macrophage RAW 264.7 cells. Pretreatment with LME was performed at non-cytotoxic concentrations of 10–100 μg/mL. LME inhibited the production of inflammatory mediators such as nitric oxide (NO). Enzyme-linked immunosorbent assay and reverse-transcriptase polymerase chain reaction (RT-PCR) revealed that pretreatment with LME suppressed the protein expression and mRNA levels of pro-inflammatory cytokines such as interleukin IL-6, and tumor necrosis factor (TNF)-α in a concentration-dependent manner, respectively. These results suggest that LME could be used as a potential therapeutic agent having potent anti-inflammatory effects that could be used to treat inflammatory bowel disease.

Yuja (Citrus junos) has been cultivated and used for food and medicinal purposes in China and Korea. Its antioxidant, anti-wrinkle, moisturizing, and whitening effects were evaluated in HaCaT, HDF, and B16F10 cells. UVB has been known to cause cellular stress and the production of reactive oxygen species (ROS). Ambivalence of oxidative stress has been reported; however, excessive levels of ROS contribute to skin aging through the loss of elasticity and collagen fibers of connective tissue in the dermis. Skin aging is one of the biological processes that is affected by various factors, including UVB. Pro-Collagen I and hyaluronic acid contents were measured in UVB-irradiated HaCaT and HDF cells to evaluate the anti-wrinkle and moisturizing effects of Yuja-peel (YJP) fractions in -EA (ethyl acetate), -Hex (hexane), and -BuOH (butanol). The expression of matrix metalloproteinases (MMPs) involved in collagen degradation was confirmed to be inhibited by YJP fractions at both the protein and mRNA levels. Filaggrin and serine palmitoyltransferase (SPT), which are moisturizing factors, were induced by YJP fractions. B16F10 cells were treated with α-MSH to induce hyperpigmentation, and then the whitening efficacy of YJP fractions was verified by observing a decrease in melanin content. Overall, our results contribute to the development of various novel skin-improving cosmetics and pharmaceuticals with YJP fractions as active ingredients.

Ilex rotunda Thunb., has been used to treat common cold, tonsillitis, and eczema. It is also a source of antioxidants. However, information regarding its antioxidative phytochemical composition is still incomplete and limited. In this present study, we initially determined DPPH radical scavenging activity of the extracts of I. rotunda fruits, twigs, and leaves. Among them, the twig extract exhibited a potential of antioxidant capacity. Based on antioxidant effect guided experiments, extraction condition using 80% EtOH was then optimized. DPPH and ABTS radical scavenging assays were also performed for fractions. The n-butanol fraction showed the highest antioxidant effect. Using chromatographic methods, eight marker compounds (1–8) were further isolated. Their structures were determined by spectroscopic and mass data. Method validation was employed to quantitate contents of these eight marker compounds. Subsequently, the HPLC-DPPH method was used to evaluate the contribution of certain compounds to total antioxidant activity of the extract. Lastly, parallel artificial membrane permeability assay for blood–brain barrier (PAMPA-BBB) was applied to investigate brain-penetrable antioxidants from I. rotunda extract. As a result, compound 7 (4,5-dicaffeoylquinic acid) showed significant antioxidant activity and penetration across the BBB via transcellular passive diffusion. Our findings suggested that compound 7 can be used as a therapeutic potential candidate in natural product-based central nervous system (CNS) drug discovery.

Purpose This study evaluated the surgical volumes and types of specific surgical procedures in a single trauma center for 3 consecutive years. Methods From January 2014 to December 2016 there were 9,530 injury cases in the trauma registry that were reviewed. Results There were 1,502 patients (15.8%) with an injury severity score over 15, of which 426 (28.4%) underwent an emergency operation or had an interventional radiology procedure. There were 186 craniotomies, 87 laparotomies, and 74 interventional radiology procedures performed. Conclusion The number of emergency operations by each dedicated trauma surgeon was very low therefore implementation of an acute-care surgery model is appropriate to consider together with changes to the training program for trauma surgeons.

Background: To report on a case of acute renal failure associated with a Retzius space hematoma that had been extended to retroperitoneal space, following pulmonary embolism treatment in the postpartum period. Case report: A 30-year-old woman was transferred to the hospital for syncope on the first postoperative day following cesarean section. There were no active vaginal bleeding or intra-abdominal bleeding. On diagnosis of pulmonary embolism, she was treated with extracorporeal membrane oxygenation with heparinization. On day 4, ultrasonography showed newly developed hematoma at the anterior side of the uterus, and transarterial embolization was performed. On day 5, she developed acute kidney injury but there were no increase in size of the hematoma on ultrasonography. She recovered after 3 days of renal replacement therapy. However, on day 10, she showed tachycardia and increased serum creatinine. Computed tomography revealed not only a 15-cm hematoma anterior to the uterus, but also another 17-cm hematoma in the retroperitoneal space under the left kidney. Exploratory laparotomy was performed for obstructive uropathy and hematomas were evacuated. The patient’s vital sign stabilized one day following surgery. Conclusion: When treating postpartum patients with pulmonary embolism, physicians should be aware of the possibility of a concealed hemorrhage in the Retzius space and of subsequent kidney injury.

Currently, the world is moving rapidly toward carbon neutrality, and renewable energy technology is very important in carbon neutrality. Among various renewable energy technologies, wind power is attracting much attention due to its sustainability, resource abundance, and high applicability. This study analyzed wind power patents from 2010 to 2021 to derive current global originality and convergence information. For IP5 countries, the growth stages of technology and the patent convergence networks were inferred by time series analysis and an association rule mining algorithm, respectively. The results showed that, during the analysis period, about 5000 patents were applied on annual average, and it was analyzed that China held the most patents at 48%, followed by the US, Europe, Korea, and Japan. According to the technology convergence network of patent codes from all the IP5 countries, patents related to ‘wind turbines with rotation axes in the wind direction’ occupied a very central position, and ‘power conversion electric or electronic aspects’ and ‘integration of patents related to renewable energy sources in buildings with wind power’ were found to show high connection strength. By country, it was analyzed that the US and China showed high patent competitiveness onshore and possessed many ‘independent power conversion cluster’ technologies. The research hypothesis was that technology development trends can be analyzed and the characteristics of each country can be understood through patent analysis in the wind power field. This hypothesis was analyzed through various patent analysis techniques, and this paper has novelty in that it presents the global megatrend in the wind power field through patent analysis and quantitatively presents the current status of technology development in five major countries.

An extraction method using 80% EtOH was selected and applied to obtain the total extracts from leaves, flowers, fruits, twigs, and roots of Vitex rotundifolia L.f. based on the antioxidant activity-guided experiments. Subsequently, total extract from each part of V. rotundifolia was successfully partitioned into fractions, which were evaluated for their antioxidant and anti-inflammatory properties via DPPH, ABTS, and NO assays, respectively. Among them, EtOAc (E) and n-butanol (B) fractions showed the potent antioxidant activity and the methylene chloride (MC) fractions of roots, leaves, and fruits that exhibited strong scavenging activity on DPPH and ABTS radicals. In the anti-inflammatory assay, n-hexane (H) and MC fractions of leaves potently inhibited NO production in LPS-stimulated RAW264.7 cells, followed by E fractions derived from fruits, flowers, twigs, and roots, along with B fractions from flowers and twigs. Additionally, a comprehensive HPLC-decoupled MS profiling was established and validated using seven isolated marker compounds (1–7), which were identified by analysis of their UV, NMR, and MS data. The established method was also applied for quantification of these marker compounds in each organ collected from different locations, and to assess their antioxidant capacity by a screening DPPH-HPLC method. Principal component analysis suggested the botanical organs from this plant correlated with the marker compound contents in association with bioactivity. The study results are a prelude to further studies involving the active fractions and provide a comprehensive insight into the functional products of this plant against oxidative diseases.

We developed membrane actuators from magnetorheological elastomers (MREs) with hard magnetic particles using a novel mold-free fabrication procedure. The fabrication method improved the manufacturing efficiency via doctor blading and the two-stage curing process. To evaluate the performances of the membrane actuators, we monitored changes in the properties of the MREs in terms of the crosslinking degree in their polymeric matrices. The microstructure, curing behavior, magnetic properties, and mechanical properties of MREs were measured using a scanning electron microscope, vibrating sample magnetometer, rheometer, uniaxial tensile testing system. Deflection of the membrane actuators was measured using a custom-designed deflection system. The saturation magnetization (Ms) and remanence (Br) of MREs decreased as the crosslinking degree of matrices increased. Their elastic moduli (E) also decreased as the crosslinking degree increased. Meanwhile, in case of integrated analysis, an anisotropic sample with an initial curing time of five minutes exhibited the largest actual deflection, although the particles were aligned with the magnetic fields after crosslinking of 6.01% was achieved. By identifying the relationship between the properties of MREs and the crosslinking degree in its polymeric matrix, the MREs used to fabricate membrane actuators can be tailored for specific applications: pumps, valves, microlenses, and cell stimulators.

Clinicians sometimes encounter patients with Parkinson’s disease complaining of dizziness in real clinical settings. We sought to identify the relationship between self-perceived dizziness and motor or non-motor symptoms, especially in Parkinsonian patients in the early stages. Eight-six patients with less than five years of Parkinson’s disease duration were recruited. We used the dizziness handicap inventory to access self-reported dizziness in patients with early Parkinson’s disease. Parkinsonian motor symptoms such as postural instability and gait difficulty and non-motor features for global cognitive function, depressive mood, anxiety state, fatigue state, and autonomic dysfunction were measured using representative scales. Linear regression analysis demonstrated that the dizziness handicap inventory score was significantly related to postural instability and gait difficulty, anxiety, gastrointestinal, and cardiovascular domain of dysautonomia. In addition, the dizziness handicap inventory score was positively correlated with scores for postural instability and gait difficulty, anxiety, gastrointestinal, and cardiovascular dysautonomia. We found that self-reported dizziness was highly linked to postural instability and gait difficulty, anxiety, gastrointestinal and cardiovascular dysfunctions in patients with early Parkinson’s disease. Further follow-up studies on the association between dizziness and the pathophysiology of Parkinson’s disease are needed.

Abstract Background The goal of the study was to investigate the current clinical practices among oncologic surgeons regarding cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). Methods From September to October 2016, an online questionnaire surveyed the oncologic surgeons by email. The questionnaire included 20 multiple-choice questions of the following: eligibility for the CRS with HIPEC procedure, perioperative staging and surgery skill, assessment of residual tumors, and method used for intraperitoneal HIPEC. Results The response rate was 16% (34/217). The majority of respondents (68%) worked at a university hospital. All respondents indicated that mesenteric invasion is the most crucial factor affecting treatment decision. Most surgeons (79%) used the Sugarbaker’s staging system to intraoperatively measure the extent of peritoneal invasion. The methods used to measure the extent of miliary pattern of residual tumor spread, and the amount of residual tumor after electrocauterization varied among the surgeons. Most responders (65%) used the closed system of HIPEC. Conclusions Despite the fact that CRS HIPEC is the standard treatment for PSM, the clinical practices are very different according to each clinical situation. Nevertheless, mesenteric invasion was found to be the most important factor impacting the treatment decision-making by the majority of responders.

Species of Podocarpus are used traditionally in their native areas for the treatment of fevers, asthma, coughs, cholera, chest pain, arthritis, rheumatism, and sexually transmitted diseases. To identify natural products having efficacy against inflammatory bowel disease (IBD), we identified a new, 16-hydroxy-4β-carboxy-O-β-D-glucopyranosyl-19-nor-totarol (4) together with three known diterpenoids from P. macrophyllus. Furthermore, all the extracts, fractions, and isolates 1–4 were investigated for their anti-inflammatory effects by assessing the expression on nitric oxide (NO) production and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 and HT-29 cells. Among them, nagilactone B (2) exhibited a potent anti-inflammatory effect against NO production on RAW 264.7 cells; therefore, nagilactone B was further assessed for anti-inflammatory activity. Western blot analysis revealed that nagilactone B significantly decreased the expression of LPS-stimulated protein, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and phosphorylated extracellular regulated kinase (pERK)1/2. In addition, nagilactone B downregulated tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 levels in LPS-induced macrophages and colonic epithelial cells. To our best knowledge, this is the first report on the inhibitory effect of nagilactone B (pure state) and rakanmakilactone G against NO production in LPS-stimulated RAW 264.7 cells. Thus, diterpenoids isolated from P. macrophyllus could be employed as potential therapeutic phytochemicals for IBD.

The aim of this study was to identify the optimal extraction conditions for leaves of Osmanthus fragrans var. aurantiacus. Inhibitory effects of various extracts on NO production were compared. Antioxidant evaluations for total phenol and flavonoid contents were carried out using various extracts of O. fragrans var. aurantiacus leaves obtained under optimal extraction conditions that showed the greatest effect on NO production. The optimal method for extracting O. fragrans var. aurantiacus leaves resulted in an extract named OP OFLE. OP OFLE showed DPPH and ABTS radical scavenging activities in a concentration-dependent manner. Phillyrin (PH) was isolated as a major compound from OP OFLE by HPLC/DAD analysis. OP OFLE and PH reduced inducible nitric oxide (iNOS) and cyclooxygenase (COX)-2 protein expression and downregulated proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 and HT-29 cells. To determine the signal pathway involved in the inhibition of NO production, a Western blot analysis was performed. Results showed that OP OFLE decreased phosphorylation of extracellular regulated kinase (pERK) 1/2 and the expression of nuclear factor-kappa B (NF-κB). Our results suggest that extracts of O. fragrans var. aurantiacus leaves and its major components have biological activities such as antioxidative and anti-inflammatory properties.

Siegesbeckia glabrescens (Compositae), an annual herb indigenous to Korean mountainous regions and has been eaten as a food in Korea. This study investigated ABTS, DPPH and nitric oxide (NO) radical-scavenging activities, and melanin production and TYR inhibitory effects-guided fractionation to identify therapeutic phytochemicals from S. glabrescens that can attenuate oxidation and melanogenesis in murine melanoma B16F10 cells. Nine compounds with inhibitory effects on melanin production, and TYR activity, and ABTS, DPPH, and NO radical scavenging activity were isolated from the 100% ethanol fraction from S. glabrescens. Among the nine compounds, kirenol (K), methyl ent-16α, 17-dihydroxy-kauran-19-oate (MDK) had strong inhibitory effects on melanin production and TYR activity with antioxidant effects. Western blot analysis revealed that K and MDK suppressed tyrosinase-related protein (TYRP)-1, TYRP-2 and microphthalmia-associated transcription factor (MITF) expression. Moreover, these two compounds inhibited intracellular reactive oxygen species (ROS) level in tert-butyl hydroperoxide (t-BHP)-treated B16F10 cells. Our results suggest that S. glabrescens containing active compounds such as K and MDK, which has antioxidant and antimelanogenesis effects, is the potent therapeutic and functional material for the prevention of oxidation-induced hyperpigmentation.

This report describes the case of a 57-year-old man with an anterior mediastinal tumor. Four years previously, he underwent laparoscopic anterior resection for sigmoid colon cancer. Thirty months after that procedure, bilateral pulmonary metastasectomy was performed. Twelve months later, follow-up computed tomography revealed a 1-cm pulmonary nodule on the upper lobe of the right lung and a solid mass on the anterior mediastinum, and the patient was also observed to have an elevated serum carcinoembryonic antigen (CEA) level. Repeated pulmonary nodule resection and total thymectomy were performed. Immunohistochemical staining of the anterior mediastinal tumor revealed adenocarcinoma, and his serum CEA level returned to normal after the operation. These findings strongly suggested metastatic thymic adenocarcinoma from a colorectal cancer.

Limonoids, a dominant group of phytochemicals in the Rutaceae family, are known to exhibit several pharmacological activities. To identify natural products having efficacy against inflammatory bowel disease (IBD), we isolated 13 limonoids including a new compound, methyl sudachinoid A, from the seeds of Citrus junos and investigated their anti-inflammatory effects by assessing the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 mouse macrophages and HT-29 human colon epithelial cells. Our findings revealed that limonoids significantly downregulated the pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and nuclear transcription factor κB. In particular, sudachinoid-type compounds, methyl sudachinoid A and sudachinoid B, and ichangensin-type compound, 1-O-methyichangensin downregulated the expression of pro-inflammatory cytokines more potently than other limonoids, nomilin and limonin, which have been previously reported to exhibit anti-inflammatory activities in other cells; nomilin and limonin were therefore employed as positive controls in this study. Herein, we reveal that the anti-inflammatory activities of limonoids including a new compound methyl sudachinoid A from C. junos were mediated via the downregulation of pro-inflammatory cytokines and these limonoids can be employed as potential therapeutic phytochemicals for IBD.

Robotic mirror therapy (MT), which allows movement of the affected limb, is proposed as a more effective method than conventional MT (CMT). To improve the rehabilitation effectiveness of post-stroke patients, we developed a sensory stimulation-based continuous passive motion (CPM)-MT system with two different operating protocols, that is, asynchronous and synchronous modes. To evaluate their effectiveness, we measured brain activation through relative and absolute power spectral density (PSD) changes of electroencephalogram (EEG) mu rhythm in three cases with CMT and CPM-MT with asynchronous and synchronous modes. We also monitored changes in muscle fatigue, which is one of the negative effects of the CPM device, based on median power frequency (MPF) and root mean square (RMS). Relative PSD was most suppressed when subjects used the CPM-MT system under synchronous control: 22.11%, 15.31%, and 16.48% on Cz, C3, and C4, respectively. The absolute average changes in MPF and RMS were 1.59% and 9.78%, respectively, with CPM-MT. Synchronous mode CPM-MT is the most effective method for brain activation, and muscle fatigue caused by the CPM-MT system was negligible. This study suggests the more effective combination rehabilitation system for MT by utilizing CPM and magnetic-based MT task to add action execution and sensory stimulation compared with CMT.

This study evaluated bioactivity-guided fractionation as a means to identify therapeutic phytochemicals from Pyracantha angustifolia that can attenuate melanogenesis and oxidation. Seven compounds with inhibitory effects on melanin production and tyrosinase (TYR) activity, and ABTS and DPPH radical-scavenging activities, which have not been reported as whitening materials, were isolated from the n-butanol fraction from P. angustifolia leaves (PAL). Among the seven compounds, p-hydroxybenzoic acid β-d-glucosylester (HG), and cimidahurinine (CH) had strong inhibitory effects on melanin production and TYR activity, as well as ABTS and DPPH radical-scavenging activities. Western blot analysis showed that HG and CH suppressed tyrosinase-related protein (TYRP)-1 and TYRP-2 expression. Moreover, HG and CH inhibited reactive oxygen species (ROS) generation in tert-butyl hydroperoxide (t-BHP)-treated B16F10 cells. These results suggest that P. angustifolia containing active compounds, such as HG and CH, is a potent therapeutic candidate for the development of hypopigmenting agents.

Chrysanthemum zawadskii var. latilobum (CZL) has been used in Eastern medicine for the treatment of various diseases, such as pneumonia, bronchitis, cough, the common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. In the present study, we isolated two strong antiallergic compounds from CZL, namely, eriodictyol-7-O-β-d-glucuronide (EDG) and 5,7-dihydroxy-4-chromene (DC), and investigated their antiallergic effects in FcεRI-mediated human basophilic KU812F cells. EDG and DC downregulated the protein and messenger RNA (mRNA) expression of FcεRI on the cell surface. Moreover, Western blotting analysis showed that EDG and DC inhibited the expression of protein tyrosine kinases such as Syk and Lyn, and extracellular-regulated kinases (ERK) 1/2. These results suggested that EDG and DC, antiallergic constituents of CZL, are potential therapeutic candidates for protection against and for the treatment of allergic disorders.

DNA wrapping around histone octamers generates nucleosomes, the basic compaction unit of eukaryotic chromatin. Nucleosome stability is carefully tuned to maintain DNA accessibility in transcription, replication, and repair. Using freely orbiting magnetic tweezers, which measure the twist and length of single DNA molecules, we monitor the real-time loading of tetramers or complete histone octamers onto DNA by Nucleosome Assembly Protein-1 (NAP1). Remarkably, we find that tetrasomes exhibit spontaneous flipping between a preferentially occupied left-handed state (ΔLk = −0.73) and a right-handed state (ΔLk = +1.0), separated by a free energy difference of 2.3 kBT (1.5 kcal/mol). This flipping occurs without concomitant changes in DNA end-to-end length. The application of weak positive torque converts left-handed tetrasomes into right-handed tetrasomes, whereas nucleosomes display more gradual conformational changes. Our findings reveal unexpected dynamical rearrangements of the nucleosomal structure, suggesting that chromatin can serve as a “twist reservoir,” offering a mechanistic explanation for the regulation of DNA supercoiling in chromatin.

Nandina domestica (Berberidaceae) has been used in traditional medicine for the treatment of cough. This plant is distributed in Korea, Japan, China, and India This study aimed to investigate the anti-inflammatory phytochemicals obtained from the N. domestica fruits. We isolated a biflavonoid-type phytochemical, robustaflavone (R), from N. domestica fruits through bioactivity-guided fractionation based on its capacity to inhibit inflammation. The anti-inflammatory mechanism of R isolated from N. domestica has not yet been studied. In the present study, we evaluated the anti-inflammatory activities of R using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We have shown that R reduces the production of nitric oxide (NO), pro-inflammatory cytokine interleukin-1 beta (IL-1β), and IL-6. Western blot analysis showed that R suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and downregulates the expression of LPS-induced nuclear factor-kappa B (NF-κB) and the phosphorylation of extracellular-regulated kinases (pERK 1/2). Moreover, R inhibited IL-8 release in LPS-induced human colonic epithelial cells (HT-29). These results suggest that R could be a potential therapeutic candidate for inflammatory bowel disease (IBD).

Obesity is reported to be associated with excessive growth of adipocyte mass tissue as a result of increases in the number and size of adipocytes differentiated from preadipocytes. To search for anti-adipogenic phytochemicals, we screened for inhibitory activities of various plant sources on adipocyte differentiation in 3T3-L1 preadipocytes. Among the sources, a methanolic extract of Salix pseudo-lasiogyne twigs (Salicaceae) reduced lipid accumulation in a concentration-dependent manner. During our search for anti-adipogenic constituents from S. pseudo-lasiogyne, five salicortin derivatives isolated from an EtOAc fraction of this plant and bearing 1-hydroxy-6-oxo-2-cyclohexene-carboxylate moieties, namely 2′,6′-O-acetylsalicortin (1), 2′-O-acetylsalicortin (2), 3′-O-acetylsalicortin (3), 6′-O-acetylsalicortin (4), and salicortin (5), were found to significantly inhibit adipocyte differentiation in 3T3-L1 cells. In particular, 2′,6′-O-acetylsalicortin (1) had the most potent inhibitory activity on adipocyte differentiation, with an IC50 value of 11.6 μM, and it significantly down-regulated the expressions of CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element binding protein 1 (SREBP1c). Furthermore, 2′,6′-O-acetylsalicortin (1) suppressed mRNA expression levels of C/EBPβ during the early stage of adipocyte differentiation and stearoyl coenzyme A desaturase 1 (SCD-1), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) expression, target genes of SREBP1c. In the present study, we demonstrate that the anti-adipogenesis mechanism of 2′,6′-O-acetylsalicortin (1) may be mediated via down-regulation of C/EBPα and SREBP1c dependent pathways. Through their anti-adipogenic activity, salicortin derivatives may be potential novel therapeutic agents against obesity.

Selaginella tamariscina (S. tamariscina) (Beauv.) Spring (Selaginellaceae) has been used in oriental medicine for the treatment of dysmenorrhea, chronic hepatitis, hyperglycemia, amenorrhea, hematuria, prolapse of the anus and metrorrhagia. In the present study, we isolated two strong anti-inflammatory compounds, the biflavonoids hinokiflavone (H) and 7′-O-methyl hinokiflavone (mH), from S. tamariscina and examined their anti-inflammatory activities in lipopolysaccharide (LPS)-mediated murine macrophages (RAW 264.7) and colon epithelial cells (HT-29). H and mH suppressed the production of the inflammatory mediators nitric oxide (NO), interleukin (IL)-6, IL-8, and tumor-necrosis factor (TNF)-α, which are most highly activated in inflammatory bowel disease (IBD). In addition, Western blot analysis revealed that H and mH suppressed the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and the activation of nuclear factor-κB (NF-κB) and extracellular regulated kinases (ERK) 1/2. These results suggest that H and mH are compounds having potent anti-inflammatory effects that could be used to treat such diseases as IBD.

Eukaryotic nucleosomes consists of an (H3-H4)2 tetramer and two H2A-H2B dimers, around which 147 bp of DNA are wrapped in 1.7 left-handed helical turns. During chromatin assembly, the (H3-H4)2 tetramer binds first, forming a tetrasome that likely constitutes an important intermediate during ongoing transcription. We recently showed that (H3-H4)2 tetrasomes spontaneously switch between a left- and right-handed wrapped state of the DNA, a phenomenon that may serve to buffer changes in DNA torque induced by RNA polymerase in transcription. Within nucleosomes of actively transcribed genes, however, canonical H3 is progressively replaced by its variant H3.3. Consequently, one may ask if and how the DNA chirality dynamics of tetrasomes is altered by H3.3. Recent findings that H3.3-containing nucleosomes result in less stable and less condensed chromatin further underline the need to study the microscopic underpinnings of H3.3-containing tetrasomes and nucleosomes. Here we report real-time single-molecule studies of (H3.3-H4)2 tetrasome dynamics using Freely Orbiting Magnetic Tweezers and Electromagnetic Torque Tweezers. We find that the assembly of H3.3-containing tetrasomes and nucleosomes by the histone chaperone Nucleosome Assembly Protein 1 (NAP1) occurs in an identical manner to that of H3-containing tetrasomes and nucleosomes. Likewise, the flipping behavior of DNA handedness in tetrasomes is not impacted by the presence of H3.3. We also examine the effect of free NAP1, H3.3, and H4 in solution on flipping behavior and conclude that the probability for a tetrasome to occupy the left-handed state is only slightly enhanced by the presence of free protein. These data demonstrate that the incorporation of H3.3 does not alter the structural dynamics of tetrasomes, and hence that the preferred incorporation of this histone variant in transcriptionally active regions does not result from its enhanced ability to accommodate torsional stress, but rather may be linked to specific chaperone or remodeler requirements or communication with the nuclear environment.

Neural stem cells (NSCs) have the ability to proliferate and differentiate into neurons and glia. Regulation of NSC fate by small molecules is important for the generation of a certain type of cell. The identification of small molecules that can induce new neurons from NSCs could facilitate regenerative medicine and drug development for neurodegenerative diseases. In this study, we screened natural compounds to identify molecules that are effective on NSC cell fate determination. We found that Kuwanon V (KWV), which was isolated from the mulberry tree (Morus bombycis) root, increased neurogenesis in rat NSCs. In addition, during NSC differentiation, KWV increased cell survival and inhibited cell proliferation as shown by 5-bromo-2-deoxyuridine pulse experiments, Ki67 immunostaining and neurosphere forming assays. Interestingly, KWV enhanced neuronal differentiation and decreased NSC proliferation even in the presence of mitogens such as epidermal growth factor and fibroblast growth factor 2. KWV treatment of NSCs reduced the phosphorylation of extracellular signal-regulated kinase 1/2, increased mRNA expression levels of the cyclin-dependent kinase inhibitor p21, down-regulated Notch/Hairy expression levels and up-regulated microRNA miR-9, miR-29a and miR-181a. Taken together, our data suggest that KWV modulates NSC fate to induce neurogenesis, and it may be considered as a new drug candidate that can regenerate or protect neurons in neurodegenerative diseases.