State of the science of sexual health among older cancer survivors: an integrative review.

PURPOSE: Sexual health is important for quality of life among older (≥65 years) cancer survivors. Yet, little is known about the extent to which their sexual health has been studied. METHODS: In this integrative review, PubMed, PsycINFO, CINAHL, and Web of Science were searched for data-based articles of sexual health among older cancer survivors. Using a matrix, study characteristics, including cancer types and areas of sexual health, were categorized. RESULTS: The sample included 82 articles (81 studies). The areas of sexual health were categorized into sexual function, body image, sexual function-related distress, sexual health-related quality of life, sexual activity, sexual enjoyment, and sexual desire. Most targeted prostate cancer (n = 56, 69.1%) and studied sexual function, e.g., erectile function (n = 53, 94.6%). Body image (n = 16, 19.8%) was next frequently studied, targeting women with breast cancer. Measures to assess areas of sexual health, largely unstandardized, varied widely. Generally, older cancer survivors reported negative changes in sexual function and other areas during and after cancer treatment. CONCLUSIONS: Studies of sexual health among older cancer survivors have been focused primarily on prostate cancer, male, and sexual function. Together with the lack of standardized sexual health measures validated for older adults, this narrow research focus contributes to the limited body of knowledge regarding sexual health among older cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Given that cancer and cancer treatment affect both men and women and many aspects of sexual health beyond functioning, broadening the scope of sexual health and cancer type is warranted for future research.

Measures of Patient and Surrogate Preparedness for End-of-Life Decision-Making.

CONTEXT: Reliable and valid measures are critical in accurately assessing outcomes of advance care planning interventions (ACP) for end-of-life (EOL) decision-making. OBJECTIVES: To develop measures of preparedness for EOL decision-making for patients with end-stage renal disease and their surrogates (an exemplar population). METHODS: In this 3-phase study, Phases 1 and 2 included a cross-discipline concept analysis of the preparedness construct, item generation for patient and surrogate scales (82 items), evaluation of content validity and readability, cognitive interviewing, and item reduction. In phase 3, the retained 26 patient and 25 surrogate items were administered to 426 patients and 426 surrogates during a multisite trial of an ACP intervention versus care-as-usual and evaluated internal consistency, 2-week test-retest reliability, and construct validity. RESULTS: Scales were reduced to 20 patient and 19 surrogate items during phase 3. Cronbach's alphas were 0.86 (patient) and 0.90 (surrogate). There was a strong correlation between preparedness at baseline and two weeks for both scales (r = 0.66-0.69, P < 0.001). Confirmatory factor analysis and item-response analyses suggested unidimensionality. A significant correlation was shown between patient preparedness and patient decisional conflict (r = -0.53, P < 0.001), and surrogate preparedness and surrogate decision-making confidence (r = 0.44, P < 0.001). Among those who received the ACP intervention, the effect size of change was medium: Cohen's d = 0.54, P < 0.001 for patients and d = 0.57, P < 0.001 for surrogates. CONCLUSIONS: The preparedness scales demonstrated strong psychometric properties. Future studies should examine scale performance in other populations.

A Qualitative Study of the Pain Experience of Black Individuals With Cancer Taking Long-Acting Opioids.

BACKGROUND: Little is known about the experience of Black individuals with cancer taking long-acting opioids for cancer pain. OBJECTIVE: This study aimed to describe the day-to-day experience of living with pain and the experiences of taking opioids for pain management among Black individuals with cancer prescribed with long-acting opioids. METHODS: This qualitative descriptive study was part of a larger investigation focused on opioid adherence. Participants (N = 14) were interviewed using a semistructured interview guide. Analysis followed conventional content analysis and constant comparison approaches. Sociodemographics, clinical information, and the Brief Pain Inventory form were collected. RESULTS: The majority of the subsample was female (64.3%), not married (78.6%), and with a median age of 52.5 years. Participants were taking either MS Contin (85.7%) or OxyContin (14.3%). The Brief Pain Inventory median "average" pain severity scores and pain interference scores were 5.1/10 (interquartile range [IQR] = 6.1) and 3.5/10 (IQR = 6.7), respectively. Three themes are reported from the analyses: desire for control, barriers to pain relief, and isolation versus connectedness. CONCLUSION: Our findings highlight the persistent nature of moderate to severe cancer pain and how pain and its treatment interfere with patients' lives. The findings describe ways that patients learn to manage and exert control over pain despite conflicting attitudes and dealing with opioid stigma. IMPLICATION FOR PRACTICE: Clinicians should partner with patients with cancer, especially people of color, who may experience intersecting stigmas related to their cancer pain and opioid use, to best provide an individualized and culturally sensitive pain treatment plan.

Development of covalent chemogenetic K2P channel activators.

K2P potassium channels regulate excitability by affecting cellular resting membrane potential in the brain, cardiovascular system, immune cells, and sensory organs. Despite their important roles in anesthesia, arrhythmia, pain, hypertension, sleep, and migraine, the ability to control K2P function remains limited. Here, we describe a chemogenetic strategy termed CATKLAMP (Covalent Activation of TREK family K+ channels to cLAmp Membrane Potential) that leverages the discovery of a site in the K2P modulator pocket that reacts with electrophile-bearing derivatives of a TREK subfamily small molecule activator, ML335, to activate the channel irreversibly. We show that the CATKLAMP strategy can be used to probe fundamental aspects of K2P function, as a switch to silence neuronal firing, and is applicable to all TREK subfamily members. Together, our findings exemplify a new means to alter K2P channel activity that should facilitate studies both molecular and systems level studies of K2P function and enable the search for new K2P modulators.

Financial Hardship and Quality of Life Among Patients With Advanced Cancer Receiving Outpatient Palliative Care: A Pilot Study.

BACKGROUND: Patients with advanced cancer are increasingly experiencing financial hardship (FH) and associated negative health outcomes. OBJECTIVE: The aims of this study were to describe FH and explore its relationship to quality of life (QOL) in patients with advanced cancer receiving outpatient palliative care (PC). METHODS: Validated questionnaires assessed FH, QOL dimensions, symptom burden, and sociodemographic and clinical characteristics. Descriptive statistics characterized the sample and described FH. Pearson correlation and linear regression assessed relationships between FH and QOL. RESULTS: The average participant (n = 78) age was 56.6 (SD, 12.2) years. Most were female (56.4%), White (50%) or Black (46.2%), and had a range of education, partner statuses, and cancer diagnoses. Median time since cancer diagnosis was 35.5 months (interquartile range, 9-57.3 months). Highest mean symptom burden scores were for pain (2.5 [SD, 1.0]) and fatigue (2.0 [SD, 1.1]), on a 0- to 3-point scale (higher score representing worse symptom burden). The median COST (COmphrehensive Score for financial Toxicity) score was 15.0 (interquartile range, 9.0-23.0). Most (70%) had some (n = 43) or extreme (n = 9) difficulty paying for basic needs. Greater than 28% (n = 21) incurred cancer-related debt. Multivariate models indicated that FH negatively affected role limitations due to physical health ( P = .008), pain ( P = .003), and emotional well-being ( P = .017) QOL dimensions. CONCLUSIONS: Financial hardship, QOL, and symptom burden scores demonstrate need for continued support for and research among patients with advanced cancer. Data support links between FH and important QOL dimensions. Larger, longitudinal studies are needed to understand how FH affects QOL in patients with advanced cancer. IMPLICATIONS FOR PRACTICE: Proactive financial assessment and interventions are needed to support patients with advanced cancer experiencing the cumulative effects of cancer and its treatment.

Obesity and patient-reported sexual health outcomes in gynecologic cancer survivors: A systematic review.

As obesity prevalence among gynecologic cancer (GC) survivors is expected to increase, the role of obesity in sexual health needs to be understood. This systematic review examined the impact of obesity on patient-reported sexual health outcomes (SHOs) in this population. PubMed, Embase, Web of Science, CINAHL, and PsycINFO were searched for original studies published between 2015 and 2020 following the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. We performed a narrative synthesis of findings via cancer type, cancer treatment, sexual health measures, and countries. Eleven observational studies were included. Most were conducted in European countries (n = 7), reported on endometrial cancer survivors (n = 7), and defined obesity as body mass index ≥30 kg/m2 (n = 10). Studies about cervical cancer survivors reported negative effects of obesity on sexual activity and body image while studies about endometrial cancer survivors reported positive effects of obesity on vaginal/sexual symptoms. Findings suggested interaction effects of radiotherapy and obesity on SHOs. Sexual functioning measured by the Female Sexual Function Index was less likely to be associated with obesity than other SHOs. A positive effect of obesity on SHOs was only found in studies conducted in European countries. Current evidence on the association between obesity and sexual health in GC survivors lacks in both quantity and quality. To better understand the effect of obesity on SHOs in the population, more studies are needed with critical evaluations of obesity and sexual health measures, careful considerations of cancer type and treatment, and a focus on the cultural context of obesity.

What type of plastic do sea turtles in Korean waters mainly ingest? Quantity, shape, color, size, polymer composition, and original usage.

Globally, sea turtles are at high risk of ingesting plastic. However, research on plastic ingestion by sea turtles in East Asia is scant, and no quantitative or qualitative investigation has been conducted in Korean waters. This study examined the plastic ingestion of sea turtles stranded, floating, or incidentally captured in Korean waters between 2012 and 2018. The quantity, shape, color, size, polymer type, and original usage of plastic debris (>1 mm) ingested by sea turtles were analyzed after being sorted from the gastrointestinal tracts of 34 turtles (21 loggerheads (Caretta caretta), 9 green turtles (Chelonia mydas), 2 leatherbacks (Dermochelys coriacea), and 2 olive ridleys (Lepidochelys olivacea)). The ingestion frequencies of greens, loggerheads, olive ridleys, and leatherbacks were 100%, 81%, 50%, and 50%, respectively. The mean amount of plastic ingested was 108 ± 253 mg/kg (38 ± 61 n/ind.). The ingested debris tended to be films and fibers (>80%), light in color (white and transparent; 65%), and light polymers (polyethylene, polypropylene, polypropylene [poly (ethylene:propylene)], expanded polystyrene; 93%). The original uses were identified for 187 pieces; single-use plastics (e.g., plastic bag and packaging) and fishing and aquaculture items (e.g., twine and net) were found to dominate. Green turtles (264 ± 433 mg/kg) ingested significantly higher amounts of plastic than loggerheads (72.8 ± 156 mg/kg). Green turtles ingested mostly fibers (51%), such as rope, twine, and net, while loggerheads ingested largely films (61%), such as plastic bags and packaging. Interspecies differences in quantities and shapes of ingested debris may be related to their distinct feeding habits and geographical range of movement. The present study demonstrates that sea turtles foraging in Korean waters are considerably affected by marine plastic debris, and indicates that proper waste management of single-use plastics and fishing gears is urgently needed to mitigate the damage that plastic debris causes to marine wildlife.

Barriers to Pain Management: Incongruence in Black Cancer Caregiving Dyads.

CONTEXT: To effectively manage cancer pain, there is a need to understand how caregiving dyads appraise symptoms. Dyadic appraisal of symptoms influences whether the dyad perceives the patient's pain is managed well and whether they are on the same page with their appraisal. Beliefs can act as barriers to the dyadic appraisal. OBJECTIVES: This secondary data analysis examined incongruence within Black cancer caregiving dyads regarding beliefs about pain management and potential medication side effects using the Barriers Questionnaire-13. Associated factors were also examined. METHODS: Guided by the Theory of Dyadic Illness Management, dyadic multilevel modeling was conducted with data from 60 Black cancer caregiving dyads to determine the dyadic appraisal of beliefs about pain management and potential medication side effects, which includes the average perception of barriers within the dyad (i.e., dyadic average) and the dyadic incongruence (i.e., gap between patient and caregiver). RESULTS: On average, Black cancer caregiving dyads reported moderate barriers regarding pain management (2.262 (SE=0.102, P<0.001) and medication side effects (2.223 (SE=0.144, P<0.001). There was significant variability across dyads regarding barriers to pain management and medication side effects. Lower patient education and higher patient-reported pain interference were significantly associated with more perceived barriers to pain management and potential medication side effects. Incongruence within dyads regarding barriers to pain management and medication side effects were significantly associated with the caregiver's report of patient's pain interference. CONCLUSION: Findings suggest the importance of appraisal that includes both members of Black cancer caregiving dyads regarding pain management.

Congruence of pain perceptions between Black cancer patients and their family caregivers.

PURPOSE: This cross-sectional study evaluated congruence in pain assessment among Black cancer patients taking opioids for pain and their family caregivers and the effects of patient-reported depressive symptoms and cognitive complaints on the congruence. METHODS: Patient-reported pain scores (current, average, and worst pain severity and pain interference) and caregiver proxy scores were independently assessed (Brief Pain Inventory). Patient-reported depressive symptoms (Patient Health Questionnaire-8) and cognitive complaints (Cognitive Difficulties Scale) were also assessed. Paired t-test, intraclass correlation coefficient (ICC), and Bland-Altman (BA) plots were used to evaluate group and dyad level congruence in pain assessment. The influence of patient depressive symptoms and cognitive complaints on congruence was examined using bivariate analyses and BA plots. RESULTS: Among 50 dyads, 62% of patients and 56% of caregivers were female. Patients were older than caregivers (57 vs. 50 years, p = .008). Neither statistically significant (t-test) nor clinically relevant mean differences in pain severity and interference were found at a group level. At the dyad level, congruence was poor in pain now (ICC = 0.343) and average pain severity (ICC = 0.435), but moderate in worst pain severity (ICC = 0.694) and pain interference (ICC = 0.603). Results indicated better congruence in pain severity between patients with depressive symptoms and their caregivers, compared to patients without depressive symptoms. Patient CDS scores had no significant correlations with score differences between patients and caregivers in any pain variables. CONCLUSION: Congruence varied depending on how the analysis was done. More information is needed to understand pain assessment between patients and caregivers.

Production of K2P2.1 (TREK-1) for structural studies.

K2P (KCNK) potassium channels form 'background' or 'leak' currents that are important for controlling cell excitability in the brain, cardiovascular system, and somatosensory neurons. K2P2.1 (TREK-1) is one of the founding members of this family and one of the first well-characterized polymodal ion channels capable of responding to a variety of physical and chemical gating cues. Of the six K2P subfamilies, the thermo-and mechano-sensitive TREK subfamily comprising K2P2.1 (TREK-1), K2P4.1 (TRAAK), and K2P10.1 (TREK-2) is the first to have structures determined for each subfamily member. These structural studies have revealed key architectural features that provide a framework for understanding how gating cues sensed by different channel elements converge on the K2P selectivity filter C-type gate. TREK family structural studies have also revealed numerous sites where small molecules or lipids bind and affect channel function. This rich structural landscape provides the framework for probing K2P function and for the development of new K2P-directed agents. Such molecules may be useful for affecting processes where TREK channels are important such as anesthesia, pain, arrythmia, ischemia, migraine, intraocular pressure, and lung injury. Production of high quality protein samples is key to addressing new questions about K2P function and pharmacology. Here, we present methods for producing pure K2P2.1 (TREK-1) suitable for advancing towards these goals through structural and biochemical studies.

Application of antihelix antibodies in protein structure determination.

Antibodies are indispensable tools in protein engineering and structural biology. Antibodies suitable for structural studies should recognize the 3-dimensional (3D) conformations of target proteins. Generating such antibodies and characterizing their complexes with antigens take a significant amount of time and effort. Here, we show that we can expand the application of well-characterized antibodies by "transplanting" the epitopes that they recognize to proteins with completely different structures and sequences. Previously, several antibodies have been shown to recognize the alpha-helical conformation of antigenic peptides. We demonstrate that these antibodies can be made to bind to a variety of unrelated "off-target" proteins by modifying amino acids in the preexisting alpha helices of such proteins. Using X-ray crystallography, we determined the structures of the engineered protein-antibody complexes. All of the antibodies bound to the epitope-transplanted proteins, forming accurately predictable structures. Furthermore, we showed that binding of these antihelix antibodies to the engineered target proteins can modulate their catalytic activities by trapping them in selected functional states. Our method is simple and efficient, and it will have applications in protein X-ray crystallography, electron microscopy, and nanotechnology.

The polyherbal composition Gyeongshingangjeehwan 18 attenuates glucose intolerance and pancreatic steatosis in C57BL/6J mice on a high-fat diet.

Ethnopharmacologic relevance: Gyeongshingangjeehwan 18 (GGEx18) is a polyherbal composition derived from Ephedra sinica Stapf (Ephedraceae), Laminaria japonica Aresch (Laminariaceae), and Rheum palmatum L. (Polygonaceae) that is used as an antiobesity drug in Korean clinics. Its constituents are traditionally known to combat obesity, dyslipidemia, and insulin resistance. OBJECTIVE: This study was undertaken to investigate the effects of GGEx18 on glucose metabolism and pancreatic steatosis in obese C57BL/6 J mice fed a high-fat diet (HFD) and to examine the related cellular and molecular mechanisms. MATERIALS AND METHODS: The mice were grouped and fed for 13 weeks as follows: 1) low-fat diet, 2) HFD, or 3) HFD supplemented with GGEx18 (500 mg/kg/day). Various factors affecting insulin sensitivity and pancreatic function were then assessed via blood analysis, histology, immunohistochemistry, and real-time polymerase chain reaction. RESULTS: GGEx18 treatment of obese mice reduced body weight, total fat, and visceral fat mass. GGEx18 inhibited hyperglycemia and hyperinsulinemia and improved glucose and insulin tolerance. GGEx18 also decreased serum leptin levels and concomitantly increased adiponectin levels. Furthermore, GGEx18-treated mice exhibited reduced pancreatic fat accumulation and normalized insulin-secreting ß-cell area. GGEx18 increased pancreatic expression of genes promoting fatty acid ß-oxidation (i.e., MCAD and VLCAD), whereas expression levels of lipogenesis-related genes (i.e., PPARγ, SREBP-1c, and FAS) declined. DISCUSSION AND CONCLUSION: GGEx18 curtailed impaired glucose metabolism and pancreatic steatosis in our mouse model by regulating pancreatic genes that govern lipid metabolism and improving insulin sensitivity. This composition may benefit patients with impaired glucose tolerance, insulin resistance, and pancreatic dysfunction.

The polyherbal drug GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica inhibits hepatic steatosis and fibroinflammtion in high-fat diet-induced obese mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbal composition Gyeongshingangjeehwan 18 (GGEx18), composed of Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae), is used as an antiobesity drug in Korean clinics. The constituents of GGEx18 have traditionally been reported to inhibit obesity and related metabolic diseases such as insulin resistance and dyslipidemia. OBJECTIVE: This study investigated the effects of GGEx18 on nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet (HFD) and the underlying cellular and molecular mechanisms involved. METHODS: C57BL/6 J mice were fed either a low-fat diet (LFD), an HFD, or an HFD supplemented with GGEx18 (125, 250, or 500 mg/kg of body weight/day). After 13 weeks, blood analyses, histology, immunohistochemistry, and real-time PCR were performed to assess NAFLD development in these mice. RESULTS: Mice fed an HFD had increases in body weight, epididymal adipose tissue mass, adipocyte size, and adipose expression of inflammation-related genes compared with those fed an LFD. These increases were ameliorated in mice treated with 500 mg/kg/day GGEx18 without affecting food consumption profiles. GGEx18 not only decreased serum levels of triglycerides, free fatty acids, and alanine aminotransferase, but also decreased hepatic lipid accumulation, numbers of mast cells and α-smooth muscle actin-positive cells, and collagen levels induced by an HFD. Consistent with the histological data, the hepatic expression of lipogenesis-, inflammation-, and fibrosis-related genes was lower, while hepatic fatty acid ß-oxidation-related gene expression was higher, in mice receiving GGEx18 compared to mice fed only the HFD. DISCUSSION AND CONCLUSION: These results indicate that GGEx18 attenuates visceral obesity and NAFLD, in part by altering the expression of genes involved in hepatic steatosis and fibroinflammation in HFD-induced obese mice. These findings suggest that GGEx18 may be effective for preventing and treating NAFLD associated with visceral obesity.

Effect of Gangjihwan on hepatic steatosis and inflammation in high fat diet-fed mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Gangjihwan (DF), a polyherbal drug composed of Ephedra intermedia Schrenk et C. A. Mayer (Ephedraceae), Lithospermum erythrorhizon Siebold et Zuccarini (Borraginaceae), and Rheum palmatum L. (Polygonaceae), is used to treat obesity in local Korean clinics. The constituents of DF have traditionally been reported to exert anti-obesity and anti-nonalcoholic fatty liver disease (NAFLD) effects. Thus, we investigated the effects of DF on obesity and NAFLD and the underlying mechanisms. MATERIALS AND METHODS: DF was extracted with water (DF-FW), 30% ethyl alcohol (DF-GA30), or 70% ethyl alcohol (DF-GA70). The chemical profile of DF was monitored using high performance liquid chromatography (HPLC)-ultraviolet analysis. The effects of DF on indices of obesity and NAFLD in high fat diet (HFD)-fed C57BL/6J mice and HepG2 cells were examined using quantitative real-time polymerase chain reaction, Oil red O staining, hematoxylin-eosin staining, toluidine blue staining, and immunohistochemistry. RESULTS: The presence of ephedrine, pseudoephedrine, aloe-emodin, and emodin in DF was determined by 3D chromatography using HPLC. Administration of DF-GA70 to HFD-fed obese mice decreased body weight, epididymal adipose tissue mass, and epididymal adipocyte size. DF-GA70 reduced serum levels of free fatty acids and triglycerides. All three DF extracts lowered serum alanine transaminase levels, hepatic lipid accumulation, and infiltration of macrophages, with the largest effects observed for DF-GA70. DF-GA70 increased mRNA levels of fatty acid oxidation genes and decreased mRNA levels of genes for lipogenesis and inflammation in the liver of obese mice. Treatment of HepG2 cells with a mixture of oleic acid and palmitoleic acid induced significant lipid accumulation, whereas all three DF extracts inhibited lipid accumulation. DF-GA70 also altered the expression of lipolytic and lipogenic genes in HepG2 cells. CONCLUSIONS: These results indicate that DF inhibits obesity and obesity-induced severe hepatic steatosis and inflammation without any adverse effects and that these effects may be mediated by regulation of the hepatic expression of lipid metabolism and inflammatory genes. These findings suggest that DF is a safe and efficient anti-obesity and anti-nonalcoholic steatohepatosis drug.

Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS.

The sodium-dependent citrate transporter of Klebsiella pneumoniae (KpCitS) belongs to the 2-hydroxycarboxylate transporter (2-HCT) family and allows the cell to use citrate as sole carbon and energy source in anaerobic conditions. Here we present crystal structures of KpCitS in citrate-bound outward-facing, citrate-bound asymmetric, and citrate-free inward-facing state. The structures reveal that the KpCitS dimerization domain remains stationary throughout the transport cycle due to a hydrogen bond network as well as extensive hydrophobic interactions. In contrast, its transport domain undergoes a ~35° rigid-body rotation and a ~17 Å translocation perpendicular to the membrane to expose the substrate-binding site alternately to either side of the membrane. Furthermore, homology models of two other 2-HCT proteins based on the KpCitS structure offer structural insights into their differences in substrate specificity at a molecular level. On the basis of our results and previous biochemical data, we propose that the activity of the 2-HCT CitS involves an elevator-like movement in which the transport domain itself traverses the lipid bilayer, carrying the substrate into the cell in a sodium-dependent manner.

The lemon balm extract ALS-L1023 inhibits obesity and nonalcoholic fatty liver disease in female ovariectomized mice.

Increasing evidence indicates that angiogenesis inhibitors regulate obesity. This study aimed to determine whether the lemon balm extract ALS-L1023 inhibits diet-induced obesity and nonalcoholic fatty liver disease (NAFLD) in female ovariectomized (OVX) mice. OVX mice received a low fat diet (LFD), a high fat diet (HFD) or HFD supplemented with ALS-L1023 (ALS-L1023) for 15 weeks. HFD mice exhibited increases in visceral adipose tissue (VAT) angiogenesis, body weight, VAT mass and VAT inflammation compared with LFD mice. In contrast, all of these effects were reduced in ALS-L1023 mice compared with HFD mice. Serum lipids and liver injury markers were improved in ALS-L1023 mice. Hepatic lipid accumulation, inflammatory cells and collagen levels were lower in ALS-L1023 mice than in HFD mice. ALS-L1023 mice exhibited a tendency to normalize hepatic expression of genes involved in lipid metabolism, inflammation and fibrosis to levels in LFD mice. ALS-L1023 also induced Akt phosphorylation and increased Nrf2 mRNA expression in livers of obese mice. Our results indicate that the angiogenesis inhibitor ALS-L1023 can regulate obesity, hepatic steatosis and fibro-inflammation, in part through improvement of VAT function, in obese OVX mice. These findings suggest that angiogenesis inhibitors may contribute to alleviation of NAFLD in post-menopausal women with obesity.

The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease through Regulating the Visceral Adipose-Tissue Function.

Similar to neoplastic tissues, growth and development of adipose tissue are thought to be angiogenesis-dependent. Since visceral adipose tissue (VAT) is associated with development and progression of nonalcoholic fatty liver disease (NAFLD), we hypothesized that angiogenesis inhibition would attenuate obesity-induced NAFLD. We fed C57BL/6J mice a low-fat diet (LFD, chow 10% kcal fat), a high-fat diet (HFD, 45% kcal fat) or HFD supplemented with the lemon-balm extract ALS-L1023 (HFD-ALS) for 15 weeks. ALS-L1023 reduced endothelial cell-tube formation in vitro. HFD increased VAT angiogenesis and induced weight gains including body weight, VAT mass and visceral adipocyte size compared with LFD. However, HFD-ALS led to weight reductions without affecting calorie intake compared with HFD. HFD-ALS also reduced serum ALT and AST levels and improved lipid metabolism. HFD-ALS suppressed steatosis, infiltration of inflammatory cells, and accumulation of collagen in livers. HFD-ALS modulated hepatic expression of genes involved in lipid metabolism, inflammation, fibrosis, antioxidation, and apoptosis. Concomitantly, analysis of VAT function revealed that HFD-ALS led to fewer CD68-positive macrophage numbers and lower expression of inflammatory cytokines compared with HFD. Our findings show that the anti-angiogenic herbal extract ALS-L1023 attenuates NAFLD by targeting VAT during obesity, suggesting that angiogenesis inhibitors could aid in the treatment and prevention of obesity-induced human NAFLD.

[The Relationships among Chemotherapy-Induced Nausea and Vomiting (CINV), Non-Pharmacological Coping Methods, and Nutritional Status in Patients with Gynecologic Cancer].

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) can cause severe malnutrition. However, relationships between CINV levels, non-pharmacological coping methods, and nutritional status of female cancer patients have rarely been investigated. Therefore, this study aimed to analyze their relationships in gynecologic cancer patients. METHODS: Participants receiving a highly and moderately emetogenic chemotherapy were recruited. The level of CINV was assessed using a numeric rating scale. Coping methods were determined using multiple-choice self-report questionnaires and categorized into seven types for statistical analysis. Nutritional status was evaluated using biochemical and anthropometric parameters. RESULTS: Among all the 485 patients, 200 eligible inpatients were included. Despite the administration of prophylactic antiemetics, 157 patients (78.5%) still experienced CINV, and several used nonmedically recommended coping methods, such as just enduring the symptom or rejecting food intake. A total of 181 patients (90.5%) had nutritional disorders. Although the level of CINV was indirectly related to the occurrence of nutritional disorders, patients who rejected food (ß=1.57, p=.023) and did not use physical measures (ß= -1.23, p=.041) as coping methods were under the high risk of nutritional disorders. CONCLUSION: Korean gynecologic cancer patients had high levels of CINV and were at high risk of nutritional disorders, which may be related to the use of nonscientific coping methods, possibly due to cultural backgrounds and lack of proper nutritional program. Therefore, developing a culturally appropriate educational program for the cancer patients with CINV is urgently needed.

The effects of herbal composition Gambigyeongsinhwan (4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty rats and HepG2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatic steatosis has risen rapidly in parallel with a dramatic increase in obesity. The aim of this study was to determine whether the herbal composition Gambigyeongsinhwan (4) (GGH(4)), composed of Curcuma longa L. (Zingiberaceae), Alnus japonica (Thunb.) Steud. (Betulaceae), and the fermented traditional Korean medicine Massa Medicata Fermentata, regulates hepatic steatosis and inflammation. MATERIALS AND METHODS: The effects of GGH(4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty (OLETF) rats and HepG2 cells were examined using Oil red O, hematoxylin and eosin, and toluidine blue staining, immunohistochemistry, quantitative real-time polymerase chain reaction, and peroxisome proliferator-activated receptor α (PPARα) transactivation assay. RESULTS: Administration of GGH(4) to OLETF rats improved hepatic steatosis and lowered serum levels of alanine transaminase, total cholesterol, triglycerides, and free fatty acids. GGH(4) increased mRNA levels of fatty acid oxidation enzymes (ACOX, HD, CPT-1, and MCAD) and decreased mRNA levels of lipogenesis genes (FAS, ACC1, C/EBPα, and SREBP-1c) in the liver of OLETF rats. In addition, infiltration of inflammatory cells and expression of inflammatory cytokines (CD68, TNFα, and MCP-1) in liver tissue were reduced by GGH(4). Treatment of HepG2 cells with a mixture of oleic acid and palmitoleic acid induced significant lipid accumulation, but GGH(4) inhibited lipid accumulation by regulating the expression of hepatic fatty acid oxidation and lipogenic genes. GGH(4) also increased PPARα reporter gene expression. These effects of GGH(4) were similar to those of the PPARα activator fenofibrate, whereas the PPARα antagonist GW6471 reversed the inhibitory effects of GGH(4) on lipid accumulation in HepG2 cells. CONCLUSIONS: These results suggest that GGH(4) inhibits obesity-induced hepatic steatosis and that this process may be mediated by regulation of the expression of PPARα target genes and lipogenic genes. GGH(4) also suppressed obesity-related hepatic inflammation. Thus, GGH(4) may be a promising drug for the treatment of obesity-related liver diseases.

Determination of S-methyl-L-methionine (SMM) from Brassicaceae Family Vegetables and Characterization of the Intestinal Transport of SMM by Caco-2 Cells.

The objectives of the current study were to determine S-methyl-L-methionine (SMM) from various Brassicaceae family vegetables by using validated analytical method and to characterize the intestinal transport mechanism of SMM by the Caco-2 cells. The SMM is well known to provide therapeutic activity in peptic ulcers. The amount of SMM from various Brassicaceae family vegetables ranged from 89.08 ± 1.68 µg/g to 535.98 ± 4.85 µg/g of dry weight by using validated ultra-performance liquid chromatography-electrospray ionization-mass spectrometry method. For elucidating intestinal transport mechanism, the cells were incubated with or without transport inhibitors, energy source, or a metabolic inhibitor. Phloridzin and verapamil as inhibitors of sodium glucose transport protein (SGLT1) and P-glycoprotein, respectively, were not responsible for cellular uptake of SMM. Glucose and sodium azide were not affected by the cellular accumulation of SMM. The efflux ratio of SMM was 0.26, implying that it is not effluxed through Caco-2 cells. The apparent coefficient permeability (Papp ) of SMM was 4.69 × 10-5 cm/s, indicating that it will show good oral absorption in in vivo.