Potential Phytotherapy of DSS-Induced Colitis: Ameliorating Reactive Oxygen Species-Mediated Necroptosis and Gut Dysbiosis with a New Crataegus pinnatifida Bunge Variety-Daehong.

Developing new plant varieties plays a crucial role in competitiveness in the agricultural and food industries and enhancing food security. Daehong (DH) is a new variety of Crataegus pinnatifida Bunge (CP); however, its physiological functions and potential as a nutraceutical ingredient remain unknown. Here, the efficacy of DH on inflammatory bowel disease (IBD) was investigated using dextran sulfate sodium (DSS)-induced colitis mice, and its relative pharmacological effects were analyzed against CP. DH improved colitis-induced weight loss, colon shortening, and inflammatory responses and reduced intestinal permeability. The reactive oxygen species (ROS)-mediated necroptotic signal that triggers enterocyte cell death in DSS-induced colitis was effectively controlled by DH, attributed to epicatechin. DSS-induced gut dysbiosis was recovered into a healthy gut microbiome environment by DH, increasing beneficial bacteria, like Akkermansia muciniphila, and changing harmful bacteria, including Bacteroides vulgatus and Peptostreptococcaceae. DH shows potential as a dietary or pharmaceutical ingredient to promote gut health and to prevent and treat IBD.

Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2021.

PURPOSE: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2021. MATERIALS AND METHODS: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2021, with survival follow-up until December 31, 2022. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea. RESULTS: The number of new cancer diagnoses in 2021 increased by 27,002 cases (10.8%) compared to 2020. In 2021, newly diagnosed cancer cases and deaths from cancer were reported as 277,523 (age-standardized rate [ASR], 289.3 per 100,000) and 82,688 (ASR, 67.6 per 100,000), respectively. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.3% from 2012 to 2015, thereafter, followed by non-significant changes. Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years (annual decrease of 2.8% from 2002 to 2013; 3.2% from 2013 to 2021). The 5-year relative survival between 2017 and 2021 was 72.1%, which contributed to prevalent cases reaching over 2.4 million in 2021. CONCLUSION: In 2021, the number of newly diagnosed cancer patients increased as healthcare utilization recovered from the coronavirus disease 2019-related declines of 2020. Revised cancer registration guidelines expanded the registration scope, particularly for stomach and colorectal cancer. Survival rates have improved over the years, leading to a growing population of cancer survivors, necessitating a comprehensive cancer control strategy. The long-term impact of the pandemic on cancer statistics requires future investigation.

Improvement in Yield of Extracellular Vesicles Derived from Edelweiss Callus Treated with LED Light and Enhancement of Skin Anti-Aging Indicators.

The process of skin aging is currently recognized as a disease, and extracellular vesicles (EVs) are being used to care for it. While various EVs are present in the market, there is a growing need for research on improving skin conditions through microbial and plant-derived EVs. Edelweiss is a medicinal plant and is currently an endangered species. Callus culture is a method used to protect rare medicinal plants, and recently, research on EVs using callus culture has been underway. In this study, the researchers used LED light to increase the productivity of Edelweiss EVs and confirmed that productivity was enhanced by LED exposure. Additionally, improvements in skin anti-aging indicators were observed. Notably, M-LED significantly elevated callus fresh and dry weight, with a DW/FW ratio of 4.11%, indicating enhanced proliferation. Furthermore, M-LED boosted secondary metabolite production, including a 20% increase in total flavonoids and phenolics. The study explores the influence of M-LED on EV production, revealing a 2.6-fold increase in concentration compared to darkness. This effect is consistent across different plant species (Centella asiatica, Panax ginseng), demonstrating the universality of the phenomenon. M-LED-treated EVs exhibit a concentration-dependent inhibition of reactive oxygen species (ROS) production, surpassing dark-cultured EVs. Extracellular melanin content analysis reveals M-LED-cultured EVs' efficacy in reducing melanin production. Additionally, the expression of key skin proteins (FLG, AQP3, COL1) is significantly higher in fibroblasts treated with M-LED-cultured EVs. These results are expected to provide valuable insights into research on improving the productivity of plant-derived EVs and enhancing skin treatment using plant-derived EVs.

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial).

BACKGROUND: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). METHODS: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. DISCUSSION: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. TRIAL REGISTRATION: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Efficiency of the Enzymatic Conversion of Flavone Glycosides Isolated from Carrot Leaves and Anti-Inflammatory Effects of Enzyme-Treated Carrot Leaves.

In traditional oriental medicine, carrots (Daucus carota L.) are considered effective medicinal herbs; however, the use of D. carota leaves (DCL) as therapeutic agents has not been explored in depth. Therefore, we aimed to demonstrate the value of DCL, generally treated as waste while developing plants for wide industrial availability. Six flavone glycosides were isolated and identified from DCL, and their constituents were identified and quantitated using an NMR and HPLC/UV method, which was optimized and validated. The structure of chrysoeriol-7-rutinoside from DCL was elucidated for the first time. The method exhibited adequate relative standard deviation (<1.89%) and recovery (94.89-105.97%). The deglycosylation of DCL flavone glycosides by Viscozyme L and Pectinex was assessed. Upon converting the reaction contents to percentages, the luteolin, apigenin, and chrysoeriol groups showed values of 85.8, 33.1, and 88.7%, respectively. The enzyme-treated DCL had a higher inhibitory effect on TNF-α and IL-2 expression than that of the carrot roots or carrot leaves without enzyme treatments. These results highlight the importance of carrot leaves and could be used as baseline standardization data for commercial development.

Does whey protein supplementation during resistance exercise have additional benefits for decreasing hepatic fat content?

BACKGROUND: Exercise and diet have positive effects on hepatic fat reduction, and protein supplementation is known to lower hepatic fat accumulation. However, the effect of a combination of exercise and whey protein supplementation (WPS) on hepatic fat content (HFC) is unknown. METHODS: We investigated the effect of WPS on HFC during resistance exercise and diet control intervention for four weeks. A total of 34 sedentary males participated and were randomly assigned to two groups: a protein supplement group (PSG, n = 18) and a control group (CG, n = 16). The PSG took 60 g of WPS per day, and the CG took 60 g of an isocaloric placebo per day. All participants were fed a calorie-controlled diet throughout the study period, with their daily caloric intake determined by their resting metabolic rate and physical activity level. Both groups performed resistance exercises supervised by experts at 60-70% of their maximum efforts for 60 min/day, 6 days/week for 4 weeks. HFC was assessed using the controlled attenuation parameter (CAP) after an 8 h fast, at pre-, mid-, and post-intervention. Liver enzymes and lipid profile were also analyzed after an 8 h fast and pre- and post-intervention. RESULTS: The CAP was significantly reduced after 4 weeks of intervention in both groups (PSG, p < .001; CG, p = .002). However, there was no significant interaction between the group and changes in CAP. Interestingly, when comparing the pre- and mid-tests, both groups also had significantly reduced CAP (PSG, p = .027; CG, p = .028), but there was a significant difference in the amount of change in CAP between the two groups (PSG, -47.2 ± 25.4 dB/m; CG, -19.5 ± 15.1 dB/m; p = .042). For liver enzymes, there was a significant interaction between the two groups and a change in aspartate transaminase (AST) (p = .038). However, alanine aminotransferase (ALT) levels were significantly decreased only in the PSG group (p = .002). In lipids, both groups showed significantly decreased total cholesterol (p < .001) and low-density lipoprotein cholesterol (p < .001) after the intervention. CONCLUSION: Our data showed that WPS may not enhance the overall effects of resistance exercise on HFC and lipid profiles. However, in part, WPS may have a beneficial effect on liver enzymatic changes and rapid response to resistance exercise-induced HFC reduction.

Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2020.

PURPOSE: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2020. Materials and Methods: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2020, with survival follow-up until December 31, 2021. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea. RESULTS: The number of new cancer diagnoses in 2020 decreased by 9,218 cases (3.6%) compared to 2019. In 2020, newly diagnosed cancer cases and deaths from cancer were reported as 247,952 (age-standardized rate [ASR], 262.2 per 100,000) and 82,204 (ASR, 69.9 per 100,000), respectively. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.0% annually from 2012 to 2015, thereafter, followed by nonsignificant changes. Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years. The 5-year relative survival between 2016 and 2020 was 71.5%, which contributed to prevalent cases reaching over 2.2 million in 2020. CONCLUSION: In 2020, the number of newly diagnosed cancer patients decreased due to the coronavirus disease 2019 pandemic, but the overall trend is on the rise. Cancer survival rates have improved over the past decades. As the number of cancer survivors increases, a comprehensive cancer control strategy should be implemented in line with the changing aspects of cancer statistics. The long-term impact of the coronavirus disease 2019 pandemic on cancer statistics needs to be investigated in the future.

Effects of Whey Protein Supplement on 4-Week Resistance Exercise-Induced Improvements in Muscle Mass and Isokinetic Muscular Function under Dietary Control.

(1) The purpose of this study was to investigate the effect of whey protein supplementation under dietary control on improvements in muscle mass and function following resistance exercise training. (2) Thirty-two men were randomly assigned to a whey protein supplementation group taking whey protein isolate (PSG, n = 17) and a placebo group (CON, n = 15). Participants were provided with three meals per day corresponding to the estimated individual daily energy intake. The supervised resistance exercise program was conducted 60 min per day, six days per week, for four weeks. (3) Post-intervention, there was a significant interaction between groups in terms of muscle mass increase (p = 0.033, η2 = 0.14), with a greater increase in the PSG. There were also significant interactions between the groups and increases in peak torque of the dominant knee flexors (p = 0.048, η2 = 0.12), dominant shoulder extensors, and non-dominant shoulder extensors (p = 0.028, η2 = 0.15; p = 0.015, η2 = 0.18), and the total work of the dominant knee and shoulder extensors (p = 0.012, η2 = 0.19; p = 0.013, η2 = 0.19), with greater increases in the PSG. (4) These results suggest that whey protein supplementation enhances resistance exercise-induced increase in muscle mass and overall muscular strength and endurance, independent of dietary influence.

Oncological impact of intraperitoneal chemotherapy after cytoreductive surgery for patients with colorectal peritoneal metastasis: A bi-institutional retrospective analysis.

BACKGROUND AND OBJECTIVES: There is a paucity of evidence on the value of intraperitoneal chemotherapy (IPC) following cytoreductive surgery (CRS) for colorectal peritoneal metastasis. This study aimed to evaluate the association between mitomycin C-IPC and survival outcomes following CRS. METHODS: The institutional databases of two tertiary hospitals were reviewed to identify patients who underwent CRS for colorectal peritoneal metastasis. The outcomes of patients who underwent CRS without IPC were compared with those of patients who underwent CRS plus early postoperative intraperitoneal chemotherapy (EPIC) or CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC). The primary endpoints were cancer-specific survival (CSS), progression-free survival (PFS), and peritoneal PFS (P-PFS). RESULTS: In 149 patients with peritoneal metastasis alone, EPIC and HIPEC use was significantly associated with better CSS, PFS, and P-PFS in the multivariate analysis. CSS was also significantly associated with perioperative systemic chemotherapy. Among 42 patients with both peritoneal and extraperitoneal metastases, CSS was independently related to the completeness of cytoreduction score, location of extraperitoneal metastasis, and grade 3-4 complications. CONCLUSIONS: Mitomycin C-IPC after CRS was associated with better survival outcomes than CRS alone in patients with resectable peritoneal metastasis of colorectal cancer. This study found that IPC had beneficial effects regarding P-PFS in patients with both peritoneal and extraperitoneal metastases.

Spatholobus suberectus Dunn Water Extract Ameliorates Atopic Dermatitis-Like Symptoms by Suppressing Proinflammatory Chemokine Production In Vivo and In Vitro.

S. patholobus suberectus Dunn, a traditional Chinese herbal medicine, has various pharmacological activities, such as anti-inflammatory properties. However, to the best of our knowledge, its therapeutic effect on atopic dermatitis (AD) has not been investigated. In this study, we explored the effect of S. suberectus Dunn water extract (SSWex) on AD in vivo and in vitro. In Dermatophagoides farina extract (DfE)-treated NC/Nga mice, the oral administration of SSWex alleviated AD-like symptoms, such as ear thickness, dermatitis score, epidermal thickness, immune cell infiltration, and levels of AD-related serum parameters (immunoglobulin E, histamine, and proinflammatory chemokines). In HaCaT cells, the production of proinflammatory chemokines induced by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) was inhibited by SSWex pretreatment. SSWex treatment inhibited the phosphorylation of mitogen-activated protein kinase and activation and translocation of transcriptional factors, such as signal transducer and activator of transcription 1 and nuclear factor kappa B in IFN-γ/TNF-α-stimulated HaCaT cells. These results indicate that SSWex may be developed as an efficient therapeutic agent for AD.

Terminalia chebula Retz. extract ameliorates the symptoms of atopic dermatitis by regulating anti-inflammatory factors in vivo and suppressing STAT1/3 and NF-ĸB signaling in vitro.

BACKGROUND: Terminalia chebula (TC) is a traditional medicinal plant used for treating various diseases in humans. However, pharmacological mechanisms underlying the effects of TC in atopic treatment remain unelucidated. HYPOTHESIS/PURPOSE: We investigated the therapeutic effects of TC extract in a mouse model of atopic dermatitis (AD) in vivo and the anti-inflammatory mechanism in vitro. STUDY DESIGN/METHODS: For the in vivo study, AD was induced by Dermatophagoides farinae extract (Dfe) in NC/Nga mice. After 14 days of oral administration, the effects of TC concentrations of 30, 100, and 300 mg/kg were analyzed by assessing morphological changes visually; measuring serum levels of inflammatory chemokines/cytokines, IgE, histamine, MDC, TARC, RANTES, and TSLP using ELISA kits; and counting infiltrated mast cells. For in vitro analyses, we used IFNγ/TNF-α-stimulated human keratinocyte cell lines to study the mechanism of action. The production of chemokines/cytokines in the IFNγ/TNF-α-stimulated HaCaT cells was measured using ELISA and a bead array kit. The signaling pathways were analyzed by western blotting and the expression of the transcriptional factors using RT-PCR and luciferase assay. RESULTS: Administration of TC significantly alleviated AD-like symptoms in vivo and decreased the ear thickness, dermatitis score, keratinization, and mast cell infiltration. It also resulted in decreased serum levels of IgE, histamine, and inflammation-related mediators MDC, TARC, RANTES, and TSLP compared with those in the Dfe treatment group. Moreover, TC downregulated the expression of the inflammatory chemokines RANTES and MDC in IFNγ/TNF-α-stimulated HaCaT cells. TC inhibited phosphorylated STAT1/3 and NK-κB subunits and nuclear translocation of NF-κB. It also suppressed the transcription of IFNγ, IL-6, IL-8 and MCP-1 in the IFNγ/TNF-α-stimulated HaCaT cells. TC and its constituents, chebulic acid, gallic acid, corlagin, chebulanin, chbulagic acid, ellagic acid, and chebulinic acid, strongly inhibited the nuclear translocation of NF-κB, STAT1, and STAT3 and decreased the expression of inflammatory cytokines at the mRNA level. CONCLUSIONS: Overall, TC extract alleviated AD-like symptoms by regulating anti-inflammatory factors in vivo and suppressing STAT1/3 and NF-κB signaling in vitro. In addition, our results show the in vivo effect of partial improvements in AD, as well as the in vitro effect on inflammatory factors by the constituents of TC. This finding provides that TC extract and its components could be potential therapeutic drugs for AD.

Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2019.

PURPOSE: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2019. MATERIALS AND METHODS: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2019, with survival follow-up until December 31, 2020. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea. RESULTS: In 2019, newly diagnosed cancer cases and deaths from cancer were reported as 254,718 (ASR, 275.4 per 100,000) and 81,203 (ASR, 72.2 per 100,000), respectively. For the first time, lung cancer (n=29,960) became the most frequent cancer in Korea, excluding thyroid cancer. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.3% annually from 2012 to 2015, thereafter, followed by nonsignificant changes. The incidence of thyroid cancer increased again from 2016 (annual percentage change, 6.2%). Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years (annual decrease of 2.7% from 2002 to 2013; 3.3% from 2013 to 2019). The 5-year relative survival between 2015 and 2019 was 70.7%, which contributed to prevalent cases reaching over 2 million in 2019. CONCLUSION: Cancer survival rates have improved over the past decades, but the number of newly diagnosed cancers is still increasing, with some cancers showing only marginal improvement in survival outcomes. As the number of cancer survivors increases, a comprehensive cancer control strategy should be implemented in line with the changing aspects of cancer statistics.

Long-term vitamin A supplementation in a preclinical mouse model for RhoD190N-associated retinitis pigmentosa.

Retinitis pigmentosa (RP) is caused by one of many possible gene mutations. The National Institutes of Health recommends high daily doses of vitamin A palmitate for RP patients. There is a critical knowledge gap surrounding the therapeutic applicability of vitamin A to patients with the different subtypes of the disease. Here, we present a case report of a patient with RP caused by a p.D190N mutation in Rhodopsin (RHO) associated with abnormally high quantitative autofluorescence values after long-term vitamin A supplementation. We investigated the effects of vitamin A treatment strategy on RP caused by the p.D190N mutation in RHO by exposing Rhodopsin p.D190N (RhoD190N/+) and wild-type (WT) mice to experimental vitamin A-supplemented and standard control diets. The patient's case suggests that the vitamin A treatment strategy should be further studied to determine its effect on RP caused by p.D190N mutation in RHO and other mutations. Our mouse experiments revealed that RhoD190N/+ mice on the vitamin A diet exhibited higher levels of autofluorescence and lipofuscin metabolites compared to WT mice on the same diet and isogenic controls on the standard control diet. Vitamin A supplementation diminished photoreceptor function in RhoD190N/+ mice while preserving cone response in WT mice. Our findings highlight the importance of more investigations into the efficacy of clinical treatments like vitamin A for patients with certain genetic subtypes of disease and of genotyping in the precision care of inherited retinal degenerations.

Anatomical and Chemical Characterization of Ulmus Species from South Korea.

Ulmus species (Ulmaceae) are large deciduous trees distributed throughout Korea. Although their root and stem bark have been used to treat gastrointestinal diseases and wounds in folk medicine, commercial products are consumed without any standardization. Therefore, we examined anatomical and chemical differences among five Ulmus species in South Korea. Transverse sections of leaf, stem, and root barks were examined under a microscope to elucidate anatomical differences. Stem and root bark exhibited characteristic medullary ray and secretary canal size. Leaf surface, petiole, and midrib exhibited characteristic inner morphologies including stomatal size, parenchyma, and epidermal cell diameter, as well as ratio of vascular bundle thickness to diameter among the samples. Orthogonal projections to latent structures discriminant analysis of anatomical data efficiently differentiated the five species. To evaluate chemical differences among the five species, we quantified (-)-catechin, (-)-catechin-7-O-ß-D-apiofuranoside, (-)-catechin-7-O-α-L-rhamnopyranoside, (-)-catechin-7-O-ß-D-xylopyranoside, (-)-catechin-7-O-ß-D-glucopyranoside, and (-)-catechin-5-O-ß-D-apiofuranoside using high-performance liquid chromatography with a diode-array detector. (-)-Catechin-7-O-ß-D-apiofuranoside content was the highest among all compounds in all species, and (-)-catechin-7-O-α-L-rhamnopyranoside content was characteristically the highest in Ulmus parvifolia among the five species. Overall, the Ulmus species tested was able to be clearly distinguished on the basis of anatomy and chemical composition, which may be used as scientific criteria for appropriate identification and standard establishment for commercialization of these species.

Alpinia officinarum water extract inhibits the atopic dermatitis-like responses in NC/Nga mice by regulation of inflammatory chemokine production.

Alpinia officinarum (AO) has been traditionally used in Asia as an herbal medicine to treat inflammatory and internal diseases. However, the therapeutic effect of AO on atopic dermatitis (AD) is unclear. Therefore, we examined whether Alpinia officinarum water extract (AOWex) affects AD in vivo and in vitro. Oral administration of AOWex to NC/Nga mice with Dermatophagoies farina extract (DfE)-induced AD-like symptoms significantly reduced the severity of clinical dermatitis, epidermal thickness, and mast cell infiltration into the skin and ear tissue. Decreased total serum IgE, macrophage-derived chemokine (MDC), and regulated on activation, normal T-cell expressed and secreted (RANTES) levels were observed in DfE-induced NC/Nga mice in the AOWex-treated group. These effects were confirmed in vitro using HaCaT cells. Treatment with AOWex inhibited the expression of proinflammatory chemokines such as MDC, RANTES, IP-10 and I-TAC in interferon-γ and tumor necrosis factor-α-stimulated HaCaT cells. The anti-inflammatory effects of AOWex were due to its inhibitory action on MAPK phosphorylation (ERK and JNK), NF-κB, and STAT1. Furthermore, galangin, protocatechuic acid, and epicatechin from AOWex were identified as candidate anti-AD compounds. These results suggest that AOWex exerts therapeutic effects against AD by alleviating AD-like skin lesions, suppressing inflammatory mediators, and inhibiting major signaling molecules.

Cinnamomum verum-derived O-methoxycinnamaldehyde prevents lipopolysaccharide-induced depressive-like behavior in mice via NFAT mRNA stability in T lymphocytes.

BACKGROUND: Depressive-like behaviors are related to inflammatory immune activation. Cinnamomum verum (CV) has anti-inflammatory effects, but the molecular mechanisms underlying the antidepressant effects after immunological activation still remain elusive. PURPOSE: The aim of the present study was to investigate the effect of CV in improving depressive-like behavior and explore its underlying mechanism in T lymphocytes. METHODS: Mice were randomly divided into Control, LPS, LPS plus fluoxetine, LPS plus CV, and LPS plus MCA groups. Behavior was evaluated using forced swimming test (FST) and tail suspension test (TST). The experimental group mice were exposed to LPS to induce depressive-like behavior. Cell viability was measured upon treating splenic T lymphocytes and Jurkat T cells with CV. Cytokine activity was measured using ELISA and RT-qPCR. The components of CV were analyzed by HPLC. NFAT expression was evaluated by western blotting, immunofluorescence, and luciferase assay. To verify the half-life of NFAT mRNA, Jurkat cells were treated with actinomycin D for 1.5, 3, and 4.5 h. RESULTS: CV effectively prevents inflammation-induced depressive-like behaviors. CV dose-dependently decreased protein and mRNA levels of TNFα and IL-2. Inhibition of TNFα and IL-2 production involves an MCA-mediated decrease in NFAT mRNA level, rather than inhibition of nuclear translocation. This mechanism was independent of NFAT transcription inducer p38 MAPK; it can be attributed to the promotion of NFAT mRNA decay. CONCLUSION: Overall, MCA might be an alternative or adjuvant to existing NFAT-targeting immunosuppressants for clinical prophylaxis or therapy in the context of inflammation-induced depressive disorder or other T-cell-associated inflammatory disorders.

Lutein and zeaxanthin reduce A2E and iso-A2E levels and improve visual performance in Abca4-/-/Bco2-/- double knockout mice.

Accumulation of bisretinoids such as A2E and its isomer iso-A2E is thought to mediate blue light-induced oxidative damage associated with age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1). We hypothesize that increasing dietary intake of the macular carotenoids lutein and zeaxanthin in individuals at risk of AMD and STGD1 can inhibit the formation of bisretinoids A2E and iso-A2E, which can potentially ameliorate macular degenerative diseases. To study the beneficial effect of macular carotenoids in a retinal degenerative diseases model, we used ATP-binding cassette, sub-family A member 4 (Abca4-/-)/ß,ß-carotene-9',10'-oxygenase 2 (Bco2-/-) double knockout (KO) mice that accumulate elevated levels of A2E and iso-A2E in the retinal pigment epithelium (RPE) and macular carotenoids in the retina. Abca4-/-/Bco2-/- and Abca4-/- mice were fed a lutein-supplemented chow, zeaxanthin-supplemented chow or placebo chow (~2.6 mg of carotenoid/mouse/day) for three months. Visual function and electroretinography (ERG) were measured after one month and three months of carotenoid supplementation. The lutein and zeaxanthin supplemented Abca4-/-/Bco2-/- mice had significantly lower levels of RPE/choroid A2E and iso-A2E compared to control mice fed with placebo chow and improved visual performance. Carotenoid supplementation in Abca4-/- mice minimally raised retinal carotenoid levels and did not show much difference in bisretinoid levels or visual function compared to the control diet group. There was a statistically significant inverse correlation between carotenoid levels in the retina and A2E and iso-A2E levels in the RPE/choroid. Supplementation with retinal carotenoids, especially zeaxanthin, effectively inhibits bisretinoid formation in a mouse model of STGD1 genetically enhanced to accumulate carotenoids in the retina. These results provide further impetus to pursue oral carotenoids as therapeutic interventions for STGD1 and AMD.

Acupuncture and herbal medicine for female infertility: an overview of systematic reviews.

BACKGROUND: Acupuncture and herbal medicine have been used as additional treatments for infertility or as an adjuvant treatment of assisted reproductive technology (ART) in infertility. Many systematic reviews (SRs) and meta-analyses (MA) have been published. This paper reviews the SRs and MA of acupuncture and herbal medicine on infertility to provide evidence for clinical decision making. METHODS: A comprehensive literature search of SRs and MA for the effects of acupuncture and herbal medicine on infertility was conducted using nine databases. Two independent reviewers extracted the data of the selected SR and MA and evaluated their methodological quality using the 'Assessment of multiple systematic reviews 2 (AMSTAR2)'. RESULTS: Twenty-one studies were included in this analysis. Eight studies were published in China, and three studies each were published in the USA, UK, and Australia. Conflicting evidence on the efficacy of acupuncture for infertile women has been reported. Herbal medicine for infertile women undergoing ART, women with anovulation, and women with polycystic ovary syndrome helped improve the clinical pregnancy rate. The methodological quality of SRs and MAs evaluated by AMSTAR 2 was low or very low because the protocol or list of excluded studies were omitted. CONCLUSION: Herbal medicine tended to be effective in infertility, but acupuncture had low evidence of an effect on infertility. The methodological quality of the published SRs and MAs was underestimated because AMSTAR2 is a more rigorous assessment tool than the previous version.

Dibenzocyclooctadiene Lignans in Plant Parts and Fermented Beverages of Schisandra chinensis.

The fruit of Schisandra chinensis, Omija, is a well-known traditional medicine used as an anti-tussive and anti-diarrhea agent, with various biological activities derived from the dibenzocyclooctadiene-type lignans. A high-pressure liquid chromatography-diode array detector (HPLC-DAD) method was used to determine seven lignans (schisandrol A and B, tigloylgomisin H, angeloylgomisin H, schisandrin A, B, and C) in the different plant parts and beverages of the fruit of S. chinensis grown in Korea. The contents of these lignans in the plant parts descended in the following order: seeds, flowers, leaves, pulp, and stems. The total lignan content in Omija beverages fermented with white sugar for 12 months increased by 2.6-fold. Omija was fermented for 12 months with white sugar, brown sugar, and oligosaccharide/white sugar (1:1, w/w). The total lignan content in Omija fermented with oligosaccharide/white sugar was approximately 1.2- and 1.7-fold higher than those fermented with white sugar and brown sugar, respectively. A drink prepared by immersion of the fruit in alcohol had a higher total lignan content than these fermented beverages. This is the first report documenting the quantitative changes in dibenzocyclooctadiene-type lignans over a fermentation period and the effects of the fermentable sugars on this eco-friendly fermentation process.

Initial experience of preoperative short-course radiotherapy followed by oxaliplatin-based consolidation chemotherapy for locally advanced rectal cancer.

PURPOSE: We analyzed the safety and feasibility of preoperative short-course radiotherapy (SCRT) followed by consolidation chemotherapy for patients with locally advanced rectal cancer (LARC). METHODS: From April 2018 to May 2019, 19 patients with LARC were treated with SCRT followed by three cycles of consolidation chemotherapy with leucovorin, fluorouracil, and oxaliplatin (FOLFOX6) before surgery. Adjuvant chemotherapy relied on oxaliplatin. Tumor response, patient compliance, and toxicities were analyzed. RESULTS: The median age was 60 years (range 44-71), and 16 of the patients were male. The median tumor height was 5 cm (range 0-9) from anal verge. All patients received a total dose of 25 Gy in five fractions. The number of cycles of FOLFOX6 before surgery was three in 17, four in one, five in one. Five patients required dose reductions in consolidation chemotherapy. The median interval between initiation of SCRT and surgery was 10.6 weeks (range 8.6-16.4). A pathologic complete response was seen in two patients (11%). Grade III toxicities to the preoperative treatment were seen in five patients (26%): diarrhea in two, a decreased white blood cell count in one, and anemia in two. Postoperative complications arising within 30 days developed in five patients (26%). During the median follow-up period of 20.4 months, there was no tumor recurrence. CONCLUSION: Preoperative SCRT followed by oxaliplatin-based consolidation chemotherapy showed acceptable toxicity and feasibility in patients with LARC. Prospective randomized trials are warranted to verify the efficacy and safety of this treatment strategy compared with conventional long-course concurrent chemoradiotherapy.