Acupuncture for hot flashes in hormone receptor-positive breast cancer: A pooled analysis of individual patient data from parallel randomized trials.

BACKGROUND: Hot flashes are a common side effect of endocrine therapy (ET) that contribute to poor quality of life and decreased treatment adherence. METHODS: Patients with breast cancer wo were receiving ET and experiencing hot flashes were enrolled through three parallel, randomized trials conducted in the United States, China, and South Korea. Participants were randomized to either immediate acupuncture (IA) or delayed acupuncture control (DAC). IA participants received 20 acupuncture sessions over 10 weeks, whereas DAC participants received usual care, then crossed over to acupuncture with a reduced intensity. The primary end point was a change in score on the endocrine symptom subscale of the Functional Assessment of Cancer Therapy (FACT)-Endocrine Symptoms between baseline and week 10. Secondary end points included the hot flash score and the FACT-Breast score. A planned pooled analysis of individual patient data was performed using longitudinal mixed models. RESULTS: In total, 158 women with stage 0-III breast cancer were randomized (United States, n = 78; China, n = 40; South Korea, n = 40). At week 10, IA participants reported statistically significant improvements in the endocrine symptom subscale score (mean change ± standard error: 5.1 ± 0.9 vs. 0.2 ± 1.0; p = .0003), the hot flash score (-5.3 ± 0.9 vs. -1.4 ± 0.9; p < .003), and the FACT-Breast total score (8.0 ± 1.6 vs. -0.01 ± 1.6; p = .0005) compared with DAC participants. The effect of the acupuncture intervention differed by site (p = .005). CONCLUSIONS: Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer-specific quality of life in women undergoing ET for breast cancer in the United States, China, and South Korea.

The Hepatokine Orosomucoid 2 Mediates Beneficial Metabolic Effects of Bile Acids.

Bile acids (BAs) are pleiotropic regulators of metabolism. Elevated levels of hepatic and circulating BAs improve energy metabolism in peripheral organs, but the precise mechanisms underlying the metabolic benefits and harm still need to be fully understood. In the current study, we identified orosomucoid 2 (ORM2) as a liver-secreted hormone (i.e., hepatokine) induced by BAs and investigated its role in BA-induced metabolic improvements in mouse models of diet-induced obesity. Contrary to our expectation, under a high-fat diet (HFD), our Orm2 knockout (Orm2-KO) exhibited a lean phenotype compared with C57BL/6J control, partly due to the increased energy expenditure. However, when challenged with a HFD supplemented with cholic acid, Orm2-KO eliminated the antiobesity effect of BAs, indicating that ORM2 governs BA-induced metabolic improvements. Moreover, hepatic ORM2 overexpression partially replicated BA effects by enhancing insulin sensitivity. Mechanistically, ORM2 suppressed interferon-γ/STAT1 activities in inguinal white adipose tissue depots, forming the basis for anti-inflammatory effects of BAs and improving glucose homeostasis. In conclusion, our study provides new insights into the molecular mechanisms of BA-induced liver-adipose cross talk through ORM2 induction.

Difference in microbiome compositions of healthy peri-implant sulcus and peri-implantitis sulcus from the same patient.

Objective: The objective of this study is to compare the microbiome of healthy peri-implant sulcus (C) and peri-implantitis sulcus (U) from the same patient and analyze the difference in the microbiome composition. Materials and methods: DNA samples of subgingival biofilms from 10 C (control group) and 10 U (uncontrolled group) sites were sent to Microbiome Center in Korea Research Institute of Biomedical Science and analyzed using 16s rRNA gene amplification and sequencing (MiSeq, Illumina) and human oral microbiome database (HOMD). Results: At the phylum level, Firmicutes and Proteobacteria were more abundant in group C, while Firmicutes and Bacteroidetes were dominant in group U. At the genus level, the core peri-implant microbiome was Streptococcus in group C. On the other hand, the core peri-implant microbiome was Porphyromonas, especially P. gingivalis in group U. Conclusion: In this study, the microbiome composition of peri-implantitis sulcus was different from that of healthy peri-implant sulcus from the same patient. The peri-implantitis microbiome was pathogen-enriched and was similar to the microbiome associated with periodontitis.

Intestinal Immune Cell Populations, Barrier Function, and Microbiomes in Broilers Fed a Diet Supplemented with Chlorella vulgaris.

This study aimed to evaluate the effects of dietary Chlorella vulgaris (CV) on the distribution of immune cells, intestinal morphology, intestinal barrier function, antioxidant markers, and the cecal microbiome in 10-day-old broiler chickens. A total of 120 day-old Ross 308 male broiler chicks were assigned to two dietary treatments using a randomized complete block design, with body weight as the blocking factor. Birds fed a diet containing CV showed an increase in CD4+ T cells (p < 0.05) compared to those fed the control diet. The relative mRNA expression of intestinal epithelial barrier function-related markers (occludin and avian ß-defensin 5) was elevated (p < 0.05) in the CV-supplemented group compared to the control group. The alpha diversity indices (Chao1 and observed features) of the cecal microbiome in 10-day-old birds increased (p < 0.05), indicating higher richness within the cecal bacterial community. In the microbiome analysis, enriched genera abundance of Clostridium ASF356 and Coriobacteriaceae CHKCI002 was observed in birds fed the diet containing CV compared to those fed the control diet. Taken together, dietary CV supplementation might alter intestinal barrier function, immunity, and microbiomes in 10-day-old broiler chickens.

Effects of Drying Methods and Blanching on Nutrient Utilization in Black Soldier Fly Larva Meals Based on In Vitro Assays for Pigs.

The objective was to determine the effects of drying and blanching methods on the nutrient utilization of black soldier fly larva (BSFL; Hermetia illucens) meal by pigs using in vitro assays. Two-step and three-step in vitro assays were employed to simulate the gastrointestinal tract of pigs. Four BSFL meals were prepared using the following pretreatment methods: (1) microwave drying at 80 °C for 32 min, (2) hot-air drying at 60 °C for 17 h, (3) blanching for 5 min in boiling water and hot-air drying at 60 °C for 17 h, and (4) 2% citric acid solution blanching for 5 min in boiling solution and hot-air drying at 60 °C for 17 h. After the drying process, each BSFL was defatted and ground to obtain BSFL meals. The nitrogen (N) concentration in the test ingredients ranged from 8.5 to 9.4%, and the ether extract ranged from 6.9 to 11.5% on an as-is basis. The amino acid (AA) concentration in the BSFL meals ranged from 2.80 to 3.24% for Lys and 0.71 to 0.89% for Met on an as-is basis. Hot-air-dried BSFL meal had a greater in vitro ileal disappearance (IVID) of N compared with microwave-dried BSFL meal (p < 0.05). However, blanched BSFL meals in water or 2% citric acid solution before hot-air drying had a lower (p < 0.05) IVID of N compared with microwave-dried or hot-air-dried BSFL meal. Blanched BSFL meals in water or 2% citric acid solution before hot-air drying showed a lower (p < 0.05) in vitro total tract disappearance of dry matter and organic matter compared with microwave-dried or hot-air-dried BSFL meal. Microwave-dried BSFL meal had a lower (p < 0.05) IVID of indispensable AA, except for His, Lys, Met, and Phe, compared with hot-air-dried BSFL meals. However, blanched BSFL meals in water or 2% citric acid solution before hot-air drying showed a lower (p < 0.05) IVID of indispensable AA compared with microwave-dried or hot-air-dried BSFL meal. In conclusion, hot-air-dried BSFL meal presented greater nutrient utilization compared with microwave-dried BSFL meal for pigs. However, blanching in water or citric acid solution negatively affected the nutrient digestibility of BSFL meal based on in vitro assays.

Integrative medicine in patients with degenerative arthritis of the knee: A pilot randomized control study.

BACKGROUND: We aimed to comparatively analyze the effect of integrative medicine treatments (lifestyle change education, use of anti-inflammatory drugs, acupuncture, manual therapy-type massage) and conventional medical treatments (lifestyle change education and use of anti-inflammatory drugs) on pain control, knee function improvement, and quality of life improvement in patients with degenerative knee arthritis. METHODS: In this study, 30 patients were randomly divided into the control group (n = 15) and the experimental group (n = 15). Both groups were prescribed anti-inflammatory drugs and lifestyle change education for 12 weeks. The experimental group underwent acupuncture including electroacupuncture, moxibustion, and manual therapy-type massage 12 times during the first 6 weeks. Evaluations were performed at 3 visits: visit 1 (before treatment), visit 2 (6 weeks after initial treatment), and visit 3 (12 weeks after initial treatment). The effect of each treatment was measured using Visual Analog Scale (VAS, 0-10), Western Ontario and McMaster Universities index (WOMAC), and SF-36. RESULTS: From visit 1 to visit 2, the mean value of VAS decreased by 0.72 and 3.17 in the control and experimental groups, respectively. From visit 2 to visit 3, the mean VAS value decreased by 0.25 in the control group but increased by 0.87 in the experimental group. Among the sub-area of SF-36, the physical role restriction area and mental health area showed significant differences between the 2 groups over time (P = .024, P = .006). CONCLUSION: Integrative medicine treatment has superior effects in pain control over conventional medical treatment. In integrative medicine treatment, pain control tends to decrease with time, but still superior over conventional medical treatment up to 6 weeks after treatment (12 weeks after initial treatment).

Acupuncture for hot flashes in hormone receptor-positive breast cancer, a coordinated multinational study: Rationale and design of the study protocol.

BACKGROUND: Acupuncture has been reported to reduce hot flashes in patients with breast cancer undergoing adjuvant hormonal therapy. Although hot flashes are common, the prevalence varies among cultures, races, and ethnicities; the efficacy of acupuncture across cultures has not been investigated. METHODS: This is a coordinated multinational study, including three parallel randomized trials with a planned analysis of individual patient data, to test the effectiveness of acupuncture on hot flash-related symptoms in hormone receptor-positive breast cancer patients on adjuvant endocrine therapy. Using a standardized acupuncture protocol (total across all three studies of n = 80) versus usual care (total n = 80), symptoms are assessed using changes in the Endocrine Symptom Subscale of Functional Assessment of Cancer Therapy-Endocrine Symptoms. Secondary outcomes include hot flash severity, quality of life, and sleep quality. Differences in response to acupuncture between participants in the three countries will also be explored. DISCUSSION: Here we describe the design of a protocol for a coordinated multinational study, with attention to the complex considerations in developing a multinational research effort testing a non-pharmacologic intervention. This protocol and approach provide guidance for future efforts to evaluate and test non-pharmacologic interventions across multinational populations. TRIAL REGISTRATION: clinicaltrials.gov (Identifier: NCT00797732, registered on December 21, 2018), Chinese Clinical Trial Registry (ChiCTR2100045888), and The Clinical Research Information Service (CRIS) of Korea (Registration number: KCT0003618).

The Effects of NF-kB Inhibition with p65-TMD-Linked PTD on Inflammatory Responses at Peri-implantitis Sites.

The objective of this study was to find out if suppression of NF-kB complex function by p65-TMD-linked PTD could reduce host inflammation and bone resorption at peri-implantitis sites in rats. Twenty-one male 5-week-old SD rats were divided into three groups: untreated control group (A), silk-induced peri-implantitis group (B), and nt (nucleus transducible)-p65-TMD-treated, silk-induced peri-implantitis group (C). Implant sulcus of a rat in group C were divided into two groups, namely group Cp and Cb. Palatal implant sulcus where nt-p65-TMD solution was applied with an insulin syringe were assigned to group Cp. Buccal implant sulcus without topical nt-p65-TMD application were assigned to group Cb. H&E staining, TRAP staining, and immunohistological staining were done. The crestal bone levels of group A were significantly higher than those of group B at p<0.01. The crestal bone levels of group Cp were significantly higher than those of group Cb at p<0.05. H-E staining showed increased apical migration of junctional epithelium and inflammatory cells in group Cb. TRAP staining revealed more multinucleated osteoclasts in group Cb. As for immunohistological staining, group Cb showed many IL-6-positive cells while group Cp had none. In this study, p65-TMD-linked PTD inhibited NF-kB functions and reduced inflammation and bone resorption at peri-implantitis sites in rats.

Effect of commercially purified deoxynivalenol and zearalenone mycotoxins on microbial diversity of pig cecum contents.

OBJECTIVE: Deoxynivalenol (DON) and zearalenone (ZEN) are mycotoxins that frequently contaminate maize and grain cereals, imposing risks to the health of both humans and animals and leading to economic losses. The gut microbiome has been shown to help combat the effects of such toxins, with certain microorganisms reported to contribute significantly to the detoxification process. METHODS: We examined the cecum contents of three different dietary groups of pigs (control, as well as diets contaminated with 8 mg DON/kg feed or 0.8 mg ZEN/kg feed). Bacterial 16S rRNA gene amplicons were acquired from the cecum contents and evaluated by next-generation sequencing. RESULTS: A total of 2,539,288 sequences were generated with ~500 nucleotide read lengths. Firmicutes, Bacteroidetes, and Proteobacteria were the dominant phyla, occupying more than 96% of all three groups. Lactobacillus, Bacteroides, Megasphaera, and Campylobacter showed potential as biomarkers for each group. Particularly, Lactobacillus and Bacteroides were more abundant in the DON and ZEN groups than in the control. Additionally, 52,414 operational taxonomic units were detected in the three groups; those of Bacteroides, Lactobacillus, Campylobacter, and Prevotella were most dominant and significantly varied between groups. Hence, contamination of feed by DON and ZEN affected the cecum microbiota, while Lactobacillus and Bacteroides were highly abundant and positively influenced the host physiology. CONCLUSION: Lactobacillus and Bacteroides play key roles in the process of detoxification and improving the immune response. We, therefore, believe that these results may be useful for determining whether disturbances in the intestinal microflora, such as the toxic effects of DON and ZEN, can be treated by modulating the intestinal bacterial flora.

Life-Sustaining Treatment in End-Stage Liver Disease Patients: Patients' Decisions and Results.

Purpose: In 2018, the Act on Decisions on Life-Sustaining Treatment for Patients in Hospice and Palliative Care or at the End of Life was implemented and the scope of official recognition for terminally ill patients was expanded. The purpose of this study was to investigate the decisions made by patients with end-stage liver disease about their life-sustaining treatment in a clinical setting. Methods: The subjects of this study were patients with endstage liver disease hospitalized at a tertiary hospital in Seoul, Korea who wrote physician orders for life-sustaining treatment (POLST). Data collection was done using patients' electronic medical records, and a retrospective analysis of POLST was conducted. Results: Among 101 patients, 18.8% were female and 81.2% were male, and their mean age was 61.8 (±10.61) years. Sixty-three patients (62.4%) wrote their POLST by themselves. Three patients withdrew the POLST, of whom two did so for liver transplantation, and one did so for chemotherapy. Conclusion: This study shows that sufficient consideration of liver transplantation is needed for end-stage liver disease patients before making decisions on life-sustaining treatment. The self-determination of patients must be respected and effective guidelines are urgently needed.

Physiological impact on layer chickens fed corn distiller's dried grains with solubles naturally contaminated with deoxynivalenol.

OBJECTIVE: An experiment was conducted to investigate the response of laying hens fed corn distiller's dried grains with solubles (DDGS) that are naturally contaminated with deoxynivalenol (DON). METHODS: One hundred and sixty 52-week-old Lohmann Brown Lite hens were randomly allotted to five dietary treatments with 8 replicates per treatment. The dietary treatments were formulated to provide a range of corn DDGS contaminated with DON from 0% to 20% (i.e., 5% scale of increment). All laying hens were subjected to the same management practices in a controlled environment. Body weight, feed intake and egg production were measured biweekly for the entire 8-week experiment. The egg quality was measured biweekly for 8 weeks. On weeks 4 and 8, visceral organ weights, blood metabolites, intestinal morphology, and blood cytokine concentrations were measured. RESULTS: The inclusion of corn DDGS contaminated with DON in the diet did not alter (p> 0.05) the body weight, feed intake, hen-day egg production, egg mass and feed efficiency of the laying hens. No difference was found (p>0.05) in the egg quality of hens that were fed the dietary treatments. Furthermore, hens that were fed a diet containing corn DDGS contaminated with DON showed no change (p>0.05) in the visceral organ weights, the blood metabolites, and the cytokine concentrations. The crypt depth increased (p<0.05) as the amount of corn DDGS contaminated with DON increased. Proportionately, the villus height to crypt depth ratio of the laying hens decreased (p<0.05) with the increasing level of corn DDGS contaminated with DON in the diet. CONCLUSION: The inclusion of corn DDGS contaminated with DON up to 20% in layer diets did not cause changes in egg production performance and egg quality, which indicates that DON is less toxic at the concentration of 1.00 mg DON/kg.

Analysis of characteristics affecting instrumental activities of daily living in Parkinson's disease patients without dementia.

Patients with Parkinson's disease (PD) are liable to experience impairment in their activities of daily living (ADL), which include ambulating, eating, dressing, bathing, and personal hygiene. The aim of this study is to assess which clinical characteristics contribute significantly to instrumental ADL (IADL) in PD patients without dementia. We included 106 PD patients in our study, and each patient's motor and non-motor status and basic and instrumental ADL were assessed using the appropriate scales. Of the 106 PD patients, 31 (29.2%) had abnormal Korean IADL (K-IADL) scores. These patients were older and had higher scores in terms of the modified Hoehn and Yahr (mHY) staging scale, Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III, UPDRS part IV motor fluctuation, Beck Depression Inventory (BDI), and total Non-Motor Symptoms assessment scale for PD (NMSS), as well as lower scores in the Mini-Mental State Examination (MMSE). Pearson's correlation analysis showed significant associations between the scores of K-IADL and each of the following characteristics of the patients: age, mHY stage, UPDRS parts II and III, UPDRS part IV motor fluctuation, BDI, total NMSS, and MMSE. Multivariate linear regression analysis showed that the significant clinical characteristics associated with the K-IADL scores were determined to be the UPDRS part II, MMSE, and BDI scores. The results of our study revealed that the cognitive, depression, and motor symptoms were the significant predictors of IADL in PD patients without dementia.

Factors associated with freezing of gait in patients with Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) is a common and debilitating problem in patients with Parkinson's disease (PD). The aim of this study was to estimate the prevalence of FOG, and to identify factors that independently contribute to FOG in patients with PD. METHOD: We included 157 PD patients. FOG was assessed using the FOG Questionnaire (FOG-Q). Patients with or without FOG were defined as item 3 in the FOG-Q. RESULTS: One hundred eleven (70.7%) out of 157 PD patients presented with FOG. Patients with FOG were older, had long disease duration, were taking higher doses of dopaminergic agents, and had higher motor and non-motor scores than those without FOG. Multivariate linear regression analysis showed that high modified Hoehn and Yahr (mHY) stage, Unified PD Rating Scale (UPDRS) part II score, and non-motor symptom assessment scale for PD (NMSS) total score were significant predictors of a high FOG-Q score. Patients with FOG had significantly higher scores for cardiovascular, gastrointestinal tract, urinary, and miscellaneous NMSS domains than those without FOG. CONCLUSIONS: FOG in PD was associated with higher mHY stage, UPDRS part II score, and total NMSS score. Therefore, clinicians should consider non-motor, motor features and activities of daily living states for the proper management of FOG.

Colon Microbiome of Pigs Fed Diet Contaminated with Commercial Purified Deoxynivalenol and Zearalenone.

Deoxynivalenol (DON) and zearalenone (ZEN) can seriously affect animal health, with potentially severe economic losses. Previous studies have demonstrated that gut microbiota plays a significant role in detoxification. We analyzed the colon contents from three groups of pigs (fed either a standard diet, or a diet with 8 mg/kg DON or ZEN). Bacterial 16S rRNA gene amplicons were obtained from the colon contents, and sequenced using next-generation sequencing on the MiSeq platform. Overall, 2,444,635 gene sequences were generated, with ≥2000 sequences examined. Firmicutes and Bacteroidetes were the dominant phyla in all three groups. The sequences of Lactobacillus, Megasphaera, and Faecalibacterium genera, and the unclassified Clostridiaceae family, represented more than 1.2% of the total, with significantly different abundances among the groups. Lactobacillus was especially more abundant in the DON (7.6%) and ZEN (2.7%) groups than in the control (0.2%). A total of 48,346 operational taxonomic units (OTUs) were identified in the three groups. Two OTUs, classified as Lactobacillus, were the most dominant in the DON and ZEN groups. The abundances of the remaining OTUs were also significantly different among the groups. Thus, the mycotoxin-contaminated feed significantly affected the colon microbiota, especially Lactobacillus, which was the most abundant. Therefore, we speculate that Lactobacillus plays a major role in detoxification of these mycotoxins.

Regulation of CD4+CD8-CD25+ and CD4+CD8+CD25+ T cells by gut microbiota in chicken.

The gut microbiota in chicken has long been studied, mostly from the perspective of growth performance. However, there are some immunological studies regarding gut homeostasis in chicken. Although CD4+CD25+ T cells are reported to act as regulatory T cells (Tregs) in chicken, there have been no studies showing the relationship between gut microbiota and Tregs. Therefore, we established a model for 'antibiotics (ABX)-treated chickens' through administration of an antibiotic cocktail consisting of ampicillin, gentamycin, neomycin, metronidazole, and vancomycin in water for 7 days. CD4+CD8-CD25+ and CD4+CD8+CD25+ T cells in cecal tonsils were significantly decreased in this model. Gram-positive bacteria, especially Clostridia, was responsible for the changes in CD4+CD8-CD25+ or CD4+CD8+CD25+ T cells in cecal tonsils. Feeding ABX-treated chickens with acetate recovered CD4+CD8-CD25+ and CD4+CD8+CD25+ T cells in cecal tonsils. GPR43, a receptor for acetate, was highly expressed in CD4+CD8-CD25+ T cells. In conclusion, our study demonstrated that the gut microbiota can regulate the population of CD4+CD8-CD25+ and CD4+CD8+CD25+ T cells, and that acetate is responsible for the induction of CD4+CD8-CD25+ T cells in cecal tonsils via GPR43.

Effects of High Levels of Deoxynivalenol and Zearalenone on Growth Performance, and Hematological and Immunological Parameters in Pigs.

Background: Deoxynivalenol (DON) and zearalenone (ZEN) are common food contaminants produced by Fusarium sp. Mycotoxins are a potential health hazard because of their toxicological effects on both humans and farmed animals. Methods: We analyzed three groups of pigs: a control group (fed a standard diet), and the DON and ZEN groups, fed a diet containing 8 mg/kg DON and 0.8 mg/kg ZEN respectively, for four weeks. Results: DON and ZEN exposure decreased body weight (BW), average daily feed intake (ADFI), food conversion rate (FCR), and the serum levels of immunoglobulin (Ig)G and IgM. The total antioxidant levels significantly decreased in serum and increased in urine samples of both treatment groups. Additionally, DON and ZEN exposure increased serotonin levels in urine. Hematological parameters were not affected by the investigated toxins. Microscopic lesions were evident in sections of kidneys from either treatment group: we found sporadic interstitial nephritis in the DON group and renal glomerulus atrophy in the ZEN group. The expression levels of inflammatory cytokines and chemokine marker genes were reduced in tissues from DON- and ZEN-exposed pigs. Conclusions: chronic ingestion of high doses of DON and ZEN alters the immune response and causes organs damage, and might be associated with various diseases in pigs.

Deoxynivalenol- and zearalenone-contaminated feeds alter gene expression profiles in the livers of piglets.

OBJECTIVE: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. METHODS: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. RESULTS: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone H2B type 1, and serum amyloid A). CONCLUSION: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

In vivo evaluation of hot water extract of Acorus gramineus root against benign prostatic hyperplasia.

BACKGROUND: Acorus gramineus has been reported to exhibit various pharmacological effects including inhibition of cholesterol synthesis, enhancement of lipid metabolism, prevention of dementia and inhibition of mast cell growth. According to the Chinese compendium of materia media, it has been reported that Acorus spp. is effective for sedation, dementia prevention as well as diuretic effect. In addition, it showed more than equivalent activity compared to furosoemide, a drug known to be effective in diuretic action in animal model study. However, their effectiveness against benign prostatic hyperplasia (BPH) of Acorus gramineus has not been reported. This study was designed to evaluate the effect of Acorus gramineus root hot water extract (AG) against BPH in vivo. METHODS: Male rats, 10 weeks of age and weighing 405 g ± 10 g, were used for this study. Biomarkers were evaluated including prostate weight, prostate weight ratio, hormonal changes, 5-α reductase type II androgen receptor (AR) of the prostate gland and anti-oxidant activation factors related to BPH. These biomarkers were measured in vivo test. RESULTS: AG showed significant effect at the 250 and 500 mg/kg/day in rats. Groups treated with AG displayed significantly lower levels of prostate gland weight (0.79 g) compared to the BPH induced group (1.19 g). Also, dihydrotestosterone (DHT) level was decreased from 61.8 to 100% and androgen receptor expression level was decreased from 111 to 658%. Any hematological toxicity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level wasn't observed. CONCLUSION: This study indicated that AG was effective for reducing BPH symptoms. TRIAL REGISTRATION: Not applicable.

Impact of pain and pain subtypes on the quality of life of patients with Parkinson's disease.

Pain is a frequent and troublesome non-motor symptom of Parkinson's disease (PD) and has a negative impact on quality of life (QoL). The aim of this study was to investigate the relative impact of pain or a specific pain subtype on the QoL of patients with PD. We included 161 patients with PD. Pain was assessed using the patients' descriptions, a structured interview, and a detailed neurological examination. QoL was assessed using the 39-item Parkinson's Disease Questionnaire (PDQ-39). One hundred and twenty (74.5%) patients with PD had chronic pain. Musculoskeletal pain was the most prevalent type, followed by radicular/neuropathic, dystonic, and central pain. PD patients with pain, regardless of the pain subtype, had a worse PDQ-39 score than those without pain. Multivariate regression analysis after adjusting for disease-related factors and motor characteristics showed that younger PD onset age and the high scores of part II of Unified Parkinson's Disease Rating Scale, Beck Depression Inventory, and Visual Analogue Scale were significant predictors of the poor PDQ-39 score. Pain along with depression, poor activities of daily living, and younger age of PD symptom onset are associated with poor QoL. All subtypes of pain affect QoL of patients with PD. Pain should be considered during the management of patients with PD.

The Ubiquitin-like with PHD and Ring Finger Domains 1 (UHRF1)/DNA Methyltransferase 1 (DNMT1) Axis Is a Primary Regulator of Cell Senescence.

As senescence develops, cells sequentially acquire diverse senescent phenotypes along with simultaneous multistage gene reprogramming. It remains unclear what acts as the key regulator of the collective changes in gene expression at initiation of senescent reprogramming. Here we analyzed time series gene expression profiles obtained in two different senescence models in human diploid fibroblasts: replicative senescence and H2O2-induced senescence. Our results demonstrate that suppression of DNA methyltransferase 1 (DNMT1)-mediated DNA methylation activity was an initial event prior to the display of senescent phenotypes. We identified seven DNMT1-interacting proteins, ubiquitin-like with PHD and ring finger domains 1 (UHRF1), EZH2, CHEK1, SUV39H1, CBX5, PARP1, and HELLS (also known as LSH (lymphoid-specific helicase) 1), as being commonly down-regulated at the same time point as DNMT1 in both senescence models. Knockdown experiments revealed that, among the DNMT1-interacting proteins, only UHRF1 knockdown suppressed DNMT1 transcription. However, UHRF1 overexpression alone did not induce DNMT1 expression, indicating that UHRF1 was essential but not sufficient for DNMT1 transcription. Although UHRF1 knockdown effectively induced senescence, this was significantly attenuated by DNMT1 overexpression, clearly implicating the UHRF1/DNMT1 axis in senescence. Bioinformatics analysis further identified WNT5A as a downstream effector of UHRF1/DNMT1-mediated senescence. Senescence-associated hypomethylation was found at base pairs -1569 to -1363 from the transcription start site of the WNT5A gene in senescent human diploid fibroblasts. As expected, WNT5A overexpression induced senescent phenotypes. Overall, our results indicate that decreased UHRF1 expression is a key initial event in the suppression of DNMT1-mediated DNA methylation and in the consequent induction of senescence via increasing WNT5A expression.