Anti-Atopic Effect of Scutellaria baicalensis and Raphanus sativus on Atopic Dermatitis-like Lesions in Mice by Experimental Verification and Compound-Target Prediction.

Scutellaria baicalensis Georgi and Raphanus Sativus Linne herbal mixture (SRE) is a Chinese herbal medicine. In this study, we aimed to evaluate the therapeutic efficacy of SRE as an active ingredient for 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) and to predict the underlying therapeutic mechanisms and involved pathways using network pharmacological analysis. Treatment with SRE accelerated the development of AD-like lesions, improving thickness and edema of the epidermis. Moreover, administering the SRE to AD-like mice suppressed immunoglobulin E and interleukin-4 cytokine and reduced T lymphocyte differentiation. In silico, network analysis was used to predict the exact genes, proteins, and pathways responsible for the therapeutic effect of the SRE against DNCB-induced AD. These results indicated that the SRE exerted protective effects on the DNCB-induced AD-like model by attenuating histopathological changes and suppressing the levels of inflammatory mediators. Therefore, the SRE can potentially be a new remedy for improving AD and other inflammatory diseases and predicting the intracellular signaling pathways and target genes involved. This therapeutic effect of the SRE on AD can be used to treat DNCB-induced AD and its associated symptoms.

Gesicles packaging dCas9-VPR ribonucleoprotein complexes can combine with vorinostat and promote HIV proviral transcription.

Despite the success of combination antiretroviral therapy (cART) in HIV treatment, a cure for HIV remains elusive. Scientists postulate that HIV latent reservoirs may be a vital target in curative strategies. Vorinostat is a latency-reversing agent that has demonstrated some effectiveness in reactivating latent HIV, but complementary therapies may be essential to enhance its efficacy. One such approach may utilize the CRISPR-Cas9 system, which has evolved to include transcriptional activators such as dCas9-VPR. In this study, we explored the effects of combining vorinostat coupled with gesicle-mediated delivery of dCas9-VPR in promoting the transcription of integrated HIV proviruses in HIV-NanoLuc CHME-5 microglia and J-Lat 10.6 lymphocytes. We confirmed that dCas9-VPR ribonucleoprotein complexes can be packaged into gesicles and application to cells successfully induced HIV transcription through interactions with the HIV LTR. Vorinostat also induced significant increases in proviral transcription but generated inhibition of cellular proliferation (microglia) or cell viability (lymphocytes) starting at 1,000 nM and higher concentrations. Experiments combining dCas9-VPR gesicles and vorinostat confirmed the enhanced transcriptional activation of the HIV provirus in microglia but not lymphocytes. Thus, a combination of dCas9-VPR gesicles with other latency-reversing agents may provide a complementary method to activate latent HIV in future studies utilizing patient-derived cells or small animal models.

Pollen nutrition structures bee and plant community interactions.

As bees' main source of protein and lipids, pollen is critical for their development, reproduction, and health. Plant species vary considerably in the macronutrient content of their pollen, and research in bee model systems has established that this variation both modulates performance and guides floral choice. Yet, how variation in pollen chemistry shapes interactions between plants and bees in natural communities is an open question, essential for both understanding the nutritional dynamics of plant-pollinator mutualisms and informing their conservation. To fill this gap, we asked how pollen nutrition (relative protein and lipid content) sampled from 109 co-flowering plant species structured visitation patterns observed among 75 subgenera of pollen-collecting bees in the Great Basin/Eastern Sierra region (USA). We found that the degree of similarity in co-flowering plant species' pollen nutrition predicted similarity among their visitor communities, even after accounting for floral morphology and phylogeny. Consideration of pollen nutrition also shed light on the structure of this interaction network: Bee subgenera and plant genera were arranged into distinct, interconnected groups, delineated by differences in pollen macronutrient values, revealing potential nutritional niches. Importantly, variation in pollen nutrition alone (high in protein, high in lipid, or balanced) did not predict the diversity of bee visitors, indicating that plant species offering complementary pollen nutrition may be equally valuable in supporting bee diversity. Nutritional diversity should thus be a key consideration when selecting plants for habitat restoration, and a nutritionally explicit perspective is needed when considering reward systems involved in the community ecology of pollination.

Analysis of the influence of host lifestyle (coffee consumption, drinking, and smoking) on Korean oral microbiome.

If a DNA sample collected in the field is old or degraded, short tandem repeat analysis is difficult to perform, a representative analysis method currently used for individual identification. Given that microorganisms exist everywhere and within the human body, in similar amounts to human cells, microbial analysis could be used to identify individuals even in cases in which human DNA-based identification is difficult. Research has demonstrated that the types of microorganisms within the human body differ depending on various internal or external factors, such as body part or bodily fluid type, lifestyle, geographical area of residence, sex, and age. In this study, we aimed to examine the relationship between lifestyle factors and the composition and diversity of the oral microbiome in individuals living in Korea. We collected 43 saliva samples from Korean individuals and analyzed the oral microbiome and its variations due to external factors, such as coffee consumption, drinking, and smoking. Linear discriminant analysis effect size revealed that Oribacterium, Campylobacter, and Megasphaera were abundant in coffee consumers, whereas Saccharimonadales, Clostridia, and Catonella were abundant in alcohol non-drinkers. We found increased levels of Stomatobaculum in the saliva of smokers, compared with that of non-smokers. Thus, our analysis revealed characteristic microorganisms for each parameter that was evaluated (coffee consumption, smoking, drinking). Consequently, our study provides insight into the oral microbiome in the Korean population and lays the foundation for developing the Korean Forensic Microbiome Database.

Tracing exploitation of egg boons: an experimental study using fatty acids and stable isotopes.

Coordinated spawning of marine animals releases millions of planktonic eggs into the environment, known as egg boons. Eggs are rich in essential fatty acids and may be an important lipid subsidy to egg consumers. Our aim was to validate the application of fatty acid and stable isotope tracers of egg consumption to potential egg consumers and to confirm egg consumption by the selected species. We conducted feeding experiments with ctenophores, crustaceans and fishes. We fed these animals a common diet of Artemia or a commercial feed (Otohime) and simulated egg boons for half of them by intermittently supplementing the common diet with red drum (Sciaenops ocellatus) eggs for 10-94 days. Controls did not receive eggs. Fatty acid profiles of consumers fed eggs were significantly different from those of controls 24 h after the last egg-feeding event. Consumers took on fatty acid characteristics of eggs. In fishes and ctenophores, fatty acid markers of egg consumption did not persist 2-5 days after the last egg-feeding event, but markers of egg consumption persisted in crustaceans for at least 5-10 days. Additionally, consumption of eggs, which had high values of δ15N, led to δ15N enrichment in crustaceans and a fish. We conclude that fatty acids and nitrogen stable isotope can be used as biomarkers of recent egg consumption in marine animals, validating their use for assessing exploitation of egg boons in nature.

Hyperbaric Oxygen Therapy for the Management of Mild and Moderate Traumatic Brain Injury: A Single-Center Experience.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has been shown to be an effective modality in the management of a variety of conditions. However, its role in the treatment of traumatic brain injury (TBI) remains an area of controversy. This study aims to evaluate the safety and outcomes of HBOT in managing the long-term sequelae of TBI. METHODS: The records of TBI patients who underwent increments of 40 sessions of HBOT at 1.5 atmosphere absolute at a single medical center were reviewed. The outcome measures included physical, cognitive (i.e., Trail Making Test, parts A and B; U.S. Department of Veterans Affairs' Evaluation of Cognitive Impairment and Subjective Symptoms tool), and single-photon emission computed tomography findings. The complications and withdrawals were recorded. RESULTS: During the study period, 17 patients underwent HBOT to manage the long-term sequelae of their TBI. Of the 17 patients, 12 (70.6%) completed 120 HBOT sessions and were evaluated 3 months after treatment. All 12 patients had statistically significant improvements in their Trail Making Test, parts A and B, and U.S. Department of Veterans Affairs' Evaluation of Cognitive Impairment and Subjective Symptoms scores (P < 0.05). Additionally, single-photon emission computed tomography depicted increased cerebral blood flow and oxygen metabolism among studied subjects compared with the baseline values. A total of 5 patients withdrew from the study, which was related to new-onset headaches associated with HBOT for 1 patient. CONCLUSIONS: HBOT using 1.5 atmosphere absolute in increments of 40 sessions was found to be a safe and effective modality in the management of the long-term sequelae of TBI. HBOT should be considered in the management of this patient population.

Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy.

Narcolepsy with cataplexy is a sleep disorder caused by deficiency in the hypothalamic neuropeptide hypocretin/orexin (HCRT), unanimously believed to result from autoimmune destruction of hypocretin-producing neurons. HCRT deficiency can also occur in secondary forms of narcolepsy and be only temporary, suggesting it can occur without irreversible neuronal loss. The recent discovery that narcolepsy patients also show loss of hypothalamic (corticotropin-releasing hormone) CRH-producing neurons suggests that other mechanisms than cell-specific autoimmune attack, are involved. Here, we identify the HCRT cell-colocalized neuropeptide QRFP as the best marker of HCRT neurons. We show that if HCRT neurons are ablated in mice, in addition to Hcrt, Qrfp transcript is also lost in the lateral hypothalamus, while in mice where only the Hcrt gene is inactivated Qrfp is unchanged. Similarly, postmortem hypothalamic tissues of narcolepsy patients show preserved QRFP expression, suggesting the neurons are present but fail to actively produce HCRT. We show that the promoter of the HCRT gene of patients exhibits hypermethylation at a methylation-sensitive and evolutionary-conserved PAX5:ETS1 transcription factor-binding site, suggesting the gene is subject to transcriptional silencing. We show also that in addition to HCRT, CRH and Dynorphin (PDYN) gene promoters, exhibit hypermethylation in the hypothalamus of patients. Altogether, we propose that HCRT, PDYN, and CRH are epigenetically silenced by a hypothalamic assault (inflammation) in narcolepsy patients, without concurrent cell death. Since methylation is reversible, our findings open the prospect of reversing or curing narcolepsy.

Traditional Chinese medicine in thyroid-associated orbitopathy.

PURPOSE: Orbital fibroblasts (OF) are considered the central target cells in the pathogenesis of thyroid-associated orbitopathy (TAO), which comprises orbital inflammation, orbital tissue edema, adipogenesis, fibrosis, oxidative stress and autophagy. Certain active ingredients of traditional Chinese medicine (TCM) demonstrated inhibition of TAO-OF in pre-clinical studies and they could be translated into novel therapeutic strategies. METHODS: The pertinent and current literature of pre-clinical studies on TAO investigating the effects of active ingredients of TCM was reviewed using the NCBI PubMed database. RESULTS: Eleven TCM compounds demonstrated inhibition of TAO-OF in-vitro and three of them (polydatin, curcumin, and gypenosides) resulted in improvement in TAO mouse models. Tanshinone IIA reduced inflammation, oxidative stress and adipogenesis. Both resveratrol and its precursor polydatin displayed anti-oxidative and anti-adipogenic properties. Celastrol inhibited inflammation and triptolide prevented TAO-OF activation, while icariin inhibited autophagy and adipogenesis. Astragaloside IV reduced inflammation via suppressing autophagy and inhibited fat accumulation as well as collagen deposition. Curcumin displayed multiple actions, including anti-inflammatory, anti-oxidative, anti-adipogenic, anti-fibrotic and anti-angiogenic effects via multiple signaling pathways. Gypenosides reduced inflammation, oxidative stress, tissue fibrosis, as well as oxidative stress mediated autophagy and apoptosis. Dihydroartemisinin inhibited OF proliferation, inflammation, hyaluronan (HA) production, and fibrosis. Berberine attenuated inflammation, HA production, adipogenesis, and fibrosis. CONCLUSIONS: Clinical trials of different phases with adequate power and sound methodology will be warranted to evaluate the appropriate dosage, safety and efficacy of these compounds in the management of TAO.

Protective Effect of Bojungikki-Tang against Radiation-Induced Intestinal Injury in Mice: Experimental Verification and Compound-Target Prediction.

Bojungikki-tang (BJIT) is a traditional herbal medicine used in Korea, Japan, and China to treat gastrointestinal disorders. In this study, we aimed to investigate whether BJIT has protective effects against radiation-induced intestinal injury and to predict the underlying therapeutic mechanisms and related pathways via network pharmacological analyses. BJIT was injected intraperitoneally (50 mg/kg body weight) to C3H/HeN mice at 36 and 12 h before exposure to partial abdominal irradiation (5 Gy and 13 Gy) to evaluate the apoptotic changes and the histological changes and variations in inflammatory cytokine mRNA levels in the jejunum, respectively. Through in silico network analysis, we predicted the mechanisms underlying BJIT-mediated regulation of radiation-induced intestinal injury. BJIT reduced the level of apoptosis in the jejunal crypts 12 h post 5-Gy irradiation. Histological assessment revealed intestinal morphological changes in irradiated mice 3.5 days post 13-Gy irradiation. Furthermore, BJIT decreased inflammatory cytokine levels following radiation exposure. Apoptosis, TNF, p53, VEGF, toll-like receptor, PPAR, PI3K-Akt, and MAPK signaling pathways, as well as inflammatory bowel disease (IBD), were found to be linked to the radioprotective effects of BJIT against intestinal injury. According to our results, BJIT exerted its potential protective effects by attenuating histopathological changes in jejunal crypts and suppressing inflammatory mediator levels. Therefore, BJIT is a potential therapeutic agent that can treat radiation-induced intestinal injury and its associated symptoms.

OnabotulinumtoxinA discontinuation in patients with prior nerve stimulation.

PURPOSE: The objective of this study is to describe the characteristics of patients who discontinue onabotulinumtoxinA treatment for overactive bladder (OAB) and to determine the impact of prior sacroneuromodulation or peripheral nerve stimulation on the discontinuation rates of onabotulinumtoxinA. MATERIALS AND METHODS: This is a retrospective cohort study of women with at least two onabotulinumtoxinA (BTX-A) treatments for OAB with a Female Pelvic Medicine and Reconstructive surgeon at a referral center between January 2014 and July 2019. Patients were excluded if they underwent BTX-A treatment in the operating room or utilized clean intermittent catheterization at baseline. Women who continued injections throughout the study period were compared to those who did not. Discontinuation was defined as stopping BTX-A during the study period. Treatment failure was defined as a documented failure in the chart and/or moving to other OAB treatments. Loss to follow-up was defined as no follow-up greater than 12 months after the last injection. Discontinuation-free and failure-free survival were estimated by Kaplan-Meier analysis. RESULTS: A total of 214 women met the inclusion criteria with a mean age of 62.9 ± 14 years. Fifty percent were Black. Eighty-six (40.2%) discontinued onabotulinumtoxinA treatment during the study period. There were no demographic differences between patients who discontinued BTX-A and those who continued with the following exceptions: patients who discontinued had higher rates of prior pelvic reconstructive surgery (19.8% vs. 10.2%, p = 0.04) and were more likely to have the concurrent diagnosis of painful bladder syndrome (9.3% vs. 2.3%, p = 0.03). Patients diagnosed with a urinary tract infection (UTI) after ≥50% of treatments were more likely to discontinue (27.9% vs. 14.1%, p = 0.01). On multivariate logistic regression analysis, patients with recurrent UTIs after treatment were significantly more likely to discontinue than those who do not (odds ratio: 2.61, [1.17, 5.82]). Of the cohort, 54 (25%) patients had previously undergone nerve stimulation. A total of 27.8% of patients with prior nerve stimulation discontinued BTX-A compared to 44.4% of those without prior third line treatment (p = 0.03). Patients with prior nerve stimulation had a higher discontinuation-free survival rate (p = 0.013) but there was no difference in failure-free survival. CONCLUSIONS: Patients who have recurrent UTIs after onabotulinumtoxinA injections are 2.6 times more likely to discontinue treatment than those who do not have infections. Patients with prior exposure to nerve stimulation have a significantly lower onabotulinumtoxinA discontinuation rate, but there is no difference in failure rates.

Novel model for chronic intestinal inflammation in chickens: (2) Immunologic mechanism behind the inflammatory response.

Intestinal inflammation in poultry is a complex response that involves immune and intestinal cells which is still not fully understood. Thus, to better understand the mechanisms that drive the chronic intestinal inflammation in fowl we conducted an experiment applying a previously established nutritional model of low-grade chronic intestinal inflammation to evaluate cytokine and chemokine profiles in the chicken intestine. For this, we placed 90 one-day chickens into two treatments: (1) a control group (CNT) fed a corn-soybean diet, and (2) a group fed a diet high in non-starch polysaccharides (NSP). At days 14, 22, 28 and 36 of age, 6 birds from each treatment were euthanized, jejunal and ileal samples were collected for histological examination and cytokine measurements. The cytokines interferon-alpha (IFN-α), IFN-γ, interleukin-16 (IL-16), IL-10, IL-21, IL-6, macrophage-colony stimulating factor (M-CSF), chemokine C-C motif ligand 20 (CCL20), CCL4, CCL5 and vascular endothelial growth factor (VEGF) were quantified in the intestinal tissue. Histologically, both jejunum and ileum of broilers fed NSP diet showed marked infiltration of mononuclear immune cells into the villi. Further, these birds exhibited a significant (P < 0.05) increase in CCL20 concentration in the jejunum at 14d, but a dramatic reduction of M-CSF at 14 and 21d. Later at 28d and 36d, birds fed the NSP diet exhibited increased IL-16 concentration in the jejunum. Since M-CSF is a monocyte stimulatory cytokine and CCL20 a chemokine of T-cells, the reduced M-CSF and increased production of CCL20 may indicate the involvement of the adaptive immune response, specifically driven by T-cells, occurring around the third week of age in the NSP model. Lastly, as a result of the mononuclear cell infiltration and activation of T-cells, IL-16, a pro-inflammatory T-cell cytokine, increased. Therefore, the current work indicates the importance of adaptive immune cells, especially T-cells, in the chronic intestinal inflammation in broiler chicken.

Evaluation of Marker Compounds and Biological Activity of In Vitro Regenerated and Commercial Rehmannia glutinosa (Gaertn.) DC. Roots Subjected to Steam Processing.

Rehmannia glutinosa (Gaertn.) DC., belonging to the family Scrophulariaceae, has been known since immemorial times as a prominent oriental drug in East Asia that can treat various ailments, such as kidney disorders, anemia, and diabetes. In order to be applied for medical purposes, R. glutinosa is commonly processed using steam to increase its efficacy and biological activity. The increasing demand for R. glutinosa in the traditional medicine industry encouraged many researchers to develop a fast, efficient, and high-quality production system using biotechnological approaches. This study aimed to compare the chemical and biological activities of in vitro regenerated R. glutinosa (PKR) and commercial R. glutinosa (PCR) samples subjected to steam processing. We assessed the effects of steam processing and the differences in R. glutinosa material on 5-Hydroxymethyl-2-furaldehyde (5-HMF) content, total flavonoid and phenolic content, antioxidant activity, nitric oxide (NO) levels, and anti-inflammatory activity. PKR samples showed a significantly higher content of 5-HMF (0.15%) as compared to PCR samples (0.05%). Compared to unprocessed R. glutinosa (UPR) and PCR samples, PKR again showed the highest total phenolic and flavonoid content of 41.578 mg GAE/g and 17.208 mg RUE/g, respectively. Meanwhile, both processed R. glutinosa samples (PKR and PCR) showed a significantly higher DPPH antioxidant activity ((67.095 + 1.005)% and (61.579 + 0.907)%, respectively) than unprocessed R. glutinosa ((31.452 + 1.371)%). In addition, both PKR and PCR samples showed good anti-inflammatory activity by showing similar effects such as the inhibition of NO production and the suppression of inducible nitric oxide synthase (iNOS). Based on these results, PKR fulfilled the Chinese pharmacopeia standards, in terms of the amount of the marker compounds and showed a high level of bioactivity. Therefore, these findings are expected to be useful in verifying the efficacy of herbal medicines and the availability of suitable materials for medicinal use.

Management strategies for adult patients with dental anxiety in the dental clinic: a systematic review.

Anxiety is an adaptive emotional response to potentially threatening or dangerous situations; moderated by the sympathetic nervous system. Dental anxiety is common and presents before, during or after dental treatment. The physiological response includes an increase in heart rate, blood pressure, respiratory rate, and cardiac output. Consequently, extensive distress leads to avoidance of dental treatment and multiple failed appointments, impacting both oral and general health. Dental anxiety can generate a variety of negative consequences for both the dentist and the patient. Evidence-based strategies are essential for mitigating and relieving anxiety in the dental clinic. Psychotherapeutic behavioural strategies can modify the patient's experience through a minimally invasive approach with nil or negligible side effects, depending on patient characteristics, anxiety level and clinical situations. These therapies involve muscle relaxation, guided imagery, physiological monitoring, utilizing biofeedback, hypnosis, acupuncture, distraction and desensitization. Pharmacological intervention utilizes either relative analgesia (nitrous oxide), conscious intravenous sedation or oral sedation, which can have undesirable side effects, risks and contraindications. These modalities increase the cost and availability of dental treatment.

MRI-Based Characterization of Intestinal Motility in Children and Young Adults With Newly Diagnosed Ileal Crohn Disease Treated by Biologic Therapy: A Controlled Prospective Study.

BACKGROUND. Changes in intestinal motility in patients with newly diagnosed Crohn disease have historically been evaluated primarily in a subjective manner. OBJECTIVE. The purpose of this study was to assess longitudinal changes in objective intestinal motility scores in children and young adults with newly diagnosed ileal Crohn disease treated with biologic (anti-tumor necrosis factor-α) medical therapy compared with those in control participants. METHODS. This prospective study included 20 children and young adults (eight female and 12 male patients; mean age, 14.6 ± 2.1 [SD] years) with newly diagnosed ileal Crohn disease who were recruited between December 2018 and October 2021 as well as 15 control participants without any known gastrointestinal conditions (eight female and seven male patients; mean age, 18.1 ± 4.4 years). All participants underwent research MRI examinations of the small bowel, including dynamic cine 2D SSFP sequences. Patients with Crohn disease underwent additional research MRI examinations performed at both 6 weeks and 6 months after initiation of biologic therapy. Two operators independently derived terminal ileal intestinal motility scores from the dynamic cine sequences by use of FDA-approved software (with higher scores indicating greater intestinal motility). Intestinal motility scores were compared between patient and control groups by use of t tests, whereas changes in intestinal motility scores after treatment were assessed using linear mixed models. Interoperator absolute agreement was assessed using the intra-class correlation coefficient (ICC). RESULTS. Mean terminal ileal intestinal motility scores were not significantly different between patients with newly diagnosed ileal Crohn disease and control participants (for operator 1, 180.9 ± 63.3 vs 229.7 ± 115.2, respectively [p = .12]; for operator 2, 175.0 ± 62.2 vs 236.4 ± 117.4, respectively [p = .05]). Mean intestinal motility scores changed over time compared with baseline in response to biologic therapy, for operator 1 (180.9 ± 63.3 at baseline, 248.1 ± 104.9 at 6 weeks after treatment initiation, and 249.1 ± 73.2 at 6 months after treatment initiation [p = .04]) and operator 2 (175.0 ± 62.2 at baseline, 247.8 ± 112.7 at 6 weeks after treatment initiation, and 239.6 ± 72.7 at 6 months after treatment initiation [p = .03]). Absolute agreement in intestinal motility scores was excellent between operators (ICC = 0.89). CONCLUSION. MRI measurements of intestinal motility are dynamic in children and adults with newly diagnosed small-bowel Crohn disease, showing early increases in response to biologic therapy. CLINICAL IMPACT. MRI-based intestinal motility scores may aid individualized assessment of disease activity and treatment response in patients with small-bowel Crohn disease.

Hypoglycemic and Hypolipogenic Action of Acetic Acid and Monascus-Fermented Grain Vinegar: A Comparative Study.

Acetic acid has been proposed to improve lifestyle-related diseases, including hyperlipidemia and hyperglycemia. This study compared the hypoglycemic and hypolipogenic effects of acetic acid vinegar (AV, contains only 4% acetic acid) and Monascus-fermented grain vinegar (MV) containing various bioactive compounds in 3T3L1 cells and C57BL/KsJ-db/db mice (DB). The DB were divided randomly into three treatment groups containing nine mice each; DB-, AV-, and MV-groups were orally administered 1 mL/kg/day of distilled water, acetic acid vinegar, and Monascus vinegar, respectively, for 8 weeks. Exposure to AV and MV inhibited the adipogenic differentiation of 3T3L1 preadipocytes and lipid accumulation during differentiation. Oral administration of AV or MV to the mice resulted in a marked reduction in the body weight, liver weight, and hepatic triglyceride content compared to the control DB-group. Moreover, treatment with AV and MV clearly increased the expression of cyclic adenosine monophosphate (cAMP) and AMP-activated protein kinase (AMPK) and suppressed the expression of fatty acid synthetase in liver tissues of DB. Significantly, lower levels of fasting blood glucose, insulin, leptin, and the glycosylated hemoglobin (HbA1c) as well as higher levels of the skeletal muscle GLUT4 expression were obtained in the AV- or MV-groups than levels determined in the control DB-group (P < .05). Although MV has the potential to be a natural alternative treatment for obesity-associated type 2 diabetes, this study suggests that acetic acid is the central ingredient in MV responsible for the hypoglycemic and hypolipogenic effects in the DB mice.

The effect of stocking rate and supplementary selenium on the fatty acid composition and subsequent peroxidisability of poultry muscle tissues.

Selenium (Se) plays a crucial role in protecting biological materials from oxidative damage through the action of the selenoprotein glutathione peroxidase (GSH-Px), and the effectiveness of this protection is often dependent upon Se supply. Recent evidence has indicated that GSH-Px mRNA expression can be upregulated in response to potential oxidative damage risk, and that this upregulation is independent of Se supply. The current study aimed to determine the effect of Se supplementation, stocking rate and tissue fatty acid profile on GSH-Px activity in breast and thigh tissue of commercial broilers. A total of 168 Ross 308 broiler chicks were enrolled onto the study. Prior to enrolment, birds were brooded as a single group and received a starter diet containing no additional Se. The study was a 2 × 2 factorial design comprising of two levels of dietary Se (high Se, 0.5 mg/kg total Se, low Se background Se only), and two stocking rates (high, 30 kg/m2, and low, 15 kg/m2). At 15 days of age, birds were blocked by live weight and randomly allocated to one of the four treatments, with six pen replicates per treatment. At 42 days of age, one bird was randomly selected from each pen replicate, euthanased and breast and thigh tissue harvested. GSH-Px activity, thiobarbituric acid reactive substances (TBARS), and fatty acid (FA) content of these tissues were determined. There was no effect (P > 0.05) of stocking rate on GSH-Px activity or TBARS. GSH-Px activity did not differ between tissue types but was greater in high Se birds (P < 0.001) compared to low Se. TBARS concentrations were greater in thigh tissue (P < 0.001), and these thigh concentrations were greater in high Se birds (P < 0.05). There were marked differences between breast and thigh tissue in most FAs (P < 0.001), with breast generally containing greater proportions of polyunsaturated FA, so that breast tissue had a higher (P < 0.001) peroxidisability index (PI) than thigh. A positive correlation between GSH-Px activity and PI in the thigh tissue of high Se birds (Pearson Correlation 0.668; P = 0.025) may indicate that increasing susceptibility to peroxidisation in lipid-rich tissues may also upregulate GSH-Px activity in Se-replete birds. This study suggests that ensuring adequate dietary selenium could be a useful tool to mitigate adverse effects on meat quality caused by oxidation, particularly in lipid-rich meat.

Running a mentalization-based treatment (MBT) programme within a public community adult mental health service setting: a feasibility study.

OBJECTIVES: This article aimed to address the feasibility of mentalization-based treatment (MBT) for patients with personality disorder in a non-specialist setting. The development and implementation of an MBT Programme is described. METHODS: A multidisciplinary Consult Group met to plan the implementation of the programme. Participants attended a psychoeducation group (MBT Introductory Group), then weekly individual and group therapy. Fourteen participants started the full programme with eight completing at least 9 months, complete data are available for five participants who completed 27 months (first cohort) and 21 months (second cohort). Data include quantitative measures and qualitative questionnaires/interviews. All had a diagnosis of personality dysfunction with co-morbid disorder including anxiety/depressive disorder, post-traumatic stress disorder and eating disorder. RESULTS: Data on five participants revealed reductions in global level of distress, improvements in psychological well-being, less interpersonal difficulties and better work and social functioning. Qualitative data from feedback questionnaires (n = 18) and in-depth interview (n = 2) are discussed under the themes of mentalizing, treatment feedback/outcomes and group factors. Therapist reflections on the process identify the challenges involved in implementing a specialist psychotherapy programme within a general service and learning points from this are discussed. CONCLUSIONS: MBT is an acceptable treatment for patients with personality dysfunction. Prior to the implementation of a programme, factors at the therapist, team and organizational level, as well as the wider context, need to be examined. This is to ensure that conditions are in place for proper adherence to the model to achieve the positive outcomes demonstrated in the RCT studies.

Anti-asthmatic effects of Phlomis umbrosa Turczaninow using ovalbumin induced asthma murine model and network pharmacology analysis.

BACKGROUND: Phlomis umbrosa Turczaninow has been used as a tradition herbal medicine for treating various inflammatory diseases. PURPOSE: In present study, we explored the effects of P. umbrosa on asthma induced by ovalbumin (OVA) and elucidated the mechanism via in vivo verification and network pharmacology prediction. METHODS: The animals were intraperitoneally injected OVA on day 1 and 14, followed by OVA inhalation on days 21, 22, and 23. The animals were daily treated P. umbrosa extract (PUE, 20 and 40 mg/kg) by oral gavage from day 18 to day 23. RESULTS: PUE significantly decreased airway hyperresponsiveness, eosinophilia, and the production of inflammatory cytokines and OVA specific immunoglobulin E in animals with asthma, along with a reduction in airway inflammation and mucus secretion in lung tissue. In network analysis, antiasthmatic effects of PUE were closely related with suppression of mitogen-activated protein kinases and matrix metalloproteinases (MMPs). Consistent with the results from network analysis, PUE suppressed the phosphorylation of ERK and p65, which was accompanied by a decline in MMP-9 expression. CONCLUSION: Administration of PUE effectively reduced allergic responses in asthmatic mice, which was associated with the suppressed phosphorylation of ERK and p65, and expression of MMP-9. These results indicate that PUE has therapeutic potential to treat allergic asthma.

Vitamin C alleviates alcoholic liver injury by suppressing neutrophil infiltration in senescence marker protein 30-knockout mice irrespective of its antioxidant effects.

AIMS: Alcoholic liver disease (ALD) comprises an important component in chronic liver diseases, and its clinical significance has increased due to the high consumption of alcohol worldwide. Vitamin C is a potent antioxidant, and several previous studies have suggested that its therapeutic role in ALD is derived from its antioxidant role. However, its anti-inflammatory role in ALD remains to be elucidated. Especially, the relationship between vitamin C and infiltration of neutrophils in ALD has not been discussed to date. For the reason, the present study investigated the precise role of vitamin C in neutrophil infiltration in ALD. MAIN METHODS: In the present study, wild-type C57BL/6 and vitamin C-deficient senescence marker protein 30-knockout mice were pair-fed with a Lieber-DeCarli control or ethanol diet. Ethanol-fed groups were fed with increasing concentrations of EtOH (Lieber-DeCarli control diet for 5 days, 3% EtOH diet for a week, and 5% diet for 2 weeks) with or without vitamin C supplementation. KEY FINDINGS: Vitamin C dramatically attenuated the ethanol-mediated liver disease in the vitamin C-deficient ethanol-fed mice group by suppressing the infiltration of neutrophils accompanied by less CD68-positive cell infiltration. This attenuating role of vitamin C in neutrophil infiltration in the liver is associated with its protective effect for the ethanol-mediated intestinal damage in vitamin C-deficient ethanol-fed mice. SIGNIFICANCE: This study provides a novel possibility of vitamin C to be used as an anti-inflammatory therapeutic agent associated with neutrophil infiltration in ALD, thereby helping to establish strategies for attenuating ALD.

Impact of short-chain fatty acid supplementation on gut inflammation and microbiota composition in a murine colitis model.

Short-chain fatty acids (SCFAs) play a pivotal role in maintaining intestinal homeostasis. We aimed to investigate the effects of SCFA supplementation on gut inflammation and microbiota composition in a murine colitis model. Mice were fed with sodium butyrate or a mixture of SCFAs in the drinking water for 2 weeks, followed by 2% dextran sulfate sodium (DSS) for 7 d. After euthanasia, mouse colons were extracted to examine histological findings. Flow cytometry of the mouse colon tissues was performed to assess T cell differentiation. Changes in gut microbiota were assessed by high-throughput sequencing of the mouse feces. There were no significant differences in weight change, colonic length, or histologic inflammation score between the DSS, butyrate, and SCFA mix groups. However, flow cytometry revealed that both the expression of CD4+Foxp3+ regulatory T cells and of IL-17-producing T cells were increased in the butyrate and SCFA mix groups. Microbial compositions of the butyrate and SCFA mix groups were significantly different from those of the control and DSS groups in principal coordinate analysis. Relative abundances of the phyla Verrucomicrobia and Proteobacteria, species Akkermansia muciniphila and Escherichia fergusonii were increased in the butyrate and SCFA mix groups. Genera Roseburia and Lactobacillus showed a negative correlation with the degree of colitis, whereas genera Escherichia and Mucispirillum showed a positive correlation. SCFA supplementation did not result in a significant reduction in colon inflammation, but it promoted both regulatory T cell and IL-17-producing T cell expression, and increased both protective and aggressive gut microbiota.