Thetis cells induce food-specific Treg cell differentiation and oral tolerance.

The intestinal immune system must establish tolerance to food antigens to prevent onset of allergic and inflammatory diseases. Peripherally generated regulatory T (pTreg) cells play an essential role in suppressing inflammatory responses to allergens; however, the antigen-presenting cell (APC) that instructs food-specific pTreg cells is not known. Here, we show that antigen presentation and TGF-ß activation by a subset of RORγt + antigen-presenting cells (APC), Thetis cells IV (TC IV), is required for food-induced pTreg cell differentiation and oral tolerance. By contrast, antigen presentation by dendritic cells (DCs) was dispensable for pTreg induction but required for T H 1 effector responses, highlighting a division of labor between tolerogenic TCs and pro-inflammatory DCs. While antigen presentation by TCs was required for food-specific pTreg generation both in early life and adulthood, the increased abundance of TCs in the peri-weaning period was associated with a window of opportunity for enhanced pTreg differentiation. These findings establish a critical role for TCs in oral tolerance and suggest that these cells may represent a key therapeutic target for the treatment of food-associated allergic and inflammatory diseases.

CDDO, an Anti-Inflammatory and Antioxidant Compound, Attenuates Vasospasm and Neuronal Cell Apoptosis in Rats Subjected to Experimental Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a type of stroke caused by bleeding into the subarachnoid space. SAH is a medical emergency and requires prompt treatment to prevent complications such as seizures, stroke, or other brain damage. Treatment options may include surgery, medication, or a combination of both. 2-Cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), a compound with anti-inflammatory and antioxidant properties, is currently being investigated as a potential treatment for various diseases, including chronic kidney disease and pulmonary arterial hypertension. In this study, the effects of CDDO on rats subjected to SAH were evaluated. Male Sprague-Dawley rats were divided into four groups (n = 6/group): (1) control group, (2) SAH group, (3) SAH + low-dose CDDO (10 mg/kg injected into the subarachnoid space at 24 h after SAH) group, and (4) SAH + high-dose CDDO (20 mg/kg) group. CDDO improved SAH-induced poor neurological outcomes and reduced vasospasm in the basal artery following SAH. It also decreased the SAH-induced expression of proinflammatory cytokines such as TNF-α, IL-1ß, and IL-6 in both the cerebrospinal fluid and serum samples as determined by ELISA. A Western blot analysis confirmed an increase in the p-NF-κB protein level after SAH, but it was significantly decreased with CDDO intervention. Immunofluorescence staining highlighted the proliferation of microglia and astrocytes as well as apoptosis of the neuronal cells after SAH, and treatment with CDDO markedly reduced the proliferation of these glial cells and apoptosis of the neuronal cells. The early administration of CDDO after SAH may effectively mitigate neuronal apoptosis and vasospasm by suppressing inflammation.

Application of whole exome sequencing in the diagnosis of muscular disorders: a study of Taiwanese pediatric patients.

Background: Muscular dystrophies and congenital myopathies encompass various inherited muscular disorders that present diagnostic challenges due to clinical complexity and genetic heterogeneity. Methods: This study aimed to investigate the use of whole exome sequencing (WES) in diagnosing muscular disorders in pediatric patients in Taiwan. Out of 161 pediatric patients suspected to have genetic/inherited myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. The remaining 46 patients were divided into three groups: Group 1 (multiplex ligation-dependent probe amplification-negative Duchenne muscular dystrophy) with three patients (6.5%), Group 2 (various forms of muscular dystrophies) with 21 patients (45.7%), and Group 3 (congenital myopathies) with 22 patients (47.8%). Results: WES analysis of these groups found pathogenic variants in 100.0% (3/3), 57.1% (12/21), and 68.2% (15/22) of patients in Groups 1 to 3, respectively. WES had a diagnostic yield of 65.2% (30 patients out of 46), detecting 30 pathogenic or potentially pathogenic variants across 28 genes. Conclusion: WES enables the diagnosis of rare diseases with symptoms and characteristics similar to congenital myopathies and muscular dystrophies, such as muscle weakness. Consequently, this approach facilitates targeted therapy implementation and appropriate genetic counseling.

Potato protein hydrolysate inhibits RANKL-induced osteoclast development by inhibiting osteoclastogenic genes via the NF-κB/MAPKs signaling pathways.

In recent times, there has been growing attention towards exploring the nutritional and functional aspects of potato protein, along with its diverse applications. In the present study, we examined the anti-osteoclast properties of potato protein hydrolysate (PP902) in vitro. Murine macrophages (RAW264.7) were differentiated into osteoclasts by receptor activator of nuclear factor-κB ligand (RANKL), and PP902 was examined for its inhibitory effect. Initially, treatment with PP902 was found to significantly prevent RANKL-induced morphological changes in macrophage cells, as determined by tartrate-resistant acid phosphatase (TRAP) staining analysis. This notion was further supported by F-actin analysis using a confocal microscope. Furthermore, PP902 treatment effectively and dose-dependently down-regulated the expression of RANKL-induced osteoclastogenic marker genes, including TRAP, CTR, RANK, NFATc1, OC-STAMP, and c-Fos. These inhibitory effects were associated with suppressing NF-κB transcriptional activation and subsequent reduced nuclear translocation. The decrease in NF-κB activity resulted from reduced activation of its upstream kinases, including I-κBα and IKKα. Moreover, PP902 significantly inhibited RANKL-induced p38MAPK and ERK1/2 activities. Nevertheless, PP902 treatment prevents RANKL-induced intracellular reactive oxygen species generation via increased HO-1 activity. The combined antioxidant and anti-inflammatory effects of PP902 resulted in significant suppression of osteoclastogenesis, suggesting its potential as an adjuvant therapy for osteoclast-related diseases.

Fusion of memristor and digital compute-in-memory processing for energy-efficient edge computing.

Artificial intelligence (AI) edge devices prefer employing high-capacity nonvolatile compute-in-memory (CIM) to achieve high energy efficiency and rapid wakeup-to-response with sufficient accuracy. Most previous works are based on either memristor-based CIMs, which suffer from accuracy loss and do not support training as a result of limited endurance, or digital static random-access memory (SRAM)-based CIMs, which suffer from large area requirements and volatile storage. We report an AI edge processor that uses a memristor-SRAM CIM-fusion scheme to simultaneously exploit the high accuracy of the digital SRAM CIM and the high energy-efficiency and storage density of the resistive random-access memory memristor CIM. This also enables adaptive local training to accommodate personalized characterization and user environment. The fusion processor achieved high CIM capacity, short wakeup-to-response latency (392 microseconds), high peak energy efficiency (77.64 teraoperations per second per watt), and robust accuracy (<0.5% accuracy loss). This work demonstrates that memristor technology has moved beyond in-lab development stages and now has manufacturability for AI edge processors.

Exploring the challenges of taiwanese nurses in the COVID-19 post-pandemic era.

In the wake of the COVID-19 pandemic, the fluctuating nurse resignation rates highlighted an understudied area in healthcare: post-pandemic challenges in clinical settings. This study, conducted from May to November 2023, employed a qualitative inquiry using focus groups to delve into these challenges. Six focus group sessions, involving 33 nurse participants recruited through snowball sampling from various hospital settings were conducted to explore their clinical experiences during and after the pandemic. Thematic analysis revealed two primary themes: the 'Invisibility of Nurses' within the healthcare system and the 'Moral Duty of Nursing Practice'. These findings illuminate a tension between the overlooked role of nurses and their ethical obligations, underscoring a critical need for policy reassessment. The study advocates for systemic changes, particularly in the undervaluation of the nursing profession and the National Health Insurance system, to address the poor working environment and mitigate long-term nursing shortages. This research deepens understanding of post-pandemic nursing workforce challenges in Taiwan, highlighting the need for policy evolution to enhance recognition and support for the nursing industry. It is suggested to provide tangible compensation to acknowledge nurses' daily care and health education for patients. A healthier working environment can be enhanced by collaborative efforts between healthcare institutions and nurses.

Illuminating the Genetic Basis of Congenital Heart Disease in Patients with Kabuki Syndrome.

Congenital heart defects (CHDs) affect a substantial proportion of patients with Kabuki syndrome. However, the prevalence and type of CHD and the genotype-phenotype correlations in Asian populations are not fully elucidated. This study performed a retrospective analysis of 23 Taiwanese patients with molecularly confirmed Kabuki syndrome. Twenty-two patients presented with pathogenic variants in the KMT2D gene. Comprehensive clinical assessments were performed. A literature review was conducted to summarize the spectrum of CHDs in patients with Kabuki syndrome. In total, 16 (73.9%) of 22 patients with pathogenic KMT2D variants had CHDs. The most common types of CHD were atrial septal defects (37.5%), ventricular septal defects (18.8%), coarctation of the aorta (18.8%), bicuspid aortic valve (12.5%), persistent left superior vena cava (12.5%), mitral valve prolapse (12.5%), mitral regurgitation (12.5%), and patent ductus arteriosus (12.5%). Other cardiac abnormalities were less common. Further, there were no clear genotype-phenotype correlations found. A literature review revealed similar patterns of CHDs, with a predominance of left-sided obstructive lesions and septal defects. In conclusion, the most common types of CHDs in Taiwanese patients with Kabuki syndrome who presented with KMT2D mutations are left-sided obstructive lesions and septal defects.

Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks.

The interaction of the tumor necrosis factor receptor (TNFR) family member CD27 on naive CD8+ T (Tn) cells with homotrimeric CD70 on antigen-presenting cells (APCs) is necessary for T cell memory fate determination. Here, we examined CD27 signaling during Tn cell activation and differentiation. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis. Internalized CD27 recruited the signaling adaptor TRAF2 and the phosphatase SHP-1, thereby modulating TCR and CD28 signals. CD27-mediated modulation of TCR signals promoted transcription factor circuits that induced memory rather than effector associated gene programs, which are induced by CD28 costimulation. CD27-costimulated chimeric antigen receptor (CAR)-engineered T cells exhibited improved tumor control compared with CD28-costimulated CAR-T cells. Thus, CD27 signaling during Tn cell activation promotes memory properties with relevance to T cell immunotherapy.

22q11.2 Deletion Syndrome in Taiwan: Clinical Presentation and Immune System Status of Patients.

Background: 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome exhibiting significant clinical phenotype variability. This study aimed to investigate the clinical features, immune profiles, and cognitive abilities of 22q11.2DS patients receiving treatment at MacKay Memorial Hospital in Taipei, Taiwan. Methods: This is a cross-sectional analysis between January 2001 and December 2022. We recruited 27 patients with 22q11.2DS using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). Our evaluation included patient history, physical examination, laboratory analysis, and cardiac and cognitive assessment. Results: We included 27 patients with 22q11.2DS, 7 (25.9%) of whom were female. The median age of the patients was 17.9 yr. Ninety-three percent of the patients exhibited the characteristic facial features associated with the syndrome. A family history of 22q11.2DS was found in 11.1% of the patients. Furthermore, 74.1% of the patients had a congenital heart defect, the most common of which was tetralogy of Fallot (40.7%). Hypocalcemia was observed in 40.7% of the patients. A low T-cell count was observed in 66.7% of the patients, whereas 18.5% had low immunoglobulin levels. Cognitive assessments revealed that four out of six evaluated patients (66.7%) had an intellectual disability, as evidenced by intellectual quotient scores less than 70. The remaining two patients (33.3%) had a borderline intellectual function. Conclusion: Tetralogy of Fallot, hypocalcemia, immunologic defects, and cognitive impairment were common among our patients. To address the potential multisystem involvement, we recommend that all affected individuals undergo a comprehensive evaluation by a multidisciplinary care team.

Thiamet G as a Potential Treatment for Polycystic Kidney Disease.

BACKGROUND/AIM: Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent genetic disorder primarily caused by mutations in Pkd1 (PC1), which account for the majority of ADPKD cases. These mutations contribute to the formation of cysts in the kidneys and other organs, ultimately leading to renal failure. Unfortunately, there are currently no available preventive treatments for this disease. MATERIALS AND METHODS: In this study, we utilized Pkd1-knockdown mice and cells to investigate the potential involvement of O-GlcNAcylation in the progression of PKD. Additionally, we examined the effects of thiamet G, an inhibitor of O-GlcNAcase (OGA), on PKD mice. RESULTS: Our findings indicate that both O-GlcNAcylation and OGT (O-GlcNAc transferase) were downregulated in the renal tissues of Pkd1-silenced mice. Furthermore, O-GlcNAcylation was shown to regulate the stability and function of the C-terminal cytoplasmic tail (CTT) of PC1. Treatment of PKD mice with thiamet G resulted in a reduction of renal cytogenesis in these animals. CONCLUSION: These results highlight the unique role of O-GlcNAcylation in the development of cyst formation in PKD and propose it as a potential therapeutic target for the treatment of PKD.

Nor-24-homoscalaranes, Neutrophilic Inflammatory Mediators from the Marine Sponge Lendenfeldia sp.

The marine sponge Lendenfeldia sp., collected from the Southern waters of Taiwan, was subjected to chemical composition screening, resulting in the isolation of four new 24-homoscalarane compounds, namely lendenfeldaranes R-U (1-4). The structures and relative stereochemistry of the new metabolites 1-4 were assigned based on NMR studies. The absolute configurations of compounds 1-4 were determined by comparing the calculated and experimental values of specific optical rotation. The antioxidant and anti-inflammatory activities of the isolated compounds were assayed using superoxide anion generation and elastase release assays. These assays are used to determine neutrophilic inflammatory responses of respiratory burst and degranulation. Compounds 2 and 4 inhibited superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB) with IC50: 3.98-4.46 µM. Compounds 2 and 4 inhibited fMLP/CB-induced elastase release, with IC50 values ranging from 4.73 to 5.24 µM. These findings suggested that these new 24-homoscalarane compounds possess unique structures and potential anti-inflammatory activity.

Unlocking the Potential of Octocoral-Derived Secondary Metabolites against Neutrophilic Inflammatory Response.

Inflammation is a critical defense mechanism that is utilized by the body to protect itself against pathogens and other noxious invaders. However, if the inflammatory response becomes exaggerated or uncontrollable, its original protective role is not only demolished but it also becomes detrimental to the affected tissues or even to the entire body. Thus, regulating the inflammatory process is crucial to ensure that it is resolved promptly to prevent any subsequent damage. The role of neutrophils in inflammation has been highlighted in recent decades by a plethora of studies focusing on neutrophilic inflammatory diseases as well as the mechanisms to regulate the activity of neutrophils during the overwhelmed inflammatory process. As natural products have demonstrated promising effects in a wide range of pharmacological activities, they have been investigated for the discovery of new anti-inflammatory therapeutics to overcome the drawbacks of current synthetic agents. Octocorals have attracted scientists as a plentiful source of novel and intriguing marine scaffolds that exhibit many pharmacological activities, including anti-inflammatory effects. In this review, we aim to provide a summary of the neutrophilic anti-inflammatory properties of these marine organisms that were demonstrated in 46 studies from 1995 to the present (April 2023). We hope the present work offers a comprehensive overview of the anti-inflammatory potential of octocorals and encourages researchers to identify promising leads among numerous compounds isolated from octocorals over the past few decades to be further developed into anti-inflammatory therapeutic agents.

Principle active metabolites of Pinus morrisonicola Hayata synergistically inhibit cell proliferation and autophagy to elevate apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC), a common primary tumor of liver is a leading cause of cancer-associated deaths. Improving cellular apoptosis and enhancing autophagic clearance is been considered to improve treatment outcomes of HCC. Polyphenols from Pinus morrisonicola (Hayata) have shown various physiological and therapeutic benefits and the flavonoid chrysin is been known for their anticancer effects. However, the main bioactive principle and the mechanism underlying the antitumor activity of pine needle extract are not clear yet. In this study, the effects of ethanol extract from pine needle on HCC cells were determined. The results show that when compared with administration of chrysin alone, a fraction containing pinocembrin, chrysin, and tiliroside significantly reduced autophagy and increased apoptosis. The results also correlated with decrease in cell cycle regulators and the autophagic proteins like LC3-II. Collectively, the results imply the fraction containing pinocembrin, chrysin, and tiliroside as an ideal complementary medicine for an effective antitumor activity.

A prolonged stress rat model recapitulates some PTSD-like changes in sleep and neuronal connectivity.

Chronic post-traumatic stress disorder (PTSD) exhibits psychological abnormalities during fear memory processing in rodent models. To simulate long-term impaired fear extinction in PTSD patients, we constructed a seven-day model with multiple prolonged stress (MPS) by modifying manipulation repetitions, intensity, and unpredictability of stressors. Behavioral and neural changes following MPS conveyed longitudinal PTSD-like effects in rats for 6 weeks. Extended fear memory was estimated through fear retrieval induced-freezing behavior and increased long-term serum corticosterone concentrations after MPS manipulation. Additionally, memory retrieval and behavioral anxiety tasks continued enhancing theta oscillation activity in the prefrontal cortex-basal lateral amygdala-ventral hippocampus pathway for an extended period. Moreover, MPS and remote fear retrieval stimuli disrupted sleep-wake activities to consolidate fear memory. Our prolonged fear memory, neuronal connectivity, anxiety, and sleep alteration results demonstrated integrated chronic PTSD symptoms in an MPS-induced rodent model.

Quercus coccinea Münchh leaves polyphenols: Appraisal acute lung injury induced by lipopolysaccharide in mice.

Genus Quercus is a well-known source for its polyphenolic content and important biological activity. Plants belonging to the Quercus genus were traditionally used in asthma, inflammatory diseases, wound healing, acute diarrhea, and hemorrhoid. Our work intended to study the polyphenolic profile of the Q. coccinea (QC) leaves and to assess the protective activity of its 80% aqueous methanol extract (AME) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Together, the potential molecular mechanism was investigated. Nineteen polyphenolic compounds (1-18), including tannins, flavone, and flavonol glycosides. Phenolic acids and aglycones were purified and identified from the AME of QC leaves. Treatment with AME of QC showed an anti-inflammatory effect evidenced by a remarkable decline in the count of white blood cells and neutrophils which was in harmony with decreasing the levels of high mobility group box-1, nuclear factor kappa B, tumor necrosis factor-α, and interleukin 1 beta. In addition, the antioxidant activity of QC was documented through the significant reduction in malondialdehyde level and elevation of reduced glutathione level and superoxide dismutase activity. Furthermore, the mechanism involved in the pulmonary protective effect of QC involved the downregulation of the TLR4/MyD88 pathway. The AME of QC showed a protective effect against LPS-induced ALI through the powerful anti-inflammatory and antioxidant activities which are linked to its abundancy with polyphenols.

Clinical Spectrum and Trajectory of Innovative Therapeutic Interventions for Insomnia: A Perspective.

Increasing incidences of insomnia in adults, as well as the aging population, have been reported for their negative impact on the quality of life. Insomnia episodes may be associated with neurocognitive, musculoskeletal, cardiovascular, gastrointestinal, renal, hepatic, and metabolic disorders. Epidemiological evidence also revealed the association of insomnia with oncologic and asthmatic complications, which has been indicated as bidirectional. Two therapeutic approaches including cognitive behavioral therapy (CBT) and drugs-based therapies are being practiced for a long time. However, the adverse events associated with drugs limit their wide and long-term application. Further, Traditional Chinese medicine, acupressure, and pulsed magnetic field therapy may also provide therapeutic relief. Notably, the recently introduced cryotherapy has been demonstrated as a potential candidate for insomnia which could reduce pain, by suppressing oxidative stress and inflammation. It seems that the synergistic therapeutic approach of cryotherapy and the above-mentioned approaches might offer promising prospects to further improve efficacy and safety. Considering these facts, this perspective presents a comprehensive summary of recent advances in pathological aetiologies of insomnia including COVID-19, and its therapeutic management with a greater emphasis on cryotherapy.

Chemometric-guided chemical marker selection: A case study of the heat-clearing herb Scrophularia ningpoensis.

The selection of medicinal plants' chemical markers focuses on bioactivity as the primary goal, followed by the nature of secondary metabolites, their stability, and availability. However, herbal medicines are valued for their complex and holistic pharmacological effects. A correct chemical marker can be carefully selected by a systematic clarification of their chemical-biological relationships. In the current study, the multi-informative molecular networking (MIMN) approach was employed to construct the anti-inflammatory metabolomic pattern of a heat-clearing herb, Scrophularia ningpoensis Hemsl. (S. ningpoensis). The MIMN molecular families characterized by cinnamic acid glycosides showed a higher bioactivity score compared with the other two major chemical classes (iridoid glycosides and iridoid-cinnamic acid glycosides). The Global Natural Product Social Molecular Networking (GNPS) and Reaxys database were used to assist in the putative annotation of eighteen metabolites from the bioactive and non-bioactive molecular families. The anti-inflammatory validation step was based on the detection of reactive oxygen species (ROS) generation by activated human neutrophils. All compounds from the bioactive MIMN molecular families dose-dependently inhibited the total ROS generation promoted by fMLF (IC50: 0.04-0.42 µM), while the compounds from non-bioactive MIMN clusters did not show any significant anti-inflammatory effect. The ROS-dependent anti-inflammatory activity of these cinnamic acid glycosides was attributed to their oxygen radical scavenging ability. The most abundant cinnamic acid glycoside, angoroside C (IC50: 0.34 µM) was suggested to be selected as a chemical marker for S. ningpoensis. In this study, the MIMN platform was applied to assist in the chemical marker selection of S. ningpoensis. The correct selection of markers will aid in the compilation and revision of herbal monographs and pharmacopeias resulting in the precise analysis and classification of medicinal plants on a scientific basis.

UHPLC-MS profiles and antidiarrheal activity of Quercus coccinea münchh. and Quercus robur L. employing in vivo technique.

Introduction: Quercus L. genus (Oak) belongs to the family Fagaceae and their galls are used commercially in leather tanning, dyeing, and ink preparation. Several Quercus species were traditionally used to manage wound healing, acute diarrhea, hemorrhoid, and inflammatory diseases. The present study aims to investigate the phenolic content of the 80% aqueous methanol extract (AME) of Q. coccinea and Q. robur leaves as well as to assess their anti-diarrheal activity. Methods: Polyphenolic content of Q. coccinea and Q. robur AME were investigated using UHPLC/MS. The antidiarrheal potential of the obtained extracts was evaluated by conducting a castor oil-induced diarrhea in-vivo model. Result and Discussion: Twenty-five and twenty-six polyphenolic compounds were tentatively identified in Q. coccinea and Q. robur AME, respectively. The identified compounds are related to quercetin, kaempferol, isorhamnetin, and apigenin glycosides and their aglycones. In addition, hydrolyzable tannins, phenolic acid, phenyl propanoides derivatives, and cucurbitacin F were also identified in both species AME of Q. coccinea (250, 500, and 1000 mg/kg) exhibited a significant prolongation in the onset of diarrhea by 17.7 %, 42.6%, and 79.7% respectively while AME of Q. robur at the same doses significantly prolonged the onset of diarrhea by 38.6%, 77.3%, and 2.4 folds respectively as compared to the control. Moreover, the percentage of diarrheal inhibition of Q. coccinea was 23.8%, 28.57%, and 42,86% respectively, and for Q. robur 33.34%, 47.3%, and 57.14% respectively as compared to the control group. Both extracts significantly decreased the volume of intestinal fluid by 27%, 39.78%, and 50.1% for Q. coccinea respectively; and by 38.71%, 51.19%, and 60% for Q. robur respectively as compared to the control group. In addition, AME of Q. coccinea exhibited a peristaltic index of 53.48, 47.18, and 42.28 with significant inhibition of gastrointestinal transit by 18.98%, 28.53%, and 35.95 % respectively; while AME of Q. robur exhibited a peristaltic index of 47.71, 37, and 26.41 with significant inhibition of gastrointestinal transit by 27.72%, 43.89%, and 59.99% respectively as compared with the control group. Notably, Q. robur showed a better antidiarrheal effect in comparison with Q. coccinea and, the highest effect was observed for Q. robur at 1000 mg/kg as it was nonsignificant from the loperamide standard group in all measured parameters.

Essential Oil from Glossogyne tenuifolia Inhibits Lipopolysaccharide-Induced Inflammation-Associated Genes in Macro-Phage Cells via Suppression of NF-κB Signaling Pathway.

Glossogyne tenuifolia Cassini (Hsiang-Ju in Chinese) is a perennial herb native to Taiwan. It was used in traditional Chinese medicine (TCM) as an antipyretic, anti-inflammatory, and hepatoprotective agent. Recent studies have shown that extracts of G. tenuifolia possess various bioactivities, including anti-oxidant, anti-inflammatory, immunomodulation, and anti-cancer properties. However, the pharmacological activities of G. tenuifolia essential oils have not been studied. In this study, we extracted essential oil from air-dried G. tenuifolia plants, then investigated the anti-inflammatory potential of G. tenuifolia essential oil (GTEO) on lipopolysaccharide (LPS)-induced inflammation in murine macrophage cells (RAW 264.7) in vitro. Treatment with GTEO (25, 50, and 100 µg/mL) significantly as well as dose-dependently inhibited LPS-induced pro-inflammatory molecules, such as nitric oxide (NO) and prostaglandin E2 (PGE2) production, without causing cytotoxicity. Q-PCR and immunoblotting analysis revealed that the inhibition of NO and PGE2 was caused by downregulation of their corresponding mediator genes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), respectively. Immunofluorescence and luciferase reporter assays revealed that the inhibition of iNOS and COX-2 genes by GTEO was associated with the suppression of nuclear export and transcriptional activation of the redox-sensitive transcription factor, nuclear factor -κB (NF-κB). In addition, GTEO treatment significantly inhibited phosphorylation and proteosomal degradation of the inhibitor of NF-κB (I-κBα), an endogenous repressor of NF-κB. Moreover, treatment with GTEO significantly blocked the LPS-mediated activation of inhibitory κB kinase α (IKKα), an upstream kinase of the I-κBα. Furthermore, p-cymene, ß-myrcene, ß-cedrene, cis-ß-ocimene, α-pinene, and D-limonene were represented as major components of GTEO. We found that treatment with p-cymene, α-pinene, and D-limonene were significantly inhibiting LPS-induced NO production in RAW 264.7 cells. Taken together, these results strongly suggest that GTEO inhibits inflammation through the downregulation of NF-κB-mediated inflammatory genes and pro-inflammatory molecules in macrophage cells.

Widespread sex ratio polymorphism in Caenorhabditis nematodes.

Although equal sex ratio is ubiquitous and represents an equilibrium in evolutionary theory, biased sex ratios are predicted for certain local conditions. Cases of sex ratio bias have been mostly reported for single species, but little is known about its evolution above the species level. Here, we surveyed progeny sex ratios in 23 species of the nematode genus Caenorhabditis, including 19 for which we tested multiple strains. For the species with multiple strains, five species had female-biased and two had non-biased sex ratios in all strains, respectively. The other 12 species showed polymorphic sex ratios across strains. Female-biased sex ratios could be due to sperm competition whereby X-bearing sperm outcompete nullo-X sperm during fertilization. In this model, when sperm are limited allowing all sperm to be used, sex ratios are expected to be equal. However, in assays limiting mating to a few hours, most strains showed similarly biased sex ratios compared with unlimited mating experiments, except that one C. becei strain showed significantly reduced female bias compared with unlimited mating. Our study shows frequent polymorphism in sex ratios within Caenorhabditis species and that sperm competition alone cannot explain the sex ratio bias.