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A micromechanical multi-level elastoplastic evolutionary damage framework is proposed to predict the overall transverse mechanical behavior and damage evolutions of cylindrical fiber-reinforced ductile composites. Progressively cracked fibers are modeled using the double-inclusion theory. The effective elastic moduli of three-phase composites, consisting of a matrix, randomly located yet monotonically aligned cylindrical uncracked fibers and cracked fibers, are derived by using a micromechanical formulation. In order to characterize the homogenized elastoplastic behavior, a micromechanical effective yield criterion is derived based on the ensemble-area averaging process and the first-order effects of eigenstrains. The resulting effective yield criterion, together with the overall associative plastic flow rule and the hardening law, constitutes the analytical framework for the estimation of effective transverse elastoplastic-damage responses of ductile composites containing both uncracked and cracked fibers. An evolutionary fiber cracking process, governed by the internal stresses and the fracture strength of fibers, is incorporated into the proposed work. The Weibull’s probabilistic distribution is employed to describe the varying probability of fiber cracking. Further, systematic numerical simulations are presented to illustrate the potential of the proposed methodology. [ABSTRACT FROM PUBLISHER]

A steel ball with a density higher than that of water can bounce on a water surface when heated to a temperature well above the Leidenfrost point. In this letter, an experiment is conducted where heated steel balls are released onto a water surface. The heated steel ball descends into the liquid, thus causing the liquid to evaporate and form a vapor cushion with an upward force that lifts the steel ball. Subsequently, the steel ball bounces off the water surface, like a solid ball bouncing off an elastic surface without sinking into the water. This phenomenon is known as the inverse Leidenfrost effect. In this letter, we evaluate the various motion behaviors of spheres at different Reynolds numbers and temperatures. Additionally, we analyze the bouncing behavior of solid spheres on a free liquid surface and examine the various force components.

Background: The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides derived from the medicinal fungus Hirsutella sinensis produced anti-inflammatory, anti-diabetic and anti-obesity effects by modulating the gut microbiota and increasing the abundance of the commensal Parabacteroides goldsteinii in mice fed with a high-fat diet., Methods: We examined the effects of the prebiotics, H. sinensis polysaccharides, and probiotic, P. goldsteinii, in a mouse model of imiquimod-induced systemic lupus erythematosus., Results: The fungal polysaccharides and P. goldsteinii reduced markers of lupus severity, including the increase of spleen weight, proteinuria, and serum levels of anti-DNA auto-antibodies and signal transducer and activator of transcription 4 (STAT4). Moreover, the polysaccharides and P. goldsteinii improved markers of kidney and liver functions such as creatinine, blood urea nitrogen, glomerulus damage and fibrosis, and serum liver enzymes. However, the prebiotics and probiotics did not influence gut microbiota composition, colonic histology, or expression of tight junction proteins in colon tissues., Conclusions: Our results indicate that H. sinensis polysaccharides and the probiotic P. goldsteinii can reduce lupus markers in imiquimod-treated mice. These prebiotics and probiotics may therefore be added to other interventions conducive of a healthy lifestyle in order to counter autoimmune diseases., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: CSMed ® wound dressing, a dressing with various herb extracts, was tested for its therapeutic effect in radiation dermatitis of breast and head-and-neck cancer patients., Methods: This study included 20 breast cancer patients and 10 head-and-neck cancer patients. Half of the irradiated area was covered with CSMed ® and the other half was under routine treatment. The severity of radiation dermatitis was evaluated with radiation therapy oncology group (RTOG) grade throughout the treatment and the follow-up period. The RTOG grade between the dressed and undressed area were compared to illustrate the therapeutic effect of CSMed ® dressing., Results: The results showed that CSMed ® dressed area had significant lower RTOG score at 3-7 weeks and final record during the treatment, and 1-3 weeks during follow-up than undressed area., Conclusions: This indicated that CSMed ® can delay the onset, reduce the severity, and enhance healing of radiation dermatitis. CSMed ® can be used for prophylaxis and management of radiation dermatitis., (© 2024. The Author(s).)

Acute respiratory distress syndrome (ARDS) is characterized by acute-onset rapid-deteriorating inflammatory lung injury. Although the preservation of spontaneous breathing may have physiological benefits in oxygenation, increasing evidence shows that vigorous spontaneous breathing may aggravate lung injury (i.e., patient self-inflicted lung injury). Increased lung stress and pendelluft, which is defined as intrapulmonary gas redistribution without a significant change in tidal volume, are important mechanisms of patient self-inflicted lung injury. The presence of pendelluft may be considered a surrogate marker of vigorous inspiratory effort, which can cause the dependent lung to overstretch. In this review, we summarized three major methods for electrical impedance tomography-based pendelluft monitoring. Future studies are warranted to compare and validate the different methods of pendelluft estimation in patients with ARDS.

The intestinal barrier protects the host against gut microbes, food antigens, and toxins present in the gastrointestinal tract. However, gut barrier integrity can be affected by intrinsic and extrinsic factors, including genetic predisposition, the Western diet, antibiotics, alcohol, circadian rhythm disruption, psychological stress, and aging. Chronic disruption of the gut barrier can lead to translocation of microbial components into the body, producing systemic, low-grade inflammation. While the association between gut barrier integrity and inflammation in intestinal diseases is well established, we review here recent studies indicating that the gut barrier and microbiota dysbiosis may contribute to the development of metabolic, autoimmune, and aging-related disorders. Emerging interventions to improve gut barrier integrity and microbiota composition are also described., Competing Interests: Declaration of interests Y-F.K. is President of Chang Gung Biotechnology. J.D.Y. is Chairman of the Board of Chang Gung Biotechnology. J.M., Y-F.K., T-L.H., J.D.Y., and D.M.O. are named on patents held by Chang Gung University and/or Chang Gung Biotechnology related to the preparation and use of prebiotics, probiotics, and bioactive compounds., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rapid eye movement (REM) sleep behavior disorder (RBD) is associated with Parkinson's disease (PD). In this study, a smartwatch-based sensor is utilized as a convenient tool to detect the abnormal RBD phenomenon in PD patients. Instead, a questionnaire with sleep quality assessment and sleep physiological indices, such as sleep stage, activity level, and heart rate, were measured in the smartwatch sensors. Therefore, this device can record comprehensive sleep physiological data, offering several advantages such as ubiquity, long-term monitoring, and wearable convenience. In addition, it can provide the clinical doctor with sufficient information on the patient's sleeping patterns with individualized treatment. In this study, a three-stage sleep staging method (i.e., comprising sleep/awake detection, sleep-stage detection, and REM-stage detection) based on an accelerometer and heart-rate data is implemented using machine learning (ML) techniques. The ML-based algorithms used here for sleep/awake detection, sleep-stage detection, and REM-stage detection were a Cole-Kripke algorithm, a stepwise clustering algorithm, and a k-means clustering algorithm with predefined criteria, respectively. The sleep staging method was validated in a clinical trial. The results showed a statistically significant difference in the percentage of abnormal REM between the control group (1.6 ± 1.3; n = 18) and the PD group (3.8 ± 5.0; n = 20) ( p = 0.04). The percentage of deep sleep stage in our results presented a significant difference between the control group (38.1 ± 24.3; n = 18) and PD group (22.0 ± 15.0, n = 20) ( p = 0.011) as well. Further, our results suggested that the smartwatch-based sensor was able to detect the difference of an abnormal REM percentage in the control group (1.6 ± 1.3; n = 18), PD patient with clonazepam (2.0 ± 1.7; n = 10), and without clonazepam (5.7 ± 7.1; n = 10) ( p = 0.007). Our results confirmed the effectiveness of our sensor in investigating the sleep stage in PD patients. The sensor also successfully determined the effect of clonazepam on reducing abnormal REM in PD patients. In conclusion, our smartwatch sensor is a convenient and effective tool for sleep quantification analysis in PD patients.

Background: Electrical impedance tomography (EIT) can be used for continuous monitoring of pulmonary ventilation. However, no proper method has been developed for the separation of pulmonary ventilation and perfusion signals and the measurement of the associated ventilation/ perfusion (V/Q) ratio. Previously, various methods have been used to extract these components; however, these have not been able to effectively separate and validate cardiac- and pulmonary- related images., Aims: This study aims at validating and developing a novel method to separate cardiac- and pulmonary- related components based on the EIT simulation field of view and to simultaneously reconstruct the individual images instantly., Methods: Our approach combines the advantages of the principal component analysis (PCA) and processes that originally measure EIT data instead of handling a series of EIT images, thus introducing the empirical mode decomposition (EMD). The PCA template functions for cardiacrelated imaging and intrinsic mode functions (IMFs) of EMD for lung-related imaging are then adapted to input signals., Results: The proposed method enables the separation of cardiac- and lung-related components by adjusting the proportion of the key components related to lung imaging, which are the fourth component (PC4) and the first component (IMF1) in PCA- and EMD-based methods, respectively. The preliminary results on the application of the method to real human EIT data revealed the consistently better performance and optimal computation compared with previous methods., Conclusion: This study proposes a novel method for applying EIT to evaluate the best time of V/Q matching on the cardiovascular and respiratory systems; this aspect can be investigated in future research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The medicinal fungus Ganoderma lucidum is used as a dietary supplement and health tonic, but whether it affects longevity remains unclear. We show here that a water extract of G. lucidum mycelium extends lifespan of the nematode Caenorhabditis elegans . The G. lucidum extract reduces the level of fibrillarin (FIB-1), a nucleolar protein that correlates inversely with longevity in various organisms. Furthermore, G. lucidum treatment increases expression of the autophagosomal protein marker LGG-1, and lifespan extension is abrogated in mutant C. elegans strains that lack atg-18 , daf-16 , or sir-2.1 , indicating that autophagy and stress resistance pathways are required to extend lifespan. In cultured human cells, G. lucidum increases concentrations of the LGG-1 ortholog LC3 and reduces levels of phosphorylated mTOR, a known inhibitor of autophagy. Notably, low molecular weight compounds (<10 kDa) isolated from the G. lucidum water extract prolong lifespan of C. elegans and the same compounds induce autophagy in human cells. These results suggest that G. lucidum can increase longevity by inducing autophagy and stress resistance.

Objective: Electrical impedance tomography (EIT) is a non-invasive technique that constitutes a promising tool for real-time imaging and long-term monitoring of the ventilation distribution at bedside. However, clinical monitoring and diagnostic evaluations depend on various methods to assess ventilation-dependent parameters useful for ventilation therapy. This study develops an automatic, robust, and rapidly accessible method for lung segmentation that can be used to define appropriate regions-of-interest (ROIs) within EIT images., Approach: To date, available methods for patients with defected lungs have the disadvantage of not being able to identify lung regions because of their poor ventilation responses. Furthermore, the challenges related to the identification of lung areas in EIT images are attributed to the low spatial resolution of EIT. In this study, a U-Net-based automatic lung segmentation model is used as a postprocessor to transform the original EIT image to a lung ROI image and refine the inherent conductivity distribution of the original EIT image. The trained U-Net network is capable of performing an automatic segmentation of conductivity changes in EIT images without requiring prior information., Main Results: The experimental design of this study was based on a finite element method (FEM) phantom used to assess the feasibility and effectiveness of the proposed method, and evaluation of the trained models on the test dataset was performed using the Dice similarity coefficient (DSC) and the mean absolute error (MAE). The FEM experimental results yielded values of 0.0065 for MAE, and values >0.99 for DSC in simulations., Significance: The use of a deep-learning-based approach attained automatic and convenient segmentation of lung ROIs into distinguishable images, which represents a direct benefit for regional lung ventilation-dependent parameter extraction and analysis. However, further investigations and validation are warranted in real human datasets with different physiology conditions with CT cross-section dataset to refine the suggested model.

Caloric restriction (CR) mimetics are molecules that produce beneficial effects on health and longevity in model organisms and humans, without the challenges of maintaining a CR diet. Conventional CR mimetics such as metformin, rapamycin and spermidine activate autophagy, leading to recycling of cellular components and improvement of physiological function. We review here novel CR mimetics and anti-aging compounds, such as 4,4'-dimethoxychalcone, fungal polysaccharides, inorganic nitrate, and trientine, highlighting their possible molecular targets and mechanisms of action. The activity of these compounds can be understood within the context of hormesis, a biphasic dose response that involves beneficial effects at low or moderate doses and toxic effects at high doses. The concept of hormesis has widespread implications for the identification of CR mimetics in experimental assays, testing in clinical trials, and use in healthy humans. We also discuss the promises and limitations of CR mimetics and anti-aging molecules for delaying aging and treating chronic diseases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Electrical impedance tomography (EIT) is widely used for bedside monitoring of lung ventilation status. Its goal is to reflect the internal conductivity changes and estimate the electrical properties of the tissues in the thorax. However, poor spatial resolution affects EIT image reconstruction to the extent that the heart and lung-related impedance images are barely distinguishable. Several studies have attempted to tackle this problem, and approaches based on decomposition of EIT images using linear transformations have been developed, and recently, U-Net has become a prominent architecture for semantic segmentation. In this paper, we propose a novel semi-Siamese U-Net specifically tailored for EIT application. It is based on the state-of-the-art U-Net, whose structure is modified and extended, forming shared encoder with parallel decoders and has multi-task weighted losses added to adapt to the individual separation tasks. The trained semi-Siamese U-Net model was evaluated with a test dataset, and the results were compared with those of the classical U-Net in terms of Dice similarity coefficient and mean absolute error. Results showed that compared with the classical U-Net, semi-Siamese U-Net exhibited performance improvements of 11.37% and 3.2% in Dice similarity coefficient, and 3.16% and 5.54% in mean absolute error, in terms of heart and lung-impedance image separation, respectively., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The positive end-expiratory pressure (PEEP) level with best respiratory system compliance (Crs) is frequently used for PEEP selection in acute respiratory distress syndrome (ARDS) patients. On occasion, two similar best Crs (where the difference between the Crs of two PEEP levels is < 1 ml/cm H 2 O) may be identified during decremental PEEP titration. Selecting PEEP under such conditions is challenging. The aim of this study was to provide supplementary rationale for PEEP selection by assessing the global and regional ventilation distributions between two PEEP levels in this situation., Methods: Eight ARDS cases with similar best Crs at two different PEEP levels were analyzed using examination-specific electrical impedance tomography (EIT) measures and airway stress index (SIaw). Five Crs were measured at PEEP values of 25 cm H 2 O (PEEP 25 ), 20 cm H 2 O (PEEP 20 ), 15 cm H 2 O (PEEP H ), 11 cm H 2 O (PEEP I ), and 7 cm H 2 O (PEEP L ). The higher PEEP value of the two PEEPs with similar best Crs was designated as PEEP upper , while the lower designated as PEEP lower ., Results: PEEP H and PEEP I shared the best Crs in two cases, while similar Crs was found at PEEP I and PEEP L in the remaining six cases. SIaw was higher with PEEP upper as compared to PEEP lower (1.06 ± 0.10 versus 0.99 ± 0.09, p = 0.05). Proportion of lung hyperdistension was significantly higher with PEEP upper than PEEP lower (7.0 ± 5.1% versus 0.3 ± 0.5%, p = 0.0002). In contrast, proportion of recruitable lung collapse was higher with PEEP lower than PEEP upper (18.6 ± 4.4% versus 5.9 ± 3.7%, p < 0.0001). Cyclic alveolar collapse and reopening during tidal breathing was higher at PEEP lower than PEEP upper (34.4 ± 19.3% versus 16.0 ± 9.1%, p = 0.046). The intratidal gas distribution (ITV) index was also significantly higher at PEEP lower than PEEP upper (2.6 ± 1.3 versus 1.8 ± 0.7, p = 0.042)., Conclusions: PEEP upper is a rational selection in ARDS cases with two similar best Crs. EIT provides additional information for the selection of PEEP in such circumstances., Supplementary Information: The online version contains supplementary material available at 10.1007/s40846-021-00668-2., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2021.)

Senescence is a state of cell cycle arrest that plays an important role in embryogenesis, wound healing and protection against cancer. Senescent cells also accumulate during aging and contribute to the development of age-related disorders and chronic diseases, such as atherosclerosis, type 2 diabetes, osteoarthritis, idiopathic pulmonary fibrosis, and liver disease. Molecules that induce apoptosis of senescent cells, such as dasatinib, quercetin, and fisetin, produce health benefits and extend lifespan in animal models. We describe here the mechanism of action of senolytics and senomorphics, many of which are derived from plants and fungi. We also discuss the possibility of using such compounds to delay aging and treat chronic diseases in humans., (© 2020 Wiley Periodicals LLC.)

Background: We designed a novel ankle foot orthosis (AFO), namely, ideal training AFO (IT-AFO), with motion feedback on the hemiparetic lower limb to improve ambulation in individuals with stroke-related hemiplegia. We, therefore sought to compare the kinematic parameters of gait between IT-AFO with and without dynamic control and conventional anterior-type AFO or no AFO., Methods: Gait parameters were measured using the RehaWatch® system in seven individuals with hemiplegia (mean 51.14 years). The parameters were compared across four conditions: no AFO, conventional anterior AFO, IT-AFO without dynamic control, and IT-AFO with dynamic control, with three trials of a 10-m walk test for each., Results: The dorsiflexion angle increased during the swing phase when the IT-AFO was worn, and it was larger with dynamic control. These data can confirm drop foot improvement; however, the difference between the parameters with- and without-AFO control conditions was not significant in the swing phase. The IT-AFO with or without dynamic control enhanced the loading response to a greater extent between the hemiparetic and unaffected lower limbs than conventional AFO or no AFO. The duration of the stance phase on the hemiparetic lower limb was also longer when using IT-AFO with and without dynamic control than that when using conventional AFO, which improved asymmetry. User comfort and satisfaction was greater with IT-AFO than with the other conditions., Conclusions: The IT-AFO with dynamic control improved gait pattern and weight shifting to the hemiparetic lower limb, reducing gait asymmetry. The difference with and without dynamic control of IT-AFO is not statistically significant, and it is limited by sample size. However, this study shows the potential of IT-AFO in applying positive motion feedback with gait training., Trial Registration: Taipei Medical University-Joint Institutional Review Board. N201510010 . Registered 12 February 2015. http://ohr.tmu.edu.tw/main.php .

The nematode Caenorhabditis elegans is a useful model to study aging due to its short lifespan, ease of manipulation, and available genetic tools. Several molecules and extracts derived from plants and fungi extend the lifespan of C. elegans by modulating aging-related pathways that are conserved in more complex organisms. Modulation of aging pathways leads to activation of autophagy, mitochondrial biogenesis and expression of antioxidant and detoxifying enzymes in a manner similar to caloric restriction. Low and moderate concentrations of plant and fungal molecules usually extend lifespan, while high concentrations are detrimental, consistent with a lifespan-modulating mechanism involving hormesis. We review here molecules and extracts derived from plants and fungi that extend the lifespan of C. elegans , and explore the possibility that these natural substances may produce health benefits in humans., Competing Interests: Conflict of interest: Y-F.K. is president of Chang Gung Biotechnology. J.D.Y. is Chairman of the Board of Chang Gung Biotechnology. The authors have filed patents related to the preparation and use of dietary supplements and probiotics., (Copyright: © 2020 Martel et al.)

Phytochemicals in fruits and vegetables produce health benefits, but questions remain regarding their bioavailability, molecular targets, and mechanism of action. Here, we address these issues by considering the prebiotic and biological properties of phytochemicals. A fraction of phytochemicals consumed orally passes through the gut lumen, where it modulates the composition of the gut microbiota and maintains intestinal integrity. Phytochemicals and microbiota-derived metabolites that are absorbed by the organism comprise compounds that, at low doses, induce stress resistance mechanisms, including autophagy, DNA repair, and expression of detoxifying and antioxidant enzymes. We propose that these mechanisms improve cellular and organ function and can account for the promiscuous bioactivities of phytochemicals, despite their limited bioavailability and extremely varied chemical structures., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aging is influenced by many lifestyle choices that are under human control, including nutrition and exercise. The most effective known antiaging intervention consists of calorie restriction (CR), which increases lifespan in yeasts, worms, fruit flies, mice, and nonhuman primates. CR also improves healthspan by preventing the development of various aging-related diseases such as cancer, cardiovascular disease, diabetes, and neurodegeneration. Many compounds isolated from plants and fungi prolong lifespan and prevent age-related diseases in model organisms. These plant and fungal compounds modulate the same cellular and physiological pathways as CR, including those involving insulin and insulin-like growth factor-1, mammalian target of rapamycin, and sirtuins. Modulation of these aging-related pathways results in the activation of various cellular processes such as autophagy, DNA repair, and neutralization of reactive oxygen species. Together, these cellular processes are believed to delay aging and prevent chronic diseases by improving bodily functions and stress resistance. We review here the mechanisms of action of plant and fungal molecules possessing antiaging properties and discuss the possibilities and challenges associated with the development of antiaging compounds isolated from natural products., (© 2019 Wiley Periodicals, Inc.)

Caloric restriction, intermittent fasting, and exercise activate defensive cellular responses such as autophagy, DNA repair, and the induction of antioxidant enzymes. These processes improve health and longevity by protecting cells and organs against damage, mutations, and reactive oxygen species. Consuming a diet rich in vegetables, fruits, and mushrooms can also improve health and longevity. Phytochemicals such as alkaloids, polyphenols, and terpenoids found in plants and fungi activate the same cellular processes as caloric restriction, fasting, and exercise. Many of the beneficial effects of fruits and vegetables may thus be due to activation of stress resistance pathways by phytochemicals. A better understanding of the mechanisms of action of phytochemicals may provide important insights to delay aging and prevent chronic diseases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We examined the effects of an Antrodia cinnamomea ethanol extract (ACEE) on lung cancer cells in vitro and tumor growth in vivo. ACEE produced dose-dependent cytotoxic effects and induced apoptosis in Lewis lung carcinoma (LLC) cells. ACEE treatment increased expression of p53 and Bax, as well as cleavage of caspase-3 and PARP, while reducing expression of survivin and Bcl-2. ACEE also reduced the levels of JAK2 and phosphorylated STAT3 in LLC cells. In a murine allograft tumor model, oral administration of ACEE significantly inhibited LLC tumor growth and metastasis without affecting serum biological parameters or body weight. ACEE increased cleavage of caspase-3 in murine tumors, while decreasing STAT3 phosphorylation. In addition, ACEE reduced the growth of human tumor xenografts in nude mice. Our findings therefore indicate that ACEE inhibits lung tumor growth and metastasis by inducing apoptosis and by inhibiting the STAT3 signaling pathway in cancer cells.

Objective: The medicinal fungus Ophiocordyceps sinensis and its anamorph Hirsutella sinensis have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut microbiota have been described in obesity and type 2 diabetes. We examined the possibility that H. sinensis mycelium (HSM) and isolated fractions containing polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the gut microbiota., Design: High-fat diet (HFD)-fed mice were treated with HSM or fractions containing polysaccharides of different molecular weights. The effects of HSM and polysaccharides on the gut microbiota were assessed by horizontal faecal microbiota transplantation (FMT), antibiotic treatment and 16S rDNA-based microbiota analysis., Results: Fraction H1 containing high-molecular weight polysaccharides (>300 kDa) considerably reduced body weight gain (∼50% reduction) and metabolic disorders in HFD-fed mice. These effects were associated with increased expression of thermogenesis protein markers in adipose tissues, enhanced gut integrity, reduced intestinal and systemic inflammation and improved insulin sensitivity and lipid metabolism. Gut microbiota analysis revealed that H1 polysaccharides selectively promoted the growth of Parabacteroides goldsteinii , a commensal bacterium whose level was reduced in HFD-fed mice. FMT combined with antibiotic treatment showed that neomycin-sensitive gut bacteria negatively correlated with obesity traits and were required for H1's anti-obesogenic effects. Notably, oral treatment of HFD-fed mice with live P. goldsteinii reduced obesity and was associated with increased adipose tissue thermogenesis, enhanced intestinal integrity and reduced levels of inflammation and insulin resistance., Conclusions: HSM polysaccharides and the gut bacterium P. goldsteinii represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes., Competing Interests: Competing interests: Y-FK is President of Chang Gung Biotechnology Corporation. JDY is Chairman of the Board of Chang Gung Biotechnology Corporation. The authors own patents related to the preparation and use of medicinal fungi and probiotics., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Ethnopharmacological Relevance: The medicinal mushroom Antrodia cinnamomea has been used to treat cancer but its anti-angiogenic effects have not been studied in detail., Aim of the Study: The main objective of this study was to determine the molecular mechanism of activity underlying the anti-angiogenic effects of A. cinnamomea., Materials and Methods: The effects of an A. cinnamomea ethanol extract (ACEE) on cell migration and microvessel formation were investigated in endothelial cells in vitro and Matrigel plugs implanted into mice in vivo. Activation of intracellular signaling pathways was examined using Western blotting. Protein expression was assessed using immunohistochemistry in a mouse model of lung metastasis., Results: We show that treatment with ACEE inhibits cell migration and tube formation in human umbilical vein endothelial cells (HUVECs). ACEE suppresses phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and expression of pro-angiogenic kinases in vascular endothelial growth factor (VEGF)-treated HUVECs, in addition to reducing expression of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3). ACEE treatment inhibits VEGF-induced microvessel formation in Matrigel plugs in vivo. In addition, ACEE significantly reduces VEGFR2 expression in Lewis lung carcinoma cells and downregulates the expression of cluster of differentiation 31 (CD31) and VEGFR2 in murine lung metastases., Conclusion: These results indicate that A. cinnamomea produces anti-angiogenic effects by inhibiting the VEGFR2 signaling pathway., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Depression is a mental disorder associated with environmental, genetic and psychological factors. Recent studies indicate that chronic neuro-inflammation may affect brain physiology and alter mood and behavior. Consumption of a high-fat diet leads to obesity and chronic systemic inflammation. The gut microbiota mediates many effects of a high-fat diet on human physiology and may also influence the mood and behavior of the host. We review here recent studies suggesting the existence of a link between obesity, the gut microbiota and depression, focusing on the mechanisms underlying the effects of a high-fat diet on chronic inflammation and brain physiology. This body of research suggests that modulating the composition of the gut microbiota using prebiotics and probiotics may produce beneficial effects on anxiety and depression., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Obesity is associated with gut microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Given the high and increasing prevalence of obesity worldwide, anti-obesity treatments that are safe, effective and widely available would be beneficial. We examined whether the medicinal mushroom Antrodia cinnamomea may reduce obesity in mice fed with a high-fat diet (HFD)., Methods: Male C57BL/6J mice were fed a HFD for 8 weeks to induce obesity and chronic inflammation. The mice were treated with a water extract of A. cinnamomea (WEAC), and body weight, fat accumulation, inflammation markers, insulin sensitivity and the gut microbiota were monitored., Results: After 8 weeks, the mean body weight of HFD-fed mice was 39.8±1.2 g compared with 35.8±1.3 g for the HFD+1% WEAC group, corresponding to a reduction of 4 g or 10% of body weight (P<0.0001). WEAC supplementation reduced fat accumulation and serum triglycerides in a statistically significant manner in HFD-fed mice. WEAC also reversed the effects of HFD on inflammation markers (interleukin-1β, interleukin-6, tumor necrosis factor-α), insulin resistance and adipokine production (leptin and adiponectin). Notably, WEAC increased the expression of intestinal tight junctions (zonula occludens-1 and occludin) and antimicrobial proteins (Reg3g and lysozyme C) in the small intestine, leading to reduced blood endotoxemia. Finally, WEAC modulated the composition of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio and increasing the level of Akkermansia muciniphila and other bacterial species associated with anti-inflammatory properties., Conclusions: Supplementation with A. cinnamomea produces anti-obesogenic, anti-inflammatory and antidiabetic effects in HFD-fed mice by maintaining intestinal integrity and modulating the gut microbiota.

This paper describes the experience of caring for a child with incontinent dermatitis that was caused by improper family care. From March 27, 2015 to April 2, 2015, the authors used Gordon's 11 functional health parameters to collect subjective and objective data on the physical, mental and social conditions of the care recipient. To understand the nursing-related problems, including impaired skin integrity, acute pain, and caregiver anxiety, the data for this case and his mother were conducted by observation, physical assessment, the process of caring, and communication. For the three nursing problems, we established a good relationship with the family by providing individual care, continuously active care, listening, and companionship. In order to reduce the pain during wound dressing, we used game therapy and an attention-transfer technique that was based on the case's preferences. We encouraged family members to participate in treatment in order to ensure that the case continued to receive proper and continuous care after returning home. The authors taught the family members the correct information for treating incontinent dermatitis in order to reduce their concerns and to enhance their confidence and care abilities. We hope that this nursing experience may provide a reference for other nursing staffs when caring for similar cases in order to ensure appropriate quality of care.

The caterpillar fungus Ophiocordyceps sinensis is a medicinal mushroom increasingly used as a dietary supplement for various health conditions, including fatigue, chronic inflammation, and male impotence. Here, we propose strategies to address the existing challenges related to the study and commercial production of this mysterious fungus., (Copyright © 2017. Published by Elsevier Ltd.)

Plants and mushrooms are used for medicinal purposes and the screening of molecules possessing biological activities. A single plant or mushroom may produce both stimulatory and inhibitory effects on immune cells, depending on experimental conditions, but the reason behind this dichotomy remains obscure. We present here a large body of experimental data showing that water extracts of plants and mushrooms usually activate immune cells, whereas ethanol extracts inhibit immune cells. The mode of extraction of plants and mushrooms may thus determine the effects produced on immune cells, possibly due to differential solubility and potency of stimulatory and inhibitory compounds. We also examine the possibility of using such plant and mushroom extracts to treat immune system disorders., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

This corrects the article DOI: 10.1038/ncomms8489.

Ethnopharmacological Relevance: The medicinal mushroom Antrodia cinnamomea possesses anticancer properties but the active compounds responsible for these effects are mostly unknown., Aim of the Study: We aimed to identify novel A. cinnamomea compounds that produce cytotoxic effects on cancer cells., Materials and Methods: Using ethanol extraction and chromatography, we isolated the lanostanoid compound lanosta-7,9(11),24-trien-3β,15α,21-triol (1) from cultured A. cinnamomea mycelium. Cytotoxicity and pro-apoptotic effects of compound 1 were evaluated using the MTS assay and flow cytometry analysis, respectively., Results: Compound 1 produced cytotoxic effects on the nasopharyngeal carcinoma cell lines TW02 and TW04, with IC 50 values of 63.3 and 115.0μM, respectively. On the other hand, no cytotoxic effects were observed on non-tumorigenic nasopharyngeal epithelial cells (NP69). In addition, compound 1 induced apoptosis in TW02 and TW04 cells as revealed by flow cytometry analysis., Conclusions: Our results demonstrate for the first time the presence of pinicolol B in A. cinnamomea mycelium and suggest that this compound may contribute to the anticancer effects of A. cinnamomea., (Copyright © 2017. Published by Elsevier B.V.)

Obesity is reaching global epidemic proportions as a result of factors such as high-calorie diets and lack of physical exercise. Obesity is now considered to be a medical condition, which not only contributes to the risk of developing type 2 diabetes mellitus, cardiovascular disease and cancer, but also negatively affects longevity and quality of life. To combat this epidemic, anti-obesogenic approaches are required that are safe, widely available and inexpensive. Several plants and mushrooms that are consumed in traditional Chinese medicine or as nutraceuticals contain antioxidants, fibre and other phytochemicals, and have anti-obesogenic and antidiabetic effects through the modulation of diverse cellular and physiological pathways. These effects include appetite reduction, modulation of lipid absorption and metabolism, enhancement of insulin sensitivity, thermogenesis and changes in the gut microbiota. In this Review, we describe the molecular mechanisms that underlie the anti-obesogenic and antidiabetic effects of these plants and mushrooms, and propose that combining these food items with existing anti-obesogenic approaches might help to reduce obesity and its complications.

The caterpillar fungus Ophiocordyceps sinensis (previously called Cordyceps sinensis) has been used for centuries in Asia as a tonic to improve health and longevity. Recent studies show that O. sinensis produces a wide range of biological effects on cells, laboratory animals and humans, including anti-fatigue, anti-infection, anti-inflammatory, antioxidant, and anti-tumor activities. In view of the rarity of O. sinensis fruiting bodies in nature, cultivation of its anamorph mycelium represents a useful alternative for large-scale production. However, O. sinensis fruiting bodies harvested in nature harbor several fungal contaminants, a phenomenon that led to the isolation and characterization of a large number of incorrect mycelium strains. We report here the isolation of a mycelium from a fruiting body of O. sinensis and we identify the isolate as O. sinensis' anamorph (also called Hirsutella sinensis) based on multi-locus sequence typing of several fungal genes (ITS, nrSSU, nrLSU, RPB1, RPB2, MCM7, β-tubulin, TEF-1α, and ATP6). The main characteristics of the isolated mycelium, including its optimal growth at low temperature (16°C) and its biochemical composition, are similar to that of O. sinensis fruiting bodies, indicating that the mycelium strain characterized here may be used as a substitute for the rare and expensive O. sinensis fruiting bodies found in nature., Competing Interests: Y.-F.K. is President of Chang Gung Biotechnology. J.-C.L. and C.-S. Lee are employees of Chang Gung Biotechnology. J.D.Y. is Chairman of the Board of Chang Gung Biotechnology. The authors have filed patent applications related to the preparation of medicinal mushrooms and their use in humans. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Medicinal mushrooms have been used for centuries in Asian countries owing to their beneficial effects on health and longevity. Previous studies have reported that a single medicinal mushroom may produce both stimulatory and inhibitory effects on immune cells, depending on conditions, but the factors responsible for this apparent dichotomy remain obscure. We show here that water and ethanol extracts of cultured mycelium from various species (Agaricus blazei Murrill, Antrodia cinnamomea, Ganoderma lucidum and Hirsutella sinensis) produce opposite effects on NK cells. Water extracts enhance NK cell cytotoxic activity against cancer cells, whereas ethanol extracts inhibit cytotoxicity. Water extracts stimulate the expression and production of cytolytic proteins (perforin and granulysin) and NKG2D/NCR cell surface receptors, and activate intracellular signaling kinases (ERK, JNK and p38). In contrast, ethanol extracts inhibit expression of cytolytic and cell surface receptors. Our results suggest that the mode of extraction of medicinal mushrooms may determine the nature of the immunomodulatory effects produced on immune cells, presumably owing to the differential solubility of stimulatory and inhibitory mediators. These findings have important implications for the preparation of medicinal mushrooms to prevent and treat human diseases., (© The Author(s) 2016.)

The inflammasome has been mainly studied in innate immune cells in which it senses microbes and cellular damage, and induces secretion of pro-inflammatory cytokines. This process induces an inflammatory response that is critical for the resolution of infections and repair of tissue damage following injury. Recent studies indicate that inflammasome complex formation also participates in many other cellular and physiological processes beyond modulation of inflammation, such as autophagy, metabolism, eicosanoids production, and phagosome maturation., (Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: The meat of spent hens is hard to use owing to its small amount and poor quality. A washing process to remove sarcoplasmic proteins and other impurities can prolong the shelf life of surimi-like products. Owing to the benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFAs), functional foods fortified with ω-3 PUFAs are increasingly being marketed. Hence, in this study, ω-3 FA-fortified chicken surimi was manufactured, and how to ameliorate its lipid peroxidation during frozen storage was investigated., Results: A 0.10% (w/v) solution of sodium chloride (NaCl) instead of distilled water in the third washing step decreased (P < 0.05) myofibrillar protein loss and moisture content of spent hen breast protein recoveries. Oil droplets in fish, flaxseed or soybean oil-added chicken surimi were well distributed. Moreover, flaxseed oil addition increased (P < 0.05) total ω-3 FAs and ω-3/ω-6 FA ratio, while only fish oil provided long-chain PUFAs. Oil addition decreased (P < 0.05) hardness and gumminess of chicken surimi, while flaxseed oil resulted in more (P < 0.05) yellow surimi than fish and soybean oil. Fish oil-added samples showed higher (P < 0.05) lipid oxidation than flaxseed or soybean oil-added samples under -15 to -10 °C storage, but α-tocopherol addition ameliorated it., Conclusion: A novel semi-manufactured chicken surimi product with nutritional benefits could be developed by fortification with fish or flaxseed oil., (© 2015 Society of Chemical Industry.)

Background/purpose: The time required to reach oxygenation equilibrium after positive end-expiratory pressure (PEEP) adjustments in mechanically ventilated patients with acute respiratory distress syndrome (ARDS) is unclear. We used electrical impedance tomography to elucidate gas distribution and factors related to oxygenation status following PEEP in patients with ARDS., Methods: Nineteen mechanically ventilated ARDS patients were placed on baseline PEEP (PEEPB) for 1 hour, PEEPB - 4 cmH2O PEEP (PEEPL) for 30 minutes, and PEEPB + 4 cmH2O PEEP (PEEPH) for 1 hour. Tidal volume and respiratory rate were similar. Impedance changes, respiratory parameters, and arterial blood gases were measured at baseline, 5 minutes, and 30 minutes after PEEPL, and 5 minutes, 15 minutes, 30 minutes, and 1 hour after PEEPH., Results: PaO2/fraction of inspired oxygen (P/F ratio) decreased quickly from PEEPB to PEEPL, and stabilized 5 minutes after PEEPL. However the P/F ratio progressively increased from PEEPL to PEEPH, and a significantly higher P/F ratio and end-expiratory lung impedance were found at 60 minutes compared to 5 minutes after PEEPH. The end-expiratory lung impedance level significantly correlated with P/F ratio (p < 0.001). With increasing PEEP, dorsal ventilation significantly increased; however, regional ventilation did not change over time with PEEP level., Conclusion: Late improvements in oxygenation following PEEP escalation are probably due to slow recruitment in ventilated ARDS patients. Electrical impedance tomography may be an appropriate tool to assess recruitment and oxygenation status in patients with changes in PEEP., (Copyright © 2015. Published by Elsevier B.V.)

Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1-induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1-treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin-induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-β1 in lung tissues, and this effect is accompanied by decreased collagen 3α1 and α-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis.

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis-as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels-but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further show that high molecular weight polysaccharides (>300 kDa) isolated from the WEGL extract produce similar anti-obesity and microbiota-modulating effects. Our results indicate that G. lucidum and its high molecular weight polysaccharides may be used as prebiotic agents to prevent gut dysbiosis and obesity-related metabolic disorders in obese individuals.

Resveratrol, a natural phenolic compound found in red grapes and wine, exists as cis and trans isomers. Recent studies have shown that trans-resveratrol possesses anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-tumor and immunomodulatory properties. However, it remains unclear whether cis-resveratrol may exhibit similar activities. The objective of the present study was to examine the effects of cis- and trans-resveratrol on the production of pro-inflammatory cytokines and mediators in human macrophages. We examined the possibility that cis- and trans-resveratrol may affect cytokine secretion by modulating inflammasomes, intracellular multi-protein complexes, the assembly of which leads to caspase-1 activation and secretion of active IL-1β by macrophages. Our results show that pre-treatment of macrophages with cis-resveratrol not only reduces pro-IL-1β production and IL-1β secretion, but also suppresses ATP-induced transcription and activation of caspase-1 and caspase-4. Notably, cis-resveratrol inhibits the expression of the purinergic receptor, P2X(7)R, and the endoplasmic reticulum stress marker, Glc-regulated protein 78, but also reduces reactive oxygen species production. Moreover, cis-resveratrol attenuates cyclooxygenase-2 expression and prostaglandin E2 production. cis-Resveratrol also decreases the phosphorylation of p38 MAPK and expression of the c-Jun protein. These results indicate that cis-resveratrol produces anti-inflammatory effects by inhibiting both the canonical and non-canonical inflammasomes, and associated pathways in human macrophages., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Recent studies have revealed that the gut microbiota regulates many physiological functions, ranging from energy regulation and cognitive processes to toxin neutralization and immunity against pathogens. Accordingly, alterations in the composition of the gut microbiota have been shown to contribute to the development of various chronic diseases. The main objectives of this review are to present recent breakthroughs in the study of the gut microbiota and show that intestinal bacteria play a critical role in the development of different disease conditions, including obesity, fatty liver disease, and lung infection. We also highlight the potential application of prebiotics and probiotics in maintaining optimal health and treating chronic inflammatory and immunity-related diseases.

Ethnopharmacological Relevance: Antrodia cinnamomea--a medicinal fungus that is indigenous to Taiwan--has been used as a health tonic by aboriginal tribes and the Asian population. Recent studies indicate that Antrodia cinnamomea extracts exhibit hepato-protective, anti-hypertensive, anti-oxidative, anti-inflammatory, immuno-modulatory, and anti-cancer effects on cultured cells and laboratory animals. This study aims to explore the anti-inflammatory activity of an Antrodia cinnamomea ethanol extract (ACEE) and elucidate its underlying mechanisms of action using lipopolysaccharide (LPS)-primed, ATP-stimulated human THP-1 macrophages., Materials and Methods: The effects of ACEE on cell viability were studied using the MTT assay. The expressions of genes, proteins, and pro-inflammatory cytokines were measured by quantitative real-time RT-PCR, Western blotting and ELISA, respectively. The ACEE was further investigated for its effects on reactive oxygen species (ROS) production using ROS detection kit., Results: Our results showed that ACEE significantly inhibits ATP-induced secretion of interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) by LPS-primed macrophages. ACEE also suppresses the transcription and activation of caspase-1, which is responsible for the cleavage and activation of IL-1β and IL-18. Of note, ACEE not only reduces expression of the inflammasome component NLRP3 and the purinergic receptor P2X7R but also inhibits ATP-induced ROS production and caspase-1 activation. Furthermore, the anti-inflammatory properties of ACEE correlate with reduced activation of the MAPK and NF-κB pathways., Conclusion: The results of the present study indicate that Antrodia cinnamomea suppresses the secretion of IL-1β and IL-18 associated with inhibition of the NLRP3 inflammasome in macrophages. These findings suggest that ACEE may have therapeutic potential for the treatment of inflammatory diseases., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ganoderma lucidum (G. lucidum) is a medicinal mushroom long used in Asia as a folk remedy to promote health and longevity. Recent studies indicate that G. lucidum activates NK cells, but the molecular mechanism underlying this effect has not been studied so far. To address this question, we prepared a water extract of G. lucidum and examined its effect on NK cells. We observed that G. lucidum treatment increases NK cell cytotoxicity by stimulating secretion of perforin and granulysin. The mechanism of activation involves an increased expression of NKG2D and natural cytotoxicity receptors (NCRs), as well as increased phosphorylation of intracellular MAPKs. Our results indicate that G. lucidum induces NK cell cytotoxicity against various cancer cell lines by activating NKG2D/NCR receptors and MAPK signaling pathways, which together culminate in exocytosis of perforin and granulysin. These observations provide a cellular and molecular mechanism to account for the reported anticancer effects of G. lucidum extracts in humans.

Cordyceps sinensis is a medicinal mushroom used for centuries in Asian countries as a health supplement and tonic. Hirsutella sinensis-the anamorphic, mycelial form of C. sinensis-possesses similar properties, and is increasingly used as a health supplement. Recently, C. sinensis extracts were shown to inhibit the production of the pro-inflammatory cytokine IL-1β in lipopolysaccharide-treated macrophages. However, the molecular mechanism underlying this process has remained unclear. In addition, whether H. sinensis mycelium (HSM) extracts also inhibit the production of IL-1β has not been investigated. In the present study, the HSM extract suppresses IL-1β and IL-18 secretion, and ATP-induced activation of caspase-1. Notably, we observed that HSM not only reduced expression of the inflammasome component NLRP1 and the P2X7R but also reduced the activation of caspase-4, and ATP-induced ROS production. These findings reveal that the HSM extract has anti-inflammatory properties attributed to its ability to inhibit both canonical and non-canonical inflammasomes.

Agaricus blazei Murill (AbM) has been reported to possess immune activity against tumors and infections through stimulation of mononuclear phagocytes. Recently, AbM extract was shown to induce the production of the pro-inflammatory cytokine, interleukin-1β (IL-1β), in human monocytes. IL-1β is a key pro-inflammatory cytokine produced by activated macrophages and monocytes and its secretion is strictly controlled by the inflammasome. The purpose of this study is to investigate the effect of AbM water extracts on the regulation of IL-1β production and activation of the NLRP3 inflammasome in human THP-1 macrophages. The NLRP3 inflammasome consists of an NLRP3 receptor, an adaptor protein called ASC, and the inflammatory protease, caspase-1. Typically, stimulation of immune cells with microbial products results in production of pro-IL-1β, but a second stress-related signal activates the inflammasome and caspase-1, leading to processing and secretion of IL-1β. Our results show that AbM enhances transcription of IL-1β and triggers NLRP3 inflammasome-mediated IL-1β secretion in human THP-1 macrophages. AbM-mediated IL-1β secretion was markedly reduced in macrophages deficient in NLRP3 and ASC, demonstrating that the NLRP3 inflammasome is essential for AbM-induced IL-1β secretion. In addition, caspase-1 was activated and involved in proteolytic cleavage and secretion of IL-1β in AbM-treated macrophages. AbM-mediated IL-1β secretion also decreased in cells treated with cathepsin B inhibitor, suggesting that AbM can induce the release of cathepsin B. Furthermore, our data show that AbM-induced inflammasome activation requires the release of ATP, binding of extracellular ATP to the purinergic receptor P2X(7), the generation of reactive oxygen species, and efflux of potassium. Taken together, these findings reveal that AbM activates the NLRP3 inflammasome via multiple mechanisms, resulting in the secretion of IL-1β.

Mycelia products from wild-form Cordyceps sinensis could be constantly produced in a large scale and would be a better source of this herbal medicine. Our purpose was to investigate the immunological effects of an orally administered hot-water extract cultured mycelium of C. sinensis in lupus-prone (NZB/NZW) F1 hybrids. Forty female mice were divided into four groups and were given 2.4 mg/g/day oral doses of C. sinensis starting at three (group A), six (group B), or eight (group C) months of age, whereas the remaining group (group D) served as a control. Survival, proteinuria, and titers of anti-double-stranded DNA autoantibodies were evaluated. Treatment with C. sinensis resulted in increased survival, decreased proteinuria, and reduced titers of anti-double-stranded DNA antibody in groups A and B. Moreover, the mice in groups A and B showed significantly reduced percentages of CD4(+) T cells (*P < 0.05) and increased percentages of CD8(+) T cells in peripheral blood mononuclear cells (PBMC) after C. sinensis administration. At 6 months of age, the proliferation rate of BrdU-incorporated spleen cells was significantly decreased after 48 and 72 h of C. sinensis treatment (**P < 0.01) in group A of mice. In conclusions, early medication with C. sinensis induced the redistribution of PBMC and attenuated the disease severity of lupus in (NZB/NZW) F1 mice.

Dextromethorphan (DM), an anti-tussive agent, has been claimed to have anti-inflammatory and immunomodulatory effects in vitro. In our preliminary screening test, LK-4, an analog of DM, can afford more protection against circulatory failure induced by LPS than that of DM. Thus, the aim of this study was to evaluate the effects of LK-4 on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS; 10 mg/kg) in anesthetized Wistar rats and survival rate by intraperitoneal administration of LPS (70 mg/kg) in conscious ICR mice. Results demonstrated that posttreatment with LK-4 (3 and 5 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and tachycardia) in rats treated with LPS. Meanwhile, LK-4 (3 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-alpha, as well as values of GOT and GPT, and BUN and creatinine caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by LK-4. Moreover, infiltration of neutrophils into the lungs and liver of rats 8 h after treatment with LPS was also reduced by LK-4. Furthermore, LK-4 increased the survival rate of mice insulted by toxic dose of LPS. In conclusion, the beneficial effects of LK-4 on LPS-induced sepsis result from its anti-inflammatory and anti-oxidant effects. Thus, LK-4 can be potentially used as a therapeutic agent for sepsis in the future.

The objective of this study was to assess individual variation in inorganic arsenic methylation capability and the association between selenium levels in urine and blood, and inorganic arsenic methylation capability among residents of the Lanyang Basin who drank groundwater and were exposed to high concentrations of inorganic arsenic. According to the arsenic concentration of their drinking water, they were equally and randomly classified into four groups of 252 persons. It turned out that the higher the concentration of arsenic in well water was and thus the cumulative arsenic exposure, the higher the total inorganic arsenic metabolites in urine (total As(i)) and the overall inorganic and organic arsenic in urine (overall As(i+o)) were. The percentage of inorganic arsenic significantly decreased and the DMA percentage significantly increased as the concentration of urinary selenium and serum alpha-tocopherol increased. It appeared that urinary selenium levels increased the metabolism by methylation of arsenic, a finding that requires further investigation.