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In this paper, we propose and investigate novel closed-form point estimators for the beta distribution. The estimators of the first type are a modified version of Pearson's method of moments. The underlying idea is to involve the sufficient statistics, i.e., log-moments in the moment estimation equations and solve the mixed type of moment equations simultaneously. The estimators of the second type are based on an approximation to Fisher's likelihood principle. The idea is to solve two score equations derived from the log-likelihood function of generalized beta distributions. Both two resulted estimators are in closed forms, strongly consistent and asymptotically normal. In addition, through theoretical analyses and extensive simulations, the proposed estimators are shown to perform very close to the maximum likelihood estimators in both small and large samples, and they significantly outperform the method of moment estimators.

The deliberately origin mislabeling of sweet cherry causes significantly disruptions to market integrity and consumers' trust. In this study, 153 cherry samples from five provinces in China and the corresponding irrigation water and soil samples were collected. 5 stable isotope ratios (δ13C, δ15N, δ2H, δ18O, 87Sr/86Sr) and 8 multi-element contents (Na, Mg, P, K, Ca, Fe, Zn, Se) of cherry were determined by EA-IRMS and ICP-MS to study isotopic fractionation and elemental enrichment mechanisms for origin traceability. The results show the δ2H and δ18O of cherry exhibit a strong correlated with its irrigation water (r2 > 0.85), while δ15N, 87Sr/86Sr, Fe, Zn and Se contents are related to its cultivated soil (r2 > 0.75), and the δ13C is related to the local microclimate. ANOVA reveals that the regional differences of δ13C, δ2H, δ18O, 87Sr/86Sr as well as Na, Mg, Ca contents of cherry are significant (P

In the high-precision optoelectronic tracking system (OTS) based on a charge-coupled device (CCD), the boresight error extracted from the tracking image contains an undeniable delay, which directly limits the control bandwidth of visual tracking. High bandwidth means high response speed and tracking accuracy. Generally, a model-based delay compensation control method called the Smith predictor is utilized to separate time delay from the closed loop to promote the control bandwidth. However, due to the existence of errors between the established model and the real object, the improvement in the bandwidth is still limited to ensure system stability, resulting in insufficient tracking performance. In this paper, to solve the problem, a Smith predictor modified with pseudo feedforward control for the OTS is proposed. The experimental results demonstrate that the proposed method achieves significant improvements in tracking performance, reducing the maximum residual error at 1 Hz from 365 arcseconds (using the classic Smith predictor) to 283 arcseconds, a 22.5% improvement. Across the main frequency band (0.2 Hz to 2 Hz), the residual errors were consistently lower using the proposed method.

Internet technology is bound to be a big opportunity for agricultural marketing, how to effectively use the Internet technology innovation of agricultural marketing for the current focus of the research direction. The paper examines agricultural product marketing that is driven by Internet technology from the perspectives of agricultural product marketing mode innovation and marketing education mode innovation. The design of a mixed teaching mode for agricultural product marketing aims to cultivate talents in agricultural product Internet marketing technologies. The analysis of the development of agricultural product marketing education mode uses a comparative method and is divided into two stages: online marketing teaching and overall marketing mode teaching. The improved RFM model is used to solve the value of agricultural product customers, and the consumption characteristics of customers of different age stages are found. Among the four types of customer groups, 25-40-year-olds accounted for the highest proportion in the developing and maintaining customer groups, and 40-55-year-olds and 10-25-year-olds accounted for the highest proportion in the low-value customer and high-value customer groups. Agricultural product marketers should focus on customers under 55 years of age as the target of agricultural products, focusing on services and implementing precision marketing of agricultural products.

Abstract Aim To investigate the status and influencing factors of health information literacy in patients with intermediate‐stage chronic kidney disease (CKD). Design A prospective clinical study. Methods We used a CKD health information literacy questionnaire to survey 130 patients with intermediate‐stage CKD and valuate their health needs and health knowledge. We performed the study in strict accordance with the Guidelines for Clinical Trial Protocols. We registered the study in the Chinese Clinical Trial Registration Center (registration No. ChiCTR2100053103; approval No. K56‐1). Results The overall health information literacy of CKD was relatively low. Low education level, advanced age and unemployment were influencing factors. The scores of assessment ability, literacy awareness, application ability, integration ability and CKD health knowledge reserve were relatively low. The generalized linear model showed that the older the men, the lower their health information literacy.

Aiming at the deformation and fracture of shaft wall caused by freezing and thawing of topsoil and water pressure of aquifer in severe cold mining area, fiber bragg grating strain sensors are installed along the circumferential and longitudinal direction of shaft wall, the damage identification method of shaft wall structure is proposed, the real-time monitoring system of shaft wall deformation is established, and the deformation and failure threshold of concrete structure is determined through the compression test of concrete samples, and the real-time monitoring and early warning of shaft lining structure are realized. The monitoring results of the auxiliary shaft wall of Lingdong Coal Mine in severe cold mining area for nearly a year show that the shaft wall fiber bragg grating monitoring system can monitor in real time, has good stability, good coupling with concrete materials, and is easy to form a sensor monitoring network. The maximum circumferential strain and axial strain of shaft wall are both lower than the yield strength threshold of concrete, indicating that the shaft wall is in a stable stage at present.

Objective: This study aimed to improve the tenderness and flavor content of Yanbian cattle beef. Methods: Rump beef of Yanbian cattle were dry-aged by using three different methods, i.e., Method A: RH（65±5）% aging for 10 days, RH（75±5）% aging for 10 days, and then RH （85±5）% aging for 20 days; Method B: RH（75±5）% aging for 20 days and then RH（85±5）% aging for 20 days; Method C: RH（85±5）% aging for 40 days. The quality changes caused by the different aging processes were then analyzed and compared. Results: The cooking loss of the beef processed by all the three methods increased significantly with the extension of aging time, but the beef loss (39.14%) in Group A was the highest. The TBARS and TVB-N values of group C were 1.387 and 14.833, respectively, significantly higher than those of the other two groups. The fat and protein contents of each group showed an increasing trend, while the shear force value decreased by 50%. No significant difference in the changes of cooking loss rate, color and pH value were found among the groups. The results showed that with dry-aging, the richness of taste attributes was elevated with higher freshness and aftertaste. The bitterness in group B was lower, and the relative content of aldehydes and ketones among volatile flavor compounds was higher. Conclusion: Method B was the best dry-aging process for Yanbian cattle rump beef.

Abstract Extensive use of thermal energy in daily life is ideal for reducing carbon emissions to achieve carbon neutrality; however, the effective collection of thermal energy is a major hurdle. Thermoelectric (TE) conversion technology based on the Seebeck effect and thermal energy storage technology based on phase change materials (PCMs) represent smart, feasible, and research‐worthy approaches to overcome this hurdle. However, the integration of multiple thermal energy sources freely existing in the environment for storage and output of thermal and electrical energy simultaneously still remains a huge challenge. Herein, three‐dimensional (3D) nanostructured metal–organic frameworks (MOFs) are in situ nucleated and grown onto carbon nanotubes (CNTs) via coordination bonding. After calcination, the prepared core–shell structural CNTs@MOFs are transformed into tightened 1D/3D carbon heterostructure loading Co nanoparticles for efficient solar–thermoelectric energy harvesting. Surprisingly, the corresponding composite PCMs show a record‐breaking solar–thermal conversion efficiency of 98.1% due to the tightened carbon heterostructure and the local surface plasmon resonance effect of Co nanoparticles. Moreover, our designed all‐in‐one composite PCMs are also capable of creating an electrical potential of 0.5 mV based on the Seebeck effect without a TE generator. This promising approach can store thermal and electrical energy simultaneously, providing a new direction in the design of advanced all‐in‐one multifunctional PCMs for thermal energy storage and utilization.

Summary: Liquid phase leakage, intrinsic rigidity, and easy brittle failure are the longstanding bottlenecks of phase change materials (PCMs) for thermal energy storage, which seriously hinder their widespread applications in advanced energy-efficient systems. Emerging flexible composite PCMs that are capable of enduring certain deformation and guaranteeing superior mutual contact with integrated devices are considered as a cutting-edge effective solution. Flexible PCMs-based thermal regulation technology can reallocate thermal energy and regulate the temperature within an optimal range. Currently, tireless efforts are devoted to the development of versatile flexible PCMs-based thermal regulation devices, and a big step forward has been taken. Herein, we systematically outline fabrication techniques, flexibility evaluation strategies, advanced functions and advances of flexible composite PCMs. Furthermore, existing challenges and future perspectives are provided in terms of flexible PCMs-based thermal regulation techniques. This insightful review aims to provide an in-depth understanding and constructive guidance of engineering advanced flexible multifunctional PCMs.

Abstract Phase change materials (PCMs) can alleviate concerns over energy to some extent by reversibly storing a tremendous amount of renewable and sustainable thermal energy. However, the low thermal conductivity, low electrical conductivity, and weak photoabsorption of pure PCMs hinder their wider applicability and development. To overcome these deficiencies and improve the utilization efficiency of thermal energy, versatile carbon materials have been increasingly considered as supporting materials to construct shape‐stabilized composite PCMs. Despite some carbon‐based composite PCMs reviews regarding thermal conductivity enhancement, a comprehensive review of carbon‐based composite PCMs does not exist. Herein, a systematic overview of recent carbon‐based composite PCMs for thermal storage, transfer, conversion (solar‐to‐thermal, electro‐to‐thermal and magnetic‐to‐thermal), and advanced multifunctional applications, including novel metal organic framework (MOF)‐derived carbon materials are provided. The current challenges and future opportunities are also highlighted. The authors hope this review can provide in‐depth insights and serve as a useful guide for the targeted design of high‐performance carbon‐based composite PCMs.

Summary: Efficient thermal energy harvesting using phase change materials (PCMs) has great potential for thermal energy storage and thermal management applications. Benefiting from these merits of pore structure diversity, convenient controllability, and excellent thermophysical stability, SiO2-based composite PCMs have comparatively shown more promising prospect. In this regard, the microstructure-thermal property correlation of SiO2-based composite PCMs is still unclear despite the significant achievements in structural design. To enrich the fundamental understanding on the correlations between the microstructure and the thermal properties, we systematically summarize the state-of-the-art advances in SiO2-based composite PCMs for tuning thermal energy storage from the perspective of tailoring chemistry strategies. In this review, the tailoring chemistry influences of surface functional groups, pore sizes, dopants, single shell, and hybrid shells on the thermal properties of SiO2-based composite PCMs are systematically summarized and discussed. This review aims to provide in-depth insights into the correlation between structural designs and thermal properties, thus showing better guides on the tailor-made construction of high-performance SiO2-based composite PCMs. Finally, the current challenges and future recommendations for the tailoring chemistry are also highlighted.

Aiming at the problem of low voltage gain of traditional boost converter and the incompatibility of tracking speed and tracking accuracy with the traditional incremental conductance algorithm (INC), this paper uses the hybrid boost converter as the DC/DC converter of photovoltaic system, and designs the variable step size INC algorithm control strategy to achieve Maximum power point tracking (MPPT) of photovoltaic. Simulink simulation model verifies the feasibility of the proposed algorithm, which effectively improves the output voltage and power generation efficiency of the photovoltaic system.

Background: Allergic rhinitis (AR) is the most prevalent form of atopic disease. Undaria pinnatifida has potent antioxidative, antidiabetic, and anti-inflammatory properties., Aims: We investigated the immunomodulatory effect of Undaria pinnatifida extract (UPE) on allergic inflammation in an AR mouse model., Materials & Methods: Mice were sensitized and intranasally challenged with ovalbumin (OVA), and the Th1/Th2 and Th17/Treg-related cytokines and histopathology were exanimated after UPE treatments. Enzyme-linked immunosorbent assay was performed using serum samples and NALF to detect OVA-specific immunoglobulins and inflammatory cytokines. Mitogen-activated protein kinases (MAPKs) were measured by western blotting analysis, and an in vitro study measured mast cell activation induced by compound 48/80., Results: After UPE treatment, nasal and lung allergy symptoms, nasal mucosal swelling, and goblet cell hyperplasia were ameliorated. Oral UPE regulated the balance of Th1/Th2 and Th17/Treg cell differentiation in AR mice in a dose-dependent manner. In addition, UPE attenuated the migration of eosinophils and mast cells to the nasal mucosa by suppressing nuclear factor kappa B (NF-κB)/MAPKs. The levels of anti-OVA IgE and IgG 1 were also decreased., Discussion: UPE inhibited inflammation by regulating the NF-κB/MAPKs signaling pathway and supressing the activation of critical immune cells such as eosinophils and mast cells., Conclusion: UPE may have therapeutic potential for AR., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Mammalian oocytes not fertilized immediately after ovulation can undergo ageing and a rapid decline in quality. The addition of antioxidants can be an efficient approach to delaying the oocyte ageing process. Onion peel extract (OPE) contains quercetin and other flavonoids with natural antioxidant activities. In this study, we investigated the effect of OPE on mouse oocyte ageing and its mechanism of action. The oocytes were aged in vitro in M16 medium for 16 h after adding OPE at different concentrations (0, 50, 100, 200, and 500 μg/ml). The addition of 100 μg/ml OPE reduced the oocyte fragmentation rate, decreased the reactive oxygen species (ROS) level, increased the glutathione (GSH) level, and improved the mitochondrial membrane potential compared with the control group. The addition of OPE also increased the expression of SOD1 , CAT , and GPX3 genes, and the caspase-3 activity in OPE-treated aged oocytes was significantly lower than that in untreated aged oocytes and similar to that in fresh oocytes. These results indicated that OPE delayed mouse oocyte ageing by reducing oxidative stress and apoptosis and enhancing mitochondrial function.

Asthma is a chronic airway inflammatory disease listed as one of the top global health problems. Phaeanthus vietnamensis BÂN is a well-known medicinal plant in Vietnam with its anti-oxidant, anti-microbial, anti-inflammatory potential, and gastro-protective properties. However, there is no study about P. vietnamensis extract (PVE) on asthma disease. Here, an OVA-induced asthma mouse model was established to evaluate the anti-inflammatory and anti-asthmatic effects and possible mechanisms of PVE. BALB/c mice were sensitized by injecting 50 μg OVA into the peritoneal and challenged by nebulization with 5% OVA. Mice were orally administered various doses of PVE once daily (50, 100, 200 mg/kg) or dexamethasone (Dex; 2.5 mg/kg) or Saline 1 h before the OVA challenge. The cell infiltrated in the bronchoalveolar lavage fluid (BALF) was analyzed; levels of OVA-specific immunoglobulins in serum, cytokines, and transcription factors in the BALF were measured, and lung histopathology was evaluated. PVE, especially PVE 200mg/kg dose, could improve asthma exacerbation by balancing the Th1/Th2 ratio, reducing inflammatory cells in BALF, depressing serum anti-specific OVA IgE, anti-specific OVA IgG1, histamine levels, and retrieving lung histology. Moreover, the PVE treatment group significantly increased the expressions of antioxidant enzymes Nrf2 and HO-1 in the lung tissue and the level of those antioxidant enzymes in the BALF, decreasing the oxidative stress marker MDA level in the BALF, leading to the relieving the activation of MAPK signaling in asthmatic condition. The present study demonstrated that Phaeanthus vietnamensis BÂN, traditionally used in Vietnam as a medicinal plant, may be used as an efficacious agent for treating asthmatic disease.

Background: Particulate matter (PM) is a major component of air pollution from emissions from anthropogenic and natural sources and is a serious problem worldwide due to its adverse effects on human health. Increased particulate air pollution increases respiratory disease-related mortality and morbidity. However, the impact of PM with an aerodynamic diameter of ≤ 2.5 μm (PM2.5) on combined allergic rhinitis and asthma syndrome (CARAS) remains to be elucidated. Accordingly, in the present study, we investigated the effect of PM2.5 in an ovalbumin (OVA)-induced CARAS mouse model with a focus on NF-κB signaling., Methodology: We established an OVA-induced mouse model of CARAS to determine the effects of exposure to PM2.5. BALB/c mice were randomly divided into four groups: (1) naive, (2) PM2.5, (3) CARAS, and (4) CARAS/PM2.5. Mice were systemically sensitized with OVA and challenged with inhalation of ultrasonically nebulized 5% OVA three times by intranasal instillation of OVA in each nostril for 7 consecutive days. Mice in the PM2.5 and CARAS/PM2.5 groups were then exposed to PM2.5 by intranasal instillation of PM2.5 for several days. We then examined the impacts of PM2.5 exposure on histopathology and NF-κB signaling in our OVA-induced CARAS mouse model., Results: PM2.5 increased infiltration of eosinophils in bronchoalveolar lavage fluid (BALF) samples and inflammatory cells in lung tissue. It also increased production of GATA3, RORγ, IL-4, IL-5, IL-13, and IL-17 in nasal lavage fluid (NALF) and BALF samples in the CARAS mouse model, but secretion of IL-12 and IFN-γ was suppressed. Exposure to PM2.5 increased OVA-specific IgE and IgG 1 levels in serum, inflammatory cell infiltration in the airways, and fibrosis in lung tissue. It also activated the NF-κB signaling pathway, increasing Th2/Th17 cytokine levels while decreasing Th1 cytokine expression, thereby inducing an inflammatory response and promoting inflammatory cell infiltration in nasal and lung tissue., Conclusion: Our results demonstrate that PM2.5 can aggravate OVA-induced CARAS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A new terminology "combined allergic rhinitis and asthma syndrome (CARAS)" was introduced to describe patients suffering from both allergic rhinitis (AR) and asthma. The pathogenesis of allergic airway inflammation has been well known, with the main contribution of TH1/TH2 imbalance and mast cell degranulation. Artemisia gmelinii has been used as an herbal medicine with its hepaprotective, anti-inflammatory, and antioxidant properties. In this study, the effect of A. gmelinii extracts (AGE) on the ovalbumin (OVA)-induced CARAS mouse model was investigated. AGE administration significantly alleviated the nasal rubbing and sneezing, markedly down-regulated both OVA-specific IgE, IgG 1 , and histamine levels, and up-regulated OVA-specific IgG 2a in serum. The altered histology of nasal and lung tissues of CARAS mice was effectively ameliorated by AGE. The AGE treatment group showed markedly increased levels of the TH1 cytokine interleukin (IL)-12 and TH1 transcription factor T-bet. In contrast, the levels of the TH2 cytokines, including IL-4, IL-5, IL-13, and the TH2 transcription factor GATA-3, were notably suppressed by AGE. Moreover, AGE effectively prevented mast cell degranulation in vitro and mast cell infiltration in lung tissues in vivo. Based on these results, we suggest that AGE could be a potential therapeutic agent in OVA-induced CARAS by virtue of its role in balancing the TH1/TH2 homeostasis and inhibiting the mast cell degranulation.

Backgroud: The biological effect of phototherapy, which involves using visible light for disease treatment, has attracted recent attention, especially in dermatological practice. Light-emitting diode (LED) irradiation increases dermal collagen level and reduces inflammation. It has been suggested that thermal therapy and LED irradiation can modulate inflammatory processes. However, little is known about the molecular mechanism of the anti-inflammatory effects of thermal therapy and LED irradiation., Objective: This study was to determine the anti-inflammatory effect of thermal therapy combined with LED irradiation on trimellitic anhydride (TMA)-induced acute contact hypersensitivity (CHS) mouse model., Methods: Twenty-four BALB/c mice were randomly divided into the following groups: Vehicle group, TMA group, TMA + alternating thermal therapy group (Alternating group), and TMA + alternating + LED group (LED group). Ear swelling was measured based on the thickness of ear before and after each TMA challenge. Vascular permeability was evaluated by the extravasation of Evans blue dye. Serum IgE level, Th1/Th2/Th17 cytokines, and related transcription factors were measured using ELISA kits, and histological examination was illustrated in ear tissue., Results: The LED group showed reduction in ear swelling response, vascular permeability, serum IgE levels, Th2/Th17 cytokine levels, and inflammatory cell infiltration. Moreover, the LED group showed increased Th1 cytokine levels., Conclusions: These results indicate that thermal therapy combined with LED irradiation alleviated TMA-induced acute CHS in the mouse model. Thermal therapy and phototherapy should be considered as a novel therapeutic tool for the treatment of skin inflammation.

Fructus Amomi Cardamomi (FA) is the mature fruit of Amomum villosum Lour (family Zingiberaceae) and is commonly used in Chinese traditional medicine to treat various gastrointestinal disorders. FA's possible benefits as an allergic rhinitis (AR) treatment, however, have not been examined. We used an ovalbumin (OVA)-induced AR mouse model to identify any anti-allergic effects associated with the administration of 200 mg/kg FA or dexamethasone (Dex) 2.5 mg/kg by oral administration. The results of our testing confirm that FA ameliorated nasal symptoms and alleviated nasal epithelium swelling, reduced the goblet cell hyperplasia and eosinophil cell infiltration in the nasal epithelium, and inhibited lung tissue inflammation and Dex as well. Significantly decreased Th2 cytokine (interleukin (IL)-1β, IL-4, and IL-5) expression, and a correspondingly significant increase in Th1 cytokine (IL-12, interferon (IFN)-γ) production, was observed in nasal lavage fluid (NALF) taken from mice that received FA or Dex treatment. FA also reduced the presence of OVA-specific immunoglobulin (Ig) E, OVA-specific IgG1, and histamine levels in serum, and inhibited mast cell degranulation in vitro. In addition, these effects were involved with the reduction in NF-κB phosphorylation. These results suggest that FA restores Th1/Th2 balance and inhibits NF-κB phosphorylation and mast cell degranulation, thereby achieving a notable anti-inflammatory effect. Accordingly, it has the potential to be used as an efficacious therapeutic treatment for AR., (© 2022 The Author(s).)

Air pollution-related particulate matter (PM) exposure reportedly enhances allergic airway inflammation. Some studies have shown an association between PM exposure and a risk for allergic rhinitis (AR). However, the effect of PM for AR is not fully understood. An AR mouse model was developed by intranasal administration of 100 μg/mouse PM with a less than or equal to 2.5 μm in aerodynamic diameter (PM 2.5 ) solution, and then by intraperitoneal injection of ovalbumin (OVA) with alum and intranasal challenging with 10 mg/mL OVA. The effects of PM 2.5 on oxidative stress and inflammatory response via the Nrf2/NF-κB signaling pathway in mice with or without AR indicating by histological, serum, and protein analyses were examined. PM 2.5 administration enhanced allergic inflammatory cell expression in the nasal mucosa through increasing the expression of inflammatory cytokine and reducing the release of Treg cytokine in OVA-induced AR mice, although PM 2.5 exposure itself induced neither allergic responses nor damage to nasal and lung tissues. Notably, repeated OVA-immunization markedly impaired the nasal mucosa in the septum region. Moreover, AR with PM 2.5 exposure reinforced this impairment in OVA-induced AR mice. Long-term PM 2.5 exposure strengthened allergic reactions by inducing the oxidative through malondialdehyde production. The present study also provided evidence, for the first time, that activity of the Nrf2 signaling pathway is inhibited in PM 2.5 exposed AR mice. Furthermore, PM 2.5 exposure increased the histopathological changes of nasal and lung tissues and related the inflammatory cytokine, and clearly enhanced PM 2.5 phagocytosis by alveolar macrophages via activating the NF-κB signaling pathway. These obtained results suggest that AR patients may experience exacerbation of allergic responses in areas with prolonged PM 2.5 exposure.

Background: Panax ginseng is one of the most important medicinal plants and is usually harvested after 5 to 6 years of cultivation in Korea. Heavy metal (HM) exposure is a type of abiotic stress that can induce oxidative stress and decrease the quality of the ginseng crop. Siderophore-producing rhizobacteria (SPR) may be capable of bioremediating HM contamination., Methods: Several isolates from ginseng rhizosphere were evaluated by in vitro screening of their plant growth-promoting traits and HM resistance. Subsequently, in planta (pot tests) and in vitro (medium tests) were designed to investigate the SPR ability to reduce oxidative stress and enhance HM resistance in P. ginseng inoculated with the SPR candidate., Results: In vitro tests revealed that the siderophore-producing Mesorhizobium panacihumi DCY119 T had higher HM resistance than the other tested isolates and was selected as the SPR candidate. In the planta experiments, 2-year-old ginseng seedlings exposed to 25 mL (500 mM) Fe solution had lower biomass and higher reactive oxygen species level than control seedlings. In contrast, seedlings treated with 10 8 CFU/mL DCY119 T for 10 minutes had higher biomass and higher levels of antioxidant genes and nonenzymatic antioxidant chemicals than untreated seedlings. When Fe concentration in the medium was increased, DCY119 T can produce siderophores and scavenge reactive oxygen species to reduce Fe toxicity in addition to providing indole-3-acetic acid to promote seedling growth, thereby conferring inoculated ginseng with HM resistance., Conclusions: It was confirmed that SPR DCY119 T can potentially be used for bioremediation of HM contamination., Competing Interests: The authors declare that they have no conflicts of interest., (© 2020 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Panax ginseng was fermented using Lactobacillus fermentum KP-3, and the levels of the minor ginsenosides were measured. Then, the effect of fermented ginseng on alcohol-induced liver injury was investigated. C57BL/6N mice were randomly assigned to 4 groups: pair fed (PF), alcohol fed (AF), alcohol with non-fermented ginseng (AF + NFG) and alcohol with fermented ginseng (AF + FG) groups. After treatment for 8 weeks, fermented ginseng intervention significantly reduced the levels of serum ALT, AST, LPS, TG and TC compared with the AF group. The western-blotting results showed that fermented ginseng activated the adenosine-monophosphate-activated protein kinase (AMPK) pathway to inhibit de novo lipogenesis in the liver and inhibited phosphorylation of p38 through the mitogen-activated protein kinase (MAPK) pathway to alleviate hepatic inflammation, and these effects were superior than those of non-fermented ginseng. Furthermore, fermented ginseng reduced alcohol-induced liver oxidative damage by upregulating the levels of antioxidant enzymes. These findings suggested that the L. fermentum KP-3-fermented ginseng product may be used as a potential dietary nutraceutical for alleviating alcoholic liver injury.

Dryopteris crassirhizoma (DC) has a wide range of pharmacological effects, including antibacterial, anti‑influenza virus, anti‑tumor, anti‑reverse transcriptase and antioxidant effects. However, the inhibitory effect of DC on allergic inflammatory response remains unclear; therefore, the current study used an experimental ovalbumin (OVA)‑induced allergic asthma mouse model and phorbol myristate acetate (PMA)‑ and A23187‑stimulated HMC‑1 cells to reveal the effects of DC in regulating airway inflammation and its possible mechanism. Allergic asthma was initiated in BALB/c mice via exposure to OVA emulsified in aluminum, on days 1 and 14. Thereafter, the mice were treated with DC or dexamethasone (Dex) orally, before being challenged, from days 15 to 26. Subsequently, the mice were challenged with OVA on days 27, 28 and 29. The results of histological analysis indicated that the administration of DC decreased the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and suppressed eosinophilic infiltration, mucus production and collagen deposition in the lung tissue. DC treatment increased the level of T helper type 1 (Th1) cytokines (IL‑10 and interferon (IFN)‑γ) and decreased the levels Th2 cytokines (IL‑4, IL‑5 and IL‑13) and proinflammatory cytokines (IL‑6 and TNF‑α). Furthermore, DC treatment inhibited the activation of NF‑κB signaling (NF‑κB, p‑NF‑κB, IκB and p‑IκB), both in BALF and lung homogenates. Serum levels of total IgE and OVA‑specific IgE and IgG1 were significantly lower after DC treatment compared with after OVA treatment. However, the anti‑inflammatory effect of OVA‑specific IgG2a was higher after DC treatment. In addition, DC treatment attenuated the production of proinflammatory cytokines, including IL‑6 and TNF‑α, and the activation of NF‑κB signaling (NF‑κB and p‑NF‑κB), in PMA and calcium ionophore A23187‑stimulated HMC‑1 cells. In summary, the current study demonstrated that DC acts a potent anti‑allergic and anti‑inflammatory drug by modulating the Th1 and Th2 response and reducing the allergic inflammatory reaction in PMA and A23187‑stimulated HMC‑1 cells via NF‑κB signaling in an OVA‑induced allergic asthma model.

An ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model was established to investigate whether α-Lipoic acid (LA) has a protective effect against upper respiratory tract inflammation. BALB/c mice were sensitized by intraperitoneal injection and challenged by intranasal application of OVA. Mice were orally administered various doses of LA once daily (2, 10, 50 mg/kg) and dexamethasone (Dex; 2.5 mg/kg) 1 h before OVA challenge. Allergic nasal symptoms, levels of OVA-specific immunoglobulins, cytokines, and transcription factors were measured. Nasal and lung histopathology were evaluated. LA administration significantly alleviated the nasal symptoms such as rubbing and sneezing, markedly reduced both serum OVA-specific IgE and IgG1 levels. The LA treatment group showed markedly up-regulated levels of the Treg cytokine IL-10 and Treg transcription factor Foxp3. In contrast, it showed down-regulated levels of the Th17 cytokine IL-17 and the Th17 transcription factor STAT3, and RORγ. LA greatly enhanced the nuclear factor erythroid-derived 2/heme oxygenase 1 (Nrf2/HO-1) pathway signaling and inhibited the activation of NF-κB/IκB, markedly suppressed the levels of pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-8 and chemokine COX-2. The histologic alterations of nasal and lung tissues of AR mice were effectively ameliorated by LA. Based on these results, we suggest that LA could be a potential therapeutic agent in OVA-induced AR by virtue of its role in controlling the Th17/Treg balance and enhancing Nrf2/HO-1 pathway signaling.

Mangiferin (MF), extracted from mango trees, is considered to have anti-inflammatory, anti-apoptotic, and antioxidant effects. However, its effects on allergic rhinitis (AR), remain unclear. We investigated the mechanisms underlying the protective action of MF in ovalbumin (OVA)-induced AR models. AR was induced by OVA challenge in BALB/c mice. Prior to this, MF and dexamethasone were administered. Mice were examined for nasal mucosal inflammation, the generation of allergen-specific cytokine response, and histopathological changes in the nasal mucosa and lung tissue. MF ameliorated nasal symptoms and nasal mucosa inflammation in OVA-induced AR and reduced inflammatory cell infiltration and epithelial disruption in these tissues. MF inhibited the overproduction of Th2/Th17 cytokines and transcription factors. MF downregulated the HO-1/Nrf2 pathways, reduced oxidative stress biomarker levels, and the NF-κB signaling pathways were inhibited. MF exerts protective effects in AR by inhibiting NF-κB and activating HO-1/Nrf2 pathways. MF could be used for the treatment of AR.

Background: Piper nigrum L. (Piperaceae) is commonly used as a spice and traditional medicine in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the protective role of P. nigrum on epithelial function of upper respiratory tract injury in an allergic rhinitis (AR) mouse model has been unclear. This study aims to investigate the effects of P. nigrum fruit extract (PNE) on the nasal epithelial barrier function of the upper respiratory tract in an ovalbumin (OVA)-induced AR model., Methods: AR mouse model was established by intraperitoneal injection with 200 µL saline containing 50 µg OVA adsorbed to 1 mg aluminum hydroxide, and intranasal challenge with 20 µL per nostril of 1 mg/ml OVA. Besides, mice were orally administrated once daily with PNE and dexamethasone (Dex) in 13 days. The nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokines, nasal histopathology, and immunohistochemistry were evaluated., Results: The PNE oral administrations inhibited allergic responses via reduction of OVA-specific antibodies levels and mast cells histamine release, accordingly, the nasal symptoms in the early-phase reaction were also clearly ameliorated. In both nasal lavage fluid and nasal tissue, PNE suppressed the inflammatory cells accumulation, specifically with eosinophils. The intravenous Evans blue injection illustrated the epithelial permeability reduction of nasal mucosa layer in PNE-treated mice. Also; PNE treatments protected the epithelium integrity by preventing the epithelial shedding from nasal mucosa; as a result of enhancing the strong expression of the E-cadherin tight junction protein in cell-to-cell junctions, as well as inhibiting the degraded levels of zonula occludens-1 (ZO-1) and occludin into the nasal cavity. Additionally, PNE protected against nasal epithelial barrier dysfunction via enhancing the expression of Nrf2 activated form which led to increasing synthesis of the anti-inflammation enzyme HO-1., Conclusions: These obtained results suggest that PNE has a promising strategy for epithelial barrier stabilization in allergic rhinitis treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Allergic rhinitis (AR) is a type I hypersensitivity immune response and is a common chronic allergic respiratory disorder characterized by one or more nasal symptoms. Despite many studies on AR therapy, the drugs of treatment for AR remain limited in effect. In the present study, we aimed to elucidate the effects of saikosaponin A (SSA) on nasal inflammation, T helper (Th)2 and Th17 cytokines, retinoic acid-related orphan nuclear receptor (ROR)-γt, signal transducer and activator of transcription (STAT)3, and nuclear factor (NF)-κB signalings in ovalbumin (OVA)-induced AR mice model. OVA-induced AR mice exhibited increase in nasal symptoms, histological alteration, OVA-specific immunoglobulin (Ig)E/IgG1, ROR-γt, STAT3 and NF-κB signalings. However, the administration of SSA significantly decreased allergic symptoms including nasal rubbing and sneezing. Additionally, histological alterations such as mucosa layer thickness, goblet cell hyperplasia, eosinophils and mast cell infiltration in nasal tissues dramatically improved by treatment with SSA. Also, SSA treatment decreased the levels of OVA-specific IgE/IgG 1 in serum and the levels of Th2 and Th17 cytokines such as interleukin (IL)-6 and IL-17 in nasal lavage fluid (NALF). Moreover, SSA inhibited the activation of transcription factor ROR-γt, STAT3 and phosphorylated STAT3 in both NALF and lung. Futher, SSA could also significantly inhibit the expressions of NF-κB p65 and phosphorylated NF-κB p65 in NALF and lung. These present results suggested that SSA may attenuate OVA-induced allergic rhinitis through regulating the expression of IL-6/ROR-γt/STAT3/IL-17/NF-κB signaling. The results indicate that SSA may be used as a therapeutic candidate for allergic rhinitis disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Allergic rhinitis (AR) is an allergic nasal disease characterized by nasal obstruction, rhinorrhea, sneezing, and itching. Type 1 helper T cells (Th1)/type 2 helper T cells (Th2) imbalance has been identified as an important immunological mechanism of AR. In addition, up-regulation of type 17 helper T cells (Th17) also increase the risk of developing AR. Gallic acid (3, 4, 5-trihydroxybenzoic acid, GA), a polyphenol natural product, is obtained from various herbs, red wine, and green tea. It is known to have diverse biological effects such as anti-oxidation, anti-inflammation, anti-microbial and anti-cancer. In the present study, the effect of GA on airway inflammation and expression of Th1, Th2 and Th17 cytokines in an ovalbumin (OVA)-induced AR mouse model were investigated. GA alleviated the nasal allergic symptoms, reduced the thickness of nasal mucosa, attenuated goblet cell hyperplasia and eosinophil cell infiltration in the nasal mucosa, decreased the levels of interleukin (IL)-4, IL-5, IL-13 and IL-17 in nasal lavage fluid (NALF), and diminished the levels of OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a in serum. However, GA increased the expression of interferon-gamma and IL-12 in NALF. Taken together, it suggests that GA may be used as a therapeutic agent for AR., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Dryopteris crassirhizoma (DC) is used as a traditional herbal remedy to treat various diseases, the tapeworm infection, common cold, and cancer in Korea, Japan, and China. DC also has the antioxidant anti-inflammatory and antibacterial activities. However, the anti-allergic inflammatory effect of DC and some of its mechanisms in allergic rhinitis model are unknown well., Aim of This Study: The purpose of this study is to investigate the anti-allergic inflammatory effect of DC on the allergic rhinitis model, mast cell activation and histamine release., Materials and Methods: Allergic rhinitis was induced in BALB/c mice by sensitization and challenge with ovalbumin (OVA). Different concentration of DC and dexamethasone was administrated by oral gavage on 1 h before the OVA challenge. Mice of the control group were treated with saline only. Then mice were evaluated for the presence of nasal mucosa inflammation, the production of allergen-specific cytokine response and the histology of nasal mucosa., Results: DC significantly ameliorated the nasal symptoms and the inflammation of nasal mucosa. DC also reduced the infiltration of eosinophils and mast cells in these tissues and the release of histamine in blood. Meanwhile, DC evidently inhibited the overproduction of Th2 cytokines and increased the Th1 and Treg cytokines in nasal lavage fluid by OVA. DC also reduced the levels of OVA-specific IgE, IgG1 and IgG2a in blood., Conclusions: This study suggests that DC has a significant anti-allergic inflammatory effect in the nasal cavity. DC may have the therapeutic effect of allergic rhinitis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Rosae Multiflorae fructus has potent antioxidative, analgesic, and anti-inflammatory properties., Purpose: We investigated the immunomodulatory effect of Rosae Multiflorae fructus extract (RMFE) on allergic inflammation in an allergic rhinitis (AR) mouse model., Methods: Mice were sensitized and intranasally challenged with ovalbumin (OVA), the Th1/Th2-related cytokines and histopathology were examinated after RMFE treatments. Primary cell culture from spleen and NALT was performed to evaluate RMFE effect on Th1/Th2 responses. Four active components of RMFE were determined using HPLC and then tested the inhibition on Th2 response., Results: Oral administration of RMFE inhibited the accumulation of eosinophils in nasal lavage fluid (NALF) and the nasal mucosa, goblet cells in the nasal epithelium, and mast cells in the respiratory region of the nasal cavity. Thus, the swelling of the nasal epithelium, nasal-associated lymphoid tissue (NALT), and lung tissue were ameliorated. Furthermore, the RMFE suppressed Th2-related cytokines, such as IL-4, IL-5, and IL-13 in NALF, NALT, and splenocytes, whereas the Th1-associated cytokine IL-12 was up-regulated by RMFE. We also revealed the active components of RMFE, such as ellagic acid, hyperoside, isoquercitrin, and miquelianin. They may inhibit IL-4 secretion in allergic responses., Conclusion: RMFE may have therapeutic potential for treating AR by modulating the relationships between Th1/Th2 responses., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Cold and hot thermal therapies are widely used as a traditional therapy in many cultures and are often prescribed in the treatment of various musculoskeletal and neurological conditions which present themselves to primary care physicians. However, there are no reports that investigated either the effects of cold and hot thermal therapies on the skin inflammation of trimellitic anhydride- (TMA-) induced dermatitis-like contact hypersensitivity (CHS) mouse model, or the mechanism of thermal therapy on allergic skin inflammation. Therefore, in this study, to reveal the anti-inflammatory effect of thermal therapy and its mechanism on TMA-induced CHS, we analyzed ear-swelling response (ear edema), vascular permeability, serum IgE levels, histological examination, and histamine and Th2 cytokine levels. Cold thermal therapy reduced the ear-swelling response, the vascular permeability, the serum IgE levels, and the infiltration of eosinophils and mast cells as well as the mast cell degranulation. To determine the mechanism by which cold thermal therapy inhibits allergic skin inflammation, detailed studies were carried out revealing that cold thermal therapy suppressed IL-4 and IL-5 secretion and mast cell activation. These results indicated that cold thermal therapy cures skin inflammation of TMA-induced CHS by decreasing Th2 cytokine release, especially IL-4 and IL-5, and mast cell activation. These data suggest that new insight into the mechanism of robust therapeutic effects of cold thermal therapy against allergic dermatitis, and cold thermal therapy may prove to be a useful therapeutic modality on allergic inflammatory diseases as traditional use as well as Th2- or mast cell-mediated allergic responses.

Bupleurum chinense is distributed in East Asia and has been used as a traditional herbal medicine for more than a thousand years. Though B. chinense has been reported to have immunomodulatory, anti-inflammatory, anti-oxidant, hepato-protective, antipyretic, analgesic and antifibrotic effects, its specific effect on allergic rhinitis disease has not been clarified. In this study, we investigated the anti-allergic and anti-inflammation effects of B. chinense extract (BCE) in an ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model. Oral administration of BCE in a dose-independent manner regulated the balance of Th1/Th2/Treg cell differentiation in AR mice. Accordingly, BCE attenuated the expression of Th2-related cytokines such as IL-4, IL-5 and IL-13 in nasal lavage fluid (NALF) and nasal tissue and up-regulated the secretion of Th1/Treg cells including IL-10, IL-12 and IFN- γ . Also, BCE inhibited the formation and migration of eosinophils to the nasal mucosa and NALF, as well as suppressed CCL24, an eosinophil-specific chemoattractant in NALF. The levels of anti-OVA specific IgE and anti-OVA specific IgG1 were decreased, and as a result, the allergic response was attenuated by BCE via inhibiting mast cells accumulation in nasal mucosa and serum histamine release. The nasal allergy symptoms, nasal mucosal swelling, epithelial barrier disruption and mucus hyperplasia were obviously ameliorated. These results suggest that BCE may have therapeutic potential for treating allergic rhinitis through modulating the accumulation and activation of important leukocytes in the immune system such as Th1, Th2, Treg, eosinophils and mast cells.

Piper nigrum L. is commonly used as a traditional medicine and food in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the effect of P. nigrum on allergic rhinitis (AR) has been unclear. In the present study, an OVA-induced AR mice model were established to investigate the anti-allergic, anti-inflammation properties of P. nigrum fruit extract (PNE). Oral administrations of PNE inhibited the allergic nasal symptoms including rubbing and sneezing in the early-phage of AR. In both NALF and nasal tissue, PNE suppressed the inflammatory cells accumulation, specifically with eosinophils in NALF. Additionally, PNE prevented the activation of STAT3 and NFκBp65 signaling in the cytoplasm which led to increasing the synthesis of the anti-inflammatory Th1 cytokines and suppressing the inflammatory Th2, Th17 cytokines. These obtained results suggest that PNE has the promising strategy for immunotherapy in allergic rhinitis disease., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Lactobacillus fermentum KP-3 was isolated from Korean pickle and used to ferment ginseng. The changes in the minor ginsenosides in the fermented ginseng were analyzed and the material was evaluated in high fat diet-fed mice. Total ginsenosides increased from 0.746 mg g-1 to 0.939 mg g-1 after fermentation, and the levels of minor ginsenosides (Rg2, Rg3, Rh1, Rh2, F2, and Ro) increased from 0.186 mg g-1 to 0.704 mg g-1. In an animal study, the serum TC and LDL levels in the HFD group were significantly higher than those of the control group. Compared with the HFD group, the probiotic-fermented ginseng significantly decreased the serum TC and LDL levels. In addition, the serum and liver ALT and AST levels were dramatically increased in the HFD group, but these increases were significantly inhibited by treatment with the probiotic-fermented ginseng. Furthermore, fermented ginseng reduced high fat diet-induced liver lipid accumulation. Overall, fermentation with L. fermentum KP-3 enhanced minor ginsenosides in ginseng and this probiotic-fermented ginseng ameliorated hyperlipidemia and liver injury induced by a high fat diet.

Objective: To investigate the effect of miR-17-5p on vascular lesion and expression of very low density lipoprotein receptor (VLDLR) in atherosclerotic (AS) mice., Methods: ApoE -/- mice were fed with high fat diet for 15 weeks to establish atherosclerotic mice models, and these mice were injected with miR-17-5p inhibitor antagomiR-17-5p 20 mg/kg from week 13 to week 15 to interfere the expression of miR-17-5p. AS model group (injection of normal saline) and NC miRNA group (injection of negative control inhibitors) were set and C57BL/6 mice were fed with normal diet for 15 weeks as normal control group (NC group, injection of normal saline during week 13-15). HE staining was used to detect the pathological changes of arterial vessels in each group and the vascular morphological changes were measured as well, so as to investigate the therapeutic effect of interfering miR-17-5p on AS vascular lesions. According to the prediction of Targetscan target gene prediction database, VLDLR as the target gene of miR-17-5p, the distribution of VLDLR in vascular tissues of mice in each group was observed by immunofluorescence. The effect of miR-17-5p on the expression of VLDLR mRNA in the arterial tissues of each group was detected by real-time PCR, and the changes of VLDLR protein expression caused by miR-17-5p in the arterial tissues in each group was detected by Western blot., Results: The results of HE staining showed thatcompared with the NC group, the AS model group had obvious plaques in vascular endothelium, smooth muscle cell disorder and intimal hyperplasia, while the antagomiR-17-5p treated mice had significantly less lesions compared with the NC miRNA group. The intimal area of mice in the AS model group was bigger compared with NC group, but decreased after the inhibition of miR-17-5p. There was no statistically significant difference in the area of the media in each group. Vascular lumen area was smaller and intima/media ratio (I/M) values were lower in the AS model group and the NC miRNA group compared with the NC group, while the antagomiR-17-5p group alleviated this effect ( P <0.05). Immunofluorescence showed that the expression of VLDLR in the AS model group was decreased, and that in the antagomiR-17-p group was higher than that in the NC miRNA group. The expression of VLDLR gene in the AS model group was lower than that in the NC group ( P <0.01), while the VLDLR gene expression was higher in the antagomiR17-p group than that in the NC miRNA group ( P <0.05). The results of VLDLR expression detected by Western blot were similar., Conclusion: miR-17-5p inhibitors may effectively alleviate the pathological changes of arterial vessels in AS mice by up-regulating the expression of VLDLR in arterial tissues, and may become a new therapeutic target for AS disease., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Piper nigrum (Piperaceae) is commonly used as a spice and traditional medicine in many countries. P. nigrum has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the effect of P. nigrum on allergic asthma has not been known. This study investigated the effect of P. nigrum ethanol extracts (PNE) on airway inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic asthma model, we analysed the number of inflammatory cells and cytokines production in bronchoalveolar lavage fluid (BALF) and lung tissue; histological structure; as well as the total immunoglobulin (Ig)E, anti-OVA IgE, anti-OVA IgG 1 and histamine levels in serum. The oral administration (200 mg/kg) of PNE reduced the accumulation of inflammatory cells (eosinophils, neutrophils in BALF and mast cells in lung tissue); regulated the balance of the cytokines production of Th1, Th2, Th17 and Treg cells, specifically, inhibited the expressions of GATA3, IL-4, IL-6, IL-1β, RORγt, IL-17A, TNF-α and increased the secretions of IL-10, INF-γ in BALF and lung homogenate. Moreover, PNE suppressed the levels of total IgE, anti-OVA IgE, anti-OVA IgG 1 and histamine release in serum. The histological analysis showed that the fibrosis and infiltration of inflammatory cells were also ameliorated in PNE treated mice. On the other hand, PNE inhibited the allergic responses via inactivation of rat peritoneal mast cells degranulation. These results suggest that PNE has therapeutic potential for treating allergic asthma through inhibiting Th2/Th17 responses and mast cells activation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Allergic rhinitis is a common heterogeneous chronic upper airway disorder and is an IgE-mediated inflammation characterized by one or more nasal symptoms such as sneezing, itching, nasal discharge, rhinorrhea, post nasal drainage and nasal blockage. In the present study, the effects of skullcapflavone II (SCFII) on upper airway inflammation, Th2 cytokines, and NF-κB signaling in an ovalbumin (OVA)-induced allergic rhinitis (AR) murine model in vivo were investigated. OVA-induced AR mice increased nasal symptoms, eosinophils and mast cells infiltration into nasal cavity, OVA-specific IgE/IgG1 and histamine in serum, Th2 cytokines including IL-13 and GATA3, and NF-κB signaling in NALF and lung homogenate. Interestingly, treatment of SCFII reduced the levels of OVA-specific IgE/IgG1 and histamine in serum, of Th2 cytokines and of NF-κB signaling in the NALF and the lung homogenate, and histopathological changes in the nasal tissue and the lung. Also, dexamethasone suppressed such increases. The results of this study suggested that SCFII may ameliorate allergic inflammation of upper airway in AR mice model by blocking the Th2 cytokine production, the NF-κB signal pathway and the mast cell histamine release. Taken together, we suggest that SCFII may be used as a therapeutic agent for patients with Th2-mediated or mast cell-mediated allergic diseases., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Our earlier study showed that the width of the intact ellipsoid zone (EZ) of the photoreceptors was significantly but weakly correlated with the amplitudes of the focal macular ERGs (FMERGs). The aim of this study was to determine a microstructure of the photoreceptors in the spectral-domain optical coherence tomographic (SD-OCT) images that was more strongly correlated with the FMERG parameters in eyes with retinitis pigmentosa (RP)., Methods: This was a retrospective, observational study. The medical records of 65 patients with RP were reviewed. FMERGs were elicited by a 15-degree stimulus spot. The width of the EZ and the outer segment (OS) area surrounded by EZ and retinal pigment epithelium in the SD-OCT images within 15 degrees of the fovea were evaluated. Spearman correlation tests and multiple stepwise regression analyses were performed., Results: There was a strong correlation between the amplitudes of FMERGs and the EZ width (r = 0.68 for a-wave amplitude; r = 0.64 for b-wave amplitude), and also between the amplitudes of the FMERGs and the OS area (r = 0.69 for a-wave amplitude; r = 0.67 for b-wave amplitude). However, some patients had long EZ widths but had severely reduced FMERGs. Multiple stepwise regression analyses showed that the OS area was the only significant independent predictor of the amplitudes of FMERGs (P < 0.001)., Conclusions: The OS area might be a better morphological structure to use to predict the physiological function of the macula.

Bupleurum chinense belongs to the Bupleurum spp. family that has been used in traditional herbal medicine for over thousand years. It has been reported to have anti-inflammatory, anti-oxidant, hepato-protective, antipyretic, analgesic, anti-fibrotic and immunomodulatory effect. However, the effect of B. Chinense on allergic asthma remains unclear. This study investigated the immunomodulatory effects of B. Chinense extracts (BCE) on airway inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic asthma model, we evaluated the number of total cells, differential inflammatory cells and the production of proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung homogenate as well as histological structure. The levels of NFκB p65, IκBα, p-NFκB p65, p-IκBα and the total immunoglobulin (Ig) E, anti-OVA IgE, anti-OVA IgG were also examined. The oral administration of 200mg/kg BCE inhibited the accumulation of inflammatory cells especially eosinophils in BALF. Also, BCE regulated the imbalance of Th1, Th2 and Th17-related production, with attenuated the expression of GATA3, IL-1β, IL-4, IL-5, IL-6, TNF-α and RORγt, IL-17A in BALF and lung homogenate, meanwhile, up-regulated the secretion of INF-γ in lung homogenate. The levels of IgE, anti-OVA IgE, anti-OVA IgG1 and anti-OVA IgG2a were also suppressed by BCE treatment in serum. Futhermore, BCE inhibited the proinflammatory cytokines via inactivation of NFκB p65 phosphorylation and IκBα degradation in cytoplasm. The histological analysis showed that the infiltration of inflammatory cells, mucus hypersecretion and collagen fiber deposits were ameliorated in BCE treated mice. In addition, BCE induced the functional differentiation of naive CD4+ T cells forward to Th1 and Tr1 through producing INF-γ and IL-10. These results suggest that BCE may have therapeutic potential for treating allergic asthma through inhibiting Th2/Th17 cytokines production by inactivation of NFκB pathway., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Asthma is a chronic inflammatory disease of bronchial airway, which is characterized by chronic airway inflammation, airway edema, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration in the lungs. In this study, the therapeutic effect and the underlying mechanism of Citrus tachibana leaves ethanol extract (CTLE) in the ovalbumin (OVA)-induced allergic asthma and compound 48/80-induced anaphylaxis were investigated. Oral administration of CTLE inhibited OVA-induced asthmatic response by reducing airway inflammation, OVA-specific IgE and IgG1 levels, and increasing OVA-specific IgG2a levels. CTLE restored Th1/Th2 balance through an increase in Th2 cytokines tumor necrosis factor-α, interleukin (IL)-4, and IL-6 and decreases in Th1 cytokines interferon-γ and IL-12. Furthermore, CTLE inhibited the total level of NF-κB and the phosphorylation of IκB-α and NF-κB by OVA. In addition, CTLE dose-dependently inhibited compound 48/80-induced anaphylaxis via blocking histamine secretion from mast cells. The anti-inflammatory mechanism of CTLE may involve the modulation of Th1/Th2 imbalance via inhibiting the NF-κB signaling and histamine secretion. Taken together, we suggest that CTLE could be used as a therapeutic agent for patients with Th2-mediated or histamine-mediated allergic asthma.

Asthma is characterized by chronic inflammation, goblet cell hyperplasia, the aberrant production of the Th2 cytokines, and eosinophil infiltration into the lungs. In this study, we examined the effects of baicalein, wogonin, and Scutellaria baicalensis ethanol extract on ovalbumin (OVA)-induced asthma by evaluating Th1/Th2 cytokine levels, histopathologic analysis, and compound 48/80-induced systemic anaphylaxis and mast cell activation, focusing on the histamine release from rat peritoneal mast cells. Baicalein, wogonin, and S. baicalensis ethanol extract also decreased the number of inflammatory cells especially eosinophils and downregulated peribronchial and perivascular inflammation in the lungs of mice challenged by OVA. Baicalein, wogonin, and S. baicalensis ethanol extract significantly reduced the levels of tumor necrosis factor α, interleukin (IL)-1β, IL-4, IL-5 and the production of OVA-specific IgE and IgG1, and upregulated the level of interferon-γ and OVA-specific IgG2a. In addition, oral administration of baicalein, wogonin, and S. baicalensis ethanol extract inhibited compound 48/80-induced systemic anaphylaxis and plasma histamine release in mice. Moreover, baicalein, wogonin, and S. baicalensis ethanol extract suppressed compound 48/80-induced mast cell degranulation and histamine release from rat peritoneal mast cells. Conclusively, baicalein and wogonin as major flavonoids of S. baicalensis may have therapeutic potential for allergic asthma through modulation of Th1/Th2 cytokine imbalance and histamine release from mast cells.

Purpose: To evaluate the relationship between morphological changes and functional improvements assessed using focal macular electroretinograms after intravitreal aflibercept (IVA) injections in eyes with wet age-related macular degeneration., Methods: The clinical records of 42 eyes of 42 consecutive patients with naive, wet age-related macular degeneration received 3 monthly IVA were reviewed. The best-corrected visual acuity, central foveal thickness, outer retinal thickness, inner retinal thickness at baseline and 1 month after each IVA, and focal macular electroretinograms at baseline and 1 month after the first and third IVA were compared., Results: Best-corrected visual acuity was improved after the third IVA (P = 0.0091). Central foveal thickness and outer retinal thickness showed decreases after every IVA (P < 0.001, respectively). Inner retinal thickness showed a decrease after the second IVA (P = 0.002), after and third IVA (P = 0.001). On focal macular electroretinograms, a- and b-wave amplitudes showed increases after the third IVA (P = 0.0028, P = 0.0012, respectively). Significant correlations were observed between best-corrected visual acuity and central foveal thickness, a-wave amplitude and outer retinal thickness, and b-wave amplitude and inner retinal thickness changes after the third IVA., Conclusion: All parameters significantly recovered after three monthly IVA, with a correlation between functional improvements and morphological changes.

Trigonella foenum-graecum, a member oldest medicinal plant in the fabaceae (legumes) family, is used as a herb, spice, and vegetable, and known for its olfactory, laxative, and galactogogue effects. However, the inhibitory effect of Trigonella foenum-graecum on allergic inflammatory response remains unclear, therefore, we investigated the precise role of Trigonella foenum-graecum in the allergic asthma and revealed the effects of Trigonella foenum-graecum in regulating airway inflammation and its possible mechanism. Allergic asthma was initiated in BALB/c mice by sensitized with OVA emulsified in aluminum on days 1 and 14, then aerosol challenged with OVA on days 27, 28 and 29. Some mice were administered Trigonella foenum-graecum by oral gavage before challenge. Then mice were evaluated for the presence of airway inflammation, production of allergen-specific cytokine response and lung pathology. Trigonella foenum-graecum significantly ameliorated the number of inflammatory cells in BALF and alleviated lung inflammation. It also reduced the collagen deposition and goblet cells. Meanwhile, Trigonella foenum-graecum treatment evidently decreased the high expression of Th2 cytokines and increased the Th1 cytokines in BALF and lung homogenates. Trigonella foenum-graecum showed a significant inhibition of serum IgE and anti-OVA IgG 1. In this study, our data suggest that Trigonella foenum-graecum has a significant anti-inflammatory effect and it may prove to be an efficacious therapeutic regent on allergic asthma., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Mast cell-mediated anaphylactic reactions are involved in many allergic diseases, including asthma and allergic rhinitis. In Korea, where it has been used as a traditional medicine, Rosae Multiflorae fructus (RMF) is known to have potent antioxidative, analgesic, and anti-inflammatory activities and to have no obvious acute toxicity. However, its specific effect on asthma is still unknown. In this study, we evaluated whether or not RMF hot water extracts (RMFW) could inhibit ovalbumin (OVA)-induced allergic asthma and evaluated compound 48/80-induced mast cell activation to elucidate the mechanisms of asthma inhibition by RMFW. Oral administration of RMFW decreased the number of eosinophils and lymphocytes in the lungs of mice challenged by OVA and downregulated histological changes such as eosinophil infiltration, mucus accumulation, goblet cell hyperplasia, and collagen fiber deposits. In addition, RMFW significantly reduced T helper 2 cytokines, TNF-α, IL-4, and IL-6 levels in the BAL fluid of mice challenged by OVA. Moreover, RMFW suppressed compound 48/80-induced rat peritoneal mast cell degranulation and inhibited histamine release from mast cells induced by compound 48/80 in a dose-dependent manner. These results suggest that RMFW may act as an antiallergic agent by inhibitingTh2 cytokine production from Th2 cells and histamine release from mast cells, and could be used as a therapy for patients with Th2-mediated or mast cell-mediated allergic diseases.

Purpose: To determine whether a correlation exists between the parameters of the focal macular ERGs (FMERGs) and the microstructural changes of the photoreceptors after successful surgery for fovea-off rhegmatogenous retinal detachment (RRD)., Methods: Twenty eyes of 20 patients who had undergone successful surgery to reattach the retina in eyes with fovea-off RRD were studied. Focal macular ERGs and spectral-domain OCT (SD-OCT) were recorded at 1 and 6 months after the surgery. Changes of the components of the FMERGs, as well as changes of the SD-OCT parameters including the length of the external limiting membrane (ELM), ellipsoid zone (EZ), cone interdigitation zone (CIZ), and size of the outer photoreceptor area (between ELM and RPE), were determined., Results: During the postoperative period, the mean amplitudes of the a-waves increased by 1.4 times and the b-waves by 1.7 times. Spectral-domain OCT showed that the mean length of the EZ and CIZ and the size of the outer photoreceptor area had increased significantly at 6 months. The degree of the increase in the CIZ and outer photoreceptor area was significantly correlated with the increase in the amplitudes of the b-waves of the FMERGs (r = 0.56, P = 0.042, r = 0.57, P = 0.040, respectively; Spearman rank correlation test). However, the length of the EZ was not significantly correlated with the increase of the b-waves., Conclusions: A restoration of the EZ alone might not be enough to improve the FMERGs, and a restoration of the EZ accompanied by that of the CIZ was essential for the recovery of the FMERGs after fovea-off RRD.

Purpose: To compare the amplitudes and implicit times of the flicker electroretinograms before and after an intravitreal injection of ranibizumab (IVR) in eyes with a central retinal vein occlusion (CRVO)., Methods: We reviewed the medical records of 15 consecutive patients who had macular oedema secondary to CRVO and had received an IVR at the Nagoya University Hospital from November 2013 to July 2014. Flicker ERGs were recorded with both the RETeval(™) system and a conventional ERG system before the IVR. One month after the IVR, recordings were repeated with only the RETeval(™) system., Results: The mean implicit times of the flicker ERGs of the affected eyes recorded with the RETeval(™) system were significantly longer than that of the fellow eyes (32.2 ± 2.6 msec versus 28.1 ± 1.2 msec, p < 0.001). One month after the IVR, the implicit times of the flicker ERGs of affected eyes were significantly shortened from 32.2 ± 2.6 to 30.6 ± 2.2 msec (p < 0.001)., Conclusions: The shortening of the implicit times of the flicker ERGs after the IVR indicates an improvement of retinal function after anti-VEGF therapy for CRVO eyes., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Hemicentral retinal vein occlusion (hCRVO) is a disease related to CRVO but not to branch retinal vein occlusion (BRVO). We reported a significant correlation between aqueous vascular endothelial growth factor (VEGF) levels and the implicit time of 30-Hz flicker electroretinogram (ERG) in CRVO eyes. The purpose of this study was to compare aqueous VEGF levels and ERG components between hCRVO and BRVO eyes., Methods: The medical records of patients with macular edema secondary to hCRVO (12 eyes) or BRVO (16 eyes) and received an intravitreal injection of bevacizumab (IVB) at the Nagoya University Hospital from July 2009 to May 2013 were reviewed. Full-field ERGs were recorded before the IVB. Aqueous humor was collected just before the IVB to measure VEGF concentration. Differences in aqueous VEGF level and ERG components between hCRVO and BRVO eyes were determined., Results: Mean aqueous VEGF concentration in hCRVO eyes was significantly higher than that in BRVO eyes (504 vs. 148 pg/ml, P < 0.05). The implicit time of 30-Hz flicker ERG was significantly longer in hCRVO than in BRVO eyes (33.5 vs. 29.8 ms, P < 0.01)., Conclusion: The significant difference in VEGF levels in aqueous and implicit times of 30-Hz flicker ERG suggest that retinal ischemia is more manifest in hCRVO than in BRVO eyes.

Purpose: To study the effect of epiretinal membrane (ERM) removal on the function and structure of the retina, and to determine whether the functional changes were correlated with the changes in the thickness of different retinal layers., Methods: Focal macular electroretinography (FMERG) and spectral-domain optical coherence tomography (SD-OCT) were performed on 17 eyes of 15 patients before and after ERM surgery. The parafoveal retina was divided into an inner layer, a middle layer, and an outer layer in the OCT images. The thickness of each layer was measured before and after the ERM surgery. The a-wave, b-wave, and oscillatory potentials (OPs) of the FMERGs were analyzed before and after the ERM surgery., Results: The thickness of the inner and middle retinal layers was significantly reduced after surgery (by 39% and 23%, respectively). The mean amplitudes of the b-waves and OPs at 6 months postoperatively were significantly larger than those recorded preoperatively (by 21% and 61%, respectively). The ratios of the pre- to postoperative b-wave and OP amplitudes were correlated with the thickness reduction of the middle retinal layer (b-wave, r = -0.51, P < 0.05; OPs, r = -0.82, P < 0.01)., Conclusions: The significant correlations between the reduction in the thickness of the middle retinal layer and increase in the amplitude of the b-waves and OPs suggest that the improvement of macular function after ERM peeling is due to the decrease in the thickness of the middle retinal layer.

Purpose: To evaluate the changes in the best-corrected visual acuity (BCVA), macular thickness, and focal macular electroretinograms (FMERGs) after three intravitreal injections of bevacizumab for a choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD)., Methods: The medical records of 18 eyes of 18 patients who had received three consecutive monthly intravitreal injections of bevacizumab were retrospectively studied. The BCVA, macular thickness determined by optical coherence tomography (OCT), and FMERGs were measured before the first injection, and 10 days after each of the intravitreal bevacizumab injections., Results: The number of eyes with improvement in BCVA after the first injection was one (6%), after the second injection was four (22%), and after the third injection was five (28%). The number of eyes with reduction in macular thickness was 4 (33%), 8 (44%), and 10 (56%) after each of the three injections. The number of eyes with increase in b-wave amplitude of the FMERGs was 7 (38%), 6 (33%), and 10 (56%) after each of the three each injections. The mean macular thickness was significantly thinner after the first injection, and the mean BCVA was significantly improved after the second injection. The mean amplitude and implicit time of the b-wave of the FMERGs were significantly improved only after the third injection (P<0.05)., Conclusions: All parameters improved but the best was after the third injection, indicating that three monthly intravitreous injections with bevacizumab may be an effective treatment regimen for AMD.

Purpose: Central retinal vein occlusion (CRVO) leads to retinal ischemia, which then induces an upregulation of vascular endothelial growth factor (VEGF). The aim of this study was to determine whether a significant correlation exists between the ocular VEGF levels and the amplitudes and implicit times of different components of the electroretinogram (ERG) in eyes with a CRVO., Methods: The medical records of the 20 consecutive patients who had macular edema secondary to CRVO and were examined at the Nagoya University Hospital from November 2008 to February 2010 were reviewed. Because all the patients were scheduled to receive an intravitreal injection of bevacizumab (IVB), it was possible to collect samples of the aqueous humor before the IVB. The correlation between the different components of the ERGs and the VEGF concentration in the aqueous was determined., Results: The mean VEGF concentration of the aqueous humor was 416 pg/mL with a range of 100-1260 pg/mL. The b/a ratio of the single flash ERGs (P = 0.049; ρ = -0.45), implicit times of the cone a-wave (P = 0.028; ρ = 0.50), cone b-wave (P = 0.0059; ρ = 0.63), and 30 Hz flicker ERGs (P = 0.0058; ρ = 0.63) were significantly correlated with the VEGF concentration in the aqueous., Conclusions: The significant correlations between the different components of the ERGs and the aqueous VEGF concentration indicate that full-field ERGs can be used to detect the CRVO patients at a high risk of developing neovascularization of the iris.