Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis.

BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.

Comprehensive metabolome characterization and comparison between two sources of Dragon's blood by integrating liquid chromatography/mass spectrometry and chemometrics.

Dragon's Blood (DB) serves as a precious Chinese medicine facilitating blood circulation and stasis dispersion. Daemonorops draco (D. draco; Qi-Lin-Jie) and Dracaena cochinchinensis (D. cochinchinenesis; Long-Xue-Jie) are two reputable plant sources for preparing DB. This work was designed to comprehensively characterize and compare the metabolome differences between D. draco and D. cochinchinenesis, by integrating liquid chromatography/mass spectrometry and untargeted metabolomics analysis. Offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), by utilizing a powerful hybrid scan approach, was elaborated for multicomponent characterization. Configuration of an XBridge Amide column and an HSS T3 column in offline mode exhibited high orthogonality (A0 0.80) in separating the complex components in DB. Particularly, the hybrid high-definition MSE-high definition data-dependent acquisition (HDMSE-HDDDA) in both positive and negative ion modes was applied for data acquisition. Streamlined intelligent data processing facilitated by the UNIFI™ (Waters) bioinformatics platform and searching against an in-house chemical library (recording 223 known compounds) enabled efficient structural elucidation. We could characterize 285 components, including 143 from D. draco and 174 from D. cochinchinensis. Holistic comparison of the metabolomes among 21 batches of DB samples by the untargeted metabolomics workflows unveiled 43 significantly differential components. Separately, four and three components were considered as the marker compounds for identifying D. draco and D. cochinchinenesis, respectively. Conclusively, the chemical composition and metabolomic differences of two DB resources were investigated by a dimension-enhanced analytical approach, with the results being beneficial to quality control and the differentiated clinical application of DB.

[Characterization and identification of chemical components from Euodiae Fructus based on UHPLC-Q-TOF-MS].

A sensitive and efficient ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) approach was established. Based on the self-developed information library, the chemical components from Euodiae Fructus were systematically characterized and identified. The chromatographic separation conditions(e. g., stationary phase,mobile phase, column temperature, and elution gradient) and MS detection conditions(nozzle voltage, capillary voltage, fragmentor,and collision energy) were optimized. Ultimately, an HSS T3 column(2. 1 mm×100 mm, 1. 8 µm) maintained at 35 ℃ was used,and 0. 1% formic acid water-acetonitrile at the flow rate of 0. 4 m L·min~(-1) was used as the mobile phase. Electrospray ionization was adopted to collect the positive and negative ion mass spectrometry data in Auto MS/MS mode. According to the reference compound comparison, fragment ion information interpretation, literature, and retrieval in the self-developed information library, 92 compounds were characterized or derived from the decoction of Euodiae Fructus, including 33 alkaloids, 23 flavonoids, 12 terpenoids, 12phenylpropanoids, and 12 others. Among them, 17 compounds were identified by comparison with the reference compounds, and 11compounds were unreported from Euodiae Fructus. This study realizes the rapid characterization and identification of multi-class chemical components in the decoction of Euodiae Fructus and provides a reference for the studies regarding its effective substances and quality control.

miR-130a targets CiGadd45bb to modulate the inflammatory response to bacterial infection in Ctenopharyngodon idella kidney (CIK) cells.

Septicemia is a systemic inflammatory response to bacterial infection that results in a hyper-inflammatory state, which could lead to septic shock and death in grass carp (Ctenopharyngodon idella). The aim of this study was to determine the underlying mechanism of microRNA (miR-130a) in bacteria-infected grass carp. Expression levels of miR-130a against Aeromonas hydrophila (A. hydrophila) infection in Ctenopharyngodon idella kidney cells (CIK) were analyzed. Luciferase reporter assay, quantitative reverse transcription-polymerase chain reaction were performed to explore whether Ctenopharyngodon idella growth arrest and DNA damage-inducible 45 (CiGadd45bb) was a target of miR-130a. MiR-130a mimic, inhibitor and miR-control were transfected to CIK respectively. After transfection, the expression levels of proinflammatory genes were determined. Here we show that CiGadd45bb as a target of miR-130a. We also confirmed that miR-130a levels were significantly higher after being stimulated for 4 h and lower after 12 h (P < 0.01). Overexpressing miR-130a strikingly inhibited p38, JNK, ERK and TNF-a genes (P < 0.01) and silencing miR-130a activated p38, JNK, ERK, TNF-a, IFN and IL-8 (P < 0.01). Our results provide a theoretical basis for studying the molecular mechanism underlying the regulation of inflammation by miR-130a in grass carp.

Imbalance of multiple neurotransmitter pathways leading to depression-like behavior and cognitive dysfunction in the triple transgenic mouse model of Alzheimer disease.

Depression is among the most frequent psychiatric comorbid conditions in Alzheimer disease (AD). However, pharmacotherapy for depressive disorders in AD is still a big challenge, and the data on the efffcacy of current antidepressants used clinically for depressive symptoms in patients with AD remain inconclusive. Here we investigated the mechanism of the interactions between depression and AD, which we believe would aid in the development of pharmacological therapeutics for the comorbidity of depression and AD. Female APP/PS1/Tau triple transgenic (3×Tg-AD) mice at 24 months of age and age- and sex-matched wild-type (WT) mice were used. The shuttle-box passive avoidance test (PAT) were implemented to assess the abilities of learning and memory, and the open field test (OFT) and the tail suspension test (TST) were used to assess depression-like behavior. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to detect the level of neurotransmitters related to depression in the hippocampus of mice. The data was identified by orthogonal projections to latent structures discriminant analysis (OPLS-DA). Most neurotransmitters exert their effects by binding to the corresponding receptor, so the expression of relative receptors in the hippocampus of mice was detected using Western blot. Compared to WT mice, 3×Tg-AD mice displayed significant cognitive impairment in the PAT and depression-like behavior in the OFT and TST. They also showed significant decreases in the levels of L-tyrosine, norepinephrine, vanillylmandelic acid, 5-hydroxytryptamine, and acetylcholine, in contrast to significant increases in 5-hydroxyindoleacetic acid, L-histidine, L-glutamine, and L-arginine in the hippocampus. Moreover, the expression of the alpha 1a adrenergic receptor (ADRA1A), serotonin 1 A receptor (5HT1A), and γ-aminobutyric acid A receptor subunit alpha-2 (GABRA2) was significantly downregulated in the hippocampus of 3×Tg-AD mice, while histamine H3 receptor (H3R) expression was significantly upregulated. In addition, the ratio of phosphorylated cAMP-response element-binding protein (pCREB) and CREB was significantly decreased in the hippocampus of 3×Tg-AD mice than WT mice. We demonstrated in the present study that aged female 3×Tg-AD mice showed depression-like behavior accompanied with cognitive dysfunction. The complex and diverse mechanism appears not only relevant to the imbalance of multiple neurotransmitter pathways, including the transmitters and receptors of the monoaminergic, GABAergic, histaminergic, and cholinergic systems, but also related to the changes in L-arginine and CREB signaling molecules.

Anterolateral thigh flow-through flap: A versatile method for reconstruction of complex extremity defects.

BACKGROUND: Flow-through flaps have been widely applied only for the reconstruction of complex defects in the extremities because they can be used for arterial reconstruction and soft tissue coverage simultaneously. This report attempts to fully demonstrate the role of the anterolateral thigh (ALT) flow-through flap as a versatile method for reconstructing complex defects in the extremities. METHODS: From February 2011 to March 2017, we retrospectively analyzed the use of a reconstructive surgical technique based on the ALT flow-through flap to treat complex extremity defects in 87 patients (trauma, n = 79; diabetic ulcers, n = 5; squamous cell carcinoma, n = 3). Emergency surgery was performed in 12 patients to bridge a major artery gap and was followed by elective reconstruction in the remaining patients. Applications of the ALT flow-through flap included bridging major artery gaps, preserving recipient blood vessel integrity, reconstructing blood vessel continuity, protecting vascular anastomoses, avoiding difficult end-to-side anastomoses in the recipient area, and balancing blood flow, as well as combined application with an additional flap. RESULTS: The flap size ranged from 6 × 3 cm to 17 × 9 cm. ALT flow-through flaps were used in combination with an additional flap (n = 4) and in vascular reconstruction (n = 83). Three patients required of the microvascular anastomostic reexploration for venous congestion, total necrosis occurred in two patients, and partial necrosis occurred in one patient. At the donor site, there were three cases of infection and two cases of wound dehiscence. At the recipient site, one case of infection and two cases of wound dehiscence were observed. One patient presented with deep infection secondary to renal failure and underwent amputation. During the follow-up period (range, 1-33 months), all other flaps (84 cases) survived uneventfully, with normal texture and color. CONCLUSION: The ALT flow-through flap plays many roles as it is a versatile method for reconstructing complex defects of the extremities and serves various other clinical purposes.

[Content determination of ten flavonoids and alkaloids in Gleditsiae Sinensis Fructus, Gleditsiae Fructus Abnormalis, and Gleditsiae Spina].

To study the quality control of three traditional Chinese medicines derived from Gleditsia sinensis [Gleditsiae Sinensis Fructus(GSF), Gleditsiae Fructus Abnormalis(GFA), and Gleditsiae Spina(GS)], this paper established a multiple reaction monitoring(MRM) approach based on ultra-high performance liquid chromatography-triple quadrupole-linear ion-trap mass spectrometry(UHPLC-Q-Trap-MS). Using an ACQUITY UPLC BEH C_(18) column(2.1 mm × 100 mm, 1.7 µm), gradient elution was performed at 40 ℃ with water containing 0.1% formic acid-acetonitrile as the mobile phase running at 0.3 mL·min~(-1), and the separation and content determination of ten chemical constituents(e.g., saikachinoside A, locustoside A, orientin, taxifolin, vitexin, isoquercitrin, luteolin, quercitrin, quercetin, and apigenin) in GSF, GFA, and GS were enabled within 31 min. The established method could quickly and efficiently determine the content of ten chemical constituents in GSF, GFA, and GS. All constituents showed good linearity(r>0.995), and the average recovery rate was 94.09%-110.9%. The results showed that, the content of two alkaloids in GSF(2.03-834.75 µg·g~(-1)) was higher than that in GFA(0.03-10.41 µg·g~(-1)) and GS(0.04-13.66 µg·g~(-1)), while the content of eight flavonoids in GS(0.54-2.38 mg·g~(-1)) was higher than that in GSF(0.08-0.29 mg·g~(-1)) and GFA(0.15-0.32 mg·g~(-1)). These results provide references for the quality control of G. sinensis-derived TCMs.

Advances and challenges in ginseng research from 2011 to 2020: the phytochemistry, quality control, metabolism, and biosynthesis.

Covering: 2011 to the end of 2020Panax species (Araliaceae), particularly P. ginseng, P. quinquefolius, and P. notoginseng, have a long history of medicinal use because of their remarkable tonifying effects, and currently serve as crucial sources for various healthcare products, functional foods, and cosmetics, aside from their vast clinical preparations. The huge market demand on a global scale prompts the continuous prosperity in ginseng research concerning the discovery of new compounds, precise quality control, ADME (absorption/disposition/metabolism/excretion), and biosynthesis pathways. Benefitting from the ongoing rapid development of analytical technologies, e.g. multi-dimensional chromatography (MDC), personalized mass spectrometry (MS) scan strategies, and multi-omics, highly recognized progress has been made in driving ginseng analysis towards "systematicness, integrity, personalization, and intelligentization". Herein, we review the advances in the phytochemistry, quality control, metabolism, and biosynthesis pathway of ginseng over the past decade (2011-2020), with 410 citations. Emphasis is placed on the introduction of new compounds isolated (saponins and polysaccharides), and the emerging novel analytical technologies and analytical strategies that favor ginseng's authentic use and global consumption. Perspectives on the challenges and future trends in ginseng analysis are also presented.

Itinerant quantum critical point with fermion pockets and hotspots.

Metallic quantum criticality is among the central themes in the understanding of correlated electronic systems, and converging results between analytical and numerical approaches are still under review. In this work, we develop a state-of-the-art large-scale quantum Monte Carlo simulation technique and systematically investigate the itinerant quantum critical point on a 2D square lattice with antiferromagnetic spin fluctuations at wavevector [Formula: see text]-a problem that resembles the Fermi surface setup and low-energy antiferromagnetic fluctuations in high-Tc cuprates and other critical metals, which might be relevant to their non-Fermi-liquid behaviors. System sizes of [Formula: see text] ([Formula: see text]) are comfortably accessed, and the quantum critical scaling behaviors are revealed with unprecedented high precision. We found that the antiferromagnetic spin fluctuations introduce effective interactions among fermions and the fermions in return render the bare bosonic critical point into a different universality, different from both the bare Ising universality class and the Hertz-Mills-Moriya RPA prediction. At the quantum critical point, a finite anomalous dimension [Formula: see text] is observed in the bosonic propagator, and fermions at hotspots evolve into a non-Fermi liquid. In the antiferromagnetically ordered metallic phase, fermion pockets are observed as the energy gap opens up at the hotspots. These results bridge the recent theoretical and numerical developments in metallic quantum criticality and can serve as the stepping stone toward final understanding of the 2D correlated fermions interacting with gapless critical excitations.

Competing Nodal d-Wave Superconductivity and Antiferromagnetism.

Competing unconventional superconductivity and antiferromagnetism widely exist in several strongly correlated quantum materials whose direct simulation generally suffers from fermion sign problem. Here, we report unbiased quantum Monte Carlo (QMC) simulations on a sign-problem-free repulsive toy model with same on site symmetries as the standard Hubbard model on a 2D square lattice. Using QMC simulations, supplemented with mean-field and continuum field-theory arguments, we find that it hosts three distinct phases: a nodal d-wave phase, an antiferromagnet, and an intervening phase which hosts coexisting antiferromagnetism and nodeless d-wave superconductivity. The transition from the coexisting phase to the antiferromagnet is described by the 2+1-D XY universality class, while the one from the coexisting phase to the nodal d-wave phase is described by the Heisenberg-Gross-Neveu theory. The topology of our phase diagram resembles that of layered organic materials which host pressure tuned Mott transition from antiferromagnet to unconventional superconductor at half-filling.

[Ganoderma lucidum polysaccharides promote T lymphocyte infiltration into tumor by regulating expression of ICAM-1 in endothelial cells].

Polysaccharide is among the main active components of Ganoderma lucidum for tumor prevention and treatment. Howe-ver, it remains unclear whether it has synergy with tumor immunotherapy. This study evaluated the effect of G. lucidum polysaccharides(GLP) on the infiltration of T lymphocytes into tumor and the underlying mechanism, in order to provide a reference for its application in tumor immunotherapy. GLP were prepared by water extraction and alcohol precipitation combined with Sevag method and then given(intraperitoneal injection) to the mice bearing B16-F10 cells at 25, 50 and 100 mg kg~(-1), respectively, to evaluate the effect on tumor growth. The infiltration of CD3~+ and CD8~+ T cells and the expression of intercellular cell adhesion molecule-1(ICAM-1) in tumor were detected by immunohistochemistry. EA.hy926 cells were treated with 50, 100 and 200 µg·mL~(-1) GLP, and the expression of ICAM-1 was determined by Western blot. The adhesion of EA.hy926 cells treated with GLP was measured with fluorescence-labeled Jurkat cells. To analyze the mechanism based on NF-κB pathway, this study determined the protein levels of nuclear factor kappa-B(NF-κB) p65, alpha inhibitor of NF-κB(IκBα), p-NF-κB p65 and p-IκBα by Western blot. The results showed that GLP can significantly inhibit the tumor growth in mice bearing B16-F10 cells, promote the infiltration of CD3~+ and CD8~+ T cells in tumor, and increase the expression of ICAM-1 in tumor. Meanwhile, GLP could also enhance the expression of ICAM-1 in EA.hy926 cells, thus strengthen the adhesion to Jurkat cells, induce phosphorylation and protein degradation of IκBα, and raise the expression and phosphorylation level of NF-κB p65. These results suggested that GLP could promote the expression of ICAM-1 through NF-κB pathway and further enhance the infiltration of T lymphocytes into tumor, thereby inhibiting tumor growth. This study lays a foundation for the further application of GLP in tumor immunotherapy.

A prospective randomized controlled study on mouse nerve growth factor in the treatment of global developmental delay in children. / é¼ ç¥žç»ç”Ÿé•¿å› å­æ²»ç–—å ¨é¢æ€§å‘è‚²è¿Ÿç¼“çš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the clinical effect of mouse nerve growth factor (mNGF) in the treatment of children with global developmental delay (GDD). METHODS: A prospective clinical trial was conducted in 60 children with GDD who were treated in the First Affiliated Hospital of Anhui Medical University between July 2016 and July 2017. These children were randomly divided into two groups: conventional rehabilitation treatment and mNGF treatment group (n=30 each). The children in the conventional rehabilitation treatment group were given neurodevelopmental therapy, and those in the mNGF treatment group were given mNGF treatment in addition to the treatment in the control group. The evaluation results of the Gesell Developmental Scale were compared between the two groups before and after treatment. RESULTS: Before treatment and after 1.5 months of treatment, there was no significant difference in the developmental quotient (DQ) of each functional area of the Gesell Developmental Scale between the mNGF treatment and conventional rehabilitation treatment groups (P>0.05). After 3 months of treatment, the mNGF treatment group had significantly higher DQs of gross motor, fine motor, and personal-social interaction than the conventional rehabilitation treatment group (P˂0.05). The incidence rate of transient injection site pain after injection of mNGF was 7% (2/30), and there was no epilepsy or other serious adverse reactions. CONCLUSIONS: In children with GDD, routine rehabilitation training combined with mNGF therapy can significantly improve their cognitive, motor, and social abilities.

The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer's Disease: A Preclinical Study in APP/PS1 Transgenic Mice.

BACKGROUND: Depression is highly related to Alzheimer's disease (AD), yet no effective treatment is available. Phosphodiesterase-4 (PDE4) has been considered a promising target for treatment of AD and depression. Roflumilast, the first PDE4 inhibitor approved for clinical use, improves cognition at doses that do not cause side effects such as emesis. METHODS: Here we examined the effects of roflumilast on behavioral dysfunction and the related mechanisms in APPswe/PS1dE9 transgenic mice, a widely used model of AD. Mice at 10 months of age were examined for memory in the novel object recognition and Morris water-maze tests and depression-like behavior in the tail-suspension test and forced swimming test before killing for neurochemical assays. RESULTS: In the novel object recognition and Morris water-maze, APPswe/PS1dE9 mice showed significant cognitive declines, which were reversed by roflumilast at 5 and 10 mg/kg orally once per day. In the tail-suspension test and forced swimming test, the AD mice showed prolonged immobility time, which was also reversed by roflumilast. In addition, the staining of hematoxylin-eosin and Nissl showed that roflumilast relieved the neuronal cell injuries, while terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling analysis indicated that roflumilast ameliorated cell apoptosis in AD mice. Further, roflumilast reversed the decreased ratio of B-cell lymphoma-2/Bcl-2-associated X protein and the increased expression of PDE4B and PDE4D in the cerebral cortex and hippocampus of AD mice. Finally, roflumilast reversed the decreased levels of cyclic AMP (cAMP) and expression of phosphorylated cAMP response element-binding protein and brain derived neurotrophic factor in AD mice. CONCLUSIONS: Together, these results suggest that roflumilast not only improves learning and memory but also attenuates depression-like behavior in AD mice, likely via PDE4B/PDE4D-mediated cAMP/cAMP response element-binding protein/brain derived neurotrophic factor signaling. Roflumilast can be a therapeutic agent for AD, in particular the comorbidity of memory loss and depression.

CD23 expression on switched memory B cells bridges T-B cell interaction in allergic rhinitis.

BACKGROUND: The contribution of B-cell subsets and T-B cell interaction to the pathogenesis of allergic rhinitis (AR) and mechanisms of allergen immunotherapy (AIT) remain poorly understood. This study aimed to outline circulating B-cell signature, the underlying mechanism, and its association with clinical response to AIT in patients with AR. METHODS: IgD/CD27 and CD24/CD38 core gating systems were used to determine frequencies and phenotypes of B cells. Correlations between B cells, T cells, antigen-specific IgE, and disease severity in AR patients were investigated. Switched memory B cells were co-cultured with type 2 follicular helper T (Tfh2) cells and follicular regulatory T (Tfr) cells. Associations between B-cell subsets and clinical benefits of AIT were analyzed. RESULTS: Frequencies and absolute numbers of circulating memory B cells were increased in AR patients. CD23 expression on CD19+ CD20+ CD27+ IgD- switched memory B cells was significantly enhanced and positively correlated with antigen-specific IgE levels, symptom scores, and Tfh2/Tfr cell ratio in AR patients. Compared with those from healthy controls, Tfh2 cells from AR patients had a greater capacity to induce CD23 expression on switched memory B cells via IL-4, which was unable to be sufficiently suppressed by AR-associated Tfr cells with defective IL-10 expression. CD23 expression on switched memory B cells was downregulated after 12-month AIT, which positively associated with disease remission in AR patients. CONCLUSION: T-B cell interaction, bridged by CD23 expression particularly on switched memory B cells, may be involved in the disease pathogenesis and mechanism of AIT in patients with AR.

Effects of microRNA-731 on inflammation and apoptosis by targeting CiGadd45aa in grass carp.

Ctenopharyngodon idellagrowth arrest and DNA damage-inducible 45aa (CiGadd45aa) is a member of the Gadd45 family of immune-related proteins in grass carp. There is increasing evidence that microRNAs (miRNAs) are involved in the regulation of inflammatory responses and apoptosis. However, little is known about the regulatory effects of miRNAs on CiGadd45aa expression in grass carp. In the present study, CiGadd45aa was identified as a target gene of miR-731 based on miRNA expression profiling and dual-luciferase reporter assay. Our study revealed that miR-731 targets CiGadd45aa and regulates the expression of proinflammatory factors, thereby regulating immune response in grass carp. In addition, CiGadd45aa and miR-731 were both found induced apoptosis. Hence, our findings provide a theoretical basis for exploring the molecular mechanism by which miR-731 regulates inflammation and apoptosis in grass carp.

miR-23a-3p and miR-23a-5p target CiGadd45ab to modulate inflammatory response and apoptosis in grass carp.

Ctenopharyngodon idella growth arrest and DNA damage-inducible 45 ab (CiGadd45ab) is a subtype of the Gadd45a gene of the Gadd45 family in grass carp. There is increasing evidence that microRNAs (miRNAs) are involved in the regulation of inflammatory and apoptotic responses. However, little is known about the regulatory effects of miRNAs on CiGadd45ab expression. In the present study, CiGadd45ab was identified as a target gene of miR-23a-3p and miR-23a-5p, based on miRNA expression profiling and a dual-luciferase reporter assay. In addition, miR-23a-3p and miR-23a-5p were both confirmed to be involved in the inflammatory response following infection with Aeromonas hydrophila by targeting CiGadd45ab. Transfection with miR-23a-3p and miR-23a-5p mimics and inhibitor altered proinflammatory gene expression and apoptosis rate, thereby suggesting that miRNAs regulate immune response and anti-apoptosis by targeting CiGadd45ab in grass carp. Our results provide a theoretical basis for exploring the molecular mechanisms by which miR-23a-3p and miR-23a-5p target CiGadd45ab to regulate inflammation and apoptosis against bacterial infection in grass carp.

Identification, characterization, and immunological analysis of complement component 4 from grass carp (Ctenopharyngodon idella).

Complement component 4 (C4) has critical immunological functions in vertebrates. In the current study, a C4 homolog (gcC4) was identified in grass carp (Ctenopharyngodon idella). The full-length 5458 bp gcC4 cDNA contained a 5148 bp open reading frame (ORF) encoding a protein of 1715 amino acids with a signal peptide and eight conservative domains. The gcC4 protein has a high level of identity with other fish C4 counterparts and is phylogenetically clustered with cyprinid fish C4. The gcC4 transcript shows wide tissue distribution and is inducible by Aeromonas hydrophila in vivo and in vitro. Furthermore, its expression also fluctuates upon lipopolysaccharide or flagellin stimulation in vitro. During infection, the gcC4 protein level decreases or increases to varying degrees, and the intrahepatic C4 expression location changes. With gcC4 overexpression, interleukin 1 beta, tumor necrosis factor alpha, and interferon transcripts are all upregulated by A. hydrophila infection. Meanwhile, overexpression of gcC4 reduces bacterial invasion or proliferation. Moreover, gcC4 may activate the NF-κB signaling pathway. These findings demonstrate the vital role of gcC4 in the innate immunity of grass carp.

Adjuvant therapy with Astragalus membranaceus for post-stroke fatigue: a systematic review.

Post-stroke fatigue (PSF) is a common symptom after stroke and interferes with the rehabilitation. There are limited pharmacological therapies for managing PSF. Astragalus membranaceus (Huangqi) is a frequently used Chinese herbal medicine (CHM) in the treatment of fatigue in China. The aim of this review was to summarize the efficacy of adjuvant therapy with CHM Huangqi (CHM-HQ) in managing fatigue after stroke. We searched the databases in both English and Chinese for randomized controlled trials (RCTs) on CHM-HQ for PSF till November 2016. The Cochrane risk of bias tool was used to assess the quality of included trials, and the Review Manager 5.3 software was used to conduct the data analysis. Sixteen RCTs with a total of 1222 participants were included. The evidence was poor in quality with unclear or high risks of bias. Compared to routine intervention, treatment with CHM-HQ decreased the fatigue severity based on the assessment of the Fatigue Severity Scale, Fugl-Meyer and Visual Analogue Scale, and improved the quality of life as measured by the Stroke Specific Quality of Life scale, the Barthel index, and the modified Barthel index, while the adverse effects were mild. In conclusions, adjuvant therapy with CHM-HQ may benefit in managing fatigue and quality of life in stroke patients. However, stronger evidence is needed for a promising conclusion and more rigorous designs of RCTs are merited in the future.

Allergen immunotherapy improves defective follicular regulatory T cells in patients with allergic rhinitis.

BACKGROUND: The function of follicular regulatory T (TFR) cells, especially in regulating IgE production in patients with allergic diseases, is poorly understood. OBJECTIVE: We sought to investigate the phenotype, function, and clinical relevance of TFR cells in patients with allergic rhinitis (AR). METHODS: The phenotype and frequency of tonsillar and circulating TFR cells were characterized by using flow cytometry. TFR cell function was examined in an assay by coculturing with follicular helper T cells and B cells. The associations between TFR cells and the clinical features in patients with AR before and after allergen immunotherapy (AIT) were analyzed. RESULTS: TFR cells were detected in germinal centers of tonsils, but compared with subjects without AR, the frequencies decreased in patients with AR who were allergic to house dust mites. Circulating TFR cells in blood were phenotypically and numerically correlated with tonsillar TFR cells, and a reduction of circulating TFR cells but not total or CXCR5- regulatory T cells was noted in patients with AR compared with healthy control subjects. Moreover, circulating TFR cells in patients with AR showed a specific defect in suppressing IgE production but were capable of suppressing production of other immunoglobulin types. We identified negative associations of circulating TFR cell frequencies and function with antigen-specific IgE levels or disease severity in patients with AR. After AIT, the frequencies and function of circulating TFR cells were improved, which positively associated with disease remission. CONCLUSION: Impairment in TFR cells might contribute to aberrant IgE production in patients with AR, and AIT improves defective TFR cell function. TFR cells might serve as a potential biomarker to monitor clinical response to AIT.

[Clinical phenotypes and genetic features of families with Duchenne muscular dystrophy].

OBJECTIVE: To study the phenotypes and genetic features of families with Duchenne muscular dystrophy (DMD). METHODS: Seven children from six families with DMD diagnosed by gene testing were enrolled. The clinical and genetic features of the families were analyzed. RESULTS: There were two new mutations and four maternal inheritance mutations in the six families. The proband of family 1 had one point de novo mutation and one insertion de novo mutation of the DMD gene. Three families had point mutation, one family had fragment deletion of exon, and one family had fragment duplication of exon. The youngest age of onset of the probands was 6 months. All probands had skeletal muscle dyskinesia and significant changes in muscle enzymes, with different severities of clinical phenotypes. Three probands had mild mental retardation. The results of echocardiography were normal for all probands. The mother of the proband in family 6 had mild clinical phenotype. CONCLUSIONS: Gene testing can be used for the confirmed diagnosis of DMD. Mental retardation is a frequent clinical phenotype of DMD. The symptoms of myocardial involvement are not obvious in the early stage. Female carriers may have mild clinical symptoms.