Acanthopanax senticosus cultures fermented by Lactobacillus rhamnosus enhanced immune response through improvement of antioxidant activity and inflammation in crucian carp (Carassius auratus).

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.

Bioinformatic Analysis on the Prognostic Value of Neurotransmitter Receptor-Related Genes in Kidney Renal Clear Cell Carcinoma.

Context: Kidney renal clear-cell carcinoma (KIRC) is a malignant tumor. At an early stage, KIRC patients may experience only mild fever and fatigue or even no symptoms, and these early nonspecific indications can delay treatment. Neurotransmitters and their receptors may be very useful in determining tumorigenesis and predicting metastasis. Objective: The study intended to investigate the predictive value of neurotransmitter receptor-related genes (NRRGs) using public KIRC data, by determining the biological processes that implicate the prognostic NRRGs and establishing a predictive NR-related risk model, to provide an empirical basis for identifying and treating KIRC patients. Design: The research team performed a genetic case-control study. Setting: The study took place at Research Center of Health, Big Data Mining and Applications, Wannan Medical College, Wuhu, China. Methods: The research team: (1) obtained the transcriptome data related to KIRC from the Cancer Genome Atlas (TCGA) and ArrayExpress databases; (2) developed the differentially expressed NRRGs (DENRRGs) by identifying the NRRGs that intersected with DEGs in KIRC and normal samples; (3) carried out functional enrichment analyses of the DENRRGs; (4) screened the characteristic genes of the DENRRGs using machine learning; (5) created a predictive model using multivariate Cox analyses of the distinctive genes; (6) obtained independent prognostic factors for KIRC patients and established a nomograph model; (7) investigated the sensitivity of KIRC patients to therapeutic agents to examine the variations in immunological features between high-risk and low-risk individuals. Results: Differential analysis found that 115 NRRGs intersected with 5275 DEGs to provide 52 DENRRGs. Functional enrichment showed that DENRRGs were mainly involved in signal transduction in the nervous system. The machine learning on the 52 DENRRGs filtered out nine characteristic genes. Subsequently, the research team found eight prognostic biomarkers-histamine receptor H2 (HRH2), gamma-aminobutyric acid (GABA) receptor subunit epsilon (GABRE), cholinergic receptor nicotinic delta subunit (CHRND), glutamate receptor ionotropic subunit 2D (GRIN2D), glutamate metabotropic receptor 4 (GRM4), glycine receptor alpha 3 (GLRA3), cholinergic receptor nicotinic beta 4 subunit (CHRNB4), and cholinergic receptor muscarinic-1 (CHRM1)-and established a predictive model. Furthermore, the team precisely predicted the KIRC patients' prognoses using a nomogram that combined their ages, risk scores, and M stages. The infiltration levels of 21 immune cells also significantly differed between the high-risk and low-risk groups, with neutrophils having a significant positive correlation with GABRE and HRH2 and a significant negative correlation with CHRNB4 and GRM4. Finally, the 50% inhibitory concentration (IC50) values for various drugs, such as 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR), 8-hydroxy-7-(6-sulfonaphthalen-2-yl)diazenyl-quinoline-5-sulfonic acid (NSC-87877), Sunitinib, c-Jun N-terminal kinase (JNK) inhibitor VIII, and tanespimyci (X17.AAG) were significantly lower for high-risk group. Conclusions: By studying the relevance of biomarkers to the immunological microenvironment of KIRC, the current research team was able to propose a new predictive model for KIRC based on NRRGs, to offer a novel viewpoint for investigating KIRC. The study's results suggest new avenues for research into the pathophysiology and therapy of KIRC. Determining the precise molecular processes by which predictive biomarkers regulate KIRC requires further evidence and analysis.

Neuroprotective Effects and Metabolomics Study of Protopanaxatriol (PPT) on Cerebral Ischemia/Reperfusion Injury In Vitro and In Vivo.

Stroke, one of the leading causes of disability and death worldwide, is a severe neurological disease that threatens human life. Protopanaxatriol (PPT), panaxatriol-type saponin aglycone, is a rare saponin that exists in Panax ginseng and Panax Noto-ginseng. In this study, we established an oxygen-glucose deprivation (OGD)-PC12 cell model and middle cerebral artery occlusion/reperfusion (MCAO/R) model to evaluate the neuroprotective effects of PPT in vitro and in vivo. In addition, metabolomics analysis was performed on rat plasma and brain tissue samples to find relevant biomarkers and metabolic pathways. The results showed that PPT could significantly regulate the levels of LDH, MDA, SOD, TNF-α and IL-6 factors in OGD-PC12 cells in vitro. PPT can reduce the neurological deficit score and infarct volume of brain tissue in rats, restore the integrity of the blood-brain barrier, reduce pathological damage, and regulate TNF-α, IL-1ß, IL-6, MDA, and SOD factors. In addition, the results of metabolomics found that PPT can regulate 19 biomarkers involving five metabolic pathways, including amino acid metabolism, arachidonic acid metabolism, sphingolipid metabolism, and glycerophospholipid metabolism. Thus, it could be inferred that PPT might serve as a novel natural agent for MCAO/R treatment.

Simplified regimen of combined low-dose rituximab for autoimmune encephalitis with neuronal surface antibodies.

BACKGROUND: Autoimmune encephalitis (AE) with neuronal surface antibodies (NSAbs) presents pathogenesis mediated by B cell-secreting antibodies. Rituximab is a second-line choice for the treatment for AE with NSAbs, which can cause B cell depletion via targeting CD20. However, the optimal protocol and dosage of rituximab combined with first-line therapy for NSAbs-associated AE remains unclear so far. In this study, we explored the efficacy and safety of low-dose rituximab combined with first-line treatment for NSAbs-associated AE. METHODS: Fifty-nine AE patients with NSAbs were enrolled, and retrospectively divided into common first-line therapy (41 patients) and combined low-dose rituximab (100 mg induction weekly with 3 circles, followed by 100 mg reinfusion every 6 months) with first-line therapy (18 patients). Outcome measures included changes in the Clinical Assessment Scale for Autoimmune Encephalitis (CASE) score (primary endpoint), changes in the modified Rankin Scale (mRS), the Mini-mental State Examination (MMSE), the patient and caregiver Neuropsychiatric Inventory (NPI) score at each visit (baseline, discharge, 6 months, 12 months and last follow-up) between two groups (secondary endpoint), as well as oral prednisone dosage, relapse and adverse effects during follow-up. RESULTS: Compared with traditional first-line therapy group, for primary outcome, CASE scores at last follow-up were significantly improved in combined rituximab group, as well as markedly improving changes of CASE scores between baseline and each visit. While changes of mRS, MMSE and NPI scores, as secondary endpoint, were all markedly accelerating improvement between baseline and each visit, as well as both oral prednisone dosage and relapse were also greatly reduced during follow-up. Meanwhile, longitudinal analysis in combination of rituximab cohort also revealed persistently marked amelioration in a series of scales from baseline even more than 1 year. Moreover, analysis in rituximab subgroup showed no difference in any clinical outcomes between combination with single first-line and with repeated first-line treatment (≥ 2 times), while compared to delayed combination with rituximab (> 3 months), early initiation of combination (≤ 3 months) might achieve better improvements in CASE and MMSE assessment even 1 year later. No rituximab-correlated serious adverse events have been reported in our patients. CONCLUSIONS: Our simplified regimen of combined low-dose rituximab firstly showed significantly accelerating short-term recovery and long-term improvement for AE with NSAbs, in parallel with markedly reduced prednisone dosage and clinical relapses. Moreover, opportunity of protocol showed earlier initiation (≤ 3 months) with better long-term improvement.

Immune enhancement effects of inactivated vaccine against extracellular products of Aeromonas caviae AC-CY on crucian carp.

Aeromonas caviae is a zoonotic pathogen that can cause disease in aquatic organisms and mammals, including humans, and it is widespread in nature, especially in freshwater environments. Previous research has reported that extracellular products (ECPs) secreted by pathogens during growth are effective protective antigens that can induce the host immune response and protect the host from pathogens. However, little is known about how ECPs enhance immunity. Here, we prepared extracellular products by the cellophane plate method, determined the total protein concentration, and analysed the protein composition of the extracellular products by SDS-PAGE. Subsequently, their enzyme activity and pathogenicity were evaluated separately. Crucian carp were randomly divided into four groups to receive formalin-inactivated A. caviae vaccine (FKC), ECPs mixed with the same amount of Freund's complete adjuvant, the same amount of ECPs mixed with an equal volume of A. caviae inactivated vaccine (FKC + ECPs), sterile PBS alone via intraperitoneal injection. On Days 7, 14, 21, and 28 after immunization, the expression levels of IgM, SOD, and CAT and the lysozyme (LYS) activity in the serum were detected by ELISA, and the relative expression levels of the TNF-α, IFN-γ, IL-1ß, and IL-10 genes in the liver, kidney, spleen, intestine, and gills were measured by qPCR. The extracellular products generated five clearly visible protein bands and exhibited lipase, protease, amylase, DNase and lysozyme but no urease or lecithinase activities. In addition, the median lethal doses of A. caviae and ECPs to crucian carp were 411.64 µg/fish and 1.6 × 105 CFU/mL, respectively. Compared with those of the control group, the IgM, SOD, and CAT contents and serum LYS activity were significantly increased in the experimental groups, and the qRT-PCR results showed that the relative expression levels of TNF-α, IFN-γ, IL-1ß, and IL-10 genes in the liver, kidney, spleen, and intestine were significantly increased after injection immunization. In addition, the relative immune protection rates of the three experimental groups were 60%, 65%, and 45%, all of which were significantly higher than those of the control group. Collectively, our findings show that the extracellular products of A. caviae can be used as a vaccine to significantly improve the immune level of crucian carp and have obvious anti-infection ability. This may represent a promising approach to prevent and control infection by A. caviae and provides strong theoretical support for the development of new inactivated vaccines.

Protective Effect of Ethyl Rosmarinate against Ulcerative Colitis in Mice Based on Untargeted Metabolomics.

Aiming at assessing the therapeutic effect of ethyl rosmarinate (ER) on ulcerative colitis (UC), the following activities were performed in vitro and in vivo in the present study. Firstly, a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model was established to determine the level of inflammatory factors. Then, a UC mice model induced by dextran sodium sulfate (DSS) was established to further investigate the effects of ER on symptoms, inflammatory factors and colon histopathology. Finally, serum and colon metabolomics studies were performed to identify the biomarkers and metabolisms closely related to the protective effect of ER on UC. The results showed that after ER intervention, the levels of inflammatory factors (NO, TNF-α, IL-1ß and IL-6) and key enzyme (MPO) in cell supernatant, serum or colon were significantly decreased, and the disease activity index and colon tissue damage in mice were also effectively improved or restored. In addition, 28 biomarkers and 6 metabolisms were found to be re-regulated by ER in the UC model mice. Therefore, it could be concluded that ER could effectively ameliorate the progression of UC and could be used as a new natural agent for the treatment of UC.

Integrated Metabolomics and Network Pharmacology to Decipher the Latent Mechanisms of Protopanaxatriol against Acetic Acid-Induced Gastric Ulcer.

Gastric ulcer (GU) is a peptic disease with high morbidity and mortality rates affecting approximately 4% of the population throughout the world. Current therapies for GU are limited by the high relapse incidence and side effects. Therefore, novel effective antiulcer drugs are urgently needed. Ginsenosides have shown good anti-GU effects, and the major intestinal bacterial metabolite of ginsenosides, protopanaxatriol (PPT), is believed to be the active component. In this study, we evaluated the anti-GU effect of PPT in rats in an acetic acid-induced GU model. High (H-PPT) and medium (M-PPT) doses of PPT (20.0 and 10.0 mg/mg/day) significantly reduced the ulcer area and the ET-1, IL-6, EGF, SOD, MDA and TNF-α levels in serum were regulated by PPT in a dose-dependent manner. We also investigated the mechanisms of anti-GU activity of PPT based on metabolomics coupled with network pharmacology strategy. The result was that 16 biomarkers, 3 targets and 3 metabolomic pathways were identified as playing a vital role in the treatment of GU with PPT and were further validated by molecular docking. In this study, we have demonstrated that the integrated analysis of metabolomics and network pharmacology is an effective strategy for deciphering the complicated mechanisms of natural compounds.

Protective Effects of Protopanaxatriol Saponins on Ulcerative Colitis in Mouse Based on UPLC-Q/TOF-MS Serum and Colon Metabolomics.

Ulcerative colitis (UC) is a chronic, nonspecific inflammation of the bowel that mainly affects the mucosa and submucosa of the rectum and colon. Ginsenosides are the main active ingredients in ginseng and show many therapeutic effects in anti-inflammatory diseases, cancer, and nervous system regulation. Protopanaxatriol saponin (PTS) is an important part of saponins, and there is no research on its pharmacological effects on colitis. In this study, a model of ulcerative colitis in mice was induced by having mice freely drink 3.5% dextran sodium sulfate (DSS) solution, and UPLC-Q-TOF-MS-based metabolomics methods were applied to explore the therapeutic effect and protective mechanism of PTS for treating UC. The results showed that PTS could significantly prevent colon shortening and pathological damage and alleviate abnormal changes in UC mouse physiological and biochemical parameters. Moreover, PTS intervention regulated proinflammatory cytokines such as TNF-α, IL-6, and IL-1 in serum, and MPO and NO in colon. Interestingly, PTS could significantly inhibit UC mouse metabolic dysfunction by reversing abnormal changes in 29 metabolites and regulating eleven metabolic pathways. PTS has potential application in the treatment of UC and could alleviate UC in mice by affecting riboflavin metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, retinol metabolism, and steroid hormone biosynthesis and by regulating pentose and glucuronate conversion, linoleic acid metabolism, phenylalanine metabolism, ether lipid metabolism, sphingolipid metabolism, and tyrosine metabolism, which points at a direction for further research and for the development of PTS as a novel natural agent.

Prediction of the molecular mechanism of eucommiae Cortex - Achyranthis bidentatae radix in the treatment of osteoarthritis: network pharmacology and molecular docking.

OBJECTIVE: To retrieve the core drug of osteoarthritis in clinic using Data Mining, predict the drug molecular action target through the Network Pharmacology, identify the key nodes of the interaction by combining with the related targtes of osteoarthritis, explore the pharmacological mechanism of Traditional Chinese Medicine against osteoarthritis and other possible mechanisms of actions. METHODS: to retrieve the commonly used therapeutic formulations for osteoarthritis patients in clinical with PubMed, CNKI, VIP, CBM, Wan Fang Database and other databases, and screen out the core drugs through the Ancient and Modern Medical Case Cloud Platform and software Gephi, filter out the core drug molecules and targets combined with TCMSP database and the targets of osteoarthritis in Genecard and OMIM database, plunge those data into R project and Cytoscape to construct the intersection model of Drug molecule-osteoarthritis, establish PPI network and GO and conduct KEGG enrichment analysis with String database. Vina molecular docking was finally implemented to draw molecular docking diagram, and the results were analyzed after comprehensive analysis. RESULTS: The core drug pairs were identified as 'Eucommiae Cortex - Achyranthis Bidentatae Radix' through correlation analysis, complex network analysis based on the coefficient. 'Eucommiae Cortex - Achyranthis Bidentatae Radix' can intervene cell behavior through multiple pathways and regulate cell metabolism, cytokine synthesis, oxidative and cellular immunity with the help of topology analysis in String Database. CONCLUSIONS: The core molecules of Quercetin and Kaempferol derived from 'Eucommia bark - achyranthes' can change the spatial conformation of PTGSs by hydrogen bonding with PTGSs, the hydrophobic bonds and van der Waals forces generated by Baicalein, Wogonin and ß-carotene, thereby changing the activity of PTGSs and affecting bone properties the process of osteoarthritis.

Effect of Electroacupuncture Treatment at Dazhui (GV14) and Mingmen (GV4) Modulates the PI3K/AKT/mTOR Signaling Pathway in Rats after Spinal Cord Injury.

Electroacupuncture (EA) is widely recognized as clinical treatment of spinal cord injury (SCI). The purpose of this study is to elucidate whether and how the PI3K/AKT/mTOR signaling pathway plays any role in EA treating SCI. Rats were randomly divided into four equal groups: Control Group, Sham-operation Group, Model Group, and EA Group, then further randomly divided into the following subgroups: 1-day (n = 12), 1-day rapamycin (n = 6), 14-day (n = 18), and 28-day (n = 18). A rat model of SCI was established by a modified Allen's weight-drop method. In the EA Group, rats were stimulated on Dazhui (GV14) and Mingmen (GV4) for 20 min by sterilized stainless steel needles. In the EA Group, the Basso, Beattie, and Bresnahan locomotor rating scale showed obvious improved locomotor function, and hematoxylin-eosin staining and magnetic resonance imaging showed that the histological morphology change of injured spinal cord tissue was obviously alleviated. Also, blocking spinal mTOR by injection of rapamycin showed that mTOR existed in the injured spinal cord, and EA could significantly activate mTOR in SCI rats. And immunohistochemistry and western blot analysis on the PI3K/AKT/mTOR signaling pathway showed that levels of PI3K, AKT, mTOR, and p70S6K in the injured spinal cord tissue were greatly increased in the EA Group, while the levels of PTEN and caspase 3 were decreased. The present study suggests that EA could affect cell growth, apoptosis, and autophagy through the PI3K/AKT/mTOR signaling pathway.

[Determination of lead in workplace air by portable X-ray fluorescence spectrometry].

OBJECTIVE: To investigate the permance index ofof portable X-ray fluorescence spectrometer in the determination of lead on filter membrane and to provide data for the determination of lead in workplace air. METHODS: Irradiated with X-ray, the lead would emit specific X-ray fluorescence during the process from the excited state back to the ground state. Rapid determination of lead was completed using fluorescence energy and wave length for qualitative analysis and fluorescence intensity for quantitative measurement. Under set conditions, a series of customized calibration samples were measured to create a standard curve for quantitative analysis of lead on filter membrane. RESULTS: The regression equation obtained using a portable X-ray fluorescence spectrometer to determine the lead on filter membrane was y=0.004x-0.182 (r2= 0.9999). The linear range was 0.00 -10.40 mg/m3, the minimum detectable concentration was 0.53 µg/m3, and the minimum quantifiable concentration was 1.76µg/m3. The relative standard deviation (RSD) of within-run precision of samples with different concentrations was 0.48%-6.22%, the RSD of between-run precision was 2.51%-5.09%, and the degree of accuracy was in the calibration range of standard samples. CONCLUSION: Portable X-ray fluorescence spectrometry is a simple, rapid, repeatable, and accurate method for the determination of lead on filter membrane.

A hybrid deep approach to recognizing student activity and monitoring health physique based on accelerometer data from smartphones.

Smartphone sensors have gained considerable traction in Human Activity Recognition (HAR), drawing attention for their diverse applications. Accelerometer data monitoring holds promise in understanding students' physical activities, fostering healthier lifestyles. This technology tracks exercise routines, sedentary behavior, and overall fitness levels, potentially encouraging better habits, preempting health issues, and bolstering students' well-being. Traditionally, HAR involved analyzing signals linked to physical activities using handcrafted features. However, recent years have witnessed the integration of deep learning into HAR tasks, leveraging digital physiological signals from smartwatches and learning features automatically from raw sensory data. The Long Short-Term Memory (LSTM) network stands out as a potent algorithm for analyzing physiological signals, promising improved accuracy and scalability in automated signal analysis. In this article, we propose a feature analysis framework for recognizing student activity and monitoring health based on smartphone accelerometer data through an edge computing platform. Our objective is to boost HAR performance by accounting for the dynamic nature of human behavior. Nonetheless, the current LSTM network's presetting of hidden units and initial learning rate relies on prior knowledge, potentially leading to suboptimal states. To counter this, we employ Bidirectional LSTM (BiLSTM), enhancing sequence processing models. Furthermore, Bayesian optimization aids in fine-tuning the BiLSTM model architecture. Through fivefold cross-validation on training and testing datasets, our model showcases a classification accuracy of 97.5% on the tested dataset. Moreover, edge computing offers real-time processing, reduced latency, enhanced privacy, bandwidth efficiency, offline capabilities, energy efficiency, personalization, and scalability. Extensive experimental results validate that our proposed approach surpasses state-of-the-art methodologies in recognizing human activities and monitoring health based on smartphone accelerometer data.

[Effect of acupuncture pretreatment of "Quchi"(LI11) and "Xuehai" (SP10) on mast cells and IL-33/ST2 in rats with urticaria].

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment at "Quchi "(LI11) and "Xuehai "(SP10) on expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and mast cell degranulation in sensitive area of skin tissue in rats with urticaria, so as to explore its mechanisms underlying prevention of urticaria. METHODS: A total of 32 male SD rats were randomly divided into blank control, model, EA preconditioning and medication groups, with 8 rats in each group. The urticaria model was established by topical injection of the prepared anti-ovalbumin serum (foreign serum, 0.1 mL/spot) along the bilateral sides of the spinal column on the back, followed by injection of mixture solution of ovalbumin, 0.5% evans blue and normal saline via the tail vein 48 h later. EA intervention (2 Hz/15 Hz, 1 mA) was applied to bilateral LI11 and SP10 for 20 min, once daily for 7 d before modeling.Back sensitization was started from the 5th day on. Rats of the medication group received gavage of loratadine, and those of the model group received gavage of the same volume of normal saline. The diameter of evans blue spots at the back skin tissue was measured; the histopathological changes of the blue spot tissues were observed by light microscope after H.E. staining. The state of degranulation of mast cells in the subcutaneous loose connective tissue was observed by using toluidine blue staining. Serum IgE and histamine contents were detected by ELISA, and the immunoactivity of IL-33 and ST2 in the skin and subcutaneous tissues of the sensitized spots (evans blue exudation spots) was observed by immunohistochemistry. RESULTS: Compared with the blank control group, the diameter of evans blue spot, degranulation rate of mast cells, serum IgE and histamine contents, and the immunoactivity of IL-33 and ST2 in the evans blue exudation spot tissues were significantly increased in the model group (P<0.01). In comparison with the model group, the increase of the above-mentioned indexes was reversed in both EA and medication groups (P<0.01，P<0.05). No significant differences were found between the EA and medication groups in down-regulating the levels of the 6 indexes. H.E. staining of the blue spot tissues of rats in the model group showed incomplete structure of the epidermal layer of the skin, unclear interface of tissues, incomplete keratinization, chaotic epidermal cells, disorderly arrangement of fibers in the dermis, and infiltration of inflammatory cells and edema, which was relatively milder in the EA and medication groups. CONCLUSION: EA preconditioning can prevent urticaria (reduce size and sensitive reactions) in rats, which may be associated with its functions in lowering the level of IgE through inhibiting IL-33 and ST2.

Pathogenesis of allergic diseases and implications for therapeutic interventions.

Allergic diseases such as allergic rhinitis (AR), allergic asthma (AAS), atopic dermatitis (AD), food allergy (FA), and eczema are systemic diseases caused by an impaired immune system. Accompanied by high recurrence rates, the steadily rising incidence rates of these diseases are attracting increasing attention. The pathogenesis of allergic diseases is complex and involves many factors, including maternal-fetal environment, living environment, genetics, epigenetics, and the body's immune status. The pathogenesis of allergic diseases exhibits a marked heterogeneity, with phenotype and endotype defining visible features and associated molecular mechanisms, respectively. With the rapid development of immunology, molecular biology, and biotechnology, many new biological drugs have been designed for the treatment of allergic diseases, including anti-immunoglobulin E (IgE), anti-interleukin (IL)-5, and anti-thymic stromal lymphopoietin (TSLP)/IL-4, to control symptoms. For doctors and scientists, it is becoming more and more important to understand the influencing factors, pathogenesis, and treatment progress of allergic diseases. This review aimed to assess the epidemiology, pathogenesis, and therapeutic interventions of allergic diseases, including AR, AAS, AD, and FA. We hope to help doctors and scientists understand allergic diseases systematically.

Effects of liraglutide on astrocyte polarization and neuroinflammation in db/db mice: focus on iron overload and oxidative stress.

Neuroinflammation plays a crucial role in the occurrence and development of cognitive impairment in type 2 diabetes mellitus (T2DM), but the specific injury mechanism is not fully understood. Astrocyte polarization has attracted new attention and has been shown to be directly and indirectly involved in neuroinflammation. Liraglutide has been shown to have beneficial effects on neurons and astrocytes. However, the specific protection mechanism still needs to be clarified. In this study, we assessed the levels of neuroinflammation and A1/A2-responsive astrocytes in the hippocampus of db/db mice and examined their relationships with iron overload and oxidative stress. First, in db/db mice, liraglutide alleviated the disturbance of glucose and lipid metabolism, increased the postsynaptic density, regulated the expression of NeuN and BDNF, and partially restored impaired cognitive function. Second, liraglutide upregulated the expression of S100A10 and downregulated the expression of GFAP and C3, and decreased the secretion of IL-1ß, IL-18, and TNF-α, which may confirm that it regulates the proliferation of reactive astrocytes and A1/A2 phenotypes polarize and attenuate neuroinflammation. In addition, liraglutide reduced iron deposition in the hippocampus by reducing the expression of TfR1 and DMT1 and increasing the expression of FPN1; at the same time, liraglutide by up-regulating the levels of SOD, GSH, and SOD2 expression, as well as downregulation of MDA levels and NOX2 and NOX4 expression to reduce oxidative stress and lipid peroxidation. The above may attenuate A1 astrocyte activation. This study preliminarily explored the effect of liraglutide on the activation of different astrocyte phenotypes and neuroinflammation in the hippocampus of a T2DM model and further revealed its intervention effect on cognitive impairment in diabetes. Focusing on the pathological consequences of astrocytes may have important implications for the treatment of diabetic cognitive impairment.

The Role of Iron Overload in Diabetic Cognitive Impairment: A Review.

It is well documented that diabetes mellitus (DM) is strongly associated with cognitive decline and structural damage to the brain. Cognitive deficits appear early in DM and continue to worsen as the disease progresses, possibly due to different underlying mechanisms. Normal iron metabolism is necessary to maintain normal physiological functions of the brain, but iron deposition is one of the causes of some neurodegenerative diseases. Increasing evidence shows that iron overload not only increases the risk of DM, but also contributes to the development of cognitive impairment. The current review highlights the role of iron overload in diabetic cognitive impairment (DCI), including the specific location and regulation mechanism of iron deposition in the diabetic brain, the factors that trigger iron deposition, and the consequences of iron deposition. Finally, we also discuss possible therapies to improve DCI and brain iron deposition.

Combined central and peripheral demyelination: a case report resembling encephalomyeloradiculoneuropathy.

Combined central and peripheral demyelination (CCPD) is an extremely rare disease characterized by inflammatory demyelination in both the central and peripheral nervous systems. Herein, we reported case of a 14-year-old teenager who initially presented with the symptoms of acute myelitis (AM). Subsequently, the patient developed symptoms consistent with Guillain-Barré syndrome (GBS), which was supported by nerve conduction studies (NCV) and cerebrospinal fluid (CSF) analysis. Throughout the course of the disease, the patient experienced abdominal pain and abnormal liver function. After a comprehensive evaluation, we determined that the abnormal liver function was a result of hepatitis E virus (HEV) infection, which may have acted as a trigger for GBS. The patient was treated with corticosteroids, intravenous immunoglobulin and Rituximab, resulting in symptom relief and clinical improvement after therapy and follow-up. This case highlights the potential responsiveness and reversibility of CCPD. Given the heterogeneous nature of CCPD, there is currently no standardized diagnostic criteria or clear consensus on its treatment. Therefore, we recommend a thorough assessment of all possibilities and the development of consolidated management guidelines based on available data for this disorder.

Finger Vein Verification on Different Datasets Based on Deep Learning with Triplet Loss.

In this study, deep learning and triplet loss function methods are used for finger vein verification research, and the model is trained and validated between different kinds of datasets including FV-USM, HKPU, and SDUMLA-HMT datasets. This work gives the accuracy and other evaluation indexes of finger vein verification calculated for different training-validation set combinations and gives the corresponding ROC curves and AUC values. The accuracy of the best result has reached 98%, and all the ROC AUC values are above 0.98, indicating that the obtained model can identify the finger veins well. Since the experiments are cross-validated between different kinds of datasets, the model has good adaptability and applicability. From the experimental results, it is also found that the model trained on the dataset that is more difficult to be distinguished will be a better and more robust model.

Liquid chromatography-mass spectrometry method for discovering the metabolic markers to reveal the potential therapeutic effects of naringin on osteoporosis.

The pharmacological effects and therapeutic targets of naringin (NG) against osteoporosis (OP) is still unclear. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) based non-targeted metabonomics has been used to explore the differentiated metabolites and potential biological pathways of NG in the pathological process of OP. Using network pharmacology analysis, the key protein targets of NG against OP were also screened. By the metabonomics analysis, a total of 33 differentiated metabolites in serum were discovered, of which 21 were significantly regulated by NG treatment. These metabolites majorly associated with to amino acid metabolism,polyunsaturated fatty acid metabolism, pyruvate metabolism and glycerophospholipidmetabolism. Using the network pharmacology prediction analysis, NG was related to the expression changes of 13 important protein targets. It showed that high-throughput metabonomics strategy integrated with network pharmacology could insight into molecular mechanisms of natural products.