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Emerging and re-emerging viral pandemics have emerged as a major public health concern. Highly pathogenic coronaviruses, which cause severe respiratory disease, threaten human health and socioeconomic development. Great efforts are being devoted to the development of safe and efficacious therapeutic agents and preventive vaccines to combat them. Nevertheless, the highly mutated virus poses a challenge to drug development and vaccine efficacy, and the use of common immunomodulatory agents lacks specificity. Benefiting from the burgeoning intersection of biological engineering and biotechnology, membrane-derived vesicles have shown superior potential as therapeutics due to their biocompatibility, design flexibility, remarkable bionics, and inherent interaction with phagocytes. The interactions between membrane-derived vesicles, viruses, and the immune system have emerged as a new and promising topic. This review provides insight into considerations for developing innovative antiviral strategies and vaccines against SARS-CoV-2. First, membrane-derived vesicles may provide potential biomimetic decoys with a high affinity for viruses to block virus-receptor interactions for early interruption of infection. Second, membrane-derived vesicles could help achieve a balanced interplay between the virus and the host's innate immunity. Finally, membrane-derived vesicles have revealed numerous possibilities for their employment as vaccines., (© 2024 Wiley‐VCH GmbH.)

Studies have reported variable effects of sex hormones on serious diseases. Severe disease and mortality rates in COVID-19 show marked gender differences that may be related to sex hormones. Sex hormones regulate the expression of the viral receptors ACE2 and TMPRSS2, which affect the extent of viral infection and consequently cause variable outcomes. In addition, sex hormones have complex regulatory mechanisms that affect the immune response to viruses. These hormones also affect metabolism, leading to visceral obesity and severe disease can result from complications such as thrombosis. This review presents the latest researches on the regulatory functions of hormones in viral receptors, immune responses, complications as well as their role in COVID-19 progression. It also discusses the therapeutic possibilities of these hormones by reviewing the recent findings of clinical and assay studies., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: Eosinophils have pivotal roles in the development of allergic rhinitis (AR) through the release of cytotoxic substances. Apolipoprotein A-I (Apo-AI) exhibits a strong inhibitory effect on eosinophil infiltration in allergic diseases. Nevertheless, the precise impact of Apolipoprotein A-I on eosinophils remains uncertain., Methods: Our study recruited a total of 15 AR children and 15 controls. The correlation between Apo-AI expression and the counts of blood eosinophils was examined. Flow cytometry was employed to assess the role of Apo-AI in eosinophil apoptosis and adhesion. The Transwell system was performed to conduct the migration assay. An animal model using AR mice was established to test the effect of Apo-AI on eosinophils., Results: Serum Apo-AI were negatively related to eosinophils counts and eosinophil chemotactic protein levels in AR. Apo-AI exerts a pro-apoptotic effect while also impeding the processes of adhesion, migration, and activation of eosinophils. The apoptosis triggered by Apo-AI was facilitated through the phosphoinositide 3-kinase (PI3K) pathway. The chemotaxis and activation of eosinophils, which are influenced by Apolipoprotein A-I, are regulated through the PI3K and MAPK signaling pathways. Apo-AI treated mice presented with decreased blood and nasal eosinophilic inflammation as well as down-regulated eosinophil related cytokines., Conclusion: Our findings provide confirmation that Apo-AI exhibits inhibitory effects on the function of eosinophils in allergic rhinitis. This suggests that Apo-AI holds potential as a therapeutic target for future treatment strategies., Competing Interests: The authors declare that they have no relevant conflicts of interest in this work., (© 2024 Zeng et al.)

Allergen-specific immunotherapy (AIT) has confirmed its efficacy in improving the symptoms of allergic rhinitis. However, no reliable biomarkers have been identified to predict the efficacy of AIT were found. We aimed to find clinical and immunological markers to predict efficacy in children after 2 years of sublingual immunotherapy (SLIT). A total of 285 children diagnosed with allergic rhinitis were recruited. The clinical efficacy was evaluated by comparing endpoint and baseline symptom and medication scores (SMS). Baseline clinical and immunological markers (serum total and specific immunoglobulin [Ig]E) and their correlation with clinical efficacy were analyzed. Of the 285 children recruited, 249 completed the 2-year SLIT program. After 2 years of SLIT, 68.3% of the children showed a significant response. Children in the Remarkable Response Group had the highest baseline SMS and most extended disease duration, followed by the Effective Relief and Unresponsive Group. Correlation analysis demonstrated that SMS improvement was positively correlated with baseline SMS (r=0.67) and disease duration (r=0.35). SMS improvement was not correlated with age, body mass index, total or specific IgE levels, or their ratios. Our results show that baseline SMS and disease duration can predict the efficacy of SLIT. Our study can guide the selection of suitable candidates for SLIT.

Background: Group 2 innate lymphoid cells (ILC2s) have been found to take part in type 2 inflammation by secreting T H 2 cytokines. Apolipoprotein A-I (Apo-AI), a major structural and functional protein of high-density lipoproteins, has anti-inflammatory effects on neutrophils, monocytes, macrophages, and eosinophils. However, its effects on ILC2s are not well characterized., Objective: We aimed to investigate the effect of Apo-AI on the proliferation and function of ILC2s as well as its possible mechanism., Methods: The protein expression of Apo-AI and the percentage of ILC2s in peripheral blood between 20 allergic rhinitis patients and 20 controls were detected by ELISA and flow cytometry. The effect of Apo-AI and miR-155 on ILC2 proliferation and function was detected by tritiated thymidine incorporation and ELISA. Anima models were adopted to verify the effect of Apo-AI in vivo ., Results: Elevated expression of Apo-AI was observed in allergic rhinitis patients. Apo-AI promotes ABCA1 expression by ILC2s, which can be inhibited by anti-Apo-AI. Apo-AI decreased ILC2 proliferation and the microRNA levels of GATA3 and RORα from ILC2s. The miR-155 overexpression promoted the upregulation of GATA3 and type II cytokines from ILC2s, while the addition of Apo-AI or miR-155 inhibitor significantly inhibited expression of GATA3 and type II cytokines by ILC2s. Apo-AI -/- mice showed as enhanced allergen-induced airway inflammation. The miR-155 inhibitor can reverse the enhanced allergen-induced airway inflammation in Apo-AI -/- mice, while miR-155 mimics can reverse the decreased allergen-induced airway inflammation in Apo-AI-treated mice., Conclusion: Apo-AI suppressed the proliferation and function of ILC2s through miR-155 in allergic rhinitis. Our data provide new insights into the mechanism of allergen-induced airway inflammation., Competing Interests: Supported by a National Natural Science Grant of China (grants 82271142 and 81970861), a Guangdong Province Natural Science grant (grant 2021A1515010940), and the Science and Technology Program of Guangzhou (grants 202201020600 and 202201011844), and the Scientific Research Capacity Improvement Project of Guangzhou Medical University (02-410-2302151XM). Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)

Background: Allergen-specific immunotherapy, including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), improves the disease progression of allergic rhinitis (AR). SCIT and SLIT exhibit similar efficacy, but SLIT has less systemic reactions. However, few studies have investigated the underlying mechanisms of SLIT treatment. In this study, we explored the efficacy of SLIT under different treatment durations and immunological changes., Methods: This retrospective study was conducted from August 2017 to August 2022 in our hospital. A total of 314 children who underwent SLIT were divided into the following groups based on their treatment duration: the 1 year group (6 months-1 year), the 2 years group (1-2 years), and the 3 years group (2-3 years). The treatment efficacy was confirmed using a combined symptom and medication score (SMS). Multiple serum cytokines were measured using Luminex. Various immune cells in PBMCs were determined using flow cytometry., Results: The total nasal symptom score (TNSS), rescue medication score (RMS), and SMS of the 3 years group was significantly different from those of the 1 years and 2 years groups. At the end of the 2 years following cessation of SLIT, the following results were observed in the 3 years group: 1) the TNSS, RMS, and SMS had significantly improved, 2) the serum IL-10, TGF-beta, and IL-35 levels had increased significantly, and 3) the percentages of regulatory T cell, regulatory B cell, and follicular regulatory T cell increased significantly., Conclusion: Our results suggest that 3 years of SLIT is necessary for long-term effects and continued immunological changes., Competing Interests: The authors declare that they have no relevant conflicts of interest., (© 2023 The Author(s).)

Background: Acute rhinosinusitis (ARS) is one of the common diseases of upper respiratory tract infection in children. Bacterial infection is a significant aggravating factor in pediatric ARS. In this research, our goal was to detected the bacterial flora and antibiotic sensitivity of ARS in Chinese children., Methods: We recruited 133 children with ARS between January 2020 and January 2022 from our hospital. Sinus secretion were collected and cultured for Gram stain as well as antimicrobial susceptibility tests., Results: Moraxella catarrhalis, Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa were detected in order in children with ARS, of which 25% were negative for bacterial culture and 10% were positive for two strains. Amoxicillin and clavulanate potassium were useful for Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Quinolones are useful for Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa., Conclusions: This research updates the proportion of ARS bacterial infection in children in southern China and the antibiotic sensitivity., (© 2023. The Author(s).)

Background: Interleukin-37b is a fundamental inhibitor of innate and acquired immunity. Type 2 innate lymphoid cells (ILC2s) can secret type 2 cytokines and regulate allergic rhinitis (AR). However, the role of IL-37b in ILC2s in children with AR was not clear., Methods: We recruited 15 AR children and controls. The serum IL-37b levels and its relation with the frequency and functional phenotype of ILC2s. The regulation of IL-37b on ILC2s proliferation and function was confirmed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-1R8, IL-18R α , and ICOSL was examined using RCR. The change of IL-37b protein level in serum during subcutaneous allergen immunotherapy (SCIT) was determined by ELISA., Results: We have demonstrated that both of the frequencies of blood ILC2s, IL-5+ILC2s, and IL-13+ILC2s in AR children were elevated compared with controls. The serum protein level of IL-37b was downregulated in AR, and it was negatively related to the frequency of ILC2s, IL-5+ILC2s, and IL-13+ILC2s. IL-37b increased the mRNA levels of IL-1R8, IL-18R α , and ICOSL expressed by ILC2s. IL-37b suppressed the proliferation of ILC2s and the secretion of IL-5 and IL-13 from ILC2s. Finally, we found that IL-37b was increased in AR children after 3 years' SLIT, especially in the good response group., Conclusion: Our findings highlight the role of IL-37b in the suppression of ILC2s and establish a new therapeutic target in AR., Competing Interests: The authors declare that they have no relevant conflicts of interest., (Copyright © 2023 Qingxiang Zeng et al.)

Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody-melittin (VAM) drug delivery platform was proposed and validated for targeted cancer combination therapy. VAM generated from the cellular plasma membrane was bio-synthetically fabricated, with the recombinant protein (hGC33 scFv-melittin) being harbored and displayed on the cell membrane. The bioactive and targetable nanomelittin conjugated by hGC33 scFv could be released in an MMP14-responsive manner at tumor sites, which reduced off-target toxicity, especially the hemolytic activity of melittin. Importantly, VAM could be loaded with small-molecule drugs or nanoparticles for combination therapy. Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co-delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM-based strategies represent a universal, promising approach to multimodal synergetic cancer therapy., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Abstract: A comprehensive analytical method based on isotope dilution-liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of acrylamide residue in cosmetics. Water-soluble cosmetic sample was extracted with water, and the extract was centrifuged, then the upper solution was cleaned up by an Oasis HLB solid phase extraction cartridge. Oil-soluble cosmetic sample was extracted by liquid-liquid partition with n-hexane and water. The qualitative and quantitative analyses were carried out for the analyte in the multiple reaction monitoring (MRM) mode after the chromatographic separation on a Waters Atlantis T3 column (150 mm x 2.1 mm, 3 microm). The quantification was performed with 13C3-acrylamide as internal standard. The limit of quantification (LOQ) for acrylamide was 0.1 mg/kg. The mean recoveries were 87.7%-95.8% at the spiked levels of 0.1-1.0 mg/kg with the intra-day precision less than 10% and the inter-day precision less than 12%. The method is suitable for the determination of acrylamide in cosmetics.

Background: The dialysis population has grown rapidly in recent decades. Despite the high cost and poor outcomes of dialysis treatment for ESRD, there are scant data about the level of renal function and the relationship of renal function and serum albumin at the start of dialysis in Chinese ESRD patients., Method: We report the level of serum creatinine (Scr), glomerular filtration rate (GFR), and serum albumin (Salb) in 514 ESRD in-patients who began their dialysis treatment between January 2001 through December 2007 at two large dialysis centers in Changsha, Hunan, China. Data were obtained through reviewing the case records of all 514 patients. GFR was predicted by an equation developed from the Modification of Diet in Renal Disease Study. In addition, serum albumin was analyzed in relation to levels of predicted GFR., Results: The mean (SD) and median predialysis serum creatinine was 1121.92 +/- 458.24 and 1032 micromol/L. The mean (SD) and median predicted GFR was 4.98 +/- 2.24 and 4.47mL/min/1.73m(2). The proportion of patients with predicted GFR of >10, 5 to 10, and <5 mL/min/1.73m(2) was 3.7, 36.2, and 60.1%, respectively. The mean predicted GFR was significantly lower among younger patients, uninsured patients, unemployed or farmer patients, patients who were employed, students, patients who selected hemodialysis, patients with ESRD caused by diseases other than diabetes, patients with BUN above the mean, and patients with hemoglobulin beneath the mean. Compared with patients who started with GFR >5mL/min, the patients who started with GFR

Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering the environment and eventually accumulating in the human body. Previous studies indicate that the impact of lanthanides on brain function cannot be neglected. Although neurological studies of trace elements are of paramount importance, up to now, little data are provided regarding the status of micronutritional elements in rats after prenatal and long-term exposure to lanthanide. The aim of this study is to determine the ytterbium (Yb) and trace elements distribution in brain and organic tissues of offspring rats after prenatal and long-term exposure to Yb. Wistar rats were exposed to Yb through oral administration at 0,0.1, 2, and 40 mg Yb/kg concentrations from gestation day 0 through 5 mo of age. Concentrations of Yb and other elements (Mg, Ca, Fe, Cu, Mn, and Zn) in the serum, liver, femur, and brain regions (cerebral cortex, hippocampus, cerebellum, and the rest) of offspring rats at the age of 0 d, 25 d, and 5 mo were analyzed by inductively coupled plasma-mass spectrometry. The accumulation of Yb in the brain, liver, and femur is observed; moreover, the levels of Fe, Cu, Mn, Zn, Ca, and Mg in the brain and organic tissues of offspring rats are also altered after Yb exposure. This disturbance of the homeostasis of trace elements might induce adverse effects on normal physiological functions of the brain and other organs.

Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering into the environment and eventually accumulated in human body. Recently, a new medicine, lanthanum carbonate (Fosrenol), has been used to treat chronic renal failure (CRF), and the dosage is much higher than the daily intake of lanthanides. However, the effects of lanthanides on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether long-term lanthanum exposure results in persistent alternations in nervous system function. Wistar rats were exposed to lanthanum chloride (LaCl(3)) through oral administration at 0, 0.1, 2 and 40mg/kg concentration from 4 weeks through 6 months of age. Morris water maze test showed that lanthanum exposure at 40mg/kg could significantly impair the behavioral performance. To fully investigate the neurotoxicological consequence of lanthanum exposure, brain elemental distributions and neurochemicals were also investigated. The distributions of brain elements such as Ca, Fe and Zn were significantly altered after lanthanum exposure. Moreover, 40mg/kg LaCl(3) significantly inhibited the activity of Ca(2+)-ATPase; the function of the central cholinergic system was also noticeably disturbed and the contents of some monoamines neurotransmitters were significantly decreased. These findings indicate that chronic exposure to lanthanum could possibly impair the learning ability and this deficit may be possibly attributed to the disturbance of the homeostasis of trace elements, enzymes and neurotransmitter systems in brain. Therefore, the application of lanthanide, especially in pharmacology, should be cautious.

The effects of subchronic exposure to lanthanum on rats' physical and neurobehavioral development were investigated. Wistar rats were exposed to lanthanum through oral administration at 0, 0.1, 2, and 40 mg/kg concentrations from gestation day 0 through 5 months of age. Prior to weaning of the pups, physical parameters and neurobehaviors were assessed, including body weight gain, pinna detachment, eye opening, surface righting reflex and swimming endurance. At 30 days of age, DNA concentration and protein/DNA ratio of the whole brain were determined. At 150 days of age, the Morris water maze test was carried out to study the memory and learning abilities of the rats. Differences were found in the body weight gain, surface righting reflex and swimming endurance. Moreover, lanthanum exposure significantly altered the DNA concentration and Protein/DNA in brain. The Morris water maze test showed that lanthanum exposure at 40 mg/kg significantly impaired memory and learning abilities. These findings indicate that lanthanum is a potential behavior teratogen. The information provided by this work should be considered in future applications of lanthanides.

It is well known that rare earth elements (REEs) have come into extensive use in a number of fields. As a result, REEs are becoming closely related to human's daily life. However, until now, the distributions of REEs in the brain are not yet very clear. In this study, Sprague-Dawley male rats were intraperitoneally injected with 0.25 mL of (153)SmCl(3) solution (containing 10 microg Sm). The brains were perfused with saline to minimize the blood influence. The radioactivities of (153)Sm in the five brain regions (hypothalamus, cerebellum, hippocampus, corpus striatum, and cerebral cortex) were counted. The results suggested that Sm did enter into the brain. Although only about 0.0003% of the given dose was accumulated in the brain, Sm seemed to be remain in the brain for a long time. The highest amounts and lowest concentrations of (153)Sm were found in the cerebral cortex, and the highest concentrations of (153)Sm were found in the hypothalamus.

It is well known that lanthanides have come into extensive and rapid use in a number of fields. As a result, more and more lanthanides are getting into the environment and food chains. However, the distributions of lanthanides in brain are not yet very clear. In this study, adult Sprague-Dawley male rats were intravenously injected with 0.5 ml of 169YbCl3 solution (containing 10 microg Yb). The brains were perfused with saline to minimize the blood influence. The radioactivities of 169Yb in the five brain regions (hypothalamus, cerebellum, hippocampus, corpus striatum and cerebral cortex) were counted. The results suggested that Yb did enter into the brain. Though only about 0.005% of the given dose was accumulated in the brain, Yb seemed to remain in the brain for long time. The highest specific activities were observed in the hypothalamus, hippocampus and cerebellum.