Effects and safety of Ginkgo biloba on depression: a systematic review and meta-analysis.

Background: Because depression is a major factor contributing to the global disease burden, we tried to analyze the effects and safety of Ginkgo biloba (GKB) on patients with depression. Methods: We conducted a literature search for articles published between January 2002 and May 2022 in seven online databases (PubMed, Scopus, Embase, Google Scholar, Web of Sciences, Cochrane Library, and China National Knowledge Infrastructure). A systematic literature review and meta-analysis were performed to compare the effects and safety of GKB on patients with depression, including subjective and objective indicators of depression evaluation. Results: In total, 21 eligible articles with nine indicators among 2074 patients were included. Several outcomes showed a difference, and the GKB group had better results than the control group, including the Hamilton Depression Scale (HAMD), after taking GKB for 4 weeks (MD = -2.86, 95%CI [-4.27, -1.46], p < 0.01), 6 weeks (mean difference (MD) = -3.36, 95%CI [-4.05, -2.67], p < 0.01), and 8 weeks (MD = -4.58, 95% CI [-6.11, -3.05], p < 0.01), modified Barthel index (MBI) (MD = 14.86, 95%CI [12.07, 17.64], p < 0.01), modified Edinburgh-Scandinavian stroke scale (MESSS) (MD = -4.57, 95%CI [-6.34, -2.79], p < 0.01), brain-derived neurotrophic factor (BDNF) (MD = 16.35, 95%CI [7.34, 25.36], p < 0.01), 5-hydroxytryptamine (5-HT) (MD = 4.57, 95%CI [3.08, 6.05], p < 0.01), and clinical efficacy (risk ratio, RR = 1.24, 95%CI [1.17, 1.32], p < 0.01). However, there were no differences in adverse events between GKB and controls. Conclusion: In conclusion, the main finding was that patients treated with GKB had better MBI, MESSS, BDNF, 5-HT, and HAMD values after 4 weeks, 6 weeks, and 8 weeks than the control group. GKB might reduce the risk of depression or depressive symptoms with safe clinical efficacy. Systematic Review Registration: identifier (INPLASY2023100052).

Epidemiological survey and risk factor analysis of high-risk human papillomavirus in women in Longgang District, Shenzhen.

Objective: The objective of this study was to assess the prevalence of high-risk HPV infection in married women in Longgang District, Shenzhen, and to analyze the distribution of HPV subtypes across different age groups while identifying risk factors associated with HPV infection. Methods: 1. From January 2018 to December 2020, 209,627 married women in Longgang District were selected as study subjects, using high-risk HPV testing as the primary screening means. HPV 16 or 18 positive directly referred to colposcopy, other types positive continued liquid-based thin-layer cytology (TCT) examination, if ≥ ASCUS, referred to colposcopy, and biopsy if necessary. 2. 210 female patients who came to our hospital for HPV testing from January 2018 to December 2020 were used for the study, including 130 HPV-positive patients and 80 HPV-negative patients. The risk factors of HPV infection were studied by questionnaire. Results: The HPV infection rate in 2018 was 13.17%, including LSIL 6.87%, HSIL 3.57%, the single type infection rate was 79.83%, top5 monotypes were 52, 53, 16, 58, 81, multiple types infection rate was 20.17%, top5 multiple types were 52/ 53, 52/68, 16/52 52/58, 52/81; 2019 HPV positivity rate was 10.23%, including LSIL 5.98%, HSIL 5.81%, the monotypic infection rate was 82.5%, top5 monotypic were: 52, 16, 58, 51, 53, multi heavy sex infection rate was 17.5%, top5 multi typic were: 52/53, 52/58, 52/68, 16/52, 51/52; HPV positive rate in 2020 was 11.28%, including LSIL 6 %, HSIL 4.84%, monotypic infection rate was 79.89%, top5 monotypic were: 52, 16, 53, 58, 51, multiheavy category infection rate was 20.11%, top5 multitypic were: 52/58, 16/52, 52/68, 52/53, 51/52. 30-50 years old is the high prevalence age of HPV susceptibility, followed by 50-60 years old, and HPV52 is the most common type. 2. 210 female patients were surveyed by filling out questionnaires: Smoking history, age at first sex, age at first pregnancy, abortion, number of sexual partners, contraceptive method, bleeding during intercourse, cervicitis, vaginitis, sleeping habits, and mental status totaling 11 factors were significant between infected and control (P < .05). Dichotomous logistic regression analysis with these 11 factors as independent variables and HPV infection as dependent variable revealed that abortion (OR=2.117, 95% CI: 1.337-3.354), number of sexual partners (OR=2.562, 95% CI: 1.222-5.373), cervicitis (OR=2.873, 95% CI: 1.407-5.868), vaginitis (OR=2.413, 95% CI: 1.158-5.026) staying up late (OR=2.408, 95% CI: 1.134-5.115) and mental status (OR=3.139, 95% CI: 1.470-6.703) were six factors that were risk factors for HPV infection. Conclusion: The common HPV infection types among women in Longgang district were mainly 52, 16, 58, 53, and 51, with a predominance of a single type of infection. The positive rate and pathogenicity of HPV 52 were higher than HPV 16. Women aged 30-60 years should be included in priority screening for cervical lesions. The six factors of miscarriage, number of sexual partners, cervicitis, vaginitis, staying up late, and mental status were risk factors for HPV infection occurrence.

Clinicopathological characteristics and gene mutations in 11 patients with lipoprotein glomerulopathy.

OBJECTIVE: Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E (APOE) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients. METHODS: Clinicopathological and follow-up data were obtained by extracting DNA, followed by APOE coding region sequencing analysis. This study analyzed clinical and pathological manifestations, gene mutations, treatment and prognosis. RESULTS: The mean age of the eleven patients was 33.82 years. Among them, five had a positive family history for LPG, ten presented with proteinuria, four exhibited nephrotic syndrome, and six presented with microscopic hematuria. Dyslipidemia was identified in ten patients. In all renal specimens, there was evident dilation of glomerular capillary lumens containing lipoprotein thrombi, and positive oil red O staining was observed in frozen sections of all samples. APOE gene testing revealed that one patient had no mutations, while the remaining ten patients exhibited mutations in the APOE gene, with three patients presenting with multiple mutations simultaneously. Following the confirmation of LPG diagnosis, treatment with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) was initiated, and the disease progressed slowly. CONCLUSION: LPG is histologically characterized by lamellated lipoprotein thrombi in glomeruli, and kidney biopsy is essential for diagnosis. Mutations in the APOE gene are the leading cause of LPG. This study revealed clinicopathological characteristics and APOE gene mutations in patients with LPG, which helps us better understand the disease.

Role of Radiation-related Lung Function Genes in Prognosis and Immune Infiltration of Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a common malignant tumor with no obvious clinical symptoms in its early stages. Patients can be divided into radiotherapysensitive groups (RS) and radiotherapy-resistant groups (RR) due to their varying conditions. The therapeutic effect of radiotherapy is quite different between the two groups. Therefore, this paper explores the role of radiation-related lung function genes in LUAD and its immune landscape. METHODS: Firstly, we divided LUAD samples from the TCGA cohort into RS and RR groups and analyzed differential expression to obtain differentially expressed genes (DEGs). Then, DEGs and patients' grouping information were input into the weighted co-expression network, and the genes in the radiotherapy-related modules were identified. Furthermore, after the intersection of DEGs and lung function-related genes, the prognosis-related genes were obtained through univariate Cox and Lasso-Cox analyses, respectively, and the risk model was constructed. Finally, the differences in prognosis and immunity of the samples in the risk model were explored. Additionally, we also performed a qPCR experiment on lung function-related genes. RESULTS: In this paper, radiation-related genes of LUAD were identified through a series of bioinformatics analyses. By conducting enrichment analysis on these genes, several pathways related to LUAD radiation were identified, and DEGs associated with significant prognosis were determined. Furthermore, a radiation-related risk model of LUAD was developed. All samples were divided into high-risk and low-risk groups based on the risk score, and the differences in immune cell infiltration abundance and immune function between these groups were evaluated. The qPCR experimental results demonstrated a significant difference in the expression of genes related to lung function. CONCLUSION: The prognosis-related genes identified in this paper and the risk model created can serve as a reference for diagnosing and treating LUAD.

Association of lipid-modifying therapy with risk of obstructive sleep apnea: A drug-target mendelian randomization study.

BACKGROUND: Obstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Thus, we aimed to investigate the genetic association of lipid-modifying therapy with risk of OSA. METHODS: A drug-target mendelian randomization (MR) study using both cis-variants and cis-expression quantitative trait loci (eQTLs) of lipid-modifying drug targets was performed. The MR analyses used summary-level data of genome wide association studies (GWAS). Primary MR analysis was conducted using inverse-variance-weighted (IVW) method. Sensitivity analysis was performed using weighted median (WM) and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. RESULTS: Genetically proxied low-density lipoprotein cholesterol (LDL-C)-lowering effect of cholesteryl ester transfer protein (CETP) was associated with reduced risk of OSA (odds ratio [OR] =0.75, 95% confidence interval [CI]: 0.60-0.94, false discovery rate [FDR] q value = 0.046). A significant MR association with risk of OSA was observed for CETP expression in subcutaneous adipose tissue (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049), lung (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049) and small intestine (OR = 0.96, 95%CI: 0.93-1.00, FDR q value = 0.049). No significant effects of high-density lipoprotein cholesterol (HDL-C)-raising effect of CETP inhibition, LDL-C-lowering and triglycerides-lowering effect of other drug targets on OSA risk were observed. CONCLUSIONS: The present study presented genetic evidence supporting the association of LDL-C-lowering therapy by CETP inhibition with reduced risk of OSA. These findings provided novel insights into the role of lipid management in patients with OSA and encouraged further clinical validations and mechanistic investigations.

Sorbs2 Deficiency and Vascular BK Channelopathy in Diabetes.

BACKGROUND: Vascular large conductance Ca2+-activated K+ (BK) channel, composed of the α-subunit (BK-α) and the ß1-subunit (BK-ß1), is a key determinant of coronary vasorelaxation and its function is impaired in diabetic vessels. However, our knowledge of diabetic BK channel dysregulation is incomplete. The Sorbs2 (Sorbin homology [SoHo] and Src homology 3 [SH3] domains-containing protein 2), is ubiquitously expressed in arteries, but its role in vascular pathophysiology is unknown. METHODS: The role of Sorbs2 in regulating vascular BK channel activity was determined using patch-clamp recordings, molecular biological techniques, and in silico analysis. RESULTS: Sorbs2 is not only a cytoskeletal protein but also an RNA-binding protein that binds to BK channel proteins and BK-α mRNA, regulating BK channel expression and function in coronary smooth muscle cells. Molecular biological studies reveal that the SH3 domain of Sorbs2 is necessary for Sorbs2 interaction with BK-α subunits, while both the SH3 and SoHo domains of Sorbs2 interact with BK-ß1 subunits. Deletion of the SH3 or SoHo domains abolishes the Sorbs2 effect on the BK-α/BK-ß1 channel current density. Additionally, Sorbs2 is a target gene of the Nrf2 (nuclear factor erythroid-2-related factor 2), which binds to the promoter of Sorbs2 and regulates Sorbs2 expression in coronary smooth muscle cells. In vivo studies demonstrate that Sorbs2 knockout mice at 4 months of age display a significant decrease in BK channel expression and function, accompanied by impaired BK channel Ca2+-sensitivity and BK channel-mediated vasodilation in coronary arteries, without altering their body weights and blood glucose levels. Importantly, Sorbs2 expression is significantly downregulated in the coronary arteries of db/db type 2 diabetic mice. CONCLUSIONS: Sorbs2, a downstream target of Nrf2, plays an important role in regulating BK channel expression and function in vascular smooth muscle cells. Vascular Sorbs2 is downregulated in diabetes. Genetic knockout of Sorbs2 manifests coronary BK channelopathy and vasculopathy observed in diabetic mice, independent of obesity and glucotoxicity.

Recent advances in tissue repair of the blood-brain barrier after stroke.

The selective permeability of the blood-brain barrier (BBB) enables the necessary exchange of substances between the brain parenchyma and circulating blood and is important for the normal functioning of the central nervous system. Ischemic stroke inflicts damage upon the BBB, triggering adverse stroke outcomes such as cerebral edema, hemorrhagic transformation, and aggravated neuroinflammation. Therefore, effective repair of the damaged BBB after stroke and neovascularization that allows for the unique selective transfer of substances from the BBB after stroke is necessary and important for the recovery of brain function. This review focuses on four important therapies that have effects of BBB tissue repair after stroke in the last seven years. Most of these new therapies show increased expression of BBB tight-junction proteins, and some show beneficial results in terms of enhanced pericyte coverage at the injured vessels. This review also briefly outlines three effective classes of approaches and their mechanisms for promoting neoangiogenesis following a stroke.

Optimization and characterization of pectin extracted from hawthorn by deep eutectic solvent.

In this study, hawthorn pectin was extracted from dried hawthorn with deep eutectic solvent(DES) and compared with the traditional extraction methods such as acid extraction (AE) and ultrasonic-assisted extraction (UAE). Under optimal conditions, with a molar ratio of choline chloride to urea at 1:3, a water content of 30 %, a liquid-to-solid ratio of 30:1 (mL/g), an extraction temperature of 80 °C, an extraction time of 60 min, and a pH of 1, the yield of hawthorn pectin was 4.33 % ± 0.02 %. The measured results were consistent with the prediction. In addition, compared with AE and UAE, the experimental results showed that DES had a higher yield, a lower degree of esterification, and a slightly different monosaccharide composition from other extraction methods. The results of infrared spectroscopy and scanning electron microscopy showed that DES had a fine microstructure and coarser surface, and the main chemical structure of DES didn't change. The rheological analysis showed that DES had lower apparent viscosity than AE and UAE. These results represent a green source for pectin extraction with high pectin yield and good performance. In conclusion, the deep eutectic solvent has good application prospects in extracting hawthorn pectin.

Early Impact of Proton Beam Therapy on Electrophysiological Characteristics in a Porcine Model.

BACKGROUND: Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved. METHODS: Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas. RESULTS: The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, P<0.0001) and conduction velocity (85±26 versus 55±13 cm/s, P=0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, P=0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, P=0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks. CONCLUSIONS: Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.

Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of potentially life-threatening disorders characterized by necrotizing small vessel vasculitis with positive serum ANCA. To date, the pathogenesis of AAV has not been fully elucidated, but remarkable progress has been achieved in the past few decades. In this review, we summarize the mechanism of AAV. The pathogenesis of AAV involves various factors. ANCA, neutrophils, and the complement system play key roles in disease initiation and progression, forming a feedback amplification loop leading to vasculitic injury. Neutrophils activated by ANCA undergo respiratory burst and degranulation, as well as releasing neutrophils extracellular traps (NETs), thus causing damage to vascular endothelial cells. Activated neutrophils could further activate the alternative complement pathway, leading to the generation of complement 5a (C5a), which amplifies the inflammatory response by priming neutrophils for ANCA-mediated overactivation. Neutrophils stimulated with C5a and ANCA could also activate the coagulation system, generate thrombin, and subsequently cause platelet activation. These events in turn augment complement alternative pathway activation. Moreover, disturbed B-cell and T-cell immune homeostasis is also involved in disease development. In-depth investigation in pathogenesis of AAV might help to offer more effective targeted therapies.

Study on Modelling Method of Resilient Mat Used under Floating Slab Track.

Kelvin's model is widely used to simulate the dynamic characteristic of a resilient mat under a slab track. To develop an effective calculation model for a resilient mat using a solid element, a three-parameter viscoelasticity model (3PVM) was employed. With the help of the user-defined material mechanical behavior, the proposed model was implemented in software ABAQUS. To validate the model, a laboratory test was performed on a slab track with a resilient mat. Then, a finite element model of the track-tunnel-soil system was built. The calculation results using the 3PVM was compared with those using Kelvin's model and the test results. The results indicate that the 3PVM can better reflect the dynamic characteristics of resilient mat than Kelvin's model, especially over 10 Hz. Compared with the test results, the 3PVM has an average error of 2.7 dB and a max error of 7.9 dB at 5 Hz.

IL-33 promotes double negative T cell survival via the NF-κB pathway.

IL-33, which is a crucial modulator of adaptive immune responses far beyond type 2 response, can enhance the function of several T cell subsets and maintain the immune homeostasis. However, the contribution of IL-33 to double negative T (DNT) cell remains unappreciated. Here, we demonstrated that the IL-33 receptor ST2 was expressed on DNT cells, and that IL-33 stimulation increased DNT cells proliferation and survival in vivo and in vitro. Transcriptome sequencing analysis also demonstrated that IL-33 enhanced the biological function of DNT cells, especially effects on proliferation and survival. IL-33 promoted DNT cells survival by regulating Bcl-2, Bcl-xl and Survivin expression. IL-33-TRAF4/6-NF-κB axis activation promoted the transmission of essential division and survival signals in DNT cells. However, IL-33 failed to enhance the expression of immunoregulatory molecules in DNT cells. DNT cells therapy combined with IL-33 inhibited T cells survival and further ameliorated ConA-induced liver injury, which mainly depended on the proliferative effect of IL-33 on DNT cells in vivo. Finally, we stimulated human DNT cells with IL-33, and similar results were observed. In conclusion, we revealed a cell intrinsic role of IL-33 in the regulation of DNT cells, thereby identifying a previously unappreciated pathway supporting the expansion of DNT cells in the immune environment.

Synthesis and biological evaluation of novel demethylzeylasteral derivatives as potential anticancer agents.

Demethylzeylasteral (DEM), a class of terpenoids isolated from natural plants, frequently exhibits moderate or limited inhibitory effect on tumor growth across multiple cancer types. Thus, here we attempted to elevate the anti-tumor efficacy of DEM by altering active groups in its chemical structure. Initially, we synthesized a series of novel DEM derivatives 1-21 through performing a series of modifications of its phenolic hydroxyl groups at C-2/3, C-4 and C-29 positions. The anti-proliferative activities of these new compounds were subsequently assessed using three human cancer cell line models (A549, HCT116 and HeLa) and CCK-8 assay. Our data showed that compared to original DEM compound, derivative 7 exhibited remarkable inhibition effect on A549 (16.73 ± 1.07 µM), HCT116 (16.26 ± 1.94 µM) and HeLa (17.07 ± 1.09 µM), almost reaching to the same level of DOX. Moreover, the structure-activity relationships (SARs) of the synthesized DEM derivatives were discussed in detail. We found that treatment with derivative 7 only led to moderate cell cycle arrest at S-phase in a concentration-dependent manner. Meanwhile, derivative 7 treatment markedly induced apoptosis in tumor cells. Consistent with this observation, our subsequent docking analysis showed that derivative 7 is capable of activating caspase-3 through interaction with the His 121 and Gly 122 residues of the enzyme. Overall, we have developed a new series of DEM derivatives with elevated anti-tumor efficacy relative to its parent form. The results suggested that derivative 7 has great potential to be employed as an anticancer agent candidate for natural product-based cancer chemotherapy.

Surface modification of biodegradable magnesium alloy with poly (L-lactic acid) and sulfonated hyaluronic acid nanoparticles for cardiovascular application.

Magnesium (Mg) and its alloys have attracted extensive attention of researchers in the field of cardiovascular implants due to their good mechanical properties and biosafety. Constructing a multifunctional hybrid coating seems to be an effective strategy to address the insufficient endothelialization and poor corrosion resistance of Mg alloy vascular stents. In this study, a dense layer of magnesium fluoride (MgF2) was prepared on the surface of Mg alloy aiming at better corrosion resistance; Thereafter, sulfonated hyaluronic acid (S-HA) was made into small sized nanoparticles (NP) which were deposited on the MgF2 surface by self-assembly method, followed with poly-L-lactic acid (PLLA) coating preparation by one-step pulling method. The blood and cell tests showed that the composite coating had good blood compatibility, pro-endothelial, anti-hyperplasia and anti-inflammatory functions. Compared to current clinical PLLA@ Rapamycin coating, our PLLA/NP@S-HA coating showed better functions of promoting endothelial cells growth. These results strongly furnished a promising and feasible strategy for the surface modification of Mg-based degradable cardiovascular stents.

Resveratrol improves hepatic ischemia-reperfusion injury by inhibiting neutrophils via the ERK signaling pathway.

Hepatic ischemia-reperfusion injury (HIRI) is the main complication and even mortality in the setting of hepatic surgery or transplantation. Inflammation, especially the neutrophil response, plays important roles during the process of HIRI. In this study, we found that resveratrol preintervention ameliorated IRI-induced hepatic injury and neutrophil inflammatory responses in the liver. Moreover, RNA-sequencing analysis showed that resveratrol inhibited the functions of neutrophils, such as survival, cell cycle, migration and chemotaxis, oxidative stress and secretion of proinflammatory cytokines. Resveratrol restrained oxidative stress and the inflammatory response of neutrophils via inhibition of endothelin 1 autocrine signaling by suppressing the ERK signaling pathway. These data provide more evidence for the immunomodulatory role of resveratrol and enrich our understanding of immune strategies to improve HIRI.

Excessive iodine induces thyroid follicular epithelial cells apoptosis by activating HIF-1α-mediated hypoxia pathway in Hashimoto thyroiditis.

BACKGROUND: Hashimoto thyroiditis (HT) is considered the most common autoimmune thyroid disease. A growing body of evidence suggests that HT incidence correlates with excessive iodine intake. We should probe the effects of excessive iodine intake in HT development and its possible mechanism. METHODS AND RESULTS: The study recruited 20 patients: 10 with HT and 10 with nodular goiter. We detected the expression of an apoptosis-related protein caspase-3 by immunohistochemistry. In vitro study, we explored the proliferation and apoptosis status in thyroid follicular cells (TFCs) stimulated with different iodine concentrations by MTT and flow cytometry. Then we performed RNA sequence analysis of Nthy-ori3-1 cells treated for 48 h with KI to probe the underlying mechanism. Finally, we used RT-PCR and siRNA interference to verify the results. We identified apoptosis in thyroid tissue obtained from HT patients coincides with the increase of caspase-3 levels. In vitro study, iodine suppressed proliferation of TFCs and promoted TFCs apoptosis in a dose-dependent manner with regulating caspase-3 activation. HIF-1α-NDRG1 mediated hypoxia pathway activation promoted the transmission of essential apoptosis signals in TFCs. CONCLUSION: Our study confirmed that excessive iodine adsorption activates the HIF-1α-mediated hypoxia pathway to promote apoptosis of TFCs, which may be an important risk factor contributing to HT development.

Virus-like Particles as Antiviral Vaccine: Mechanism, Design, and Application.

Virus-like particles (VLPs) are viral structural protein that are noninfectious as they do not contain viral genetic materials. They are safe and effective immune stimulators and play important roles in vaccine development because of their intrinsic immunogenicity to induce cellular and humoral immune responses. In the design of antiviral vaccine, VLPs based vaccines are appealing multifunctional candidates with the advantages such as self-assembling nanoscaled structures, repetitive surface epitopes, ease of genetic and chemical modifications, versatility as antigen presenting platforms, intrinsic immunogenicity, higher safety profile in comparison with live-attenuated vaccines and inactivated vaccines. In this review, we discuss the mechanism of VLPs vaccine inducing cellular and humoral immune responses. We outline the impact of size, shape, surface charge, antigen presentation, genetic and chemical modification, and expression systems when constructing effective VLPs based vaccines. Recent applications of antiviral VLPs vaccines and their clinical trials are summarized.

Inhibitor of apoptosis proteins antagonist SM164 ameliorates experimental MPO-ANCA-associated vasculitis via enhancing fatty acid oxidation in neutrophils.

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening autoimmune diseases. Inhibitors of apoptosis proteins (IAPs) are a class of molecules engaged in cell death and inflammation, interventions of which are proven effective in a number of inflammatory diseases. Here we tested whether targeting IAPs could ameliorate AAV and explored the potential mechanism. METHODS: We collected 19 kidney specimens from patients with myeloperoxidase (MPO)-AAV to investigate the expression of IAPs. The IAP pan-inhibitor SM164 was used to treat the experimental autoimmune vasculitis (EAV) rat model of AAV. RNA sequencing of renal cortex and enrichment analysis were developed to interpret gene expression. Functional experiments were performed to investigate the role of SM164 on neutrophils and endothelial cells. RESULTS: The expression of three IAPs (cIAP1, cIAP2 and XIAP) was upregulated in kidneys of AAV patients compared with normal controls. SM164 dramatically reduced renal injury in EAV rats. Transcriptomic analysis revealed prominent alterations in fatty acid oxidation and respiratory burst following SM164 treatment. Functional studies demonstrated that SM164 inhibited neutrophil activation induced by MPO-ANCA positive IgG or serum from MPO-AAV patients, and such inhibitory effect was abolished by gene silencing or pharmacological inhibition of fatty acid oxidation. SM164 also inhibited the adhesion of neutrophils to endothelial cells with little effect on the endothelial injury induced by serum from MPO-AAV patients. CONCLUSION: Inhibition of IAPs with SM164 played a protective role in AAV through enhancing intracellular fatty acid oxidation in neutrophils.

Metabolomic and systematic biochemical analysis of sheep infected with Fasciola hepatica.

Fasciolosis is a neglected zoonotic parasitic disease caused by liver flukes, Fasciola hepatica. F. hepatica is harmful to livestock and human health. However, changes in host metabolism caused by F. hepatica infection are unclear. An artificial sheep model was established as follows. The sheep in the infection group were fed with 220 metacercariae obtained by incubating F. hepatica miracidia with the intermediate host snail (Galba pervia). Thereafter, serum and blood were collected from these sheep periodically. Changes in 31 biochemical parameters were systematically tested over different periods of infection. Metabolomic analysis was performed based on liquid chromatography/mass spectrometry (LC-MS) technology using a UHPLC system. Differentially expressed metabolites were analyzed for biomarkers, and changes in the metabolic pathways of the host were evaluated. Ten biochemical parameters (TP, ALB, GLB, DBIL, IBIL, GGT, LDH, CHOL, HDL-C, and BUN) showed significant dynamic changes during the study period. For metabolomic analysis: 13, 27, and 82 differential metabolites (ESI+ mode) and 0, 37, and 83 differential metabolites (ESI- mode) were found on 7, 56, and 98 dpi, respectively. The number of different metabolic pathways increased with disease development. Five metabolites had the highest area under the curve (AUC) value as joint diagnostic factors, indicating their potential use as biomarkers for diagnosing F. hepatica infection. This study establishes the F. hepatica life cycle in an artificial model of sheep infected with F. hepatica to identify changes in metabolic pathways in the host due to infection. Biochemical parameters and metabolomic analysis revealed that not only the biomarkers screened by differentially expressed metabolites have the potential to diagnose F. hepatica infection in sheep, but the differential pathways and biochemical parameters also explain the metabolic pathway changes in the sheep infected with F. hepatica. F. hepatica absorbs the nutrients of the host and destroys the essential metabolic pathways of the host. This result suggests that animal metabolism can be altered in the host as a response to parasitic infections such as F. hepatica. In addition, this finding will provide the basis for studying the pathogenic mechanisms and biomarkers for F. hepatica infection.