Reduction of TRPV1 expression on neurons due to downregulation of P2X7R in neonatal rat dorsal root ganglion satellite glial cells under co-culture conditions.

BACKGROUND INFORMATION: The purinergic ligand-gated ion channel 7 receptor (P2X7R) is an ATP-gated ion channel that transmits extracellular signals and induces corresponding biological effects, transient receptor potential vanilloid type 1 (TRPV1) is a non-selective cation channel that maintains normal physiological functions; numerous studies showed that P2X7R and TRPV1 are associated with inflammatory reactions. RESULTS: The effect of P2X7R knockdown in satellite glial cells (SGCs) on neuronal TRPV1 expression under high glucose and high free fat (HGHF) environment was investigated. P2X7 short hairpin RNA (shRNA) was utilized to downregulate P2X7R in SGCs, and treated and untreated SGCs were co-cultured with neuronal cell lines. The expression levels of inflammatory factors and signaling pathways in SGCs and neurons were measured using Western blot analysis, RT-qPCR, immunofluorescence, and enzyme-linked immunosorbent assays. Results suggested that P2X7 shRNA reduced the expression levels of P2X7R protein and mRNA in SGCs surrounding DRG neurons and downregulated the release of tumor necrosis factor-alpha and interleukin-1 beta via the Ca2+/p38 MAPK/NF-κB pathway. Additionally, the downregulation of P2X7R might decrease TRPV1 expression in neurons via the Ca2+/PKC-ɛ/p38 MAPK pathway. CONCLUSIONS: Reducing P2X7R expression in SCGs in an HGHF environment could decrease neuronal TRPV1 expression via the Ca2+/PKC-ɛ/p38 MAPK pathway.

Phloretin inhibits transmissible gastroenteritis virus proliferation via multiple mechanisms.

Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, has caused huge economic losses to the pig industry, with 100% mortality in piglets aged 2 weeks and intestinal injury in pigs of other ages. However, there is still a shortage of safe and effective anti-TGEV drugs in clinics. In this study, phloretin, a naturally occurring dihydrochalcone glycoside, was identified as a potent antagonist of TGEV. Specifically, we found phloretin effectively inhibited TGEV proliferation in PK-15 cells, dose-dependently reducing the expression of TGEV N protein, mRNA, and virus titer. The anti-TGEV activity of phloretin was furthermore refined to target the internalization and replication stages. Moreover, we also found that phloretin could decrease the expression levels of proinflammatory cytokines induced by TGEV infection. In addition, we expanded the potential key targets associated with the anti-TGEV effect of phloretin to AR, CDK2, INS, ESR1, ESR2, EGFR, PGR, PPARG, PRKACA, and MAPK14 with the help of network pharmacology and molecular docking techniques. Furthermore, resistant viruses have been selected by culturing TGEV with increasing concentrations of phloretin. Resistance mutations were reproducibly mapped to the residue (S242) of main protease (Mpro). Molecular docking analysis showed that the mutation (S242F) significantly disrupted phloretin binding to Mpro, suggesting Mpro might be a potent target of phloretin. In summary, our findings indicate that phloretin is a promising drug candidate for combating TGEV, which may be helpful for developing pharmacotherapies for TGEV and other coronavirus infections.

Modulating the RPS27A/PSMD12/NF-κB pathway to control immune response in mouse brain ischemia-reperfusion injury.

BACKGROUND: Investigating immune cell infiltration in the brain post-ischemia-reperfusion (I/R) injury is crucial for understanding and managing the resultant inflammatory responses. This study aims to unravel the role of the RPS27A-mediated PSMD12/NF-κB axis in controlling immune cell infiltration in the context of cerebral I/R injury. METHODS: To identify genes associated with cerebral I/R injury, high-throughput sequencing was employed. The potential downstream genes were further analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses. For experimental models, primary microglia and neurons were extracted from the cortical tissues of mouse brains. An in vitro cerebral I/R injury model was established in microglia using the oxygen-glucose deprivation/reoxygenation (OGD/R) technique. In vivo models involved inducing cerebral I/R injury in mice through the middle cerebral artery occlusion (MCAO) method. These models were used to assess neurological function, immune cell infiltration, and inflammatory factor release. RESULTS: The study identified RPS27A as a key player in cerebral I/R injury, with PSMD12 likely acting as its downstream regulator. Silencing RPS27A in OGD/R-induced microglia decreased the release of inflammatory factors and reduced neuron apoptosis. Additionally, RPS27A silencing in cerebral cortex tissues mediated the PSMD12/NF-κB axis, resulting in decreased inflammatory factor release, reduced neutrophil infiltration, and improved cerebral injury outcomes in I/R-injured mice. CONCLUSION: RPS27A regulates the expression of the PSMD12/NF-κB signaling axis, leading to the induction of inflammatory factors in microglial cells, promoting immune cell infiltration in brain tissue, and exacerbating brain damage in I/R mice. This study introduces novel insights and theoretical foundations for the treatment of nerve damage caused by I/R, suggesting that targeting the RPS27A and downstream PSMD12/NF-κB signaling axis for drug development could represent a new direction in I/R therapy.

The improvement of inflammatory infiltration and pregnancy outcome in mice with recurrent spontaneous abortion by human amniotic mesenchymal stem cells.

Recurrent spontaneous abortion is thought to be mostly triggered by immune-related causes. Mesenchymal stem cells, which exhibit the traits of multi-directional differentiation capacity and low immunogenicity, have recently been recommended as a viable treatment for spontaneous abortion-prone mice to increase the success of pregnancy. Amniotic membrane tissue is a byproduct of pregnancy and delivery that has a wide range of potential uses due to its easy access to raw materials and little ethical constraints. To construct an abortion-prone mouse model for this investigation, CBA/J female mice were coupled with male DBA/2 mice, while CBA/J female mice were paired with male BALB/c mice as a control. The identical volume of human amniotic mesenchymal stem cells or phosphate buffer was injected intraperitoneally on the 4.5th day of pregnancy. CBA/J female mice were sacrificed by cervical dislocation on the 13.5th day of pregnancy, the embryo absorption rate was calculated, and the uterus, decidua tissues and placenta were gathered for examination. Through detection, it was discovered that human amniotic mesenchymal stem cells significantly increased the expression of interleukin 10 and transforming growth factor beta, while they significantly decreased the expression of interleukin 1 beta and interleukin 6, improved vascular formation and angiogenesis, and minimized the embryo absorption rate and inflammatory cell infiltration in the recurrent spontaneous abortion + human amniotic mesenchymal stem cells group. In any case, human amniotic mesenchymal stem cells regulate inflammatory factors and cell balance at the maternal-fetal interface, which result in a reduction in the rate of embryo absorption and inflammatory infiltration and provide an innovative perspective to the clinical therapy of recurrent spontaneous abortion.

Targeting osteopontin alleviates endometriosis and inflammation by inhibiting the RhoA/ROS axis and achieves non-invasive in vitro detection via menstrual blood.

STUDY QUESTION: How does osteopontin (OPN) in endometriosis ectopic stromal cells (EESCs) participate in the pathogenesis of endometriosis and achieve non-invasive detection in vitro? SUMMARY ANSWER: Targeted OPN regulates endometriosis's necroptosis and inflammatory state by inhibiting the RhoA/reactive oxygen species (ROS) axis, thereby alleviating endometriosis and enabling non-invasive detection of menstrual blood in vitro. WHAT IS KNOWN ALREADY: Endometriosis is a chronic inflammatory disease. Recent studies have shown that OPN plays an important role in disease progression by regulating cell death and inflammation. STUDY DESIGN, SIZE, DURATION: The study included 20 patients diagnosed with endometriosis (confirmed by laparoscopy and histology) and 10 controls without endometriosis. Endometriotic stromal cells were isolated from endometrial samples, while menstrual blood endometrial cells (MESCs) were isolated from menstrual blood. These cells were then cultured in vitro and utilized in subsequent experiments. PARTICIPANTS/MATERIALS, SETTING, METHODS: OPN expression in EESCs was assessed using inflammatory factor sequencing, immunohistochemical staining (IHC), quantitative real-time PCR (qRT-PCR) analysis, and Western blotting (WB). The biological behavior of OPN and its effects on inflammatory factors were examined using EdU, wound-healing, Transwell, and ELISA assays. Necroptosis in EESCs and its impact on inflammatory factors were detected through qRT-PCR, WB, and Calcein-AM/PI fluorescence assays. The examination of mitochondrial stress in EESCs involved the use of the Mitochondrial Membrane Potential (ΔΨm) Assay, ROS detection, and Calcein-AM Loading/cobalt chloride Quenching. qRT-PCR, WB, and other experiments were conducted to verify the regulation of necroptosis and inflammatory factor levels in EESCs by OPN through the RhoA/ROS axis. Knockdown of OPN and its inhibitory effect on endometriosis lesion size were confirmed using AAV9 virus, IHC, qRT-PCR, WB, and other experiments. Additionally, OPN expression in MESCs was detected using transcriptome sequencing, RT-PCR, WB, and other experiments. MAIN RESULTS AND THE ROLE OF CHANCE: In vitro assays demonstrated a significant upregulation of OPN in EESCs, and the knockdown of OPN effectively inhibited necroptosis and the release of inflammatory factors. OPN inhibited necroptosis and inflammatory factor release by mediating RhoA-dependent ROS production and blocking mixed lineage kinase domain-like protein phosphorylation at the cell membrane. In vivo, targeting of OPN can inhibit the growth of endometriosis lesions. Clinically, OPN was also significantly upregulated in the menstrual blood of patients with endometriosis. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Due to limitations in obtaining surgical specimens, our study primarily involved collecting endometriosis tissues from women during the proliferative and secretory phases of the menstrual cycle. We observed a significant overexpression of OPN in the samples used for our investigation. However, the expression of OPN in endometriosis tissues during the intermenstrual phase remains unknown. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the pivotal role of the OPN/RhoA/ROS axis in the regulation of necroptosis and the release of inflammatory factors. OPN knockdown exerts a therapeutic effect in vivo, and the high expression detection of OPN in menstrual blood in vitro. In summary, targeting OPN provides possibilities for the treatment and detection of endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (82071626), the Zhejiang Province Public Welfare Technology Application Research Project (LGF21H040010), and the Clinical Research project of the Second Affiliated Hospital of Wenzhou Medical University (1010293). The authors have no conflicts of interest.

Correlation of circulating fibroblast growth factor 21 levels with inflammatory factors and the degree of coronary artery stenosis in patients with acute myocardial infarction.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is a secreted protein that plays an important role in atherosclerosis and pathological cardiac remodeling. However, the correlation between FGF21 and the degree of coronary artery stenosis and its potential role in acute myocardial infarction (AMI) remain unclear. We examined whether changes in FGF21 levels in AMI correlate with the degree of coronary artery stenosis and the levels of inflammatory factors, and preliminarily investigated the effects of FGF21 on inflammatory factor levels and myocardial injury in rats with AMI. METHODS: Serum levels of FGF21 and inflammatory factors in the AMI group and control group were measured, and the correlation between FGF21 and clinical indicators and inflammatory factors was analyzed. The effects of FGF21 on cardiac function and inflammatory response were evaluated through echocardiography and measurement of inflammatory factors. RESULTS: Multivariate logistic regression analysis showed that neutrophil percentage (NEUT%, odds ratio [OR]: 1.232; 95 % confidence interval [CI]: 1.028-1.477; p = 0.024) and FGF21 levels (OR: 2.063; 95 % CI: 1.187-3.586; p = 0.01) had independent effects on AMI. Spearman's rank correlation test showed that FGF21 levels were positively correlated with leukocyte count, NEUT%, neutrophil count, neutrophil to lymphocyte ratio, C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and Gensini scores (p < 0.01), but negatively correlated with lymphocyte count (p < 0.01). FGF21 levels in myocardial tissues and serum levels of FGF21, IL-6, TNF-a, and MCP-1 were significantly higher in AMI rats than in the sham-operated group (p < 0.01). After overexpression of FGF21, serum levels of IL-6, TNF-a, and MCP-1 in rats were significantly decreased (p < 0.01), and cardiac function improved significantly. CONCLUSIONS: FGF21 levels were independently associated with AMI and may be related to the severity of coronary artery stenosis. Overexpression of FGF21 reduced serum inflammatory factor levels and improved cardiac function in AMI rats.

Development of IL-17A inhibitor-induced atopic dermatitis-like rash in psoriasis patients: Insights into immune shift.

Cases of atopic dermatitis (AD)-like rash induced by IL-17A inhibitor secukinumab treatment (SI-AD) have been recently reported in psoriasis patients. To identify immune and inflammatory factors expression in SI-AD. A panel of 15 immune and inflammatory factors in peripheral blood samples from various groups, including patients with patients with SI-AD, psoriasis with secukinumab (S-stable), advanced psoriasis patients (Advanced) and healthy controls (HC). Interleukin-10 (IL-10), IL-4 and IL-17A were detected in skin tissue biopsy samples by immunohistochemistry and real-time quantitative polymerase chain reaction. The immunoglobulin E levels in the SI-AD patients exceeded normal values. The IL-10 levels in SI-AD patients were higher than those in S-stable patients, advanced patients and HC. The IL-4 levels in SI-AD patients were higher than that in S-stable patients and HC. The IL-17A levels in SI-AD patients were higher than those in advanced psoriasis patients and HC, but no significant differences were observed between SI-AD patients and S-stable patients. IL-10 and IL-4 levels were higher in AD-like rashes than in healthy skin, while IL-17A did not differ significantly between the two. Upon discontinuing secukinumab, and switching to oral cyclosporine, antihistamines, Janus kinase 1 inhibitor and topical glucocorticoids, SI-AD patients experienced significant improvement in their skin lesions. Upon reexamination, all 15 immune and inflammatory factors returned to normal levels. Immune shift from Th17 towards Th2 may occur in SI-AD, as indicated by abnormal expression of multiple immune and inflammatory factors observed in peripheral blood and skin tissues.

Soybean Agglutinin Alters the Gut Microbiota and Promotes Inflammation in Lupus-Prone MRL/lpr Mice.

BACKGROUND: Certain foods can trigger flares in patients with systemic lupus erythematosus. Lectins in edible plants have been reported to increase inflammation. OBJECTIVE: This study aimed to determine the effects of 1-time intake of soybean agglutinin (SBA) on the gut microbiota and immune response in lupus-prone MRL/MpJ (MRL)/lpr mice. METHODS: MRL/MpJ-Faslpr/J (MRL/lpr) and MRL mice were randomly assigned into 4 groups (8 mice/group): MRL mice + phosphate-buffered saline (PBS) (CON), MRL mice + SBA (CS), MRL/lpr mice + PBS (LPR), and MRL/lpr + SBA (LS). PBS and SBA were orally administered at 16 wk of age, and all mice were killed 24 h after oral challenge. The disease phenotype, levels of proinflammatory cytokines, and composition of the intestinal microbiota were determined. RESULTS: Interferon-gamma (IFN-γ) in the serum was significantly higher, whereas the level of serum IL-10 was significantly lower in LS mice than in LPR mice [fold change (FC) = 1.31 and FC = 0.36, respectively]. The expression levels of IL-6 and TNF-α in the spleen of LS mice were significantly higher than those in LPR mice (FC = 1.66 and FC = 1.96, respectively). The expression levels of IL-6, TNF-α, and IL-1ß in the kidney were also significantly higher in LS mice than in LPR mice (FC = 2.89, FC = 3.78, and FC = 2.02, respectively). The relative abundances of Erysipelotrichaceae and Turicibacter in LS mice were significantly higher than those in LPR mice (FC = 1.73 and FC = 1.74, respectively). The percentage of Breg cells in the mesenteric lymph nodes was significantly lower in LS mice than in LPR mice (FC = 0.53) (P < 0.05). No change was found between SBA treatment or not in the control (MRL) mice. CONCLUSIONS: One-time intake of SBA can promote the secretion of proinflammatory cytokines, downregulate Breg cells, and alter the intestinal flora in MRL/lpr mice within 24 h of oral challenge, which may contribute to exacerbation of lupus.

MRI Diagnosis of Coronary Artery Lesions in Children With Kawasaki Disease and Their Correlation With Inflammatory Factors.

BACKGROUND: Ultrasonography (US), as a routine examination for evaluating coronary artery lesions (CAL) in children with Kawasaki disease (KD), has strong subjectivity and limitations. Non-contrast enhanced coronary magnetic resonance angiography (NCE-CMRA) is sensitive and reliable in displaying the segments of coronary arteries (CA). PURPOSE: To evaluate the CA using NCE-CMRA, to compare NCE-CMRA with US, and to assess the correlation between KD-related inflammatory factors and the occurrence of CAL. STUDY TYPE: Retrospective. POPULATION: 61 children with KD who had undergone NCE-CMRA. Ultimately, 52 cases were included (32 males and 20 females), with an average of 5.9 ± 0.3 years old. FIELD STRENGTH/SEQUENCE: 3-T, 3D balanced turbo field echo sequence. ASSESSMENT: NCE-CMRA and US coronary visualization rates were compared in 41 children who were imaged with both techniques. Inflammatory factors were compared between CAL and normal coronary artery (NCA) subgroups. In the CAL group, correlations of these inflammatory factors with CAL parameters were investigated. STATISTICAL TESTS: Comparison between groups was performed by the two independent samples t-test; the comparison of enumeration data between groups was performed by chi-square test. Receiver operating characteristic (ROC) curve analysis was performed to determine the sensitivity of inflammatory factors for detecting CAL. The correlation between CAL and inflammatory indexes was analyzed by multiple linear regression. A P value <0.05 was considered statistically significant. RESULTS: NCE-CMRA visualized significantly more segments than US (76% vs. 46%). There were significant differences in PLT, CRP, ESR, and D-dimer between the CAL and NCA groups. ROC curve analysis showed that the sensitivities of these four indicators in diagnosing CAL were 39%, 44%, 72%, and 61%, respectively, at cut-off points of 562.5 × 109 /L, 48.93 mg/L, 45.5 mm/h, and 0.5 mg/L, respectively. DATA CONCLUSION: The combination of NCE-CMRA and inflammatory factors is helpful for the early diagnosis and disease severity of CAL in children with KD. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Efficacy of different doses of corticosteroids in treating severe COVID-19 pneumonia.

BACKGROUND: To investigate the efficacy of different doses of corticosteroids in treating severe coronavirus disease 2019 (COVID-19) pneumonia. METHODS: Between May 01, 2023, and June 20, 2023, 48 patients with severe COVID-19 pneumonia were treated at the Department of Respiratory and Critical Care Medicine of Jinan Fourth People's Hospital. The observation group (21 patients) received standard care and high-dose corticosteroids, (high-dose group). The control group (27 patients) received standard care and low-dose corticosteroids (low-dose group). We collected baseline data and recorded inflammatory marker levels after 3 days of treatment, body temperature recovery time, length of stay, and 28-day all-cause mortality. The results of outpatient follow-up were recorded after 1 month. RESULTS: There were no significant differences in 28-day mortality and length of stay. The number of days it took for body temperature to return to normal in the high-dose group was less than in the low-dose group. The high-dose group had significantly more reduced inflammatory factors (C-reactive protein (CRP), interleukin-6 (IL-6). A total of 20 discharged patients were given 8-16 mg of methylprednisolone, depending on chest computed tomography (CT) and clinical symptoms after 1 month; in all discharged patients using oral corticosteroids, CT features improved. CONCLUSION: High-dose corticosteroids had a significantly positive effect on the reduction of inflammatory factors and shortening body temperature recovery time. In the treatment of severe COVID-19 pneumonia, early administration of high-dose, short-course corticosteroids should be implemented.

Impact of Sleep Deprivation on the Brain's Inflammatory Response Triggered by Lipopolysaccharide and Its Consequences on Spatial Learning and Memory and Long-Term Potentiation in Male Rats.

INTRODUCTION: Both sleep deprivation (SD) and inflammation can negatively affect cognitive function. This study aimed to investigate how SD impacts the brain's inflammatory response to lipopolysaccharide (LPS) and its subsequent effects on cognitive functions. METHODS: To this end, male rats were tested through a Morris water maze (MWM) to assess their spatial learning and memory. Also, in vivo field potential recordings (to evaluate synaptic plasticity) were done in the Saline, SD, LPS1 (1 mg/kg/7 days), and LPS1+SD groups. Cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Based on the results, the LPS1+SD group showed increased total distance and escape latency compared to the other groups in the MWM test. Besides, the LPS1+SD group exhibited a significant decrease in long-term potentiation (LTP) induction and maintenance in the CA1 area of the brain. Finally, the inflammatory cytokine interleukin-1ß (IL-1ß) levels were significantly higher in the LPS1+SD group than in the Saline group. CONCLUSION: These findings suggest that the combined effects of SD and brain inflammatory response can have more harmful effects on cognitive function, LTP, and inflammatory factors than either SD or LPS1 alone.

Effect of aerosol inhalation of budesonide on respiratory symptoms and inflammatory factors in patients with asthma: a meta-analysis.

OBJECTIVE: To review the efficacy, symptoms, inflammatory factors and pulmonary function of different doses of budesonide aerosol inhalation in the treatment of patients with asthma. METHODS: The Chinese and English literature databases were searched with "Effects of different doses of budesonide aerosol inhalation on the efficacy, lung function, inflammation, symptoms and adverse reactions in patients with asthma" as the search direction, and a Meta-analysis was performed. RESULTS: Compared with the low dose group, the efficacy, PEF and FEV1 were significantly increased and the clinical symptom score, TNF-α and IL-4 were significantly decreased in the high dose group (p < 0.05). There was no significant difference in IFN-γ level and the incidence of adverse reactions between the two groups (p > 0.05). CONCLUSION: High-dose budesonide aerosol inhalation therapy can improve the efficacy and lung function of patients, reduce inflammation and clinical symptoms, and does not increase the risk of adverse reactions, which is worthy of clinical promotion.

Natural anti-neuroinflammatory inhibitors in vitro and in vivo from Aglaia odorata.

Fifty compounds including seven undescribed (1, 13, 18-20, 30, 31) and forty-three known (2-12, 14-17, 21-29, 32-50) ones were isolated from the extract of the twigs and leaves of Aglaia odorata with anti-neuroinflammatory activities. Their structures were determined by a combination of spectral analysis and calculated spectra (ECD and NMR). Among them, compounds 13-25 were found to possess tertiary amide bonds, with compounds 16, 17, and 19-21 existing detectable cis/trans mixtures in 1H NMR spectrum measured in CDCl3. Specifically, the analysis of the cis-trans isomerization equilibrium of tertiary amides in compounds 19-24 was conducted using NMR spectroscopy and quantum chemical calculations. Bioactivity evaluation showed that the cyclopenta[b]benzofuran derivatives (2-6, 8, 10, 12) could inhibit nitric oxide production at the nanomolar concentration (IC50 values ranging from 2 to 100 nM) in lipopolysaccharide-induced BV-2 cells, which were 413-20670 times greater than that of the positive drug (minocycline, IC50 = 41.34 µM). The cyclopenta[bc]benzopyran derivatives (13-16), diterpenoids (30-35), lignan (40), and flavonoids (45, 47, 49, 50) also demonstrated significant inhibitory activities with IC50 values ranging from 1.74 to 38.44 µM. Furthermore, the in vivo anti-neuroinflammatory effect of rocaglaol (12) was evaluated via immunofluorescence, qRT-PCR, and western blot assays in the LPS-treated mice model. The results showed that rocaglaol (12) attenuated the activation of microglia and decreased the mRNA expression of iNOS, TNF-α, IL-1ß, and IL-6 in the cortex and hippocampus of mice. The mechanistic study suggested that rocaglaol might inhibit the activation of the NF-κB signaling pathway to relieve the neuroinflammatory response.

Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia.

BACKGROUND: This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. METHODS: 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. RESULTS: 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The ß-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. CONCLUSION: This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.

Crosstalk between Myopia and Inflammation: A Mini Review.

Myopia represents a significant public health concern worldwide, particularly affecting the ocular health of children and adolescents. The escalating prevalence of myopia in recent years underscores its urgency as a health issue among this demographic. Research indicates a profound connection between the onset of myopia, inflammatory processes and fibrosis. Individuals with inflammatory conditions like allergic conjunctivitis, choroiditis, systemic lupus erythematosus, and diabetes exhibit a heightened susceptibility to myopia. Conversely, myopic patients are at an increased risk of developing ocular inflammatory disorders, notably idiopathic multifocal choroiditis. We postulate that the expression of inflammatory markers, including NF-κB, TGF-ß, IL-1ß, IL-6, IL-8, and TNF-α, may contribute to the chronic inflammatory state observed in myopia. This paper highlights a substantial correlation between myopia and inflammation, suggesting the potential efficacy of anti-inflammatory agents in managing inflammation and slowing myopia progression.

No role of the third-trimester inflammatory factors in the association of gestational diabetes mellitus with postpartum cardiometabolic indicators.

BACKGROUND: The influence of gestational diabetes mellitus (GDM) on postpartum cardiometabolic indicators is primarily restricted to glucose and lipid metabolism, however the indicators for liver and kidney function have been rarely explored, and the role of the third-trimester inflammatory factors in these associations has never been investigated. METHODS: Based on the Ma'anshan birth cohort (MABC), women with or without GDM history were selected and invited to participate in a 6-year postpartum follow-up. The fasting blood samples were collected to measure 16 comprehensive metabolic indicators during a 6-year postpartum follow-up: fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), uric acid (UA), blood urea nitrogen (BUN), serum creatinine (SCR), etc. Seven inflammatory factors, including TNF-α, IFN-γ, IL-1ß, IL-6, IL-10, IL-12p70, and IL-17 A, were measured with serum samples collected during the third trimester of pregnancy. Linear regression models were used to analyze the associations between GDM and 6-year postpartum metabolic indicators, GDM and third-trimester inflammatory factors, and the third-trimester inflammatory factors and 6-year postpartum metabolic indicators. Mediating and moderating effect analyses were further performed to explore if the third-trimester inflammatory factors mediate or modify the association between GDM and postpartum cardiometabolic indicators. RESULTS: From July 2021 to August 2022, 307 participants have been followed up, with 99 women with a prior GDM history. Compared with those without GDM, individuals with a prior history of GDM had significantly elevated levels of FPG (ß = 0.40, 95% CI: 0.18 to 0.62, PFDR < 0.001), HbA1c (ß = 0.22, 95% CI: 0.09 to 0.34, PFDR = 0.009), TyG (ß = 0.22, 95% CI: 0.07 to 0.37, PFDR = 0.024) at 6 years postpartum, and the association between GDM and SCR (ß = 2.43, 95% CI: 0.02 to 4.85, PFDR = 0.144) reached nominal significance level. GDM history was associated with a decreased level of third-trimester IL-17 A (ß = -0.58, 95% CI: -0.99 to -0.18, PFDR = 0.035). No significant association between third-trimester inflammatory factors and 6-year postpartum metabolic indicators was observed. And no mediating or moderating effect of third-trimester inflammatory factors was observed in those associations. CONCLUSION: A prior history of GDM was significantly associated with elevated FPG, HbA1c, and TyG in women at 6 years postpartum, whereas third-trimester inflammatory factors had no role in mediating or moderating these associations.

Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.

Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the myocardium. This phenomenon is known as myocardial ischemia-reperfusion injury (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) is known to play a significant role in regulating the immune response and inflammation, and has been studied for its potential impact on the improvement of heart function after myocardial injury. However, the delivery of miR-146a to the heart in a specific and efficient manner remains a challenge as extracellular RNAs are unstable and rapidly degraded. Milk exosomes (MEs) have been proposed as ideal delivery platform for miRNA-based therapy as they can protect miRNAs from RNase degradation. In this study, the effects of miR-146a containing MEs (MEs-miR-146a) on improvement of cardiac function were examined in a rat model of MIRI. To enhance the targeting delivery of MEs-miR-146a to the site of myocardial injury, the ischemic myocardium-targeted peptide IMTP was modified onto the surfaces, and whether the modified MEs-miR-146a could exert a better therapeutic role was examined by echocardiography, myocardial injury indicators and the levels of inflammatory factors. Furthermore, the expressions of miR-146a mediated NF-κB signaling pathway-related proteins were detected by western blotting and qRT-PCR to further elucidate its mechanisms. MiR-146 mimics were successfully loaded into the MEs by electroporation at a square wave 1000 V voltage and 0.1 ms pulse duration. MEs-miR-146a can be up-taken by cardiomyocytes and protected the cells from oxygen glucose deprivation/reperfusion induced damage in vitro. Oral administration of MEs-miR-146a decreased myocardial tissue apoptosis and the expression of inflammatory factors and improved cardiac function after MIRI. The miR-146a level in myocardium tissues was significantly increased after the administration IMTP modified MEs-miR-146a, which was higher than that of the MEs-miR-146a group. In addition, intravenous injection of IMTP modified MEs-miR-146a enhanced the targeting to heart, improved cardiac function, reduced myocardial tissue apoptosis and suppressed inflammation after MIRI, which was more effective than the MEs-miR-146a treatment. Moreover, IMTP modified MEs-miR-146a reduced the protein levels of IRAK1, TRAF6 and p-p65. Therefore, IMTP modified MEs-miR-146a exerted their anti-inflammatory effect by inhibiting the IRAK1/TRAF6/NF-κB signaling pathway. Taken together, our findings suggested miR-146a containing MEs may be a promising strategy for the treatment of MIRI with better outcome after modification with ischemic myocardium-targeted peptide, which was expected to be applied in clinical practice in future.

Characterization of intestinal fungal community diversity in people living with HIV/AIDS (PLWHA).

Acquired Immune Deficiency Syndrome (AIDS) is a highly dangerous infectious disease caused by the Human Immunodeficiency Virus (HIV), a virus that attacks the human immune system. To explore the correlation between intestinal fungal community and immune function (Immune cells and inflammatory factors) in people living with HIV/AIDS (PLWHA). The feces and blood samples were collected from two groups of subjects: PLWHA and healthy controls. High-throughput sequencing of the internal transcribed spacer 1, flow cytometry, and ELISA were performed to analyze the differences and correlations between fungal microbiota, cellular immune status and serum inflammatory factors in the two groups. There were significant differences in the composition of fungal microbiota between the two groups. The relative abundance of Candida, Bjerkandera, and Xeromyces in PLWHA was significantly higher than that of healthy volunteers (P < 0.01), while the relative abundance of Mycospaerella, Xeroxysium, Penicillium, and Glomerella in PLWHA was significantly lower than that of healthy volunteers. The correlation analysis results show that Mycospaerella and Xeromyces are significantly positively correlated with CD4+/CD8+ T cells and the anti-inflammatory cytokine IL-4. On the other hand, Candida was positively correlated with pro-inflammatory factors negatively correlated with CD4+/CD8+ T cells and the anti-inflammatory cytokine IL-4, while it is positively correlated with pro-inflammatory cytokines. The significant increase in the relative abundance of Candida may be one of the important causes of intestinal damage in PLWHA. The results of this study contribute to the understanding of the relationship between fungal microbiota structure and immune function in the gut ecology of PLWHA.

Explore the genetic exposure to alopecia areata.

BACKGROUND: Alopecia areata is an autoimmune hair loss disorder with an incompletely understood etiology. Although trace elements, serum metabolites, and inflammatory factors are implicated in the disease, the potential causal relationships between these factors and alopecia areata require further investigation. METHODS: This study employed Mendelian randomization (MR), utilizing data from genome-wide association studies, to explore the causal relationships between 15 trace elements, 1400 serum metabolites, and 91 inflammatory factors and alopecia areata. The analysis was conducted using the inverse variance weighted (IVW) method complemented by various sensitivity analyses, including Cochran's Q test, MR-Egger regression intercept test, MR-PRESSO global test, and leave-one-out analysis, to assess the robustness of the results. RESULTS: MR analysis indicated a negative correlation between copper levels and the risk of developing alopecia areata (odds ratio = 0.86, 95% confidence interval: 0.75-0.99, p = 0.041). Additionally, causal relationships were identified between 15 serum metabolites and 6 inflammatory factors and the risk of alopecia areata (IVW, all p values < 0.05). CONCLUSION: This study provides genetic evidence of the relationships between trace elements, serum metabolites, and alopecia areata, underscoring the potential value of targeted therapeutic strategies and preventive measures. Future research should expand to diverse populations and further explore the specific roles of these biomarkers in the disease mechanism.

Predictive value of inflammatory factors and lymphocyte counts in tracheal intubation and death after infection with COVID-19.

OBJECTIVE: This study aims to investigate the prognostic significance of inflammatory cytokines and lymphocyte levels in predicting disease progression among patients with COVID-19 infection. METHODS: Ninety-two hospitalized COVID-19 patients were retrospectively included as subjects for this study. General clinical information and various indicators, including lymphocyte count, interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor (TNF), were collected. All patients received treatment according to the ninth edition of the guidelines for COVID-19. Incidences of endotracheal intubation and mortality within 28 days were observed. RESULTS: 1.In the analysis of intubation impact, multivariate analysis identified age, immunoglobulins, lymphocytes, and IL-6 as independent risk factors. When analyzing the impact on patient mortality, multivariate analysis revealed age, prealbumin, and BNP as independent risk factors. 2. Lymphocyte count and inflammatory factors demonstrated predictive value for endotracheal intubation in COVID-19 patients. The critical lymphocyte count value was 0.91, with a sensitivity of 38.8%, specificity of 92.9%, and AUC of 0.687 (95% CI: 0.580-0.795). The critical IL-6 value was 38.21, with a sensitivity of 81%, specificity of 63.3%, and AUC of 0.771 (95% CI: 0.6670.872). The area under the ROC curve for IL-8, IL-10 and TNF is 0.665, 0.712 and 0.648, respectively. 3.Lymphocyte count and inflammatory factors also exhibited predictive value for death in COVID-19 patients. The critical lymphocyte count value was 0.56, with a sensitivity of 71.2%, specificity of 57.5%, and AUC of 0.641 (95% CI: 0.528-0.754). The critical IL-6 value was 53.05, with a sensitivity of 75%, specificity of 71.2%, and AUC of 0.770 (95% CI: 0.6690.870). The area under the ROC curve for IL-8, IL-10 and TNF is 0.687, 0.683 and 0.636, respectively. CONCLUSION: Elevated inflammatory factors and decreased lymphocyte levels have prognostic value for predicting endotracheal intubation and mortality in COVID-19 patients, providing valuable insights for clinicians in anticipating disease progression.