Serum Levels Of Factor Research Articles

Conditioned Medium from Human Amniotic Membrane-Derived Mesenchymal Stem Cells Modulates Inflammatory and Myofibrotic Factors in Vivo

Background: Heart failure (HF) is a common condition associated with a high mortality rate, and while various treatment options exist, the therapeutic potential of human adipose-derived mesenchymal stem cells-conditioned medium (hAMSCs-CM) has garnered attention. To elucidate the mechanism behind hAMSCs-CM’s effects on HF, we conducted an animal study focusing on specific inflammatory and fibrotic factors. Methods: Forty adult male Wistar rats were divided into 4 groups: control, HF, culture medium, and CM. All rats, except those in the control group, received an injection of isoproterenol to induce an animal model of HF. The CM group was administered the CM, while those in the culture medium group received standard culture media. Subsequently, serum levels of fibrotic factors, including TGF-β/galectin-3, MCP1, BNP, and ALD, were measured using ELISA. Statistical analysis was performed using one-way analysis of variance and the Tukey test. Results: Serum levels of TGF-β/galectin-3, MCP1, BNP, and ALD were significantly elevated in the HF, CM, and culture medium groups compared with the control group (P<0.001). Additionally, these fibrotic factors were significantly reduced in the CM group compared with the HF group (P<0.001). Notably, CM therapy could not restore TGF-β/galectin-3, MCP1, BNP, or ALD levels to the normal range observed in the control group. Conclusion: Our findings indicate that hAMSCs-CM modulates the expression of inflammatory and fibrotic cytokines, such as TGF-β/galectin-3, MCP1, BNP, and ALD, in isoproterenol-induced HF in male rats. These results contribute to a better understanding of the therapeutic mechanisms underlying hAMSCs-CM treatment for HF.

Clinical effects of phospholipase D2 in attenuating acute pancreatitis.

The objective of the current study was to elucidate the clinical mechanism through which phospholipase D2 (PLD2) exerted a regulatory effect on neutrophil migration, thereby alleviating the progression of acute pancreatitis. To elucidate the clinical mechanism through which PLD2 exerted a regulatory effect on neutrophil migration, thereby alleviating the progression of acute pancreatitis. The study involved 90 patients diagnosed with acute pancreatitis, admitted to our hospital between March 2020 and November 2022. A retrospective analysis was conducted, categorizing patients based on Ranson score severity into mild (n = 25), moderate (n = 30), and severe (n = 35) groups. Relevant data was collected for each group. Western blot analysis assessed PLD2 protein expression in patient serum. Real-time reverse transcription polymerase chain reaction was used to evaluate the mRNA expression of chemokine receptors associated with neutrophil migration. Serum levels of inflammatory factors in patients were detected using enzyme-linked immunosorbent assay. Transwell migration tests were conducted to compare migration of neutrophils across groups and analyze the influence of PLD2 on neutrophil migration. Overall data analysis did not find significant differences between patient groups (P > 0.05). The expression of PLD2 protein in the severe group was lower than that in the moderate and mild groups (P < 0.05). The expression level of PLD2 in the moderate group was also lower than that in the mild group (P < 0.05). The severity of acute pancreatitis is negatively correlated with PLD2 expression (r = -0.75, P = 0.002). The mRNA levels of C-X-C chemokine receptor type 1, C-X-C chemokine receptor type 2, C-C chemokine receptor type 2, and C-C chemokine receptor type 5 in the severe group are significantly higher than those in the moderate and mild groups (P < 0.05), and the expression levels in the moderate group are also higher than those in the mild group (P < 0.05). The levels of C-reactive protein, tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the severe group were higher than those in the moderate and mild groups (P < 0.05), and the levels in the moderate group were also higher than those in the mild group (P < 0.05). The number of migrating neutrophils in the severe group was higher than that in the moderate and mild groups (P < 0.05), and the moderate group was also higher than the mild group (P < 0.05). In addition, the number of migrating neutrophils in the mild group combined with PLD2 inhibitor was higher than that in the mild group (P < 0.05), and the number of migrating neutrophils in the moderate group combined with PLD2 inhibitor was higher than that in the moderate group (P < 0.05). The number of migrating neutrophils in the severe group + PLD2 inhibitor group was significantly higher than that in the severe group (P < 0.05), indicating that PLD2 inhibitors significantly stimulated neutrophil migration. PLD2 exerted a crucial regulatory role in the pathological progression of acute pancreatitis. Its protein expression varied among patients based on the severity of the disease, and a negative correlation existed between PLD2 expression and disease severity. Additionally, PLD2 appeared to impede acute pancreatitis progression by limiting neutrophil migration.

Impact of Emergency Warning Nursing on CRP, PCT, TNF-α and Clinical Indicators in Patients with Acute Stress Disorder under Hierarchical Analysis.

In emergency warning nursing, the pre-alert system significantly influences the biochemical markers and clinical outcomes of patients with Acute Stress Disorder. Therefore, this study applies hierarchical analysis to explore the impact of early warning nursing on crucial indicators such as C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and assess their clinical efficacy. The study selected patients with acute stress disorder who were hospitalized in Southwest Hospital of Chongqing from December 2021 to December 2022, and collected data from 250 patients. Through PSM score matching, 170 patients were finally scored and grouped, 85 patients in each group, which were divided into routine group and stratified analysis group. The changes in serum inflammatory markers, psychological resilience, and post-traumatic growth were compared between the two experimental groups on day 1 of admission and after 14 days of intervention. After one day of admission, there was no significant difference in the serum factor levels, psychological resilience, and post-traumatic growth among the participants (p > 0.05). However, after 14 days of intervention, patients in the hierarchical analysis group showed better outcomes in serum inflammatory markers such as C-reactive protein, procalcitonin, tumor necrosis factor-alpha, and interleukin-6 compared to the conventional group (p < 0.05). The hierarchical analysis group had higher psychological resilience scores regarding strength, optimism, and resilience compared to the conventional group (p < 0.05). Furthermore, the hierarchical analysis group showed higher post-traumatic growth scores regarding mental changes, personal strength, appreciation of life, interpersonal relationship, and new possibilities relative to the conventional group (p < 0.05). Analytic Hierarchy Process (AHP)-based emergency warning nursing can help improve the serum inflammatory factor levels, strengthen psychological resilience, and enhance post-traumatic growth levels in patients with Acute Stress Disorder.

Serum Periostin as a Potential Biomarker in the Evaluation of Allergic Rhinitis: A Pilot Study.

Although periostin has recently emerged as a new mediator in chronic allergic diseases, particularly in upper airway disease, its significance as a biomarker for allergic rhinitis (AR) is still unclear. Therefore, we aimed to assess the potential of periostin as a novel candidate biomarker for diagnosing and assessing the severity of AR. A total of 40 patients with AR and 22healthy controls, all aged over 18 years, were recruited for the study. Participants underwent examinations to assess serum levels of total IgE (tIgE), specific IgE (sIgE), periostin, and remodeling-related factors, as well as fractional exhaled nitric oxide (FeNO) and fractional nasal nitric oxide (FnNO). Additionally, clinical characteristics questionnaire and nasal function assessments were completed by AR patients. The levels of serum periostin were significantly higher in patients with AR compared to healthy controls (Z=-3.605, p<0.001). There was a notable positive correlation between serum periostin and FeNO (r=0.398, p=0.012), FnNO (r=0.379, p=0.017), as well as the visual analogue scale (VAS) score for ocular tearing (r=0.351, p=0.026) in AR patients. Furthermore, the serum periostin levels were higher in moderate-to-severe AR compared to mild AR cases (Z=-2.007, p=0.045). The level of serum periostin in AR patients showed a sequential increase corresponding to shortness of breath scores from 0 to 3 (Z=10.137, p=0.017). The predicted probability of serum periostin demonstrated moderate diagnostic accuracy in detecting AR (AUC=0.773, p<0.001). Serum periostin shows potential as a candidate biomarker for detecting AR and can serve as a surrogate biomarker for assessing airway inflammation in AR patients.

Serum BAFF levels are associated with the prognosis of idiopathic membranous nephropathy

Objective High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear. Methods Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression. Results Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6–72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405–0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202–0.648; p < 0.001). Conclusions A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.

Protective effect of Streptococcus salivarius K12 against Mycoplasma pneumoniae infection in mice

To investigate the protective effect of the probiotic bacterium Streptococcus salivarius K12 (K12) against Mycoplasma pneumoniae (Mp) infection in mice. Forty male BALB/c mice were randomized into normal control group, K12 treatment group, Mp infection group, and K12 pretreatment prior to Mp infection group. The probiotic K12 was administered daily by gavage for 14 days before Mp infection induced by intranasal instillation of Mp. Three days after Mp infection, the mice were euthanized for analysis of bronchoalveolar lavage fluid (BALF) cell counts and serum levels of secretory immunoglobulin A (sIgA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). RT-qPCR was performed to detect the P1 and community-acquired respiratory distress syndrome ( CARDS ) toxin of Mp in the lung tissues and the mRNA expressions of TNF-α, IL-6, chemokine 1 (CXCL1), matrix metalloproteinase 9 (MMP9), mucin 5ac (MUC5ac), collagen 3a1 (Col3a1), Toll-like receptor 2 (TLR2) and TLR4; the protein expressions of TLR2 and TLR4 in the lung tissue were detected using Western blotting. Pathological changes in the lung tissue and airway remodeling were examined with HE staining and AB/PAS staining. Compared with the Mp-infected mice with PBS treatment, the infected mice with K12 treatment showed significantly lowered mRNA levels of P1 and CARDS in the lung tissue and reduced white blood cell counts in the BALF (P<0.05). In spite of the absence of significant differences in serum levels of inflammatory factors between the two groups, the mRNA expressions of TNF‑α, IL-6, CXCL1, MMP9, MUC5ac and COL3A1 and the mRNA and protein levels of TLR2 and TLR4 in the lung tissues were significantly lower in K12-treated mice, in which AB/PAS staining showed obviously decreased mucus secretion. K12 pretreatment can effectively reduce pulmonary inflammatory responses, improve airway remodeling and alleviate lung injury in Mp-infected mice.

Serum levels of auto-antibodies (rheumatoid factor and anti-double stranded DNA) in Nigerian COVID-19 patients

BackgroundA thorough understanding of how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to autoantibody development is essential to clarify the possibility of autoimmune disorders in COVID-19 patients. Consequently, this study measured serum levels of rheumatoid factor (RF) and anti-double stranded DNA antibody (dsDNA ab), two key markers of autoimmune disorders, in COVID-19 patients and in apparently healthy controls.MethodsSerum levels of rheumatoid factor and anti-dsDNA antibody were determined using turbidimetric immunoassay and enzyme linked immunosorbent assay (ELISA) respectively in both COVID-19 patients (n = 40) and healthy controls (n = 28).ResultsSerum levels of RF and anti-dsDNA antibody were similar in COVID-19 patients compared with controls. A significant positive correlation was observed between RF and anti-dsDNA antibody in healthy controls. The correlation between RF and anti-dsDNA antibody in COVID-19 patients was not significant.ConclusionSARS-CoV-2 infection did not significantly impact serum RF and anti-dsDNA antibody levels in the present infected individuals. Thus, autoimmune disorders are not indicated in these COVID-19 patients, and using therapeutic antagonists to target auto-antibodies may not be beneficial in managing COVID-19, as these patients are unlikely to develop an autoimmune disorder related to COVID-19.

HDC downregulation induced by chronic stress promotes ovarian cancer progression via the IL-6/STAT3/S100A9 pathway

ObjectiveThis study aimed to investigate the underlying mechanism of chronic stress promoting ovarian cancer growth comorbid with depression and evaluate the potential role of histamine (HIS) in treating this comorbidity.MethodsChronic unpredictable mild stress (CUMS) was used to establish a comorbid mouse model of ovarian cancer and depression. The behavioral phenotypes were assessed using the sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Ovarian cancer growth was monitored by tracking the tumor volume and weight. Histidine decarboxylase (HDC) expression in the tumor tissue was analyzed using Western blot and qRT-PCR techniques. The serum levels of inflammatory factors (IL-6 and IL-17A), stress hormones (norepinephrine, NE and cortisol, and COR), histamine, and 5-hydroxytryptamine (5-HT) were detected by enzyme-linked immunosorbent assay (ELISA). In vitro experiments were conducted to explore the direct impacts of stress hormones on A2780 and ES-2 ovarian cancer cell lines, as well as the modulation of these effects by histamine. HDC knockdown and overexpression approaches were used to study its regulatory role in the IL-6/STAT3/S100A9 signaling pathway.ResultsChronic stress not only induced depressive behaviors but also accelerated ovarian cancer growth in mice by downregulating HDC expression in tumors, whereas exogenous HIS treatment alleviated depressive symptoms, suppressed cancer growth, and countered the decreased levels of HIS and increased levels of IL-6, IL-17A, NE, COR, and 5-HT induced by CUMS. Furthermore, HIS positively modulated the immune response by increasing the populations of CD3+T and CD8+ T cells and reducing IL-17A secretion. In vitro experiments revealed that stress hormones downregulated HDC expression, consequently promoting cancer cell proliferation, migration, and invasion via the IL-6/STAT3/S100A9 pathway. Knockdown of HDC activated this pathway, whereas HDC overexpression inhibited its activation.ConclusionChronic stress leads to the downregulation of HDC expression, thereby facilitating the progression of ovarian cancer through the IL-6/STAT3/S100A9 pathway. HIS might serve as a potential molecule for treating the comorbidities of ovarian cancer and depression.

Human adenovirus type 7 (HAdV-7) infection induces pulmonary vascular endothelial injury through the activation of endothelial autophagy

BackgroundHAdV-7 is a prevalent pathogen that can cause severe pneumonia in children. Previous studies have shown a significant increase in serum levels of vascular permeability factor (VPF/VEGF) and viral load in pediatric patients with fatal HAdV-7 infection, suggesting potential damage to the pulmonary vascular endothelium. Further research is necessary to elucidate the underlying mechanism.MethodsThe human lung microvascular endothelial cell line-5a and human CD46 mice were used for in vitro and in vivo experiments, respectively. RNA-seq was employed for correlative omics analysis. Viral infection and copy status were examined using transmission electron microscopy to observe virus particles, immunofluorescence to detect the viral protein Hexon, and qPCR to assess HAdV-7 fiber gene copies. Various methods, including ELISAs for VEGF and other injury markers, the CCK8 assay for cell viability, and flow cytometry for endothelium numbers, were employed to evaluate endothelial damage. Acute lung injury severity was evaluated by scoring pathological inflammation and measuring pulmonary vascular permeability. Autophagy activation was assessed by observing autophagosomes and validating marker proteins.ResultsGSEA analysis showed significant enrichment of gene sets related to endothelial functions (barrier, defense, and regeneration) and ALI in the HAdV-7-infected group. GO analysis indicated an enrichment of autophagy-related pathways linked to cell death. Subsequently, successful signs of HAdV-7 infection and replication were observed in the endothelium, including cytopathic effects, intracellular virions, and increased HAdV-7 fiber gene copies. Endothelial injury, including mitochondrial damage, decreased endothelium, and elevated levels of endothelial injury markers such as VEGF, sICAM-1, sVCAM-1, E-selectin, ESM1, MCP1, and IL1β were observed after HAdV-7 infection. Additionally, evidence of leaky lung blood vessels and ALI was observed, including progressive weight loss, elevated pulmonary vascular permeability, and severe lung consolidation. Furthermore, HAdV-7 infection induced autophagosome formation in the endothelium and triggered complete cell autophagy. Importantly, inhibiting autophagic flux reduced VEGF levels and other endothelial injury markers, decreased viral load, improved cell survival rate, alleviated pulmonary vessel leakage, and mitigated lung inflammation.ConclusionsHAdV-7 successfully infects pulmonary vascular endothelium and replicates effectively, causing injury to the endothelium, high VEGF expression and viral load in the serum, as well as ALI/ARDS. Autophagy inhibitors can alleviate endothelial injury, inhibit viral replication, relieve leakage from the vasculature, and reduce lung inflammation.

Study on the mechanism on Yi-guan-jian decoction alleviating cognitive dysfunction in type 2 diabetes mellitus.

Yi-guan-jian decoction (YGJ) is a traditional Chinese medicine prescription commonly used for treating syndromes associated with Yin deficiency in the liver and kidney, as well as Qi-obstructed in liver. YGJ has shown potential alleviating cognitive dysfunction in type 2 diabetes mellitus (T2DM). However, the precise mechanisms are not yet fully understood. This study aims to reveal the mechanism by which YGJ alleviates cognitive dysfunction in T2DM. Various doses of YGJ were administered to T2DM rats with cognitive dysfunction for 8 weeks. The positive control group received a combination of metformin and memantine. Cognitive function was assessed in T2DM rats using the Morris water maze test during treatment. Changes in gut microbiota and bile acids in the intestine were evaluated, and their interactions analyzed. Additionally, this study also evaluated the expressions of inflammatory markers (IL-1β,TNF-α, IL-16, IL-18 and CRP protein), Tau protein, neurotransmitter (5-HT and GABA), and bile acid receptor (FXR, PXR, VDR, and TGR5). YGJ significantly alleviated insulin resistance and hyperlipidemia, reduce the levels of inflammatory factors in serum and hippocampus, and decreased mortality in T2DM rats. The Morris water maze test indicated that YGJ reduced the escape latency and increased platform crossing frequency, thereby improving cognitive function in T2DM rats. Furthermore, YGJ regulated the abundance of microorganisms associated with bile acid metabolism, including Romboutsia, Bacteroides, Turicibacter, Blautia, and Ruminococcus, thus regulating bile acid metabolism in T2DM rats. Additionally, YGJ also regulated bile acid metabolism by regulating intestinal FXR, PXR, VDR and TRG5 receptors. YGJ can alleviate glucose homeostasis, insulin sensitivity, lipid metabolism, neuroinflammation, cognitive function, as well as remodel intestinal flora and BA composition in CDT2DM rats, which is a potential complementary and alternative therapy for the prevention and treatment of CDT2DM. These effects may be associated that YGJ regulates the structure of intestinal flora and BA metabolism, and inhibits intestinal BA receptors FXR, PXR, TGR5, and VDR.

The Effect of Dexmedetomidine on Inflammatory Factors and Clinical Outcomes in Patients With Septic Shock: A Randomized Clinical Trial

PurposeDexmedetomidine is a sedative-analgesic that is widely used in sepsis. However, its effect on septic shock remains unclear. This study aimed to investigate dexmedetomidine's effect on inflammatory biomarkers in septic shock. MethodsThe present study was a randomized controlled clinical trial. Patients with inclusion criteria were randomly allocated into either the dexmedetomidine (n = 24) or morphine + midazolam group (n = 24). The primary outcome was changes in inflammatory factors, including IL-1, IL-6, TNF-α, ESR, and CRP. The serum levels of inflammatory factors were measured at baseline and the end of the intervention. Secondary outcomes included the change in norepinephrine dose, vital signs, and SOFA scores. FindingsOf the 48 subjects, 52.08% were male. After intervention, IL-1, IL-6, and TNF-α levels significantly differed between the 2 groups (p = 0.011 and p < 0.001 and p < 0.001, respectively). Heart rate and systolic blood pressure decreased over time, but the two groups had no significant difference (p-value > 0.05). In addition, there was no significant difference in norepinephrine dose and SOFA score between the 2 groups (p-value > 0.05). ImplicationsSedation with dexmedetomidine can attenuate the inflammatory factors in septic shock. Also, dexmedetomidine did not worsen the hemodynamic parameters in septic shock patients.

Volatile Oil of Magnolia biondii Pamp. for Transnasal Administration: Its Preparation, Characterization, and Mechanism of Action in the Treatment of Allergic Rhinitis.

Allergic Rhinitis (AR) is a common chronic nasal condition usually caused by allergens. The immune system overreacts when the body is exposed to allergens, releasing a lot of tissue chemicals that cause congestion, more secretions, and an inflammatory reaction in the nasal mucosa. In clinical practice, it remains a significant public health issue. Modern pharmacological studies have demonstrated that Magnolia Volatile Oil (MVO) has good anti-inflammatory, antibacterial, immunomodulatory, and other pharmacological effects. Previous research and literature reports have reported that MVO has good therapeutic effects on allergic rhinitis. However, due to the poor water solubility of Magnolia, its bioavailability is low. The purpose of this present work is to develop a new microemulsion formulation to improve the stability and bioavailability of MVO. The droplet size, PDI, and zeta potential of Magnolia volatile oil microemulsion (MVOME) were characterized along with its physical characteristics, and these values were found to be 14.270.03 nm, 0.09410.31, and -0.35850.12 mV, respectively, demonstrating the successful formation of microemulsion. In OVA-induced AR rats, MVO-ME dramatically reduced the serum levels of TNF-α, IL-1β, and IL-6 inflammatory factors. In addition, MVO-ME significantly inhibited the expression of protein levels of PPAR-γ and P65 in the nasal mucosa of AR rats. In this regard, we hypothesized that MVO-ME may play a therapeutic role in AR by activating the PPAR signaling pathway as well as inhibiting the activation of the NF/κB signaling pathway. MVO-ME has systematic advantages, such as high solubility, bioavailability, etc. It is expected to be an efficient nano-drug delivery system for the clinical treatment of allergic rhinitis.

Tanshinone IIA, a component of Salvia miltiorrhiza Bunge, attenuated sepsis-induced liver injury via the SIRT1/Sestrin2/HO-1 signaling pathway

Ethnopharmacological relevanceAs a traditional Chinese medicine, Salvia miltiorrhiza Bunge has been widely used to treat ischemic and inflammation-related diseases for more than 2000 years. S. miltiorrhiza Bunge has hepatoprotective effects, but the underlying mechanism is not fully understood. ObjectiveTo verify the effect of tanshinone IIA (Tan IIA), the main fat-soluble component of S. miltiorrhiza Bunge, on liver damage induced by sepsis/LPS-induced inflammation and further explore the underlying mechanisms. Materials and methodsMice were administered Tan IIA 2 h before cecal ligation and puncture (CLP). Liver damage was evaluated by hematoxylin-eosin staining and changes in related serum factor levels. The expression of silent information regulator sirtuin 1 (SIRT1), Sestrin2, HO-1 and inflammatory cytokines was examined by immunohistochemistry or western blotting. LPS was used to induce the inflammatory response in vitro, and the activity of the related signaling pathway in response to Tan IIA was detected by western blotting. The SIRT1 inhibitor EX-527 and small interfering RNAs (siRNAs) were employed to determine the key roles of SIRT1 and Sestrin2 in Tan IIA's function. ResultsWe found that Tan IIA significantly improved the pathological changes and function of the liver, and alleviated liver damage in CLP mice. Additionally, SIRT1, Sestrin2, and HO-1 expression was significantly elevated after Tan IIA treatment compared with that in the CLP group both in vivo and in vitro, and Tan IIA treatment additionally suppressed pro-inflammatory cytokine release. However, inhibition of either SIRT1 or Sestrin2 remarkably abrogated the protective effects of Tan IIA. Most importantly, Sestrin2 appeared to function downstream of SIRT1 based on their expression changes after EX-527 or siRNA treatment. ConclusionTan IIA inhibited sepsis/LPS-induced inflammation through the SIRT1/Sestrin2/HO-1 pathway, thereby protecting against sepsis-induced liver injury (SLI). This study suggests that Tan IIA has therapeutic potential against SLI and that the SIRT1/Sestrin2/HO-1 signaling pathway might be a viable target for SLI treatment.

ILF2 protein is a promising serum biomarker for early detection of gastric cancer

BackgroundOur previous small-sample study indicated that serum levels of interleukin enhancer binding factor 2 (ILF2) may have the potential for gastric cancer (GC) detection. The present study was conducted to further validate the diagnostic value of serum ILF2 protein for GC.MethodsSerum specimens and clinical data were collected from patients with GC (n = 99) or benign gastric disease (BGD) (n = 49) and healthy controls (HC) (n = 51). Serum ILF2 levels were measured using enzyme-linked immunosorbent assay. The diagnostic performance of ILF2 was evaluated using the area under the receiver operating characteristic curve (AUC). The independence and synergy of ILF2 in GC diagnosis were analyzed by modeling with conventional blood indicators.ResultsThe median serum ILF2 level was higher in the GC group (227.8ng/mL) than in the BGD group (72.0ng/mL) and the HC group (56.8ng/mL) (p < 0.001), and no significant difference across GC subgroups. The AUCs of ILF2 were 0.915 (95%CI 0.873–0.957) for GC vs. HC, 0.854 (95%CI 0.793–0.915) for GC vs. BGD, 0.885 (95%CI 0.841–0.929) for GC vs. BGD + HC, and 0.888 (95% CI 0.830–0.945) for TNM I stage GC vs. BGD + HC, outperforming conventional blood indicators (corresponding AUCs ranging from 0.641 to 0.782). ILF2 was independent of and synergistic with conventional blood indicators in GC diagnosis, and a simple diagnostic model based on ILF2 and red blood cell count improved the diagnostic performance, with positive rates of approximately 90% in various subgroups of GC.ConclusionsSerum ILF2 protein is a novel and potential serum biomarker for the detection of GC, especially for early GC.

Prodigiosin hydrogel to promote healing of trauma-infected multidrug-resistant Staphylococcus aureus mice wounds

Wound infections caused by Multidrug-resistant Staphylococcus aureus (MRSA) have been regarded as a challenging problem in clinic for the long time. In this study, based on the excellent antimicrobial effect of prodigiosin(PG) and the ability of hydrogel dressing in terms of tissue repair and regeneration, we prepared the PG hydrogel as a treatment for the wound infection induced by MRSA. Rheological tests indicated that PG hydrogel as a semi-solid gel had good mechanical properties. In ex vitro drug permeation studies and dermatokinetic studies showed that PG hydrogel had high PG permeability and were capable of short-term retention in the skin. In addition, in vivo experiments for mouse skin wounds showed that the serum levels of inflammatory factors including IL-β and other inflammatory factors were reduced, the inflammatory infiltration of tissues was reduced, the transcript levels of genes such as COL1A1 were up-regulated at different stages of wound healing, and the relative abundance of genera such as Desulfovibrio was lowered after treatment with PG hydrogel, which facilitated wound healing in mice. Our study would provide a new solution to the clinical shortage of drugs for the treatment of MRSA infection and provide a research basis for improving the comprehensive values of PG.

Plumbagin protect against sepsis-induced myocardial injury in mice by inhibiting the JAK2/STAT3 signaling pathway to reduce cardiomyocyte pyroptosis

To explore the mechanism of plumbagin for protecting against sepsis-induced myocardial injury in mice. Network pharmacology analysis was used to obtain the key targets of plumbagin and diseases, which were subjected to GO and KEGG analysis, and the binding energy was verified using molecular docking. In a mouse model of cecal ligation and puncture (CLP), the protective effect of plumbagin treatment prior to CLP against sepsis-induced myocardial injury was evaluated by examination of myocardial function and pathology using echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-1β and IL-18 and myocardial ROS level in the mice were detected, and Western blotting was used to determine the protein expression levels of STAT3, GSDMD, caspase-11, JAK2, P-STAT3, P-JAK2, GSDMD-N and HMGB1 in the myocardial tissues. Five core targets were screened from the 10 intersecting genes. Molecular docking showed strong binding affinity of plumbagin to STAT3, p-STAT3, and JAK2. Compared with the sham-operated mice, the mouse models of CLP-induced sepsis had significantly decreased CO, LVEF, LVFS and SV and increased serum levels of CK-MB, LDH, MDA and myocardial inflammatory factors and ROS. HE staining and Western blotting showed obvious myocardial injury in the septic mice with increased expressions of JAK2/STAT3 signaling pathway and pyroptosis-related proteins (P < 0.05). Pretreatment with plumbagin significantly improved cardiac functions of CLP mice, lowered serum levels of CK-MB, LDH, MDA, inflammatory factors and myocardial ROS, and decreased the expression levels of JAK2/STAT3 signaling pathway and pyroptosis-related proteins. Plumbagin pretreatment alleviates myocardial injury in septic mice possibly by inhibiting the STAT3 signaling pathway to reduce cardiomyocyte pyroptosis.

Efficacy of combined tympanostomy tube insertion and adenoidectomy in the treatment of otitis media with effusion in children.

To assess the efficacy of combined tympanostomy tube insertion (TTI) and adenoidectomy (Ad) versus Ad alone in the treatment of otitis media with effusion (OME) in children. Clinical data of 145 children with OME who underwent surgical treatment in Jiaxing University Affiliated TCM Hospital from January 2022 to November 2023, were retrospectively analyzed. Patients were grouped based on whether or not Ad was performed with TTI: children who underwent Ad alone were grouped as Ad group (n=71), and children who underwent a combined TTI and Ad were grouped as TTI+Ad group (n=74). Clinical efficacy, clinical indicators (recovery of hearing, disappearance of tinnitus, eardrum healing, and disappearance time of middle ear effusion), serum levels of inflammatory factors, recurrence, and incidence of complications were compared between the two groups. Combined TTI+Ad resulted in a significantly better therapeutic effect three months after the surgery compared Ad alone (P<0.05). Combined treatment was associated with significantly shorter time needed for hearing recovery, disappearance of tinnitus, eardrum healing, and disappearance of middle ear effusion (P<0.05). Combined procedure significantly lowered levels of inflammatory factors (P<0.05), and was associated with lower postoperative recurrence rate (P<0.05) compared to Ad alone. There was no significant difference in the incidence of complications between the two methods of surgical OME treatment (P>0.05). Compared to Ad alone, combined TTI+Ad treatment is equally safe and more effective in the treatment of OME in children. This surgical approach is associated with reduced local inflammatory reactions and lower recurrence rate.

Liuwei Buqi Formula delays progression of chronic obstructive pulmonary disease in rats by regulating the NLRP3/caspase-1/GSDMD pyroptosis pathway

To explore the therapeutic mechanism of Liuwei Buqi (LWBQ) Formula for chronic obstructive pulmonary disease (COPD) in rat models. SD rat models of COPD established by cigarette smoking combined with intratracheal lipopolysaccharide (LPS) instillation and hormone injection were treated with LWBQ Formula by gavage with or without intraperitoneal injection of MCC950 for 3 weeks, starting at the 5th week of modeling. After the treatments, the rats were examined for lung pathologies, lung function, total cell count and white blood cell count in bronchoalveolar lavage fluid (BALF), and serum levels of IL-6, TNF-α, IL-18 and NO. The mRNA expressions of NLRP3, ASC, caspase-1, GSDMD-N, IL-1β, and IL-18 in the lung tissue were detected with qRT-PCR. Compared with the normal control rats, the COPD rat models had severe lung pathologies and showed significantly decreased lung function, increased total cell and leukocyte subset counts in BALF, and increased serum levels of IL-6, TNF-α, IL-18 and NO and mRNA expressions of pyroptosis-related proteins in the lung tissue. Treatment of the rat models with LWBQ Formula significantly improved lung pathology and lung function, reduced total cell and leukocyte counts in BALF, and decreased serum levels of the inflammatory factors and expressions of pyroptosis-related proteins in the lung tissue. The combined treatment with MCC950 further improved lung pathology and function in spite of a significant difference, but BALF cell counts, serum inflammatory factor levels and pulmonary expressions of pyroptosis-related proteins were all significantly reduced following the treatment. LWBQ Formula can delay the progression of COPD in rats possibly by inhibiting lung tissue pyroptosis via regulating the NLRP3/caspase-1/GSDMD pathway to reduce inflammatory response and lung damage.

Analysis of musculoskeletal ultrasound findings and cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica

We sought to clarify the musculoskeletal ultrasound (MSUS) findings and serum concentrations of cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica (GC-R PMR). Patients with PMR admitted to Nagasaki University Hospital (n = 41) were enrolled. MSUS of both shoulder joints was performed in 36 patients. Patients’ sera were analyzed for cytokines/growth factors using multiplex assay kits. We examined the cases of 17 males and 24 females (median age 70 years). There were 27 GC-R patients and 14 non-GC-R patients. PD signals were detected in significantly more GC-R patients (65.2%) than non-GC-R patients (23.1%) (p = 0.035). The median serum level of vascular endothelial growth factor (VEGF) was significantly higher in the GC-R group at 871.4 pg/mL than the non-GC-R group (422.8 pg/mL) (p = 0.03) and significantly higher in the PD-positive versus PD-negative patients (p = 0.04). A multivariate analysis revealed that a high serum VEGF level was an independent variable contributing to GC resistance (p = 0.017, odds ratio: 10.34). These results suggest that a high serum VEGF level is a biomarker of GC resistance in PMR, which might be explained by PD-positive neovascularization in inflamed joints of PMR.

Choroid plexus extracellular vesicle transport of blood-borne insulin-like growth factor 1 to the hippocampus of the immature brain.

Reduced serum level of insulin-like growth factor 1 (IGF-1), a major regulator of perinatal development, in extremely preterm infants has been shown to be associated with neurodevelopmental impairment. To clarify the mechanism of IGF-1 transport at the blood-cerebrospinal fluid (CSF) barrier of the immature brain, we combined studies of in vivo preterm piglet and rabbit models with an in vitro transwell cell culture model of neonatal primary murine choroid plexus epithelial (ChPE) cells. We identified IGF-1-positive intracellular vesicles in ChPE cells and provided data indicating a directional transport of IGF-1 from the basolateral to the apical media in extracellular vesicles (EVs). Exposure of the ChPE cells to human IGF-1 on the basolateral side increased the secretion of IGF-1-positive EVs in the apical media. Mass spectrometry analysis displayed similarities in protein content between EVs derived from preterm piglet CSF-derived and ChPE cell-derived EVs. Furthermore, exposure of ChPE cells to human IGF-1 caused an enrichment of human IGF-1 and transmembrane p24 trafficking protein 2, proteins important for perinatal development, in apical media-derived EVs. Moreover, intraventricular injections of ChPE cell-derived EVs in preterm rabbit pups resulted in an uptake of EVs in the brain, displaying penetration through the ependymal lining and deep into the hippocampus. Finally, exposure of rat hippocampus neurons to ChPE cell-derived EVs resulted in internalization of the EVs in hippocampal soma and neurites. In summary, we describe a transport pathway for blood-borne IGF-1 in EVs through the blood-CSF barrier to the hippocampus in the immature brain.