Impact of nutritional support on immunity, nutrition, inflammation, and outcomes in elderly gastric cancer patients after surgery.

BACKGROUND: Postoperative rehabilitation of elderly patients with gastric cancer has always been the focus of clinical attention. Whether the intervention by a full-course nutritional support team can have a positive impact on the postoperative immune function, nutritional status, inflammatory response, and clinical outcomes of this special population has not yet been fully verified. AIM: To evaluate the impact of full-course nutritional support on postoperative comprehensive symptoms in elderly patients with gastric cancer. METHODS: This is a retrospective study, including 60 elderly gastric cancer patients aged 70 years and above, divided into a nutritional support group and a control group. The nutritional support group received full postoperative nutritional support, including individualized meal formulation, and intravenous and parenteral nutrition supplementation, and was regularly evaluated and adjusted by a professional nutrition team. The control group received routine postoperative care. RESULTS: After intervention, the proportion of CD4+ lymphocytes (25.3% ± 3.1% vs 21.8% ± 2.9%, P < 0.05) and the level of immunoglobulin G (12.5 G/L ± 2.3 G/L vs 10.2 G/L ± 1.8 G/L, P < 0.01) were significantly higher in the nutritional support group than in the control group; the changes in body weight (-0.5 kg ± 0.8 kg vs -1.8 kg ± 0.9 kg, P < 0.05) and body mass index (-0.2 ± 0.3 vs -0.7 ± 0.4, P < 0.05) were less significant in the nutritional support group than in the control group; and the level of C-reactive protein (1.2 mg/L ± 0.4 mg/L vs 2.5 mg/L ± 0.6 mg/L, P < 0.01) and WBC count (7.2 × 109/L ± 1.5 × 109/L vs 9.8 × 109/L ± 2.0 × 109/L, P < 0.01) were significantly lower in the nutritional support group than in the control group. In addition, patients in the nutritional support group had a shorter hospital stay (10.3 d ± 2.1 d vs 14.8 d ± 3.6 d, P < 0.05) and lower incidence of infection (15% vs 35%, P < 0.05) in those of the control group. CONCLUSION: The intervention by the nutritional support team has a positive impact on postoperative immune function, nutritional status, inflammatory response, and clinical outcomes in elderly patients with gastric cancer.

Molecular mechanisms of diabetic nephropathy: A narrative review.

Diabetic nephropathy (DN) is the predominant secondary nephropathy resulting in global end-stage renal disease. It is attracting significant attention in both domestic and international research due to its widespread occurrence, fast advancement, and limited choices for prevention and treatment. The pathophysiology of this condition is intricate and involves multiple molecular and cellular pathways at various levels. This article provides a concise overview of the molecular processes involved in the development of DN. It discusses various factors, such as signaling pathways, cytokines, inflammatory responses, oxidative stress, cellular damage, autophagy, and epigenetics. The aim is to offer clinicians a valuable reference for DN's diagnosis, treatment, and intervention.

Unexpected regulatory functions of cyprinid Viperin on inflammation and metabolism.

BACKGROUND: Viperin, also known as radical S-adenosyl-methionine domain containing protein 2 (RSAD2), is an interferon-inducible protein that is involved in the innate immune response against a wide array of viruses. In mammals, Viperin exerts its antiviral function through enzymatic conversion of cytidine triphosphate (CTP) into its antiviral analog ddhCTP as well as through interactions with host proteins involved in innate immune signaling and in metabolic pathways exploited by viruses during their life cycle. However, how Viperin modulates the antiviral response in fish remains largely unknown. RESULTS: For this purpose, we developed a fathead minnow (Pimephales promelas) clonal cell line in which the unique viperin gene has been knocked out by CRISPR/Cas9 genome-editing. In order to decipher the contribution of fish Viperin to the antiviral response and its regulatory role beyond the scope of the innate immune response, we performed a comparative RNA-seq analysis of viperin-/- and wildtype cell lines upon stimulation with recombinant fathead minnow type I interferon. CONCLUSIONS: Our results revealed that Viperin does not exert positive feedback on the canonical type I IFN but acts as a negative regulator of the inflammatory response by downregulating specific pro-inflammatory genes and upregulating repressors of the NF-κB pathway. It also appeared to play a role in regulating metabolic processes, including one carbon metabolism, bone formation, extracellular matrix organization and cell adhesion.

Machine learning models to predict systemic inflammatory response syndrome after percutaneous nephrolithotomy.

OBJECTIVE: The objective of this study was to develop and evaluate the performance of machine learning models for predicting the possibility of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL). METHODS: We retrospectively reviewed the clinical data of 337 patients who received PCNL between May 2020 and June 2022. In our study, 80% of the data were used as the training set, and the remaining data were used as the testing set. Separate prediction models based on the six machine learning algorithms were created using the training set. The predictive performance of each machine learning model was determined by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity using the testing set. We used coefficients to interpret the contribution of each variable to the predictive performance. RESULTS: Among the six machine learning algorithms, the support vector machine (SVM) delivered the best performance with accuracy of 0.868, AUC of 0.942 (95% CI 0.890-0.994) in the testing set. Further analysis using the SVM model showed that prealbumin contributed the most to the prediction of the outcome, followed by preoperative urine culture, systemic immune-inflammation (SII), neutrophil to lymphocyte ratio (NLR), staghorn stones, fibrinogen, operation time, preoperative urine white blood cell (WBC), preoperative urea nitrogen, hydronephrosis, stone burden, sex and preoperative lymphocyte count. CONCLUSION: Machine learning-based prediction models can accurately predict the possibility of SIRS after PCNL in advance by learning patient clinical data, and should be used to guide surgeons in clinical decision-making.

Graft-to-recipient weight ratio and risk of systemic inflammatory response syndrome early after liver transplantation in children.

BACKGROUND: Systemic inflammatory responses soon after liver transplantation in children can lead to complications and poor outcomes, so here we examined potential risk factors of such responses. METHODS: Data were retrospectively analyzed for 69 children who underwent liver transplantation at a single center between July 2017 and November 2019 through follow-up lasting up to one years. Numerous clinicodemographic factors were compared between those who suffered early systemic inflammatory response syndrome (SIRS) or not. RESULTS: Of the 69 patients in our analysis, early SIRS occurred in 35 [50.7%, 95% confidence interval (CI), 38.6-62.8%]. Those patients showed significantly higher graft-to-recipient weight ratio (3.69 ± 1.26 vs. 3.12 ± 0.99%, P = 0.042) and lower survival rate at one year (85.7% vs. 100%, P = 0.023). Multivariate analysis found graft-to-recipient weight ratio > 4% to be an independent risk factor for early SIRS [odds ratio (OR) 3.8, 95% CI 1.08-13.371, P = 0.037], and a cut-off value of 4.04% predicted the syndrome in our patients, and area under the receiver operating characteristic curve of 0.656 (95% CI 0.525-0.788, P = 0.026). CONCLUSIONS: Graft-to-recipient weight ratio > 4% may predict higher risk of SIRS soon after liver transplantation in children.

The Effect of Transurethral Holmium Laser Enucleation of the Prostate in the Treatment of High-Risk Elderly Patients with BPH and Its Influence on Quality of Life.

BACKGROUND: Transurethral holmium laser enucleation of the prostate (HoLEP) has a good therapeutic effect on benign prostatic hyperplasia (BPH). The purpose of this study was to investigate the clinical efficacy of HoLEP in the treatment of high-risk elderly patients with BPH and assess its impact on the inflammatory response, vascular endothelial function and quality of life (QoL). METHODS: Patients at high risk of BPH who were hospitalised in Chengde Central Hospital from February 2021 to December 2022 were retrospectively selected as the study objects, and a total of 100 cases were included. The control group underwent transurethral resection of the prostate, and the observation group underwent HoLEP. Perioperative indexes, urodynamic indexes, QoL 6 months after surgery and incidence of postoperative complications were compared between the two groups. Moreover, serum levels of inflammatory factors and vascular endothelial factors were detected in two groups. RESULTS: We found no significant difference in general data between the two groups of patients (p > 0.05). The operation time, perioperative bleeding, bladder flushing time and hospitalisation time of the observation group were significantly shorter than those of the control group (p < 0.05). On the 7th day after surgery, the serum levels of tumour necrosis factor alpha, interleukin-1ß, interleukin-6, vascular endothelial growth factor, basic fibroblast growth factor and endothelin-1 in the observation group were significantly lower than those in the control group (p < 0.05). Six months after surgery, the maximal urinary flow rate and QoL scores of the patients in the observation group were significantly higher than those of the control group (p < 0.05), and the residual urine volume and International Prostate Symptom Score of observation group were significantly lower than those of the control group (p < 0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group (χ2 = 7.440, p = 0.006). CONCLUSIONS: HoLEP can effectively remove hyperplasia of the prostate and reduce the inflammatory response in the patient's body when treating BPH in high-risk elderly patients. It can also regulate the levels of vascular endothelial factors and effectively improve the patient's QoL.

A Novel Inflammatory Indicator for Tuberculosis-Associated Obstructive Pulmonary Disease (TOPD): The Systemic Inflammatory Response Index (SIRI).

Background: The development of chronic obstructive pulmonary disease (COPD) following tuberculosis (TB) is known as tuberculosis-associated obstructive pulmonary disease (TOPD). This study aimed to explore the predictive value of inflammatory indicators for TOPD in TB patients. Methods: Data for this cross-sectional study were collected between January 2014 and January 2022 at Wuhan Jinyintan Hospital. The ratio of inflammatory indicators, including Systemic Inflammatory Response Index (SIRI), C-reactive protein-to-lymphocyte ratio (CLR), eosinophil count-to-lymphocyte count ratio (ELR), were calculated. Univariate and multivariate logistic regression analyses were conducted to explore the association between the ratio of inflammatory indicators and TOPD. Furthermore, the relationship between the ratio of inflammatory indicators and TOPD was investigated using propensity score matching (PSM) and receiver operating characteristic (ROC) curve analysis was performed to evaluate their predictive value for TOPD. Results: The present study included a total of 737 patients, of whom 83 participants (11.26%) had TOPD. Sixty-nine TOPD patients and 69 non-TOPD (NTOPD) patients were successfully matched. Univariate and multivariable logistics regression analysis, conducted before and after PSM, revealed that SIRI was independently significantly associated with an increased risk of TOPD. The area under curve (AUC) of SIRI were 0.702 and 0.668 before and after PSM, respectively. Additionally, patients were stratified into four different groups based on SIRI quartiles for further analysis. The prevalence of TOPD in TB patients showed an increase with higher SIRI values, both before and after PSM. Conclusion: Levels of inflammatory indicators were higher in TOPD patients when compared to NTOPD patients. SIRI may be a simple and useful inflammatory index for assessing TOPD, and TB patients with higher values of SIRI are more likely to be high-risk group for TOPD.

The Association of Pretreatment Systemic Immune Inflammatory Response Index (SII) and Neutrophil-to-Lymphocyte Ratio (NLR) with Lymph Node Metastasis in Patients with Papillary Thyroid Carcinoma.

Objective: Immunoinflammatory response can participate in the development of cancer. To investigate the relationship between pretreatment systemic immune inflammatory response index (SII), systemic inflammatory response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and lymph node metastasis in patients with papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was performed on 547 PTC patients treated in Meizhou People's Hospital from January 2018 to December 2021. Clinicopathological data were collected, including gender, age, Hashimoto's thyroiditis, maximum tumor diameter, extra-membrane infiltration, disease stage, BRAF V600E mutation, pretreatment inflammatory index levels, and lymph node metastasis. The optimal cutoff values of SII, SIRI, NLR, PLR and LMR were calculated by receiver operating characteristic (ROC) curve, and the relationship between inflammatory indexes and other clinicopathological features and lymph node metastasis was analyzed. Results: There were 303 (55.4%) PTC patients with lymph node metastasis. The levels of SII, SIRI, NLR, and PLR in patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis, while the levels of LMR were significantly lower than those in patients without lymph node metastasis (all p<0.05). When lymph node metastasis was taken as the endpoint, the critical value of SII was 625.375, the SIRI cutoff value was 0.705, the NLR cutoff value was 1.915 (all area under the ROC curve >0.6). The results of regression logistic analysis showed that age <55 years old (OR: 1.626, 95% CI: 1.009-2.623, p=0.046), maximum tumor diameter >1cm (OR: 2.681, 95% CI: 1.819-3.952, p<0.001), BRAF V600E mutation (OR: 2.709, 95% CI: 1.542-4.759, p=0.001), SII positive (≥625.375/<625.375, OR: 2.663, 95% CI: 1.560-4.546, p<0.001), and NLR positive (≥1.915/<1.915, OR: 1.808, 95% CI: 1.118-2.923, p=0.016) were independent risk factors for lymph node metastasis of PTC. Conclusion: Age <55 years old, maximum tumor diameter >1cm, BRAF V600E mutation, SII positive, and NLR positive were independent risk factors for lymph node metastasis in PTC.

The Inflammatory Response and Long-Term Outcomes Between Open and Laparoscopic Pancreatoduodenectomy:A Propensity-Matched Single-Institution Study.

Background: In recent years, although laparoscopic pancreatoduodenectomy (LPD) has experienced rapid development both domestically and internationally, however, there are still varying opinions toward LPD. Methods: From January 2020 to July 2022, the data were collected. We compared the inflammatory response at various postoperative time points and evaluated long-term outcomes between the two groups. Results: In the early stage, the LPD group exhibited lower values of white blood cells, C-reactive protein, neutrophils, and platelets after surgery compared with open pancreatoduodenectomy (OPD) (P all<0.05). However, no statistically significant differences were observed in terms of procalcitonin, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Before propensity score matching, no statistical significance was observed between two groups, whether in terms of disease-free survival (DFS) (P = .406) or overall survival (OS) (P = .851). However, to further control for confounding factors, propensity score matching was used. The analysis revealed that DFS still showed no significant difference (P = .928), but, in the term of OS, a statistical significance was observed between the two groups. Conclusion: LPD demonstrates a comparable long-term outcomes to OPD and even slightly superior OS. Moreover, the LPD group exhibits a lower inflammatory response during early postoperative period.

Impact of refining on phytochemicals and anti-inflammatory activity of papaya (Carica papaya L.) seed oil in LPS-stimulated THP-1 cells.

This study investigated the changes in phytochemical composition and inflammatory response of crude papaya (Carica papaya L.) seed oil (CPO) and its refined forms (degummed, PDG; deacidified, PDA; decolorized, PDC; deodorized, PDO). Oils were analyzed for their phytochemical composition, oil quality parameters, antioxidant activity, and their inflammatory response in LPS-stimulated THP-1 macrophages. At higher refining degrees, particularly after deacidification, the contents of phytochemicals (sterols, tocopherols, and polyphenols) decreased while oxidation products increased. Both CPO (0.1-1.0 mg/mL) and PDG reduced the secretion and mRNA expression of LPS-stimulated inflammatory cytokines and mediators and also blocked the activation of the NF-κB pathway. PDA, PDC, and PDO showed low anti-inflammatory or even pro-inflammatory activity. Correlation analysis showed that 4 polyphenols and 2 phytosterols were responsible for the oil's anti-inflammatory effects. These findings indicated that moderate refining is suggested for papaya seed oil processing for retaining bioactive ingredients and anti-inflammatory ability.

Mechanisms and treatment of anemia related to cardiac arrest. / å¿ƒè„éª¤åœåŽç›¸å ³æ€§è´«è¡€çš„æœºåˆ¶åŠæ²»ç–—.

Cardiac arrest is a common and fatal emergency situation. Recently, an increasing number of studies have shown that anemia in patients with cardiac arrest is closely related to high mortality rates and poor neurological outcomes. Anemia is prevalent among patients with post-cardiac arrest syndrome (PCAS), but its specific pathogenesis remains unclear. The mechanisms may involve various factors, including reduced production of erythropoietin, oxidative stress/inflammatory responses, gastrointestinal ischemic injury, hepcidin abnormalities, iatrogenic blood loss, and malnutrition. Measures to improve anemia related to cardiac arrest may include blood transfusions, administration of erythropoietin, anti-inflammation and antioxidant therapies, supplementation of hematopoietic materials, protection of gastrointestinal mucosa, and use of hepcidin antibodies and antagonists. Therefore, exploring the latest research progress on the mechanisms and treatment of anemia related to cardiac arrest is of significant guiding importance for improving secondary brain injury caused by anemia and the prognosis of patients with cardiac arrest.

Identification of key differentially expressed immune related genes in patients with persistent atrial fibrillation: an integrated bioinformation analysis.

OBJECTIVE: We aimed to investigate key differentially expressed immune related genes in persistent atrial fibrillation. METHODS: Gene expression profiles were downloaded from Gene Expression Omnibus (GEO) using "GEO query" package. "limma" package and "sva" package were used to conduct normalization and eliminate batch effects, respectively. We screened out differentially expressed genes (DEGs) based on "limma" package with the standard of |log fold change (FC)| ≥ 1.5 and false discovery rate (FDR) < 0.05. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed by "clusterProfler" package. We further applied LASSO to select key DEGs, and intersected key DEGs with immune related genes from ImmPort database. The ROC curve of each DEIRG was constructed to evaluate its diagnostic efficiency for AF. RESULTS: A total of 103 DEGs we were screened out, of them, 48 genes were down-regulated and 55 genes were up-regulated. Result of functional enrichment analysis show that, most of DEGs were related to immune response, inflammation, and oxidative stress. Ultimately, CYBB, RORB, S100A12, and CHGB were determined as key DEIRGs, each of which displayed a favor efficiency for diagnosing persistent AF. CONCLUSION: CYBB, RORB, S100A12, and CHGB were identified as key DEIRGs in persistent AF, and future studies are needed to further explore the underlying roles of CYBB, RORB, S100A12, and CHGB in persistent AF.

Impact of minimal invasive extracorporeal circulation on systemic inflammatory response - a randomized trial.

BACKGROUND: Extracorporeal circulation causes a systemic inflammatory response, that may cause postoperative haemodynamic instability and end-organ dysfunction. This study aimed to investigate the impact of minimal invasive extracorporeal circulation (MiECC) on the systemic inflammatory response compared with conventional extracorporeal circulation (CECC). METHODS: Patients undergoing coronary artery bypass grafting were randomized to MiECC (n = 30) and CECC (n = 30). Primary endpoint was tumor necrosis factor-α. Secondary endpoints were other biochemical markers of inflammation (IL1ß, IL6 and IL8, C-reactive protein, leukocytes), and markers of inadequate tissue perfusion and tissue damage (lactate dehydrogenase, lactate and creatine kinase-MB). In addition, we registered signs of systemic inflammatory response syndrome, haemodynamic instability, atrial fibrillation, respiratory dysfunction, and infection. RESULTS: Patients treated with MiECC showed significantly lower levels of tumor necrosis factor-α than CECC during and early after extracorporeal circulation (median: MiECC 3.4 pg/mL; CI 2.2-4.5 vs. CECC 4.6 pg/mL; CI 3.4-5.6; p = 0.01). Lower levels of creatine kinase-MB and lactate dehydrogenase suggested less tissue damage. However, we detected no other significant differences in any other markers of inflammation, tissue damage or in any of the clinical outcomes. CONCLUSIONS: Lower levels of TNF-α after MiECC compared with CECC may reflect reduced inflammatory response, although other biochemical markers of inflammation were comparable. Our results suggest better end-organ protection with MiECC compared with CECC. Clinical parameters related to systemic inflammatory response were comparable in this study. CLINICAL REGISTRATION NUMBER: NCT03216720.

Wogonin ameliorates the proliferation, inflammatory response, and pyroptosis in keratinocytes via NOD-like receptor family pyrin domain containing 3/Caspase-1/Gasdermin-D pathway.

BACKGROUND: Psoriasis refers to a highly prevalent and immunologically mediated dermatosis with considerable deterioration in life quality. Wogonin, a sort of flavonoid, has been mentioned to elicit protective activities in skin diseases. However, whether Wogonin is implicated in the treatment of psoriasis and its specific mechanisms are not fully understood. AIM: The present work attempted to elaborate the role of Wogonin during the process of psoriasis and to concentrate on the associated action mechanism. METHODS: Cell counting kit-8 (CCK-8) method was initially applied to assay the viability of human keratinocyte HaCaT cells treated by varying concentrations of Wogonin. To mimic psoriasis in vitro, HaCaT cells were exposed to M5 cytokines. CCK-8 and 5-Ethynyl-2'-deoxyuridine  assays were adopted for the measurement of cell proliferation. Inflammatory levels were examined with enzyme-linked immunosorbent assay. Immunofluorescence staining tested nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) and Caspase-1 expressions. Western blot examined the protein expressions of proliferation-, inflammation-, pyroptosis-associated factors, and NLRP3. RESULTS: Wogonin treatment antagonized the proliferation, inflammatory response, and NLRP3/caspase-1/Gasdermin-D (GSDMD)-mediated pyroptosis in M5-challenged HaCaT cells. Besides, NLRP3 elevation partially abrogated the effects of Wogonin on M5-induced proliferation, inflammatory response, and NLRP3/caspase-1/GSDMD-mediated pyroptosis in HaCaT cells. CONCLUSION: In a word, Wogonin might exert anti-proliferation, anti-inflammatory and anti-pyroptosis activities in M5-induced cell model of psoriasis and the blockade of NLRP3/Caspase-1/GSDMD pathway might be recognized as a potential mechanism underlying the protective mechanism of Wogonin in psoriasis, suggesting Wogonin as a prospective anti-psoriasis drug.

HGF ameliorates cardiomyocyte apoptosis and inflammatory response in sepsis via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.

OBJECTIVE: This study aimed to analyze the impact of HGF on cardiomyocyte injury, apoptosis, and inflammatory response induced by lipopolysaccharide (LPS). METHODS: Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of HGF, interleukin (IL)-6, IL-10, creatine phosphokinase-isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) in the samples. qPCR and Western blotting (WB) were employed to assess the mRNA and protein expressions of HGF, IL-10, IL-6, PI3K, AKT, p-PI3K, and p-AKT. RESULTS: The outcomes of the in vivo experiment revealed that serum levels of IL-6, IL-10, HGF and SOFA scores in the SC group were elevated in contrast to the non-SC group. The correlation analysis indicated a substantial and positive association among serum HGF, IL-6, and IL-10 levels and SOFA scores. Relative to IL-6, IL-10 levels, and SOFA scores, serum HGF demonstrated the highest diagnostic value for SC. Following LPS administration to stimulate H9c2 cells across various periods (0, 12, 24, 48, and 72 h), the levels of myocardial injury markers (CK-MB and cTnI) in the cell supernatants, intracellular inflammatory factors (mRNA and protein levels of IL-10 and IL-6), apoptosis and ROS levels, exhibited a gradual increase followed by a subsequent decline. Following the overexpression of HGF, there was an increase in cell viability, and a decrease in apoptosis, inflammation, oxidative stress injuries, and the protein phosphorylation expressions of PI3K and AKT. After knockdown of HGF expression, the activity of LPS-induced H9c2 cells was further reduced, leading to increased cell injury, apoptosis, inflammation, oxidative stress,and the expression levels of PI3K and Akt protein phosphorylation were further elevated. CONCLUSION: HGF was associated with decreased LPS-induced H9c2 apoptosis and inflammation in H9c2 cells, alongside an improvement in cell viability, indicating potential cytoprotective effects. The mechanism underlying these impacts may be ascribed to the suppression of the PI3K/AKT signaling pathway.

Multifunctional Glycopeptide-Based Hydrogel via Dual-Modulation for the Prevention and Repair of Radiation-Induced Skin Injury.

The radiation-induced skin injury (RISI) remains a great challenge for clinical wound management and care after radiotherapy, as patients will suffer from the acute radiation injury and long-term chronic inflammatory damage during the treatment. The excessive ROS in the early acute stage and prolonged inflammatory response in the late healing process always hinder therapeutic efficiency. Herein, we developed an extracellular matrix (ECM)-mimetic multifunctional glycopeptide hydrogel (oCP@As) to promote and accelerate RISI repair via a dual-modulation strategy in different healing stages. The oCP@As hydrogel not only can form an ECM-like nanofiber structure through the Schiff base reaction but also exhibits ROS scavenging and DNA double-strand break repair abilities, which can effectively reduce the acute radiation damage. Meanwhile, the introduction of oxidized chondroitin sulfate, which is the ECM polysaccharide-like component, enables regulation of the inflammatory response by adsorption of inflammatory factors, accelerating the repair of chronic inflammatory injury. The animal experiments demonstrated that oCP@As can significantly weaken RISI symptoms, promote epidermal tissue regeneration and angiogenesis, and reduce pro-inflammatory cytokine expression. Therefore, this multifunctional glycopeptide hydrogel dressing can effectively attenuate RISI symptoms and promote RISI healing, showing great potential for clinical applications in radiotherapy protection and repair.

Transcriptomic and proteomic profiling of bi-partite and tri-partite murine iPSC-derived neurospheroids under steady-state and inflammatory condition.

induced-pluripotent stem cell (iPSC)-derived neurospheroid (NSPH) models are an emerging in vitro toolkit to study the influence of inflammatory triggers on neurodegeneration and repair in a 3D neural environment. In contrast to their human counterpart, the absence of murine iPSC-derived NSPHs for profound characterisation and validation studies is a major experimental research gap, even though they offer the only possibility to truly compare or validate in vitro NSPH responses with in vivo brain responses. To contribute to these developments, we here describe the generation and characterisation of 5-week-old CX3CR1eGFP+/- CCR2RFP+/- murine (m)iPSC-derived bi-partite (neurons + astrocytes) and tri-partite (neurons + astrocytes + microglia) NSPH models that can be subjected to cellular activation following pro-inflammatory stimulation. First, cytokine analysis demonstrates that both bi-partite and tri-partite NSPHs can be triggered to release IL6 and CXCL10 following three days of stimulation with, respectively, TNFα + IL1ß + IFNγ and LPS + IFNγ. Additionally, immunocytochemical analysis for G3BP1 and PABPC1 revealed the development of stress granules in both bi-partite and tri-partite NSPHs after 3 days of stimulation. To further investigate the observed signs of inflammatory response and cellular stress, we performed an untargeted transcriptomic and proteomic analysis of bi- and tri-partite NSPHs under steady-state and inflammatory conditions. Here, using the combined differential gene and protein expression profiles between unstimulated and stimulated NSPHs, Ingenuity Pathway Analysis (IPA) confirms the activation of canonical pathways associated with inflammation and cellular stress in both bi-partite and tri-partite NSPHs. Moreover, our multi-omics analysis suggests a higher level of downstream inflammatory responses, impairment of homeostatic and developmental processes, as well as activation of cell death processes in stimulated tri-partite NSPHs compared to bi-partite NSPHs. Concluding, these results emphasise the advantages of including microglia in NSPH research to study inflammation-induced neurodegeneration in a 3D neural environment.

Exploring the anti-inflammatory and immunomodulatory potential of licochalcone B against psoralidin-induced liver injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Herb-induced liver injury (HILI) represents an exacerbated inflammatory response, with Psoraleae fructus (PF) and its preparations recently associated with hepatotoxicity. Licorice, historically recognized as a detoxifying herbal remedy, is considered to possess hepatoprotective properties. Our previous research identified bavachin, bakuchiol, and psoralidin (PSO) as potential toxic constituents in PF, while licochalcone B (LCB) and echinatin were identified as bioactive components in licorice. However, evidence regarding the interactions of active compounds in herbs and their underlying mechanisms remains limited. AIM OF THE STUDY: The objective of this study is to assess the potential mechanisms through which LCB modulates immunological and anti-inflammatory responses to treat PSO-induced liver injury by using human hepatocyte cells (L02) and LPS-primed mice. METHODS: The ameliorative effects of LCB and echinatin on bavachin, bakuchiol, and PSO-induced liver injury were demonstrated in L02 cells. Subsequently, the efficacy of LCB on PSO-induced idiosyncratic liver injury was further validated in C57BL/6 mice under moderate inflammatory stress induced by LPS priming. The mechanisms were preliminarily explored with an integrated strategy of molecular docking, RT-PCR verification, and untargeted metabolomics. RESULTS: The study shows that LCB significantly reduced cell injury induced by the three chemicals in PF and provided substantial protection against PSO-induced hepatic damage, as indicated by the levels of ALT, AST, and LDH. LCB normalized liver function and remarkedly alleviated hepatic lesions and inflammation caused by PSO in mice under moderate inflammatory stress. The mRNA profiles of both L02 cells and mice liver tissue revealed that LCB mitigated PSO-induced hepatotoxicity by regulating the gene expression of pro-inflammatory cytokines IL1B and TNF, as well as immunoinflammatory genes PIK3CA, AKT1, NFKB1, and NLRP3. Furthermore, untargeted metabolomics of liver tissue indicated that LCB could reverse the abnormal expression of 11 discriminatory metabolites, with the interrelationship between differential metabolites and target genes primarily clustering in glycerophospholipid metabolism, arachidonic acid metabolism, and phosphatidylinositol signaling system. CONCLUSION: LCB demonstrated a superior anti-inflammatory and immunomodulatory effect on PSO-induced hepatotoxicity by modulating the inflammatory response and metabolic signaling system. Key interactive targets included phosphatidylcholine, phosphatidic acid, and subunit isoforms of PI3K.

Association between systemic inflammatory response index and bone turnover markers in Chinese patients with osteoporotic fractures: a retrospective cross-sectional study.

Background: The systemic inflammatory response index (SIRI) is a novel composite biomarker of inflammation. However, there is limited information on its use in the context of osteoporotic fractures. Hence, this study aimed to investigate the association between baseline SIRI values and bone turnover markers (BTMs) in Chinese patients diagnosed with osteoporotic fractures (OPFs), to offer a more precise method for assessing bone health and inflammation in clinical settings. Methods: A retrospective cross-sectional study was conducted on 3,558 hospitalized patients with OPFs who required surgery or hospitalization at the First People's Hospital of Kunshan City from January 2017 to July 2022. Baseline measurements of SIRI, ß-CTX (beta-C-terminal telopeptide of type I collagen), and P1NP (procollagen type I N-terminal propeptide) were obtained. The analyses were adjusted for variables, including age, sex, body mass index (BMI), and other initial laboratory and clinical findings. Furthermore, multivariable logistic regression, smooth curve fitting, and threshold analysis were also performed. Results: The results revealed a negative correlation between baseline SIRI values and both ß-CTX and P1NP levels. After adjusting for covariates in the regression analysis, each unit increase in SIRI was found to be inked to a reduction of 0.04 (ß = -0.04; 95% confidence interval [CI], -0.05 to -0.03; with p-value <0.001) in ß-CTX levels and a decrease of 3.77 (ß = 3.77; 95% CI, 5.07 to 2.47; with p-value <0.001) in P1NP levels. Furthermore, a curvilinear relationship and threshold effect were also identified. Turning points were identified at SIRI values of 1.41 and 1.63 on the adjusted smooth curve. Conclusion: The results showed a negative correlation between the baseline SIRI value and ß-CTX level, as well as the level of P1NP. This suggests a possible link between the systemic inflammatory response and reduced bone metabolism. If these findings are verified, SIRI has the potential to function as a predictive indicator for BTMs. Nevertheless, additional research is necessary to verify these findings.

Ovarian Puncture Triggers an Inflammatory Response that did not Affect Late Folliculogenesis, Ovulation Rate, and Fertility.

Ovarian puncture has been widely used in assisted reproduction, but there are still gaps about its effects on ovarian morphophysiology, as well as the relationship between inflammation caused by this procedure and the follicular growth and fertility. The aim of this study was to investigate the effects of ovarian puncture on folliculogenesis and fertility. Mice (n = 24) were divided into two groups: (1) SHAM-both ovaries were exposed and repositioned and (2) Punctured-ovaries were exposed, punctured, and repositioned. After 96 h of surgery, ovaries were collected for morphofunctional analysis. New females were used for the superovulation (n = 10) and fertility assays (n = 10). Increased volumetric density of inflammatory cells-p = 0.0005, p = 0.0013; hemorrhagic foci-p < 0.0001; and inflammatory exudate-p < 0.0001 could be noticed on the punctured group, compared to SHAM. The percentage of primordial follicles was lower on the punctured ovaries (p = 0.00294). Ovarian puncture has also induced an increase in the proliferation of granulosa cells of primary (p = 0.0321) and antral follicles (p = 0.0395), and an increased apoptotic index of antral follicles (p = 0.0100). There was no influence on expression of some genes related to inflammation, collagen deposition and folliculogenesis progression. The reproductive aspects (oocyte retrieval and number of fetuses per female) were not altered (p > 0.05). Taken together, our findings strongly suggest that ovarian puncture results in a local inflammation that affects follicular growth and atresia. However, it does not affect female fertility, which strengthens the safety of this procedure.