Gelsemium low doses protect against serum deprivation-induced stress on mitochondria in neuronal cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Gelsemium dynamized dilutions (GDD) are known as a remedy for a wide range of behavioral and psychological symptoms of depression and anxiety at ultra-low doses, yet the underlying mechanisms of the mode of action of G. sempervirens itself are not well understood. AIM OF THE STUDY: The present study was designed to examine the neuroprotective effects of Gelsemium preparations in counteracting stress-related mitochondrial dysfunctions in neuronal cells. MATERIALS AND METHODS: We started by studying how serum deprivation affects the mitochondrial functions of human neuroblastoma (SH-SY5Y) cells. Next, we looked into the potential of various Gelsemium dilutions to improve cell survival and ATP levels. After identifying the most effective dilutions, 3C and 5C, we tested their ability to protect SH-SY5Y cells from stress-induced mitochondrial deficits. We measured total and mitochondrial superoxide anion radicals using fluorescent dyes dihydroethidium (DHE) and the red mitochondrial superoxide indicator (MitoSOX). Additionally, we assessed total nitric oxide levels with 4,5-diaminofluorescein diacetate (DAF-2DA), examined the redox state using pRA305 cells stably transfected with a plasmid encoding a redox-sensitive green fluorescent protein, and analyzed mitochondrial network morphology using an automated high-content analysis device, Cytation3. Furthermore, we investigated bioenergetics by measuring ATP production with a bioluminescence assay (ViaLighTM HT) and evaluated mitochondrial respiration (OCR) and glycolysis (ECAR) using the Seahorse Bioscience XF24 Analyzer. Finally, we determined cell survival using an MTT reduction assay. RESULTS: Our research indicates that Gelsemium dilutions (3C and 5C) exhibited neuroprotective effects by: - Normalizing total and mitochondrial superoxide anion radicals and total nitric oxide levels. - Regulating the mitochondrial redox environment and mitochondrial networks morphology. - Increasing ATP generation as well as OCR and ECAR levels, thereby reducing the viability loss induced by serum withdrawal stress. CONCLUSIONS: These findings highlight that dynamized Gelsemium preparations may have neuroprotective effects against stress-induced cellular changes in the brain by regulating mitochondrial functions, essential for the survival, plasticity, and function of neurons in depression.

In vivo and in vitro study on the regulatory mechanism of XiaoChaiHu decoction on PANoptosis in sepsis-induced cardiomyopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: In accordance with the tenets of traditional Chinese medicine, sepsis is categorized into three distinct syndromes: heat syndrome, blood stasis syndrome, and deficiency syndrome. Xiaochaihu decoction (XCHD) has many functions, including the capacity to protect the liver, cholagogue, antipyretic, anti-inflammatory, and anti-pathogenic microorganisms. XCHD exerts the effect of clearing heat and reconciling Shaoyang. The XCHD contains many efficacious active ingredients, yet the mechanism of sepsis-induced cardiomyopathy (SIC) remains elusive. AIM OF THE STUDY: To investigate the molecular mechanisms underlying the protective effects of XCHD against SIC using an integrated approach combining network pharmacology and molecular biology techniques. MATERIALS AND METHODS: Network pharmacology methods identified the active ingredients, target proteins, and pathways affected by XCHD in the context of SIC. We conducted in vivo experiments using mice with lipopolysaccharide-induced SIC, evaluating cardiac function through echocardiography and histology. XCHD-containing serum was analyzed to determine its principal active components using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The effects of XCHD-containing serum on SIC were further tested in vitro in LPS-treated H9c2 cardiac cells. Protein expression levels were quantified via Western blotting and enzyme-linked immunosorbent assay (ELISA). Additionally, molecular docking was performed between the active components and ZBP1, a potential target protein. Overexpression of ZBP1 in H9c2 cells allowed for a deeper exploration of its role in modulating SIC-associated gene expression. RESULTS: UPLC-MS/MS identified 31 shared XCHD and XCHD-containing serum components. These included organic acids, terpenoids, and flavonoids, which have been identified as the active components of XCHD. Our findings revealed that XCHD alleviated LPS-induced myocardial injury, improved cardiac function, and preserved cardiomyocyte morphology in mice. In vitro studies, we demonstrated that XCHD-containing serum significantly suppressed the expression of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) in LPS-induced H9c2 cells. Mechanistic investigations showed that XCHD downregulated genes associated with PANoptosis, a novel cell death pathway, suggesting its protective role in sepsis-damaged hearts. Conversely, overexpression of ZBP1 abolished the protective effects of XCHD and amplified PANoptosis-related gene expression. CONCLUSIONS: Our study provides the first evidence supporting the protective effects of XCHD against SIC, both in vitro and in vivo. The underlying mechanism involves the inhibition of ZBP1-initiated PANoptosis, offering new insights into treating SIC using XCHD.

Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population.

Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

Nanoparticles of nucleotide-free analogue of vitamin B12 formed in protein nanocarriers and their neuroprotective activity in vivo.

Recently, we have described the first supermolecular nanoentities of vitamin B12 derivative, viz. monocyano form of heptabutyl cobyrinate, unique nanoparticles with strong noncovalent intermolecular interactions, emerging optical and catalytic properties. Their nearest analogue, heptamethyl cobyrinate (ACCby), exhibits bioactivity. Here, we demonstrate the first example of the formation of nanoparticles of this nucleotide-free analogue of vitamin B12 in protein nanocarriers and neuroprotective activity in vivo of the own nanoform of the drug. The preparation and characterization of nanocarriers based on bovine serum albumin (BSA) loaded with vitamin B12 (viz. cyano- and aquacobalamins) and ACCby were performed. Nucleotide-free analogue of vitamin B12 is tightly retained by the protein structure and exists in an incorporated state in the form of nanoparticles. The effect of encapsulated drugs on the character and severity of primary generalized seizures in rats induced by the pharmacotoxicant thiosemicarbazide was studied. Cyanocobalamin and ACCby exhibited a neuroprotective effect. The best influence of the encapsulation on the effectiveness of the drugs was achieved in the case of AСCby, whose bioavailability as a neuroprotector did not change upon introduction in BSA particles, i.e., 33 % of surviving animals were observed upon ACCby administration in free form and in encapsulated state. No surviving rats were observed without the administration of drugs. Thus, BSA nanocarriers loaded by nanoparticles of nucleotide-free analogues of vitamin B12, including hydrophobic ones, can be recommended for neuroprotection and targeted delivery.

Expression and significance of CEMIP and CYP11B2 in serum in women with foetal growth restriction.

BACKGROUND: Foetal growth restriction (FGR) occurs when a foetus fails to reach its growth potential. This observational study assessed the expression and significance of cell migration-including protein (CEMIP) and aldosterone synthase (CYP11B2) in the serum of pregnant women with FGR. METHODS: 40 singleton FGR-suffered pregnant women, as well as 40 normal singleton pregnant women, were enrolled. The expression of CEMIP and CYP11B2 in serum was detected in early pregnancy. The correlations between parameters were evaluated. The predictive variables for FGR were determined. The diagnostic value of CEMIP and CYP11B2 for FGR was analysed. RESULTS: CEMIP and CYP11B2 mRNA expression in the serum of pregnant women with FGR decreased (both P < 0.001). CEMIP (95%CI: 0.802-0.921, P < 0.001) and CYP11B2 (95%CI: 0.795-0.907, P < 0.001) mRNA expression in serum and soluble fms like tyrosine kinase-1 (sFLT1)/placental growth factor (PlGF) ratio (95%CI: 0.866-0.974, P < 0.001) were independent predictors of FGR, and CEMIP (r = -0.578, P = 0.001) and CYP11B2 (r = -0.602, P < 0.001) mRNA expression in serum were negatively correlated with sFLT1/PlGF ratio. CEMIP (AUC = 0.741) and CYP11B2 (AUC = 0.764) mRNA expression in serum had good diagnostic value for FGR. CONCLUSION: The expression of CEMIP and CYP11B2 is reduced in the serum of pregnant women with FGR and may become new diagnostic markers for FGR.

Foetal growth restriction is the inability of the foetus to reach its growth potential in the uterus due to various factors. This study aimed to investigate the expression and significance of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction. In our study, we found that the expression of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction were decreased. Cell migration-including protein and aldosterone synthase expression was negatively correlated with soluble fms like tyrosine kinase-1/placental growth factor ratio. In addition, the study also found that cell migration-including protein and aldosterone synthase expression in serum had good diagnostic value for foetal growth restriction.

Preoperative low serum albumin increases the rate of perioperative blood transfusion in patients undergoing total joint arthroplasty: propensity score matching.

BACKGROUND: To investigate the relationship between preoperative low serum albumin and perioperative blood transfusion in patients undergoing total joint arthroplasty (TJA). METHODS: We enrolled 2,772 TJA patients from our hospital between January 1, 2017, and January 1, 2022. Clinical data were extracted from electronic medical records, including patient ID, sex, BMI (Body Mass Index), age, and diagnoses. Receiver operating characteristic curves were constructed to establish thresholds for serum albumin levels categorization. Propensity score matching (PSM) was developed with preoperative serum albumin as the dependent variable and perioperative blood transfusion-related factors as covariates, including BMI grade, age grade, sex, diagnosis, hypertension, diabetes, coronary heart disease, chronic obstructive pulmonary disease, chronic bronchitis, cerebral infarction, major surgeries within the last 12 months, renal failure, cancer, depression, corticosteroid use, smoking, drinking, and blood type. The low serum albumin group was matched with the normal albumin group at a 1:2 ratio, employing a caliper value of 0.2. Binary logistic regression was employed to analyze the outcomes. RESULTS: An under the curve of 0.601 was discovered, indicating a cutoff value of 37.3 g/L. Following PSM, 892 cases were successfully paired in the low serum (< 37.3 g/L) albumin group, and 1,401 cases were matched in the normal serum albumin (≥ 37.3 g/L) group. Binary logistic regression in TJA patients showed that the albumin OR was 0.911 with 95%CI 0.888-0.935, P < 0.001. Relative to the preoperative normal serum albumin group, TJA patients in the low serum albumin group experienced a 1.83-fold increase in perioperative blood transfusion rates (95% CI 1.50-2.23, P < 0.001). Compared to the normal serum albumin group, perioperative blood transfusion rates for TJA patients with serum albumin levels of 30-37.3 g/L, 25-30 g/L, and ≤ 25 g/L increased by 1.63 (95% CI 1.37-1.99, P < 0.001), 5.4 (95% CI 3.08-9.50, P < 0.001), and 6.43 times (95% CI 1.80-22.96, P = 0.004), respectively. CONCLUSION: In TJA patients, preoperative low serum albumin levels have been found to be associated with an increased risk of perioperative blood transfusion. Furthermore, it has been observed that the lower the preoperative serum albumin level is, the higher the risk of perioperative blood transfusion. TRIAL REGISTRATION: 28/12/2021, Chinese Clinical Trial Registry, ChiCRT2100054844.

Relationship between urinary tract infections and serum vitamin D level in adults and children- a literature review.

Over time, researchers have accumulated significant evidence indicating that vitamin D deficiency not only impacts skeletal health but also contributes to the development and progression of various diseases, including cancer, diabetes, and cardiovascular conditions. The risk of low serum 1, 25(OH)2D3 level ultimately directs the way to morbidity, the beginning of new diseases, and numerous infections. Infections are the first entity that affects those with vitamin D deficiency. The common infection is urinary tract infection (UTI), and its relationship with vitamin D deficiency or insufficiency remains controversial. This infection affects both men and women, but comparatively, women are more prone to this infection because of the short length of the urethra, which makes an easy entry for the bacteria. The low level of serum vitamin D increases the risk of UTIs in children. Recurrent UTIs are one of the major weaknesses in women; if left untreated, they progress to appallingly serious conditions like kidney dysfunction, liver damage, etc. Hence improving the vitamin D status may help to improve the immune system, thus making it more resistant to infections. In this review, we have focused on examining whether vitamin D deficiency and insufficiency are the causes of UTIs and the association between them in women and children. We have also described the connection between vitamin D deficiency and insufficiency with UTIs and additional nanotechnology- based treatment strategies.

A "turn-on" fluorescence sensor for hydroquinone detection based on BSA doped carbon dots (BSA@CDs) from crawfish shells.

By using crawfish shells as the precursor and hydrothermal synthesis, Bovine serum albumin doped carbon dots (BSA@CDs) were prepared without excessive chemical reagents. The relationship between the fluorescence properties of different BSA@CDs and BSA amount was investigated by variouscharacterization techniques. When the amount of BSA added was 30 %, the prepared BSA@CDs' quantum yield (QY) reached 25.01 %, which was the highest. Inner Filter Effect (IFE) suggested that Cr (VI) can selectively quench the fluorescence of BSA@CDs. Cr (VI) can be reduced to Cr (III) by Hydroquinone (HQ), thus recovering the fluorescence. Accordingly, using BSA@CDs as a probe, a "turn-on" fluorescence sensor applied in HQ determination was constructed. The linear range was 10-200 µmol/L and limit of detection (LOD) was 0.18 µmol/L. Further, it has been employed to the determination of HQ in both crawfish tail meat and aquaculture water with good performance.

Prediction for Risk of Hypouricemia in Hospitalized Patients: A Single-center, Retrospective Cohort Study.

Background Hypouricemia, defined as a serum uric acid (SUA) level ≤2 mg/dL, could be a risk factor for death in hospitalized patients. However, how explanatory variables can explain hypouricemia as an objective variable in a logistic regression analysis remains unknown. Purpose To predict the risk factors for hypouricemia in hospitalized patients using a robust Bayesian logistic (RBL) model. Methods This study retrospectively enrolled patients who visited Yonago Medical Center between April 2020 and March 2021. The association between potential risk factors and hypouricemia was analyzed using the RBL model in Python-modulated PyMC3. The final model was selected based on the lowest Watanabe-Akaike information criterion (WAIC). Results Of the 618 patients, 64 (10.4%) had hypouricemia. Based on the model according to the lowest WAIC, independent risk factors for hypouricemia were febuxostat [odds ratio (OR) 5.46, 95% confidence interval (CI) 2.32-13.4], amino acids in parenteral nutrition (OR 5.19, 95% CI 1.62-15.1), TMP-SMX (OR 4.20, 95% CI 1.66-10.9), emaciation (OR 3.48, 95% CI 1.75-7.21), and serum sodium level (OR 0.90, 95% CI 0.84-0.96). Conclusion The RBL model predicted amino acids in parenteral nutrition, TMP-SMX, emaciation, and low serum sodium levels for hypouricemia, in addition to the authentic risk factor febuxostat.

Association between 25 hydroxyvitamin D and serum uric acid level in the Chinese general population: a cross-sectional study.

BACKGROUD: The relationship between serum uric acid (SUA) and 25-hydroxyvitamin D (25(OH)D) has been variably characterized in existing literature, with inconsistent results regarding its nature and implications in the Chinese population. This study aims to clarify this association, considering the potential impact of vitamin D levels on SUA. METHODS: This cross-sectional study involved 7,086 individuals from the Second Affiliated Hospital of Zhejiang University School of Medicine, screened throughout 2020. We collected data on 25(OH)D, SUA, and other metabolic markers. Logistic regression models adjusted for confounding factors were utilized to analyze the relationships. RESULTS: Our findings illustrate a statistically significant inverted U-shaped relationship between 25(OH)D and SUA. The identified threshold effect at 28.82 ng/ml is pivotal; with 25(OH)D levels below this point associated with an increased risk of hyperuricemia (odds ratio: 1.0146, p = 0.0148), and levels above it offering protective benefits (odds ratio: 0.9616, p = 0.0164). CONCLUSIONS: Our findings confirm a nonlinear, inverted U-shaped correlation between 25(OH)D and SUA, emphasizing the importance of maintaining vitamin D levels within a specific range to effectively manage hyperuricemia. These results support the implementation of personalized vitamin D supplementation strategies to optimize metabolic health outcomes, highlighting the complex interplay between vitamin D status and uric acid levels.

Predictive value of serum markers for mucosal healing in patients with inflammatory bowel disease.

OBJECTIVE: To investigate the value of serum markers in assessing mucosal healing (MH) and inflammatory activity in patients with inflammatory bowel disease (IBD). METHODS: In this retrospective analysis, we examined data from 320 IBD patients, including 176 with ulcerative colitis (UC) and 144 with Crohn's disease (CD), alongside 100 healthy controls during the same period. Serum levels of various markers, including white blood cell (WBC), platelet count (PLT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) were evaluated. These indices were analyzed for their diagnostic value in endoscopic MH in IBD patients. The independent influencing factors affecting MH in IBD patients were identified by univariate and multivariate analyses. RESULTS: The levels of WBC, PLT, ESR, CRP, PLR, and NLR were significantly higher in IBD patients, UC patients, and CD patients than in healthy controls (all P < 0.05). For those achieving MH, their WBC, PLT, ESR, CRP, PLR, and NLR levels were significantly lower than patients who did not achieve MH (all P < 0.05). The AUCs of WBC, PLT, ESR, CRP, PLR, and NLR for the diagnosis of MH were 0.729, 0.756, 0.673, 0.707, 0791, and 0.724, respectively. A multifactorial analysis found that the presence of abdominal pain (OR: 2.155, 95% CI: 1.081-4.297, P < 0.05), higher WBC (OR: 3.927, 95% CI: 2.008-7.681, P < 0.001), higher PLT (OR: 4.181, 95% CI: 2.078-8.412, P < 0.001), higher ESR (OR: 2.221, 95% CI: 1.082-4.562, P < 0.05), higher CRP (OR: 3.874, 95% CI: 1.861-8.065, P < 0.001), higher PLR (OR: 4.087, 95% CI: 1.586-10.534, P < 0.01), and higher NLR ( OR: 2.688, 95% CI: 1.292-5.592, P < 0.01) were independent risk factors for failure in achieving MH. CONCLUSION: WBC, PLT, ESR, CRP, PLR, and NLR can be used as noninvasive markers for predicting MH in patients with IBD, and they hold promise for clinical application.

ICP: A midwifery perspective.

Background: ICP is a liver condition specific to pregnancy affecting 0.5-0.6% of pregnancies in Australia. Aims: to review the SOMANZ guidelines and extrapolate information relevant to midwives proving care for women with ICP. Findings: Multidisciplinary input is essential in caring for women with ICP and their families. Non-fasting TSBA samples ≥19 µmol/L are diagnostic in the presence of pruritus. Peak TSBA denotes the severity of the disease. Increased risk of stillbirth is small when peak TSBA ≥100 µmol/L. Conclusion: Midwives play an essential role in supporting women with ICP helping them navigate complex appointments and manage the pruritus and concomitant issues.

Biofluid GPNMB/osteoactivin as a potential biomarker of ageing: A cross-sectional study.

Background: Glycoprotein non-metastatic melanoma B (GPNMB)/osteoactivin was first identified in the human melanoma cell lines. GPNMB plays a key role in the anti-inflammatory and antioxidative functions as well as osteoblast differentiation, cancer progression, and tissue regeneration. Recently, GPNMB was used as an anti-aging vaccine for mice. The present study aimed to investigate the potential of biofluid GPNMB as an aging biomarker in humans using serum and urine samples from an aging Chinese population. Methods: We analyzed RNA-sequencing data (GSE132040) from 17 murine organs across different ages to assess the gene expression of potential ageing biomarkers. Spearman's correlation coefficients were used to evaluate the relationship between gene expression and age. Meanwhile, a cross-sectional population study was conducted, which included 473 participants (aged 25-91 years), a representative subset of participants from the Peng Zu Study on Healthy Ageing in China (Peng Zu Cohort). Biofluid GPNMB levels were measured by ELISA. The associations of serum and urine GPNMB levels with various clinical and anthropometrical indices were assessed using ANOVA, Kruskal-Wallis H test, and univariate and multivariate linear regression analyses. Results: In mice, the Gpnmb mRNA expression levels showed a significant positive association with age in multiple organs in mice (P < 0.05). In Peng Zu Cohort, biofluid (both serum and urine) GPNMB levels showed a positive correlation with age (P < 0.05). Univariate linear regression analysis revealed that serum GPNMB levels were negatively associated with skeletal muscle mass index (SMI, P < 0.05) and insulin-like growth factor 1 (IGF-1, P < 0.05), and urine GPNMB levels showed a negative association with total bile acids (TBA, P < 0.05). Multivariate linear regression analysis further indicated that serum GPNMB levels negatively correlated with the systemic immune-inflammation index (SII, P < 0.05), and the urine GPNMB levels maintained a negative association with TBA (P < 0.05), additionally, urine GPNMB levels in men were significantly lower than in women (P < 0.05). Conclusions: The biofluid GPNMB was a strong clinical biomarker candidate for estimating biological aging.

Evaluation of Serum Proteome Sample Preparation Methods to Support Clinical Proteomics Applications.

Serum contains several proteins that are associated with disease-related processes. Mass spectrometry (MS)-based proteomics approaches greatly facilitate serum protein biomarker development. However, the serum proteome complexity presents a technical challenge for the accurate, sensitive, and reproducible quantification of proteins by MS. Thus, efficient sample preparation methods are of critical importance for serum proteome analyses. In this study, we evaluated the technical performance of two serum proteome sample preparation methods using sera from patients with high-grade serous ovarian cancer and patients with benign nongynecological conditions with a goal of providing insight into their compatibility with clinical proteomics workflows. One method entailed the use of immobilized trypsin (SMART Digest Trypsin) with RapiGest SF, an acid-labile surfactant designed to enhance the in-solution enzymatic digestion of proteins. The other method incorporated a commercially available sample preparation kit, iST-BCT, which contains standardized reagents. Significantly higher protein sequence coverage, albeit with lower digestion efficiency, was obtained with the immobilized trypsin + RapiGest SF workflow, whereas the iST-BCT workflow was quicker and had marginally better reproducibility. Protein relative abundance analysis revealed that the serum proteomes clustered primarily by the sample processing workflow and secondarily by disease state. We conducted a time course study to determine whether differences in the relative abundance of diagnostic high-grade serous ovarian cancer serum protein biomarker candidates were biased according to the duration of enzymatic digestion. Our results highlight the importance of optimizing enzymatic digestion kinetics according to the peptide targets of interest while considering the sensitivity of the downstream analytical method utilized in clinical proteomics workflows designed to measure biomarkers.

Levels of serum lipids predict responses to PD-L1 inhibitors as first-line treatment in small cell lung cancer: an observational study.

BACKGROUND: Immunotherapy provides new hope to individuals with small cell lung cancer (SCLC). Predicting biomarkers for clinical effects is crucial for SCLC patients receiving programed death-ligand 1 (PD-L1) inhibitor treatment. AIM: The aim of this study was to clarify the value of serum lipids as predictors of immune related adverse events (irAEs) and the anti-tumour effects in SCLC patients who received PD-L1 inhibitors as first-line treatment. METHOD: This study included patients with SCLC who received at least one cycle of PD-L1inhibitors at Shanghai Pulmonary Hospital from August 2020 to December 2023. We collected the clinical data of the SCLC patients, including basic information and serum lipid levels, before immunotherapy. RESULTS: The irAEs rate was 16.1% of 124 enrolled patients. In multivariate analysis, the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio was an independent predictor of irAEs (p = 0.045). Tumour response analysis indicated that the objective response rate (ORR) was 43.4% and the disease control rate (DCR) was 79.5%. Seventy-seven patients experienced any progression-free survival (PFS) event. The median PFS was longer in the HDL-C-high group (10.03 months) than in the HDL-C-low group (6.67 months) (p = 0.043). In Cox regression analysis, the serum HDL-C level was an independent predictor of PFS (p = 0.002). For patients of the high TG/HDL-C ratio, the ORR significantly differed between patients who suffered from any irAEs and those who did not (p = 0.0139). CONCLUSION: This study found that serum lipid levels might predict the responses to anti-PD-L1 as first-line treatment for SCLC.

Measurement of changes in serum-based inflammatory indicators to monitor response to nivolumab monotherapy in advanced gastric cancer: a multicenter retrospective study.

BACKGROUND: Nonresectable gastric cancer develops rapidly; thus, monitoring disease progression especially in patients receiving nivolumab as late-line therapy is important. Biomarkers may facilitate the evaluation of nivolumab treatment response. Herein, we assessed the utility of serum-based inflammatory indicators for evaluating tumor response to nivolumab. METHODS: This multicenter retrospective cohort study included 111 patients treated with nivolumab monotherapy for nonresectable advanced or recurrent gastric cancer from October 2017 to October 2021. We measured changes in the C-reactive protein (CRP)-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) in serum from baseline to after the fourth administration of nivolumab. Furthermore, we calculated the area under the receiver operating characteristic curves (AUC ROCs) for CAR, PLR, and NLR to identify the optimal cutoff values for treatment response. We also investigated the relationship between clinicopathologic factors and disease control (complete response, partial response, and stable disease) using the chi-squared test. RESULTS: The overall response rate (complete and partial response) was 11.7%, and the disease control rate was 44.1%. The median overall survival (OS) was 14.0 (95% CI 10.7‒19.2) months, and the median progression-free survival (PFS) was 4.1 (95% CI 3.0‒5.9) months. The AUC ROCs for CAR, PLR, and NLR before nivolumab monotherapy for patients with progressive disease (PD) were 0.574 (95% CI, 0.461‒0.687), 0.528 (95% CI, 0.418‒0.637), and 0.511 (95% CI, 0.401‒0.620), respectively. The values for changes in CAR, PLR, and NLR were 0.766 (95% CI, 0.666‒0.865), 0.707 (95% CI, 0.607‒0.807), and 0.660 (95% CI 0.556‒0.765), respectively. The cutoff values for the treatment response were 3.0, 1.3, and 1.4 for CAR, PLR, and NLR, respectively. The PFS and OS were significantly longer when the treatment response values for changes in CAR, PLR, and NLR were below these cutoff values (CAR: OS, p < 0.0001 and PFS, p < 0.0001; PLR: OS, p = 0.0289 and PFS, p = 0.0302; and NLR: OS, p = 0.0077 and PFS, p = 0.0044). CONCLUSIONS: Measurement of the changes in CAR, PLR, and NLR could provide a simple, prompt, noninvasive method to evaluate response to nivolumab monotherapy. TRIAL REGISTRATION: This study is registered with number K2023006.

Genetic liability to human serum metabolites is causally linked to telomere length: insights from genome-wide Mendelian randomization and metabolic pathways analysis.

Background: Telomere has been recognized as a biomarker of accelerating aging, and telomere length (TL) shortening is closely related to diverse chronic illnesses. Human serum metabolites have demonstrated close correlations with TL maintenance or shortening in observational studies. Nevertheless, little is known about the underlying pathological mechanisms, and Mendelian randomization (MR) analysis of serum metabolites may provide a more comprehensive understanding of the potential biological process. Methods: We employed a two-sample MR analysis method to assess the causal links between 486 serum metabolites and TL. We applied the inverse-variance weighted (IVW) approach as our primary analysis, and to assure the stability and robustness of our results, additional analysis methods including the weighted median, MR-Egger, and weighted mode were conducted. MR-Egger intercept test was utilized to detect the pleiotropy. Cochran's Q test was implemented to quantify the extent of heterogeneity. Furthermore, the pathway analysis was conducted to identify potential metabolic pathways. Results: We identified 11 known blood metabolites associated with TL. Among these metabolites, four were lipid (taurocholate, dodecanedioate, 5,8-tetradecadienoate, and 15-methylpalmitate), one amino acid (levulinate (4-oxovaleate)), one carbohydrate (lactate), one nucleotide (pseudouridine), one energy (phosphate), and three xenobiotics (2-hydroxyacetaminophen sulfate, paraxanthine, and ergothioneine). The known protective metabolites included levulinate (4-oxovaleate), dodecanedioate, 5,8-tetradecadienoate, lactate, phosphate, paraxanthine, and ergothioneine. Multiple metabolic pathways have been identified as being implicated in the maintenance of telomere length. Conclusion: Our MR analysis provided suggestive evidence supporting the causal relationships between 11 identified blood metabolites and TL, necessitating further exploration to clarify the mechanisms by which these serum metabolites and metabolic pathways may affect the progression of telomeres.

Phase separation of triton X-100 and bovine serum albumin mixture: Impacts of nature and composition of polyols on associated physicochemical parameters.

Bovine serum albumin (BSA) is widely used in tissue engineering and pharmaceutical research. It is readily available as a byproduct of the cattle industry, collected from blood. In this study, we conducted a physicochemical investigation of the phase separation in a mixture of Triton X-100 (TX-100) and BSA, influenced by various polyols, using the well-established cloud point (CP) determination method. The addition of polyols resulted in a significant reduction in CP values for the TX-100 + BSA mixture. For the system under investigation with polyols, the CP values followed the order: [Formula: see text] Under identical conditions, the system exhibited maximum solubility in the xylose solution and minimum solubility in the maltose solution. At lower polyol content, negative values of standard enthalpy (∆Hc0) and standard entropy (∆Sc0) changes were observed, suggesting that electrostatic forces dominate as the driving force for clouding. At highest employed polyol concentration in some case, positive values for ∆Hc0 and ∆Sc0 were achieved, which indicated that hydrophobic interactions likely dominate the phase partitioning of the amphiphile and protein mixture. Additionally, entropy-enthalpy compensation parameters were calculated and analyzed with a rational approach. Molecular docking analysis further demonstrated the presence of hydrogen bonds and hydrophobic interactions between TX-100 and BSA.

Serum neuron-specific enolase can predict the severity and outcome of anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: Little is known about the association between serum neuron-specific enolase (NSE) concentration and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. This study aims to investigate if serum NSE concentration is related to the clinical features of anti-NMDAR encephalitis. METHODS: Serum NSE levels were detected in 58 anti-NMDAR encephalitis cases, 58 matched healthy controls and 58 matched disease controls. Demographic features, clinical symptoms, cerebrospinal fluid parameters and brain MRI indexes of the cases were evaluated. RESULTS: Serum NSE concentrations were significant higher in case group than those in healthy controls and disease controls (both p < 0.001). Serum NSE concentrations in patients with mRS≥3 one year after onset were obviously higher than in those with mRS<3 (p < 0.001). Patients with status epilepticus or central hypoventilation had higher serum NSE levels than those without (p = 0.003 and p = 0.006). Serum NSE concentrations in cases with brain lesions or brain atrophy were significant higher than in those without (p = 0.001 and p < 0.001, respectively). Serum NSE concentrations were found to be significant higher in cases with limited response to treatment compared to those with favourable therapy outcomes (p < 0.001). Spearman's correlation analysis showed a significant positive association between serum NSE concentration and mRS score at the most critical time (max mRS) (r = 0.575, p < 0.001) and one year after onset (r = 0.705, p < 0.001). Cox regression results reflected that high serum NSE level was an independent predictor of poor prognosis in anti-NMDAR encephalitis group (p = 0.001), and the ROC curve threshold value was 15.72 ng/ml. CONCLUSIONS: Serum NSE concentrations in anti-NMDAR encephalitis cases are higher than those in controls. It can be used to predict the brain damage degree and prognosis of anti-NMDAR encephalitis cases.

Wenshenqianlie capsule improves benign prostatic hyperplasia via its anti-inflammatory and antioxidant effects.

Anti-inflammatory and antioxidant effects play crucial roles in the recovery of benign prostatic hyperplasia (BPH). Wenshenqianlie (WSQL) capsule, a typical traditional Chinese medicine formulation combining 14 Chinese herbs, has been reported to exert tonic effects on the kidneys and improve clinical symptoms of BPH. However, its potential antioxidative and anti-inflammatory properties and effects on the improvement of hormone levels have not been reported in depth. In this study, mice were subcutaneously injected with TP (5 mg/kg·d-1) to induce BPH. Forty-eight adult BALB/c male mice were randomly allocated to six groups based on the type of drug administered by gavage: control, BPH, BPH+WSQL (40 and 80 mg/kg·d-1), BPH+finasteride (1 mg/kg·d-1), and WSQL-only treated (80 mg/kg·d-1). We investigated the anti-inflammatory and antioxidant effect and mechanism of WSQL on BPH via histopathological examination, immunohistochemistry, enzyme-linked immunosorbent assay, and western blotting combined with in vivo serum metabolomics, gut microbiomics analysis. WSQL alleviated prostate hyperplasia and reduced prostate-specific antigen, dihydrotestosterone, testosterone, and inflammation levels. Gut microbiomics and serum non-targeted metabolomics determined that the protective effect of WSQL against BPH may be related to the improvement of inflammation and testosterone-related gut microbiota and serum metabolites. Further studies showed that WSQL ameliorated nuclear factor-kappa B, its downstream inflammatory factors, and nuclear factor E2-related factor 2 pathway.