Genetically Predicted Association of 91 Circulating Inflammatory Proteins with Multiple Sclerosis: A Mendelian Randomization Study.

Previous studies have validated a close association between inflammatory factors and multiple sclerosis (MS), but their causal relationship is not fully profiled yet. This study used Mendelian randomization (MR) to investigate the causal effect of circulating inflammatory proteins on MS. Data from a large-scale genome-wide association study (GWAS) were analyzed using a two-sample MR method to explore the relationship between 91 circulating inflammatory proteins and MS. The inverse-variance-weighted (IVW) analysis was employed as the main method for evaluating exposures and outcomes. Furthermore, series of the methods of MR Egger, weighted median, simple mode, and weighted mode were used to fortify the final results. The results of the IVW method were corrected with Bonferroni (bon) and false discovery rate (fdr) for validating the robustness of results and ensuring the absence of heterogeneity and horizontal pleiotropy. The sensitivity analysis was also performed. The results of the forward MR analysis showed that higher levels of CCL25 were found to be associated with an increased risk of MS according to IVW results, OR: 1.085, 95% CI (1.011, 1.165), p = 2.42 × 10-2, adjusted p_adj_bon = 1, p_adj_fdr = 0.307. Similarly, higher levels of CXCL10 were found to be associated with an increased risk of MS, OR: 1.231, 95% CI (1.057, 1.433), p = 7.49 × 10-3, adjusted p_adj_bon = 0.682, p_adj_fdr = 0.227. In contrast, elevated levels of neurturin (NRTN) were associated with a decreased risk of MS, OR: 0.815, 95% CI (0.689, 0.964), p = 1.68 × 10-2, adjusted p_adj_bon = 1, p_adj_fdr = 0.307. Reverse MR analysis showed no causal relationship between MS and the identified circulating inflammatory cytokines. The effects of heterogeneity and level pleiotropy were further excluded by sensitivity analysis. This study provides new insights into the relationship between circulating inflammatory proteins and MS and brings up a new possibility of using these cytokines as potential biomarkers and therapeutic targets. The data in this study show that there are only weak associations between inflammatory molecules and MS risk, which did not survive bon and fdr correction, and the obtained p-values are quite low. Therefore, further studies on larger samples are needed.

Review of the Predictive Value of Biomarkers in Sepsis Mortality.

Sepsis is a leading cause of mortality among severely ill individuals, primarily due to its potential to induce fatal organ dysfunction. For clinicians, it is vital to have appropriate indicators, including the physiological status and personal experiences of patients with sepsis, to monitor the condition and assess prognosis. This approach aids in preventing the worsening of the illness and reduces mortality. Recent guidelines for sepsis focus on improving patient outcomes through early detection and timely treatment. Nonetheless, identifying severe cases and predicting their prognoses remain challenging. In recent years, there has been considerable interest in utilising the C-reactive protein (CRP)/albumin ratio (CAR) to evaluate the condition and forecast the prognosis of patients with sepsis. This research concentrates on the significance of CAR in the pathological process of sepsis, its association with prognosis, and the latest developments in employing procalcitonin, lactic acid, CRP, and other potential biomarkers. The CAR, with its predictive value for sepsis prognosis and mortality, is increasingly used as a clinical biochemical marker in diagnosing and monitoring patients with sepsis.

Chemical constitutes from Tuber indicum with immunosuppressive activity uncovered by transcriptome analysis.

Three previously undescribed compounds including a polyketide (1) and two lactams (2 and 3) were obtained from Tuber indicum. The structures of new findings were elucidated by HRESIMS, NMR as well as NMR and ECD calculations. Transcriptome analysis through RNA-seq revealed that compound 2 exhibits immunosuppressive activity. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were employed as a model to explore the effect of these compounds in immunosuppressive activity. The results showed that 2 could reduce the generation of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Western blotting analysis demonstrated that 2 could suppressed the PI3K pathway by decreasing the levels of p-PI3K and p-Akt, while increasing the levels of p-PTEN. The anti-inflammatory activity of 2 was further confirmed using a zebrafish in vivo model.

Neuropeptide B (NPB) and NPB receptor 2b (NPBWR2b) in the ricefield eel Monopterus albus: expression and potential involvement in the regulation of gonadotropins.

The neuropeptide B/W signaling system is composed of neuropeptide B (NPB), neuropeptide W (NPW), and two cognate receptors, NPBWR1 and NPBWR2, which are involved in diverse physiological processes, including the central regulation of neuroendocrine axes in vertebrates. The components of this signaling system are not well conserved during vertebrate evolution, implicating its functional diversity. The present study characterized the ricefield eel neuropeptide B/W system, generated a specific antiserum against the neuropeptide B/W receptor, and examined the potential roles of the system in the regulation of adenohypophysial functions. The ricefield eel genome contains npba, npbb, and npbwr2b but lacks the npw, npbwr1, and npbwr2a genes. The loss of npw and npbwr1 probably occurred at the base of ray-finned fish radiation and that of npbwr2a species specifically in ray-finned fish. Npba and npbb genes are produced through whole-genome duplication (WGD) in ray-finned fish. The ricefield eel npba was expressed in the brain and some peripheral tissues, while npbb was predominantly expressed in the brain. The ricefield eel npbwr2b was also expressed in the brain and in some peripheral tissues, such as the pituitary, gonad, heart, and eye. Immunoreactive Npbwr2b was shown to be localized to Lh and Fsh cells but not to Gh or Prl cells in the pituitary of ricefield eels. Npba upregulated the expression of fshb and cga but not lhb mRNA in pituitary fragments of ricefield eels cultured in vitro. The results of the present study suggest that the NPB system of ricefield eels may be involved in the neuroendocrine regulation of reproduction.

Comparative study of characteristic compounds of three species of truffle.

The Panxi area in Sichuan Province is the main area for the production of truffles in China, and several species of truffle are known to exist in this region. Nevertheless, it is unclear what the differences in chemical composition between the truffles are. Using an ultra-high-performance liquid chromatography quadrupole/orbitrap high-resolution mass spectrometry coupled with Compound Discoverer 3.0, we identified chemical components in three mainly known truffles from the Panxi region. Further analysis of chemical composition differences was conducted using principal component analysis, and orthogonal partial least squares discriminant analysis. Note that, 78.9% of the variance was uncovered by the principal component analysis model. As a result of the orthogonal partial least squares discriminant analysis model, the three species of truffles (Tuber pesudohimalayense, Tuber indicum, and Tuber sinense) from Panxi were better discriminated, with R2 X, R2 Y, and Q2 being 0.821, 0.993, and 0.947, respectively. In this study, 87 components were identified. T. pesudohimalayense contained significantly higher levels of nine different compounds than the other two species. Hence, it was possible to identify similarities and differences between three species of truffles from Panxi in terms of chemical composition. This can be used as a basis for quality control.

Two previously undescribed phthalides from Talaromyces amestolkiae, a symbiotic fungus of Syngnathus acus.

Amestolkins A (1) and B (2), two previously undescribed phthalides sharing the same planar structure of (1, 5-dihydroxyhexyl)-7-hydroxyisobenzofuran-1(3H)-one were isolated from Talaromyces amestolkiae. Their absolute configurations were elucidated by comprehensive analyses of spectroscopic evidences in high-resolution electrospray mass spectra (HRESIMS) and nuclear magnetic resonance (NMR) combined with electronic circular dichroism (ECD) and NMR calculations. 1 and 2 showed anti-neuroinflammatory activity by inhibiting the gene expressions of proinflammatory factors including C-C motif chemokine ligand 2 (CCL-2), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), as well as attenuating the excretion of inducible nitric oxide synthase (iNOS) in BV-2 microglial cells at the concentration of 30 µM.

Association between cigarette smoking and mortality in patients with hip fracture: A systematic review and meta-analysis.

INTRODUCTION: Hip fracture is associated with substantial morbidity and mortality, especially among the elderly. Current evidence on the association between cigarette smoking and mortality in hip-fracture patients is controversial. We performed a systematic review and meta-analysis of studies on this association. METHODS: The databases Medline/PubMed, Embase, Web of Science, and Cochrane Library were searched for studies that estimated the effect of smoking on the risk of mortality in hip-fracture patients. Pooled analyses were conducted of the associations, expressed in relative risk (RR) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic. Study quality was assessed by the modified Newcastle-Ottawa Scale (NOS) and publication bias was evaluated by a funnel plot, Begg's and Egger's tests. Subgroup analyses were performed by study design, race/ethnicity, age ≥60 years, smoking status, and follow-up period. RESULTS: A total of six articles involving 3739 hip-fracture patients were included in the meta-analysis. Our results indicate that ever-active smoking was significantly associated with an increased risk of death in hip-fracture patients (pooled RR=1.26; 95% CI: 1.08-1.46). In further subgroup analysis, the risk of death was significantly higher in ever-active smokers than in never smokers in White participants (pooled RR=1.23; 95% CI: 1.05-1.44) and elderly aged ≥60 years (pooled RR=1.19; 95% CI: 1.01-1.40), with no significant association in Asian participants (pooled RR=1.42; 95% CI: 0.95-2.11). Current smokers had more risk of death than never smokers (pooled RR=1.26; 95% CI: 1.08-1.46). The association was significant in follow-up periods of ≤1 year (pooled hazard ratio, HR=1.34; 95% CI: 1.05-1.71), 3 years (pooled HR=1.22; 95% CI: 1.05-1.43), and 5 years (pooled HR=1.26; 95% CI: 1.08-1.46). CONCLUSIONS: Cigarette smoking is associated with an increased risk of mortality in hip-fracture patients, especially in elderly patients aged ≥60 years, current smokers, and White participants. With the extension of follow-up period, the effect on mortality of smoking is profound and lasting.

Analysis of susceptibility genes and myocardial infarction risk correlation of ischemic cardiomyopathy based on bioinformatics.

Background: The present study was to investigated differential expressed genes (GEGs) in ischemic cardiomyopathy (ICM), and to construct regulation networks, and to study the correlation between myocardial infarction risk. Methods: Data sets were downloaded from the Gene Expression Omnibus (GEO) to screen out messenger RNA (mRNA) and long non-coding RNA (lncRNA) differentially expressed between ICM samples and normal samples. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Differentially expressed mRNA and lncRNA were analyzed, and bioinformatics methods were used to predict and analyze microRNA (miRNA), and a competing endogenous RNA (Hub gene) regulatory network was constructed. Using the Limma software package in R language, DEGs of ICM were screened with non-heart failure donors as the control group under the conditions that the differential expression ratio was not less than 2 times, and the corrected P value was <0.05. The ClusterProfiler software package was used for GO enrichment analysis and KEGG enrichment analysis. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) 11.0 online database was used to screen key genes for protein-protein interaction (PPI) network analysis. Results: The GO function analysis and KEGG pathway analysis showed that the DEGs were significantly enriched in metabolic pathways, oxidative phosphorylation, extracellular matrix receptor interactions, and other pathways, and were closely related to fibrosis, collagen catabolic process, and inflammatory response function, and a Hub gene regulatory network related to ICM lncRNA was constructed. Bioinformatics methods were used to effectively analyze the DEGs of ICM, and the Hub gene regulatory network of ICM was successfully constructed. Conclusions: This study identified a certain risk correlation between ICM susceptibility genes and myocardial infarction.

Association between smoking and risk of death in patients with sepsis: A systematic review and meta-analysis.

INTRODUCTION: Although some research papers have suggested that smoking may increase mortality in patients with sepsis, no evidence has been produced in this regard. This systematic research evaluated the risk of death in patients with sepsis who were smokers to facilitate better clinical decision making. METHODS: This is a systematic review registered in PROPERO (CRD42022296654). Searches were conducted to identify suitable studies from the databases of PubMed, Embase, Web of Science and the Cochrane Controlled Register of Trials from January 1980 to June 2021. Two independent reviewers screened the articles using keywords and extracted the data. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of evidence. The primary endpoints included the mortality of patients with sepsis. RESULTS: Five studies involving 2694 participants were included in our study. Among the five included articles, three studies had an NOS score of 6, while the other two had an NOS score of 7. The results showed that a significantly higher risk of death was observed in smokers with sepsis compared with non-smokers with sepsis (hazard ratio, HR=1.62; 95% CI: 1.11-2.37, p=0.01). Among the patients followed for more than 2 months, the mortality rate of smokers was significantly higher (2.33 times) than that of non-smokers (HR=2.33; 95% CI: 1.83-2.96, p<0.01). The difference in mortality did not reach statistical significance when the follow-up period was shorter than 2 months (HR=1.22; 95% CI: 0.96-1.56, p=0.10). CONCLUSIONS: Smoking increased mortality in patients with sepsis when the follow-up period was longer than 2 months.

Hydroanthraquinones from Nigrospora sphaerica and Their Anti-inflammatory Activity Uncovered by Transcriptome Analysis.

Transcriptome analysis is shown to be an effective strategy to understand the potential function of natural products. Here, it is reported that 11 previously undescribed hydroanthraquinones [nigroquinones A-K (1-11)], along with eight known congeners, were isolated from Nigrospora sphaerica. Their structures were elucidated by interpreting spectroscopic and spectrometric data including high-resolution mass spectra and nuclear magnetic resonance. The absolute configurations of 1-11 were confirmed by electronic circular dichroism calculations. Transcriptome analysis revealed that 3 (isolated in the largest amount) might be anti-inflammatory. Assays based on LPS-induced RAW264.7 macrophages and zebrafish embryos confirmed that some of the isolated hydroanthraquinones attenuated the secretion of pro-inflammatory mediators in vitro and in vivo. Further Western blotting and immunofluorescence experiments indicated that 4 (which showed the most obvious nitric oxide inhibition) could suppress the expression of nuclear factor-kappa-B (NF-κB), phosphorylation of the inhibitor of NF-κB kinase and inhibit the transportation of NF-κB to the nucleus. Hence, the suppression of the NF-κB signaling pathway may be responsible for the anti-inflammatory effect. These results show that bioactivity evaluation on the basis of transcriptome analysis may be effective in the functional exploration of natural products.

The safety and efficacy of amrubicin in the treatment of previously untreated extensive-disease small-cell lung cancer: a meta-analysis.

Background: Extensive-disease small-cell lung cancer (ED-SCLC) has been known to be rapid progression and relapse, despite highly sensitive to chemotherapy. Amrubicin (AMR), a third-generation synthetic anthracycline, was accepted as a feasible alternative compared with the standard first-line chemotherapy for previously untreated ED-SCLC. While, the efficacies of these amrubicin-based regimens are unsatisfactory. Aim: Our meta-analysis was performed to assess the efficacy and toxicity of first-line therapy comparing AMR and chemotherapy in patients with ED-SCLC. Methods: Electronic databases were searched for eligible trials updated on November 2018. Randomized-controlled trials assessing the efficacy and safety of AMR in ED-SCLC were included, of which the interested results were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: A total of 6 randomized controlled trials were included in this analysis. There are no significant differences in OS (OR=1.03, 95% CI=0.66-1.60, P=0.91), PFS (OR=1.2, 95% CI=10.77-1.88, P=0.41) or ORR (OR=1.31, 95% CI=0.90-1.92, P=0.16) with AMR (OR=0.90, 95% CI=0.76-1.05, P=0.17). The most common treatment-related AEs in the AMR group are leukopenia (OR=3.13, 95% CI=1.22-7.99, P=0.02) and neutropenia (OR=3.25, 95% CI=1.38-7.65, P=0.007). Fatigue, anemia, nausea, vomiting, diarrhea the difference between the two groups had no statistical significance. Conclusion: The results of our analysis indicated that AMR therapy demonstrated non-inferiority to the standard first-line chemotherapy for previously untreated ED-SCLC. Whether it can be accepted as an alternative regimen to the standard first-line chemotherapy is still warranted.

Shenqi Fuzheng Injection (SFI) Enhances IFN-α Inhibitory Effect on Hepatocellular Carcinoma Cells by Reducing VEGF Expression: Validation by Gene Silencing Technique.

Shenqi Fuzheng Injection (SFI) is a traditional Chinese medicine injection with anticancer properties and is mainly composed of ginseng and astragalus. Its efficacy has been confirmed in clinical trials, but the mechanism remains unclear. We investigated the effect of SFI on vascular endothelial growth factor (VEGF) gene expression in hepatocellular carcinoma (HCC) cells and identified its possible mechanism of synergistic effects when combined with the chemotherapeutic drug interferon (IFN-) α. An MTT assay was used to measure the inhibition effects of low-dose IFN-α (6000 IU) with or without SFI (0.5 g/L) on the HCC cell line MHCC97. VEGF-silenced MHCC97L-mir200 cell lines were prepared using lentiviral vectors and evaluated by real-time PCR to determine the inhibition effect. We examined MHCC97L-mir200 and MHCC97L cells by MTT assay, using IFN-α alone or in combination with SFI. The inhibition ratio of IFN-α (6000 IU) was -29.5%, while that for IFN-α (6000 IU) + SFI (0.5 g/L) was 17.0%, which was significantly higher than that for the IFN-α group (P < 0.01). The VEGF gene was silenced successfully in MHCC97-L cells. After interference of VEGF, the inhibition by SFI and IFN-α in MHCC97L-mir200 did not differ from that in MHCC97-L cells (P > 0.05). SFI can reduce the expression of VEGF in HCC, which can increase the efficacy of IFN-α, providing a theoretical basis for clinical application.

Enhancement of protective immune responses induced by Toxoplasma gondii dense granule antigen 7 (GRA7) against toxoplasmosis in mice using a prime-boost vaccination strategy.

Effective vaccines against Toxoplasma gondii may contribute to preventing and controlling the spread of toxoplasmosis, which is important for improving outcomes of infections in humans and livestock animals. The dense granule antigen 7 (GRA7) of T. gondii might be an immunodominant antigen for a vaccine candidate. In the present study, a further exploration of its vaccine effect, a heterologous prime-boost vaccination strategy with a recombinant eukaryotic plasmid pEGFP-GRA7 and a recombinant protein GRA7 expressed from a prokaryotic plasmid pET30-GRA7, was performed in BALB/c mice. The data reveal that a DNA prime-protein boost vaccination induces both humoral and cellular immune responses against T. gondii associated with high levels of total IgG, IgG2a isotype and gamma interferon (IFN-γ). Challenge experiments further show that the DNA prime-protein boost vaccination significantly increases survival rate (60%), compared with controls in which all died within 8 days of challenge. Therefore, the DNA prime-protein boost vaccination based on GRA7 might be a promising regimen for further development of an effective vaccine against T. gondii.

Determination of chloride, chlorate and perchlorate by PDMS microchip electrophoresis with indirect amperometric detection.

In this work, chloride, chlorate and perchlorate are fast separated on PDMS microchip and detected via in-channel indirect amperometric detection mode. With PDMS/PDMS microchip treated by oxygen plasma, anions chloride (Cl-), chlorate (ClO3-), and perchlorate (ClO4-) are separated within 35s. Some parameters including buffer salt concentration, buffer pH, separation voltage and detection potential are investigated in detail. The separation conditions using 15 mM (pH 6.12) of 2-(N-morpholino)ethanesulfonic acid (MES)+L-histidine (L-His) as running buffer, -2000 V as separation voltage and 0.7 V as detection potential are optimized. Under this condition, the detection limits of Cl-, ClO3-, and ClO4- are 1.9, 3.6, and 2.8 microM, respectively.

In-channel indirect amperometric detection of heavy metal ions for electrophoresis on a poly(dimethylsiloxane) microchip.

In-channel indirect amperometric detection mode for microchip capillary electrophoresis with positive separation electric field is successfully applied to some heavy metal ions. The influences of separation voltage, detection potential, the concentration and pH value of running buffer on the response of the detector have been investigated. An optimized condition of 1200V separation voltage, -0.1V detection potential, 20mM (pH 4.46) running buffer of 2-(N-morpholino)ethanesulfonic acid (MES)+l-histidine (l-His) was selected. The results clearly showed that Pb(2+), Cd(2+), and Cu(2+) were efficiently separated within 80s in a 3.7cm long native separation PDMS/PDMS channel and successfully detected at a single carbon fibre electrode. The theoretical plate numbers of Pb(2+), Cd(2+), and Cu(2+) were 1.2x10(5), 2.5x10(5), and 1.9x10(5)m(-1), respectively. The detection limits for Pb(2+), Cd(2+), and Cu(2+) were 1.3, 3.3 and 7.4muM (S/N=3).

[Effect of chlorpyrifos residue in red soil on crops].

The pot cultivation experiment method, integrating with laboratory analysis, was employed for exploring the influence of chlorpyrifos residue in red soil on growth of wheat and oil-seed rape seedlings, and the uptake of crops to chlorpyrifos residue. The results show that, wheat seedlings and oil-seed rape seedlings can absorb chlorpyrifos residue from soil to reach the concentration of 0.257 to approximately 4.50 microg/g and 0.249 to approximately 2.021 microg/g, respectively, 20 days later since chlorpyrifos was introduced into the pots, on condition that the initial concentration of chlorpyrifos residue in red soil was 1 to approximately 10 microg/g. The initial concentration of chlorpyrifos residue in red soil equivalent to or below 10 micro/g has not significant influence on growth of wheat seedlings. Similarly, the concentration equivalent to or below 5 microg/g has not significant influence on growth of oil-seed rape seedlings. The degradation rate in oil-seed rape rhizosphere soil is 1.4 to approximately 4.2 times more than in that in unvegetated soil. The amount of bacterium and fungus in oil-seed rape rhizosphere is 3.18 times and 1.84 times as much as these in unvegetated soil, respectively. However, there is no substantial difference of actinomyces between in rhizosphere soil and in unvegetated soil. Compared with unvegetated soil, pH in rhizosphere soil is lowered by 0. 19 to approximately 0.23.

[Effects of land use type on soil organic carbon, total nitrogen, and microbial biomass carbon and nitrogen contents in Karst region of South China].

A total of 721 surface (0-20 cm) soil samples were collected from the paddy field, upland, and woodland in the Karst region of Dacai, Huanjiang County, Guangxi Province, and the contents of their organic carbon (Oc ), total nitrogen (TN), microbial biomass carbon (Bc) , and microbial biomass nitrogen (BN) were determined. The results showed that the Oc and BN contents and soil pH value showed the trend of paddy field = woodland > upland, while TN and Bc contents had the trend of woodland > paddy field > upland. There was a significant positive correlation between Bc and Oc, and between B5 and TN. Soil microbial biomass C and N had rapid responses to the changes of land use type, which could be used as the sensitive biological indicators in evaluating soil quality and fertility in Karst region.