Analysis of changes in high-mobility group box 1, receptor for advanced glycation endproducts, and T helper 17/regulatory T balance in severe preeclampsia with acute heart failure.

We measured the levels of High-Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child-care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme-linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)-17, IL-6, transforming growth factor ß (TGF-ß), IL-10, and NT-proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P < .05). In patients with SPE with AHF, plasma HMGB1 was positively correlated with RAGE, Th17, Th17/Treg, IL-17, and IL-6 and was negatively correlated with TGF-ß and IL-10 (P < .05). Our findings revealed that patients with SPE with AHF had elevated levels of HMGB1 and RAGE while exhibiting Th17/Treg immune imbalance, suggesting that the abnormal expression of these indicators may be involved in the pathogenesis of SPE with AHF.

Transcriptome analyses reveal the potential mechanisms for color changes of a sweet orange peel induced by Candidatus Liberibacter asiaticus.

'Shatangju' mandarin (Citrus reticulate Blanco cv. Shatangju) is a Chinese citrus specialty in southern China with a delicious taste and an attractive appearance. Huanglongbing (HLB) caused by Candidatus Liberibacter asiaticus (CLas) threatens the Shatangju industry seriously. Fruits from citrus trees with HLB show 'red nose' peels with a serious reduction in fruit value. Differentially expressed genes (DEGs) have been identified in the leaves of several citrus species with HLB infection. However, similar studies on the fruit peels of citrus trees with HLB infection are very limited. In this study, the pathogen CLas was diagnosed in the 'red nose' fruit peels of Shatangju. The chlorophyll and carotenoid contents in different peels were also analyzed. Besides, we identified DEGs in the comparison between peels from normal red-colored and 'red nose' fruits via RNA-seq. A total of 1922 unigenes were identified as DEGs, of which 434 were up-regulated and 1488 were down-regulated in the 'red nose' fruit peels. DEGs involved in chlorophyll and carotenoids biosynthesis, photosynthesis, and transcription factors could be responsible for fruit color changes after HLB infection. Our findings provide a preliminary understanding of the mechanism underlying the formation of a 'red nose' on fruit peel from HLB-infected trees.

Characterization of the complete mitochondrial genome of a nematode species, Caenorhabditis tribulationis (Nematoda, Rhabditidae).

In the present study, we reported the complete mitogenome sequence of Caenorhabditis tribulationis Stevens & Félix 2019. The whole mitogenome of C. tribulationis is 14006 bp in length with an extreme bias of high AT content (75.26%) (GenBank accession no. OL362111). The mitochondrial genome contains 12 protein-coding genes (PCGs), 22 transfer RNA (tRNAs) genes, 2 ribosomal RNA (12S rRNA and 16S rRNA) genes, and a control region. All genes were unidirectionally transcribed on the same strand, typical for other nematode mitogenomes. 9 PCGs were initiated by typical ATN codons, except for NAD2, CYTB and NAD4, which were start with TTG codons. All the PCGs were predicted to use the typical TAN as the stop codons. The phylogenetic analysis showed that the relationship of C. tribulationis is very close to other species in the family Rhabditidae and separated form species of the families Ascarididae, Toxocaridae, Anisakidae and Ascaridiidae with high bootstrap value support.

Pretreatment of Sulfonylureas Reducing Perihematomal Edema in Diabetic Patients With Basal Ganglia Hemorrhage: A Retrospective Case-Control Study.

Background: The sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel is a target key mediator of brain edema. Sulfonylureas (SFUs) are blockers of the SUR1-TRPM4 channel. We made two assessments for the pretreatment of SFUs: (1) whether it associates with lower perihematomal edema (PHE) and (2) whether it associates with improved clinical outcomes in diabetic patients who have acute basal ganglia hemorrhage. Methods: This retrospective case-control study was conducted in diabetic adults receiving regular SFUs before the onset of intracerebral hemorrhage (ICH). All of the patients received the clinical diagnosis of spontaneous basal ganglia hemorrhage. The diagnosis was confirmed by a CT scan within 7 days after hemorrhage. For each case, we selected two matched controls with basal ganglia hemorrhage based on admission time (≤5 years) and age differences (≤5 years), with the same gender and similar hematoma volume. The primary outcome was PHE volume, and the secondary outcomes were relative PHE (rPHE), functional independence according to modified Rankin Scale score and Barthel Index at discharge, and death rate in the hospital. Results: A total of 27 patients (nine cases and 18 matched controls), admitted between January 1, 2009 and October 31, 2018, were included in our study. There was no significant association between SFU patients and non-SFU patients on PHE volumes [15.4 (7.4-50.2 ml) vs. 8.0 (3.1-22.1) ml, p = 0.100]. Compared to non-SFU patients, the SFU patients had significantly lower rPHE [0.8 (0.7-1.3) vs. 1.5 (1.2-1.9), p = 0.006]. After we adjusted the confounding factors, we found that sulfonylureas can significantly reduce both PHE volume (regression coefficient: -13.607, 95% CI: -26.185 to -1.029, p = 0.035) and rPHE (regression coefficient: -0.566, 95% CI: -0.971 to -0.161, p = 0.009). However, we found no significant improvement in clinical outcomes at discharge, in the event of pretreatment of SFUs before the onset of ICH, even after we adjusted the confounding factors. Conclusion: For diabetic patients with acute basal ganglia hemorrhage, pretreatment of sulfonylureas may associate with lower PHE and relative PHE on admission. No significant effect was found on the clinical outcomes when the patients were discharged. Future studies are needed to assess the potential clinical benefits using sulfonylureas for ICH patients.

Study on the Fingerprints and Quality Evaluation of Angelica Sinensis Radix by HPLC Coupled With Chemometrics Based on Traditional Decoction Process of ACPTCM.

OBJECTIVE: To establish a HPLC fingerprints evaluation method for Angelica Sinensis Radix (ASR) based on traditional decoction process of Ancient Classical Prescriptions of Traditional Chinese Medicine (ACPTCM). METHODS: The fingerprints of 10 batches of ASR were further evaluated by chemometrics methods. The similarity analyzed with "Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine 2004A," and hierarchical clustering analysis (HCA) and principal component analysis (PCA) were performed by SPSS (version 22.0, SPSS Inc., Chicago, IL, USA). RESULTS: There were 12 common peaks, and the similarity degrees of 10 batches of samples were more than 0.923 and showed that all the samples from different origins were of good consistency. The samples were divided into 4 clusters by HCA. The results of PCA showed that the 3 factors were chosen, the quality of samples could be evaluated basically. The comprehensive score results show that the ASR with Lot.Nos.DG-18007, DG-18008 in Weiyuan County, Gansu and DG-18009 produced in Minle County, Gansu Province rank among the top 3 in all samples. CONCLUSIONS: These results demonstrated that the combination of HPLC chromatographic fingerprint and chemometrics offers an efficient and reliable approach for quality evaluation of ASR from different sources as Ancient Classical Prescriptions ingredients.

Antitumor activities of Liver-targeting peptide modified Recombinant human Endostatin in BALB/c-nu mice with Hepatocellular carcinoma.

In our previous study, a liver-targeting peptide CSP I-plus modified recombinant human Endostatin (rEndostatin, endostar) (rES-CSP) was constructed and showed potent antiangiogenic capability and could specifically bind to human hepatocellular carcinoma cells to make a direct inhibition in vitro. In this study, the biological activities of rES-CSP in vivo were evaluated by subcutaneous and orthotopic xenograft nude mice model of human hepatocellular carcinoma cells HepG2. We found that rES-CSP significantly decreased tumor volume to 54.9% in the nude mice with subcutaneous xenograft compared with the control. In orthotopic xenograft model, rES-CSP not only decreased tumor volume (to 39.6% compared with the control) and tumor weight, it also increased its biodistribution in the liver tissue and hepatoma tissue. Moreover, lower microvessel density (MVD) and higher apoptotic index (AI) were also observed in the tumor tissues. It had no significant side-effects on the heart, liver, spleen, lung and kidney of mice. Results indicated CSP I-plus modified Endostar may be a potential candidate for a targeting therapy on hepatocellular carcinoma.

MicroRNA-24 Modulates Staphylococcus aureus-Induced Macrophage Polarization by Suppressing CHI3L1.

Macrophages play a crucial role in host innate anti-Staphylococcus aureus defense, which is tightly regulated by multiple factors, including microRNAs. A recent study showed that miR-24 plays an important role in macrophage polarization. Here, we investigated the biological function of miR-24 in S. aureus-stimulated macrophages. The results revealed that miR-24 expression was significantly decreased in both human and mouse macrophage cell lines with S. aureus stimulation in a time-dependent manner. Moreover, miR-24 overexpression significantly decreased the production of M1 phenotype markers, such as IL-6, iNOS, TNF-α, CD86, and CD80, whereas it increased the production of M2 markers, such as Arg1, CCL17, CCL22, CD163, and CD206, in S. aureus-stimulated macrophages. Conversely, knockdown of miR-24 promoted M1 macrophage polarization but diminished M2 macrophage polarization in S. aureus-stimulated macrophages. Furthermore, CHI3L1 was predicted as a target gene of miR-24 using bioinformatics software and identified by luciferase reporter assay. Additionally, miR-24 overexpression inhibited CHI3L1 expression and downregulated the downstream MAPK pathway in S. aureus-stimulated macrophages. Finally, CHI3L1 overexpression rescued macrophage polarization and MAPK pathway inhibition induced by miR-24 mimic transfection in S. aureus-stimulated macrophages. In conclusion, the data suggest that miR-24 serves as a molecular regulator in S. aureus-induced macrophage polarization through targeting of CHI3L1 and regulation of the MAPK pathway, which may provide a promising therapeutic target for S. aureus-related infections and inflammatory diseases.

MicroRNA-424/E2F6 feedback loop modulates cell invasion, migration and EMT in endometrial carcinoma.

Our previous study explored the roles of microRNA-424 (miR-424) in the development of endometrial carcinoma (EC) and analyzed the miR-424/E2F7 axis in EC cell growth. In this study, we investigated the status of miR-424 in human endometrial cancer tissues, which were collected from a cohort of Zunyi patients. We found that the expression level of miR-424 was associated with clinical tumor stage, cell differentiation, lymph node metastasis and cell migration ability. Cell function experiments demonstrated that miR-424 overexpression suppressed the invasion and migration abilities of endometrial carcinoma cells in vitro. Bioinformatic predictions and dual-luciferase reporter assays suggested E2F6 as a possible target of miR-424. RT-PCR and western blot assays demonstrated that miR-424 transfection reduced the expression level of E2F6, while inhibiting miR-424 with ASO-miR-424 (antisense oligonucleotides of miR-424) increased the expression level of E2F6. Cell function experiments indicated that E2F6 transfection rescued the EC cell phenotype induced by miR-424. In addition, we also found that E2F6 negatively regulated miR-424 expression in EC cells. In summary, our results demonstrated that the miR-424/E2F6 feedback loop modulates cell invasion, migration and EMT in EC and that the miR-424/E2Fs regulation network may serve as a new and potentially important therapeutic target in EC.

Long Noncoding RNA CPS1-IT1 Suppresses Cell Proliferation and Metastasis in Human Lung Cancer.

The long noncoding CPS1 intronic transcript 1 (lncRNA CPS1-IT1) is a recently identified tumor suppressor in the lncRNA family of proteins. Whether this lncRNA plays any functional role in solid tumors remains largely unknown. The present study aimed to investigate the role of lncRNA CPS1-IT1 in human lung cancer. Expression of lncRNA CPS1-IT1 was initially assessed in human lung cancer and in a series of lung cancer cell lines. The effects of CPS1-IT1 overexpression on cell proliferation, migration, and invasion were examined in lung cancer cell lines A549 and 95D. It was found that lncRNA CPS1-IT1 was significantly lower in cancerous tissues than in noncancerous tissues. lncRNA CPS1-IT1 was differentially expressed in lung cancer cell lines and expressed the least in two highly invasive cell lines, A549 and 95D. Overexpression of CPS1-IT1 slowed down cell proliferation by 35.7% in A549 cells and 30.8% in 95D cells on the fifth day. Cell migration was inhibited by 59% in A549 cells and 48% in 95D cells, and cell invasion was suppressed by 60% in both cell lines after overexpression of CPS1-IT1. While cell apoptosis was induced, CPS1-IT1 overexpression promoted the activities of caspase 3 and caspase 9 without affecting that of caspase 8. These observations were suggestive of the tumor-suppressive role of lncRNA CPS1-IT1 in lung cancer. Our data suggest that CPS1-IT1 may be used as a biomarker for early diagnosis and therapeutic targets against lncRNA and may be promising in the treatment of lung cancer.

Label-free selective SERS detection of PCB-77 based on DNA aptamer modified SiO2@Au core/shell nanoparticles.

A label-free approach to selective detection of 3,3',4,4'-tetrachlorobiphenyl (PCB77) using aptamer modified silica-Au/core-shell nanoparticles (denoted as SiO2@Au core/shell NPs) through surface enhanced Raman scattering (SERS) spectroscopy was proposed. The devised system consisted of SiO2@Au core/shell NPs fixed on the amino-silane functionalized glass slides with the PCB77-binding aptamers attached covalently to the gold surfaces through a thiol linker. The aptamers made of single-stranded DNA (ssDNA) oligomers with one end standing on the Au surface changed the conformation upon conjugation with PCB77, which correspondingly caused the spectral response of the ssDNA oligomers. The intensity ratio I(660 cm(-1))/I(736 cm(-1)) decreased with the amount of PCB77 added, which thus allowed us to measure trace amounts of PCB77 in a selective and quantitative way. This work therefore demonstrates that the design of aptamer-modified SiO2@Au core/shell NPs can be utilized for label-free SERS detection of persistent organic pollutants (POPs) in the environment.

Serum trypsin and TCR as novel markers for predicting disease activity in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a novel disease named in recent years. Because of its varied clinical manifestations, like tumor but not tumor, it brings a great challenge to clinical diagnosis. Trypsin and T-cell receptor (TCR) are thought to mediate the regulation of B cell maturation, survival and antibody production. In this study, we investigated the clinical features and important novel markers of IgG4-RD. MATERIAL AND METHODS: A prospective cohort study of 22 patients with IgG4-RD was carried out from May 2009 to December 2012, and 65 cases with acute pancreatitis, 60 cases with pancreatic cancer and 120 healthy individuals were studied as controls. Serum TCR, trypsin and IgG4 levels were measured during pre- and post-treatment in the patients with IgG4-RD and their correlations with IgG4 were also assessed. RESULTS: Serum IgG4 and IgE levels in all patients were significantly increased, and tumor markers (carbohydrate antigen 19-9 and/or carbohydrate antigen 125) were also increased (12/22). Serum trypsin in patients with IgG4-RD was lower than in the ones with acute pancreatitis, pancreatic cancer, and healthy individuals. But serum TCR of IgG4-RD was significantly higher than in the pancreatic cancer group and normal controls and it was inversely correlated with the levels of IgG4 (r = -3.160, p = 0.042). CONCLUSIONS: The results indicate that serum TCR and trypsin might be useful markers for predicting disease activity in IgG4-RD.

Development of an ion mobility spectrometer with a paper spray ionization source.

Paper spray (PS) ionization is a recently developed ion source that has been used to analyze samples in their native environments at ambient pressure without requiring sample preparation or pre-separation. The design of an ion mobility spectrometer (IMS) coupled with PS ionization can help expand IMS applications to on-site detection of complex liquid samples. We report a paper spray ionization ion mobility spectrometer prototype that consists of a PS source and an ion mobility spectrometer optimized using a numerical simulation. The performance of the design was evaluated by measuring 2, 6-di-tert-butylpyridine (2, 6-DtBP). The mobility spectra of the 2, 6-DtBP exhibited a single-product ion peak with reduced mobility calculated at 1.42 cm(2)∕(V s) and a linear response of 0.1-10 µg∕ml, with an estimated detection limit of 0.05 µg∕ml. The Relative Standard Deviation for 1 µg∕ml was 5.7% over 11 measurements. The highest resolving power (47) was measured for 2, 6-DtBP. Based on these preliminary results, the present PSIMS design is expected to become a tool of choice for the rapid analysis of complex liquid samples.