Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer.

BACKGROUND: 5-Hydroxymethylcytosine-enriched gene profiles and regions show tissue-specific and tumor specific. There is a potential value to explore cell-free DNA 5-hydroxymethylcytosine feature biomarkers for early gastric cancer detection. METHODS: A matched case‒control study design with 50 gastric cancer patients and 50 controls was performed to sequence the different 5-hydroxymethylcytosine modification features of cell free DNA. Significantly differential 5-hydroxymethylcytosine modification genes were identified to construct a gastric cancer diagnostic model. Data set from GEO was used as an external testing set to test the robustness of the diagnostic model. RESULTS: Accounting for more than 90% of 5-hydroxymethylcytosine peaks were distributed in the gene body in both the gastric cancer and control groups. The diagnostic model was developed based on five different 5-hydroxymethylcytosine modification genes, FBXL7, PDE3A, TPO, SNTG2 and STXBP5. The model could effectively distinguish gastric cancer patients from controls in the training (AUC = 0.95, sensitivity = 88.6%, specificity = 94.3%), validation (AUC = 0.87, sensitivity = 73.3%, specificity = 93.3%) and testing (AUC = 0.90, sensitivity = 81.9%, specificity = 90.2%) sets. The risk scores of the controls from the model were significantly lower than those of gastric cancer patients in both our own data (P < 0.001) and GEO external testing data (P < 0.001), and no significant difference between different TNM stage patients (P = 0.09 and 0.66). Furthermore, there was no significant difference between the healthy control and benign gastric disease patients in the testing set from GEO (P = 0.10). CONCLUSIONS: The characteristics of 5-hydroxymethylcytosine in cell free DNA are specific to gastric cancer patients, and the diagnostic model constructed by five genes' 5-hydroxymethylcytosine features could effectively identify gastric cancer patients.

Xylooligosaccharides ameliorate insulin resistance by increasing Akkermansia muciniphila and improving intestinal barrier dysfunction in gestational diabetes mellitus mice.

Little is known regarding the effects of xylooligosaccharides (XOS) on insulin resistance (IR) in gestational diabetes mellitus (GDM). We aimed to investigate this issue and its mechanism. Sixty female mice were randomly allotted to 4 groups (n = 15): control, high fat diet (HFD), GDM, and GDM + XOS. The control mice were fed an AIN-93 diet, while the mice in the other groups were fed 45% HFD. After pregnancy, mice in GDM and GDM + XOS groups were intraperitoneally injected with 30 mg kg-1 streptozocin for 3 days from the first day of pregnancy. Mice in the GDM + XOS group were then fed an HFD containing 2% XOS. Fasting glucose and insulin levels were monitored. The fecal Akkermansia muciniphila (Akk. muciniphila) and Bifidobacterium were measured by qPCR. The Chiu scores were calculated from hematoxylin-eosin (HE)-stained ileal tissues. Phosphorylated Akt in the liver and occludin and ZO-1 in the intestinal tissues were determined by western blotting. XOS reduced (p < 0.05) fasting blood glucose and insulin and HOMA-IR, and increased (p < 0.05) Akt phosphorylation in the livers of GDM mice. Moreover, XOS decreased (p < 0.05) TNFα, IL-1ß, IL-15 and LPS in the serum, increased (p < 0.05) fecal Akk. muciniphila abundance, lowered (p < 0.05) Chiu's scores, and enhanced (p < 0.05) occludin and ZO-1 expression. XOS ameliorate IR by increasing Akk. muciniphila and improving intestinal barrier dysfunction in GDM mice.

Appraising associations between signature lipidomic biomarkers and digestive system cancer risk: novel evidences from a prospective cohort study of UK Biobank and Mendelian randomization analyses.

BACKGROUND: The roles of serum lipids on digestive system cancer (DSC) risk were still inconclusive. In this study, we systematically assessed indicative effects of signature lipidomic biomarkers (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)) on DSC (oesophagus, stomach, colorectal, liver, gallbladder, and pancreas cancers) risk. METHODS: HDL-C, LDL-C, and TG concentration measurements were respectively analyzed with enzyme immunoinhibition, enzymatic selective protection, and GPO-POD methods in AU5800 supplied from Beckman Coulter. The diagnoses of DSCs were coded using International Classification of Diseases, Tenth Revision (ICD-10) codes updated until October 2022 in the UK Biobank (UKB). In this study, we assessed phenotypic association patterns between signature lipidomic biomarkers and DSC risk using restricted cubic splines (RCSs) in multivariable-adjusted Cox proportional hazards regression models. Moreover, linear and nonlinear causal association patterns of signature lipidomic biomarkers with DSC risk were determined by linear and nonlinear Mendelian randomization (MR) analyses. RESULTS: A median follow-up time of 11.8 years was recorded for 319,568 participants including 6916 DSC cases. A suggestive independent nonlinear phenotypic association was observed between LDL-C concentration and stomach cancer risk (Pnonlinearity < 0.05, Poverall < 0.05). Meanwhile, a remarkable independent linear negative phenotypic association was demonstrated between HDL-C concentration and stomach cancer risk (Pnonlinearity > 0.05, Poverall < 0.008 (0.05/6 outcomes, Bonferroni-adjusted P)), and suggestive independent linear positive associations were observed between HDL-C concentration and colorectal cancer risk, and between TG concentration and gallbladder cancer risk (Pnonlinearity > 0.05, Poverall < 0.05). Furthermore, based on nonlinear and linear MR-based evidences, we observed an suggestive independent negative causal association (hazard ratio (HR) per 1 mmol/L increase: 0.340 (0.137-0.843), P = 0.020) between LDL-C and stomach cancer risk without a nonlinear pattern (Quadratic P = 0.901, Cochran Q P = 0.434). Meanwhile, subgroup and stratified MR analyses both supported the category of LDL-C ≥ 4.1 mmol/L was suggestively protective against stomach cancer risk, especially among female participants (HR: 0.789 (0.637-0.977), P = 0.030) and participants aged 60 years or older (HR: 0.786 (0.638-0.969), P = 0.024), and the category of TG ≥ 2.2 mmol/L concluded to be a suggestive risk factor for gallbladder cancer risk in male participants (HR: 1.447 (1.020-2.052), P = 0.038) and participants aged 60 years or older (HR: 1.264 (1.003-1.593), P = 0.047). CONCLUSIONS: Our findings confirmed indicative roles of signature lipidomic biomarkers on DSC risk, notably detecting suggestive evidences for a protective effect of high LDL-C concentration on stomach cancer risk, and a detrimental effect of high TG concentration on gallbladder cancer risk among given participants.

Erzhiwan Ameliorates Restraint Stress- and Monobenzone-Induced Depigmentation in Mice by Inhibiting Macrophage Migration Inhibitory Factor and 8-Hydroxy-2-Deoxyguanosine.

Purpose: Vitiligo is an autoimmune disease that results in the loss of epidermal melanocytes. The treatments for patients with vitiligo remain lacking. Erzhiwan (EZW), a traditional Chinese Medicine composed of Ligustri Lucidi Fructus and Ecliptae Herba, was used to ameliorate depigmentation since ancient China. This study aims to investigate the effect of EZW on vitiligo-related depigmentation. Methods: A vitiligo-related depigmentation mouse model was induced by monobenzone and restraint stress. The experimental depigmentation mice were treated with EZW. Histological observation of skin was conducted. Cutaneous oxidative damage and inflammation were determined. A network pharmacology analysis was carried out. Results: EZW reduced depigmentation score (p<0.01), cutaneous inflammatory infiltration (p<0.01), and CD8α-positive expression (p<0.01), and increased cutaneous melanin content in experimental depigmentation mice. EZW reduced stress reaction in experimental depigmentation mice (p<0.01). EZW inhibited 8-hydroxy-2-deoxyguanosine (8-OHdG)-related DNA oxidative damage in the skin (p<0.05, p<0.01). In addition, EZW reduced cutaneous macrophage migration inhibitory factor (MIF)-CD74-NF-κB signaling (p<0.01). The network pharmacology analysis demonstrated that EZW regulated necroptosis, apoptosis, and FoxO signaling pathways in vitiligo. An in vitro experiment showed that the main ingredient of EZW, specnuezhenide, protected against monobenzone and MIF-induced cell death in HaCaT cells (p<0.01). Conclusion: EZW ameliorates restraint stress- and monobenzone-induced depigmentation via the inhibition of MIF and 8-OHdG signaling. The findings provide a data basis of an utilization of EZW in vitiligo.

A model for predicting postoperative persistent acute kidney injury (AKI) in AKI after cardiac surgery patients with normal baseline renal function.

BACKGROUND: Persistent acute kidney injury (AKI) after cardiac surgery is not uncommon and linked to poor outcomes. HYPOTHESIS: The purpose was to develop a model for predicting postoperative persistent AKI in patients with normal baseline renal function who experienced AKI after cardiac surgery. METHODS: Data from 5368 patients with normal renal function at baseline who experienced AKI after cardiopulmonary bypass cardiac surgery in our hospital were retrospectively evaluated. Among them, 3768 patients were randomly assigned to develop the model, while the remaining patients were used to validate the model. The new model was developed using logistic regression with variables selected using least absolute shrinkage and selection operator regression. RESULTS: The incidence of persistent AKI was 50.6% in the development group. Nine variables were selected for the model, including age, hypertension, diabetes, coronary heart disease, cardiopulmonary bypass time, AKI stage at initial diagnosis after cardiac surgery, postoperative serum magnesium level of <0.8 mmol/L, postoperative duration of mechanical ventilation, and postoperative intra-aortic balloon pump use. The model's performance was good in the validation group. The area under the receiver operating characteristic curve was 0.761 (95% confidence interval: 0.737-0.784). Observations and predictions from the model agreed well in the calibration plot. The model was also clinically useful based on decision curve analysis. CONCLUSIONS: It is feasible by using the model to identify persistent AKI after cardiac surgery in patients with normal baseline renal function who experienced postoperative AKI, which may aid in patient stratification and individualized precision treatment strategy.

Clinical efficacy of Kuanxiong aerosol for patients with prehospital chest pain: A randomized controlled trial.

BACKGROUND: Kuanxiong Aerosol (KXA)(CardioVent®), consisting of Asarum sieboldii Miq. oil, Santalum album L. oil, Alpinia officinarum Hance oil, Piper longum L. oil and borneol, seems to relieve the symptoms of chest pain and serve as a supplementary treatment for prehospital chest pain in emergency department. STYLE OF THE STUDY: This randomized controlled trial aimed to determine the clinical effect and safety of KXA for patients with prehospital chest pain. METHODS: A total of 200 patients were recruited from Guangdong Provincial Hospital of Chinese Medicine and randomly divided into KXA group (n = 100) and Nitroglycerin Aerosol (NA) group (n = 100) by SAS 9.2 software. All patients were treated with standardized Western medicine according to the pre-hospital procedure. The experimental group and NA group was additionally treated with KXA and NA respectively. The primary outcome was the relieving time of prehospital chest pain (presented as relief rate) after first-time treatment. The secondary outcomes included the evaluation of chest pain (NRS scores, degree of chest pain, frequency of chest pain after first-time treatment), efficacy in follow-up time (the frequency of average aerosol use, emergency department visits, 120 calls, medical observations and hospitalization at 4 weeks, 8 weeks, 12 weeks), alleviation of chest pain (Seattle angina questionnaire, chest pain occurrence, and degree of chest pain at 12-weeks treatment) and the change of TCM symptoms before and after 12-weeks treatment. In addition, the safety of KXA was also assessed by the occurrence of adverse events. The database was created using Epidata software, and statistical analysis was conducted by SPSS 23.0 software. RESULTS: A total of 194 participants finally completed the trial, the results showed that after first-time treatment, KXA had a higher relief rate (72.2%) of chest pain within 30 min than that of NA group (59.4%, p = 0.038), KXA group had a lower degree of chest pain (p = 0.005), lower NRS score (p = 0.011) and higher reduction of NRS score (p = 0.005) than the NA. In the follow-up period, KXA group decreased the frequency of 120 call better than that of NA group at 4 weeks (p = 0.040), but KXA had a similar efficacy as NA in the improvement on the of frequency of chest pain, aerosol use, emergency department visits, 120 call, medical observation and hospitalization at 4 weeks, 8 weeks and 12 weeks (p>0.05). There also had no difference between the two groups on the occurrence of chest pain, degree of chest pain, physical limitation, angina stability, treatment satisfaction, and disease perception between the two groups at 12 weeks (p>0.05). In addition, KXA and NA both improved the patient's chest pain, but not the TCM symptoms. In terms of safety, KXA showed similar safety as NA in this study. CONCLUSIONS: KXA relieved prehospital chest pain faster than NA and had a better remission effect on the prehospital chest pain than that of the NA group in short-period. In long-period, KXA showed similar efficacy on the improvement of prehospital chest pain as NA. KXA may be a safe and reliable therapy for prehospital chest pain.

Predictive value of hepatitis B serological indicators for mortality among cancer survivors and validation in a gastric cancer cohort.

Hepatitis B virus (HBV) infection has gradually been considered to associate with cancer development and progression. This study aimed to explore the associations of serological indicators of HBV infection with mortality risk among cancer survivors and further validated using a gastric cancer (GC) cohort from China, where HBV infection is endemic. National Center for Health Statistics' National Health and Nutrition Examination Survey (NHANES) data were used in this study. Individuals with positive results of hepatitis B core antigen (anti-HBc) were considered to have current or past HBV infection. Serological indicators were positive only for hepatitis B surface antibodies (anti-HBs), indicating vaccine-induced immunity, whereas negativity for all serologic indicators was considered to indicate the absence of HBV infection and immunity to HBV. The GC cohort included patients from the First Hospital of Jilin University, China. The median follow-up time of the NHANES was 10 years; during the follow-up, 1505 deaths occurred. The results revealed that anti-HBs-positive cancer survivors had a 39% reduced risk of mortality (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.44-0.85). Men and individuals aged <65 years old with past exposure to HBV had higher mortality risk (HR 1.52, 95% CI 1.09-2.13; HR 2.07, 95% CI 1.13-3.83). In this GC cohort, individuals who were only anti-HBs-positive showed a reduced risk of mortality (HR 0.77, 95% CI 0.62-0.95). Thus, anti-HBs positivity was a significant factor of decreased mortality among cancer survivors. More rigorous surveillance is necessary for cancer survivors with anti-HBc positivity, particularly men, and younger individuals.

Rare variants in GPR3 in POI patients: a case series with review of literature.

BACKGROUND: Premature ovarian insufficiency (POI) is a highly heterogeneous disease, and up to 25% of the cases can be explained by genetic causes. G protein-coupled receptor 3 (GPR3) plays an important role in oocyte arrest, and Gpr3-deficient mice exhibited POI-like phenotypes. CASE PRESENTATION: We identified two heterozygous missense variants of GPR3: NM_005281: c.C973T (p.R325C) and c.G772A (p.A258T) in two sporadic Han Chinese POI cases through whole exome sequencing and genetic analysis. The two patients were diagnosed as POI in their late 20s, presenting elevated serum levels of follicle stimulating hormone and secondary amenorrhea. Both variants are very rare in the population databases of ExAC, gnomAD and PGG.Han. The affected amino acids are conserved across species and the mutated amino acids are predicted deleterious with bioinformatics prediction tools and the protein three-dimensional structure analysis. CONCLUSIONS: It is the first report of rare GPR3 variants associated with POI women, providing an important piece of evidence for GPR3 as a candidate gene which should be screened in POI. This finding suggested the necessity of including GPR3 in etiology study and genetic counseling of POI patients.

HELQ as a DNA helicase: Its novel role in normal cell function and tumorigenesis (Review).

Helicase POLQ­like (HELQ or Hel308), is a highly conserved, 3'­5' superfamily II DNA helicase that contributes to diverse DNA processes, including DNA repair, unwinding, and strand annealing. HELQ deficiency leads to subfertility, due to its critical role in germ cell stability. In addition, the abnormal expression of HELQ has been observed in multiple tumors and a number of molecular pathways, including the nucleotide excision repair, checkpoint kinase 1­DNA repair protein RAD51 homolog 1 and ATM/ATR pathways, have been shown to be involved in HELQ. In the present review, the structure and characteristics of HELQ, as well as its major functions in DNA processing, were described. Molecular mechanisms involving HELQ in the context of tumorigenesis were also described. It was deduced that HELQ biology warrants investigation, and that its critical roles in the regulation of various DNA processes and participation in tumorigenesis are clinically relevant.

The role and implication of autophagy in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a malignant tumor that originates from the biliary epithelial cells. It is characterized by a difficult diagnosis and limited treatment options. Autophagy is a cellular survival mechanism that maintains nutrient and energy homeostasis and eliminates intracellular pathogens. It is involved in various physiological and pathological processes, including the development of cancer. However, the role, mechanism, and potential therapeutic targets of autophagy in CCA have not been thoroughly studied. In this review, we introduce the classification, characteristics, process, and related regulatory genes of autophagy. We summarize the regulation of autophagy on the progression of CCA and collect the latest research progress on some autophagy modulators with clinical potential in CCA. In conclusion, combining autophagy modulators with immunotherapy, chemotherapy, and targeted therapy has great potential in the treatment of CCA. This combination may be a potential therapeutic target for CCA in the future.

Risk-stratified approach by aMAP score for community population infected with hepatitis B and C to guide subsequent liver cancer screening practice: A cohort study with 10-year follow-up.

The aim of this study was to determine whether the age-Male-ALBI-Platelet (aMAP) score is applicable in community settings and how to maximise its role in risk stratification. A total of thousand five hundred and three participants had an aMAP score calculated at baseline and were followed up for about 10 years to obtain information on liver cancer incidence and death. After assessing the ability of aMAP to predict liver cancer incidence and death in terms of differentiation and calibration, the optimal risk stratification threshold of the aMAP score was explored, based on absolute and relative risks. The aMAP score achieved higher area under curves (AUCs) (almost all above 0.8) within 10 years and exhibited a better calibration within 5 years. Regarding absolute risk, the risk of incidence of and death from liver cancer showed a rapid increase after an aMAP score of 55. The cumulative incidence (5-year: 8.3% vs. 1.3% and 10-year: 20.9% vs. 3.6%) and mortality (5-year: 6.7% vs. 1.1% and 10-year: 17.5% vs. 3.1%) of liver cancer in individuals with an aMAP score of ≥55 were significantly higher than in those with a score of <55 (Grey's test p < .001). In terms of relative risk, the risk of death from liver cancer surpassed that from other causes after an aMAP score of ≥55 [HR = 1.38(1.02-1.87)]. Notably, the two types of death risk had opposite trends between the subpopulation with an aMAP score of ≥55 and < 55. To conclude, this study showed the value of the aMAP score in community settings and recommends using 55 as a new risk stratification threshold to guide subsequent liver cancer screening.

The performance of interferon gamma release assays in patients with nontuberculous mycobacterial infection: a systematic review and meta-analysis.

BACKGROUND: The actual positive rate of interferon gamma release assays (IGRAs) in patients with nontuberculous mycobacteria (NTM) infections remains unclear. This review and meta-analysis present the prevalence of positive IGRAs (T-SPOT.TB and QuantiFERON [QFT] tests) among patients infected with NTM isolates (with or without ESAT-6/CFP-10). METHODS: Several databases, including PubMed, Scopus, Embase, and Web of Science were searched (until June 18th, 2022). Studies that had the following data were included: (1) results of T-SPOT.TB, QuantiFERON (QFT) test, or both, (2) NTM species, and (3) NTM diseases, or NTM colonization. The metaprop command that incorporates a Freeman-Tukey double arcsine transformation is used for pooling proportions. RESULTS: A total of 11 articles (n = 929) were deemed eligible for inclusion. Meta-analysis identified that the overall pooled positive and indeterminate rates of IGRA results in patients with NTM infections was 16% and 5%, respectively. Subgroup analysis showed that the positive rate of IGRAs in patients infected with NTM (without ESAT-6/CFP-10) was 7% (95% CI, 1%-18%), and 44% (95%CI, 22%-68%) in patients infected with NTM (with ESAT-6/CFP-10). In addition, the indeterminate rate of QFT (7%, 95% CI: 4%-12%) was higher than that of T-SPOT.TB (0%; 95% CI, 0%-2%) among the overall population with NTM infections. CONCLUSIONS: The IGRAs have a moderate positive rate for the diagnosis of NTM (expressing ESAT-6/CFP-10) infections, and a significant indeterminate rate is observed among the overall population infected with NTM. However, these findings should be interpreted with caution because of the high heterogeneity among studies.

Zika virus infection leads to hormone deficiencies of the hypothalamic-pituitary-gonadal axis and diminished fertility in mice.

IMPORTANCE: Zika virus (ZIKV) infection in pregnant women during the third trimester can cause neurodevelopmental delays and cryptorchidism in children without microcephaly. However, the consequences of congenital ZIKV infection on fertility in these children remain unclear. Here, using an immunocompetent mouse model, we reveal that congenital ZIKV infection can cause hormonal disorders of the hypothalamic-pituitary-gonadal axis, leading to reduced fertility and decreased sexual preference. Our study has for the first time linked the hypothalamus to the reproductive system and social behaviors after ZIKV infection. Although the extent to which these observations in mice translate to humans remains unclear, these findings did suggest that the reproductive health and hormone levels of ZIKV-exposed children should receive more attention to improve their living quality.

Identification of Critical Biomarkers and Mechanisms of Fructus Ligustri Lucidi on Vitiligo Using Integrated Bioinformatics Analysis.

Objective: Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Fructus Ligustri Lucidi (FLL) has been used for premature graying of hair since ancient China and is currently used to treat vitiligo. However, the key biomarkers and mechanisms underlying FLL in vitiligo remain unclear. This study aimed to identify the potential biomarkers and mechanisms of FLL in vitiligo using network pharmacology analysis. Methods: The expression profiles of GSE65127 and GSE75819 were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) between the vitiligo and healthy samples. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of DEGs were performed using R analyses. We performed R to further understand the functions of the critical targets. Cytoscape tools have facilitated network topology analysis. Molecular docking was performed using Auto Dock Vina software. Results: The results showed that 13 DEGs were screened in vitiligo. Based on bioinformatics, network pharmacology and Western blot, we found that the critical targets of melanoma antigen recognized by 5,6-dihydroxyindole-2-carboxylic acid oxidase (TYRP1) may be related to the mechanism of action of FLL in the treatment of vitiligo. Conclusion: TYRP1, as a melanocyte molecular biomarker, may be closely related to the underlying mechanism of FLL in the treatment of vitiligo via the inhibition of melanocyte death.

Restraint stress promotes monobenzone-induced depigmentation in mice via the activation of glucocorticoid receptor/macrophage migration inhibitory factor signaling pathway.

Psychological stress triggers onset and development of vitiligo in humans. However, the mechanism of psychological stress on vitiligo remains unclear. The study aims to investigate whether psychological stress promotes vitiligo and explore the underlying mechanism. A depigmentation mouse model induced by applying a skin-bleaching reagent monobenzone to dorsal skin and an in vitro HaCaT keratinocyte death model induced by monobenzone were employed to explore the effect of restraint stress, which mimics psychological stress, on depigmentation. The results indicated that restraint stress promoted vitiligo-related depigmentation, vacuolisation, spongiosis, CD8+ T lymphocyte infiltration, and loss of melanocytes in the skin. Restraint stress activated cutaneous NLR family containing pyrin domain protein 3 (NLRP3) inflammasome. In addition, restraint stress aggravated anxiety-like behaviors and increased levels of macrophage migration inhibitory factor (MIF) and corticosterone in the circulation, accompanied with decreasing the expression of cutaneous 8-oxoguanine DNA glycosylase (OGG1) in depigmentation mice. In vitro experiments demonstrated that activation of glucocorticoid receptor (GR) by cortisol upregulated NLRP3 expression dependent on MIF, and directly decreased the transcription of OGG1. Blockade of MIF reversed the NLRP3 signal in restraint stress-induced depigmentation mice. In conclusion, restraint stress promotes vitiligo-related depigmentation in mice via the activation of GR/MIF signaling pathway. The findings provide a theoretical basis for prevention and treatments of vitiligo with therapies of targeting GR, MIF, and OGG1.

Evaluating the Activity of Neuraminidase in Bacterial Vaginosis Microflora and Imaging Sialic Acid on the Cell Membrane by Boron and Nitrogen Codoped Fluorescent Carbon Dots.

Sialic acids (SAs) are commonly located on the cell surface as terminal ends of glycoproteins and glycolipids. Neuraminidase (NEU) is a class of glycoside hydrolase enzymes that can cleave SAs from receptors. Both SA and NEU play important roles in human physiological and pathological processes of cell-cell interaction, communication, and signaling. Additionally, bacterial vaginosis (BV), a form of gynecological inflammation caused by dysbiosis of the vaginal microbiome, results in the abnormal activity of NEU in vaginal fluid. Here, we developed a novel probe for rapidly and selectively sensing SA and NEU based on a one-step prepared boron and nitrogen codoped fluorescent carbon dots (BN-CDs). The selective recognition reaction between SA and the phenylboronic acid groups on the surface of BN-CDs inhibits fluorescence emission from BN-CDs, while the NEU-catalyzed hydrolysis of SA bound on BN-CDs leads to fluorescence recovery. The probe was applied in diagnosing BV and showed consistent results to Amsel criteria. Moreover, the low cytotoxicity of BN-CDs facilitates its application in fluorescence imaging of SA on the membrane of red blood cells (RBCs) and leukemia cell lines (U937, KAS-1). The excellent sensitivity, accuracy, and applicability of the developed probe support its broad potential applications in future clinical diagnosis and treatment.

Elder and booster vaccination associates with decreased risk of serious clinical outcomes in comparison of Omicron and Delta variant: A meta-analysis of SARS-CoV-2 infection.

Background: The COVID-19 pandemic brings great pressure to the public health systems. This meta-analysis aimed to compare the clinical outcomes among different virus variants, to clarify their impact on medical resources and to provide evidence for the formulation of epidemic prevention policies. Methods: A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases using the key words "Omicron" and "Delta." The adjusted Risk ratios (RRs), Odds ratios (ORs) and Hazard ratios (HRs) were extracted, and RRs and Rate difference % (RD%) were used to interpret the risk estimates of the outcomes ultimately. Results: Forty-three studies were included, with 3,812,681 and 14,926,841 individuals infected with SARS-CoV-2 Delta and Omicron variant, respectively. The relative risks of hospitalization, death, ICU admission, and mechanical ventilation use after infection with the Omicron variant were all significantly reduced compared those after infection with the Delta variant (RRhospitalization = 0.45, 95%CI: 0.40-0.52; RRdeath = 0.37, 95%CI: 0.30-0.45; RRICU = 0.35, 95%CI: 0.29-0.42; RRmechanical ventilation = 0.33, 95%CI: 0.25-0.44). The change of both absolute and relative risks for hospitalization was more evident (RR = 0.47, 95%CI: 0.42-0.53；RD% =10.61, 95%CI: 8.64-12.59) and a significant increase was observed for the absolute differences in death in the elderly (RD% = 5.60, 95CI%: 4.65-6.55); the change of the absolute differences in the risk of hospitalization and death were most markedly observed in the patients with booster vaccination (RD%hospitalization = 8.60, 95CI%: 5.95-11.24; RD%death = 3.70, 95CI%: 0.34-7.06). Conclusion: The ability of the Omicron variant to cause severe clinical events has decreased significantly, as compared with the Delta variant, but vulnerable populations still need to be vigilant. There was no interaction between the vaccination doses and different variants.

Specnuezhenide ameliorates ultraviolet-induced skin photoaging in mice by regulating the Sirtuin 3/8-Oxoguanine DNA glycosylase signal.

PURPOSE: Ultraviolet-induced skin photoaging was involved in DNA oxidative damage. Specnuezhenide, one of the secoiridoids extracted from Ligustri Lucidi Fructus, possesses antioxidant and anti-inflammatory effects. Whether specnuezhenide ameliorates skin photoaging remains unclear. This study aimed to investigate the effect of specnuezhenide on skin photoaging induced by ultraviolet and explore the underlying mechanism. METHODS: Mice were employed to treat with ultraviolet to induce skin photoaging, then administrated 10 and 20 mg/kg of specnuezhenide. Histological analysis, protein expression, network pharmacology, and autodock analysis were conducted. RESULTS: Specnuezhenide ameliorated ultraviolet-induced skin photoaging in mice via the increase in collagen contents, and decrease in epidermal thickness, malondialdehyde content, and ß-galactosidase expression in the skin. Specnuezhenide reduced cutaneous apoptosis and inflammation in mice with skin photoaging. In addition, network pharmacology data indicated that specnuezhenide possessed potential targets on the NOD-like receptor signaling pathway. Validation experiment found that specnuezhenide inhibited the expression of NOD-like receptor family pyrin domain-containing 3, gasdermin D-C1, and Caspase 1. Furthermore, the expression of 8-Oxoguanine DNA glycosylase (OGG1), sirtuin 3 (SIRT3), and superoxide dismutase 2 was increased in specnuezhenide-treated mice with photoaging. CONCLUSION: Specnuezhenide protected against ultraviolet-induced skin photoaging in mice via a probable activation of SIRT3/OGG1 signal.

A network causal relationship between type-1 diabetes mellitus, 25-hydroxyvitamin D level and systemic lupus erythematosus: Mendelian randomization study.

BACKGROUND: Observational studies have suggested a relationship between type-1 diabetes mellitus (T1DM) and systemic lupus erythematosus (SLE). In both autoimmunities, 25-hydroxyvitamin D (25-OHD) deficiency is common. However, the causality between T1DM, 25-OHD level and SLE remains largely unknown. METHODS: Independent genetic variants associated with T1DM, 25-OHD level, and SLE from the largest genome-wide association studies were used to conduct two-sample bidirectional Mendelian randomization (BIMR) and two-step Mendelian randomization (MR) analysis to estimate causal relationship between T1DM, 25-OHD level and SLE, and further multivariable Mendelian randomization (MVMR) was used to verify direct causality of T1DM and 25-OHD level on SLE. A series of sensitivity analysis as validation of primary MR results were performed. RESULTS: Consistent with the results of BIMR, there was strong evidence for a direct causal effect of T1DM on the risk of SLE (ORMVMR-IVW = 1.249, 95% CI = 1.148-1.360, PMVMR-IVW = 1.25×10-5), and 25-OHD level was negatively associated with the risk of SLE (ORMVMR-IVW = 0.305, 95% CI = 0.109-0.857, PMVMR-IVW = 0.031). We also observed a negative causal effect of T1DM on 25-OHD level (ORBIMR-IVW = 0.995, 95% CI = 0.991-0.999, PBIMR-IVW = 0.030) while the causal effect of 25-OHD level on the risk of T1DM did not exist (PBIMR-IVW = 0.106). In BIMR analysis, there was no evidence for causal effects of SLE on the risk of T1DM and 25-OHD level (PBIMR-IVW > 0.05, respectively). CONCLUSION: Our MR analysis suggested that there was a network causal relationship between T1DM, 25-OHD level and SLE. T1DM and 25-OHD level both have causal associations with the risk of SLE, and 25-OHD level could be a mediator in the causality of T1DM and SLE.