Ketogenic Diets Alter the Gut Microbiome, Resulting in Decreased Susceptibility to and Cognitive Impairment in Rats with Pilocarpine-Induced Status Epilepticus.

A ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that exerts antiepileptic effects by attenuating spontaneous recurrent seizures, ameliorating learning and memory impairments, and modulating the gut microbiota composition. However, the role of the gut microbiome in the antiepileptic effects of a KD on temporal lobe epilepsy (TLE) induced by lithium-pilocarpine in adult rats is still unknown. Our study provides evidence demonstrating that a KD effectively mitigates seizure behavior and reduces acute-phase epileptic brain activity and that KD treatment alleviates hippocampal neuronal damage and improves cognitive impairment induced by TLE. We also observed that the beneficial effects of a KD are compromised when the gut microbiota is disrupted through antibiotic administration. Analysis of gut microbiota components via 16S rRNA gene sequencing in fecal samples collected from TLE rats fed either a KD or a normal diet. The Chao1 and ACE indices showed decreased species variety in KD-fed rats compared to TLE rats fed a normal diet. A KD increased the levels of Actinobacteriota, Verrucomicrobiota and Proteobacteria and decreased the level of Bacteroidetes. Interestingly, the abundances of Actinobacteriota and Verrucomicrobiota were positively correlated with learning and memory ability, and the abundance of Proteobacteria was positively correlated with seizure susceptibility. In conclusion, our study revealed the significant antiepileptic and neuroprotective effects of a KD on pilocarpine-induced epilepsy in rats, primarily mediated through the modulation of the gut microbiota. However, whether the gut microbiota mediates the antiseizure effects of a KD still needs to be better elucidated.

Associations between multiple sleep dimensions and suicide and non-suicidal self-injury: a cross-sectional study of 3828 Chinese young people.

PURPOSE: Suicide and non-suicidal self-injury (NSSI) are preventable concerns in young people. Suicidal ideation (SI), suicidal plans (SP) and suicidal attempt (SA) are closely related to death. Sleep problems are known risk factors for suicide and NSSI. This study aimed to explore the relationship between sleep, suicidality and NSSI. METHODS: Participants were 3,828 middle school and college students aged 11-23 years from urban and rural areas of Henan Province. Sleep, suicidal phenomena and NSSI were assessed by applying self-reported questionnaires. Chi-squared tests were utilized to demonstrate the demographic data and sleep variables. The correlation between sleep, suicidality and NSSI were explored by using binary logistic regression, while adjusting socio-demographic characteristics with multivariate models. RESULTS: Sleep variables except mid-sleep time were related to suicidal phenomena (P < 0.05). Greater social jet lag (SJL) [≥ 2 h (h)] was associated with increased risk of SI [Odds ratios (OR) = 1.72, 95% confidence intervals (CI):1.40-2.11], SP (OR = 2.10, 95%CI:1.59-2.79) and SA (OR = 1.50, 95%CI:1.00-2.26). Non-only child participants with SJL (≥ 2 h) had significantly increased odds of SI (OR = 1.75, 95%CI: 1.41-2.18) and SP (OR = 2.25, 95%CI: 1.66-3.05). Eveningness chronotype had the strongest correlation with SI (OR = 3.87, 95%CI:2.78-5.38), SP (OR = 4.72, 95%CI:2.97-7.50), SA (OR = 6.69, 95%CI:3.08-14.52) and NSSI (OR = 1.39, 95%CI:1.02-1.90). CONCLUSION: Overlong or short sleep duration, SJL, eveningness chronotype and other sleep abnormalities (e.g., daytime dysfunction, low sleep efficiency) were associated with a higher prevalence of SI, SP and SA. Additionally, eveningness was significantly correlated with NSSI among young people. These findings suggested the importance of assessing and intervening in sleep habits to prevent suicide and NSSI in young people.

Factors affecting the incidence of pulmonary tuberculosis based on the GTWR model in China, 2004-2021.

Contra-posing panel data on the incidence of pulmonary tuberculosis (PTB) at the provincial level in China through the years of 2004-2021 and introducing a geographically and temporally weighted regression (GTWR) model were used to explore the effect of various factors on the incidence of PTB from the perspective of spatial heterogeneity. The principal component analysis (PCA) was used to extract the main information from twenty-two indexes under six macro-factors. The main influencing factors were determined by the Spearman correlation and multi-collinearity tests. After fitting different models, the GTWR model was used to analyse and obtain the distribution changes of regression coefficients. Six macro-factors and incidence of PTB were both correlated, and there was no collinearity between the variables. The fitting effect of the GTWR model was better than ordinary least-squares (OLS) and geographically weighted regression (GWR) models. The incidence of PTB in China was mainly affected by six macro-factors, namely medicine and health, transportation, environment, economy, disease, and educational quality. The influence degree showed an unbalanced trend in the spatial and temporal distribution.

Sleep-Body Composition Relationship: Roles of Sleep Behaviors in General and Abdominal Obesity in Chinese Adolescents Aged 17-22 Years.

This study aimed to investigate the association between sleep behaviors and body composition, which was measured by bioelectrical impedance analysis (BIA) among Chinese adolescents. Overall, 444 students (65.3% females, 19.12 ± 1.177 years) completed questionnaires describing sleep characteristics. Sleep characteristics were derived from subjective means. Body composition was obtained from BIA by InBody 720 (Biospace Co. Ltd., Seoul, Republic of Korea). Regression models tested relationships between sleep and body composition after adjustment for covariates. Students with weekday nap duration (>30 min/d) exerted higher waist-height ratio (WHtR) (B = 0.013, FDR-corrected p = 0.080). Average sleep duration (≤7 h/d) was linked to more WHtR (B = 0.016, FDR-corrected p = 0.080). People with high social jetlag showed gained visceral fat area (B = 7.475), WHtR (B = 0.015), waist to hip ratio (B = 0.012), fat mass index (B = 0.663) and body fat percentage (B = 1.703) (all FDR-corrected p < 0.1). Individuals with screen time before sleep (>0.5 h) exhibited higher visceral fat area (B = 7.934, FDR-corrected p = 0.064), WHtR (B = 0.017, FDR-corrected p = 0.080), waist to hip ratio (B = 0.016, FDR-corrected p = 0.090), fat mass index (B = 0.902, FDR-corrected p = 0.069) and body fat percentage (B = 2.892, FDR-corrected p = 0.018). We found poor sleep characteristics were closely related to general and abdominal obesity.

Unhealthy lifestyles and clusters status among 3637 adolescents aged 11-23 years: a school-based cross-sectional study in China.

BACKGROUND: Unhealthy lifestyles are risk factors for non-communicable diseases (NCDs) and tend to be clustered, with a trajectory that extends from adolescence to adulthood. This study investigated the association of diets, tobacco, alcohol, physical activity (PA), screen time (ST) and sleep duration (SD) in a total of six lifestyles, separately and as cumulative lifestyle scores, with sociodemographic characteristics among school-aged adolescents in the Chinese city of Zhengzhou. METHODS: In the aggregate, 3,637 adolescents aged 11-23 years were included in the study. The questionnaire collected data on socio-demographic characteristics and lifestyles. Healthy and unhealthy lifestyles were identified and scored, depending on the individual score (0 and 1 for healthy and unhealthy lifestyles respectively), with a total score between 0 and 6. Based on the sum of the dichotomous scores, the number of unhealthy lifestyles was calculated and divided into three clusters (0-1, 2-3, 4-6). Chi-square test was used to analyze the group difference of lifestyles and demographic characteristics, and multivariate logistic regression was used to explore the associations between demographic characteristics and the clustering status of unhealthy lifestyles. RESULTS: Among all participants, the prevalence of unhealthy lifestyles was: 86.4% for diet, 14.5% for alcohol, 6.0% for tobacco, 72.2% for PA, 42.3% for ST and 63.9% for SD. Students who were in university, female, lived in country (OR = 1.725, 95% CI: 1.241-2.398), had low number of close friends (1-2: OR = 2.110, 95% CI: 1.428-3.117; 3-5: OR = 1.601, 95% CI: 1.168-2.195), and had moderate family income (OR = 1.771, 95% CI: 1.208-2.596) were more likely to develop unhealthy lifestyles. In total, unhealthy lifestyles remain highly prevalent among Chinese adolescents. CONCLUSION: In the future, the establishment of an effective public health policy may improve the lifestyle profile of adolescents. Based on the lifestyle characteristics of different populations reported in our findings, lifestyle optimization can be more efficiently integrated into the daily lives of adolescents. Moreover, it is essential to conduct well-designed prospective studies on adolescents.

Inhibition of inflammatory factor TNF-α by ferrostatin-1 in microglia regulates necroptosis of oligodendrocyte precursor cells.

OBJECTIVE: Inflammation of the surrounding environment is a major reason causing loss or injury of oligodendrocyte precursor cells (OPCs) in myelin-associated diseases. Lipopolysaccharide-activated microglia can release various inflammatory factors such as tumor necrosis factor-α (TNF-α). One of the ways of OPC death is necroptosis, which can be triggered by TNF-α, a death receptor ligand, by activating receptor-interacting protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL) signaling pathway. This study investigated whether inhibiting microglia ferroptosis can decrease TNF-α release to alleviate OPC necroptosis. METHODS: Lipopolysaccharide and Fer-1 stimulate BV2 cells. The expressions of GPX4 and TNF-α were detected by western blot and quantitative real-time PCR; malondialdehyde, glutathione, iron, and reactive oxygen species were measured by the assay kits. After lipopolysaccharide stimulation of BV2 cells, the supernatant was taken to culture OPC. The protein expression levels of RIPK1, p-RIPK1, RIPK3, p-RIPK3, MLKL, and p-MLKL were detected by western blot. RESULTS: Lipopolysaccharide administration could induce ferroptosis in microglia by decreasing ferroptosis marker GPX4, while ferroptosis inhibitor Fer-1 could significantly increase GPX4 level. Fer-1 prevented oxidative stress and iron concentration elevation and alleviated mitochondrial damage in lipopolysaccharide-induced BV2 cells. The results revealed that Fer-1 downregulated the release of lipopolysaccharide-induced TNF-α in microglia and attenuated OPC necroptosis by significantly decreasing the expression levels of RIPK1, p-RIPK1, MLKL, p-MLKL, RIPK3, and p-RIPK3. CONCLUSION: Fer-1 may be a potential agent for inhibiting inflammation and treating myelin-related diseases.

Corrigendum: Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis.

[This corrects the article DOI: 10.3389/fphar.2023.1145407.].

Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis.

Background: Ferroptosis is a new form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxides and membrane damages. Recent studies have identified an important role for cancer cell ferroptosis in antitumor therapy. On the other hand, polyphyllin I (PPI) has been reported to exert antitumor effects on some types of cancers. However, it remains unknown whether or not PPI regulates cancer cell ferroptosis. Methods: Two types of human gastric cancer cells (AGS and MKN-45) were used to establish tumor xenograft models in nude mice that were treated with polyphyllin I (PPI) to observe tumor growth, while cells also were cultured for in vitro studies. Ferroptosis, based on the intracellular ROS/lipid ROS production and accumulation of ferrous ions, was detected using a fluorescence microscope and flow cytometer, while the expression of NRF2/FTH1 was measured using Western blotting assays. Results: Here we found that PPI inhibited the gastric cancer growth in vivo and in vitro while increasing the intracellular reactive oxygen species (ROS)/lipid peroxides and ferrous ions in the gastric cancer cells. PPI also decreased the levels of nuclear factor erythroid 2-related factor 2 (NRF2) and ferritin heavy chain 1 (FTH1) in gastric cancer cells in vitro. Moreover, liproxstain-1, an inhibitor of cell ferroptosis, mostly reversed the cell ferroptosis and tumor growth arrest induced by PPI. Finally, the effects of PPI on cancer cell ferroptosis were diminished by the overexpression of NRF2. Conclusion: For the first time, our results have demonstrated that PPI exerts its antitumor activity on the gastric cancer by, at least partially, inducing cancer cell ferroptosis via regulating NRF2/FTH1 pathway. These findings may be implicated for clinical replacement therapy of the gastric cancer.

Endophilin A2 protects against renal fibrosis by targeting TGF-ß/Smad signaling.

Renal fibrosis underlies all forms of end-stage kidney disease. Endophilin A2 (EndoA2) plays a role in nephrotic syndrome; however, its effect on renal fibrosis remains unknown. Here, we demonstrate that EndoA2 protects against kidney interstitial fibrosis via the transforming growth factor-ß (TGF-ß)/Smad signaling pathway. Mouse kidneys with fibrosis or kidney biopsy specimens from patients with fibrotic nephropathy had lower levels of EndoA2 protein expression than that in kidneys without fibrosis. In vivo overexpression of EndoA2 with the endophilin A2 transgene (EndoA2Tg ) notably prevented renal fibrosis, decreased the protein expression of profibrotic molecules, suppressed tubular injury, and reduced apoptotic tubular cells in the obstructed kidney cortex of mice with unilateral ureteral obstruction (UUO). In vivo and in vitro overexpression of EndoA2 markedly inhibited UUO- or TGF-ß1-induced phosphorylation of Smad2/3 and tubular epithelial cells dedifferentiation. Furthermore, EndoA2 was co-immunoprecipitated with the type II TGF-ß receptor (TßRII), thus inhibiting the binding of the type I TGF-ß receptor (TßRI) to TßRII. These findings indicate that EndoA2 mitigates renal fibrosis, at least partially, via modulating the TGF-ß/Smad signaling. Targeting EndoA2 may be a new potential therapeutic strategy for treatment of renal fibrosis.

A randomized controlled trial to evaluate efficacy and safety of early conversion to a low-dose calcineurin inhibitor combined with sirolimus in renal transplant patients.

BACKGROUND: The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation. METHODS: Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients' vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/ cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded. CONCLUSION: The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017277.

Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathway.

BACKGROUND: Circular RNA (circRNA) is involved in the process of acute kidney injury (AKI), but only a few circRNAs have been reported. In the study, we investigated a new circRNA and its association with AKI. METHODS: An AKI model was established in Sprague-Dawley rats, followed by serum creatinine and urea nitrogen tests measured by a biochemical analyzer. The pathological changes and apoptosis in the renal tissue were detected by Hematoxylin and Eosin, and TUNEL staining. Then, circRNA expression in AKI was determined by quantitative real-time-PCR (qRT-PCR). NRK-52E cells were induced with hypoxia/reoxygenation (H/R) as in vitro models and the circ-Snrk level was tested by qRT-PCR. The effects of circ-Snrk in H/R-induced NRK-52E cells were assessed by flow cytometry, western blot, and enzyme-linked immunosorbent assay. Finally, RNA sequencing and western blot analysis were used to validate the mRNA profile and pathways involved in circ-Snrk knockdown in H/R-induced NRK-52E. RESULTS: A reliable AKI rat model and H/R cell model were established. qRT-PCR demonstrated that circ-Snrk level was upregulated in AKI left kidney tissue and NRK-52E cells with H/R treatment. Circ-Snrk knockdown inhibited apoptosis of NRK-52E cells and secretion of inflammatory factors (IL-6 and TNF-α). RNA sequencing showed that the mRNA profile changed after inhibition of circ-Snrk and differential expression of mRNA mainly enriched various signaling pathways, including MAPK signaling pathway. Furthermore, western blot indicated that circ-Snrk knockdown could inhibit the activation of p-JNK and p-38 transcription factors. CONCLUSIONS: Circ-Snrk is involved in AKI development and associated with the MAPK signaling pathway in AKI.

The Clinical Significance of sICAM-1 in Differentiating Benign Breast Lesions from Breast Cancer.

OBJECTIVE: Breast cancer is a common type of malignant tumour worldwide and the second leading cause of death in women. The present study aims to investigate the clinical significance of serum soluble intercellular adhesion molecule-1 (sICAM-1) in differentiating benign breast lesions from breast cancer. METHODS: Plasma samples were obtained from 200 breast cancer patients, 47 patients with benign breast lesions and 50 age- and sex-matched healthy individuals as controls. Plasma levels of sICAM-1 were measured in all the samples using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. The serum levels of carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) were detected by the UniCel® DxI 800 Immunoassay System with matched kits. RESULTS: The plasma levels of CEA and CA15-3 were 1.22±0.2 (ng/mL) and 6.39±1.5 (ng/mL) in the healthy control group, 1.40±0.3 (ng/mL) and 5.81±2.1 (ng/mL) in the benign breast lesion (BBL) group, and 5.29±0.6 (ng/mL) and 27.08±5.7 (ng/ mL) in the breast cancer (BC) group. Plasma levels of CEA and CA15-3 in the BC group were significantly higher than those in the BBL and healthy control groups (all P<0.05), but the plasma levels of CEA and CA15-3 were not significantly different between the BBL group and the healthy control group, P=0.548 and P=0.2976, respectively. The diagnostic sensitivity and specificity were 13.4% and 98.0% for CEA and 22.2% and 100.0% for CA15-3. For plasma sICAM-1, the diagnostic sensitivity and specificity were 98% and 94% at a cut-off value of 20.0 (ng/mL), with an area under the receiver operating characteristic (ROC) curve of 0.99, which could be used to distinguish between healthy controls and the BC group; the diagnostic sensitivity and specificity were 95.5% and 94.0% at a cut-off value of 20.0 (ng/mL) with an area under the ROC curve of 0.98, which could be used to distinguish between healthy controls and the BBL group; and the diagnostic sensitivity and specificity were 44.6% and 94.1% at a cut-off value of 40.0 (ng/mL), with an area under ROC curve of 0.68, which could be used to distinguish between the BBL group and the BC group. The plasma levels of sICAM-1 were 15.43±2.3 (ng/mL) in healthy controls, 29.8±3.5 (ng/ mL) in the BBL group, and 50.07±12.2 (ng/mL) in the BC group. The plasma level of sICAM-1 in the BC group was the highest among all three groups (all P<0.05). CONCLUSIONS: The CEA, CA15-3 and sICAM-1 levels were increased in breast cancer patients, especially in those with node and/or organ metastasis. After diagnosis, CEA, CA15-3 and sICAM-1 levels are closely related to tumour metastasis. sICAM-1 has great potential value in the clinical diagnosis of benign breast lesions and breast cancer.

METTL3 contributes to renal ischemia-reperfusion injury by regulating Foxd1 methylation.

To investigate the mechanism of renal ischemia-reperfusion injury (IRI) via regulation of N6-methyl-adenosine (m6A) and relevant genes, IRI was induced in Sprague-Dawley rats, and urine and serum creatinine levels and tissue structure changes were observed. m6A and methyltransferase-like 3 (METTL3) protein levels were assessed via dot-blot and Western blot analyses, respectively. The hypoxia/reoxygenation (H/R) cell model was constructed using NRK-52E cells, and METTL3 protein levels were assessed. METTL3 was inhibited to observe its impact on NRK-52E cell apoptosis and m6A expression in H/R processes. Methylated RNA immunoprecipitation (MeRIP) sequencing was conducted followed by MeRIP-quantitative RT-PCR and quantitative RT-PCR validation. Our results indicated that urine and serum creatinine levels increased and that renal injury and cell apoptosis were both observed in the IRI model. In additon, m6A expression increased in the IRI model, and METTL3 protein levels significantly increased in the IRI and H/R models. When METTL3 was inhibited, m6A levels were accordingly decreased and cell apoptosis was suppressed in the H/R in vitro model. Based on MeRIP sequencing, transcription factor activating enhancer binding protein 2α (tfap2a), cytochrome P-450 1B1 (cyp1b1), and forkhead box D1 (foxd1) were significantly differentially expressed, as was m6A, which is involved in the negative regulation of cell proliferation and kidney development. We confirmed that foxd1 mRNA and its methylation levels contributed to IRI and H/R.

Novel Strategy for Organic Cocrystals of n-Type and p-Type Organic Semiconductors with Advanced Optoelectronic Properties.

Cocrystallization has been applied widely for material synthesis. Recently cocrystal of organic molecules has been developing rapidly, taking the advantages of the flexibility and self-assembly of organic molecules. Here we report an experimental study of a cocrystal of copper-phthalocyanines and fluorinated ones. We have grown the samples via the vapor-phase deposition of the mixture with different mass ratios from 1:13.5 to 6:1. As suggested by our scanning electron microscopy (SEM), X-ray diffraction (XRD), and Raman spectroscopy, new crystal structures and morphologies through our novel strategy for the cocrystallization of these molecules have been found. Our work will provide a solid foundation to systematically synthesize the cocrystal of phthalocyanine molecules with new crystal structures, thus providing the opportunity to advance material properties.

Clinical Significance of let-7a-5p and miR-21-5p in Patients with Breast Cancer.

OBJECTIVE: To investigate the clinical significance of serum let-7a-5p and miR-21-5p in the diagnosis of breast cancer. METHODS: We examined 32 healthy people and 30 patients with benign breast lesions as controls and 90 breast cancer patients as study subjects. The expression of let-7a-5p and miR-21-5p were detected in all subjects' samples, and Cel-miR-39-3p was used as a spike-in reference. Serum miRNAs were extracted by the TRIzol method, and reverse transcription was performed with specific primers for let-7a-5p, miR-21-5p and Cel-miR-39-3p, and 2-µL reverse transcription products were used as PCR templates. A SLAN-96P fluorescent quantitative PCR instrument was used for quantitative PCR detection. RESULTS: (1) The serum levels of carcinoembryonic antigen (CEA)and carbohydrate antigen 15-3 (CA15-3) in the breast cancer group were higher than those in the healthy controls and patients with benign breast lesions; (2) The expression level of let-7a-5p in the serum of the breast cancer group was lower than that in the healthy control group (P<0.05), but there was no significant difference compared to the breast benign lesion group (P>0.05); (3) The serum expression level of miR-21-5p in the breast cancer group was lower than that in the healthy control group (P<0.05) but was not significantly different from that in the patients with benign breast lesions (P>0.05). CONCLUSION: Reduced expression of Let-7a-5p and miR-21-5p levels is of little value for early diagnosis of breast cancer; however reduced expression of Let-7a-5p and miRNA-21-5p may serve as non-invasive biomarkers for the diagnosis of breast cancer metastasis, and combination of these markers with CEA and CA15-3 can help to distinguish benign breast lesions from breast cancer.

The Distribution Frequency of Interferon-Gamma Receptor 1 Gene Polymorphisms in Interferon-γ Release Assay-Positive Patients.

Tuberculosis is caused by mycobacterium, a potentially fatal infectious bacterium. In recent years, TB cases increased in the whole world. WHO statistics data shows that the world's annual tuberculosis incidence was 8~10 million with about 3 million deaths. Several studies have shown that susceptibility to tuberculosis may be associated with IFNGR1 gene polymorphisms. Here, we report the distribution frequency of IFNGR1 gene polymorphisms in 103 cases of IGA-negative patients and 100 cases of IGA-positive patients from China by sequencing the IFNGR1 proximal ~750 bp promoter region. We found a total of 5 types of site mutations: -611 (G/A), -56 (T/C), -255 (C/T), -359 (T/C), and -72 (C/T). The two main types of gene polymorphisms among the IGA-negative and IGA-positive groups were -611 (G/A), with mutation rates of 88.3% and 78.4%, respectively, and -56 (T/C), with mutation rates of 84.5% and 83.8%, respectively, which had no statistical significance, and there was no correlation with the incidence of tuberculosis.

The Chinese medicine, Jianpi Huayu Decoction, inhibits the epithelial mesenchymal transition via the regulation of the Smad3/Smad7 cascade.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors in the world. In China, traditional medicine is commonly used in the treatment of cancer. Among these medicines, Jianpi Huayu Decoction (JHD) is a typical clinical prescription against multiple tumors. However, the exact function and targets of JHD are currently unknown. The aim of this study is to assess the efficacy of JHD against HCC. METHODS AND RESULTS: Hepatic carcinoma SMMC7221 cells were treated with JHD drug-serum in a dose- and time-dependent manner. Real-time PCR (RT-PCR), western-blot (WB), and immunofluorescence microscopy revealed that JHD increased both the mRNA and protein levels of Smad7 and decreased the protein level of p-Smad3. It subsequently increased the E-cadherin expression level and decreased those of N-cadherin and Vimentin. Metastasis and invasion were eventually inhibited, as determined by the wound healing and transwell invasion assays. Treatment of Tanshinone IIA (Tan IIA) showed similar results as JHD, indicating that it is most likely the main functional drug monomer of JHD. The in vivo assay in nude mice also revealed the efficacy of JHD to inhibit epithelial mesenchymal transition (EMT). CONCLUSION: JHD was shown to be an effective therapeutic strategy against HCC.

Value of Combined Detection of Serum CEA, CA72-4, CA19-9, CA15-3 and CA12-5 in the Diagnosis of Gastric Cancer.

BACKGROUND: To examine whether the combined detection of serum tumor markers (CEA, CA72-4, CA19-9, CA15-3 and CA12-5) improves the sensitivity and accuracy in the diagnosis of gastric cancer (GC). MATERIALS AND METHODS: An automatic chemiluminescence immune analyzer with matched kits was used to determine the levels of serum CEA, CA72-4, CA19-9, CA15-3, and CA12-5 in 87 patients with gastric cancer (GC group), 60 patients with gastric benign diseases (GBD group) who were hospitalized during the same period, and 40 healthy subjects undergoing a physical examination. The values of these 5 tumor markers in the diagnosis of gastric cancer were analyzed. RESULTS: The levels of serum CEA, CA72-4, CA19-9, and CA12-5 were higher in the GC group than in the GBD group and healthy subjects, and these differences were significant (P<0.001). Although the level of CA15-3 was higher than those of benign lesion and healthy control groups, the difference was not statistically significant (P>0.05). The combined detection of CEA, CA72-4, CA19-9, and CA12-5 had a higher diagnostic value for gastric cancer than did single detection, and the positive detection rate of the combined detection of the four tumor markers was 60.9%. The diagnostic power when using the combined detection of CA72-4, CEA, CA19-9, and CA12-5 was the best. CONCLUSIONS: The combined detection of serum CA72-4, CEA, CA19-9 and CA12-5 increases the sensitivity and accuracy in the diagnosis of GC and can thus be considered an important tool for early diagnosis.

Identification of Methicillin-Resistant Staphylococcus aureus (MRSA) Using Simultaneous Detection of mecA, nuc, and femB by Loop-Mediated Isothermal Amplification (LAMP).

The aim of this study was to develop a rapid detection assay to identify methicillin-resistant Staphylococcus aureus by simultaneous testing for the mecA, nuc, and femB genes using the loop-mediated isothermal amplification (LAMP) method. LAMP primers were designed using online bio-software ( http://primerexplorer.jp/e/ ), and amplification reactions were performed in an isothermal temperature bath. The products were then examined using 2% agarose gel electrophoresis. MecA, nuc, and femB were confirmed by triplex TaqMan real-time PCR. For better naked-eye inspection of the reaction result, hydroxy naphthol blue (HNB) was added to the amplification system. Within 60 min, LAMP successfully amplified the genes of interest under isothermal conditions at 63 °C. The results of 2% gel electrophoresis indicated that when the Mg2+ concentration in the reaction system was 6 µmol, the amplification of the mecA gene was relatively good, while the amplification of the nuc and femB genes was better at an Mg2+ concentration of 8 µmol. Obvious color differences were observed by adding 1 µL (3.75 mM) of HNB into 25 µL reaction system. The LAMP assay was applied to 128 isolates cases of methicillin-resistant Staphylococcus aureus, which were separated from the daily specimens and identified by Vitek microbial identification instruments. The results were identical for both LAMP and PCR. LAMP offers an alternative detection assay for mecA, nuc, and femB and is faster than other methods.