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Background: Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction. Methods: Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin–eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD4+ and CD8+ proteins in the thymus and spleen tissues. Results: The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD4+ content, decreased CD8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood. Conclusions: LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions. [ABSTRACT FROM AUTHOR]

A new disaccharide glycoside, franchoside A (1), and 17 known compounds were isolated from the tubers of Arisaema franchetianum Engler. The chemical structure of the previously undescribed compound 1 was elucidated on the basis of detailed spectroscopic analyses. Compounds 1, 2, 6, 10, 14 and 18 showed significant cytotoxic activities at varying IC50 values in the range of 4.0–10.6 μM against five cancer cell lines. Compounds 8, 10, 13 and 17 (10 μM) exhibited moderate anti-inflammatory activities by inhibiting the NF-κB signaling pathway and the release of NO from RAW264.7 macrophages induced by lipopolysaccharide (LPS), while compounds 1, 9, 14, 15 and 16 showed weak anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder that is common in women of reproductive age. The clinical features of PCOS include hyperandrogenemia and polycystic ovarian changes. Bailing capsule (BL), a proprietary Chinese medicine that contains fermented Cordyceps sinensis powder, has been applied to treat PCOS. However, the specific active ingredients of BL and its mechanisms of action are yet to be elucidated. Methods: Initially, the effectiveness of BL on PCOS model mice was evaluated. Subsequently, the active ingredients of BL were searched in the TCMSP and TCM Systems Pharmacology databases, and their targets were predicted using Swiss Target Prediction and SEA databases. Furthermore, the GEO gene database was used to screen for differentially expressed genes (DEGs) related to PCOS. Data from Gene Card, OMIM, DDT, and Drugbank databases were then combined to establish a PCOS disease gene library. Cross targets were imported into the STRING database to construct a protein–protein interaction network. In addition, GO and KEGG pathway enrichment analyses were performed using Metascape and DAVID databases and visualized using Cytoscape software and R 4.2.3. The core targets were docked with SYBYL-X software, and their expressions in PCOS mice were further verified using qPCR. Results: The core active ingredients of BL were identified to be linoleyl acetate, cholesteryl palmitate, arachidonic acid, among others. Microarray data sets from four groups containing disease and normal samples were obtained from the GEO database. A total of 491 DEGs and 106 drug–disease cross genes were selected. Estrous cycle and ovarian lesions were found to be improved in PCOS model mice following BL treatment. While the levels of testosterone, progesterone, and prolactin decreased, that of estradiol increased. qPCR findings indicated that the expressions of JAK2, PPARG, PI3K, and AKT1 were upregulated, whereas those of ESR1 and IRS1 were downregulated in PCOS model mice. After the administration of BL, the expressions of associated genes were regulated. This study demonstrated that BL exerted anti-PCOS effects via PIK3CA, ESR1, AKT, PPARG, and IRS1 targets affecting PI3K-Akt signaling pathways. Discussion: This research clarified the multicomponent, multitarget, and multichannel action of BL and provided a theoretical reference for further investigations on its pharmacological basis and molecular mechanisms against PCOS. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the roles of duration and burden of atrial high‐rate episode (AHRE) on ischemic stroke in patients with pacemaker implantation. Methods: Patients with pacemaker implantation for bradycardia from 2013 to 2017 were consecutively enrolled. Data such as gender, age, combined diseases, type of AF, left atrial size, left ventricular size, left ventricular ejection fraction, CHA2DS2‐VASc score, and anticoagulants were collected. The burden and duration of AHRE based on different interval partition were also recorded in detail to evaluate the impacts on ischemic stroke. Cox regression analysis with time‐dependent covariates was conducted. Results: A total of 220 patients with AHRE were enrolled. The average follow‐up time was 48.42 ± 17.20 months. Univariate regression analysis showed that diabetes (p =.024), high CHA2DS2‐VASc score (≥ 2) (p =.021), long mean AHRE burden (p =.011), long maximal AHRE burden (p =.015), long AHRE duration lasting≥48 h (p =.001) or 24 h (p =.001) or 12 h (p =.005) were prone to ischemic stroke. Further multivariate regression analysis showed that long duration of AHRE (≥48 h) (HR 10.77; 95% CI 3.22–55.12; p =.030) were significantly correlated with stroke in patients with paroxysmal AF. There was no significant correlation between the type of AF and stroke (p =.927). Conclusion: The longer duration of AHRE (≥48 h) was more favorable in predicting ischemic stroke than high CHA2DS2‐VASc score (≥2). [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer (LC) is the leading cause of cancer deaths. While the current immunotherapies are beneficial to patients, the effects are minimal and heterogeneous, which calls for improvements in patient selection and treatment effectiveness. We discovered taxifolin to inhibit LC. The inhibition was associated with alterations of gene expressions. Among those genes affected, a panel of 12 genes, which we named TxflSig (taxifolin signature), and its subpanel of 7 genes (TxflSig1) effectively predicted responses of lung cancer patients to immunotherapy; TxflSig and TxflSig1 are valuable biomarkers for patient selection. Among both TxflSig and TxflSig1 multigene panels are ITGAL, ITGAX, and TMEM119 genes. These three genes were robustly associated with immunosuppressive activities, and their expressions were inhibited by taxifolin. Collectively, this research contributes to improvement in the management of lung cancer patients via patient selection and suggests that taxifolin could be a promising addition to immunotherapy in treating LC patients. Using an LL2 cell-based syngeneic mouse LC model, taxifolin suppressed allografts along with the appearance of 578 differentially expressed genes (DEGs). These DEGs were associated with enhancement of processes related to the extracellular matrix and lymphocyte chemotaxis as well as the reduction in pathways relevant to cell proliferation. From these DEGs, we formulated 12-gene (TxflSig) and 7-gene (TxflSig1) panels; both predicted response to ICB (immune checkpoint blockade) therapy more effectively in non-small-cell lung cancer (NSCLC) than numerous well-established ICB biomarkers, including PD-L1. In both panels, the mouse counterparts of ITGAL, ITGAX, and TMEM119 genes were downregulated by taxifolin. They were strongly associated with immune suppression in LC, evidenced by their robust correlations with the major immunosuppressive cell types (MDSC, Treg, and macrophage) and multiple immune checkpoints in NSCLC and across multiple human cancer types. ITGAL, ITGAX, and IIT (ITGAL-ITGAX-TMEM119) effectively predicted NSCLC's response to ICB therapy; IIT stratified the mortality risk of NSCLC. The stromal expressions of ITGAL and ITGAX, together with tumor expression of TMEM119 in NSCLC, were demonstrated. Collectively, we report multiple novel ICB biomarkers—TxflSig, TxflSig1, IIT, ITGAL, and ITGAX—and taxifolin-derived attenuation of immunosuppressive activities in NSCLC, suggesting the inclusion of taxifolin in ICB therapies for NSCLC. [ABSTRACT FROM AUTHOR]

Objective: To identify the predictors of pacing‐induced cardiomyopathy (PICM) and illustrate the safety and feasibility of conduction system pacing (CSP) upgrade on patients with long‐term persistent atrial fibrillation (AF). Methods: All patients with long‐term persistent AF and normal left ventricular ejection fraction (LVEF) ≥50% were consecutively enrolled from January 2008 to December 2017, and all the patients with atrioventricular block (AVB) and high right ventricular pacing (RVP) percentage of at least 40%. The predictors of PICM were identified, and patients with PICM were followed up for at least 1 year regardless of CSP upgrade. Cardiac performances and lead outcomes were investigated in all patients before and after CSP upgrade. Results: The present study included 139 patients, out of which 37 (26.62%) developed PICM, resulting in a significant decrease in the left ventricular ejection fraction (LVEF) from 56.11 ± 2.56% to 38.10 ± 5.81% (p<.01). The median duration for the development of PICM was 5.43 years. Lower LVEF (≤52.50%), longer paced QRS duration (≥175 ms), and higher RVP percentage (≥96.80%) were identified as independent predictors of PICM. Furthermore, the morbidity of PICM progressively increased with an increased number of predictors. The paced QRS duration (183.90 ± 22.34 ms vs. 136.57 ± 20.71 ms, p <.01), LVEF (39.35 ± 2.71% vs. 47.50 ± 7.43%, p <.01), and left ventricular end‐diastolic diameter (LVEDD) (55.53 ± 5.67 mm vs. 53.20 ± 5.78 mm, p =.03) improved significantly on patients accepting CSP upgrade. CSP responses and complete reverse remodeling (LVEF ≥50% and LVEDD < 50 mm) were detected in 80.95% (17/21) and 42.9% (9/21) of patients. The pacing threshold (1.52 ± 0.78 V/0.4 ms vs. 1.27 ± 0.59 V/0.4 ms, p =.16) was stable after follow‐up. Conclusion: PICM is very common in patients with long‐term persistent AF, and CSP upgrade was favorable for better cardiac performance in this patient population. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the leading cause of cancer deaths in women. The current management of patients with breast cancer needs improvement in two aspects: risk estimation, which forms the basis for treatment, and effective therapies. In our research, we discovered taxifolin to inhibit breast cancer via increasing the expression of 36 genes. These genes, as a group, effectively predict the death probability in patients with breast cancer. Importantly, aggressive breast cancers are frequently associated with increases in the 1q21.3 DNA region, which is home to the HNRN, KPRP, CRCT1, and FLG2 genes. These four genes can inhibit breast cancer, and their expressions are induced by taxifolin, revealing a novel mechanism by which taxifolin suppresses breast cancer. This study thus advances our ability in relation to the risk estimation and treatment of breast cancer. Through using taxifolin as a nutritional supplement, our research reveals an intriguing application of taxifolin in the clinical management of patients with breast cancer. Taxifolin inhibits breast cancer (BC) via novel mechanisms. In a syngeneic mouse BC model, taxifolin suppressed 4T-1 cell-derived allografts. RNA-seq of 4T-1 tumors identified 36 differentially expressed genes (DEGs) upregulated by taxifolin. Among their human homologues, 19, 7, and 2 genes were downregulated in BCs, high-proliferative BCs, and BCs with high-fatality risks, respectively. Three genes were established as tumor suppressors and eight were novel to BC, including HNRN, KPRP, CRCT1, and FLG2. These four genes exhibit tumor suppressive actions and reside in 1q21.3, a locus amplified in 70% recurrent BCs, revealing a unique vulnerability of primary and recurrent BCs with 1q21.3 amplification with respect to taxifolin. Furthermore, the 36 DEGs formed a multiple gene panel (DEG36) that effectively stratified the fatality risk in luminal, HER2+, and triple-negative (TN) equivalent BCs in two large cohorts: the METABRIC and TCGA datasets. 4T-1 cells model human TNBC cells. The DEG36 most robustly predicted the poor prognosis of TNBCs and associated it with the infiltration of CD8+ T, NK, macrophages, and Th2 cells. Of note, taxifolin increased the CD8+ T cell content in 4T-1 tumors. The DEG36 is a novel and effective prognostic biomarker of BCs, particularly TNBCs, and can be used to assess the BC-associated immunosuppressive microenvironment. [ABSTRACT FROM AUTHOR]

Aim. Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods. Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results. DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion. DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats. [ABSTRACT FROM AUTHOR]

Background: The role of beta-blockers in acute myocardial infarction patients without heart failure and with preserved left ventricular ejection fraction (LVEF ≥ 50%) is unknown. Our study aimed to retrospectively analyze the associations of beta-blockers on such patients.Methods: This is a multicenter, retrospective study. After screening 5,332 acute myocardial infarction patients, a total of 2519 patients without heart failure and with LVEF ≥ 50% were included. The patients were divided into two groups: the prescribed (n = 2049) and unprescribed (n = 470) beta-blockers group. The propensity score inverse probability treatment weighting was used to control confounding factors. We analyzed the associations between beta-blockers and outcomes in the short-term (1-year) and long-term (median, 3.61 years).Results: The primary outcome was all-cause mortality. The secondary outcomes were all-cause rehospitalization, cardiac death, recurrent myocardial infarction, new-onset heart failure rehospitalization. This study shows no statistically significant association between discharged with beta-blockers and all-cause mortality, either in the short-term [IPTW Adjusted, HR 1.02; 95%CI 0.43-2.40; P = 0.966] or long-term [IPTW Adjusted, HR 1.17; 95%CI 0.70-1.94; P = 0.547]. Discharged with beta-blockers was significantly associated with a reduced risk of short-term recurrent myocardial infarction [IPTW Adjusted, HR 0.44; 95%CI 0.20-0.97; P = 0.043], but there was no long-term relationship [IPTW Adjusted, HR 1.11; 95%CI 0.61-2.03; P = 0.735]. Other outcomes, such as new-onset heart failure rehospitalization and all-cause rehospitalization, were not observed with meaningful differences in either the short- or long-term. The results of sensitivity analysis were consistent with this.Conclusions: Beta-blockers might be associated with a reduced risk of recurrent myocardial infarction in patients without heart failure and with preserved left ventricular ejection fraction after acute myocardial infarction, in the short term. Beta-blockers might not be related to all-cause mortality in those patients, either in the short-term or long-term. Clinical trial registration Influence of Beta-blockers on Prognosis in Patients with Acute Myocardial Infarction Complicated with Normal Ejection Fraction, NCT04485988, Registered on 24/07/2020. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: The etiology of Rasmussen's encephalitis (RE), a rare chronic neurological disorder characterized by CD8+ T cell infiltration and unihemispheric brain atrophy, is still unknown. Various human herpes viruses (HHVs) have been detected in RE brain, but their contribution to RE pathogenesis is unclear.Methods: HHVs infection and relevant immune response were compared among brain tissues from RE, temporal lobe epilepsy (TLE) and traumatic brain injury (TBI) patients. Viral antigen or genome, CD8+ T cells, microglia and innate immunity molecules were analyzed by immunohistochemical staining, DNA dot blot assay or immunofluorescence double staining. Cytokines were measured by multiplex flow cytometry. Cell apoptosis was visualized by TUNEL staining. Viral infection, immune response and the severity of unihemispheric atrophy were subjected to correlation analysis.Results: Antigens of various HHVs were prevalent in RE and TLE brains, and the cumulative viral score of HHVs positively correlated with the unihemispheric atrophy in RE patients. CD8+ T cells infiltration were observed in both RE and TLE brains and showed co-localization with HHV antigens, but their activation, as revealed by Granzyme B (GZMB) release and apoptosis, was found only in RE. In comparison to TLE, RE brain tissues contained higher level of inflammatory cytokines, but the interferon-β level, which was negatively correlated with cumulative viral score, was relatively lower. In line with this, the DNA sensor STING and IFI16, rather than other innate immunity signaling molecules, were insufficiently activated in RE.Conclusions: Compared with TBI, both RE and TLE had prevalently HHV infection and immune response in brain tissues. However, in comparison to TLE, RE showed insufficient activation of antiviral innate immunity but overactivation of cytotoxic T cells. Our results show the relatively lower level of antiviral innate immunity and overactivation of cytotoxic T cells in RE cases upon HHV infection, the overactivated T cells might be a compensate to the innate immunity but the causative evidence is lack in our study and need more investigation in the future. [ABSTRACT FROM AUTHOR]

Profound physiological changes during pregnancy may affect the requirement of retinol and tocopherol, which are essential micronutrients for the maintenance of maternal health and foetal development. However, the current reference intervals (RIs) of retinol and tocopherol are based on non‐pregnant population. In the present study, a liquid chromatography–tandem mass spectrometry quantitation method for serum retinol and α‐tocopherol was established and validated. In addition, we established trimester‐specific RIs of retinol and α‐tocopherol using the data from paired screening test for 31,301 outpatients who participated in the prenatal vitamins A/E evaluation program at our hospital using the Hoffmann method, which is a simple indirect RI estimation method that does not require the recruitment of healthy subjects. Further, to explore the associations between the levels of retinol and α‐tocopherol and the parameters of complete blood count (CBC), the results of retinol, α‐tocopherol, and CBC of 1,977 pregnant outpatients in the third trimester were analysed. The testing interval between the levels of vitamins and CBC was no more than 7 days. Although no significant changes were noticed in the levels of retinol, the α‐tocopherol levels continuously increased with normal physiological changes throughout pregnancy. Lower retinol levels were associated with the higher incidence of anaemia, whereas higher levels of retinol and lower levels of α‐tocopherol were associated with higher platelet count. [ABSTRACT FROM AUTHOR]

Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown.Methods: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records.Results: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death.Conclusion: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19.Trial Registration: ClinicalTrials, NCT04292964. Registered 03 March 2020. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the latest prevalence of abdominal obesity in China based on nationally representative data.Methods: A stratified, multistage, random sampling method was used to obtain a nationally representative sample of residents aged ≥ 18 years from 31 provinces in mainland China from October 2012 to December 2015. Abdominal obesity was defined as a waist circumference ≥ 90 cm for men and a waist circumference ≥ 85 cm for women.Results: The data of 441,306 participants were analyzed. The prevalence of abdominal obesity was 29.1% (28.6% in men and 29.6% in women); the number of adults with abdominal obesity was estimated to be 277.8 million (approximately 140.1 million in men and 137.7 million in women). The prevalence of abdominal obesity varied considerably among provinces. In general, the prevalence of abdominal obesity was higher in the northern, lower in the southern, higher in the western, and lower in the eastern areas of China. Besides the regional disparities, the prevalence of abdominal obesity varied greatly among different population subgroups.Conclusions: Abdominal obesity is highly prevalent among Chinese adults. National and provincial obesity control and prevention strategies should be public health priorities in China. To better control obesity, the underlying reasons for the regional disparities need to be addressed. [ABSTRACT FROM AUTHOR]

Background: We attempted to determine whether the inflammatory pathway HMGB1-TLR4 and the downstream pro-inflammatory cytokines is upregulated in focal cortical dysplasia (FCD) type II and whether there is a correlation between the TLR4 upregulation and disease duration or frequency of epileptic seizures.Methods: FCD type II and peri-FCD paired tissues resected from eight children with refractory epilepsy were collected. Through real-time qPCR, Western blot, and co-immunoprecipitation, we examined the differences between FCD lesions and peri-FCD tissues with respect to mRNA expression, protein expression, and protein interaction in HMGB1-TLR4 pathway biomarker and downstream pro-inflammatory factors in whole brain tissue. Then, we used immunofluorescence to examine the difference between FCD lesions and peri-FCD tissues with respect to protein expression and intracellular distribution of HMGB1-TLR4 pathway biomarker in neurons, astrocytes, and oligodendrocytes. Correlation between level of TLR4 expression and disease duration or frequency of epileptic seizures in patients was also analyzed.Results: The protein expression levels of TLR4, cytoplasm HMGB1, TLR4/MyD88 complex, ubiquitination of TRAF6, p-IKK, p-IκB-α, p-NF-κB p65, and IL-1β and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls. Total mRNA expression levels of TLR4, IL-1β, and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls, but HMGB1 had no significant change. In neurons and astrocytes inside the lesions, the expression of TLR4 protein was significantly higher than that in peri-FCD tissues, and HMGB1 was mainly expressed in the cytoplasm, while expressed in the nuclei in peri-FCD tissues. But in oligodendrocytes, there was no upregulation of HMGB1-TLR4 pathway in both lesions and peri-FCD tissues. We did not identify the correlation between the level of TLR4 activation and disease duration or frequency of epileptic seizures.Conclusion: The HMGB1-TLR4 pathway was upregulated in the neurons and astrocytes inside FCD type II lesions, which led to an increase in the release of downstream pro-inflammatory cytokines. Correlation between the level of TLR4 activation and duration or frequency of epileptic seizures was not identified. [ABSTRACT FROM AUTHOR]

Background. After initial treatment of breast cancer (BC), monitoring locoregional recurrence and distant metastases is a great clinical challenge. Objective. To evaluate the efficacy of PET/CT in association with serum tumor makers in BC follow-up. Methods. Twenty-six women with a history of modified radical mastectomy were evaluated by 18F-FDG PET/CT. The results of PET/CT were compared with those of conventional imaging techniques (CITs) (including mammography, chest radiography, CT, MRI, ultrasound, and bone scintigraphy). Serum tumor markers of CEA, CA 125, and CA 15-3 in the BC patients were also analyzed in association with the results of PET/CT. Results. Compared with CITs, PET/CT was more sensitive to detect the malignant foci and had better patient-based sensitivity and specificity. The mean CA 15-3 serum level was significantly higher in the confirmed positive patients of PET/CT results than in the confirmed negative ones, while there were no significant differences in the serum levels of CEA and CA 125 of both groups. Conclusion. PET/CT is a highly efficient tool for BC follow-up compared with CITs. The high serum levels of CA 15-3 in confirmed positive PET/CT patients indicated the clinical value of CA 15-3 in BC follow-up. [ABSTRACT FROM AUTHOR]

Aim. To investigate the correlation of Fuzheng-Huayu tablet (FZHY) efficacy on chronic hepatitis B caused cirrhosis (HBC) and single nucleotide polymorphisms (SNPs) of CYP1A2. Methods. After 111 cases of HBC with 69 excess, 21 deficiency-excess, and 21 deficiency ZHENGs (ZHENG, also called traditional Chinese medicine syndrome) were treated by FZHY for 6 months, clinical symptoms, Child-Pugh score, and ZHENG score were observed. Three of the SNPs in CYP1A2 gene were detected and analyzed using SNaPshot assay. Results. In ZHENG efficacy between effective and invalid groups, there was significant difference (P < 0.001). The ZHENG deficiency was significantly correlated with FZHY efficacy (P < 0.05). AA genotype of CYP1A2-G2964A was significantly different with GG genotype (P < 0.05) between CYP1A2 Genotypes and FZHY efficacy on ZHENG. More importantly, GA plus AA genotype of CYP1A2-G2964A was significantly different with deficiency ZHENG (P < 0.05) between CYP1A2 genotypes and FZHY efficacy on ZHENG. Conclusion. FZHY improved ZHENG score of HBC, and these efficacies may relate to CYP1A2-G2964A sites. It was suggested that CYP1A2-G2964A locus is probably a risk factor for ZHENG-based FZHY efficacy in HBC. [ABSTRACT FROM AUTHOR]

Aim. To evaluate and predict the therapeutic efficacy of Fuzheng-Huayu tablet (FZHY) based traditional Chinese Medicine (TCM) syndrome differentiation or TCM symptoms on chronic hepatitis B caused cirrhosis (HBC). Methods. The trial was designed according to CONSORT statement. It was a multi-center, double-blind, randomized, placebo-controlled trail. Several clinical parameters, Child-Pugh classification and TCM symptoms were detected and evaluated. The FZHY efficacy was predicted by an established Bayes forecasting method following the Bayes classification model. Results. The levels of HA and TCM syndrome score in FZHY group were significantly decreased (P < 0.05) compared to placebo group, respectively. The efficacy of FZHY on TCM syndrome score in HBC patients with some TCM syndromes was better. In TCM syndrome score evaluation, there were 53 effective and 22 invalid in FZHY group. TCM symptoms predicted FZHY efficacy on HBC were close to Child-Pugh score prediction. Conclusion. FZHY decreases the levels of HA and TCM syndrome scores, improves the life quality of HBC patients. Moreover, there were different therapeutic efficacies among different TCM syndromes, indicating that accurate TCM syndrome differentiation might guide the better TCM treatment. Furthermore, the FZHY efficacy was able to predict by Bayes forecasting method through the alteration of TCM symptoms. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) causes memory changes, but the underlying mechanisms are poorly understood. Epigenetic mechanisms, including DNA methylation, can potentially cause synaptic changes in the brain. Oxytocin (OT) plays a central role in learning and memory, but little is known of the impact of OT on METH-associated memory changes. Here, we explored the role of OT in METH-induced epigenetic alterations that underlie spatial and cognitive memory changes. METH (2.0 mg/kg, i.p.) was administered to male C57BL/6 mice once every other day for 8 days. OT (2.5 μg, i.c.v.) or aCSF was given prior to METH. Spatial and cognitive memory were assessed. In Hip and PFC, synaptic structures and proteins were examined, levels of DNA methyltransferases (DNMTs) and methyl CpG binding protein 2 (MECP2) were determined, and the DNA methylation status at the Synaptophysin (Syn) promoter was assessed. METH enhanced spatial memory, decreased synapse length, downregulated DNMT1, DNMT3A, DNMT3B, and MECP2, and induced DNA hypomethylation at the Syn promoter in Hip. In contrast, METH reduced cognitive memory, increased synapse thickness, upregulated DNMT1, DNMT3A, and MECP2, and induced DNA hypermethylation at the Syn promoter in PFC. OT pretreatment specifically ameliorated METH-induced learning and memory alterations, normalized synapse structures, and regulated DNMTs and MECP2 to reverse the DNA methylation status changes at the Syn promoter in Hip and PFC. DNA methylation is an important gene regulatory mechanism underlying METH-induced learning and memory alterations. OT can potentially be used to specifically manipulate METH-related memory changes. [ABSTRACT FROM AUTHOR]

Background: To investigate the biological characteristics and capacity of tumorigenicity of bone marrow mesenchymal stem cells (BMSCs) in the cancer environment. Methods: Bone marrow mesenchymal stem cells from 45 cancer patients and 20 non-cancer adults were separated and identified. Their biological characteristics and tumorigenicity ability were compared. Results: Compared with BMSCs of non-cancer adults, BMSCs of hepatocellular carcinoma and leukemia patients presented a lower growth curve, longer first passage time, and fewer passaging generation numbers. However, both shared the same appearances and surface markers. Neither of these BMSCs formed tumor in vivo and in vitro. The sequences of exons 5-8 of the P53 gene, exons 19-21 of the Rb1 gene and, exons 1-2 of the P16 gene in BMSCs were all consistent with the wide types, without any mutations found. Conclusion: The biological characteristics of BMSCs from cancer patients changed in the cancer environment. The BMSCs of cancer patients are non-tumorigenic and safe for clinical transplantation within 15 generations. [ABSTRACT FROM AUTHOR]

Eight new sesquiterpenoids named melongenaterpenes M-T (1 – 8), together with nine known compounds (9 – 17), were isolated from the 70% ethanol extract of the sepals of Solanum melongena L. The structures of all isolated compounds were elucidated based on 1D and 2D NMR spectra and a comprehensive comparison of their spectroscopic and physical data with values from the published literatures. Meanwhile, the cytotoxicity of all the isolated compounds was evaluated on the three human cancer lines of Hela, Ishikawa and MGC-803 by CCK8 assay, respectively. Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract: Aim of the study: Boehmeria nivea (L.) Gaud. was commonly used to treat miscarriages clinically. The aim of this study was to examine its safety for embryonic development. Materials and methods: Pregnant mice were randomly assigned into 5 groups, i.e. mice were oral-treated with distilled water (G1), with Boehmeria nivea extract of 2, 8 or 32g/kg/day (G2, G3 or G4), and with 3 doses of vitamin A of 200,000IU/kg as positive controls (G5). Meanwhile, IC50 values for both embryonic stem cells (ESCs) and 3T3 cells were detected by cytotoxicity assays. Results: (1) The resorptions and malformed fetuses in G5 were significantly higher than G1 (P <0.001), whereas the maternal body-weight and uterus-weight were lower than G1 (P <0.05); (2) there was no difference in the fetal body-weight, maternal relative body-weight gain, liver-, kidney- or heart-weight, relative organ-weight, and histological examination among five groups; (3) there was no difference in IC50 values between ESCs and 3T3 cells, but high concentration of Boehmeria nivea extract might significantly lower ESCs’ viability (P <0.05). Conclusion: Boehmeria nivea extract at 32g/kg/day did not cause significant embryotoxicity or maternal toxicity in mice, although it might cause cytotoxicity in cultured ESCs at a high dose. [Copyright &y& Elsevier]