The neutrophil-to-lymphocyte ratio is associated with all-cause and cardiovascular mortality among individuals with hypertension.

BACKGROUND: Identifying reliable prognostic markers is crucial for the effective management of hypertension. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential inflammatory marker linked to cardiovascular outcomes. This study aims to investigate the association of NLR with all-cause and cardiovascular mortality among patients with hypertension. METHODS: This study analyzed data from 3067 hypertensive adults in the National Health and Nutritional Examination Surveys (NHANES) from 2009 to 2014. Mortality details were obtained from the National Death Index (NDI). Restricted cubic spline (RCS) was deployed to visualize the association of the NLR with mortality risk. Weighted Cox proportional hazards models were employed to assess the independent association of NLR with mortality risk. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to access the predictive ability of NLR for survival. Mediation analysis was used to explore the indirect impact of NLR on mortality mediated through eGFR. RESULTS: Over a median 92.0-months follow-up, 538 deaths occurred, including 114 cardiovascular deaths. RCS analysis revealed a positive association between NLR and both all-cause and cardiovascular mortality. Participants were stratified into higher (> 3.5) and lower (≤ 3.5) NLR groups. Weighted Cox proportional hazards models demonstrated that individuals with higher NLR had a significantly increased risk of all-cause (HR 1.96, 95% confidence interval (CI) 1.52-2.52, p < 0.0001) and cardiovascular mortality (HR 2.33, 95% CI 1.54-3.51, p < 0.0001). Stratified and interaction analysis confirmed the stability of the core results. Notably, eGFR partially mediated the association between NLR and both all-cause and cardiovascular mortality by a 5.4% and 4.7% proportion, respectively. Additionally, the areas under the curve (AUC) of the 3-, 5- and 10- year survival was 0.68, 0.65 and 0.64 for all-cause mortality and 0.68, 0.70 and 0.69 for cardiovascular mortality, respectively. CONCLUSION: Elevated NLR independently confers an increased risk for both all-cause and cardiovascular mortality in individuals with hypertension.

Drug-repurposing by virtual and experimental screening of PFKFB3 inhibitors for pancreatic cancer therapy.

Pancreatic cancer (PC) is the most frequently occurring cancer, with few effective treatments and a 5-year survival rate of only about 11%. It is characterized by stiff interstitium and pressure on blood vessels, leading to an increased glycolytic metabolism. PFKFB3 plays an important role in glycolysis, and its products (fructose-2,6-bisphosphate), which are allosteric PFK1 activators, limit the glycolytic rate. In this study, 14 PFKFB3 inhibitors were obtained by virtually screening the FDA-approved compound library. Subsequently, the in-vitro investigations confirmed that Lomitapide and Cabozantinib S-malate exhibit the excellent potential to inhibit PFKFB3. The combined administration of Lomitapide and Gemcitabine at a certain molar ratio indicated an enhanced anti-tumor effect in Orthotopic Pancreatic Cancer (OPC) models. This investigation provides a new treatment strategy for PC therapy.

In silico and in vitro analyses of a novel FoxO1 agonist reducing Aß levels via downregulation of BACE1.

AIMS: FoxO1 is an important target in the treatment of Alzheimer's disease (AD). However, FoxO1-specific agonists and their effects on AD have not yet been reported. This study aimed to identify small molecules that upregulate the activity of FoxO1 to attenuate the symptoms of AD. METHODS: FoxO1 agonists were identified by in silico screening and molecular dynamics simulation. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to assess protein and gene expression levels of P21, BIM, and PPARγ downstream of FoxO1 in SH-SY5Y cells, respectively. Western blotting and enzyme-linked immunoassays were performed to explore the effect of FoxO1 agonists on APP metabolism. RESULTS: N-(3-methylisothiazol-5-yl)-2-(2-oxobenzo[d]oxazol-3(2H)-yl) acetamide (compound D) had the highest affinity for FoxO1. Compound D activated FoxO1 and regulated the expression of its downstream target genes, P21, BIM, and PPARγ. In SH-SY5Y cells treated with compound D, BACE1 expression levels were downregulated, and the levels of Aß1-40 and Aß1-42 were also reduced. CONCLUSIONS: We present a novel small-molecule FoxO1 agonist with good anti-AD effects. This study highlights a promising strategy for new drug discovery for AD.

Effects of nutritional indices and inflammatory parameters on patients received immunotherapy for non-small cell lung cancer.

OBJECTIVE: This research explored the relationship between a patient's nutritional state and inflammatory markers and the prognosis of their non-small cell lung cancer (NSCLC) treatment while receiving a combination of chemotherapy and immunotherapy. METHOD: This retrospective and single-center analysis included NSCLC patients who received a combination of chemotherapy and immunotherapy at the Department of Oncology at Shanghai Lung Hospital. Patients were categorized based on malnutrition, sarcopenia, sarcopenic obesity, and advanced-lung-cancer-inflammation-index (ALI) scores after collecting nutritional and inflammatory indices. Kaplan-Meier and the Cox models were utilized to analyze survival. RESULTS: There was a significant correlation between malnutrition, sarcopenia, sarcopenic obesity, and low ALI scores with lower overall survival (OS) and progression-free survival (PFS) (p < 0.05). Low ALI score and malnutrition were independent factors influencing patient survival in terms of both OS and PFS (p < 0.01). CONCLUSION: The nutritional and inflammatory indices of immunotherapy-treated NSCLC patients substantially affect their prognosis. Assessing these variables could aid in optimizing treatment strategies and improving patient outcomes. Additional research is required to comprehend the intricate relationship between nutrition, inflammation, and cancer progression and to develop individualized therapies.

The global burden of type 2 diabetes attributable to high body mass index in 204 countries and territories, 1990-2019: An analysis of the Global Burden of Disease Study.

Background: High body mass index (BMI) plays a critical role in the initiation and development of type 2 diabetes (T2D). Up to now, far too little attention has been paid to the global burden of T2D attributable to high BMI. This study aims to report the deaths and disability-adjusted life years (DALYs) of T2D related to high BMI in 204 countries and territories from 1990 to 2019. Methods: Data on T2D burden attributable to high BMI were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The global cases, age-standardized rates of mortality (ASMR), and disability-adjusted life years (ASDR) attributable to high BMI were estimated by age, sex, geographical location, and socio-demographic index (SDI). The estimated annual percentage change (EAPC) was calculated to quantify the trends of ASMR and ASDR during the period 1990-2019. Results: Globally, there were 619,494.8 deaths and 34,422,224.8 DALYs of T2D attributed to high BMI in 2019, more than triple in 1990. Moreover, the pace of increase in ASMR and ASDR accelerated during 1990-2019, with EAPC of 1.36 (95% CI: 1.27 to 1.45) and 2.13 (95% CI: 2.10 to 2.17) separately, especially in men, South Asia, and low-middle SDI regions. Oceania was the high-risk area of standardized T2D deaths and DALYs attributable to high BMI in 2019, among which Fiji was the country with the heaviest burden. In terms of SDI, middle SDI regions had the biggest T2D-related ASMR and ASDR in 2019. Conclusion: The global deaths and DALYs of T2D attributable to high BMI substantially increased from 1990 to 2019. High BMI as a major public health problem needs to be tackled properly and timely in patients with T2D.

Serum potassium level, variability and in-hospital mortality in acute myocardial infarction.

OBJECTIVE: Clinical guidelines recommend an optimal serum potassium concentration between 4.0 and 5.0 mmol/L in patients with acute myocardial infarction (AMI), which was based on lower-quality evidence from more than 20 years ago. Therefore, it is essential to re-evaluate the range of optimal potassium levels in patients with AMI in intensive care unit (ICU). METHODS: This was a retrospective study based on Philips eICU Collaborative Research Database, which covered 9776 patients with AMI between 2014 and 2015. All patients had more than or equal to 2 serum potassium measurements and were categorized by the mean serum potassium level (<3.5, 3.5-4.5, 4.5-5.5, ≥5.5 mmol/L) and potassium variability (1st, 2nd, and ≥3rd standard deviation (SD)). Binary logistic regression was used to determine the association between mean potassium levels, variability and in-hospital mortality in AMI. RESULTS: Of all 9776 AMI patients in ICU, 8731 (89.3%) patients were included. A total of 69847 potassium measurements were performed in these patients. There was a J-shaped relationship between mean serum potassium level and in-hospital mortality. The lowest mortality (mortality rate, 7.2%; 95% CI, 6.57%-7.76%) was observed in patients with mean potassium level between 3.5 and 4.5 mmol/L and a low potassium variability within the 1st SD. Logistic regression showed that the risk of in-hospital mortality is highest when the mean potassium level ≥5.5 mmol/L (57.6%; 95% Cl, 45.02%-70.24%; multivariable adjusted OR, 14.8; 95% CI, 8.4-26.2) compared to the reference group of 3.5-4.5 mmol/L and potassium variability within the 3rd SD (16.5%; 95% Cl, 15.19%-17.88%; multivariable adjusted OR, 3.3; 95% CI, 2.7-4.1) compared to 1st SD. Several sensitivity analyses confirmed these results. CONCLUSION: Among AMI patients in ICU, the minimum risk of in-hospital mortality was observed in those with mean potassium levels between 3.5 and 4.5 mmol/L or a minimal potassium variability compared to those who had higher or lower values.

Role of deep-sea equipment in promoting the forefront of studies on life in extreme environments.

The deep-sea environment creates the largest ecosystem in the world with the largest biological community and extensive undiscovered biodiversity. Nevertheless, these ecosystems are far from well known. Deep-sea equipment is an indispensable approach to research life in extreme environments in the deep-sea environment because of the difficulty in obtaining access to these unique habitats. This work reviewed the historical development and the state-of-the-art of deep-sea equipment suitable for researching extreme ecosystems, to clarify the role of this equipment as a promoter for the progress of life in extreme environmental studies. Linkages of the developed deep-sea equipment and the discovered species are analyzed in this study. In addition, Equipment associated with researching the deep-sea ecosystems of hydrothermal vents, cold seeps, whale falls, seamounts, and oceanic trenches are introduced and analyzed in detail. To clarify the thrust and key points of the future promotion of life in extreme environmental studies, prospects and challenges related to observing equipment, samplers, laboratory simulation systems, and submersibles are proposed. Furthermore, a blueprint for the integration of in situ observations, sampling, controllable culture, manned experiments in underwater environments, and laboratory simulations is depicted for future studies.

Physalin B reduces Aß secretion through down-regulation of BACE1 expression by activating FoxO1 and inhibiting STAT3 phosphorylation.

Physalin B (PB), one of the major active steroidal constituents of Solanaceae Physalis plants, has a wide variety of biological activities. We found that PB significantly down-regulated ß-amyloid (Aß) secretion in N2a/APPsw cells. However, the underlying mechanisms are not well understood. In the current study, we investigated the changes in key enzymes involved in ß-amyloid precursor protein (APP) metabolism and other APP metabolites by treating N2a/APPsw cells with PB at different concentrations. The results indicated that PB reduced Aß secretion, which was caused by down-regulation of ß-secretase (BACE1) expression, as indicated at both the protein and mRNA levels. Further research revealed that PB regulated BACE1 expression by inducing the activation of forkhead box O1 (FoxO1) and inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). In addition, the effect of PB on BACE1 expression and Aß secretion was reversed by treatment with FoxO1 siRNA and STAT3 antagonist S3I-201. In conclusion, these data demonstrated that PB can effectively down-regulate the expression of BACE1 to reduce Aßsecretion by activating the expression of FoxO1 and inhibiting the phosphorylation of STAT3.

Relationship between periodontitis and microangiopathy in type 2 diabetes mellitus: a meta-analysis.

OBJECTIVE: Whether periodontitis increases the risk of diabetic microangiopathy remains controversial. The present meta-analysis aims to investigate the relationship between periodontitis and diabetic microangiopathy in patients with type 2 diabetes mellitus. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library, CNKI, and WanFang data were searched without language restrictions. The methodological quality of the studies included was assessed using Newcastle-Ottawa Scale method, and meta-analysis was performed by Review Manager 5.3. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the risk of periodontitis for diabetic microangiopathy among patients with type 2 diabetes. RESULTS: Thirteen cross-sectional studies, covering 10 570 participants, were included in the present meta-analysis. The results demonstrated that periodontitis was associated with increased risk of type 2 diabetic microangiopathy (OR: 2.43, 95% CI: 1.65-3.56), diabetic retinopathy (OR: 4.33, 95% CI: 2.19-8.55), and diabetic nephropathy (OR: 1.75, 95% CI: 1.07-2.85), while periodontitis was not associated with diabetic neuropathy (OR: 0.99, 95% CI: 0.19-5.12). Subgroup analysis among the studies in Asian (OR: 3.06, 95% CI: 1.94-4.84) and North American (OR: 1.42, 95% CI: 1.08-1.86) populations confirmed the existed association between periodontitis and type 2 diabetic microangiopathy. The relationship still existed in groups with sample size larger than 500 (OR: 1.77, 95% CI: 1.34-2.34) and smaller than 500 (OR: 3.33, 95% CI: 1.38-8.03). A sensitivity analysis confirmed the stability of the results by excluding moderate quality studies or removing articles one after the other. CONCLUSION: Current evidences have proved that periodontitis is associated with increased risk of diabetic microangiopathy in patients with type 2 diabetes mellitus. This conclusion may provide useful evidence for correlated clinical researches. PROSPERO registration number CRD42021247773.

Alkaloid derivative ION-31a inhibits breast cancer metastasis and angiogenesis by targeting HSP90α.

Breast cancer has become the number one killer of women. In our previous study, an active compound, ION-31a, with potential anti-metastasis activity against breast cancer was identified through the synthesis of ionone alkaloid derivatives. In the present study, we aimed to identify the therapeutic target of ION-31a. We used a fluorescence tag labeled probe, molecular docking simulation, and surface plasmon resonance (SPR) analysis to identify the target of ION-31a. The main target of ION-31a was identified as heat shock protein 90 (HSP90). Thus, ION-31a is a novel HSP90 inhibiter that could suppress the metastasis of breast cancer and angiogenesis significantly in vitro and in vivo. ION-31a acts via inhibiting the HSP90/hypoxia inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway and downregulating downstream signal pathways, including protein kinase B (AKT)/mammalian target of rapamycin (mTOR), AKT2/protein kinase C epsilon (PKCζ), extracellular regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and mitogen-activated protein kinase 14 (p38MAPK) pathways. ION-31a affects multiple effectors implicated in tumor metastasis and has the potential to be developed as an anti-metastatic agent to treat patients with breast cancer.

Comparison of New Oral Hypoglycemic Agents on Risk of Urinary Tract and Genital Infections in Type 2 Diabetes: A Network Meta-analysis.

INTRODUCTION: Dipeptidyl peptidase 4 (DPP4) inhibitors and sodium-glucose co-transporter 2 (SGLT2) inhibitors have often been used for patients with T2DM because of the reduced risk of hypoglycemia. However, DPP4 inhibitors and SGLT2 inhibitors may increase the risk of infectious diseases. This network meta-analysis (NMA) was performed to investigate the risk of urinary tract and genital infections associated with the use of two new glucose-lowering drug classes in patients with type 2 diabetes. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were comprehensively searched for articles from the date of database inception until September 8, 2020. Placebo-controlled or head-to-head trials of the two new drug classes used for treatment of adults with type 2 diabetes were included. The primary outcome was the incidence of any confirmed urinary tract infection; genital infection was also used as an important outcome indicator. RESULTS: Fifty-five studies were identified, covering 29,574 participants. Regarding urinary tract infections, SGLT2 inhibitors were not associated with increased risk, and among all drugs, sitagliptin, ipragliflozin, and linagliptin were the safest according to probability ranking. Regarding genital infections, saxagliptin was associated with significantly reduced risk in pairwise comparisons with placebo (RR 0.12, 95% CI 0.00-0.78), linagliptin (RR 0.09, 95% CI 0.00-0.78), canagliflozin (RR 0.04, 95% CI 0.00-0.31), dapagliflozin (RR 0.04, 95% CI 0.00-0.26), empagliflozin (RR 0.03, 95% CI 0.00-0.25), and ertugliflozin (RR 0.03, 95% CI 0.00-0.24). Among all drugs, saxagliptin, sitagliptin, and ipragliflozin were the safest according to probability ranking. Considering both urinary tract and genital infection risks, DPP4 inhibitors showed greater reductions than SGLT2 inhibitors and placebo. Saxagliptin was the safest drug according to probability ranking for both infection risks. CONCLUSIONS: This NMA showed that, to reduce genital infection risk, current evidence favors DPP4 inhibitors over SGLT2 inhibitors. Most SGLT2 inhibitors may not be associated with the risk of urinary tract infections. Considering both infection risks, saxagliptin may be the safest drug. Finally, mechanistic studies are needed to better understand the physiological basis for these effects.

Fusion with matrix attachment regions enhances expression of recombinant protein in human HT-1080 cells.

Like endogenous proteins, recombinant foreign proteins produced in human cell lines also need post-translational modifications. However, high and long-term expression of a gene of interest (GOI) presents significant challenges for recombinant protein production in human cells. In this work, the effect of human matrix attachment region elements (MARs), including the ß-globin MAR (gMAR), chicken lysozyme MAR (cMAR), and a combination of these two, on the stable expression of GOI was assessed in human HT-1080 cells. After transfection with vectors containing the MAR elements and eGFP, stably HT-1080 cell pools were obtained under selective pressure. eGFP protein expression was analyzed by flow cytometry, while transgene copy number and eGFP mRNA expression levels were determined with qPCR and qRT-PCR technology. We found that MARs could not enhance transfection efficiency, but gMAR could significantly increase eGFP expression in stable HT-1080 cell pools by approximately 2.69-fold. Moreover, gMAR could also increase eGFP expression stability during long-term culture. Lastly, we showed that the effect of the MARs on transgenes was related to the gene copy number. In summary, this study found that MARs could both enhance the transgene expression and stability in HT-1080 cells.

Novel short synthetic matrix attachment region for enhancing transgenic expression in recombinant Chinese hamster ovary cells.

Matrix attachment regions (MARs) are DNA fragments with specific motifs that enhance transgenic expression; however, the characteristics and functions of these elements remain unclear. In this study, we designed and synthesized three short chimeric MARs, namely, SM4, SM5, and SM6, with different numbers and orders of motifs on the basis of the features and motifs of previously reported MARs, namely, SM1, SM2, and SM3, respectively. Expression vectors with six synthetic MARs flanking the down or upstream of the expression cassette for enhanced green fluorescence protein (EGFP) were constructed and introduced into Chinese hamster ovary (CHO) cells. Results indicated that the EGFP expression of the CHO cells with transfection bySM4, SM5, or SM6-containing vectors was higher than that of those containing SM1, SM2, or SM3 regardless of the MAR insertion position. The improving effect of SM5 was particularly pronounced. Transgenic expression was further enhanced with the increasing SM5 copy number. Bioinformatics analysis indicated that several arrangements of the DNA-binding motifs for CEBP, FAST, Hox, glutathione, and NMP4 may help increase transgenic expression levels and the average population of highly expressed cells. Our findings on novel synthetic MARs will help establish stable expression systems in mammalian cells.

Competitive adsorption of heavy metals in aqueous solution onto biochar derived from anaerobically digested sludge.

Heavy metals often coexist in contaminated wastewater systems and their competitive behavior could affect the adsorption capacity of biochar. Till now, the competitive adsorption of heavy metals by biochar derived from anaerobically digested sludge has never been reported. In this work, biochar from anaerobically digested sludge was synthesized and characterized to explore the competitive behavior of widely co-existed Pb(II) and Cd(II). The mutual effects and inner mechanisms of their adsorption on studied biochar were systematically investigated via single-metal and binary-metals systems. In single-metal system, the biochar exhibited much higher adsorption capacity for Pb(II) compared to that for Cd(II). The maximum adsorption capacities of Pb(II) and Cd(II) based on single-component adsorption isotherm were 0.75 and 0.55 mmoL/g, respectively, which were much higher than those reported biochars from different materials. In binary-metals system, the Cd(II) adsorption on biochar was severely inhibited, while the uptake of Pb(II) was not affected significantly. The results of binary-components adsorption isotherm clearly demonstrated the competitive adsorption between two metals occurred as well as the preference of biochar for Pb(II) compared to Cd(II). FTIR and metal characteristics analysis results revealed that Pb(II) had exactly the same adsorption sites with Cd(II), but Pb(II) has a greater affinity than Cd(II), thereby exhibiting a competitive advantage in the coexisting system.

Experimental Study on the Fire Performance of Tubular Steel Columns with Membrane Protections for Prefabricated and Modular Steel Construction.

Experimental research was conducted to study the fire resistance of steel tubular columns used in prefabricated and modular construction. In order to achieve high-efficient prefabrication and fast on-site installation, membrane protections using board products and thermal insulation blankets are adopted as the favorable protection method. Three protected tubular columns were tested in a full-scale column furnace with axial load applied. The study variables were different membranes, including fiber reinforced calcium silicate (FRCS) boards, rock wool and aluminum silica (Fiberfrax) insulations. The results suggest that one layer of 12 mm FRCS board with rock wool insulation has insufficient fire protection. However, steel columns protected with two layers of 12 mm FRCS boards with insulation appeared to have good fire resistances and could achieve a fire resistance rating as high as 2.5~3.0 h.

Influence of straw incorporation with and without straw decomposer on soil bacterial community structure and function in a rice-wheat cropping system.

To study the influence of straw incorporation with and without straw decomposer on bacterial community structure and biological traits, a 3-year field experiments, including four treatments: control without fertilizer (CK), chemical fertilizer (NPK), chemical fertilizer plus 7500 kg ha-1 straw incorporation (NPKS), and chemical fertilizer plus 7500 kg ha-1 straw incorporation and 300 kg ha-1 straw decomposer (NPKSD), were performed in a rice-wheat cropping system in Changshu (CS) and Jintan (JT) city, respectively. Soil samples were taken right after wheat (June) and rice (October) harvest in both sites, respectively. The NPKS and NPKSD treatments consistently increased crop yields, cellulase activity, and bacterial abundance in both sampling times and sites. Moreover, the NPKS and NPKSD treatments altered soil bacterial community structure, particularly in the wheat harvest soils in both sites, separating from the CK and NPK treatments. In the rice harvest soils, both NPKS and NPKSD treatments had no considerable impacts on bacterial communities in CS, whereas the NPKSD treatment significantly shaped bacterial communities compared to the other treatments in JT. These practices also significantly shifted the bacterial composition of unique operational taxonomic units (OTUs) rather than shared OTUs. The relative abundances of copiotrophic bacteria (Proteobacteria, Betaproteobacteria, and Actinobacteria) were positively correlated with soil total N, available N, and available P. Taken together, these results indicate that application of straw incorporation with and without straw decomposer could particularly stimulate the copiotrophic bacteria, enhance the soil biological activity, and thus, contribute to the soil productivity and sustainability in agro-ecosystems.

Flavonoid derivative (Fla-CN) inhibited adipocyte differentiation via activating AMPK and up-regulating microRNA-27 in 3T3-L1 cells.

Fla-CN (3-O-[(E)-4-(4-cyanophenyl)-2-oxobut-3-en-1-yl] kaempferol) is a semi-synthesized flavonoid derivative of tiliroside which exhibited anti-diabetic effect in vivo. Our previous study revealed the role of Fla-CN in anti-obesity and anti-diabetes in vivo, but the underlying mechanism remained to be addressed. The present study aimed to investigate the mechanism of anti-adipogenesis in vitro. Fla-CN markedly inhibited intracellular lipid accumulation in a dose-dependent manner, and the inhibitory effect was mainly limited to the early stage of adipocyte differentiation in vitro. Further investigations revealed that Fla-CN up-regulated the expression level of miR-27a/b and suppressed its target genes expression including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). Furthermore, the phosphorylation of AMP-activated protein kinase (AMPK) was also enhanced by Fla-CN in pre-adipocyte differentiation. These effects were abolished when cells were treated with miR-27a/b inhibitor and AMPK inhibitor Compound C. Additionally, Fla-CN reduced the expressions of adipocyte-specific genes such as sterol regulatory element-binding transcription factor 1c (SREBP-1c), fatty acid synthase (FAS) and adipocyte fatty acid binding protein (aP2). In conclusion, these results suggested a mechanism of Fla-CN for adipocyte differentiation inhibition of 3T3-L1 cells through miR-27a/b induction and AMPK activation.

Effects of schisandrin B on P21 and Caspase-3 expression in HK-2 cells injuried by CDDP / 中草药

Objective: To explore the effect of schisandrin B (SchB) on P21 and Caspase-3 expression in cisplatin induced human proximal renal tubular epithelial (HK-2) cells injuried by CDDP in vitro. Methods: HK-2 cells were randomly divided into five groups: control group (untreated), CDDP group (treated with 50 μmol/L CDDP for 24 h), SchB pretreat groups (CDDP + SchB, cells were pretreated with 5, 10, and 20 μmol/L SchB for 2 h, and the rest of the operation was the same as CDDP group). CCK-8 kit was used to detect the cell viability of five groups. Flow cytometry was used to detect the apoptotic rate of five groups. The morphology of cells was observed by inverted microscope. The protein expression of P21 and Caspase-3 was assessed by Western blotting assay. Results: Compared with the control group, the cell viability decreased, and the apoptosis increased, the protein expression of P21 and Caspase-3 was up-regulated in HK-2 cells after treated with 50 μmol/L CDDP. Cell volume was reduced, and the mutual connection disappeared. Compared with the CDDP group, the cell viability increased and the apoptosis was decreased, the expression of Caspase-3 was down-regulated and the expression of P21 was up-regulated in HK-2 cells after pretreated with 5, 10, and 20 μmol/L SchB. Cell morphological damage lightened, the volume slightly decreased, and the mutual connection reduced. Conclusion: SchB has a protective effect on HK-2 cells damage induced by cisplatin. The mechanism may be related to up-regulation of P21 and down-regulation of Caspase-3 expression, and its protective effect is dose dependent.

[Effect of 1, 2, 3, 4, 6, 7, 8, 9-octachlorodibenzo-p-dioxin on testicular gene expression profiles in male mice].

OBJECTIVE: To investigate the effect of 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD) on the testicular gene expression profile in the testis of mice. METHODS: Twenty male C57BL/6j mice were randomly divided into normal control group (fed with maize oil) and 3 OCDD groups treated with OCDD by gavage for 30 days at low-, moderate-, and high doses of 1.25×10(-6), 1.25 ×10(-5), and 1.25×10(-4) g/mL, respectively (8 mL/kg daily). The testicular gene expression profiles of the mice were investigated using gene chip technique and compared between OCDD-exposed groups and the control group. RESULTS: Compared with the control group, the mice in low-dose OCDD group showed 1133 differentially expressed genes, including 659 up-regulated and 474 down-regulated ones; in the moderate-dose OCDD group, 978 genes were differentially expressed, including 487 up-regulated and 491 down-regulated ones; in the high-dose group, 895 genes were differentially expressed, including 424 up-regulated and 471 down-regulated ones. CONCLUSION: The effect of sub-chronic exposure to OCDD on testicular gene expression profiles in male C57BL/6j mice indicates that the testis is probably the target organ of OCDD.