Effect of apheresis plasma donation on plasma uric acid levels, the lipid profile, and major plasma proteins in plasma donors in China: A multicenter, prospective cohort study.

Abnormal plasma uric acid (UA) levels, the lipid profile, and plasma proteins in blood are associated with a range of adverse health outcomes. This multicenter, prospective cohort study aimed to determine the possible effects of multiple apheresis plasma donations on plasma UA levels, the lipid profile, and major proteins in plasma donors. Participants were enrolled from 1 April 2021 to 31 August 2022. When their plasma UA (men: >420 µmol/L, women: >360 µmol/L) and/or lipid levels (total cholesterol [TC]: ≥6.2 mmol/L, triglycerides [TGs]: ≥2.3 mmol/L, low-density lipoprotein cholesterol: ≥4.1 mmol/L, or high-density lipoprotein cholesterol [HDL-C]: <1.0 mmol/L) were abnormal at their first plasma donation, the enrolled participants were followed up until they had completed 10 plasma donations. A total of 11485 participants were enrolled, of whom 1861 met the inclusion criteria. During the study period, 320 donors completed 10 plasma donations. None of the participants took any corrective medicine for their abnormal index. The measured parameters were significantly different from the first to the tenth plasma donations (donors with asymptomatic hyperuricemia: UA, P < 0.001; donors with asymptomatic hyperlipidemia: HDL-C, P < 0.001; TC, P = 0.025; TGs, P < 0.001; apolipoprotein B, P = 0.025; all of the plasma donors, immunoglobulin G, P < 0.001). The levels of HDL-C, TC, and apolipoprotein B were increased, and the levels of UA, TGs, and immunoglobulin G were decreased over this time. However, immunoglobulin G levels were still in the normal range. Moreover, the changes in these parameters were closely associated with the frequency of plasma donation during the study period. Repeated apheresis plasma donations can reduce plasma UA and TG levels and increase HDL-C levels; and further evaluation of the clinical significance with a larger sample size is required.

Decision-Making Error in Platelet Transfusion Caused by EDTA-Dependent Pseudothrombocytopenia: a Case Report and Literature Review.

BACKGROUND: Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP) is a rare phenomenon characterized by pseudo low platelet counts when using EDTA as anticoagulant and can result in false decision making of platelet transfusion. METHODS: An application for platelet transfusion from a patient who planned to undergo spinal surgery was received by the Department of Transfusion service. The preoperative laboratory test results showed thrombocytopenia (platelet counts: 27 x 109/L). The surgeon planned to transfuse platelets before the operation to avoid bleeding in operation due to thrombocytopenia. However, the lab technologist found that there was aggregation of platelets under the microscope. Samples used with sodium citrate and heparin as anticoagulants were rechecked. RESULTS: The platelet count of the patient was normal in sodium citrate and heparin anticoagulant tubes. The patient had no history and clinical symptoms of thrombocytopenia. Therefore, the doctor canceled the platelet order. We also reviewed the relevant literature of EDTA-PTCP. CONCLUSIONS: EDTA-PTCP is rare and may result of a wrong decision of platelet transfusion. Correct understanding and treatment of this situation can avoid unnecessary platelet transfusion.

Molecular cloning of estrogen receptor and its function on vitellogenesis in pompano (Trachinotus ovatus).

Estrogen receptors (ERs) play a critical role in vitellogenesis (Vtgs). However, the contribution of each ER for the regulation of vtgs expression was not analyzed clearly in teleosts. In the present study, three ers isoforms (erα, erß1, and erß2) were cloned in pompano (Trachinotus ovatus). Real-time PCR and enzyme-linked immunosorbent assay (ELISA) was used to detect the effects of 17ß-estradiol (E2) on ERs and Vtgs in the liver of pompano. In vivo injection experiments showed that E2 significantly increased the expressions of ers and vtgs. ER broad spectrum antagonist Fulvestrant significantly attenuated the E2- induced up-regulation of ers and vtgs in a dose-dependent manner. ERα antagonist Methyl-piperidino pyrazole (MPP) significantly attenuated the up-regulation of erα, erß2, vtg-B and vtg-C, and promoted the expressions of erß1 and vtg-A. ERß antagonist Cyclofenil significantly inhibited the expressions of erß1, erß2, vtg-A and vtg-C, and promoted the expressions of erα and vtg-B. In addition, E2 significantly increased the protein level of Vtg, while Fulvestrant, MPP and Cyclofenil significantly inhibited the protein level of Vtg in a dose-dependent manner. Our results indicate that E2 may regulate the expression of each vtg with different subtypes of ERs, and shows a distinct compensatory expression effect on the regulation for ers and vtgs, which provides a theoretical basis for reproductive endocrinology study in pompano.

Unraveling a Combined Inactivation Mechanism of Cytochrome P450s by Genipin, the Major Reactive Aglycone Derived from Gardeniae Fructus.

Genipin (GP) is the reactive aglycone of geniposide, the main component of traditional Chinese medicine Gardeniae Fructus (GF). The covalent binding of GP to cellular proteins is suspected to be responsible for GF-induced hepatotoxicity and inhibits drug-metabolizing enzyme activity, although the mechanisms remain to be clarified. In this study, the mechanisms of GP-induced human hepatic P450 inactivation were systemically investigated. Results showed that GP inhibited all tested P450 isoforms via distinct mechanisms. CYP2C19 was directly and irreversibly inactivated without time dependency. CYP1A2, CYP2C9, CYP2D6, and CYP3A4 T (testosterone as substrate) showed time-dependent and mixed-type inactivation, while CYP2B6, CYP2C8, and CYP3A4 M (midazolam as substrate) showed time-dependent and irreversible inactivation. For CYP3A4 inactivation, the kinact/KI values in the presence or absence of NADPH were 0.26 or 0.16 min-1 mM-1 for the M site and 0.62 or 0.27 min-1 mM-1 for the T site. Ketoconazole and glutathione (GSH) both attenuated CYP3A4 inactivation, suggesting an active site occupation- and reactive metabolite-mediated inactivation mechanism. Moreover, the in vitro and in vivo formation of a P450-dependent GP-S-GSH conjugate indicated the involvement of metabolic activation and thiol residues binding in GP-induced enzyme inactivation. Lastly, molecular docking analysis simulated potential binding sites and modes of GP association with CYP2C19 and CYP3A4. We propose that direct covalent binding and metabolic activation mediate GP-induced P450 inactivation and alert readers to potential risk factors for GP-related clinical drug-drug interactions.

CircSETDB1 contributes to paclitaxel resistance of ovarian cancer cells by sponging miR-508-3p and regulating ABCC1 expression.

Ovarian cancer is a gynecological tumor with a poor prognosis. The chemotherapy failure and recurrence induced by paclitaxel (Ptx) resistance are the main reason for the failure of ovarian cancer treatment. In this study, we aimed to explore the role of circular RNA (circRNA) in the regulation of Ptx resistance in ovarian cancer. Quantitative reverse transcription PCR was performed to detect the expression of circRNA SET domain bifurcated histone lysine methyltransferase 1 (circSETDB1), microRNA (miR)-508-3p and ATP-binding cassette subfamily C member 1 ( ABCC1 ) mRNA. The effects of circSETDB1 on Ptx resistance were explored by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and flow cytometry experiments in vitro . The protein level was assessed by western blot. Dual-luciferase reporter and RNA pull-down assays were carried out to confirm the interactions among circSETDB1, miR-508-3p, and ABCC1 . Xenograft tumor experiment was performed to investigate the effect of circSETDB1 on Ptx resistance in vivo . CircSETDB1 was highly expressed in Ptx-resistant ovarian cancer. CircSETDB1 knockdown inhibited cell proliferation viability, half maximal inhibitory concentration value of Ptx, cell cycle progression, and induced cell apoptosis in Ptx-resistant ovarian cancer cells. miR-508-3p was a target of circSETDB1, and inhibition of miR-508-3p overturned the effects of circSETDB1 knockdown on the Ptx resistance of ovarian cancer cells. miR-508-5p could bind to ABCC1 . Overexpression of ABCC1 reversed the effects of circSETDB1 knockdown on the Ptx resistance of ovarian cancer cells. CircSETDB1 knockdown also enhanced Ptx sensitivity in vivo . In conclusion, circSETDB1 regulated Ptx resistance of ovarian cancer by targeting miR-508-3p/ ABCC1 axis.

Study on extraction and characterization of new antibiotics violacein from engineered Escherichia coli VioABCDE-SD.

To better understand the characteristic properties of violacein biosynthesized by engineered Escherichia coli VioABCDE-SD, a convenient and simplified method was designed to extract violacein and its stability, antimicrobial activity, and antioxidant capacity were analyzed. Different from the traditional extraction methods, our new method is easier and less time consuming and can directly obtain violacein dry powder product with a higher extraction rate. Low temperature, dark condition, neutral pH, reducing agents, Ba2+ , Mn2+ , Ni2+ , Co2+ , and some food additives of sucrose, xylose, and glucose were conducive to maintaining its stability. The violacein also exhibited surprisingly high bacteriostatic action against Gram-positive Bacillus subtilis, Deinococcus radiodurans R1, and Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, but no effect on E. coli. The violacein of VioABCDE-SD exhibited strong antioxidant activity, with the scavenging rate of 1,1-diphenyl-2-picrylhydrazyl free radicals reaching 60.33%, the scavenging efficiency of hydroxyl radical scavenging reaching 56.34%, and the total antioxidant capacity reaching 0.63 U/mL. Violacein from VioABCDE-SD can be synthesized directionally with better stability, antibacterial, and antioxidant properties compared with that from the original strain Janthinobacterium sp. B9-8. Therefore, our study indicated that violacein from engineered E. coli VioABCDE-SD was a kind of new antibiotic with potential biological activities, which may have potential utility in multiple areas such as pharmacological, cosmetics, and healthy food industries.

Why elderly in rural China didn't wear masks during the COVID-19 pandemic? A qualitative narrative interview study.

BACKGROUND: During the COVID-19 pandemic, ageism and stigmatization towards the elderly have been prominent issues. In addition, there have been debates on Chinese social media as to why elderly people in rural areas are not wearing masks. While some factors that affect the mask-wearing behaviour of the elderly have been analyzed, little attention has been given to the lived experiences and behavioral intentions of rural elderly people who choose not to wear masks, despite government mandates to do so. METHOD: In this research, 50 semi-structured interviews with 30 elderly individuals in three Chinese villages were carried out using the qualitative method of semi-structured interviews. Following verbatim recording and transcription of the conversations, the subject was analyzed using the Theory of Reasoned Action. RESULTS: We identified four factors that influence the non-masking behaviour of rural elderly, including past experiences, cultural concepts, cognitive attitudes, and health and safety anxiety, and identified nine sub-themes based on the four overarching themes. Past knowledge, experience, and history have led rural elderly people to distrust the government's mandatory "mask mandate," believing that they do not need to wear masks. Rural cultural concepts and habits make the elderly feel that masks not only fail to provide protection but also become obstacles, resulting in poor daily experiences. Cognitive attitudes and emotions determine the elderly's evaluation of masks, which in turn affects their use of masks. Finally, elderly individuals'chronic diseases directly affect the physical pain and life safety caused by their use of masks, which is a major objective factor for their non-masking. CONCLUSIONS: Although numerous studies have concluded that Chinese people wore masks out of collectivism and conformity during the pandemic, marginalized groups' opposition to wearing masks also contains distinctive, individualized elements and underlying causes. By exposing these elements and reasons, we can better comprehend the peculiar behavior of particular groups while fighting the pandemic. The needs of marginalized populations should be prioritized by public health policy makers to provide more equitable services.

Transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy for bilateral vocal fold paralysis: A retrospective study.

OBJECTIVES: To investigate the effect of transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy for bilateral vocal fold paralysis (BVFP). DESIGN: A retrospective study with medical records from 2017 to 2021 in our hospital. SETTING: A single-centre study. PARTICIPANTS: This retrospective study included 22 patients with BVFP. They underwent transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy in our hospital from 2017 to 2021. MAIN OUTCOME MEASURES: Preoperative and postoperative swallowing and phonation functions were evaluated in all patients. RESULTS: All 22 patients with a tracheostomy were successfully decannulated within 6 months after surgery without subsequent revision operations, and the width of the posterior glottis was more than 3.9 mm in all patients when they inspired. The statistical analysis showed that there was no difference in vocal function and swallowing function in all patients compared to preoperative (p > .05). CONCLUSION: Transoral CO2 laser-modified posterior cordotomy combined with plasma ablation subtotal arytenoidectomy enlarges the posterior glottis in patients with BVFP, which maintains airway patency without significant worsening in voice and swallowing function.

Esterase-Activated Precipitating Strategy to Achieve Highly Specific Detection and Long-Term Imaging of Calcium Ions by Aggregation-Induced Phosphorescence Probe.

Spatial and temporal monitoring of bioactive targets such as calcium ions is vitally significant for their essential roles in physiological and biochemical functions. Herein, we proposed an esterase-activated precipitating strategy to achieve highly specific identification and long-term bioimaging of calcium ions via lighting up the calcium ions by precipitation using a water-soluble aggregation-induced phosphorescence (AIP) probe. The designed probe CaP2 has an AIP behavior and can be efficiently aggregated by calcium ions through the coupling coordination of carboxylic acid and cyanide groups, which enables it to light up Ca2+ by precipitating-triggered phosphorescence. Four hydrophilic groups of tetraethylene glycol were introduced to endow the resulting probe CaP3 with extraordinary water solubility as well as excellent cellular penetration. Only when the probe CaP3 penetrates inside the live cells the existing esterase in cells can activate the probe to be transformed active CaP2 probe selectively binding with calcium ion in the surroundings. The probe was used to further evaluate the imaging of intracellular calcium ions in model organisms. The excellent imaging performance of CaP3 in Arabidopsis thaliana seedling roots demonstrates that CaP3 has the excellent capability of monitoring calcium ions in live-cell imaging, and furthermore CaP3 exhibits much better photostability and thereby greater potential in long-term imaging. This work established a general esterase-activated precipitating strategy to achieve specific detection and bioimaging in situ triggered by esterase in live cells, and established a water-soluble aggregation-induced phosphorescence probe with high selectivity to achieve specific sensing and long-term imaging of calcium ions in live cells.

Bioinformatics analysis for identifying micro-RNAs, long noncoding RNAs, transcription factors, and immune genes regulatory networks in diabetic cardiomyopathy using an integrated bioinformatics analysis.

OBJECTIVES: We identified functional genes and studied the underlying molecular mechanisms of diabetic cardiomyopathy (DCM) using bioinformatics tools. METHODS: Original gene expression profiles were obtained from the GSE21610 and GSE112556 data sets. We used GEO2R to screen the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on DEGs. Protein-protein interaction (PPI) networks of DEGs were constructed using STRING and hub genes of signaling pathways were identified using Cytoscape. Aberrant hub gene expression was verified using The Cancer Genome Atlas data set. RESULTS: The DEGs in DCM were mainly enriched in the nuclei and cytoplasm and involved in DCM and chemokine-related signaling pathways. In the PPI network, 32 nodes were chosen as hub nodes and an RNA interaction network was constructed with 517 interactions. The expression of key genes (JPIK3R1, CCR9, XIST, WDFY3.AS2, hsa-miR-144-5p, and hsa-miR-146b-5p) was significantly different between DCM and normal tissues. CONCLUSIONS: The identified hub genes could be associated with DCM pathogenesis and could be used for treating DCM.

Functional characterization of a novel violacein biosynthesis operon from Janthinobacterium sp. B9-8.

Violacein is a secondary metabolite mainly produced by Gram-negative bacteria that is formed from tryptophan by five enzymes encoded by a single operon. It is a broad-spectrum antibacterial pigment with various important biological activities such as anti-tumor, antiviral, and antioxidative effects. The newly discovered violacein operon vioABCDE was identified in the genome of the extremophile Janthinobacterium sp. B9-8. The key enzyme-encoding genes were cloned to construct the multigene coexpression plasmids pET-vioAB and pRSF-vioCDE. The violacein biosynthesis pathway was heterologously introduced into engineered Escherichia coli VioABCDE and VioABCDE-SD. The factors affecting violacein production, including temperature, pH, inoculum size, carbon and nitrogen source, precursor, and inducers were investigated. The violacein titer of VioABCDE-SD reached 107 mg/L in a two-stage fermentation process, representing a 454.4% increase over the original strain. The violacein operon from B9-8 provides a new microbial gene source for the analysis of the violacein synthesis mechanism, and the constructed engineering E. coli strains lay a foundation for the efficient and rapid synthesis of other natural products.Key points• The newly discovered violacein operon vioABCDE was identified in the genome of the extremophile Janthinobacterium sp. B9-8.• The violacein synthesis pathway was reconstructed in E. coli using two compatible plasmids.• A two-stage fermentation process was optimized for improved violacein accumulation.

The value of transthoracic echocardiography in the detection of extra-cardiac lesions.

OBJECTIVE: Transthoracic echocardiography (TTE) is generally recognized as the top choice for detecting myocardial and cardiac cavity lesions. Sonographers mostly focus on myocardium, cardiac cavity and cardiac hemodynamics, whereas the abnormal extra-cardiac lesions are easily remain unrecognized. The aim of this study was to investigate the ultrasonic image features in abnormal extra-cardiac lesions and the value of TTE in the detection of extra-cardiac lesions. METHODS: 49 cases of abnormal extra-cardiac lesion detected by TTE from January 2014 to December 2019 were collected, which were confirmed by surgical pathology. The two-dimensional ultrasonic characteristics and the relationships with the cardiac and great vessels were summarized on the basis of multi-view by TTE. All patients were also examined by computed tomography (CT). RESULTS: In 49 patients with abnormal extra-cardiac lesions, 37 malignant cases and 12 benign cases were included. There were 41 cases (41/49, 86.67%) of mediastinal lesions and 8 cases (8/49, 16.33%) of lung lesions. The maximum diameter ranged from 3.2 cm to 13.66 cm, and the median diameter was about 7.4 cm, among which 29 cases (29/49, 59.18%) were larger than 5 cm. 4 cases (4/49, 8.16%) of cystic anechoic lesions were pericardial cyst. 2 cases (2/49, 4.08%) of cystic-solid echogenic lesions were teratoma. The remaining 43 cases (43/49, 87.76%) presented as solid hypoechoic or heterogeneous masses. 6 cases compressed the heart and 21 cases encroached on the heart and vessels. Diagnosis coincidence rates of TTE and CT were respectively 77.55% and 93.88%, with a statistical difference (p = 0.012). CONCLUSION: Although the diagnostic coincidence rate of TTE is slightly lower than that of CT, TTE has certain diagnostic value for extra-cardiac lesions.

Impact of fresh frozen plasma transfusion on mortality in extracorporeal membrane oxygenation.

BACKGROUND: Patients who receive extracorporeal membrane oxygenation (ECMO) support require substantial transfusions. Red blood cell (RBC) and platelet (PLT) transfusions have been reported to be associated with adverse outcomes in ECMO patients. However, little is known about whether the transfusion of fresh frozen plasma (FFP) is associated with mortality and morbidity among patients receiving ECMO. The aim of this study was to examine the relationship between FFP transfusion and mortality in ECMO patients and assess risk factors for the transfusion of FFP. METHODS: The clinical parameters of 116 ECMO patients were collected. The machine learning approach of the Boruta algorithm was employed to select the variables associated with ECMO patients' in-hospital mortality. Univariate and multivariate logistic regression analyses were applied to identify the association between the selected variables and in-hospital mortality. Spearman correlation and backwards stepwise multiple linear regression analyses were used to examine parameters contributing to FFP transfusion. RESULTS: Among the 116 patients who received ECMO support, the in-hospital mortality was 32.8%. The median FFP (mL/kg/d) transfusion was higher in dead patients (5.07, IQR 1.78-8.90) when compared to alive patients (2.16, IQR 0.79-4.66) (p = 0.007). After adjustment for confounders, FFP transfusion (mL/kg/d) was associated with in-hospital mortality (OR 1.09, 95% CI, 1.01-1.18; p = 0.035). Further analysis found that higher activated partial thromboplastin time (APTT), higher levels of uric acid (UA) and lower PLT counts were significant risk factors for FFP transfusion, with estimated values of 0.06 (95% CI, 0.02-0.11; p = 0.009), 0.01 (95% CI, 0.00-0.02; p = 0.003) and -0.03 (95% CI, -0.05--0.01; p = 0.007), respectively. CONCLUSION: FFP transfusion is markedly associated with in-hospital mortality among patients receiving ECMO, and higher APTT, higher levels of UA and lower PLT counts are risk factors for FFP transfusion. This suggests that better management of patients' coagulation system and kidney function may reduce the utilization of FFP, thus improving ECMO patient outcomes.

The role of the cd99l2 gene on leukocyte interstitial migration in zebrafish.

Leukocytes play an essential role in ontogeny, tissue regeneration, and innate and adaptive immunity. The migration of leukocytes to the infected or traumatized areas is necessary for their immune response function. As an adhesion molecule, CD99L2 is crucial in the extravasation of leukocytes, however, its role in the interstitial migration of leukocytes remains unclear. In this study, the cd99l2 gene was knock-out by TALEN (transcription activator-like effector nuclease) in zebrafish and discovered that the deletion had no effect on zebrafish development. The number of granulocytes and macrophages recruited to the wounded tissue was significantly reduced in the cd99l2 mutants following caudal fin damage. Further research revealed that the expression of mfap4 was drastically decreased in the cd99l2 mutants, which may be one of the reasons that affect the migration of macrophages to the wound site. Moreover,transgenic lines with labeled vasculature, neutrophils and macrophages demonstrated that neutrophils and macrophages migrate throughout the interstitial space to the wound tissue in both wild-type and mutant zebrafish at 60 hours post-fertilization, indicating that the cd99l2 gene is involved in the interstitial migration of leukocytes. Finally, RNA transcription, protein folding, and the P450 pathway were enriched in cd99l2 mutants by RNA-seq analysis. Previous research had demonstrated that the regulation of transcription and signal transduction could be affected by adhesion molecules, which may suggest that the cd99l2 gene is involved in the cascade signaling pathway of leukocyte migration as an adhesion molecule. In conclusion, this study uncovered a novel function of the cd99l2 gene in the process of leukocyte migration in zebrafish, which is expected to provide a theoretical foundation for inflammatory and immune-related diseases.

Betulin terpenoid targets OVCAR-3 human ovarian carcinoma cells by inducing mitochondrial mediated apoptosis, G2/M phase cell cycle arrest, inhibition of cell migration and invasion and modulating mTOR/PI3K/AKT signalling pathway.

The main purpose of the current research work was to study in vitro anticancer effects of betulin in OVCAR-3 human ovarian carcinoma cells along with examining its effects on cellular apoptosis, cell cycle phase distribution, cell migration and invasion and mTOR/PI3K/AKT signalling pathway. The cell proliferation of OVCAR-3 cells at various doses of the drug was studied by CCK8 cell viability assay. Effects on cell apoptosis were studied by fluorescence microscopy and western blot. Effects on cell cycle were evaluated by flow cytometry and western blot. Transwell assays were used to study effects on cell migration and invasion. The results indicated that betulin led to significant reduction of OVCAR-3 cell viability in a dose-dependent as well as time dependent manner. Betulin also led to reduction in cell colonies. The anticancer effects of betulin were due to the induction of apoptosis which was seen by increased apoptotic cells with yellow and orange fluorescence. Betulin prompted mitochondrial apoptosis which was also associated with alteration in the apoptosis-related protein expression (Bax, Bad and Bcl-2 and Bcl-xL). The molecule also led to G2/M phase cell cycle arrest on OVACR-3 ovarian carcinoma cells. It was also observed that betulin could inhibit the migration and invasion of the ovarian cancer cells in a concentration-dependent manner. Betulin molecule also resulted in blocking of mTOR/PI3K/AKT signalling pathway.  In conclusion, this study clearly indicates the anticancer effects of betulin natural product in OVCAR-3 human ovarian cancer cells are mediated via apoptosis induction, G2/M phase cell cycle arrest, cell migration and invasion inhibition and targeting of mTOR/PI3K/AKT signalling pathway.

Arsenic trioxide induces expression of BCL-2 expression via NF-κB and p38 MAPK signaling pathways in BEAS-2B cells during apoptosis.

Inorganic arsenic compounds are environmental toxicants that are widely distributed in air, water, and food. B-cell lymphoma 2 (BCL-2) is an oncogene having anti-apoptotic function. In this study, we clarify that BCL-2, as a pro-apoptotic factor, participates in As2O3-induced apoptosis in BEAS-2B cells. Specifically, As2O3 stimulated the expression of BCL-2 mRNA and protein in a dose-dependent manner which was highly accumulated in the nucleus of BEAS-2B cell together with chromatin condensation and DNA fragmentation during apoptosis. Mechanistically, the process described above is mediated through the NF-κB and p38 MAPK signaling pathways, which can be abated by corresponding inhibitors, such as BAY11-7082 and SB203580, respectively. Additionally, BAY11-7082, actinomycin D, and cycloheximide have inhibitory effects on As2O3-induced expression of BCL-2 mRNA and protein, and restore the cell viability of BEAS-2B cells. Suppression of BCL-2 protein activation by ABT-199 also restored viability of BEAS-2B cell in As2O3-induced apoptosis. Furthermore, As2O3 increased the level of BCL-2 phosphorylation. These results suggest that in BEAS-2B cells, As2O3-induced apoptosis is mainly dominated by BCL-2 upregulation, nuclear localization and phosphorylation. The study presented here provides a novel insight into the molecular mechanism of BCL-2-induced apoptosis.

Blood utilization in five Chinese hospitals shows low hemoglobin thresholds in medical patients.

BACKGROUND: The number of red blood cell units transfused per capita in China is lower than in western countries and the reason(s) for the difference is unknown. STUDY DESIGN AND METHODS: We randomly chose 5050 transfused patients from five Chinese hospitals. We compared transfused cases to nontransfused controls matched for the same underlying diagnosis. We assessed the pretransfusion hemoglobin (Hb) trigger and other clinical characteristics associated with transfusion. After stratifying by underlying disease, we compared pretransfusion Hb level in Chinese hospitals to 12 US hospitals. RESULTS: In 5050 patients who received transfusion, the pretransfusion Hb levels were lower in medical (6.3 g/dL) compared to surgical patients receiving transfusion postoperatively (8.1 g/dL). In patients with nonsurgical diagnoses, the pretransfusion Hb was much lower than that in the United States; the difference in mean Hb level varied by underlying diagnosis from 0.4 to 1.8 g/dL. In case-control analysis of cases (n = 1356) compared to controls (n = 1201), the pretransfusion Hb showed the strongest association with transfusion. Compared to 10 g/dL, the odds ratio (95% confidence interval) for pretransfusion Hb of 7 to 7.9 g/dL was 37.7 (24.8-57.4). CONCLUSION: Transfusion triggers in five Chinese hospitals appear comparable to those in the United States for surgical patients; however, medical patients have lower pretransfusion Hb levels (approx. 6 g/dL). Of the factors assessed, the pretransfusion Hb was most strongly associated with transfusion. The clinical impact of lower transfusion thresholds used in China is unknown.

Characterization, Antioxidant, Anti-Aging and Organ Protective Effects of Sulfated Polysaccharides from Flammulina velutipes.

As an irreversible and complex degenerative physiological process, the treatment for aging seems strategically necessary, and polysaccharides play important roles against aging owing to their abundant bioactivities. In this paper, the antioxidant and anti-aging activities of Flammulina velutipes polysaccharides (FPS) and its sulfated FPS (SFPS) on d-galactose-induced aging mice were investigated. The in vitro antioxidant activities demonstrated that SFPS had strong reducing power and superior scavenging effects on 2, 2-diphenylpicrylhydrazyl (DPPH), hydroxyl radicals and the chelating activities of Fe2+. The in vivo animal experiments manifested that the SFPS showed superior antioxidant and protective abilities against the d-galactose-induced aging by increasing the antioxidant enzyme activities, decreasing lipid peroxidation, improving the inflammatory response and ameliorating the anile condition of mice. Furthermore, the structural analysis of SFPS was investigated through FT-IR, NMR, and HPLC analysis, and the results indicated that SFPS was a homogeneous heteropolysaccharide with a weight-average molecular weight of 2.81 × 103 Da. Furthermore, SFPS has also changed in characteristic functional groups and monosaccharide composition compared to FPS. These results suggested that sulfated modification could enhance the anti-oxidation, anti-aging and protective activities of F. velutipes polysaccharides, which may provide references for the development of functional foods and natural medicines.

Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk of aplastic anemia and the effect of immunosuppressive therapy.

Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related genes may contribute to AA risk. In the current study, we investigated the association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China. In the current 164 AA cases and 211 controls study, we found T allele and TT genotype of rs7574865 were more frequent in the cases than that in the controls. In the additive model, individual carrying rs7574865 T allele demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08-fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017). Additionally, we showed that G allele and GG genotype of rs11209032 were more frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our study also found G allele and GG genotype of rs11209032, and GG-genotype of rs744166 associated with the immunosuppressive therapy outcome in AA patients. Current study results support that functional STAT4 (rs7574865), IL23R (rs11209032), and STAT3 (rs744166) variants may associate with occurrence, severity, and immunosuppressive outcome of AA in the Han population in southwest China.