Characteristics of adverse drug reactions induced by flutamide and bicalutamide: a real-world pharmacovigilance study using FAERS

Flutamide and bicalutamide are indicated for the management of prostate metastatic carcinoma. The current study evaluated the adverse drug reactions related to flutamide and bicalutamide in a real-world setting. To quantify the signals of flutamide and bicalutamide associated adverse events (AEs), we used the US Food and Drug Administration Adverse Event Reporting System (FAERS) for this pharmacovigilance study using established pharmacovigilance methods. A total of 2711 AEs of flutamide were investigated as the primary suspected; 522 AEs were related to prostate cancer. A total of 4459 AEs were investigated as the primary suspected for bicalutamide; 2251 AEs were related to prostate cancer. The analysis demonstrated 29 signals for flutamide and 84 for bicalutamide. Liver function test was the most common AEs for flutamide, and malignant neoplasm progression was the most common for bicalutamide. The signal strength of Dementia Alzheimer’s type was 26.53 (17.89–39.35) and 26.33 (607.34), which had the highest strength for flutamide. Anti-androgen withdrawal syndrome exhibited the strongest signal for bicalutamide. Generating awareness of rare AEs that were not listed on the label is critical. The analysis of the AE signals may provide support for prescribing flutamide and bicalutamide.</p

ZIF-8-Templated Hollow Cubelike Si/SiO₂@C Nanocomposites for Superior Lithium Storage Performance

Silicon-based anodes are of particular interest for the application of next generation large-capacity lithium-ion batteries (LIBs) because of their natural abundance and ultrahigh theoretical lithium storage ability. However, the huge volume expansion and inferior cyclic stability severely limit their practical applications. To address this challenge, herein, hollow cubelike hybrid composites consisting of a Si/SiO2 cross-link covered by a carbon layer (Si/SiO2@C) have been rationally synthesized through a facile zeolitic imidazolate framework template method. Within hybrid composites, the porous Si/SiO2 cross-link with an internal void can effectively mitigate volume changes and facilitate fast channels for Li+ during the charge–discharge process while the coated carbon layer not only can improve the electrical conductivity of the composites but also guarantees the structural integrity. As expected, the hollow Si/SiO2@C composite electrode has outstanding electrochemical properties including excellent reversible capacity (1280 mAh g–1 at 500 mA g–1 after cycled for 200 times) and superior rate performance (782 and 660 mAh g–1 at current densities of 3.2 and 6.4 A g–1, respectively). Considering the convenient preparation and naturally abundant of composites as well as their excellent electrochemical performance, the hollow Si/SiO2@C may hold great promise as advanced electrodes for next-generation LIBs

Filamentation induced by glucanase.

<p>A: Photomicrograph of hyphae induced by glucanase (100 µg/ml). The cells were grown in 5 ml YPD medium in BD 14 ml plastic tubes at 22°C without shaking for 18 h. Heat-inactivated glucanase was used as control at the same concentration. B: Mannosidase (100 µg/ml) did not induce hyphae under the same conditions as glucanase. Heat- inactivated mannosidase was used as control at the same concentration. C, D: Glucanase (100 µg/ml) induced all planktonic cells to grow as filaments in DMEM or RPMI media. Cells were incubated in respective media at 22°C without shaking for 18 h. Heat inactivated glucanase was used as control at the same concentration. E: Hypha formation was dependent on glucanase concentration in YPD medium. Cells were inoculated in YPD media containing 0.1–100 µg/ml of glucanase and incubated at 22°C without shaking for 18 h. F, G: Glucanase (100 µg/ml) enhanced filamentation at 30°C and 37°C in YPD medium. Cells were incubated in a water bath without shaking for 18 h. Filaments were longer than those at 22°C.</p

Farnesol effect on the yeast-hyphae transition induced by glucanase in YPD at 22°C.

<p>A: Farnesol (200 μmol) inhibits filamentation induced by glucanase (100 μg/ml). Methanol was used as vehicle control. Methanol did not affect <i>C. albicans</i> filamentation under this condition. B: Live-Dead cell viability staining assay. Live cells were stained with SYTO9 (green) and dead cells were stained with propidium iodide (red). Staining shows that hyphal inhibition of farnesol (200 μmol) presence of glucanase (100 μg/ml) is mediated by germ tube death (red). Methanol vehicle control did not affect the <i>C. albicans</i> viability.</p

Microscopic examination of glucanase-induced hyphae.

<p>A: Calcofluor white stain of serum –induced (10% FBS at 37°C) and glucanase-induced hyphae (YPD 22°C) of wild type organisms and <i>cht2</i> mutant. Glucanase-induced filaments of the wild type organisms did not stain as brightly with CFW compared to serum-induced hyphae. In addition, the first septum was located at the mother-bud neck, whereas in serum-induced hyphae, the first septum was located within the germ tube. In the <i>cht2</i> mutant, glucanase-induced filaments had a similar septal localization but the intensity of the CFW staining was indistinguishable from serum-induced hyphae (lower panel). B: Real-time RT-PCR of the CHT2 and CHT3 genes in glucanase-treated SC5314 cells. CHT2 gene expression was significantly increased in glucanase-induced hyphae (p<0.05). C: Hoechst 33258 DNA dye showing nuclear divisions of serum –induced and glucanase-induced filaments. Mitosis of serum –induced germ tubes took place within the tubes but mitosis of glucanase-induced hyphae was at the neck between mother cells and germ tubes. D: The biosensor reporter strain SGH284 was exposed to 100 µg/ml glucanase for 18 h at 22°C without shaking. GFP (green) is expressed both by yeast and hyphae under these conditions, since it is driven by a constitutive promoter (<i>TDH3</i>-<i>GFP</i>). In contrast, only filaments express RFP (red) driven by the <i>HWP1</i> promoter (<i>HWP1-RFP</i>), indicating that glucanase induces a hyphal response. E: Real-time RT-PCR of hypha-specific genes showed that <i>HWP1</i> gene expression was increased more than 2000 fold, <i>HYR1</i> more than 100 fold, <i>ALS3</i> more than 20 fold and <i>UME6</i> more than 40 fold, compared to controls treated by inactivated glucanase.</p

Hypha formation was absent in the efg1/cph1 double mutant, efg1 mutant and cek1 mutant.

<p>Effect of glucanase (100 µg/ml) or inactivated glucanase on filamentation of reference strain (A), <i>efg1/cph1</i> double mutant (B), <i>efg1</i> single mutant (C), <i>cph1</i> single mutant (D) and <i>cek1</i> single mutant (E). Only the <i>cph1</i> single mutant formed filaments when exposed to glucanase (D).</p

Thyroid function analysis after roxadustat or erythropoietin treatment in patients with renal anemia: a cohort study

This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia. The study involved 110 patients with renal anemia. Thyroid profile and baseline investigations were carried out for each patient. The patients were divided into two groups: 60 patients taking erythropoietin served as the control group (rHuEPO group) and 50 patients using roxadustat served as the experimental group (roxadustat group). The results indicated that there were no significant differences in serum total thyroxine (TT4), total triiodothyronine (TT3), free triiodothyronine (FT3), free thyroxine (FT4) or thyroid stimulating hormone (TSH) between the two groups at baseline. After treatment, TSH, FT3, and FT4 were significantly lower in the roxadustat group than in the rHuEPO group (p p p  Roxadustat may lead to a higher risk of thyroid dysfunction, including low TSH, FT3 and FT4, than rHuEPO in patients with renal anemia.</p

Table_2_Systematic Understanding of Anti-Aging Effect of Coenzyme Q10 on Oocyte Through a Network Pharmacology Approach.xlsx

BackgroundMaternal oocyte aging is strongly contributing to age-related decline in female fertility. Coenzyme Q10 (CoQ10) exerts positive effects in improving aging-related deterioration of oocyte quality, but the exact mechanism is unclear.ObjectiveTo reveal the system-level mechanism of CoQ10’s anti-aging effect on oocytes based on network pharmacology.MethodsThis study adopted a systems network pharmacology approach, including target identification, data integration, network and module construction, bioinformatics analysis, molecular docking, and molecular dynamics simulation.ResultA total of 27 potential therapeutic targets were screened out. Seven hub targets (PPARA, CAT, MAPK14, SQSTM1, HMOX1, GRB2, and GSR) were identified. Functional and pathway enrichment analysis indicated that these 27 putative targets exerted therapeutic effects on oocyte aging by regulating signaling pathways (e.g., PPAR, TNF, apoptosis, necroptosisn, prolactin, and MAPK signaling pathway), and are involved oxidation-reduction process, mitochondrion, enzyme binding, reactive oxygen species metabolic process, ATP binding, among others. In addition, five densely linked functional modules revealed the potential mechanisms of CoQ10 in improving aging-related deterioration of oocyte quality are closely related to antioxidant, mitochondrial function enhancement, autophagy, anti-apoptosis, and immune and endocrine system regulation. The molecular docking study reveals that seven hub targets have a good binding affinity towards CoQ10, and molecular dynamics simulation confirms the stability of the interaction between the hub targets and the CoQ10 ligand.ConclusionThis network pharmacology study revealed the multiple mechanisms involved in the anti-aging effect of CoQ10 on oocytes. The molecular docking and molecular dynamics simulation provide evidence that CoQ10 may act on these hub targets to fight against oocytes aging.</p

Table_1_Systematic Understanding of Anti-Aging Effect of Coenzyme Q10 on Oocyte Through a Network Pharmacology Approach.xlsx

BackgroundMaternal oocyte aging is strongly contributing to age-related decline in female fertility. Coenzyme Q10 (CoQ10) exerts positive effects in improving aging-related deterioration of oocyte quality, but the exact mechanism is unclear.ObjectiveTo reveal the system-level mechanism of CoQ10’s anti-aging effect on oocytes based on network pharmacology.MethodsThis study adopted a systems network pharmacology approach, including target identification, data integration, network and module construction, bioinformatics analysis, molecular docking, and molecular dynamics simulation.ResultA total of 27 potential therapeutic targets were screened out. Seven hub targets (PPARA, CAT, MAPK14, SQSTM1, HMOX1, GRB2, and GSR) were identified. Functional and pathway enrichment analysis indicated that these 27 putative targets exerted therapeutic effects on oocyte aging by regulating signaling pathways (e.g., PPAR, TNF, apoptosis, necroptosisn, prolactin, and MAPK signaling pathway), and are involved oxidation-reduction process, mitochondrion, enzyme binding, reactive oxygen species metabolic process, ATP binding, among others. In addition, five densely linked functional modules revealed the potential mechanisms of CoQ10 in improving aging-related deterioration of oocyte quality are closely related to antioxidant, mitochondrial function enhancement, autophagy, anti-apoptosis, and immune and endocrine system regulation. The molecular docking study reveals that seven hub targets have a good binding affinity towards CoQ10, and molecular dynamics simulation confirms the stability of the interaction between the hub targets and the CoQ10 ligand.ConclusionThis network pharmacology study revealed the multiple mechanisms involved in the anti-aging effect of CoQ10 on oocytes. The molecular docking and molecular dynamics simulation provide evidence that CoQ10 may act on these hub targets to fight against oocytes aging.</p