ABSTRACT
Cardiovascular diseases (CVDs) are a leading factor driving mortality worldwide. Iron, an essential trace mineral, is important in numerous biological processes, and its role in CVDs has raised broad discussion for decades. Iron-mediated cell death, namely ferroptosis, has attracted much attention due to its critical role in cardiomyocyte damage and CVDs. Furthermore, ferritinophagy is the upstream mechanism that induces ferroptosis, and is closely related to CVDs. This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy, and the regulatory pathways and molecular targets involved in ferritinophagy, and to determine their roles in CVDs. Furthermore, we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs. Collectively, this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.
Subject(s)
Humans , Cardiovascular Diseases , Ferroptosis , Iron , Trace ElementsABSTRACT
Purpose@#This study assessed the correlation between Epstein-Barr virus (EBV) biomarkers and the eighth American Joint Committee on Cancer staging system and the prognostic values of IgG antibodies against replication and transcription activator (Rta-IgG), IgA antibodies against Epstein-Barr nuclear antigen 1, and BamH1 Z transactivator (Zta-IgA) in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. @*Materials and Methods@#Serum EBV antibody levels were measured by enzyme-linked immunosorbent assay in 435 newly diagnosed stage III-IVA NPC patients administered intensity-modulated radiation therapy±chemotherapy. The primary endpoint was progression-free survival (PFS). @*Results@#Rta-IgG and Zta-IgA levels were positively correlated with the N category and clinical stage. Patients with high Rta-IgG levels (> 29.07 U/mL) showed a significantly inferior prognosis as indicated by PFS (77% vs. 89.8%, p=0.004), distant metastasis–free survival (DMFS) (88.3% vs. 95.8%, p=0.021), and local recurrence-free survival (LRFS) (91.2% vs. 98.3%, p=0.009). High Rta-IgG levels were also significantly associated with inferior PFS and LRFS in multivariable analyses. In the low-level EBV DNA group (≤ 1,500 copies/mL), patients with high Rta-IgG levels had significantly inferior PFS and DMFS (both p < 0.05). However, in the high-level EBV DNA group, Rta-IgG levels were not significantly associated with PFS, DMFS, and LRFS. In the advanced T category (T3-4) subgroup, high Rta-IgG levels were also significantly associated with inferior PFS, DMFS, and LRFS (both p < 0.05). @*Conclusion@#Rta-IgG and Zta-IgA levels were strongly correlated with the TNM classification. Rta-IgG level was a negative prognostic factor in locoregionally advanced NPC patients, especially those with advanced T category or low EBV DNA level.
ABSTRACT
This study aims to investigate metabolic activities of psoralidin in human liver microsomes( HLM) and intestinal microsomes( HIM),and to identify cytochrome P450 enzymes( CYPs) and UDP-glucuronosyl transferases( UGTs) involved in psoralidin metabolism as well as species differences in the in vitro metabolism of psoralen. First,after incubation serial of psoralidin solutions with nicotinamide adenine dinucleotide phosphate( NADPH) or uridine 5'-diphosphate-glucuronic acid( UDPGA)-supplemented HLM or HIM,two oxidic products( M1 and M2) and two conjugated glucuronides( G1 and G2) were produced in HLM-mediated incubation system,while only M1 and G1 were detected in HIM-supplemented system. The CLintfor M1 in HLM and HIM were 104. 3,and57. 6 μL·min~(-1)·mg~(-1),respectively,while those for G1 were 543. 3,and 75. 9 μL·min~(-1)·mg~(-1),respectively. Furthermore,reaction phenotyping was performed to identify the main contributors to psoralidin metabolism after incubation of psoralidin with NADPH-supplemented twelve CYP isozymes( or UDPGA-supplemented twelve UGT enzymes),respectively. The results showed that CYP1 A1( 39. 5 μL·min~(-1)·mg~(-1)),CYP2 C8( 88. 0 μL·min~(-1)·mg~(-1)),CYP2 C19( 166. 7 μL·min~(-1)·mg~(-1)),and CYP2 D6( 9. 1 μL·min~(-1)·mg~(-1)) were identified as the main CYP isoforms for M1,whereas CYP2 C19( 42. 0 μL·min~(-1)·mg~(-1)) participated more in producing M2. In addition,UGT1 A1( 1 184. 4 μL·min~(-1)·mg~(-1)),UGT1 A7( 922. 8 μL·min~(-1)·mg~(-1)),UGT1 A8( 133. 0 μL·min~(-1)·mg~(-1)),UGT1 A9( 348. 6 μL·min~(-1)·mg~(-1)) and UGT2 B7( 118. 7 μL·min~(-1)·mg~(-1)) played important roles in the generation of G1,while UGT1 A9( 111. 3 μL·min~(-1)·mg~(-1)) was regarded as the key UGT isozyme for G2. Moreover,different concentrations of psoralidin were incubated with monkey liver microsomes( MkLM),rat liver microsomes( RLM),mice liver microsomes( MLM),dog liver microsomes( DLM) and mini-pig liver microsomes( MpLM),respectively. The obtained CLintwere used to evaluate the species differences.Phase Ⅰ metabolism and glucuronidation of psoralidinby liver microsomes showed significant species differences. In general,psoralidin underwent efficient hepatic and intestinal metabolisms. CYP1 A1,CYP2 C8,CYP2 C19,CYP2 D6 and UGT1 A1,UGT1 A7,UGT1 A8,UGT1 A9,UGT2 B7 were identified as the main contributors responsible for phase Ⅰ metabolism and glucuronidation,respectively. Rat and mini-pig were considered as the appropriate model animals to investigate phase Ⅰ metabolism and glucuronidation,respectively.
Subject(s)
Animals , Dogs , Mice , Rats , Benzofurans , Coumarins , Glucuronides , Glucuronosyltransferase/metabolism , Kinetics , Microsomes, Liver/metabolism , Phenotype , Species Specificity , Swine , Swine, Miniature/metabolismABSTRACT
Objective · To investigate the effect of hyperthermic intraperitoneal chemotherapy on postoperative gastrointestinal function recovery in patients with gastrointestinal cancer. Methods · Sixty-two cases of gastrointestinal cancer patients were enrolled who accepted cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Department of General Surgery, Shanghai Public Health Clinical Center, Fudan University, from July 2014 to June 2017. The gastrointestinal function of patients were evaluated according to the I-FEED scoring system. The patients were divided into normal recovery group (I-FEED score＜6, n=38) and delayed recovery group (I-FEED score ≥ 6, n=24). Univariate and multivariate Logistic analyses were performed on characteristic factors that may affect the recovery of postoperative gastrointestinal function including gender, age, presence of diabetes, preoperative albumin, and so on. Results · There were significantly differences in the preoperative serum albumin level (P=0.040), intraoperative bleeding (P=0.044), the time of extraction of the peritoneal cavity drainage tube (P=0.026), the time of urethral tube extraction (P=0.021) and the time of hospitalization (P=0.017) in the two groups of patients with normal or delayed gastrointestinal function recovery. Multivariate Logistic regression results suggested that preoperative serum albumin level may be beneficial for the recovery of postoperative gastrointestinal function (OR=0.84, 95％ CI 0.17-4.27, P=0.041).Conclusion · The preoperative serum albumin level can be used as an independent predictor of postoperative gastrointestinal functional recovery in patients with gastrointestinal cancer after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy.
ABSTRACT
OBJECTIVE: To investigate the feasibility of abdominal surgical resection of intracardiac leiomyomatosis.METHODS: The clinical data of 4 cases of intracardiac leiomyomatosis performed in zhongshan Hospital,Fudan University from December 2015 to August 2017 were analyzed retrospectively. RESULTS: Four patients underwent onestage surgery through an abdominal approach,without death. The operative time was 185-420(315.3 ± 86.4) min.Extracorporeal circulation time was 22-175(71.8±60.4)min and blood loss was 600-3000(1475.0±941.7)mL. Acute renal failure occurred in one of the patients after operation,the rest had no surgical complications. After 8-26 months of follow-up,there was no sign of recurrence and metastasis. CONCLUSION: One-stage surgery of intracardiac leiomyomatosis through an abdominal approach is feasible. But,how to determine the indications of surgery remains to be further explored and studied.
ABSTRACT
Objective: To establish a new specific and high-throughput method for CYP450 quantification, and to investigate the effect of drugs on rat liver CYP450 using Salvia miltiorrhiza and Panax ginseng as tool drugs. Methods: Mass spectrometry with multiple reaction monitoring (MRM) was applied to quantify nine rat liver enzyme CYP450 isoforms from the rat model with S. miltiorrhiza and P. ginseng. With QconCAT heavy peptides as internal standard, we aimed to assess the effects of S. miltiorrhiza and P. ginseng on CYP450 isoforms. Results: The relative standard deviation and relative error of this method were less than 5.9% and 6.8%, respectively, with good linearity (r2>0.9). Nine CYP450s isoforms (CYP1A1, CYP1A2, CYP2B1, CYP2B2, CYP2C6, CYP2C11, CYP3A1, CYP3A2, and CYP17A1) in rat liver microsome treated with S. miltiorrhiza and P. ginseng were also quantified. Compared with the control, S. miltiorrhiza downregulated the expression levels of CYP1A1, CYP2B2, CYP3A2, CYP2C11, and CYP17A1, while upregulated CYP1A2 and CYP2B1. For the effects of P. ginseng, the expression of CYP1A1 and CYP2B2 was decreased, while CYP1A2, CYP2B1, CYP3A2, CYP2C11, and CYP17A1 were increased. Conclusion: We successfully construct a method with MRM to quantify rat liver CYP450 isoforms. And we firstly quantify CYP2B1, CYP2B2, and CYP17A1 in rat liver. The results reveal the regulation of CYP450 by S. miltiorrhiza and P. ginseng, which could provide clinical application for drug compatibility in practice, and avoid adverse drug reactions.
ABSTRACT
Acteoside (verbascoside), a phenylethanoid glycoside widely distributed in various plants, has been shown to have potential activity against Alzheimer's disease, attracting great attentions recently. The present study was designed to develop a selective and sensitive LC-MS/MS method for the determination of acteoside in biological samples and carry our a pharmacokinetic (PK) study in beagle dogs. The PK parameters were calculated using non-compartmental models. Following a single-dose oral administration, acteoside was rapidly absorbed and eliminated, with Tmax being between 30 to 45 min and terminal half-life being about 90 min. The areas under the time-concentration curve (AUC) were 47.28 ± 8.74, 87.86 ± 13.33, and 183.14 ± 28.69 mg · min · L(-1) for oral administration of 10, 20, and 40 mg · kg(-1), respectively, demonstrating that the exposure of acteoside proportionally increased with the dose level. The absolute bioavailability of acteoside was around 4%. For all the PK parameters, there were large variations between individual dogs. In conclusion, the pharmacokinetic characteristics observed in the present study can be of great value to help better understand the pharmacological properties of acteoside and to improve the outcome of its clinical use.
Subject(s)
Animals , Dogs , Female , Male , Administration, Intravenous , Administration, Oral , Alzheimer Disease , Drug Therapy , Area Under Curve , Biological Availability , Chromatography, High Pressure Liquid , Glucosides , Pharmacokinetics , Intestinal Absorption , Phenols , Pharmacokinetics , Plant Extracts , Pharmacokinetics , Tandem Mass Spectrometry , Verbenaceae , ChemistryABSTRACT
The aim of this study was to explore cytogenetic characteristics of acute promyelocytic leukemia (APL) and compare the interphase fluorescence in situ hybridization (I-FISH) with conventional cytogenetic (CC) analysis. A total number of 157 APL patients were recruited in this study, and the I-FISH and CC were applied to analyze cytogenetic features. Chromosome samples of bone marrow cells were prepared by short-term culture. Out of all 157 cases, 136 were observed with CC assay, 66 with I-FISH, of which 45 samples were analyzed with both methods. The results showed that among all 136 CC samples, t(15;17)(q22;q21) was found in 120 cases, of which 107 cases was isolated t(15;17)(q22;q21) abnormality, 13 cases was complex abnormalities and 12 case without mitotic figure. Among all 66 cases of I-FISH group, PMI/RARα fusion gene was found in 64 cases (97.0%), suggesting that I-FISH group was more sensitive than CC group (p = 0.041). It is concluded that combination of I-FISH and CC techniques plays a pivotal role for diagnosis and detection of minimal residual disease in APL.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Cytogenetic Analysis , Methods , In Situ Hybridization, Fluorescence , Methods , Karyotyping , Leukemia, Promyelocytic, Acute , Diagnosis , GeneticsABSTRACT
This study was aimed to explore the effect and adverse reaction of cyclosporine A (CsA) in treatment of pancytopenia without reticulocyte decrease but with elevated LDH. 10 patients were selected according to our standards and were treated by CsA. The curative effect and adverse reaction of patients were evaluated by following up for 6 - 116 months. The effect of CsA in the maintenance treatment of AA patient with an obvious rise of LDH was illustrated by means of typical case. The results indicated that 10 patients had different diagnosis, but had similar clinical and laboratory characteristics. Among them, 9 patients showed a relatively good curative reaction to CsA. Treatment of 1 patient was stopped because of pneumonia tuberculosis. It is concluded that the elevated LDH without reticuleocyte decrease may be a biomarker to predict the curative reaction to CsA for patients with pancytopenia. Selectively treating pancytopenia with CsA can obtain a higher curative reaction and maintenance treatment with CsA is an important factor for reducing recurrence of this disease.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Cyclosporine , Therapeutic Uses , Immunosuppressive Agents , Therapeutic Uses , Pancytopenia , Drug Therapy , Treatment OutcomeABSTRACT
<p><b>AIM</b>To rapidly separate and determine the nucleosides from natural and cultured Cordyceps kyushuensis Kob., and to compare the content of cordycepin and adenosine in different parts of Cordyceps kyushuensis Kob., which are the main nucleoside active components in medicinal fungus belonging to Cordyceps (Fr.) Link.</p><p><b>METHODS</b>The nucleosides were separated and determined by the high performance capillary zone electrophoresis (CZE). Beckman P/ACE system MDQ apparatus equipped with a PDA detector and a uncoated fused-silica capillary (41 cm x 45 microns ID, 30 cm effective length) were used. The experimental conditions were as follows: the running buffer was borax solution (adjust to pH 9.4 with sodium hydroxide), applied voltage was 20 kV, operated temperature was 20 degrees C and the detector wavelength was 258 nm. The content of cordycepin and adenosine in the fruiting body, stroma and host worm of natural and cultured C. kyushuensis were respectively investigated and quantitatively analyzed.</p><p><b>RESULTS</b>There are at least 8 kinds of nucleoside or nitrogen base in Cordyceps kyushuensis Kob. The content of cordycepin which is a bio-active substance with anti-tumor activity in C. kyushuensis is significantly higher than that in C. sinensis and C. militaris, and furthermore the cordycepin in the cultured C. kyushuensis is notably higher than the natural one. Adenosine was mainly found from the stroma of C. kyushuensis, While the cordycepin content is high in the stroma of both natural and cultured C. kyushuensis as well as in the host worm of the cultured one.</p><p><b>CONCLUSION</b>There are some differences about the nucleoside components between the natural and cultured C. kyushuensis and between the different parts of them. With a high cordycepin content, C. kyushuensis should have a considerable medicinal potential.</p>
Subject(s)
Animals , Adenosine , Cordyceps , Chemistry , Classification , Deoxyadenosines , Lepidoptera , Chemistry , Microbiology , NucleosidesABSTRACT
Flammulin, an anti-tumor protein, was purified from the aqueous extract of basidiomes of Flammulina Velutipes. Purified flammulin emulsified with Freund's adjuvant was injected subcutaneously into New Zealand white rabbits. After several immune enhancements, these animals were bled and sera were separated. Antiserum against flammulin in Western blots were applied to determine if flammulin be present in the liquid state culture or fruiting body. The result showed that anti-flammulin serum could recognize the aqueous extract of fruiting body in SDS-PAGE gels under the reducing conditions, no flammulin was detected in mycelia of Flammulina Velutipes.