Psychoactive drugs citalopram and mirtazapine caused oxidative stress and damage of feeding behavior in Daphnia magna.

As the emerging contaminants, the environmental risks of drug-derived pollutants have attracted extensive attention. Citalopram (CTP) and mirtazapine (MTP) are commonly used as modern antidepressant drugs. Previous studies had proved that CTP and MTP entered the aquatic environment, but less reported the negative effects of the drugs on aquatic organisms. Herein, the effects on the feeding rate of Daphnia magna (D. magna) induced by psychotropic drugs CTP and MTP were investigated, which the possible mechanisms were analyzed with the oxidative stress and damage. Generally, the feeding rates of exposed D. magna under all concentrations of CTP and 1.03 mg/L of MTP were significantly decreased after exposure (p < 0.05 or p < 0.01). The inhibitory effect of CTP on the feeding rate of D. magna was time- and dose-dependent. The levels of reactive oxygen species (ROS) were particularly increased in D. magna after CTP and MTP exposure (p < 0.05 or p < 0.01). The level of antioxidant molecules glutathione S-transferase (GST) and the activity of scavenging enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) of D. magna were increased (p < 0.05 or p < 0.01). In consequence, the levels of malondialdehyde (MDA), protein carbonyl, and 8-hydroxydeoxyguanosine (8-OHdG) were increased (p < 0.05 or p < 0.01), which indicated oxidative damage caused by MTP and CTP, due to the imbalance of antioxidative stress system. These findings indicated that psychoactive drugs posed a high toxic threat to the aquatic organisms, and the aquatic environmental risks caused by using psychoactive drugs deserve more attention.

Silica microbeads capture fetal nucleated red blood cells for noninvasive prenatal testing of fetal ABO genotype.

ABO hemolytic disease of the newborn (ABO-HDN), which may cause neonatal jaundice and polycythemia, or even stillbirth or neonatal death, is widespread in China. Prenatal testing for the fetal ABO blood group can reduce unnecessary concerns or ensure prompt treatment. Herein, we presented a method to employ high-density silica microbeads (SiO2 MBs) for capturing fetal nucleated red blood cells (fnRBCs) in maternal peripheral blood, and we detected the ABO genotype of the fetus using these captured cells. We evaluated 52 patients using the SiO2 MBs. Among 26 pregnant women with type O blood, 8 (30.8%) of the fetuses had type A blood, 5 (19.2%) had type B blood, and 13 (50%) had type O blood. SRY genes were detected in all 27 male fetuses. This study represents a simple and effective method for noninvasive prenatal detection of the fetal ABO genotype. We believe that this method has great potential for noninvasive prenatal testing of the fetal Rh blood group and other fetal diseases as well.

A Retrospective Study on the Effects of Convalescent Plasma Therapy in 24 Patients Diagnosed with COVID-19 Pneumonia in February and March 2020 at 2 Centers in Wuhan, China.

BACKGROUND This retrospective study aimed to describe the effects of convalescent plasma therapy in 24 patients diagnosed with coronavirus disease 2019 (COVID-19) pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during February and March 2020 in Wuhan, China. MATERIAL AND METHODS The confirmation of SARS-CoV-2 infection was made by the reverse transcription-polymerase chain reaction test. We retrospectively analyzed the clinical data and laboratory test reports of patients with severe COVID-19 pneumonia who received a convalescent plasma transfusion. RESULTS A total of 24 patients with COVID-19 pneumonia who were transfused with ABO-compatible convalescent plasma were enrolled in the study. Convalescent plasma transfusion showed an effective clinical outcome in 14 of 24 patients (an effective rate of 58.3%). No patients had an adverse reaction to the transfusion. Compared with before convalescent plasma transfusion, the lymphocyte count after convalescent plasma transfusion increased to a normal level (median: 0.80×109/L vs. 1.12×109/L, P=0.004). Other laboratory indicators such as white blood cells, high-sensitivity C-reactive protein, procalcitonin, alanine aminotransferase, and aspartate transaminase showed a decreasing trend after transfusion. CONCLUSIONS This retrospective observational clinical study showed that convalescent plasma therapy could have beneficial effects on patient outcomes. Recently, regulatory authorization has been given for the use of convalescent plasma therapy, and clinical guidelines have been developed for the collection and use of convalescent plasma and hyperimmune immunoglobulin in patients with COVID-19.

Positive correlation between human exposure to organophosphate esters and gastrointestinal cancer in patients from Wuhan, China.

As kinds of endocrine disruptors, organophosphate esters (OPEs) pollution in the environment had received increasing attention recently. Food and water intake were two important exposure pathways for OPEs. However, the studies about the potential association between OPEs and gastrointestinal cancer were limited. This study investigated the possible association between OPEs and gastrointestinal cancer. All cancer patients were diagnosed with gastrointestinal cancer from a Grade 3 A hospital in Wuhan, China, while the control group was non-cancer healthy persons. The results showed that 6 OPEs were found in the control samples, while 8 in the samples from patients with gastrointestinal cancer. The detection frequencies of OPEs in gastrointestinal cancer patients were significantly higher than those in the control group (p < 0.05 or p < 0.01), except for triethyl phosphate (TEP) and tris (methylphenyl) phosphate (TMPP) in the gastric cancer group. The concentrations of OPEs in the control group were significantly lower than those in the gastric cancer group and colorectal cancer group (p < 0.01). In the control group and gastrointestinal cancer group, TEP was the dominant pollutant. Correlation analysis found that concentrations of TEP, tris(2-chloroisopropyl) phosphate (TCIPP), triphenyl phosphate (TPHP), TMPP, tris(2-ethylhexyl) phosphate (TEHP), and 2-ethylhexyl diphenyl phosphate (EHDPP) were associated with gastric cancer (p < 0.01), and concentrations of TEP, TCIPP, TPHP, TMPP and TEHP were associated with colorectal cancer (p < 0.01). A cluster analysis divided the 34 patients with gastric cancer and 40 patients with colorectal cancer in four groups. The results showed that the elderly male patients with gastric cancer were more sensitive to the exposure of EHDPP, while the TEP exposure was more sensitive to the relatively young gastrointestinal cancer patients. These findings indicated that OPEs might play a role in developing gastrointestinal cancer.

MGC29506 induces cell cycle arrest and is downregulated in gastric cancer.

The proapoptotic caspase adaptor protein (PACAP) is involved in cell-cycle regulation and promotes apoptosis. Both MGC29506 and PACAP are isoforms of the MGC29506 gene and are generated by differential splicing of the alternative splice-acceptor. In studying PACAP, we inadvertently constructed the eukaryotic expression vector MGC29506. At present, the function of the MGC29506 gene is largely unknown with the key exception of information obtained by bioinformatics. We studied the role of MGC29506 in gastric cancer cell proliferation, the cell cycle and apoptosis. In addition, we studied MGC29506 expression in gastric cancer patients and explored its significance. We found that the expression of MGC29506 in gastric cancer samples was lower than in samples from adjacent non-tumor tissues. We found that the MGC29506 protein was localized in the cell nucleus of AGS cells and inhibited their proliferation. Higher percentages of G0/G1 and S phase cells were induced by transfection with the MGC29506 gene than were induced by transfection with the negative control. We showed that cells transfected with MGC29506 were arrested at the G0/G1 and S phases of the cell cycle. However, we found no significant increases in apoptosis of cells transfected with MGC29506 compared with cells transfected with the negative control. Our results suggested that MGC29506 has the potential of functioning as a novel suppressor gene in gastric cancer. Downregulation of MGC29506 may also promote the progression of gastric cancer.

The risk and impact of organophosphate esters on the development of female-specific cancers: Comparative analysis of patients with benign and malignant tumors.

Environmental pollution has become a concern for public health. As endocrine disruptors, organophosphate esters (OPEs) causes many diseases via human exposure. However, there is limited research on the risk of OPE exposure to female-specific cancers. Blood measurements are biomarkers for chemical exposures by their definition. Thus, in the present study, 11 OPEs were analyzed in the plasma of patients with 4 female-specific tumors. 2-Ethylhexyl diphenyl phosphate (EHDPP) was detected at the highest levels in all groups. The Spearman correlation test results showed significantly positive correlations between some OPEs in each group, which indicated that those OPEs had similar sources and/or behaved similarly in the patients of each group. However, compared with different patient groups, obvious differences in the correlation results were noted, implying the differences in the metabolism of OPEs between different groups. The results of the correlation analysis showed that EHDPP concentration was associated with the risk of breast cancer (p < 0.05), while tri-n-butyl phosphate (TNBP), tris (methylphenyl) phosphate (TMPP), triphenyl phosphate (TPHP), and EHDPP concentrations were associated with the risk of cervical cancer (p < 0.05 or p < 0.01). These findings indicated that OPEs were associated with the risk of breast and cervical cancer.

Rapid thrombelastography predicts perioperative massive blood transfusion in patients undergoing coronary artery bypass grafting: A retrospective study.

Massive blood transfusion (MBT) is a relatively common complication of cardiac surgery, which is independently associated with severe postoperative adverse events. However, the value of using rapid thrombotomography (r-TEG) to predict MBT in perioperative period of cardiac surgery has not been explored. This study aimed to identify the effect of r-TEG in predicting MBT for patients undergoing coronary artery bypass grafting (CABG).This retrospective study included consecutive patients first time undergoing CABG at the Zhongnan Hospital of Wuhan University between March 2015 and November 2017. All the patients had done r-TEG tests before surgery. The MBT was defined as receiving at least 4 units of red blood cells intra-operatively and 5 units postoperatively (1 unit red blood cells from 200 mL whole blood).Lower preoperative hemoglobin level (P = .001) and longer cardiopulmonary bypass time (P = .001) were the independent risk factors for MBT during surgery, and no components of the r-TEG predicted MBT during surgery. Meanwhile, longer activated clotting time (P < .001), less autologous blood transfusion (P = .001), and older age (P = .008) were the independent risk factors for MBT within 24 hours of surgery.Preoperative r-TEG activated clotting time can predict the increase of postoperative MBT in patients undergoing CABG. We recommend the careful monitoring of coagulation system with r-TEG, which allows rapid diagnosis of coagulation abnormalities even before the start of surgery.

Presence of organophosphate esters in plasma of patients with hypertension in Hubei Province, China.

Organophosphate esters (OPEs) are widely used as fire retardants, so they are almost ubiquitous pollutants. Recent studies had found that OPEs were detectable in human blood samples. However, the studies on the presence of OPEs in hypertensive patients were limited. In this study, 12 OPEs were detected and analyzed in plasma samples collected from hypertensive patients (case group) and unpaid blood donors (control group). The values of ∑12 OPEs concentrations ranged from ND to 8.84 µg/L and ND to 20.11 µg/L in the case group and control group, respectively, with the average concentrations of 0.62 µg/L and 1.46 µg/L, respectively. Triethyl phosphate (TEP) was detected as the most abundant chemical in the case group while triphenyl phosphate (TPHP) in the control group. Correlation analysis showed that there was a significant correlation among OPEs. The correlation coefficients and principal component analysis (PCA) indicated different sources and/or metabolism existed between the case group and control group. Diastolic blood pressure (DBP) was associated with TEP concentration (p < 0.05) in hypertensive patients. Clustering analysis showed that a trend of OPEs exposure and hypertension. This study provided data on the composition profile of OPEs in plasma and human exposure to OPEs, which was the first to identify the association of OPEs with hypertension.

Screening and identification of RhD antigen mimic epitopes from a phage display random peptide library for the serodiagnosis of haemolytic disease of the foetus and newborn.

BACKGROUND: Identification of RhD antigen epitopes is a key component in understanding the pathogenesis of haemolytic disease of the foetus and newborn. Research has indicated that phage display libraries are useful tools for identifying novel mimic epitopes (mimotopes) which may help to determine antigen specificity. MATERIALS AND METHODS: We selected the mimotopes of blood group RhD antigen by affinity panning a phage display library using monoclonal anti-D. After three rounds of biopanning, positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA) and then sent for sequencing and peptides synthesis. Next, competitive ELISA and erythrocyte haemagglutination inhibition tests were carried out to confirm the inhibitory activity of the synthetic peptide. To evaluate the diagnostic performance of the synthetic peptide, a diagnostic ELISA was examined. RESULTS: Fourteen of 35 phage clones that were chosen randomly from the titering plate were considered to be positive. Following DNA sequencing and translation, 11 phage clones were found to represent the same peptide - RMKMLMMLMRRK (P4) - whereas each of the other three clones represented a unique peptide. Through the competitive ELISA and erythrocyte haemagglutination inhibition tests, the peptide (P4) was verified to have the ability to mimic the RhD antigen. The diagnostic ELISA for P4 proved to be sensitive (82.61%) and specific (88.57%). DISCUSSION: This study reveals that the P4 peptide can mimic RhD antigen and paves the way for the development of promising targeted diagnostic and therapeutic platforms for haemolytic disease of the foetus and newborn.

Erythrocyte-derived vesicles for circulating tumor cell capture and specific tumor imaging.

The precise diagnosis of cancer remains a great challenge; therefore, it is our research interest to develop safe, tumor-specific reagents. In this study, we designed nanovesicles derived from erythrocyte membranes; the nanovesicles are capable of recognizing tumor cells for both circulating tumor cell (CTC) capture and tumor imaging. The tumor-targeting molecules folic acid (FA) and fluorescein Cy5 were modified on the nanovesicle surface. The developed nanovesicles exhibit excellent tumor targeting ability both in vitro and in vivo for CTC capture and in tumor imaging. Compared with traditional immunomagnetic beads, the proposed nanovesicles are capable of avoiding non-specific adsorption as a derivative of red blood cells. Combined with a non-invasive means of micromanipulation, the nanometer-sized vesicles show a high purity of CTC capture (over 90%). In vivo, the nanovesicles can also be employed for efficient tumor imaging without obvious toxicity and side effects. In brief, the nanovesicles prepared herein show potential clinical application for integrated diagnosis in vitro and in vivo.

The associations between five polymorphisms of vascular endothelial growth factor and renal cell carcinoma risk: an updated meta-analysis.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a key mediator that plays an important role in angiogenesis, tumor growth, and tumor metastasis. The associations between five polymorphisms of VEGF (rs3025039, rs699947, rs10434, rs1570360, and rs2010963) and renal cell carcinoma (RCC) risk have been extensively investigated, but the currently available results are inconsistent and inconclusive. To obtain a more accurate assessment of the associations, we conducted a meta-analysis in this study. MATERIALS AND METHODS: Relevant studies were collected systemically from the following three electronic databases: MEDLINE, Web of Science, and CNKI (Chinese National Knowledge Infrastructure). Statistical analyses were performed using Review Manager 5.2 in a fixed- or random-effects model. Pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to establish the strength of associations. RESULTS: A total of eight case-control studies with 1,936 RCC cases and 2,770 controls fulfilling the inclusion criteria were selected for this meta-analysis. The pooled OR indicated that rs699947 polymorphism was significantly associated with RCC risk in all genetic models. A significant association was also found between the rs3025039 polymorphism and RCC risk in a homozygous model (TT vs CC: OR =1.38, 95% CI =1.11-1.72, P=0.004), a dominant model (CT+TT vs CC: OR =1.21, 95% CI =1.05-1.39, P=0.01), and a recessive model (TT vs CC+CT: OR =1.28, 95% CI =1.04-1.57, P=0.02). After a subgroup analysis of ethnicity in the allele contrast model of rs3025039 polymorphism, we found a significant relationship in the allele contrast model (T vs C: OR =1.21, 95% CI =1.05-1.40, P=0.007) in the Asian population. With regard to rs10434 polymorphism, significant association was observed only in a homozygous model (GG vs AA: OR =0.75, 95% CI =0.57-0.98, P=0.03). As to rs1570360 or rs2010963, we did not observe any relationship between the two polymorphisms and RCC risk in our study. CONCLUSION: Our meta-analysis confirmed the fact that rs699947, rs3025039, and rs10434 polymorphisms were significantly relevant to elevated RCC risk. In the meanwhile, this study also demonstrated that the allele contrast model of rs3025039 polymorphism was likely to be associated with risk of RCC in the Asian population.

Fast-melting tablets based on highly plastic granules.

Highly plastic granules that can be compressed into tablets at low pressure were developed to make fast-melting tablets (FMTs) by compression method. The highly plastic granules are composed of three components: a plastic material, a material enhancing water penetration, and a wet binder. One of the unique properties of the highly plastic granules is that they maintain a porous structure even after compression into tablets. The porous and plastic nature of the granules allows fast absorption of water into the compressed tablet for fast melting/dissolution of the tablet. The prepared tablets possess tablet strength and friability that are suitable for multi-tablet packages. The three-component highly plastic granules provide an effective way of making FMTs by compression.

Frosta: a new technology for making fast-melting tablets.

The fast-melting tablet (FMT) technology, which is known to be one of the most innovated methods in oral drug delivery systems, is a rapidly growing area of drug delivery. The initial success of the FMT formulation led to the development of various technologies. These technologies, however, still have some limitations. Recently, a new technology called Frosta (Akina) was developed for making FMTs. The Frosta technology utilises the conventional wet granulation process and tablet press for cost-effective production of tablets. The Frosta tablets are mechanically strong with friability of < 1% and are stable in accelerated stability conditions when packaged into a bottle container. They are robust enough to be packaged in multi-tablet vials. Conventional rotary tablet presses can be used for the production of the tablets and no other special instruments are required. Thus, the cost of making FMTs is lower than that of other existing technologies. Depending on the size, Frosta tablets can melt in < 10 s after placing them in the oral cavity for easy swallowing. The Frosta technology is ideal for wide application of FMTs technology to various drug and nutritional formulations.

Orally fast disintegrating tablets: developments, technologies, taste-masking and clinical studies.

Fast disintegrating tablets (FDTs) have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray-drying, moisture treatment, sintering, and use of sugar-based disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and clinical studies are also discussed.

A study of drug release from homogeneous PLGA microstructures.

The hydrogel template method was used to fabricate homogeneous drug-PLGA microparticles. Four drugs (felodipine, risperidone, progesterone, and paclitaxel) were loaded into the PLGA particles with the homogeneous size of 10microm, 20microm, and 50microm. The drug loading into the PLGA microparticles was 50% and higher. The felodipine-PLGA microstructures of four different sizes showed that the drug release kinetics is dependent on the total surface area available for drug release. The smaller the particle size, the release rate was faster. Two types of microparticles (10microm diameter and 10microm height, and 50microm diameter and 5microm height) showed zero-order release and complete release was observed within 2weeks. The release rate, however, was not exactly proportional to the surface area. Different drugs which were loaded into the same PLGA formulation showed different release profiles. The main difference was on the initial burst release. The overall release profile seems to be similar for different drugs, if the release profile is adjusted to eliminate the burst release. The initial burst release appears to be inversely related to the water-solubility of a drug, i.e., the lower the water-solubility of a drug, the higher the burst release. The hydrogel template method allowed preparation of homogeneous particles with predefined sizes with high drug loading. It allowed study on the effect of size and shape on the drug release kinetics. With the microparticles of homogeneous size and shape, the drug release kinetics can be projected based on the size of microparticles and water-solubility of a drug. The ability of making homogeneous particles is expected to provide better prediction and reproducibility of the drug release property of a given formulation.