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1.
Eur J Pharm Biopharm ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32006605

RESUMO

We have observed an interesting phenomenon in which grinding of freeze-dried monoclonal antibody X (mAb-X) formulation powder resulted to significant protein sub-visible particles (SbVPs) in the reconstituted liquid, which could only be observed by sensitive particle analytical methods such as MFI and DLS. Effects of grinding temperature and the free radical scavengers methionine and 3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidin-yloxy free radical (CTPO) on the formation of SbVPs were also evaluated. Free radicals were observed by EPR and the amount of free radicals was correlated to the sample temperature prior to grinding. Formation of SbVPs could be partially inhibited by methionine and CTPO. The amount of SbVPs formed was dependent on the amount of free radicals / sample temperature prior to grinding. At higher temperatures, more free radicals and SbVPs formed. Other than the previously known protein degradation due to high temperature formed during mechanical grinding, we propose an unreported and supplementary mechanism, i.e., the formation of free radicals (i.e., due to break of C-O or C-S bonds) in the dried state during mechanical grinding, leading to protein particle formation in the reconstituted solution. Our observation suggested that mechanical grinding of protein powder should be avoided or used cautiously (i.e., grinding temperature, strength and time) and the effects on radical and particle formation be fully evaluated.

2.
Cancer Imaging ; 20(1): 17, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041672

RESUMO

BACKGROUND: To explore the relationship between the lymph node status and preoperative computed tomography images texture features in pancreatic cancer. METHODS: A total of 155 operable pancreatic cancer patients (104 men, 51 women; mean age 63.8 ± 9.6 years), who had undergone contrast-enhanced computed tomography in the arterial and portal venous phases, were enrolled in this retrospective study. There were 73 patients with lymph node metastases and 82 patients without nodal involvement. Four different data sets, with thin (1.25 mm) and thick (5 mm) slices (at arterial phase and portal venous phase) were analysed. Texture analysis was performed by using MaZda software. A combination of feature selection algorithms was used to determine 30 texture features with the optimal discriminative performance for differentiation between lymph node positive and negative groups. The prediction performance of the selected feature was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: There were 10 texture features with significant differences between two groups and significance in ROC analysis were identified. They were WavEnLH_s-2(wavelet energy with rows and columns are filtered with low pass and high pass frequency bands with scale factors 2) from wavelet-based features, 135dr_LngREmph (long run emphasis in 135 direction) and 135dr_Fraction (fraction of image in runs in 135 direction) from run length matrix-based features, and seven variables of sum average from coocurrence matrix-based features (SumAverg). The ideal cutoff value for predicting lymph node metastases was 270 for WavEnLH_s-2 (positive likelihood ratio 2.08). In addition, 135dr_LngREmph and 135dr_Fraction were correlated with the ratio of metastatic to examined lymph nodes. CONCLUSIONS: Preoperative computed tomography high order texture features provide a useful imaging signature for the prediction of nodal involvement in pancreatic cancer.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32043718

RESUMO

We report an organic crystal, i.e. 4,4'-bis(N-carbazolyl)-1,1'-biphenyl ( p CBP ), which exhibits time-dependent afterglow color from blue to orange over 1 s. Both experimental and computational data agree that the color evolution results from well-separated, long-persistent thermally activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP) with different but comparable decay rates. TADF is enabled by a small S 1 -T 1 energy gap of 0.7 kcal/mol. The good separation of TADF and RTP is due to a 11.8 kcal/mol difference in the S 0 energies of the S 1 and T 1 structures indicating that in addition to excited-state properties, tuning ground-state ones is also important for luminescence properties. This afterglow color evolution of p CBP allows its applications in anticounterfeiting and data encryption with high security levels.

4.
Perit Dial Int ; : 896860819896134, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-32063187

RESUMO

BACKGROUND: To investigate the value of effluent lipopolysaccharide (LPS) for early detection of gram-negative peritonitis (GNP) in peritoneal dialysis (PD) patients. METHODS: PD-related peritonitis episodes occurring between January 2016 and December 2018 were included in the study. Effluent LPS and the other infectious parameters were measured at peritonitis presentation, and peritonitis was categorized as GNP, non-GNP, and culture-negative peritonitis. Receiver operating characteristic (ROC) analysis was employed to evaluate the efficacy of effluent LPS to distinguish GNP. RESULTS: A total of 161 peritonitis episodes were analyzed, including 49 GNP episodes and 82 non-GNP episodes. In contrast with non-GNP, GNP presented with higher effluent leukocyte count (3236 (1497-6144) vs. 1904 (679-4071) cell mm-3, p = 0.008), increased effluent LPS (1.552 (0.502-2.500) vs. 0.016 (0.010-0.030) EU mL-1, p < 0.001), lower blood leukocyte count (9.95 ± 3.18 vs. 11.56 ± 4.37 × 109 L-1, p = 0.017), greater neutrophil predominance (87.1 ± 4.6% vs. 83.4 ± 7.7%, p = 0.001), and greater "procalcitonin" (PCT, 4.90 (2.20-12.60) vs. 1.00 (0.51-4.07) µg L-1, p < 0.001). It took 5.2 ± 3.1 h to report the results of effluent LPS. Effluent LPS cutoff value of >0.035 EU mL-1 showed an area under the ROC curve of 0.972 (95% CI 0.951-0.994, p < 0.001) in differentiating GNP from non-GNP with a sensitivity of 100% and a specificity of 80.5%, and its joint utilization with PCT further increased the specificity (91.4%) to discriminate GNP. CONCLUSIONS: PD effluent LPS could be an applicable early marker of gram-negative organism-related peritonitis in PD patients.

5.
J Pharm Biomed Anal ; 180: 113078, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31911286

RESUMO

The occurrence of chronic obstructive pulmonary disease (COPD) will lead to physiological and pathological variations and endogenous metabolic disorders. A traditional Chinese medicine formula, HuaTanJiangQi decoction (HTJQ), exhibits an unambiguous therapeutic effect on COPD in China. Nevertheless, the mechanism of its therapeutic effect on COPD is not clear. With this purpose, pulmonary function, histopathological and the inflammatory factors in bronchoalveolar lavage fluid (BALF) in rats model of COPD were investigated. Then, ultra high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) analysis and multivariate statistical analysis were used to further reveal the mechanism of HTJQ therapeutic effect on COPD via metabolomics study. The results showed that the characteristics of lung tissues were significantly reversed, the concentration of LTB4 and LTC4 were gradually decreased, and the lung function began to recover after HTJQ treatment. These typical indicators of COPD in HTJQ intervention group were reversed similar to the control group, suggested that HTJQ has a therapeutic effect on COPD. Moreover, 32 dysregulated metabolites, including Thromboxane a2, Sphingosine 1-phosphate, PC(18:2(9Z,12Z)/18:1(11Z)), Leukotriene B4, Glutathione, Arachidonic acid, Sphingosylphosphocholine acid, N-Acetyl-leukotriene e4, Lysopc(18:1(11Z)), L-Cysteine, and Guanosine diphosphate. All the altered metabolites were associated with the onset and development of COPD, and involved in glycerophospholipid metabolism, sphingolipid metabolism, glutathione metabolism, and arachidonic acid metabolism, which were significantly changed in rats model with COPD. Generally, these findings provide a systematic view of metabolic changes linked to the onset and development of COPD, also indicated that HTJQ could provide satisfactory therapeutic effects on COPD and metabolomics study can be utilized to further understand the molecular mechanisms.

6.
ACS Appl Mater Interfaces ; 12(4): 4333-4342, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31935068

RESUMO

The abuse of antibiotics resulted in the emergence of antibiotics-resistant bacteria, which has raised a great social concern together with the impetus to develop effective antibacterial materials. Herein, the synthesis of biocompatible enzyme-responsive Ag nanoparticle assemblies (ANAs) and their application in the high-efficiency targeted antimicrobial treatment of methicillin-resistant Staphylococcus aureus (MRSA) have been demonstrated. The ANAs could collapse and undergo stable/collapsed transition on approaching MRSA because of the serine protease-like B enzyme proteins (SplB)-triggered decomposition of the branched copolymers which have been employed as the macrotemplate in the synthesis of responsive ANAs. This transition contributed greatly to the high targeting affinity and efficiency of ANAs to MRSA. The minimum inhibitory concentration and minimum bactericidal concentration against MRSA were 2.0 and 32.0 µg mL-1, respectively. Skin wound healing experiments confirmed that the responsive ANAs could serve as an effective wound dressing to accelerate the healing of MRSA infection.

7.
Clin Cancer Res ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996389

RESUMO

PURPOSE: Gastrointestinal cancers remain areas of high unmet need despite advances in targeted- and imumunotherapies. Here we demonstrate potent, tumor selective efficacy with PF-07062119, a T-cell engaging CD3-bispecific targeting tumors expressing GUCY2C, which is expressed widely across CRC and other gastrointestinal malignancies. Additionally, to address immune evasion mechanisms, we explore combinations with immune checkpoint blockade agents, and with anti-angiogenesis therapy. EXPERIMENTAL DESIGN: PF-07062119 activity was evaluated in vitro in multiple tumor cell lines, and in vivo in established subcutaneous and orthotopic human CRC xenograft tumors with adoptive transfer of human T cells. Efficacy was also evaluated in mouse syngeneic tumors using human CD3ε transgenic mice. Immunohistochemistry and mass cytometry were performed to demonstrate drug biodistribution, recruitment of activated T cells, and to identify markers of immune evasion. Combination studies were performed with anti-PD-1/PD-L1 and anti-VEGF antibodies. Toxicity and pharmacokinetic studies were done in cynomolgus macaque. RESULTS: We demonstrate that GUCY2C-positive tumors can be targeted with an anti-GUCY2C/anti-CD3ε bispecific, with selective drug biodistribution to tumors. PF-07062119 showed potent T-cell mediated in vitro activity and in vivo efficacy in multiple CRC human xenograft tumor models, including KRAS and BRAF mutant tumors, as well as in the immunocompetent mouse syngeneic tumor model. PF-07062119 activity was further enhanced when combined with anti-PD-1/PD-L-1 treatment or in combination with anti-angiogenic therapy. Toxicity studies in cynomolgus indicated a monitorable and manageable toxicity profile. CONCLUSION: These data highlight the potential for PF-07062119 to demonstrate efficacy and improve patient outcomes in CRC and other gastrointestinal malignancies.

8.
Neurol Sci ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31897952

RESUMO

OBJECTIVE: This is the first cross-region epidemiological study of myasthenia gravis (MG) in China. We estimated the incidence, prevalence, and medical costs of MG in southern China and explored the differences between the southern and northern Chinese populations. METHODS: We collected and analyzed records from 20 hospitals in the southern city, Guangzhou, 13 hospitals in the northern city, Harbin, and two healthcare insurance systems: job based and residence based in Guangzhou during 2000-2017. RESULTS: (1) The estimated annual incidence of MG was 1.55-3.66 per 100,000, and the estimated prevalence of MG was 2.19-11.07 per 100,000 in southern China based on insurance records. (2) The proportion of hospitalized MG patients in the south-based hospital records was three times as high as that in the north-based hospital records. (3) Female MG prevalence was significantly higher than male MG prevalence in Guangzhou, while the similar gender difference in Harbin was not statistically significant due to higher variation in earlier years. (4) The average expense was $35-42 for each outpatient service and $2526-2673 for each hospitalization expense in the south. (5) Contrary to the increase of insurance-based estimate of MG prevalence, the proportion of hospitalized MG patients did not increase over the years, suggesting rising awareness and utilization of health insurance. CONCLUSIONS: The southern MG population had a significantly higher prevalence and a lower response threshold to medication than the northern MG population. These results are calling for further investigations on the genetic, cultural, and environmental variations of the Chinese MG populations between north and south.

9.
Sci Total Environ ; 712: 136502, 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-31931197

RESUMO

What the extent of meteorological drought could trigger the corresponding hydrological drought with different levels? This question is an important topic in the field of drought propagation, which however has not been resolved. Therefore, a novel model based on a Bayesian network was proposed to address this issue in this study. In this model, the drought pooling and excluding methods were applied to eliminate minor drought events. A drought matching approach based on drought propagation time was proposed to achieve the one by one matching between different types of drought. Moreover, based on the matched drought events and the copula-based conditional probability model, the drought propagation thresholds of meteorological drought for triggering hydrological drought at various levels were determined. In addition, the interval conditional probability was calculated to further explore the sensitivity of hydrological drought response to different meteorological drought conditions. Furthermore, the propagation ratio was proposed to characterize the differences of drought propagation threshold among various regions. The Wei River Basin was selected as a case study. Results indicated that the results of drought propagation threshold were reliable and accurate. The increase of interval conditional probability showed a typical S-curve, which can intuitively obtain the probability of hydrological drought occurrence at different levels under specific meteorological drought condition, so as to effectively guide drought preparedness and mitigation. The propagation ratio can describe the overall resistance of the basin to meteorological drought, and it mainly depended on the meteorological and underlying surface conditions as well as groundwater supply.

10.
J Cell Mol Med ; 24(3): 2123-2134, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31957179

RESUMO

Fibroblast growth factor receptor-like 1 (FGFRL1), a member of the FGFR family, has been demonstrated to play important roles in various cancers. However, the role of FGFRL1 in small-cell lung cancer (SCLC) remains unclear. Our study aimed to investigate the role of FGFRL1 in chemoresistance of SCLC and elucidate the possible molecular mechanism. We found that FGFRL1 levels are significantly up-regulated in multidrug-resistant SCLC cells (H69AR and H446DDP) compared with the sensitive parental cells (H69 and H446). In addition, clinical samples showed that FGFRL1 was overexpressed in SCLC tissues, and high FGFRL1 expression was associated with the clinical stage, chemotherapy response and survival time of SCLC patients. Knockdown of FGFRL1 in chemoresistant SCLC cells increased chemosensitivity by increasing cell apoptosis and cell cycle arrest, whereas overexpression of FGFRL1 in chemosensitive SCLC cells produced the opposite results. Mechanistic investigations showed that FGFRL1 interacts with ENO1, and FGFRL1 was found to regulate the expression of ENO1 and its downstream signalling pathway (the PI3K/Akt pathway) in SCLC cells. In brief, our study demonstrated that FGFRL1 modulates chemoresistance of SCLC by regulating the ENO1-PI3K/Akt pathway. FGFRL1 may be a predictor and a potential therapeutic target for chemoresistance in SCLC.

11.
Bioresour Technol ; 297: 122447, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31784247

RESUMO

White rot fungi using P. sajor-caju and T. versicolor was examined to pretreat raw champost (lignin-rich) and oyster champost (cellulose-rich) for enhancement of fermentative volatile fatty acid (VFA) production. Results showed that the efficiency of pretreatment and VFA production was influenced by the fungal strains and substrates. P. sajor-caju pretreatment showed preferential lignin degradation on raw champost and obtained the maximum VFA yield (203 ± 9 mg COD/g VSadded), which increased by 60% and 74% compared to that of control and unpretreated champost, respectively. For cellulose-rich oyster champost, however, fungal pretreatment decreased VFA yield compared to unpretreated champost. Further mechanisms analysis demonstrated the two strains grow and secreted ligninolytic enzymes, which substantially influenced the characteristics of two champosts such as cellulose/lignin ratio and morphology in different extents. P. sajor-caju was highly efficient to lignin-rich champost on selectively degrading lignin and further enhancing digestibility such as VFA production.


Assuntos
Agaricales , Anaerobiose , Ácidos Graxos Voláteis , Fermentação , Fungos , Lignina
12.
Toxicon ; 173: 62-67, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759921

RESUMO

Amanita neoovoidea (genus Amanita Pers.) poisoning leads to acute renal failure. Here, we present seven case reports of acute renal failure with acute hepatic failure due to ingestion of A. neoovoidea. Clinical manifestations included gastrointestinal symptoms 1-72 h after ingestion; elevation of renal parameters and blood uric acid, blood urea nitrogen, and creatinine levels; a few abnormal hepatic parameters, primarily albumin decrease and alanine aminotransferase increase; and elevation of zymogram parameters such as cholinesterase and lactate dehydrogenase. To determine whether the hepatic/renal lesions were caused by amanitins, we analyzed the blood and urine samples of patients and specimens of poisonous mushrooms. Morphological and molecular biological analyses indicated that the mushroom was A. neoovoidea. However, no amatoxins and phallotoxins were detected in its basidiomata.

13.
ACS Chem Neurosci ; 11(2): 191-196, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31799825

RESUMO

Dementia frequently occurs in Down syndrome (DS) patients, and early intervention is important in its management. We have previously demonstrated a positive correlation of plasma ß-amyloid Aß42 levels and negative correlations of Aß40 and tau levels with dementia in DS. In this study, we examined more cases and constructed composite scores with both tau and amyloids to correlate with dementia in DS. Plasma Aß42, Aß40, and tau proteins were measured by an immunomagnetic reduction assay in DS patients. Data were randomly and repeatedly split into training and validating sets, and logistic regression was applied to calculate the area under the curve (AUC) for each biomarker. A total of 73 DS patients (among them, 23 had neurodegeneration) and 77 controls were recruited. In DS patients without dementia, plasma Aß40 and tau levels were highly elevated, but Aß42 levels were lower than those of the healthy controls. DS patients with dementia, compared with DS patients with no dementia, had a large decline in Aß40 and tau but a rise in Aß42. For biomarker scores correlating with dementia, Aß40 revealed an AUC of 0.912; the composite score of Aß40 × tau revealed an AUC of 0.953; and a combined composite score of 0.1 for Aß40 × Tau +0.9 Tau × Aß40/Aß42 achieved the highest AUC of 0.965. Therefore, composite biomarker scores including both plasma tau and ß-amyloid levels correlate with dementia in DS better than using individual biomarker scores. The pattern of tau decline and Aß42 rise in DS patients with dementia are also different from previous findings in Alzheimer's disease.

14.
J Agric Food Chem ; 68(1): 17-32, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31809036

RESUMO

Weeds had caused significant loss for crop production in the process of agriculture. Herbicides have played an important role in securing crop production. However, the high reliance on herbicides has led to environmental issues as well as the evolution of herbicide resistance. Thus, there is an urgent need for new herbicides with safer toxicological profiles and novel modes of action. Actinomycetes produce very diverse bioactive compounds, of which some show potent biopesticidal activity. The herbicidal secondary metabolites from actinomycetes can be classified into several groups, such as amino acids, peptides, nucleosides, macrolides, lactones, amide, amines, etc., some of which have been successfully developed as commercial herbicides. The structure diversity and evolved biological activity of secondary metabolites from actinomycetes can offer opportunities for the development of both directly used bioherbicides and synthetic herbicides with new target sites, and thus, this review focuses on the structure, herbicidal activity, and modes of action of secondary metabolites from actinomycetes.


Assuntos
Actinobacteria/química , Herbicidas/química , Herbicidas/farmacologia , Actinobacteria/metabolismo , Descoberta de Drogas , Herbicidas/metabolismo , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/crescimento & desenvolvimento , Metabolismo Secundário , Controle de Plantas Daninhas
15.
Biochem Biophys Res Commun ; 521(4): 997-1002, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31727364

RESUMO

Laccases (benzenediol: oxygen oxidoreductases, EC1.10.3.2) can oxidize various substrates, and those which are tolerant to and even activated by salts have attracted a lot of attention due to their application potential in certain industries. The mechanism of the salt activation of laccases is awaiting to be elucidated yet. Our previous study (Li, Xie et al. 2018) supposed that the salt activation of marine laccase Lac15 might be attributed to Cl- ion specifically binding to some local sites to interfere substrate binding and/or electron transfer. In this study, we found two sites whose mutations resulted in elimination of the salt activation of Lac15's activity towards catechol and dopamine respectively, and revealed that the mutations affected the activity by altering both Em and kcat, demonstrating the supposed mechanism. A model for the salt activation of laccases was accordingly proposed, albeit some details are to be elucidated.

16.
Prep Biochem Biotechnol ; 50(1): 74-81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31517565

RESUMO

Ectoine has fostered the development of products for skin care and cosmetics. In this study, we employed the marine bacterial strain Marinococcus sp. MAR2 to increase ectoine production by optimizing medium constituents using Response Surface Methodology (RSM) and a fed-batch strategy. The results from the steepest ascent and central composite design indicated that 54 g/L of yeast extract, 14.0 g/L of ammonium acetate, 74.4 g/L of sodium glutamate, and 6.2 g/L of sodium citrate constituted the optimal medium with maximum ectoine production (3.5 g/L). In addition, we performed fed-batch culture in the bioreactor, combining pH and dissolved oxygen to produce ectoine by Marinococcus sp. MAR2. The ectoine production, content, and productivity of 5.6 g/L, 10%, and 3.9 g/L/day were further reached by a fed-batch culture. Thus, the ectoine production by Marinococcus sp. MAR2 using RSM and fed-batch strategy shows its potential for industrial production.

17.
J Invest Surg ; 33(3): 211-217, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30909770

RESUMO

Background: Acute aorta dissection (AD) is a fatal emergency, however, studies addressing the clinical characteristics, management, and outcome of acute AD in young adult patients aged under 45 years in China are very few.Methods: A retrospective study including 490 patients with acute AD as the final diagnosis was conducted. Patients' demographics, clinical characteristics, medical history, and laboratory and diagnostic imaging findings were retrieved from medical records. Results: The median age of young adult patients with acute AD was 38 years old with an interquartile range from 33 to 41. Male and smoker constituted 84.49% and 50.61% of the cohort, respectively. Hypertension was found in 54.49%, while Marfan syndrome was seen in 4.29% of the patients. Abrupt onset of chest or back pain was the most common symptoms (85.31%), while altered consciousness, coma and oliguria were less reported. Most patients (89.39%) were managed with surgical interventions. Typical complications (central nervous system complications, spinal cord ischemia, myocardial ischemia/infarction, mesenteric ischemia/infarction and acute renal failure) were seen in a small portion of treated patients during perioperative period. For in-hospital mortality there were 24 (∼5%) cases recorded. Correlation analysis indicated that perioperative complications were associated with the length of cardiopulmonary bypass (CPB) (P < 0.0001), and mortality after surgery correlated history of prior cardiac surgery (P = 0.043). Conclusion: CPB and prior cardiac surgery were associated with perioperative complications and mortality after surgery, respectively. The findings are valuable to the further refinement of diagnosis and surgical management of patients with acute aortic dissection.

18.
Int J Soc Psychiatry ; 66(1): 84-92, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31647367

RESUMO

OBJECTIVES: Pathological social withdrawal (PSW) has become a public health concern, especially in Asia. However, few studies have investigated the presence of PSW and its characteristics in Taiwan. In this study, we aimed to discover whether individuals in Taiwan display PSW behaviours, the demographic characteristics and psychiatric history of those meeting criteria for PSW and the associated psychological risks. METHODS: An online self-report survey collected participants' demographic characteristics, social behaviours and their psychiatric history, along with information on adherence to cultural norms and mental health. RESULTS: Among 1,046 valid respondents, 9% reported behaviours consistent with PSW for at least 6 months, commensurate with other online surveys in Asian countries. Around 20% of these also reported current or past psychiatric disorders, although this was lower than previous findings (50%-80%). Participants with PSW reported poorer mental health and lower confidence in social/academic/work skills than unaffected participants. CONCLUSION: This study identified for the first time the presence of PSW in Taiwan. Except the lower rates of psychiatric comorbidity (which could be explained by sociocultural factors and sampling methods), data were consistent with previous findings. We also extended our understanding of possible psychological risk factors associated with this pathological condition.

19.
Environ Int ; 135: 105383, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31835022

RESUMO

Organophosphorus pesticides (OPs) remain one of the most commonly used pesticides, and their detection rates and residues in agricultural products, foods and environmental samples have been underestimated. Humans and environmental organisms are at high risk of exposure to OPs. Most OPs can be degraded and metabolized into dialkyl phosphates (DAPs) in organisms and the environment, and can be present in urine as biomarkers for exposure to OPs, of which diethyl phosphate (DEP) is a high-exposure metabolite. Epidemiological and cohort studies have found that DAPs are associated with endocrine hormone disorders, especially sex hormone disorders and thyroid hormone disorders, but there has been no direct causal evidence to support these findings. Our study explored the effects of chronic exposure to DEP on endocrine hormones and related metabolic indicators in adult male rats at actual doses that can be reached in the human body. The results showed that chronic exposure to DEP could cause thyroid-related hormone disorders in the serum of rats, causing symptoms of hyperthyroidism in rats, and could also lead to abnormal expression of thyroid hormone-related genes in the rat liver. However, DEP exposure did not seem to affect serum sex hormone levels, spermatogenesis or sperm quality in rats. The molecular interactions between DEP and thyroid hormone-related enzymes/proteins were investigated by molecular docking and molecular dynamics methods in silico. It was found that DEP could strongly interact with thyroid hormone biosynthesis, blood transport, receptor binding and metabolism-related enzymes/proteins, interfering with the production and signal regulation of thyroid hormones. In vivo and in silico experiments showed that DEP might be a potential thyroid hormone-disrupting chemical, and therefore, we need to be more cautious and rigorous regarding organophosphorus chemical exposure.

20.
Acta Pharmacol Sin ; 41(1): 22-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31431734

RESUMO

Long non-coding RNAs (lncRNAs) have been identified as essential mediators in neurological dysfunction. Our previous study shows that berberine (BBR) hampers the nuclear-to-cytosolic translocation of high-mobility group box 1 (HMGB1) in the process of poststroke inflammation. In this study, we explored the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) in the process of BBR-induced inhibition of HMGB1 in ischemic brain. Before the 60-min MCAO surgery, the mice were pretreated with BBR (50 mg· kg-1 per day, ig) for 14 days or ICV injected with specific lentiviral vector or shRNA. We showed that MCAO caused marked increase in the expression Malat1 and HMGB1 in the ipsilateral cortex, which was significantly attenuated by pretreatment with BBR. Knockdown of Malat1 attenuated the inflammatory injury after brain ischemia, whereas overexpression of Malat1 exacerbated ischemic brain inflammation. Overexpression of Malat1 also reversed BBR-induced reduction of HMGB1 and proinflammatory cytokines. The above results suggested a potential correlation between Malat1 and stroke inflammation. Based on informatics analysis we predicted that HMGB1 was a direct downstream target of miR-181c-5p, whereas Malat1 acted as a competitive endogenous RNA (ceRNA) for miR-181c-5p targeted the 3'-UTR of HMGB1 to promote inflammation after ischemic stroke. Knockdown of Malat1 significantly decreased HMGB1 level, which could be abrogated by transfection with miR-181c-5p inhibitors. Taken together, our results demonstrate for the first time that Malat1/miR-181c-5p/HMGB1 axis may be a key pathway of BBR-induced antiinflammation effects in stroke, and they may provide a novel avenue for targeted therapy.

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