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2.
Anal Bioanal Chem ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34993597

RESUMO

As a common heavy metal ion with strong toxicity and wide distribution, lead ions (Pb2+) had great harm to the human body. In this work, a low-noise ratiometric fluorescence biosensor was developed based on Pb2+-dependent DNAzyme and exonuclease III (Exo III)-assisted cascade signal amplification. Firstly, the substrate chain of DNAzyme (S-DNA) was modified on the surface of magnetic beads (MBs) through the combination of biotin and streptavidin, and then the enzyme chain of DNAzyme (E-DNA) was connected to the MBs by forming a double-stranded DNA (dsDNA) with S-DNA. A hairpin DNA (HP) labelled with Cy3 and Cy5 respectively at both ends was used as a fluorescence probe. The emission peaks of Cy3 and Cy5 can appear at 562 nm and 665 nm respectively, and their fluorescence intensity ratio (F562/F665) was chosen as the acquisition signal. The ratiometric sensor can reduce the interference of detection environment and avoid false positive reactivity. Due to the cleavage of DNAzyme and the release of single-stranded DNA (ssDNA) in the presence of Pb2+, the hairpin structure of HP was opened and the FRET between two fluorophores disappeared, resulting in the strengthened signal of Cy3 and the weakened signal of Cy5. Furthermore, the ratio [Formula: see text] signal increased gradually with the increase of Pb2+ concentration. When the concentration of Pb2+ was in the range of 0.1-1000 nM, [Formula: see text] had a good linear relationship with [Formula: see text], the correlation coefficient (R2) was 0.997, and the limit of detection (LOD) was 77 pM. The presented ratiometric fluorescence biosensor had lower LOD and wider detection range via comparing with other methods. At the same time, the sensor also obtained the satisfactory results for detection of Pb2+ in tap water, tea, and rice flour samples. The provided ratiometric biosensor has great potential in the monitoring of various targets. A low-noise ratiometric fluorescence biosensor based on the FRET between two fluorophores was developed, and the DNAzyme and exonuclease III-assisted cascade signal amplification was used to improve the sensitivity of the method. The biosensor had a detection limit as low as 77 pM.

3.
Sci Rep ; 12(1): 303, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996924

RESUMO

Targeting the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) axis with monoclonal antibodies (mAbs) represents a crucial breakthrough in anticancer therapy, but mAbs are limited by their poor oral bioavailability, adverse events in multiple organ systems, and primary, adaptive, and acquired resistance, amongst other issues. More recently, the advent of small molecule inhibitors that target the PD-1/PD-L1 axis have shown promising cellular inhibitory activity and the potential to counteract the disadvantages of mAbs. In this study, structure-based virtual screening identified small molecule inhibitors that effectively inhibited the PD-1/PD-L1 interaction. Six of those small molecule inhibitors were applied to cell-based experiments targeting PD-1: CH-1, CH-2, CH-3, CH-4, CH-5, and CH-6. Of all 6, CH-4 displayed the lowest cytotoxicity and strongest inhibitory activity towards the PD-1/PD-L1 interaction. The experiments revealed that CH-4 inhibited the interaction of soluble form PD-L1 (sPD-L1) with PD-1 surface protein expressed by KG-1 cells. Investigations into CH-4 analogs revealed that CH-4.7 effectively blocked the PD-1/sPD-L1 interaction, but sustained the secretion of interleukin-2 and interferon-γ by Jurkat cells. Our experiments revealed a novel small molecule inhibitor that blocks the interaction of PD-1/sPD-L1 and potentially offers an alternative PD-1 target for immune checkpoint therapy.

5.
Curr Biol ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35021048

RESUMO

Patients with Parkinson's disease (PD) suffer from severe sleep disorders. Pathophysiology of the basal ganglia (BG) underlies PD, and the dorsal striatum represents the major input pathway of the BG. However, the roles and mechanisms of the dorsal striatum in controlling sleep-wake cycles remain unknown. To demonstrate the contribution of dopamine D1 receptor (D1R)-positive neurons within the dorsal striatum in promoting wakefulness, we combined optogenetic manipulations and fiber photometry with electroencephalography/electromyography recording in D1R-Cre mice. As a result, optogenetic activation of striatal D1R neurons induced immediate transitions from non-rapid eye movement (NREM) sleep to wakefulness, whereas inhibition of striatal D1R neurons attenuated wakefulness by chemogenetics. Multi-channel fiber photometry recordings revealed that the activity of striatal D1R neurons synchronized with that of BG upstreams, namely the prefrontal cortex and mediodorsal thalamus, in terms of immediate increase in activity during NREM-to-wake transitions and rapid decease during wake-to-NREM transitions. Further optogenetic manipulations revealed a prominent contribution of striatal D1R neurons in control of wakefulness by upstream, corticostriatal, thalamostriatal, and nigrostriatal projections and via downstream, striato-entopeduncular, or striatonigral pathways. Taken together, our findings revealed a circuit regulating wakefulness through striatal D1R neurons. Striatal D1R neurons play an important role in controlling wakefulness by integrating the corticostriatal, thalamostriatal, and nigrostriatal projections and innervation of striato-entopeduncular or striatonigral pathways.

6.
Environ Pollut ; : 118816, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35016984

RESUMO

As primary anthropogenic emission source of toxic pollutants such as heavy metals and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), municipal solid waste (MSW) incineration has caused worldwide concern. However, a comprehensive analysis of the pollution characteristics and health risks of PCDD/Fs and heavy metals in soils around MSW incineration plants is lacking. In this study, 17 PCDD/Fs and 11 heavy metals in soil samples collected near MSW incineration plants in Sichuan province were investigated to evaluate their pollution characteristics and potential health risk. Sichuan was selected as the study area because the MSW incineration amount in this province ranks first among all inland provinces in China. The PCDD/Fs concentrations ranged from 0.30 to 7.50 ng I-TEQ/kg, which were significantly below risk screening and intervention thresholds. Regarding heavy metals, principal component analysis suggested that Hg, Pb and Zn were the primary metals emitted from the MSW incineration plants. Cluster analysis of PCDD/Fs and heavy metals showed that of PCDD/Fs homologs and heavy metals (e.g., Hg, Pb, Zn and Cd) were clustered into one group, indicating the coexistence and coaccumulation of heavy metals (especially Hg, Pb, Zn, and Cd) and PCDD/Fs in soil. These heavy metals are thus candidate tracers for PCDD/Fs in soil near MSW incineration plants. A health risk analysis found that the carcinogenic and non-carcinogenic risks of PCDD/Fs and heavy metals (except for Ni) in the soil samples were all within acceptable levels. This study provides new insights into correlations and health risks of PCDD/Fs and heavy metals in surface soil near MSW incineration plants. The findings have implications for future studies of environmental and human health risk analysis related to waste incineration.

7.
J Cheminform ; 14(1): 1, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991690

RESUMO

Human oral bioavailability (HOB) is a key factor in determining the fate of new drugs in clinical trials. HOB is conventionally measured using expensive and time-consuming experimental tests. The use of computational models to evaluate HOB before the synthesis of new drugs will be beneficial to the drug development process. In this study, a total of 1588 drug molecules with HOB data were collected from the literature for the development of a classifying model that uses the consensus predictions of five random forest models. The consensus model shows excellent prediction accuracies on two independent test sets with two cutoffs of 20% and 50% for classification of molecules. The analysis of the importance of the input variables allowed the identification of the main molecular descriptors that affect the HOB class value. The model is available as a web server at www.icdrug.com/ICDrug/ADMET for quick assessment of oral bioavailability for small molecules. The results from this study provide an accurate and easy-to-use tool for screening of drug candidates based on HOB, which may be used to reduce the risk of failure in late stage of drug development.

8.
Neurol Sci ; 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35000015

RESUMO

BACKGROUND AND OBJECTIVE: There are indicates that raphe nuclei may be involved in the occurrence of chronic pain in Parkinson's disease (PD). In the study, we investigated the functional connectivity pattern of raphe nuclei in Parkinson's disease with chronic pain (PDP) to uncover its possible pathophysiology. METHODS: Fifteen PDP, who suffered from pain, lasted longer than 3 months, sixteen Parkinson's disease patients with no pain (nPDP) and eighteen matched normal health controls (NCs) were recruited. All subjects completed the King's Parkinson's Pain Scale (KPPS) besides Parkinson-related scale and demographics. We performed a seed-based resting-state analysis of functional magnetic resonance imaging to explore whole-brain functional connectivity of the raphe nuclei. Multiple regression model was used to explore the related factors of pain including disease duration, disease severity, Hamilton Depression Rating Scale, age, sex, levodopa equivalent dose and the strength of network functional connectivity. RESULTS: Compared with the nPDP, the PDP group showed stronger functional connectivity between raphe nuclei and pain-related brain regions, including parietal lobe, insular lobe, cingulum cortex and prefrontal cortex, and the functional connectivity values of those areas were significantly positively correlated with KPPS independent of the clinical variables. Compared with NCs, the combined PD groups showed decreased functional connectivity including prefrontal cortex and cingulum cortex. CONCLUSIONS: Abnormal functional connectivity model of raphe nuclei may be partly involved in pathophysiological mechanism of pain in PD.

9.
Cell Mol Immunol ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983944

RESUMO

Exploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising strategy. Here, we show that ACE2-overexpressing A549 cell-derived microparticles (AO-MPs) are a potential therapeutic agent against SARS-CoV-2 infection. Intranasally administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages (AMs). Then, AO-MPs increase the endosomal pH but decrease the lysosomal pH in AMs, thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for degradation. This pH regulation is attributable to oxidized cholesterol, which is enriched in AO-MPs and translocated to endosomal membranes, thus interfering with proton pumps and impairing endosomal acidification. In addition to promoting viral degradation, AO-MPs also inhibit the proinflammatory phenotype of AMs, leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side effects. These findings highlight the potential use of AO-MPs to treat SARS-CoV-2-infected patients and showcase the feasibility of MP therapies for combatting emerging respiratory viruses in the future.

10.
Microbiol Res ; 254: 126912, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34742105

RESUMO

Sapindus saponins extracted from Sapindus mukorossi Gaertn. have been reported to exert antibacterial activity against Cutibacterium acnes (C. acnes). However, there are no reports about their potentials against its biofilm, which is a major contributor to the antibiotic resistance of C. acnes. This study aimed to investigate the synergistic antibiofilm activity and action of the combination of Sapindoside A and B (SAB) against C. acnes. SAB with sub-MICs significantly inhibited the early-formed and mature biofilm of C. acnes and decreased the adhesion and cell surface hydrophobicity (p < 0.05). Also, SAB greatly reduced the production of exopolysaccharide and lipase (p < 0.05), and the binding mode of SAB and lipase was predicted by molecular docking, via hydrogen bonds and hydrophobic interactions. Biofilm observed with electron microscopies further confirmed the high antibiofilm activity of SAB against C. acnes. Furthermore, a significant down-regulation of biofilm biosynthesis-associated genes was observed. The combination index explained the synergistic effects of SAB leading to the above results, and the contribution of SA was greater than that of SB. The current results showed that SAB had synergistic antibiofilm activity against C. acnes, and the Sapindoside A played a major role, indicating that SAB could be a natural antiacne additive against C. acnes biofilm-associated infections.


Assuntos
Biofilmes , Ácido Oleanólico/análogos & derivados , Propionibacteriaceae , Saponinas , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Sinergismo Farmacológico , Simulação de Acoplamento Molecular , Ácido Oleanólico/farmacologia , Propionibacteriaceae/efeitos dos fármacos , Saponinas/farmacologia
11.
J Med Chem ; 65(1): 688-709, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34951310

RESUMO

Development of new bacterial biofilm inhibitors as antibacterial synergists is an effective strategy to solve the resistance of Pseudomonas aeruginosa. In this paper, a series of 3-hydroxy-pyridin-4(1H)-ones were synthesized and evaluated, and the hit compound (20p) was identified with the effects of inhibiting the production of pyocyanin (IC50 = 8.6 µM) and biofilm formation (IC50 = 4.5 µM). Mechanistic studies confirmed that 20p inhibits the formation of bacterial biofilm by inhibiting the expression of pqsA, blocking pqs quorum sensing system quinolone biosynthesis. Moreover, we systematically investigated the bactericidal effects of combining currently approved antibiotics for CF including tobramycin, ciprofloxacin, and colistin E with 20p, which showed obvious antibacterial synergy to overcome antibiotics resistance in multidrug-resistant P. aeruginosa biofilms. The result indicates that compound 20p may be used in the future as a potentially novel antibacterial synergist candidate for the treatment of P. aeruginosa infections.

12.
Nature ; 600(7887): 81-85, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34853456

RESUMO

Understanding the structure and dynamic process of water at the solid-liquid interface is an extremely important topic in surface science, energy science and catalysis1-3. As model catalysts, atomically flat single-crystal electrodes exhibit well-defined surface and electric field properties, and therefore may be used to elucidate the relationship between structure and electrocatalytic activity at the atomic level4,5. Hence, studying interfacial water behaviour on single-crystal surfaces provides a framework for understanding electrocatalysis6,7. However, interfacial water is notoriously difficult to probe owing to interference from bulk water and the complexity of interfacial environments8. Here, we use electrochemical, in situ Raman spectroscopic and computational techniques to investigate the interfacial water on atomically flat Pd single-crystal surfaces. Direct spectral evidence reveals that interfacial water consists of hydrogen-bonded and hydrated Na+ ion water. At hydrogen evolution reaction (HER) potentials, dynamic changes in the structure of interfacial water were observed from a random distribution to an ordered structure due to bias potential and Na+ ion cooperation. Structurally ordered interfacial water facilitated high-efficiency electron transfer across the interface, resulting in higher HER rates. The electrolytes and electrode surface effects on interfacial water were also probed and found to affect water structure. Therefore, through local cation tuning strategies, we anticipate that these results may be generalized to enable ordered interfacial water to improve electrocatalytic reaction rates.

13.
Front Plant Sci ; 12: 757936, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868152

RESUMO

Many basic helix-loop-helix transcription factors (TFs) have been reported to promote anthocyanin biosynthesis in numerous plant species, but little is known about bHLH TFs that inhibit anthocyanin accumulation. In this study, SmbHLH1 from Solanum melongena was identified as a negative regulator of anthocyanin biosynthesis. However, SmbHLH1 showed high identity with SmTT8, which acts as a SmMYB113-dependent positive regulator of anthocyanin-biosynthesis in plants. Overexpression of SmbHLH1 in eggplant caused a dramatic decrease in anthocyanin accumulation. Only the amino acid sequences at the N and C termini of SmbHLH1 differed from the SmTT8 sequence. Expression analysis revealed that the expression pattern of SmbHLH1 was opposite to that of anthocyanin accumulation. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays showed that SmbHLH1 could not interact with SmMYB113. Dual-luciferase assay demonstrated that SmbHLH1 directly repressed the expression of SmDFR and SmANS. Our results demonstrate that the biological function of bHLHs in anthocyanin biosynthesis may have evolved and provide new insight into the molecular functions of orthologous genes from different plant species.

14.
Materials (Basel) ; 14(23)2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34885606

RESUMO

Among the various phases of bismuth oxide, the high temperature metastable face-centered cubic δ phase attracts great attention due to its unique properties. It can be used as an ionic conductor or an endodontic radiopacifying material. However, no reports concerning tantalum and bismuth binary oxide prepared by high energy ball milling and serving as a dental radiopacifier can be found. In the present study, Ta2O5-added Bi2O3 composite powders were mechanically milled to investigate the formation of these metastable phases. The as-milled powders were examined by X-ray diffraction and scanning electron microscopy to reveal the structural evolution. The as-milled composite powders then served as the radiopacifier within mineral trioxide aggregates (i.e., MTA). Radiopacity performance, diametral tensile strength, setting times, and biocompatibility of MTA-like cements solidified by deionized water, saline, or 10% calcium chloride solution were investigated. The experimental results showed that subsequent formation of high temperature metastable ß-Bi7.8Ta0.2O12.2, δ-Bi2O3, and δ-Bi3TaO7 phases can be observed after mechanical milling of (Bi2O3)95(Ta2O5)5 or (Bi2O3)80(Ta2O5)20 powder mixtures. Compared to its pristine Bi2O3 counterpart with a radiopacity of 4.42 mmAl, long setting times (60 and 120 min for initial and final setting times) and 84% MG-63 cell viability, MTA-like cement prepared from (Bi2O3)95(Ta2O5)5 powder exhibited superior performance with a radiopacity of 5.92 mmAl (the highest in the present work), accelerated setting times (the initial and final setting time can be shortened to 25 and 40 min, respectively), and biocompatibility (94% cell viability).

15.
Front Plant Sci ; 12: 745110, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858453

RESUMO

The atmospheric vapour pressure deficit (VPD) has been demonstrated to be a significant environmental factor inducing plant water stress and affecting plant photosynthetic productivity. Despite this, the rate-limiting step for photosynthesis under varying VPD is still unclear. In the present study, tomato plants were cultivated under two contrasting VPD levels: high VPD (3-5 kPa) and low VPD (0.5-1.5 kPa). The effect of long-term acclimation on the short-term rapid VPD response was examined across VPD ranging from 0.5 to 4.5 kPa. Quantitative photosynthetic limitation analysis across the VPD range was performed by combining gas exchange and chlorophyll fluorescence. The potential role of abscisic acid (ABA) in mediating photosynthetic carbon dioxide (CO2) uptake across a series of VPD was evaluated by physiological and transcriptomic analyses. The rate-limiting step for photosynthetic CO2 utilisation varied with VPD elevation in tomato plants. Under low VPD conditions, stomatal and mesophyll conductance was sufficiently high for CO2 transport. With VPD elevation, plant water stress was gradually pronounced and triggered rapid ABA biosynthesis. The contribution of stomatal and mesophyll limitation to photosynthesis gradually increased with an increase in the VPD. Consequently, the low CO2 availability inside chloroplasts substantially constrained photosynthesis under high VPD conditions. The foliar ABA content was negatively correlated with stomatal and mesophyll conductance for CO2 diffusion. Transcriptomic and physiological analyses revealed that ABA was potentially involved in mediating water transport and photosynthetic CO2 uptake in response to VPD variation. The present study provided new insights into the underlying mechanism of photosynthetic depression under high VPD stress.

16.
Orthop Surg ; 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34862745

RESUMO

OBJECTIVE: To evaluate the proprioceptive and clinical function of the knee joint after anterior cruciate ligament reconstruction (ACLR) with various amounts of remnant preserved with as few confounding factors as possible. METHODS: This retrospective study included 46 patients who underwent ACLR with remnant preservation between March 2013 and February 2019. These patients had less than 6 months injury-to-surgery interval and no concomitant injuries. The researchers divided these subjects into two groups based on the length of the remnant preserved after ACLR, with group A defined as having more than 1/3 of the original length preserved and group B defined as less than 1/3 of the original length preserved. Clinical scores were obtained using the Lysholm knee scoring scale and the Tegner activity scale. The Lysholm score was calculated preoperatively, at 3, 6, and 12 months postoperatively, and at the last follow up. The Tegner score was calculated preoperatively, at 12 months postoperatively and at the last follow up. Anterior laxity was measured using the KT2000 arthrometer preoperatively and at 12 months postoperatively. Proprioceptive function was evaluated through reproduction of passive positioning (RPP) and threshold to detection of passive motion (TDPM). Both RPP and TDPM were measured at the angle of 15° at 3, 6, and 12 months postoperatively. Unpaired t-tests were performed to investigate the difference in each parameters between the two groups. RESULTS: In the present study, 20 patients were classified into group A and 26 into group B. All patients were followed up for an average of 34.70 ± 12.79 months. All 46 patients were satisfied with the outcome of the surgery and no complications were reported at the end of the study. No significant differences were found between the two groups in terms of the Lysholm score and anterior laxity by KT2000 at all time points. The Tegner score was significantly higher in group A at 12 months postoperatively and at the final follow-up. In addition, group A's RPP was significantly better than that of group B's when tested at the angles of 15° and 30° at 3 months postoperatively, and at the angle of 15° at 6 months postoperatively. Group A's TDPM was also significantly better than that of group B's at all three tested angles at 3 months postoperatively, and at the angle of 15° at 6 months postoperatively. CONCLUSION: Patients with ACLR with more than 1/3 of the original length preserved demonstrated a higher activity level 12 months postoperatively and better proprioceptive function at 15° of extension at 3 and 6 months postoperatively.

17.
Bioorg Chem ; 119: 105534, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34894576

RESUMO

Fourteen previously undescribed diterpenoids, including an unusual diterpenoid (1) with a 9,10-seco-jatrophane skeleton, ten jatrophane-type diterpenoids (2-11), two lathyrane-type diterpenoids (12, 13), and an abietane-type diterpenoid (14), together with thirty-six known ones (15-50), were isolated from the whole plants of Euphorbia helioscopia L. The structures of the new isolates were characterized by spectroscopic methods, single-crystal X-ray diffraction analysis, and computational prediction of ECD and chemical shifts. Thirty-nine abundant diterpenoids were evaluated for their enhancement of NK cell-mediated killing of NSCLC cells. As a result, compounds 24, 33, and 41 were found to significantly enhance the killing activity of NK cells towards H1299-luci cells and A549-luci cells at the concentration of 2.5 µM.

18.
Org Biomol Chem ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34939627

RESUMO

Herein, we present the first organocatalytic oxygen/sulfur atom exchange reaction (O/S ER) of isatins by employing carbonyl sulfide (COS) as a novel sulfuring reagent under mild reaction conditions. 8-Diazabicyclo[5.4.0]undec-7-ene (DBU) exhibited excellent activity in this approach. Remarkably, the chemical transformations of in situ generated 3-thioisatins can be tuned via the judicious choice of reaction solvents in a one pot process, enabling the selective formation of either functionalized isoindigos in CH3CN via a self-condensation process or spirothiopyrans in DMSO in the presence of conjugated dienes via the thio-Diels-Alder reaction. Mechanistic studies with experimental and density functional theory approaches revealed that the O/S ER between isatins and COS results in the formation of 3-thioisatins as the key intermediates, which further undergo solvent-controlled transformations to generate isoindigos or spirothiopyrans, respectively. The easily-accessible substrates and operational simplicity make the process suitable for further exploration. The practicality of this transformation was demonstrated by the gram-scale synthesis of isoindigo-based drug molecules and donor-acceptor conjugated polymers.

19.
BMC Nephrol ; 22(1): 408, 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895150

RESUMO

BACKGROUND: Transient antenatal Bartter's syndrome caused by MAGED2 mutation is a rare X-linked recessive renal tubular disorder. Cases reported are mostly infants, and the long-term prognosis of the disease is still under investigation. CASE PRESENTATION: We encountered a preterm male infant with polyhydramnios, polyuria, salt loss, hypercalciuria, nephrocalcinosis and alkalosis. Antenatal Bartter's syndrome was suspected, but these clinical symptoms surprisingly disappeared after about 2 months. This led to the clinical diagnosis of transient antenatal Bartter's syndrome. Gene analysis in this patient disclosed a novel variant (c.1598C > T, p.Ala533Val) in exon 12 of MAGED2 gene, and his mother was a heterozygous carrier. This patient was followed up in clinic for 4 years without recurrence of imbalance of potassium, sodium and chloride. His height and weight were in normal range, and all laboratory examinations and nephrotic ultrasound were also normal. CONCLUSIONS: We reported the first Chinese case of transient antenatal Bartter's syndrome caused by MAGED2 mutation. The 4-year follow-up of our case further demonstrates the benign prognosis of the disease and indicates that early recognition of this phenotype could avoid unnecessary treatments.

20.
Ann Clin Lab Sci ; 51(6): 818-826, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34921035

RESUMO

OBJECTIVE: Inflammatory mediators have been implicated in the pathophysiology of acute pulmonary embolism (PE). However, the role of inflammatory mediator activation in the development of pulmonary embolism remains elusive. Here, we determined the reliability of the plasma levels of inflammatory markers tumor necrosis factor-alpha (TNF-α) and high mobility histone 1 (HMGB1) as diagnostic biomarkers of PE. METHODS: Eighty-seven patients with PE and ninety-two healthy adults were enrolled. Plasma levels of TNF-α and HMGB1 were measured before and after anticoagulation treatment using conventional commercialized ELISA. RESULTS: The mean concentrations of plasma TNF-α and HMGB1 in patients with PE before anticoagulation treatment were 3.36- and 2.54-fold higher than those in controls (p<0.0001), respectively. Similar results were obtained in patients with PE before anticoagulation treatment, in which plasma levels of TNF-α and HMGB1 were 3.99- and 1.99-fold higher (p<0.0001), respectively, than in PE patients after anticoagulation treatment. Among the two potential markers, TNF-α performed best in distinguishing patients with PE from controls. A significant positive correlation was found between the two markers' concentrations. CONCLUSIONS: These findings suggest that the plasma levels of TNF-α and HMGB1 may serve as potential biomarkers for PE.

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