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1.
Shock ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33555844

RESUMO

BACKGROUND: Therapeutic temperature management (TTM) is the standard treatment protocol for unconscious post-resuscitation patients. However, there is still controversy about the ideal targeted temperature of mild hypothermia therapy. Additionally, studies about protective therapy for post-resuscitation intestinal injury are very limited. Therefore, this study was performed to explore: 1) whether mild hypothermia therapy can exert a protective effect on post-resuscitation intestinal injury; 2) the protective effect of different targeted temperatures on post-resuscitation intestinal injury and the ideal targeted temperature; 3) the potential protective mechanism of mild hypothermia therapy for post-resuscitation intestinal injury. METHODS: Ventricular fibrillation was electrically induced and untreated for 6 min while defibrillation was attempted after 8 min of cardiopulmonary resuscitation in 15 rats. After successful resuscitation, animals were randomized into three groups: (i) control; (ii) TTM-35; (iii) TTM-33. In animals of the control group, temperature was maintained at 37 ±â€Š0.2°C for 6 hours. In animals of the two TTM groups, temperature was maintained at 33 ±â€Š0.2°C or 35 ±â€Š0.2°C for 6 hours, respectively. During mild hypothermia therapy, intestinal microcirculation was measured at 60, 240, and 360 min after resuscitation. Animals were euthanized 6.5 h after resuscitation. The morphological changes in the intestinal tissue, systemic and local inflammatory factors, and intestinal injury markers were measured and analyzed. The tight junction proteins in the intestinal epithelium, cell-cell contact protein E-cadherin expression, myosin light chain (MLC) and myosin light chain kinase (MLCK) levels, and the NF-κB p65 signaling pathway were analyzed by western blotting. RESULTS: Compared with results in the control group, mild hypothermia therapy (TTM-33 and TTM-35 groups) significantly improved post-resuscitation intestinal microcirculation and pathological scores, decreased systemic and local intestinal tissue inflammatory factor levels, inhibited the NF-κB signaling pathway and downstream MLC phosphorylation, and significantly decreased MLC phosphorylation-associated loss of intestinal tight junction proteins and E-cadherin (P < 0.05). A 33°C target temperature could exert more protective effects than 35°C on post-resuscitation intestinal injury, such as improving intestinal microcirculation, decreasing intestinal ischemia factor iFABP and plasma endotoxin levels, inhibiting the NF-κB signaling pathway and downstream MLC phosphorylation, and suppressing the loss of intestinal tight junctions and E-cadherin (P < 0.05). CONCLUSIONS: Mild hypothermia therapy can improve post-resuscitation intestinal injury, and a targeted temperature of 33°C may confer more benefit for mitigation of intestinal injury as compared with a targeted temperature of 35°C.

2.
J Med Chem ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33539088

RESUMO

GM3, a typical tumor-associated carbohydrate antigen, is considered as an important target for cancer vaccine development, but its low immunogenicity limits its application. αGalCer, an iNKT cell agonist, has been employed as an adjuvant via a unique immune mode. Herein, we prepared and investigated two types of antitumor vaccine candidates: (a) self-adjuvanting vaccine GM3-αGalCer by conjugating GM3 with αGalCer and (b) noncovalent vaccine GM3-lipid/αGalCer, in which GM3 is linked with lipid anchor and coassembled with αGalCer. This demonstrated that ßGalCer is an exceptionally optimized lipid anchor, which enables the noncovalent vaccine candidate GM3-ßGalCer/αGalCer to evoke a comparable antibody level to GM3-αGalCer. However, the antibodies induced by GM3-αGalCer are better at recognition B16F10 cancer cells and more effectively activate the complement system. Our study highlights the importance of vaccine constructs utilizing covalent or noncovalent assembly between αGalCer with carbohydrate antigens and choosing an appropriate lipid anchor for use in noncovalent vaccine formulation.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 181-187, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554816

RESUMO

OBJECTIVE: To deeply understand the clinical manifestation, laboratory examination characteristics, diagnosis and treatment of an eight p11 myeloproliferative syndrome (EMS) with rare phenotypes. METHODS: The clinical and laboratory characteristics and the process of allogeneic hematopoietic stem cell transplantation (allo-HSCT) were summarized in 1 rare EMS case involving T/B/myeloid cells. Meanwhile, 2 similar cases in the previous literature were also discussed. RESULTS: The bone marrow examination indicated that the patient with B-cell acute lymphocytic leukemia. The lymph node biopsy showed that the patient was T lymphoblastic/myeloid lymphoma. The 8p11 abnormality was found by the examination of bone marrow chromosomes. The RT-PCR examination showed that the BCR-ABL fused gene was negtive. The FGFR1 breakage was found by using the FISH with FGFR1 probe in lymph node. The Mutation of FMNL3, NBPF1 and RUNX1 genes was found by using the whole exome sequencing. The patient received allo-HSCT under CR2. By the follow-up till to September 2019, the patient survived without the above-mentioned disease. CONCLUSION: EMS manifest as neoplasms involving T-lineage, B-lineage, and myeloid-lineage simultaneously is extremely rare. Although the FGFR1 gene-targeted therapy can be conducted, allo-HSCT should be actively considered.


Assuntos
Neoplasias Hematológicas , Transtornos Mieloproliferativos , Medula Óssea , Cromossomos Humanos Par 8 , Forminas , Humanos , Transtornos Mieloproliferativos/genética , Fenótipo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Translocação Genética
4.
Mol Cancer Res ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563765

RESUMO

Gefitinib is suitable for the treatment of locally advanced or metastatic non-small cell lung cancer. However, the development of acquired resistance limits its long-term efficacy in regardless of significant clinical benefit to patients. Therefore, to elucidate the mechanism of gefitinib resistance in addition to target gene mutation may greatly increase its clinical efficacy. It was found first that N 6-methyladenosine RNA demethylase FTO was significantly enriched in serum exosomes of gefitinib-resistant (GR) patients compared with that of gefitinib-sensitive (GS) patients through exosomal RNA sequencing. Meanwhile, the average m6A proportion in GR patients was significantly lower when compared with that in GS patients. Besides, GR cell-derived exosome internalization attenuated the total m6A abundance and gefitinib sensitivity of PC9 cells. Not only FTO knockdown enhanced the gefitinib sensitivity of GR cells but also FTO reduction in donor exosomes alleviated the acquired resistance of recipient PC9 cells. GR cell-derived exosomal-FTO promoted ABCC10 of recipient cells in a m6A-dependent manner. FTO/YTHDF2/ABCC10 axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance both in vitro and in vivo. In general, this research showed that m6A modification was involved in the decrease of gefitinib sensitivity. GR cell-derived exosomes could decrease gefitinib sensitivity of recipient cells in exosomal delivery of FTO-dependent manner. FTO/YTHDF2/ABCC10 axis played a role in intercellular transmission of GR cell-derived exosome-mediated gefitinib resistance. IMPLICATIONS: Our results elucidated another potential molecular mechanism of gefitinib resistance in non-small cell lung cancer besides secondary EGFR mutations.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33606076

RESUMO

Butanol inhibits bacterial activity by destroying the cell membrane of Clostridium acetobutylicum strains and altering functionality. Butanol toxicity also results in destruction of the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS), thereby preventing glucose transport and phosphorylation and inhibiting transmembrane transport and assimilation of sugars, amino acids, and other nutrients. In this study, based on the addition of exogenous butanol, the tangible macro indicators of changes in the carbon ion beam irradiation-mutant Y217 morphology were observed using scanning electron microscopy (SEM). The mutant has lower microbial adhesion to hydrocarbon (MATH) value than C. acetobutylicum ATCC 824 strain. FDA fluorescence intensity and conductivity studies demonstrated the intrinsically low membrane permeability of the mutant membrane, with membrane potential remaining relatively stable. Monounsaturated FAs (MUFAs) accounted for 35.17% of the mutant membrane, and the saturated fatty acids (SFA)/unsaturated fatty acids (UFA) ratio in the mutant cell membrane was 1.65. In addition, we conducted DNA-level analysis of the mutant strain Y217. Expectedly, through screening, we found gene mutant sites encoding membrane-related functions in the mutant, including ATP-binding cassette (ABC) transporter-related genes, predicted membrane proteins, and the PTS transport system. It is noteworthy that an unreported predicted membrane protein (CAC 3309) may be related to changes in mutant cell membrane properties. KEY POINTS: • Mutant Y217 exhibited better membrane integrity and permeability. • Mutant Y217 was more resistant to butanol toxicity. • Some membrane-related genes of mutant Y217 were mutated.

6.
Int J Mol Sci ; 22(3)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525649

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease characterized by decreased glucose metabolism and increased neuroinflammation. Hexokinase (HK) is the key enzyme of glucose metabolism and is associated with mitochondria to exert its function. Recent studies have demonstrated that the dissociation of HK from mitochondria is enough to activate the NOD-like receptor protein 3 (NLRP3) inflammasome and leads to the release of interleukin-1ß (IL-1ß). However, the effect of increased IL-1ß on the expression of HK is still unclear in AD. In this paper, we used positron emission tomography (PET), Western blotting and immunofluorescence to study the glucose metabolism, and the expression and distribution of HK in AD. Furthermore, we used lipopolysaccharide (LPS), nigericin (Nig), CY-09 and lonidamine (LND) to treat N2a and N2a-sw cells to investigate the link between IL-1ß and HK in AD. The results show decreased expression of HK and the dissociation of HK from mitochondria in AD. Furthermore, a reduction of the expression of IL-1ß could increase the expression of HK in AD. These results suggest that inhibiting inflammation may help to restore glucose metabolism in AD.

7.
BMC Cardiovasc Disord ; 21(1): 73, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541272

RESUMO

BACKGROUND: There is an individual variation in response to antihypertensive effect of the angiotensin II receptor antagonist. This study aimed to determine the allele and genotype frequencies of CYP2C9 and AGTR1 genetic polymorphisms and explore the potential role of these polymorphisms in guiding the selection of angiotensinIIreceptor antagonist in Han Chinese hypertensive patients. METHODS: Totally 2419 Han Chinese hypertensive patients and 126 normotensive controls were recruited in this study. Venous blood samples were collected from each patient, and the genetic polymorphisms of CYP2C9 and AGTR1 were assessed using a gene chip platform. The allele and genotype frequency of each gene and the combined genotypes in this study were analyzed respectively. RESULTS: The gene chip analysis identified an allelic frequency of 96.51% for CYP2C9*1 and 3.49% for CYP2C9*3 in the cohort of Han Chinese hypertensive patients. Statistical analysis showed that the frequency of wild-type homozygous for CYP2C9*1/*1 was 93.30%, while the frequency of heterozygous for *1/*3 or mutant homozygous for *3/*3 was 6.41% or 0.29%. Meanwhile, we detected allelic frequencies of 95.06% and 4.94% for the A and C allele of AGTR1, respectively. While the genotype frequency of wild-type homozygous for AA was 90.41%, the frequency of heterozygous for AC or mutant homozygous for CC was 9.30% or 0.29%. Notably, we observed that 84.66% (2048/2419) of the subjects exhibited a combined genotype of CYP2C9 and AGTR1 as *1/*1 + AA, while the combined genotypes *3/*3 + AC or *3/*3 + CC were not detected in hypertension patients. Besides, no significant association was found between normotensive controls and hypertensive patients, or among the three grades of hypertensive patients. CONCLUSIONS: These data revealed the polymorphisms characteristics of CYP2C9 and AGTR1 in Han Chinese hypertensive patients, providing valuable information for genotype-based antihypertension therapy in prospective clinical studies in the future.

8.
Cell ; 184(4): 943-956.e18, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33571432

RESUMO

Dopamine receptors, including D1- and D2-like receptors, are important therapeutic targets in a variety of neurological syndromes, as well as cardiovascular and kidney diseases. Here, we present five cryoelectron microscopy (cryo-EM) structures of the dopamine D1 receptor (DRD1) coupled to Gs heterotrimer in complex with three catechol-based agonists, a non-catechol agonist, and a positive allosteric modulator for endogenous dopamine. These structures revealed that a polar interaction network is essential for catecholamine-like agonist recognition, whereas specific motifs in the extended binding pocket were responsible for discriminating D1- from D2-like receptors. Moreover, allosteric binding at a distinct inner surface pocket improved the activity of DRD1 by stabilizing endogenous dopamine interaction at the orthosteric site. DRD1-Gs interface revealed key features that serve as determinants for G protein coupling. Together, our study provides a structural understanding of the ligand recognition, allosteric regulation, and G protein coupling mechanisms of DRD1.

9.
J Med Chem ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33619958

RESUMO

As a flavin adenine dinucleotide (FAD)-dependent monoamine oxidase, lysine specific demethylase 1 (LSD1/KDM1A) functions as a transcription coactivator or corepressor to regulate the methylation of histone 3 lysine 4 and 9 (H3K4/9), and it has emerged as a promising epigenetic target for anticancer treatment. To date, numerous inhibitors targeting LSD1 have been developed, some of which are undergoing clinical trials for cancer therapy. Although only two reversible LSD1 inhibitors CC-90011 and SP-2577 are in the clinical stage, the past decade has seen remarkable advances in the development of reversible LSD1 inhibitors. Herein, we provide a comprehensive review about structures, biological evaluation, and structure-activity relationship (SAR) of reversible LSD1 inhibitors.

10.
Opt Lett ; 46(2): 218-221, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33448991

RESUMO

We report on a short-cavity polarization beat-frequency distributed Bragg reflector (DBR) fiber laser that can operate in an unprecedentedly wide range of temperatures from -200∘ C to 500°C. The beat-frequency signal inherited by the intrinsic fiber birefringence enables implementation of the laser as an eligible temperature or hydrostatic pressure sensor. Furthermore, type-IIa Bragg reflectors allow the annealing of high temperature on the laser cavity to suppress the phase noise of the lasing signal effectively. This research will guide future attempts to achieve high-precision sensing and high-performance signal generation using polarized beat-frequency DBR fiber lasers in harsh environments.

11.
J Exp Clin Cancer Res ; 40(1): 31, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446221

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are abundant in tumor-derived extracellular vesicles (EVs) and the functions of extracellular miRNA to recipient cells have been extensively studied with tumorigenesis. However, the role of miRNA in EV secretion from cancer cells remains unknown. METHODS: qPCR and bioinformatics analysis were applied for determining extracellular let-7a expression from CRC patient serum and cells. Nanosight particle tracking analysis was performed for investigating the effect of let-7a on EV secretion. Luciferase reporter assays was used for identifying targeted genes synaptosome-associated protein 23 (SNAP23). In vitro and in vivo assays were used for exploring the function of let-7a/SNAP23 axis in CRC progression. Bioenergetic assays were performed for investigating the role of let-7a/SNAP23 in cellular metabolic reprogramming. RESULTS: let-7a miRNA was elevated in serum EVs from CRC patients and was enriched in CRC cell-derived EVs. We determined that let-7a could suppress EV secretion directly targeting SNAP23. In turn, SNAP23 promotes EV secretion of let-7a to downregulate the intracellular let-7a expression. In addition, we found a novel mechanism of let-7a/SNAP23 axis by regulating mitochondrial oxidative phosphorylation (OXPHOS) through Lin28a/SDHA signaling pathway. CONCLUSIONS: Let-7a plays an essential role in not only inhibiting EV secretion, but also suppressing OXPHOS through SNAP23, resulting in the suppression of CRC progression, suggesting that let-7a/SNAP23 axis could provide not only effective tumor biomarkers but also novel targets for tumor therapeutic strategies.

12.
J Am Chem Soc ; 143(3): 1278-1283, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33428381

RESUMO

Deferasirox, ExJade, is an FDA-approved iron chelator used for the treatment of iron overload. In this work, we report several fluorescent deferasirox derivatives that display unique photophysical properties, i.e., aggregation-induced emission (AIE), excited state intramolecular proton transfer, charge transfer, and through-bond and through-space conjugation characteristics in aqueous media. Functionalization of the phenol units on the deferasirox scaffold afforded the fluorescent responsive pro-chelator ExPhos, which enabled the detection of the disease-based biomarker alkaline phosphatase (ALP). The diagnostic potential of these deferasirox derivatives was supported by bacterial biofilm studies.

13.
Bioorg Chem ; 107: 104599, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33421954

RESUMO

Human pregnane-X-receptor (hPXR) is considered to be the key target for the treatment of cholestasis and liver injury. Agonists of hPXR are potential drug leads. Potent and selective inhibitors of human carboxylesterase 2 (hCES2) could be utilized to alleviate the toxicity induced by ester drugs. In this work, fifteen new tetranortriterpenoids with structure diversity, named thaigranatins F-T (1-15), including four limonoids containing a C1-O-C29 bridge (1-4), four mexicanolides (5-8), three phragmalins (9-11), two limonoids belonging to the small group of trichiliton A (12-13), and two apotirucallanes (14-15), were isolated from seeds of the Thai mangrove, Xylocarpus granatum. The structures of these compounds were established by high resolution-electrospray ionization mass spectroscopy, extensive NMR spectroscopic investigations, single-crystal X-ray diffraction analyses, and the comparison of experimental electronic circular dichroism spectra. Most notably, thaigranatins L (7) and P (11) exhibited agonistic effects on hPXR at the concentration of 10.0 µM and 10.0 nM, respectively, whereas thaigranatins J (5), M (8), and T (15) showed inhibitory activities against hCES2 with IC50 values of 6.63, 11.35, and 5.05 µM, respectively. The 8α,30α-epoxy moiety of mexicanolide and the Δ8,14 double bond of phragmalin are pivotal for agonistic effects of these limonoids on hPXR, whereas the 6-OAc group of mexicanolide is crucial for its inhibitory activity against hCES2. Additionally, the flexible C-17-side-chain with appropriate hydroxy groups is considered to be important for the inhibitory activity of apotirucallane against hCES2.

14.
Anticancer Drugs ; 32(3): 314-322, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33394687

RESUMO

Evodiamine (Evo), a quinazoline alkaloid and one of the most typical polycyclic heterocycles, is mainly isolated from Evodia rugulosa. Vasculogenic mimicry (VM) is a newly identified way of angiogenesis during tumor neovascularization, which is prevalent in a variety of highly invasive tumors. The purpose of this study was to investigate the effect and mechanism of Evo on VM in human colorectal cancer (CRC) cells. The number of VM structures was calculated by the three-dimensional culture of human CRC cells. Wound-healing was used to detect the migration of HCT116 cells. Gene expression was detected by reverse transcription-quantitative PCR assay. CD31/PAS staining was used to identify VM. Western blotting and immunofluorescence were used to detect protein levels. The results showed that Evo inhibited the migration of HCT116 cells, as well as the formation of VM. Furthermore, Evo reduced the expression of hypoxia-inducible factor 1-alpha (HIF-1α), VE-cadherin, VEGF, MMP2, and MMP9. In a model of subcutaneous xenotransplantation, Evo also inhibited tumor growth and VM formation. Our study demonstrates that Evo could inhibit VM in CRC cells HCT116 and reduce the expression of HIF-1α, VE-cadherin, VEGF, MMP2, and MMP9.

15.
Anal Methods ; 13(5): 626-635, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33480916

RESUMO

C-reactive protein (CRP) is one of the most commonly used biomarkers for inflammation. The standardisation of a procedure for the detection of CRP has attracted significant attention globally, and primary reference materials of CRP based on the recombinant expression of E. coli that exist in the form of monomers have been developed. However, a primary reference material of natural CRP is still required to achieve the exact matching of CRP measurements in secondary reference materials (e.g. CRP in frozen human serum). Herein, the development process for a certified reference material of natural CRP is reported, namely GBW09228. The raw material employed in this study was CRP extracted and purified from human body fluid, and exhibits a natural and verified pentameric structure. Through the use of amino acid analysis isotope dilution mass spectrometry (AAA-IDMS) and signature peptide-IDMS, this reference material was certified, and its certification results can be traced to SI units. The developed method was evaluated for its accuracy using the international comparison tests of the National Metrology Institute of Japan (NMIJ) and the Korea Research Institute of Standards and Science (KRISS). Overall, a CRP primary certified reference material (CRM) of well-characterised purity was determined that could be used to calibrate an IDMS-based reference method, that could then be used to assign target values to secondary CRMs. These secondary CRMs could in turn be used to calibrate and verify the accuracy of immunoassays, thereby giving a good foundation for establishing a complete traceability chain for CRP.

16.
Proc Natl Acad Sci U S A ; 118(5)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33495332

RESUMO

We examine the health implications of electricity generation from the 2018 stock of coal-fired power plants in India, as well as the health impacts of the expansion in coal-fired generation capacity expected to occur by 2030. We estimate emissions of SO2, NOX, and particulate matter 2.5 µm (PM2.5) for each plant and use a chemical transport model to estimate the impact of power plant emissions on ambient PM2.5 Concentration-response functions from the 2019 Global Burden of Disease (GBD) are used to project the impacts of changes in PM2.5 on mortality. Current plus planned plants will contribute, on average, 13% of ambient PM2.5 in India. This reflects large absolute contributions to PM2.5 in central India and parts of the Indo-Gangetic plain (up to 20 µg/m3). In the south of India, coal-fired power plants account for 20-25% of ambient PM2.5 We estimate 112,000 deaths are attributable annually to current plus planned coal-fired power plants. Not building planned plants would avoid at least 844,000 premature deaths over the life of these plants. Imposing a tax on electricity that reflects these local health benefits would incentivize the adoption of renewable energy.

17.
Nature ; 589(7843): 620-626, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33408414

RESUMO

Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available1-3. Here we report that glucocorticoid stress hormones activate adhesion G-protein-coupled receptor G3 (ADGRG3; also known as GPR97)4-6, a prototypical adhesion GPCR. The cryo-electron microscopy structures of GPR97-Go complexes bound to the anti-inflammatory drug beclomethasone or the steroid hormone cortisol revealed that glucocorticoids bind to a pocket within the transmembrane domain. The steroidal core of glucocorticoids is packed against the 'toggle switch' residue W6.53, which senses the binding of a ligand and induces activation of the receptor. Active GPR97 uses a quaternary core and HLY motif to fasten the seven-transmembrane bundle and to mediate G protein coupling. The cytoplasmic side of GPR97 has an open cavity, where all three intracellular loops interact with the Go protein, contributing to the high basal activity of GRP97. Palmitoylation at the cytosolic tail of the Go protein was found to be essential for efficient engagement with GPR97 but is not observed in other solved GPCR complex structures. Our work provides a structural basis for ligand binding to the seven-transmembrane domain of an adhesion GPCR and subsequent G protein coupling.

18.
Anal Bioanal Chem ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33404742

RESUMO

With the development of biomedical technology, epitope mapping of proteins has become critical for developing and evaluating new protein drugs. The application of hydrogen-deuterium exchange for protein epitope mapping holds great potential. Although several reviews addressed the hydrogen-deuterium exchange, to date, only a few systematic reviews have focused on epitope mapping using this technology. Here, we introduce the basic principles, development history, and review research progress in hydrogen-deuterium exchange epitope mapping technology and discuss its advantages. We summarize the main hurdles in applying hydrogen-deuterium exchange epitope mapping technology, combined with relevant examples to provide specific solutions. We describe the epitope mapping of virus assemblies, disease-associated proteins, and polyclonal antibodies as examples of pattern introduction. Finally, we discuss the outlook of hydrogen-deuterium exchange epitope mapping technology. This review will help researchers studying protein epitopes to gain a more comprehensive understanding of this technology.

19.
Int J Med Sci ; 18(1): 176-186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390786

RESUMO

Objective: The aim of this study was to observe the liver function recovery of COVID-19 patients after discharge. Patients and Methods: A total of 253 discharged COVID-19 patients in Shenzhen city, China were selected. The clinical characteristics of these patients were assessed. A 2-month follow-up and laboratory hematology test were performed to examine the status of patients' liver function. Results: Patients combined with liver diseases, especially fatty liver, are more likely to progress to severe condition (P<0.05). Patients in severe condition and those with liver diseases have higher rates of liver injuries during hospitalization, characterized by a significant increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.01). The ALT, AST/ALT, gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), and A/G levels showed significant differences in comparison with the control group (P<0.05, and P<0.001); and the outlier ratio of A/G, ALT, GGT and ALP of patients remained abnormal higher within 14 days after discharge (P<0.001). Liver injuries of COVID-19 patients may be related to the epidemiological characteristics, clinical indexes, basic diseases, symptoms, drug treatment during hospitalization and the complications. Indicators of liver function were correlated with cardiac function, renal function, thyroid function, lipid metabolism, glucose metabolism, immune index, leukocyte, erythrocyte, hemoglobin and platelet related indexes. The outlier ratio of TP, ALB and GLB remained extremely low throughout the follow-up period; the outlier ratio of ALT, AST and GGT decreased below 10% from a high level at 40 days after discharged. However, the outlier ratio of A/G, AST/ALT and ALP remained high during the follow-up period. Conclusions: Abnormal liver function might indicate worse recovery of COVID-19 patients. Changes in liver function should be emphasized during long-term follow-up of COVID-19 patients after hospital discharge; the necessity of employing appropriate interventions for liver function repair should be emphasized.


Assuntos
/complicações , Insuficiência Hepática/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Lactente , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Adulto Jovem
20.
Int J Med Sci ; 18(2): 347-355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390803

RESUMO

Objectives: Research on recovering COVID-19 patients could be helpful for containing the pandemic and developing vaccines, but we still do not know much about the clinical features, recovery process, and antibody reactions during the recovery period. Methods: We retrospectively analysed the epidemiological information, discharge summaries, and laboratory results of 324 patients. Results: In all, 15 (8.62%) patients experienced chest distress/breath shortness, where 8 of the 15 were severely ill. This means severely ill patients need an extended amount of time to recover after discharge; next, 20 (11.49%) patients experienced anxiety and 21 (12.07%) had headache/insomnia and a small fraction of them complained of anosmia/ageusia, indicating that these patients need treatment for mental and psychological health issues. Regarding the re-positive patients, their CT and laboratory test results showed no obvious evidence of illness progress or infectivity but a high anti-SARS-CoV-2 antibody expression. Conclusion: Recovered COVID-19 patients need psychological and physiological care and treatment, re-positivity can occur in any person, but juveniles, females, and patients with mild/moderate existing symptoms have higher rates of re-positivity, While there is no evidence that turning re-positive has an impact on their infectivity, but it still alerted us that we need differentiate them in the following managements.


Assuntos
/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ageusia , /reabilitação , Criança , Pré-Escolar , China/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Adulto Jovem
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