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1.
Microvasc Res ; 139: 104275, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34717969

RESUMO

Negative pressure wound therapy (NPWT) has been widely used in the treatment of chronic wounds, including diabetic foot ulcers (DFU) as the severe manifestation of diabetic foot. Hsa-miR-203 is proven to be correlated with the severity of DFU. To investigate whether NPWT influences hsa-miR-203 levels in persons with DFU, we detected hsa-miR-203 levels in peripheral plasma and wound margin tissue from the following patients: type 2 diabetic (T2D) patients with DFU (DFU group), T2D patients without DFU (NDFU group), patients with chronic skin ulcer and normal glucose tolerance (SUC group), and healthy volunteers with normal glucose tolerance (NC group). All patients in SUC group received NPWT. As contrast, some of patients in DFU group received NPWT (NPWT group) while others chose routine dressing therapy (non-NPWT group). In vitro experiments were also performed to determine influences of negative pressure on cell proliferation and migration of HaCaT cells (human keratinocytes). Results showed that before NPWT, levels of hsa-miR-203 in peripheral plasma (P-miR-203) and wound margin tissue (T-miR-203) of DFU group were obviously increased compared to SUC group while expression of P-miR-203 decreased in NDFU group compared with NC group. After NPWT, levels of P-miR-203 and T-miR-203 in DFU and SUC group were significantly lower than before. Changes of P-miR-203 and T-miR-203 after NPWT were positively correlated with 4-week ulcer healing rate in NPWT and SUC group. In vitro, negative pressure lowered the expression of hsa-miR-203, enhancing cell proliferation and migration in HaCaT cells via up-regulation of p63 protein. Meanwhile, the effects of negative pressure on cells were remarkable reduced by high-glucose intervention. Our study suggests that NPWT promotes DFU healing by reducing the expression of hsa-miR-203 in peripheral blood and wound tissue. The changes of hsa-miR-203 in peripheral blood and wound tissue may be related to the therapeutic effect of NPWT.

2.
Talanta ; 237: 122967, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736691

RESUMO

Taking advantage of an exquisite hairpin DNA for strand displacement amplification (SDA) and the magnetic Fe3O4-graphene oxide nanosheets (MGN) as the carrier, an immobilization-free ECL biosensor was constructed for ultra-trace detection of Cd2+. Firstly, the ECL probe Ru (phen)32+ easily diffuses in the solution and reaches the electrode surface to induce strong ECL signal. This is because the pre-designed hairpin DNA is constrained by MGN in the absence of Cd2+. The presence of Cd2+ releases cDNA by binding to its corresponding aptamer, leading to removal of hairpin DNA away from the surface of MGN. In this case, SDA amplification was evoked and generated numerous dsDNA which further trapped Ru (phen)32+ in its groove. It is difficult for the embedded ECL probe to touch the electrode surface to generate ECL signal. Therefore, the concentration of Cd2+ was monitored according to the attenuation of ECL signal. This method showed high sensitivity to Cd2+ with a detection limit of 1.1 × 10-4 ppb. Moreover, it not only avoids many condition optimizations required in the conventional SDA method, but also circumvent the modification and immobilization of DNA probe. This sensor is further applied in the detection of Cd2+ in the sample of traditional Chinese medicine.


Assuntos
Técnicas Biossensoriais , Cádmio , Sondas de DNA , Medições Luminescentes , Fenômenos Magnéticos
3.
Anal Chem ; 93(45): 15216-15223, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34736322

RESUMO

The development of a sensitive, facile, and cost-effective colorimetric method is of great significance for the point-of-care testing of viral nucleic acid. Herein, we reported a strand displacement amplification assisted CRISPR-Cas12a (SDACC) method for the colorimetric analysis of viral nucleic acid. The hepatitis B virus (HBV) DNA was chosen as the target to trigger strand displacement amplification (SDA) and generate abundant single-strand DNA (ssDNA) products. The ssDNA amplicon hybridized with template DNA to activate the trans-cleavage activity of CRISPR-Cas12a, leading to the nonspecific cleavage of ssDNA on GOx-ssDNA-modified magnetic beads and the release of GOx. The released GOx was capable of catalyzing the substrate solution to generate a color change, which could be directly observed by naked eyes. The SDACC strategy could identify a single-base mismatch located in the DNA sequence and achieve a sensitive detection for HBV DNA with the limit of detection as low as 41.8 fM. Notably, the sophisticated primer design for target amplification and complicated detection process could be circumvented. The current approach realizes a simple, low-cost, and sensitive colorimetric detection for viral nucleic acid and holds great promise for the practical application of virus infection diagnosis.


Assuntos
Técnicas Biossensoriais , Ácidos Nucleicos , Sistemas CRISPR-Cas/genética , Colorimetria , DNA , DNA de Cadeia Simples/genética , Técnicas de Amplificação de Ácido Nucleico
4.
Front Genet ; 12: 783128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804131

RESUMO

Given the limitation of technologies, the subcellular localizations of proteins are difficult to identify. Predicting the subcellular localization and the intercellular distribution patterns of proteins in accordance with their specific biological roles, including validated functions, relationships with other proteins, and even their specific sequence characteristics, is necessary. The computational prediction of protein subcellular localizations can be performed on the basis of the sequence and the functional characteristics. In this study, the protein-protein interaction network, functional annotation of proteins and a group of direct proteins with known subcellular localization were used to construct models. To build efficient models, several powerful machine learning algorithms, including two feature selection methods, four classification algorithms, were employed. Some key proteins and functional terms were discovered, which may provide important contributions for determining protein subcellular locations. Furthermore, some quantitative rules were established to identify the potential subcellular localizations of proteins. As the first prediction model that uses direct protein annotation information (i.e., functional features) and STRING-based protein-protein interaction network (i.e., network features), our computational model can help promote the development of predictive technologies on subcellular localizations and provide a new approach for exploring the protein subcellular localization patterns and their potential biological importance.

5.
Nat Plants ; 7(11): 1495-1504, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34764442

RESUMO

Strigolactones (SLs) are carotenoid-derived plant hormones that control shoot branching and communications between host plants and symbiotic fungi or root parasitic plants. Extensive studies have identified the key components participating in SL biosynthesis and signalling, whereas the catabolism or deactivation of endogenous SLs in planta remains largely unknown. Here, we report that the Arabidopsis carboxylesterase 15 (AtCXE15) and its orthologues function as efficient hydrolases of SLs. We show that overexpression of AtCXE15 promotes shoot branching by dampening SL-inhibited axillary bud outgrowth. We further demonstrate that AtCXE15 could bind and efficiently hydrolyse SLs both in vitro and in planta. We also provide evidence that AtCXE15 is capable of catalysing hydrolysis of diverse SL analogues and that such CXE15-dependent catabolism of SLs is evolutionarily conserved in seed plants. These results disclose a catalytic mechanism underlying homoeostatic regulation of SLs in plants, which also provides a rational approach to spatial-temporally manipulate the endogenous SLs and thus architecture of crops and ornamental plants.

6.
Comput Struct Biotechnol J ; 19: 5722-5734, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745457

RESUMO

Cholangiocarcinomas (CCAs) are tumors that arise from the cholangiocytes. Although some genes have been shown with important roles in pathological process, interactions or cross-talks among different RNAs are important to understand the detailed molecular mechanisms in cancer development, especially discussing cross-talks among isomiRs and other RNAs. Herein, to characterize crucial genes in CCA, the protein expression profile was performed to survey potential crucial mRNAs and related non-coding RNAs (ncRNAs) in mRNA-ncRNA network, mainly including miRNAs/isomiRs and lncRNAs. Deregulated mRNAs were firstly obtained if consistent expression patterns were found at protein and mRNA levels, and related miRNAs/isomiRs were screened according to regulatory relationships. Diverse isomiRs from a given miRNA locus also contributed to interactions between the small RNAs and target mRNAs, and miRNAs were further used to survey related lncRNAs to expand the interactions. Thus, several groups of RNAs were constructed as candidate competitive endogenous RNA (ceRNA) networks. Finally, we found that RAB11FIP1:miR-101-3p:MIR3142HG may be a potential ceRNA network, and the interactions among them may be more complex due to variety of isomiRs. Simultaneously, RAB11FIP1 and miR-194-5p were also detected other related lncRNAs (FBXL19-AS1, SNHG1 and PVT1) that may be crucial in coding-non-coding RNA regulatory network. Our results show that diverse isomiRs with sequence and expression heterogeneities contribute to ceRNA regulatory network that may have crucial roles in CCA, which will expand our understanding of interactions among diverse RNAs and their contributions in cancer development.

7.
Kidney Cancer J ; 19(3): 64-72, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34765076

RESUMO

Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC treated with the mTOR inhibitor everolimus (n=57) or the vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib (n=51), stratified by MSKCC risk and histology. The primary endpoint was overall survival (OS) and secondary efficacy endpoints for this exploratory biomarker analysis were radiographic progression-free survival (rPFS) defined by intention-to-treat using the RECIST 1.1 criteria and radiographic response rates. Tissue biomarkers (n=78) of mTOR pathway activation (phospho-S6 and -Akt, c-kit) and VEGF pathway activation (HIF-1α, c-MET) were prospectively explored in tumor tissue by immunohistochemistry prior to treatment and associated with clinical outcomes. We found that S6 activation was more common in poor risk NC-RCC tumors and S6/Akt activation was associated with worse PFS and OS outcomes with both everolimus and sunitinib, while c-kit was commonly expressed in chromophobe tumors and associated with improved outcomes with both agents. C-MET was commonly expressed in papillary tumors and was associated with lower rates of radiographic response but did not predict PFS for either agent. In multivariable analysis, both pAkt and c-kit were statistically significant prognostic biomarkers of OS. No predictive biomarkers of treatment response were identified for clinical outcomes. Most biomarker subgroups had improved outcomes with sunitinib as compared to everolimus.

8.
Sensors (Basel) ; 21(21)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34770415

RESUMO

In the past few decades, biosensors have been gradually developed for the rapid detection and monitoring of human diseases. Recently, functional nucleic-acid (FNA) biosensors have attracted the attention of scholars due to a series of advantages such as high stability and strong specificity, as well as the significant progress they have made in terms of biomedical applications. However, there are few reports that systematically and comprehensively summarize its working principles, classification and application. In this review, we primarily introduce functional modes of biosensors that combine functional nucleic acids with different signal output modes. In addition, the mechanisms of action of several media of the FNA biosensor are introduced. Finally, the practical application and existing problems of FNA sensors are discussed, and the future development directions and application prospects of functional nucleic acid sensors are prospected.


Assuntos
Técnicas Biossensoriais , Ácidos Nucleicos , Humanos
9.
Adv Mater ; : e2104120, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632647

RESUMO

High selectivity to specific analyte is essential for chemical sensors but difficult to achieve. For most chemical sensors, although the response to the target analyte can be more significant than interference analytes, they still show obvious responses to the interference analytes. Here, highly selective chemical sensors are developed with negligible responses to other interference vapors. Instead of the widely investigated electronically conductive metal-organic frameworks (EC-MOFs), ionically conductive MOFs (IC-MOFs) are used as the sensing materials, and the unique interaction between the ion charge carrier and the analyte is utilized to achieve high sensing selectivity. Through the modulation of the metal nodes (Cu, Co, Ni, Zn, Mg) and organic ligands (H2 TCPP, H2 THPP, H4 BTEC), sensor arrays based on a set of IC-MOFs are fabricated and achieve highly selective detection toward volatile sulfur compounds (VSCs). H2 S and CH3 SH can be selectively detected at concentrations down to 1 ppb and 1 ppm, respectively. The facile preparation and low cost endow the device with disposability. These results suggest new approaches for the development of highly selective chemical sensors.

10.
Front Nutr ; 8: 750355, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692753

RESUMO

Our previous research showed that capsaicin exhibits hypoglycemic effects by activating the transient receptor potential vanilloid 1 (TRPV1) channel in diabetic rats. Interestingly, capsiate was also able to activate the TRPV1 channel, but with a non-significant hypoglycemic effect. This study aimed to investigate the effect of capsaicin on the glycometabolism of streptozotocin (STZ)-induced diabetic rats by blocking the TRPV1 channel. After a 4-week capsaicin treatment (6 mg/kg·bw), the serum insulin level of STZ-induced diabetic rats increased from 15.2 to 22.1 mIU/L, the content of hepatic glycogen and muscle glycogen increased by 81.2 and 20.2%, respectively, and the blood glucose level decreased significantly from 19.3 to 14.7 mmol/L. When the TRPV1 channel was blocked, capsaicin lost the above-mentioned effects, and the hypoglycemic effect was no longer significant. It was concluded that a combined up-regulation of both TRPV1 receptors and pancreatic duodenal homeobox-1 (PDX-1) led to the hypoglycemic effect of capsaicin, which partially explains our previous observation: capsiate activating TRPV1 without showing a significant hypoglycemic effect was due to the lack of a significant up-regulation of PDX-1. Based on the experimental results, we speculated that two signaling pathways [TRPV1-(PDX1)-(GLUT2/GK) and TRPV1-(PDX-1)-(IRS1/2)] exist in the pancreas of STZ-induced diabetic rats.

11.
J Int Med Res ; 49(10): 3000605211051225, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34670424

RESUMO

OBJECTIVE: To evaluate the prevalence of type 2 diabetes mellitus (T2DM) with chronic kidney disease (DM-CKD) and identify the associated factors in patients attending primary hospitals in Anhui Province, China. METHODS: A multi-stage sampling method was used to collect the demographic information, general clinical data, and details of the kidney disease of patients in 2019 through a questionnaire survey, physical examination, and laboratory examination. RESULTS: A total of 1067 patients with T2DM were studied, of whom 345 had chronic kidney disease (CKD; 32.33%); 18.8%, 12.2%, 58.0%, 9.9% and 1.2% of the participants had stages 1 to 5 CKD. Fifty-point-three percent of the participants were female and they were 59 ± 11.3 years old. Multivariate regression analysis revealed that age, systolic blood pressure, the duration of diabetes, hyperlipidaemia, and smoking were associated with DM-CKD. The duration of diabetes was positively associated with body mass index, 2-hour postprandial glucose, fasting blood glucose concentration, glycosylated haemoglobin, total cholesterol concentration and triglyceride concentration. CONCLUSIONS: The incidence of DM-CKD is relatively high in primary hospitals in Anhui Province. Appropriate preventive and therapeutic measures should be instituted according to the age, the duration of diabetes, sex, hypertension, smoking habits, and lipidaemia of patients.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Idoso , China/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/epidemiologia , Feminino , Hospitais , Humanos , Pessoa de Meia-Idade , Prevalência
12.
Front Vet Sci ; 8: 726731, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513977

RESUMO

DNA methylation, mediated by DNA methyltransferases (Dnmts), is a typical epigenetic process that plays an important role in affecting organism acclimatization and adaptation to environmental changes. However, information about Dnmts and their associations with the cold tolerance of ticks remains meager. Hence, in the present study, the Dnmts in important vector ticks Dermacentor silvarum and Haemaphysalis longicornis were cloned and identified, and their functions in cold response were further explored. Results showed that the length of DsDnmt and DsDnmt1 in D. silvarum, and HlDnmt1 and HlDnmt in H. longicornis were 1,284, 549, 1,500, and 1,613 bp, respectively. Bioinformatics in protein analysis revealed that they were all unstable hydrophilic proteins and were mainly characterized with Dcm (DNA cytosine methyltransferase domain), Dnmt1-RFD (DNA methyltransferase replication foci domain), zf-CXXC (zinc finger-CXXC domain), and BAH (Bromo adjacent homology domain). The relative expression of these Dnmts was reduced after cold treatment for 3 days (P < 0.05), and increased with the extension of treatment. Western blot revealed that Dnmt1 decreased first and then increased significantly (P < 0.05) in both tick species, whereas other Dnmts fluctuated at varying degrees. RNA interference significantly silenced the genes Dnmts (P < 0.01), and mortality increased significantly (P < 0.05), when exposed to sub-lethal temperature, underscoring the important roles of Dnmts during the cold response of D. silvarum and H. longicornis. The above results lay the foundation for further understanding of the epigenetic regulation of DNA methylation in cold acclimatization and adaptation of ticks.

13.
Molecules ; 26(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34500708

RESUMO

The purpose of this study is to investigate the potential effects of 5-hydroxytryptophan (5-HTP) duodenal perfusion on melatonin (MT) synthesis in the gastrointestinal (GI) tract of sheep. 5-hydroxytryptophan is a precursor in the melatonin synthetic pathway. The results showed that this method significantly increased melatonin production in the mucosa of all segments in GI tract including duodenum, jejunum, ileum, cecum and colon. The highest melatonin level was identified in the colon and this indicates that the microbiota located in the colon may also participate in the melatonin production. In addition, portion of the melatonin generated by the GI tract can pass the liver metabolism and enters the circulation via portal vein. The current study provides further evidence to support that GI tract is the major site for melatonin synthesis and the GI melatonin also contributes to the circulatory melatonin level since plasma melatonin concentrations in 5-HTP treated groups were significantly higher than those in the control group. In conclusion, the results show that 10-50 mg of 5-HTP flowing into the duodenum within 6 h effectively improve the production of melatonin in the GI tract and melatonin concentration in sheep blood circulation during the day.

14.
Int J Mol Sci ; 22(18)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34575828

RESUMO

Food microbial contamination not only poses the problems of food insecurity and economic loss, but also contributes to food waste, which is another global environmental problem. Therefore, effective packaging is a compelling obstacle for shielding food items from outside contaminants and maintaining its quality. Traditionally, food is packaged with plastic that is rarely recyclable, negatively impacting the environment. Bio-based materials have attracted widespread attention for food packaging applications since they are biodegradable, renewable, and have a low carbon footprint. They provide a great opportunity to reduce the extensive use of fossil fuels and develop food packaging materials with good properties, addressing environmental problems and contributing significantly to sustainable development. Presently, the developments in food chemistry, technology, and biotechnology have allowed us to fine-tune new methodologies useful for addressing major safety and environmental concerns regarding packaging materials. This review presents a comprehensive overview of the development and potential for application of new bio-based materials from different sources in antimicrobial food packaging, including carbohydrate (polysaccharide)-based materials, protein-based materials, lipid-based materials, antibacterial agents, and bio-based composites, which can solve the issues of both environmental impact and prevent foodborne pathogens and spoilage microorganisms. In addition, future trends are discussed, as well as the antimicrobial compounds incorporated in packaging materials such as nanoparticles (NPs), nanofillers (NFs), and bio-nanocomposites.


Assuntos
Materiais Biocompatíveis , Contaminação de Alimentos , Microbiologia de Alimentos , Embalagem de Alimentos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Materiais Biocompatíveis/química , Biopolímeros/química , Fenômenos Químicos , Contaminação de Alimentos/prevenção & controle , Embalagem de Alimentos/métodos , Embalagem de Alimentos/tendências , Conservação de Alimentos , Humanos , Nanocompostos/química
15.
Medicine (Baltimore) ; 100(30): e26714, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397704

RESUMO

BACKGROUND: It is necessary to systematically evaluate the clinical efficacy and safety of bevacizumab (BEV) combined with 5-fluorouracil + leucovorin + oxaliplatin (FOLFOX) regimen in the treatment of advanced colorectal cancer. METHODS: We searched the PubMed et al databases for randomized controlled trials (RCTs) on the BEV combined with the FOLFOX regimen in the treatment of advanced colorectal cancer up to January 20, 2021. The Cochrane Collaborations' risk of bias tool was used for the quality assessment of included RCTs. Revman5.3 software was used for meta-analysis. RESULTS: Eleven RCTs with a total of 3178 patients with advanced colorectal cancer were included, meta-analysis results showed that the objective response rate (odds ratio [OR] = 3.15, 95% confidence intervals [CI]: 2.25-4.40, P < .001) and cancer control rate (OR = 2.73, 95% CI: 1.91-3.90, P < .001) of BEV + FOLFOX were higher than that of FOLFOX group. And the incidence of gastrointestinal adverse reactions (OR = 1.29, 95% CI: 1.07-1.55, P = .008) in the BEV + FOLFOX group was higher than that of the FOLFOX group, there were no significant differences in the incidence of leukopenia (OR = 1.04, 95% CI: 0.72-1.50, P = .83), hypertension (OR = 3.92, 95% CI: 0.81-18.88, P = .09) and neurotoxicity (OR = 1.00, 95% CI: 0.8-1.27, P = .98) between the 2 groups. CONCLUSION: BEV combined with the FOLFOX regimen is more effective than the FOLFOX regimen alone in the treatment of advanced colorectal cancer, but it may also increase the risk of gastrointestinal adverse reactions.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico
16.
Anal Chem ; 93(35): 11899-11909, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34427091

RESUMO

Timely diagnosis is of great benefit to improve the survival rate of cancer patients. Body fluid cancer biomarker detection is a critical kind of noninvasive method for cancer diagnosis. Nevertheless, traditional methods for cancer biomarker detection always rely on a large-scale instrument and involve sophisticated operation. Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas)-based in vitro diagnosis can simplify the detection procedures and improve sensitivity and specificity, holding great promise as the next-generation molecular diagnostic technology. In this Feature, we introduce the working mechanisms of different kinds of CRISPR/Cas systems for biosensing and CRISPR/Cas-mediated detection strategies for different kinds of cancer biomarkers including nucleic acids, proteins, and extracellular vesicles. In addition, the perspective and challenges of CRISPR/Cas-based strategies for cancer biomarkers are discussed.


Assuntos
Neoplasias , Ácidos Nucleicos , Biomarcadores Tumorais/genética , Sistemas CRISPR-Cas/genética , Humanos , Neoplasias/diagnóstico , Neoplasias/genética
17.
Org Lett ; 23(17): 6819-6824, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34406013

RESUMO

α-Imino ketone is a useful building block for the preparation of α-amino ketones and α-amino alcohols. However, its preparation has been seldomly seen. Herein, a metal-free and operationally simple strategy has been developed to generate α-imino ketones with high regioselectivity. Meanwhile, the method allowed for the preparation of various N,O-ketals with high regioselectivities and diastereoselectivities through cascade reactions in one pot.

18.
Front Microbiol ; 12: 711244, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305880

RESUMO

Type 2 diabetes (T2D) is a systematic chronic metabolic condition with abnormal sugar metabolism dysfunction, and its complications are the most harmful to human beings and may be life-threatening after long-term durations. Considering the high incidence and severity at late stage, researchers have been focusing on the identification of specific biomarkers and potential drug targets for T2D at the genomic, epigenomic, and transcriptomic levels. Microbes participate in the pathogenesis of multiple metabolic diseases including diabetes. However, the related studies are still non-systematic and lack the functional exploration on identified microbes. To fill this gap between gut microbiome and diabetes study, we first introduced eggNOG database and KEGG ORTHOLOGY (KO) database for orthologous (protein/gene) annotation of microbiota. Two datasets with these annotations were employed, which were analyzed by multiple machine-learning models for identifying significant microbiota biomarkers of T2D. The powerful feature selection method, Max-Relevance and Min-Redundancy (mRMR), was first applied to the datasets, resulting in a feature list for each dataset. Then, the list was fed into the incremental feature selection (IFS), incorporating support vector machine (SVM) as the classification algorithm, to extract essential annotations and build efficient classifiers. This study not only revealed potential pathological factors for diabetes at the microbiome level but also provided us new candidates for drug development against diabetes.

19.
Endocr Pract ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34216800

RESUMO

OBJECTIVE: Agranulocytosis is a rare but serious adverse drug reaction (ADR) of thionamide antithyroid drugs (ATDs). We explored the characteristics of ADRs in patients with hyperthyroidism. METHODS: This retrospective study included 3558 inpatients with Graves disease treated in a Class A Grade 3 hospital between 2015 and 2019. The clinical presentation and laboratory workup of patients with antithyroid drug (ATD)-induced agranulocytosis was analyzed. RESULTS: Agranulocytosis was thought to be caused by ATDs in 36 patients. The hospital length of stay was 12 (10-16) days, and hospitalization costs were approximately $2810.89 ($2156.50-$4164.67). The median duration of ATD therapy prior to agranulocytosis development was 30 (20-40) days. Fever (83.33%) and sore throat (75%) were the most common symptoms as early signs of agranulocytosis. The lowest neutrophil counts were 0.01 (0.00-0.03) × 109/L and 0.14 (0.02-0.29) × 109/L in the methimazole and propylthiouracil groups, respectively (P = .037). The recovery times of agranulocytosis were 9.32 ± 2.89 days and 5.60 ± 4.10 days in the methimazole and propylthiouracil groups, respectively (P = .016). Patients with severe agranulocytosis required a longer time to recover (P < .001) and had closer to normal serum thyroxine and triiodothyronine levels. The interval between the first symptom of agranulocytosis and ATD withdrawal was 1 (0-3) day. CONCLUSIONS: Patients with agranulocytosis needed a long hospital length of stay and incurred high costs. Methimazole was prone to causing a more serious agranulocytosis than propylthiouracil. High thyroid hormone was unlikely to play a role in adverse drug reactions. Patient education is important.

20.
Seizure ; 91: 278-286, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34252880

RESUMO

PURPOSE: Glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) are assessed as oxidative stress markers to determine the impact of oxidation on the levels of GSH-Px and SOD in patients with epilepsy (PWE) and healthy controls. METHODS: A meta-analysis was completed on twenty-nine published studies. A total of 636 PWE and 665 healthy controls, 303 PWE and 191 controls, and 22 PWE and 22 controls were included to study GSH-Px levels in erythrocytes, serum and plasma, respectively. For SOD studies, there were 610 PWE and 680 controls, 464 PWE and 382 controls, and 62 PWE with 77 controls for erythrocytes, serum and plasma, respectively. RESULTS: Meta-analysis showed that the erythrocyte SOD level was significantly lower in PWE than in healthy controls (SMD =-1.96; 95% CI [-2.93, -0.99]; P<0.0001). Moreover, the meta-analysis demonstrated that in serum and plasma, SOD levels in PWE were significantly lower than those in healthy controls (SMD =-1.47; 95% CI [-2.47, -0.48]; P<0.0001). Erythrocyte GSH-Px levels had a tendency to decrease in PWE compared with healthy controls (SMD =-0.31; 95% CI [-1.48, 0.85]; P=0.598), but the results showed no significant difference. CONCLUSION: Our results showed reduced SOD levels in erythrocytes, serum and plasma in PWE, which may be an indicator of oxidative damage in epilepsy. This is the first meta-analysis of circulating GSH-Px and SOD levels in PWE and healthy controls.


Assuntos
Epilepsia , Glutationa Peroxidase/sangue , Superóxido Dismutase/sangue , Eritrócitos/metabolismo , Humanos , Estresse Oxidativo
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