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1.
Drug Metab Dispos ; 2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36116790

RESUMO

The human gut is home to trillions of microorganisms that are responsible for the modification of many orally administered drugs, leading to a wide range of therapeutic outcomes. Prodrugs bearing an azo bond are designed to treat inflammatory bowel disease (IBD) and colorectal cancer (CRC) via microbial azo reduction, allowing for topical application of therapeutic moieties to the diseased tissue in the intestines. Despite the inextricable link between microbial azo reduction and the efficacy of azo prodrugs, the prevalence, abundance, and distribution of azoreductases have not been systematically examined across the gut microbiome. Here, we curated and clustered amino acid sequences of experimentally confirmed bacterial azoreductases and conducted a Hidden Markov Model (HMM)-driven homolog search for these enzymes across 4,644 genome sequences present in the representative Unified Human Gastrointestinal Genomes (UHGG) collection. We identified 1,958 putative azo-reducing species, corroborating previous findings that azo reduction appears to be a ubiquitous function of the gut microbiome. However, through a systematic comparison of predicted and confirmed azo-reducing strains, we hypothesize the presence of uncharacterized azoreductases in 25 prominent strains of the human gut microbiome. Finally, we confirmed the azo reduction of Acid Orange 7 by multiple strains of Fusobacterium nucleatum, Bacteroides fragilis, and Clostridium clostridioforme Together, these results suggest the presence and activity of many uncharacterized azoreductases in the human gut microbiome and motivate future studies aimed at characterizing azoreductase genes in prominent members of the human gut microbiome. Significance Statement In this work, we systematically examined the prevalence, abundance, and distribution of azoreductases across the healthy and IBD human gut microbiome revealing potentially uncharacterized azoreductase genes. We also confirmed the reduction of Acid Orange 7 by strains of Fusobacterium nucleatum, Bacteroides fragilis, and Clostridium clostridioforme.

2.
Eur Radiol ; 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36169686

RESUMO

OBJECTIVES: The purpose of this study was to establish two preoperative nomograms to evaluate the risk for axillary lymph node (ALN) metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features. METHODS: We prospectively evaluated 593 consecutive female participants who were diagnosed with cT1-3N0-1M0 breast cancer between March 2018 and May 2019 at Sun Yat-Sen Memorial Hospital. The participants were randomly classified into training and validation sets in a 4:1 ratio for the development and validation of the nomograms, respectively. Multivariate logistic regression analysis was performed to identify independent predictors of ALN status. We developed Nomogram A and Nomogram B to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2), respectively. RESULTS: A total of 528 participants were evaluated in the final analyses. Multivariable analysis revealed that the number of suspicious lymph nodes, long axis, short-to-long axis ratio, cortical thickness, tumor location, and histological grade were independent predictors of ALN status. The AUCs of nomogram A in the training and validation groups were 0.83 and 0.78, respectively. The AUCs of nomogram B in the training and validation groups were 0.87 and 0.87, respectively. Both nomograms were well-calibrated. CONCLUSION: We developed two preoperative nomograms that can be used to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2) in early breast cancer patients. Both nomograms are useful tools that will help clinicians predict the risk of ALN metastasis and facilitate therapy decision-making about axillary surgery. KEY POINTS: • We developed two preoperative nomograms to predict axillary lymph node status based on ultrasonographic-clinicopathologic features. • Nomogram A was used to predict axillary lymph node metastasis (presence vs. absence). The AUCs in the training and validation groups were 0.83 and 0.78, respectively. Nomogram B was used to estimate the number of metastatic lymph nodes ( ≤ 2 vs. > 2). The AUCs in the training and validation group were 0.87 and 0.87, respectively. • Our nomograms may help clinicians weigh the risks and benefits of axillary surgery more appropriately.

3.
Cell Signal ; 99: 110435, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35953026

RESUMO

BACKGROUND: Allergic rhinitis (AR) is a common disease worldwide. Imbalances in T helper (Th) cell differentiation and the dysregulation of related cytokines form the immunological basis of AR. miR-126 may play an important regulatory role in AR as a new marker and predictor of the disease. Therefore, the aim of this study was to explore the regulatory effects of miR-126 on Th cell differentiation and cytokine expression in AR. METHODS: T lymphocytes and rat models were transfected with a miR-126 mimic and an inhibitor. The expression of miR-126 and Th cell-related cytokines was detected by RT-qPCR and western blotting. The serum IgE levels were detected using ELISA. In the nasal mucosa, pathological changes were observed by HE staining, protein expression was detected by immunohistochemistry, and the differentiation ratio of Th cell subsets was detected by flow cytometry. RESULTS: During the occurrence and development of AR, the expression of miR-126 and the IgE levels were increased in the AR group. The number of Treg cell subsets decreased in the AR rats, increased after the miR-126 agomir intervention and decreased after miR-126 antagomir intervention. The number of Th1 and Th2 cell subsets increased in the AR rats, decreased after miR-126 agomir intervention and increased after the miR-126 antagomir intervention. CONCLUSION: We propose that miR-126 may be involved in the pathogenesis of AR by positively regulating the expression of Treg cytokines and negatively regulating the expression of the Th1 and Th2 cytokines.

4.
NAR Genom Bioinform ; 4(3): lqac057, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35937545

RESUMO

Temperate phages (active prophages induced from bacteria) help control pathogenicity, modulate community structure, and maintain gut homeostasis. Complete phage genome sequences are indispensable for understanding phage biology. Traditional plaque techniques are inapplicable to temperate phages due to their lysogenicity, curbing their identification and characterization. Existing bioinformatics tools for prophage prediction usually fail to detect accurate and complete temperate phage genomes. This study proposes a novel computational temperate phage detection method (TemPhD) mining both the integrated active prophages and their spontaneously induced forms (temperate phages) from next-generation sequencing raw data. Applying the method to the available dataset resulted in 192 326 complete temperate phage genomes with different host species, expanding the existing number of complete temperate phage genomes by more than 100-fold. The wet-lab experiments demonstrated that TemPhD can accurately determine the complete genome sequences of the temperate phages, with exact flanking sites, outperforming other state-of-the-art prophage prediction methods. Our analysis indicates that temperate phages are likely to function in the microbial evolution by (i) cross-infecting different bacterial host species; (ii) transferring antibiotic resistance and virulence genes and (iii) interacting with hosts through restriction-modification and CRISPR/anti-CRISPR systems. This work provides a comprehensively complete temperate phage genome database and relevant information, which can serve as a valuable resource for phage research.

5.
J Agric Food Chem ; 70(28): 8569-8581, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35816090

RESUMO

Diabetes mellitus (DM) is a serious metabolic disease characterized by persistent hyperglycemia, with a continuously increasing morbidity and mortality. Although traditional treatments including insulin and oral hypoglycemic drugs maintain blood glucose levels within the normal range to a certain extent, there is an urgent need to develop new drugs that can effectively improve glucose metabolism and diabetes-related complications. Notably, accumulated evidence implicates that the gut microbiota is unbalanced in DM individuals and is involved in the physiological and pathological processes of this metabolic disease. In this review, we introduce the molecular mechanisms by which the gut microbiota contributes to the development of DM. Furthermore, we summarize the preclinical studies of bioactive natural products that exert antidiabetic effects by modulating the gut microbiota, aiming to expand the novel therapeutic strategies for DM prevention and management.


Assuntos
Produtos Biológicos , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina/farmacologia
6.
mSystems ; 7(3): e0017922, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35582907

RESUMO

Insertions in the SARS-CoV-2 genome have the potential to drive viral evolution, but the source of the insertions is often unknown. Recent proposals have suggested that human RNAs could be a source of some insertions, but the small size of many insertions makes this difficult to confirm. Through an analysis of available direct RNA sequencing data from SARS-CoV-2-infected cells, we show that viral-host chimeric RNAs are formed through what are likely stochastic RNA-dependent RNA polymerase template-switching events. Through an analysis of the publicly available GISAID SARS-CoV-2 genome collection, we identified two genomic insertions in circulating SARS-CoV-2 variants that are identical to regions of the human 18S and 28S rRNAs. These results provide direct evidence of the formation of viral-host chimeric sequences and the integration of host genetic material into the SARS-CoV-2 genome, highlighting the potential importance of host-derived insertions in viral evolution. IMPORTANCE Throughout the COVID-19 pandemic, the sequencing of SARS-CoV-2 genomes has revealed the presence of insertions in multiple globally circulating lineages of SARS-CoV-2, including the Omicron variant. The human genome has been suggested to be the source of some of the larger insertions, but evidence for this kind of event occurring is still lacking. Here, we leverage direct RNA sequencing data and SARS-CoV-2 genomes to show that host-viral chimeric RNAs are generated in infected cells and two large genomic insertions have likely been formed through the incorporation of host rRNA fragments into the SARS-CoV-2 genome. These host-derived insertions may increase the genetic diversity of SARS-CoV-2 and expand its strategies to acquire genetic material, potentially enhancing its adaptability, virulence, and spread.

7.
Adv Sci (Weinh) ; 9(20): e2201046, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35557501

RESUMO

The low-energy layer edge states (LESs) from quasi 2D hybrid perovskite single crystals have shown great potential because of their nontrivial photoelectrical properties. However, the underlying formation mechanism of the LESs still remains controversial. Also, the presence or creation of the LESs is of high randomness due to the lack of proper techniques to manually generate these LESs. Herein, using a single crystals platform of quasi-2D (BA)2 (MA)n-1 Pbn I3n+1 (n > 1) perovskites, the femtosecond laser ablation approach to design and write the LESs with a high spatial resolution is reported. Fundamentally, these LESs are of smaller bandgap 3D MAPbI3 nanocrystals which are formed by the laser-induced BA escaping from the lattice and thus the lattice shrinkage from quasi-2D to 3D structures. Furthermore, by covering the crystal with tape, an additional high-energy emission state corresponding to the reformation of (BA)2 PbI4 (n = 1) within the irradiation region is generated. This work presents a simple and efficient protocol to manually write LESs on single crystals and thus lays the foundation for utilizing these LESs to further enhance the performance of future photoelectronic devices.

8.
Front Microbiol ; 13: 818881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35516432

RESUMO

Antimicrobial resistance (AMR) represents one of the main challenges in Tuberculosis (TB) treatment. Investigating the genes involved in AMR and the underlying mechanisms holds promise for developing alternative treatment strategies. The results indicate that dehydroquinate synthase (DHQS) regulates the susceptibility of Mycobacterium bovis BCG to first-line anti-TB drug streptomycin. Perturbation of the expression of aroB encoding DHQS affects the susceptibility of M. bovis BCG to streptomycin. Purified DHQS impairs in vitro antibacterial activity of streptomycin, but did not hydrolyze or modify streptomycin. DHQS directly binds to streptomycin while retaining its own catalytic activity. Computationally modeled structure analysis of DHQS-streptomycin complex reveals that DHQS binds to streptomycin without disturbing native substrate binding. In addition, streptomycin treatment significantly induces the expression of DHQS, thus resulting in DHQS-mediated susceptibility. Our findings uncover the additional function of DHQS in AMR and provide an insight into a non-canonical resistance mechanism by which protein hijacks antibiotic to reduce the interaction between antibiotic and its target with normal protein function retained.

9.
Cancer Manag Res ; 14: 1475-1492, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463798

RESUMO

Purpose: To explore the mechanism of AP1S1 in breast cancer. Methods and Results: In different datasets, we found that AP1S1 is more highly expressed in breast tumors, which was furthermore verified in our local cohort.Immune infiltration analysis showed that AP1S1 was related to a variety of immune cells. The higher AP1S1 expression was negatively correlated with a variety of immune infiltrating cells, suggesting that AP1S1 may affect cellular immunity.Clinical analysis showed that patients with higher AP1S1 expression had higher estrogen receptor gene expression and were more prone to distant metastasis and lymph node metastasis.The overall survival rate, disease-specific survival rate, and progression-free interval time were worse in the group with higher AP1S1 expression. AP1S1 may be a potential oncogene of breast cancer, and overexpression is related to the poor prognosis of breast cancer.Therefore, a nomogram was constructed, along with correlated gene analysis and functional analysis to further explore the carcinogenic mechanism, practical clinical issues, and value of AP1S1. Conclusion: AP1S1 is a potential oncogene of breast cancer.

10.
Front Nutr ; 9: 784114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273985

RESUMO

Objective: Stroke-associated pneumonia (SAP) is a frequent complication in stroke patients. This present study aimed to investigate the association between stress hyperglycemia and SAP. Methods: Patients were screened between February 2013 and August 2020 from the First Affiliated Hospital of Wenzhou Medical University. We divided the blood glucose of the patients at admission by the glycated hemoglobin to calculate the stress hyperglycemia ratio (SHR). Binary logistic regression analysis was used to identify the association between SAP and SHR, with the confounders being controlled. Further, subgroup analyses were separately performed for stroke patients with and without diabetes. Results: A total of 2,039 patients were finally recruited, of which 533 (26.14%) were diagnosed with SAP. SHR were divided into four quartiles in the logistic regression analysis, the highest SHR quartile (SHR ≥ 1.15) indicated a higher risk of SAP (OR = 1.57; 95% CI = 1.13-2.19, p = 0.01) in total patients. In patients without diabetes, the third quantile (SHR = 0.96-1.14) and the highest quantile (SHR ≥ 1.15) were both related to a higher risk of SAP (both p < 0.05). However, we did not find such an association in diabetic patients. Conclusion: SHR was significantly associated with the risk of SAP in patients without diabetes. Adequate attention should be paid to the patients with high SHR levels at admission, especially those without diabetes.

11.
Front Nutr ; 9: 850355, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273991

RESUMO

Background: Post-stroke fatigue (PSF) is a frequent complication of stroke. Serum uric acid (SUA) is frequently thought to be a risk factor for stroke. This study aimed to investigate whether SUA also played a role in PSF. Methods: Subjects with ischemic stroke were screened from The First Affiliated Hospital of Wenzhou Medical University between January 2020 and October 2020. Patients' fatigue symptoms were assessed by the Fatigue severity scale (FSS). To investigate the relationship between SUA and PSF, binary logistic regression analysis was conducted, with the confounders being controlled. SUA levels were divided into four layers (Q1 ≤ 245 µmol/L; Q2 246-308 µmol/L; Q3 309-365 µmol/L; Q4 ≥366 µmol/L) based on the quartiles. Results: SUA levels were significantly higher in the PSF group (345.96 ± 73.78 µmol/L) than the non-PSF group (295.97 ± 87.8 µmol/L, P < 0.001). There were no differences in any other variables between these two groups. After adjusting the confounders, the risk of PSF in the Q4 layer (≥366 µmol/L) was 6.05 times (95% CI 1.79-20.43, P = 0.004) higher than that in Q1 (≤245 µmol/L). Conclusion: High SUA at admission was an independent risk factor for fatigue 1 year after stroke onset. High SUA (≥366 µmol/L) during stroke deserves more attention, and active control of high SUA levels may be beneficial to reduce the incidence of PSF in the chronic stage following stroke.

12.
BMC Genomics ; 23(1): 182, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247986

RESUMO

BACKGROUND: Equol, an isoflavonoid metabolite with possible health benefits in humans, is known to be produced by some human gut bacteria. While the genes encoding the equol production pathway have been characterized in a few bacterial strains, a systematic analysis of the equol production pathway is currently lacking. RESULTS: This study presents an analysis of the taxonomic distribution and evolutionary history of the gene cluster encoding the equol production pathway. A survey for equol gene clusters within the Genome Taxonomy Database bacterial genomes and human gut metagenomes resulted in the identification of a highly conserved gene cluster found in nine bacterial species from the Eggerthellaceae family. The identified gene clusters from human gut metagenomes revealed potential variations in the equol gene cluster organization and gene content within the equol-producing Eggerthellaceae clades. Subsequent analysis showed that in addition to the four genes directly involved in equol production, multiple other genes were consistently found in the equol gene clusters. These genes were predicted to encode a putative electron transport complex and hydrogenase maturase system, suggesting potential roles for them in the equol production pathway. Analysis of the gene clusters and a phylogenetic reconstruction of a putative NAD kinase gene provided evidence of the recent transfer of the equol gene cluster from a basal Eggerthellaceae species to Slackia_A equolifaciens, Enteroscipio sp000270285, and Lactococcus garvieae 20-92. CONCLUSIONS: This analysis demonstrates that the highly conserved equol gene cluster is taxonomically restricted to the Eggerthellaceae family of bacteria and provides evidence of the role of horizontal gene transfer in the evolutionary history of these genes. These results provide a foundation for future studies of equol production in the human gut and future efforts related to bioengineering and the use of equol-producing bacteria as probiotics.


Assuntos
Actinobacteria , Isoflavonas , Actinobacteria/genética , Equol/metabolismo , Humanos , Isoflavonas/metabolismo , Família Multigênica , Filogenia
13.
Shock ; 57(5): 666-671, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35234206

RESUMO

BACKGROUND: Septic acute kidney injury (AKI) is a common condition in ICU with poor outcomes. Septic AKI patients have a progressively decreased urine output and increased serum creatinine. However, urine volume and serum creatinine showed poor sensitivity to early diagnosis of septic AKI. Searching for potential biomarkers to early detect AKI is crucial in day-to-day clinical practice. Macrophage migration inhibitory factor (MIF), primarily released by renal tubular epithelial cells, vascular endothelial cells, and immune cells, was found to be closely associated with the inflammatory response in sepsis. MIF may be used as a biomarker of septic AKI indicating aggravation of systemic inflammatory response. METHODS: Our study included sepsis patients admitted to the ICU. The KDIGO guideline was used to confirm the diagnosis and staging of septic AKI. Blood samples were collected and tested, as well as clinical data were recorded. Independent risk factors were selected via logistic regression analysis. By drawing the receiver operating characteristic (ROC) curves, the area under the ROC curves (AUC) was computed. The relationship between serum MIF level and mortality of septic AKI was analyzed using Cox regression analysis. RESULTS: With high serum MIF level at ICU admission, the patients were more likely to develop AKI. The AUC of serum MIF (MIFAUC = 0.797) was found to be a good predictor of septic AKI. In addition, higher serum MIF levels corresponded to more severe AKI as well as a higher mortality rate. CONCLUSIONS: Serum MIF might be a biomarker for predicting the occurrence, development, and outcomes of septic AKI. This conclusion will need to be confirmed by more robust investigations in the future.


Assuntos
Injúria Renal Aguda , Fatores Inibidores da Migração de Macrófagos , Sepse , Injúria Renal Aguda/diagnóstico , Biomarcadores/sangue , Creatinina , Células Endoteliais , Humanos , Oxirredutases Intramoleculares , Fatores Inibidores da Migração de Macrófagos/sangue , Curva ROC , Sepse/diagnóstico
14.
NPJ Biofilms Microbiomes ; 8(1): 1, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013297

RESUMO

Antibiotic-resistance genes (ARGs) regulated by invertible promoters can mitigate the fitness cost of maintaining ARGs in the absence of antibiotics and could potentially prolong the persistence of ARGs in bacterial populations. However, the origin, prevalence, and distribution of these ARGs regulated by invertible promoters remains poorly understood. Here, we sought to assess the threat posed by ARGs regulated by invertible promoters by systematically searching for ARGs regulated by invertible promoters in the human gut microbiome and examining their origin, prevalence, and distribution. Through metagenomic assembly of 2227 human gut metagenomes and genomic analysis of the Unified Human Gastrointestinal Genome (UHGG) collection, we identified ARGs regulated by invertible promoters and categorized them into three classes based on the invertase-regulating phase variation. In the human gut microbiome, ARGs regulated by invertible promoters are exclusively found in Bacteroidales species. Through genomic analysis, we observed that ARGs regulated by invertible promoters have convergently originated from ARG insertions into glycan-synthesis loci that were regulated by invertible promoters at least three times. Moreover, all three classes of invertible promoters regulating ARGs are located within integrative conjugative elements (ICEs). Therefore, horizontal transfer via ICEs could explain the wide taxonomic distribution of ARGs regulated by invertible promoters. Overall, these findings reveal that glycan-synthesis loci regulated by invertible promoters in Bacteroidales species are an important hotspot for the emergence of clinically-relevant ARGs regulated by invertible promoters.


Assuntos
Antibacterianos , Microbioma Gastrointestinal , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos , Microbioma Gastrointestinal/genética , Humanos , Metagenômica
15.
bioRxiv ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35043112

RESUMO

Insertions in the SARS-CoV-2 genome have the potential to drive viral evolution, but the source of the insertions is often unknown. Recent proposals have suggested that human RNAs could be a source of some insertions, but the small size of many insertions makes this difficult to confirm. Through an analysis of available direct RNA sequencing data from SARS-CoV-2 infected cells, we show that viral-host chimeric RNAs are formed through what are likely stochastic RNA-dependent RNA polymerase template switching events. Through an analysis of the publicly available GISAID SARS-CoV-2 genome collection, we identified two genomic insertions in circulating SARS-CoV-2 variants that are identical to regions of the human 18S and 28S rRNAs. These results provide direct evidence of the formation of viral-host chimeric sequences and the integration of host genetic material into the SARS-CoV-2 genome, highlighting the potential importance of host-derived insertions in viral evolution. IMPORTANCE: Throughout the COVID-19 pandemic, the sequencing of SARS-CoV-2 genomes has revealed the presence of insertions in multiple globally circulating lineages of SARS-CoV-2, including the Omicron variant. The human genome has been suggested to be the source of some of the larger insertions, but evidence for this kind of event occurring is still lacking. Here, we leverage direct RNA sequencing data and SARS-CoV-2 genomes to show host-viral chimeric RNAs are generated in infected cells and two large genomic insertions have likely been formed through the incorporation of host rRNA fragments into the SARS-CoV-2 genome. These host-derived insertions may increase the genetic diversity of SARS-CoV-2 and expand its strategies to acquire genetic materials, potentially enhancing its adaptability, virulence, and spread.

16.
Mol Microbiol ; 117(1): 10-19, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34748246

RESUMO

In many bacteria, the stabilities and functions of small regulatory RNAs (sRNAs) that act by base pairing with target RNAs most often are dependent on Hfq or ProQ/FinO-domain proteins, two classes of RNA chaperone proteins. However, while all bacteria appear to have sRNAs, many have neither Hfq nor ProQ/FinO-domain proteins raising the question of whether another factor might act as an sRNA chaperone in these organisms. Several recent studies have reported that KH domain proteins, such as KhpA and KhpB, bind sRNAs. Here we describe what is known about the distribution, structures, RNA-binding properties, and physiologic roles of KhpA and KhpB and discuss evidence for and against these proteins serving as sRNAs chaperones.


Assuntos
Proteínas de Bactérias/metabolismo , Chaperonas Moleculares/metabolismo , RNA Bacteriano/metabolismo , Pequeno RNA não Traduzido/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Bactérias/genética , Fator Proteico 1 do Hospedeiro/genética , Fator Proteico 1 do Hospedeiro/metabolismo , Modelos Moleculares , Chaperonas Moleculares/genética , Domínios Proteicos , RNA Bacteriano/genética , Pequeno RNA não Traduzido/genética , Proteínas de Ligação a RNA/genética
17.
J Diabetes Investig ; 13(3): 552-559, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34637185

RESUMO

AIMS/INTRODUCTION: We aimed to explore the clinical factors associated with glycemic variability (GV) assessed with flash glucose monitoring (FGM), and investigate the impact of FGM on glycemic control among Chinese type 1 diabetes mellitus patients in a real-life clinical setting. MATERIALS AND METHODS: A total of 171 patients were included. GV was assessed from FGM data. A total of 110 patients wore FGM continuously for 6 months (longitudinal cohort). Hemoglobin A1c (HbA1c), fasting and 2-h postprandial C-peptide, and glucose profiles were collected. Changes in HbA1c and glycemic parameters were assessed during a 6-month FGM period. RESULTS: Individuals with high residual C-peptide (HRCP; 2-h postprandial C-peptide >200 pmol/L) had less GV than patients with low residual C-peptide ( 2-h postprandial C-peptide ≤200 pmol/L; P < 0.001). In the longitudinal cohort (n = 110), HbA1c and mean glucose decreased, time in range (TIR) increased during the follow-up period (P < 0.05). The 110 patients were further divided into age and residual C-peptide subgroups: (i) HbA1c and mean glucose were reduced significantly only in the subgroup aged ≤14 years during the follow-up period, whereas time below range also increased in this subgroup at 3 months (P = 0.047); and (ii) HbA1c improved in the HRCP subgroup at 3 and 6 months (P < 0.05). The mean glucose decreased and TIR improved significantly in the low residual C-peptide subgroup; however, TIR was still lower and time below range was higher than those of the HRCP subgroup at all time points (P < 0.05). CONCLUSIONS: HRCP was associated with less GV. FGM wearing significantly reduced HbA1c, especially in pediatric patients and those with HRCP. Additionally, the mean glucose and TIR were also found to improve.


Assuntos
Diabetes Mellitus Tipo 1 , Adolescente , Glicemia , Automonitorização da Glicemia , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucose , Hemoglobina A Glicada/análise , Controle Glicêmico , Humanos , Hipoglicemiantes
18.
Front Microbiol ; 12: 705583, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745023

RESUMO

As one of the three mammalian gasotransmitters, hydrogen sulfide (H2S) plays a major role in maintaining physiological homeostasis. Endogenously produced H2S plays numerous beneficial roles including mediating vasodilation and conferring neuroprotection. Due to its high membrane permeability, exogenously produced H2S originating from the gut microbiota can also influence human physiology and is implicated in reducing intestinal mucosal integrity and potentiating genotoxicity and is therefore a potential target for therapeutic interventions. Gut microbial H2S production is often attributed to dissimilatory sulfate reducers such as Desulfovibrio and Bilophila species. However, an alternative source for H2S production, cysteine degradation, is present in some gut microbes, but the genes responsible for cysteine degradation have not been systematically annotated in all known gut microbes. We classify mechanisms of cysteine degradation into primary, secondary, and erroneous levels of H2S production and perform a comprehensive search for primary, secondary, and erroneous cysteine-degrading enzymes in 4,644 non-redundant bacterial genomes from the Unified Human Gastrointestinal Genome (UHGG) catalog. Of the 4,644 genomes we have putatively identified 2,046 primary, 1,951 secondary, and 5 erroneous cysteine-degrading species. We identified the presence of at least one putative cysteine-degrading bacteria in metagenomic data of 100% of 6,623 healthy subjects and the expression of cysteine-degrading genes in metatranscriptomic data of 100% of 736 samples taken from 318 individuals. Additionally, putative cysteine-degrading bacteria are more abundant than sulfate-reducing bacteria across healthy controls, IBD patients and CRC patients (p < 2.2e-16, Wilcoxon rank sum test). Although we have linked many taxa with the potential for cysteine degradation, experimental validation is required to establish the H2S production potential of the gut microbiome. Overall, this study improves our understanding of the capacity for H2S production by the human gut microbiome and may help to inform interventions to therapeutically modulate gut microbial H2S production.

19.
Opt Lett ; 46(22): 5759-5762, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780455

RESUMO

Formaldehyde (FA) is one of the most common pollutants, which has tremendous harm to humans and environment. In this work, 4-amino-3-pentene-2-one (Fluoral-p) and SiO2 coated quantum dot (QD@SiO2) were combined to implement a new ratiometric fluorescence probe QD@SiO2-Fluoral-p for FA detection. In addition, by utilization of polyvinyl alcohol (PVA) and SiO2 microsphere (SM), a kind of PVA-SM microstructure was assembled with QD@SiO2-Fluoral-p to composite a signal enhanced sensing film. The QD@SiO2-Fluoral-p exhibited good response to 0-400 mg/L FA solution and an enhancement around 15 folds was realized after introducing PVA-SM. In both situations, the probe showed linear relationship to FA concentration (CFA), with detection limits of 14 and 0.5 mg/L, respectively. Also, the sensing film showed a good linear response to FA gas in the range of 0 to 2 ppm, with a detection limit 0.03 ppm. As a result, the PVA-SM enhanced ratiometric fluorescence probe features high sensitivity, low detection limit, good selectivity, as well as portable, which can serve as a useful tool for investigating FA in solution and gas at room temperature.

20.
Nanoscale ; 13(40): 17049-17056, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34622916

RESUMO

Nanoparticle-sensitized photoporation for intracellular delivery of external compounds usually relies on the use of spherical gold nanoparticles as sensitizing nanoparticles. As they need stimulation with visible laser light, they are less suited for transfection of cells in thick biological tissues. In this work, we have explored black phosphorus quantum dots (BPQDs) as alternative sensitizing nanoparticles for photoporation with a broad and uniform absorption spectrum from the visible to the near infra-red (NIR) range. We demonstrate that BPQD sensitized photoporation allows efficient intracellular delivery of both siRNA (>80%) and mRNA (>40%) in adherent cells as well as in suspension cells. Cell viability remained high (>80%) irrespective of whether irradiation was performed with visible (532 nm) or near infrared (800 nm) pulsed laser light. Finally, as a proof of concept, we used BPQD sensitized photoporation to deliver macromolecules in cells with thick phantom tissue in the optical path. NIR laser irradiation resulted in only 1.3× reduction in delivery efficiency as compared to photoporation without the phantom gel, while with visible laser light the delivery efficiency was reduced 2×.


Assuntos
Ouro , Nanopartículas Metálicas , Substâncias Macromoleculares , Fósforo , RNA Interferente Pequeno
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