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1.
Food Microbiol ; 102: 103922, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34809948

RESUMO

This study evaluated the impact of 1-methylcyclopropene (1-MCP), an ethylene synthesis inhibitor, followed by long-term commercial cold storage with low-dose gaseous ozone on the microbiological safety and quality of fresh apples. Granny Smith apples were inoculated with or without Listeria innocua, treated with or without 1.0 mg/L 1-MCP for 24 h, then subjected to commercial cold storage conditions including refrigerated air (RA, 0.6 °C, control), controlled atmosphere (CA, 2% O2, 1% CO2, 0.6 °C), and CA with 51-87 µg/L ozone gas for up to 36 weeks. RA storage reduced L. innocua on apples by up to 3.6 log10 CFU/apple. CA had no advantage over RA in controlling Listeria. Continuous ozone gas application resulted in an additional ∼2.0 log10 CFU/apple reduction of L. innocua (total reduction up to 5.7 log10 CFU/apple) and suppressed native bacteria and fungi. Treatment with 1-MCP had a minor impact on survival of L. innocua or background microbiota on apples, while it significantly delayed fruit ripening and reduced the incidence of superficial scald and internal browning. In summary, 1-MCP treatment followed by CA storage with low-dose continuous ozone gas can effectively control Listeria on fresh apples and delay fruit ripening.

2.
Front Nutr ; 8: 765414, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805249

RESUMO

The gut microbiota is believed to play a significant role in psychological and gastrointestinal symptoms in heroin addicts. However, the underlying mechanism remains largely unknown. We show here that heroin addicts had a decrease in body mass index (BMI) and abnormal serum D-lactic acid (DLA), endotoxin (ET) and diamine oxidase (DAO) levels during their withdrawal stage, suggesting a potential intestinal injury. The gut microbial profiles in the mouse model with heroin dependence showed slightly decreased alpha diversity, as well as higher levels of Bifidobacterium and Sutterella and a decrease in Akkermansia at genus level compared to the control group. Fecal microbiota transplantation (FMT) further confirmed that the microbiota altered by heroin dependence was sufficient to impair body weight and intestinal mucosal barrier integrity in recipient mice. Moreover, short-chain fatty acids (SCFAs) profiling revealed that microbiota-derived propionic acid significantly decreased in heroin dependent mice compared to controls. Overall, our study shows that heroin dependence significantly altered gut microbiota and impaired intestinal mucosal barrier integrity in mice, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.

3.
Ann Palliat Med ; 10(10): 10804-10820, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763442

RESUMO

BACKGROUND: Acupuncture therapy is a method of piercing needles into acupoints to treat diseases with/without corresponding manipulations, which could serve as a useful supplementary therapy for psoriasis. The present study aimed to outline and sum up current evidence from systematic reviews (SRs)/meta-analyses (MAs) that investigate the clinical efficacy of acupuncture on psoriasis. METHODS: A comprehensive search involving eight electronic databases was conducted from the date of inception to July 2021, and grey literatures were manually searched. The research was selected according to prespecified inclusion criteria and relevant data were obtained. The methodological quality of the included SRs was scrutinized using the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2) tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to appraise the reporting quality of the included SRs. Risk of Bias in Systematic Reviews (ROBIS) was selected for the evaluation of bias risk of the included SRs. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was applied to determine the quality of evidence from primary outcome measures. RESULTS: After screening, seven SRs/MAs met the inclusion criteria, including two English and five Chinese articles. All of the SRs were published between 2015 and 2020. Based on AMSTAR-2, the quality of all SRs was rated as dangerously low. Using the PRISMA-A checklist, major reporting flaws were observed in the financial statements, protocols, and registrations of the included literature. According to the ROBIS tool, two SRs/MAs were classed as low bias risk. Using the GRADE tool, this review contained 27 outcomes, with only one being classified as high-quality evidence, seven moderate-quality evidences, and 19 as low-quality evidence. The present research results advocated acupuncture therapy as a supplementary treatment for psoriasis patients; however, the evidence should still be treated with caution due to certain limitations. CONCLUSIONS: Our overview suggests that acupuncture could be used as a complementary therapy to produce effective clinical result for psoriasis. Nonetheless, considering the poor quality of SRs/Mas that advocate these findings, studies with more rigorous design, larger populations samples and of higher quality are called for to provide stronger evidence for definitive conclusions.


Assuntos
Terapia por Acupuntura , Psoríase , Humanos , Psoríase/terapia , Projetos de Pesquisa , Relatório de Pesquisa
4.
Nat Commun ; 12(1): 6845, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824246

RESUMO

Maternal obesity (MO) predisposes offspring to obesity and metabolic disorders but little is known about the contribution of offspring brown adipose tissue (BAT). We find that MO impairs fetal BAT development, which persistently suppresses BAT thermogenesis and primes female offspring to metabolic dysfunction. In fetal BAT, MO enhances expression of Dio3, which encodes deiodinase 3 (D3) to catabolize triiodothyronine (T3), while a maternally imprinted long noncoding RNA, Dio3 antisense RNA (Dio3os), is inhibited, leading to intracellular T3 deficiency and suppression of BAT development. Gain and loss of function shows Dio3os reduces D3 content and enhances BAT thermogenesis, rendering female offspring resistant to high fat diet-induced obesity. Attributing to Dio3os inactivation, its promoter has higher DNA methylation in obese dam oocytes which persists in fetal and adult BAT, uncovering an oocyte origin of intergenerational obesity. Overall, our data uncover key features of Dio3os activation in BAT to prevent intergenerational obesity and metabolic dysfunctions.

5.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 665-672, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821103

RESUMO

Objective: To investigate the effects of aerobic exercise plus spirulina polysaccharide(SP) supplement on the related protein expressions of p75NTR signal in hippocampal and the improvement of learning and memory of type 2 diabetes rats. Methods: The model of type 2 diabetic rats was established by fed high-fat diet for four weeks together with intraperitoneal injecting a low dose of STZ. The model rats were randomly divided into diabetic model group(B),diabetic exercise group(C),diabetic+SP group(D)and diabetic exercise+SP group(E), another normal control group(A)without any intervention was set up,12 rats in each group. The rats in Group C and E were treated with intervention of swimming training for six weeks. The rats in Group D and E were treated with SP intragastrically for 6 weeks. Learning and memory abilities were observed by Morris water maze test. The hippocampus cell apoptosis was observed by Tunnel staining, and BDNF content and the expressions of p75NTR, cleaved caspase-3 of hippocampus were tested by ELISA, Western blot and immunohistochemistry, respectively. At the same time, the changes of blood glucose and levels of serum insulin were examined. Results: ①Compared with Group A at different time points, the body weight of Group B was decreased significantly(P<0.01). Compared with Group B at different time points, the body weight of Group C,D and E had no difference (P>0.05). Compared with Group A, levels of the blood glucose and serum insulin Group B were increased significantly(P<0.01).Compared with Group B, the levels in the intervention groups were decreased significantly (P<0.01); ②Compared with Group A, the escape latencies of Group B were prolonged significantly(P<0.01), platform quadrant residence duration and the times of crossing platform were decreased (P<0.01). Compared with Group B, the escape latencies of the intervention groups were shortened (P<0.05 or P<0.01), and the times of crossing platform were increased (P<0.05 or P<0.01). ③Compared with Group B, the neural cells apoptosis of the intervention rats was decreased, and the protein expressions of p75NTR and cleaved caspase-3 were decreased (P<0.05 or P<0.01), however the expression of BDNF was increased significantly (P<0.05 or P<0.01). Conclusion: Aerobic exercise and SP supplement can improve the learning-memory ability of type 2 diabetes rats, and the improvement effect of exercise combined with SP is markedly better than that of exercise and SP alone, the mechanism might be related to better regulating p75NTR signal related protein expressions and then inhibiting apoptosis in hippocampus of rats with type 2 diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Spirulina , Animais , Diabetes Mellitus Experimental/terapia , Hipocampo , Polissacarídeos , Ratos , Ratos Sprague-Dawley , Natação
6.
Thyroid ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34806437

RESUMO

Background: Despite the implementation of the universal salt iodization (USI) program for correction of iodine deficiency in China for ∼20 years, the actual iodine nutrition status of Chinese residents and the prevalence of iodine deficiency and iodine excess are issues that need to be addressed. This nationally representative cross-sectional study was conducted across all 31 provinces of mainland China to gather extensive data on iodine nutrition status and the influential factors. Methods: This study included 78,470 participants, aged 18 years or older, who were interviewed and asked to answer a questionnaire. Urine iodine concentration (UIC) was measured by the inductively coupled plasma mass spectrometry method, and goiter was examined by thyroid ultrasonography. In addition, sixty 9-11 years old school children in each province were randomly selected to evaluate the UIC and thyroid ultrasonography. The iodine nutrition status was determined according to the World Health Organization guidelines. Results: The iodized salt coverage was 95.37%. The median urine iodine (MUI) was 177.89 µg/L (interquartile range [IQR], 117.89-263.90 µg/L) and goiter prevalence was 1.17% (confidence interval [95% CI 0.95-1.43]) in the adult population. The MUI was 199.75 µg/L (IQR, 128.41-303.37 µg/L) in school-age children, and goiter prevalence was 3.50% [95% CI, 2.93-4.13]. The percentage of individuals with UIC <50 µg/L was 3.43%, <20%. Analysis indicated that sex, age, geographic factors, body mass index, and smoking habits influence the iodine nutrition level. Conclusion: The mandatory USI program has successfully eliminated iodine deficiency disorders, and the findings indicate that the iodine nutrition level in the general population is within the safe range.

7.
Tree Physiol ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34730183

RESUMO

Mycorrhizal helper bacteria (MHB) play an important role in mediating mycorrhizal symbiosis, which improves the growth and nutrient uptake of plants. This study examined the growth-promoting effects and mechanisms of pine growth after inoculation with the MHB Bacillus pumilus HR10 and/or Hymenochaete sp. Rl. The effect of B. pumilus HR10 on Hymenochaete sp. Rl growth, enzyme activity and gene expression related to mycorrhiza formation were determined. The growth, root activity, nitrogen (N), phosphorus (P), and potassium (K) content and chlorophyll fluorescence activity of Pinus thunbergii and the mycorrhizal colonization intensity of Hymenochaete sp. Rl-inoculated pine seedlings after inoculation with B. pumilus HR10 were also evaluated. The results showed that B. pumilus HR10 promoted growth, regulated the expression of mycorrhizal-related genes and affected the ß-1,3-glucanase activity of Hymenochaete sp. Rl. The mycorrhizal colonization intensity of pine seedlings co-inoculated with B. pumilus HR10 and Hymenochaete sp. Rl was 1.58-fold higher than seedlings inoculated with only Hymenochaete sp. Rl. Inoculation with B. pumilus HR10 and/or Hymenochaete sp. Rl increased lateral root number and root activity of pine seedlings and chlorophyll fluorescence activity of pine needles compared to the control. B. pumilus HR10 facilitated nutrient uptake by enhancing the mycorrhizal proliferation of pine and induced greater photosynthesis and root activity of pine seedlings, which confirms its role as an outstanding plant-growth-promoting rhizobacterium. These findings improve our understanding of the mechanism of B. pumilus HR10 promotion of mycorrhizal symbiosis.

8.
Front Neurosci ; 15: 773883, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776858

RESUMO

In a typical electrophysiology experiment, synaptic stimulus is delivered in a cortical layer (1-6) and neuronal responses are recorded intracellularly in individual neurons. We recreated this standard electrophysiological paradigm in brain slices of mice expressing genetically encoded voltage indicators (GEVIs). This allowed us to monitor membrane voltages in the target pyramidal neurons (whole-cell), and population voltages in the surrounding neuropil (optical imaging), simultaneously. Pyramidal neurons have complex dendritic trees that span multiple cortical layers. GEVI imaging revealed areas of the brain slice that experienced the strongest depolarization on a specific synaptic stimulus (location and intensity), thus identifying cortical layers that contribute the most afferent activity to the recorded somatic voltage waveform. By combining whole-cell with GEVI imaging, we obtained a crude distribution of activated synaptic afferents in respect to the dendritic tree of a pyramidal cell. Synaptically evoked voltage waves propagating through the cortical neuropil (dendrites and axons) were not static but rather they changed on a millisecond scale. Voltage imaging can identify areas of brain slices in which the neuropil was in a sustained depolarization (plateau), long after the stimulus onset. Upon a barrage of synaptic inputs, a cortical pyramidal neuron experiences: (a) weak temporal summation of evoked voltage transients (EPSPs); and (b) afterhyperpolarization (intracellular recording), which are not represented in the GEVI population imaging signal (optical signal). To explain these findings [(a) and (b)], we used four voltage indicators (ArcLightD, chi-VSFP, Archon1, and di-4-ANEPPS) with different optical sensitivity, optical response speed, labeling strategy, and a target neuron type. All four imaging methods were used in an identical experimental paradigm: layer 1 (L1) synaptic stimulation, to allow direct comparisons. The population voltage signal showed paired-pulse facilitation, caused in part by additional recruitment of new neurons and dendrites. "Synaptic stimulation" delivered in L1 depolarizes almost an entire cortical column to some degree.

9.
J Nutr Biochem ; : 108908, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801687

RESUMO

Succinic acid widely exists in foods and is used as a food additive. Succinate not only serves as an energy substrate, but also induces protein succinylation. Histone succinylation activates gene transcription. The brown adipose tissue (BAT) is critical for prevention of obesity and metabolic dysfunction, and the fetal stage is pivotal for BAT development. Up to now, the role of maternal succinate supplementation on fetal BAT development and offspring BAT function remains unexamined. To test, female C57BL/6J mice (2-month-old) were separated into two groups, received with or without 0.5% succinic acid in drinking water during gestation and lactation. After weaning, female offspring were challenged with high fat diet (HFD) for 12 weeks. Newborn, female weanling, and HFD female offspring mice were analyzed. For neonatal and weaning mice, the BAT weight relative to the whole body weight was significantly increased in the succinate group. The expression of PGC-1α, a key transcription co-activator promoting mitochondrial biogenesis, was elevated in BAT of female neonatal and offspring born to succinate-fed dams. Consistently, maternal succinate supplementation enhanced thermogenesis and the expression of thermogenic genes in offspring BAT. Additionally, maternal succinate supplementation protected female offspring against HFD-induced obesity. Furthermore, in C3H10T1/2 cells, succinate supplementation promoted PGC-1α expression and brown adipogenesis. Mechanistically, succinate supplementation increased permissive histone succinylation and H3K4me3 modification in the Ppargc1a promoter, which correlated with the higher expression of Ppargc1a. In conclusion, maternal succinate supplementation during pregnancy and lactation enhanced fetal BAT development and offspring BAT thermogenesis, which prevented HFD-induced obesity and metabolism dysfunction in offspring.

10.
Adv Sci (Weinh) ; 8(22): e2102157, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34647690

RESUMO

Obesity during pregnancy leads to adverse health outcomes in offspring. However, the initial effects of maternal obesity (MO) on embryonic organogenesis have yet to be thoroughly examined. Using unbiased single-cell transcriptomic analyses (scRNA-seq), the effects of MO on the myogenic process is investigated in embryonic day 9.5 (E9.5) mouse embryos. The results suggest that MO induces systematic hypoxia, which is correlated with enhanced BMP signaling and impairs skeletal muscle differentiation within the dermomyotome (DM). The Notch-signaling effectors, HES1 and HEY1, which also act down-stream of BMP signaling, suppress myogenic differentiation through transcriptionally repressing the important myogenic regulator MEF2C. Moreover, the major hypoxia effector, HIF1A, enhances expression of HES1 and HEY1 and blocks myogenic differentiation in vitro. In summary, this data demonstrate that MO induces hypoxia and impairs myogenic differentiation by up-regulating BMP signaling within the DM, which may account for the disruptions of skeletal muscle development and function in progeny.

11.
Chem Commun (Camb) ; 57(88): 11713-11716, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34695173

RESUMO

A spatially segregative coacervate-in-proteinosome hybrid microcompartment is constructed by co-encapsulation of either positively or negatively charged polyelectrolytes within proteinosomes with enhanced cascade enzymatic reactions, providing a step towards the development of artificial eukaryotic cell like microcompartments.

12.
J Clin Sleep Med ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34710037

RESUMO

STUDY OBJECTIVES: To compare the efficiency of TCM scoring system that include three independent predictors obtained by physical examination, computed tomography (CT), and polysomnography (PSG) with the standard Friedman staging system that includes only physical examination variables for predicting surgical outcomes in patients with obstructive sleep apnea syndrome (OSAS) who undergo velopharyngeal surgery. METHODS: This prospective study was carried out in 265 OSAS patients who underwent velopharyngeal surgery. All these patients were re-examined with PSG for evaluation of surgical outcomes at least three months after surgery. The efficacies in surgical outcomes prediction of two systems were calculated and compared. RESULTS: The overall response rate and cure rate was 63.8% (169/265) and 22.3% (59/265), respectively. There were 32 patients with Friedman stage I, with a response rate and cure rate of 81.3% (26/32) and 28.1% (9/32), respectively, and 70 patients with TCM scores of <14 with a response rate and cure rate of 91.4% (64/70) and 42.9% (30/70), respectively. Friedman stage and TCM grade were the only two factors independently predictive of surgical response (P<0.05, OR value = 0.642 and 0.382). The Receiver Operating Characteristic curve analysis for surgical response showed that the area under curve value was 0.600 for Friedman stage, which was significantly lower than that for TCM grade (P = 0.005), 0.718. Apnea-hypopnea index and TCM grade were the only two factors independently predictive of surgical cure (P<0.05, OR value = 0.981 and 0.465). CONCLUSIONS: Compared with the Friedman staging system, the TCM scoring system was efficient in selecting proper candidates for velopharyngeal surgery. The main reason may be its better utilization of patients' pre-operative information, especially the inclusion of physiological factors. CLINICAL TRIAL REGISTRATION: Registry: Chinese Clinical Trials Registry; Title: Clinical phenotypes and Precise Treatment of Adult OSA (Obstructive Sleep Apnea): A Multicenter Study; Identifier: ChiCTR-ONC-17013132; URL: http://www.chictr.org.cn/showproj.aspx?proj=21189.

13.
Front Microbiol ; 12: 712757, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659142

RESUMO

This study aimed to investigate the effects of low-dose continuous ozone gas in controlling Listeria innocua and quality attributes and disorders of Red Delicious apples during long-term commercial cold storage. Red Delicious apples were inoculated with a three-strain L. innocua cocktail at ∼6.2 log10 CFU/apple, treated with or without 1-methylcyclopropene, and then subjected to controlled atmosphere (CA) storage with or without continuous gaseous ozone in a commercial facility for 36 weeks. Uninoculated Red Delicious apples subjected to the above storage conditions were used for yeast/mold counts and quality attributes evaluation. The 36 weeks of refrigerated air (RA) or CA storage caused ∼2.2 log10 CFU/apple reduction of L. innocua. Ozone gas application caused an additional > 3 log10 CFU/apple reduction of L. innocua compared to RA and CA storage alone. During the 36-week CA storage, low-dose continuous gaseous ozone application significantly retarded the growth of yeast/mold, delayed apple firmness loss, and had no negative influence on ozone burn, lenticel decay, russet, CO2 damage, superficial scald, and soft scald of Red Delicious apples compared to CA-alone storage. In summary, the application of continuous low-dose gaseous ozone has the potential to control Listeria on Red Delicious apples without negatively influencing apple quality attributes.

14.
Bioorg Med Chem ; 49: 116438, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34610571

RESUMO

Liver fibrosis is one of the most common pathological consequences of chronic liver diseases (CLD). To develop effective antifibrotic strategies, a novel class of 1-(substituted phenyl)-1,8-naphthalidine-3-carboxamide derivatives were designed and synthesized. By means of the collagen type I α 1 (COL1A1)-based screening and cytotoxicity assay in human hepatic stellate cell (HSC) line LX-2, seven compounds were screened out from total 60 derivatives with high inhibitory effect and relatively low cytotoxicity for further COL1A1 mRNA expression analysis. It was found that compound 17f and 19g dose-dependently inhibited the expression of fibrogenic markers, including α-smooth muscle actin (α-SMA), matrix metalloprotein 2 (MMP-2), connective tissue growth factor (CTGF) and transforming growth factor ß1 (TGFß1) on both mRNA and protein levels. Further mechanism studies indicated that they might suppress the hepatic fibrogenesis via inhibiting both PI3K/AKT/Smad and non-Smad JAK2/STAT3 signaling pathways. Furthermore, 19g administration attenuated hepatic histopathological injury and collagen accumulation, and reduced fibrogenesis-associated protein expression in liver tissues of bile duct ligation (BDL) rats, showing significant antifibrotic effect in vivo. These findings identified 1,8-naphthalidine derivatives as potent anti-hepatic fibrosis agents, and provided valuable information for further structure optimization.

15.
Front Immunol ; 12: 730300, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489980

RESUMO

Heroin addiction and withdrawal influence multiple physiological functions, including immune responses, but the mechanism remains largely elusive. The objective of this study was to investigate the molecular inflammatory interactome, particularly the cytokines and transcriptome regulatory network in heroin addicts undergoing withdrawal, compared to healthy controls (HCs). Twenty-seven cytokines were simultaneously assessed in 41 heroin addicts, including 20 at the acute withdrawal (AW) stage and 21 at the protracted withdrawal (PW) stage, and 38 age- and gender-matched HCs. Disturbed T-helper(Th)1/Th2, Th1/Th17, and Th2/Th17 balances, characterized by reduced interleukin (IL)-2, elevated IL-4, IL-10, and IL-17A, but normal TNF-α, were present in the AW subjects. These imbalances were mostly restored to the baseline at the PW stage. However, the cytokines TNF-α, IL-2, IL-7, IL-10, and IL-17A remained dysregulated. This study also profiled exosomal long non-coding RNA (lncRNA) and mRNA in the plasma of heroin addicts, constructed co-expression gene regulation networks, and identified lncRNA-mRNA-pathway pairs specifically associated with alterations in cytokine profiles and Th1/Th2/Th17 imbalances. Altogether, a large amount of cytokine and exosomal lncRNA/mRNA expression profiling data relating to heroin withdrawal was obtained, providing a useful experimental and theoretical basis for further understanding of the pathogenic mechanisms of withdrawal symptoms in heroin addicts.

16.
Front Microbiol ; 12: 728216, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531844

RESUMO

A novel plasmid-encoded aminoglycoside 3''-nucleotidyltransferase ANT(3")-IId, was discovered in Acinetobacter lwoffi strain H7 isolated from a chick on an animal farm in Wenzhou, China. The whole-genome of A. lwoffii H7 consisted of one chromosome and five plasmids (pH7-250, pH7-108, pH7-68, pH7-48, and pH7-11). ant(3")-IId was identified as being encoded on pH7-250, sharing the highest amino acid identity of 50.64% with a function-known resistance gene, ant(3")-IIb (KB849358.1). Susceptibility testing and enzyme kinetic parameter analysis were conducted to determine the function of the aminoglycoside 3"-nucleotidyltransferase. The ant(3")-IId gene conferred resistance to spectinomycin and streptomycin [the minimum inhibitory concentration (MIC) levels of both increased 16-fold compared with the control strain]. Consistent with the MIC data, kinetic analysis revealed a narrow substrate profile including spectinomycin and streptomycin, with K cat/K m ratios of 4.99 and 4.45×103M-1 S-1, respectively. Sequencing analysis revealed that the ant(3")-IId gene was associated with insertion sequences (IS) element [ΔISAba14-ΔISAba14-hp-orf-orf-orf1-ant(3")-IId], and ant(3")-IId were identified in plasmids from various Acinetobacter species. This study of the novel aminoglycoside 3"-nucleotidyltranferase ANT(3")-IId helps us further understand the functional and sequence characteristics of aminoglycoside 3"-nucleotidyltranferases, highlights the risk of resistance gene transfer among Acinetobacter species and suggests that attention should be given to the emergence of new aminoglycoside 3"-nucleotidyltranferase genes.

17.
J Infect Dis ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558604

RESUMO

BACKGROUND: Resistance to anti-tuberculosis (TB) drug is a major issue in TB control, and demands the discovery of new drugs targeting virulence factor ESX-1. METHODS: We first established a high-throughput screen (HTS) assay for the discovery of ESX-1 secretion inhibitors. The positive hits were then evaluated for the potency of diminishing the survival of virulent mycobacterium and reducing bacterial virulence. We further investigated the probability of inducing drug-resistance and the underlying mechanism using M-PFC. RESULTS: A robust HTS assay was developed to identify small molecules that inhibit ESX-1 secretion without impairing bacterial growth in vitro. A hit named IMB-BZ specifically inhibits the secretion of CFP-10 and reduces virulence in an ESX-1-dependent manner, therefore resulting in significant reduction in intracellular and in vivo survival of mycobacteria. Blocking the CFP-10-EccCb1 interaction directly or indirectly underlies the inhibitory effect of IMB-BZ on the secretion of CFP-10. Importantly, our finding shows that the ESX-1 inhibitors pose low risk of drug resistance development by mycobacteria in vitro as compared with traditional anti-TB drug, and exhibit high potency against chronic mycobacterial infection. CONCLUSION: Targeting ESX-1 may lead to the development of novel therapeutics for tuberculosis. IMB-BZ holds the potential for future development into a new anti-TB drug.

19.
Biosci Rep ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398191

RESUMO

Diabetic foot ulcer (DFU) is a kind of common and disabling complications of Diabetes Mellitus (DM). Emerging studies have demonstrated that tendon fibroblasts play a crucial role in remodeling phase of wound healing. However, little is known about the mechanism underlying high glucose (HG)-induced decrease of tendon fibroblasts viability. In the present study the rat models of DFU were established, and collagen deposition, autophagy activation and cell apoptosis in tendon tissues were assessed using hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and TdT-Mediated dUTP Nick-End Labeling (TUNEL) assay, respectively. Tendon fibroblasts were isolated from Achilles tendon of the both limbs, and the effect of HG on autophagy activation in tendon fibroblasts was assessed using western blot analysis, Cell Counting Kit-8 (CCK-8) assay, and flow cytometry. We found that cell apoptosis was increased significantly and autophagy activation was decreased in foot tendons tissues of DFU rats compared with normal tissues. The role of HG in regulating tendon fibroblasts viability was then investigated in vitro, and data showed that HG repressed cell viability and increased cell apoptosis. Furthermore, HG treatment reduced LC3-II expression and increased p62 expression, indicating that HG repressed the activation of tendon fibroblasts. The autophagy activator rapamycin reversed the effect. More important, rapamycin alleviated the suppressive role of HG in tendon fibroblasts viability. Taken together, our data demonstrate that HG represses tendon fibroblasts proliferation by inhibiting autophagy activation in tendon injury.

20.
Front Microbiol ; 12: 691087, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394031

RESUMO

Coagulase-negative Staphylococcus warneri is an opportunistic pathogen that is capable of causing several infections, especially in patients with indwelling medical devices. Here, we determined the complete genome sequence of a clinical S. warneri strain isolated from the blood culture of a 1-year-old nursling patient with acute upper respiratory infection. Genome-wide phylogenetic analysis confirmed the phylogenetic relationships between S. warneri and other Staphylococcus species. Using comparative genomics, we identified three cell wall-anchored (CWA) proteins at the same locus (sdr), named SdrJ, SdrK, and SdrL, on the chromosome sequences of different S. warneri strains. Structural predictions showed that SdrJ/K/L have structural features characteristic of Sdr proteins but exceptionally contained an unusual N-terminal repeat region. However, the C-terminal repetitive (R) region of SdrJ contains a significantly larger proportion of alanine (142/338, 42.01%) than the previously reported SdrI (37.00%). Investigation of the genetic organization revealed that the sdrJ/K/L genes were always followed by one or two glycosyltransferase genes, gtfA and gtfB and were present in an ∼56 kb region bordered by a pair of 8 bp identical direct repeats, named Sw-Sdr. This region was further found to be located on a 160-kb region subtended by a pair of 160-bp direct repeats along with other virulence genes and resistance genes. Sw-Sdr contained a putative integrase that was probably a remnant of a functional integrase. Evidence suggests that Sw-Sdr is improbably an efficient pathogenicity island. A large-scale investigation of Staphylococcus genomes showed that sdr loci were a potential hotspot of insertion sequences (ISs), which could lead to intraspecific diversity at these loci. Our work expanded the repository of Staphylococcus Sdr proteins, and for the first time, we established the connection between sdr loci and phylogenetic relationships and compared the sdr loci in different Staphylococcus species, which provided large insights into the genetic environment of CWA genes in Staphylococcus.

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