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1.
Mol Biol Evol ; 41(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38319744

RESUMO

Nitrogen is essential for all organisms, but biological nitrogen fixation (BNF) occurs only in a small fraction of prokaryotes. Previous studies divided nitrogenase-gene-carrying prokaryotes into Groups I to IV and provided evidence that BNF first evolved in bacteria. This study constructed a timetree of the evolution of nitrogen-fixation genes and estimated that archaea evolved BNF much later than bacteria and that nitrogen-fixing cyanobacteria evolved later than 1,900 MYA, considerably younger than the previous estimate of 2,200 MYA. Moreover, Groups III and II/I diverged ∼2,280 MYA, after the Kenorland supercontinent breakup (∼2,500-2,100 MYA) and the Great Oxidation Event (∼2,400-2,100 MYA); Groups III and Vnf/Anf diverged ∼2,086 MYA, after the Yarrabubba impact (∼2,229 MYA); and Groups II and I diverged ∼1,920 MYA, after the Vredefort impact (∼2,023 MYA). In summary, this study provided a timescale of BNF events and discussed the possible effects of geological events on BNF evolution.


Assuntos
Cianobactérias , Fixação de Nitrogênio , Fixação de Nitrogênio/genética , Nitrogenase/genética , Nitrogenase/metabolismo , Cianobactérias/genética , Archaea/metabolismo , Nitrogênio
2.
BMC Health Serv Res ; 24(1): 116, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254152

RESUMO

BACKGROUND: Patient follow-up is an essential component of hospital management. In the current information era, the patient follow-up scheme is expected to be replaced by Internet technology. This study constructed a cloud follow-up platform for gynecological chemotherapy patients and assessed its cost-effectiveness and patients' feedback. METHODS: A total of 2,538 patients were followed up using a cloud follow-up system between January and October 2021. Prior to this, 690 patients were followed manually via telephone calls. Patients' characteristics, follow-up rate, satisfaction, and session duration were compared between the cloud follow-up and manual follow-up groups. In addition, the read rate of health education materials in the cloud follow-up group was analyzed. RESULTS: General information, including age, education attainment, cancer stage, and disease category, and follow-up rate (cloud: 6,957/7,614, 91.4%; manual: 1,869/2,070, 90.3%; P = 0.13) did not significantly differ between the two groups. The follow-up satisfaction of the cloud follow-up patients was significantly better than that of the manual follow-up group (cloud: 7,192/7,614, 94.5%; manual: 1,532/2,070, 74.0%; P<0.001). The time spent on the follow-up was approximately 1.2 h for 100 patients in the cloud follow-up group and 10.5 h in the manual follow-up group. Multivariate analysis indicated that the cloud follow-up group had significantly greater follow-up satisfaction (odds ratio: 2.239, 95% CI: 1.237 ~ 5.219). Additionally, the average follow-up duration of the cloud follow-up group decreased by 9.287 h (coefficient: -9.287, 95% CI: -1.439~-0.165). The read rate of health education materials was 72.9% in the cloud follow-up group. CONCLUSIONS: The follow-up effect of the cloud follow-up group was not inferior to that of the manual follow-up group. The cloud follow-up was more effective for prevention and control requirements in the post-epidemic era. Cloud follow-up can save medical resources, improve cost-effectiveness, provide sufficient health education resources for patients, and improve their satisfaction.


Assuntos
Epidemias , Ginecologia , Humanos , Seguimentos , Escolaridade , Educação em Saúde
3.
Biopreserv Biobank ; 22(2): 174-178, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37540078

RESUMO

Background: PAXgene® Blood RNA tubes are routinely used in clinical research and molecular biology applications to preserve the stability of RNA in whole blood. However, in practice, blood clots are occasionally observed after blood collection and are often ignored. Currently, there are few studies on whether blood clots affect the quality of RNA extracted from these tubes. Materials and Methods: Fifteen pairs of non-clot and clot PAXgene Blood RNA tube samples (n = 30) were collected to form two matched groups from 15 patients. According to the maximum diameter (d) of the blood clot observed visually at the time of sample reception, the clot groups were divided into a small-clot group (0 cm < d < 0.5 cm) and a large-clot group (d ≥ 0.5 cm). RNA was extracted by the PAXgene Blood RNA Kit. To analyze the quality of RNA, its yield and purity were assessed by spectrophotometry, and integrity was measured by microfluidic electrophoresis. An A260/280 ratio between 1.8 and 2.2 indicated purified RNA, and RNA integrity number (RIN) values ≥7.0 were considered to represent qualified integrity. Results: The median yields of RNA from the non-clot and clot groups were 3.84 (2.80-6.38) µg and 4.87 (2.77-8.30) µg, respectively. The median A260/280 ratios were 2.08 (2.06-2.09) and 2.09 (2.07-2.11), whereas the median A260/230 ratios were 1.77 (1.31-1.91) and 1.67 (1.21-1.94) in the two groups. In addition, the median RINs were 8.20 (8.00-8.40) and 7.20 (6.60-7.70), respectively. There were no significant differences in RNA yields, A260/280, or A260/230 between the two groups. However, the RIN value of the clot group was significantly lower compared with the non-clot group (p < 0.05), with RIN ≥7.0 found in all non-clot samples and 60% of clot samples (p < 0.05). Furthermore, in the clot groups, the small-clot samples had higher RIN values than large-clot samples (8.25 [7.75-8.75] vs. 6.90 [6.60-7.30], p < 0.001). Conclusions: The formation of large blood clots in PAXgene Blood RNA tubes will reduce the integrity of extracted RNA.


Assuntos
RNA , Trombose , Humanos , Coleta de Amostras Sanguíneas/métodos , Kit de Reagentes para Diagnóstico
4.
Int J Mol Sci ; 24(23)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38069141

RESUMO

With the increasing prevalence of sleep deprivation (SD)-related disorders, the effective treatment of sleep disorders has become a critical health research topic. Thus, we hypothesized and investigated the effectiveness of a 3-week melatonin intervention on neuropsychiatric behavioral responses mediated throughout melatonin receptors, gut microbiota, and lipid metabolites in rats with chronic SD. Eighteen 6-week-old Wistar rats were used and divided into the control grup (C, n = 6), SD group (n = 6), and melatonin-supplemented group (SDM, n = 6). During weeks 0 to 6, animals were provided with the AIN-93M diet and free access to water. Four-week chronic SD was conducted from weeks 7 to 10. Exogenous melatonin administration (10 mg/kg BW) was injected intraperitoneally 1 h before the daily administration of SD for 3 weeks in the SDM group. SD rats exhibited anxiety-like behavior, depression-like behavior, and cognitive impairment. Exogenous melatonin administration ameliorated neuropsychiatric behaviors induced by chronic SD. Analysis of fecal metabolites indicated that melatonin may influence brain messaging through the microbiota-gut-brain axis by increasing the production of short-chain fatty acids (SCFA) and decreasing the production of secondary bile acids (SBA). Four-week SD reduced the cerebral cortex expression of MT1, but not in the colon. Chronic SD led to anxiety and depression-like behaviors and cognitive decline, as well as the reduced intestinal level of SCFAs and the enhanced intestinal level of SBAs in rats. In this work, we confirmed our hypothesis that a 3-week melatonin intervention on neuropsychiatric behavioral response mediated throughout melatonin receptors, gut microbiota, and lipid metabolites in rats with chronic SD.


Assuntos
Microbioma Gastrointestinal , Melatonina , Microbiota , Ratos , Animais , Privação do Sono/tratamento farmacológico , Privação do Sono/complicações , Melatonina/farmacologia , Melatonina/uso terapêutico , Receptores de Melatonina , Ratos Wistar , Ácidos Graxos Voláteis/farmacologia
5.
Nat Commun ; 14(1): 5755, 2023 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-37716995

RESUMO

The diversification of effector function, driven by a co-evolutionary arms race, enables pathogens to establish compatible interactions with hosts. Structurally conserved plant pathogenesis-related PR-1 and PR-1-like (PR-1L) proteins are involved in plant defense and fungal virulence, respectively. It is unclear how fungal PR-1L counters plant defense. Here, we show that Ustilago maydis UmPR-1La and yeast ScPRY1, with conserved phenolic resistance functions, are Ser/Thr-rich region mediated cell-surface localization proteins. However, UmPR-1La has gained specialized activity in sensing phenolics and eliciting hyphal-like formation to guide fungal growth in plants. Additionally, U. maydis hijacks maize cathepsin B-like 3 (CatB3) to release functional CAPE-like peptides by cleaving UmPR-1La's conserved CNYD motif, subverting plant CAPE-primed immunity and promoting fungal virulence. Surprisingly, CatB3 avoids cleavage of plant PR-1s, despite the presence of the same conserved CNYD motif. Our work highlights that UmPR-1La has acquired additional dual roles to suppress plant defense and sustain the infection process of fungal pathogens.


Assuntos
Basidiomycota , Virulência , Proteínas de Membrana , Saccharomyces cerevisiae , Fenóis
6.
J Fungi (Basel) ; 9(9)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37755059

RESUMO

White-rot fungi are the most important group of lignin biodegraders. Phanerochaete sordida YK-624 has higher ligninolytic activity than that of model white-rot fungi. However, the underlying mechanism responsible for lignin degradation by white-rot fungi remains unknown, and the induced compounds isolated from white-rot fungi for lignin degradation have never been studied. In the present study, we tried to screen ligninolytic-inducing compounds produced by P. sordida YK-624. After large-scale incubation of P. sordida YK-624, the culture and mycelium were separated by filtration. After the separation and purification, purified compounds were analyzed by high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance. The sterilized unbleached hardwood kraft pulp was used for the initial evaluation of ligninolytic activity. Ergosterol was isolated and identified and it induced the lignin-degrading activity of this fungus. Moreover, we investigated ergosterol metabolites from P. sordida YK-624, and the ergosterol metabolites ergosta-4,7,22-triene-3,6-dione and ergosta-4,6,8(14),22-tetraen-3-one were identified and then chemically synthesized. These compounds significantly improved the lignin-degrading activity of the fungus. This is the first report on the ligninolytic-inducing compounds produced by white-rot fungi.

7.
Front Oncol ; 13: 1173838, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37614506

RESUMO

Background: Patients with gynecologic cancers experience side effects of chemotherapy cardiotoxicity. We aimed to quantify cardiac magnetic resonance (CMR) markers of myocardial fibrosis in patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy. Methods: This study is part of a registered clinical research. CMR T1 mapping was performed in patients with gynecologic cancer and low cardiovascular risk undergoing chemotherapy. The results were compared with those of age-matched healthy control subjects. Results: 68 patients (median age = 50 years) and 30 control subjects were included. The median number of chemotherapy cycles of patients was 9.0 (interquartile range [IQR] 3.3-17.0). Extracellular volume fraction (ECV) (27.2% ± 2.7% vs. 24.5% ± 1.7%, P < 0.001) and global longitudinal strain (-16.2% ± 2.8% vs. -17.4% ± 2.0%, P = 0.040) were higher in patients compared with controls. Patients with higher chemotherapy cycles (>6 cycles) (n=41) had significantly lower intracellular mass indexed (ICMi) compared with both patients with lower chemotherapy cycles (≤6 cycles) (n=27) (median 27.44 g/m2 [IQR 24.03-31.15 g/m2] vs. median 34.30 g/m2 [IQR 29.93-39.79 g/m2]; P = 0.002) and the control group (median 27.44 g/m2 [IQR 24.03-31.15 g/m2] vs. median 32.79 g/m2 [IQR 27.74-35.76 g/m2]; P = 0.002). Patients with two or more chemotherapy regimens had significantly lower ICMi compared with both patients with one chemotherapy regimen (27.45 ± 5.16 g/m2 vs. 33.32 ± 6.42 g/m2; P < 0.001) and the control group (27.45 ± 5.16 g/m2 vs. 33.02 ± 5.52 g/m2; P < 0.001). The number of chemotherapy cycles was associated with an increase in the ECV (Standard regression coefficient [ß] = 0.383, P = 0.014) and a decrease in the ICMi (ß = -0.349, P = 0.009). Conclusion: Patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy have diffuse extracellular volume expansion, which is obvious with the increase of chemotherapy cycles. Myocyte loss may be part of the mechanism in patients with a higher chemotherapy load. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR-DDD-17013450.

9.
Food Funct ; 14(13): 5977-5993, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37334912

RESUMO

Clinical evidence suggests that a bidirectional relationship is present between sleep loss and psychiatric disorders. Both melatonin receptor agonist ramelteon (RMT) and n-3 polyunsaturated fatty acids (n-3 PUFAs) exhibit antidepressant effects, while their underlying molecular mechanisms might be different. Thus, the present study aims to investigate the add-on effects and possible mechanisms of how RMT and different n-3 PUFAs modulate the melatonin receptor pathway as well as brain lipidome to ameliorate the neuropsychiatric behaviors displayed in rats under chronic sleep deprivation. Thirty-one 6-week-old male Wistar rats were divided into five groups: control (C), sleep deprivation (S), sleep deprivation treated with RMT (SR), sleep deprivation treated with RMT and eicosapentaenoic acid (C20:5n-3, EPA) (SRE), and sleep deprivation treated with RMT and docosahexaenoic acid (C22:6n-3, DHA) (SRD) groups. The results reveal that RMT plus EPA alleviated depressive-like behavior when the rats were subjected to the forced swimming test, whereas RMT plus DHA alleviated anxiety-like behavior when the rats were subjected to the elevated plus maze test. The results of a western blot analysis further revealed that compared with the rats in the S group, those in the SRE and SRD groups exhibited a significantly increased expression of MT2 in the prefrontal cortex, with greater benefits observed in the SRE group. In addition, decreased BDNF and TrkB expression levels were upregulated only in the SRE group. Lipidomic analysis further revealed possible involvement of aberrant lipid metabolism and neuropsychiatric behaviors. RMT plus EPA demonstrated promise as having the effects of reversing the levels of the potential biomarkers of depressive-like behaviors. RMT plus EPA or DHA could ameliorate depressive- and anxiety-like behaviors in sleep-deprived rats through the alteration of the lipidome and MT2 receptor pathway in the brain, whereas EPA and DHA exerted a differential effect.


Assuntos
Ácidos Graxos Ômega-3 , Ratos , Masculino , Animais , Ácidos Graxos Ômega-3/farmacologia , Lipidômica , Privação do Sono/tratamento farmacológico , Receptores de Melatonina , Ratos Wistar , Encéfalo , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos Insaturados/farmacologia
10.
J Clin Med ; 12(11)2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37297926

RESUMO

This study investigated differences in lipidomic profile features in nonalcoholic steatohepatitis (NASH) between mild and significant liver fibrosis cases among patients with morbid obesity. Wedge liver biopsy was performed during sleeve gastrectomy and significant liver fibrosis was defined as a fibrosis score ≥ 2. We selected patients with NASH with non/mild fibrosis (stage F0-F1; n = 30) and NASH with significant fibrosis (stage F2-F4; n = 30). The results of the liver tissue lipidomic analysis revealed that the fold changes of triglyceride (TG) (52:6); cholesterol ester (CE) (20:1); phosphatidylcholine (PC) (38:0) and (50:8); phosphatidic acid (PA) (40:4); phosphatidylinositol (PI) (49:4); phosphatidylglycerol (PG) (40:2); and sphingomyelin (SM) (35:0) and (37:0) were significantly lower in patients with NASH with F2-F4 than those with NASH with F0-F1 (p < 0.05). However, the fold changes of PC (42:4) were relatively higher in patients with NASH with stage 2-4 fibrosis (p < 0.05). Moreover, predictive models incorporating serum markers levels, ultrasonographic studies, and levels of specific lipid components [PC (42:4) and PG (40:2)] yielded the highest area under receiver operating curve (0.941), suggesting a potential correlation between NASH fibrosis stages and liver lipid accumulation among specific lipid species subclasses. This study demonstrated that the concentrations of particular lipid species in the liver correlate with NASH fibrosis stages and may indicate hepatic steatosis regression or progression in patients with morbid obesity.

11.
Sci Total Environ ; 892: 164767, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37308012

RESUMO

Environmental exposure to fine particulate matter PM2.5 is known to be associated with many hazardous health effects, including cardiovascular diseases (CVDs). To reduce the related health burden, it is crucial that policy-makers throughout the world set regulation levels according to their own evidence-based study outcomes. However, there appears to be a lack of decision-making methods for the control level of PM2.5 based on the burden of disease. In this study, 117,882 CVD-free participants (≥30-years-old) of the MJ Health Database were followed-up (for a median of 9 years) between 2007 and 2017. Each participant's residential address was matched to the 3× 3 km grid PM2.5 concentration estimates with a 5-year average for long-term exposure. We used a time-dependent nonlinear weight-transformation Cox regression model for the concentration-response function (CRF) between exposure to PM2.5 and CVD incidence. Town/district-specific PM2.5-attributable years of life in disability (YLDs) in CVD incidence were calculated by using the relative risk (RR) of the PM2.5 concentration level relative to the reference level. A cost-benefit analysis was proposed by assessing the trade-off between the gain in avoidable YLDs (given a reference level at u and considering mitigation cost) versus the loss in unavoidable YLDs by not setting at the lowest observed health effect level u0. The CRF varied across different areas with dissimilar PM2.5 exposure ranges. Areas with low PM2.5 concentrations and population sizes provided crucial information for the CVD health effect at the lower end. Additionally, women and older participants were more susceptible. The avoided town/district-specific YLDs in CVD incidence due to lower RRs ranged from 0 to 3000 person-years comparing the PM2.5 concentration levels in 2019 with the levels in 2011. Based on the cost-benefit analysis, an annual PM2.5 concentration of 13 µg/m3 would be optimal, which provides a guideline for the updated regulation level (currently at 15 µg/m3). The proposed cost-benefit analysis method may be applied to other countries/regions for regulation levels that are most suitable for their air pollution status and population health.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doenças Cardiovasculares , Humanos , Feminino , Adulto , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Análise Custo-Benefício , Material Particulado/análise , Poluição do Ar/análise , Exposição Ambiental/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise
12.
Sci Total Environ ; 896: 165152, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37391160

RESUMO

Steroidal estrogens are ubiquitous contaminants that have garnered attention worldwide due to their endocrine-disrupting and carcinogenic activities at sub-nanomolar concentrations. Microbial degradation is one of the main mechanisms through which estrogens can be removed from the environment. Numerous bacteria have been isolated and identified as estrogen degraders; however, little is known about their contribution to environmental estrogen removal. Here, our global metagenomic analysis indicated that estrogen degradation genes are widely distributed among bacteria, especially among aquatic actinobacterial and proteobacterial species. Thus, by using the Rhodococcus sp. strain B50 as the model organism, we identified three actinobacteria-specific estrogen degradation genes, namely aedGHJ, by performing gene disruption experiments and metabolite profile analysis. Among these genes, the product of aedJ was discovered to mediate the conjugation of coenzyme A with a unique actinobacterial C17 estrogenic metabolite, 5-oxo-4-norestrogenic acid. However, proteobacteria were found to exclusively adopt an α-oxoacid ferredoxin oxidoreductase (i.e., the product of edcC) to degrade a proteobacterial C18 estrogenic metabolite, namely 3-oxo-4,5-seco-estrogenic acid. We employed actinobacterial aedJ and proteobacterial edcC as specific biomarkers for quantitative polymerase chain reaction (qPCR) to elucidate the potential of microbes for estrogen biodegradation in contaminated ecosystems. The results indicated that aedJ was more abundant than edcC in most environmental samples. Our results greatly expand the understanding of environmental estrogen degradation. Moreover, our study suggests that qPCR-based functional assays are a simple, cost-effective, and rapid approach for holistically evaluating estrogen biodegradation in the environment.


Assuntos
Ecossistema , Estrogênios , Estrogênios/metabolismo , Estrona/metabolismo , Biodegradação Ambiental , Bactérias/metabolismo , Proteobactérias/genética
14.
Free Radic Biol Med ; 204: 301-312, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37217090

RESUMO

Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Approximately 40% of CRC patients are KRAS sequence variation, including KRAS G13D mutation (KRASG13D) CRC patients, accounting for approximately 8% of all KRAS mutations in CRC patients and showing little benefit from anti-EGFR therapy. Therefore, there is an urgent need for new and effective anticancer agents in patients with KRASG13D CRC. Here, we identified a natural product, erianin, that directly interacted with purified recombinant human KRASG13D with a Kd of 1.1163 µM, which also significantly improve the thermal stability of KRASG13D. The cell viability assay showed that KRASG13D cells were more sensitive to erianin than KRASWT or KRASG12V cells. In vitro, results showed that erianin suppressed the migration, invasion and epithelial-mesenchymal transition (EMT) of KRASG13D CRC cells. Furthermore, erianin induced ferroptosis, as evidenced by the accumulation of Fe2+ and reactive oxygen species (ROS), lipid peroxidation, and changes in the mitochondrial morphology of KRASG13D CRC cells. Interestingly, we also found that erianin-induced ferroptosis was accompanied by autophagy. Moreover, the occurrence of erianin-induced ferroptosis is reversed by autophagy inhibitors (NH4Cl and Bafilomycin A1) and ATG5 knockdown, suggesting that erianin-induced ferroptosis is autophagy-dependent. In addition, we evaluated the inhibition of tumor growth and metastasis by erianin in vivo using a subcutaneous tumor model and a spleen-liver metastasis model, respectively. Collectively, these data provide novel insights into the anticancer activity of erianin, which is valuable for the further discussion and investigation of the use of erianin in clinical anticancer chemotherapy for KRASG13D CRC.


Assuntos
Neoplasias Colorretais , Ferroptose , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Ferroptose/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Mutação , Autofagia
15.
Eur J Pharmacol ; 949: 175727, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37062502

RESUMO

Heart failure is one of the most significant public health problems faced by millions of medical researchers worldwide. And pathological cardiac hypertrophy is considered one of the possible factors of increasing the risk of heart failure. Here, we introduce apelin/ELABELA-APJ system as a novel therapeutic target for cardiac hypertrophy, bringing about new directions in clinical treatment. Apelin has been proven to regulate cardiac hypertrophy through various pathways. And an increasing number of studies on ELABELA, the newly discovered endogenous ligand, suggest it can alleviate cardiac hypertrophy through mechanisms similar or different to apelin. In this review, we elaborate on the role that apelin/ELABELA-APJ system plays in cardiac hypertrophy and the intricate mechanisms that apelin/ELABELA-APJ affect cardiac hypertrophy. We also illuminate and make comparisons of the newly designed peptides and small molecules as agonists and antagonists for APJ, updating the breakthroughs in this field.


Assuntos
Cardiomegalia , Insuficiência Cardíaca , Humanos , Apelina/metabolismo , Receptores de Apelina , Cardiomegalia/tratamento farmacológico , Receptores Acoplados a Proteínas G
16.
Gut Microbes ; 15(1): 2183685, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36843073

RESUMO

Abnormally high circulating androgen levels have been considered a causative factor for benign prostatic hypertrophy and prostate cancer in men. Recent animal studies on gut microbiome suggested that gut bacteria are involved in sex steroid metabolism; however, the underlying mechanisms and bacterial taxa remain elusive. Denitrifying betaproteobacteria Thauera spp. are metabolically versatile and often distributed in the animal gut. Thauera sp. strain GDN1 is an unusual betaproteobacterium capable of catabolizing androgen under both aerobic and anaerobic conditions. We administered C57BL/6 mice (aged 7 weeks) with strain GDN1 through oral gavage. The strain GDN1 administration caused a minor increase in the relative abundance of Thauera (≤0.1%); however, it has profound effects on the host physiology and gut bacterial community. The results of our ELISA assay and metabolite profile analysis indicated an approximately 50% reduction in serum androgen levels in the strain GDN1-administered male mice. Moreover, androgenic ring-cleaved metabolites were detected in the fecal extracts of the strain GDN1-administered mice. Furthermore, our RT - qPCR results revealed the expression of the androgen catabolism genes in the gut of the strain GDN1-administered mice. We found that the administered strain GDN1 regulated mouse serum androgen levels, possibly because it blocked androgen recycling through enterohepatic circulation. This study discovered that sex steroids serve as a carbon source of gut bacteria; moreover, host circulating androgen levels may be regulated by androgen-catabolizing gut bacteria. Our data thus indicate the possible applicability of androgen-catabolic gut bacteria as potent probiotics in alternative therapy of hyperandrogenism.


Assuntos
Androgênios , Microbioma Gastrointestinal , Camundongos , Masculino , Animais , Androgênios/metabolismo , Microbioma Gastrointestinal/genética , Camundongos Endogâmicos C57BL , Bactérias , Metabolismo dos Lipídeos
17.
Am J Clin Nutr ; 117(2): 383-391, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36811562

RESUMO

BACKGROUND: Dietary diversity is widely advocated as a means to promote health, but little is known regarding whether the beneficial effects still apply in older adults. OBJECTIVE: To examine the association between the dietary diversity score (DDS) and frailty among older Chinese adults. METHODS: A total of 13,721 adults aged ≥65 y without frailty at baseline were enrolled. The DDS at baseline was constructed based on 9 items of a food frequency questionnaire. We used 39 self-reported health items to construct a frailty index (FI), with FI ≥ 0.25 indicating frailty. Cox models with restricted cubic splines were used to evaluate the dose-response relationships of DDS (continuous) with frailty. In addition, Cox proportional hazard models were used to examine the association between DDS (categorized as scores ≤4, 5-6, 7, and ≥8) and frailty. RESULTS: During the mean follow-up of 5.94 y, 5250 participants met the criteria for frailty. Each 1-unit increase in DDS corresponded to a 5% lower risk of frailty (hazard ratio [HR]; 0.95; 95% CI: 0.94, 0.97]. Compared with participants with DDS ≤4 points, those with a DDS of 5-6, 7, and ≥8 points exhibited a lower frailty risk, with HRs of 0.79 (95% CI: 0.71, 0.87), 0.75 (95% CI: 0.68, 0.83), and 0.74 (95% CI: 0.67, 0.81), respectively (P-trend < 0.001). Protein-rich food items, such as meat; eggs; and beans, were associated with protective effects against frailty. In addition, a significant association was observed between higher consumption of 2 high-frequency foods, tea and fruits, and lower risk of frailty. CONCLUSIONS: A higher DDS was associated with a lower risk of frailty among older Chinese adults. This study highlights the importance of a diverse diet as a potential modifiable behavioral factor for preventing frailty in older Chinese adults.


Assuntos
Fragilidade , Humanos , Pessoa de Meia-Idade , Idoso , Fragilidade/epidemiologia , Fragilidade/prevenção & controle , População do Leste Asiático , Promoção da Saúde , Dieta , Frutas
18.
Chemosphere ; 322: 138200, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36828109

RESUMO

The disposal of soybean pulp (okara) (∼14 M tons annually) represents a global concern. α-ketoisocaproate (KIC) is an intrinsic l-leucine metabolite boosting mammalian muscle growth and has great potential in animal husbandry. However, the use of pure l-leucine (5000 USD/kg) for KIC (22 USD/kg) bioproduction is cost-prohibitive in practice, while okara rich in l-leucine (10%) could serve as an economical alternative. Following the concept of a circular bioeconomy, we managed to develop a cost-efficient platform to valorize okara into KIC. In this study, proteolytic Bacillus subtilis strain 168 capable of utilizing okara as a comprehensive substrate was employed as the whole-cell biocatalyst for KIC bioproduction. First, we elucidated the function of genes involved in KIC downstream metabolism in strain 168, including those encoding 2-oxoisovalerate dehydrogenase (bkdAA), 2-oxoisovalerate decarboxylase (bkdAB), enoyl-CoA hydratase (fadB), and bifunctional enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (fadN). Among those KIC downstream metabolizing mutants of strain 168, the 2-oxoisovalerate decarboxylase gene knockout strain (ΔbkdAB) was found to have a better accumulation of KIC. To further improve the KIC yield, a soluble l-amino acid deaminase (LAAD) from Proteus vulgaris was heterologously expressed in the ΔbkdAB strain and a ∼50% conversion of total l-leucine contained in okara was catalyzed into KIC, along with a ∼50% reduction of CO2 emission compared to the wild-type cultures. Altogether, this renovated biocatalytic system provides an alternative platform to valorize okara for producing value-added chemicals in an eco-friendly manner.


Assuntos
Carboxiliases , Glycine max , Animais , Leucina/metabolismo , Glycine max/genética , Glycine max/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Enoil-CoA Hidratase , Mamíferos/metabolismo
19.
Singapore Med J ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36695278

RESUMO

Introduction: There is increasing evidence demonstrating the safety and benefits of physical activity (PA) in uncomplicated pregnancies. Literature has shown that pregnant women around the world do not engage in adequate exercise. This study aims to assess the current practices of exercise among pregnant women in Singapore, determine the proportion of women meeting different PA targets and evaluate the factors influencing the practice of exercise. Methods: In this cross-sectional study, pregnant women in different trimesters of pregnancy from KK Women's and Children's Hospital and Singapore General Hospital were surveyed. Information regarding patient demographics, attitudes and perceptions of exercise, and practice of exercise was collected. The International Physical Activity Questionnaire (IPAQ) was used to determine the amount of PA. Results: A total of 201 pregnant women aged 20-44 years were surveyed. Almost all (99.0%) participants thought that exercise was beneficial in pregnancy. Only 31.6% of them engaged in any moderate or vigorous leisure-time PA (LTPA) and they were active for a median of 120 min/week. Only 12.6% of the pregnant women met the national recommendations of at least 150 min of moderate exercise per week. The amount of total PA performed was lower among women in later trimesters of pregnancy and higher among working mothers. Conclusion: Although most Singaporean pregnant women perceived exercise as beneficial, the majority did not engage in PA. Most of the participants did not meet the international PA targets and recently published national guidelines. More can be done to promote the uptake of exercise in pregnancy and optimise metabolic management of pregnant women in Singapore.

20.
Environ Technol ; 44(15): 2280-2287, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34986752

RESUMO

Acetamiprid (ACE) belongs to the group of neonicotinoid pesticides, which have become the most widely utilised pesticides around the world in the last two decades. The ability of Phanerochaete sordida YK-624 to degrade ACE under ligninolytic conditions has been demonstrated; however, the functional genes involved in ACE degradation have not been fully elucidated. In the present study, the differentially expressed genes of P. sordida YK-624 under ACE-degrading conditions and in the absence of ACE were elucidated by RNA sequencing (RNA-Seq). Based on the gene ontology enrichment results, the cell wall and cell membrane were significantly affected under ACE-degrading conditions. This result suggested that intracellular degradation of ACE might be mediated by this fungus. In addition, genes in metabolic pathways were the most enriched upregulated differentially expressed genes according to the KEGG pathway analysis. Eleven differentially expressed genes characterised as cytochrome P450s were upregulated, and these genes were determined to be particularly important for ACE degradation by P. sordida YK-624 under ligninolytic conditions.


Assuntos
Praguicidas , Phanerochaete , Praguicidas/metabolismo , Neonicotinoides , Phanerochaete/genética , Phanerochaete/metabolismo , Análise de Sequência de RNA
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