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1.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21264371

RESUMO

We recently performed 568 rapid neutralizing antibody (NAb) tests on 164 fully vaccinated individuals who received either Moderna or Pfizer COVID-19 vaccine regimens over 7 weeks. The NAb levels against the wild type (WA1/2020), Delta, and Kappa variants were measured and compared. Depending on each individuals medical condition and vaccination status, the NAb levels for most of the fully vaccinated people decreased within 2-6 months, while a small number of individuals either generated non-detectable amount of NAbs after full vaccination (e.g., immunocompromised), or had high NAb levels lasting beyond 6 months. Since the NAb levels vary significantly among different individuals and decrease over time, the deployment of a low-cost rapid test to monitor NAb levels against both the wild type and emerging variants among fully vaccinated individuals can play a very crucial role to control the current pandemic. Our study provides an example of using such a rapid NAb test to fill this currently unmet medical need.

2.
World J Gastroenterol ; 27(31): 5152-5170, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34497441

RESUMO

Helicobacter pylori (H. pylori) infects approximately 50% of all humans globally. Persistent H. pylori infection causes multiple gastric and extragastric diseases, indicating the importance of early diagnosis and timely treatment. H. pylori eradication produces dramatic changes in the gastric mucosa, resulting in restored function. Consequently, to better understand the importance of H. pylori eradication and clarify the subsequent recovery of gastric mucosal functions after eradication, we summarize histological, endoscopic, and gastric microbiota changes to assess the therapeutic effects on the gastric mucosa.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Microbiota , Antibacterianos/uso terapêutico , Mucosa Gástrica , Infecções por Helicobacter/tratamento farmacológico , Humanos , Estômago
3.
BMC Public Health ; 21(1): 1648, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503467

RESUMO

BACKGROUND: Hypertension remains the major modifiable risk factor of stroke recurrence. The study aimed to determine the up-to-date epidemiological features of hypertension among the survivors of ischemic stroke. METHODS: Our cross-sectional study included 18,796 adults aged ≥40 years and residing in northeast China. Ischemic stroke was diagnosed according to the World Health Organization's criteria, which requires the clinical record, computed tomography (CT) and/or magnetic resonance imaging (MRI) during the hospital stay. Hypertension was defined according to the Chinese hypertension guidelines (mean SBP ≥140 mmHg and/or mean DBP ≥90 mmHg, and/or self-reported use of anti-hypertensive medication in the past 2 weeks). RESULTS: Of the 986 survivors of ischemic stroke, 819 (83.1%) were identified with hypertension (535 were pre-stroke hypertension and 284 were post-stroke hypertension). Among hypertensive patients, the awareness and treatment rates were 76.8 and 66.7% respectively. Only 11.0% achieved an appropriate blood pressure (< 140 mmHg and < 90 mmHg) among those who took hypertensive medications. 16.8% of treated hypertensive patients received combination therapy, and calcium channel blockers were the most frequently used anti-hypertensive medication as monotherapy. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the stroke population was 155.3 ± 22.9 mmHg and 89.2 ± 12.3 mmHg. Both SBP and DBP were higher in rural patients than in urban patients (158.5 ± 23.8 mmHg vs. 146.4 ± 17.5 mmHg and 90.3 ± 12.9 mmHg vs. 85.9 ± 10.1 mmHg, respectively; p < 0.001). The rates of stage 2 and above hypertension in the ischemic stroke population were 32.5 and 18.7%, and was significantly higher in rural areas than in urban areas. CONCLUSIONS: The prevalence of poorly-controlled hypertension and the high rates of blood pressures at stages 2 and above in patients with prior ischemic stroke demonstrated an alarming situation in northeast China.


Assuntos
Hipertensão , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , China/epidemiologia , Estudos Transversais , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Sobreviventes
4.
J Hematol Oncol ; 14(1): 152, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556152

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy has shown tremendous success in eradicating hematologic malignancies. However, this success has not yet been extrapolated to solid tumors due to the limited infiltration and persistence of CAR-T cells in the tumor microenvironment (TME). In this study, we screened a novel anti-CD70 scFv and generated CD70 CAR-T cells that showed effective antitumor functions against CD70+ renal carcinoma cells (RCCs) both in vitro and in vivo. We further evaluated the effect and explored the molecular mechanism of a PARP inhibitor (PARPi) in CAR-T cell immunotherapy by administering the PARPi to mouse xenografts model derived from human RCC cells. Treatment with the PARPi promoted CAR-T cell infiltration by stimulating a chemokine milieu that promoted CAR-T cell recruitment and the modulation of immunosuppression in the TME. Moreover, our data demonstrate that PARPi modulates the TME by activating the cGAS-STING pathway, thereby altering the balance of immunostimulatory signaling and enabling low-dose CAR-T cell treatment to induce effective tumor regression. These data demonstrate the application of CD70 CAR-T cell therapeutic strategies for RCC and the cross-talk between targeting DNA damage responses and antitumor CAR-T cell therapy. These findings provide insight into the mechanisms of PARPis in CAR-T cell therapy for RCC and suggest a promising adjuvant therapeutic strategy for CAR-T cell therapy in solid tumors.

5.
Korean J Radiol ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34564958

RESUMO

OBJECTIVE: The role of preoperative overt hepatic encephalopathy (OHE) in the neurophysiological mechanism of cognitive improvement after liver transplantation (LT) remains elusive. This study aimed to explore changes in sub-regional thalamic functional connectivity (FC) after LT and their relationship with neuropsychological improvement using resting-state functional MRI (rs-fMRI) data in cirrhotic patients with and without a history of OHE. MATERIALS AND METHODS: A total of 51 cirrhotic patients, divided into the OHE group (n = 21) and no-OHE group (n = 30), and 30 healthy controls were enrolled in this prospective study. Each patient underwent rs-fMRI before and 1 month after LT. Using 16 bilateral thalamic subregions as seeds, we conducted a seed-to-voxel FC analysis to compare the thalamic FC alterations before and after LT between the OHE and no-OHE groups, as well as differences in FC between the two groups of cirrhotic patients and the control group. Correction for multiple comparisons was conducted using the false discovery rate (p < 0.05). RESULTS: We found abnormally increased FC between the thalamic sub-region and prefrontal cortex, as well as an abnormally decreased FC between the bilateral thalamus in both OHE and no-OHE cirrhotic patients before LT, which returned to normal levels after LT. Compared with the no-OHE group, the OHE group exhibited more extensive abnormalities prior to LT, and the increased FC between the right thalamic subregions and right inferior parietal lobe was markedly reduced to normal levels after LT. CONCLUSION: The renormalization of FC in the cortico-thalamic loop might be a neuro-substrate for the recovery of cognitive function after LT in cirrhotic patients. In addition, hyperconnectivity between thalamic subregions and the inferior parietal lobe might be an important feature of OHE. Changes in FC in the thalamus might be used as potential biomarkers for recovery of cognitive function after LT in cirrhotic patients.

6.
J Hous Built Environ ; : 1-25, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34545277

RESUMO

Given Hong Kong's unique high-density urban environment and limited land resources, more and more general public has been concerned about the living quality. Based on three waves of census data (2006, 2011 and 2016), combined with our spatial-temporal urban environmental database consisting of three local datasets of urban climate and air quality, this paper assesses the impacts of social, economic and environmental factors on the logarithm of housing prices in Hong Kong through linear regression analysis. Specifically, both supply- and demand-side economic factors have significant impacts on housing prices. Demographic factors are not as significant as expected in affecting housing prices. Transportation factors have more significant effects in the short run than in the long run. Environmental factors, including the number of hot night hours, Annual Air Quality Index (AAQI) of nitrogen dioxide (NO2) and particulates with particle sizes less than 10 microns (PM10), significantly affect housing prices over time. The results have important implications: current policy instruments to prevent housing price escalation are focused on increasing property tax or land supply (economic factors), while little attention is paid to social or environmental factors, which are geographically heterogeneous. Our findings suggest that housing provision in the New Territories may be a feasible solution to alleviate the housing crisis as its demographic pattern, transportation connectivity and air quality are significantly different from Hong Kong Island or Kowloon Peninsula. In regard to urban environmental problems brought by the high-density development in Hong Kong despite land-use saving, intensified urban infrastructure and promotion of public transportation, our study contributes to the understanding of its housing price dynamics from a more holistic perspective by comparing the impacts of economic, social and environmental factors.

7.
Transl Stroke Res ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553324

RESUMO

Mammalian cell-produced recombinant human erythropoietin (rhuEPOM) has been shown to be a multimodal neuroprotectant targeting an array of key pathological mechanisms in experimental stroke models. However, the rhuEPOM clinical trials were terminated due to increased risk of thrombosis, largely ascribed to its erythropoietic function. We recently took advantage of a plant-based expression system lacking sialylation capacity to produce asialo-rhuEPOP, a rhuEPO derivative without sialic acid residues. In the present study, we proved that asialo-rhuEPOP is non-erythropoietic by repeated intravenous injection (44 µg/kg bw) in mice showing no increase in hemoglobin levels and red blood cell counts, and confirmed that it is non-immunogenic by measuring humoral response after immunizing the mice. We demonstrate that it is neuroprotective in a cerebral ischemia and reperfusion (I/R) mouse model, exhibiting ~ 50% reduction in cerebral infarct volume and edema, and significant improvement in neurological deficits and histopathological outcome. Our studies further revealed that asialo-rhuEPOP, like rhuEPOM, displays pleiotropic neuroprotective effects, including restoring I/R-interrupted mitochondrial fission and fusion proteins, preventing I/R injury-induced increase in mitophagy and autophagy markers, and inhibiting apoptosis to benefit nerve cell survival. Most importantly, asialo-rhuEPOP lacking erythropoietic activity and immunogenicity holds great translational potential as a multimodal neuroprotectant for stroke treatment.

8.
eNeuro ; 8(4)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34376523

RESUMO

Neurocognitive impairment is present in cirrhosis and may be more severe in cirrhosis with overt hepatic encephalopathy (OHE). Liver transplantation (LT) can restore liver function, but how it reverses the impaired brain function is still unclear. MRI of resting-state functional connectivity can help reveal the underlying mechanisms that lead to these cognitive deficits and cognitive recovery. In this study, 64 patients with cirrhosis (28 with OHE; 36 without OHE) and 32 healthy control subjects were recruited for resting-state fMRI. The patients were scanned before and after LT. We evaluated presurgical and postsurgical neurocognitive performance in cirrhosis patients using psychomotor tests. Network-based statistics found significant disrupted connectivity in both groups of cirrhotic patients, with OHE and without OHE, compared with control subjects. However, the presurgical connectivity disruption in patients with OHE affected a greater number of connections than those without OHE. The decrease in functional connectivity for both OHE and non-OHE patient groups was reversed after LT to the level of control subjects. An additional hyperconnected network (i.e., higher connected than control subjects) was observed in OHE patients after LT. Regarding the neural-behavior relationship, the functional network that predicted cognitive performance in healthy individuals showed no correlation in presurgical cirrhotic patients. The impaired neural-behavior relationship was re-established after LT for non-OHE patients, but not for OHE patients. OHE patients displayed abnormal hyperconnectivity and a persistently impaired neural-behavior relationship after LT. Our results suggest that patients with OHE may undergo a different trajectory of postsurgical neurofunctional recovery compared with those without, which needs further clarification in future studies.


Assuntos
Encefalopatia Hepática , Transplante de Fígado , Encéfalo/diagnóstico por imagem , Cognição , Encefalopatia Hepática/diagnóstico por imagem , Encefalopatia Hepática/etiologia , Humanos , Imageamento por Ressonância Magnética
9.
Asian Pac J Cancer Prev ; 22(8): 2529-2539, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34452568

RESUMO

PURPOSE: To investigate the effect of 20(S)-ginsenoside Rh2 (Rh2) on anti HepG2 liver cancer cells and HepG2 cell-derived xenograft tumors, and explore the underlying mechanisms. MATERIALS AND METHODS: The activity of total HDACs and HAT were assessed with a HDACs colorimetric kit. Expression of HDAC1, HDAC2, HDAC6, p-ERK, ERK, p-P38, P38, p-JNK and JNK proteins was tested by Western blotting.H3K9 and H3K14 proteins were also checked by immunofluorescence, changes in cell cycle distribution with flow cytometry, cell apoptosis with annexin V-FTIC/PI double staining. Activity of Renilla luciferase (HIF) was detected using the Luciferase Reporter Assay system reagent. Gene expression for CyclinD1, Bcl-2, Bax, HIF, IL-1, IL-6, IL-10 and TNF-α was tested by q-PCR. Expression levels of CD31 and Ki-67 was tested by immunohistochemical staining. RESULTS: Total HDAC activity was decreased and total histone acetyltransferase (HAT)activity was increased in a time-dependent manner. Expression of HDAC1 and p-JNK proteins was significantly increased, expression levels of p-ERK was decreased. H3K9 and H3K14 fluorescence protein were increased. Flow cytometric analysis of the cell cycle revealed that the percentage of cells in the G0/G1 phase in the treatment group(64.35±1.36%) was significantly increased compared with the untreated group(61.61±1.23%).The apoptotic rate of the HepG2 group was 10.03±1.92%, which increased to 17.87±1.67% in the treatment group. Expression levels of the transcription factor HIF were also increased in HepG2 cells following induction by Rh2. Expression of CyclinD1 and Bcl-2 at the genetic level was significantly decreased, while expression levels of Bax, HIF, IL-1, IL-6, IL-10 and TNF-α was increased. In vivo, the expression levels of both CD31 and Ki-67 proteins were significantly down-regulated in the treatment group compared with the control group. CONCLUSIONS: The effects of Rh2 were suggested to occur through the inhibition of total HDAC activity, which subsequently induced MAPK signaling and down-regulated the expression of HIF.
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10.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21262188

RESUMO

There is a threat of COVID-19 resurgence in Fall 2021 in Canada. To understand the probability and severity of this threat, quantification of the level of immunity/protection of the population is required. We use an age-structured model including infection, vaccination and waning immunity to estimate the distribution of immunity to COVID-19 in the Canadian population. By late Summer 2021, coinciding with the end of the vaccination program, we estimate that 60 - 80% of the Canadian population will have some immunity to COVID-19. Model results show that this level of immunity is not sufficient to stave off a Fall 2021 resurgence. The timing and severity of a resurgence, however, varies in magnitude given multiple factors: relaxation of non-pharmaceutical interventions such as social distancing, the rate of waning immunity, the transmissibility of variants of concern, and the protective characteristics of the vaccines against infection and severe disease. To prevent large-scale resurgence, booster vaccination and/or re-introduction of public health mitigation may be needed.

11.
J Glob Antimicrob Resist ; 27: 41-45, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34438107

RESUMO

OBJECTIVES: Clostridium perfringens (C. perfringens) can cause intestinal diseases in livestock and humans, which seriously threatens the healthy development of animal husbandry and human food safety. Here, the characteristics of antimicrobial resistance and molecular typing of ruminant-borne strains of C. perfringens in Xinjiang, China were explored and profiled. METHODS: A total of 307 clinical feces collected from ruminants (cattle and sheep) with diarrheal symptoms were screened for C. perfringens. The recovered isolates were characterized in respect to their antimicrobial resistance pattern and molecular typing. RESULTS: A total of 109 isolates of C. perfringens were isolated from 307 clinical feces of ruminants, most of which displayed the multidrug resistance (MDR) phenotype. Demonstration of the quinolone-resistance gene was the highest among the isolates (70.6%). The multiplex PCR typing based on toxin genes showed that type A and type D strains made up 82.6% (90/109) and 17.4% (19/109), among which, the isolates carrying ß2 gene occupied 43.3% (39/90) of type A strains and 31.6% (6/19) of type D strains. These isolates were divided into 6 genotypes (I-VI) by enterobacterial repetitive intergenic consensus sequence-based PCR (ERIC-PCR) method. A total of 33 ST types (ST1-ST33) were identified by multilocus sequence typing (MLST) method. CONCLUSION: C. perfringens isolates with multidrug resistance (MDR) were frequent and circulating in ruminants. Among them, type A-Ⅰ-ST19 was the dominant genotype of C. perfringens, displaying obvious genetic diversity. This study provided important epidemiological data for the risk assessment of food safety associated with ruminant-borne C. perfringens in Xinjiang, China.

12.
Langmuir ; 37(31): 9547-9552, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34333979

RESUMO

Supramolecular chemotherapy has drawn increasing interest due to its ability to improve the efficiency of antitumor drugs and fewer associated toxic side effects. In this study, the smart supramolecular cargo, the doxorubicin-ZnO-cucurbit[7]uril (CDZ) nanocomplex, was constructed through ion-dipole interactions between cucurbit[7]uril {CB[7]} and doxorubicin-ZnO (dox-ZnO). The binding affinity of CB[7] and dox-ZnO was determined to be 104 M-1 by isothermal titration calorimetry. Importantly, spermine had a stronger binding affinity (106 M-1) with CB[7] than dox-ZnO through host-guest interactions. In the tumor microenvironment, spermine disassembled the CDZ nanocomplex, and dox was released from the nanocomplex by XRD, UV-visible spectra, and contact angle analysis. Compared to the single drug dox, the CDZ nanocomplex was demonstrated to possess higher activity of killing colorectal tumor cells by confocal laser scanning microscopy and cytotoxicity, which could be attributed to spermine concentration, spermine synthase, free radical damage, and G1 cell cycle arrest. Overall, the supramolecular delivery of dox can enhance the inhibition of human colorectal tumor cell proliferation and reduce cytotoxicity in human myocardial cells through the noncovalent bond synergy of {CB[7]}.


Assuntos
Hidrocarbonetos Aromáticos com Pontes , Neoplasias Colorretais , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/farmacologia , Humanos , Imidazóis , Microambiente Tumoral
13.
Int J Mol Med ; 48(3)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34296284

RESUMO

Ischemic stroke is a leading cause of mortality and disability. Diabetes mellitus, characterized by hyperglycemia, is a common concomitant disease of ischemic stroke, which is associated with autophagy dysfunction and blood­brain barrier (BBB) damage following cerebral ischemia/reperfusion (I/R) injury. At present, there is no effective treatment strategy for the disease. The purpose of the present study was to explore the molecular mechanisms underlying the protective effects of selenium on the BBB following I/R injury in hyperglycemic rats. Middle cerebral artery occlusion was performed in diabetic Sprague­Dawley rats. Treatment with selenium and the autophagy inhibitor 3­methyladenine significantly reduced cerebral infarct volume, brain water content and Evans blue leakage, while increasing the expression of tight junction (TJ) proteins and decreasing that of autophagy­related proteins (P<0.05). In addition, selenium increased the phosphorylation levels of PI3K, AKT and mTOR (P<0.05). A mouse bEnd.3 brain microvascular endothelial cell line was co­cultured in vitro with an MA­h mouse astrocyte­hippocampal cell line to simulate the BBB. The cells were then subjected to hyperglycemia, followed by oxygen­glucose deprivation for 1 h and reoxygenation for 24 h. It was revealed that selenium increased TJ protein levels, reduced BBB permeability, decreased autophagy levels and enhanced the expression of phosphorylated (p)­AKT/AKT and p­mTOR/mTOR proteins (P<0.05). Treatment with wortmannin (an inhibitor of PI3K) significantly prevented the beneficial effects of selenium on the BBB, whereas insulin­like growth factor 1 (a PI3K activator) mimicked the effects of selenium. In conclusion, the present findings indicated that selenium can inhibit autophagy by regulating the PI3K/AKT/mTOR signaling pathway, significantly preventing BBB damage following cerebral I/R injury in hyperglycemic conditions.

14.
Angew Chem Int Ed Engl ; 60(37): 20535-20542, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34288301

RESUMO

The Co-based electrocatalyst is among the most promising candidates for electrochemical oxidation of 5-hydroxymethylfurfural (HMF). However, the intrinsic active sites and detailed mechanism of this catalyst remains unclear. We combine experimental evidence and a theoretical study to show that electrogenerated Co3+ and Co4+ species act as chemical oxidants but with distinct roles in selective HMF oxidation. It is found that Co3+ is only capable of oxidizing formyl group to produce carboxylate while Co4+ is required for the initial oxidation of hydroxyl group with significantly faster kinetics. As a result, the product distribution shows explicit dependence on the Co oxidation states and selective production of 5-hydroxymethyl-2-furancarboxylic acid (HMFCA) and 2,5-furandicarboxylic acid (FDCA) are achieved by tuning the applied potential. This work offers essential mechanistic insight on Co-catalyzed organic oxidation reactions and might guide the design of more efficient electrocatalysts.

15.
J Clin Pathol ; 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193534

RESUMO

AIMS: Objective to investigate whether D2-40 can be used as a marker of early lung adenocarcinoma and precursor lesions. METHODS: In order to explore the value of D2-40, a monoclonal antibody that recognises the podoplanin, as an auxiliary diagnostic marker to aid the diagnosis of these conditions, we performed the immunohistochemical (IHC) staining using early lung adenocarcinoma, infiltrating adenocarcinoma, benign lung lesions and relevant peritumour normal tissues. The microscopic examination was performed to analyse the D2-40 IHC staining. RESULTS: We found that there was no D2-40 staining in 47 cases of early stage lung adenocarcinoma and precursor lesions; only 1 of the 32 cases (3.13%) of infiltrating adenocarcinoma stained positive. There was 100% D2-40 staining in 30 cases of benign lung lesions and 79 cases of peritumour normal tissues. The positivity rate in carcinoma group was 1.27% and the normal tissue group was 100%, (p<0.01). Based on our findings, we concluded that D2-40 IHC staining in lung adenocarcinoma and precursor lesions compared with normal alveolar epithelia displayed the 'none or all' phenomenon. CONCLUSIONS: The results from our study suggested that D2-40 can be sued as auxiliary diagnostic tool in early lung adenocarcinoma and its precursor lesions.

16.
Plant Genome ; : e20096, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34275212

RESUMO

Characterization of genomic regions underlying adaptation of landraces can reveal a quantitative genetics framework for local wheat (Triticum aestivum L.) adaptability. A collection of 512 wheat landraces from the eastern edge of the Fertile Crescent in Iran and Pakistan were genotyped using genome-wide single nucleotide polymorphism markers generated by genotyping-by-sequencing. The minor allele frequency (MAF) and the heterozygosity (H) of Pakistani wheat landraces (MAF = 0.19, H = 0.008) were slightly higher than the Iranian wheat landraces (MAF = 0.17, H = 0.005), indicating that Pakistani landraces were slightly more genetically diverse. Population structure analysis clearly separated the Pakistani landraces from Iranian landraces, which indicates two separate adaptability trajectories. The large-scale agro-climatic data of seven variables were quite dissimilar between Iran and Pakistan as revealed by the correlation coefficients. Genome-wide association study identified 91 and 58 loci using agroclimatic data, which likely underpin local adaptability of the wheat landraces from Iran and Pakistan, respectively. Selective sweep analysis identified significant hits on chromosomes 4A, 4B, 6B, 7B, 2D, and 6D, which were colocalized with the loci associated with local adaptability and with some known genes related to flowering time and grain size. This study provides insight into the genetic diversity with emphasis on the genetic architecture of loci involved in adaptation to local environments, which has breeding implications.

17.
Acta Radiol ; : 2841851211032441, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34282631

RESUMO

BACKGROUND: Sjögren's syndrome (SjS) associated with systemic lupus erythematosus (SjS-SLE) was considered a standalone but often-overlooked entity. PURPOSE: To assess altered spontaneous brain activity in SjS-SLE and SjS using amplitude of low-frequency fluctuation (ALFF). MATERIAL AND METHODS: Sixteen patients with SjS-SLE, 17 patients with SjS, and 17 matched controls underwent neuropsychological tests and subsequent resting-state functional magnetic resonance imaging (fMRI) examinations. The ALFF value was calculated based on blood oxygen level dependent (BOLD) fMRI. Statistical parametric mapping was utilized to analyze between-group differences and multiple comparison was corrected with Analysis of Functional NeuroImages 3dClustSim. Then, the ALFFs of brain regions with significant differences among the three groups were correlated to corresponding clinical and neuropsychological variables by Pearson correlation. RESULTS: ALFF differences in the bilateral precuneus/posterior cingulate cortex (PCC), right parahippocampal gyrus/caudate/insula, and left insula were found among the three groups. Both SjS-SLE and SjS displayed decreased ALFF in the right parahippocampal gyrus, right insula, and left insula than HC. Moreover, SjS-SLE showed wider decreased ALFF in the bilateral precuneus and right caudate, while the SjS group exhibited increased ALFF in the bilateral PCC. Additionally, patients with SjS-SLE exhibited lower ALFF values in the bilateral PCC and precuneus than SjS. Moreover, ALFF values in the right parahippocampal gyrus and PCC were negatively correlated to fatigue score and disease duration, respectively, in SjS-SLE. CONCLUSION: SjS-SLE and SjS exhibited common and different alteration of cerebral functional segregation revealed by AlFF analysis. This result appeared to indicate that SjS-SLE might be different from SjS with a neuroimaging standpoint.

18.
J Clin Endocrinol Metab ; 106(10): e3852-e3864, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34214160

RESUMO

CONTEXT: Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. OBJECTIVE: This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. METHODS: We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. RESULTS: This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. CONCLUSION: This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34288351

RESUMO

Phosphate-solubilizing microbes (PSMs) drive the biogeochemical cycling of phosphorus (P) and hold promise for sustainable agriculture. However, their global distribution, overall diversity and application potential remain unknown. Here, we present the first synthesis of their biogeography, diversity and utility, employing data from 399 papers published between 1981 and 2017, the results of a nationwide field survey in China consisting of 367 soil samples, and a genetic analysis of 12986 genome-sequenced prokaryotic strains. We show that at continental to global scales, the population density of PSMs in environmental samples is correlated with total P rather than pH. Remarkably, positive relationships exist between the population density of soil PSMs and available P, nitrate-nitrogen and dissolved organic carbon in soil, reflecting functional couplings between PSMs and microbes driving biogeochemical cycles of nitrogen and carbon. More than 2704 strains affiliated with at least nine archaeal, 88 fungal and 336 bacterial species were reported as PSMs. Only 2.59% of these strains have been tested for their efficiencies in improving crop growth or yield under field conditions, providing evidence that PSMs are more likely to exert positive effects on wheat growing in alkaline P-deficient soils. Our systematic genetic analysis reveals five promising PSM genera deserving much more attention.

20.
Chemosphere ; 286(Pt 1): 131550, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34293569

RESUMO

Decabromodiphenyl ethane (DBDPE) is one of the most commonly used novel brominated flame retardants (NBFRs), and its mass production and widespread application have caused health threats to the human being. Existing studies have shown that DBDPE has hepatotoxicity. And we have found that DBDPE could change cytochrome P450 3A (CYP3A) expression levels in rat livers, whereas the mechanism is unclear. In this study, we exposed human normal hepatocyte (L-02) to DBDPE to further study the effect and mechanism of DBDPE on hepatocellular injury and liver metabolic enzyme CYP3A changes in vitro. The results showed that DBDPE caused L-02 cell viability decrease, lactate dehydrogenase (LDH) and transaminase release, ultrastructural damage, and apoptosis. Moreover, DBDPE exposure induced oxidative stress (i.e., increased ROS generation and MDA levels and decreased GSH content, SOD activity, and mitochondrial membrane potential) and endoplasmic reticulum (ER) stress in L-02 cells as evidenced by the elevated PERK and IRE-1α expression levels. These results confirmed that DBDPE is toxic to hepatocytes. Besides, the CYP3A expression level was decreased in DBDPE exposed L-02 cells. However, pretreatment of L-02 cells with antioxidant N-Acetyl-l-cysteine (NAC) and endoplasmic reticulum stress inhibitor 4-PBA inhibited DBDPE-induced oxidative stress, endoplasmic reticulum stress, CYP3A expression decrease, and apoptosis. Therefore, we demonstrated that DBDPE could exert toxic effects and decrease CYP3A expression on L-02 cells by inducing ER stress and oxidative stress.

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