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2.
Nat Prod Res ; : 1-8, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722769

RESUMO

Viburnum luzonicum Rolfe is widely used in China as folk medicine. The bioactivity evaluation indicated that the n-BuOH fraction of V. luzonicum leaves (VLLB) could significantly inhibit α­amylase and α-glucosidase. In order to clarify its active constituents, the phytochemical analysis on VLLB was first performed using HPLC-QTOF-MS/MS, and three new phenolic compounds, viburosides A-C (1-3), along with seven known analogues (4-10) were isolated through preparative HPLC. The undescribed compounds were determined by extensive spectroscopic analyses (1H and 13C NMR, HSQC, HMBC, HRESIMS, and ORD) and enzymatic hydrolysis. In the in vitro enzyme assays, compounds 1-8 showed potent α­amylase and α-glucosidase inhibitory activities. The enzymatic kinetics and molecular docking of the strongest inhibitors 2 and 3 against the corresponding target enzyme were also performed.

3.
J Nat Prod ; 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36729068

RESUMO

Territrem F (1), a drimane meroterpenoid bearing a unique borate ring system, was isolated together with its diol precursor territrem B (2) from the fungus Alternaria sp. ZH-15 associated with the soft coral Lobophytum crassum collected in the South China Sea. The structure of the new compound was elucidated by spectroscopic analysis and an X-ray single-crystal diffraction study, representing a new type of boron-containing natural product. Both compounds significantly inhibited spontaneous synchronous Ca2+ oscillations (SCOs) and epileptic discharges induced by 4-aminopyridine, showing the potential for antiepileptic drug research. The 5,9-boronic ester derivative of 2 did not change its SCO inhibitory activity.

4.
Curr Med Chem ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650655

RESUMO

According to the 2017 ILAE's official definition, epilepsy is a slow brain disease state characterized by recurrent episodes. Due to information released by ILAE in 2017, it can be divided into four types, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and unknown epilepsy. Since 1989, 24 new antiepileptic drugs have been approved to treat different types of epilepsy. Besides, there are a variety of antiepileptic medications under clinical monitoring. These novel antiepileptic drugs have plenty of advantages. Over the past 33 years, there have been many antiepileptic drugs on the mearket, but no one has been found that can completely cure epilepsy. In this paper, the mentioned drugs were classified according to their targets, and the essential information, and clinical studies of each drug were described. The structure-activity relationship of different chemical structures was summarized. This paper provides help for the follow-up research on epilepsy drugs.

5.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36674676

RESUMO

Excess Manganese (Mn) is toxic to plants and reduces crop production. Although physiological and molecular pathways may drive plant responses to Mn toxicity, few studies have evaluated Mn tolerance capacity in roots and leaves. As a result, the processes behind Mn tolerance in various plant tissue or organ are unclear. The reactivity of peanut (Arachis hypogaea) to Mn toxicity stress was examined in this study. Mn oxidation spots developed on peanut leaves, and the root growth was inhibited under Mn toxicity stress. The physiological results revealed that under Mn toxicity stress, the activities of antioxidases and the content of proline in roots and leaves were greatly elevated, whereas the content of soluble protein decreased. In addition, manganese and iron ion content in roots and leaves increased significantly, but magnesium ion content decreased drastically. The differentially expressed genes (DEGs) in peanut roots and leaves in response to Mn toxicity were subsequently identified using genome-wide transcriptome analysis. Transcriptomic profiling results showed that 731 and 4589 DEGs were discovered individually in roots and leaves, respectively. Furthermore, only 310 DEGs were frequently adjusted and controlled in peanut roots and leaves, indicating peanut roots and leaves exhibited various toxicity responses to Mn. The results of qRT-PCR suggested that the gene expression of many DEGs in roots and leaves was inconsistent, indicating a more complex regulation of DEGs. Therefore, different regulatory mechanisms are present in peanut roots and leaves in response to Mn toxicity stress. The findings of this study can serve as a starting point for further research into the molecular mechanism of important functional genes in peanut roots and leaves that regulate peanut tolerance to Mn poisoning.


Assuntos
Fabaceae , Transcriptoma , Arachis/genética , Arachis/metabolismo , Manganês/toxicidade , Manganês/metabolismo , Regulação da Expressão Gênica de Plantas , Fabaceae/genética , Perfilação da Expressão Gênica , Folhas de Planta/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Estresse Fisiológico/genética
6.
Phytomedicine ; 109: 154617, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610140

RESUMO

BACKGROUND: Searching the targets of natural products is very important for drug discovery and elucidating the mechanism of drug action and disease. Honokiol (HK), as the major active component of Magnolia officinalis Rehder & E.H.Wilson, has been widely used in medicine and cosmetics. Among its bioactivities, its anti-inflammatory activity is particularly impressive. However, the target protein of HK in anti-inflammatory action and its regulatory mechanism are unclear. PURPOSE: Here, we identified the target protein and molecular mechanism of the anti- inflammatory action of HK. METHODS: First, an LPS-induced septic shock model and DSS-induced ulcerative colitis model were used to assess the anti-inflammatory efficacy of HK. Second, the drug affinity responsive target stability, proteomics analysis, thermal shift assays and cellular thermal shift assays were used to identify and validate the target of HK. Finally, western blot, ELISA, LDH immunofluorescence staining, shRNA and LC/MS for L-leucine analysis were performed to determine the mechanism of the anti-inflammatory action of HK. RESULTS: This study revealed that HK significantly alleviated LPS-induced septic shock and DSS-induced ulcerative colitis in vivo, suggesting that HK has significant anti-inflammatory activity. HK treatment dramatically reduced IL-1ß release and caspase-1 activation at different time points, showing that HK could inhibit both NLRP3 inflammasome priming and activation processes in cells. HK also suppressed adaptor apoptosis speck-like protein oligomerization. Mechanistically, SLC3A2 was identified as a direct target of HK in THP-1 cells. HK downregulated SLC3A2 expression by promoting its degradation via proteasome-mediated proteolysis. Further study demonstrated that HK triggered SLC3A2 to suppress NLRP3 inflammasome activation by significantly reducing the content of L-leucine transported into cells and lysosomes to block the mTORC1 pathway. CONCLUSIONS: Our work identified HK as a promising anti-inflammatory drug candidate through the SLC3A2/L-leucine/mTORC1/NLRP3 pathways.


Assuntos
Colite Ulcerativa , Choque Séptico , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Lipopolissacarídeos , Leucina , Anti-Inflamatórios/farmacologia
7.
Heliyon ; 9(2): e13090, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36713626

RESUMO

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, an increased mental burden has been widely reported among medical health workers such as physicians and nurses. However, data on laboratory technicians exposed to COVID-19 have rarely been published. The aim of this study was to assess the magnitude of psychological symptoms among laboratory technicians and analyze potential risk factors associated with these symptoms. Methods: A cross-sectional online survey was performed via the Wenjuanxing platform (a professional online questionnaire platform) (https://www.wjx.cn/mobile/statnew.aspx) to investigate the mental health of laboratory technicians during the COVID-19 pandemic in Hebei, China from October 4, 2021, to November 3, 2021. The online questionnaire included demographic and occupational characteristics data of responders, and the Symptom Check List-90-Revised (SCL90-R)was used to quantify the magnitude of psychological symptoms among laboratory technicians. Participants' demographic and occupational characteristics were analyzed using descriptive statistical analyses. Chi-square tests were applied to compare the severity of each symptom between two or more groups. A binary logistic regression model was developed to identify the predictors of laboratory technicians' mental health in response to the COVID-19 pandemic, and outcomes are presented as odds ratios and 95% confidence interval. Statistical analysis was performed using SPSS version 21 (SPSS, New Orchard Road, Armonk, New York, USA). Results: A total of 3081 valid questionnaires were collected. Of these 3081 participants, 338 (11.0%) reported a total SCL90-R score >160, which indicated positive psychological symptoms. Among the 338 participants who reported psychological problems, most of them were mild symptoms. Several factors associated with mental health problems in laboratory technicians during COVID-19 were found, which include a history of physical and/or psychological problems (all 10 symptoms p < 0.001), more than 10 years of work experience (depression symptoms: OR = 2.350, p = 0.024; anxiety symptoms: OR = 2.642, p = 0.038), frontline work (depression symptoms: OR = 1.761, p = 0.001; anxiety symptoms: OR = 2.619, p < 0.001; hostility symptoms: OR = 1.913, p = 0.001), participant in more than 3 times large-scale SARS-CoV-2 screenings and more than 36 h per week in SARS-CoV-2 nucleic acid testing. Conclusion: A portion of laboratory technicians reported experiencing varying levels of psychological burden. During the COVID-19 pandemic, multiple interventions should be developed and implemented to address existing psychosocial challenges and promote the mental health of laboratory technicians.

8.
Biosens Bioelectron ; 225: 115098, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36701949

RESUMO

In this work, PtPd nanoparticles functionalized porphyrin metal-organic framework nanoenzymes (PtPd@PCN-224 nanoenzymes) are exploited as signal amplification tags to fabricate a rapid and ultrasensitive sensitive CRISPR/Cas14a-based electrochemical biosensor for Burkholderia pseudomallei (B. pseudomallei) specific DNA sequences detection. The prepared PtPd@PCN-224 nanoenzymes not only catalyze the reduction peak current of H2O2 to obtain a strong electrochemical signal output, but also provide massive active sites for the assembly of nucleic acids by Zr-O-P bonds. Besides, the designed target-activated CRISPR/Cas14a is able to recognize the target DNA sequences and further trigger the trans-cleavage of ssDNA for signal amplification. Benefiting from the target-activated CRISPR/Cas14a and PtPd@PCN-224 nanoenzymes, the developed electrochemical biosensor for B. pseudomallei DNA detection exhibits high sensitivity with detection of limit down to 12.8 aM and excellent specificity for distinguishing non-targeted bacteria. Moreover, the CRISPR/Cas14a-based electrochemical detection platform can also apply for other pathogenic bacteria diagnostic by well-designing sgRNA for target sequence recognition, possessing high flexibility and versatility in clinical diagnosis.

9.
Fitoterapia ; 165: 105428, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36632918

RESUMO

Seven previously undescribed meroterpenoids, peniscmeroterpenoids H - N (1-7), were isolated from the marine-derived fungus Penicillium sclerotiorum GZU-XW03-2. Their structures were established by the spectroscopic methods and the electronic circular dichroism (ECD) calculations. Peniscmeroterpenoid H was a 6/6/6/5/6 rearranged pentacyclic meroterpenoid, featuring a unique 2-oxaspiro[5.5] undeca-4,7-dien-3-one motif. Peniscmeroterpenoids I and J (2 and 3) owned rare 6(D)/5(E) fused rings were not common in natural products, and compound 2 was the second example of a berkeleyone analogue stripped of the methyl ester fragment. Peniscmeroterpenoid K (4) was the first case where the C-24 was oxidized. In bioassay, compound 5 showed moderate anti-inflammatory activity.

10.
Cell Biosci ; 13(1): 4, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624495

RESUMO

BACKGROUND: Neural stem cells (NSCs) are considered as candidates for cell replacement therapy in many neurological disorders. However, the propensity for their differentiation to proceed more glial rather than neuronal phenotypes in pathological conditions limits positive outcomes of reparative transplantation. Exogenous physical stimulation to favor the neuronal differentiation of NSCs without extra chemical side effect could alleviate the problem, providing a safe and highly efficient cell therapy to accelerate neurological recovery following neuronal injuries. RESULTS: With 7-day physiological electric field (EF) stimulation at 100 mV/mm, we recorded the boosted neuronal differentiation of NSCs, comparing to the non-EF treated cells with 2.3-fold higher MAP2 positive cell ratio, 1.6-fold longer neuronal process and 2.4-fold higher cells ratio with neuronal spontaneous action potential. While with the classical medium induction, the neuronal spontaneous potential may only achieve after 21-day induction. Deficiency of either PI3Kγ or ß-catenin abolished the above improvement, demonstrating the requirement of the PI3K/Akt/GSK-3ß/ß-catenin cascade activation in the physiological EF stimulation boosted neuronal differentiation of NSCs. When transplanted into the spinal cord injury (SCI) modelled mice, these EF pre-stimulated NSCs were recorded to develop twofold higher proportion of neurons, comparing to the non-EF treated NSCs. Along with the boosted neuronal differentiation following transplantation, we also recorded the improved neurogenesis in the impacted spinal cord and the significantly benefitted hind limp motor function repair of the SCI mice. CONCLUSIONS: In conclusion, we demonstrated physiological EF stimulation as an efficient method to boost the neuronal differentiation of NSCs via the PI3K/Akt/GSK-3ß/ß-catenin activation. Pre-treatment with the EF stimulation induction before NSCs transplantation would notably improve the therapeutic outcome for neurogenesis and neurofunction recovery of SCI.

11.
Anal Chim Acta ; 1239: 340721, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628771

RESUMO

Viscosity and sulfur dioxide levels are important factors to evaluate the changes of cell micro-environment because a series of diseases usually occur when they are abnormal. At present, dual-response probes that can detect both viscosity and sulfur dioxide are rare. Therefore, we developed a novel fluorescent probe CBN for simultaneous detection of sulfur dioxide and viscosity. Besides, probe CBN could target lysosome of which normal function will be disrupted by the abnormality of viscosity. Therefore, probe CBN has the potential to be served as an effective biological tool to monitor the intracellular micro-environment.


Assuntos
Corantes Fluorescentes , Dióxido de Enxofre , Humanos , Viscosidade , Lisossomos , Células HeLa
12.
Theranostics ; 13(1): 77-94, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593968

RESUMO

Rationale: microRNAs (miRNAs) are frequently deregulated and play important roles in the pathogenesis and progression of acute myeloid leukemia (AML). miR-182 functions as an onco-miRNA or tumor suppressor miRNA in the context of different cancers. However, whether miR-182 affects the self-renewal of leukemia stem cells (LSCs) and normal hematopoietic stem progenitor cells (HSPCs) is unknown. Methods: Bisulfite sequencing was used to analyze the methylation status at pri-miR-182 promoter. Lineage-negative HSPCs were isolated from miR-182 knockout (182KO) and wild-type (182WT) mice to construct MLL-AF9-transformed AML model. The effects of miR-182 depletion on the overall survival and function of LSC were analyzed in this mouse model in vivo. Results: miR-182-5p (miR-182) expression was lower in AML blasts than normal controls (NCs) with hypermethylation observed at putative pri-miR-182 promoter in AML blasts but unmethylation in NCs. Overexpression of miR-182 inhibited proliferation, reduced colony formation, and induced apoptosis in leukemic cells. In addition, depletion of miR-182 accelerated the development and shortened the overall survival (OS) in MLL-AF9-transformed murine AML through increasing LSC frequency and self-renewal ability. Consistently, overexpression of miR-182 attenuated AML development and extended the OS in the murine AML model. Most importantly, miR-182 was likely dispensable for normal hematopoiesis. Mechanistically, we identified BCL2 and HOXA9 as two key targets of miR-182 in this context. Most importantly, AML patients with miR-182 unmethylation had high expression of miR-182 followed by low protein expression of BCL2 and resistance to BCL2 inhibitor venetoclax (Ven) in vitro. Conclusions: Our results suggest that miR-182 is a potential therapeutic target for AML patients through attenuating the self-renewal of LSC but not HSPC. miR-182 promoter methylation could determine the sensitivity of Ven treatment and provide a potential biomarker for it.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , MicroRNAs , Animais , Camundongos , Linhagem Celular Tumoral , DNA , Regulação Leucêmica da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
13.
Opt Express ; 31(1): 21-30, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36606946

RESUMO

In this study, a curvature fiber sensor based on an enhanced core diameter mismatch is experimentally proposed and theoretically investigated. The structure is fabricated by splicing two types of step multimode and coreless fibers to excite the high-order cladding modes to improve the curvature sensitivity. Experimental results show that the highest curvature sensitivities of the structure reach -114.74 nm/m-1 in the Dip 1272 nm, -91.08 nm/m-1 in Dip 1408 nm, and -61.10 nm/m-1 in Dip 1644 nm in the measuring range of 0-0.49778 m-1. Meanwhile, the sensor's temperature and strain responses were also tested, which shows little influence on the curvature measurement. Additionally, the proposed fiber sensor exhibits features of easy fabrication, simple structure, and high mechanical strength. This study proposes a device for curvature measurement with potential use in material mechanics and optical fiber sensor design.

14.
Zhongguo Gu Shang ; 36(1): 5-11, 2023 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-36652999

RESUMO

OBJECTIVE: To compare the clinical efficacy of full endoscopic lamina fenestration discectomy (Endo-LOVE) with full endoscopic transforaminal approach discectomy in the treatment of degenerative lumbar lateral recess stenosis. METHODS: A retrospective analysis of 48 patients with degenerative lumbar lateral recess stenosis between March 2018 and March 2019 was performed. There were 32 males and 16 females, aged from 60 to 83 years old with an average of (72.9±6.5) years, course of disease ranged from 5 to 16 years with an average of (8.0±2.8) years. The patients were divided into observation group and control group according to surgical approaches. There were 28 cases in observation group, underwent Endo-LOVE surgery;and 20 cases in control group, underwent full endoscopic foraminal approach discectomy. The operation time, intraoperative blood loss, hospitalization day and complications were observed between two groups. Visual analgue scale (VAS), Japanese Orthopaedic Association(JOA), Oswestry Disability Index(ODI), lateral crypt angle were compared between two groups. And clinical effects were evaluated by modified Macnab standard. RESULTS: There was no significant difference in follow-up and operation time between two groups (P>0.05). Intraoperative blood loss was from 5 to 15 ml with an average of (8.4±3.6) ml in observation group and 5 to 25 ml with an average of (11.5±5.4) ml in control group. The hospitalization day was from 5 to 8 days with an average of (6.0±1.0) days in observation group and 6 to 9 days with an average (7.2±1.1) days in control group. Intraoperative blood loss and hospitalization day were significantly lower in observation group(P<0.05). There were no serious complications in both groups. The VAS, JOA scores, and ODI at 3-month and final follow-up were significantly improved in both groups (P<0.05), and observation group was significantly better than control group (P<0.05). The skeletal lateral crypt angle and soft lateral crypt angle were significantly greater than the preoperative angle at 3 days postoperatively(P<0.05), and observation group was significantly better than control group(P<0.05). At the final follow-up, the modified Macnab criteria was used to assess clinical efficacy, in observation group, 22 patients obtained excellent results, 5 good and 1 fair;while 11 excellent, 4 good and 5 fair in control group;the clinical efficacy of observation group was significantly better than that of control group(P<0.05). CONCLUSION: Both surgical methods are performed under direct vision, with high safety and good clinical efficacy. However, Endo-LOVE enlarged the lateral crypt more fully.


Assuntos
Discotomia Percutânea , Deslocamento do Disco Intervertebral , Estenose Espinal , Masculino , Feminino , Humanos , Pré-Escolar , Criança , Adolescente , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Constrição Patológica/cirurgia , Vértebras Lombares/cirurgia , Endoscopia/métodos , Discotomia/métodos , Resultado do Tratamento , Estenose Espinal/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Discotomia Percutânea/métodos
15.
Heliyon ; 9(1): e12826, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36685457

RESUMO

Emerging and existing viruses from various human and animal samples have been studied and analyzed using viral metagenomics, which has proven to be an effective technique. Foxes, as a kind of significant economic animal, are widely raised in China. Viruses carried by foxes may potentially infect humans or other animals. There are currently very few studies of faecal virome in farmed foxes. Using viral metagenomics, we evaluated the faecal virome of twenty-four foxes collected from the same farm in Jilin Province, China. Some sequences more closely related to the families Parvoviridae, Picornaviridae, Smacoviridae, Anelloviridae, and Herpesviridae were detected in the faecal sample. The main animal viruses that infect farmed red foxes were parvovirus and picornavirus. Five smacovirus strains were found and provided evidence for genetic diversity in the genus Smacoviridae. In addition, some viruses infecting avian species or rats were detected in this study. The study helped us better understand faecal virome in farmed red foxes and assisted in the surveillance and prevention of viral diseases in these animals.

16.
Sci Rep ; 13(1): 1051, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658272

RESUMO

Positron imaging technology has shown good practical value in industrial non-destructive testing, but the noise and artifacts generated during the imaging process of flow field images will directly affect the accuracy of industrial fault diagnosis. Therefore, how to obtain high-quality reconstructed images of the positron flow field is a challenging problem. In the existing image denoising methods, the denoising performance of positron images of industrial flow fields in special fields still needs to be strengthened. Considering the characteristics of few sample data and strong regularity of positron flow field image,in this work, we propose a new method for image denoising of positron flow field, which is based on a generative adversarial network with zero-shot learning. This method realizes image denoising under the condition of small sample data, and constrains image generation by constructing the extraction model of image internal features. The experimental results show that the proposed method can reduce the noise while retaining the key information of the image. It has also achieved good performance in the practical application of industrial flow field positron imaging.

17.
Am J Transplant ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36695693

RESUMO

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.

18.
J Immunol ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36695776

RESUMO

The chicken MHC is known to confer decisive resistance or susceptibility to various economically important pathogens, including the iconic oncogenic herpesvirus that causes Marek's disease (MD). Only one classical class I gene, BF2, is expressed at a high level in chickens, so it was relatively easy to discern a hierarchy from well-expressed thermostable fastidious specialist alleles to promiscuous generalist alleles that are less stable and expressed less on the cell surface. The class I molecule BF2*1901 is better expressed and more thermostable than the closely related BF2*1501, but the peptide motif was not simpler as expected. In this study, we confirm for newly developed chicken lines that the chicken MHC haplotype B15 confers resistance to MD compared with B19. Using gas phase sequencing and immunopeptidomics, we find that BF2*1901 binds a greater variety of amino acids in some anchor positions than does BF2*1501. However, by x-ray crystallography, we find that the peptide-binding groove of BF2*1901 is narrower and shallower. Although the self-peptides that bound to BF2*1901 may appear more various than those of BF2*1501, the structures show that the wider and deeper peptide-binding groove of BF2*1501 allows stronger binding and thus more peptides overall, correlating with the expected hierarchies for expression level, thermostability, and MD resistance. Our study provides a reasonable explanation for greater promiscuity for BF2*1501 compared with BF2*1901, corresponding to the difference in resistance to MD.

19.
J Agric Food Chem ; 71(3): 1713-1726, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36634352

RESUMO

The widespread use of titanium dioxide nanoparticles (TiO2 NPs) in the food industry has brought about human safety risks related to nanotoxicity. In this study, food-related TiO2 NPs (anatase, 40 nm) were given to rats by oral gavage for 90 days at doses of 10, 100, and 1000 mg/kg bw. An additional two satellite groups underwent the same protocol for 45 days and for 90 days followed by a 28 day recovery. TiO2 NPs tended to agglomerate together in H2O, AGJ, and AIJ. No systemic toxicity was observed after 90 day agglomerated TiO2 NP exposure with no Ti distribution in major tissues/organs. Furthermore, TiO2 NP consumption for 90 days had no impact on microbiota diversity; the community structure of the gut microbiota is shifted to some extent at the genus level. Collectively, the NOAEL of agglomerated TiO2 NPs for 90 days of oral administration was 1000 mg/kg bw, the highest dose tested in male and female rats.


Assuntos
Microbioma Gastrointestinal , Nanopartículas Metálicas , Nanopartículas , Humanos , Ratos , Masculino , Feminino , Animais , Titânio/toxicidade , Titânio/química , Distribuição Tecidual , Nanopartículas/toxicidade , Administração Oral , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química
20.
BMC Cardiovasc Disord ; 23(1): 42, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690952

RESUMO

BACKGROUND: A subset of patients with hypertrophic cardiomyopathy (HCM) will experience adverse clinical events such as heart failure (HF), cardiovascular death, and new-onset atrial fibrillation (AF). Current risk stratification methods are imperfect and limit the identification of patients at high risk for HCM. This study aimed to evaluate the role of cardiac magnetic resonance (CMR)-derived left atrial strain parameters in the occurrence of adverse clinical events in patients with HCM. METHODS: Left atrial (LA) structural, functional, and strain parameters were evaluated in 99 patients with HCM and compared with 89 age-, sex-, and BMI-matched control subjects. LA strain parameters were derived from CMR two- and four-chamber cine images by a semiautomatic method. LA strain parameters include global longitudinal strain (GLS) and global circumferential strain (GCS). The LA GLS includes reservoir strain (GLS reservoir), conduit strain (GLS conduit), and booster strain (GLS booster). Three LA GLS strain rate (SR) parameters were derived: SR reservoir, SR conduit, and SR booster. The primary endpoint was set as a composite of adverse clinical events, including SCD, new-onset or worsening to hospitalized HF, new-onset AF, thromboembolic events, and fatal ventricular arrhythmias. RESULTS: LA GLS, GLS SR and GCS were impaired in HCM patients compared to control subjects (all p < 0.001). After a mean follow-up of 37.94 ± 23.69 months, 18 HCM patients reached the primary endpoint. LA GLS, GLS SR, and GCS were significantly lower in HCM patients with adverse clinical events than in those without adverse clinical events (all p < 0.05). In stepwise multiple Cox regression analysis, LV SV, LA diameter, pre-contraction LAV (LAV pre-ac), passive LA ejection fraction (EF), and LA GLS booster were all independent determinants of adverse clinical events. LA GLS booster ≤ 8.9% was the strongest determinant (HR = 8.9 [95%CI (1.951, 40.933)], p = 0.005). Finally, LA GLS booster provided predictive adverse clinical events value (AUC = 0.86 [95%CI 0.77-0.98]) that exceeded traditional outcome predictors. CONCLUSION: LA strain assessment, a measure of LA function, provides additional predictive information for established predictors of HCM patients. LA GLS booster was independently associated with adverse clinical events in patients with HCM.


Assuntos
Fibrilação Atrial , Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Humanos , Átrios do Coração , Volume Sistólico , Imagem Cinética por Ressonância Magnética , Função Ventricular Esquerda
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