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1.
BMJ Open ; 14(5): e079631, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719291

RESUMO

PURPOSE: The Adverse Childhood Experiences (ACE) cohort of the Malawi Longitudinal Study of Families and Health (MLSFH-ACE) is a study of adolescents surveyed during 2017-2021. It provides an important opportunity to examine the longitudinal impact of ACEs on health and development across the early life course. The MLSFH-ACE cohort provides rich data on adolescents, their children and adult caregivers in a low-income, high-HIV-prevalence context in sub-Saharan Africa (SSA). PARTICIPANTS: The MLSFH-ACE cohort is a population-based study of adolescents living in three districts in rural Malawi. Wave 1 enrolment took place in 2017-2018 and included 2061 adolescents aged 10-16 years and 1438 caregivers. Wave 2 took place in 2021 and included data on 1878 adolescents and 208 offspring. Survey instruments captured ACEs during childhood and adolescence, HIV-related behavioural risk, mental and physical health, cognitive development and education, intimate partner violence (IPV), marriage and aspirations, early transitions to adulthood and protective factors. Biological indicators included HIV, herpes simplex virus and anthropometric measurements. FINDINGS TO DATE: Key findings include a high prevalence of ACEs among adolescents in Malawi, a low incidence of HIV and positive associations between ACE scores and composite HIV risk scores. There were also strong associations between ACEs and both IPV victimisation and perpetration. FUTURE PLANS: MLSFH-ACE data will be publicly released and will provide a wealth of information on ACEs and adolescent outcomes in low-income, HIV-endemic SSA contexts. Future expansions of the cohort are planned to capture data during early adulthood.


Assuntos
Experiências Adversas da Infância , Infecções por HIV , Humanos , Malaui/epidemiologia , Adolescente , Estudos Longitudinais , Experiências Adversas da Infância/estatística & dados numéricos , Masculino , Feminino , Criança , Infecções por HIV/epidemiologia , Adulto , Cuidadores/estatística & dados numéricos , Prevalência , População Rural/estatística & dados numéricos , Violência por Parceiro Íntimo/estatística & dados numéricos , Pobreza , Nível de Saúde
2.
Acta Pharmacol Sin ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491161

RESUMO

Inflammatory bowel disease (IBD) is characterized by persistent damage to the intestinal barrier and excessive inflammation, leading to increased intestinal permeability. Current treatments of IBD primarily address inflammation, neglecting epithelial repair. Our previous study has reported the therapeutic potential of notoginsenoside R1 (NGR1), a characteristic saponin from the root of Panax notoginseng, in alleviating acute colitis by reducing mucosal inflammation. In this study we investigated the reparative effects of NGR1 on mucosal barrier damage after the acute injury stage of DSS exposure. DSS-induced colitis mice were orally treated with NGR1 (25, 50, 125 mg·kg-1·d-1) for 10 days. Body weight and rectal bleeding were daily monitored throughout the experiment, then mice were euthanized, and the colon was collected for analysis. We showed that NGR1 administration dose-dependently ameliorated mucosal inflammation and enhanced epithelial repair evidenced by increased tight junction proteins, mucus production and reduced permeability in colitis mice. We then performed transcriptomic analysis on rectal tissue using RNA-sequencing, and found NGR1 administration stimulated the proliferation of intestinal crypt cells and facilitated the repair of epithelial injury; NGR1 upregulated ISC marker Lgr5, the genes for differentiation of intestinal stem cells (ISCs), as well as BrdU incorporation in crypts of colitis mice. In NCM460 human intestinal epithelial cells in vitro, treatment with NGR1 (100 µM) promoted wound healing and reduced cell apoptosis. NGR1 (100 µM) also increased Lgr5+ cells and budding rates in a 3D intestinal organoid model. We demonstrated that NGR1 promoted ISC proliferation and differentiation through activation of the Wnt signaling pathway. Co-treatment with Wnt inhibitor ICG-001 partially counteracted the effects of NGR1 on crypt Lgr5+ ISCs, organoid budding rates, and overall mice colitis improvement. These results suggest that NGR1 alleviates DSS-induced colitis in mice by promoting the regeneration of Lgr5+ stem cells and intestinal reconstruction, at least partially via activation of the Wnt/ß-Catenin signaling pathway. Schematic diagram of the mechanism of NGR1 in alleviating colitis. DSS caused widespread mucosal inflammation epithelial injury. This was manifested by the decreased expression of tight junction proteins, reduced mucus production in goblet cells, and increased intestinal permeability in colitis mice. Additionally, Lgr5+ ISCs were in obviously deficiency in colitis mice, with aberrant down-regulation of the Wnt/ß-Catenin signaling. However, NGR1 amplified the expression of the ISC marker Lgr5, elevated the expression of genes associated with ISC differentiation, enhanced the incorporation of BrdU in the crypt and promoted epithelial restoration to alleviate DSS-induced colitis in mice, at least partially, by activating the Wnt/ß-Catenin signaling pathway.

3.
JCI Insight ; 9(5)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319716

RESUMO

Pattern recognition receptor responses are profoundly attenuated before the third trimester of gestation in the relatively low-oxygen human fetal environment. However, the mechanisms regulating these responses are uncharacterized. Herein, genome-wide transcription and functional metabolic experiments in primary neonatal monocytes linked the negative mTOR regulator DDIT4L to metabolic stress, cellular bioenergetics, and innate immune activity. Using genetically engineered monocytic U937 cells, we confirmed that DDIT4L overexpression altered mitochondrial dynamics, suppressing their activity, and blunted LPS-induced cytokine responses. We also showed that monocyte mitochondrial function is more restrictive in earlier gestation, resembling the phenotype of DDIT4L-overexpressing U937 cells. Gene expression analyses in neonatal granulocytes and lung macrophages in preterm infants confirmed upregulation of the DDIT4L gene in the early postnatal period and also suggested a potential protective role against inflammation-associated chronic neonatal lung disease. Taken together, these data show that DDIT4L regulates mitochondrial activity and provide what we believe to be the first direct evidence for its potential role supressing innate immune activity in myeloid cells during development.


Assuntos
Citocinas , Recém-Nascido Prematuro , Recém-Nascido , Humanos , Citocinas/metabolismo , Monócitos/metabolismo , Imunidade Inata , Mitocôndrias/metabolismo
5.
China Pharmacy ; (12): 38-43, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005211

RESUMO

OBJECTIVE To study the effects of the Mongolian medicine Sugemule-4 on the metabolism of insomnia rats, and to preliminarily explore its possible mechanisms for improving insomnia. METHODS The rat model of chronic stress insomnia was established by tail clipping stimulation and intraperitoneal injection of p-chlorophenyl alanine solution. Twenty-four male rats were randomly divided into the normal group, model group, diazepam group (positive control, 0.92 mg/kg), and Sugemule-4 group (5.2 g/kg), with 6 rats in each group. Since the 7th day of tail clipping stimulation, the Sugemule-4 group and diazepam group began to be intragastrically administered with relevant medicine; the normal group and model group were intragastrically administered with an equal volume of distilled water, once a day, for 14 consecutive days. The learning and memory abilities of rats were tested using a water maze experiment, and the non-invasive sleep activity monitoring system was used to monitor the 24- hour sleep time of rats. A metabolomics study was conducted on rat serum and hippocampal tissue by using ultra-high-performance liquid chromatography-tandem mass spectrometry. The multivariate statistical analysis method was adopted to analyze the differential metabolites in serum and hippocampal tissue of rats, and screen for differential metabolites and metabolic pathways among those groups. RESULTS Compared with the normal group, the escape latency of rats in the model group was significantly increased, the times of crossing platforms were significantly reduced, and the percentage of average 24-hour sleep time was significantly reduced (P<0.05). Compared with the model group, the levels of the above indicators were significantly reversed in the diazepam group and Sugemule-4 group (P<0.05). Metabolomics studies found that a total of 9 differential metabolites were identified in rat serum and hippocampal tissue, including 5-hydroxyindoleacetic acid, canine urate, canine urinary quinolinic acid, 5-hydroxytryptamine, phenol sulfate, 1-carboxyethyltyrosine, 3-(4-hydroxyphenyl) lactate, N-acetyl tyrosine, tyrosine and phenol sulfate, mainly involving 2 metabolic pathways of tryptophan and tyrosine.CONCLUSIONS Sugemule-4 can improve the sleep time and behavioral performance of insomnia rats, and its mechanism may be associated with affecting amino acid metabolic pathways such as tryptophan and tyrosine.

6.
Journal of Clinical Hepatology ; (12): 621-625, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013148

RESUMO

Pharmacotherapy is the primary treatment method for hyperthyroidism. Antithyroid drugs can induce liver injury, and the diagnosis of drug-induced liver injury is mostly exclusive based on medical history collection, clinical symptoms, serum biochemistry, radiological examination, and histology. According to the severity of liver injury, drug-induced liver injury can be classified into mild, moderate, severe, and fatal degrees. Drug withdrawal may not be necessary for patients with mild liver injury, but regular monitoring of liver function is required; in severe cases, patients may develop liver failure, which may lead to a mortality rate, and early identification, timely drug withdrawal, and reasonable pharmacotherapy can help to avoid fatal consequences. The treatment principles of liver injury induced by antithyroid drugs include promoting the recovery of liver injury, preventing the severe exacerbation and chronicity of liver injury, and reducing the risk of death. Standardized medication, timely monitoring, early identification, and early treatment are important measures for the prevention and treatment of liver injury induced by antithyroid drugs.

7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012303

RESUMO

Objective: To investigate the clinical characteristics, treatments and fertility recovery of rudimentary horn pregnancy (RHP). Methods: The clinical data of 12 cases with RHP diagnosed and treated in Peking University Third Hospital from January 1, 2010 to December 31, 2022 were retrospectively analyzed. Clinical informations, diagnosis and treatments of RHP and the pregnancy status after surgery were analyzed. Results: The median age of 12 RHP patients was 29 years (range: 24-37 years). Eight cases of pregnancy in residual horn of uterus occurred in type Ⅰ residual horn of uterus, 4 cases occurred in type Ⅱ residual horn of uterus; among which 5 cases were misdiagnosed by ultrasound before surgery. All patients underwent excision of residual horn of uterus and affected salpingectomy. After surgery, 9 patients expected future pregnancy, and 3 cases of natural pregnancy, 2 cases of successful pregnancy through assisted reproductive technology. Four pregnancies resulted in live birth with cesarean section, and 1 case resulted in spontaneous abortion during the first trimester of pregnancy. No uterine rupture or ectopic pregnancy occurred in subsequent pregnancies. Conclusions: Ultrasonography could aid early diagnosis of RHP while misdiagnosis occurred in certain cases. Thus, a comprehensive judgment and decision ought to be made based on medical history, physical examination and assisted examination. Surgical exploration is necessary for diagnosis and treatment of RHP. For infertile patients, assisted reproductive technology should be applied when necessary. Caution to prevent the occurrence of pregnancy complications such as uterine rupture, and application of cesarean section to terminate pregnancy are recommended.


Assuntos
Gravidez , Humanos , Feminino , Adulto Jovem , Adulto , Cesárea/efeitos adversos , Estudos Retrospectivos , Gravidez Ectópica/cirurgia , Gravidez Cornual/cirurgia , Útero/cirurgia , Ruptura Uterina/etiologia , Aborto Espontâneo
8.
Acta Pharmaceutica Sinica B ; (6): 392-404, 2024.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1011240

RESUMO

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

10.
J Gen Intern Med ; 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38100008

RESUMO

BACKGROUND: For over 50 years, the United States (US) used affirmative action as one strategy to increase diversity in higher education including medical programs, citing benefits including training future public and private sector leaders. However, the recent US Supreme Court ending affirmative action in college admissions threatens advancements in the diversity of medical college faculty. OBJECTIVE: Our study evaluated the demographic trends in Internal Medicine (IM) faculty in the US by assessing sex and race/ethnicity diversity to investigate who is likely to be impacted most with the end of affirmative action. DESIGN: Longitudinal retrospective analysis SUBJECTS: IM faculty from the Association of American Medical Colleges faculty roster from 1966 to 2021 who self-reported sex and ethnicity MAIN OUTCOMES: The primary study measurement was the annual proportion of women and racial/ethnic groups among IM faculty based on academic rank and department chairs. RESULTS: Although racial/ethnic diversity increased throughout the era of affirmative action, African American, Hispanic, and American Indian populations remain underrepresented. White physicians occupied > 50% of faculty positions across academic ranks and department chairs. Among the non-White professors, Asian faculty had the most significant increase in proportion from 1966 to 2021 (0.6 to 16.6%). The percentage of women increased in the ranks of professor, associate professor, assistant professor, and instructor by 19.5%, 27.8%, 25.6%, and 26.9%, respectively. However, the proportion of women and racial/ethnic minority faculty decreased as academic rank increased. CONCLUSION: Despite an increase in the representation of women and racial/ethnic minority IM faculty, there continues to be a predominance of White and men physicians in higher academic ranks. With the end of affirmative action, this trend has the danger of being perpetuated, resulting in decreasing diversity among IM faculty, potentially impacting patient access and health outcomes.

11.
Front Microbiol ; 14: 1287802, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149271

RESUMO

Due to its traditional fermentation, there are obvious limits on the quality improvements in black tea. However, microbial fermentation can provide an abundance of metabolites and improve the flavor of tea. The "golden flower" fungi are widely used in the microbial fermentation of tea and has unique uses in healthcare. To further explore the improvements in black tea quality achieved via microbial fermentation, we used widely targeted metabolomics and metagenomics analyses to investigate the changes in and effects of metabolites and other microorganisms during the interaction between the "golden flower" fungi and black tea. Five key flavor metabolites were detected, the levels of catechin, epigallocatechin gallate, (-)-epicatechin gallate were decreased by different degrees after the inoculation of the "golden flower" fungus, whereas the levels of caffeine and (+)-gallocatechin increased. Botryosphaeriaceae, Botryosphaeriales, Dothideomycetes, Aspergillaceae, Trichocomaceae, and Lecanoromycetes play a positive role in the black tea fermentation process after inoculation with the "golden flower" fungi. D-Ribose can prevent hypoxia-induced apoptosis in cardiac cells, and it shows a strong correlation with Botryosphaeriaceae and Botryosphaeriales. The interaction between microorganisms and metabolites is manifested in tryptophan metabolism, starch and sucrose metabolism, and amino sugar and nucleotide sugar metabolism. In conclusion, the changes in metabolites observed during the fermentation of black tea by "golden flower" fungi are beneficial to human health. This conclusion extends the knowledge of the interaction between the "golden flower" fungi and black tea, and it provides important information for improving the quality of black tea.

12.
Sci Rep ; 13(1): 20077, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973984

RESUMO

Hospital emergency departments frequently receive lots of bone fracture cases, with pediatric wrist trauma fracture accounting for the majority of them. Before pediatric surgeons perform surgery, they need to ask patients how the fracture occurred and analyze the fracture situation by interpreting X-ray images. The interpretation of X-ray images often requires a combination of techniques from radiologists and surgeons, which requires time-consuming specialized training. With the rise of deep learning in the field of computer vision, network models applying for fracture detection has become an important research topic. In this paper, we use data augmentation to improve the model performance of YOLOv8 algorithm (the latest version of You Only Look Once) on a pediatric wrist trauma X-ray dataset (GRAZPEDWRI-DX), which is a public dataset. The experimental results show that our model has reached the state-of-the-art (SOTA) mean average precision (mAP 50). Specifically, mAP 50 of our model is 0.638, which is significantly higher than the 0.634 and 0.636 of the improved YOLOv7 and original YOLOv8 models. To enable surgeons to use our model for fracture detection on pediatric wrist trauma X-ray images, we have designed the application "Fracture Detection Using YOLOv8 App" to assist surgeons in diagnosing fractures, reducing the probability of error analysis, and providing more useful information for surgery.


Assuntos
Fraturas Ósseas , Traumatismos do Punho , Humanos , Criança , Punho , Raios X , Fraturas Ósseas/diagnóstico por imagem , Algoritmos
13.
Fa Yi Xue Za Zhi ; 39(5): 465-470, 2023 Oct 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38006266

RESUMO

OBJECTIVES: To explore the feasibility of genetic marker detection of semen-specific coding region single nucleotide polymorphism (cSNP) based on SNaPshot technology in semen stains and mixed body fluid identification. METHODS: Genomic DNA (gDNA) and total RNA were extracted from 16 semen stains and 11 mixtures composed of semen and venous blood, and the total RNA was reverse transcribed into complementary DNA (cDNA). The cSNP genetic markers were screened on the validated semen-specific mRNA coding genes. The cSNP multiplex detection system based on SNaPshot technology was established, and samples were genotyped by capillary electrophoresis (CE). RESULTS: A multiplex detection system containing 5 semen-specific cSNPs was successfully established. In 16 semen samples, except the cSNP located in the TGM4 gene showed allele loss in cDNA detection results, the gDNA and cDNA typing results of other cSNPs were highly consistent. When detecting semen-venous blood mixtures, the results of cSNP typing detected were consistent with the genotype of semen donor and were not interfered by the genotype of venous blood donor. CONCLUSIONS: The method of semen-specific cSNPs detection by SNaPshot technology method can be applied to the genotyping of semen (stains) and provide information for determining the origin of semen in mixed body fluids (stains).


Assuntos
Líquidos Corporais , Sêmen , Marcadores Genéticos , Polimorfismo de Nucleotídeo Único , DNA Complementar/genética , RNA Mensageiro/genética , DNA , Saliva , Genética Forense/métodos
14.
ACS Nano ; 17(23): 24141-24153, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37979190

RESUMO

Seeded heteroepitaxial growth is a "living" crystallization-driven self-assembly (CDSA) method that has emerged as a promising route to create uniform segmented nanoparticles with diverse core chemistries by using chemically distinct core-forming polymers. Our previous results have demonstrated that crystallization kinetics is a key factor that determines the occurrence of heteroepitaxial growth, but an in-depth understanding of controlling heteroepitaxy from the perspective of crystallization thermodynamics is yet unknown. Herein, we select crystallizable aliphatic polycarbonates (PxCs) with a different number of methylene groups (xCH2, x = 4, 6, 7, 12) in their repeating units as model polymers to explore the effect of lattice match and core compatibility on the seeded growth behavior. Seeded growth of PxCs-containing homopolymer/block copolymer blend unimers from poly(ε-caprolactone) (PCL) core-forming seed platelet micelles exhibits distinct crystal growth behavior at subambient temperatures, which is governed by the lattice match and core compatibility. A case of seeded growth with better core compatibility and a smaller lattice mismatch follows epitaxial growth, where the newly created crystal domain has the same structural orientation as the original platelet substrate. In contrast, a case of seeded growth with better core compatibility but a larger lattice mismatch shows nonepitaxial growth with less-defined crystal orientations in the platelet plane. Additionally, a case of seeded growth with poor core compatibility and larger lattice mismatch results in polydisperse platelet micelles, whereby crystal formation is not nucleated from the crystalline substrate. These findings reveal important factors that govern the specific crystal growth during a seeded growth approach by using compositionally distinct cores, which would further guide researchers in designing 2D segmented materials via polymer crystallization approaches.

15.
Lancet Reg Health Am ; 25: 100582, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37705884

RESUMO

Background: The COVID-19 pandemic has perturbed the seasonality of respiratory syncytial virus (RSV) infections. However, we lack data on how this impacted the severity of paediatric RSV cases. The objective of this study was to describe the clinical severity of RSV cases before, during and after pandemic measures in British Columbia (BC), Canada. Methods: Retrospective study of RSV cases from September 1st, 2017 to May 15th, 2023, with a review of RSV outcomes in children below 18 years old at BC's paediatric hospital. Temporal changes in RSV cases and hospitalisations were quantified using interrupted time series. Findings: BC experienced only 11 RSV cases (from 95,266 tests) between September 2020 and August 2021. This was followed by a resurgence of 9,529 RSV cases (219,566 tests [4.3% positive tests]) in 2021-22 and 8,215 cases (124,449 tests [6.6% positive tests]) in 2022-23, increased compared to 1,750 cases (48,664 tests [3.6% positive tests]) per corresponding yearly period in 2017-20. From September 2017 to May 2023, the median age of children with RSV at BC Children's Hospital increased from 8.7 [IQR: 2.0-26.0] to 19.6 [3.9-43.7] months per yearly period. More children were hospitalised in 2022-23 (n = 360), compared to 2017-20 (n = 168 per period) and 2021-22 (n = 172). However, we detected no increase in hospitalisations or ICU admissions in children born prematurely or with chronic cardiorespiratory conditions. Interpretation: The increased detection of symptomatic RSV cases in older children in 2021-22 and increased RSV-related hospitalisations in 2022-23 suggest a gradual increase in the pool of immunologically vulnerable children due to a prolonged lack of viral exposure. Funding: Government of Canada via its COVID-19 Immunity Task Force.

16.
Interdiscip Sci ; 15(4): 602-615, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37525066

RESUMO

Classification of glomerular pathology based on histology sections is the key to diagnose the type and degree of kidney diseases. To address problems in the classification of glomerular lesions in children, a deep learning-based complete glomerular classification framework was designed to detect and classify glomerular pathology. A neural network integrating Resnet and Senet (RS-INet) was proposed and a glomerular classification algorithm implemented to achieve high-precision classification of glomerular pathology. SE-Resnet was applied with improvement by transforming the convolutional layer of the original Resnet residual block into a convolutional block with smaller parameters as well as reduced network parameters on the premise of ensuring network performance. Experimental results showed that our algorithm had the best performance in differentiating mesangial proliferative glomerulonephritis (MsPGN), crescent glomerulonephritis (CGN), and glomerulosclerosis (GS) from normal glomerulus (Normal) compared with other classification algorithms. The accuracy rates were 0.960, 0.940, 0.937, and 0.968, respectively. This suggests that the classification algorithm proposed in the present study is able to identify glomerular lesions with a higher precision, and distinguish similar glomerular pathologies from each other.

17.
Zhongguo Zhong Yao Za Zhi ; 48(8): 2212-2221, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37282909

RESUMO

This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.


Assuntos
Neoplasias Colorretais , Humanos , Irinotecano , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Resveratrol , Simulação de Acoplamento Molecular , Receptores ErbB/genética
18.
Phys Chem Chem Phys ; 25(20): 14257-14265, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37171203

RESUMO

An advanced optical terahertz (THz) fingerprint sensor based on coherent perfect absorption (CPA) is proposed. Based on a one-dimensional layered photonic structure, the sensor contains a cavity that is developed for THz fingerprint measurement. Utilizing the magneto-optical effect of magnetized InSb, CPA is excited in the structure of the sensor. Taking α-lactose as exemplar material, this numerical simulation is integrated with a Drude-Lorentz model. The transfer matrix method (TMM) is used to calculate the sensitivity (S), linear range (LR), quality (Q), the figure of merit (FOM*), and detection limit (DL) theoretically. Employing the amplitude modulation detection method, the qualitative and quantitative analysis of the α-lactose thickness of 0-0.5 µm could be realized. Because of the fragility of CPA, the S is 0.78255 µm-1, the value of average Q is up to 8019.2, the value of average FOM* is 13 234.4 (THz µm)-1, and the lower DL is 4.21 × 10-6. Moreover, the evolutions of ensemble-averaged absorption in the vicinity of the absorption peaks for different types of disorder effects are considered, which will be considered in the fabrication of sensors.

19.
Opt Lett ; 48(10): 2627-2630, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37186725

RESUMO

To date there have been many studies on multi-channel absorbers for conventional photonic crystals (PCs). However, the number of absorption channels is small and uncontrollable, which cannot satisfy applications such as multispectral or quantitative narrowband selective filters. To address these issues, a tunable and controllable multi-channel time-comb absorber (TCA) based on continuous photonic time crystals (PTCs), is theoretically proposed. Compared with conventional PCs with fixed refractive index (RI), this system forms a stronger local electric field enhancement in the TCA by absorbing externally modulated energy, resulting in sharp multi-channel absorption peaks (APs). Tunability can be achieved by adjusting the RI, angle, and time period unit (T) of the PTCs. Diversified tunable methods allow the TCA to have more potential applications. In addition, changing T can adjust the number of multi-channels. More importantly, changing the primary term coefficient of n1(t) of PTC1 can control the number of time-comb absorption peaks (TCAPs) in multi-channels within a certain range, and the mathematical relationship between the coefficients and the number of multiple channels is summarized. This will have potential applications in the design of quantitative narrowband selective filters, thermal radiation detectors, optical detection instruments, etc.

20.
Nutrients ; 15(4)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36839287

RESUMO

Parkinson's disease (PD) is a prevalent type of neurodegenerative disease. There is mounting evidence that the gut microbiota is involved in the pathogenesis of PD. Sodium butyrate (NaB) can regulate gut microbiota and improve brain functioning in neurological disorders. Hence, we examined whether the neuroprotective function of NaB on PD was mediated by the modulation of gut microbial dysbiosis and revealed its possible mechanisms. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to construct the PD model. NaB gavage was given 2 h after the daily MPTP injections for 21 days. NaB improved the motor functioning of PD mice, increased striatal neurotransmitter levels, and reduced the death of dopaminergic neurons. The 16S rRNA sequencing analysis revealed that NaB restored the gut microbial dysbiosis. NaB also attenuated the intestinal barrier's disruption and reduced serum, colon, and striatal pro-inflammatory cytokines, along with inhibiting the overactivation of glial cells, suggesting an inhibitory effect on inflammation from NaB throughout the gut-brain axis of the PD mice. Mechanistic studies revealed that NaB treatment suppressed the TLR4/MyD88/NF-kB pathway in the colon and striatum. In summary, NaB had a neuroprotective impact on the PD mice, likely linked to its regulation of gut microbiota to inhibit gut-brain axis inflammation.


Assuntos
Microbioma Gastrointestinal , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Doença de Parkinson , Animais , Camundongos , Doença de Parkinson/metabolismo , Ácido Butírico/farmacologia , Microbioma Gastrointestinal/fisiologia , Fármacos Neuroprotetores/farmacologia , Receptor 4 Toll-Like , Disbiose/metabolismo , RNA Ribossômico 16S/genética , Inflamação , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
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