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1.
Carbohydr Polym ; 335: 122078, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38616098

RESUMO

Microbial polysaccharides (MPs) are biopolymers secreted by microorganisms such as bacteria and fungi during their metabolic processes. Compared to polysaccharides derived from plants and animals, MPs have advantages such as wide sources, high production efficiency, and less susceptibility to natural environmental influences. The most attractive feature of MPs lies in their diverse biological activities, such as antioxidative, anti-tumor, antibacterial, and immunomodulatory activities, which have demonstrated immense potential for applications in functional foods, cosmetics, and biomedicine. These bioactivities are precisely regulated by their sophisticated molecular structure. However, the mechanisms underlying this precise regulation are not yet fully understood and continue to evolve. This article presents a comprehensive review of the most representative species of MPs, including their fermentation and purification processes and their biomedical applications in recent years. In particular, this work presents an in-depth analysis into the structure-activity relationships of MPs across multiple molecular levels. Additionally, this review discusses the challenges and prospects of investigating the structure-activity relationships, providing valuable insights into the broad and high-value utilization of MPs.


Assuntos
Antibacterianos , Antioxidantes , Animais , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Transporte Biológico , Fermentação , Alimento Funcional
2.
ACS Omega ; 9(14): 15854-15860, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38617703

RESUMO

The porous skeleton structure of oxidizers can effectively enlarge the contact area with fuels and boost the reactivity of thermites, but the overly complex preparation processes tend to limit their use to some extent. To overcome this issue, water-soluble starch and copper nitrate were used as a template to form a carbon skeleton copper oxide (C-CuO) after spray drying and calcination. By adding nanoaluminum into the spray drying process, the n-Al@C-CuO was prepared and compared with the physically mixed n-Al/C-CuO in the context. Scanning electron microscopy and differential scanning calorimetry were used to observe the morphology and analyze the thermal process. The pressure-time test and the electrostatic sensitivity test were used to measure the energy release properties and the safety of the thermites. Results indicated that the n-Al@C-CuO had 60.97 °C earlier initial exothermic temperature and 1.74 times higher peak pressure than that of the physically mixed sample. The n-Al@C-CuO was not ignited under 25 kV in the electrostatic sensitivity test, showing the great electrostatic safety of the sample. These findings are expected to facilitate the development of spray drying and promote energy release of traditional thermites.

3.
J Neurotrauma ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623777

RESUMO

Cognitive impairment is a common complication following spinal cord injury (SCI) and imposes a significant negative impact on adjustment, functional independence, physical and mental health, and quality of life. It is unclear whether interventions for cognitive impairment following SCI are effective. A systematic review of controlled trials was performed to evaluate the effect of interventions on cognitive functions in adults with SCI using search engines: Embase, The Cochrane Library, MEDLINE, Scopus, CINAHL, and Web of Science up to December 2023. Two reviewers independently screened the articles and study findings were synthesized and summarized. The risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Eight moderate-quality studies were found that investigated the effects of physical exercise/activity-based therapy plus cognitive training or intermittent hypoxia, diet modification and dietary supplements, tibial nerve or cortical stimulation, and drug therapy on cognitive function in SCI. Physical exercise/activity-based therapy plus cognitive training showed most promise for improving cognitive functions while drug therapy, diet modification and dietary supplements showed potential for improving cognitive function. However, about half of the participants experienced heightened instability in blood pressure following the administration of midodrine, and one participant reported gastrointestinal side effects after taking omega-3 fatty acids. There was no evidence of improvement in cognitive function for stimulation techniques. The current review highlights the scarcity of research investigating the effectiveness of interventions that target cognitive function after SCI. Furthermore, the effects of these eight studies are uncertain due to concerns about the quality of designs and small sample sizes utilized in the trials, as well as the employment of insensitive neurocognitive tests when applied to adults with SCI. This review highlights a significant gap in knowledge related to SCI cognitive rehabilitation.

4.
Huan Jing Ke Xue ; 45(5): 2748-2756, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629538

RESUMO

It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are complex, and distinguishing the contribution of different sources has become a key issue. A total of 262 influent samples from 61 representative wastewater treatment plants in a typical city were collected from October 2022 to March 2023. The concentrations of morphine, codeine, thebaine, papaverine, noscapine, and monoacetylmorphine were analyzed in wastewater and poppy straws. Combined with the proportion of alkaloids in poppy straws, the source analysis of alkaloids in wastewater was analyzed using the ratio method and positive matrix factorization model (PMF). Only five alkaloids were detected in wastewater, and monoacetylmorphine, a metabolite of heroin, was not detected. The concentrations of morphine and codeine were significantly higher than those of noscapine, papaverine, and thebaine. By constructing the ratios of codeine/(morphine + codeine) and noscapine/(noscapine + codeine), the source of poppy straw could be qualitatively distinguished. The PMF results showed that three sources of morphine for medical use, poppy straw, and codeine contributed 44.9%, 43.7%, and 9.4%, respectively. The different sources varied in these months due to the COVID-19 and influenza A outbreaks, in which the use of drugs containing poppy straws and codeine was the main source, whereas the use of morphine analgesics remained relatively stable. Inventory analysis further demonstrated the reliability of the source contributions from the PMF model, and morphine was not abused in this city.


Assuntos
Alcaloides , Noscapina , Papaver , Morfina/análise , Águas Residuárias , Papaverina/análise , Tebaína/análise , Noscapina/análise , Reprodutibilidade dos Testes , Codeína/análise , Derivados da Morfina/análise , Alcaloides/análise
5.
Mol Pharm ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630656

RESUMO

Small interfering RNAs (siRNAs) are promising therapeutic strategies, and five siRNA drugs have been approved by the Food and Drug Administration (FDA) and the European Commission (EC). This marks a significant milestone in the development of siRNA for clinical applications. The approved siRNA agents can effectively deliver siRNAs to the liver and treat liver-related diseases. Currently, researchers have developed diverse delivery platforms for transporting siRNAs to different tissues such as the brain, lung, muscle, and others, and a large number of siRNA drugs are undergoing clinical trials. Here, these delivery technologies and the latest advancements in clinical applications are summarized, and this Review provides a concise overview of the strategies employed for siRNA delivery to both hepatic and extrahepatic tissues.

6.
Adv Med Sci ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631609

RESUMO

PURPOSE: Smooth muscle cell (SMC) dysregulation is part of the pathological basis of pulmonary artery hypertension (PAH). We aimed to explore the heterogeneity of SMCs in PAH. METHODS: The profile GSE210248 was obtained from NCBI Gene Expression Omnibus, containing the scRNA-seq data of pulmonary arteries (PA) from three patients with PAH and three healthy donors. After quality control, normalization, and dimension reduction, cell clustering analysis was performed. Differential expression analysis and functional enrichment analysis were carried out successively in smooth muscle cells (SMCs). The enrichment scores of cell cycle and cell migration gene sets in SMCs were calculated. Then, the Spearman correlation coefficients between antisense non-coding RNA in the INK4 locus (ANRIL) expression and two gene sets were computed. RESULTS: Eight cell clusters were identified in PA from samples. The proportion of SMCs was increased in PAH samples. SMCs were divided into five subclusters with diverse biological functions. Muscle contraction-related SMC1 was decreased, while extracellular matrix organization-related SMC2, immune and inflammatory response-related SMC4 and SMC5 were increased in PAH samples compared with healthy donors. The enrichment scores of cell cycle and cell migration gene sets in SMCs were higher in PAH samples than in donors. ANRIL was down-regulated significantly in PAH samples and was negatively related to the scores of two gene sets. CONCLUSION: SMCs exhibited significant heterogeneity in PAH. The altered abilities of SMC proliferation and migration in PAH were associated with ANRIL expression.

7.
Br J Haematol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632670

RESUMO

Splenectomy is an effective treatment for immune thrombocytopenia (ITP). The effect of COVID-19 vaccination on splenectomized patients with ITP during the COVID-19 pandemic has not been reported. Therefore, this study aimed to investigate the effect of COVID-19 vaccination on clinical outcomes in these patients. This was a longitudinal study of splenectomized patients with ITP. A total of 191 splenectomized patients were included in this study. After a median follow-up of 114 months, 146 (76.4%) patients had a sustained response to splenectomy. During COVID-19 infection, vaccinated patients showed a lower risk of severe infections (odds ratio [OR], 0.13; 95% confidence interval [CI]: 0.05-0.36; p < 0.001), hospitalization (OR, 0.13; 95% CI, 0.04-0.48; p = 0.002), and ITP exacerbation (OR, 0.16; 95% CI, 0.04-0.67; p = 0.012). These findings indicate that COVID-19 vaccination plays a protective role in splenectomized patients with ITP.

8.
J Inorg Biochem ; 256: 112552, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38608554

RESUMO

In this work, we report the generation and characterization of two new Co(III)-peroxo complexes 2 and 3. 2 is best described as a mononuclear CoIII-(O2) complex that exhibits an 18O-isotope sensitive OO bond stretching vibration at 845(-49) cm-1, indicating a relatively weak peroxo moiety compared to those of other CoIII-(O2) complexes reported previously. Complex 3 is a CoIII-peroxo-arylboronate species having a rare {CoIIIOOBO} five-membered metallocycle, which is structurally characterized using X-ray crystallography. Investigations of the reaction mechanism using density functional theory calculations show that 2 likely undergoes a nucleophilic attack to an arylboronic acid, which is generated by hydrolysis of the BPh4- anion in wet acetonitrile solution, to first form a CoIII-peroxo-arylboronic acid adduct, followed by the loss of one benzene molecule to generate the five-membered metallocycle. The entire reaction is thermodynamically favorable. Taken together, the conversion of 2 to 3 represents the discovery of a novel nucleophilic reactivity that can be carried out by mononuclear Co(III)-peroxo complexes.

9.
Nat Cancer ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609488

RESUMO

Tumor-specific T cells are crucial in anti-tumor immunity and act as targets for cancer immunotherapies. However, these cells are numerically scarce and functionally exhausted in the tumor microenvironment (TME), leading to inefficacious immunotherapies in most patients with cancer. By contrast, emerging evidence suggested that tumor-irrelevant bystander T (TBYS) cells are abundant and preserve functional memory properties in the TME. To leverage TBYS cells in the TME to eliminate tumor cells, we engineered oncolytic virus (OV) encoding TBYS epitopes (OV-BYTE) to redirect the antigen specificity of tumor cells to pre-existing TBYS cells, leading to effective tumor inhibition in multiple preclinical models. Mechanistically, OV-BYTE induced epitope spreading of tumor antigens to elicit more diverse tumor-specific T cell responses. Remarkably, the OV-BYTE strategy targeting human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory efficiently inhibited tumor progression in a human tumor cell-derived xenograft model, providing important insights into the improvement of cancer immunotherapies in a large population with a history of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination.

10.
Nat Commun ; 15(1): 3164, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605026

RESUMO

Two-dimensional organic-inorganic hybrid halide perovskites possess diverse structural polymorphs with versatile physical properties, which can be controlled by order-disorder transition of the spacer cation, making them attractive for constructing semiconductor homojunctions. Here, we demonstrate a space-cation-dopant-induced phase stabilization approach to creating a lateral homojunction composed of ordered and disordered phases within a two-dimensional perovskite. By doping a small quantity of pentylammonium into (butylammonium)2PbI4 or vice versa, we effectively suppress the ordering transition of the spacer cation and the associated out-of-plane octahedral tilting in the inorganic framework, resulting in phase pining of the disordered phase when decreasing temperature or increasing pressure. This enables epitaxial growth of a two-dimensional perovskite homojunction with tunable optical properties under temperature and pressure stimuli, as well as directional exciton diffusion across the interface. Our results demonstrate a previously unexplored strategy for constructing two-dimensional perovskite heterostructures by thermodynamic tuning and spacer cation doping.

11.
Am J Primatol ; : e23627, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613565

RESUMO

Black-and-white snub-nosed monkeys (Rhinopithecus bieti) rely on behavioral and dietary flexibility to survive in temperate latitudes at high-elevation habitats characterized by climate and resource seasonality. However, little is known about how elevation influences their behavioral and dietary flexibility at monthly or seasonal scales. We studied an isolated R. bieti population at Mt. Lasha in the Yunling Provincial Nature Reserve, Yunnan, China, between May 2008 and August 2016 to assess the impacts of elevation on feeding behavior and diet. Across our sample, R. bieti occupied elevations between 3031 and 3637 m above mean sea level (amsl), with a 315.1 m amsl range across months and a 247.3 m amsl range across seasons. Contrary to expectations, individuals spent less time feeding when ranging across higher elevations. Lichen consumption correlated with elevation use across months and seasons, with individuals spending more time feeding on this important resource at higher elevations. Leaf consumption only correlated with elevation use during the spring. Our results suggest that R. bieti do not maximize their food intake at higher elevations and that monthly and seasonal changes in lichen and leaf consumption largely explain variation in elevation use. These findings shed light on the responses of R. bieti to environmental change and offer insight into strategies for conserving their habitats in the face of anthropogenic disturbance.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38615275

RESUMO

This study aimed to analyze the relationship between human epididymal protein 4 (HE4) and infiltration depth, postoperative recurrence, and metastasis of epithelial ovarian cancer (OVCA). Immunohistochemistry was used to detect the expression level of HE4 in cancer tissues and adjacent tissues of 90 patients with epithelial OVCA admitted to our hospital from May 2017 to January 2018. Cox regression was used to analyze the factors affecting the prognosis of epithelial OVCA. The relationship between HE4 and the prognosis of epithelial OVCA was analyzed by the receiver operating characteristic curve and Kaplan-Meier survival curve. The positive expression rate of HE4 in epithelial OVCA was 85.56%, which was higher than 34.44% in adjacent tissues (p < 0.01). The International Federation of Gynecology and Obstetrics stage, infiltration depth, lymph node metastasis, postoperative recurrence and metastasis, and HE4 positivity were independent risk factors for the prognosis, and platinum-based chemotherapy sensitivity was an independent protective factor for the prognosis of patients with epithelial OVCA (p < 0.05). The area under the curve of HE4 in diagnosing epithelial OVCA and predicting recurrence was 0.863 and 0.700, the sensitivity was 91.60% and 85.60%, and the specificity was 90.20% and 65.60%. The median progression-free survival and overall survival were 26.1 and 30.2 months in HE4-positive epithelial OVCA patients, while these were 31.4 and 35.6 months in HE4-negative epithelial OVCA patients (p < 0.05). In conclusion, HE4 was highly expressed in epithelial OVCA tissues. Its expression level was related to the depth of tumor invasion, postoperative recurrence and metastasis, and other clinicopathological characteristics of patients with epithelial OVCA.

13.
Nutrients ; 16(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38613012

RESUMO

Aging-associated hepatic fatty acid (FA) oxidation dysfunction contributes to impaired adaptive thermogenesis. 5-Heptadecylresorcinol (AR-C17) is a prominent functional component of whole wheat and rye, and has been demonstrated to improve the thermogenic capacity of aged mice via the regulation of Sirt3. However, the effect of AR-C17 on aging-associated hepatic FA oxidation dysfunction remains unclear. Here, 18-month-old C57BL/6J mice were orally administered with AR-C17 at a dose of 150 mg/kg/day for 8 weeks. Systemic glucose and lipid metabolism, hepatic FA oxidation, and the lipolysis of white adipose tissues (WAT) were measured. The results showed that AR-C17 improved the hepatic FA oxidation, and especially acylcarnitine metabolism, of aged mice during cold stimulation, with the enhancement of systemic glucose and lipid metabolism. Meanwhile, AR-C17 improved the WAT lipolysis of aged mice, promoting hepatic acylcarnitine production. Furthermore, the adipose-specific Sirt3 knockout mice were used to investigate and verify the regulation mechanism of AR-C17 on aging-associated hepatic FA oxidation dysfunction. The results showed that AR-C17 failed to improve the WAT lipolysis and hepatic FA oxidation of aged mice in the absence of adipose Sirt3, indicating that AR-C17 might indirectly influence hepatic FA oxidation via regulating WAT Sirt3. Our findings suggest that AR-C17 might improve aging-associated hepatic FA oxidation dysfunction via regulating adipose Sirt3.


Assuntos
Carnitina/análogos & derivados , Resorcinóis , Sirtuína 3 , Animais , Camundongos , Camundongos Endogâmicos C57BL , Obesidade , Metabolismo dos Lipídeos , Envelhecimento , Glucose , Camundongos Knockout , Ácidos Graxos
14.
J Chem Phys ; 160(15)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38619459

RESUMO

Integrating both electrical and light-modulated multi-type neuromorphic functions in a single synaptic memristive device holds the most potential for realizing next-generation neuromorphic systems, but is still challenging yet achievable. Herein, a simple bi-terminal optoelectronic synaptic memristor is newly proposed based on kesterite Cu2ZnSnS4, exhibiting stable nonvolatile resistive switching with excellent spatial uniformity and unique optoelectronic synaptic behaviors. The device demonstrates not only low switching voltage (-0.39 ± 0.08 V), concentrated Set/Reset voltage distribution (<0.08/0.15 V), and long retention time (>104 s) but also continuously modulable conductance by both electric (different width/interval/amplitude) and light (470-808 nm with different intensity) stimulus. These advantages make the device good electrically and optically simulated synaptic functions, including excitatory and inhibitory, paired-pulsed facilitation, short-/long-term plasticity, spike-timing-dependent plasticity, and "memory-forgetting" behavior. Significantly, decimal arithmetic calculation (addition, subtraction, and commutative law) is realized based on the linear conductance regulation, and high precision pattern recognition (>88%) is well achieved with an artificial neural network constructed by 5 × 5 × 4 memristor array. Predictably, such kesterite-based optoelectronic memristors can greatly open the possibility of realizing multi-functional neuromorphic systems.

16.
Int Immunopharmacol ; 133: 111955, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626544

RESUMO

Renal tubular injury is an important pathological change associated with diabetic nephropathy (DN), in which ferroptosis of renal tubular epithelial cells is critical to its pathogenesis. Inhibition of the glutathione/glutathione peroxidase 4 (GSH/GPX4) axis is the most important mechanism in DN tubular epithelial cell ferroptosis, but the underlying reason for this is unclear. Our biogenic analysis showed that a zinc-dependent metalloproteinase, dipeptidase 1 (DPEP1), is associated with DN ferroptosis. Here, we investigated the role and mechanism of DPEP1 in DN tubular epithelial cell ferroptosis. DPEP1 upregulation was observed in the renal tubular epithelial cells of DN patients and model mice, as well as in HK-2 cells stimulated with high glucose. Furthermore, the level of DPEP1 upregulation was associated with the degree of tubular injury in DN patients and HK-2 cell ferroptosis. Mechanistically, knocking down DPEP1 expression could alleviate the inhibition of GSH/GPX4 axis and reduce HK-2 cell ferroptosis levels in a high glucose environment. HK-2 cells with stable DPEP1 overexpression also showed GSH/GPX4 axis inhibition and ferroptosis, but blocking the GSH/GPX4 axis could mitigate these effects. Additionally, treatment with cilastatin, a DPEP1 inhibitor, could ameliorate GSH/GPX4 axis inhibition and relieve ferroptosis and DN progression in DN mice. These results revealed that DPEP1 can promote ferroptosis in DN renal tubular epithelial cells via inhibition of the GSH/GPX4 axis.

17.
Med Biol Eng Comput ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38627356

RESUMO

Accurate and efficient motion estimation is a crucial component of real-time ultrasound elastography (USE). However, obtaining radiofrequency ultrasound (RF) data in clinical practice can be challenging. In contrast, although B-mode (BM) data is readily available, elastographic data derived from BM data results in sub-optimal elastographic images. Furthermore, existing conventional ultrasound devices (e.g., portable devices) cannot provide elastography modes, which has become a significant obstacle to the widespread use of traditional ultrasound devices. To address the challenges above, we developed a teacher-student guided knowledge distillation for an unsupervised convolutional neural network (TSGUPWC-Net) to improve the accuracy of BM motion estimation by employing a well-established convolutional neural network (CNN) named modified pyramid warping and cost volume network (MPWC-Net). A pre-trained teacher model based on RF is utilized to guide the training of a student model using BM data. Innovations outlined below include employing spatial attention transfer at intermediate layers to enhance the guidance effect of the model. The loss function consists of smoothness of the displacement field, knowledge distillation loss, and intermediate layer loss. We evaluated our method on simulated data, phantoms, and in vivo ultrasound data. The results indicate that our method has higher signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values in axial strain estimation than the model trained on BM. The model is unsupervised and requires no ground truth labels during training, making it highly promising for motion estimation applications.

18.
Huan Jing Ke Xue ; 45(5): 2757-2766, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629539

RESUMO

Hutuo River Basin straddles Shanxi and Hebei provinces, and Hutuo River was once cut off due to economic development and urban expansion after 2000; however, with the national emphasis on ecological civilization and the implementation of the South-North Water Diversion Project, the ecological protection of Hutuo River Basin has been significantly improved. MODIS data, Landsat data, and night light remote sensing data were selected based on the google earth engine (GEE) platform, and a new evaluation index system was generated by combining the biological richness index, vegetation cover index, land stress index, and pollution load index in the ecological environment index (EI) and the humidity index in the remote sensing ecological index (RSEI), using the variation coefficient method and entropy weighting method to assign weights to these indices. An ecological environment evaluation model was constructed to evaluate and classify the ecological environment quality of Hutuo River Basin from 2000 to 2020, and the driving factors were interpreted by using geographic probes. The results showed that:① on a time scale, the ecological environment of Hutuo River Basin was in a decline period from 2000 to 2015 and a recovery period from 2015 to 2020. From a grid scale, the ecological environment quality in the central part of the basin showed a state of improvement year by year, and in the western and eastern parts of the basin, the ecological environment quality in the decline period decreased year by year, whereas the ecological environment quality in the recovery period improved. ② Hot spot analysis showed that the spatial distribution of the ecological environment quality in Hutuo River Basin was high in the middle and low on both sides. Cold spot regions were mainly located in major cities and towns in the eastern and southern parts and scattered in the river valley area on the west side. ③ Geodetection analysis showed that the single factor detection drivers were mainly population density, vegetation net primary productivity (NPP), fractional vegetation cover (FVC), and geomorphological type. The dominant factor of cross-detection was "geomorphological type + FVC." With the deepening of ecological civilization construction and the implementation of Hutuo River Protection Regulations, in combination with different factors such as the natural environment and social characteristics in this basin, the research on ecological environment evaluation in Hutuo River Basin can provide data support for proposing localized policies to improve the ecological environment.

19.
J Asian Nat Prod Res ; : 1-12, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629733

RESUMO

Bicyclol is a hepatoprotective agent widely used for treating chronic hepatitis and drug-induced liver injuries in clinics. The purpose of the study was to elucidate the contribution of CYP450 enzymes to the metabolism of bicyclol using the relative activity factor approach. After incubation with human liver microsomes and recombinant human liver CYP450 enzymes, the calculated contribution of CYP3A4 and 2C19 to the metabolism of bicyclol was 85.6-90.3% and 9.2-9.7%, respectively. The metabolism was interrupted in the presence of CYP3A4 and 2C19 selective inhibitors. These findings help to predict or avoid metabolic drug-drug interactions or toxicity in clinical applications of bicyclol.

20.
Wei Sheng Yan Jiu ; 53(2): 229-236, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38604958

RESUMO

OBJECTIVE: To investigate the association of polymorphisms in SEC16B rs633715, DNAJC27 rs713586, FTO rs11642015 and MC4R rs6567160 with overweight and obesity in Han Chinese preschool children. METHODS: A total of 749 Han Chinese preschool children from Henan and Guizhou Province of Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack were selected for the study and divided into an overweight and obese group and a normal control group in 2022. rs633715, rs713586, rs11642015 and rs6567160 were genotyped using Kompetitive allele-specific PCR(KASP) technology. The distribution of genotypic polymorphisms was compared using the χ~2 test. The association between the four loci and overweight and obesity in preschool children was analyzed using a multifactorial logistic regression model. RESULTS: The statistical analysis revealed a significant disparity(P<0.05) in the distribution of genotypic polymorphisms of rs633715 and rs6567160 among preschoolers in Henan and Guizhou Province. CC heterozygous mutant and recessive models at rs633715 locus were associated with susceptibility to overweight and obesity in preschool children [OR and 95% CI 2.915(1.163-7.305), and 2.997(1.226-7.323), respectively, both P<0.05]. TC heterozygous mutant and dominant models at rs713586 locus were also associated susceptibility to overweight and obesity in preschool children(OR and 95% CI were 2.362(1.054-5.289)and 2.362(1.054-5.289), respectively, both P<0.05). rs11642015 and rs6567160 loci were not associated with susceptibility to overweight and obesity in preschool children(P>0.05). The result of the analysis of the cumulative effect of rs633715 and rs713586 showed that the number of genotypes carrying the risk genotype was positively associated with the risk of overweight and obesity in preschool children(P_(trend)<0.01). CONCLUSION: Among Han Chinese preschool children, SEC16B rs633715 and DNAJC27 rs713586 were associated with susceptibility to overweight and obesity in preschool children. Moreover, rs633715 and rs713586 had a cumulative effect on susceptibility to overweight and obesity in preschool children, the number of risk genotypes carried was positively associated with childhood overweight and obesity risk.


Assuntos
Sobrepeso , Obesidade Pediátrica , Lactente , Humanos , Pré-Escolar , Criança , Sobrepeso/genética , Polimorfismo de Nucleotídeo Único , Obesidade Pediátrica/genética , Genótipo , Alelos , Predisposição Genética para Doença , Índice de Massa Corporal , Receptor Tipo 4 de Melanocortina/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética
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