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1.
Food Chem X ; 23: 101541, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38974197

RESUMO

The utilization of byproducts from foxtail millet polishing can reduce food loss and waste. Thus, it is necessary to know the chemical compounds from the millet and the segregation of the layers. The nutrients including minerals were compared among the husk, bran, and millet, and a LC-MS metabolomics analysis was also performed among them. The results showed that the protein, crude fat and 4 fatty acids, seven minerals, the nitrogen-containing compounds and phenolic acids were at much higher levels in the bran part than the husk and millet, whereas the husk only contained higher levels of dietary fibre, and some minerals. The millet section, as the edible part, contained the lowest level of chemical constituents. It illustrated that the bran part contained more functional and nutritional components than the millet and husk part. Therefore, the bran of the foxtail millet should be a food resources instead of wasting.

2.
Cells ; 13(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38994965

RESUMO

High-density lipoprotein (HDL) is a group of small, dense, and protein-rich lipoproteins that play a role in cholesterol metabolism and various cellular processes. Decreased levels of HDL and HDL dysfunction are commonly observed in individuals with type 2 diabetes mellitus (T2DM), which is also associated with an increased risk for cardiovascular disease (CVD). Due to hyperglycemia, oxidative stress, and inflammation that develop in T2DM, HDL undergoes several post-translational modifications such as glycation, oxidation, and carbamylation, as well as other alterations in its lipid and protein composition. It is increasingly recognized that the generation of HDL modifications in T2DM seems to be the main cause of HDL dysfunction and may in turn influence the development and progression of T2DM and its related cardiovascular complications. This review provides a general introduction to HDL structure and function and summarizes the main modifications of HDL that occur in T2DM. Furthermore, the potential impact of HDL modifications on the pathogenesis of T2DM and CVD, based on the altered interactions between modified HDL and various cell types that are involved in glucose homeostasis and atherosclerotic plaque generation, will be discussed. In addition, some perspectives for future research regarding the T2DM-related HDL modifications are addressed.


Assuntos
Diabetes Mellitus Tipo 2 , Lipoproteínas HDL , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Humanos , Lipoproteínas HDL/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Processamento de Proteína Pós-Traducional
3.
Antiviral Res ; 229: 105954, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964615

RESUMO

Selecting appropriate adjuvants is crucial for developing an effective vaccine. However, studies on the immune responses triggered by different adjuvants in COVID-19 inactivated vaccines are scarce. Herein, we evaluated the efficacy of Alum, CpG HP021, Alum combined with CpG HP021 (Alum/CpG), or MF-59 adjuvants with COVID-19 inactivated vaccines in K18-hACE2 mice, and compared the different immune responses between K18-hACE2 and BALB/c mice. In K18-hACE2 mice, the Alum/CpG group produced a 6.5-fold increase in anti-receptor-binding domain (RBD) IgG antibody titers compared to the Alum group, and generated a comparable level of antibodies even when the antigen amount was reduced by two-thirds, possibly due to the significant activation of germinal center (GC) structures in the central region of the spleen. Different adjuvants induced a variety of binding antibody isotypes. CpG HP021 and Alum/CpG were biased towards Th1/IgG2c, while Alum and MF-59 were biased toward Th2/IgG1. Cytokines IFN-γ, IL-2, and TNF-α were significantly increased in the culture supernatants of splenocytes specifically stimulated in the Alum/CpG group. The antibody responses in BALB/c mice were similar to those in K18-hACE2 mice, but with lower levels of neutralizing antibodies (NAbs). Notably, the Alum/CpG-adjuvanted inactivated vaccine induced a higher number of T cells secreting IFN-γ and IL-2, increased the percentage of effector memory T (TEM) cells among CD8+ T cells, and effectively protected K18-hACE2 mice from Delta variant challenge. Our results showed that Alum/CpG complex adjuvant significantly enhanced the immune response to inactivated COVID-19 antigens and could induce a long-lasting immune response.

4.
Eur Radiol ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38987398

RESUMO

OBJECTIVES: To investigate the effect of motion-compensated reconstruction (MCR) algorithm on improving the image quality of coronary computed tomography angiography (CCTA) using second-generation dual-layer spectral detector computed tomography (DLCT), and to evaluate the influence of heart rate (HR) on the motion-correction efficacy of this algorithm. MATERIALS AND METHODS: We retrospectively enrolled 127 patients who underwent CCTA for suspected coronary artery disease using second-generation DLCT. We divided the patients into two subgroups according to their average HR during scanning: the "HR < 75 bpm" group and the "HR ≥ 75 bpm" group. All images were reconstructed by the standard (STD) algorithm and MCR algorithm. Subjective image quality (4-point Likert scale), interpretability, and objective image quality between the STD and MCR in the whole population and within each subgroup were compared. RESULTS: MCR showed significantly higher Likert scores and interpretability than STD on the per-segment (3.58 ± 0.69 vs. 2.82 ± 0.93, 98.4% vs. 91.9%), per-vessel (3.12 ± 0.81 vs. 2.12 ± 0.74, 96.3% vs. 78.7%) and per-patient (2.57 ± 0.76 vs. 1.62 ± 0.55, 90.6% vs. 59.1%) levels (all p < 0.001). In the analysis of HR subgroups on a per-vessel basis of interpretability, significant differences were observed only in the right coronary artery in the low HR group, whereas significant differences were noted in three major coronary arteries in the high HR group. For objective image quality assessment, MCR significantly improved the SNR (13.22 ± 4.06 vs. 12.72 ± 4.06) and the contrast-to-noise ratio (15.84 ± 4.82 vs. 15.39 ± 4.38) compared to STD (both p < 0.001). CONCLUSION: MCR significantly improves the subjective image quality, interpretability, and objective image quality of CCTA, especially in patients with higher HRs. CLINICAL RELEVANCE STATEMENT: The motion-compensated reconstruction algorithm of the second-generation dual-layer spectral detector computed tomography is helpful in improving the image quality of coronary computed tomography angiography in clinical practice, especially in patients with higher heart rates. KEY POINTS: Motion artifacts from cardiac movement affect the quality and interpretability of coronary computed tomography angiography (CCTA). This motion-compensated reconstruction (MCR) algorithm significantly improves the image quality of CCTA in clinical practice. Image quality improvement by using MCR was more significant in the high heart rate group.

5.
BMC Cardiovasc Disord ; 24(1): 307, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886700

RESUMO

BACKGROUND: Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome, affecting over 80% of individuals with this condition. This syndrome is characterized by a triad of myxomas, skin pigmentation, and endocrine hyperfunction, featuring multiple endocrine neoplasms with skin and cardiac involvement. Dilated cardiomyopathy, a primary cardiomyopathy, is defined as the dilation and impaired systolic function of the left or both ventricles. Its clinical presentation varies from being asymptomatic to heart failure or sudden cardiac death, making it a leading global cause of heart failure. Currently, Dilated cardiomyopathy has an estimated prevalence of 1/2500-1/250 individuals, predominantly affecting those aged 30-40 years, with a male-to-female ratio of 3:1. This case report describes a heart failure patient with cardiac myxoma caused by Carney syndrome combined with dilated cardiomyopathy. The patient was successfully treated for heart failure by heart transplantation. CASE PRESENTATION: Herein, we report a case of heart failure due to Carney syndrome that resulted in cardiac myxoma combined with dilated cardiomyopathy. A 35-year-old male was admitted to the hospital three years ago because of sudden chest tightness and shortness of breath. Echocardiography indicated myxoma, and a combination of genetic screening and physical examination confirmed Carney syndrome with cardiac myxoma. Following symptomatic management, he was discharged. Surgical interventions were not considered at the time. However, the patient's chest tightness and shortness of breath symptoms worsened, and he returned to the hospital. A New York Heart Association grade IV heart function was confirmed, and echocardiography indicated the presence of dilated cardiomyopathy accompanied by cardiac myxoma. Ultimately, the patient's heart failure was successfully treated with heart transplantation. CONCLUSIONS: Cardiac myxoma caused by Carney syndrome combined with heart failure caused by dilated cardiomyopathy can be resolved by heart transplantation.


Assuntos
Cardiomiopatia Dilatada , Complexo de Carney , Insuficiência Cardíaca , Neoplasias Cardíacas , Transplante de Coração , Mixoma , Humanos , Cardiomiopatia Dilatada/cirurgia , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/diagnóstico por imagem , Masculino , Complexo de Carney/genética , Complexo de Carney/diagnóstico , Complexo de Carney/cirurgia , Complexo de Carney/complicações , Adulto , Mixoma/complicações , Mixoma/cirurgia , Mixoma/diagnóstico por imagem , Mixoma/diagnóstico , Mixoma/genética , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/cirurgia , Neoplasias Cardíacas/cirurgia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/genética , Resultado do Tratamento , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética
6.
bioRxiv ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38826205

RESUMO

Whole-brain intrinsic activity as detected by resting-state fMRI can be summarized by three primary spatiotemporal patterns. These patterns have been shown to change with different brain states, especially arousal. The noradrenergic locus coeruleus (LC) is a key node in arousal circuits and has extensive projections throughout the brain, giving it neuromodulatory influence over the coordinated activity of structurally separated regions. In this study, we used optogenetic-fMRI in rats to investigate the impact of LC stimulation on the global signal and three primary spatiotemporal patterns. We report small, spatially specific changes in global signal distribution as a result of tonic LC stimulation, as well as regional changes in spatiotemporal patterns of activity at 5 Hz tonic and 15 Hz phasic stimulation. We also found that LC stimulation had little to no effect on the spatiotemporal patterns detected by complex principal component analysis. These results show that the effects of LC activity on the BOLD signal in rats may be small and regionally concentrated, as opposed to widespread and globally acting.

7.
Front Oncol ; 14: 1357419, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863637

RESUMO

Purpose: To evaluate the capability of dual-layer detector spectral CT (DLCT) quantitative parameters in conjunction with clinical variables to detect malignant lesions in cytologically indeterminate thyroid nodules (TNs). Materials and methods: Data from 107 patients with cytologically indeterminate TNs who underwent DLCT scans were retrospectively reviewed and randomly divided into training and validation sets (7:3 ratio). DLCT quantitative parameters (iodine concentration (IC), NICP (IC nodule/IC thyroid parenchyma), NICA (IC nodule/IC ipsilateral carotid artery), attenuation on the slope of spectral HU curve and effective atomic number), along with clinical variables, were compared between benign and malignant cohorts through univariate analysis. Multivariable logistic regression analysis was employed to identify independent predictors which were used to construct the clinical model, DLCT model, and combined model. A nomogram was formulated based on optimal performing model, and its performance was assessed using receiver operating characteristic curve, calibration curve, and decision curve analysis. The nomogram was subsequently tested in the validation set. Results: Independent predictors associated with malignant TNs with indeterminate cytology included NICP in the arterial phase, Hashimoto's Thyroiditis (HT), and BRAF V600E (all p < 0.05). The DLCT-clinical nomogram, incorporating the aforementioned variables, exhibited superior performance than the clinical model or DLCT model in both training set (AUC: 0.875 vs 0.792 vs 0.824) and validation set (AUC: 0.874 vs 0.792 vs 0.779). The DLCT-clinical nomogram demonstrated satisfactory calibration and clinical utility in both training set and validation set. Conclusion: The DLCT-clinical nomogram emerges as an effective tool to detect malignant lesions in cytologically indeterminate TNs.

8.
Heliyon ; 10(11): e31731, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38828333

RESUMO

Objective: To monitor post-vaccination antibody production, neutralizing activity, and their dynamics over time in people living with HIV (PLWH). Methods: We collected sera from 147 PLWH and 94 healthy controls after vaccination at different time points and examined changes in antibody levels and neutralizing activity using enzyme-linked immunosorbent assay (ELISA) and pseudovirus neutralization assay. Results: IgG levels were substantially increased in both PLWH and healthy controls after the booster injection. Antibody levels decreased significantly in both PLWH and controls five months after the booster injection. However, the rate of decrease was not significantly different between the two groups. The generated antibodies demonstrated protective efficacy against the wild-type SARS-CoV-2 strain, but very low protection against the mutant strains. Furthermore, the protection decreased over time. The vaccine was less effective in PLWH with <200/µl CD4 T cells. During the SARS-CoV-2 recovery period, participants had substantially increased serum antibody levels and protective efficacy compared with those who received the booster. Conclusion: Both PLWH and controls demonstrated comparable antibody production ability. Vaccines and booster development against SARS-CoV-2 mutant strains should be prioritized in PLWH, especially in those with low CD4 counts.

9.
bioRxiv ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38746246

RESUMO

A few large-scale spatiotemporal patterns of brain activity (quasiperiodic patterns or QPPs) account for most of the spatial structure observed in resting state functional magnetic resonance imaging (rs-fMRI). The QPPs capture well-known features such as the evolution of the global signal and the alternating dominance of the default mode and task positive networks. These widespread patterns of activity have plausible ties to neuromodulatory input that mediates changes in nonlocalized processes, including arousal and attention. To determine whether QPPs exhibit variations across brain conditions, the relative magnitude and distribution of the three strongest QPPs were examined in two scenarios. First, in data from the Human Connectome Project, the relative incidence and magnitude of the QPPs was examined over the course of the scan, under the hypothesis that increasing drowsiness would shift the expression of the QPPs over time. Second, using rs-fMRI in rats obtained with a novel approach that minimizes noise, the relative incidence and magnitude of the QPPs was examined under three different anesthetic conditions expected to create distinct types of brain activity. The results indicate that both the distribution of QPPs and their magnitude changes with brain state, evidence of the sensitivity of these large-scale patterns to widespread changes linked to alterations in brain conditions.

10.
Front Pharmacol ; 15: 1374485, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741593

RESUMO

Background: Fufang Xiaohuoluo pill (FFXHL) is a commonly used prescription in clinical practice for treating rheumatoid arthritis in China, yet its specific mechanism remains unclear. This study aims to elucidate the pharmacological mechanisms of FFXHL using both in vivo and in vitro experiments. Methods: The collagen-induced arthritis (CIA) rat model was established to evaluate FFXHL's therapeutic impact. Parameters that include paw swelling, arthritis scores, and inflammatory markers were examined to assess the anti-inflammatory and analgesic effects of FFXHL. Human fibroblast-like synoviocytes (MH7A cells) is activated by tumour necrosis factor-alpha (TNF-α) were used to explore the anti-inflammatory mechanism on FFXHL. Results: Our findings indicate that FFXHL effectively reduced paw swelling, joint pain, arthritis scores, and synovial pannus hyperplasia. It also lowered serum levels of TNF-α, interleukin-1ß (IL1ß), and interleukin-6 (IL-6). Immunohistochemical analysis revealed decreased expression of nuclear factor-kappa B (NF-κB) p65 in FFXHL-treated CIA rat joints. In vitro experiments demonstrated FFXHL's ability to decrease protein secretion of IL-1ß and IL-6, suppress mRNA expression of matrix metalloproteinases (MMP) -3, -9, and -13, reduce reactive oxygen species (ROS) levels, and inhibit NF-κB p65 translocation in TNF-α stimulated MH7A cells. FFXHL also suppressed protein levels of extracellular signal-regulated kinase (ERK), c-Jun Nterminal kinase (JNK), p38 MAP kinase (p38), protein kinase B (Akt), p65, inhibitor of kappa B kinase α/ß (IKKα/ß), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) induced by TNF-α in MH7A cells. Conclusion: The findings imply that FFXHL exhibits significant anti-inflammatory and antiarthritic effects in both CIA rat models and TNF-α-induced MH7A cells. The potential mechanism involves the inactivation of TLR4/MyD88, mitogen-activated protein kinases (MAPKs), NF-κB, and Akt pathways by FFXHL.

11.
BMC Gastroenterol ; 24(1): 146, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689244

RESUMO

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.


Assuntos
Neoplasias da Vesícula Biliar , Pólipos , Ultrassonografia , Humanos , Pessoa de Meia-Idade , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/patologia , Feminino , Masculino , Estudos Retrospectivos , Adulto , Pólipos/diagnóstico por imagem , Pólipos/patologia , Fatores Etários , Idoso , Fatores de Risco , Colecistectomia , China/epidemiologia , Período Pré-Operatório , Adulto Jovem , Cuidados Pré-Operatórios
12.
Food Chem ; 450: 139219, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38640531

RESUMO

Foxtail millet and sourdough are used to make foxtail millet sourdough steamed bread to improve the flavor and taste. Compared with the conventional freeze-thaw treatment (CFT), the effect of magnetic field-assisted freeze-thaw treatment (MFT) on the storage quality of foxtail millet sourdough and steamed bread is explored. The results showed that compared with CFT, MFT shortened the phase transition time of dough; decreased the water loss rate, the water mobility, and the freezable water content; increased the fermentation volume; stabilized the rheological properties; and minimized the damage of freezing and thawing to the secondary structure and microstructure of the gluten. In addition, an analysis of the specific volume, texture, surface color, and texture structure showed that MFT was beneficial to slowing the deterioration of the steamed bread texture. Finally, MFT effectively inhibited the growth and recrystallization of ice crystals during freezing and thawing, improving the quality of millet dough and steamed bread.


Assuntos
Pão , Congelamento , Setaria (Planta) , Paladar , Pão/análise , Setaria (Planta)/química , Setaria (Planta)/crescimento & desenvolvimento , Manipulação de Alimentos , Fermentação , Farinha/análise , Campos Magnéticos , Glutens/química , Glutens/análise , Reologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-38436878

RESUMO

BACKGROUND: AMPK is considered an important protein signaling pathway that has been shown to exert prominent cardioprotective effects on the pathophysiological mechanisms of numerous diseases. Following myocardial infarction, severe impairment of cardiac function occurs, leading to complications such as heart failure and arrhythmia. Therefore, protecting the heart and improving cardiac function are important therapeutic goals after myocardial infarction. Currently, there is substantial ongoing research on exercise-centered rehabilitation training, positioning exercise training as a significant nonpharmacological approach for preventing and treating numerous cardiovascular diseases. OBJECTIVE: Previous studies have reported that exercise can activate AMPK phosphorylation and upregulate the AMPK signaling pathway to play a cardioprotective role in coronary artery disease, but the specific mechanism involved remains to be elucidated. CONCLUSION: This review discusses the role and mechanism of the exercise-mediated AMPK pathway in improving postinfarction cardiac function through existing studies and describes the mechanism of exercise-induced myocardial repair of AMPK from multiple perspectives to formulate a reasonable and optimal exercise rehabilitation program for the prevention and treatment of myocardial infarction patients in the clinic.

14.
Sci Rep ; 14(1): 7006, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38523178

RESUMO

The low loading rate of the thin coal seam shearer drum is a severe obstacle to the efficient mining of thin seam resources, and the auxiliary drum loading through the cowl is an effective measure to alleviate this situation. However, the working mechanism of the coal cowl still remains unclear. In this paper, with the help of the discrete element method and the modeling experiment method, the effects of coal cowl's offset distance, tilt angle and wrap angle on the coal loading rate under different loading modes of the drum are investigated; and the significance of various factors and their interactions to the drum coal loading rate is explored by designing response surface experiments. The findings show that a monotonous negative correlation between the offset distance of the coal cowl and the coal loading rate is identified, and that a smaller offset distance can effectively improve the coal loading rate of the drum. The conveying torque is significantly increased, easily inducing the drum choking, coal recycling coal over-crushing. Along with the increasing tilt angle, the rate of ejection loading decreases monotonically, and the rate of pushing loading increases first and then decreases. Coal loading rate is weakly affected by changes in coal cowl's wrap angle. The results of response surface analysis reveal that the most significant factors affecting the drum's coal loading rate are tilt angle and offset distance in ejection and pushing loading modes, respectively. The conclusions drawn here offer implications for improving the coal loading performance of the thin coal seam shearer drum, as well as certain guidance on the optimal design of coal cowl parameters.

15.
Eur J Pharmacol ; 969: 176457, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38395375

RESUMO

Neuropeptide FF (NPFF) plays a critical role in various physiological processes through the activation of neuropeptide FF receptor 1 and 2 (NPFFR1 and NPFFR2). Numerous evidence has indicated that NPFF exhibits opposite opioid-modulating effects on opioid-induced analgesia after supraspinal and spinal administrations, while the detailed role of NPFFR1 and NPFFR2 remains unclear. In this study, we employed pharmacological and genetic inhibition of NPFFR to investigate the modulating roles of central NPFFR1 and NPFFR2 in opioid-induced analgesia and hyperalgesia, using a male mouse model of acute fentanyl-induced analgesia and secondary hyperalgesia. Our findings revealed that intrathecal (i.t.) injection of the nonselective NPFFR antagonist RF9 significantly enhanced fentanyl-induced analgesia, whereas intracerebroventricular (i.c.v.) injection did not show the same effect. Moreover, NPFFR2 deficient (npffr2-/-) mice exhibited stronger analgesic responses to fentanyl compared to wild type (WT) or NPFFR1 knockout (npffr1-/-) mice. Intrathecal injection of RF9 in npffr1-/- mice also significantly enhanced fentanyl-induced analgesia. These results indicate a crucial role of spinal NPFFR2 in the enhancement of opioid analgesia. Contrastingly, hyperalgesia induced by fentanyl was markedly reversed in npffr1-/- mice but remained unaffected in npffr2-/- mice. Similarly, i.c.v. injection of the selective NPFFR1 antagonist RF3286 effectively prevented fentanyl-induced hyperalgesia in WT or npffr2-/- mice. Notably, co-administration of i.c.v. RF3286 and i.t. RF9 augmented fentanyl-induced analgesia while reducing hyperalgesia. Collectively, these findings highlight the modulating effects of blocking spinal NPFFR2 and supraspinal NPFFR1 on fentanyl-induced analgesia and hyperalgesia, respectively, which shed a light on understanding the pharmacological function of NPFF system in future studies.


Assuntos
Analgesia , Hiperalgesia , Camundongos , Masculino , Animais , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Fentanila/farmacologia , Analgésicos Opioides/farmacologia , Dor , Receptores de Neuropeptídeos/genética
16.
J Med Chem ; 67(1): 272-288, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38118143

RESUMO

The cyclic peptide c[d-Lys2, Asp5]-DN-9 has recently been identified as a multifunctional opioid/neuropeptide FF receptor agonist, displaying potent analgesic activity with reduced side effects. This study utilized Tyr-c[d-Lys-Gly-Phe-Asp]-d-Pro-NH2 (0), a cyclic hexapeptide derived from the opioid pharmacophore of c[d-Lys2, Asp5]-DN-9, as a chemical template. We designed, synthesized, and characterized 22 analogs of 0 with a single amino acid substitution to investigate its structure-activity relationship. Most of these cyclic hexapeptide analogs exhibited multifunctional activity at µ and δ opioid receptors (MOR and DOR, respectively) and produced antinociceptive effects following subcutaneous administration. The lead compound analog 15 showed potent agonistic activities at the MOR, κ opioid receptor (KOR), and DOR in vitro and produced a strong and long-lasting analgesic effect through peripheral MOR and KOR in the tail-flick test. Further biological evaluation identified that analog 15 did not cause significant side effects such as tolerance, withdrawal, or reward liability.


Assuntos
Analgésicos Opioides , Analgésicos , Analgésicos Opioides/uso terapêutico , Relação Estrutura-Atividade , Analgésicos/farmacologia , Receptores Opioides kappa/metabolismo , Peptídeos Cíclicos/química , Receptores Opioides mu/agonistas
17.
J Med Chem ; 66(24): 17138-17154, 2023 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-38095323

RESUMO

Our previous study reported the multifunctional agonist for opioid and neuropeptide FF receptors DN-9, along with its cyclic peptide analogues c[D-Cys2, Cys5]-DN-9 and c[D-Lys2, Asp5]-DN-9. These analogues demonstrated potent antinociceptive effects with reduced opioid-related side effects. To develop more stable and effective analgesics, we designed, synthesized, and evaluated seven hydrocarbon-stapled cyclic peptides based on DN-9. In vitro calcium mobilization assays revealed that most of the stapled peptides, except 3, displayed multifunctional agonistic activities at opioid and neuropeptide FF receptors. Subcutaneous administration of all stapled peptides resulted in effective and long-lasting antinociceptive activities lasting up to 360 min. Among these stapled peptides, 1a and 1b emerged as the optimized compounds, producing potent central antinociception following subcutaneous, intracerebroventricular, and oral administrations. Additionally, subcutaneous administration of 1a and 1b caused nontolerance antinociception, with limited occurrence of constipation and addiction. Furthermore, 1a was selected as the final optimized compound due to its wider safety window compared to 1b.


Assuntos
Analgésicos Opioides , Oligopeptídeos , Analgésicos Opioides/efeitos adversos , Oligopeptídeos/química , Analgésicos/química , Peptídeos/química , Receptores de Neuropeptídeos/agonistas , Encéfalo , Receptores Opioides mu/agonistas
18.
Eur Radiol ; 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37938382

RESUMO

OBJECTIVES: To develop and validate a contrast-enhanced computed tomography (CECT)-based radiomics nomogram for the preoperative evaluation of Ki-67 proliferation status in pancreatic ductal adenocarcinoma (PDAC). METHODS: In this two-center retrospective study, a total of 181 patients (95 in the training cohort; 42 in the testing cohort, and 44 in the external validation cohort) with PDAC who underwent CECT examination were included. Radiomic features were extracted from portal venous phase images. The radiomics signatures were built by using two feature-selecting methods (relief and recursive feature elimination) and four classifiers (support vector machine, naive Bayes, linear discriminant analysis (LDA), and logistic regression (LR)). Multivariate LR was used to build a clinical model and radiomics-clinical nomogram. The predictive performances of the models were evaluated using area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: The relief selector and LDA classifier using twelve features built the optimal radiomics signature, with AUCs of 0.948, 0.927, and 0.824 in the training, testing, and external validation cohorts, respectively. The radiomics-clinical nomogram incorporating the optimal radiomics signature, CT-reported lymph node status, and CA19-9 showed better predictive performance with AUCs of 0.976, 0.955, and 0.882 in the training, testing, and external validation cohorts, respectively. The calibration curve and DCA demonstrated goodness-of-fit and improved benefits in clinical practice of the nomogram. CONCLUSIONS: The radiomics-clinical nomogram is an effective and non-invasive computer-aided tool to predict the Ki-67 expression status in patients with PDAC. CLINICAL RELEVANCE STATEMENT: The radiomics-clinical nomogram is an effective and non-invasive computer-aided tool to predict the Ki-67 expression status in patients with pancreatic ductal adenocarcinoma. KEY POINTS: The radiomics analysis could be helpful to predict Ki-67 expression status in patients with pancreatic ductal adenocarcinoma (PDAC). The radiomics-clinical nomogram integrated with the radiomics signature, clinical data, and CT radiological features could significantly improve the differential diagnosis of Ki-67 expression status. The radiomics-clinical nomogram showed satisfactory calibration and net benefit for discriminating high and low Ki-67 expression status in PDAC.

19.
bioRxiv ; 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37808706

RESUMO

One prominent brain dynamic process detected in functional neuroimaging data is large-scale quasi-periodic patterns (QPPs) which display spatiotemporal propagations along brain cortical gradients. QPP associates with the infraslow neural activity related to attention and arousal fluctuations and has been identified in both resting and task-evoked brains across various species. Several QPP detection and analysis tools were developed for distinct applications with study-specific parameter methods. This MATLAB package provides a simplified and user-friendly generally applicable toolbox for detecting, analyzing, and visualizing QPPs from fMRI timeseries of the brain. This paper describes the software functions and presents its ease of use on any brain datasets. Metadata: [Table: see text].

20.
Heart Surg Forum ; 26(4): E358-E362, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37679089

RESUMO

BACKGROUND: To retrospectively study the experience with application of no-touch technique in radial artery (RA)-based coronary artery bypass grafting (CABG). METHODS: Clinical data of patients who underwent RA-based multi- (n = 45) or full-arterial CABG (n = 27) between January 2019 and June 2022 in the Affiliated Hospital of ZunYi Medical University were collected. The incidence of main cardiovascular events at 30-day follow-up, the antebrachial union condition and the vessel patency rate were analyzed. RESULTS: A total of 66 RAs were harvested and 70 RAs used as grafts. The number of RA used per patient was 1.46. Delayed antebrachial union occurred in 1 patient (1.45%). There was no death, cerebral infarction, myocardial infarction or revascularization at follow-up. Early coronary computed tomography (CT) after surgery revealed occlusion in 1 RA, with the patency rate being 98.57%. CONCLUSIONS: The No-touch RA harvesting technique, preservation and postoperative management applied in this study are effective and rational, and the application of RA as the graft in CABG is safe.


Assuntos
Infarto do Miocárdio , Artéria Radial , Humanos , Estudos Retrospectivos , Ponte de Artéria Coronária , Coração
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