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1.
Plants (Basel) ; 13(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38732386

RESUMEN

Nicosulfuron, an acetolactate synthase (ALS) inhibitor herbicide, is a broad-spectrum and highly effective post-emergence herbicide. Glycosyltransferases (GTs) are widely found in organisms and transfer sugar molecules from donors to acceptors to form glycosides or sugar esters, thereby altering the physicochemical properties of the acceptor molecule, such as participating in detoxification. In this study, nine glycosyltransferases in group D of the apple glycosyltransferase family I were predicted to possibly be involved in the detoxification metabolism of ALS-inhibiting herbicides based on gene chip data published online. In order to confirm this, we analysed whether the expression of the nine glycosyltransferase genes in group D was induced by the previously reported ALS-inhibiting herbicides by real-time PCR (polymerase chain reaction). It was found that the ALS-inhibiting herbicide nicosulfuron significantly increased the expression of the MdUGT73CG22 gene in group D. Further investigation of the mechanism of action revealed that the apple glycosyltransferase MdUGT73CG22 glycosylated and modified nicosulfuron both in vivo and ex vivo to form nicosulfuron glycosides, which were involved in detoxification metabolism. In conclusion, a new glycosyltransferase, MdUGT73CG22, was identified for the first time in this study, which can glycosylate modifications of the ALS-inhibiting herbicide nicosulfuron and may be involved in the detoxification process in plants, which can help to further improve the knowledge of the non-targeted mechanism of herbicides.

2.
Chin J Traumatol ; 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38744544

RESUMEN

PURPOSE: The aim of the present study was to analyze the influence of muscle activation on lumbar injury under a specific +Gz load. METHODS: A hybrid finite element human body model with detailed lumbar anatomy and lumbar muscle activation capabilities was developed. Using the specific +Gz loading acceleration as input, the kinematic and biomechanical responses of the occupant's lower back were studied for both activated and deactivated states of the lumbar muscles. RESULTS: The results indicated that activating the major lumbar muscles enhanced the stability of the occupant's torso, which delayed the contact between the occupant's head and the headrest. Lumbar muscle activation led to higher strain and stress output in the lumbar spine under +Gz load, such as the maximum Von-Mises stress of the vertebrae and intervertebral discs increased by 177.9% and 161.8%, respectively, and the damage response index increased by 84.5%. CONCLUSION: In both simulations, the occupant's risk of lumbar injury does not exceed 10% probability. Therefore, the activation of muscles could provide good protection for maintaining the lumbar spine and reduce the effect of acceleration in vehicle travel direction.

3.
ACS Pharmacol Transl Sci ; 7(4): 1178-1190, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38633583

RESUMEN

A promising alternative for cancer treatment involves targeted inhibition of the epigenetic regulator bromodomain-containing protein 4 (BRD4); however, available BRD4 inhibitors are constrained by their potency, oral bioavailability, and cytotoxicity. Herein, to overcome the drawback of the translational BRD4 inhibitors, we describe a novel BRD4-p53 inhibitor, SDU-071, which suppresses BRD4 interaction with the p53 tumor suppressor and its biological activity in MDA-MB-231 triple-negative breast cancer (TNBC) cells in vitro and in vivo. This novel small-molecule BRD4-p53 inhibitor suppresses cell proliferation, migration, and invasion by downregulating the expression of BRD4-targeted genes, such as c-Myc and Mucin 5AC, and inducing cell cycle arrest and apoptosis, as demonstrated in cultured MDA-MB-231 TNBC cells. Its antitumor activity is illustrated in an orthotopic mouse xenograft mammary tumor model. Overall, our results show that SDU-071 is a viable option for potentially treating TNBC as a new BRD4-p53 inhibitor.

4.
J Agric Food Chem ; 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38599785

RESUMEN

To develop aryloxyphenoxypropionate herbicides with a novel structure and improved activity, a total of 39 aryloxyphenoxypropionate/amide derivatives containing quinazolinone moiety were synthesized and further bioevaluated. The bioassay results in the greenhouse showed that most of the target compounds had good herbicidal activity under postemergence conditions, of which, QPP-I-6 displayed excellent herbicidal activity against Echinochloa crusgalli, Digitaria sanguinalis, Spartina alterniflora, Eleusine indica, and Pennisetum alopecuroides with inhibition rates >90% at a dosage of 187.5 g ha-1. More importantly, QPP-I-6 displayed higher crop safety to Gossypium hirsutum, Glycine max, and Arachis hypogaea than the commercial herbicide quizalofop-p-ethyl. Studying the molecular mode of action by phenotypic observation, membrane permeability evaluation, transcriptomic analysis, and in vivo ACCase activity evaluation reveals that QPP-I-6 is a novel ACCase inhibitor. The present work demonstrates that QPP-I-6 can serve as a lead compound for further developing novel ACCase-inhibiting herbicides.

5.
J Autoimmun ; 143: 103171, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38306953

RESUMEN

CD57+ CD8+ T cells, also referred as effector memory cells, are implicated in various conditions including tumor immunity, virus immunity, and most recently with autoimmunity. However, their roles in the progression and remission of T1D are still unclear. Here, we noted an increase in peripheral CD57+ CD8+ T cells in a T1D patient harboring an activator of transcription 3 (STAT3) mutation. Our in-depth study on the role of CD57+ CD8+ T cells within a T1D patient cohort revealed that these cells undergo significant compositional shifts during the disease's progression. Longitudinal cohort data suggested that CD57+ CD8+ T cell prevalence may be a harbinger of ß-cell function decline in T1D patients. Characterized by robust cytotoxic activity, heightened production of pro-inflammatory cytokines, and increased intracellular glucose uptake, these cells may be key players in the pathophysiology of T1D. Moreover, in vitro assays showed that the CXCL12-CXCR4 axis promotes the expansion and function of CD57+ CD8+ T cells via Erk1/2 signaling. Notably, the changes of serum CXCL12 concentrations were also found in individuals during the peri-remission phase of T1D. Furthermore, treatment with the CXCR4 antagonist LY2510924 reduced the immunological infiltration of CD57+ CD8+ T cells and mitigated hyperglycemia in a STZ-induced T1D mouse model. Taken together, our work has uncovered a novel role of the CXCL12-CXCR4 axis in driving CD57+ CD8+ T cells responses in T1D, and presented a promising therapeutic strategy for delaying the onset and progression of diabetes.


Asunto(s)
Linfocitos T CD8-positivos , Diabetes Mellitus Tipo 1 , Animales , Humanos , Ratones , Antígenos CD57/metabolismo , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismo , Citocinas/metabolismo , Receptores CXCR4/metabolismo , Transducción de Señal
6.
Trends Plant Sci ; 29(1): 1-3, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37838518

RESUMEN

Despite many years of research, the molecular mechanisms underlying the activation and regulation of host plant resistance (HPR) to insects remain elusive. Recently, Guo et al. reported that a nucleotide-binding leucine-rich repeat NLR protein activates HPR through direct recognition of an insect effector and that autophagy-mediated degradation of this effector negatively regulates HPR.


Asunto(s)
Proteínas NLR , Plantas , Plantas/genética , Plantas/metabolismo , Proteínas NLR/metabolismo , Inmunidad de la Planta/genética , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Resistencia a la Enfermedad/genética
7.
Diabetologia ; 67(1): 42-51, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37889319

RESUMEN

AIMS/HYPOTHESIS: The aim of this work was to define a unique remission status using glycaemia risk index (GRI) and other continuous glucose monitoring (CGM) metrics in individuals with type 1 diabetes for improved phenotyping. METHODS: A group of 140 individuals with type 1 diabetes were recruited for a cross-sectional study. The participants were categorised into four groups based on their remission status, which was defined as insulin-dose-adjusted A1c (IDAA1c) <9 or C-peptide ≥300 pmol/l: new-onset (n=24); mid-remission (n=44); post-remission (n=44); and non-remission (individuals who did not experience remission, n=28). Participants in the remission phase were referred to as 'remitters', while those who were not in the remission phase were referred to as 'non-remitters', the latter group including new-onset, post-remission and non-remission participants. Clinical variables such as HbA1c, C-peptide and insulin daily dose, as well as IDAA1C and CGM data, were collected. The patterns of CGM metrics were analysed for each group using generalised estimating equations to investigate the glycaemic variability patterns associated with remission status. Then, unsupervised hierarchical clustering was used to place the participants into subgroups based on GRI and other CGM core metrics. RESULTS: The glycaemic variability patterns associated with remission status were found to be distinct based on the circadian CGM metrics. Remitters showed improved control of blood glucose levels over 14 days within the range of 3.9-10 mmol/l, and lower GRI compared with non-remitters (p<0.001). Moreover, GRI strongly correlated with IDAA1C (r=0.62; p<0.001) and was sufficient to distinguish remitters from non-remitters. Further, four subgroups demonstrating distinct patterns of glycaemic variability associated with different remission status were identified by clustering on CGM metrics: remitters with low risk of dysglycaemia; non-remitters with high risk of hypoglycaemia; non-remitters with high risk of hyperglycaemia; and non-remitters with moderate risk of dysglycaemia. CONCLUSIONS/INTERPRETATION: GRI, an integrative index, together with other traditional CGM metrics, helps to identify different glycaemic variability patterns; this might provide specifically tailored monitoring and management strategies for individuals in the various subclusters.


Asunto(s)
Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucemia/análisis , Péptido C , Automonitorización de la Glucosa Sanguínea , Estudios Transversales , Insulina/uso terapéutico
8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(4): 676-682, 2023 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-37666757

RESUMEN

This paper studies the active force characteristics of the neck muscles under the condition of rapid braking, which can provide theoretical support for reducing the neck injury of pilots when carrier-based aircraft blocks the landing. We carried out static loading and real vehicle braking experiments under rapid braking conditions, collected the active contraction force and electromyography (EMG) signals of neck muscles, and analyzed the response characteristics of neck muscle active force response. The results showed that the head and neck forward tilt time was delayed and the amplitude decreased during neck muscle pre-tightening. The duration of the neck in the extreme position decreased, and the recovery towards the seat direction was faster. The EMG signals of trapezius muscle was higher than sternocleidomastoid muscle. This suggests that pilots can reduce neck injury by pre-tightening the neck muscles during actual braking flight. In addition, we can consider the design of relevant fittings for pre-tightening the neck muscles.


Asunto(s)
Músculos del Cuello , Cuello , Electromiografía , Cabeza
9.
Diabetologia ; 66(8): 1532-1543, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37300581

RESUMEN

AIMS/HYPOTHESIS: Notwithstanding the irreversible beta cell failure seen in type 1 diabetes, some individuals may experience a special phase named 'partial remission' or 'the honeymoon period', in which there is a transient recovery of beta cell function. Importantly, this stage of partial remission shows spontaneous immune downregulation, although the exact mechanisms are unclear. Intracellular energy metabolism is crucial for the differentiation and function of T cells, and provides promising targets for immunometabolic intervention strategies, but its role during partial remission is unknown. In this study, we aim to investigate the association between T cell intracellular glucose and fatty acid metabolism and the partial remission phase. METHODS: This is a cross-sectional study with a follow-up component. Intracellular uptake of glucose and fatty acids by T cells was detected in participants with either new-onset type 1 diabetes or type 1 diabetes that was already in partial remission, and compared with heathy individuals and participants with type 2 diabetes. Subsequently, the participants with new-onset type 1 diabetes were followed up to determine whether they experienced a partial remission (remitters) or not (non-remitters). The trajectory of changes in T cell glucose metabolism was observed in remitters and non-remitters. Expression of programmed cell death-1 (PD-1) was also analysed to investigate possible mechanisms driving altered glucose metabolism. Partial remission was defined when patients had convalescent fasting or 2 h postprandial C-peptide >300 pmol/l after insulin treatment. RESULTS: Compared with participants with new-onset type 1 diabetes, intracellular glucose uptake by T cells decreased significantly in individuals with partial remission. The trajectory of these changes during follow-up showed that intracelluar glucose uptake in T cells fluctuated during different disease stages, with a decreased uptake during partial remission that rebounded after remission. This dynamic in T cell glucose uptake was only detected in remitters and not in non-remitters. Further analysis demonstrated that changes of intracellular glucose uptake were found in subsets of CD4+ and CD8+ T cells, including Th17, Th1, CD8+ naive T cells (Tn) and CD8+ terminally differentiated effector memory T cells (Temra). Moreover, glucose uptake in CD8+ T cells was negatively related to PD-1 expression. The intracellular metabolism of fatty acids was not found to be different between new-onset participants and those in partial remission. CONCLUSIONS/INTERPRETATION: Intracellular glucose uptake in T cells was specifically decreased during partial remission in type 1 diabetes and may be related to PD-1 upregulation, which may be involved in the down-modulation of immune responses during partial remission. This study suggests that altered immune metabolism could be a target for interventions at the point of diagnosis of type 1 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Linfocitos T CD8-positivos/metabolismo , Estudios Transversales , Receptor de Muerte Celular Programada 1 , Glucosa
10.
Chem Biodivers ; 20(1): e202200814, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36471492

RESUMEN

Diabetes mellitus (DM) is a serious disease affecting human health. Numerous attempts have been made to develop safe and effective new antidiabetic drugs. Recently, a series of G protein-coupled receptors for free fatty acids (FFAs) have been described and characterized, and small molecule agonists and antagonists of these receptors show considerable promise for managing diabetes and related complications. FFA-activated GPR120 could stimulate the release of glucagon-like peptide-1(GLP-1), which can enhance the glucose-dependent secretion of insulin from pancreatic ß cells. GPR120 is a promising target for treating type 2 DM (T2DM). Herein we designed and synthesized a series of novel GPR120 agonists based on the structure of TUG-891, which was the first potent and selective GPR120 agonist. Among the designed compounds, 18 f showed excellent GPR120 activation activity and high selectivity for GPR40 in vitro. Compound 18 f dose-dependently improved glucose tolerance in normal mice, and no hypoglycemic side effects were observed at high dose. In addition, compound 18 f increased insulin release and displayed good antidiabetic effect in diet-induced obese mice. Molecular simulations illustrated that compound 18 f could enter the active site of GPR120 and interact with Arg99. Based on these observations, compound 18 f may be a promising lead compound for the design of novel GPR120 agonists to treat T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ratones , Humanos , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/uso terapéutico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Ácidos Grasos no Esterificados , Glucosa
11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-995617

RESUMEN

Objective:To observe the clinical and multimodal imaging characteristics of eyes with acute macular neuroretinopathy (AMN) associated with COVID-19.Methods:A retrospective clinical study. From December 18 to 26, 2022, 16 eyes of 8 patients with AMN associated with COVID-19 were included in the study. There were 4 males and 4 females; all cases were bilateral. The age was (31.5±9.6) years old. The time from fever to decreased vision was (3.75±1.04) days. The best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, indirect fundus microscopy, fundus color photography, and optical coherence tomography (OCT) were performed in all patients. Infrared fundus photography (IR), OCT angiography (OCTA) and fluorescein fundus angiography (FFA) were performed in 14, 6 and 4 eyes respectively. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for statistics. The clinical data, IR, OCT and OCTA imaging features of the patients were retrospectively analyzed.Results:The logMAR BCVA of AMN eyes was 4.21±0.74, intraocular pressure was (14.87±1.50) mm Hg (1 mm Hg=0.133 kPa). Fundus color photography showed that multiple gray-white petal-shaped lesions were arranged around the macular fovea in 2 eyes; no obvious abnormality was found in the macular area in 14 eyes. Of the 14 eyes examined by IR, 6 eyes had irregular weak reflective lesions around the macular fovea. OCT showed strong reflex in the outer nuclear layer and outer plexiform layer of all eyes, including 15 eyes with elliptical zone injury. In 6 eyes examined by OCTA, the blood flow density of the superficial and deep capillary plexus (DCP) of retina decreased, and the blood flow density of DCP decreased significantly. The en-face image of DCP showed the wedge-shaped strong reflective lesion area with the tip pointing to the central fovea in 2 eyes. No abnormal fluorescence was observed in FFA.Conclusions:The characteristic manifestation of AMN associated with COVID-19 is weak reflex focus in IR; OCT shows strong reflection in outer core layer and outer plexiform layer; OCTA showed that retinal DCP blood flow density decreased.

12.
Front Immunol ; 13: 941962, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35990660

RESUMEN

As an important form of posttranslational modification, protein ubiquitination regulates a wide variety of biological processes, including different aspects of T cell development and differentiation. During T cell development, thymic seeding progenitor cells (TSPs) in the thymus undergo multistep maturation programs and checkpoints, which are critical to build a functional and tolerant immune system. Currently, a tremendous amount of research has focused on the transcriptional regulation of thymocyte development. However, in the past few years, compelling evidence has revealed that the ubiquitination system also plays a crucial role in the regulation of thymocyte developmental programs. In this review, we summarize recent findings on the molecular mechanisms and cellular pathways that regulate thymocyte ubiquitination and discuss the roles of E3 ligases and deubiquitinating enzymes (DUBs) involved in these processes. Understanding how T cell development is regulated by ubiquitination and deubiquitination will not only enhance our understanding of cell fate determination via gene regulatory networks but also provide potential novel therapeutic strategies for treating autoimmune diseases and cancer.


Asunto(s)
Enfermedades Autoinmunes , Ubiquitina-Proteína Ligasas , Diferenciación Celular , Humanos , Linfocitos T , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación
13.
Ying Yong Sheng Tai Xue Bao ; 33(3): 775-783, 2022 Mar.
Artículo en Chino | MEDLINE | ID: mdl-35524531

RESUMEN

Nitrogen limitation is an important factor for the improvement of crop water production potential in rain-fed areas of the Loess Plateau. The reasonable deep application of nitrogen fertilizer is a promising method to increase yield of rain-fed crop. Based on APSIM model, this study simulated spring wheat yield under different nitrogen application rates and depths, by using meteorological observation data from 1990 to 2020 in the semiarid areas of central Gansu Province, aiming to provide theoretical reference for optimizing wheat fertilization strategy. The results showed that the determination coefficient of simulated spring wheat yield, biomass and soil water content in 0-200 cm soil profile was greater than 0.80, the normalized root mean square error was less than 0.2, and the model validity index was greater than 0.5. These results indicated that the model had good fitting and adaptability in the test area. Across all the levels within the experimental design, increasing nitrogen application rates could significantly increase the yield of spring wheat in different precipitation years, and increasing nitrogen application depth could significantly increase spring wheat yield in wet and normal years, but had no effect in dry years. The rate and depth of nitrogen application had significant interaction effects on spring wheat yield in wet and normal years, but not in dry years. According to the binary quadratic regression fitting equation, when the potential maximum yield reached 2749 kg·hm-2 in wet year, nitrogen application depth was 22.7 cm, and nitrogen application rate was 245 kg·hm-2. When the maximum potential yield reached 2596 kg·hm-2 in normal year, nitrogen application depth was 20.6 cm, and nitrogen application rate was 235 kg·hm-2. Integrating the effects of nitrogen application rate and depth on yield, biomass and agronomic efficiency of nitrogen fertilizer, and farmer's fertilizer application habits, the recommended nitrogen application depth was 20-23 cm, and nitrogen application amount was 120-150 kg·hm-2, which could further improve water productivity and nitrogen use efficiency of spring wheat in arid areas of central Gansu Province.


Asunto(s)
Fertilizantes , Nitrógeno , Agricultura/métodos , China , Nitrógeno/análisis , Suelo , Triticum , Agua
14.
RSC Adv ; 12(10): 5732-5742, 2022 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-35424534

RESUMEN

GPR120, also called FFAR4, is preferentially expressed in the intestines, and can be stimulated by long-chain free fatty acids to increase the secretion of glucagon-like peptide-1 (GLP-1) from intestinal endocrine cells. It is known that GLP-1, as an incretin, can promote the insulin secretion from pancreatic cells in a glucose-dependent manner. Therefore, GPR120 is a potential drug target to treat type 2 diabetes. In this study, thiazolidinedione derivatives were found to be novel potent GPR120 agonists. Compound 5g, with excellent agonistic activity, selectivity, and metabolic stability, improved oral glucose tolerance in normal C57BL/6 mice in a dose-dependent manner. Moreover, compound 5g exhibited anti-diabetic activity by promoting insulin secretion in diet-induced obese mice. In summary, compound 5g might be a promising drug candidate for the treatment of type 2 diabetes.

15.
Chinese Journal of Urology ; (12): 301-302, 2022.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-933218

RESUMEN

Three children with Skene duct cyst were presented in this article. By reviewing literature, in pediatric population, Skene duct cycts mostly occur in newborns and conservative therapy is the first choice in this group.In contrast, it is extremely rare between the ages of 1 and 12, and surgical excised is the preferred therapy because of having a similar pathogenesis to adults.

16.
Chinese Journal of Urology ; (12): 62-66, 2022.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-933163

RESUMEN

Objective:To explore the clinical features and treatment strategy of congenital anterior urethrocutaneous fistula.Methods:A total of 7 cases with congenital anterior urethrocutaneous fistula were repaired by surgery between January 2006 and February 2019 in Affiliated Children’s Hospital of Xi’an Jiaotong University. The median age was 30 (18-92) months. All of cases had a intact prepucs and a normal external urethal meatus located at the tip of glans. Fistula located at subcoronal culus in 2 cases, midshaft in 3 cases, penioscrotal region in 1 case, scrotum in 1 case, respectively.Defect longitudinal diameter was 0.5-1.5cm. Associated anomalies including division of scrotum in 3 cases, penile chordee in 2 cases, urethral meatus stenosis in 1 case, right hydrocele in 1 case. Six cases had underwent one-stage fistula repair incluing Duplay procedure in 4 cases(case 1, 2, 4 and 6), Onlay preputial flap in 1 case(case 3), TIP repair with dorsal plication for straightening and urethrotomy in 1 case(case 5). Case 7 had underwent a two-stage repair, which received Duckett flap repair with urethrostomy simultaneously at the base of the penis, and the defect was closed in second procedure. All of neourethras were reinforced by soft tissues from different places.Results:Of 6 cases with one-stage repair, the catheter was removed 10-14 days after surgery in 5 cases. Removal of the catheter was delayed until 3 weeks in case 3 because of poor wound healing. Case 7 received Duckett flap repair with urethrostomy in the initial surgery, who recovered uneventfully and was resolved during the second operation. No recurrence, urethral stricture or chordee occurence were noted in all after a 1-8 years followup period.Conclusions:Congenital anterior urethrocutaneous fistula have a high overall success rate.Duplay could be applied to cases without penile curvature, and well-developed urethral plate. Onlay or TIP is more suitable for cases with narrow urethral plate. The principle of hypospadias repair should be followed for those cases with severe penile curvature.

17.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-932895

RESUMEN

Multiple myeloma (MM) is a malignant tumor of the blood system that is more common in the elderly with abnormal proliferation of bone marrow plasma cells. The current diagnostic methods mainly rely on the detection of M protein and invasive bone marrow aspiration biopsy. The sensitivity and specificity of conventional imaging tests are low. Molecular imaging technology provides new options and methods for the noninvasive diagnosis of MM. Whole-body MRI (WB-MRI) has good soft tissue contrast and spatial resolution, which can show bone marrow infiltration and vascular conditions. Metabolic imaging such as 18F-FDG, acetate, choline, and methionine are highly sensitive. ImmunoPET imaging screens specific targets for targeted therapy or immunotherapy and evaluates the efficacy. This article reviews the progress of molecular imaging in MM, especially immunoPET imaging.

18.
Molecules ; 26(22)2021 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-34833999

RESUMEN

GPR120 is a promising target for the treatment of type 2 diabetes (T2DM), which is activated by free fatty acids (FFAs) and stimulates the release of glucagon-like peptide-1(GLP-1). GLP-1, as an incretin, can enhance glucose-dependent secretion of insulin from pancreatic beta cells and reduce blood glucose. In this study, a series of novel GPR120 agonists were designed and synthesized to improve the stability and hydrophilicity of the phenylpropanoic acid GPR120 agonist TUG-891. Compound 11b showed excellent GPR120 agonistic activity and pharmacokinetic properties, and could reduce the blood glucose of normal mice in a dose-dependent manner. In addition, no hypoglycemic side effects were observed even at a dose of 100 mg/kg. Moreover, 11b showed good anti-hyperglycemic effects in diet-induced obese (DIO) mice. Molecular simulation illustrated that compound 11b could enter the active site of GPR120 and interact with ARG99. Taken together, the results indicate that compound 11b might be a promising drug candidate for the treatment of T2DM.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes , Receptores Acoplados a Proteínas G/agonistas , Animales , Células CHO , Cricetulus , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Masculino , Ratones , Ratones Endogámicos ICR , Receptores Acoplados a Proteínas G/metabolismo
19.
Molecules ; 26(18)2021 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-34577028

RESUMEN

In this study, a series of coumarin derivatives were designed and synthesized, their structures were characterized using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) testing methods. In the pharmacological experiment, two behavior-monitoring methods, the forced swim test (FST) and the tail suspension test (TST), were used to determine the antidepressant activity of coumarin derivatives. Compounds that showed potential activity were analyzed for their effects on 5-hydroxytryptamine (5-HT) levels in the brains of mice. Molecular docking experiments to simulate the possible interaction of these compounds with the 5-HT1A receptor was also be predicted. The results of the pharmacological experiments showed that most coumarin derivatives exhibited significant antidepressant activity. Among these compounds, 7-(2-(4-(4-fluorobenzyl)piperazin-1-yl)-2-oxoethoxy)-2H-chromen-2-one (6i) showed the highest antidepressant activity. The results of the measurement of 5-HT levels in the brains of mice indicate that the antidepressant activity of coumarin derivatives may be mediated by elevated 5-HT levels. The results of molecular docking demonstrated that compound 6i had a significant interaction with amino acids around the active site of the 5-HT1A receptor in the homology model. The physicochemical and pharmacokinetic properties of the target compounds were also predicted using Discovery Studio (DS) 2020 and Chemdraw 14.0.


Asunto(s)
Antidepresivos , Simulación del Acoplamiento Molecular , Animales , Depresión , Suspensión Trasera , Ratones , Natación
20.
Mitochondrial DNA B Resour ; 6(5): 1650-1651, 2021 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-34027082

RESUMEN

Toddalia asiatica (L.) Lam. belongs to family Rutaceae and mainly distributes in dry areas of bushes in tropical Africa, Asia, and Swaziland. Sometimes it can be used as fodder for goats, but it has been used as herbs in traditional medical treatment for 1000 years. In this study, we sequenced the sample of T. asiatica and determined its complete chloroplast genome. The length of CP genome is 158,434 bp, includes two invert repeats (IR) regions of 27,008 bp, a large single-copy (LSC) region of 86,132 bp, and a short single-copy (SSC) region of 18,286 bp. There are 133 genes, which includes 88 protein-coding genes, 8 rRNA and 37 tRNA, and 38.5% overall GC content. Each of trnK-UUU, rps16, trnG-UCC, atpF, rpoC1, trnL-UAA, trnV-UAC, petB, petD, rpl16, rpl2, ndhB, trnI-GAU, trnA-UGC, and ndhA genes contains a intron, clpP and ycf3 contains 2 intron. The phylogenetic analysis result shows that T. asiatica has the closest relationship with Zanthoxylum armatum (MT990984) and Zanthoxylum nitidum (MN508801).

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