Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Ophthalmol ; 17(6): 1001-1006, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895683

RESUMO

AIM: To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy (DR) and in patients with or without diabetic macular edema (DME). METHODS: The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study. The severity of DR patients was graded as mild, moderate and severe non-proliferative diabetic retinopathy (NPDR) according to the international clinical diabetic retinopathy (ICDR) disease severity scale classification, and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods. The presence of DME was determined by optical coherence tomography (OCT), and differences in vascular morphological characteristics were compared between patients with and without DME. RESULTS: Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99% and a Dice metric of 0.76. Compared with the healthy group, the DR group had smaller vessel angles (33.68±3.01 vs 37.78±1.60), smaller fractal dimension (Df) values (1.33±0.05 vs 1.41±0.03), less vessel density (1.12±0.44 vs 2.09±0.36) and fewer vascular branches (206.1±88.8 vs 396.5±91.3), all P<0.001. As the severity of DR increased, Df values decreased, P=0.031. No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics. CONCLUSION: In this study, an artificial intelligence retinal vessel segmentation system is used with 99% accuracy, thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology. DR patients have a tendency of vascular occlusion and dropout. The presence of DME does not compromise the integral retinal vascular pattern.

2.
Front Cell Infect Microbiol ; 14: 1371916, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716199

RESUMO

Porcine epidemic diarrhea virus (PEDV) has become a challenging problem in pig industry worldwide, causing significant profit losses. Lactobacillus rhamnosus GG (LGG) has been regarded as a safe probiotic strain and has been shown to exert protective effects on the intestinal dysfunction caused by PEDV. This study evaluated the effect of LGG on the gut health of lactating piglets challenged with PEDV. Fifteen piglets at 7 days of age were equally assigned into 3 groups (5 piglets per group): 1) control group (basal diet); 2) PEDV group: (basal diet + PEDV challenged); 3) LGG + PEDV group (basal diet + 3×109 CFU/pig/day LGG + PEDV). The trial lasted 11 days including 3 days of adaptation. The treatment with LGG was from D4 to D10. PEDV challenge was carried out on D8. PEDV infection disrupted the cell structure, undermined the integrity of the intestinal tract, and induced oxidative stress, and intestinal damage of piglets. Supplementation of LGG improved intestinal morphology, enhanced intestinal antioxidant capacity, and alleviated jejunal mucosal inflammation and lipid metabolism disorders in PEDV-infected piglets, which may be regulated by LGG by altering the expression of TNF signaling pathway, PPAR signaling pathway, and fat digestion and absorption pathway.


Assuntos
Infecções por Coronavirus , Suplementos Nutricionais , Lacticaseibacillus rhamnosus , Vírus da Diarreia Epidêmica Suína , Probióticos , Doenças dos Suínos , Animais , Suínos , Probióticos/administração & dosagem , Doenças dos Suínos/prevenção & controle , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/terapia , Estresse Oxidativo , Intestinos/patologia , Pós , Mucosa Intestinal/patologia
3.
Animals (Basel) ; 14(10)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38791729

RESUMO

Porcine epidemic diarrhea virus (PEDV) has developed as a global problem for the pig business, resulting in significant financial losses. Black soldier fly extract (BFE) has been proven to improve intestinal growth in pigs after weaning. Consequently, the goal of the present investigation was to explore the effects of BFE supplementation on intestinal function in PEDV-infected piglets. Eighteen piglets were randomly allocated to three groups: control, PEDV, and BFE + PEDV. The piglets in the BFE + PEDV group received 500 mg/kg BW of BFE orally for seven days from day 4 to 10 of the study. On day 9 of the study, six pigs from each group received either clean saline or PEDV solution at a dosage of 106 TCID50 (50% tissue culture infectious dose) per pig. On day 11, samples of blood and intestine were taken for additional investigation. The results indicated a significant decrease in the average daily gain (ADG) of piglets infected with PEDV (p < 0.05). Additionally, PEDV infection led to an alteration of blood indexes and a reduction in plasma D-xylose concentration and villi height in the small intestine, while it increased plasma diamine oxidase activity and small intestinal crypt depth in piglets (p < 0.05). The PEDV infection significantly reduced antioxidant enzyme activity in plasma and the gut, including total superoxide dismutase and catalase, while increasing contents of oxidation-relevant products such as malondialdehyde and hydrogen peroxide in piglets. Moreover, PEDV infection increased the mRNA expression level of antiviral-related genes (p < 0.05). Nutritional supplementation with BFE improved intestinal histomorphological indicators and reduced oxidative stress produced by PEDV infection in piglets. Interestingly, BFE could significantly promote the mRNA expression level of antiviral-related genes in the ileum (p < 0.05). Overall, the preliminary results suggest that dietary BFE could improve intestinal function in piglets after PEDV infection. Currently, the findings put a spotlight on the role of BFE in the prevention and treatment of PED in piglets.

4.
Front Microbiol ; 15: 1378070, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655081

RESUMO

Porcine epidemic diarrhea virus (PEDV) has caused huge economic losses to the pig industry. Yeast polysaccharides (YP) has been used as a feed additive in recent years and poses good anti-inflammatory and antiviral effects. The present study aimed to explore the protective effect of YP on intestinal damage in PEDV-infected piglets. Eighteen 7-day-old piglets with similar body weights were randomly divided into three groups: Control group (basal diet), PEDV group (basal diet), and PEDV+YP group (basal diet +20 mg/kg BW YP), six replicates per group and one pig per replicate. Piglets in PEDV group and PEDV+YP group were orally given PEDV (dose: 1 × 106 TCID50) at 19:30 PM on the 8th day of the experiment. The control group received the same volume of PBS solution. Weight was taken on an empty stomach in the morning of the 11th day, blood was collected and then anesthetic was administered with pentobarbital sodium (50 mg/kg·BW) by intramuscular injection, and samples were slaughtered after the anesthetic was complete. The results showed that YP could alleviate the destruction of intestinal villus morphology of piglets caused by PEDV. Meanwhile, PEDV infection can reduce the activity of glutathione peroxidase, superoxide dismutase and catalase, and increase the content of malondialdehyde. YP can improve the antioxidative capacity in the serum and small intestine of PEDV-infected piglets. In addition, YP inhibited the replication of PEDV in the jejunum ileum and colon. Moreover, YP can regulate the mRNA levels of inflammatory genes (IL-1ß and iNOS) and lipid metabolic genes (APOA4 and APOC3) in the small intestine. In summary, YP could inhibit virus replicates, improve intestinal morphology, enhance antioxidant capacity, relieve inflammation and regulate the metabolism of the intestine in PEDV-infected piglets.

5.
Org Lett ; 26(16): 3458-3462, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38630985

RESUMO

Current methods for arene hydrogenation generally need either harsh reaction conditions or complex catalyst preparation. Here we describe a mild and convenient protocol that only utilizes commercially available catalysts. Using [Rh(nbd)Cl]2 and Pd/C together as catalysts, arenes bearing various functional groups can be hydrogenated under 1 atm of H2 at room temperature. This arene hydrogenation can also be achieved using catalysts of [Rh(cod)Cl]2 and PtO2, thus avoiding glovebox manipulations and simplifying the reaction procedure.

6.
Toxicol Appl Pharmacol ; 485: 116876, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437955

RESUMO

BACKGROUND: Olanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. METHODS: Rats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5-40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. RESULTS: In adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. CONCLUSIONS: These results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.


Assuntos
Antipsicóticos , Aripiprazol , Benzodiazepinas , Bromocriptina , Glândulas Mamárias Animais , Olanzapina , Prolactina , Animais , Olanzapina/toxicidade , Feminino , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/patologia , Aripiprazol/toxicidade , Ratos , Prolactina/sangue , Antipsicóticos/toxicidade , Antipsicóticos/efeitos adversos , Benzodiazepinas/toxicidade , Masculino , Ratos Sprague-Dawley , Receptores da Prolactina/metabolismo , Estradiol/sangue , Relação Dose-Resposta a Droga , Progesterona/sangue , Quinolonas/toxicidade , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Piperazinas/toxicidade
7.
Lipids Health Dis ; 22(1): 222, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093311

RESUMO

BACKGROUND: Previous studies demonstrated that mast cells with their degranulated component heparin are the major endogenous factors that stimulate preadipocyte differentiation and promote fascial adipogenesis, and this effect is related to the structure of heparin. Regarding the structural and physiological properties of the negatively charged polymers, hexasulfonated suramin, a centuries-old medicine that is still used for treating African trypanosomiasis and onchocerciasis, is assumed to be a heparin-related analog or heparinoid. This investigation aims to elucidate the influence of suramin on the adipogenesis. METHODS: To assess the influence exerted by suramin on adipogenic differentiation of primary white adipocytes in rats, this exploration was conducted both in vitro and in vivo. Moreover, it was attempted to explore the role played by the sulfonic acid groups present in suramin in mediating this adipogenic process. RESULTS: Suramin demonstrated a dose- and time-dependent propensity to stimulate the adipogenic differentiation of rat preadipocytes isolated from the superficial fascia tissue and from adult adipose tissue. This stimulation was concomitant with a notable upregulation in expression levels of pivotal adipogenic factors as the adipocyte differentiation process unfolded. Intraperitoneal injection of suramin into rats slightly increased adipogenesis in the superficial fascia and in the epididymal and inguinal fat depots. PPADS, NF023, and NF449 are suramin analogs respectively containing 2, 6, and 8 sulfonic acid groups, among which the last two moderately promoted lipid droplet formation and adipocyte differentiation. The number and position of sulfonate groups may be related to the adipogenic effect of suramin. CONCLUSIONS: Suramin emerges as a noteworthy pharmaceutical agent with the unique capability to significantly induce adipocyte differentiation, thereby fostering adipogenesis.


Assuntos
Adipogenia , Suramina , Ratos , Animais , Suramina/farmacologia , Antiparasitários/farmacologia , Diferenciação Celular , Adipócitos Brancos , Heparina/farmacologia
8.
Pharmaceutics ; 15(9)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37765247

RESUMO

The development of novel antimicrobial agents to replace antibiotics has become urgent due to the emergence of multidrug-resistant microorganisms. Antimicrobial peptides (AMPs), widely distributed in all kingdoms of life, present strong antimicrobial activity against a variety of bacteria, fungi, parasites, and viruses. The potential of AMPs as new alternatives to antibiotics has gradually attracted considerable interest. In addition, AMPs exhibit strong anticancer potential as well as anti-inflammatory and immunomodulatory activity. Many studies have provided evidence that AMPs can recruit and activate immune cells, controlling inflammation. This review highlights the scientific literature focusing on evidence for the anti-inflammatory mechanisms of different AMPs in immune cells, including macrophages, monocytes, lymphocytes, mast cells, dendritic cells, neutrophils, and eosinophils. A variety of immunomodulatory characteristics, including the abilities to activate and differentiate immune cells, change the content and expression of inflammatory mediators, and regulate specific cellular functions and inflammation-related signaling pathways, are summarized and discussed in detail. This comprehensive review contributes to a better understanding of the role of AMPs in the regulation of the immune system and provides a reference for the use of AMPs as novel anti-inflammatory drugs for the treatment of various inflammatory diseases.

9.
J Am Chem Soc ; 145(31): 17087-17095, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37523458

RESUMO

Transition-metal-catalyzed [4 + 1] reaction of dienes and carbon monoxide (CO) is the most straightforward and easily envisioned cyclization for the synthesis of five-membered carbocycles, which are ubiquitously found in natural products and functional molecules. Unfortunately, no test of this reaction was reported, and consequently, chemists do not know whether such kind of reaction works or not. Herein, we report that the [4 + 1] reaction of common dienes and CO cannot work, at least under the catalysis of [Rh(cod)Cl]2. However, using cyclopropyl-capped dienes (also named allylidenecyclopropanes) as substrates, the corresponding [4 + 1] reaction with CO proceeds smoothly in the presence of [Rh(cod)Cl]2. This [4 + 1] reaction, with a broad scope, provides efficient access to five-membered carbocyclic compounds of spiro[2.4]hept-6-en-4-ones. The [4 + 1] cycloadducts can be further transformed into other molecules by using the unique chemistry of cyclopropyl groups present in these molecules. The mechanism of this [4 + 1] reaction has been investigated by quantum chemical calculations, uncovering that cyclopropyl-capped dienes are strained dienes and the oxidative cyclization step in the [4 + 1] catalytic cycle can release this (angular) strain both kinetically and thermodynamically. The strain release in this step then propagates to all followed CO coordination/CO insertion/reductive elimination steps in the [4 + 1] catalytic cycle, helping the realization of this cycloaddition reaction. In contrast, common dienes (including cyclobutyl-capped dienes) do not have such advantages and their [4 + 1] reaction suffers from energy penalty in all steps involved in the [4 + 1] catalytic cycle. The reactivity of ene-allenes for the [4 + 1] reaction with CO is also discussed.

10.
Neural Netw ; 165: 677-688, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37385022

RESUMO

Deep reinforcement learning (DRL) has been proven as a powerful approach for robot navigation over the past few years. DRL-based navigation does not require the pre-construction of a map, instead, high-performance navigation skills can be learned from trial-and-error experiences. However, recent DRL-based approaches mostly focus on a fixed navigation target. It is noted that when navigating to a moving target without maps, the performance of the standard RL structure drops dramatically on both the success rate and path efficiency. To address the mapless navigation problem with moving target, the predictive hierarchical DRL (pH-DRL) framework is proposed by integrating the long-term trajectory prediction to provide a cost-effective solution. In the proposed framework, the lower-level policy of the RL agent learns robot control actions to a specified goal, and the higher-level policy learns to make long-range planning of shorter navigation routes by sufficiently exploiting the predicted trajectories. By means of making decisions over two level of policies, the pH-DRL framework is robust to the unavoidable errors in long-term predictions. With the application of deep deterministic policy gradient (DDPG) for policy optimization, the pH-DDPG algorithm is developed based on the pH-DRL structure. Finally, through comparative experiments on the Gazebo simulator with several variants of the DDPG algorithm, the results demonstrate that the pH-DDPG outperforms other algorithms and achieves a high success rate and efficiency even though the target moves fast and randomly.


Assuntos
Aprendizagem , Reforço Psicológico , Algoritmos , Tomada de Decisões , Políticas
11.
Ann Med ; 54(1): 3286-3298, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36411543

RESUMO

OBJECTIVE: To explore the clinical manifestations and search for the variants of six related genes (LRP5, FZD4, TSPAN12, NDP, KIF11 and ZNF408) in Chinese patients with familial exudative vitreoretinopathy (FEVR), and investigate the correlation between the genetic variants and the clinical characteristics. PATIENTS AND METHODS: Clinical data, including the retinal artery angle, acquired from wide-field fundus imaging, structural and microvascular features of the retina obtained from optical coherence tomography (OCT) and OCT angiography (OCTA) were collected from 33 pedigrees. Furthermore, mutation screening was performed. Variants filtering, bioinformatics analysis and Sanger sequencing were conducted to verify the variants. RESULTS: Twenty-one variants were successfully detected in 16 of 33 families, of which 10 variants were newly identified. The proportion of variants in LRP5, FZD4, TSPAN12, NDP and KIF11 was 38.1% (8/21), 33.3% (7/21), 19.1% (4/21), 4.8% (1/21) and 4.8% (1/21), respectively. Three new variants were considered to be pathogenic or likely pathogenic. The FEVR group tended to exhibit a smaller retinal artery angle, higher incidence of foveal hypoplasia and lower vascular density compared to the control group. Patients who harboured variants of FZD4 exhibited greater severity of FEVR than those with LRP5 variants. However, those who harboured LRP5 variants tended to possess lower foveal vascular density. CONCLUSIONS: Six known pathogenic genes were screened in 33 pedigrees with FEVR in our study, which revealed 10 novel variants. These findings enrich the clinical features and mutation spectrum in Chinese patients with FEVR, revealing the genotype-phenotype relationship, and contributing to the diagnosis and treatment of the disease.Key messagesWe identified 21 variants in 5 genes (LRP5, FZD4, TSPAN12, NDP and KIF11) associated with FEVR, 10 of which are novel (three were pathogenic or likely pathogenic).The proportion of variants was the highest for the LRP5 gene.FZD4 variants may be responsible for greater FEVR severity than LRP5 variants.


Assuntos
Oftalmopatias Hereditárias , Doenças Retinianas , Humanos , Vitreorretinopatias Exsudativas Familiares , Análise Mutacional de DNA , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Oftalmopatias Hereditárias/genética , Receptores Frizzled/genética , Tetraspaninas/genética , Doenças Retinianas/genética , Doenças Retinianas/epidemiologia , Mutação , China/epidemiologia , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/genética
12.
Br J Cancer ; 126(12): 1663-1675, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35228677

RESUMO

The binding of T cell immune checkpoint proteins programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to their ligands allows immune evasion by tumours. The development of therapeutic antibodies, termed checkpoint inhibitors, that bind these molecules or their ligands, has provided a means to release this brake on the host anti-tumour immune response. However, these drugs are costly, are associated with potentially severe side effects, and only benefit a small subset of patients. It is therefore important to identify biomarkers that discriminate between responders and non-responders. This review discusses the determinants for a successful response to antibodies that bind PD-1 or its ligand PD-L1, dividing them into markers found in the tumour biopsy and those in non-tumour samples. It provides an update on the established predictive biomarkers (tumour PD-L1 expression, tumour mismatch repair deficiency and tumour mutational burden) and assesses the evidence for new potential biomarkers.


Assuntos
Antígeno B7-H1 , Neoplasias Colorretais , Animais , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Biomarcadores Tumorais/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/imunologia , Humanos , Ligantes , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
13.
Nanotechnology ; 33(21)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35147519

RESUMO

In this paper, nanostructured molybdenum selenide (MoSe2) with composited phases are synthesized by hydrothermal method, and the products are modified by metal anoparticles to improve the gas sensing performance. Microstructure characterization shows that few layered 1T/2H-MoSe2nanosheets have been successfully prepared. Both the morphology and component of nanosheets could be tuned by the reaction parameters. It is shown the MoSe2-based nanomaterials have excellent selectivity to nitrogen dioxide (NO2) according to gas sensing properties measurement. The sensitivity of 1T/2H-MoSe2nanosheets modified by Cu nanoparticles is 17.73 (50 ppm NO2) at the optimal operating temperature, which is the highest compared with other samples. The sensors also exhibit rapid response/recovery time and high stability. The sensing mechanism of MoSe2nanosheets toward NO2is investigated based on the first-principles calculation. The results suggest the modification by metal nanoparticles could significantly improve the adsorption energy and charge transfer between gas molecule and MoSe2. This work demonstrates a promising guidance for the design of new NO2gas sensing materials and devices.

14.
Nanotechnology ; 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35144246

RESUMO

In this paper, nanostructured Molybdenum Selenide (MoSe2) with composited phases are synthesized by hydrothermal method, and the products are modified by metal anoparticles to improve the gas sensing performance. Microstructure characterization shows that few layered 1T/2H-MoSe2 nanosheets have been successfully prepared. Both the morphology and composition of nanosheets could be tuned by the reaction parameters. It is shown the MoSe2-based nanomaterials have excellent selectivity to Nitrogen dioxide (NO2) according to gas sensing properties measurement. The sensitivity of 1T/2H-MoSe2 nanosheets modified by Cu nanoparticles is 17.73 (50 ppm NO2) at the optimal operating temperature, which is the highest compared with other samples. The sensors also exhibit rapid response/recovery time and high stability. The sensing mechanism of MoSe2 nanosheets toward NO2 is investigated based on the first-principles calculation. The results suggest the modification by metal nanoparticles could significantly improve the adsorption energy and the charge transfer between gas molecule and MoSe2. This work demonstrates a promising guidance for the design of new NO2 gas sensing materials and devices.

15.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1866(11): 159024, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34389520

RESUMO

Fascial adipocytes are recently identified as a unique population of adipose cells, which have different developmental origins, anatomical locations, cytological and functional characteristics compared with subcutaneous or visceral adipocytes. Superficial fascia in rats (also in pigs but not obviously in mice) contains numbers of lineage committed preadipocytes which possess adipogenic potential in vivo. The present study aimed to investigate the physiological factors that contribute to fascial adipogenesis in rats. We detected that mast cells, adipose progenitor cells, and mature adipocytes distributed in certain fascia areas were closely associated with each other, and numerous heparin-loaded granules released from mast cells were distributed around fascial preadipocytes. The culture supernatants of rat peritoneal mast cells and RBL-2H3 mast cells contained 20-30 µg/ml of heparin, effectively activated PPAR-responsive luciferase activity, promoted mRNA and protein expressions of key adipogenic genes, and hence increased adipogenic differentiation of fascia- or epididymal adipose-derived stromal cells. Adipogenic effects of mast cell supernatants were mimicked by heparin but not by histamine or 5-hydroxytryptamine, and were antagonized by protamine sulfate. In rats, local administration of heparin-loaded microspheres for 30 days induced adipogenesis in local areas of superficial fascia. This adipogenic effects of heparin might be related by chain length of glucosamine units, because heparin stimulated stronger adipogenesis than dalteparin and enoxaparin with relatively short chains. Our findings suggested that mast cell and its granule heparin could serve as the endogenous physiological factors to initiate and accelerate local adipogenesis in superficial fascia, or in adipose tissue with the fascia naturally embedded inside.


Assuntos
Heparina/metabolismo , Mastócitos/metabolismo , Tela Subcutânea/metabolismo , Adipogenia , Animais , Células Cultivadas , Masculino , Ratos , Ratos Sprague-Dawley
16.
Mol Pharm ; 18(6): 2285-2297, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33998814

RESUMO

Cholecystokinin-2 receptor (CCK2R) has been proven to be a specific biomarker for colorectal malignancies. Immunotoxins are a valuable class of immunotherapy agents consisting of a targeting element and a bacterial or plant toxin. Previous work demonstrated that targeting CCK2R is a good therapeutic strategy for the treatment of colorectal cancer (CRC). In the present study, we developed a new version of CCK2R-targeting immunotoxin GD9P using a targeted peptide, GD9, as the binding motif and a truncated Pseudomonas exotoxin A (PE38) as the cytokiller. BALB/c nude mice were treated with different doses of GD9P, and pharmacodynamics, pharmacokinetic, and toxicological data were obtained throughout this study. Compared to the parental immunotoxin rCCK8PE38, GD9P exhibited about 1.5-fold yield, higher fluorescence intensity, and increased antitumor activity against human CRC in vitro and in vivo. The IC50 values of GD9P in vitro ranged from 1.61 to 4.55 nM. Pharmacokinetic studies were conducted in mice with a T1/2 of 69.315 min. When tumor-bearing nude mice were treated with GD9P at doses ≥2 mg/kg for five doses, a rapid shrinkage in tumor volume and, in some cases, complete remission was observed. A preliminary safety evaluation demonstrated a good safety profile of GD9P as a Pseudomonas exotoxin A-based immunotherapy. The therapy in combination with oxaliplatin can increase the antitumor efficacy and reduce the toxic side effects caused by chemotherapy. In conclusion, the data support the use of GD9P as a promising immunotherapy targeting CCK2R-expressing colorectal malignancies.


Assuntos
ADP Ribose Transferases/farmacologia , Antineoplásicos/farmacologia , Toxinas Bacterianas/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Exotoxinas/farmacologia , Receptor de Colecistocinina B/antagonistas & inibidores , Proteínas Recombinantes de Fusão/farmacologia , Fatores de Virulência/farmacologia , ADP Ribose Transferases/genética , ADP Ribose Transferases/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Toxinas Bacterianas/genética , Toxinas Bacterianas/uso terapêutico , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Exotoxinas/genética , Exotoxinas/uso terapêutico , Humanos , Camundongos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/uso terapêutico , Distribuição Tecidual , Testes de Toxicidade Aguda , Fatores de Virulência/genética , Fatores de Virulência/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Exotoxina A de Pseudomonas aeruginosa
17.
Anal Biochem ; 621: 114157, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33705723

RESUMO

Pathogenic Yersinia (Y.) enterocolitica is the primary causative agent of Yersiniosis, with outbreaks in numerous countries around the world, and causes diarrhea and vomiting in animals and humans. Therefore, an instrument-free and convenient nucleic acid visualization method, RPA-SYBR Green I, was established, which combines recombinase polymerase amplification (RPA) with the fluorescent dye SYBR Green I for the detection of the adhesion gene ail in pathogenic Y. enterocolitica. After optimization of a series of conditions such as primer concentration, the detection of pathogenic Y. enterocolitica could be finally completed within about 20 min (from DNA extraction to observation of results) at an isothermal temperature of 39°C. RPA-SYBR Green I had no cross-reactivity with other bacteria and the detection limit was 101 CFU/µL, with sensitivity equal to that of conventional PCR. The method established in this paper and conventional PCR identified a total of 5 spiked samples and 15 meat samples stored in refrigerated, and it was concluded that there was 100% consistency between the two methods. Overall, RPA-SYBR Green I is a visual and facilitate detection assay that can accurately discover pathogenic Y. enterocolitica.


Assuntos
Benzotiazóis/química , Diaminas/química , Fluorometria/métodos , Microbiologia de Alimentos/métodos , Carne/microbiologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Quinolinas/química , Yersinia enterocolitica/genética , Proteínas da Membrana Bacteriana Externa/genética , DNA Bacteriano/análise , DNA Bacteriano/genética , Carne/análise , Recombinases/metabolismo , Reprodutibilidade dos Testes , Temperatura , Yersinia enterocolitica/isolamento & purificação
18.
Emerg Microbes Infect ; 10(1): 356-364, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33560938

RESUMO

Listeria monocytogenes is an important foodborne pathogen, and is ubiquitously distributed in the natural environment. Cattle and sheep, as natural hosts, can transmit L. monocytogenes to related meat and dairy products. In this study, the prevalence, distribution, and transmission characteristics of Listeria were analysed by investigating 5214 samples of cattle and sheep in farm and slaughtering environments in China. A low contamination incidence of L. monocytogenes (0.5%, 20/4430) was observed in farm environment, but there was a high contamination incidence in slaughtering environment (9.4%, 74/784). The incidence of L. innocua in cattle and sheep farm and slaughtering environments is more common and significantly higher (9.7%, 508/5214) than that of L. monocytogenes (1.8%, 94/5214). The distinct molecular and genetic characteristics of Listeria by PFGE and MLST indicated that L. monocytogenes and L. innocua were gradually transmitted from the farm and slaughtering environments to end products, such as beef and mutton along the slaughtering chain. The ST7, ST9, ST91, and ST155 found in our study were associated with the human listeriosis cases in China. In addition, the findings of virulence markers (inlC, inlJ, LIPI-3, LIPI-4, and ECIII) concerned with the pathogenesis of human listeriosis and antibiotics resistance of L. monocytogenes in this study implies a potential public health risk. This study fills the gap in the epidemiology of beef cattle and sheep that carry Listeria in farm and slaughtering environments in major cattle and sheep producing areas in China.


Assuntos
Doenças dos Bovinos/microbiologia , Listeria/isolamento & purificação , Listeriose/veterinária , Doenças dos Ovinos/microbiologia , Matadouros/estatística & dados numéricos , Animais , Bovinos , China , Fazendas , Manipulação de Alimentos , Inocuidade dos Alimentos , Listeria/classificação , Listeria/genética , Listeriose/microbiologia , Carne/microbiologia , Prevalência , Ovinos
19.
Phys Rev Lett ; 126(6): 063201, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33635700

RESUMO

The dissociative above-threshold double ionization (ATDI) of H_{2} in strong laser fields involves the sequential releasing of two electrons at specific instants with the stretching of the molecular bond. By mapping the releasing instants of two electrons to their emission directions in a multicycle polarization-skewed femtosecond laser pulse, we experimentally clock the dissociative ATDI of H_{2} via distinct photon-number-resolved pathways, which are distinguished in the kinetic energy release spectrum of two protons measured in coincidence. The timings of the experimentally resolved dissociative ATDI pathways are in good accordance with the classical predictions. Our results verify the multiphoton scenario of the dissociative ATDI of H_{2} in both time and energy fashion, strengthening the understanding of the strong-field phenomenon and providing a robust tool with a subcycle time resolution to clock abundant ultrafast dynamics of molecules.

20.
RSC Adv ; 11(40): 25004-25009, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35481043

RESUMO

Tin dioxide (SnO2) nanomaterials are important acid catalysts. It is therefore crucial to obtain details about the surface acidic properties in order to develop structure-property relationships. Herein, we apply 31P solid-state NMR spectroscopy combined with a trimethylphosphine (TMP) probe molecule, to study the facet-dependent acidity of SnO2 nanosheets and nanoshuttles. With the help of density functional theory calculations, we show that the tin cations exposed on the surfaces are Lewis acid sites and their acid strengths rely on surface geometries. As a result, the (001), (101), (110), and (100) facets can be differentiated by the 31P NMR shifts of adsorbed TMP molecules, and their fractions in different nanomaterials can be extracted according to deconvoluted 31P NMR resonances. The results provide new insights on nanosized oxide acid catalysts.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...