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2.
Sci China Life Sci ; 65(12): 2341-2353, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36374369

RESUMO

Goldfish (Carassius auratus) have long fascinated evolutionary biologists and geneticists because of their diverse morphological and color variations. Recent genome-wide association studies have provided a clue to uncover genomic basis underlying these phenotypic variations, but the causality between phenotypic and genotypic variations have not yet been confirmed. Here, we edited proposed candidate genes to recreate phenotypic traits and developed a rapid biotechnology approach which combines gene editing with high-efficiency breeding, artificial gynogenesis, and temperature-induced sex reversal to establish homozygous mutants within two generations (approximately eight months). We first verified that low-density lipoprotein receptor-related protein 2B (lrp2aB) is the causal gene for the dragon-eye variation and recreated the dragon-eye phenotype in side-view Pleated-skirt Lion-head goldfish. Subsequently, we demonstrated that the albino phenotype was determined by both homeologs of oculocutaneous albinism type II (oca2), which has subfunctionalized to differentially govern melanogenesis in the goldfish body surface and pupils. Overall, we determined two causal genes for dragon-eye and albino phenotypes, and created four stable homozygous strains and more appealing goldfish with desirable traits. The developed biotechnology approach facilitates precise genetic breeding, which will accelerate re-domestication and recreation of phenotypically desirable goldfish.

3.
Bioengineering (Basel) ; 9(11)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36421085

RESUMO

With the incidence of harmful algal blooms (HABs) increasing in recent years, the urgent demand for the detection of domoic acid (DA), an amnesic shellfish toxin mainly produced by red tide algae Pseudonitzschia, has aroused increasing attention. Aptamers, a new molecular recognition element, provide clarity in the monitoring of DA. In this study, aptamers of DA were successfully screened by Capture-SELEX. Through identification and truncation optimization, aptamer C1-d with a high affinity (KD value, 109 nM) and high specificity for DA was obtained. The binding mechanism between DA and the aptamer was explored by molecular docking and molecular dynamics (MD) simulation, revealing the critical sites for DA-aptamer interaction. Meanwhile, a BLI-based aptasensor was constructed by C1-d, which displayed a linear range from 0.625 to 10 µM and a LOD of 13.7 nM. This aptasensor exhibited high specificity, good precision and repeatability, and high recovery rates for real samples; the process of detection could be completed in 7 min. This study is the first to identify and investigate the binding mechanism of DA-aptamer interaction and constructed a BLI-based aptasensor for DA, which lays a theoretical foundation for the detection and prevention of DA.

4.
Sci Rep ; 12(1): 18661, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333334

RESUMO

To evaluate the clinical therapeutic effects of a technique in which biological amniotic membranes (bAMs) are used in the treatment of patients with recurrent macular holes. In this prospective nonrandomized case series study, 23 eyes of 23 patients with recurrent macular holes who had already undergone surgery with pars plana vitrectomy with internal limiting membrane peeling were evaluated. In the surgery, a bAM was used to cover the macular area, and C3F8 tamponade was performed on these patients. Phacoemulsification combined with intraocular lens implantation was performed simultaneously in patients who had cataracts. Patients were followed up for at least half a year. The main outcomes were whether the macular hole closed, the morphological changes in the macular graft, the best-corrected visual acuity, intraocular pressure (IOP) and other indicators. In all eyes, the recurrent macular holes were closed. Two cases (8.69%, 2/23) had bAM shifting half a month after surgery, and these patients underwent a second surgery to adjust the position of the bAM and perform C3F8 tamponade. In the 6-month follow-up, 21 patients (91.30%, 21/23) had improved visual acuity (VA), and 2 patients (8.69%, 2/23) had no change in VA. The mean VA increased from 1.73 ± 0.32 before surgery to 1.12 ± 0.42 after surgery (t = 10.63, P = 0.00 < 0.01), and the mean IOP decreased from 22.13 ± 5.56 before surgery to 17.23 ± 1.71 after surgery (t = 5.14, P = 0.00 < 0.01). No serious complications occurred in any of the cases. The technique of using a biological amniotic membrane can be an effective treatment for patients with recurrent macular holes.


Assuntos
Membrana Epirretiniana , Perfurações Retinianas , Humanos , Perfurações Retinianas/cirurgia , Membrana Epirretiniana/cirurgia , Âmnio , Membrana Basal , Estudos Prospectivos , Vitrectomia/métodos , Resultado do Tratamento , Estudos Retrospectivos , Tomografia de Coerência Óptica
5.
Gene Expr Patterns ; 46: 119286, 2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36341978

RESUMO

Foxl2 plays conserved central function in ovarian differentiation and maintenance in several fish species. However, its expression pattern and function in fish embryogenesis are still largely unknown. In this study, we first presented a sequential expression pattern of zebrafish foxl2a and foxl2b during embryo development. They were predominantly expressed in the cranial paraxial mesoderm (CPM) and cranial venous vasculature (CVV) during somitogenesis and subsequently expressed in the pharyngeal arches after 48 h post-fertilization (hpf). Then, we compared the brain structures among zebrafish wildtype (WT) and three homozygous foxl2 mutants (foxl2a-/-, foxl2b-/- and foxl2a-/-;foxl2b-/-) and found the reduction of the fourth ventricle in the three foxl2 mutants, especially in foxl2a-/-;foxl2b-/- mutant. Finally, we detected several key transcription factors involved in the gene regulatory network of midbrain-hindbrain boundary (MHB) patterning, such as wnt1, en1b and pax2a. Their expression levels were obviously downregulated in MHB of foxl2a-/- and foxl2a-/-;foxl2b-/- mutants. Thus, we suggest that Foxl2a and Foxl2b are involved in MHB and the fourth ventricle development in zebrafish. The current study provides insights into the molecular mechanism underlying development of brain ventricular system.

6.
Cell Host Microbe ; 30(11): 1602-1614.e5, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36240763

RESUMO

Plants employ cell-surface-localized pattern recognition receptors (PRRs) to recognize immunogenic patterns and activate defenses. How these receptors regulate immune signaling in the nucleus is not well understood. Our previous studies showed that BIK1, a central kinase associated with PRRs, phosphorylates a plant-specific Gα protein called extra-large G protein 2 (XLG2) to positively regulate immunity. Here, we show that this phosphorylation promotes XLG2 nuclear translocation, which is essential for antibacterial immunity. XLG2 interacts with nuclear-localized MUT9-like kinases (MLKs) to regulate transcriptome programming. MLKs negatively regulate plant immunity in a kinase activity-dependent manner, whereas XLG2 promotes defense gene expression and antibacterial immunity likely by inhibiting MLK kinase activity. A C-terminal motif in MLKs is essential for the interaction with XLG2, and this motif is required for the XLG2-mediated defense activation. Together, our findings reveal a previously unknown pathway and mechanisms by which cell surface receptors regulate transcriptome during pathogen invasion.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas Quinases/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Serina-Treonina Quinases , Imunidade Vegetal/fisiologia , Receptores de Reconhecimento de Padrão , Fosforilação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Antibacterianos/metabolismo
7.
Nat Plants ; 8(10): 1160-1175, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36241731

RESUMO

Rapid production of H2O2 is a hallmark of plant responses to diverse pathogens and plays a crucial role in signalling downstream of various receptors that perceive immunogenic patterns. However, mechanisms by which plants sense H2O2 to regulate immunity remain poorly understood. We show that endogenous H2O2 generated upon immune activation is sensed by the thiol peroxidase PRXIIB via oxidation at Cys51, and this is essential for stomatal immunity against Pseudomonas syringae. We further show that in immune-stimulated cells, PRXIIB conjugates via Cys51 with the type 2C protein phosphatase ABA insensitive 2 (ABI2), subsequently transducing H2O2 signal to ABI2. This oxidation dramatically sensitizes H2O2-mediated inhibition of the ABI2 phosphatase activity in vitro and is required for stomatal immunity in plants. Together, our results illustrate a redox relay, with PRXIIB as a sensor for H2O2 and ABI2 as a target protein, that mediates reactive oxygen species signalling during plant immunity.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Peróxido de Hidrogênio/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peroxidase/metabolismo , Compostos de Sulfidrila/metabolismo , Imunidade Vegetal , Oxirredução , Peroxidases/metabolismo
8.
Front Cell Infect Microbiol ; 12: 984835, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189354

RESUMO

Sepsis is a significant cause of mortality in critically ill patients. Acute lung injury (ALI) is a leading cause of death in these patients. Endothelial cells exposed to the bacterial endotoxin lipopolysaccharide (LPS) can progress into pyroptosis, a programmed lysis of cell death triggered by inflammatory caspases. It is characterized by lytic cell death induced by the binding of intracellular LPS to caspases 4/5 in human cells and caspase-11 in mouse cells. In mice,caspase-11-dependent pyroptosis plays an important role in endotoxemia. HMGB1 released into the plasma binds to LPS and is internalized into lysosomes in endothelial cells via the advanced glycation end product receptor. In the acidic lysosomal environment, HMGB1 permeates the phospholipid bilayer, which is followed by the leakage of LPS into the cytoplasm and the activation of caspase-11. Heparin is an anticoagulant widely applied in the treatment of thrombotic disease. Previous studies have found that heparin could block caspase-11-dependent inflammatory reactions, decrease sepsis-related mortality, and reduce ALI, independent of its anticoagulant activity. Heparin or modified heparin with no anticoagulant property could inhibit the alarmin HMGB1-LPS interactions, minimize LPS entry into the cytoplasm, and thus blocking caspase-11 activation. Heparin has been studied in septic ALI, but the regulatory mechanism of pulmonary endothelial cell pyroptosis is still unclear. In this paper, we discuss the potential novel role of heparin in the treatment of septic ALI from the unique mechanism of pulmonary endothelial cell pyroptosis.


Assuntos
Lesão Pulmonar Aguda , Proteína HMGB1 , Sepse , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Alarminas , Animais , Caspases , Células Endoteliais/metabolismo , Endotoxinas , Produtos Finais de Glicação Avançada , Proteína HMGB1/metabolismo , Heparina/farmacologia , Humanos , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Fosfolipídeos , Piroptose , Sepse/complicações , Sepse/tratamento farmacológico
9.
Open Life Sci ; 17(1): 1182-1190, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185410

RESUMO

Matrix metalloproteinase-2 (MMP-2) and cluster of differentiation 147 (CD147) both play important roles in the development of kidney fibrosis, and CD147 can induce the production and activation of MMP-2. In the early stage of kidney fibrosis, MMP-2 promotes extracellular matrix (ECM) production and accelerates the development of kidney fibrosis, while in the advanced stage, MMP-2 activity decreases, leading to reduced ECM degradation and making it difficult to alleviate kidney fibrosis. The reason for the decrease in MMP-2 activity in the advanced stage is still unclear. On the one hand, it may be related to hypoxia and endocytosis, which lead to changes in the expression of MMP-2-related active regulatory molecules; on the other hand, it may be related to insufficient CD147 function. At present, the specific process by which CD147 is involved in the regulation of MMP-2 activity is not completely clear, and further in-depth studies are needed to clarify the roles of both factors in the pathophysiology of kidney fibrosis.

10.
Orthop Surg ; 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36217905

RESUMO

OBJECTIVE: Research on proximal fractures in the humeral bicipital groove (BG), a region in which bones are not commonly fractured, is considered sparse in the literature. The objective of this research was to present the definite characteristics and distribution of BG fractures. METHODS: This retrospective study included and enrolled 119 proximal humeral fractures in adult patients with complete radiography data to identify the fracture distribution in the BG from January 2021 to August 2021. The bicipital region was divided into three parts, i.e. the upper 1/3, middle 1/3, and lower 1/3 of the BG, and the distribution of fracture lines was transcribed on the male or female template, as appropriate. In addition, the normal contralateral humerus was used to calculate the cortical thickness of the supratubercular groove and different parts of the BG (upper, middle, and lower parts). The Mann-Whitney test or one-way ANOVA along with LSD tests were used to determine differences in the fracture distribution and cortical thickness between men and women. RESULTS: Fractures of the BG in both men and women were mainly located in the upper 2/3 region of the BG, especially in the middle 1/3 of the BG. There were significant differences in the cortical thickness of the BG in men compared with that in women. The cortical thickness was highest in the supratubercular ridge but not the BG in men and women, respectively. CONCLUSION: This research concluded that bony BG fractures were always observed in the middle part of the BG and were mainly found in patients with four fractures of the proximal humerus. As a unique fracture pattern, the existence of a bony BG fracture always means that a patient has been injured by a relatively severe mechanism, and more attention should be given to these proximal humeral fractures.

11.
Toxins (Basel) ; 14(10)2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36287974

RESUMO

Conotoxins (CTXs) are a variety of mixed polypeptide toxins, among which α-conotoxin MI (CTX-MI) is the most toxic. Serious toxic symptoms, a lack of counteracting drugs, and cumbersome detection processes have made CTX-MI a hidden danger for humans. One of the obstacles to resolving this problem is the absence of specific recognition elements. Aptamers have shown great advantages in the fields of molecule detection, drug development, etc. In this study, we screened and characterized aptamers for CTX-MI through a programmed process. MBMI-01c, the isolated aptamer, showed great affinity, with an affinity constant (KD) of 0.524 µM, and it formed an antiparallel G-quadruplet (GQ) structure for the specific recognition of CTX-MI. Additionally, an aptasensor based on the biolayer interferometry (BLI) platform was developed and displayed high precision, specificity, and repeatability with a limit of detection (LOD) of 0.26 µM. This aptasensor provides a potential tool for the rapid detection of CTX-MI in 10 min. The aptamer can be further developed for the enrichment, detoxification, and biological studies of CTX-MI. Additionally, the programmed process is applicable to screening and characterizing aptamers for other CTXs.


Assuntos
Aptâmeros de Nucleotídeos , Conotoxinas , Humanos , Técnica de Seleção de Aptâmeros , Aptâmeros de Nucleotídeos/química , Limite de Detecção
12.
Medicina (Kaunas) ; 58(10)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36295613

RESUMO

Background and Objectives: The role of α-enolase (ENO1) in Helicobacter pylori-related gastric lesions might be a critical factor in the pathogenesis, but remains undefined. Materials and Methods: This study investigated the differential expression of α-enolase in clinical gastric specimens and cultured normal/cancer cells in response to H. pylori (cagA+) infection and cagA transfection using qPCR, Western blots and histochemical methods. Results: A total of 172 gastric specimens were collected from 142 patients, the former comprising chronic superficial gastritis (CSG), precancerous diseases (PCDs, including atrophic gastritis, intestinal metaplasia and dysplasia) and gastric cancer (GC) cases. Among the CSG and PCD cases, the H. pylori-infected group had significantly elevated ENO1 mRNA levels compared with the uninfected group. In the GC cases, differential ENO1 expressions were detected between the cancer tissues and the paracancerous tissues. Notably, significant difference was first detected between the GC cell (AGS) and the normal cell (GES-1) as a response of ENO1 to H. pylori infection and cagA transfection. Conclusions: This report reveals that ENO1 expression is associated with H. pylori infection, cagA transfection, co-culture duration, multiplicity of infection, gastric normal/cancerous cell lines and cellular differentiation. The findings may be crucial bases for further ascertaining H. pylori pathogenic mechanism and formulating novel therapeutic and diagnostic strategies.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Infecções por Helicobacter/complicações , Helicobacter pylori/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/complicações , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/metabolismo , Linhagem Celular , Transfecção , RNA Mensageiro/metabolismo , Mucosa Gástrica/metabolismo
13.
Medicine (Baltimore) ; 101(41): e31010, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36254090

RESUMO

Primary trigeminal neuralgia (PTN) is characterized by chronic neuropathic pain. There are few studies exploring masticatory muscle changes in patients with PTN. This study evaluated the changes in the masticatory muscles using magnetic resonance imaging (MRI) and the predictive factors of masticatory muscle changes in patients with PTN. The radiologic outcomes of 52 patients with PTN and 58 healthy adults were evaluated. The temporalis, lateral pterygoid, medial pterygoid, and masseter muscles were assessed using MRI. Atrophy and edema of the masticatory muscles were noted. Multivariate analyses were conducted to identify factors associated with masticatory muscle atrophy. Among the PTN group, the right side (61.5%) and mandibular branch (53.9%) were the most affected. Muscle atrophy of the temporalis (P < .001), medial pterygoid (P = .016), lateral pterygoid (P = .031), and masseter (P = .001) were significantly higher in the PTN group than in the control group. Lateral pterygoid edema was significantly higher in the PTN group (P < .001). However, no significant difference was found in the temporalis and masseter edema between the two groups. Logistic regression analysis demonstrated that neurovascular conflict (NVC) significantly predicted mastication muscle atrophy (P = .037). Patients with PTN had higher rates of masticatory muscle atrophy and edema. The assessment of NVC may be a preoperative imaging biomarker to predict atrophy in PTN.


Assuntos
Cirurgia de Descompressão Microvascular , Neuralgia do Trigêmeo , Adulto , Humanos , Imageamento por Ressonância Magnética , Músculo Masseter/diagnóstico por imagem , Músculos da Mastigação/diagnóstico por imagem , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Neuralgia do Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/patologia , Neuralgia do Trigêmeo/cirurgia
14.
Food Funct ; 13(20): 10665-10679, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36172720

RESUMO

The improvement of lipid metabolism by capsaicin (CAP) has been extensively studied, mostly with respect to the vanilloid type 1 (TRPV1) ion channel and intestinal flora. In this study, a model was established in germ-free mice by using resiniferatoxin (RTX) to ablate TRPV1 ion channels. Bile acid composition, blood parameters, and colonic transcriptome analyses revealed that CAP could improve dyslipidemia caused by high-fat diet even in the absence of TRPV1 ion channels and intestinal flora. CAP fed to germ mice decreased the concentrations of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), fasting blood glucose and fasting insulin, increased the concentration of high-density lipoprotein (HDL-C), and decreased the levels of plasma endotoxin and pro-inflammatory factor interleukin 6 (IL-6). Furthermore, CAP could affect both classical and alternative pathways of cholesterol conversion by changing the composition of bile acids, reducing the concentrations of glycocholic acid (GCA), ursodeoxycholic acid (UDCA) and glycochenodeoxycholic acid (GCDCA). First, changing the composition of bile acids inhibited the expression of colon Fgf15. CAP promoted the expression of Cyp7a1 (Cytochrome p450, family 7, subfamily a, and polypeptide 1) in the liver, and thus reduced TC and TG levels. In addition, it could change the composition of bile acids and increase the expression of Cyp7b1 (Cytochrome p450, family 7, subfamily b, and polypeptide 1) in the colon, increase Cyp7b1 protein in the liver and thus inhibit fat accumulation. In conclusion, CAP could alter the composition of bile acids and promote the conversion of cholesterol to bile acids, thereby improving lipid metabolism abnormalities caused by a high-fat diet.


Assuntos
Dislipidemias , Insulinas , Animais , Ácidos e Sais Biliares/metabolismo , Glicemia/metabolismo , Capsaicina , Colesterol/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , Dislipidemias/metabolismo , Endotoxinas , Ácido Glicoquenodesoxicólico/metabolismo , Insulinas/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipoproteínas HDL , Fígado/metabolismo , Camundongos , Triglicerídeos/metabolismo , Ácido Ursodesoxicólico/metabolismo
15.
Int J Lab Hematol ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064206

RESUMO

INTRODUCTION: Paediatric AML patients with hyperleukocytosis have a poor prognosis and higher early mortality. Therefore, more studies are needed to explore relevant prognostic indicators and develop effective prevention strategies for this type of childhood AML. METHODS: All original data were obtained from the TARGET database. First, we explored meaningful differentially expressed genes (DEGs) between the hyperleukocytosis group and the non-hyperleukocytosis group. Next, we screened and identified valuable target genes using univariate Cox regression, Cytoscape software, and Kaplan-Meier survival curves. Finally, the coexpressed genes, functional networks, and immune-related activities associated with the target gene were deeply analysed by the GeneMANIA, LinkedOmics, GEPIA2021, TISIDB, and GSCA databases. RESULTS: We selected 1229 DEGs between the hyperleukocytosis group and the non-hyperleukocytosis group in paediatric AML patients. Among them, 495 DEGs were significantly linked with the overall survival of paediatric AML patients. Further, we discovered that CX3CR1 was a promising target gene. Meanwhile, we identified CX3CR1 as an independent prognostic predictor. Besides, we showed that CX3CR1 had strong physical interactions with CX3CL1. Additionally, functional network analysis suggested that CX3CR1 and its coexpressed genes modulated immune response pathways. Subsequent analysis found that immune cells with a high median value of CX3CR1 were monocytes, resting NK cells and CD8 T cells. Finally, we observed that CX3CR1 expression correlated with infiltrating levels of immune cells and immune signatures. CONCLUSION: Elevated CX3CR1 expression may be an adverse prognostic indicator in paediatric AML patients undergoing hyperleukocytosis. Moreover, CX3CR1 may serve as an immunotherapeutic target for AML with hyperleukocytosis in children.

16.
Front Endocrinol (Lausanne) ; 13: 962303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120426

RESUMO

Objective: The treatment of osteoporotic fractures is difficult, and to minimize the negative result or poor functional rehabilitation, this study focuses on hydrogen water (HRW) to test its effect on the process of menopausal osteoporotic fracture healing and its relationship with autophagy and to try to reveal the potential mechanism of action of HRW on osteoporotic fractures. Materials and methods: A rat osteoporotic fracture model was established, and HRW was systematically applied with or without 3MA. The results were analyzed with X-rays, micro-CT scans, serum biomarker analysis, biomechanical tests, histopathology, immunohistochemistry, and Western blotting. The sham, OVX, OH (OVX+HRW) and OHA (OVX+HRW+3MA) groups were formed and compared. Results: Increased oxidative stress and autophagy levels were necessary physiological responses in the process of fracture healing. It was found that systemic HRW treatment slightly suppressed autophagy and then activated the Keap1-Nrf2 signaling pathway by maintaining the Keap1-Nrf2-P62 interaction and improved the osteoporotic fracture healing process. Conclusion: HRW treatment activated the Keap1-Nrf2 signaling pathway to antagonize cellular stress by suppressing autophagy levels, especially at the early stage of the fracture healing process, and this was beneficial to osteoporotic fracture healing in rats.


Assuntos
Consolidação da Fratura , Fraturas por Osteoporose , Animais , Autofagia , Consolidação da Fratura/fisiologia , Hidrogênio/farmacologia , Hidrogênio/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch , Fator 2 Relacionado a NF-E2 , Ratos , Águas Salinas
17.
Artigo em Inglês | MEDLINE | ID: mdl-36155887

RESUMO

Cognitive impairment is a major complication of diabetes mellitus, which is caused by constitutive hyperglycaemia. Ponicidin is a diterpenoid isolated from a Chinese traditional herb (Rabdosia rubescens) and demonstrates the various pharmacological effects. The goal of this study was to scrutinise the neuroprotective effect of ponicidin against diabetic nephropathy (DN) induced by streptozotocin (STZ). Intraperitoneal administration of STZ (55 mg/kg) was used for the induction of diabetes and rats were received oral administration of ponicidin (5, 10 and 15 mg/kg) until 28 days. The body weight, food intake, water intake and blood glucose level were assessed at regular time interval. Plasma insulin level, antioxidant, inflammatory cytokines, apoptosis marker and faecal gut microbiota compositions were estimated. DN-induced group rats revealed the augmented glucose level, water intake, food intake and reduced body weight. Ponicidin significantly (P < 0.001) repressed the glucose level and water food intake and improved the body weight and plasma insulin. Ponicidin significantly (P < 0.001) repressed the malonaldehyde (MDA) level and boosted the level of glutathione (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) in the brain and serum level. Ponicidin significantly (P < 0.001) repressed the level of interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and enhanced the level of interleukin-4 (IL-4), interleukin-10 (IL-10) in the brain and serum level. DN group rats exhibited the enhanced relative abundance of Firmicutes, along with enhancing the Firmicutes/Bacteroidetes ratio and repressing the Bacteroidetes relative abundance. Ponicidin effectually restored the relative abundance of Allobaculum, Lactobacillus and Ruminococcus genera. Our findings clearly demonstrated that ponicidin has a neuroprotective effect against diabetic cognitive impairment through modulating the gut microbiome.

18.
Materials (Basel) ; 15(18)2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36143789

RESUMO

For achieving successful chemotherapy against cancer, designing biocompatible drug delivery systems (DDSs) with long circulation times, high cellular endocytosis efficiency, and targeted drug release is of upmost importance. Herein, a well-defined PEG-b-P(MASSChol-co-MANBoc) block copolymer bearing redox-sensitive cholesteryl-side group was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization (with non-redox PEG-b-P(MACCChol-co-MAN-DCA) as the reference), and 1,2-dicarboxylic-cyclohexene acid (DCA) was then grafted onto the hydrophobic block to endow it with charge-convertible characteristics under a tumor microenvironment. The amphiphilic copolymer could be assembled into polymeric spherical micelles (SSMCs) with polyethylene glycol (PEG) as the corona/shell, and anti-cancer drug doxorubicin (DOX) was successfully encapsulated into the micellar core via strong hydrophobic and electrostatic interactions. This nanocarrier showed high stability in the physiological environment and demonstrated "smart" surface charge conversion from negative to positive in the slightly acidic environment of tumor tissues (pH 6.5~6.8), as determined by dynamic light scattering (DLS). Moreover, the cleavage of a disulfide bond linking the cholesterol grafts under an intracellular redox environment (10 mM GSH) resulted in micellar dissociation and accelerated drug release, with the non-redox-responsive micelles (CCMCs) as the control. Additionally, a cellular endocytosis and tumor proliferation inhibition study against MCF-7 tumor cells demonstrated the enhanced endocytosis and tumor cell inhibitory efficiency of dual-responsive SSMCs/DOX nanomedicines, revealing potentials as multifunctional nanoplatforms for effective oncology treatment.

19.
Front Surg ; 9: 916483, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090344

RESUMO

Objective: We sought to develop novel nomograms to accurately predict overall survival (OS) of chemotherapy cycles <9 and chemotherapy cycles ≥9 and construct risk stratification to differentiate low-risk and high-risk of two cohorts. Methods: Patients who underwent curative-intent resection for gastric cancer between January 2002 and May 2020 at a single China institution were identified. Variables associated with OS were recorded and analyzed according to multivariable Cox models. Nomograms predicting 3- and 5-year OS were built according to variables resulting from multivariable Cox models. Discrimination ability was calculated using the Harrell's Concordance Index. The constructed nomogram was subjected to 1,000 resamples bootstrap for internal validation. Calibration curves for the new nomograms were used to test the consistency between the predicted and actual 3- and 5-year OS. Decision curve analysis (DCA) was performed to assess the clinical net benefit. The Concordance index (C-index) and time-dependent receiver operating characteristic (t-ROC) curves were used to evaluate and compare the discriminative abilities of the new nomograms. Finally, prognostic risk stratification of gastric cancer was conducted with X-tile software and nomograms converted into a risk-stratified prognosis model. Results: For the nomogram predict OS of chemotherapy cycles <9, C-index was 0.711 (95% CI, 0.663-0.760) in internal validation and 0.722 (95% CI, 0.662-0.783) in external validation, which was better than AJCC 8th edition TNM staging (internal validation: 0.627, 95% CI, 0.585-0.670) and (external validation: 0.595,95% CI, 0.543-0.648). The C-index of the nomogram for chemotherapy cycles ≥9 in internal validation was 0.755 (95% CI, 0.728-0.782) and 0.785 (95% CI, 0.747-0.823) in external validation, which was superior to the AJCC 8th edition TNM staging (internal validation: 0.712 95% CI, 0.688-0.737) and (external validation 0.734, 95% CI, 0.699-0.770).The calibration curves, t-ROC curves and DCA of the two nomogram models show that the recognition performance of the two nomogram models was outstanding. The statistical differences in the prognosis among the two risk stratification groups further showed that our model had an excellent risk stratification performance. Conclusion: This is first reported risk stratification for chemotherapy cycles of gastric carcinoma. Our proposed nomograms can effectively evaluate postoperative prognosis of patients with different chemotherapy cycles of gastric carcinoma. Chemotherapy cycles ≥9 is therefore recommended for high-risk patients with chemotherapy cycles <9, but not for low-risk patients. Meanwhile, combination with multiple therapies are essential to high-risk patients with chemotherapy cycles ≥9 and unnecessary for low-risk patients.

20.
RSC Adv ; 12(38): 24596-24606, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36128397

RESUMO

Polyaspartic acid (PASP), a well-known green scale inhibitor for industrial water treatment, might be decomposed with prolonged duration, and its anti-scaling performance against CaCO3 and CaSO4 is diminished at a low concentration (<10 mg L-1) and a high temperature. With semi-ethylenediaminetetraacetic acid (EDTA) tetrasodium salt as the mimicking model, novel phosphorus-free PASP-capped 2-aminoethylamino acid (PASP-ED2A) containing side chains bearing multi-functional groups is rationally designed and successfully prepared via the ring-opening reaction of cheap poly(succinimide) under mild reaction conditions with the assistance of readily available 2-aminoethyl amino acid. The static scale inhibition method is used to evaluate the scale inhibition performance of the as-synthesized PASP derivative. Scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy are utilized to monitor the crystallization process of calcium carbonate and calcium sulfate scales, and density functional theory calculations are conducted to shed light on the relationship between the molecular structure and scale inhibition mechanism of PASP-ED2A. Results show that the as-prepared PASP-ED2A shows better scale inhibition performance for CaCO3 and CaSO4 than PASP with a low concentration, a high temperature, and an extended duration. Particularly, PASP-ED2A with a concentration of 10 mg L-1 exhibits the best scale inhibition performance for CaCO3; its scale inhibition capacity is about two times as much as that of PASP. The reason lies in that the coordination atoms in the molecular structure of PASP-ED2A can chelate with Ca2+ to inhibit the combination of Ca2+ with anions and prevent the generation of CaCO3 and CaSO4 scales. The PASP-ED2A derivative can more efficiently retard the formation and growth of CaCO3 and CaSO4 crystal nuclei and exerts better inhibition performance against CaCO3 and CaSO4 scales than PASP.

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