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1.
Toxicol Mech Methods ; : 1-15, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38872277

RESUMO

In biomedical research, the fruit fly (Drosophila melanogaster) is among the most effective and flexible model organisms. Through the use of the Drosophila model, molecular mechanisms of human diseases can be investigated and candidate pharmaceuticals can be screened. White rot fungus Inonotus obliquus is a member of the family Hymenochaetaceae. Due to its multifaceted pharmacological effects, this fungus has been the subject of scientific investigation. Nevertheless, the precise mechanisms by which Inonotus obliquus treats diseases remain unclear. In this study, we prepared an aqueous extract derived from Inonotus obliquus and demonstrated that it effectively prevented the negative impacts of inflammatory agents on flies, including overproliferation and overdifferentiation of intestinal progenitor cells and decreased survival rate. Furthermore, elevated reactive oxygen species levels and cell death were alleviated by Inonotus obliquus aqueous extract, suggesting that this extract inhibited intestinal inflammation. Additionally, Inonotus obliquus aqueous extract had an impact on the insulin pathway, as it alleviated growth defects in flies that were fed a high-sugar diet and in chico mutants. In addition, we determined the composition of Inonotus obliquus aqueous extract and conducted a network pharmacology analysis in order to identify prospective key compounds and targets. In brief, Inonotus obliquus aqueous extract exhibited considerable potential as a therapeutic intervention for human diseases. Our research has established a foundational framework that supports the potential clinical implementation of Inonotus obliquus.

2.
J Ethnopharmacol ; 330: 118215, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38641073

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys malacophylla (Pall.) Fisch (O. malacophylla) is a succulent herbaceous plant that is the Orostachys genus of Crassulaceae family. O. malacophylla has been widely used as a traditional Chinese medicine with antioxidant, anti-inflammatory, anti-febrile, antidote, anti-Toxoplasma gondii properties. However, the biological function of alleviating intestinal inflammation and key bioactive compounds were still unknown. AIM OF THE STUDY: We used a Drosophila model to study the protective effects and bioactive compounds of O. malacophylla water extract (OMWE) and butanol extract (OMBE) on intestinal inflammation. MATERIALS AND METHODS: Drosophila intestinal inflammation was induced by oral invasion of dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15). We revealed the protective effects of two extracts by determining intestinal reactive oxygen species (ROS) and antimicrobial peptide (AMP) levels and intestinal integrity, and using network pharmacology analysis to identify bioactive compounds. RESULTS: We demonstrated that both OMWE and OMBE could ameliorate the detrimental effects of DSS, including a decreased survival rate, elevated ROS levels, increased cell death, excessive proliferation of ISCs, acid-base imbalance, and disruption of intestinal integrity. Moreover, the overabundance of lipid droplets (LDs) and AMPs by Ecc15 infection is mitigated by these extracts, thereby enhancing the flies' resistance to adverse stimuli. In addition, we used widely targeted metabolomics and network pharmacology analysis to identify bioactive compounds associated with IBD healing that are present in OMWE and OMBE. CONCLUSIONS: In summary, our research indicates that OMWE and OMBE significantly mitigate intestinal inflammation and have the potential to be effective therapeutic agents for IBD in humans.


Assuntos
Sulfato de Dextrana , Pectobacterium carotovorum , Extratos Vegetais , Espécies Reativas de Oxigênio , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Pectobacterium carotovorum/efeitos dos fármacos , Crassulaceae/química , Intestinos/efeitos dos fármacos , Intestinos/patologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Drosophila melanogaster/efeitos dos fármacos , Modelos Animais de Doenças , Drosophila , Farmacologia em Rede , Inflamação/tratamento farmacológico , Peptídeos Catiônicos Antimicrobianos/farmacologia
3.
J Cell Biochem ; 125(6): e30545, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38436545

RESUMO

To maintain the integrity of the adult gut, the proliferation and differentiation of stem cells must be strictly controlled. Several signaling pathways control the proliferation and differentiation of Drosophila intestinal epithelial cells. Although the modulatory effects of insulin pathway components on cell proliferation have been characterized, their specific role in which cell type and how these components interact with other regulatory signaling pathways remain largely unclear. In this study, we found that InR/Pi3K has major functions in enteroblasts (EBs) that were not previously described. The absence of InR/Pi3K in progenitors leads to a decrease in the number of EBs, while it has no significant effect on intestinal stem cells (ISCs). In addition, we found that InR/Pi3K regulates Notch activity in ISCs and EBs in an opposite way. This is also the reason for the decrease in EB. On the one hand, aberrantly low levels of Notch signaling in ISCs inhibit their proper differentiation into EBs; on the other hand, the higher Notch levels in EBs promote their excessive differentiation into enterocytes (ECs), leading to marked increases in abnormal ECs and decreased proliferation. Moreover, we found that Upd/JAK/STAT signaling acts as an effector or modifier of InR/Pi3K function in the midgut and cooperates with EGFR signaling to regulate cell proliferation. Altogether, our results demonstrate that InR and Pi3K are essential for coordinating stem cell differentiation and proliferation to maintain intestinal homeostasis.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Fosfatidilinositol 3-Quinases , Transdução de Sinais , Animais , Diferenciação Celular , Proliferação de Células , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Enterócitos/metabolismo , Enterócitos/citologia , Receptores ErbB/metabolismo , Homeostase , Mucosa Intestinal/metabolismo , Mucosa Intestinal/citologia , Intestinos/citologia , Fosfatidilinositol 3-Quinases/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptores de Peptídeos de Invertebrados , Receptores Notch/metabolismo , Fatores de Transcrição STAT/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia
4.
Dev Med Child Neurol ; 66(8): 1096-1105, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38303153

RESUMO

AIM: We compared three different intensities of robot-assisted gait training (RAGT) for achieving favourable outcomes in children with cerebral palsy (CP). METHOD: This study was conducted using a randomized controlled, single-blind design. Thirty children (19 males and 11 females; mean age 6 years 1 month, SD 2 years) with CP classified in Gross Motor Function Classification System levels II and III were assigned to three different RAGT intensity groups: high-intensity (fastest walking speed and lowest body weight support [BWS]), low-intensity (slowest speed and highest BWS), and comfortable intensity (intermediate speed and intermediate BWS). The RAGT intervention was performed three times a week for 6 weeks. Outcome measures included the 88-item Gross Motor Function Measure, stability index, spatiotemporal parameters of gait analysis, paediatric functional independence measure, and the Canadian Occupational Performance Measure. RESULTS: The 88-item Gross Motor Function Measure was significantly improved after training in the high-intensity (D Δ8.3 ± 15.6; E Δ3.8 ± 4.1) and comfortable intensity (D Δ2.9 ± 3.1; E Δ1.2 ± 2.0) groups, whereas gait speed was improved in the comfortable intensity group, without statistically significant group differences. Only the low-intensity group showed improvement on the stability index (Δ -0.6 ± 0.9, p = 0.05). Everyday functional performance significantly improved in all three groups, with the comfortable intensity group showing the greatest improvement. INTERPRETATION: Different training intensities produced improvement in different areas; individualized RAGT intensity adjustment is therefore needed based on the rehabilitation goal.


Assuntos
Paralisia Cerebral , Robótica , Humanos , Paralisia Cerebral/reabilitação , Paralisia Cerebral/fisiopatologia , Criança , Masculino , Feminino , Método Simples-Cego , Terapia por Exercício/métodos , Pré-Escolar , Resultado do Tratamento , Marcha/fisiologia , Transtornos Neurológicos da Marcha/reabilitação , Transtornos Neurológicos da Marcha/etiologia , Avaliação de Resultados em Cuidados de Saúde
5.
Life Sci ; 340: 122485, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38311220

RESUMO

AIM: Aging is a process characterized by a time-dependent decline in the functionality of adult stem cells and is closely associated with age-related diseases. However, understanding how aging promotes disease and its underlying causes is critical for combating aging. MAIN METHODS: The offspring of UAS-Gal4 and CG12744RNAiDrosophila were cultured for 33 days to evaluate the role of CG12744 in the aging intestine. Immunofluorescence was performed to detect specific cell type markers for assessing proliferation and differentiation. qRT-PCR was used to observe the changes in signaling regulating intestinal homeostasis in the aging intestine after CG12744 knockdown. 16S rRNA-seq analysis was also conducted to elucidate the role of gut microbes in CG12744-mediated intestinal dysfunction. KEY FINDINGS: The mRNA levels of CG12744 were significantly increased in the aged midguts. Knockdown of CG12744 in progenitor cells further exacerbates the age-related intestinal hyperplasia and dysfunction. In particular, upon depletion of CG12744 in progenitors, enteroblasts (EBs) exhibited an increased propensity to differentiate along the enteroendocrine cell (EE) lineage. In contrast, the overexpression of CG12744 in progenitor cells restrained age-related gut hyperplasia in Drosophila. Moreover, CG12744 prevented age-related intestinal stem cell (ISC) overproliferation and differentiation by modulating the EGFR, JNK, and BMP pathways. In addition, the inhibition of CG12744 resulted in a significant increase in the gut microbial composition in aging flies. SIGNIFICANCE: This study established a role for the CG12744 in regulating the proliferation and differentiation of adult stem cells, thereby identifying a potential therapeutic target for diseases caused by age-related dysfunction stem cell dysfunction.


Assuntos
Proteínas de Ligação a DNA , Proteínas de Drosophila , Drosophila , Animais , Diferenciação Celular , Proliferação de Células , Drosophila/genética , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Receptores ErbB/metabolismo , Hiperplasia/metabolismo , Intestinos , RNA Ribossômico 16S/metabolismo , Células-Tronco , Dedos de Zinco , Proteínas de Ligação a DNA/metabolismo
6.
Food Funct ; 14(21): 9707-9724, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37814808

RESUMO

Walnut Oil (WO) is recognized for its potential to improve cognition, but the mechanisms of its action related to improving cognitive impairment are not yet clear. In this study, the components of walnut oil were measured, and it was found that WO supplementation for 8 weeks could significantly prevent cognitive behavioral deficits and synaptic dysfunction induced by intraperitoneal injection of scopolamine (SCOP) in mice. By comparing and analyzing the changes in the hippocampal synaptic structure, oxidative stress, neurotransmitter fluctuations, brain transcriptome, inflammatory factors and gut microbiota in mice from different treatment groups, we observed a significant correlation between synaptic transmission genes, gut microbiota and neurotransmission in the WO supplemented group. It was found that WO supplementation could influence the secretion of neurotransmitters Ach and 5-HT by modulating the gut microbiota in vivo, thereby improving cognitive impairment through the central nervous system and hypothalamic-pituitary-adrenal (HPA) axis regulation.


Assuntos
Disfunção Cognitiva , Microbioma Gastrointestinal , Juglans , Animais , Camundongos , Microbioma Gastrointestinal/fisiologia , Escopolamina/efeitos adversos , Encéfalo/fisiologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Perfilação da Expressão Gênica
7.
Insects ; 14(8)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37623416

RESUMO

Autophagy is a process that promotes the lysosomal degradation of cytoplasmic proteins and is highly conserved in eukaryotic organisms. Autophagy maintains homeostasis in organisms and regulates multiple developmental processes, and autophagy disruption is related to human diseases. However, the functional roles of autophagy in mediating innate immune responses are largely unknown. In this study, we sought to understand how Atg2, an autophagy-related gene, functions in the innate immunity of Drosophila melanogaster. The results showed that a large number of melanotic nodules were produced upon inhibition of Atg2. In addition, inhibiting Atg2 suppressed the phagocytosis of latex beads, Staphylococcus aureus and Escherichia coli; the proportion of Nimrod C1 (one of the phagocytosis receptors)-positive hemocytes also decreased. Moreover, inhibiting Atg2 altered actin cytoskeleton patterns, showing longer filopodia but with decreased numbers of filopodia. The expression of AMP-encoding genes was altered by inhibiting Atg2. Drosomycin was upregulated, and the transcript levels of Attacin-A, Diptericin and Metchnikowin were decreased. Finally, the above alterations caused by the inhibition of Atg2 prevented flies from resisting invading pathogens, showing that flies with low expression of Atg2 were highly susceptible to Staphylococcus aureus and Erwinia carotovora carotovora 15 infections. In conclusion, Atg2 regulated both cellular and humoral innate immunity in Drosophila. We have identified Atg2 as a crucial regulator in mediating the homeostasis of immunity, which further established the interactions between autophagy and innate immunity.

8.
World J Clin Cases ; 11(8): 1847-1856, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36970011

RESUMO

BACKGROUND: Breast abscess during lactation is a severe complication of acute mastitis, which can lead to discomfort, high fever, breast fistula, sepsis, septic shock, breast damage, disease persistence and frequent hospitalization. Breast abscesses may also lead the mother to discontinue breastfeeding, thereby harming the infant's health. The predominant pathogenic bacteria are Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus. The incidence of breastfeeding abscesses in breastfeeding women ranges between 4.0% and 11.0%. In cases of breast abscess, the rate of cessation of lactation is 41.0%. In instances of breast fistula, the rate of cessation of lactation is very high (66.7%). Furthermore, 50.0% of women with breast abscesses must be hospitalized and treated with intravenous antibiotics. Treatment includes antibiotics, abscess puncture and surgical incision and drainage. The patients suffer from stress, pain and easily induced breast scarring; the disease's progression is prolonged and recurrent, interfering with infant feeding. Consequently, it is crucial to discover an adequate cure. CASE SUMMARY: A 28-year-old woman with a breast abscess was treated with Gualou Xiaoyong decoction and painless breast opening manipulation 24 d after cesarean delivery. On the 2nd d of treatment, the patient's breast mass was significantly reduced, the pain was significantly reduced, and the general asthenia was improved. All conscious symptoms disappeared after 3 d, breast abscesses faded after 12 d of treatment, inflammation images disappeared after 27 d, and normal lactation images were restored. CONCLUSION: In treating breast abscesses during breastfeeding, the combination of Gualou Xiaoyong decoction and painless lactation provides a positive therapeutic impact. This disease's treatment offers the advantages of a short course of treatment, no need to discontinue breastfeeding and the ability to rapidly mitigate symptoms, which can be used as a reference in clinical practice.

9.
Cells ; 12(4)2023 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-36831328

RESUMO

The Drosophila lymph gland is an ideal model for studying hematopoiesis, and unraveling the mechanisms of Drosophila hematopoiesis can improve our understanding of the pathogenesis of human hematopoietic malignancies. Bone morphogenetic protein (BMP) signaling is involved in a variety of biological processes and is highly conserved between Drosophila and mammals. Decapentaplegic (Dpp)/BMP signaling is known to limit posterior signaling center (PSC) cell proliferation by repressing the protooncogene dmyc. However, the role of two other TGF-ß family ligands, Glass bottom boat (Gbb) and Screw (Scw), in Drosophila hematopoiesis is currently largely unknown. Here, we showed that the loss of Gbb in the cortical zone (CZ) induced lamellocyte differentiation by overactivation of the EGFR and JNK pathways and caused excessive differentiation of plasmatocytes, mainly by the hyperactivation of EGFR. Furthermore, we found that Gbb was also required for preventing the hyperproliferation of the lymph glands by inhibiting the overactivation of the Epidermal Growth Factor Receptor (EGFR) and c-Jun N-terminal Kinase (JNK) pathways. These results further advance our understanding of the roles of Gbb protein and the BMP signaling in Drosophila hematopoiesis and the regulatory relationship between the BMP, EGFR, and JNK pathways in the proliferation and differentiation of lymph gland hemocytes.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Humanos , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Transdução de Sinais/fisiologia , Hematopoese , Receptores ErbB/metabolismo , Proliferação de Células , Mamíferos/metabolismo , Receptores de Peptídeos de Invertebrados
10.
Front Immunol ; 13: 905370, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911716

RESUMO

The innate immune response provides the first line of defense against invading pathogens, and immune disorders cause a variety of diseases. The fruit fly Drosophila melanogaster employs multiple innate immune reactions to resist infection. First, epithelial tissues function as physical barriers to prevent pathogen invasion. In addition, macrophage-like plasmatocytes eliminate intruders through phagocytosis, and lamellocytes encapsulate large particles, such as wasp eggs, that cannot be phagocytosed. Regarding humoral immune responses, the fat body, equivalent to the mammalian liver, secretes antimicrobial peptides into hemolymph, killing bacteria and fungi. Drosophila has been shown to be a powerful in vivo model for studying the mechanism of innate immunity and host-pathogen interactions because Drosophila and higher organisms share conserved signaling pathways and factors. Moreover, the ease with which Drosophila genetic and physiological characteristics can be manipulated prevents interference by adaptive immunity. In this review, we discuss the signaling pathways activated in Drosophila innate immunity, namely, the Toll, Imd, JNK, JAK/STAT pathways, and other factors, as well as relevant regulatory networks. We also review the mechanisms by which different tissues, including hemocytes, the fat body, the lymph gland, muscles, the gut and the brain coordinate innate immune responses. Furthermore, the latest studies in this field are outlined in this review. In summary, understanding the mechanism underlying innate immunity orchestration in Drosophila will help us better study human innate immunity-related diseases.


Assuntos
Drosophila melanogaster , Drosophila , Animais , Hemócitos , Humanos , Imunidade Inata , Mamíferos , Transdução de Sinais
11.
Toxicol Appl Pharmacol ; 439: 115939, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35217026

RESUMO

Drosophila is often exposed to harmful environments, and the intestinal epithelium is the first line of defense against external infection. Intestinal stem cells (ISCs) in the Drosophila midgut play a crucial role in maintaining tissue homeostasis and compensating for cell loss caused by tissue damage. Crocus sativus L. (saffron) can protect against intestinal injury in response to inflammation; however, the specific protective components of saffron and the related mechanisms remain unclear. Safranal is one of the main components of saffron. Here, we used dextran sodium sulfate (DSS) or Erwinia carotovora carotovora 15 (Ecc15) to create an intestinal injury model and explored the protective effect of safranal against tissue damage. Excessive proliferation and differentiation of ISCs in the Drosophila midgut were observed after DSS or Ecc15 feeding; however, these phenotypes were rescued after safranal feeding. In addition, we found that this process occurred through inhibition of the c-Jun N-terminal kinase (JNK), epidermal growth factor receptor (EGFR) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways. Furthermore, safranal inhibited the Ecc15- and DSS-induced increases in antimicrobial peptide (AMP) and reactive oxygen species (ROS) levels and intestinal epithelial cell death, thereby protecting gut integrity. In summary, safranal was found to have a significant protective effect and maintain intestinal homeostasis in Drosophila; these findings provide a foundation for the application of safranal in clinical research and the treatment of intestinal injury.


Assuntos
Cicloexenos , Drosophila , Animais , Cicloexenos/farmacologia , Drosophila/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Terpenos/farmacologia
12.
J Insect Physiol ; 134: 104309, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34496279

RESUMO

The adult Drosophila intestinal epithelium must be tightly regulated to maintain regeneration and homeostasis. The dysregulation of the regenerative capacity is frequently associated with intestinal diseases such as inflammation and tumorigenesis. Here, we showed that the G protein-coupled receptor Anchor maintains Drosophila adult midgut homeostasis by restricting Jun-N-terminal kinase (JNK) and Notch pathway activity. anchor inactivation resulted in aberrant JNK pathway activation, which led to excessive enteroblast (EB) production and premature enterocyte (EC) differentiation. In addition, increased Notch levels promoted premature EC differentiation following the loss of anchor. This defect induced by the loss of anchor ultimately caused sensitivity to stress or environmental challenge in adult flies. Taken together, our results demonstrate that the activity of anchor is essential to coordinate stem cell differentiation and proliferation to maintain intestinal homeostasis.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Homeostase/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Proliferação de Células , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Drosophila melanogaster/fisiologia , Enterócitos , Trato Gastrointestinal/citologia , Trato Gastrointestinal/metabolismo , Sistema de Sinalização das MAP Quinases , Receptores Notch/metabolismo , Transdução de Sinais
13.
Elife ; 102021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33560224

RESUMO

The hematopoietic system of Drosophila is a powerful genetic model for studying hematopoiesis, and vesicle trafficking is important for signal transduction during various developmental processes; however, its interaction with hematopoiesis is currently largely unknown. In this article, we selected three endosome markers, Rab5, Rab7, and Rab11, that play a key role in membrane trafficking and determined whether they participate in hematopoiesis. Inhibiting Rab5 or Rab11 in hemocytes or the cortical zone (CZ) significantly induced cell overproliferation and lamellocyte formation in circulating hemocytes and lymph glands and disrupted blood cell progenitor maintenance. Lamellocyte formation involves the JNK, Toll, and Ras/EGFR signaling pathways. Notably, lamellocyte formation was also associated with JNK-dependent autophagy. In conclusion, we identified Rab5 and Rab11 as novel regulators of hematopoiesis, and our results advance the understanding of the mechanisms underlying the maintenance of hematopoietic homeostasis as well as the pathology of blood disorders such as leukemia.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Hematopoese/genética , Homeostase/genética , Transdução de Sinais , Proteínas rab de Ligação ao GTP/genética , Proteínas rab5 de Ligação ao GTP/genética , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab5 de Ligação ao GTP/metabolismo
14.
Brain Sci ; 10(11)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143214

RESUMO

PURPOSE: The effectiveness of robot-assisted gait training (RAGT) in children with cerebral palsy (CP), especially in terms of improving the performance of daily activities, remains unclear. Therefore, we aimed to investigate the effectiveness of RAGT in children with CP. METHODS: In this single-center, single-blinded, randomized cross-over trial, we enrolled 20 children with CP with Gross Motor Function Classification System (GMFCS) levels II-IV (13 males; age range, 6.75 ± 2.15 years). The participants were randomized into the RAGT/standard care (SC) (n = 10) and SC/RAGT/SC sequence groups (n = 10). Using a Walkbot-K system, the RAGT program comprised 3 × 30-min sessions/week for 6 weeks with a continued SC program. The SC program comprised 2-4 conventional physiotherapy sessions/week for 6 weeks. The Gross Motor Function Measure-88 (GMFM-88), the pediatric functional independence measure (WeeFIM), and the Canadian occupational performance measure (COPM) scores were assessed pre- and post-RAGT or SC periods and treatment, period, follow-up, and carry-over effects were analyzed. Energy expenditure and body composition were measured pre- and post-RAGT. RESULTS: Significant treatment effects were observed in dimensions D and E of the GMFM (D: p = 0.018; E: p = 0.021) scores, WeeFIM mobility subtotal (p = 0.007), and COPM performance (p < 0.001) and satisfaction (p = 0.001) measure scores. The period, follow-up, and carry-over effects were not statistically significant. The gross energy cost significantly decreased (p = 0.041) and the skeletal muscle mass increased (p = 0.014) at post-RAGT assessment. The factors associated with functional outcomes showed significant improvements in the GMFM D scores and were mainly observed in children with GMFCS levels II-III compared to those classified at level IV (p = 0.038). CONCLUSION: RAGT had training benefits for children with CP. Specifically, it improved locomotor function and functional capability for daily activities. These effects were better in ambulatory children with CP. However, as SC interventions continued during the RAGT period, these improvements may be also related to multiple treatment effects.

15.
Front Cell Dev Biol ; 8: 382, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32509789

RESUMO

Hematopoiesis is a necessary process for development and immune defense in Drosophila from the embryonic period to adulthood. There are two main stages in this process: the first stage occurs in the head mesoderm during the embryonic stage, and the second occurs in a specialized hematopoietic organ along the dorsal vessel, the lymph gland, during the larval stage. The lymph gland consists of paired lobes, each of which has distinct regions: the cortical zone (CZ), which contains mature hemocytes; the medullary zone (MZ), which contains hematopoietic progenitors; and the posterior signaling center (PSC), which specifically expresses the early B-cell factor (EBF) transcription factor Collier (Col) and the HOX factor Antennapedia (Antp) to form a microenvironment similar to that of the mammalian bone marrow hematopoietic stem cell niche. The PSC plays a key role in regulating hematopoietic progenitor differentiation. Moreover, the PSC contributes to the cellular immune response to wasp parasitism triggered by elevated ROS levels. Two recent studies have revealed that hematopoietic progenitor maintenance is directly regulated by Col expressed in the MZ and is independent of the PSC, challenging the traditional model. In this review, we summarize the regulatory networks of PSC cell proliferation, the controversy regarding PSC-mediated regulation of hematopoietic progenitor differentiation, and the wasp egg infection response. In addition, we discuss why the PSC is an ideal model for investigating mammalian hematopoietic stem cell niches and leukemia.

16.
Phytother Res ; 34(1): 193-200, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31736181

RESUMO

The intestinal epithelium provides the first line of defense against pathogens and toxic compounds. The ingestion of toxic compounds causes an enhanced epithelial cell death and an excessive proliferation of intestinal stem cells, eventually resulting in the disruption of gut homeostasis. In this study, Drosophila gut inflammation model induced by toxic compounds was exploited to analyze the ameliorative effect of Acanthopanax senticosus polysaccharide on the disruption of gut homeostasis. As a result, it was found that A. senticosus polysaccharide can significantly increase the survival rate of Drosophila adults as well as reduce the excessive proliferation and differentiation of intestinal stem cells through epidermal growth factor receptor, jun-N-terminal kinase, and Notch signaling pathways under the exposure to toxic compounds dextran sodium sulfate. Moreover, the polysaccharide effectively decreased the epithelial cell death and the accumulation of reactive oxygen species and antimicrobial peptides induced by sodium dodecyl sulfate. In addition, it was found that A. senticosus polysaccharide can extend the lifespan of only female flies but not male flies. In conclusion, A. senticosus polysaccharide has an obvious protective effect on the gut homeostasis of Drosophila melanogaster.


Assuntos
Intestinos/efeitos dos fármacos , Polissacarídeos/metabolismo , Animais , Drosophila , Feminino , Homeostase , Masculino
17.
J Zhejiang Univ Sci B ; 20(5): 414-427, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31090267

RESUMO

Bile acids (BAs) are originally known as detergents essential for the digestion and absorption of lipids. In recent years, extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes, including glucose and lipid metabolism, energy expenditure, inflammation, tumorigenesis, cardiovascular disease, and even the central nervous system in addition to cholesterol homeostasis, enterohepatic protection and liver regeneration. BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs. The signaling actions of BAs can also be mediated through specific nuclear receptors and membrane-bound G protein-coupled receptors. Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling. In this mini-review, we summarize recent advances in bile-ology, focusing on its translational studies.


Assuntos
Ácidos e Sais Biliares/metabolismo , Lipídeos/química , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Carcinogênese , Colesterol/metabolismo , Detergentes/química , Diabetes Mellitus Tipo 2/fisiopatologia , Descoberta de Drogas , Microbioma Gastrointestinal , Homeostase , Humanos , Inflamação , Doenças Inflamatórias Intestinais/fisiopatologia , Metabolismo dos Lipídeos , Doenças Metabólicas/fisiopatologia , Camundongos , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/fisiopatologia , Transdução de Sinais , Pesquisa Translacional Biomédica
18.
Apoptosis ; 24(5-6): 465-477, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30796611

RESUMO

Previous studies in several model organisms have revealed that members of the Forkhead (Fkh) transcription factor family have multiple functions. Drosophila Jumeau (Jumu), a member of this family, participates in cardiogenesis, hematopoiesis and immune system homeostasis. Here, we show that loss of jumu function positively regulates or triggers apoptosis via a JNK-dependent pathway in wing development. jumu mutants showed reduced wing size and increased apoptosis. Moreover, we observed a loss of the anterior cross vein (ACV) phenotype that was similar to that observed in wings in which JNK signaling has been ectopically activated. The JNK signaling markers puckered (puc) and p-JNK were also significantly increased in the wing discs of jumu mutants. In addition, apoptosis induced by the loss of jumu was rescued by knocking down JNK, indicating a role for JNK in reducing jumu-induced apoptosis. Jumu could also control wing margin development via the positive regulation of cut expression, and the observed wing margin defect did not result from a loss of jumu-induced apoptosis. Further, jumu deficiency in the pupal wing could induce multiple wing hairs via a Rho1-mediated planar cell polarity pathway, but abnormal Rho1 expression was not why jumu loss induced apoptosis via a JNK-dependent pathway in wing discs.


Assuntos
Apoptose , Proteínas de Drosophila/metabolismo , Drosophila/fisiologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose/genética , Morte Celular/genética , Proliferação de Células/genética , Drosophila/genética , Drosophila/crescimento & desenvolvimento , Drosophila/metabolismo , Proteínas de Drosophila/genética , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Mutação com Perda de Função , Fenótipo , Fosfoproteínas Fosfatases/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/genética , Asas de Animais/crescimento & desenvolvimento , Asas de Animais/metabolismo , Asas de Animais/patologia , Proteína Wnt1/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo
19.
Cell Commun Signal ; 16(1): 95, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518379

RESUMO

BACKGROUND: The regulatory mechanisms of hematopoiesis and cellular immunity show a high degree of similarity between insects and mammals, and Drosophila has become a good model for investigating cellular immune responses. Jumeau (Jumu) is a member of the winged-helix/forkhead (FKH) transcription factor family and is required for Drosophila development. Adult jumu mutant flies show defective hemocyte phagocytosis and a weaker defense capability against pathogen infection. Here, we further investigated the role of jumu in the regulation of larval hemocyte development and phagocytosis. METHODS: In vivo phagocytosis assays, immunohistochemistry, Real-time quantitative PCR and immunoblotting were performed to investigate the effect of Jumu on hemocyte phagocytosis. 5-Bromo-2-deoxyUridine (BrdU) labeling, phospho-histone H3 (PH3) and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining were performed to analyze the proliferation and apoptosis of hemocyte; immunohistochemistry and Mosaic analysis with a repressible cell marker (MARCM) clone analysis were performed to investigate the role of Jumu in the activation of Toll pathway. RESULTS: Jumu indirectly controls hemocyte phagocytosis by regulating the expression of NimC1 and cytoskeleton reorganization. The loss of jumu also causes abnormal proliferation and differentiation in circulating hemocytes. Our results suggest that a severe deficiency of jumu leads to the generation of enlarged multinucleate hemocytes by affecting the normal cell mitosis process and induces numerous lamellocytes by activating the Toll pathway. CONCLUSIONS: Jumu regulates circulating hemocyte differentiation and phagocytosis in Drosophila. Our findings provide new insight into the mechanistic roles of cytoskeleton regulatory proteins in phagocytosis and establish a basis for further analyses of the regulatory mechanism of the mammalian ortholog of Jumu in mammalian innate immunity.


Assuntos
Diferenciação Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Hemócitos/citologia , Fagocitose , Fatores de Transcrição/metabolismo , Animais , Proteínas de Drosophila/deficiência , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Pseudópodes/metabolismo , Receptores Imunológicos/metabolismo , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética
20.
Exp Ther Med ; 16(3): 2564-2572, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30186490

RESUMO

Flos Chrysanthemi Indici (CI) is a traditional medicinal plant used in the treatment of inflammatory diseases. However, the pharmacological role of CI in metabolic diseases, especially in diseases induced by insulin metabolism disorders, remains poorly understood. In the present study, Drosophila melanogaster (Drosophila) were fed with high-sugar diet (HSD) to induce a model similar to Type 2 diabetes (T2D) in order to determine whether CI extracts improve the metabolic disorder. It was demonstrated that the CI extracts could improve growth rate, body size, lifespan, reproductive capacity and fat storage, and CI especially improved the fat metabolism and cell size in S6k and Akt1 mutant flies. In conclusion, the present study provides novel evidence that CI may be an effective drug for the treatment of T2D.

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