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1.
Heliyon ; 10(18): e38173, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39364246

RESUMO

Objective: Jinbei oral liquid (JBOL), which is derived from a traditional hospital preparation, is frequently utilized to treat idiopathic pulmonary fibrosis (IPF) and has shown efficacy in clinical therapy. However, there are now several obstacles facing the mechanism inquiry, including target proteins, active components, and the binding affinity between crucial compounds and target proteins. To gain additional insight into the mechanisms underlying JBOL in anti-IPF, this study used bioinformation technologies, including network pharmacology, molecular docking, and molecular dynamic simulation, with a substantial amount of data based on realistic constituents. Methods: Using network pharmacology, we loaded 118 realistic compounds into the SwissTargetPrediction and SwissADME databases and screened the active compounds and target proteins. IPF-related targets were collected from the OMIM, DisGeNET, and GeneCards databases, and the network of IPF-active constituents was built with Cytoscape 3.10.1. The GO and KEGG pathway enrichment analyses were carried out using Metascape, and the protein-protein interaction (PPI) network was constructed to screen the key targets with the STRING database. Finally, the reciprocal affinity between the active molecules and the crucial targets was assessed through the use of molecular docking and molecular dynamics simulation. Results: A total of 122 targets and 34 tested active compounds were summarized in this investigation. Among these, kaempferol, apigenin, baicalein were present in high degree. PPI networks topological analysis identified eight key target proteins. AGE-RAGE, EGFR, and PI3K-Akt signaling pathways were found to be regulated during the phases of cell senescence, inflammatory response, autophagy, and immunological response in anti-IPF of JBOL. It was verified by molecular docking and molecular dynamics simulation that the combining way and binding energy between active ingredients and selected targets. Conclusions: This work forecasts the prospective core ingredients, targets, and signal pathways of JBOL in anti-IPF, which has confirmed the multiple targets and pathways of JBOL in anti-IPF and provided the first comprehensive assessment with bioinformatic approaches. With empirical backing and an innovative approach to the molecular mechanism, JBOL is being considered as a potential new medication.

2.
J Agric Food Chem ; 72(37): 20483-20495, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39248366

RESUMO

Mechanical stimuli can affect plant growth, development, and defenses. The role of water spray stimulation, as a prevalent mechanical stimulus in the environment, in crop growth and defense cannot be overlooked. In this study, the effects of water spray on tomato plant growth and defense against the chewing herbivore Helicoverpa armigera and necrotrophic fungus Botrytis cinerea were investigated. Suprathreshold water spray stimulus (LS) was found to enhance tomato plant defenses against pests and pathogens while concurrently modifying plant architecture. The results of the phytohormone and chemical metabolite analysis revealed that LS improved the plant defense response via jasmonic acid (JA) signaling. LS significantly elevated the level of a pivotal defensive metabolite, chlorogenic acid, and reduced the emissions of volatile organic compounds (VOCs) from tomato plants, thereby defending against pest and pathogen attacks. The most obvious finding to emerge from this study is that LS enhances tomato plant defenses against biotic stresses, which will pave the way for further work on the application of mechanical stimuli for pest management.


Assuntos
Botrytis , Ciclopentanos , Oxilipinas , Doenças das Plantas , Solanum lycopersicum , Compostos Orgânicos Voláteis , Água , Solanum lycopersicum/microbiologia , Solanum lycopersicum/parasitologia , Solanum lycopersicum/imunologia , Solanum lycopersicum/química , Solanum lycopersicum/metabolismo , Água/metabolismo , Animais , Botrytis/fisiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/parasitologia , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/metabolismo , Mariposas/fisiologia , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Estresse Fisiológico , Herbivoria , Defesa das Plantas contra Herbivoria
3.
Interdiscip Sci ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150470

RESUMO

Abnormal interaction between granulosa cells and oocytes causes disordered development of ovarian follicles. However, the interactions between oocytes and cumulus granulosa cells (CGs), oocytes and mural granulosa cells (MGs), and CGs and MGs remain to be fully explored. Using single-cell RNA-sequencing (scRNA-seq), we determined the transcriptional profiles of oocytes, CGs and MGs in antral follicles. Analysis of scRNA-seq data revealed that CGs may regulate follicular development through the BMP15-KITL-KIT-PI3K-ARF6 pathway with elevated expression of luteinizing hormone receptor (LHR). Because internalization of the LHR is regulated by Arf6, we constructed LHRN316S mice by CRISPR/Cas9 to further explore mechanisms of follicular development and novel treatment strategies for female infertility. Ovaries of LHRN316S mice exhibited reduced numbers of corpora lutea and ovulation. The LHRN316S mice had a reduced rate of oocyte maturation in vitro and decreased serum progesterone levels. Mating LHRN316S female mice with ICR wild type male mice revealed that the infertility rate of LHRN316S mice was 21.4% (3/14). Litter sizes from LHRN316S mice were smaller than those from control wild type female mice. The oocytes from LHRN316S mice had an increased rate of maturation in vitro after progesterone administration in vitro. Furthermore, progesterone treated LHRN316S mice produced offspring numbers per litter equivalent to WT mice. These findings provide key insights into cellular interactions in ovarian follicles and provide important clues for infertility treatment.

4.
Front Genet ; 15: 1410145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957810

RESUMO

Background: Osteosarcoma (OS) is highly malignant and prone to local infiltration and distant metastasis. Due to the poor outcomes of OS patients, the study aimed to identify differentially expressed genes (DEGs) in OS and explore their role in the carcinogenesis and progression of OS. Methods: RNA sequencing was performed to identify DEGs in OS. The functions of the DEGs in OS were investigated using bioinformatics analysis, and DEG expression was verified using RT-qPCR and Western blotting. The role of SLC25A4 was evaluated using gene set enrichment analysis (GSEA) and then investigated using functional assays in OS cells. Results: In all, 8353 DEGs were screened. GO and KEGG enrichment analyses indicated these DEGs showed strong enrichment in the calcium signaling pathway and pathways in cancer. Moreover, the Kaplan-Meier survival analysis showed ten hub genes were related to the outcomes of OS patients. Both SLC25A4 transcript and protein expression were significantly reduced in OS, and GSEA suggested that SLC25A4 was associated with cell cycle, apoptosis and inflammation. SLC25A4-overexpressing OS cells exhibited suppressed proliferation, migration, invasion and enhanced apoptosis. Conclusion: SLC25A4 was found to be significantly downregulated in OS patients, which was associated with poor prognosis. Modulation of SLC25A4 expression levels may be beneficial in OS treatment.

5.
Children (Basel) ; 11(7)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39062333

RESUMO

Anthracyclines have significantly improved the survival of children with malignant tumors, but the associated cardiotoxicity, an effect now under the purview of pediatric cardio-oncology, due to its cumulative and irreversible effects on the heart, limits their clinical application. A systematic screening and risk stratification approach provides the opportunity for early identification and intervention to mitigate, reverse, or prevent myocardial injury, remodeling, and dysfunction associated with anthracyclines. This review summarizes the risk factors, surveillance indexes, and preventive strategies of anthracycline-related cardiotoxicity to improve the safety and efficacy of anthracyclines.

6.
Plant Physiol Biochem ; 214: 108927, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39067104

RESUMO

Grafting is applied in Solanaceae to improve growth and quality traits. However, grafting potato onto a wooden goji rootstock is rare. Our study introduces a novel distant grafting technique to investigate potato scion responses, specifically regarding photosynthetic and tuber nutritional quality. The physiological and transcriptomic findings reveal an increase in photosynthesis ratio and carbon fixation in potato leaves after 45 days of grafting due to the upregulation of pivotal genes (PsbA, PPC1, rbcl, and GAPDH). After 95 days of long-term growth, the leaf redox balance was maintained with intensified chlorophyll synthesis, facilitated by the enrichment of crucial genes (GUN4, CHLH, CHLP, CAO) and several light-harvesting proteins (Lhca and Lhcb) in potato leaves. The tubers of grafted plants showed a 6.5% increase in crude protein, 51% in anthocyanin, and lower carbohydrate content. Goji altered the expression of tubers genes involved in assimilatory sulfate reduction, which subsequently affects cysteine-methionine biosynthesis. Furthermore, the tuber transcriptome shows ABA signaling and transcription factors regulate the expression of key biosynthetic genes involved in inducing the secondary metabolites, such as scopoletin and anthocyanin accumulation, which are primary polyphenols in goji. Our innovative grafting approach offers valuable insights into the interactions between woody and herbaceous plants for developing future strategies to modulate growth efficiency and tuber quality in the face of climate challenges and to meet the demand for nutritious food.


Assuntos
Tubérculos , Solanum tuberosum , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Tubérculos/metabolismo , Tubérculos/genética , Tubérculos/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Fotossíntese , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/genética
7.
Front Neurol ; 15: 1415106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915796

RESUMO

Objective: To determine whether a combination therapy with abatacept (CTLA4-Ig) and interleukin-2 (IL-2) is safe and suppresses markers of oxidative stress, inflammation, and degeneration in ALS. Methods: In this open-label study, four participants with ALS received subcutaneous injections of low dose IL-2 (1 × 106 IU/injection/day) for 5 consecutive days every 2 weeks and one subcutaneous injection of CTLA4-Ig (125 mg/mL/injection) every 2 weeks coinciding with the first IL-2 injection of each treatment cycle. Participants received a total of 24 treatment cycles during the first 48 weeks in this 56-week study. They were closely monitored for treatment-emergent adverse events (TEAEs) and disease progression with the ALSFRS-R. Phenotypic changes within T cell populations and serum biological markers of oxidative stress [4-hydroxynonenal (4-HNE) and oxidized-LDL (ox-LDL)], inflammation (IL-18), and structural neuronal degeneration [neurofilament light chain (Nf-L)] were assessed longitudinally. Results: CTLA4-Ig/IL-2 therapy was safe and well-tolerated in all four participants over the 56-week study. During the first 24 weeks, the average rate of change in the ALSFRS-R was +0.04 points/month. Over the 48-week treatment period, the average rate of change was -0.13 points/month with one participant improving by 0.9 points/month while the other three participants experienced an average decrease of -0.47 points/month, which is slower than the average - 1.1 points/month prior to initiation of therapy. Treg suppressive function and numbers increased during treatment. Responses in the biological markers during the first 16 weeks coincided with minimal clinical progression. Mean levels of 4-HNE decreased by 30%, ox-LDL decreased by 19%, IL-18 decreased by 23%, and Nf-L remained the same, on average, in all four participants. Oxidized-LDL levels decreased in all four participants, 4-HNE and IL-18 levels decreased in three out of four participants, and Nf-L decreased in two out of four participants. Conclusion: The combination therapy of CTLA4-Ig and IL-2 in ALS is safe and well-tolerated with promising results of clinical efficacy and suppression of biomarkers of oxidative stress, neuroinflammation and neuronal degeneration. In this open-label study, the efficacy as measured by the ALSFRS-R and corresponding biomarkers suggests the therapeutic potential of this treatment and warrants further study in a phase 2 double-blind, placebo-controlled trial. Clinical trial registration: ClinicalTrials.gov, NCT06307301.

8.
Reprod Biol Endocrinol ; 22(1): 69, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886751

RESUMO

BACKGROUND: Among the POSEIDON criteria, group 3 and group 4 have an expected low prognosis. For those patients with inadequate ovary reserve, embryo accumulated from consecutive oocyte retrieval cycles for multiple frozen-thawed embryo transfers (FET) has become more common. It is necessary to inform them of the pregnancy outcomes after single or multiple FET cycles before the treatment. However few studies about cumulative live birth rate (CLBR) for those with low prognosis have been reported. METHODS: This retrospective study included 4712 patients undergoing frozen embryo transfer cycles from July 2015 to August 2020. Patients were stratified as POSEIDON group 3, group 4, control 1 group (< 35 years) and control 2 group (≥ 35 years). The primary outcome is CLBRs up to six FET cycles and the secondary outcomes were LBRs per transfer cycle. Optimistic approach was used for the analysis of CLBRs and the depiction of cumulative incidence curves. RESULTS: Under optimistic model analyses, control 1 group exhibited the highest CLBR (93.98%, 95%CI 91.63-95.67%) within 6 FET cycles, followed by the CLBR from women in POSEIDON group 3(92.51%, 95%CI 77.1-97.55)was slightly lower than that in control 1 group. The CLBR of POSEIDON group 4(55% ,95%CI 39.34-70.66%)was the lowest and significantly lower than that of control 2 group(88.7%, 95%CI 80.68-96.72%). Further, patients in POSEIDON group 4 reached a CLBR plateau after 5 FET cycles. CONCLUSIONS: The patients of POSEIDON group 3 may not be considered as traditional "low prognosis" in clinical practice as extending the number of FET cycles up to 6 can archive considerably CLBR as control women. While for the POSEIDON group 4, a simple repeat of the FET cycle is not recommended after four failed FET cycles, some strategies such as PGT-A may be beneficial.


Assuntos
Hormônio Antimülleriano , Coeficiente de Natalidade , Criopreservação , Transferência Embrionária , Nascido Vivo , Humanos , Feminino , Transferência Embrionária/métodos , Transferência Embrionária/estatística & dados numéricos , Transferência Embrionária/tendências , Gravidez , Adulto , Estudos Retrospectivos , Prognóstico , Hormônio Antimülleriano/sangue , Nascido Vivo/epidemiologia , Taxa de Gravidez , Reserva Ovariana/fisiologia , Fatores Etários , Fertilização in vitro/métodos , Resultado da Gravidez/epidemiologia
9.
Signal Transduct Target Ther ; 9(1): 152, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38918390

RESUMO

CD8+ T cell immune responses are regulated by multi-layer networks, while the post-translational regulation remains largely unknown. Transmembrane ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane proteins. Here, by targeting the sheddase A Disintegrin and Metalloprotease (ADAM)17, we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8+ T cells. Transcriptomic and proteomic analysis revealed the involvement of post-translational regulation in CD8+ T cells. T cell-specific deletion of ADAM17 led to a dramatic increase in effector CD8+ T cell differentiation and enhanced cytolytic effects to eliminate pathogens and tumors. Mechanistically, ADAM17 regulated CD8+ T cells through cleavage of membrane CD122. ADAM17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8+ T cells. Intriguingly, inhibition of ADAM17 in CD8+ T cells improved the efficacy of chimeric antigen receptor (CAR) T cells in solid tumors. Our findings reveal a critical post-translational regulation in CD8+ T cells, providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.


Assuntos
Proteína ADAM17 , Linfócitos T CD8-Positivos , Diferenciação Celular , Proteína ADAM17/genética , Proteína ADAM17/imunologia , Linfócitos T CD8-Positivos/imunologia , Animais , Camundongos , Humanos , Diferenciação Celular/imunologia , Diferenciação Celular/genética , Diferenciação Celular/efeitos dos fármacos , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/patologia
11.
Mol Genet Genomics ; 299(1): 35, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489045

RESUMO

Asthenoteratospermia is a significant cause of male infertility. FAM71D (Family with sequence similarity 71, member D), as a novel protein exclusively expressed in the testis, has been found to be associated with sperm motility. However, the association of FAM71D mutation with male infertility has yet to be examined. Here, we conducted whole-exome sequencing and identified a homozygous missense mutation c.440G > A (p. Arg147Gln) of FAM71D in an asthenoteratospermia-affected man from a consanguineous family. The FAM71D variant is extremely rare in human population genome databases and predicted to be deleterious by multiple bioinformatics tools. Semen analysis indicated decreased sperm motility and obvious morphological abnormalities in sperm cells from the FAM71D-deficient man. Immunofluorescence assays revealed that the identified FAM71D mutation had an important influence on the assembly of sperm structure-related proteins. Furthermore, intra-cytoplasmic sperm injection (ICSI) treatment performed on the infertile man with FAM71D variant achieved a satisfactory outcome. Overall, our study identified FAM71D as a novel causative gene for male infertility with asthenoteratospermia, for which ICSI treatment may be suggested to acquire good prognosis. All these findings will provide effective guidance for genetic counselling and assisted reproduction treatments of asthenoteratospermia-affected subjects.


Assuntos
Infertilidade Masculina , Sêmen , Masculino , Humanos , Motilidade dos Espermatozoides , Espermatozoides , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Testículo/metabolismo , Mutação
12.
Nat Commun ; 15(1): 2156, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461154

RESUMO

This study establishes the physiological role of Fused in Sarcoma (FUS) in mitochondrial DNA (mtDNA) repair and highlights its implications to the pathogenesis of FUS-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Endogenous FUS interacts with and recruits mtDNA Ligase IIIα (mtLig3) to DNA damage sites within mitochondria, a relationship essential for maintaining mtDNA repair and integrity in healthy cells. Using ALS patient-derived FUS mutant cell lines, a transgenic mouse model, and human autopsy samples, we discovered that compromised FUS functionality hinders mtLig3's repair role, resulting in increased mtDNA damage and mutations. These alterations cause various manifestations of mitochondrial dysfunction, particularly under stress conditions relevant to disease pathology. Importantly, rectifying FUS mutations in patient-derived induced pluripotent cells (iPSCs) preserves mtDNA integrity. Similarly, targeted introduction of human DNA Ligase 1 restores repair mechanisms and mitochondrial activity in FUS mutant cells, suggesting a potential therapeutic approach. Our findings unveil FUS's critical role in mitochondrial health and mtDNA repair, offering valuable insights into the mechanisms underlying mitochondrial dysfunction in FUS-associated motor neuron disease.


Assuntos
Esclerose Lateral Amiotrófica , Doenças Mitocondriais , Doença dos Neurônios Motores , Proteína FUS de Ligação a RNA , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/metabolismo , DNA Mitocondrial/genética , Ligases/metabolismo , Camundongos Transgênicos , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/metabolismo , Mutação , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismo , DNA Ligase Dependente de ATP/genética , DNA Ligase Dependente de ATP/metabolismo
13.
iScience ; 27(3): 109046, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38384848

RESUMO

Poor endometrial receptivity results in embryo implantation failure. Acquisition of endometrial receptivity involves substantial structural alterations in the cytoskeleton and plasma membrane of epithelial cells, which facilitate embryo adhesion. However, the underlying molecular mechanism remains largely unknown. In this study, we identified that α-actinin-1 (ACTN1) was significantly downregulated in the mid-secretory phase of the endometrium compared with other phases; however, ACTN1 significantly increased in women with recurrent implantation failure (RIF). In Ishikawa and human endometrial epithelial cells (HEECs), ACTN1 overexpression significantly decreased NEBL levels, enhanced F-actin fiber levels, and caused a notable impairment in blastocyst adhesion, which mimicked the process of embryo adhesion. However, NEBL overexpression notably restored adhesion. Moreover, NEBL expression was reduced in patients with RIF compared with that in controls. Finally, our data showed that ACTN1 upregulation impaired endometrial receptivity in women with RIF, possibly by regulating NEBL expression and subsequent cell-adhesion capability.

14.
PLoS One ; 19(2): e0289300, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306334

RESUMO

Nitrous oxide (N2O) and ammonia (NH3) volatilization (AV) are the major pathways of nitrogen (N) loss in soil, and recently, N2O and NH3 mitigation has become urgently needed in agricultural systems worldwide. However, the influence of straw incorporation (SI) and biochar addition (BC) on N2O and NH3 emissions are still unclear. To fill this knowledge gap, a soil column experiment was conducted with two management strategies using straw - straw incorporation (S1) and straw removal (S0) - and four biochar application rates (0 (C0), 15 (C1), 30 (C2), and 45 t ha-1 (C3)) to evaluate the impacts of their interactions on N2O and NH3 emissions. The results showed that NO3--N concentration and pH was the major contributors to affect the N2O and NH3 losses. Without biochar addition, N2O emissions was decreased by 59.6% (P<0.05) but AV was increased by 97.3% (P<0.05) under SI when compared to SR. Biochar was beneficial for N2O mitigation when straw was removed, but increased N2O emission by 39.4%-83.8% when straw was incorporated. Additionally, biochar stimulated AV by 27.9%-60.4% under S0 and 78.6%-170.3% under S1. Consequently, SI was found to significantly interact with BC in terms of affecting N2O (P<0.001) and NH3 (P<0.001) emissions; co-application of SI and BC promoted N2O emissions and offset the mitigation potential by SI or BC alone. The indirect N2O emissions caused by AV, however, might offset the reduction of direct N2O caused by SI or BC, thus leading to an increase in overall N2O emission. This paper recommended that SI combined BC at the amount of 8.2 t ha-1 for maintaining a lower overall N2O emission for future agriculture practices, but the long-term impacts of straw incorporation and biochar addition on the trade-off between N2O and NH3 emissions and reactive N losses should be further examined and assessed.


Assuntos
Óxido Nitroso , Solo , Óxido Nitroso/análise , Fertilizantes/análise , Agricultura/métodos , Carvão Vegetal
15.
Sci Rep ; 14(1): 4896, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418830

RESUMO

This work prepared and investigated the impact of carboxymethyl chitosan nanoparticles (MC-NPs) on the proliferative capability of keloid fibroblasts (KFBs) while analyzing the mechanistic roles of miR-214 and adenosine A2A receptor (A2AR) in fibroblasts within hypertrophic scars. MC-NPs were synthesized through ion cross-linking, were characterized using transmission electron microscopy (TEM) and laser particle size scattering. The influence of MC-NPs on the proliferation capacity of KFBs was assessed using the MTT method. Changes in the expression levels of miR-214 and A2AR in KFBs, normal skin fibroblasts (NFBs), hypertrophic scar tissue, and normal skin tissue were analyzed. KFBs were categorized into anti-miR-214, anti-miR-NC, miR-214 mimics, miR-NC, si-A2AR, si-con, anti-miR-214+ si-con, and anti-miR-214+ si-A2AR groups. Bioinformatics target prediction was conducted to explore the interaction between miR-214 and A2AR. Real-time quantitative PCR and immunoblotting (WB) were employed to detect the expression levels of miR-214, A2AR, apoptotic protein Bax, and TGF-ß in different cells. Cell counting kit-8 (CCK8) and flow cytometry were employed to assess cell proliferation activity and apoptosis. The results indicated that MC-NPs exhibited spherical particles with an average diameter of 236.47 ± 4.98 nm. The cell OD value in the MC-NPs group was lower than that in KFBs (P < 0.05). The mRNA levels of miR-214 in KFBs and hypertrophic scar tissue were lower than those in NFBs and normal tissue (P < 0.001), while the mRNA and protein levels of A2AR were significantly elevated (P < 0.05). Compared to the control group and anti-miR-NC, the anti-miR-214 group showed significantly increased cell OD values and Bcl-2 protein expression (P < 0.001), decreased levels of apoptotic gene Bax protein, TGF-ß gene mRNA, and protein expression (P < 0.001). Continuous complementary binding sites were identified between miR-214 and A2AR. Compared to the control group, the si-A2AR group exhibited a significant decrease in A2AR gene mRNA and protein expression levels (P < 0.001), reduced cell viability (P < 0.001), increased apoptosis rate (P < 0.001), and a significant elevation in TGF-ß protein expression (P < 0.001). miR-214 targetedly regulated the expression of A2AR, inducing changes in TGF-ß content, promoting the proliferation of keloid fibroblasts, and inhibiting cell apoptosis.


Assuntos
Quitosana , Cicatriz Hipertrófica , Queloide , MicroRNAs , Humanos , Queloide/patologia , Cicatriz Hipertrófica/metabolismo , Receptor A2A de Adenosina/genética , Receptor A2A de Adenosina/metabolismo , Antagomirs/metabolismo , Quitosana/farmacologia , Quitosana/metabolismo , Proliferação de Células , Fator de Crescimento Transformador beta/metabolismo , Apoptose , MicroRNAs/metabolismo , Fibroblastos/metabolismo , RNA Mensageiro/metabolismo
16.
Br J Haematol ; 204(5): 1958-1965, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38362793

RESUMO

Avatrombopag (AVA) is a novel thrombopoietin receptor agonist (TPO-RA) that has been recently approved as a second-line therapy for immune thrombocytopenia (ITP) in adults; however, its safety and efficacy data in children are lacking. Here, we demonstrated the efficacy and safety of AVA as second-line therapy in children with ITP. A multicentre, retrospective, observational study was conducted in children with persistent or chronic ITP who did not respond to or relapsed from previous treatment and were treated with AVA for at least 12 weeks between August 2020 and December 2022. The outcomes were the responses (defined as achieving a platelet count ≥30 × 109/L, twofold increase in platelet count from baseline and absence of bleeding), including rapid response within 4 weeks, sustained response at weeks 12 and 24, bleeding control and adverse events (AEs). Thirty-four (18 males) patients with a mean age of 6.3 (range: 1.9-15.3) years were enrolled. The median number of previous treatment types was four (range: 1-6), and 41.2% patients switched from other TPO-RAs. Within 4 weeks, overall response (OR) was achieved in 79.4% patients and complete response (CR, defined as a platelet count ≥100 × 109/L and the absence of bleeding) in 67.7% patients with a median response time of 7 (range: 1-27) days. At 12 weeks, OR was achieved in 88.2%, CR in 76.5% and sustained response in 44% of patients. At 24 weeks, 22/34 (64.7%) patients who achieved a response and were followed up for 24 weeks were evaluated; 12/22 (54.55%) achieved a sustained response. During AVA therapy, median platelet counts increased by week 1 and were maintained throughout the treatment period. The proportion of patients with grade 1-3 bleeding decreased from 52.95% at baseline to 2.94% at 12 weeks, while concomitant ITP medications decreased from 36.47% at baseline to 8.82% at 12 weeks, with only 9 (26.47%) patients receiving rescue therapy 23 times within 12 weeks. There were 61.8% patients with 59 AEs: 29.8% with Common Terminology Criteria for Adverse Events grade 1 and the rest with grade 2. These findings show that AVA could achieve a rapid and sustained response in children with persistent or chronic ITP as a second-line treatment, with good clinical bleeding control and reduction of concomitant ITP therapy, without significant AEs.


Assuntos
Púrpura Trombocitopênica Idiopática , Humanos , Criança , Masculino , Feminino , Estudos Retrospectivos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/sangue , Pré-Escolar , Adolescente , Lactente , China , Doença Crônica , Resultado do Tratamento , Contagem de Plaquetas , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Hemorragia/induzido quimicamente , Receptores de Trombopoetina/agonistas , População do Leste Asiático , Tiazóis , Tiofenos
17.
Aesthetic Plast Surg ; 48(12): 2330-2342, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38413446

RESUMO

BACKGROUND: Autologous fat transplantation has been a cornerstone of tissue regeneration for decades. However, there is no standardized selection system or criteria for fat graft selection, often relying heavily on the surgeon's experience. OBJECTIVES: This study aimed to investigate various types of fat derivatives, both in vitro and in vivo at the same condition. METHODS: We collected traditional fat granules of different sizes and SVF-gel, evaluating the viability of ADSCs isolated from them and their performance after grafting into mice. RESULTS: Large fat granules exhibited more complete adipocyte structures, and the isolated ADSCs demonstrated superior differentiation, proliferation, and secretion capacities. They also showed excellent volume retention after 12 weeks. In contrast, ADSCs isolated from SVF-gel displayed lower vitality. However, grafts from SVF-gel exhibited the highest volume maintenance rate among the four groups after 12 weeks, closely resembling normal adipose tissue and displaying significant vascularization. Compared to large fat granule and SVF-gel group, medium and small fat granule grafts exhibited lower volume retention and less angiogenesis. CONCLUSIONS: Through preclinical studies, the flexible clinical use of different fat grafts can be tailored to their unique characteristics. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Tecido Adiposo , Transplante Autólogo , Animais , Camundongos , Tecido Adiposo/transplante , Adipócitos/transplante , Sobrevivência de Enxerto , Feminino , Humanos , Células Cultivadas , Modelos Animais , Modelos Animais de Doenças , Diferenciação Celular , Distribuição Aleatória
18.
World J Psychiatry ; 14(1): 8-14, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38327881

RESUMO

Breast cancer (BC)is the most common malignant tumor in women, and the treatment process not only results in physical pain but also significant psychological distress in patients. Psychological intervention (PI) has been recognized as an important approach in treating postoperative psychological disorders in BC patients. It has been proven that PI has a significant therapeutic effect on post-operative psychological disorders, improving patients' negative emotions, enhancing their psychological resilience, and effectively enhancing their quality of life and treatment compliance.

19.
World J Gastrointest Surg ; 16(1): 248-256, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38328313

RESUMO

BACKGROUND: Intestinal tuberculosis is a chronic disease caused by Mycobacterium tuberculosis that mainly affects the ileum and cecum. Small bowel tuberculosis, characterized by predominant involvement of the small intestine, is an extremely rare condition with highly atypical clinical presentations, making diagnosis even more challenging. CASE SUMMARY: We report three cases of small intestinal tuberculosis, two of the patients presented primarily with abdominal pain, and one presented with gastrointestinal bleeding. All patients underwent blood tests and imaging examinations. Small bowel endoscopy (SBE) revealed that the main lesions in these patients were intestinal stenosis or gastrointestinal bleeding caused by small intestinal ulcers. One patient ultimately underwent surgical treatment. Following a complex diagnostic process and comprehensive analysis, all patients were confirmed to have small intestinal tuberculosis and received standard antituberculosis treatment, leading to an improvement in their condition. CONCLUSION: Patients with SBTs present with nonspecific symptoms such as abdominal pain, weight loss, and occasional gastrointestinal bleeding. Accurate diagnosis requires a thorough evaluation of clinical symptoms and various tests to avoid misdiagnosis and complications.

20.
Sensors (Basel) ; 24(2)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38257624

RESUMO

Current road extraction models from remote sensing images based on deep learning are computationally demanding and memory-intensive because of their high model complexity, making them impractical for mobile devices. This study aimed to develop a lightweight and accurate road extraction model, called Road-MobileSeg, to address the problem of automatically extracting roads from remote sensing images on mobile devices. The Road-MobileFormer was designed as the backbone structure of Road-MobileSeg. In the Road-MobileFormer, the Coordinate Attention Module was incorporated to encode both channel relationships and long-range dependencies with precise position information for the purpose of enhancing the accuracy of road extraction. Additionally, the Micro Token Pyramid Module was introduced to decrease the number of parameters and computations required by the model, rendering it more lightweight. Moreover, three model structures, namely Road-MobileSeg-Tiny, Road-MobileSeg-Small, and Road-MobileSeg-Base, which share a common foundational structure but differ in the quantity of parameters and computations, were developed. These models varied in complexity and were available for use on mobile devices with different memory capacities and computing power. The experimental results demonstrate that the proposed models outperform the compared typical models in terms of accuracy, lightweight structure, and latency and achieve high accuracy and low latency on mobile devices. This indicates that the models that integrate with the Coordinate Attention Module and the Micro Token Pyramid Module surpass the limitations of current research and are suitable for road extraction from remote sensing images on mobile devices.

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