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1.
Diagn Pathol ; 19(1): 122, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39244586

RESUMO

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare but severe complications that occur after solid organ or allogeneic hematopoietic stem cell transplantations (allo-HSCT), with rapid progression and high mortality. Primary central nervous system (CNS)-PTLD are rarely recognized histo-pathologically. In addition, the diagnostic value of the Epstein-Barr virus (EBV) DNA copies in CNS-PTLD remains poorly understood. OBJECTIVES: We herein report a case of monomorphic EBV-associated CNS-PTLD (diffuse large B-cell lymphoma, DLBCL) after allo-HSCT and perform a meta-analysis to assess the efficacy of PTLD treatment strategies in recent years. METHODS: We present the case report covering clinical manifestations, diagnosis, treatment, and outcomes of a patient with primary CNS-PTLD. Additionally, we include a systematic review and meta-analysis of the clinical characteristics of 431 patients with PTLD after allo-HSCT. We evaluate the main treatment options and outcomes of PTLD management, including rituximab, chemotherapies, and autologous or human leukocyte antigen (HLA)-matched EBV-specific cytotoxic T lymphocyte infusion (EBV-CTLs)/donor lymphocyte infusion (DLI). RESULTS: The meta-analysis revealed an overall response rate of 69.0% for rituximab alone (95% CI: 0.47-0.84), 45.0% for rituximab plus chemotherapies (95% CI: 0.15-0.80), and 91.0% for rituximab plus EBV-CTLs/DLI (95% CI: 0.83-0.96). The complete response (CR) rate after treatments for PTLD was 67.0% (95% CI: 0.56-0.77). Moreover, the 6-month and 1-year overall survival (OS) rate was 64.0% (95% CI: 0.31-0.87) and 49.0% (95% CI: 0.31-0.68), respectively. CONCLUSIONS: This case highlighted the urgent need for effective, low-toxic treatment regimens for CNS-PTLD. Our meta-analysis suggested that rituximab combined with EBV-CTLs/DLI could be a favorable strategy for the management of PTLD after allo-HSCT.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Transtornos Linfoproliferativos , Humanos , Infecções por Vírus Epstein-Barr/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/genética , Linfoma Difuso de Grandes Células B/virologia , Linfoma Difuso de Grandes Células B/terapia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/terapia , Rituximab/uso terapêutico , Transplante Homólogo/efeitos adversos
2.
Sci Rep ; 14(1): 14626, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918486

RESUMO

Under Taiwan's National Health Insurance (NHI) system, it's crucial for all healthcare providers to accurately submit medical expense claims to the National Health Insurance Administration (NHIA) to avoid incorrect deductions. With changes in healthcare policies and adjustments in hospital management strategies, the complexity of claiming rules has resulted in hospitals expending significant manpower and time on the medical expense claims process. Therefore, this study utilizes the Lean Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) management approach to identify wasteful and non-value-added steps in the process. Simultaneously, it introduces Robotic Process Automation (RPA) tools to replace manual operations. After implementation, the study effectively reduces the process time by 380 min and enhances Process Cycle Efficiency (PCE) from 69.07 to 95.54%. This research validates a real-world case of Lean digital transformation in healthcare institutions. It enables human resources to be allocated to more valuable and creative tasks while assisting hospitals in providing more comprehensive and patient-centric services.


Assuntos
Automação , Robótica , Robótica/métodos , Humanos , Taiwan , Atenção à Saúde , Eficiência Organizacional , Programas Nacionais de Saúde
3.
Tob Induc Dis ; 222024.
Artigo em Inglês | MEDLINE | ID: mdl-38638420

RESUMO

INTRODUCTION: Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. METHODS: Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. RESULTS: Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02-2.02; I2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74-1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14-1.87; I2=5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. CONCLUSIONS: Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.

4.
Foods ; 13(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38472905

RESUMO

Green tea catechins (GTCs) are dietary polyphenols with broad bioactivities that undergo extensive microbial metabolism in the human gut. However, microbial-transferred metabolites and their health benefits are not fully understood. Herein, the microbial metabolism of GTCs by human fecal microbiota and dynamic alteration of the microbiota were integrally investigated via in vitro anaerobic fermentation. The results showed that the human gut microbiota exhibited a strong metabolic effect on GTCs via UHPLC-MS/MS analysis. A total of 35 microbial-transferred metabolites were identified, far more than were identified in previous studies. Among them, five metabolites, namely EGCG quinone, EGC quinone, ECG quinone, EC quinone, and mono-oxygenated EGCG, were identified for the first time in fermented GTCs with the human gut microbiota. Consequently, corresponding metabolic pathways were proposed. Notably, the antioxidant, α-amylase, and α-glucosidase inhibitory activities of the GTCs sample increased after fermentation compared to those of the initial unfermented sample. The results of the 16S rRNA gene sequence analysis showed that the GTCs significantly altered gut microbial diversity and enriched the abundancy of Eubacterium, Flavonifractor, etc., which may be further involved in the metabolisms of GTCs. Thus, these findings contribute to a better understanding of the interactions between GTCs and gut microbiota, as well as the health benefits of green tea consumption.

5.
Front Pharmacol ; 15: 1242525, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510651

RESUMO

Background: Acute respiratory tract infections (ARTIs) are the most common cause of morbidity and mortality worldwide, with most people experiencing at least one episode per year. Current treatment options are mainly symptomatic therapy. Antivirals, antibiotics, and glucocorticoids are of limited benefit for most infections. Traditional Chinese medicine has shown potential benefits in the treatment of ARTIs. Objective: The objective of this study was to determine the efficacy, effectiveness, and safety of Phragmites communis Trin. (P. communis, a synonym of Phragmites australis (Cav.) Trin. ex Steud) as monotherapy or as part of an herb mixture for ARTIs. Method: Eight databases and two clinical trial registries were searched from inception to 8 February 2023 for randomized controlled trials (RCTs) evaluating any preparation involving P. communis without language restrictions. The Risk of Bias Tool 2.0 was used to assess the risk of bias of the included trials. RevMan 5.3 software was used for data analyses with effects estimated as risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals (CIs). The online GRADEpro tool was used to assess the certainty of the evidence, if available. Results: Forty-two RCTs involving 6,879 patients with ARTIs were included, with all trials investigating P. communis as part of an herbal mixture. Of the included trials, the majority (38/42) were considered high risk. Compared to the placebo, P. communis preparations improved the cure rate [RR = 1.60, 95% CI (1.13, 2.26)] and fever clearance time [MD = -2.73 h, 95% CI (-4.85, -0.61)]. Compared to usual care alone, P. communis preparations also significantly improved the cure rate [RR = 1.57, 95% CI (1.36, 1.81)] and fever clearance time [SMD = -1.24, 95% CI (-2.37, -0.11)]. P. communis preparations plus usual care compared to usual care alone increased the cure rate [RR = 1.55, 95% CI (1.35, 1.78)], shortened the fever clearance time [MD = -19.31 h, 95% CI (-33.35, -5.27)], and improved FEV1 [ MD = 0.19 L, 95% CI (0.13, 0.26)] and FVC [ MD = 0.16 L, 95% CI (0.03, 0.28)]. Conclusion: Low- or very low-certainty evidence suggests that P. communis preparations may improve the cure rate of ARTIs, shorten the fever clearance time in febrile patients, and improve the pulmonary function of patients with acute exacerbation of chronic obstructive pulmonary disease or chronic bronchitis. However, these findings are inconclusive and need to be confirmed in rigorously designed trials. Systematic review registration: PROSPERO, identifier CRD42021239936.

7.
J Cell Biol ; 222(10)2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37584589

RESUMO

Mitochondria are dynamic organelles regulated by fission and fusion processes. The fusion of membranes requires elaborative coordination of proteins and lipids and is particularly crucial for the function and quality control of mitochondria. Phosphatidic acid (PA) on the mitochondrial outer membrane generated by PLD6 facilitates the fusion of mitochondria. However, how PA promotes mitochondrial fusion remains unclear. Here, we show that a mitochondrial outer membrane protein, NME3, is required for PLD6-induced mitochondrial tethering or clustering. NME3 is enriched at the contact interface of two closely positioned mitochondria depending on PLD6, and NME3 binds directly to PA-exposed lipid packing defects via its N-terminal amphipathic helix. The PA binding function and hexamerization confer NME3 mitochondrial tethering activity. Importantly, nutrient starvation enhances the enrichment efficiency of NME3 at the mitochondrial contact interface, and the tethering ability of NME3 contributes to fusion efficiency. Together, our findings demonstrate NME3 as a tethering protein promoting selective fusion between PLD6-remodeled mitochondria for quality control.


Assuntos
Mitocôndrias , Nucleosídeo NM23 Difosfato Quinases , Ácidos Fosfatídicos , Fosfolipase D , Humanos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Ácidos Fosfatídicos/metabolismo , Fosfolipase D/metabolismo
8.
Molecules ; 28(15)2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37570841

RESUMO

Theaflavins (TFs), the primary bioactive components in black tea, are poorly absorbed in the small intestine. However, the biological activity of TFs does not match their low bioavailability, which suggests that the gut microbiota plays a crucial role in their biotransformation and activities. In this study, we aimed to investigate the biotransferred metabolites of TFs produced by the human gut microbiota and these metabolites' function. We profiled the microbial metabolites of TFs by in vitro anaerobic human gut microbiota fermentation using liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. A total of 17 microbial metabolites were identified, and their corresponding metabolic pathways were proposed. Moreover, full-length 16S rRNA gene sequence analysis revealed that the TFs altered the gut microbiota diversity and increased the relative abundance of specific members of the microbiota involved in the catabolism of the TFs, including Flavonifractor_plautii, Bacteroides_uniformis, Eubacterium_ramulus, etc. Notably, the antioxidant capacity of the TF sample increased after fermentation compared to the initial sample. In conclusion, the results contribute to a more comprehensive understanding of the microbial metabolites and antioxidant capacity of TFs.


Assuntos
Camellia sinensis , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/genética , Cromatografia Líquida , Antioxidantes/farmacologia , Antioxidantes/análise , Chá/química , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/análise , Fezes/química , Espectrometria de Massas em Tandem , Camellia sinensis/genética
9.
Qual Theory Dyn Syst ; 22(3): 113, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304646

RESUMO

To investigate the influence of human behavior on the spread of COVID-19, we propose a reaction-diffusion model that incorporates contact rate functions related to human behavior. The basic reproduction number R0 is derived and a threshold-type result on its global dynamics in terms of R0 is established. More precisely, we show that the disease-free equilibrium is globally asymptotically stable if R0≤1; while there exists a positive stationary solution and the disease is uniformly persistent if R0>1. By the numerical simulations of the analytic results, we find that human behavior changes may lower infection levels and reduce the number of exposed and infected humans.

10.
Entropy (Basel) ; 25(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37372231

RESUMO

A large number of complex biochemical reaction networks are included in the gene expression, cell development, and cell differentiation of in vivo cells, among other processes. Biochemical reaction-underlying processes are the ones transmitting information from cellular internal or external signaling. However, how this information is measured remains an open question. In this paper, we apply the method of information length, based on the combination of Fisher information and information geometry, to study linear and nonlinear biochemical reaction chains, respectively. Through a lot of random simulations, we find that the amount of information does not always increase with the length of the linear reaction chain; instead, the amount of information varies significantly when this length is not very large. When the length of the linear reaction chain reaches a certain value, the amount of information hardly changes. For nonlinear reaction chains, the amount of information changes not only with the length of this chain, but also with reaction coefficients and rates, and this amount also increases with the length of the nonlinear reaction chain. Our results will help to understand the role of the biochemical reaction networks in cells.

11.
Adv Sci (Weinh) ; 10(18): e2300043, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37083226

RESUMO

Mammalian oogenesis features reliance on the mRNAs produced and stored during early growth phase. These are essential for producing an oocyte competent to undergo meiotic maturation and embryogenesis later when oocytes are transcriptionally silent. The fate of maternal mRNAs hence ensures the success of oogenesis and the quality of the resulting eggs. Nevertheless, how the fate of maternal mRNAs is determined remains largely elusive. RNA-binding proteins (RBPs) are crucial regulators of oogenesis, yet the identity of the full complement of RBPs expressed in oocytes is unknown. Here, a global view of oocyte-expressed RBPs is presented: mRNA-interactome capture identifies 1396 RBPs in mouse oocytes. An analysis of one of these RBPs, LSM family member 14 (LSM14B), demonstrates that this RBP is specific to oocytes and associated with many networks essential for oogenesis. Deletion of Lsm14b results in female-specific infertility and a phenotype characterized by oocytes incompetent to complete meiosis and early embryogenesis. LSM14B serves as an interaction hub for proteins and mRNAs throughout oocyte development and regulates translation of a subset of its bound mRNAs. Therefore, RNP complexes tethered by LSM14B are found exclusively in oocytes and are essential for the control of maternal mRNA fate and oocyte development.


Assuntos
Oócitos , RNA Mensageiro Estocado , Feminino , Animais , Camundongos , RNA Mensageiro Estocado/genética , RNA Mensageiro Estocado/metabolismo , Oócitos/metabolismo , Oogênese/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Mamíferos/metabolismo
12.
Brief Bioinform ; 24(1)2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36642412

RESUMO

Machine learning-based scoring functions (MLSFs) have become a very favorable alternative to classical scoring functions because of their potential superior screening performance. However, the information of negative data used to construct MLSFs was rarely reported in the literature, and meanwhile the putative inactive molecules recorded in existing databases usually have obvious bias from active molecules. Here we proposed an easy-to-use method named AMLSF that combines active learning using negative molecular selection strategies with MLSF, which can iteratively improve the quality of inactive sets and thus reduce the false positive rate of virtual screening. We chose energy auxiliary terms learning as the MLSF and validated our method on eight targets in the diverse subset of DUD-E. For each target, we screened the IterBioScreen database by AMLSF and compared the screening results with those of the four control models. The results illustrate that the number of active molecules in the top 1000 molecules identified by AMLSF was significantly higher than those identified by the control models. In addition, the free energy calculation results for the top 10 molecules screened out by the AMLSF, null model and control models based on DUD-E also proved that more active molecules can be identified, and the false positive rate can be reduced by AMLSF.


Assuntos
Proteínas , Proteínas/metabolismo , Bases de Dados Factuais , Ligantes , Simulação de Acoplamento Molecular , Ligação Proteica
13.
Hum Factors ; 65(7): 1407-1421, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-34974764

RESUMO

OBJECTIVE: To investigate the digit force control during a five-digit precision grasp in aligned (AG) and unaligned grasping (UG) configurations. BACKGROUND: The effects of various cylindrical handles for tools on power grasp performance have been previously investigated. However, there is little information on force control strategy of precision grasp to fit various grasping configurations. METHOD: Twenty healthy young adults were recruited to perform a lift-hold-lower task. The AG and UG configurations on a cylindrical simulator with force transducers were adjusted for each individual. The applied force and moment, the force variability during holding, and force correlations between thumb and each finger were measured. RESULT: No differences in applied force, force correlation, repeatability, and variability were found between configurations. However, the moments applied in UG were significantly larger than those in AG. CONCLUSION: The force control during precision grasp did not change significantly across AG and UG except for the digit moment. The simulator is controlled efficiently with large moment during UG, which is thus the optimal configuration for precision grasping with a cylindrical handle. Further research should consider the effects of task type and handle design on force control, especially for individuals with hand disorders. APPLICATION: To design the handle of specific tool, one should consider the appropriate configuration according to the task requirements of precision grasping to reduce the risk of accumulating extra loads on digits with a cylindrical handle.


Assuntos
Dedos , Força da Mão , Adulto Jovem , Humanos , Desempenho Psicomotor
14.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1002947

RESUMO

Background/Aims@#Gastrointestinal (GI) bezoars are relatively rare diseases with clinical characteristics and treatment modalities that depend on the location of the bezoars. This study evaluated the clinical characteristics and treatment outcomes in patients with GI bezoars. @*Methods@#Seventy-five patients diagnosed with GI bezoars were enrolled in this study. Data were collected on the demographic and clinical characteristics and the characteristics of the bezoars, such as type, size, location, treatment modality, and clinical outcomes. @*Results@#Among the 75 patients (mean age 71.2 years, 38 males), 32 (42.6%) had a history of intra-abdominal surgery. Hypertension (43%) and diabetes (30%) were common morbidities. The common location of the bezoars was the stomach in 33 (44%) and the small intestine in 33 (44%). Non-surgical management, including adequate hydration, chemical dissolution, and endoscopic removal, was successful in 2/2 patients with esophageal bezoars, 26/33 patients with gastric bezoars, 7/9 patients with duodenal bezoars, and 20/33 patients with small intestinal bezoars. The remaining patients had undergone surgical management. @*Conclusions@#The management of GI bezoars requires multidisciplinary approaches, including the appropriate correction of fluid and electrolyte imbalances, chemical dissolution, and endoscopic and surgical treatments. (Korean J Gastroenterol 2023;81:253-258)

15.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1002982

RESUMO

Colonic interposition is the main procedure used in esophageal reconstruction. We report a rare case of simultaneous treatment of an anastomotic site stricture and a neoplasm in the interpositioned colon. A 69-year-old female visited our outpatient clinic with symptoms of progressive dysphagia for 1 year. At the age of 30 years, the patient underwent esophagectomy with retrosternal colonic interposition because of severe esophageal burns after chemical ingestion. Upper gastrointestinal endoscopy revealed stricture at the anastomosis site and a 10-mm flat elevated high-grade dysplasia in the interpositioned colon. First, through-the-scope balloon dilatation was performed for strictures. However, stenosis was observed during the second upper gastrointestinal endoscopy session.Therefore, a second session of through-the-scope balloon dilatation was performed, and simultaneously, endoscopic submucosal dissection was also successfully performed. After 2 months of follow-up, stenosis persisted; consequently, balloon dilatation was performed. No recurrence of neoplasm was confirmed endoscopically. Through-the-scope balloon dilatation of the stricture site and simultaneous endoscopic submucosal dissection of the neoplasm in the interpositioned colon were successfully performed.

16.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1002993

RESUMO

Objectives@#Gastrointestinal cytomegalovirus (CMV) disease is a major contributor to mortality in immunocompromised patients. Few studies have discussed upper gastrointestinal CMV (UGICMV) disease in immunocompetent patients. We compared the clinical outcomes of UGI-CMV between immunocompromised and immunocompetent patients. @*Methods@#This retrospective study included patients with UGI-CMV disease from five tertiary hospitals across Korea (2010– 2022). Patients’ clinical data and outcomes were recorded. @*Results@#UGI-CMV was diagnosed in 54 patients; 27 (50.0%) had esophageal, 24 (44.4%) had gastric, and 3 patients (5.6%) had duodenal involvement. Patients’ median age was 64 years (interquartile range 53–75 years), and the most common comorbidities included hypertension (57.4%) and diabetes (38.9%). The predominant symptom was abdominal pain (46.3%), and the most common endoscopic finding was ulcers (70.4%). Antiviral treatment was administered to 31 patients, and 23 patients underwent observation without treatment. We investigated 32 immunocompromised (59.3%) and 22 immunocompetent (40.7%) patients and observed no intergroup differences in comorbidities and in laboratory and endoscopic findings. Immunocompromised patients had longer length of hospitalization (median 46.2 days vs. 20.0 days, p=0.001). However, treatment outcomes, including the need for intensive care unit admission and mortality did not significantly differ. The overall mortality rate was 13.0%; one patient from the immunocompromised group died of UGI-CMV disease. The treatment success rate was higher in immunocompromised patients who received antiviral therapy (p=0.011). @*Conclusions@#UGI-CMV disease is not uncommon in immunocompetent patients, although symptoms are milder than those in immunocompromised patients. Our findings emphasize the importance of clinical vigilance for accurate diagnosis of CMV infection, particularly in susceptible symptomatic patients and highlight the need for active antiviral treatment for management of immunocompromised patients.

17.
Commun Biol ; 5(1): 1327, 2022 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463362

RESUMO

As the time of ovulation draws near, mouse spermatozoa move out of the isthmic reservoir, which is a prerequisite for fertilization. However, the molecular mechanism remains unclear. The present study revealed that mouse cumulus cells of oocytes-cumulus complexes (OCCs) expressed transforming growth factor-ß ligand 1 (TGFB1), whereas ampullary epithelial cells expressed the TGF-ß receptors, TGFBR1 and TGFBR2, and all were upregulated by luteinizing hormone (LH)/human chorionic gonadotropin (hCG). OCCs and TGFB1 increased natriuretic peptide type C (NPPC) expression in cultured ampullae via TGF-ß signaling, and NPPC treatment promoted spermatozoa moving out of the isthmic reservoir of the preovulatory oviducts. Deletion of Tgfb1 in cumulus cells and Tgfbr2 in ampullary epithelial cells blocked OCC-induced NPPC expression and spermatozoa moving out of the isthmic reservoir, resulting in compromised fertilization and fertility. Oocyte-derived paracrine factors were required for promoting cumulus cell expression of TGFB1. Therefore, oocyte-dependent and cumulus cell-derived TGFB1 promotes the expression of NPPC in oviductal ampulla, which is critical for sperm migration in the oviduct and subsequent fertilization.


Assuntos
Peptídeo Natriurético Tipo C , Oócitos , Oviductos , Ovulação , Transporte Espermático , Espermatozoides , Animais , Feminino , Masculino , Camundongos , Oócitos/metabolismo , Oócitos/fisiologia , Oviductos/metabolismo , Oviductos/fisiologia , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Sêmen , Espermatozoides/metabolismo , Peptídeo Natriurético Tipo C/genética , Peptídeo Natriurético Tipo C/metabolismo , Ovulação/genética , Ovulação/metabolismo , Fertilização/genética , Fertilização/fisiologia , Transporte Espermático/genética , Transporte Espermático/fisiologia
18.
Pharmaceuticals (Basel) ; 15(7)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35890172

RESUMO

Breast cancer is one of the most prevalent malignancies with poor prognosis. Inhibition of angiogenesis is becoming a valid and evident therapeutic strategy to treat cancer. Recent studies uncovered the antiangiogenic activity of ZLM-7 (a combretastain A-4 derivative), but the regulatory mechanism is unclear. ZLM-7 treatment was applied in estrogen receptor-positive cell MCF-7, triple-negative breast cancer cell MDA-MB-231 and xenograft models. Transfections were conducted to overexpress or knockdown targeted genes. The gene and protein expressions were measured by qPCR and Western blotting assay, respectively. Cell proliferation and apoptosis were evaluated using the CCK8 method, clone formation assay and flow cytometry. We found that ZLM-7 upregulated 14-3-3 sigma expression but downregulated MDM2 expression in breast cancer cells. ZLM-7 delayed cell proliferation, promoted apoptosis and blocked cell-cycle progression in human breast cancer cells in vitro, while those effects were abolished by 14-3-3 sigma knockdown; overexpression of 14-3-3 sigma reproduced the actions of ZLM-7 on the cell cycle, which could be reversed by MDM2 overexpression. In xenograft models, ZLM-7 treatment significantly inhibited tumor growth while the inhibition was attenuated when 14-3-3 sigma was silenced. Collectively, ZLM-7 could inhibit MDM2 via upregulating 14-3-3 sigma expression, thereby blocking the breast cancer progression.

19.
Biol Reprod ; 107(1): 76-84, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35552649

RESUMO

Coordinated development of the germline and the somatic compartments within a follicle is an essential prerequisite for creating a functionally normal oocyte. Bi-directional communication between the oocyte and the granulosa cells enables the frequent interchange of metabolites and signals that support the development and functions of both compartments. Mechanistic target of rapamycin (MTOR), a conserved serine/threonine kinase and a widely recognized integrator of signals and pathways key for cellular metabolism, proliferation, and differentiation, is emerging as a major player that regulates many facets of oocyte and follicle development. Here, we summarized our recent observations on the role of oocyte- and granulosa cell-expressed MTOR in the control of the oocyte's and granulosa cell's own development, as well as the development of one another, and provided new data that further strengthen the role of cumulus cell-expressed MTOR in synchronizing oocyte and follicle development. Inhibition of MTOR induced oocyte meiotic resumption in cultured large antral follicles, as well as cumulus expansion and the expression of cumulus expansion-related transcripts in cumulus-oocyte complexes in vitro. In vivo, the activity of MTOR in cumulus cells was diminished remarkably by 4 h after hCG administration. These results thus suggest that activation of MTOR in cumulus cells contributes to the maintenance of oocyte meiotic arrest before the LH surge. Based on the observations made by us here and previously, we propose that MTOR is an essential mediator of the bi-directional communication between the oocyte and granulosa cells that regulates the development and function of both compartments.


Assuntos
Células da Granulosa , Meiose , Oócitos , Serina-Treonina Quinases TOR , Animais , Feminino , Células da Granulosa/metabolismo , Camundongos , Oócitos/metabolismo , Folículo Ovariano/metabolismo , Serina-Treonina Quinases TOR/metabolismo
20.
ACS Appl Mater Interfaces ; 14(24): 28247-28257, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35604841

RESUMO

Soft ionotronics are emerging materials as wearable sensors for monitoring physiological signals, sensing environmental hazards, and bridging the human-machine interface. However, the next generation of wearable sensors requires multiple sensing capabilities, mechanical toughness, and 3D printability. In this study, a metal-organic framework (MOF) and three-dimensional (3D) printing were integrated for the synthesis of a tough MOF-based ionogel (MIG) for colorimetric and mechanical sensing. The ink for 3D printing contained deep eutectic solvents (DESs), cellulose nanocrystals (CNCs), MOF crystals, and acrylamide. After printing, further photopolymerization resulted in a second covalently cross-linked poly(acrylamide) network and solidification of MIG. As a porphyrinic Zr-based MOF, MOF-525 served as a functional filler to provide sharp color changes when exposed to acidic compounds. Notably, MOF-525 crystals also provided another design space to tune the printability and mechanical strength of MIG. In addition, the printed MIG exhibited high stability in the air because of the low volatility of DESs. Thereafter, wearable auxetic materials comprising MIG with negative Poisson's ratios were prepared by 3D printing for the detection of mechanical deformation. The resulting auxetic sensor exhibited high sensitivity via the change in resistance upon mechanical deformation and a conformal contact with skins to monitor various human body movements. These results demonstrate a facile strategy for the construction of multifunctional sensors and the shaping of MOF-based composite materials.

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