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BACKGROUND: At present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear. METHODS: RNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation. RESULTS: In the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation. CONCLUSIONS: The present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS. TRIAL REGISTRATION: Not applicable.
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Quimiocina CXCL10 , Células da Granulosa , Liraglutida , Folículo Ovariano , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/genética , Humanos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Animais , Camundongos , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Adulto , Ovulação/efeitos dos fármacos , Líquido Folicular/metabolismo , Células Cultivadas , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêuticoRESUMO
Recurrent spontaneous abortion (RSA) is a complex pathological process involving diverse factors, in which the dysregulated functions of trophoblasts cannot be ignored. Long noncoding RNA (lncRNA) has been reported to play a significant role in regulating the functions of trophoblasts in RSA. However, the impact and potential mechanism of lncRNA small nucleolar RNA host gene 12 (lncSNHG12) remain unclear. The role of lncSNHG12 in RSA was investigated through in vivo experiments and clinical samples. Co-IP and RNA pull down were conducted to explore the molecular mechanisms in trophoblasts. Our results showed that lncSNHG12 promoted the migration and invasion of trophoblasts by interacting with Iodothyronine deiodinase 2 (Dio2), which regulating the EMT process of trophoblasts by interacting with Snail. Moreover, in vivo experiments confirmed that lncSNHG12 could improve the fetal absorption rate of the abortion mice. The clinical samples revealed that lncSNHG12, Dio2 and Snail were down-regulated in the villous tissues of RSA patients, and positive correlations were confirmed between lncSNHG12 and Dio2, as well as Dio2 and Snail. In summary, the lncSNHG12/Dio2/Snail axis might be involved in the development of RSA by regulating the invasion and migration of trophoblasts. Abbreviations: RSA, recurrent spontaneous abortion; EVTs, extravillous trophoblasts; EMT, epithelial-to-mesenchymal transition; lncRNA, long non-coding RNA; Dio2, iodothyronine deiodinase 2; SNHGs, small nuclear RNA host genes; snoRNAs, small nuclear cell RNAs; LPS, lipopolysaccharide; De, derived decidua; Jz, junctional zone; Lz, labyrinth zones; RIP, RNA Binding Protein Immunoprecipitation; Co-IP, Co-Immunoprecipitation; RPISeq, RNA-Protein Interaction Prediction.
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The increasing discharge of oily wastewater from life poses a serious threat to the ecological environment and human health. To develop green, efficient, and low-cost materials for oil-water separation, a superhydrophobic photothermal oil-absorbing sponge (CAC-PDA@MF) was prepared by using nanoscale coconut shell activated carbon (CAC) loaded on a melamine sponge in this study. The sponge had excellent superhydrophobicity (WCA of 159.53°) due to the reduction of surface energy by grafting long-chain silanes. The adsorption capacity of the sponge was 69.04 g/g-158.27 g/g for a wide range of oils and organic solvents, and the sponge had excellent mechanical properties for multiple adsorption and recovery of oil. After 50 cycles of oil-water separation, its separation efficiency was maintained at over 98 %. In addition, the material had high acid, alkali, and salt resistance as well as excellent photothermal conversion properties. Its surface temperature rose rapidly to 100 °C and above, at a light intensity of 1.0 kW/m2. The material was capable of adsorbing and recovering high-viscosity oils that were solid or semi-solid at room temperature. Its versatility and commercial value made it a promising candidate for a wide range of applications.
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BACKGROUND: No consensus has been concluded with regarding to the scope of lymph node (LN) dissection for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). This study aimed to explore risk factors for lower perigastric LN (LPLN) metastases (including no. 4d, 5, 6, and 12a LN stations) and analyze the indications for LPLN dissection. METHODS: In total, 302 consecutive patients with Siewert type II and III AEG who underwent total gastrectomy (TG) were enrolled. The logistic regression model was used to perform uni- and multivariate analyses of risk factors for LPLN metastases. Kaplan-Meier curves were used for survival analysis, and log-rank tests were used for group comparisons. Basing on the guidelines of Japanese Gastric Cancer Association, the LN metastases (LNM) as well as the efficiency index (EI) of each LN station was further evaluated. RESULTS: The independent risk factors for LPLN metastases in patients with Siewert type II and III AEG were distance from the esophagogastric junction (EGJ) to the distal end of the tumor (> 4.0 cm), preoperative carcinoembryonic antigen (CEA) ( +), pT4 stage, and HER-2 ( +). LPLN metastases was an independent risk factor for overall survival following TG. The LNM and EI of LPLN were 8.6% and 2.31%, respectively. The LNM of LPLN > 10% under the stratification of the distance from the EGJ to the distal end of the tumor (> 4.0 cm), pT4, preoperative CEA ( +), and HER-2 ( +) exhibited EI values of 3.55%, 2.09%, 2.51%, and 3.64%, respectively. CONCLUSIONS: LPLN metastases was a malignant factor for the prognosis of patients with Siewert type II and III AEG. For patients with preoperative CEA ( +), pT4 stage, HER-2 ( +), and the distance from the EGJ to the distal end of the tumor (> 4.0 cm), TG with LPLN dissection is prioritized for clinical recommendation.
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Adenocarcinoma , Neoplasias Esofágicas , Junção Esofagogástrica , Gastrectomia , Excisão de Linfonodo , Metástase Linfática , Neoplasias Gástricas , Humanos , Junção Esofagogástrica/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Risco , Gastrectomia/métodos , Idoso , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Adulto , Linfonodos/patologia , Relevância ClínicaRESUMO
Intramuscular fat (IMF) in pork holds significant importance for economic performance within the pig industry and dietary calcium supplementation enhances the accumulation of intramuscular fat. Additionally, calcium ions inhibit translation and reduce protein synthesis. However, the mechanism by which calcium regulates IMF deposition in muscle through translation remains largely unknown. In this study, we compared the ribosome profiles of the longissimus dorsi muscles of Duroc × Landrace × Large white pigs from the normal calcium (NC) group or calcium supplement (HC) group by Ribo-seq, and RNA-seq. By integrating multiple-omics analysis, we further discovered 437 genes that were transcriptionally unchanged but translationally altered and these genes were significantly enriched in the oxidative phosphorylation signaling pathway. Furthermore, experimental data showed that inhibiting the expression of COX10 and mtND4L increased triglyceride accumulation in C2C12 cells, providing new targets for intramuscular fat deposition. Finally, this work links dietary calcium, translation regulation and IMF deposition, providing a new strategy for both meat quality and economic performance within the pig industry.
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Cálcio da Dieta , Músculo Esquelético , Animais , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Suínos , Cálcio da Dieta/metabolismo , Tecido Adiposo/metabolismo , Suplementos Nutricionais , Camundongos , Biossíntese de Proteínas/efeitos dos fármacos , Triglicerídeos/metabolismo , Cálcio/metabolismoRESUMO
Polycystic ovary syndrome (PCOS), an endocrine disorder afflicting 6-20% of women of reproductive age globally, has been linked to alterations in the gut microbiome. We previously showed that in PCOS, elevation of Bacteroides vulgatus in the gut microbiome was associated with altered bile acid metabolism. Here we show that B. vulgatus also induces a PCOS-like phenotype in female mice via an alternate mechanism independent of bile acids. We find that B. vulgatus contributes to PCOS-like symptoms through its metabolite agmatine, which is derived from arginine by arginine decarboxylase. Mechanistically, agmatine activates the farnesoid X receptor (FXR) pathway to subsequently inhibit glucagon-like peptide-1 (GLP-1) secretion by L cells, which leads to insulin resistance and ovarian dysfunction. Critically, the GLP-1 receptor agonist liraglutide and the arginine decarboxylase inhibitor difluoromethylarginine ameliorate ovarian dysfunction in a PCOS-like mouse model. These findings reveal that agmatine-FXR-GLP-1 signalling contributes to ovarian dysfunction, presenting a potential therapeutic target for PCOS management.
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Agmatina , Microbioma Gastrointestinal , Síndrome do Ovário Policístico , Receptores Citoplasmáticos e Nucleares , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Animais , Feminino , Camundongos , Agmatina/farmacologia , Agmatina/metabolismo , Agmatina/uso terapêutico , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças , Resistência à Insulina , Bacteroides/efeitos dos fármacos , Humanos , Carboxiliases/metabolismoRESUMO
In this study, the family GH10 xylanase AnXylA10 derived from Aspergillus niger JL15 strain was expressed in Pichia pastoris X33. The recombinant xylanase, reAnXylA10 exhibited optimal activity at 40 â and pH 5.0. The hydrolysates generated from beechwood xylan using reAnXylA10 primarily consisted of xylobiose (X2) to xylohexaose (X6) and demonstrated remarkable antioxidant capacity. Furthermore, the rice xylanase inhibitory protein (riceXIP) was observed to competitively inhibit reAnXylA10, exhibiting an inhibition constant (Ki) of 140.6â¯nM. Molecular dynamics (MD) simulations of AnXylA10-riceXIP complex revealed that the α-7 helix (Q225-S238) of riceXIP intruded into the catalytic pocket of AnXylA10, thereby obstructing substrate access to the active site. Specifically, residue K226 of riceXIP formed robust interactions with E136 and E242, the two catalytic sites of AnXylA10, predominantly through high-occupied hydrogen bonds. Based on QTAIM, electron densities for the atom pairs K226riceXIP@HZ1-E136AnXylA10@OE2 and K226riceXIP@HZ3-E242AnXylA10@OE1 were determined to be 0.04628 and 0.02914â¯a.u., respectively. Binding free energy of AnXylA10-riceXIP complex was -59.0±7.6â¯kcal/mol, significantly driven by electrostatic and van der Waals forces. Gaining insights into the interaction between xylanase and its inhibitors, and mining the inhibition mechanism in depth, will facilitate the design of innovative GH10 family xylanases that are both highly efficient and resistant to inhibitors.
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Antioxidantes , Aspergillus niger , Endo-1,4-beta-Xilanases , Proteínas Fúngicas , Glucuronatos , Oligossacarídeos , Proteínas Recombinantes , Xilanos , Glucuronatos/metabolismo , Glucuronatos/química , Xilanos/metabolismo , Endo-1,4-beta-Xilanases/metabolismo , Endo-1,4-beta-Xilanases/genética , Endo-1,4-beta-Xilanases/química , Aspergillus niger/enzimologia , Aspergillus niger/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/química , Oligossacarídeos/metabolismo , Antioxidantes/metabolismo , Antioxidantes/química , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/química , Simulação de Dinâmica Molecular , Oryza , Fagus , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Madeira , Pichia/genética , Pichia/metabolismo , Hidrólise , Domínio CatalíticoRESUMO
Disrupted mitochondrial dynamics and mitophagy contribute to functional deterioration of skeletal muscle (SM) during aging, but the regulatory mechanisms are poorly understood. Our previous study demonstrated that the expression of thyroid hormone receptor α (TRα) decreased significantly in aged mice, suggesting that the alteration of thyroidal elements, especially the decreased TRα, might attenuate local THs action thus to cause the degeneration of SM with aging, while the underlying mechanism remains to be further explored. In this study, decreased expression of myogenic regulators Myf5, MyoD1, mitophagy markers Pink1, LC3II/I, p62, as well as mitochondrial dynamic factors Mfn1 and Opa1, accompanied by increased reactive oxygen species (ROS), showed concomitant changes with reduced TRα expression in aged mice. Further TRα loss- and gain-of-function studies in C2C12 revealed that silencing of TRα not only down-regulated the expression of above-mentioned myogenic regulators, mitophagy markers and mitochondrial dynamic factors, but also led to a significant decrease in mitochondrial activity and maximum respiratory capacity, as well as more mitochondrial ROS and damaged mitochondria. Notedly, overexpression of TRα could up-regulate the expression of those myogenic regulators, mitophagy markers and mitochondrial dynamic factors, meanwhile also led to an increase in mitochondrial activity and number. These results confirmed that TRα could concertedly regulate mitochondrial dynamics, autophagy, and activity, and myogenic regulators rhythmically altered with TRα expression. Summarily, these results suggested that the decline of TRα might cause the degeneration of SM with aging by regulating mitochondrial dynamics, mitophagy and myogenesis.
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Mitocôndrias , Músculo Esquelético , Sarcopenia , Receptores alfa dos Hormônios Tireóideos , Animais , Camundongos , Envelhecimento/metabolismo , Linhagem Celular , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/patologia , Dinâmica Mitocondrial , Mitofagia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Espécies Reativas de Oxigênio/metabolismo , Sarcopenia/metabolismo , Sarcopenia/patologia , Receptores alfa dos Hormônios Tireóideos/genética , Receptores alfa dos Hormônios Tireóideos/metabolismoRESUMO
Organophosphorus pesticides play an important role as broad-spectrum inactivating herbicides in agriculture. Developing a method for rapid and efficient organophosphorus pesticides detection is still urgent due to the increasing concern on food safety. An organo-probe (ZDA), synthesized by purine hydrazone derivative and 2,2'-dipyridylamine derivative, was applied in sensitive recognition of Cu2+ with detection limit of 300 nM. Mechanism study via density functional theory (DFT) and job's plot experiment revealed that ZDA and Cu2+ ions form a 1:2 complex quenching the fluorescence emission. Moreover, this fluorescent complex ZDA-Cu2+ was applicable for detecting glyphosate and glufosinate ammonium following fluorescence enhancement mechanism, with detection limits of 11.26 nM and 11.5 nM, respectively. Meanwhile, ZDA-Cu2+ was effective and sensitive when it is used for pesticide detection, reaching the maximum value and stabilizing in 1 min. Finally, the ZDA-Cu2+ probe could also be tolerated in cell assay environment, implying potential bio-application.
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Aminobutiratos , Glifosato , Praguicidas , Compostos Organofosforados , Fluorescência , Corantes Fluorescentes , Purinas , Espectrometria de Fluorescência , CobreRESUMO
Gouty arthritis (GA) is an inflammatory disease characterized by pain. The primary goal of current treatment strategies during GA flares remains the reduction of inflammation and pain. Research suggests that the gut microbiota and microbial metabolites contribute to the modulation of the inflammatory mechanism associated with GA, particularly through their effect on macrophage polarization. The increasing understanding of the gut-joint axis emphasizes the importance of this interaction. The primary objective of this review is to summarize existing research on the gut-immune-joint axis in GA, aiming to enhance understanding of the intricate processes and pathogenic pathways associated with pain and inflammation in GA, as documented in the published literature. The refined comprehension of the gut-joint axis may potentially contribute to the future development of analgesic drugs targeting gut microbes for GA.
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BACKGROUND: Despite advances in medical imaging technology, the accurate preoperative prediction of lymph node status remains challenging in ovarian cancer. This retrospective study aimed to investigate the feasibility of using ultrasound-based radiomics combined with preoperative clinical characteristics to predict lymph node metastasis (LNM) in patients with high-grade serous ovarian cancer (HGSOC). RESULTS: Patients with 401 HGSOC lesions from two institutions were enrolled: institution 1 for the training cohort (n = 322) and institution 2 for the external test cohort (n = 79). Radiomics features were extracted from the three preoperative ultrasound images of each lesion. During feature selection, primary screening was first performed using the sample variance F-value, followed by recursive feature elimination (RFE) to filter out the 12 most significant features for predicting LNM. The radscore derived from these 12 radiomic features and three clinical characteristics were used to construct a combined model and nomogram to predict LNM, and subsequent 10-fold cross-validation was performed. In the test phase, the three models were tested with external test cohort. The radiomics model had an area under the curve (AUC) of 0.899 (95% confidence interval [CI]: 0.864-0.933) in the training cohort and 0.855 (95%CI: 0.774-0.935) in the test cohort. The combined model showed good calibration and discrimination in the training cohort (AUC = 0.930) and test cohort (AUC = 0.881), which were superior to those of the radiomic and clinical models alone. CONCLUSIONS: The nomogram consisting of the radscore and preoperative clinical characteristics showed good diagnostic performance in predicting LNM in patients with HGSOC. It may be used as a noninvasive method for assessing the lymph node status in these patients.
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Nomogramas , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Radiômica , Neoplasias Ovarianas/diagnóstico por imagem , Metástase Linfática , Linfonodos/diagnóstico por imagemRESUMO
Cancer remains a highly lethal disease due to its elusive early detection, rapid spread, and significant side effects. Nanomedicine has emerged as a promising platform for drug delivery, diagnosis, and treatment monitoring. In particular, carbon dots (CDs), a type of fluorescent nanomaterial, offer excellent fluorescence properties and the ability to carry multiple drugs simultaneously through covalent bonding. In this work, CDs with carbonyl groups on the surface were prepared by aldol condensation and reacted with amine groups in the structure of doxorubicin (DOX) through Schiff base reaction to generate pH-responsive CDs-DOX. On the other hand, cubosomes with three-dimensional lattice structures formed by lipid bilayers have advantageous capabilities of encapsulating various hydrophilic, amphiphilic, and hydrophobic substances. The pH-responsive CDs-DOX are subsequently loaded into cubosomes to form an anticancer therapeutic nanosystem, CDs-DOX@cubosome. Leveraging the unique properties of CDs-DOX and cubosomes, our CDs-DOX@cubosome can enter tumor tissue through the enhanced permeation and retention effect first and conduct membrane fusion with tumor cells to intracellularly release CDs-DOX. Then, the imine bond in CDs-DOX breaks under acidic conditions within human cancer cell lines (HeLa and HepG-2 cells), releasing DOX and achieving enhanced treatment of tumors. Additionally, fluorescent CDs can synchronously achieve real-time in situ diagnosis of tumor tissue. We demonstrate that our CDs-DOX@cubosome works as an excellent drug delivery system with therapeutic efficiency enhancement to the tumor and reduced side effects.
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Carbono , Doxorrubicina , Humanos , Carbono/farmacologia , Carbono/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Sistemas de Liberação de Medicamentos/métodos , Células HeLa , Concentração de Íons de HidrogênioRESUMO
CRISPR-Cas9 systems constitute bacterial adaptive immune systems that protect against phage infections. Bacteriophages encode anti-CRISPR proteins (Acrs) that mitigate the bacterial immune response. However, the structural basis for their inhibitory actions from a molecular perspective remains elusive. In this study, through microsecond atomistic molecular dynamics simulations, we demonstrated the remarkable flexibility of Streptococcus pyogenes Cas9 (SpyCas9) and its conformational adaptability during interactions with AcrIIA4 and AcrIIA2. Specifically, we demonstrated that the binding of AcrIIA4 and AcrIIA2 to SpyCas9 induces a conformational rearrangement that causes spatial separation between the nuclease and cleavage sites, thus making the endonuclease inactive. This separation disrupts the transmission of signals between the protospacer adjacent motif recognition and nuclease domains, thereby impeding the efficient processing of double-stranded DNA. The simulation also reveals that AcrIIA4 and AcrIIA2 cause different structural variations of SpyCas9. Our research illuminates the precise mechanisms underlying the suppression of SpyCas9 by AcrIIA4 and AcrIIA2, thus presenting new possibilities for controlling genome editing with higher accuracy.
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OBJECTIVE: Studies have shown a correlation between obesity and mitochondrial calcium homeostasis, yet it is unclear whether and how Mcu regulates adipocyte lipid deposition. This study aims to provide new potential target for the treatment of obesity and related metabolic diseases, and to explore the function of Mcu in adipose tissue. METHODS: We firstly investigated the role of mitoxantrone, an Mcu inhibitor, in the regulation of glucose and lipid metabolism in mouse adipocytes (3T3-L1 cells). Secondly, C57BL/6J mice were used as a research model to investigate the effects of Mcu inhibitors on fat accumulation and glucose metabolism in mice on a high-fat diet (HFD), and by using CRISPR/Cas9 technology, adipose tissue-specific Mcu knockdown mice (Mcufl/+ AKO) and Mcu knockout of mice (Mcufl/fl AKO) were obtained, to further investigate the direct effects of Mcu on fat deposition, glucose tolerance and insulin sensitivity in mice on a high-fat diet. RESULTS: We found the Mcu inhibitor reduced adipocytes lipid accumulation and adipose tissues mass in mice fed an HFD. Both Mcufl/+ AKO mice and Mcufl/fl AKO mice were resistant to HFD-induced obesity, compared to control mice. Mice with Mcufl/fl AKO showed improved glucose tolerance and insulin sensitivity as well as reduced hepatic lipid accumulation. Mechanistically, inhibition of Mcu promoted mitochondrial biogenesis and adipocyte browning, increase energy expenditure and alleviates diet-induced obesity. CONCLUSIONS: Our study demonstrates a link between adipocyte lipid accumulation and mCa2+ levels, suggesting that adipose-specific Mcu deficiency alleviates HFD-induced obesity and ameliorates metabolic disorders such as insulin resistance and hepatic steatosis. These effects may be achieved by increasing mitochondrial biosynthesis, promoting white fat browning and enhancing energy metabolism.
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Canais de Cálcio , Resistência à Insulina , Animais , Camundongos , Tecido Adiposo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético , Glucose/metabolismo , Resistência à Insulina/fisiologia , Lipídeos , Camundongos Endogâmicos C57BL , Obesidade/metabolismoRESUMO
OBJECTIVE: Medial opening-wedge high tibial osteotomy (MOWHTO) is considered to be an effective treatment for symptomatic knee osteoarthritis (KOA) of isolated the medial compartment with varus alignment of the lower extremity. However, the choice of material to fill the void remains controversial. This study aims to evaluate the bone union of the osteotomy gap using a novel wedge-shaped cancellous allograft after MOWHTO and its effect on clinical outcomes. METHODS: All patients who underwent MOWHTO using a novel wedge-shaped cancellous allograft combined with TomoFix locking compression plate (LCP) fixation between January 2016 and July 2020 were enrolled. The radiographic parameters including hip-knee-ankle angle (HKAA), medial proximal tibial angle (MPTA), femorotibial angle (FTA) and posterior tibial slope angle (PTSA) were measured between pre-operative and post-operative radiographs. Knee Society score (KSS) and range of motion (ROM) were assessed preoperatively and at last follow-up. Patients included in this study were divided into two groups according to the correction angle: small correction group (< 10°; SC group) and large correction group (≥ 10°; LC group). The modified Radiographic Union score for tibial fractures (mRUST) was used to assess the difference in bone healing between the two groups at 1, 3, 6, and 12 months postoperatively and at the final follow-up. A paired student's t test was conducted for comparison of differences of the relevant data pre-operatively and post-operatively. RESULTS: A total of 82 patients (88 knees) were included in this study. The HKAA, MPTA, FTA and PTSA increased from -6.4° ± 3.0°, 85.1° ± 2.6°, 180.1° ± 3.2° and 7.7° ± 4.4° preoperatively to 1.2° ± 4.3° (p < 0.001), 94.4° ± 3.3° (p < 0.001), 171.0° ± 2.8° and 11.8° ± 5.8° (p < 0.001) immediately postoperatively, respectively. However, no significant statistic difference was found in above-mentioned parameters at last follow-up compared to immediate postoperative data (p > 0.05). All patients in this study achieved good bone healing at the final follow-up and no significant differences in mRUST scores were seen between the SC group and LC group. The KSS-Knee score and KSS-Function score improved significantly from 55.4 ± 3.7 and 63.3 ± 4.6 preoperatively to 86.4 ± 2.8 (p < 0.001) and 89.6 ± 2.9 (p < 0.001) at last follow-up, respectively. Nevertheless, there was no significant difference in ROM between pre-operation and last follow-up (p > 0.05). CONCLUSION: For MOWHTO, the wedge-shaped cancellous allograft was a reliable choice for providing good bone healing and clinical outcomes.
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Osteoartrite do Joelho , Pirenos , Fraturas da Tíbia , Humanos , Tíbia/cirurgia , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/etiologia , Osteotomia/efeitos adversos , Aloenxertos , Estudos RetrospectivosRESUMO
Anastomotic leakage (AL), one of the most severe complications in rectal surgery, is often diagnosed late because of the low specificity of the clinical symptoms and limitations of current clinical investigations. Identification of patients with early AL remains challenging. Here, we explored the protein expression profiles of AL patients to provide potential biomarkers to identify AL in patients who undergo surgery for rectal cancer. We screened differentially expressed proteins (DEPs) in drainage fluid from AL and non-AL patients using a tandem mass tag method. A total of 248 DEPs, including 98 upregulated and 150 downregulated proteins, were identified between AL and non-AL groups. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that DEPs were enriched in neutrophil degranulation, bacterial infection, proteolysis, hemostasis, and complement and coagulation cascades. The results of enzyme-linked immunosorbent assay validated that the expression of the top three upregulated DEPs, AMY2A, RETN, and CELA3A, was significantly increased in the drainage fluid of AL patients, compared with that of non-AL patients (AMY2A, P = 0.001; RETN, P < 0.0001; and CELA3A, P = 0.023). Thus, our findings provide several potential biomarkers for the early diagnosis of AL after rectal cancer resection.
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Fístula Anastomótica , Neoplasias Retais , Humanos , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Proteômica , Detecção Precoce de Câncer , Neoplasias Retais/cirurgia , Neoplasias Retais/complicações , Drenagem/efeitos adversos , Drenagem/métodos , BiomarcadoresRESUMO
Cutaneous hyphomycosis caused by Purpureocillium lilacinus is a relatively uncommon event in patients, but there has been a gradual increase in reported cases. A 71-year-old female patient was hospitalized in May 2022 due to an acute episode of chronic obstructive pulmonary disease and received glucocorticoid infusion. The skin around the puncture point on the back of her right hand showed erythema, nodules, scabs, and pus discharge, which gradually worsened. Fungal examination revealed the presence of hyphae, while treatment with terbinafine was ineffective. After fungal culture, pathological analysis, and molecular biology identification techniques, this case was diagnosed as cutaneous and subcutaneous infections caused by Purpureocillium lilacinus. After 2 weeks of treatment with itraconazole, the patient recovered. Patients on long-term hormone preparations who undergo superficial venipuncture should be aware of the risk of skin damage and potential infection by Purpureocillium lilacinus. Prompt fungal culture, histopathological analysis, and molecular identification are crucial for accurate diagnosis. Antifungal susceptibility testing should be considered for effective treatment.
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Background and Aims: Sarcopenia is a common disease in the elderly, and the thyroid hormone (TH) might participate in the pathogenesis of sarcopenia. However, the results of previous studies were not completely consistent. We performed this study to investigate the association between THs and sarcopenia in a Chinese elderly euthyroid population. Subjects and Methods: A total of 309 Chinese elderly euthyroid subjects with an average age of 85.19 ± 7.8 years were enrolled. Participants were divided into four groups (non-sarcopenia, possible sarcopenia, sarcopenia and serve sarcopenia) according to the consensus update of AWGS in 2019. Serum levels of TT3, FT3, TT4, FT4, TSH, rT3 and TBG were measured. Muscle mass was measured by multifrequency bioelectrical impedance analysis, hand grip (HG) was represented by spring-type dynamometer, and gait speed (GS) was determined by 6-metre walk test. The FRAIL scale was used to assess frailty. Results: Compared to the non-sarcopenia group, the sarcopenia group showed a significant increase in age and FRIAL score, while FT3 and TT3 levels decreased significantly. Partial correlation analysis (adjusted by age, gender and the scores of FRIAL scale) indicated that FT3, TT3 and TSH had significant positive correlations with HG, and there also was a significant positive correlation between TT3 and GS. In addition, after adjusting for age, gender, BMI, ALT, sCr, and score on the FRAIL scale, the multivariate linear regression analysis showed that TT3 was positively associated with muscle strength and negatively associated with sarcopenia risk. Conclusion: There is an association between the low TT3 level and sarcopenia. Therefore, maintaining higher T3 concentrations within the normal range appears to be beneficial for sarcopenia in the elderly. In addition, due to the fluctuation of FT3, TT3 is a more stable and practical indicator to evaluate the relationship between sarcopenia and thyroid hormone in the elderly euthyroid population.
Assuntos
Força da Mão , Sarcopenia , Humanos , Idoso , Idoso de 80 Anos ou mais , Hormônios Tireóideos , Sarcopenia/epidemiologia , Força Muscular , TireotropinaRESUMO
Polycystic ovary syndrome (PCOS) is a well-recognized, multi-system metabolic disorder affecting fertility. Although various classification methods have been proposed to assess the phenotypic heterogeneity of PCOS, there is currently no reliable phenotype for predicting clinical IVF outcomes. This retrospective study, as a comprehensive phenotypic assessment across all PCOS classifications, aimed to identify dependable phenotypes that can serve as predictors for IVF and pregnancy outcomes. The study included 1313 PCOS patients who received their initial IVF treatment between January 2019 and December 2021. The phenotypes reflect the diverse metabolic and hormonal characteristics in this study. Phenotype A, within the Rotterdam criteria classification, exhibited the highest anti-Müllerian hormone levels (AMH), while phenotype D displayed the lowest Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) values. Both the hyperandrogenism (HA) phenotype within HA-based classification and the overweight phenotype within the body-mass-index-based classification showed increased HOMA-IR and metabolic syndrome (MetS). The MetS phenotype had higher free androgen index and a lower AMH. Notably, the MetS-based classification system demonstrated an independent association of MetS with cumulative live birth, preterm birth, and gestational diabetes mellitus as a contributing risk factor for PCOS patients undergoing IVF (p < 0.05). These findings carry noteworthy implications for advancing clinical management strategies for PCOS.