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1.
J Neuroinflammation ; 21(1): 136, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802924

RESUMO

Autoimmune uveitis is a leading cause of severe vision loss, and animal models provide unique opportunities for studying its pathogenesis and therapeutic strategies. Here we employ scRNA-seq, RNA-seq and various molecular and cellular approaches to characterize mouse models of classical experimental autoimmune uveitis (EAU), revealing that EAU causes broad retinal neuron degeneration and marker downregulation, and that Müller glia may act as antigen-presenting cells. Moreover, EAU immune response is primarily driven by Th1 cells, and results in dramatic upregulation of CC chemokines, especially CCL5, in the EAU retina. Accordingly, overexpression of CCR5, a CCL5 receptor, in mesenchymal stem cells (MSCs) enhances their homing capacity and improves their immunomodulatory outcomes in preventing EAU, by reducing infiltrating T cells and activated microglia and suppressing Nlrp3 inflammasome activation. Taken together, our data not only provide valuable insights into the molecular characteristics of EAU but also open an avenue for innovative MSC-based therapy.


Assuntos
Células-Tronco Mesenquimais , Camundongos Endogâmicos C57BL , Receptores CCR5 , Análise de Célula Única , Uveíte , Animais , Camundongos , Células-Tronco Mesenquimais/metabolismo , Uveíte/imunologia , Receptores CCR5/metabolismo , Receptores CCR5/genética , Doenças Autoimunes/terapia , Perfilação da Expressão Gênica , Modelos Animais de Doenças , Feminino , Análise da Expressão Gênica de Célula Única
2.
Anal Bioanal Chem ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38772972

RESUMO

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) represent trace lipids with significant natural biological functions. While exogenous FAHFAs have been extensively studied, research on FAHFAs in milk remains limited, constraining our grasp of their nutritional roles. This study introduces a non-targeted mass spectrometry approach combined with chemical networking of spectral fragmentation patterns to uncover FAHFAs. Through meticulous sample handling and comparisons of various data acquisition and processing modes, we validate the method's superiority, identifying twice as many FAHFAs compared to alternative techniques. This validated method was then applied to different milk samples, revealing 45 chemical signals associated with known and potential FAHFAs, alongside findings of 66 ceramide/hexosylceramide (Cer/HexCer), 48 phosphatidyl ethanolamine/lyso phosphatidyl ethanolamine (PE/LPE), 21 phosphatidylcholine/lysophosphatidylcholine (PC/LPC), 16 phosphatidylinositol (PI), 7 phosphatidylserine (PS), and 11 sphingomyelin (SM) compounds. This study expands our understanding of the FAHFA family in milk and provides a fast and convenient method for identifying FAHFAs.

3.
World J Gastrointest Surg ; 16(5): 1443-1448, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38817285

RESUMO

BACKGROUND: The treatment of postoperative anastomotic stenosis (AS) after resection of colorectal cancer is challenging. Endoscopic balloon dilation is used to treat stenosis in such cases, but some patients do not show improvement even after multiple balloon dilations. Magnetic compression technique (MCT) has been used for gastrointestinal anastomosis, but its use for the treatment of postoperative AS after colorectal cancer surgery has rarely been reported. CASE SUMMARY: We report a 72-year-old man who underwent radical resection of colorectal cancer and ileostomy one year ago. An ileostomy closure was prepared six months ago, but colonoscopy revealed a narrowing of the rectal anastomosis. Endoscopic balloon dilation was performed three times, but colonoscopy showed no significant improvement in stenosis. The AS was successfully treated using MCT. CONCLUSION: MCT is a minimally invasive method that can be used for the treatment of postoperative AS after colorectal cancer surgery.

4.
Cancer Biomark ; 40(2): 185-198, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578883

RESUMO

Cuproptosis a novel copper-dependent cell death modality, plays a crucial part in the oncogenesis, progression and prognosis of tumors. However, the relationships among DNA-methylation located in cuproptosis-related genes (CRGs), overall survival (OS) and the tumor microenvironment remain undefined. In this study, we systematically assessed the prognostic value of CRG-located DNA-methylation for lower-grade glioma (LGG). Clinical and molecular data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We employed Cox hazard regression to examine the associations between CRG-located DNA-methylation and OS, leading to the development of a prognostic signature. Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) analyses were utilized to gauge the accuracy of the signature. Gene Set Enrichment Analysis (GSEA) was applied to uncover potential biological functions of differentially expressed genes between high- and low-risk groups. A three CRG-located DNA-methylation prognostic signature was established based on TCGA database and validated in GEO dataset. The 1-year, 3-year, and 5-year area under the curve (AUC) of ROC curves in the TCGA dataset were 0.884, 0.888, and 0.859 while those in the GEO dataset were 0.943, 0.761 and 0.725, respectively. Cox-regression-analyses revealed the risk signature as an independent risk factor for LGG patients. Immunogenomic profiling suggested that the signature was associated with immune infiltration level and immune checkpoints. Functional enrichment analysis indicated differential enrichment in cell differentiation in the hindbrain, ECM receptor interactions, glycolysis and reactive oxygen species pathway across different groups. We developed and verified a novel CRG-located DNA-methylation signature to predict the prognosis in LGG patients. Our findings emphasize the potential clinical implications of CRG-located DNA-methylation indicating that it may serve as a promising therapeutic target for LGG patients.


Assuntos
Neoplasias Encefálicas , Metilação de DNA , Glioma , Microambiente Tumoral , Humanos , Glioma/genética , Glioma/patologia , Microambiente Tumoral/genética , Prognóstico , Feminino , Masculino , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/mortalidade , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Gradação de Tumores , Regulação Neoplásica da Expressão Gênica , Estimativa de Kaplan-Meier , Curva ROC
5.
J Food Sci ; 89(6): 3194-3207, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38660921

RESUMO

In this paper, the compatibility, phase behavior, and crystallization properties of the binary blends of palm kernel stearin (PKS) and anhydrous milk fat (AMF) were investigated by analyzing the solid fat content (SFC), thermal properties, polymorphism, and microstructure, with the aim of providing theoretical guidance for the blending of oils. The results showed that the PKS content primarily determined the SFC trend of the binary blends. However, the binary blends demonstrated poor miscibility and eutectic behavior was predominantly observed in the system, particularly at higher temperatures. Only α and ß' forms appeared in this blended system. Simultaneously, the addition of PKS elevated the liquid phase transition temperature of the binary blends, considerably significantly increased their crystallization rate when the addition of PKS was more than 20% and increased the density and size of the fat crystals. Finally, the mixing design optimization method was used to get the most suitable ratio of the binary blends in the refrigerated cream system with PKS:AMF to be 0.914:0.086. The cream prepared with the above binary blends was indeed superior in overrun and firmness and had high stability. PRACTICAL APPLICATION: Some fats with special advantages are often limited in their wide application because of their poor crystallization ability. In this paper, the crystallization ability of fats is improved, and their application scenarios are increased through the combination of fats, so as to provide reference for the production of special fats for food.


Assuntos
Cristalização , Leite , Óleo de Palmeira , Leite/química , Animais , Óleo de Palmeira/química , Manipulação de Alimentos/métodos , Gorduras/química , Temperatura de Transição
6.
World J Gastroenterol ; 30(6): 599-606, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38463020

RESUMO

BACKGROUND: Treatment of postoperative anastomotic stenosis for colorectal cancer is often challenging, especially for patients who do not respond well to endoscopy. In cases where patients have undergone an enterostomy, the stenosis can be easily resolved through magnetic compression. However, common magnetic compression techniques cannot be performed on those without enterostomy. We designed a novel Y-Z deformable magnetic ring (Y-Z DMR) and successfully applied it to a patient with a stenosis rectal anastomosis and without enterostomy after rectal cancer surgery. CASE SUMMARY: We here report the case of a 57-year-old woman who had undergone a laparoscopic radical rectum resection (Dixon) for rectal cancer. However, she started facing difficulty in defecation 6 months after surgery. Her colonoscopy indicated stenosis of the rectal anastomosis. Endoscopic balloon dilation was performed six times on her. However, the stenosis still showed a trend of gradual aggravation. Because the patient did not undergo an enterostomy, the conventional endoscopic magnetic compression technique could not be performed. Hence, we implemented a Y-Z DMR implemented through the anus under single channel. The magnetic ring fell off nine days after the operation and the rectal stenosis was relieved. The patient was followed up for six months and reported good defecation. CONCLUSION: The Y-Z DMR deformable magnetic ring is an excellent treatment strategy for patients with rectal stenosis and without enterostomy.


Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Feminino , Pessoa de Meia-Idade , Constrição Patológica/cirurgia , Constrição Patológica/etiologia , Neoplasias Retais/complicações , Neoplasias Retais/cirurgia , Reto/diagnóstico por imagem , Reto/cirurgia , Laparoscopia/efeitos adversos , Anastomose Cirúrgica/efeitos adversos , Complicações Pós-Operatórias/etiologia , Fenômenos Magnéticos , Estudos Retrospectivos
7.
Nutr Rev ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38412339

RESUMO

With the continuous advancements in detection methods and the exploration of unknown substances, an increasing number of bioactive compounds are being discovered. Fatty acid esters of hydroxyl fatty acids (FAHFAs), a class of endogenous lipids found in 2014, exhibit various physiological activities, such as improving glucose tolerance and insulin sensitivity, stimulating insulin secretion, and demonstrating broad anti-inflammatory effects. Moreover, some FAHFAs are closely linked to intestinal health and can serve as potential biomarkers for gut health. Various FAHFAs have been observed in food, including palmitic acid esters of hydroxy stearic acids (PAHSA), oleic acid esters of hydroxy stearic acids (OAHSA), linoleic acid esters of hydroxy linoleic acid (LAHLA). As a type of lipid regularly consumed in the daily diet, it is highly important to ascertain the types and quantities of FAHFAs present in the diet. This article, based on existing research, provides a review of the analysis methods for FAHFAs, particularly focusing on the separation of chiral isomers. It also summarizes the sources and contents of dietary FAHFAs, emphasizing their bioavailability and impact on the gut. Understanding the beneficial effects of these lipids in the diet can serve as a valuable reference for the development of specific functional foods.

8.
Invest Ophthalmol Vis Sci ; 65(2): 18, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324299

RESUMO

Purpose: TGF-ß/BMP signaling pathway plays a significant role in fibrotic cataract. Smurf1, a ubiquitin protein ligase, regulates the TGF-ß/BMP signaling pathway through the ubiquitin-proteasome system (UPS). This study aims to investigate the role of Smurf1 in the progression of fibrotic cataract and its underlying mechanism. Methods: We used a mouse model of injury-induced anterior subcapsular cataract (ASC) and administered the Smurf1 inhibitor A01 for in vivo investigations. RNA sequencing was performed to examine global gene expression changes. Protein levels were assessed by Simple Western analysis. The volume of subcapsular opacity was determined using whole-mount immunofluorescence of lens anterior capsules. Lentivirus was utilized to establish cell lines with Smurf1 knockdown or overexpression in SRA01/04. Lens epithelial cell (LEC) proliferation was evaluated by CCK8 and EdU assays. Cell cycle profile was determined by flow cytometry. LEC migration was measured using Transwell and wound healing assays. Results: The mRNA levels of genes associated with cell proliferation, migration, epithelial-mesenchymal transition (EMT), TGF-ß/BMP pathway, and UPS were upregulated in mouse ASC model. Smurf1 mRNA and protein levels were upregulated in lens capsules of patients and mice with ASC. Anterior chamber injection of A01 inhibited ASC formation and EMT. In vitro, Smurf1 knockdown reduced proliferation, migration and TGF-ß2-induced EMT of LECs, concomitant with the upregulation of Smad1, Smad5, and pSmad1/5. Conversely, overexpression of Smurf1 showed opposite phenotypes. Conclusions: Smurf1 regulates fibrotic cataract progression by influencing LEC proliferation, migration, and EMT through the modulation of the Smad signaling pathway, offering a novel target for the fibrotic cataract treatment.


Assuntos
Catarata , Transdução de Sinais , Ubiquitina-Proteína Ligases , Animais , Humanos , Camundongos , Linhagem Celular , Modelos Animais de Doenças , RNA Mensageiro , Fator de Crescimento Transformador beta , Ubiquitina-Proteína Ligases/genética
9.
World J Clin Cases ; 11(24): 5692-5699, 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37727708

RESUMO

BACKGROUND: Biliary adenomas that occur in the extrahepatic biliary tree are rare. It is difficult to distinguish it from cholangiocarcinoma or cholangiolithiasis by various imaging examinations, and it is very easy to be misdiagnosed. AIM: To evaluate the cumulative experiences including clinical characteristics and treatments of nine patients diagnosed with extrahepatic biliary adenoma admitted to the First Affiliated Hospital of Xi'an Jiaotong University from 2016 to 2022. METHODS: A total of nine patients were included in our study. The laboratory examinations, disease diagnosis, therapy and pathological characteristics, and follow-up of every patient were evaluated. RESULTS: Our cohort consisted of six females and three males with an average diagnosis age of 65.1 years (range 46-87). Six extrahepatic biliary adenomas were located in the common bile ducts and three in the hepatic duct. On initial presentation, all of the patients have symptom of biliary origin, including obstructive jaundice (4/9, 44.4%), abdominal pain (6/9, 66.7%), and fever (3/9, 33.3%). Preoperative imaging examination considered bile duct carcinoma in 6 cases and bile duct calculi in 3 cases. All the patients received surgical treatment and were confirmed by pathology as biliary adenoma. The symptoms improved significantly in all 9 patients after surgery. Seven of nine patients recovered well at follow-up without tumor recurrence. One patient died 2 mo after the surgery due to heart failure. One patient developed jaundice again 8 mo after surgery, underwent endoscopic retrograde cholangiopancreatography and biliary stent placement. CONCLUSION: Benign extrahepatic biliary tumors are rare and difficult to diagnosis preoperatively. Intraoperative choledochoscopy and timely biopsy may offer great advantages.

10.
Food Funct ; 14(14): 6312-6319, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37378416

RESUMO

Background: branched-chain fatty acids (BCFAs) have recently emerged as a group of functional fatty acids that are widely distributed in various foodstuffs, including dairy products, ruminant meat products, and fermented foods. Several studies have investigated the differences in the levels of BCFAs among individuals with varying risks of metabolic syndrome (MetS). In this study, we conducted a meta-analysis to explore the relationship between BCFAs and MetS, and to assess the feasibility of BCFAs as potential biomarkers for diagnosing MetS. Methods: in accordance with the PRISMA guidelines, we conducted a systematic literature search on PubMed, Embase, and the Cochrane Library up to March 2023. Both longitudinal and cross-sectional studies were included. The quality of the longitudinal and cross-sectional studies was evaluated using the Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) criteria, respectively. Heterogeneity detection and sensitivity analysis of the included research literature were carried out using R 4.2.1 software with a random-effects model. Results: Our meta-analysis included 685 participants and revealed a significant negative correlation between the endogenous BCFAs (serum BCFAs and adipose tissue BCFAs) and the risk of developing MetS, with lower BCFA levels found in individuals at a high risk of MetS (WMD: -0.11%, 95% CI: [-0.12, -0.09] %, P < 0.0001). However, there was no difference in fecal BCFAs among different MetS risk groups (SMD: -0.36, 95% CI: [-1.32, 0.61], P = 0.4686). Conclusion: our study provides insights into the relationship between BCFAs and the risk of developing MetS, and lays the groundwork for the development of novel biomarkers for diagnosing MetS in the future.


Assuntos
Síndrome Metabólica , Humanos , Síndrome Metabólica/diagnóstico , Estudos Transversais , Ácidos Graxos/metabolismo , Fatores de Risco , Biomarcadores
11.
J Pain Res ; 16: 1813-1823, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37273274

RESUMO

Objective: To investigate the clinical efficacy of percutaneous kyphoplasty (PKP) with a unilateral versus bilateral approach in the treatment of osteoporotic vertebral compression fractures (OVCFs). Methods: We retrospectively analyzed a total of 147 patients (unilateral group: 79, bilateral group: 68) with OVCFs treated with PKP at the Department of Spine Surgery, Wuhan Fourth Hospital between August 2020 and January 2022. Patients' personal information, operation time, bone cement injection volume, as well as pre- and post-operative visual analogue scale (VAS), Oswestry disability index (ODI), anterior vertebral body height and Cobb angle were recorded. Results: All 147 patients were successfully treated with PKP and were followed up for at least 6 months. Our results showed that the operative time was significantly shorter in the unilateral group (41.60±5.64) minutes than in the bilateral group (66.53±9.40) minutes, and the volume of bone cement injected was also significantly less in the unilateral group (5.27±0.73) mL than in the bilateral group (6.87±0.93) mL (P<0.01). The VAS score, ODI index, vertebral height and Cobb angle at postoperative follow-up were significantly improved in both groups compared to the preoperative period (P<0.01); However, the difference between the two groups was not statistically significant (P>0.05). Repeat thoracic and lumbar radiographs showed cement leakage in seven cases (8.86%) in the unilateral group and five cases (7.35%) in the bilateral group, but all were asymptomatic and required no further management. During our entire follow-up period, there were five adjacent vertebral fractures in the unilateral group (6.33%) and four in the bilateral group (5.88%). Conclusion: There was no significant difference between the two groups in terms of improvement in VAS score, ODI index, restoration of vertebral body height, and posterior convexity deformity, but unilateral puncture had the advantage of shorter operative time and less cement injection.

12.
Crit Rev Food Sci Nutr ; : 1-13, 2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37140184

RESUMO

As an emerging group of bioactive fatty acids, monomethyl branched-chain fatty acids (mmBCFAs) have sparked the interest of many researchers both domestically and internationally. In addition to documenting the importance of mmBCFAs for growth and development, there is increasing evidence that mmBCFAs are highly correlated with obesity and insulin resistance. According to previous pharmacological investigations, mmBCFAs also exhibit anti-inflammatory effects and anticancer properties. This review summarized the distribution of mmBCFAs, which are widely found in dairy products, ruminants, fish, and fermented foods. Besides, we discuss the biosynthesis pathway in different species and detection methods of mmBCFAs. With the hope to unveil their mechanisms of action, we recapitulated detailed the nutrition and health benefits of mmBCFAs. Furthermore, this study provides a thorough, critical overview of the current state of the art, upcoming difficulties, and trends in mmBCFAs.

13.
Zhongguo Zhong Yao Za Zhi ; 48(5): 1393-1401, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-37005822

RESUMO

Quantity is the key factor to ensure the safety and effectiveness of medicines. It is very important to study and determine the traditional measuring units and their quantity values of Tibetan medicine. Based on the literature records of Tibetan medicine and combined with modern experimental verification and investigation research, this study determined the reference, name, and conversion rate of traditional measuring units of Tibetan medicine. Meanwhile, through large sample sampling and repeated quantification of refe-rence of basic units, its weight and volume were clarified. The modern SI volume and weight unit values corresponding to the traditional volume and weight units of Tibetan medicine were deduced, and the correctness, reliability, and practicability of these determination results were demonstrated. This study also put forward some specific suggestions and reference values for formulating the standards of measuring units of weight and volume of Tibetan medicine. It is of great significance in guiding the processing, production, and clinical treatment of Tibetan medicine, and promoting the standardization and standardized development of Tibetan medicine.


Assuntos
Medicina Tradicional Tibetana , Reprodutibilidade dos Testes
14.
J Agric Food Chem ; 71(10): 4371-4381, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36857113

RESUMO

Oxidized triglyceride monomers are the main cytotoxic products of deep-frying oil. However, its impact on the intestinal barrier, the first health guardian, remains unknown. In this study, HPLC-MS/MS analysis revealed that the epoxy group is the main oxidation product, indicating that it may be the main cytotoxic factor. Therefore, 1-9,10-epoxystearic ester, 2,3-dioleic acid (EGT) and glycerol trioleate (GT) were used to reveal the effect of the epoxy group on the intestinal barrier of dextran sulfate sodium-induced colitis. Characteristics analysis showed that EGT could aggravate intestinal damage. The relative mRNA expression analysis suggested that EGT could activate Caspase-1/NLRP3/GSDMD, thereby inducing pyroptosis. The proinflammatory cytokines activated by pyroptosis and the cGAS-STING pathway were released through the pores, thus inducing the disintegration of the tight junction between the intestinal epithelial cells and enhancing intestinal permeability. Metabonomics further confirmed that EGT can change the composition and content of phospholipids on the cell membrane, indicating the morphological changes of the intestinal epithelial cell membrane. In conclusion, this study highlights that EGT induced intestinal dysfunction via Caspase-1/NLRP3/GSDMD and cGAS-STING pathways.


Assuntos
Colite , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sulfato de Dextrana/metabolismo , Caspase 1/genética , Caspase 1/metabolismo , Triglicerídeos/metabolismo , Espectrometria de Massas em Tandem , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Nucleotidiltransferases/metabolismo , Permeabilidade
15.
Biochem Biophys Res Commun ; 655: 118-126, 2023 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-36934587

RESUMO

Electroretinogram (ERG) is the most common clinical and basic visual electrodiagnostic test, which has long been used to evaluate the retinal function through photic stimulation. Despite its wide application, there are still some pitfalls often neglected in ERG recording, such as the recording time point, active electrode location, and the animal strain. In this study, we systematically analyzed and compared the effects of multiple factors on ERG, which would provide an important reference for ERG detection by other investigators. ERG was recorded using the Celeris D430 rodent ERG testing system. The amplitudes and latencies of a wave, b wave and oscillatory potentials (OPs) recorded from different electrode locations (subdermal and invasive), different times of day (day time 8:00 to 13:00 and night time 18:00 to 23:00), bilateral eyes (left and right), and different mouse strains (C57 and CD1) were analyzed and compared. Our results revealed that ERG was affected by active electrode locations and difference between day and night, while OPs seemed not to be influenced. There was no significant difference in the amplitudes or latencies of ERG and OPs between left and right eyes, irrespective of measurements at day or night, or which method was used. Compared to C57 mice, both ERG and OP responses were significantly decreased in Brn3bAP/AP mice, a model for retinal ganglion cell (RGC) loss. In addition, there were some non-negligible differences in visual responses between C57 and CD1 mouse strains. Our results suggest that the invasive procedure is a reliable method for evaluating the visual function including VEP, ERG and OP responses in mice. Moreover, these comparative analyses provide valuable references for future studies of mammalian visual electrophysiology.


Assuntos
Eletrorretinografia , Retina , Camundongos , Animais , Eletrorretinografia/métodos , Células Ganglionares da Retina/fisiologia , Mamíferos
16.
iScience ; 26(3): 106241, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36922996

RESUMO

Neural organoids have been shown to serve as powerful tools for studying the mechanism of neural development and diseases as well as for screening drugs and developing cell-based therapeutics. Somatic cells have previously been reprogrammed into scattered autonomic ganglion (AG) neurons but not AG organoids. Here we have identified a combination of triple transcription factors (TFs) Ascl1, Phox2a/b, and Hand2 (APH) capable of efficiently reprogramming mouse fibroblasts into self-organized and networked induced AG (iAG) organoids, and characterized them by immunostaining, qRT-PCR, patch-clamping, and scRNA-seq approaches. The iAG neurons exhibit molecular properties, subtype diversity, and electrophysiological characteristics of autonomic neurons. Moreover, they can integrate into the superior cervical ganglia following transplantation and innervate and control the beating rate of co-cultured ventricular myocytes. Thus, iAG organoids may provide a valuable tool to study the pathogenesis of autonomic nervous system diseases and screen for drugs, as well as a source for cell-based therapies.

17.
Cell Death Dis ; 14(2): 126, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36792584

RESUMO

As a common pathology of many ocular disorders such as diabetic retinopathy and glaucoma, retinal ischemia/reperfusion (IR) triggers inflammation and microglia activation that lead to irreversible retinal damage. The detailed molecular mechanism underlying retinal IR injury, however, remains poorly understood at present. Here we report the bioinformatic identification of a lncRNA 1810058I24Rik (181-Rik) that was shown to encode a mitochondrion-located micropeptide Stmp1. Its deficiency in mice protected retinal ganglion cells from retinal IR injury by attenuating the activation of microglia and the Nlrp3 inflammasome pathway. Moreover, its genetic knockout in mice or knockdown in primary microglia promoted mitochondrial fusion, impaired mitochondrial membrane potential, and reactive oxygen species (ROS) production, diminished aerobic glycolysis, and ameliorated inflammation. It appears that 181-Rik may trigger the Nlrp3 inflammasome activation by controlling mitochondrial functions through inhibiting expression of the metabolic sensor uncoupling protein 2 (Ucp2) and activating expression of the Ca2+ sensors S100a8/a9. Together, our findings shed new light on the molecular pathogenesis of retinal IR injury and may provide a fresh therapeutic target for IR-associated neurodegenerative diseases.


Assuntos
RNA Longo não Codificante , Traumatismo por Reperfusão , Camundongos , Animais , Microglia/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RNA Longo não Codificante/metabolismo , Doenças Neuroinflamatórias , Mitocôndrias/metabolismo , Inflamação/genética , Inflamação/metabolismo , Traumatismo por Reperfusão/metabolismo , Isquemia/metabolismo , Micropeptídeos
18.
Zhongguo Zhong Yao Za Zhi ; 47(10): 2825-2832, 2022 May.
Artigo em Chinês | MEDLINE | ID: mdl-35718503

RESUMO

Tibetan medicine processing ensures the safety of clinical application of Tibetan medicine. It is of great significance to analyze the principles of Tibetan medicine processing in the development, inheritance, and innovation of Tibetan medicine. However, due to the late start of modern Tibetan medicine research and the disciplinary division, the current research on Tibetan medicine processing focuses on the exploration and collation of traditional techniques and the analysis of the processing mechanism of Tibetan medicine through chemical and pharmacological research, but its principles and traditional theories have been rarely reported. In view of this, after analyzing the concept, essence, theories, purposes, and functions of Tibetan medicine processing through the integration of Tibetan medicine, Tibetan pharmacology, and clinical research of Tibetan medicine, this study proposed that the essence of Tibetan medicine processing was to change the "five sources" composition of medicinal materials through physical, chemical, and biological means, or the comprehensive means, and the theoretical principle of Tibetan medicine processing was to change or transform the positive and adverse effects or the obvious and recessive effects by altering the "five sources" composition of the drug to maximize the positive effect and minimize the adverse effect and the damage to the body, thereby achieving the purposes of toxicity reduction, efficacy enhancement, and drug property harmonization represented by sharpening, softening, nourishing, and reasonable compatibility. This study is expected to provide references for the construction of the theoretical system of Tibetan medicine processing, the inheritance of processing techniques, and innovative research.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Medicina Tradicional Tibetana , Plantas Medicinais/química
19.
Asian J Androl ; 24(5): 540-548, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35142655

RESUMO

The limited treatment options for advanced prostate cancer (PCa) lead to the urgent need to discover new anticancer drugs. Mannose, an isomer of glucose, has been reported to have an anticancer effect on various tumors. However, the anticancer effect of mannose in PCa remains unclear. In this study, we demonstrated that mannose inhibits the proliferation and promotes the apoptosis of PCa cells in vitro, and mannose was observed to have an anticancer effect in mice without harming their health. Accumulation of intracellular mannose simultaneously decreased the mitochondrial membrane potential, increased mitochondrial and cellular reactive oxygen species (ROS) levels, and reduced adenosine triphosphate (ATP) production in PCa cells. Mannose treatment of PCa cells induced changes in mitochondrial morphology, caused dysregulated expression of the fission protein, such as fission, mitochondrial 1 (FIS1), and enhanced the expression of proapoptotic factors, such as BCL2-associated X (Bax) and BCL2-antagonist/killer 1 (Bak). Furthermore, lower expression of mannose phosphate isomerase (MPI), the key enzyme in mannose metabolism, indicated poorer prognosis in PCa patients, and downregulation of MPI expression in PCa cells enhanced the anticancer effect of mannose. This study reveals the anticancer effect of mannose in PCa and its clinical significance in PCa patients.


Assuntos
Manose , Neoplasias da Próstata , Animais , Apoptose , Linhagem Celular Tumoral , Humanos , Masculino , Potencial da Membrana Mitocondrial , Camundongos , Mitocôndrias , Espécies Reativas de Oxigênio
20.
Food Chem ; 373(Pt B): 131285, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-34740049

RESUMO

The digestion behavior of epoxy triglyceride, the main cytotoxic product of deep-frying oil, remains unknown, which may affect its biosafety. In this study, epoxy triglyceride (EGT) and triglyceride (GT) were used to reveal the effect of epoxy group on digestion. Digestibility rate analysis showed that the free fatty acids release rate of EGT was slower. To clarify this phenomenon, binding ability with salt ions in digestive juice and particle size were also been studied. Cluster size analysis indicated that epoxy group increased triglyceride particle size, resulting in smaller contact area between EGT and lipase. Interface behaviors displayed EGT decreased binding ability with salt ions in digestive juice. Spectroscopic analysis showed EGT caused the red shift of lipase peak, indicating that epoxy group changed lipase structure. Molecular dynamics simulation suggested EGT leads to loosen lipase structure. In conclusion, this study highlights that epoxy group could weaken the triglyceride digestion.


Assuntos
Digestão , Simulação de Dinâmica Molecular , Emulsões , Lipase/metabolismo , Triglicerídeos
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