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1.
FASEB J ; 38(17): e70045, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39259551

RESUMO

Epithelial ovarian cancer is the deadliest gynecologic malignancy, characterized by high metastasis. Transforming growth factor-ß1 (TGF-ß1) drives epithelial- mesenchymal transformation (EMT), a key process in tumor metastasis. Tumor necrosis factor-α-induced protein 8 (TNFAIP8)-like 2 (TIPE2) acts as a negative regulator of innate and adaptive immunity and involves in various cancers. However, its relationship with TGF-ß1 in ovarian cancer and its role in reversing TGF-ß1-induced EMT remain unclear. This study examined TIPE2 mRNA and protein expression using quantitative RT-PCR (qRT-PCR), western blot and immunohistochemistry. The effects of TIPE2 overexpression and knockdown on the proliferation, migration and invasion of epithelial ovarian cancer cells were assessed through 5-ethynyl-2-deoxyuridine, colony-forming, transwell migration and invasion assays. The relationship between TIPE2 and TGF-ß1 was investigated using qRT-PCR and enzyme-linked immunosorbent assay, while the interaction between TIPE2 and Smad2 was identified via co-immunoprecipitation. The results revealed that TIPE2 protein was significantly down-regulated in epithelial ovarian cancer tissues and correlated with the pathological type of tumor, patients' age, tumor differentiation degree and FIGO stage. TIPE2 and TGF-ß1 appeared to play an opposite role to each other during the progression of human ovarian cancer cells. Furthermore, TIPE2 inhibited the metastasis and EMT of ovarian cancer cells by combining with Smad2 in vitro or in an intraperitoneal metastasis model. Consequently, these findings suggest that TIPE2 plays a crucial inhibitory role in ovarian cancer metastasis by modulating the TGF-ß1/Smad2/EMT signaling pathway and may serve as a potential target for ovarian cancer, providing important direction for future diagnostic and therapeutic strategies.


Assuntos
Carcinoma Epitelial do Ovário , Movimento Celular , Transição Epitelial-Mesenquimal , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Ovarianas , Proteína Smad2 , Fator de Crescimento Transformador beta1 , Proteína Smad2/metabolismo , Proteína Smad2/genética , Humanos , Feminino , Fator de Crescimento Transformador beta1/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/genética , Linhagem Celular Tumoral , Animais , Camundongos , Invasividade Neoplásica , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Camundongos Endogâmicos BALB C , Transdução de Sinais
2.
Bioresour Technol ; 413: 131411, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39277052

RESUMO

A membrane-aerated conductive biofilm reactor (MA-CBR) was constructed for carbon-limited wastewater treatment and to reduce the stress of the electric field on nitrous oxide reductase (NosZ). Counter-diffusion with an embedded aerobic layer declined the effect of current on NosZ (K00376) for N2O reduction. Other coding genes for denitrification in cathodic membrane aerated biofilms, including K02568, K00368, K15864, K02305, and K04561, were also positively affected by the electric field and significantly accumulate in Thauera. NH4+-N oxidation can occur at the anode and cathode (membrane aeration biofilm). This cathodic synergistic NH4+-N oxidation provided more electrons to be directly utilized by the denitrifying bacteria at the cathode. Compared to the MABR, the total nitrogen removal efficiency of MA-CBR increased by 5.68 mg/L, 11.02 mg/L, and 15.63 mg/L at voltages of 0.25 V, 0.50 V, and 0.75 V, respectively.

3.
Cell ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39270656

RESUMO

In a rigorous 40-month study, we evaluated the geroprotective effects of metformin on adult male cynomolgus monkeys, addressing a gap in primate aging research. The study encompassed a comprehensive suite of physiological, imaging, histological, and molecular evaluations, substantiating metformin's influence on delaying age-related phenotypes at the organismal level. Specifically, we leveraged pan-tissue transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to develop innovative monkey aging clocks and applied these to gauge metformin's effects on aging. The results highlighted a significant slowing of aging indicators, notably a roughly 6-year regression in brain aging. Metformin exerts a substantial neuroprotective effect, preserving brain structure and enhancing cognitive ability. The geroprotective effects on primate neurons were partially mediated by the activation of Nrf2, a transcription factor with anti-oxidative capabilities. Our research pioneers the systemic reduction of multi-dimensional biological age in primates through metformin, paving the way for advancing pharmaceutical strategies against human aging.

4.
Research (Wash D C) ; 7: 0444, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247806

RESUMO

High levels of tumor necrosis factor receptor type II (TNFR2) are preferentially expressed by immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs), especially those present in the tumor microenvironment, as initially reported by us. There is compelling evidence that targeting TNFR2 markedly enhances antitumor immune responses. Furthermore, a broad spectrum of human cancers also expresses TNFR2, while its expression by normal tissue is very limited. We thus hypothesized that TNFR2 may be harnessed for tumor-targeted delivery of chemotherapeutic agents. In this study, we performed a proof-of-concept study by constructing a TNFR2-targeted PEGylated poly(dl-lactic-co-glycolic acid) (PLGA-PEG) nanodrug delivery system [designated as TNFR2-PLGA-ADR (Adriamycin)]. The results of in vitro study showed that this TNFR2-targeted delivery system had the properties in cellular binding and cytotoxicity toward mouse colon cancer cells. Further, upon intravenous injection, TNFR2-PLGA-ADR could efficiently accumulate in MC38 and CT26 mouse colon tumor tissues and preferentially bind with tumor-infiltrating Tregs. Compared with ADR and ISO-PLGA-ADR, the in vivo antitumor effect of TNFR2-PLGA-ADR was markedly enhanced, which was associated with a decrease of TNFR2+ Tregs and an increase of IFNγ+CD8+ cytotoxic T lymphocytes in the tumor tissue. Therefore, our results clearly show that targeting TNFR2 is a promising strategy for designing tumor-specific chemoimmunotherapeutic agent delivery system.

5.
Int J Biol Macromol ; 279(Pt 3): 135422, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39245098

RESUMO

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia. Type 2 diabetes mellitus (T2DM) represents approximately 90 % of all DM cases and is primarily caused by an imbalance in blood glucose homeostasis due to inadequate insulin secretion or insulin resistance. This study explores the potential therapeutic effects of chitosan guanidine (CSG) on a T2DM mouse model. The findings reveal that CSG significantly enhances oral glucose tolerance (OGTT) and insulin sensitivity (ITT), reduces fasting blood glucose (FBG) levels, and suppresses the expression of proinflammatory cytokines in T2DM mice. These changes improve insulin resistance and diminish inflammation. Additionally, CSG markedly ameliorates lipid metabolism disorders, lowers total cholesterol (TC) and triglyceride (TG) levels, and inhibits hepatic fat accumulation. 16S rRNA and Spearman correlation analyses indicate that CSG promotes the relative abundance of probiotic genera such as Bacteroidota, Patescibacteria, Actinobacteria, and Cyanobacteria. These bacteria are positively correlated with short-chain fatty acids (SCFAs) and high-density lipoprotein cholesterol (HDLC) levels. Conversely, CSG reduces the relative abundance of pathogenic bacteria, including Proteobacteria and Ralstonia, leading to an improved intestinal microbial community composition in T2DM mice and alleviating T2DM symptoms. These results suggest that CSG holds significant potential as a non-insulin therapeutic agent for diabetes management.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39181730

RESUMO

Our limited understanding of metabolic aging poses major challenges to comprehending the diverse cellular alterations that contribute to age-related decline, and to devising targeted interventions. This review provides insights into the heterogeneous nature of cellular metabolism during aging and its response to interventions, with a specific focus on cellular heterogeneity and its implications. By synthesizing recent findings using single-cell approaches, we explored the vulnerabilities of distinct cell types and key metabolic pathways. Delving into the cell type-specific alterations underlying the efficacy of systemic interventions, we also discuss the complexity of integrating single-cell data and advocate for leveraging computational tools and artificial intelligence to harness the full potential of these data, develop effective strategies against metabolic aging, and promote healthy aging.

7.
J Sci Food Agric ; 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39183171

RESUMO

BACKGROUND: The delayed drying of newly harvested tiger nuts can lead to mold and rancidity. Timely drying is therefore important. However, few studies have analyzed the impact of hot-air drying on the quality of tiger-nut oil and starch, making it essential to establish optimal drying conditions. RESULTS: The results showed that the drying temperature was the most important factor affecting the drying speed, followed by drying airflow rate and loading capacity. A logarithmic model can describe the hot-air drying process of tiger nuts. The oil yield of tiger nut was highest after drying at 60 °C, reaching 22.40%. Meanwhile, the starch extracted from after drying at 60 °C had the highest solubility and expansion rate, 4.77% and 9.74%, respectively. Starch has the highest viscosity after drying at 70 °C, and it forms gel easily after aging. CONCLUSION: High-quality tiger nuts should be produced under optimal conditions: a hot-air drying temperature of 60 °C, an airflow rate of 1.0 m s-1, and a loading capacity of 100 g. The results of this study have practical implications for the effective drying of tiger nuts. © 2024 Society of Chemical Industry.

8.
ACS Appl Mater Interfaces ; 16(28): 36973-36982, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38966874

RESUMO

Personal thermal management technology, which adjusts the heat exchange between the human body and the environment, can passively heat or cool the body to maintain a comfortable core temperature, thereby enhancing comfort and reducing energy consumption. However, most existing personal thermal management materials have static properties, such as fixed solar reflectance and infrared emissivity, which do not support real-time dynamic temperature regulation. Moreover, sweat accumulation on the skin surface, while contributing to temperature regulation, can significantly reduce comfort. This study constructs a unidirectional moisture-permeable intelligent thermal management fabric system to achieve superior thermal and moisture comfort in complex environments. The fabric incorporates thermochromic microcapsules into PAN nanofibers by using electrospinning technology for intelligent thermal management. Subsequent hydrophobic treatment of the fiber film surface imparts the fabric with unidirectional wetting properties. The nanofibrous structure provides intrinsic elasticity and breathability. In heating mode, the fabric's average sunlight reflectance is 42.1%, which increases to 82.2% in cooling mode, resulting in a reflectance difference of approximately 40%. The hydrophobic treatment endows the fabric with excellent moisture absorption and perspiration properties, demonstrated by a unidirectional moisture transport index of 696.63 and a perspiration evaporation rate of 5.88 mg/min. When the fabric temperature matches the ambient temperature, the photothermal conversion power difference of the Janus metafabric in two modes reaches 248.37 W m-2. Additionally, Janus metafabrics show the potential for temperature-responsive design and repeated writing applications. The outstanding wearability and dynamic spectral properties of these metafabrics open new pathways for sustainable energy, smart textiles, and thermal-moisture comfort applications.

9.
ACS Appl Mater Interfaces ; 16(31): 40641-40652, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39051862

RESUMO

Photothermal therapy (PTT) has emerged as a noninvasive and precise cancer treatment modality known for its high selectivity and lack of drug resistance. However, the clinical translation of many PTT agents is hindered by the limited biodegradability of inorganic nanoparticles and the instability of organic dyes. In this study, a peptide conjugate, IR820-Cys-Trp-Glu-Trp-Thr-Trp-Tyr (IR820-C), was designed to self-assemble into nanoparticles for both potent PTT and vascular disruption in melanoma treatment. When co-assembled with the poorly soluble vascular disrupting agent (VDA) combretastatin A4 (CA4), the resulting nanoparticles (IR820-C@CA4 NPs) accumulate efficiently in tumors, activate systemic antitumor immune responses, and effectively ablate melanoma with a single treatment and near-infrared irradiation, as confirmed by our in vivo experiments. Furthermore, by exploiting the resulting tumor hypoxia, we subsequently administered the hypoxia-activated prodrug tirapazamine (TPZ) to capitalize on the created microenvironment, thereby boosting therapeutic efficacy and antimetastatic potential. This study showcases the potential of short-peptide-based nanocarriers for the design and development of stable and efficient photothermal platforms. The multifaceted therapeutic strategy, which merges photothermal ablation with vascular disruption and hypoxia-activated chemotherapy, holds great promise for advancing the efficacy and scope of cancer treatment modalities.


Assuntos
Melanoma , Animais , Camundongos , Melanoma/patologia , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Linhagem Celular Tumoral , Humanos , Terapia Fototérmica , Nanopartículas/química , Peptídeos/química , Peptídeos/farmacologia , Estilbenos/química , Estilbenos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Tirapazamina/química , Tirapazamina/farmacologia , Verde de Indocianina/análogos & derivados
10.
Front Pharmacol ; 15: 1370263, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756372

RESUMO

Background: Single atrium is very rare congenital cardiac anomaly in adults. The prognosis of patients with single atrium is very poor, with 50% of patients dying owing to cardiopulmonary complications in childhood. Herein, we focused on anesthesia management for noncardiac surgery in patients with single atrium. Case presentation: A 58-year-old male with a history of bilateral varicocele underwent laparotomy for high-position ligation of the spermatic vein. The patient also had a history of single atrium, atrial fibrillation, chronic heart failure, pulmonary hypertension (PH), and complete right bundle branch block (CRBBB). Given the significant complications associated with general anesthesia in patients with PH, we preferred to use low-dose epidural anesthesia for this patient. Transthoracic echocardiography was used to assess cardiac function before and during surgery and guide perioperative fluid therapy. To limit the stress response, we used a regional nerve block for reducing postoperative pain. Furthermore, we used norepinephrine to appropriately increase the systemic vascular resistance in response to the reduction of systemic vascular resistance caused by epidural anesthesia. Conclusion: Low-dose epidural anesthesia can be safely used in patients with single atrium and PH. The use of perioperative transthoracic echocardiography is helpful in guiding fluid therapy and effectively assessing the cardiac structure and function of patients. Prophylactic administration of norepinephrine before epidural injection may make it easier to maintain the patient's BP.

11.
Sci Total Environ ; 930: 172601, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38657817

RESUMO

Antibiotic residues in mariculture wastewater seriously affect the aquatic environment. Antibiotic Resistance Genes (ARGs) produced under antibiotic stress flow through the environment and eventually enter the human body, seriously affecting human health. Microalgal-bacterial symbiotic system (MBSS) can remove antibiotics from mariculture and reduce the flow of ARGs into the environment. This review encapsulates the present scenario of mariculture wastewater, the removal mechanism of MBSS for antibiotics, and the biomolecular information under metagenomic assay. When confronted with antibiotics, there was a notable augmentation in the extracellular polymeric substances (EPS) content within MBSS, along with a concurrent elevation in the proportion of protein (PN) constituents within the EPS, which limits the entry of antibiotics into the cellular interior. Quorum sensing stimulates the microorganisms to produce biological responses (DNA synthesis - for adhesion) through signaling. Oxidative stress promotes gene expression (coupling, conjugation) to enhance horizontal gene transfer (HGT) in MBSS. The microbial community under metagenomic detection is dominated by aerobic bacteria in the bacterial-microalgal system. Compared to aerobic bacteria, anaerobic bacteria had the significant advantage of decreasing the distribution of ARGs. Overall, MBSS exhibits remarkable efficacy in mitigating the challenges posed by antibiotics and resistant genes from mariculture wastewater.


Assuntos
Antibacterianos , Resistência Microbiana a Medicamentos , Microalgas , Águas Residuárias , Águas Residuárias/microbiologia , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Microalgas/genética , Microalgas/fisiologia , Eliminação de Resíduos Líquidos/métodos , Bactérias , Metagenômica , Aquicultura , Poluentes Químicos da Água/análise , Simbiose , Genes Bacterianos
12.
Bioresour Technol ; 399: 130550, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38460562

RESUMO

Sunlight illumination has the potential to control the stability and sustainability of dynamic membrane (DM) systems. In this study, an up-flow anaerobic sludge blanket (UASB) reactor was combined with DM under different illumination positions (direct, indirect and no illumination) to treat wastewater. Results indicated that the UASB achieved a COD removal up to 87.05 % with an average methane production of 0.28 L/d. Following treatment by the UASB, it was found that under illumination, the removal of organic substances by DM exhibited poor performance due to algal proliferation. However, the DM systems demonstrated efficient removal of ammonia nitrogen, ranging from 96.21 % to 97.67 % after stabilization. Total phosphorus removal was 45.72 %, and membrane flux remained stable when directly illuminated. Conversely, the DM system subjected to indirect illumination showed unstable membrane flux and severe fouling resistance. These findings offer valuable insights into optimizing illumination positions in DM systems under anaerobic conditions.


Assuntos
Eliminação de Resíduos Líquidos , Purificação da Água , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Iluminação , Metano , Reatores Biológicos , Esgotos
13.
Cell Discov ; 10(1): 33, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531851

RESUMO

Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research.

14.
ACS Appl Mater Interfaces ; 16(13): 15752-15760, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38507518

RESUMO

Chronic wound healing impairment is a significant complication in diabetes. Hydrogels that maintain wound moisture and enable sustained drug release have become prominent for enhancing chronic wound care. Particularly, hydrogels that respond to reactive oxygen species (ROS) are sought-after for their dual capacity to mitigate ROS and facilitate controlled drug delivery at the wound site. We have strategically designed an ROS-responsive and scavenging supramolecular hydrogel composed of the simple hexapeptide Glu-Phe-Met-Phe-Met-Glu (EFM). This hydrogelator, composed solely of canonical amino acids without additional ROS-sensitive motifs, forms a hydrogel rapidly upon sonication. Interaction with ROS leads to the oxidation of Met residues to methionine sulfoxide, triggering hydrogel disassembly and consequent payload release. Cellular assays have verified their biocompatibility and efficacy in promoting cell proliferation and migration. In vivo investigations underscore the potential of this straightforward hydrogel as an ROS-scavenger and drug delivery vehicle, enhancing wound healing in diabetic mice. The simplicity and effectiveness of this hydrogel suggest its broader biomedical applications in the future.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus , Animais , Camundongos , Hidrogéis/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Espécies Reativas de Oxigênio , Aminoácidos , Cicatrização , Antibacterianos
15.
Heliyon ; 10(3): e24496, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38333842

RESUMO

A series of GdY2SbO7:Bi3+, Eu3+ phosphors were prepared using the conventional solid-state reaction. In this study, the photoluminescence properties and temperature sensitivity of the samples were investigated. When Bi3+ and Eu3+ were codoped into GdY2SbO7, the intensity of Bi3+ decreased with increasing Eu3+ concentration, indicating a potential energy transfer from Bi3+ to Eu3+. To examine the temperature sensitivity of the sample, its emission spectrum was investigated in the range of 300-500 K. Based on different temperature dependences of Bi3+ and Eu3+, the relative sensitivity (Sr) and absolute sensitivity (Sa) of the samples were calculated using the fluorescence intensity ratio (FIR) and thermochromic methods. In FIR modes, Sr based on IEu3+/IBi3+ reached 1.26 % K-1 at 500 K, while Sr on double excitation method reached 1.36 % K-1 at 340 K. In addition, according to the thermochromic properties of GdY2SbO7:Bi3+, Eu3+ phosphor, the temperature-sensing ability of the sample was investigated, and Sr reached a maximum value of 0.5996 % K-1 at 300 K.

16.
Cell Prolif ; 57(5): e13591, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38319150

RESUMO

Highly aggressive gastric cancer (HAGC) is a gastric cancer characterized by bone marrow metastasis and disseminated intravascular coagulation (DIC). Information about the disease is limited. Here we employed single-cell RNA sequencing to investigate peripheral blood mononuclear cells (PBMCs), aiming to unravel the immune response of patients toward HAGC. PBMCs from seven HAGC patients, six normal advanced gastric cancer (NAGC) patients, and five healthy individuals were analysed by single-cell RNA sequencing. The expression of genes of interest was validated by bulk RNA-sequencing and ELISA. We found a massive expansion of neutrophils in PBMCs of HAGC. These neutrophils are activated, but immature. Besides, mononuclear phagocytes exhibited an M2-like signature and T cells were suppressed and reduced in number. Analysis of cell-cell crosstalk revealed that several signalling pathways involved in neutrophil to T-cell suppression including APP-CD74, MIF-(CD74+CXCR2), and MIF-(CD74+CD44) pathways were increased in HAGC. NETosis-associated genes S100A8 and S100A9 as well as VEGF, PDGF, FGF, and NOTCH signalling that contribute to DIC development were upregulated in HAGC too. This study reveals significant changes in the distribution and interactions of the PBMC subsets and provides valuable insight into the immune response in patients with HAGC. S100A8 and S100A9 are highly expressed in HAGC neutrophils, suggesting their potential to be used as novel diagnostic and therapeutic targets for HAGC.


Assuntos
Leucócitos Mononucleares , Análise de Sequência de RNA , Análise de Célula Única , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/sangue , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/imunologia , Neutrófilos/metabolismo , Neutrófilos/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Transdução de Sinais , Idoso , Linfócitos T/imunologia , Linfócitos T/metabolismo
17.
Adv Sci (Weinh) ; 11(5): e2304755, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38010945

RESUMO

Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single-cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA-seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high-throughput and high-sensitivity method called snHH-seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full-length RNA-seq data is also established. snHH-seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan-cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full-length RNA at the single-nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.


Assuntos
Ecossistema , Neoplasias , Humanos , Análise de Sequência de RNA/métodos , RNA-Seq/métodos , Neoplasias/genética , RNA/genética
18.
Protein Cell ; 15(2): 98-120, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37378670

RESUMO

Aging increases the risk of liver diseases and systemic susceptibility to aging-related diseases. However, cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized. Here, we constructed the first single-nucleus transcriptomic landscape of primate liver aging, in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells. Upon in-depth dissection of this rich dataset, we identified impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging. In particular, hyperactivated sterol regulatory element-binding protein (SREBP) signaling was a hallmark of the aged liver, and consequently, forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes, manifesting as impaired detoxification and accelerated cellular senescence. This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.


Assuntos
Hepatócitos , Fígado , Animais , Humanos , Idoso , Fígado/metabolismo , Hepatócitos/metabolismo , Primatas/genética , Perfilação da Expressão Gênica , Envelhecimento/genética
19.
Stem Cell Reports ; 18(12): 2464-2481, 2023 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-37995704

RESUMO

In vivo differentiation of human pluripotent stem cells (hPSCs) has unique advantages, such as multilineage differentiation, angiogenesis, and close cell-cell interactions. To systematically investigate multilineage differentiation mechanisms of hPSCs, we constructed the in vivo hPSC differentiation landscape containing 239,670 cells using teratoma models. We identified 43 cell types, inferred 18 cell differentiation trajectories, and characterized common and specific gene regulation patterns during hPSC differentiation at both transcriptional and epigenetic levels. Additionally, we developed the developmental single-cell Basic Local Alignment Search Tool (dscBLAST), an R-based cell identification tool, to simplify the identification processes of developmental cells. Using dscBLAST, we aligned cells in multiple differentiation models to normally developing cells to further understand their differentiation states. Overall, our study offers new insights into stem cell differentiation and human embryonic development; dscBLAST shows favorable cell identification performance, providing a powerful identification tool for developmental cells.


Assuntos
Células-Tronco Pluripotentes , Humanos , Diferenciação Celular/genética , Células-Tronco Pluripotentes/metabolismo , Regulação da Expressão Gênica , Desenvolvimento Embrionário
20.
Food Res Int ; 174(Pt 1): 113519, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37986421

RESUMO

The lack of research on the rich sucrose in tiger nut meal has been a major obstruction to the comprehensive utilization of tiger nut (Cyperus esculentus L.). In this study, for the first time, tiger nut meal was used to producing non-centrifugal sugar (NCS). Three samples - NCS-W1 (NCS prepared by water extraction and concentrated at 115 °C), NCS-W2 (NCS prepared by water extraction and concentrated at 135 °C), and NCS-E (NCS prepared by 70 % ethanol-water extraction and concentrated at 115 °C) were obtained, with yields of 14.25-14.59 %. These samples and sugarcane NCS products (NCS-C1, NCS-C2, NCS-L) were compared and analyzed in terms of color, pH, turbidity, soluble solid content, and proximate composition. Their Fourier-transformed infrared spectra, crystal patterns, and thermal stabilities were also analyzed. The NCS-W1, -W2, and -E showed excellent performance, and they were better than sugarcane NCS products in terms of free radical scavenging ability and cytoprotective effects. Differences in phenolic acid composition, flavonoid composition, amino acid, mineral content, and vitamins C and E content were also analyzed. This work demonstrates that tiger nut meal might be a new source of NCS. As such it would contribute to the full utilization of tiger nut.


Assuntos
Cyperus , Saccharum , Açúcares/metabolismo , Cyperus/química , Vitaminas , Água/metabolismo
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