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1.
Front Aging Neurosci ; 16: 1417989, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962561

RESUMO

Background: Ferroptosis, a newly proposed concept of programmed cell death, has garnered significant attention in research across different diseases in the last decade. Despite thorough citation analyses in neuroscience, there is a scarcity of information on ferroptosis research specifically related to neurodegenerative diseases. Method: The Web of Science Core Collection database retrieved relevant articles and reviews. Data on publications, countries, institutions, authors, journals, citations, and keywords in the included studies were systematically analyzed using Microsoft Excel 2019 and CiteSpace 6.2.R7 software. Result: A comprehensive analysis and visualization of 563 research papers on ferroptosis in neurodegenerative diseases from 2014 to 2023 revealed emerging research hotspots and trends. The number of annual publications in this field of study has displayed a pattern of stabilization in the early years of the decade, followed by a notable increase in the later years and peaking in 2023 with 196 publications. Regarding publication volume and total citations, notable research contributions were observed from countries, institutions, and authors in North America, Western Europe, and China. Current research endeavors primarily focus on understanding the intervention mechanisms of neurodegenerative diseases through the ferroptosis pathway and exploring and identifying potential therapeutic targets. Conclusion: The study highlights key areas of interest and emerging trends in ferroptosis research on neurodegenerative diseases, offering valuable insights for further exploration and potential directions for diagnosing and treating such conditions.

2.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 646-651, 2024 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-38926383

RESUMO

Neonatal necrotizing enterocolitis (NEC) is the most common inflammatory intestinal disease in preterm infants, with a high incidence and mortality rate. The etiology and mechanisms of NEC are not yet fully understood, and multiple factors contribute to its occurrence and development. Recent studies have found that anemia is a risk factor for NEC in neonates, but the specific pathogenic mechanism remains unclear. This article reviews recent research on the relationship between anemia and NEC, providing a reference for further understanding the impact of anemia on intestinal injury and its association with NEC.


Assuntos
Anemia , Enterocolite Necrosante , Enterocolite Necrosante/etiologia , Humanos , Recém-Nascido , Anemia/etiologia
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124695, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38936212

RESUMO

The extraction process plays a crucial role in the production of Tibetan medicines. This study focused on assembling a set of online near-infrared (NIR) spectroscopy detection devices for the extraction of medicinal herbs. The original infrared device was transformed into an online detection system. After evaluating the stability of the system, we applied online NIR spectroscopy monitoring to the flavonoid contents (total flavonoids, quercetin-3-O-sophoroside, and luteolin) of Meconopsis quintuplinervia Regel. during the ultrasonic extraction process and determined the extraction endpoint. Nine batches of samples were employed to construct quantitative and discriminant models, half of the remaining two batches of samples are used for external verification. Our research shows that the residual predictive deviation (RPD) values of total flavonoids, quercetin-3-O-sophoroside and luteolin models exceeded 2.5. The R values for external verification of the three ingredients were above 0.9, with RPD values generally exceeding 2 and RSEP values within 10 %, demonstrating the model's strong predictive performance. Most of the extraction endpoints of the flavonoid components in M. quintuplinervia ranged from 18 to 58 min, with high consistency between the predicted extraction endpoints of the external validation, suggesting accurate determination of extraction endpoints based on predicted values. This study can provide a reference for the online NIR spectroscopy quality monitoring of the extraction process of Chinese and Tibetan herbs.

4.
Clin Exp Med ; 24(1): 136, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916672

RESUMO

Dysregulated lipid metabolism in the bone marrow microenvironment (BMM) plays a vital role in multiple myeloma (MM) development, progression, and drug resistance. However, the exact mechanism by which lipid metabolism impacts the BMM, promotes tumorigenesis, and triggers drug resistance remains to be fully elucidated.By analyzing the bulk sequencing and single-cell sequencing data of MM patients, we identified lipid metabolism-related genes differential expression significantly associated with MM prognosis, referred to as LMRPgenes. Using a cohort of ten machine learning algorithms and 117 combinations, LMRPgenes predictive models were constructed. Further exploration of the effects of the model risk score (RS) on the survival status, immune status of patients with BMM, and response to immunotherapy was conducted. The study also facilitated the identification of personalized therapeutic strategies targeting specified risk categories within patient cohorts.Analysis of the scRNA-seq data revealed increased lipid metabolism-related gene enrichment scores (LMESs) in erythroblasts and progenitor, malignant, and Tprolif cells but decreased LMESs in lymphocytes. LMESs were also strongly correlated with most of the 50 hallmark pathways within these cell populations. An elevated malignant cell ratio and reduced lymphocytes were observed in the high LMES group. Moreover, the LMRPgenes predictive model, consisting of 14 genes, showed great predictive power. The risk score emerged as an independent indicator of poor outcomes. Inverse relationships between the RS and immune status were noted, and a high RS was associated with impaired immunotherapy responses. Drug sensitivity assays indicated the effectiveness of bortezomib, buparlisib, dinaciclib, staurosporine, rapamycin, and MST-312 in the high-RS group, suggesting their potential for treating patients with high-RS values and poor response to immunotherapy. Ultimately, upon verification via qRT-PCR, we observed a significant upregulation of ACBD6 in NDMM group compared to the control group.Our research enhances the knowledge base regarding the association between lipid metabolism-related genes (LMRGs) and the BMM in MM patients, offering substantive insights into the mechanistic effects of the BMM mediated by LMRGs.


Assuntos
Metabolismo dos Lipídeos , Mieloma Múltiplo , Microambiente Tumoral , Humanos , Metabolismo dos Lipídeos/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Mieloma Múltiplo/tratamento farmacológico , Medula Óssea/metabolismo , Medula Óssea/patologia , Transcriptoma , Perfilação da Expressão Gênica , Prognóstico , Regulação Neoplásica da Expressão Gênica
5.
Biomed Pharmacother ; 177: 117017, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38917762

RESUMO

5-HT clearance, commonly mediated by transporters in the uptake-1 and uptake-2 families, has been linked to 5-HT1B receptor's action on behaviors. Since no specific transporters identified yet, effects of serotonin transporter (SERT) and organic cation transporter (OCTs) on 5-HT1B-elicited immobility phenotype, and 5-HT and HIS uptake were then investigated. Intraperitoneal injections of SERT inhibitor fluoxetine (FLX) and/or OCTs inhibitor decynium (D22) were used prior to local perfusion of 5-HT1B agonist CP93129 into the ventral hippocampus to measure immobility times in the FST and TST, to measure 5-HT uptake efficiencies and HIS uptake efficiencies derived from linear regressions using the transient no-net-flux quantitative microdialysis in C57BL/6 mice. Exogenous 5-HT and HIS uptake were measured following incubation of FLX and/or D22 with CP93129 in the RBL-2H3 cells. Moreover, surface membrane levels of SERT and OCT were detected in response to CP93129. Local CP93129 prolonged immobility times, which were attenuated following pretreatment of either inhibitor. Local CP93129 lowered the slopes obtained from the lineal regressions for 5-HT and HIS (slope is reciprocal to uptake efficiency), which were then weakened following pretreatment of either inhibitor. Similar findings were obtained following CP93129 incubation, and co-incubation of CP93129 with either inhibitor in the RBL-2H3. Moreover, CP93129 dose-dependently moved SERT and OCT3 in the cytosol to the surface membrane. Both SERT and OCT are the target effectors mediating 5-HT1B regulation of immobility time and 5-HT uptake, OCT mediates 5-HT1B regulation of HIS uptake. Their underlying signal transductions need to be further explored.

6.
Heliyon ; 10(10): e31014, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38774314

RESUMO

Objective: This study aimed to assess the surgical outcomes and identify the conversion risk factors of Transvaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) in treating ovarian cyst. Methods: This was a retrospective study of 505 patients who underwent vNO TES for treating ovarian cyst from March 2019 to February 2022 wherein the patients were classified into "converted" or "nonconverted" groups. T-tests, χ2 tests, and logistic regression were used for statistical analyses. Results: There were 16 (3.17 %) surgical conversions and 12 (2.38 %) other surgical complications in our study cohort. Teratomas accounted for 56.8 % of complications in nonconverted cases and 18.8 % in converted cases. Adenocystomas were found in 12.3 % of nonconverted cases and 18.8 % of converted cases. Other types included paraovarian cysts (3.3 % and 0 %), fibroma, granulosa cell tumor, Brenner tumor (1.2 % and 0 %), corpus luteum cysts, follicular cysts (7.6 % and 6.3 %), old abscess (0.2 % and 0 %), and simple cysts (17.6 % and 12.5 %) in the nonconverted and converted groups, respectively. The converted group included more cases of endometriotic cysts (43.8 % vs 12.3 %, p = 0.023), bilateral cysts (37.5 % vs 8.2 %, p < 0.001), severe pelvic adhesion (68.8 % vs 3.3 %, p < 0.001), deep endometriosis (12.5 % vs 0.4 %, p < 0.001), and at least two cysts (37.5 % vs 8.81 %; p < 0.001). Severe pelvic adhesion (adjusted odds ratio [OR], 86.96; range, 18.33-431.77; p < 0.001), bilateral cysts (adjusted OR, 4.75; range, 1.05-21.57, p = 0.043) and endometriotic cysts (adjusted OR, 7.69; range, 3.11-17.08; p < 0.001) were also predictors of surgical conversion. Conclusion: vNOTES demonstrates low complication and conversion rates in treating ovarian cyst compared with TU-LESS. Surgical conversion is associated with severe pelvic adhesions, bilateral cysts, and endometriotic cysts.

7.
Nat Food ; 5(5): 413-422, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38724686

RESUMO

Salmonella enterica causes severe food-borne infections through contamination of the food supply chain. Its evolution has been associated with human activities, especially animal husbandry. Advances in intensive farming and global transportation have substantially reshaped the pig industry, but their impact on the evolution of associated zoonotic pathogens such as S. enterica remains unresolved. Here we investigated the population fluctuation, accumulation of antimicrobial resistance genes and international serovar Choleraesuis transmission of nine pig-enriched S. enterica populations comprising more than 9,000 genomes. Most changes were found to be attributable to the developments of the modern pig industry. All pig-enriched salmonellae experienced host transfers in pigs and/or population expansions over the past century, with pigs and pork having become the main sources of S. enterica transmissions to other hosts. Overall, our analysis revealed strong associations between the transmission of pig-enriched salmonellae and the global pork trade.


Assuntos
Salmonella enterica , Animais , Salmonella enterica/genética , Salmonella enterica/isolamento & purificação , Suínos , Europa (Continente)/epidemiologia , Humanos , Salmonelose Animal/epidemiologia , Salmonelose Animal/transmissão , Salmonelose Animal/microbiologia , Doenças dos Suínos/microbiologia , Doenças dos Suínos/transmissão , Doenças dos Suínos/epidemiologia , Criação de Animais Domésticos/métodos , Carne de Porco/microbiologia , América/epidemiologia , Microbiologia de Alimentos
8.
Am J Clin Nutr ; 120(1): 66-79, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795741

RESUMO

BACKGROUND: Our previous studies showed that curcumin prevented hepatic steatosis in animal models. OBJECTIVES: This study aimed to assess the effects of curcumin on hepatic fat content, body composition, and gut microbiota-dependent bile acid (BA) metabolism in patients with nonalcoholic simple fatty liver (NASFL). METHODS: In a 24-wk double-blind randomized trial, 80 patients with NASFL received 500 mg/d curcumin or placebo. Hepatic fat content was measured using FibroTouch-based controlled attenuation parameters (CAPs). Microbial composition and BA metabolites were analyzed using 16S rRNA sequencing and metabolomics. RESULTS: Curcumin consumption significantly reduced CAP value compared with placebo (-17.5 dB/m; 95% confidence interval [CI]: -27.1, -7.8 dB/m; P < 0.001). This corresponded to reduction in weight (-2.6 kg; 95% CI: -4.4, -0.8 kg; P < 0.001) and BMI (-1.0 kg/m2; 95% CI: -2.0, -0.1 kg/m2; P = 0.032) compared with placebo group. Additionally, free fatty acid (-0.12 mmol/L; 95% CI: -0.20, -0.04 mmol/L; P = 0.004), triglycerides (-0.29 mmol/L; 95% CI: -0.41, -0.14 mmol/L; P < 0.001), fasting blood glucose (-0.06 mmol/L; 95% CI: -0.12, -0.01 mmol/L; P = 0.038), hemoglobin A1c (-0.06%; 95% CI: -0.33, -0.01%; P = 0.019), and insulin (-4.94 µU/L; 95% CI: -9.73, -0.15 µU/L; P = 0.043) showed significant reductions in the curcumin group compared with placebo group. Gut microbiota analysis indicated that curcumin significantly decreased Firmicutes to Bacteroidetes ratio and significantly increased Bacteroides abundance. Serum levels of deoxycholic acid, the most potent activator of Takeda G protein-coupled receptor 5 (TGR5), were significantly elevated after curcumin intervention (37.5 ng/mL; 95% CI: 6.7, 68.4 ng/mL; P = 0.018). Curcumin treatment also increased TGR5 expression in peripheral blood mononuclear cells and serum glucagon-like peptide-1 levels (0.73 ng/mL; 95% CI: 0.16, 1.30 ng/mL; P = 0.012). CONCLUSIONS: Improvements in gut microbiota-dependent BA metabolism and TGR5 activation after 24-wk curcumin intervention were associated with a reduction in hepatic fat content in patients with NASFL, providing evidence that curcumin is a potential nutritional therapy for NASFL. The trial was registered at www.chictr.org.cn as ChiCTR2200058052.


Assuntos
Ácidos e Sais Biliares , Curcumina , Suplementos Nutricionais , Microbioma Gastrointestinal , Fígado , Hepatopatia Gordurosa não Alcoólica , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/administração & dosagem , Masculino , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Feminino , Pessoa de Meia-Idade , Ácidos e Sais Biliares/metabolismo , Método Duplo-Cego , Fígado/metabolismo , Fígado/efeitos dos fármacos , Adulto
10.
PLoS One ; 19(5): e0298572, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38758947

RESUMO

Aiming at the problem of load increase in distribution network and low satisfaction of vehicle owners caused by disorderly charging of electric vehicles, an optimal scheduling model of electric vehicles considering the comprehensive satisfaction of vehicle owners is proposed. In this model, the dynamic electricity price and charging and discharging state of electric vehicles are taken as decision variables, and the income of electric vehicle charging stations, the comprehensive satisfaction of vehicle owners considering economic benefits and the load fluctuation of electric vehicles are taken as optimization objectives. The improved NSGA-III algorithm (DJM-NSGA-III) based on dynamic opposition-based learning strategy, Jaya algorithm and Manhattan distance is used to solve the problems of low initial population quality, easy to fall into local optimal solution and ignoring potential optimal solution when NSGA-III algorithm is used to solve the multi-objective and high-dimensional scheduling model. The experimental results show that the proposed method can improve the owner's satisfaction while improving the income of the charging station, effectively alleviate the conflict of interest between the two, and maintain the safe and stable operation of the distribution network.


Assuntos
Algoritmos , Eletricidade , Automóveis , Humanos , Modelos Teóricos
11.
Front Immunol ; 15: 1381308, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745670

RESUMO

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient's complete remission has persisted for 20 months after HSCT.


Assuntos
Antígenos CD7 , Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Antígenos CD7/imunologia , Receptores de Antígenos Quiméricos/imunologia , Masculino , Doadores de Tecidos , Linfócitos T/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Resultado do Tratamento , Adulto
12.
Sci Total Environ ; 927: 172155, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38575028

RESUMO

As of 2022, China's rural sewage treatment rate is only approximately 31 %. Rapid rural development has led to higher demand. However, China's rural areas are complex and face many problems, such as uneven economic development, population distribution, and water availability. Long-lasting and low-cost wastewater treatment measures are needed for application in rural areas. The quantity and quality of rural domestic wastewater in China were characterized first. Next, the hot topic of domestic wastewater in Chinese villages was confirmed via bibliometric analysis using CiteSpace, and the treatment technologies for rural domestic wastewater were compared. Specifically, the technical status and challenges of the most common technology in rural domestic wastewater treatment, constructed wetlands, were summarized.


Assuntos
Eliminação de Resíduos Líquidos , Águas Residuárias , China , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Áreas Alagadas
13.
Nat Prod Res ; : 1-9, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684021

RESUMO

Three isocoumarins, ascoisocoumarin A (1), embeurekol (2), and sclerotinin A (3), and five biosynthetically related derivatives, ascospinols A-C (4, 6, and 7), and talaflavuols C and B (5 and 8), together with twelve polyketides or terpenes (9-20) were isolated from the fungus Aspergillus sp. LY-1-2 inhabited in a sample of Cordyceps sp. Most of them belong to the family of oxygen-containing aromatic compounds and compounds 1, 4, 6, and 7 are previously undescribed compounds. Their planar structures were established by a combined spectroscopic analysis of HRESIMS and NMR, and their stereochemistry was determined by 13C NMR calculations with sorted training set (STS) protocol analysis, and ECD calculations. New compounds 1 and 6 displayed potential anti-inflammatory effects in lipopolysaccharide (LPS)-induced BV2 microglia cells.

14.
RSC Adv ; 14(11): 7910-7914, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38449819

RESUMO

Herein, the design of a novel aggregation-induced emission (AIE) supramolecular fluorescence sensor (TA-PEGn) based on a tridentate melphalan derivative and three different molecular weight PEGs is presented. The three TA-PEGn sensors could self-assemble into a supramolecular system in water and show sensitive and selective responses toward trinitrophenol.

15.
Chin Med J (Engl) ; 137(9): 1115-1117, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38310445
16.
Mol Ther ; 32(4): 890-909, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38369751

RESUMO

Long-term use of conventional drugs to treat inflammatory bowel diseases (IBD) and colitis-associated cancer (CAC) has an adverse impact on the human immune system and easily leads to drug resistance, highlighting the urgent need to develop novel biotherapeutic tools with improved activity and limited side effects. Numerous products derived from plant sources have been shown to exert antibacterial, anti-inflammatory and antioxidative stress effects. Plant-derived vesicle-like nanoparticles (PDVLNs) are natural nanocarriers containing lipids, protein, DNA and microRNA (miRNA) with the ability to enter mammalian cells and regulate cellular activity. PDVLNs have significant potential in immunomodulation of macrophages, along with regulation of intestinal microorganisms and friendly antioxidant activity, as well as overcoming drug resistance. PDVLNs have utility as effective drug carriers and potential modification, with improved drug stability. Since immune function, intestinal microorganisms, and antioxidative stress are commonly targeted key phenomena in the treatment of IBD and CAC, PDVLNs offer a novel therapeutic tool. This review provides a summary of the latest advances in research on the sources and extraction methods, applications and mechanisms in IBD and CAC therapy, overcoming drug resistance, safety, stability, and clinical application of PDVLNs. Furthermore, the challenges and prospects of PDVLN-based treatment of IBD and CAC are systematically discussed.


Assuntos
Neoplasias Associadas a Colite , Colite , Doenças Inflamatórias Intestinais , Nanopartículas , Animais , Humanos , Neoplasias Associadas a Colite/complicações , Neoplasias Associadas a Colite/tratamento farmacológico , Neoplasias Associadas a Colite/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/etiologia , Anti-Inflamatórios/farmacologia , Macrófagos/metabolismo , Colite/etiologia , Colite/complicações , Mamíferos
17.
Reprod Biol ; 24(2): 100852, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38354656

RESUMO

BACKGROUND: Intrauterine adhesions (IUA) refers to endometrial fibrosis caused by irreversible damage of the endometrial basal layer. As the key regulators in tissue repair, regeneration, and fibrosis, macrophages play an essential role in endometrial regeneration and repair during the normal menstrual cycle. However, the mechanism of macrophages involved in IUA remains unclear. METHODS: In the late stages of proliferation, the endometrium was collected to make paraffin sections. HE and Masson staining were used to observing endometrial morphology and endometrial fibrosis. Immunohistochemistry and Western blotting were used to detect the expression level of fibrosis indexes COL1A1 and α-SMA. The macrophage infiltration was evaluated by immunohistochemistry for the expression levels of CD 206 and CD163. Next, we cultured the primary human endometrial stromal cells (HESCs), and then an IUA cell model was established with 10 ng/ml TGF-ß1 for 72 h. THP 1 cells were differentiated by 100 ng/ml PMA into macrophages for 48 h, then macrophages were polarized to M2 macrophages by 20 ng/ml IL-4 for 24 h. The culture supernatants (M(IL-4) -S) of M2 macrophages were applied to the IUA cell model. The expression of fibrosis markers was then assessed using immunofluorescence and Western blotting. RESULTS: The results show that Patients with IUA have fewer endometrial glands and significantly increased fibrosis levels. Moreover, the infiltration of CD206-positive (M2) macrophages was significantly reduced in IUA patients, and negatively correlated with the expression of endometrial fibrosis indexes α-SMA and COL1A1. In addition, the primary HESCs treated with 10 ng/ml TGF-ß1 for 72 h were found to have significantly increased levels of fibrosis indexes. Furthermore, supernatants from IL4-induced M2 macrophages inhibit the TGF-ß1-induced fibrosis of HESCs. CONCLUSIONS: M2 macrophages may negatively regulate the expression of COL1A1 and α-SMA, inhibiting the TGF-ß1-induced fibrosis of HESCs. Our study suggests that targeting macrophage phenotypes and promoting the polarization of macrophages to M2 may become a novel strategy for the clinical treatment of IUA.


Assuntos
Endométrio , Fibrose , Interleucina-4 , Macrófagos , Células Estromais , Humanos , Feminino , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Endométrio/patologia , Células Estromais/metabolismo , Células Estromais/efeitos dos fármacos , Interleucina-4/metabolismo , Adulto , Células Cultivadas , Fator de Crescimento Transformador beta1/metabolismo
18.
Bioorg Med Chem Lett ; 102: 129659, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38373465

RESUMO

Depletion of cellular levels of geranylgeranyl diphosphate by inhibition of the enzyme geranylgeranyl diphosphate synthase (GGDPS) is a potential strategy for disruption of protein transport by limiting the geranylgeranylation of the Rab proteins that regulate intracellular trafficking. As such, there is interest in the development of GGDPS inhibitors for the treatment of malignancies characterized by abnormal protein production, including multiple myeloma. Our previous work has explored the structure-function relationship of a series of isoprenoid triazole bisphosphonate-based GGDPS inhibitors, with modifications having impact on enzymatic, cellular and in vivo activities. We have synthesized a new series of α-amino bisphosphonates to understand the impact of modifying the alpha position with a moiety that is potentially linkable to other agents. Bioassays evaluating the enzymatic and cellular activities of these compounds demonstrate that incorporation of the α-amino group affords compounds with GGDPS inhibitory activity which is modulated by isoprenoid tail chain length and olefin stereochemistry. These studies provide further insight into the complexity of the structure-function relationship and will enable future efforts focused on tumor-specific drug delivery.


Assuntos
Difosfonatos , Inibidores Enzimáticos , Difosfonatos/farmacologia , Difosfonatos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Farnesiltranstransferase , Triazóis/química , Terpenos/química
19.
Anal Chim Acta ; 1294: 342217, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38336406

RESUMO

BACKGROUND: Microfluidic techniques have emerged as powerful tools in single-cell research, facilitating the exploration of omics information from individual cells. Cell morphology is crucial for gene expression and physiological processes. However, there is currently a lack of integrated analysis of morphology and single-cell omics information. A critical challenge remains: what platform technologies are the best option to decode omics data of cells that are complex in morphology and size? RESULTS: This review highlights achievements in microfluidic-based single-cell omics and isolation of cells based on morphology, along with other cell sorting methods based on physical characteristics. Various microfluidic platforms for single-cell isolation are systematically presented, showcasing their diversity and adaptability. The discussion focuses on microfluidic devices tailored to the distinct single-cell isolation requirements in plants and animals, emphasizing the significance of considering cell morphology and cell size in optimizing single-cell omics strategies. Simultaneously, it explores the application of microfluidic single-cell sorting technologies to single-cell sequencing, aiming to effectively integrate information about cell shape and size. SIGNIFICANCE AND NOVELTY: The novelty lies in presenting a comprehensive overview of recent accomplishments in microfluidic-based single-cell omics, emphasizing the integration of different microfluidic platforms and their implications for cell morphology-based isolation. By underscoring the pivotal role of the specialized morphology of different cells in single-cell research, this review provides robust support for delving deeper into the exploration of single-cell omics data.


Assuntos
Dispositivos Lab-On-A-Chip , Microfluídica , Animais , Separação Celular/métodos
20.
Heliyon ; 10(1): e23723, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38205313

RESUMO

N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation mediates glutamate (Glu) toxicity and involves bleomycin (BLM)-induced acute lung injury (ALI). We have reported that bone marrow-derived mesenchymal stem cells (BM-MSCs) are NMDAR-regulated target cells, and NMDAR activation inhibits the protective effect of BM-MSCs on BLM-induced pulmonary fibrosis, but its effect on ALI remains unknown. Here, we found that Glu release was significantly elevated in plasma of mice at d 7 after intratracheally injected with BLM. BM-MSCs were pretreated with NMDA (the selective agonist of NMDAR) and transplanted into the recipient mice after the BLM challenge. BM-MSCs administration significantly alleviated the pathological changes, inflammatory response, myeloperoxidase activity, and malondialdehyde content in the damaged lungs, but NMDA-pretreated BM-MSCs did not ameliorate BLM-induced lung injury in vivo. Moreover, NMDA down-regulated prostaglandin E2 (PGE2) secretion and cyclooxygenase (COX)-2 expression instead of COX-1 expression in BM-MSCs in vitro. We also found that NMDAR1 expression was increased and COX-2 expression was decreased, but COX-1 expression was not changed in primary BM-MSCs of BLM-induced ALI mice. Further, the cultured supernatants of lipopolysaccharide (LPS)-pretreated RAW264.7 macrophages were collected to detect inflammatory factors after co-culture with NMDA-pretreated BM-MSCs. The co-culture experiments showed that NMDA precondition inhibited the anti-inflammatory effect of BM-MSCs on LPS-induced macrophage inflammation, and PGE2 could partially alleviate this inhibition. Our findings suggest that NMDAR activation attenuated the protective effect of BM-MSCs on BLM-induced ALI in vivo. NMDAR activation inhibited COX-2 expression and PGE2 secretion in BM-MSCs and weakened the anti-inflammatory effect of BM-MSCs on LPS-induced macrophage inflammation in vitro. In conclusion, NMDAR activation attenuates the protective effect of BM-MSCs on BLM-induced ALI via the COX-2/PGE2 pathway. Keywords: Acute Lung Injury, BM-MSCs, NMDA receptor, COX-1/2, PGE2.

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