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1.
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
2.
Nat Food ; 2024 May 09.
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.

3.
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 , Áreas Alagadas , População Rural , Purificação da Água/métodos , População do Leste Asiático
4.
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.

5.
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.

6.
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
7.
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
8.
Chin Med J (Engl) ; 137(9): 1115-1117, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38310445
9.
Reprod Biol ; 24(2): 100852, 2024 Feb 13.
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.

10.
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
11.
Int J Biochem Cell Biol ; 169: 106530, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38246263

RESUMO

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has a high mortality rate and incidence of complications. The pathophysiology of ALI/ARDS is still not fully understood. The lipopolysaccharide (LPS)-induced mouse model of ALI has been widely used to study human ALI/ARDS. Sulfasalazine (SASP) has antibacterial and anti-inflammatory effects and is used for treating inflammatory bowel and rheumatic diseases. However, the effect of SASP on LPS-induced ALI in mice has not yet been reported. Therefore, we aimed to investigate the effect of SASP on LPS-induced ALI in mice. Mice were intraperitoneally injected with SASP 2 h before or 4 h after LPS modeling. Pulmonary pathological damage was measured based on inflammatory factor expression (malondialdehyde and superoxide dismutase levels) in the lung tissue homogenate and alveolar lavage fluid. The production of inflammatory cytokines and occurrence of oxidative stress in the lungs induced by LPS were significantly mitigated after the prophylactic and long-term therapeutic administration of SASP, which ameliorated ALI caused by LPS. SASP reduced both the production of inflammatory cytokines and occurrence of oxidative stress in RAW264.7 cells, which respond to LPS. Moreover, its mechanism contributed to the suppression of NF-κB and nuclear translocation. In summary, SASP treatment ameliorates LPS-induced ALI by mediating anti-inflammatory and antioxidant effects, which may be attributed to the inhibition of NF-κB activation and promotion of antioxidant defenses. Thus, SASP may be a promising pharmacologic agent for ALI therapy.


Assuntos
Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Camundongos , Humanos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Sulfassalazina/efeitos adversos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Pulmão/patologia , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia
12.
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.

13.
Ecotoxicol Environ Saf ; 271: 115953, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244512

RESUMO

The widespread use of biogas slurry could potentially raise the environmental risk of antibiotics. Dissolved organic matter (DOM), as the most active part of biogas slurry, was able to interact with antibiotics and play a crucial role in the structure and function of soil and aquatic ecosystems. The recent shifts in global climate patterns have garnered significant attention due to their substantial impact on temperature, thereby exerting a direct influence on the characteristics of DOM and subsequently on the environmental behavior of antibiotics. However, there is limited research concerning the impact of temperature on the binding of DOM and antibiotics. Thus, this study aimed to explore the temperature-dependent structural transformation and driving factors of biogas slurry-derived DOM (BSDOM). Additionally, the binding characteristics between BSDOM and the commonly used antibiotic norfloxacin (NOR) at different temperatures were studied by using multi spectroscopic methods and two-dimensional correlation spectroscopy (2D-COS) analysis. The results suggested that the temperature-dependent structural transformation of BSDOM was reversible, with a slight lag in the transition temperature under cooling (13 °C for heating and 17 °C for cooling). Heating promoted the conversion of protein-like to humic-like substances while cooling favored the decomposition of humic-like substances. BSDOM and NOR were static quenching, with oxygen-containing functional groups such as C-O and -OH playing an important role. Temperature influenced the order of binding, the activity of the protein fraction, and its associated functional groups. At temperatures of 25 °C and 40 °C, the fluorescent components were observed to exhibit consistent binding preferences, whereby the humic-like component demonstrated a greater affinity for NOR compared to the protein-like component. However, the functional group binding order exhibited an opposite trend. At 10 °C, a new protein-like component appeared and bound preferentially to NOR, when no C-O stretch corresponding to the amide was observed. The finding will contribute to a comprehensive understanding of the interaction mechanisms between DOM and antibiotics under climate change, as well as providing a theoretical basis to reduce the environmental risks of biogas slurry and antibiotics.


Assuntos
Matéria Orgânica Dissolvida , Norfloxacino , Temperatura , Biocombustíveis , Ecossistema , Espectrometria de Fluorescência/métodos , Substâncias Húmicas/análise , Antibacterianos , Proteínas
14.
Int J Gynaecol Obstet ; 164(2): 541-549, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37621209

RESUMO

OBJECTIVE: To reflect on the complications of transvaginal natural orifice transluminal endoscopic surgery (vNOTES), identify the corresponding risk factors, and provide caution to surgeons when performing this novel surgery. METHODS: A retrospective study was carried out among 2000 patients in our hospital who underwent vNOTES between May 2019 and May 2022. Perioperative complications were stratified in chronological order and divided into those developed while establishing the vNOTES approach, during surgery, postoperatively, and 1 month after discharge. The complications were classified based on the Modified Clavien-Dindo classifications. The causes of each type III/IV complication were analyzed. RESULTS: Of the 2000 patients, 88 (4.4%) experienced complications, which is not higher than that reported in laparoendoscopic surgery in previous studies. Grade I, II, III, IV, and V complications developed in 19 (0.95%), 57 (2.85%), 11 (0.55%), 1 (0.05%), and 0 (0%) patients, respectively. Complications were developed while establishing the approach platform, during the surgery, postoperatively, and within 1 month after discharge in 5 (0.25%), 30 (1.50%), 50 (2.50%), and 3 (0.15%) patients, respectively. Eight patients (0.4%) underwent conversion, including five cases of rectal injury repair. CONCLUSION: The summarized suggestions were divided into three levels. Considering the security and effectiveness of vNOTES, it can be routinely used in various gynecologic operations. However, surgeons should focus on preoperative evaluation, strictly conduct preoperative disinfection, conform to prompt conversion during surgery, call for the presence of experienced doctors, and have routine use of antibiotics to prevent postoperative infections. TRIAL REGISTRATION: ChiCTR2100053483.


Assuntos
Laparoscopia , Cirurgia Endoscópica por Orifício Natural , Médicos , Humanos , Feminino , Estudos Retrospectivos , Procedimentos Cirúrgicos em Ginecologia , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Reto , Vagina/cirurgia
15.
CNS Neurosci Ther ; 30(4): e14515, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37905594

RESUMO

OBJECTIVE: Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease-modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD. METHODS: The neuroprotective effect of CFE in H2O2- or 6-OHDA-induced PC-12 cells and α-synuclein-overexpressing PC-12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α-synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α-synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging-related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria. RESULTS: In cellular models of PD, CFE significantly attenuated H2O2- or 6-OHDA-induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α-synuclein in wide type (WT)-, A53T-, A30P-, or E46K-α-synuclein-overexpressing PC-12 cells. Our further findings reveal that CFE administration reduced α-synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6-OHDA-induced degeneration in BZ555 worms, extended lifespan, delayed aging-related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo. CONCLUSION: Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Animais , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/metabolismo , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Oxidopamina/toxicidade , Peróxido de Hidrogênio/toxicidade , Peróxido de Hidrogênio/metabolismo , Neurônios Dopaminérgicos/metabolismo , Modelos Animais de Doenças
16.
Drug Dev Res ; 85(1): e22129, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37961833

RESUMO

Osteosarcoma (OS) is a primary malignant bone tumor characterized by frequent metastasis, rapid disease progression, and a high rate of mortality. Treatment options for OS have remained largely unchanged for decades, consisting primarily of cytotoxic chemotherapy and surgery, thus necessitating the urgent need for novel therapies. Tropolones are naturally occurring seven-membered non-benzenoid aromatic compounds that possess antiproliferative effects in a wide array of cancer cell types. MO-OH-Nap is an α-substituted tropolone that has activity as an iron chelator. Here, we demonstrate that MO-OH-Nap activates all three arms of the unfolded protein response (UPR) pathway and induces apoptosis in a panel of human OS cell lines. Co-incubation with ferric chloride or ammonium ferrous sulfate completely prevents the induction of apoptotic and UPR markers in MO-OH-Nap-treated OS cells. MO-OH-Nap upregulates transferrin receptor 1 (TFR1) protein levels, as well as TFR1, divalent metal transporter 1 (DMT1), iron-regulatory proteins (IRP1, IRP2), ferroportin (FPN), and zinc transporter 14 (ZIP14) transcript levels, demonstrating the impact of MO-OH-Nap on iron-homeostasis pathways in OS cells. Furthermore, MO-OH-Nap treatment restricts the migration and invasion of OS cells in vitro. Lastly, metabolomic profiling of MO-OH-Nap-treated OS cells revealed distinct changes in purine and pyrimidine metabolism. Collectively, we demonstrate that MO-OH-Nap-induced cytotoxic effects in OS cells are dependent on the tropolone's ability to alter cellular iron availability and that this agent exploits key metabolic pathways. These studies support further evaluation of MO-OH-Nap as a novel treatment for OS.


Assuntos
Osteossarcoma , Tropolona , Humanos , Tropolona/farmacologia , Ferro/metabolismo , Ferro/farmacologia , Apoptose , Linhagem Celular , Osteossarcoma/tratamento farmacológico , Linhagem Celular Tumoral
17.
Nutr Metab (Lond) ; 20(1): 53, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38041095

RESUMO

BACKGROUND: Interplay between gut microbiota and heart, termed "gut-heart" axis, has a crucial role in the pathogenesis of atherosclerosis. Our previous study showed that lycopene possesses anti-inflammatory and anti-atherosclerotic effects, but its link to the gut microbiota is poorly understood. Herein, we surmised that lycopene could regulate the gut microbiota, exert anti-atherosclerotic effect by regulating the "gut-heart" axis. METHODS: Male ApoE-/- mice were fed a high-fat diet (HFD) with or without lycopene (0.1% w/w) for 19 weeks. Gut microbiota was analyzed by 16 S rRNA sequencing, the protein levels of zonula occludens-1 (ZO-1), occludin, toll-like receptor 4 (TLR4) and phospho-nuclear factor-κB (NF-κB) p65 were measured by Western blotting, the levels of serum inflammatory factors including monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were assayed using ELISA kits. Also, the concentrations of serum lipopolysaccharide (LPS), D-lactic acid (D-LA) and diamine peroxidase (DAO) were measured through ELISA method. RESULTS: The aortic sinus sections revealed that lycopene supplementation significantly reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development caused by HFD. The analysis of gut microbiota showed that lycopene reduced the ratio of Firmicutes/Bacteroides and increased the relative abundance of Verrucomicrobia, Akkermansia and Alloprevotella, which were related to elevated intestinal barrier function and reduced inflammation. Moreover, lycopene up-regulated the expression of intestinal ZO-1 and occludin and decreased serum LPS, D-LA and DAO levels. In addition, lycopene inhibited the expression of TLR4 and phospho-NF-κB p65 in aortic sinus plaque, serum MCP-1, TNF-α, IL-1ß, and IL-6 levels were also lowered by lycopene treatment. CONCLUSIONS: Our results indicated the protective effect of lycopene against atherosclerosis induced by HFD and further revealed that its mechanism might be its prebiotic effect on maintaining gut microbiota homeostasis and improving intestinal barrier function, consequently reducing serum LPS-triggered inflammatory response in the heart.

18.
Chempluschem ; : e202300609, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38031890

RESUMO

As promising alternatives for natural enzymes, much attention has been paid to nanozymes. And our recent study showed that the medium acid sites on the support are the active sites for the adsorption and oxidation of the substrate. Thus, in this work, due to the abundance of medium acid sites, Al2 O3 was chosen as the support to prepare Pt/Al2 O3 nanozymes. Through the Pt/Al2 O3 samples, we further proved that the distribution of the Pt clusters and the amount of the medium acid sites can significantly influence the peroxidase-like activity. Then the Pt/Al2 O3 sample was used for the detection of glucose. And as low as 0.96 µM glucose could be detected with a linear range from 5-60 µM via our method. This work showed the great potential applications of the easily prepared Pt/Al2 O3 samples in varieties of simple, robust, and easy-to-make analytical approaches in the future.

19.
Sci Rep ; 13(1): 20937, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38017022

RESUMO

The magnetic chitosan/sludge biochar composite adsorbent was prepared using chitosan, Fe3O4, and sludge biochar as raw materials. The composite adsorbent was able to achieve rapid solid-liquid separation under an applied magnetic field. The morphology and microstructure of the composite adsorbent were characterized by FTIR, XRD, SEM, VSM, and BET analysis. The adsorption performance of the composite adsorbent on Cu2+ was investigated through static adsorption experiments, and the effects of adsorbent dosage, initial concentration of Cu2+, initial pH of the solution, and adsorption temperature on the adsorption efficiency of Cu2+ were discussed. The results showed that chitosan and Fe3O4 were successfully loaded on sludge biochar. When the initial concentration of Cu2+ was 30 mg/L, the dosage of the magnetic chitosan/sludge biochar composite material was 0.05 g, the adsorption time was 180 min, pH was 5, and the temperature was room temperature, the maximum removal rate of Cu2+ reached 99.77%, and the maximum adsorption capacity was 55.16 mg/g. The adsorption kinetics and adsorption isotherm data fitted well with the pseudo-second-order kinetic model and Langmuir adsorption isotherm model, indicating that the adsorption process was chemisorption with monolayer coverage.

20.
BMC Anesthesiol ; 23(1): 373, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968646

RESUMO

BACKGROUND: Literature regarding the advantages of gasless vNOTES is insufficient. The aim of our study is to compare gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease. We hypothesize that compared with those in the traditional vNOTES group, hemodynamic profiles will be changed less during gasless vNOTES, while safety can be promised. METHODS: This is a single-center, prospective, single-blind, randomized controlled clinical trial, which has been approved by the Institutional Review Board of Chengdu Women's and Children's Hospital on September 27, 2022. One hundred and twenty patients will be recruited and randomly assigned to either the traditional vNOTES group or the gasless vNOTES group in a 1:1 ratio. For patients allocated to the traditional vNOTES group, after insertion of one port through the vagina, CO2 gas is infused with a pressure of 12-14 mmHg; while for those allocated to the gasless vNOTES group, a special device is used as an abdominal wall-lifting device to facilitate gasless surgery. CO2 pneumoperitoneum will not be used during the whole gasless vNOTES procedure. The primary outcome is vital signs at different time points. The secondary outcomes include surgical conversion rate, duration of surgery and anesthesia, anesthetic consumption, intraoperative estimated blood loss, VAS and PONV scores at postoperative 2 h and 24 h, administration of vasopressor drugs from the beginning of general anesthesia induction to 15 min after endotracheal intubation, including times, dosage, and type, intraoperative and postoperative complications, time of first getting out of bed after surgery, and time of first eating after surgery, including light drink. DISCUSSION: This is the first randomized controlled trial to compare the impacts of gasless vNOTES vs. traditional vNOTES on hemodynamic profiles and outcomes in patients with benign gynecological disease. If a favorable effect and safety of gasless vNOTES for hemodynamic profiles and outcomes in patients are shown, gasless vNOTES would be an optimal treatment option for patients with benign gynecological disease. TRIAL REGISTRATION: The trial was registered at https://www.chictr.org.cn/showproj.html?proj=182441 with registration No. ChiCTR2200064779 on Oct 17, 2022.


Assuntos
Doenças dos Genitais Femininos , Laparoscopia , Criança , Humanos , Feminino , Dióxido de Carbono , Estudos Prospectivos , Método Simples-Cego , Laparoscopia/métodos , Hemodinâmica , Ensaios Clínicos Controlados Aleatórios como Assunto
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