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1.
Cureus ; 16(3): e55713, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586790

RESUMO

Introduction Iron deficiency anemia is associated with an increased risk of adverse maternal and perinatal outcomes. Intravenous iron preparation containing ferric carboxymaltose has been shown to be a safe and effective way of increasing hemoglobin (Hb) and mean corpuscular volume (MCV) levels and reducing the need for blood transfusion. In our center, it used to be given as an inpatient procedure because of the risks of potential drug reactions. In 2021, we initiated the administration of intravenous ferric carboxymaltose as an outpatient procedure. We compared the outcomes of patients between 2021 and 2023 after the initiation of outpatient administration of intravenous ferric carboxymaltose in 127 obstetric patients with iron deficiency anemia in the second and third trimesters. Methods In this study conducted in a large maternity unit in Singapore between 2021 to 2023, we compared the changes in maternal hematological parameters among obstetric patients with iron deficiency anemia presenting to the day care unit in the second or third trimester with a Hb level of <8 g/dl treated with a single dose of ferric carboxymaltose injection (Ferinject) against a control group who were referred for treatment but defaulted on and declined treatment. Results Ferric carboxymaltose significantly increased the Hb and MCV levels at delivery in obstetric patients with iron deficiency. The mean Hb at delivery was 10.8 g/dL in the case group compared to 8.8 g/dL in the control group. The percentage of patients with Hb ≥10.0 g/dL was 73.4% in the case group compared to 27.8% in the control group. The incidence of adverse side effects was low and mild (2/127; 1.6%). None of the patients received were hospitalized because of ferric carboxymaltose. Conclusion A single injection dose of ferric carboxymaltose as an outpatient antenatal procedure was easily administered and well tolerated. Obstetric patients with iron deficiency anemia who received intravenous ferric carboxymaltose had a significantly higher level of Hb than those who did not.

2.
Environ Geochem Health ; 46(5): 165, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592368

RESUMO

Soil pollution around Pb-Zn smelters has attracted widespread attention around the world. In this study, we compiled a database of eight potentially toxic elements (PTEs) Pb, Zn, Cd, As, Cr, Ni, Cu, and Mn in the soil of Pb-Zn smelting areas by screening the published research papers from 2000 to 2023. The pollution assessment and risk screening of eight PTEs were carried out by geo-accumulation index (Igeo), potential ecological risk index (PERI) and health risk assessment model, and Monte Carlo simulation employed to further evaluate the probabilistic health risks. The results suggested that the mean values of the eight PTEs all exceeded the corresponding values in the upper crust, and more than 60% of the study sites had serious Pb and Cd pollution (Igeo > 4), with Brazil, Belgium, China, France and Slovenia having higher levels of pollution than other regions. Besides, PTEs in smelting area caused serious ecological risk (PERI = 10912.12), in which Cd was the main contributor to PREI (86.02%). The average hazard index (HI) of the eight PTEs for adults and children was 7.19 and 9.73, respectively, and the average value of total carcinogenic risk (TCR) was 4.20 × 10-3 and 8.05 × 10-4, respectively. Pb and As are the main contributors to non-carcinogenic risk, while Cu and As are the main contributors to carcinogenic risk. The probability of non-carcinogenic risk in adults and children was 84.05% and 97.57%, while carcinogenic risk was 92.56% and 79.73%, respectively. In summary, there are high ecological and health risks of PTEs in the soil of Pb-Zn smelting areas, and Pb, Cd, As and Cu are the key elements that cause contamination and risk, which need to be paid attention to and controlled. This study is expected to provide guidance for soil remediation in Pb-Zn smelting areas.


Assuntos
Cádmio , Chumbo , Adulto , Criança , Humanos , Chumbo/toxicidade , Carcinogênese , Carcinógenos , Poluição Ambiental , Probabilidade , Medição de Risco , Solo , Zinco
3.
Artigo em Inglês | MEDLINE | ID: mdl-38548489

RESUMO

Macrophage migration inhibitory factor (MIF) is a cytokine in the immune system, participated in both innate and adaptive immune responses. Except from immune cells, MIF is also secreted by a variety of non-immune cells, including hematopoietic cells, endothelial cells (ECs), and neurons. MIF plays a crucial role in various diseases, such as sepsis, rheumatoid arthritis, acute kidney injury, and neurodegenerative diseases. The role of MIF in the neuropathogenesis of cognitive impairment disorders is emphasized, as it recruits multiple inflammatory mediators, leading to activating microglia or astrocyte-derived neuroinflammation. Furthermore, it contributes to the cell death of neurons and ECs with the binding of apoptosis-inducing factor (AIF) through parthanatos-associated apoptosis-inducing factor nuclease (PAAN) / MIF pathway. This review comprehensively delves into the relationship between MIF and the neuropathogenesis of cognitive impairment disorders, providing a series of emerging MIF-targeted pharmaceuticals as potential treatments for cognitive impairment disorders.

4.
Mol Immunol ; 169: 1-9, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447462

RESUMO

Myocardial ischemia-reperfusion injury (MIRI) is a complex process that occurs when blood flow is restored after myocardium infarction (MI) with exacerbated tissue damage. Macrophages, essential cell type of the immune response, play an important role in MIRI. Macrophage subpopulations, namely M1 and M2, are distinguished by distinct phenotypes and functions. In MIRI, macrophages infiltrate in infarcted area, shaping the inflammatory response and influencing tissue healing. Resident cardiac macrophages interact with monocyte-derived macrophages in MIRI, and influence injury progression. Key factors including chemokines, cytokines, and toll-like receptors modulate macrophage behavior in MIRI. This review aims to address recent findings on the classification and the roles of macrophages in the myocardium, spanning from MI to subsequent MIRI, and highlights various signaling pathways implicated in macrophage polarization underlining the complexity of MIRI. This article will shed light on developing advanced therapeutic strategies for MIRI management.


Assuntos
Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Humanos , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio , Macrófagos/metabolismo , Infarto do Miocárdio/metabolismo , Transdução de Sinais
5.
Comput Biol Med ; 173: 108322, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554658

RESUMO

Patient-derived organoids have proven to be a highly relevant model for evaluating of disease mechanisms and drug efficacies, as they closely recapitulate in vivo physiology. Colorectal cancer organoids, specifically, exhibit a diverse range of morphologies, which have been analyzed with image-based profiling. However, the relationship between morphological subtypes and functional parameters of the organoids remains underexplored. Here, we identified two distinct morphological subtypes ("cystic" and "solid") across 31360 bright field images using image-based profiling, which correlated differently with viability and apoptosis level of colorectal cancer organoids. Leveraging object detection neural networks, we were able to categorize single organoids achieving higher viability scores as "cystic" than "solid" subtype. Furthermore, a deep generative model was proposed to predict apoptosis intensity based on a apoptosis-featured dataset encompassing over 17000 bright field and matched fluorescent images. Notably, a significant correlation of 0.91 between the predicted value and ground truth was achived, underscoring the feasibility of this generative model as a potential means for assessing organoid functional parameters. The underlying cellular heterogeneity of the organoids, i.e., conserved colonic cell types and rare immune components, was also verified with scRNA sequencing, implying a compromised tumor microenvironment. Additionally, the "cystic" subtype was identified as a relapse phenotype featuring intestinal stem cell signatures, suggesting that this visually discernible relapse phenotype shows potential as a novel biomarker for colorectal cancer diagnosis and prognosis. In summary, our findings demonstrate that the morphological heterogeneity of colorectal cancer organoids explicitly recapitulate the association of phenotypic features and exogenous perturbations through the image-based profiling, providing new insights into disease mechanisms.


Assuntos
Neoplasias Colorretais , Aprendizado Profundo , Humanos , Neoplasias Colorretais/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Organoides/metabolismo , Organoides/patologia , Recidiva , Microambiente Tumoral
6.
Bioresour Technol ; 396: 130421, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38320713

RESUMO

Large quantities of greenhouse gases (GHGs) are emitted into the atmosphere during wastewater treatment. In this study, GHG and microbial samples were collected from four wastewater treatment plants (WWTPs), and their differences and relationships were assessed. The study showed that, compared with conventionally constructed WWTPs, well-established gas collection systems in underground WWTPs facilitate comprehensive collection and accurate accounting of GHGs. In aboveground WWTPs, capped anoxic ponds promote methane production releasing it at 2-8 times the rate of uncapped emissions, in contrast to nitrous oxide emissions. Moreover, a stable subsurface environment allows for smaller fluctuations in daily GHG emissions and higher microbial diversity and abundance. This study highlights differences in GHG emission fluxes and microbial communities in differently constructed WWTPs, which are useful for control and accurate accounting of GHG emissions.


Assuntos
Gases de Efeito Estufa , Microbiota , Purificação da Água , Gases de Efeito Estufa/análise , Águas Residuárias , Metano/análise
7.
Front Microbiol ; 15: 1328324, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38419631

RESUMO

Recent studies have indicated that gut microbiota-mediated oxidative stress is significantly associated with intestinal diseases such as colorectal cancer, ulcerative colitis, and Crohn's disease. The level of reactive oxygen species (ROS) has been reported to increase when the gut microbiota is dysregulated, especially when several gut bacterial metabolites are present. Although healthy gut microbiota plays a vital role in defending against excessive oxidative stress, intestinal disease is significantly influenced by excessive ROS, and this process is controlled by gut microbiota-mediated immunological responses, DNA damage, and intestinal inflammation. In this review, we discuss the relationship between gut microbiota and intestinal disease from an oxidative stress perspective. In addition, we also provide a summary of the most recent therapeutic approaches for preventing or treating intestinal diseases by modifying gut microbiota.

8.
Cancer Lett ; 588: 216734, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38401886

RESUMO

Telomerase activity is upregulated in head and neck squamous cell carcinoma (HNSCC), yet its regulatory mechanisms remain unclear. Here, we identified a cancer-specific lncRNA (LINC02454) associated with poor prognosis by using LncRNA chip of our HNSCC cohorts and external datasets. Through employing negative-stain transmission electron microscopy (NS-TEM), we discovered an interaction between LINC02454 and CCT complex which would augment telomerase activity for maintaining telomere homeostasis. Supporting this, in the telomerase repeat amplification protocol (TRAP) assay and quantitative fluorescence in situ hybridization (Q-FISH) analysis, LINC02454 depletion significantly reduced telomerase activity and shortened telomere length. Consistently, pathways related to telomerase, mitosis, and apoptosis were significantly impacted upon LINC02454 knockdown in RNAseq analysis. Functionally, LINC02454-deficient cells exhibited a more significant senescence phenotype in ß-galactosidase staining, cell cycle, and apoptosis assays. We further confirmed the role of LINC02454 in HNSCC proliferation through a combination of in vitro and in vivo experiments. The therapeutic potential of targeting LINC02454 was verified by adenovirus-shRNA approach in HNSCC patient-derived xenograft (PDX) models. In summary, our findings provided valuable insights into the molecular mechanisms of HNSCC tumorigenesis and potential targets for future treatment modalities.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , RNA Longo não Codificante , Telomerase , Humanos , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Hibridização in Situ Fluorescente , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Telomerase/genética , Telomerase/metabolismo , Telômero/genética , Telômero/metabolismo , Encurtamento do Telômero
10.
Artigo em Inglês | MEDLINE | ID: mdl-38275033

RESUMO

BACKGROUND: Mass spectrometry imaging (MSI) is an imaging method based on mass spectrometry technology that can simultaneously visualize the spatial distribution of various biological molecules. The use of MSI in cancer detection and drug discovery has been extensively investigated in recent years. OBJECTIVE: This review aims to summarize the latest advances of MSI and its specific applications in cancer detection and drug discovery, providing a basic understanding of the development and application of MSI in the past five years and offering references for the further application of MSI in cancer detection and drug discovery. METHODS: In the database, "mass spectrometry imaging", "cancer treatment", and "drug discovery" were used as keywords for literature retrieval, and the time range was limited to "2018- 2023". After organizing and analyzing the literature and patents, a review was conducted. RESULTS: Based on the literature, it was found that the updated progress of MSI in the past five years mostly focused on concrete methods, operation procedures, facilities, and composite applications. The patents of MSI were mainly correlated with the mass spectrometry imaging system and its application in cancer treatment. MSI is conducive to investigating the therapeutic schedule of cancer and searching for new drugs. CONCLUSION: MSI is a convenient, fast and powerful technology that has made great progress in sample preparation, instrumentation, quantitation, and multimodal imaging. MSI has emerged as a powerful technique in various biomedical applications, which has strong potential in cancer detection, treatment, formation mechanism research, discovery of biomarkers, and drug discovery process.

11.
BMJ Case Rep ; 17(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238168

RESUMO

Postpartum haemorrhage (PPH) is an obstetric emergency and a leading cause of severe maternal morbidity and mortality. Timely and accurate diagnosis of the underlying cause of PPH is critical in achieving optimal care for the patient as any potential delays may result in severe morbidity and even mortality. We present a rare case of a patient presenting with PPH secondary to acquired haemophilia. This case highlights the importance of early diagnosis and multidisciplinary management in achieving optimal management of this complex condition.


Assuntos
Hemofilia A , Hemorragia Pós-Parto , Gravidez , Feminino , Humanos , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/terapia , Hemofilia A/complicações , Período Pós-Parto
12.
Cell Signal ; 114: 110979, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38000525

RESUMO

Chronic inflammation is a key driver for colitis-associated colorectal cancer (CAC). It has been reported that inflammatory cytokines, such as IL-1ß, could promote CAC. Zinc finger protein 70 (ZNF70) is involved in multiple biological processes. Here, we identified a previously unknown role for ZNF70 regulates macrophages IL-1ß secretion to promote HCT116 proliferation in CAC, and investigated its underlying mechanism. We showed ZNF70 is much higher expressed in CAC tumor tissues compared with adjacent normal tissues in clinical CAC samples. Further experiments showed ZNF70 promoted macrophages IL-1ß secretion and HCT116 proliferation. In LPS/ATP-stimulated THP-1 cells, we found ZNF70 activated NLRP3 inflammasome, resulting in robust IL-1ß secretion. Interestingly, we discovered the ZnF domain of ZNF70 could interact with NLRP3 and decrease the K48-linked ubiquitination of NLRP3. Moreover, ZNF70 could activate STAT3, thereby promoting IL-1ß synthesis. Noteworthy, ZNF70 enhanced proliferation by upregulating STAT3 activation in HCT116 cells cultured in the conditioned medium of THP-1 macrophages treated with LPS/ATP. Finally, the vivo observations were confirmed using AAV-mediated ZNF70 knockdown, which improved colitis-associated colorectal cancer in the AOM/DSS model. The correlation between ZNF70 expression and overall survival/IL-1ß expression in colorectal cancer was verified by TCGA database. Taken together, ZNF70 regulates macrophages IL-1ß secretion to promote the HCT116 cells proliferation via activation of NLRP3 inflammasome and STAT3 pathway, suggesting that ZNF70 may be a promising preventive target for treating in CAC.


Assuntos
Neoplasias Associadas a Colite , Inflamassomos , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células HCT116 , Neoplasias Associadas a Colite/metabolismo , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Trifosfato de Adenosina/metabolismo , Proliferação de Células , Interleucina-1beta/metabolismo , Fator de Transcrição STAT3/metabolismo
13.
BMC Mol Cell Biol ; 24(1): 35, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38082229

RESUMO

Mitochondria are key cytoplasmic organelles in eukaryotic cells that generate adenosine triphosphate (ATP) through the electron transport chain and oxidative phosphorylation. Mitochondrial DNA (mtDNA) copy number (mtDNAcn) is considered a biomarker for both mitochondrial quantity and function as well as cellular oxidative stress level. Previous epidemiologic findings revealed that weight gain, higher body mass index (BMI), smoking, and high insulinemic potential of lifestyle were associated with lower leukocyte mtDNAcn. Carnitines are a group of compounds that play a critical role in energy production. We quantified the associations of plasma L-carnitine levels with leukocyte mtDNAcn. We then examined the association between mtDNAcn and L-carnitine (HMDB0000062) in 538 U.S. men without cancers, diabetes, or cardiovascular disease at blood collection from the Health Professionals Follow-Up Study (HPFS). We found a significant inverse association between L-carnitine and mtDNAcn (ρ = -0.1, P = 0.02). This implies that the carnitine metabolic pathway may be associated with mitochondrial function and oxidative stress.


Assuntos
Variações do Número de Cópias de DNA , DNA Mitocondrial , Masculino , Humanos , DNA Mitocondrial/genética , Seguimentos , Variações do Número de Cópias de DNA/genética , Mitocôndrias/genética , Estresse Oxidativo
14.
Int J Gen Med ; 16: 5377-5387, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38021052

RESUMO

Purpose: This study aimed to explore the sexual behaviors and intimate relationships of sexual partners of young patients with cervical cancer. Patients and Methods: This study employed a descriptive phenomenological research design, which falls within the realm of qualitative research methods. Qualitative research typically utilizes interview techniques for gathering participants' experiences, perceptions, and behaviors. This study conduct face-to-face semi-structured interviews with the sexual partners of 15 young cervical cancer patients receiving cancer treatment to collect their experiences and perspectives on intimate relationships and sexual behavior with cervical cancer patients, and use the Colaizzi method for data analysis. Results: Four themes were identified through the interview analysis: (1) reduction or absence of sexual behavior, (2) unpleasant sexual experiences, (3) adjustment of intimate relationships, and (4) lack of sexual health education. Conclusion: The sexual partners of young cervical cancer patients have experienced significant shifts in their perspectives on sexual behavior and intimate relationships. These changes include reduction or absence of sexual behavior, unpleasant sexual experiences, adjustment of intimate relationships, and lack of sexual health education. Hospitals should pay more attention to the sexual behavior and intimate relationships of patients with cervical cancer and their sexual partners, and social support systems and psychological and emotional counselling services should be established for providing relevant knowledge and guidance.

15.
Mar Drugs ; 21(11)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37999417

RESUMO

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.


Assuntos
Diterpenos , Fármacos Neuroprotetores , Penicillium , Ratos , Animais , Células PC12 , Proteínas Proto-Oncogênicas c-akt/metabolismo , Oxidopamina/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Penicillium/química , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Diterpenos/farmacologia , Diterpenos/química , Indóis/farmacologia , Indóis/química , Antibacterianos/farmacologia , Fármacos Neuroprotetores/farmacologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-37931977

RESUMO

OBJECTIVE: Assess whether local health facilities can adequately support the performance of general practitioners (GPs) trained by China's national compulsory services programme (CSP). DESIGN: Prospective cohort study. SETTING: Health facilities in middle and western rural areas in China, 2015-2022. PARTICIPANTS: Cohorts of CSP graduates from 2015 to 2019 in four major medical universities. MAIN OUTCOMES: Job performance measured by a 12-item Job Performance Scale; productivity measured by outpatient volume per day; turnover measured by ever changing jobs within the past year. RESULTS: 91.2%, 92.0% and 90.5% GPs working in township health centres reported inadequate medication, equipment and external assistance from higher level hospitals, while CSP graduates working in secondary or tertiary hospitals reported a lower rate of less than 60%. The top three tests reported as lacking were blood gases (67.7%), microbiology (61.6%) and cancer biomarkers (49.7%); the top three lacked procedures were CT scan (64.8%), MRI scan (58.1%) and ambulatory BP monitoring (55.8%); and the top three lacked drugs were drugs for cardiovascular diseases (23.3%), systematic hormonal preparations (17.7%) and traditional Chinese medicines (13.0%). Multivariable analysis showed that facility support was positively associated with job performance-adequate medication increased job performance by 2.2 points (95% CI 0.7 to 3.8), and adequate external assistance increased job performance by 3.3 points (95% CI 1.8 to 4.8). Facility support was also positively associated with productivity-adequate medication increased outpatients seen per day by 20% (95% CI 0.1 to 0.3), and adequate equipment increased outpatients seen per day by 12% (95% CI 0.0 to 0.2). Facility support did not have significant impact on turnover, but GPs who changed jobs in the past year were 1.9-2.3 times more likely to report adequate facility support. CONCLUSION: GPs in township health centres experienced a high prevalence of shortage in facility support. The identification of a positive association between facility support and performance and productivity has implications for future research and resources deployment in primary healthcare.


Assuntos
Clínicos Gerais , Humanos , Estudos Prospectivos , Recursos Humanos , Atenção Primária à Saúde , China
17.
Cell Death Dis ; 14(8): 548, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612265

RESUMO

Obesity/overweight and lipid metabolism disorders have become increased risk factors for lung cancer. Fatty acid translocase CD36 promotes cellular uptake of fatty acids. Whether and how CD36 facilitates lung adenocarcinoma (LUAD) growth in high-fat environment is unknown. Here, we demonstrated that palmitic acid (PA) or high-fat diet (HFD) promoted LUAD cell proliferation and metastasis in a CD36-dependent manner. Mechanistically, CD36 translocated from cytoplasm to cell membrane and interacted with Src kinase upon PA stimulation in human LUAD cells. Akt and ERK, downstream of Src, were then activated to mediate LUAD cell proliferation and metastasis. Furthermore, PA treatment promoted CD36 sarcolemmal translocation, where it activated Rac1 and upregulated MMP-9 through Src-Akt/ERK pathway, resulting in redistribution of cortactin, N-WASP and Arp2/3, and finally led to occurrence of finger-like protrusions of actin on cell surface to enhance cell metastasis. Compared with normal-chew diet (NCD) mice, the HFD group exhibited higher level of blood free fatty acid (FFA) and cholesterol (TC), developed larger xenograft LUAD tumors and enhanced tumor cell metastatic potential, which were accompanied by obvious sarcolemmal actin remodeling and were blocked by simultaneous CD36 knockdown in LUAD cells. Consistently, xenografted and tail vein-injected scramble-RNA-A549 cells but not CD36-shRNA-A549 in HFD mice formed metastatic LUAD tumors on the lung. CD36 inhibitor SSO significantly inhibited LUAD cell metastasis to the lung. Collectively, CD36 initiates Src signaling to promote LUAD cell proliferation and actin remodeling-involved metastasis under high-fat environment. Our study provides the new insights that CD36 is a valid target for LUAD therapy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Actinas , Adenocarcinoma de Pulmão/genética , Antígenos CD36/genética , Proliferação de Células , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo
18.
Cell Metab ; 35(9): 1563-1579.e8, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37543034

RESUMO

In response to adverse environmental conditions, embryonic development may reversibly cease, a process termed diapause. Recent reports connect this phenomenon with the non-genetic responses of tumors to chemotherapy, but the mechanisms involved are poorly understood. Here, we establish a multifarious role for SMC4 in the switching of colorectal cancer cells to a diapause-like state. SMC4 attenuation promotes the expression of three investment phase glycolysis enzymes increasing lactate production while also suppressing PGAM1. Resultant high lactate levels increase ABC transporter expression via histone lactylation, rendering tumor cells insensitive to chemotherapy. SMC4 acts as co-activator of PGAM1 transcription, and the coordinate loss of SMC4 and PGAM1 affects F-actin assembly, inducing cytokinesis failure and polyploidy, thereby inhibiting cell proliferation. These insights into the mechanisms underlying non-genetic chemotherapy resistance may have significant implications for the field, advancing our understanding of aerobic glycolysis functions in tumor and potentially informing future therapeutic strategies.


Assuntos
Neoplasias Colorretais , Diapausa , Humanos , Animais , Histonas/metabolismo , Glicólise , Proliferação de Células , Neoplasias Colorretais/metabolismo , Lactatos , Adenosina Trifosfatases/metabolismo , Proteínas Cromossômicas não Histona/metabolismo
19.
iScience ; 26(8): 107477, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37599821

RESUMO

Smoking carcinogen nicotine-derived nitrosamine ketone (NNK) is the most potent contributor to lung adenocarcinoma (LUAD) development, but the mechanism has not been fully elucidated. Here, we reported that fatty acid translocase CD36 was significantly overexpressed in both human LUAD tissues and NNK-induced A/J mice LUAD tumors. The overexpressed CD36 was positively correlated with Src kinase activation, smoking status, metastasis, and worse overall survival of patients with smoking history. Upon NNK binding with α7 nicotinic acetylcholine receptor (α7nAChR), sarcolemmal CD36 was increased and it interacted with surface α7nAChR and cytosol Src simultaneously, which in turn activated Src and downstream pro-carcinogenic kinase ERK1/2 and Akt, and finally caused LUAD cells to form subcutaneous and pulmonary metastatic tumors. This process could be blocked by CD36 knockdown and CD36 irreversible inhibitor SSO. Furthermore, the effect of NNK was inhibited obviously in CD36-/- A/J mice. Thus, targeting CD36 may provide a breakthrough therapy of LUAD.

20.
Aging Clin Exp Res ; 35(11): 2453-2462, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37620639

RESUMO

BACKGROUND: The relationship between preoperative frailty and pulmonary complications after cardiac surgery in elderly patients is unclear. This study was designed to evaluate the relationship between frailty and postoperative pulmonary complications (PPCs) in elderly patients undergoing cardiac surgery and to provide a basis for their prevention and treatment. AIMS: This study aimed to investigate the predictive value of preoperative frailty on pulmonary complications after cardiac surgery in elderly patients. METHODS: Frailty was assessed using the CAF. The diagnosis of PPCs was based on the criteria defined by Hulzebos et al., and patients were classified into a PPCs group and a non-PPCs group. Factors with clinical significance and P < 0.05 in univariate regression analysis were included in multivariate logistic regression analysis to determine the relationship between preoperative frailty and PPCs. The area under the receiver operating characteristic (ROC) curve (AUC) was used to compare the predictive effects of the CAF, EuroSCORE II, and ASA + age on the occurrence of PPCs. RESULTS: A total of 205 patients were enrolled in this study, 31.7% of whom developed PPCs. Univariate logistic regression analysis showed that frailty, ASA grade, EuroSCORE II, hemoglobin concentration, FVC, time of operation, and postoperative AKI were associated with the development of PPCs. However, after adjustments for all possible confounding factors, multivariate logistic regression results showed that frailty, prolonged operation time, and postoperative AKI were risk factors for PPCs, and the risk of postoperative PPCs in frail patients was approximately 4.37 times that in nonfrail patients (OR = 4.37, 95%CI: 1.6-11.94, P < 0.05). The predictive efficacy of the traditional perioperative risk assessment tools EuroSCORE II and ASA + age was lower than that of CAF. CONCLUSIONS: Frailty before surgery, prolonged operation time, and postoperative AKI were independent risk factors for pulmonary complications after heart surgery in elderly individuals, and CAF was more effective than the traditional risk predictors EuroSCORE II and ASA + age.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Fragilidade , Humanos , Idoso , Fragilidade/epidemiologia , Estudos Prospectivos , Fatores de Risco , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/etiologia
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