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1.
Front Oncol ; 14: 1343239, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38764584

RESUMO

Ovarian cancer is a prevalent malignant tumor of the female reproductive system, often remaining concealed until it reaches an advanced stage. The standard treatment protocol includes cytoreductive surgery for ovarian cancer plus postoperative consolidation chemotherapy and maintenance therapy, although it carries a high recurrence rate. During the treatment period, chemotherapy can lead to bone marrow suppression, a condition known as Chemotherapy-Induced Myelosuppression (CIM). This suppression may necessitate dose reduction or chemotherapy treatment cycle delay. In severe cases, CIM can result in infection, fever, and potential harm to the patient's life. Here, we report a case of a female patient with ovarian malignant tumor of biochemical recurrence who treated with chemotherapy combined with Trilaciclib, following previous perioperative chemotherapy with occurrence of severe CIM. It involves an intravenous injection of Trilaciclib before chemotherapy, which significantly abates the side effects of chemotherapy, reduces the occurrence of severe CIM, improves the patients' quality of life, and decreases the economic burden of hospitalization. We hope that this retrospective analysis of the case may serve as a reference in preventing and treating severe CIM during chemotherapy in some patients with malignant tumors, ultimately benefiting more patients with tumors.

2.
Sheng Wu Gong Cheng Xue Bao ; 40(5): 1365-1379, 2024 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-38783803

RESUMO

Globally, colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related fatalities. According to the World Health Organization, there are over 1.9 million annual cases of CRC diagnosed worldwide, resulting in more than 900 000 deaths. In recent years, chimeric antigen receptor T (CAR-T) cell therapy has shown clinical success in treating certain hematological malignancies and is now being explored for its potential in targeting solid tumors like CRC. Currently, CAR-T cell therapies targeting carcinoembryonic antigen (CEA), natural killer group 2, member D ligand (NKG2DL), and other markers have achieved remarkable results in clinical trials, albeit encountering significant challenges. This review summarizes the promising targets of CAR-T cell therapy for CRC and highlights progress made in clinical trials and preclinical studies. Additionally, the review discusses the challenges faced by CAR-T cell therapy in CRC treatment, including a shortage of tumor-specific antigens, cytokine release syndrome, adverse tumor microenvironment, and limited infiltration of CAR-T cells. In summary, this review provides an overview of the latest research progress and challenges in CAR-T cell therapy for CRC, aiming to contribute fresh insights for the clinical treatment of this disease.


Assuntos
Neoplasias Colorretais , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Humanos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/imunologia , Receptores de Antígenos Quiméricos/imunologia , Antígeno Carcinoembrionário/imunologia , Microambiente Tumoral , Antígenos de Neoplasias/imunologia , Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Animais
3.
Artigo em Inglês | MEDLINE | ID: mdl-38747701

RESUMO

Two Gram-stain-negative strains, designed SYSU M86414T and SYSU M84420, were isolated from marine sediment samples of the South China Sea (Sansha City, Hainan Province, PR China). These strains were aerobic and could grow at pH 6.0-8.0 (optimum, pH 7.0), 4-37 °C (optimum, 28 °C), and in the presence of 0-10 % NaCl (w/v; optimum 3 %). The predominant respiratory menaquinone of strains SYSU M86414T and SYSU M84420 was MK-6. The primary cellular polar lipid was phosphatidylethanolamine. The major cellular fatty acids (>10 %) in both strains were iso-C15 : 0, iso-C15 : 1 G, and iso-C17 : 0 3-OH. The DNA G+C content of strains SYSU M86414T and SYSU M84420 were both 42.10 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that these novel strains belonged to the genus Flagellimonas and strain SYSU M86414T showed the highest 16S rRNA gene sequence similarity to Flagellimonas marinaquae JCM 11811T (98.83 %), followed by Flagellimonas aurea BC31-1-A7T (98.62 %), while strain SYSU M84420 had highest 16S rRNA gene sequence similarity to F. marinaquae JCM 11811T (98.76 %) and F. aurea BC31-1-A7T (98.55 %). Based on the results of polyphasic analyses, strains SYSU M86414T and SYSU M84420 should be considered to represent a novel species of the genus Flagellimonas, for which the name Flagellimonas halotolerans sp. nov. is proposed. The type strain of the proposed novel isolate is SYSU M86414T (=GDMCC 1.3806T=KCTC 102040T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Filogenia , RNA Ribossômico 16S , Água do Mar , Análise de Sequência de DNA , Vitamina K 2 , China , RNA Ribossômico 16S/genética , Sedimentos Geológicos/microbiologia , Ácidos Graxos/análise , Água do Mar/microbiologia , DNA Bacteriano/genética , Vitamina K 2/análogos & derivados , Vitamina K 2/análise , Fosfatidiletanolaminas , Dados de Sequência Molecular
4.
Int J Gen Med ; 17: 1395-1403, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617055

RESUMO

Background: Circular RNAs (circRNAs) exhibit unique patterns of expression and high levels of stability in patient plasma samples such that they represent ideal non-invasive biomarkers that can be leveraged to detect a wide array of diseases including endometrial cancer (EC). This study was designed to identify circRNAs with potential diagnostic utility in serum samples from EC patients while also evaluating the utility of macrophage migration inhibitory factor (MIF) as a biomarker when screening for this form of cancer in the clinic. Methods: Levels of circEPSTI1 and MIF were assessed in the plasma of EC patients and healthy subjects (n=186 each) through qPCR and ELISAs. The diagnostic utility of these biomarkers was assessed with receiver operating characteristic curve (ROC) analyses. Results: Relative to healthy subjects, EC patient serum contained significantly elevated circEPSTI1 and MIF. An association was noted between circEPSTI1 expression in stages, histologic grade, and residual tumor. ROC curves confirmed that serum circEPSTI1 levels distinguished between controls and patients with EC with an Area of 0.835 and serum MIF levels distinguished between controls and patients with EC with an Area of 0.6646. When instead diagnosing patients based on the combination of MIF and circEPSTI1, the Area further rose to 0.8604. Conclusion: Assessing the combination of circEPSTI1 and MIF may be a viable approach to reliably diagnosing EC.

5.
BMC Pediatr ; 24(1): 157, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443865

RESUMO

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.


Assuntos
Displasia Broncopulmonar , Corioamnionite , Lesão Pulmonar , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Feminino , Gravidez , Lactente , Humanos , Corioamnionite/epidemiologia , Recém-Nascido Prematuro , Inflamação , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/etiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia
6.
Nutrients ; 16(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38542707

RESUMO

As one of the malignant diseases globally, cancer seriously endangers human physical and mental health because of its high morbidity and mortality. Conventional cancer treatment strategies, such as surgical resection and chemoradiotherapy, are effective at the early stage of cancer but have limited efficacy for advanced cancer. Along with cancer progress and treatment, resistance develops gradually within the population of tumor cells. As a consequence, drug resistance become the major cause that leads to disease progression and poor clinical prognosis in some patients. The mechanisms of cancer drug resistance are quite complex and involve various molecular and cellular mechanisms. Therefore, exploring the mechanisms and finding specific targets are becoming imperative to overcome drug resistance. In recent years, plant-derived natural products have been evaluated as potential therapeutic candidates against cancer with drug resistance due to low side effects and high anticancer efficacy. A growing number of studies have shown that natural products can achieve superior antitumor effects through multiple signaling pathways. The mechanisms include regulation of multiple drug resistance (MDR)-related genes, inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, induction of autophagy, and blockade of the cell cycle. This paper reviews the molecular and cellular mechanisms of cancer drug resistance, as well as the therapeutic effects and mechanisms of plant-derived natural products against cancer drug resistance. It provides references for developing therapeutic medication for drug-resistant cancer treatment with high efficacy and low side effects.


Assuntos
Produtos Biológicos , Neoplasias , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Resistencia a Medicamentos Antineoplásicos , Transdução de Sinais , Linhagem Celular Tumoral
7.
J Lipid Res ; 65(4): 100534, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38522750

RESUMO

The deposition of cholesterol-rich lipoproteins in the arterial wall triggers macrophage inflammatory responses, which promote atherosclerosis. The NLRP3 inflammasome aggravates atherosclerosis; however, cellular mechanisms connecting macrophage cholesterol accumulation to inflammasome activation are poorly understood. We investigated the mechanisms of NLRP3 inflammasome activation in cholesterol-loaded macrophages and in atherosclerosis-prone Ldlr-/- mice with defects in macrophage cholesterol efflux. We found that accumulation of cholesterol in macrophages treated with modified LDL or cholesterol crystals, or in macrophages defective in the cholesterol efflux promoting transporters ABCA1 and ABCG1, leads to activation of NLRP3 inflammasomes as a result of increased cholesterol trafficking from the plasma membrane to the ER, via Aster-B. In turn, the accumulation of cholesterol in the ER activates the inositol triphosphate-3 receptor, CaMKII/JNK, and induces NLRP3 deubiquitylation by BRCC3. An NLRP3 deubiquitylation inhibitor or deficiency of Abro1, an essential scaffolding protein in the BRCC3-containing cytosolic complex, suppressed inflammasome activation, neutrophil extracellular trap formation (NETosis), and atherosclerosis in vivo. These results identify a link between the trafficking of cholesterol to the ER, NLRP3 deubiquitylation, inflammasome activation, and atherosclerosis.


Assuntos
Aterosclerose , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Colesterol , Retículo Endoplasmático , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologia , Camundongos , Colesterol/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Retículo Endoplasmático/metabolismo , Inflamassomos/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Transporte Biológico , Camundongos Knockout
8.
JCO Oncol Pract ; 20(4): 517-524, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38301188

RESUMO

PURPOSE: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment. MATERIALS AND METHODS: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined as ≥60% completion of dietary recalls and ≥280 mg average daily dietary magnesium intake across all patients. RESULTS: Twenty-one of 26 patients enrolled completed at least five chemotherapy cycles and were included in the analysis. Adherence to the study diet was 76%. Daily dietary magnesium intake was 100.5 mg at baseline and increased throughout each cycle: 6% of patients at baseline, 24% after the first cycle, and 67% after the fifth cycle reached ≥280-mg/day magnesium intake. Seven (33%) of 21 had at least one incident of hypomagnesemia. Patients who were adherent had significantly lower incidence of hypomagnesemia (19% v 80%, P = .03) and less need for intravenous magnesium (6% v 60%, P = .03) than those who were nonadherent. CONCLUSION: The study achieved primary feasibility objectives of retention and adherence to the study intervention. Weekly education about magnesium-rich diets was effective in increasing dietary magnesium intake. Adequate dietary magnesium appeared to be protective against hypomagnesemia.


Assuntos
Magnésio , Neoplasias Ovarianas , Humanos , Feminino , Carboplatina/efeitos adversos , Magnésio/farmacologia , Magnésio/uso terapêutico , Estudos Prospectivos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/induzido quimicamente
9.
Diabetes Metab Syndr Obes ; 17: 517-531, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38327734

RESUMO

Purpose: To evaluate the association of the systemic immune-inflammatory index (SII) and systemic inflammatory response index (SIRI) with the clinical and pathological features and progression of diabetic kidney disease (DKD). Patients and Methods: We analyzed 303 patients with type 2 diabetes mellitus (T2DM), classifying them into distinct groups: T2DM, early DKD (EDKD), and clinical DKD (Cli-DKD). Variations in SII and SIRI levels across these groups and their association with renal function were assessed. Logistic regression analysis was used to identify independent risk factors for DKD. Additionally, in 43 patients with biopsy-confirmed DKD, we analyzed the relationship between SII, SIRI, and pathological changes. Kaplan-Meier survival analysis and the Cox proportional hazards model were used to assess the influence of SII and SIRI levels on outcomes in patients with DKD. Results: SII and SIRI were significantly higher in the Cli-DKD group than in the T2DM and EDKD groups, and were positively correlated with the urinary albumin-creatinine ratio and negatively correlated with estimated glomerular filtration rate. Notably, SIRI was identified as an independent risk factor for DKD development. Additionally, a lower SII score was associated with a higher cumulative survival rate. Conclusion: This study demonstrates an association between SII, SIRI, and renal function in patients with T2DM. A high SIRI was an independent risk factor for DKD, while an elevated SII was associated with an increased risk of kidney disease progression in biopsy-confirmed DKD cases. Our findings underscore the potential implications of utilizing SII and SIRI as cost-effective and readily available inflammatory indicators for monitoring DKD in primary care settings.

10.
Integr Cancer Ther ; 22: 15347354231213045, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37978821

RESUMO

BACKGROUND: With rising interest in complementary approaches to symptom management, awareness of real-world practice patterns in the incorporation of integrative oncology (IO) into cancer care is limited. Therefore, we examined the reasons for referral, symptom burdens, and clinical outcomes for cancer patients who underwent initial IO consultations. METHODS: The records of adult patients with cancer who underwent initial outpatient IO consultations at our cancer center for a representative 10-day period at the start of each month for 12 months starting January 1, 2017, were reviewed retrospectively. Patient demographic and medical characteristics and outpatient IO consultation details, including patient-reported outcome measures of symptom burden, were extracted. Descriptive summary statistics and logistic regression were used to analyze the data. RESULTS: Among the 473 study patients, 71% were women, breast cancer (42%) was the most common cancer type, and 31% had metastatic cancer. Referring clinicians listed an integrative approach (57%) as the most common reason for referral, followed by diet (26%), pain (19%), discussion of herbs and supplements (18%), and stress (18%). In comparison, patients listed their primary concerns as diet (16%), pain (15%), and an integrative approach to overall health (11%). After the IO consultations, the highest likelihood of subsequent recommendations were acupuncture for hot flashes (odds ratio [OR], P = .002) or peripheral neuropathy (OR = 6.59, P < .001), oncology massage for pain (OR = 3.04, P < .001), psychology referral for patient's self-reported anxiety (OR = 2.35, P < .001), and mind-body therapies for stress (OR = 2.57, P < .001). CONCLUSION: Cancer patients' top concerns regarding IO consultation may not always match providers' reasons for referral. Longitudinal data analysis is needed to determine the effect of integrative interventions on symptom burden.


Assuntos
Neoplasias da Mama , Medicina Integrativa , Adulto , Humanos , Feminino , Masculino , Estudos Retrospectivos , Oncologia , Neoplasias da Mama/terapia , Dor
11.
Trials ; 24(1): 647, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37803402

RESUMO

BACKGROUND: Health problems in neonates with gestational age (GA) ≥ 32 weeks remain a major medical concern. Respiratory distress (RD) is one of the common reasons for admission of neonates with GA ≥ 32 weeks. Noninvasive ventilation (NIV) represents a crucial approach to treat RD, and currently, the most used NIV modes in neonatal intensive care unit include high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), and nasal intermittent positive pressure ventilation. Although extensive evidence supports the use of NIPPV in neonates with a GA < 32 weeks, limited data exist regarding its effectiveness in neonates with GA ≥ 32 weeks. Therefore, the aim of this study is to compare the clinical efficacy of HFNC, CPAP, and NIPPV as primary NIV in neonates with GA ≥ 32 weeks who experience RD. METHODS: This trial is designed as an assessor-blinded, three-arm, multi-center, parallel, randomized controlled trial, conducted in neonates ≥ 32 weeks' GA requiring primary NIV in the first 24 h of life. The neonates will be randomly assigned to one of three groups: HFNC, CPAP or NIPPV group. The effectiveness, safety and comfort of NIV will be evaluated. The primary outcome is the occurrence of treatment failure within 72 h after enrollment. Secondary outcomes include death before discharge, surfactant treatment within 72 h after randomization, duration of both noninvasive and invasive mechanical ventilation, duration of oxygen therapy, bronchopulmonary dysplasia, time to achieve full enteral nutrition, necrotizing enterocolitis, duration of admission, cost of admission, air leak syndrome, nasal trauma, and comfort score. DISCUSSION: Currently, there is a paucity of data regarding the utilization of NIPPV in neonates with GA ≥ 32 weeks. This study will provide clinical evidence for the development of respiratory treatment strategies in neonates at GA ≥ 32 weeks with RD, with the aim of minimizing the incidence of tracheal intubation and reducing the complications associated with NIV. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2300069192. Registered on March 9, 2023, https://www.chictr.org.cn/showproj.html?proj=171491 .


Assuntos
Ventilação não Invasiva , Síndrome do Desconforto Respiratório do Recém-Nascido , Recém-Nascido , Humanos , Lactente , Ventilação com Pressão Positiva Intermitente/efeitos adversos , Ventilação com Pressão Positiva Intermitente/métodos , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Idade Gestacional , Recém-Nascido Prematuro , Cânula , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Ventilação não Invasiva/efeitos adversos , Dispneia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
12.
Circulation ; 148(22): 1764-1777, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37781816

RESUMO

BACKGROUND: Clonal hematopoiesis (CH) has emerged as an independent risk factor for atherosclerotic cardiovascular disease, with activation of macrophage inflammasomes as a potential underlying mechanism. The NLRP3 (NLR family pyrin domain containing 3) inflammasome has a key role in promoting atherosclerosis in mouse models of Tet2 CH, whereas inhibition of the inflammasome product interleukin-1ß appeared to particularly benefit patients with TET2 CH in CANTOS (Cardiovascular Risk Reduction Study [Reduction in Recurrent Major CV Disease Events]). TET2 is an epigenetic modifier that decreases promoter methylation. However, the mechanisms underlying macrophage NLRP3 inflammasome activation in TET2 (Tet methylcytosine dioxygenase 2) deficiency and potential links with epigenetic modifications are poorly understood. METHODS: We used cholesterol-loaded TET2-deficient murine and embryonic stem cell-derived isogenic human macrophages to evaluate mechanisms of NLRP3 inflammasome activation in vitro and hypercholesterolemic Ldlr-/- mice modeling TET2 CH to assess the role of NLRP3 inflammasome activation in atherosclerosis. RESULTS: Tet2 deficiency in murine macrophages acted synergistically with cholesterol loading in cell culture and with hypercholesterolemia in vivo to increase JNK1 (c-Jun N-terminal kinase 1) phosphorylation and NLRP3 inflammasome activation. The mechanism of JNK (c-Jun N-terminal kinase) activation in TET2 deficiency was increased promoter methylation and decreased expression of the JNK-inactivating dual-specificity phosphatase Dusp10. Active Tet1-deadCas9-targeted editing of Dusp10 promoter methylation abolished cholesterol-induced inflammasome activation in Tet2-deficient macrophages. Increased JNK1 signaling led to NLRP3 deubiquitylation and activation by the deubiquitinase BRCC3 (BRCA1/BRCA2-containing complex subunit 3). Accelerated atherosclerosis and neutrophil extracellular trap formation (NETosis) in Tet2 CH mice were reversed by holomycin, a BRCC3 deubiquitinase inhibitor, and also by hematopoietic deficiency of Abro1, an essential scaffolding protein in the BRCC3-containing cytosolic complex. Human TET2-/- macrophages displayed increased JNK1 and NLRP3 inflammasome activation, especially after cholesterol loading, with reversal by holomycin treatment, indicating human relevance. CONCLUSIONS: Hypercholesterolemia and TET2 deficiency converge on a common pathway of NLRP3 inflammasome activation mediated by JNK1 activation and BRCC3-mediated NLRP3 deubiquitylation, with potential therapeutic implications for the prevention of cardiovascular disease in TET2 CH.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Dioxigenases , Hipercolesterolemia , Animais , Humanos , Camundongos , Aterosclerose/metabolismo , Colesterol/metabolismo , Hematopoiese Clonal , Enzimas Desubiquitinantes , Proteínas de Ligação a DNA/genética , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-37773605

RESUMO

A Gram-stain-negative, aerobic, motile, ovoid-shaped and yellow-coloured strain, designated SYSU M79828T, was isolated from seawater collected from the South China Sea. Growth of this strain was observed at 4-37 °C (optimum, 28 °C), pH 6.0-8.0 (optimum, pH 7.0) and with 0-6% NaCl (optimum, 3.0 %, w/v). The respiratory quinone was found to be Q-10. Major fatty acid constituents were C18 : 1 ω7c/C18 : 1 ω6c, C18 : 1 ω7c11-methyl and C18 : 0 (>5 % of total). The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, phosphoglycolipid, two unidentified phospholipid, one unidentified lipid and an unidentified glycolipid. The genomic DNA G+C content was 64.5 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that strain SYSU M79828T belonged to the genus Cereibacter and had the highest sequences similarity to 'Rhodobacter xinxiangensis' TJ48T (98.41 %). Based on 16S rRNA gene phylogeny, physiological and chemotaxonomic characterizations, we consider that strain SYSU M79828T represents a novel species of the genus Cereibacter, for which the name Cereibacter flavus sp. nov. is proposed. The type strain is SYSU M79828T (=GDMCC 1.3803T=KCTC 92893T). In addition, according to the results of phylogenetic analysis and similar taxonomic characteristics, we propose that Rhodobacter alkalitolerans should be reclassified as Cereibacter alkalitolerans comb. nov.


Assuntos
Ácidos Graxos , Rhodobacteraceae , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Rhodobacter , Água do Mar , China
14.
Cell Mol Biol (Noisy-le-grand) ; 69(7): 168-173, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37715397

RESUMO

Chronic active EBV infection (CAEBV) is associated with poor prognosis and high mortality. We performed bioinformatics analysis to screen out key genes associated with CAEBV. Weighted gene co-expression network analysis (WGCNA) was used to identify the gene module which was most correlated with pediatric CAEBV. Furthermore, the differentially expressed genes (DEGs) between pediatric acute infectious mononucleosis (AIM) and pediatric CAEBV were investigated. Least absolute shrinkage and selection operator (LASSO) and random forest then were performed to identify the key variables associated with pediatric CAEBV. We also explored the correlation between these hub genes with EBV infection related pathway and immune cell abundance. Compared with pediatric AIM, 1561 DEGs were up-regulated in pediatric CAEBV, and these genes were mainly enriched in inflammatory response and inflammation-related pathways. WGCNA analysis showed that genes in blue module were mostly related to pediatric CAEBV. Genes in the blue module and DEGs are intersected to get 174 genes and these genes are also enriched in inflammatory response-related pathways. The key CAEBV-related genes were selected from these 174 genes by applying the random Forest and LASSO algorithm, resulting in TPST1, TNFSF8 and RAB3GAP1. These three genes showed good diagnostic performance in distinguishing pediatric CAEBV from pediatric AIM. Furthermore, Cibersort and GSEA analysis indicated that these three genes were positively correlated with myeloid cell enrichment and persistent EBV infection pathway, respectively. Our finding systematically analyzed the difference between AIM and CAEBV and identified TPST1, TNFSF8 and RAB3GAP1 were the key genes in the development of CAEBV.


Assuntos
Infecções por Vírus Epstein-Barr , Humanos , Criança , Infecções por Vírus Epstein-Barr/genética , Herpesvirus Humano 4/genética , Algoritmos , Biologia Computacional , Perfilação da Expressão Gênica , Proteínas rab3 de Ligação ao GTP
15.
J Hazard Mater ; 460: 132470, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37683341

RESUMO

Here, polypyrrole (PPY) was first used to the bioreduction of toxic selenite, while the acceleration effect and mechanism were explored. Experiment results suggested that PPY could enhance the selenite bioreduction from 0.42 to 1.04 mg/(L·h). The tests of electrochemical analysis and cytochrome c (cyt-c) content confirmed that PPY promoted the intracellular/intracellular electron transfer of Shewanella oneidensis·MR-1 in selenite bioreduction process. The enhancement of metabolic activity by PPY contributed to biological detoxification, which was manifested in the increased extracellular polymeric substances (EPS), adenosine triphosphate (ATP), electron transfer system activity (ETSA), membrane permeability and enzyme activity. Transcriptome analysis of DEGs, KEGG pathway enrichment and GO functional classification verified that the environmental adaptability of Shewanella oneidensis·MR-1 was enhanced with the addition of PPY. The transmission electron microscopy (TEM) images indicated that PPY promoted the biosynthesis of selenium nanoparticles (SeNPs), which was beneficial to reduce cell damage. Combined with the above results, a multifaceted synergistic facilitation mechanism based on "conductive cross-linking network" was elaborated from electron transfer, microbial metabolism and environmental adaptability. This study shed light the effect of conductive polymers (CPs) on selenite bioreduction and provided new insights into the bioremediation of toxic pollutants.


Assuntos
Polímeros , Pirróis , Transporte de Elétrons , Trifosfato de Adenosina
16.
J Phys Chem Lett ; 14(38): 8599-8603, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37726868

RESUMO

The carbon suboxide anion with an asymmetric zigzag structure, C3O2-, which was recently characterized in a solid neon matrix, has not been observed in the gas phase. Here, we have experimentally generated C3O2- in a supersonic plasma jet expansion and studied it by negative ion photoelectron spectroscopy. A spectral analysis based on the calculated Franck-Condon factors, in combination with quantum chemical calculations, has for the first time yielded a determination of the electron affinity of the neutral carbon suboxide, EA = +0.48(8) eV. Molecular orbital (MO) analysis indicates that, upon linear-to-zigzag geometric change, additional σ-π MO mixing significantly reduces the energy of the singly occupied MO of C3O2- and thus stabilizes the negative ion in the gas phase. This work provides a benchmark understanding of the gas-phase stability of the C3O2- anion.

17.
Trials ; 24(1): 536, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587501

RESUMO

BACKGROUND: Mechanical ventilation (MV) is essential in the management of critically ill neonates, especially preterm infants. However, inappropriate or prolonged use of invasive MV may result in ventilator-associated lung injury. A systemic review comparing pressure control ventilation (PCV) with volume-targeted ventilation mode (VTV) approved that VTV reduces the incidence of death or bronchopulmonary dysplasia (BPD) in neonates; however, this study did not analyze subgroups of very low birthweight (VLBW) infants. Therefore, the aim of this study was to compare the use of VTV and PCV in VLBW infants and to provide clinical evidence for reducing mortality and complications of MV in VLBW infants. METHOD: A single-center randomized controlled trial will be performed. All eligible infants will be randomized and assigned to either VTV or PCV group with 1:1 ratio using sealed envelopes. Death or BPD at 36 weeks' postmenstrual age will be used as the primary outcome. Secondary outcomes include BPD, death, length of invasive MV, noninvasive mechanical ventilation, and oxygen use, length of hospital stay, failure of conventional MV, rate of using high-frequency oscillatory ventilation (HFOV) as rescue therapy, rate of reintubation within 48 h, and hospital expenses. DISCUSSION: Systemic review suggested that VTV decreases the incidence of death or BPD in neonates compared to PLV; however, this study did not specifically analyze subgroups of VLBW infants. We designed this single-center randomized controlled trials (RCT) to add a significant contribution regarding the benefits of VTV for VLBW patients.


Assuntos
Displasia Broncopulmonar , Lesão Pulmonar , Recém-Nascido , Lactente , Humanos , Respiração , Displasia Broncopulmonar/prevenção & controle , Respiração Artificial/efeitos adversos , Recém-Nascido de muito Baixo Peso , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto
18.
J Gene Med ; 25(11): e3552, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37337736

RESUMO

BACKGROUND: ß-1,4-N-Acetyl galactosaminyltransferase1 (B4GALNT1) has been reported to play important roles in tumor progression and metastasis. Herein, we investigate the oncogenic roles of B4GALNT1 for hepatocellular carcinoma (HCC) based on immune microenvironment. METHODS: The Cancer Genome Atlas database and Genotype-Tissue Expression, cBioportal, ImmuCellAI, TIMER2 and other databases were searched to analyze the expression and clinical applications of B4GALNT1 in liver cancer patients. Kaplan-Meier survival analysis, Cox regression analysis, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis were utilized. Moreover, western blot assay, immune histochemistry staining, Cell Counting Kit-8 (CCK-8) assay, invasion and migration assay were performed to evaluate the function of B4GALNT1 in HCC. RESULTS: B4GALNT1 is overexpressed in 14 tumors, and the mRNA expression levels of B4GALNT1 were remarkably elevated in most tumor types, including HCC. In addition, B4GALNT1 expression was an independent prognostic factor, and a low expression of B4GALNT1 showed a better overall survival and disease-specific recurrence-free survival in patients with HCC. Gene set variation analysis indicated that B4GALNT1 presented a positive correlation with the epithelial-mesenchymal transition (EMT) pathway in HCC. B4GALNT1 expression was closely associated with immune activation genes in the HCC microenvironment. Moreover, B4GALNT1 expression was higher in HCC tissue than that in surrounding tissues. B4GALNT1 promoted the expression of apoptosis-related or EMT-related proteins and then decreased the expression of Bcl-2 and Bcl-xl in HCC cells, suggesting that B4GALNT1 knockdown significantly inhibited the proliferation and invasion of HCC cells. CONCLUSIONS: B4GALNT1 may promote HCC development through regulating the EMT pathway, which suggests that B4GALNT1 may serve as a promising predictive biomarker and a potential therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Biomarcadores , Carcinogênese/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Microambiente Tumoral/genética
20.
Integr Cancer Ther ; 22: 15347354221148710, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36680352

RESUMO

BACKGROUND: We explored the use of a novel smart phone-based application (APP) for delivery and monitoring of meditation to treat mood symptoms experienced by cancer patients. METHODS: We assessed the feasibility of using a meditation delivery and tracking APP over 2-weeks and its impact on cancer patients' self-reported anxiety and depression. Outpatients reporting depression and/or anxiety were recruited and randomized to the APP or waitlist control group. Assessments included an expectancy scale, exit survey, mood rating before and after each meditation, and the Edmonton Symptom Assessment Scale (ESAS-FS), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) at baseline and after 2-weeks. The primary aim was to assess feasibility; secondary aims included satisfaction with the APP, association between meditation frequency and length with self-reported symptoms, and change in symptom measures (symptoms, anxiety, depression, and sleep). RESULTS: Our study included 35 participants (17 meditation group; 18 controls) who were primarily female (94%) with breast cancer (60%). The 61% enrollment rate and 71% adherence rate met pre-specified feasibility criteria. Most meditation group participants described the APP as "Useful" to "Very Useful" and would "Probably" or "Definitely" recommend its use. Mixed model analysis revealed a statistically significant association between meditation length (5, 10, or 15 minutes) and change in anxiety, with 15-minute sessions associated with greater reductions in anxiety. In the exit survey, more meditation group vs. control group participants reported improved focus, mood, and sleep. Study groups differed significantly by ESAS fatigue score change; the meditation group decreased a median of 1.5 pts (IQR 2.5) and the control group increased a median of 0.5 points (IQR 2). The meditation group, but not the control group, experienced statistically significant improvement in ESAS fatigue, depression, anxiety, appetite, and physical, psychological, and global distress. Change in PSQI and HADS anxiety and depression scores did not reveal any statistically significant between-group differences. CONCLUSIONS: This pilot study demonstrated the feasibility and acceptability of a meditation APP for cancer patients. Meditation APP users reported improvement in several measures of symptom distress. Future studies should explore ways to enhance the APP's usability and clinical benefit.


Assuntos
Neoplasias da Mama , Meditação , Humanos , Feminino , Meditação/psicologia , Projetos Piloto , Depressão/terapia , Depressão/psicologia , Fadiga/terapia
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