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1.
Plants (Basel) ; 13(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732459

RESUMO

Arbuscular mycorrhizal (AM) fungi can establish a mutualistic relationship with the roots of most terrestrial plants to increase plant nutrient uptake. The effects of potassium uptake and transport by AM symbiosis are much less reported compared to other nutrients. In this research, a heterologous yeast system was used to verify that the LbHAK has capacity for potassium uptake. The split-roots system implemented using seedlings of Lycium barbarum confirmed that R. irregularis locally induced LbHAK expression, which means that LbHAK is only expressed in mycorrhizal roots. Furthermore, the impacts of overexpression of LbHAK on the growth, nutrients and water uptake, and transport of mycorrhizal tobacco (inoculation with Rhizophagus irregularis) at 0.2 mM and 2 mM K conditions were assessed. The mycorrhizal tobacco growth and potassium accumulation were significantly enhanced through LbHAK overexpression in tobacco. In addition, overexpression of LbHAK substantially enhanced phosphorus content, while stimulating the expression of NtPT4, Rir-AQP1, and Rir-AQP2 in mycorrhizal tobacco. Moreover, LbHAK overexpression greatly promoted AM colonization. LbHAK has a potential role in facilitating potassium absorption through the mycorrhizal pathway, and overexpression of LbHAK in tobacco may promote the transport of potassium, phosphorus, and water from AM fungi to tobacco. These data imply the important roles played by the LbHAK in AM-fungi-induced potassium uptake in L. barbarum and in improving plant nutrients and AM colonization.

2.
Biol Res Nurs ; : 10998004241226948, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38196248

RESUMO

BACKGROUND: Postoperative urinary tract infection is a common complication that not only significantly prolongs the hospital stay and amplifies the economic burden on patients, but also affects their quality of life and prognosis. This study aimed to investigate risk factors and distribution of pathogenic bacteria in urinary tract infections among bladder cancer patients who underwent cutaneous ureterostomy following radical cystectomy. METHODS: A total of 137 bladder cancer patients, who underwent cutaneous ureterostomy after radical cystectomy at our hospital from November 2018 to October 2022, were enrolled in this retrospective study. Univariate and multivariate logistic regression analyses were employed to investigate the risk factors associated with postoperative urinary tract infection and the distribution of pathogenic bacteria among the infected patients. RESULTS: The results of both univariate and multivariate analyses confirmed that age, proficiency in ostomy knowledge, frequency of ureteral stent tube replacement, ureteral stent tube dislodgement, urine immersion at the outer end of the ureteral stent tube, and the interval of ostomy bag replacement were independent risk factors for urinary tract infection after radical cystectomy and cutaneous ureterostomy in bladder cancer patients. A total of 55 pathogenic bacteria were isolated from 52 patients with infections. Predominantly, these were gram-negative bacteria (34 strains, 61.8%), with Proteus mirabilis having the highest proportion. CONCLUSION: Urinary tract infections after radical cystectomy and cutaneous ureterostomy predominantly involve gram-negative bacteria. This is correlated with factors such as the age of bladder cancer patients, the level of nursing education, the duration of ureteral stent tubes and ostomy bag usage, as well as issues related to impaired urine drainage.

3.
Blood ; 143(17): 1713-1725, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38194692

RESUMO

ABSTRACT: Tisagenlecleucel is approved for adults with relapsed/refractory (r/r) follicular lymphoma (FL) in the third- or later-line setting. The primary analysis (median follow-up, 17 months) of the phase 2 ELARA trial reported high response rates and excellent safety profile in patients with extensively pretreated r/r FL. Here, we report longer-term efficacy, safety, pharmacokinetic, and exploratory biomarker analyses after median follow-up of 29 months (interquartile range, 22.2-37.7). As of 29 March 2022, 97 patients with r/r FL (grades 1-3A) received tisagenlecleucel infusion (0.6 × 108-6 × 108 chimeric antigen receptor-positive viable T cells). Bridging chemotherapy was allowed. Baseline clinical factors, tumor microenvironment, blood soluble factors, and circulating blood cells were correlated with clinical response. Cellular kinetics were assessed by quantitative polymerase chain reaction. Median progression-free survival (PFS), duration of response (DOR), and overall survival (OS) were not reached. Estimated 24-month PFS, DOR, and OS rates in all patients were 57.4% (95% confidence interval [CI], 46.2-67), 66.4% (95% CI, 54.3-76), and 87.7% (95% CI, 78.3-93.2), respectively. Complete response rate and overall response rate were 68.1% (95% CI, 57.7-77.3) and 86.2% (95% CI, 77.5-92.4), respectively. No new safety signals or treatment-related deaths were reported. Low levels of tumor-infiltrating LAG3+CD3+ exhausted T cells and higher baseline levels of naïve CD8+ T cells were associated with improved outcomes. Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r FL enrolled in ELARA. This trial was registered at www.clinicaltrials.gov as #NCT03568461.


Assuntos
Linfoma Folicular , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/mortalidade , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Adulto , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Receptores de Antígenos de Linfócitos T/uso terapêutico , Seguimentos , Resultado do Tratamento
4.
Open Life Sci ; 18(1): 20220688, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37791062

RESUMO

Lung cancer is the cancer with the highest mortality rate and the highest incidence in the world at this stage. Among them, non-small lung cancer is the most common type of lung cancer, and most small cancers have disappeared, which is the optimal time for surgery at the time of diagnosis. To explore and systematically evaluate the clinical efficacy of CYP1B1 gene polymorphism in the treatment of epidermal growth factor receptor (EGFR) Mutant non-small cell lung cancer, this article proposes the principles of lung cancer screening based on CYP1B1 gene polymorphism and polarization imaging and explores the diagnosis and treatment of non-EGFR mutant lung cancer. Based on a large number of medical image data, imageomics can directly reflect the correlation between tumor molecular phenotype and image characteristics by deeply mining some imaging features of the image, which has important value in the early diagnosis of disease, the formulation of personalized treatment plan, and efficacy evaluation and prognosis prediction. A total of 141 NSCLC patients with sensitive EGFR mutation were included in this study, including 101 patients with EGFR single-gene mutation and 40 patients with EGFR multigene mutation coexisting mutation. Both groups of patients were female, aged ≥60 years, no smoking history, no family history of leukemia, adenocarcinoma, lung cancer, stage IV, lymph node metastasis, living, far from metastasis, and ECOG score of 0-2. This study examined the relative number of gene expression and PFS in EGFR multigene co-existing mutations. When the number of mixed genes is 1, 2, and higher, the PFS is 9 months, 8 months, and 6 months, respectively. The PFS time of this group of patients gradually shortened. Therefore, this study examined the benefit of polygenic mutation in estimation by comparing the clinical characteristics of patients with EGFR single-gene mutation and polygenic mutation, to provide measurement of EGFR-TKI and to provide suggestions for future drug selection.

5.
Horm Metab Res ; 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37832580

RESUMO

To investigate the safety and efficacy of the islet-like cell (cell) induced from human umbilical cord mesenchymal stem cell (UCMSC) with different methods for the treatment of diabetic animal model. UCMSCs were induced to ßcells with cytokines (CY) and neonatal bovine pancreatic mesenchymal cell exosomes (Ex) combined with CY (EX+CY). The insulin secretion of UCMSC and ßcell was measured with ELISA when the cells were growing in different concentrations of glucose media for different times. UCMSCs (4×105) and the same number of cells prepared with two methods were transplanted to type I diabetic rat models. UCMSCs could be induced into islet ßcells by CY or EX+CY in vitro. The insulin secretion of the prepared ß cells growing in 25.0 mM glucose medium was over 5-fold of that in 6.0 mM glucose. The transplantation of the ßcells to type I diabetic rat models could reduce the blood glucose and prolong the survival time. The ß cells induced by EX+CY had much more significant effects on decreasing blood glucose and increasing survival time (p<0.01). The cells did not affect blood sugar level and had no serious side-effects in human health. UCMSC could be induced to islet ßcells with either CY or EX+CY. The transplantation of the induced islet ßcells could reduce blood glucose and prolong the survival time of diabetic animal models. Although the cells induced with EX+CY had more significant effects on diabetic rats, they did not affect blood glucose level and had no serious side-effects in human health.

6.
Open Life Sci ; 18(1): 20220705, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854320

RESUMO

Non-small cell lung cancer (NSCLC) is one of the most common cancers worldwide, and chemotherapy is one of its main treatment methods. However, there are significant differences in patients' reactions to chemotherapy, leading to unsatisfactory treatment outcomes. Therefore, identifying relevant factors that affect the efficacy of chemotherapy can help doctors better develop personalized treatment plans, improve the treatment effectiveness, and quality of life of patients. This article aims to understand the specific clinical role of CYP1B1 gene in NSCLC. Therefore, based on the individualized health model of CYP1B1 gene polymorphism, this article analyzes the prediction of postoperative chemotherapy efficacy for NSCLC. Through a study on the control variables of postoperative recovery of stage III NSCLC in a hospital, according to the findings of this study, 14 of the 32 patients in the EGFR mutation-positive group relapsed. In the EGFR-negative group, 13 of the 36 patients relapsed. It can be considered that CYP1B1 gene polymorphism has a good curative effect in postoperative chemotherapy of NSCLC, and it can effectively control the recurrence rate of cancer.

7.
Neonatology ; 120(6): 699-708, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37573777

RESUMO

INTRODUCTION: Maternal pregnancy smoking has adverse perinatal outcomes and the relationship between maternal smoking and neonatal death has not been fully elucidated. We aimed to examine the risk of neonatal death in relation to maternal smoking and to quantify potential mediators of these associations. METHODS: We did a population-based cohort study using Period Linked Birth-Infant Death data from 2016 to 2019 in the US National Vital Statistics System. The exposure was maternal smoking status. The main outcome was neonatal death. Association between maternal smoking and neonatal death was estimated through logistic regression. Mediation analysis was performed to assess the extent to which the association between maternal smoking and neonatal death was mediated by neonatal complications. RESULTS: The final sample consisted of 14,717,020 mothers with live singleton births. The overall neonatal mortality rate was 2.2 per 1,000 live births. Maternal pregnancy smoking was associated with an increased risk of neonatal death {adjusted odds ratio (aOR, 1.33 [95% CI, 1.28-1.38]; p < 0.001)}, while smoking cessation during the whole pregnancy showed a comparable risk of neonatal death with nonsmokers (aOR, 1.06 [95% CI, 0.99-1.14]; p = 0.116). Mediation analysis indicated that the association between pregnancy smoking and neonatal death might be mainly mediated by preterm birth and low Apgar score at 5 min. CONCLUSIONS: Maternal pregnancy smoking, regardless of pregnancy trimester and intensity, was associated with increased risk of neonatal death. Efforts are needed for policymakers to promote smoking cessation before pregnancy, and professional perinatal care should be provided for those who smoked during pregnancy.


Assuntos
Fumar Cigarros , Morte Perinatal , Nascimento Prematuro , Feminino , Gravidez , Recém-Nascido , Humanos , Nascimento Prematuro/epidemiologia , Estudos de Coortes , Fumar Cigarros/efeitos adversos , Mães
8.
Front Plant Sci ; 14: 1161220, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37409300

RESUMO

Potassium plays important roles in most plant physiological processes. Arbuscular mycorrhizal (AM) fungi promote plant water and mineral nutrient acquisition to promote plant growth. However, few studies have focused on the effect of AM colonization on potassium uptake by the host plant. In this study, the effects of an AM fungus (Rhizophagus irregularis) and potassium concentration (0, 3, or 10 mM K+) on Lycium barbarum were evaluated. A split-root test with L. barbarum seedlings was conducted, and the potassium uptake capacity of LbKAT3 was verified in yeast. A tobacco line overexpressing LbKAT3 was generated and mycorrhizal functions under two potassium concentrations (0.2 and 2 mM K+) were studied. Inoculation of R. irregularis and application of potassium increased the dry weight, and potassium and phosphorus contents of L. barbarum, and increased the colonization rate and arbuscule abundance of R. irregularis. In addition, the expression of LbKAT3 and AQP genes in L. barbarum was upregulated. Inoculation of R. irregularis induced LbPT4, Rir-AQP1, and Rir-AQP2 expression, and application of potassium upregulated the expression of these genes. Inoculation with the AM fungus locally regulated the expression of LbKAT3. Inoculation of R. irregularis improved the growth, and potassium and phosphorus contents, and induced NtPT4, Rir-AQP1, and Rir-AQP2 expression in tobacco overexpressing LbKAT3 under both potassium concentrations. Overexpression of LbKAT3 in tobacco improved the growth, potassium accumulation, and AM colonization, and upregulated the expression of NtPT4 and Rir-AQP1 in mycorrhizal tobacco. The results suggest that LbKAT3 may assist in mycorrhizal potassium uptake, and overexpression of LbKAT3 may promote potassium, phosphorus, and water transport from the AM fungus to tobacco.

9.
Heliyon ; 9(6): e16873, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37484385

RESUMO

Background: The efficacy of therapy in cervical cancer (CESC) is blocked by high molecular heterogeneity. Thus, the sub-molecular characterization remains primarily explored for personalizing the treatment of CESC patients. Methods: Datasets with 741 CESC patients were obtained from TCGA and GEO databases. The NMF algorithm, random forest algorithm, and multivariate Cox analysis were utilized to construct a classifier for defining the sub-molecular characterization. Then, the biological characteristics, genomic variations, prognosis, and immune landscape in molecular subtypes were explored. The significance of classifier genes was validated by quantitative Real-Time PCR, cell transfection, cell colony formation assay, wound healing assay, cell proliferation assay, and Western blot. Results: The CESC patients were classified into two subtypes, and the high classifier-score patients with significant differences in ECM-receptor interaction, PI3K-Akt signaling pathway, and MAPK signaling pathway showed a poorer prognosis in OS (p < 0.001), DFI (p = 0.016), PFI (p < 0.001) and DSS (p < 0.001), and with high the M0 Macrophage and resting Mast cells infiltration and low HLA family gene expression. Moreover, the constructed classifier owns a high identified accuracy in the tumor/normal groups (AUC: 0.993), the tumor/CIN1-CIN3 groups (AUC: 0.963), and normal/CIN1-CIN3 groups (AUC: 0.962), and the total prediction performance is better than currently published signatures in CESC (C-index: 0,763). The combined prediction performance further indicated that Nomogram (AUC = 0.837) is superior to the classifier (AUC = 0.835) and Stage (AUC = 0.568), and the C-index of calibration curves is 0.784. The potential biological function of classifier genes indicated that silencing GALNT2 inhibited the cancer cell's proliferation, migration, and colony formation; Conversely, the cancer cell's proliferation, migration, and colony formation were increased after the upregulation of GALNT2. The Epithelial-Mesenchymal Transition Experiment showed that GALNT2 knockdown might reduce the levels of Snail and Vimentin proteins and increase E-cadherin; Conversely, the levels of Snail and Vimentin proteins were increased, E-cadherin was reduced by GALNT2 upregulation. Conclusion: The classifier we constructed may help improve our understanding of subtype characteristics and provide a new strategy for developing CESC therapeutics. Remarkably, GALNT2 may be an option to directly target drivers in CESC cancer therapy.

10.
Chin J Physiol ; 66(3): 129-136, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37322623

RESUMO

Atherosclerosis, a leading cause of mortality worldwide, is driven by multiple risk factors such as diabetes. Oxidative stress and inflammation assist interrelated roles in diabetes-accelerated atherosclerosis. Thereby, treatment of diabetic atherosclerosis from an oxidative stress/inflammatory perspective seems to be a more effective modality to prevent and delay plaque formation and progression. This study aimed to evaluate the effects of l-limonene (LMN) on oxidative stress/inflammatory responses in the aortic artery of diabetic atherosclerosis-modeled rats. Male Wistar rats (n = 30, 250-280 g, 12 weeks old) were used to establish a diabetic atherosclerosis model (8 weeks) using high-fat diet/low-dose streptozotocin. LMN (200 mg/kg/day) was administered orally, starting on day 30th before tissue sampling. Plasma lipid profiles, aortic histopathological changes, atherogenic index, aortic artery levels of oxidative stress markers (manganese superoxide dismutase, glutathione, and 8-isoprostane), inflammatory markers (tumor necrosis factor-alpha, interleukin (IL)-6, and IL-10), and expression of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK)/AMPK, Sirtuin 1 (SIRT1), and p-p65/p65 proteins were evaluated. The administration of LMN to diabetic rats improved lipid profiles, aortic histopathological morphology, and atherogenic index (P < 0.05 to P < 0.001). It also increased enzymatic antioxidant activities, decreased 8-isoprostane level, suppressed inflammatory response, upregulated p-AMPK and SIRT1 proteins, and downregulated p-p65 protein (P < 0.05 to P < 0.01). Inhibiting the AMPK through the administration of compound C significantly abolished or reversed the positive effects of LMN in diabetic rats (P < 0.05 to P < 0.01). LMN treatment had dual anti-oxidative and anti-inflammatory actions against atherosclerosis in the aortic artery of diabetic rats. Atheroprotection by LMN was mediated partly through modulation of AMPK/SIRT1/p65 nuclear factor kappa B signaling pathway. LMN appears to be a promising anti-atherosclerotic modality to improve the quality of life in diabetic patients.


Assuntos
Aterosclerose , Diabetes Mellitus Experimental , Ratos , Masculino , Animais , Dieta Hiperlipídica , Limoneno/uso terapêutico , Limoneno/farmacologia , Ratos Wistar , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia , Sirtuína 1/uso terapêutico , Qualidade de Vida , Estresse Oxidativo , Aterosclerose/tratamento farmacológico , Aterosclerose/etiologia , Aorta/metabolismo , Interleucina-6 , Lipídeos/farmacologia , Lipídeos/uso terapêutico
11.
J Inflamm Res ; 16: 809-826, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36876154

RESUMO

Purpose: Intra-abdominal infection is considered the second most common cause of sepsis and results in localized or diffused inflammation of the peritoneum. The main treatment for abdominal sepsis is an emergency laparotomy for source control. However, surgical trauma also causes inflammation, and patients become susceptible to postoperative complications. Therefore, it is necessary to identify biomarkers that can be used to distinguish sepsis from abdominal infection. This prospective study investigated whether cytokine levels in the peritoneum could predict complications and indicate severity of sepsis following emergency laparotomy. Methods: We prospectively observed 97 patients with abdominal infection admitted to the Intensive Care Unit (ICU). After emergency laparotomy,SEPSIS-3 criteria were used for the diagnosis of sepsis or septic shock. Blood and peritoneal fluid samples were drawn at postoperative admission to the ICU and cytokine concentrations were measured by flow cytometry. Results: Fifty-eight postoperative patients were enrolled. We found significant elevations in the peritoneal concentrations of IL-1ß, IL-6, TNF-α, IL-17, and IL-2 in patients with sepsis or septic shock compared to the patients without sepsis after surgery. Positive correlations between levels of these peritoneal cytokines with APACHE II scores were found: IL-6, in particular, had the highest correlation coefficient of 0.833. Meanwhile, IL-10 in blood, MCP-1 and IL-8 in both blood and peritoneum were simultaneously increased in patients with sepsis and septic shock, and also positively correlated with disease severity. Conclusion: The cytokine storm that occurs in the abdominal cavity after emergency laparotomy may be the main mechanism leading to sepsis. It may be valuable to measure IL-1ß, IL-6, TNF-α,IL-17, IL-2, MCP-1, and IL-8 in the peritoneal fluid, combined with serum IL-10, MCP-1 and IL-8, in a panel of cytokines, to assess the severity of sepsis and predict mortality from abdominal infection after emergency laparotomy.

12.
Front Med (Lausanne) ; 10: 1096529, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817761

RESUMO

Background: The long-term overall survival of children with T-cell acute lymphoblastic leukemia (T-ALL) is limited to approximately 80-85% because of a high incidence of relapse after achieving remission with intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Novel treatment strategies inducing long-term remission are needed to improve the outcome. Histone deacetylase inhibitors (HDACis) have been reported to be effective in a series of T-ALL cases. Preclinical studies suggested that T-ALL cells are sensitive to Chidamide, which is a selective HDACi. Methods: This preliminary clinical study evaluated the efficacy and safety of Chidamide in combination with chemotherapy or post-HSCT for children with T-ALL at a dose of 0.5 mg/kg weight of patient twice per week for at least 6 months. Results: In total, 27 children with a mean age of 7.88 years were included. The high-risk proportion was 66.7%. After a median follow-up period of 37.8 months (9.5-67.9 months), the overall survival and event-free survival in the patients treated with Chidamide were 94.1 and 95.2%, respectively. All patients except two maintained persistent remission with <0.01% blast cells in minimal residual disease. Conclusion: The combination therapy with Chidamide in a case series of T-ALL shows the promising clinical efficacy and good safety in children. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2000030357.

13.
J Oncol ; 2023: 4512698, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778917

RESUMO

Objective: Uterine corpus endometrial carcinoma (UCEC) is a frequent epithelial cancer in females. The rate of UCEC occurrence increases year by year and the age is getting younger and younger, which requires more active treatments to improve its prognosis. Ferroptosis is a kind of regulatory cell death that relies on iron and may be triggered by sorafenib, which has been elucidated in several cancers, but the mechanism of ferroptosis-related genes in UCEC has yet to be fully defined and will need more investigation. Methods: The mRNA expression profiles and accompanying clinical data of UCEC patients included in this research were obtained from a publicly available database. We subsequently classified the patients into experimental and training sets. Next, utilizing the least absolute shrinkage and selection operator (LASSO) Cox regression model, we established the multigene features of the TCGA experimental set and verified them in the validation set. Results: Per the findings of our investigation, the TCGA experimental set cohort had four differentially expressed genes (DEGs) that were linked to overall survival (OS). An analysis was conducted using univariate Cox regression (with all variables corrected for P < 0.05). To stratify the patients into two distinct categories, high- and low-risk, a diagnostic model premised on the identified four genes was formulated. In contrast with the low-risk population, the high-risk category exhibited a considerably lower OS (P < 0.0001). The findings of the multivariate Cox regression analysis illustrated that the risk score independently served as a predictor of OS (HR > 1, P < 0.01). The predictive capability of the model was verified by ROC curve analysis. Immune-related pathway enrichment was found using functional analysis, which illustrated that the two risk groups had significantly different immunological statuses. Conclusions: A unique model of genes linked to ferroptosis has the potential to be a treatment option for UCEC and can be utilized for the prognostic prediction of the disease.

14.
Nat Commun ; 14(1): 344, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670126

RESUMO

Mesenchymal stem cells (MSCs) reside in microenvironments, referred to as niches, which provide structural support and molecular signals. Sensory nerves are niche components in the homeostasis of tissues such as skin, bone marrow and hematopoietic system. However, how the sensory nerve affects the behavior of MSCs remains largely unknown. Here we show that the sensory nerve is vital for mesenchymal tissue homeostasis and maintenance of MSCs in the continuously growing adult mouse incisor. Loss of sensory innervation leads to mesenchymal disorder and a decrease in MSCs. Mechanistically, FGF1 from the sensory nerve directly acts on MSCs by binding to FGFR1 and activates the mTOR/autophagy axis to sustain MSCs. Modulation of mTOR/autophagy restores the MSCs and rescues the mesenchymal tissue disorder of Fgfr1 mutant mice. Collectively, our study provides insights into the role of sensory nerves in the regulation of MSC homeostasis and the mechanism governing it.


Assuntos
Células-Tronco Mesenquimais , Camundongos , Animais , Células-Tronco Mesenquimais/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Autofagia/fisiologia , Medula Óssea/metabolismo , Homeostase , Nicho de Células-Tronco
15.
Blood Adv ; 7(11): 2283-2286, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-36044388

RESUMO

Tisagenlecleucel demonstrated high response rates and a manageable safety profile in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. However, lack of response and chimeric antigen receptor (CAR) T-cell exhaustion were observed in patients with programmed cell death protein 1 (PD-1) overexpression. Hence, pembrolizumab, a PD-1 inhibitor, was hypothesized to improve efficacy and cellular expansion of CAR T-cells in vivo. Here, we report the final analysis of the PORTIA trial in adult patients with r/r DLBCL who had ≥2 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of ≤1. Patients received 1 tisagenlecleucel infusion on day 1. Pembrolizumab (200 mg) was given every 21 days, for up to 6 doses. Three cohorts initiated pembrolizumab on days 15 (n = 4), 8 (n = 4), or -1 (n = 4). Safety, efficacy, cellular kinetics, and biomarker analyses were included. Tisagenlecleucel plus pembrolizumab was feasible and showed a manageable safety profile, without dose-limiting toxicities. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159).


Assuntos
Anticorpos Monoclonais Humanizados , Linfoma Difuso de Grandes Células B , Adulto , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Receptores de Antígenos de Linfócitos T/uso terapêutico , Linfoma Difuso de Grandes Células B/patologia
17.
Open Med (Wars) ; 17(1): 2036-2045, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568518

RESUMO

The long noncoding RNA DARS-AS1 was aberrantly expressed and participated in several human cancer progressions, whereas whether DARS-AS1 is involved in human gastric cancer remains unclear. This study aimed to investigate the influence of DARS-AS1 on gastric cancer progression and explore the potential regulatory network of DARS-AS1/miR-330-3p/NAT10. The expression levels of DARS-AS1, miR-330-3p, and NAT10 were measured by quantitative real-time polymerase chain reaction. The CCK-8 assay and Transwell assay were used to determine the cell viability, migration, and invasion capacities, respectively. The target association between miR-330-3p and DARS-AS1 or NAT10 was confirmed using a luciferase reporter assay. In result, DARS-AS1 levels were elevated in tumor tissues and associated with shorter overall survival in patients with gastric cancer. Knockdown of DARS-AS1 could hamper cell viability, migration, and invasion in gastric cancer cells. DARS-AS1 acts as a competitive endogenous RNA to regulate the NAT10 expression by sponging miR-330-3p in gastric cancer cells. In conclusion, DARS-AS1 was elevated in gastric cancer, and DARS-AS1/miR-330-3p/NAT10 signaling offered some new horizons for predicting prognosis and a novel therapeutic method for the treatment of gastric cancer.

18.
BMC Cancer ; 22(1): 1190, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401208

RESUMO

BACKGROUND: Umbilical cord blood transplantation (UCBT) from unrelated donors is one of the successful treatments for acute leukemia in childhood. The most frequent side effect of UCBT is peri-engraftment syndrome (PES), which is directly associated with the greater prevalence of acute and chronic graft-versus-host-disease (aGvHD and cGvHD). In haploidentical stem cell transplantation, posttransplant cyclophosphamide (PTCY) has been demonstrated to be an effective method against GvHD. However, the effects of PTCY as a GvHD prophylactic in UCBT had not been investigated. This study aimed to evaluate the effects of PTCY on the outcomes of UCBT for pediatric acute leukemia. METHODS: This retrospective study included 52 children with acute leukemia who underwent unrelated single-unit UCBT after myeloablative conditioning regimens. The results from the PTCY and non-PTCY groups were compared. RESULTS: The incidence of transplantation-related mortality in non-PTCY and PTCY were 5% and 10% (p = 0.525), respectively. The incidence of relapse in non-PTCY and PTCY were 5% and 23% (p = 0.095), respectively. Second complete remission status (CR2) was an independent risk factor for relapse-free survival (hazard ratio = 9.782, p = 0.001). The odds ratio for sepsis or bacteremia incidence was significantly greater in the PTCY group (9.524, p = 0.017). PTCY group had increased rates of cytomegalovirus activity and fungal infection. The incidence of PES, aGvHD, cGvHD, and hemorrhagic cystitis in the PTCY group was lower than that in the non-PTCY group, although it was not significantly different. Additionally, higher doses of PTCY (29 mg/kg and 40 mg/kg) were associated with lower incidences of aGvHD and severe GvHD (65% and 29%, respectively) than lower doses (93% and 57%, respectively). Engraftment time and graft failure incidence were similar across groups. CONCLUSION: The results support the safety and efficiency of PTCY as part of PES controlling and GvHD prophylaxis in single-unit UCBT for children with acute leukemia. A PTCY dosage of 29 mg/kg to 40 mg/kg appears to be more effective in GvHD prophylaxis for UCBT patients.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda , Humanos , Criança , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Estudos Retrospectivos , Ciclofosfamida , Leucemia Mieloide Aguda/tratamento farmacológico , Doença Aguda , Recidiva , Doença Crônica
19.
Biomed Res Int ; 2022: 5217625, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193313

RESUMO

To address the issue of genetic mutations in medical records, clinical studies on minimally invasive surgery for breast cancer have been proposed. The CYP1B1 gene is mainly a single-nucleotide mutation, which affects the enzymatic reaction related to carcinogens and causes the susceptibility differences of different individuals. First, the survival rate and other factors influencing the estimation of 120 leukemia patients were examined with the help of various medical records by establishing an organization for auxiliary diagnosis of lung cancer based on expertise. Secondly, through the treatment of 120 leukemia patients after minor surgery, the average life expectancy of 120 patients was 19 months, the one-year survival rate was 74.61%, and the two-year survival rate was 32.70%. Currently, there are more than 160 cases of CYP1B1 discovered. In recent years, people have gradually entered into in-depth research on the correlation between genes and lung cancer, which is of great significance to the treatment and research of lung cancer. An analysis showed patients' age, stage, whether they would work, whether radiation therapy and antibiotics were offered, and so on. s has a direct impact on patient survival, and many tests have shown that the patient's age, stage, whether it will work, and whether fire radiation and drug therapy are provided are important interventions for patients with anemia. Finally, in patients with leukemia, especially during the restricted period, combined treatment with a physician, radiologist, and surgeon should be initiated as soon as possible. For a wide range of disease, depending on the use of chemotherapy, local metastasis with antibiotics can improve the disease. After success, it is more beneficial to choose second-line treatment.


Assuntos
Leucemia , Neoplasias Pulmonares , Antibacterianos/uso terapêutico , Carcinógenos , Citocromo P-450 CYP1B1/genética , Análise de Dados , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Nucleotídeos/uso terapêutico , Polimorfismo Genético , Prognóstico
20.
Contrast Media Mol Imaging ; 2022: 7042014, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36128170

RESUMO

The rapid development of science and technology has become an indispensable part of human life. Minimally invasive lung cancer surgery, that is, thoracoscopic surgery and da Vinci robotic surgery, has many advantages over previous surgeries, there is no need to make a large incision in the chest, the patient after such surgery, and recovery is also better and can also reduce the incision of the operation. Therefore, with the rapid development of science and technology today, how to detect changes in patients' health and establish an intelligent health monitoring system has become a development trend. This paper proposes to apply health monitoring in CYP1B1 gene polymorphism and nursing after clinical treatment of minimally invasive lung cancer surgery, after analyzing the society's demand for real-time health monitoring in this paper. It also studies the health monitoring system based on the advantages of smart phones. The system is suitable for the Android operating system and can monitor the temperature, weight, and other data of the human body. The experimental results show that the data value of the information displayed by the android software has a high degree of matching with the measured value, which basically keeps floating around 80, and the data consistency is strong.


Assuntos
Neoplasias Pulmonares , Procedimentos Cirúrgicos Robóticos , Citocromo P-450 CYP1B1/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Polimorfismo Genético , Procedimentos Cirúrgicos Robóticos/métodos , Toracoscopia/métodos
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