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Frontiers in Bioscience (Landmark... Jun 2024Gastric cancer (GC) is a leading cause of cancer-associated death worldwide. Its molecular mechanisms, especially concerning autophagy and various signaling pathways,...
BACKGROUND
Gastric cancer (GC) is a leading cause of cancer-associated death worldwide. Its molecular mechanisms, especially concerning autophagy and various signaling pathways, are not fully understood. Fatty Acid Binding Protein 6 () and RE1 Silencing Transcription Factor () emerge as potential key players in this context. This study sought to analyze the functional relationship of and concerning autophagy and their implications on the Akt/mTOR signaling pathway within GC cells.
METHODS
A comprehensive bioinformatics approach was used to identify key prognostic markers in GC. The effects of and on autophagy along with Akt/mTOR signaling pathways were analyzed by techniques including Western blotting (WB), flow cytometry, Transwell assay, dual luciferase reporter assay, and others.
RESULTS
was identified as overexpressed in GC, linked with poor prognosis. silencing reduces GC cell proliferation, induces S- and G2-phase arrest, and downregulates cyclins CDK2 and CDK4. It also inhibited GC cell invasion/migration and autophagy, effects that were counteracted by MG132. When combined with PI3K inhibitor LY294002c, knockdown showed synergistic anti-proliferative effects, modulating the Akt/mTOR pathway. Besides, the transcription factor has been shown to directly regulate expression, affecting autophagy and the Akt/mTOR signaling pathway in a -dependent manner.
CONCLUSIONS
positively regulates autophagy and negatively affects the Akt/mTOR signaling pathway in GC cells in a FABP6-dependent manner, providing valuable insights into regulatory networks involving and .
Topics: Humans; Stomach Neoplasms; TOR Serine-Threonine Kinases; Autophagy; Proto-Oncogene Proteins c-akt; Signal Transduction; Cell Line, Tumor; Fatty Acid-Binding Proteins; Cell Proliferation; Gene Expression Regulation, Neoplastic
PubMed: 38940038
DOI: 10.31083/j.fbl2906212 -
Frontiers in Bioscience (Landmark... May 2024Lung cancer is the primary cause of cancer-related deaths, with one of the highest incidence and mortality rates of all malignant tumors. Dysregulated expression of...
BACKGROUND
Lung cancer is the primary cause of cancer-related deaths, with one of the highest incidence and mortality rates of all malignant tumors. Dysregulated expression of DEPDC1B has been reported to occur in various tumor types. However, the functional implications of this alteration in lung adenocarcinoma (LUAD) and the underlying molecular mechanism remains unclear. In this study, we investigated the role and clinical significance of DEPDC1B in LUAD.
METHODS
The expression of DEPDC1B in LUAD and its relationship with prognosis were systematically evaluated in several publically available datasets. The effects of DEPDC1B knockdown on the proliferation and motility of LUAD cells were assessed using the JULI Stage Real-time Cell History Recorder, while the effect of knockdown on the cell cycle was studied by flow cytometry. Furthermore, RNA-Sequencing (RNA-Seq) analysis was conducted to identify the downstream target genes and pathways regulated by DEPDC1B. Correlations between the expression of DEPDC1B and immune cell infiltration, immunotherapy resistance, and chemoresistance were also examined. Additionally, molecular biological methods were used to explore the regulatory mechanism of B-Myb on DEPDC1B expression.
RESULTS
DEPDC1B was found to be upregulated in LUAD patients and this was associated with poor clinical outcomes. Knockdown of inhibited cell growth, migration and motility, as well as cell cycle progression. Knockdown also resulted in the down-regulation of several downstream genes, including , , and , as well as the inactivation of multiple critical pathways, such as the ERK and PI3K-AKT pathways. Analysis of the tumor immuno-environment in LUAD revealed that high DEPDC1B expression was associated with an abundance of activated CD4+ memory T cells, M0 macrophages, M1 macrophages, and CD8+ T cells. Moreover, these tumors responded poorly to immunotherapy. Analysis of chemo-drug sensitivity showed that LUADs with high DEPDC1B expression were more responsive to frontline chemotherapeutic drugs such as Vinorelbine, Cisplatin, and Etoposide. Additionally, mechanistic investigations revealed that DEPDC1B is a direct target gene of B-Myb, and that its knockdown attenuated the proliferation and motility effects of B-Myb.
CONCLUSIONS
In summary, our findings indicate that DEPDC1B is a critical regulator during the malignant progression of LUAD. DEPDC1B could therefore be a promising prognostic marker and therapeutic target in LUAD diagnosis and treatment.
Topics: Humans; Adenocarcinoma of Lung; GTPase-Activating Proteins; Lung Neoplasms; Cell Proliferation; Cell Movement; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Disease Progression; Cell Cycle Proteins; Prognosis; Drug Resistance, Neoplasm; Male; Gene Knockdown Techniques; Signal Transduction; Neoplasm Proteins; Trans-Activators
PubMed: 38940035
DOI: 10.31083/j.fbl2906204 -
JACC. Advances Jan 2024
PubMed: 38939816
DOI: 10.1016/j.jacadv.2023.100738 -
Journal of Arrhythmia Jun 2024Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often...
Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN-ICD/WCD study): Rationale and design of a...
BACKGROUND
Despite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients.
METHODS
We are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all-cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints.
RESULTS
Not applicable.
CONCLUSION
This study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.
PubMed: 38939793
DOI: 10.1002/joa3.13028 -
Journal of Arrhythmia Jun 2024A notched P-wave is associated with the occurrence of atrial fibrillation (AF). However, the association between a notched P-wave and AF recurrence in patients who have...
BACKGROUND
A notched P-wave is associated with the occurrence of atrial fibrillation (AF). However, the association between a notched P-wave and AF recurrence in patients who have undergone a catheter ablation for AF is unclear.
METHODS
We enrolled 100 subjects who underwent catheter ablation for AF (paroxysmal AF: 60 cases; persistent AF: 40 cases). Twelve-lead electrocardiography (ECG) was conducted, and the peak-to-peak distance in the M shape was calculated automatically using a 12-lead ECG analysis system. A notched P-wave was defined as a P-wave with an M-shape and a peak-to-peak distance of ≥20 ms in lead II. We compared the recurrence of AF in the patients with notched P-wave and the others.
RESULTS
The mean follow-up period was 12 ± 8 months, and a recurrence of AF was observed in 28 patients. The recurrence of AF in the notched P-wave group was significantly higher than that in the controls (log rank 5.14, = .023). A notched P-wave was a significant predictor of the recurrence of AF after adjustment for age, gender, history of heart failure, history of catheter ablation, persistent AF, use of antiarrhythmic drugs, and the left atrial volume index (hazard ratio 2.470, 95% confidence interval 1.065-5.728, = .035).
CONCLUSIONS
Automatically identified notched P-waves with peak-to-peak distance ≥20 ms were associated with AF recurrence in patients who had undergone catheter ablation.
PubMed: 38939783
DOI: 10.1002/joa3.13050 -
American Journal of Preventive... Jun 2024The American Heart Association's (AHA) Life's Essential 8 (LE8) score is a helpful tool to quantify cardiovascular health (CVH) metrics. We sought to assess sex...
BACKGROUND
The American Heart Association's (AHA) Life's Essential 8 (LE8) score is a helpful tool to quantify cardiovascular health (CVH) metrics. We sought to assess sex differences in relation to LE8 and its components along with association with mortality.
METHODS
The National Health and Nutrition Examination Survey (NHANES) between 2009 and 2018 was utilized to evaluate the prevalence of health metrics included in LE8 among adult participants > age 18, stratified by sex. We categorized overall CVH, health factors, and health behaviors into 3 levels (low: <50, moderate: 50 -79, high: ≥80) following the AHA's algorithm. Health metrics were further subdivided into health behaviors (diet, physical activity, nicotine exposure, and sleep) and health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure). LE8 scores were also evaluated based on age, race/ethnicity, and socioeconomic status. Cox proportional hazard models were used to evaluate the association between the levels of CVH and risk of all-cause and cardiovascular mortality, with adjustment for age group and race.
RESULTS
Among 22,761 participants, 52 % were female. Overall CVH score was similar in both females and males (65.8 vs. 65.9). Females had higher health factors score (64.3 vs. 63.1, < 0.001) and lower health behaviors score (67.2 vs 68.6, < 0.001). Amongst individual metrics, blood pressure score was higher in females (73.2 vs. 67.7, < 0.001) while males had higher physical activity score (70.6 vs. 54.9, < 0.001). For individuals under 65 years of age, overall CVH and health factors scores were higher in females while in those age 65 or older, males had higher scores. The most prominent sex differences were noted in non-Hispanic Black females who had significantly lower CVH scores than Black males (62.6 vs. 74.7, respectively, < 0.001. High LE8 scores vs. low LE8 scores demonstrated lower all-cause (HR 0.37 vs 0.35) and CV mortality (HR 0.35 vs. 0.36) in both males and females, respectively (p-interaction 0.21 and 0.28). High health behaviors scores also demonstrated a significant association with lower all-cause (0.34 vs. 0.24) and CV mortality (HR 0.47 vs. 0.26) in both males and females, respectively (p-interaction 0.20 and 0.11).
CONCLUSIONS
We demonstrate important sex differences in CVH metrics along with notable variations based on age and race/ethnicity. Furthermore, we highlight that CVH metrics including health factors and health behaviors are associated with mortality in both females and males. These findings underscore the importance of designing and implementing effective strategies for both sexes, aimed at targeting these specific factors.
PubMed: 38939696
DOI: 10.1016/j.ajpc.2024.100685 -
JACC. Advances Apr 2024A treatment strategy for congenital heart defects with moderate to severe pulmonary arterial hypertension (PAH) has not been established.
BACKGROUND
A treatment strategy for congenital heart defects with moderate to severe pulmonary arterial hypertension (PAH) has not been established.
OBJECTIVES
The purpose of this study was to identify patients in whom a treat and repair strategy was considered and to examine pretreatment variables associated with successful defect repair.
METHODS
Patients with atrial or ventricular septal defect and PAH (pulmonary vascular resistance [PVR] ≥ 5 Wood units) eligible for the treat and repair strategy were included. Hemodynamics among pretreatment, pre-repair, and post-defect repair were compared. Clinical outcomes in patients with or without defect repair were also compared. Clinical outcomes included all-cause death, hospitalization for worsening pulmonary hypertension, and lung transplantation.
RESULTS
Among 25 eligible for the treat and repair strategy, 20 underwent successful repair (repaired group) and 5 did not have a repair (unrepaired group). In the repaired group, PVR significantly decreased from 9.6 ± 2.6 WU at pretreatment to 5.0 ± 3.4 pre-repair (ß coefficient -4.6 [95% CI: -5.9 to -3.3]). The pulmonary to systemic blood flow ratio (Qp/Qs) increased from 1.5 ± 0.6 at pretreatment to 2.4 ± 1.3 pre-repair (ß coefficient 0.9 [95% CI: 0.4-1.38]). In the unrepaired group, pretreatment PVR decreased with treatment; however, PVR remained elevated. Qp/Qs did not change between pretreatment and post-treatment. The repaired group had a better prognosis than the unrepaired group (HR 0.092 [95% CI: 0.009-0.905]). Pretreatment mean pulmonary artery pressure, PVR, Qp/Qs, and arterial oxygen saturations were associated with undergoing defect repair.
CONCLUSIONS
In this small cohort, a treat and repair strategy was successfully used in a significant proportion of the patients with congenital heart defects with moderate to severe PAH.
PubMed: 38939653
DOI: 10.1016/j.jacadv.2024.100887 -
JACC. Advances May 2024The prognostic value of cardiac damage staging classification based on the extent of extravalvular damage has been proposed in moderate/severe aortic stenosis (AS).
BACKGROUND
The prognostic value of cardiac damage staging classification based on the extent of extravalvular damage has been proposed in moderate/severe aortic stenosis (AS).
OBJECTIVES
The purpose of this study was to assess the association of cardiac damage staging with mortality across the spectrum of patients with AS following aortic surgical or transcatheter aortic valve replacement (AVR).
METHODS
We conducted a pooled meta-analysis of Kaplan-Meier-derived reconstructed time-to-event data from studies published through February 2023.
RESULTS
In total, 16 studies (n = 14,499) met our eligibility criteria and included 12,282 patients with symptomatic severe AS and 2,217 patients with asymptomatic severe/moderate AS. For patients with symptomatic severe AS, all-cause mortality was 24.0%, 27.7%, 38.0%, 56.3%, and 57.3% at 5 years in patients with cardiac damage stage 0, 1, 2, 3, and 4, respectively (stage 0 as reference; HR in stage 1: 1.30 [95% CI: 1.03-1.64]; = 0.029; stage 2: 1.74 [95% CI: 1.41-2.16]; < 0.001; stage 3: 2.92 [95% CI: 2.35-3.64]; < 0.001, and stage 4: 3.51 [95% CI: 2.79-4.41]; < 0.001). For patients with asymptomatic moderate/severe AS, all-cause mortality was 19.3%, 36.9%, 51.7%, and 67.8% at 8 years in patients with cardiac damage stage 0, 1, 2, and 3 to 4, respectively (HR in stage 1: 1.70 [95% CI: 1.21-2.38]; = 0.002; stage 2: 2.20 [95% CI: 1.60-3.02]; < 0.001; and stage 3 to 4: 3.90 [95% CI: 2.79-5.47]; < 0.001).
CONCLUSIONS
In patients undergoing AVR across the symptomatic and severity spectrum of AS, cardiac damage staging at baseline has important prognostic implications. This pooled meta-analysis in patients undergoing AVR suggests that staging of baseline cardiac damage could be considered for timing and selection of therapy in patients with moderate or severe AS to determine the need for earlier AVR or adjunctive pharmacotherapy to prevent irreversible cardiac damage and improve the long-term prognosis.
PubMed: 38939639
DOI: 10.1016/j.jacadv.2024.100959 -
Gynecologic Oncology Reports Aug 2024Endometrial large cell neuroendocrine carcinoma (LCNEC) is a highly malignant tumor that presents with neuroendocrine function. It is difficult to diagnose at an early...
Endometrial large cell neuroendocrine carcinoma (LCNEC) is a highly malignant tumor that presents with neuroendocrine function. It is difficult to diagnose at an early stage. Moreover, the diagnosis depends on the pathological and immunohistochemical findings. It is also prone to distant metastasis, but is difficult to treat and shows poor prognosis. Presently, there exists no unified treatment plan, and the prognosis of this disease is also poor. We reported here an analysis and literature review of a case of endometrial LCNEC to facilitate the comprehension of this disease and provide help toward clinical diagnosis and treatment.
PubMed: 38939507
DOI: 10.1016/j.gore.2024.101429 -
JACC. Advances Feb 2024
PubMed: 38939408
DOI: 10.1016/j.jacadv.2023.100791