Sleep apnea is a common sleep disorder. The availability of an easy-to-use sleep apnea predictor would provide a public health benefit by promoting early diagnosis and treatment. Our goal was to develop a prediction tool that used commonly available variables and was accessible to the public through a web site. Using data from polysomnography (PSG) studies that measured the apnea-hypopnea index (AHI), we built a machine learning tool to predict the presence of moderate to severe obstructive sleep apnea (OSA) (defined as AHI ≥15). Our tool employs only seven widely available predictor variables: age, sex, weight, height, pulse oxygen saturation, heart rate and respiratory rate. As a preliminary step, we used 16,958 PSG studies to examine eight machine learning algorithms via five-fold cross validation and determined that XGBoost exhibited superior predictive performance. We then refined the XGBoost predictor by randomly partitioning the data into a training and a test set (13,566 and 3392 PSGs, respectively) and repeatedly subsampling from the training set to construct 1000 training subsets. We evaluated each of the resulting 1000 XGBoost models on the single set-aside test set. The resulting classification tool correctly identified 72.5 % of those with moderate to severe OSA as having the condition (sensitivity) and 62.8 % of those without moderate to-severe OSA as not having it (specificity); overall accuracy was 66 %. We developed a user-friendly publicly available website (https://manticore.niehs.nih.gov/OSApredictor). We hope that our easy-to-use tool will serve as a screening vehicle that enables more patients to be clinically diagnosed and treated for OSA.
BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, Pâ =â .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, Pâ =â .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.
SOS1, a guanine nucleotide exchange factor (GEF), plays a critical role in catalyzing the conversion of KRAS from its GDP- to GTP-bound form, regardless of KRAS mutation status, and represents a promising new drug target to treat all KRAS-driven tumors. Herein, we employed a scaffold hopping strategy to design, synthesize, and optimize a series of novel binary ring derivatives as SOS1 inhibitors. Among them, compound 10f (HH0043) displayed potent activities in both biochemical and cellular assays and favorable pharmacokinetic profiles. Oral administration of HH0043 resulted in a significant tumor inhibitory effect in a subcutaneous KRAS G12C-mutated NCI-H358 (human lung cancer cell line) xenograft mouse model, and the tumor inhibitory effect of HH0043 was superior to that of BI-3406 at the same dose (total growth inhibition, TGI: 76% vs 49%). On the basis of these results, HH0043, with a novel 1,7-naphthyridine scaffold that is distinct from currently reported SOS1 inhibitors, is nominated as the lead compound for this discovery project.
Recent studies have highlighted the biological significance of cuproptosis in disease occurrence and development. However, it remains unclear whether cuproptosis signaling also has potential impacts on tumor initiation and prognosis of gastric cancer (GC). In this study, 16 cuproptosis-related genes (CRGs) transcriptional profiles were harnessed to perform the regularized latent variable model-based clustering in GC. A cuproptosis signature risk scoring (CSRS) scheme, based on a weighted sum of principle components of the CRGs, was used to evaluate the prognosis and risk of individual tumors of GC. Four distinct cuproptosis signature-based clusters, characterized by differential expression patterns of CRGs, were identified among 1136 GC samples across three independent databases. The four clusters were also associated with different clinical outcomes and tumor immune contexture. Based on the CSRS, GC patients can be divided into CSRS-High and CSRS-Low subtypes. We found that DBT, MTF1, and ATP7A were significantly elevated in the CSRS-High subtype, while SLC31A1, GCSH, LIAS, DLAT, FDX1, DLD, and PDHA1 were increased in the CSRS-Low subtype. Patients with CSRS-Low score were characterized by prolonged survival time. Further analysis indicated that CSRS-Low score also correlated with greater tumor mutation burden (TMB) and higher mutation rates of significantly mutated genes (SMG) in GC. In addition, the CSRS-High subtype harbored more significantly amplified focal regions related to tumorigenesis (3q27.1, 12p12.1, 11q13.3, etc.) than the CSRS-Low tumors. Drug sensitivity analyses revealed the potential compounds for the treatment of gastric cancer with CSRS-High score, which were experimentally validated using GC cells. This study highlights that cuproptosis signature-based subtyping is significantly associated with different clinical features and molecular landscape of GC. Quantitative evaluation of the CSRS of individual tumors will strengthen our understanding of the occurrence and development of cuproptosis and the treatment progress of GC.
Background and Objective: With advances in gut microbiome research, it has been recognized that the gut microbiome has an important and far-reaching impact on many human diseases, including cancer. Therefore, more and more researchers are focusing on the treatment of gut flora in tumors. In this article, we present a review of the mechanisms of gut microbes in tumor immunotherapy and related studies to provide reference for further research and insights into the clinical application of gut microbes. Methods: Between April 25, 2023, and November 25, 2023, we searched for articles published only in English between 1984 and 2023 using the databases PubMed, American Medical Association and Elsevier ScienceDirect using the keywords "gut microbiology" and "tumor" or "immunotherapy". Key Content and Findings: The gastrointestinal tract contains the largest number of microorganisms in the human body. Microorganisms are involved in regulating many physiological activities of the body. Studies have shown that gut microbes and their derivatives are involved in the occurrence and development of a variety of inflammations and tumors, and changes in their abundance and proportion affect the degree of cancer progression and sensitivity to immunotherapy. Gut microbiota-based drug research is ongoing, and some anti-tumor studies have entered the clinical trial stage. Conclusions: The abundance and proportion of intestinal microorganisms influence the susceptibility of tumors to tumor immunotherapy. This article reviewed the effects and mechanisms of gut microbes on tumor immunotherapy to further explore the medical value of gut microbes in tumor immunotherapy.
Background: Brain waves during sleep are involved in sensing and regulating peripheral glucose level. Whether brain waves in patients with diabetes differ from those of healthy subjects is unknown. We examined the hypothesis that patients with diabetes have reduced sleep spindle waves, a form of brain wave implicated in periphery glucose regulation during sleep. Methods: From a retrospective analysis of polysomnography (PSG) studies on patients who underwent sleep apnea evaluation, we identified 1,214 studies of patients with diabetes mellitus (>66% type 2) and included a sex- and age-matched control subject for each within the scope of our analysis. We similarly identified 376 patients with prediabetes and their matched controls. We extracted spindle characteristics from artifact-removed PSG electroencephalograms and other patient data from records. We used rank-based statistical methods to test hypotheses. We validated our finding on an external PSG dataset. Results: Patients with diabetes mellitus exhibited on average about half the spindle density (median=0.38 spindles/min) during sleep as their matched control subjects (median=0.70 spindles/min) (P<2.2e-16). Compared to controls, spindle loss was more pronounced in female patients than in male patients in the frontal regions of the brain (P=0.04). Patients with prediabetes also exhibited signs of lower spindle density compared to matched controls (P=0.01-0.04). Conclusions: Patients with diabetes have fewer spindle waves that are implicated in glucose regulation than matched controls during sleep. Besides offering a possible explanation for neurological complications from diabetes, our findings open the possibility that reversing/reducing spindle loss could improve the overall health of patients with diabetes mellitus.
STUDY OBJECTIVES: Randomized controlled trials have shown that combining norepinephrine reuptake inhibitors and antimuscarinics can ameliorate the severity of obstructive sleep apnea (OSA). This article explores whether the effectiveness and safety of combining norepinephrine reuptake inhibitors with antimuscarinic agents surpass monotherapy for treating OSA. METHODS: We searched the randomized controlled trials (RCTs) with adult patients of OSA who received combination and monotherapy in eight databases from inception until April 5, 2023, next evaluated the included studies' quality, and conducted a meta-analysis and systematic review. The primary outcome was the apnea-hypopnea index (AHI). Secondary outcome measures included loop gain, hypoxic load, oxygen desaturation index, and Vpassive, among other indicators. We assessed the quality of the studies using Cochrane Methods criteria. RESULTS: Identifying four RCTs for systematic review and two for meta-analysis. The results of the meta-analysis showed that norepinephrine reuptake inhibitors combined with antimuscarinic agents in patients with OSA prolonged total sleep time by a mean of 28.20 min [95% CI (5.78, 50.61), P = 0.01], increased sleep efficiency by 4.73% [95%CI (0.50, 8.97), P = 0.03] compared with norepinephrine reuptake inhibitors alone. Other indices and adverse events were no statistical significance. The systematic reviews revealed that norepinephrine reuptake inhibitors combined with antimuscarinics may be superior to monotherapy in improving AHI and endotypic traits. CONCLUSIONS: This article demonstrated the potential advantages of combining norepinephrine reuptake inhibitors plus antimuscarinics for treating OSA, contrasting with the norepinephrine reuptake inhibitors alone, and revealed no statistically significant safety.
Electroencephalograms can capture brain oscillatory activities during sleep as a form of electrophysiological signals. We analysed electroencephalogram recordings from full-night in-laboratory polysomnography from 100 patients with Down syndrome, and 100 age- and sex-matched controls. The ages of patients with Down syndrome spanned 1 month to 31 years (median 4.4 years); 84 were younger than 12 years, and 54 were male. From each electroencephalogram, we extracted relative power in six frequency bands or rhythms (delta, theta, alpha, slow sigma, fast sigma, and beta) from six channels (frontal F3 and F4, central C3 and C4, and occipital O1 and O2) during five sleep stages (N3, N2, N1, R and W)-180 features in all. We examined differences in relative power between Down syndrome and control electroencephalograms for each feature separately. During wake and N1 sleep stages, alpha rhythms (8.0-10.5 Hz) had significantly lower power in patients with Down syndrome than controls. Moreover, the rate of increase in alpha power with age during rapid eye movement sleep was significantly slower in Down syndrome than control subjects. During wake and N1 sleep, delta rhythms (0.25-4.5 Hz) had higher power in patients with Down syndrome than controls. During N2 sleep, slow sigma rhythms (10.5-12.5 Hz) had lower power in patients with DS than controls. These findings extend previous research from routine electroencephalogram studies demonstrating that patients with Down syndrome had reduced circadian amplitude-the difference between wake alpha power and deep sleep delta power was smaller in Down syndrome than control subjects. We envision that these brain oscillatory activities may be used as surrogate markers for clinical trials for patients with Down syndrome.
Malignant tumours of the digestive system cover a wide range of diseases that affect the health of people to a large extent. Angiogenesis is indispensable in the development, and metastasis of tumours, mainly in two ways: occupation or formation. Vessels can provide nutrients, oxygen, and growth factors for tumours to encourage growth and metastasis, so cancer progression depends on simultaneous angiogenesis. Recently, exosomes have been proven to participate in the angiogenesis of tumours. They influence angiogenesis by binding to tyrosine kinase receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 with different affinities, regulating Yap-VEGF pathway, Akt pathway or other signaling pathway. Additionally, exosomes are potential therapeutic vectors that can deliver many types of cargoes to different cells. In this review, we summarize the roles of exosomes in the angiogenesis of digestive system tumours and highlight the clinical application prospects, directly used as targers or delivery vehicles, in antiangiogenic therapy.
BACKGROUND: Tumor mutational load (TML) has emerged as a potential biomarker for multiple solid tumors. However, data on its prognostic impact on upper gastrointestinal (UGI) cancer are limited. Therefore, the aim of this systematic review and meta-analysis was to assess the prognostic value of TML for the survival of patients with UGI cancer. METHOD: A comprehensive search of the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to February 13, 2023. Eleven studies met our inclusion criteria. Hazard ratios (HRs) for progression-free survival and overall survival and their 95% confidence intervals (CIs) were calculated. Subsequently, the combined HR and its 95% CI were calculated for UGI tract cancers in the high and low TML groups. I2 statistics and p-values were used to evaluate heterogeneity. Publication bias, sensitivity, and subgroup analyses were performed to determine sources of heterogeneity. RESULTS: In total, 932 patients with UGI tract cancer from 11 publications were included. The high TML group treated with immunotherapy showed significantly improved overall survival (HR = 0.68; 95% CI: 0.53, 0.86; p = .001) and progression-free survival (HR = 0.74; 95% CI: 0.58, 0.95; p = .020) compared with the low TML group. CONCLUSION: Our study demonstrated that patients with UGI tumors and higher TML have a better prognosis with immunotherapy, suggesting that TML is a promising predictive biomarker for immunotherapy. REGISTRATION: The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO Registration No: CRD42023405596).
Gastrointestinal Neoplasms , Immune Checkpoint Inhibitors , Humans , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/genetics , Prognosis , Mutation , Biomarkers
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration. The expression of LHPP was assessed in human GC specimens and cell lines. Various assays were employed to evaluate the impact of LHPP on GC cells. RNA sequencing and Gene Set Enrichment Analysis were conducted to unravel the mechanism through which LHPP regulates GC cell behavior. Additionally, xenograft nude mouse models were utilized to investigate the in vivo effects of LHPP. The findings indicate that LHPP, functioning as a tumor suppressor, is downregulated in both GC tissues and cells. LHPP emerges as an independent risk factor for GC patients, and its expression level exhibits a positive correlation with patient prognosis. LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin-like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.
BACKGROUND: For gastric cancer with total gastrectomy, the usual laparoscopic surgical approaches are totally laparoscopic total gastrectomy (TLTG) and laparoscopic-assisted total gastrectomy (LATG). Due to its difficult anastomotic technique, the adoption of TLTG is limited. Therefore, surgeons prefer using LATG, which also led to TLTG being somewhat overlooked, so there is no clear conclusion today as to which surgical procedure is more favorable to the patient's recovery. This article aimed to compare the safety and short-term outcomes of the two surgical approaches. MATERIALS AND METHODS: Studies comparing TLTG and LATG, published up to December 2022, were searched in PubMed, Web of Science, and Embase databases. The study outcomes, including operative time, blood loss, anastomosis time, number of retrieved lymph nodes, proximal and distal resection margins, time to first fluid and soft diet, hospitalization duration, time to first flatus, and postsurgical and anastomotic complications, were compared between these two different surgical procedures. Statistics were analyzed with RevMan 5.4 and Stata 13.1. RESULTS: Fifteen publications were included in this study. The total sample included 3023 cases. The meta-analysis revealed no significant difference in overall postoperative complications between the two surgical approaches ( P >0.05). Compared with LATG, TLTG led to reduced intraoperative blood loss ( P <0.0001), an increased number of lymphatic node dissections ( P <0.0001), and decreased hospitalization duration ( P =0.002). However, operative time, anastomosis time, pulmonary infection, resection margins, time to first fluid and soft diet, time to first flatus and anastomosis-related complications were no significant difference between TLTG and LATG groups ( P >0.05). CONCLUSION: TLTG did not lead to an increase in overall postoperative complications, which is a reliable surgical approach for treatment of gastric cancer. Moreover, it may reduce harm to patients and enable them to obtain better surgical outcomes.
Laparoscopy , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Flatulence/complications , Flatulence/surgery , Margins of Excision , Laparoscopy/adverse effects , Laparoscopy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Gastrectomy/adverse effects , Gastrectomy/methods , Treatment Outcome , Retrospective Studies
Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors.
Carcinogenesis , Fanconi Anemia Complementation Group D2 Protein , Neoplasms , Humans , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Carcinogenesis/genetics , DNA Damage , Fanconi Anemia/genetics , Fanconi Anemia/metabolism , Fanconi Anemia Complementation Group D2 Protein/genetics , Fanconi Anemia Complementation Group D2 Protein/metabolism , Neoplasms/genetics , Neoplasms/pathology
INTRODUCTION: Gastric cancer (GC) diagnosed in the elderly population has become a serious public health problem worldwide. Given the combined effects of frailty and the consequences of cancer treatment, older individuals with GC are more likely than young patients to suffer from postoperative complications and poor clinical outcomes. Nutrition, functional capacity and psychological state-based multimodal prehabilitation, which is dominated by Enhanced Recovery After Surgery (ERAS) pathway management, has been shown to reduce postoperative complications, promote functional recovery and decrease hospitalisation time in certain malignancies. However, no previous studies have investigated the clinical application of multimodal prehabilitation in frail older patients with GC. METHODS AND ANALYSIS: The study is a prospective, multicentre randomised controlled trial in which a total of 368 participants who meet the inclusion criteria will be randomised into either a prehabilitation group or an ERAS group. The prehabilitation group will receive multimodal prehabilitation combined with ERAS at least 2 weeks before the gastrectomy is performed, including physical and respiratory training, nutritional support, and therapy and psychosocial treatment. The ERAS group patients will be treated according to the ERAS pathway. All interventions will be supervised by family members. The primary outcome measures are the incidence and severity of postoperative complications. Secondary outcomes include survival, functional capacity and other short-term postoperative outcomes. Overall, the multimodal prehabilitation protocol may improve functional capacity, reduce the surgical stress response and concomitant systemic inflammation, and potentially modulate the tumour microenvironment to improve short-term and long-term clinical outcomes and patients' quality of life. ETHICS AND DISSEMINATION: All procedures and participating centres of this study were approved by their respective ethics committees (QYFYKYLL 916111920). The final study results will be published separately in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05352802.
Frail Elderly , Stomach Neoplasms , Humans , Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/complications , Preoperative Exercise , Preoperative Care/methods , Prospective Studies , Quality of Life , Postoperative Complications/epidemiology , Tumor Microenvironment , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
The vast majority of severe (Type 0) spinal muscular atrophy (SMA) cases are caused by homozygous deletions of survival motor neuron 1 (SMN1). We report a case in which the patient has two copies of SMN1 but clinically presents as Type 0 SMA. The patient is an African American male carrying a homozygous maternally inherited missense variant (c.796T>C) in a cis-oriented SMN1 duplication on one chromosome and an SMN1 deletion on the other chromosome (genotype: 2*+0). Initial extensive genetic workups including exome sequencing were negative. Deletion analysis used in the initial testing for SMA also failed to detect SMA as the patient has two copies of SMN1. Because of high clinical suspicion, SMA diagnosis was finally confirmed based on full-length SMN1 sequencing. The patient was initially treated with risdiplam and later gene therapy with onasemnogene abeparvovec at 5 months without complications. The patient's muscular weakness has stabilized with mild improvement. The patient is now 28 months old and remains stable and diffusely weak, with stable respiratory ventilatory support. This case highlights challenges in the diagnosis of SMA with a non-deletion genotype and provides a clinical example demonstrating that disruption of functional SMN protein polymerization through an amino acid change in the YG-box domain represents a little known but important pathogenic mechanism for SMA. Clinicians need to be mindful about the limitations of the current diagnostic approach for SMA in detecting non-deletion genotypes.
Organoids are established through in vitro 3D culture, and they can mimic the structure and physiological functions of organs or tissues in vivo. Organoids have attracted much attention in recent years. They can provide a reliable technology platform for cancer research and treatment and are a valuable preclinical model for academic research and personalized medicine. A number of studies have confirmed that organoids have great application prospects in new drug development, drug screening, tumour mechanism research, and precision medicine. In this review, we mainly focus on recent advances in the application of organoids in cancer research. We also discussed the opportunities and challenges facing organoids, hoping to indicate directions for the development of organoids in the future.
DNASE1L3, an enzyme highly expressed in DCs, is functionally important for regulating autoimmune responses to self-DNA and chromatin. Deficiency of DNASE1L3 leads to development of autoimmune diseases in both humans and mice. However, despite the well-established causal relationship between DNASE1L3 and immunity, little is known about the involvement of DNASE1L3 in regulation of antitumor immunity, the foundation of modern antitumor immunotherapy. In this study, we identify DNASE1L3 as a potentially new regulator of antitumor immunity and a tumor suppressor in colon cancer. In humans, DNASE1L3 is downregulated in tumor-infiltrating DCs, and this downregulation is associated with poor patient prognosis and reduced tumor immune cell infiltration in many cancer types. In mice, Dnase1l3 deficiency in the tumor microenvironment enhances tumor formation and growth in several colon cancer models. Notably, the increased tumor formation and growth in Dnase1l3-deficient mice are associated with impaired antitumor immunity, as evidenced by a substantial reduction of cytotoxic T cells and a unique subset of DCs. Consistently, Dnase1l3-deficient DCs directly modulate cytotoxic T cells in vitro. To our knowledge, our study unveils a previously unknown link between DNASE1L3 and antitumor immunity and further suggests that restoration of DNASE1L3 activity may represent a potential therapeutic approach for anticancer therapy.
Colonic Neoplasms , Humans , Mice , Animals , Colonic Neoplasms/metabolism , Chromatin/metabolism , Immunotherapy , T-Lymphocytes, Cytotoxic , Tumor Microenvironment , Endodeoxyribonucleases/genetics , Endodeoxyribonucleases/metabolism
Lung adenocarcinoma (LUAD) is the most common type of lung cancer. LRP1B was initially identified as a cancer suppressor in several cancers. However, the potential biological phenotypes and molecular mechanisms of LRP1B in LUAD have not been fully investigated. In our study, we showed that the expression of LRP1B in LUAD tissues was lower than that in normal tissues. Knockdown of LRP1B markedly enhanced malignancy of LUAD cells. Genomic analysis indicated that the population expressing low-levels of LRP1B had higher genomic instability, which accounted for a larger proportion of aneuploidy and inflammation subtyping. Enrichment analysis of bulk and cell-line transcriptomic data both showed that the low expression of LRP1B could induce the activation of IL-6-JAK-STAT3, chemokine, cytokine, and other inflammation signaling pathways. Moreover, our findings revealed that knockdown LRP1B enhanced the secretion of IL-6 and IL-8, as confirmed by ELISA assays. Further validation using PCR and WB confirmed that downregulation of LRP1B mRNA significantly upregulated the activity of the IL-6-JAK-STAT3 pathway. Collectively, this study highlights LRP1B as a tumor suppressor gene and reveals that LRP1B knockdown promotes malignant progression in LUAD by inducing inflammation through the IL-6-JAK-STAT3 pathway.
Human sleep architecture is structured with repeated episodes of rapid-eye-movement (REM) and non-rapid-eye-movement (NREM) sleep. An overnight sleep study facilitates identification of macro and micro changes in the pattern and duration of sleep stages associated with sleep disorders and other aspects of human mental and physical health. Overnight sleep studies record, in addition to electroencephalography (EEG) and other electro-physiological signals, a sequence of sleep-stage annotations. SSAVE, introduced here, is open-source software that takes sleep-stage annotations and EEG signals as input, identifies and characterizes periods of NREM and REM sleep, and produces a hypnogram and its time-matched EEG spectrogram. SSAVE fills an important gap for the rapidly growing field of sleep medicine by providing an easy-to-use tool for sleep-period identification and visualization. SSAVE can be used as a Python package, a desktop standalone tool or through a web portal. All versions of the SSAVE tool can be found on: https://manticore.niehs.nih.gov/ssave.
