The role of the nuclear pore protein NUP54 in tumorigenesis and progression remains unclear. By integrating multiomics data from TCGA, GTEx, CPTAC, and other sources, in this study, the first pan-cancer landscape of NUP54 was systematically delineated: its mRNA and protein expression levels are significantly upregulated in most types of cancer, including lung adenocarcinoma, hepatocellular carcinoma, and gastric cancer. It has a high diagnostic value across several types of cancer, including cholangiocarcinoma and pancreatic cancer. Its prognostic value has high tissue specificity: serving as an independent risk factor in low-grade glioma, lung adenocarcinoma, and pancreatic cancer, while protecting against renal clear cell carcinoma. Focusing on lung adenocarcinoma, multi-cohort clinical assessment, single-cell transcriptomics analysis, and functional experiments confirmed that high expression of NUP54 is an independent predictor of poor patient prognosis and significantly promotes the proliferation of cancer cells, colony formation, and in vivo tumorigenesis. NUP54 activates the HIF-1α signaling pathway to upregulate key glycolytic molecules LDHA, PKM2, and GLUT1, thereby driving glucose uptake, lactate production, and high ATP levels to promote metabolic reprogramming. This NUP54-associated phenotype was attenuated by the HIF-1α inhibitor PX-478 in vitro and in vivo. Overall, this study identifies NUP54 as a potential prognostic biomarker in LUAD and suggests that the NUP54/HIF-1α/glycolysis-related pathway may represent a biological mechanism worthy of further investigation.

Abstract Background Based on efficacy data from early phase study, the synergistic effect of ACT001 with WBRT/ICI was evaluated in expanded cohorts of NSCLC subjects. Methods Pretreated NSCLC with 4 or more metastatic brain lesions, most negative for driver mutations, were randomized with 2:1 ratio to ACT001 and Placebo cohorts and treated with WBRT and ACT001 or placebo at 400mg, BID followed by maintenance treatment. Concomitant ICI or chemotherapies were allowed. Brain MRI and CT scans were performed for intracranial and extracranial tumor assessments per RECIST 1.1 or RANO-BM criteria with intracranial ORR at 3-month after WBRT and OS as primary and secondary endpoints. Results 32 and 17 NSCLC subjects including 78.1% and 88.2% with adenocarcinoma were randomly enrolled to ACT001 and Placebo cohorts. 71.9% and 70.5% subjects received at least two lines of prior anti-tumor treatments. Subjects were balanced in age, GPA/KPS and other baseline characteristics. 9 and 7 subjects took ICI in ACT001 and Placebo cohorts during study. With similar ratio of TEAEs and TRAEs reported in two cohorts, most common TRAEs were grade 1 or 2 events and related to laboratory, gastrointestinal and metabolic abnormalities in two cohorts. Comparable overall QLQ-C30 scores were observed in two cohorts within three months after WBRT. Improved intracranial ORRs were noted in FAS (25.0% in ACT001 vs 5.9% in Placebo, p = 0.0653), PPS (33.3% vs 7.7%, p = 0.0974) and IN-REAS (not shown). Although no OS improvement was noted in FAS, the ICI sub-group analysis revealed a trend of median OS improvement by ACT001: 11.4 vs 4.7 months, HR: 0.5, p = 0.2419. Conclusion Data from early and current trials revealed an encouraging synergistic effect between ACT001 and WBRT/ICI warranting in-depth efficacy assessment of ACT001, the first dual enhancer of ICI and genotoxic treatments through STAT3 and NF-κB inhibition, in newly diagnosed NSCLC patients.

BACKGROUND:Chemoresistance by stemness in HPV-induced cervical carcinogenesis has significant implications for the overall disease-specific survival of the patients. To date, there are no reports related to the implications of significant aspects of inflammation and microbiome-mediated epigenetics in cervical cancers. OBJECTIVE:The current systematic review delineates the significant aspects of the inflammation-related pathophysiology, cervical cancer diagnosis based on the HPV-indued stemness, and microbiome-mediated epigenetic markers to develop personalized therapies to target the stemness-acquired indefinitely dividing cancer stem cells. METHODS:We performed a systematic review without a meta-analysis. We searched several public databases, such as Pubmed, ReleMed, National Library of Medicine, and Scopus, related to inflammation, metabolomics, microbiome-mediated epigenetic markers, and HPV-induced stemness. RESULTS AND CONCLUSION:The review significantly described the correlation between microbial inflammation and stem cell stochasticity of HPV-Induced cervical cancer and the expression of epigenetics-based biomarkers through microbiome and metabolome to foster the cervical cancer progression. These are major risk factors that can cause cervical dysplasia with substantial therapy resistance in cervical cancer patients. The qualitative and quantitative examination of the spatial transcriptomic expression of these stemness markers in the dividing cervical cancer stem cells has significant implications in the clinical sector to develop early personalized medicine to prevent cervical precancerous lesions depending on the prognosis of the cervical cancer patients. Mainly, the combinatorial regimen of current therapeutic modalities, along with microbiome-related therapies with future landscape of epigenetics-modulated therapies, may enhance overall disease-specific survival by modulating the stochastic dynamics of basal epithelial cells across the cervical region.

BACKGROUND:Breast cancer is the most common malignancy among women, posing major health, social, and economic challenges worldwide. This study analyzed global breast cancer incidence and mortality in 2022 using Global Cancer Observatory (GLOBOCAN) 2022 data and projected the disease burden to 2050. METHODS:Breast cancer incidence and mortality were categorized by region and age. Correlations between age-standardized rates (ASRs) and the Human Development Index (HDI) were assessed using Spearman's rank correlation coefficient (ρ). Future burden estimates for 2050 were projected based on current trends. RESULTS:In 2022, approximately 2.30 million new breast cancer cases and 666,103 deaths were reported globally. Age-specific patterns of breast cancer incidence and mortality differed across development HDI levels with incidence peaking at ages 45-69 years and mortality at ages 50-≥85 years across HDI levels. The proportion of cases and deaths among women aged ≥50 years relative to those aged ≤49 years increased with HDI, ranging from 79% vs . 21% for incidence and 90% vs . 10% for deaths in very high HDI countries to 51% vs . 49% and 59% vs . 41% in low HDI countries. HDI showed strong positive correlations with age-standardized incidence rates (ρ = 0.773), period incidence rates (ρ = 0.958), and period mortality rates (ρ = 0.907), and a negative correlation with mortality-to-incidence ratios (ρ = -0.817). Projections indicate that by 2050, breast cancer cases may rise to 3.55 million and deaths to 1.14 million if current patterns continue. CONCLUSIONS:Breast cancer remains a major global health concern. Strengthening prevention, early detection, and therapeutic strategies is essential to reduce incidence, improve survival, and alleviate its global burden.

Conventional therapeutic modalities against the cancers such as surgery, chemotherapy (CT) and radiotherapy (RT) have limited efficacy due to drug resistance, and adverse effects. Recent developments in nanoscience emphasized novel approaches to overcome the aforementioned limitations and subsequently improve overall clinical outcomes in cancer patients. Photodynamic therapy (PDT), photothermal therapy (PTT), and radiodynamic therapy (RDT) can be used as cancer treatments due to their high selectivity, low drug resistance, and low toxicity. Mitocans are the therapeutic molecules that can produce anti-cancer effects by modulating mitochondria functions and they have significant implications in cancer therapy. Mitochondria- targeted therapy is a promising strategy in cancer treatment as these organelles play a crucial function in the regulation of apoptosis and metabolism in tumor cells and are more vulnerable to hyperthermia and oxidative damage. The aim of this review is used to explore the targeting efficacy of mitocans in the nanotherapeutic formulation when combined with therapies like PDT, PTT, RDT. We searched several databases include Pubmed, relemed, scopus, google scholar, Embase and collected the related information to the efficacy of mitocans in nanotherapeutics when combined with photo-radiotherapy to target chemo/radio-resisant tumor cells. In this review, we vividly described research reports pertinent to the selective delivery of chemotherapy molecules into specific sub-organelles which can significantly improve the efficiency of cancer treatment by targeting tumor cell metabolism. Furthermore, the rational design, functionalization and application of various mitochondrial targeting units, including organic phosphine/sulfur salts, quaternary ammonium salts, transition metal complexes, and mitochondria-targeted cancer therapy such as PDT, PTT, RDT, and others were summarized. Mainly, the efficacy of these modalities against mtDNA and additional nanotherapeutic strategies with photosensitizers, or radiotherapy to target mitochondrial metabolism in tumor cells with chemo/radio-resistance were delineated. This review can benefit nanotechnologists, oncologists, and radiation oncologists to develop rational designs and application of novel mitochondrial targeting drugs mainly to target metabolism in chemo/radio-resistant cancer cells in cancer therapy.

BACKGROUND:Diagnosing the presence of metastasis of pancreatic cancer is pivotal for patient management and treatment, with contrast-enhanced CT scans (CECT) as the cornerstone of diagnostic evaluation. However, this diagnostic modality requires a multifaceted approach. OBJECTIVE:To develop a convolutional neural network (CNN)-based model (PMPD, Pancreatic cancer Metastasis Prediction Deep-learning algorithm) to predict the presence of metastases based on CECT images of the primary tumour. DESIGN:CECT images in the portal venous phase of 335 patients with pancreatic ductal adenocarcinoma (PDAC) from the PanGenEU study and The First Affiliated Hospital of Zhengzhou University (ZZU) were randomly divided into training and internal validation sets by applying fivefold cross-validation. Two independent external validation datasets of 143 patients from the Radboud University Medical Center (RUMC), included in the PANCAIM study (RUMC-PANCAIM) and 183 patients from the PREOPANC trial of the Dutch Pancreatic Cancer Group (PREOPANC-DPCG) were used to evaluate the results. RESULTS:The area under the receiver operating characteristic curve (AUROC) for the internally tested model was 0.895 (0.853-0.937) and 0.779 (0.741-0.817) in the PanGenEU and ZZU sets, respectively. In the external validation sets, the mean AUROC was 0.806 (0.787-0.826) for the RUMC-PANCAIM and 0.761 (0.717-0.804) for the PREOPANC-DPCG. When stratified by the different metastasis sites, the PMPD model achieved the average AUROC between 0.901-0.927 in PanGenEU, 0.782-0.807 in ZZU and 0.761-0.820 in PREOPANC-DPCG sets. A PMPD-derived Metastasis Risk Score (MRS) (HR: 2.77, 95% CI 1.99 to 3.86, p=1.59e-09) outperformed the Resectability status from the National Comprehensive Cancer Network guideline and the CA19-9 biomarker in predicting overall survival. Meanwhile, the MRS could potentially predict developed metastasis (AUROC: 0.716 for within 3 months, 0.645 for within 6 months). CONCLUSION:This study represents a pioneering utilisation of a high-performance deep-learning model to predict extrapancreatic organ metastasis in patients with PDAC.

Objectives: Previous studies described the prognostic significance of nuclear factor erythroid 2-related factor 2 (Nrf2) in breast cancers. Nrf2 is significantly involved in inducing antioxidant responses in tumor cells to neutralize oxidative stress. A recent study by V Sanghvi et al 2019 demonstrated the role of fructosamine-3-kinase (FN3K) in Nrf2 deglycation in cancer but the prognostic significance based on pathological, clinical relevance has remained unknown in In this study, we determined the relevance of FN3K based on Prediction Analysis of Microarray 50 (PAM-50)algorithmbased breast cancer classification & FN3K gene expression patterns on tumor-node-metastasis (TNM) wise using The Cancer Genome Atlas (TCGA) database subsequently determined its expression patterns in luminal A (HR+/HER2 - (human epidermal growth factor receptor 2), ER (Estrogen Receptor positive)+/PR+(Progesterone Receptor positive), ER+/PR-, and ER-/PR+), luminal B (HR+/HER2+, ER+/PR+, ER+/PR-, and ER-/PR+ ), HER 2+ (ER-, PR-, HER2+), and TNBCs (Triple -Negative Breast Cancers) (ER-, PR-, HER2-) along differential protein expression patterns of Nrf2, and NQO1(NAD(P)H quinone oxidoreductase) (markers of oxidative stress). Methods: R -statistical computing, Kaplan Meier survival curves, immunohistochemistry, Western blotting was used to explore the expression of FN3K relative to the expression of Nrf2, and NQO1. Results: We observed significantly a higher FN3K gene expression in luminal B when compared to its expression in other cancer types, Basal, Her2, Luminal A, and normal tissue as per TCGA database. FN3K gene expression is significantly higher (P<0.05) in stage IV, and T4 compared to the other stages or sizes of breast cancer. Correlated expression of both genes confers significant implications in the patient's overall survival. A control study pertinent to FN3K, Nrf2, and NQO1 immunoreactivity is performed and the expression was highly evident in luminal A, luminal B when compared to HER 2+, TNBCs and adjacent normal breast tissue. Breast cancer disease -specific survival was determined based on the FN3K and Nrf2 gene expression patterns. Conclusion: Hence, this study described the relevance of FN3K-Nrf2 signaling in the breast cancers.

BACKGROUND:Sesquiterpene lactones are secondary plant metabolites with a wide variety of biological activities. The process of lactone conjugation to other pharmacophores can increase the efficacy and specificity of the conjugated agent effect on molecular targets in various diseases, including brain pathologies. Derivatives of biogenic indoles, including neurotransmitter serotonin, are of considerable interest as potential pharmacophores. Most of these compounds have neurotropic activity and, therefore, can be used in the synthesis of new drugs with neuroprotective properties.AIM:The aim of this experimental synthesis was to generate potential treatment agents for Alzheimer's disease using serotonin conjugated with natural sesquiterpene lactones.METHODS:Three novel compounds were obtained via the Michael reaction and used for biological testing. The obtained conjugates demonstrated complex neuroprotective activities. Serotonin conjugated to isoalantolactone exhibited strong antioxidant and mitoprotective activities.RESULTS:The agent was also found to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), prevent the aggregation of β-amyloid peptide 1-42, and protect SH-SY5Y neuroblastoma cells from neurotoxins such as glutamate and H2O2. In a transgenic animal model of Alzheimer's disease (5xFAD line), the conjugated agent restored declined cognitive functions and improved learning and memory.CONCLUSION:In conclusion, the obtained results indicate that serotonin conjugates to sesquiterpene lactones are promising agents for the treatment of symptoms associated with Alzheimer's disease.

Incidence of liver cancer as one of the most common cancers worldwide and become the significant contributor for the mortality among cancer patients. The disease burden, risk factors, and trends in incidence and mortality of liver cancer globally was described subsequently estimated the projections of liver cancer incidence or mortality by 2040. Data regarding age-standardized incidence and mortality rates for liver cancer was obtained from multiple databases, including GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD)-2019. Concentrating on worldwide variations, this thorough analysis offers insights into patterns of incidence and mortality based on gender and age. Our findings encompass significant indicators, including age-standardized rates (ASRs), average annual percentage change (AAPC), and future projections extending up to the year 2040. Liver cancer holds the sixth position in terms of most frequently diagnosed cancers and stands as the sixth leading cause of cancer-related deaths worldwide in 2020, accounting for 905,677 new cases and 782,000 fatalities. Additionally, liver cancer contributed to 12,528,421 age-standardized disability-adjusted life years (DALYs), with an age-standardized DALYs rate of 161.92 in 2019 worldwide. The age-specific incidence rates exhibited significant variations across different regions, showing a fivefold difference in males and females. A significant increase in incidence was observed in North Europe and Asia, while North African countries reported a higher mortality burden (ASR, 10 per 100,000) compared to developed countries. Since last few years, the incidence and mortality rates have increased and attained Annual Average Percentage Change (AAPC) incidence rate of 7.7 (95% CI 3.9-11.6) for men and the highest AAPC mortality rate of 12.2 (95% CI 9.5-15.0) for women. In 2019, Western Europe emerged as the high-risk region for DALYs related to smoking and alcohol consumption, while high-income North America carried a high risk for DALYs associated with a high body-mass index. The projected trend indicates a surge in new liver cancer incident cases, expected to rise from around 905,347 to an estimated 1,392,474 by 2040. This study described the evidence pertinent to higher incidence trends in liver cancer, particularly among both young and older adults, encompassing males and females, as well as those who are HIV-infected and HBsAg positive. A significant rise in the young population poses a significant public health concern that warrants attention from healthcare professionals to prioritize the promotion of health awareness and the development of effective cancer prevention strategies, particularly in many developing countries.

Hematopoiesis within the bone marrow (BM) is a complex and tightly regulated process predominantly influenced by immune factors. Aging, diabetes, and obesity are significant contributors to BM niche damage, which can alter hematopoiesis and lead to the development of clonal hematopoiesis of intermediate potential (CHIP). Genetic/epigenetic alterations during aging could influence BM niche reorganization for hematopoiesis or clonal hematopoiesis. CHIP is driven by mutations in genes such as Tet2, Dnmt3a, Asxl1, and Jak2, which are associated with age-related hematological malignancies. This literature review aims to provide an updated exploration of the functional aspects of BM niche cells within the hematopoietic microenvironment in the context of age-related hematological malignancies. The review specifically focuses on how immunological stressors modulate different signaling pathways that impact hematopoiesis. Methods: An extensive review of recent studies was conducted, examining the roles of various BM niche cells in hematopoietic stem cell (HSC) trafficking and the development of age-related hematological malignancies. Emphasis was placed on understanding the influence of immunological stressors on these processes. Recent findings reveal a significant microheterogeneity and temporal stochasticity of niche cells across the BM during hematopoiesis. These studies demonstrate that niche cells, including mesenchymal stem cells, osteoblasts, and endothelial cells, exhibit dynamic interactions with HSCs, significantly influenced by the BM microenvironment as the age increases. Immunosurveillance plays a crucial role in maintaining hematopoietic homeostasis, with alterations in immune signaling pathways contributing to the onset of hematological malignancies. Novel insights into the interaction between niche cells and HSCs under stress/aging conditions highlight the importance of niche plasticity and adaptability. The involvement of age-induced genetic/epigenetic alterations in BM niche cells and immunological stressors in hematopoiesis is crucial for understanding the development of age-related hematological malignancies. This comprehensive review provides new insights into the complex interplay between niche cells and HSCs, emphasizing the potential for novel therapeutic approaches that target niche cell functionality and resilience to improve hematopoietic outcomes in the context of aging and metabolic disorders. This review introduces novel concepts regarding the plasticity and adaptability of BM niche cells in response to immunological stressors and epigenetics. It proposes that targeted therapeutic strategies aimed at enhancing niche cell resilience could mitigate the adverse effects of aging, diabetes, and obesity on hematopoiesis and clonal hematopoiesis. Additionally, the review suggests that understanding the precise temporal and spatial dynamics of niche-HSC interactions and epigenetics influence may lead to innovative treatments for age-related hematological malignancies.

Objectives: Uterine corpus endometrial carcinoma (UCEC) is a malignant cancer that exhibits significant molecular heterogeneity, leading to distinct clinical outcomes. The aim of this study is to identify long non-coding RNAs (lncRNAs) with independent and superior prognostic value based on the tumor clinical stages in UCEC patients. Methods: The Cancer Genome Atlas (TCGA) was utilized to acquire clinical data and expression levels of lncRNAs and mRNAs in UCEC patients. Tumor samples were compared with normal samples using R-statistical computing and Cytoscape. Four lncRNA-expression signatures (LINC01224, AC015849.16, LINC00908, and LINC00092) were identified through tenfold cross-validation, t-tests, and univariate COX regression. Results: LINC00908 and LINC00092 exhibited a negative correlation with tumor stages and were downregulated in expression compared to normal samples. Conversely, LINC01224 and AC015849.16 were upregulated in tumor samples and positively correlated with the overall survival of UCEC patients. The lncRNAs-mRNAs network and functional enrichment analysis indicated the involvement of these four lncRNA signatures in UCEC tumor progression by modulating pathways such as TGF-beta signaling, cell cycle, DNA replication, NF-kB signaling, and Notch signaling. Conclusion: LINC01224, AC015849.16, LINC00908, and LINC00092 could be considered as alternate prognostic markers for UCEC prediction, potentially improving overall survival and enabling patient-tailored treatment strategies.

Background: Circular RNAs (circRNAs) play critical roles in the tumorigenesis and radiosensitivity of multiple cancers. Nevertheless, the biological functions of circRNA periostin (circ-POSTN) in esophageal cancer (EC) progression and radiosensitivity have not been well elucidated. Methods: The expression of circ-POSTN, microRNA-876-5p (miR-876-5p), and proto-oncogene tyrosine-protein kinase (FYN) was analyzed by quantitative reverse transcription PCR (RT-qPCR). Cell proliferation was assessed by MTT, colony formation, and 5-ethynyl-2 '-deoxyuridine (EDU) assays. All protein levels were detected by western blot assay. Cell apoptosis and invasion were assessed by flow cytometry analysis and transwell assay, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction between miR-876-5p and circ-POSTN or FYN. The role of circ-POSTN in vivo was explored by establishing mice xenograft model. Results: Circ-POSTN was overexpressed in EC tissues and cells. Knockdown of circ-POSTN inhibited cell proliferation and invasion and elevated apoptosis and radiosensitivity in EC cells. MiR-876-5p was a direct target of circ-POSTN, and its knockdown reversed the role of sh-circ-POSTN in EC cells. FYN was a direct target of miR-876-5p, and FYN elevation weakened the effects of miR-876-5p overexpression on the progression and radiosensitivity of EC cells. Moreover, circ-POSTN acted as a miR-876-5p sponge to regulate FYN expression. Circ-POSTN interference also suppressed tumor growth and enhanced radiosensitivity in vivo. Conclusion: Circ-POSTN knockdown inhibited proliferation and invasion, but increased apoptosis and enhanced radiosensitivity in EC cells via modulating miR-876-5p/FYN axis, which might be a potential diagnostic and therapeutic target for EC.

Anticancer immune surveillance and immunotherapies trigger activation of cytotoxic cytokine signaling, including tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) pathways. The pro-inflammatory cytokine TNF-α may be secreted by stromal cells, tumor-associated macrophages, and by cancer cells, indicating a prominent role in the tumor microenvironment (TME). However, tumors manage to adapt, escape immune surveillance, and ultimately develop resistance to the cytotoxic effects of TNF-α. The mechanisms by which cancer cells evade host immunity is a central topic of current cancer research. Resistance to TNF-α is mediated by diverse molecular mechanisms, such as mutation or downregulation of TNF/TRAIL receptors, as well as activation of anti-apoptotic enzymes and transcription factors. TNF-α signaling is also mediated by sphingosine kinases (SphK1 and SphK2), which are responsible for synthesis of the growth-stimulating phospholipid, sphingosine-1-phosphate (S1P). Multiple studies have demonstrated the crucial role of S1P and its transmembrane receptors (S1PR) in both the regulation of inflammatory responses and progression of cancer. Considering that the SphK/S1P/S1PR axis mediates cancer resistance, this sphingolipid signaling pathway is of mechanistic significance when considering immunotherapy-resistant malignancies. However, the exact mechanism by which sphingolipids contribute to the evasion of immune surveillance and abrogation of TNF-α-induced apoptosis remains largely unclear. This study reviews mechanisms of TNF-α-resistance in cancer cells, with emphasis on the pro-survival and immunomodulatory effects of sphingolipids. Inhibition of SphK/S1P-linked pro-survival branch may facilitate reactivation of the pro-apoptotic TNF superfamily effects, although the role of SphK/S1P inhibitors in the regulation of the TME and lymphocyte trafficking should be thoroughly assessed in future studies.

Background:Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods:This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results:In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion:An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

BACKGROUND Retinoblastoma is the most common intraocular malignant tumor occurring among children, with an incidence rate of 1/15 000. This study built a joinpoint regression model to assess the incidence trend of retinoblastoma from 2004 to 2015 and constructed a nomogram to predict the overall survival (OS) in children. MATERIALS AND METHODS Patients less than 19 years diagnosed with retinoblastoma from 2004 to 2015 were selected from the SEER database. Joinpoint regression analysis (version 4.9.0.0) was performed to evaluate the trends in retinoblastoma incidence rates from 2004 to 2015. Cox Regression Analysis was applied to investigate prognostic risk factors that influence OS. RESULTS Joinpoint regression revealed that retinoblastoma incidence exhibited no significant increase or decrease from 2004 to 2015. As per the multiple Cox regression, tumor size, laterality, and residence (rural-urban continuum code) were correlated with OS and were used to construct a nomogram. The nomogram exhibited a good C-index of 0.71 (95% CI, 0.63 to 0.79), and the calibration curve for survival probability demonstrated that the predictions corresponded well with actual observations. CONCLUSIONS AND RELEVANCE A prognostic nomogram integrating the risk factors for retinoblastoma was constructed to provide comparatively accurate individual survival predictions. If validated, this type of assessment could be used to guide therapy in patients with retinoblastoma.

BACKGROUND:Glyphosate-based herbicide (GBH) formulations are organophosphorus pesticides implicated for agricultural use. Several epidemiological reports have reported that the occupational exposure of farmers to glyphosate can cause age-related neurodegeneration. OBJECTIVE:The objective of this study is to examine the neurotoxic effects of glyphosate and its intricate role in triggering several neurodegenerative diseases like dementia, nootropic defects, Parkinson's disease, and neurological teratogenic effects due to its negative effects on the nervous system. Furthermore, the efficacy of phytochemicals against glyphosate-induced neurotoxicity was discussed. METHODS:We have searched public databases such as NLM, Pubmed, google scholar and collected a total of 113 articles including reviews, original articles, and obtained information related to glyphosate-induced neurotoxicity and novel phytochemicals implicated to ameliorate the glyphosate-induced neurotoxicity. We performed a systematic review without comprehensive meta-analysis. RESULTS:The efficacy of several phytochemicals as a nutritional intervention against glyphosate-induced neurotoxicity including Parkinsonism was elucidated by vivid review analysis of neurobehavioral alterations from in vitro and in vivo study models. CONCLUSION:These kinds of research projects will bring awareness about the neurotoxic effects of glyphosate and the protective nutritional intervention strategies against glyphosate-induced neurotoxicity including Parkinsonism for farmers.

Previous studies described that asthma patients who received corticosteroid therapy have been constrained by the corticosteroid resistance subsequently fostered to severe refractory asthma. In this review, we discussed the implications of TSLP, RXR, the role of STAT5-activating cytokines, and IL-33/NH-cell signaling pathways, and recent clinical evidence on TSLP blockers in steroid-resistant asthma. We have searched several public databases such as Pubmed, Scopus, and Relemed and obtained information pertinent to the TSLP, RXR, TSLP blockers, the STAT5-activating cytokines, and IL-33. We discussed the multiple cell signaling mechanisms underlying steroid resistance. Blocking the TSLP and other key signaling molecules like STAT5 can retrieve the sensitivity of natural helper-cells to corticosteroids. RXR derivatives treatment can modulate the activity of TSLP, which further modulates steroid resistance in severe asthmatic patients and in patients with refractory asthma. We discussed the steroid-resistance mediated by the Th2 cells and Th2-driven eosinophilia upon corticosteroid intake. Thus, this review will be beneficial for clinicians and molecular biologists to explore the inflammatory pathways associated with refractory asthma conditions and develop novel therapies against corticosteroid-resistant asthma.

Circ_0081069 plays a key role in tumor growth; however, its effect on radiosensitivity in esophageal squamous cell carcinoma (ESCC) remains unknown. The study is performed to reveal the association of circ_0081069 expression and radiosensitivity in ESCC and the underlying mechanism. Circ_0081069, miR-195-5p, and spindlin 1 (SPIN1) RNA expression were detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis or immunohistochemistry assay. Cell viability, proliferation, cell apoptosis, migration, and invasion were investigated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, scratch test, and transwell assays, respectively. The sensitivity of ESCC cells to radiation was investigated by cell colony formation assay. The interactions among circ_0081069, miR-195-5p, and SPIN1 were identified by dual-luciferase reporter assay and RNA Immunoprecipitation assay. Xenograft mouse model assay was performed to determine the effect of circ_0007841 on radiosensitivity in vivo. Circ_0081069 and SPIN1 expression were upregulated, whereas miR-195-5p was downregulated in ESCC tissues, ESCC cells, and radiation-stimulated ESCC cells. Circ_0081069 silencing inhibited ESCC cell proliferation, invasion, and migration but improved cell apoptosis. In addition, circ_0081069 knockdown enhanced ESCC cell radiosensitivity in vitro and in vivo. Circ_0081069 bound to miR-195-5p and regulated radiosensitivity by binding to miR-195-5p in ESCC cells. Moreover, SPIN1, a target of miR-195-5p, rescued miR-195-5p-mediated effects in ESCC cells. Circ_0081069 was secreted from ESCC cells by being packaged into exosomes. Further, circ_0081069-Exo inhibited radiosensitivity in ESCC cells. Exosome-mediated transfer of circ_0081069 induced SPIN1 production by binding to miR-195-5p, further inhibiting radiosensitivity in ESCC. Circ_0081069 expression was upregulated in esophageal squamous cell carcinoma (ESCC) tissues and cells. Circ_0081069 depletion inhibited ESCC cell tumor properties and enhanced radiosensitivity. Circ_0081069 regulated spindlin 1 expression through miR-195-5p. Circ_0081069 was secreted by being packaged into exosomes.