DRP1 inhibition-mediated mitochondrial elongation abolishes cancer stemness, enhances glutaminolysis, and drives ferroptosis in oral squamous cell carcinoma.

BACKGROUND: Mitochondrial dynamics play a fundamental role in determining stem cell fate. However, the underlying mechanisms of mitochondrial dynamics in the stemness acquisition of cancer cells are incompletely understood. METHODS: Metabolomic profiling of cells were analyzed by MS/MS. The genomic distribution of H3K27me3 was measured by CUT&Tag. Oral squamous cell carcinoma (OSCC) cells depended on glucose or glutamine fueling TCA cycle were monitored by 13C-isotope tracing. Organoids and tumors from patients and mice were treated with DRP1 inhibitors mdivi-1, ferroptosis inducer erastin, or combination with mdivi-1 and erastin to evaluate treatment effects. RESULTS: Mitochondria of OSCC stem cells own fragment mitochondrial network and DRP1 is required for maintenance of their globular morphology. Imbalanced mitochondrial dynamics induced by DRP1 knockdown suppressed stemness of OSCC cells. Elongated mitochondria increased α-ketoglutarate levels and enhanced glutaminolysis to fuel the TCA cycle by increasing glutamine transporter ASCT2 expression. α-KG promoted the demethylation of histone H3K27me3, resulting in downregulation of SNAI2 associated with stemness and EMT. Significantly, suppressing DRP1 enhanced the anticancer effects of ferroptosis. CONCLUSION: Our study reveals a novel mechanism underlying mitochondrial dynamics mediated cancer stemness acquisition and highlights the therapeutic potential of mitochondria elongation to increase the susceptibility of cancer cells to ferroptosis.

Acetyl-11-keto-beta-boswellic acid inhibits cell proliferation and growth of oral squamous cell carcinoma via RAB7B-mediated autophagy.

Natural products can overcome the limitations of conventional chemotherapy. Acetyl-11-keto-beta-boswellic acid (AKBA) as a natural product extracted from frankincense, exhibited chemotherapeutic activities in different cancers. However, whether AKBA exerts inhibiting effect of oral squamous cell carcinoma (OSCC) cells growth and the mechanism need to be explored. We attempted to investigate the therapeutic effects of AKBA against OSCC and explore the mechanism involved. Here we attempt to disclose the cell-killing effect of AKBA on OSCC cell lines and try to figure out the specifical pathway. The presence of increase autophagosome and the production of mitochondrial reactive oxygen species were confirmed after the application of AKBA on OSCC cells, and RAB7B inhibition enhanced autophagosome accumulation. Though the increase autophagosome was detected induced by AKBA, autophagic flux was inhibited as the failure fusion of autophagosome and lysosome. Cal27 xenografts were established to verify the role of anti-OSCC cells of AKBA in vivo. Based above findings, we speculate that natural product AKBA suppresses OSCC cells growth via RAB7B-mediated autophagy and may serve as a promising strategy for the therapy of OSCC.

Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction.

Fetal growth restriction (FGR) is associated with increased susceptibility to perinatal morbidity and mortality. Evidence suggests that epigenetic changes play critical roles in the regulation of fetal growth. We sought to present a comprehensive analysis of the associations between placental DNA methylation and selective fetal growth restriction (sFGR), which is a severe complication of monochorionic twin pregnancies, characterized by one fetus experiencing restricted growth. Genome-wide methylation analysis was performed on 24 placental samples obtained from 12 monochorionic twins with sFGR (Cohort 1) using Illumina Infinium MethylationEPIC BeadChip. Integrative analysis of our EPIC data and two previous placental methylation studies of sFGR (a total of 30 placental samples from 15 sFGR twins) was used to identify convincing differential promoter methylation. Validation analysis was performed on the placentas from 15 sFGR twins (30 placental samples), 15 FGR singletons, and 14 control singletons (Cohort 2) using pyrosequencing, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry (IHC). A globe shift toward hypomethylation was identified in the placentas of growth-restricted fetuses compared with the placentas of normal fetuses in monochorionic twins, including 5625 hypomethylated CpGs and 452 hypermethylated CpGs, especially in the regions of CpG islands, gene-body and promoters. The analysis of pathways revealed dysregulation primarily in steroid hormone biosynthesis, metabolism, cell adhesion, signaling transduction, and immune response. Integrative analysis revealed a differentially methylated promoter region in the CYP11A1 gene, encoding a rate-limiting enzyme of steroidogenesis converting cholesterol to pregnenolone. The CYP11A1 gene was validated to have hypomethylation and higher mRNA expression in sFGR twins and FGR singletons. In conclusion, our findings suggested that the changes in placental DNA methylation pattern in sFGR may have functional implications for differentially methylated genes and regulatory regions. The study provides reliable evidence for identifying abnormally methylated CYP11A1 gene in the placenta of sFGR.

Prevalence and risk factors of subsyndromal delirium among postoperative patients: A systematic review and meta-analysis.

AIM: The aim of this study is to determine the prevalence and risk factors for subsyndromal delirium in the postoperative patient. DESIGN: A systematic review and meta-analysis. METHODS: The Review Manager 5.3 statistics platform and the Newcastle-Ottawa Scale were used for quality evaluation. DATA SOURCES: The following databases were searched: PubMed, Web of Science, EMBASE, The Cochrane Library, Scopus and EBSCO from January 2000 to December 2021. Additional sources were found by looking at relevant articles' citations. RESULTS: A total of 1744 titles were originally identified, and five studies including 962 patients were included in the systematic review, with a pooled prevalence of postoperative subsyndromal delirium (PSSD) of 30% (95% CI: 0.28-0.32). Significant risk variables for PSSD were older age, low levels of education (≤9 years), cognitive impairment, higher comorbidity score, and the duration of operation. CONCLUSION: PSSD is prevalent and is associated with a variety of risk factors as well as low academic performance. IMPACT: Identification and clinical management of patients with PSSD should be improved. Future research on PSSD risk factors should look at a wider range of intraoperative and postoperative risk factors that can be changed. PATIENT AND PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Pregnancy Loss After Amniocentesis with Double-Needle Insertions in Twin Pregnancies.

The aim of this study was to determine the pregnancy loss rate of amniocentesis with double-needle insertions in twin pregnancies. This was a retrospective study of twin pregnancies who underwent amniocentesis with double-needle insertion between 2010 and 2019 at a single center. The pregnancy loss rates were recorded as single or double fetal loss before 24 weeks' gestation and within 4 weeks after the procedure. Risk factors for pregnancy loss after amniocentesis were also assessed. A total of 678 twin pregnancies with amniocentesis were finally included. The pregnancy loss rates before 24 weeks' gestation and within 4 weeks after the procedure were 0.9% and 1.9%, respectively. Only one fetal loss was presumed to be a direct result of the procedure. All other cases were complicated by structural or chromosomal anomalies. Twin pregnancies with abnormal ultrasound findings had a significantly higher rate of pregnancy loss with a relative risk of 4.81 (95% CI [1.03, 22.2]). Our study showed a low pregnancy loss rate after amniocentesis in twin pregnancies with double-needle insertions technique of sampling, which can help decision making in prenatal screening and diagnosis for twin pregnancies.

PD-1 blockade prevents the progression of oral carcinogenesis.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the head and neck with a poor prognosis. Oral cancer development is a multistep process involving carcinogenesis. Though significant advances in cancer immunotherapy over the years, there is lack of evidence for T-cell exhaustion during oral carcinogenesis. Clinical specimens from healthy donors and patients diagnosed with oral leukoplakia (OLK) or OSCC were collected for immunohistochemical staining with PD-L1, CD86, CD8, PD-1 and CTLA-4 antibodies. Meanwhile, chemically induced mouse models of oral carcinogenesis were constructed with 4-nitroquinolone-N-oxide induction. Exhaustion status of T cells was measured by flow cytometry for spleens and by multiplex immunohistochemistry for formalin-fixed paraffin-embedded lesions in multiple stages of oral carcinogenesis. The efficacy of PD-1 blockade with or without cisplatin treatment was evaluated on the mice in precancerous and OSCC stages. We observed higher expression of PD-1 in the human OLK and OSCC tissues compared with the normal, while low expression CTLA-4 in all oral mucosa tissues. Animal experiments showed that the exhausted CD4+ T cells existed much earlier than exhausted CD8+ T cells, and an increased ratio of stem-like exhausted T cells and partially exhausted T cells were detected in the experimental groups. Besides, the expression of immune checkpoint markers (PDCD1, CTLA4 and HAVCR2) was strongly positively correlated with cytokines (IFNG and IL-2). In summary, T-cell exhaustion plays a vital role in oral carcinogenesis, and PD-1 blockade can prevent the progression of oral carcinogenesis.

Repurposing disulfiram to induce OSCC cell death by cristae dysfunction promoted autophagy.

OBJECTIVE: Disulfiram has been repurposed as a potential candidate to suppress various cancers. However, its anti-tumor effects and molecular mechanisms of oral squamous cell carcinoma remain unclear. In this study, we aimed to assess the anti-cancer activity and underlying mechanisms of disulfiram in the context of oral squamous cell carcinoma. MATERIALS AND METHODS: We tested the cytotoxicity of disulfiram in oral squamous cell carcinoma using a 3D culture model and a PDX model. Cell proliferation, cell death, and related signaling pathways were evaluated. Mitochondrial DNA copy number, mitochondrial respiration, mitochondrial mass, and mitochondrial complexes were analyzed. RESULTS: Disulfiram can induce excessive autophagy in oral squamous cell carcinoma cells as a result of OXPHOS deficiency. Disulfiram-induced OPA1 degradation can impair the functional cristae structure, which results in a dramatic reduction in mitochondrial respiration capability as well as ATP production. Subsequently, energy deprivation leads to excessive autophagy through AMPK activation. In addition, exogenous ATP blocked the activation of AMPK and rescued disulfiram-induced cell death. CONCLUSION: DSF targets mitochondrial inner membrane protein OPA1 to disturb the energy supply, triggering excessive autophagy, and cell death in OSCC. Our study suggests OPA1-dependent ATP generation is pharmacologically targetable in OSCC treatment.

HMGB1 is mechanistically essential in the development of experimental pulmonary hypertension.

Pulmonary hypertension (PH) is a mortal disease featuring pulmonary vascular constriction and remodeling, right heart failure, and eventual death. Several reports showed that high-mobility group box 1 (HMGB1) appears to be critical for the development of PH; the underlying mechanism, however, has not been revealed. Experiments in the present study demonstrated that HMGB1 levels were elevated in the lung tissue and blood plasma of rats after chronic hypoxia exposure and monocrotaline treatment. HMGB1 was originally located within the nucleus and translocated to the cytoplasm of pulmonary artery smooth muscle cells (PASMCs) upon hypoxia exposure, a process that appeared to be mediated by endogenous H2O2. Exposure to HMGB1 mobilized calcium signaling in PASMCs, a response that was attenuated by extracellular Ca2+ removal, Toll-like receptor 4 (TLR4) inhibition by TAK-242, or transient receptor potential channel (TRPC) suppression with 2-aminoethoxydiphenyl borate (2-APB) and SKF-96365. The sustained phosphorylation of the Akt pathway modulated HMGB1-induced migration of PASMCs. The blockage of HMGB1 with glycyrrhizin or anti-HMGB1 neutralizing antibody attenuated lung inflammation and PH establishment in rats after hypoxia exposure and monocrotaline treatment. The above findings reveal the mechanistic importance of HMGB1 in PH through TLR4- and TRPC-associated Ca2+ influx and Akt phosphorylation-driven PASMC migration.

Long-term exposure to PM2.5 and stroke: A systematic review and meta-analysis of cohort studies.

BACKGROUND: Stroke is one of the world's leading causes of death. Many studies have checked the relationship between short-term exposure to particulate matter (PM) and stroke, but few have focused on the effect of long-term exposure to PM2.5 (particulate matters with an aerodynamic diameter of ≤2.5 µm). This study aimed to quantitatively examine the relationship of long-term exposure to PM2.5 with stroke incidence and mortality. METHODS: We identified relevant studies by searching the PubMed, EMBASE and MEDLINE. After the systematical review of pertinent studies, random-effect meta-analysis was conducted to investigate the association between long-term exposure to PM2.5 and stroke. RESULTS: Our meta-analysis included 16 cohort studies with more than 2.2 million people and above 49 149 endpoint events (incident stroke and death from stroke). The pooled hazard ratio (HR) for each 5 µg/m3 increment in PM2.5 was 1.11 (95% CI: 1.05, 1.17) (CI for confidence interval) for incidence of stroke and 1.11 (95% CI:1.05, 1.17) for mortality of stroke. In the region-specific analysis, significant association between PM2.5 and incidence of stroke was found in North America (HR=1.09, 95% CI:1.05, 1.14) and Europe (HR=1.07, 95% CI:1.05, 1.10), while the pooled result of Asia showed no significance (HR=2.31, 95% CI:0.49, 10.95). CONCLUSIONS: Long-term exposure to PM2.5 is an important risk factor for stroke. Since air quality is intimately related to everyone, policies aimed at reducing particulate matters will benefit public health a lot.

Analysis of telomere length and the relationship with neurocognitive functions in euthymic bipolar disorder: A cross-sectional pilot study.

BACKGROUND: Telomere shortening has been considered a potential biological marker related to disease susceptibility and aging in psychiatric disorders. However, the relationship between telomere length and bipolar disorder (BD-I and BD-II) is uncertain. Moreover, whether telomere shortening is an independent factor of cognitive impairment in BD patients is still inconclusive. METHODS: We explore telomere length and cognitive function in patients with bipolar disorder and the relationship between them. We enrolled three groups (35 patients with euthymic BD-I, 18 with euthymic BD-II, and 38 healthy controls). Telomere length was measured by fluorescent quantitative polymerase chain reaction (q-PCR), and cognitive function was evaluated by the MATRICS Consensus Cognitive Battery (MCCB). SPSS 24.0 was used for statistical analysis. RESULTS: The telomere length of euthymic patients with BD-I and BD-II was shorter than that of healthy controls (F = 8.228, P = 0.001, η2 = 0.176). Telomere length was not significantly different between BD-I and BD-II. Compared to HCs, poor performance was detected in attention and vigilance in BD-I patients (F = 3.473, P = 0.036). Working memory was positively correlated with telomere length in BD-II patients (Beta = 0.5, P = 0.041, Adjusted R2 = 0.2). CONCLUSIONS: The current study provided evidence of shortened telomere length in euthymic BD patients, indicating that telomere shortening might be a promising biomarker of susceptibility to bipolar disorder. The telomere length predicted the working memory in BD-II patients. Further studies are needed to clarify the role of accelerated aging on cognitive functioning in a young group of patients with BD.

Rapid evaluation of the quality of Smilax glabra Roxb. using QADS based on FT-NIR combined with multiple intelligent algorithms.

Smilax glabra Roxb. (SGR) is known for its high nutritional and therapeutic value. However, the frequent appearance of counterfeit products causes confusion and inconsistent quality among SGR varieties. Herein, this study collected the proportion of SGR adulteration and used high-performance liquid chromatography (HPLC) to measure the astilbin content of SGR. Then Fourier-transform near-infrared (FT-NIR) technology, combined with multivariate intelligent algorithms, was used to establish partial least squares regression quantitative models for detecting SGR adulteration and measuring astilbin content, respectively. The method conducted a quantitative analysis of dual indicators through single-spectrum data acquisition (QADS) to comprehensively evaluate the authenticity and superiority of SGR. The coefficients of determination (R2) for both the calibration and prediction sets exceeded 0.96, which successfully leverages FT-NIR combined with multivariate intelligent algorithms to considerably enhance the accuracy and reliability of quantitative models. Overall, this research holds substantial value in the comprehensive quality evaluation in functional health foods.

A comparative study on three different transducers for the measurement of nonlinear solitary waves.

In the last decade there has been an increasing interest in the use of highly- and weakly- nonlinear solitary waves in engineering and physics. Nonlinear solitary waves can form and travel in nonlinear systems such as one-dimensional chains of particles, where they are conventionally generated by the mechanical impact of a striker and are measured either by using thin transducers embedded in between two half-particles or by a force sensor placed at the chain's base. These waves have a constant spatial wavelength and their speed, amplitude, and duration can be tuned by modifying the particles' material or size, or the velocity of the striker. In this paper we propose two alternative sensing configurations for the measurements of solitary waves propagating in a chain of spherical particles. One configuration uses piezo rods placed in the chain while the other exploits the magnetostrictive property of ferromagnetic materials. The accuracy of these two sensing systems on the measurement of the solitary wave's characteristics is assessed by comparing experimental data to the numerical prediction of a discrete particle model and to the experimental measurements obtained by means of a conventional transducer. The results show very good agreement and the advantages and limitations of the new sensors are discussed.

Efficacy and safety profiles of mood stabilizers and antipsychotics for bipolar depression: a systematic review.

The whole picture of psychotropics for bipolar depression (BPD) remains unclear. This review compares the differences in efficacy and safety profiles among common psychotropics for BPD. MEDLINE, EMBASE, and PsycINFO were searched for proper studies. The changes in the depressive rating scale, remission/response rates, nervous system adverse events (NSAEs), gastrointestinal adverse events (GIAEs), metabolic parameters, and prolactin were compared between medication and placebo or among medications with the Cohen's d or number needed to treat/harm. The search provided 10 psychotropics for comparison. Atypical antipsychotics (AAPs) were superior to lithium and lamotrigine at alleviating acute depressive symptoms. Lithium was more likely to induce dry mouth and nausea. Cariprazine and aripiprazole seemed to be associated with an increased risk of akathisia and upper GIAEs. Lurasidone was associated with an increased risk of developing akathisia and hyperprolactinemia. Olanzapine, olanzapine-fluoxetine combination (OFC), and quetiapine were associated with an increased risk of NSAEs, metabolic risk, dry mouth, and constipation. Cariprazine, lurasidone, OFC, or quetiapine was optimal monotherapy for BPD. Further studies are needed to assess the efficacy and safety of lamotrigine for treating BPD. Adverse events varied widely across different drug types due to variations in psychopharmacological mechanisms, dosages, titration, and ethnicities.

Emerging roles of circular RNAs in the invasion and metastasis of head and neck cancer: Possible functions and mechanisms.

Head and neck cancer (HNC) is the seventh most prevalent malignancy worldwide in 2020. Cancer metastasis is the main cause of poor prognosis in HNC patients. Recently, circular RNAs (circRNAs), initially thought to have no biological function, are attracting increasing attention, and their crucial roles in mediating HNC metastasis are being extensively investigated. Existing studies have shown that circRNAs primarily function through miRNA sponges, transcriptional regulation, interacting with RNA-binding proteins (RBPs) and as translation templates. Among these functions, the function of miRNA sponge is the most prominent. In this review, we summarized the reported circRNAs involved in HNC metastasis, aiming to elucidate the regulatory relationship between circRNAs and HNC metastasis. Furthermore, we summarized the latest advances in the epidemiological information of HNC metastasis and the tumor metastasis theories, the biogenesis, characterization and functional mechanisms of circRNAs, and their potential clinical applications. Although the research on circRNAs is still in its infancy, circRNAs are expected to serve as prognostic markers and effective therapeutic targets to inhibit HNC metastasis and significantly improve the prognosis of HNC patients.

Detection of the peripheral blood antigens and clinical value in recurrent aphthous ulcer: A cross-section study.

Abstract Background/purpose: Recurrent aphthous ulcer (RAU) is one of the most common diseases of oral mucosa, which is generally believed to be related to immunity, though the etiology is still unclear. It is suspected that allergies are directly related to RAU. So we sought to explore the relationship between hypersensitivity and RAU. Materials and methods: 40 RAU patients who were in ulceration period and 40 people who were in good health were selected from Jan 2016 to Feb 2017, matched in age and sex. The peripheral blood antigens of 40 RAU patients and 40 healthy people was tested, and serum specific IgE (sIgE) with 6 groups of antigens and total IgE (tIgE) analysis was performed to identify IgE-mediated allergic reaction possibly affecting RAU. We then investigated the food intolerance and IgG levels to discover the correlation between non-IgE mediated allergic reaction and RAU. Results: The positive cases and rate of sIgE in RAU group was higher than that of control, but the difference was not statistically significant (P＞0.05). Positive grade of animal fur scraps (EX1), house dust mixed (HX2) and the serum tIgE concentration of the RAU group were significantly higher than the control group (P＜0.05).The number of food intolerance in RAU group was significantly higher than that in control group (P＜0.05). Conclusion: Our findings suggested certain correlation between RAU and anaphylaxis. Daily contact allergens and food intolerance may be one of the causes of RAU. Moreover, this provides reference value for clinical diagnosis and treatment.

Identification of key miRNAs and targeted genes involved in the progression of oral squamous cell carcinoma.

Background/purpose: Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck squamous cell carcinoma. Accurate biomarkers are needed for early diagnosis and prognosis of OSCC. MicroRNAs (miRNAs) have shown great values in different types of cancers including OSCC. However, most of the miRNAs involved in the development of OSCC remain uncovered. This study aimed to identify hub miRNAs and mRNAs in OSCC. Materials and methods: We explored the roles of key miRNAs, target genes and their relationships in OSCC using an integrated bioinformatics approach. Initially, Two OSCC microarray datasets from the Gene Expression Omnibus database were obtained to analyze miRNA expression. MiRNA-targeted mRNAs were acquired, and gene ontology/kyoto encyclopedia of genes and genomes analyses were performed. Thereafter, we constructed a protein-protein interaction (PPI) network to identify hub genes and a miRNA-mRNA interaction network was used to identify key miRNAs. Furthermore, differential gene expression and Kaplan-Meier Plotter survival analysis was performed to evaluate their potential clinical application values. Results: Four upregulated, two downregulated miRNAs and 608 target genes of the differentially expressed miRNAs were identified. The PPI and miRNA-mRNA interaction networks highlighted 10 hub genes and two key miRNAs, and pathway analyses showed their correlative involvement in tumorigenesis-related processes. Of these miRNAs and genes, miR-125b, ß-actin, vinculin and histone deacetylase 1 were correlated with overall survival (P < 0.05). Conclusion: These findings indicate that miR-21 and miR-125b, associated with the 10 hub genes, jointly participate in OSCC tumorigenesis, offering insight into the molecular mechanisms underlying OSCC as potential targets for early diagnosis, treatment and prognosis.

Direct immunofluorescence and immune function in patients with oral lichen planus.

Background/Purpose: Direct immunofluorescence and immune function and patients with oral lichen planusThe etiology of oral lichen planus (OLP) is unknown, our purpose was to evaluate the diagnostic value of direct immunofluorescence (DIF) and to investigate the immune functions in OLP. Materials and methods: We enrolled 65 patients with suspected lesions of OLP and 47 controls. In all participants, clinical and serologic testing were conducted. The histopathologic and DIF tests were conducted in 65 patients. The severity of OLP was evaluated by reticular/hyperkeratotic, erosive/erythematous, ulcerative (REU) scoring system. Results: By hematoxylin and eosin (H&E) staining and DIF examination, 71.2% (42/59) were diagnosed as OLP, 28.8% (17/59) were diagnosed as non-OLP. DIF demonstrated 64.3% positive reactivity with 2 distinct distribution patterns and 8 staining patterns. Compared to the controls, serum IgA in OLP was higher (P < 0.01), and serum CD3+ cells, IgM, IgE, C3 and C4 were lower (P < 0.05). Pearson correlation analysis in OLP revealed correlations between REU score and IgM, IgA of DIF (r = 0.54, P = 0.026; and r = 0.56, P = 0.020, respectively), between serum IgG and IgG of DIF (r = 0.51, P = 0.038), between serum CD4+ and the ratio of CD4+/CD8+, IgM in DIF (r = -0.50, P = 0.048; and r = -0.54, P = 0.031, respectively), between serum CD8+ and IgM, IgA in DIF (r = 0.52, P = 0.038; and r = -0.50, P = 0.047, respectively). Conclusion: A combination of H&E test and DIF is useful for the diagnosis of OLP. Compared to controls, immune changes happen to patients with OLP. There are significant associations between the OLP lesions and general cellular and humoral immune status, localized humoral immune response.

Predisposition of hypersensitivity in patients with exfoliative cheilitis.

BACKGROUND/PURPOSE: Exfoliative cheilitis (EC) is a chronic and reversible inflammatory disease of the lips without definite etiology. Clinically, different types of allergens can be found in exfoliative cheilitis patients, however, few studies have focused on the relationship between exfoliative cheilitis and hypersensitivity. This research aimed to investigate the prevalence of hypersensitivity in EC patients. MATERIALS AND METHODS: A prospective study was conducted in 30 patients with exfoliative cheilitis and 30 healthy controls, matched in age and sex. Laboratory tests included serum total IgE, allergen-specific IgE, and food-specific IgG. RESULTS: Increased serum total IgE level, positive food-specific IgG were seen more frequently in exfoliative cheilitis patients than in healthy control (P < 0.05). Special IgE level to FX5 and the degree of food-specific IgG to wheat were seen higher in exfoliative cheilitis patients than in healthy control (P < 0.05). CONCLUSION: This study suggests that patients with exfoliative cheilitis may have predisposition of hypersensitivity. The detection of allergens should be strengthened in the future clinical work.

Identification of a Novel Cuproptosis-Related Gene Signature for Prognostic Implication in Head and Neck Squamous Carcinomas.

Head and neck squamous carcinoma (HNSC) is a frequent and deadly malignancy that is challenging to manage. The existing treatment options have considerable efficacy limitations. Hence, the identification of new therapeutic targets and the development of efficacious treatments are urgent needs. Cuproptosis, a non-apoptotic programmed cell death caused by excess copper, has only very recently been discovered. The present study investigated the prognostic importance of genes involved in cuproptosis through the mRNA expression data and related clinical information of HNSC patients downloaded from public databases. Our results revealed that many cuproptosis-related genes were differentially expressed between normal and HNSC tissues in the TCGA cohort. Moreover, 39 differentially expressed genes were associated with the prognosis of HNSC patients. Then, a 24-gene signature was identified in the TCGA cohort utilizing the LASSO Cox regression model. HNSC expression data used for validation were obtained from the GEO database. Consequently, we divided patients into high- and low-risk groups based on the 24-gene signature. Furthermore, we demonstrated that the high-risk group had a worse prognosis when compared to the low-risk group. Additionally, significant differences were found between the two groups in metabolic pathways, immune microenvironment, etc. In conclusion, we found a cuproptosis-related gene signature that can be used effectively to predict OS in HNSC patients. Thus, targeting cuproptosis might be an alternative and promising strategy for HNSC patients.