Cucurbitacin B targets STAT3 to induce ferroptosis in non-small cell lung cancer.

Cucurbitacin B (CuB) is a compound found in plants like Cucurbitaceae that has shown promise in fighting cancer, particularly in lung cancer. However, the specific impact of CuB on ferroptosis and how it works in lung cancer cells has not been fully understood. Our research has discovered that CuB can effectively slow down the growth of non-small cell lung cancer (NSCLC) cells. Even in small amounts, it was able to inhibit the growth of various NSCLC cell lines. This inhibitory effect was reversed when ferroptosis inhibitors DFO, Lip-1 and Fer-1 were introduced. CuB was found to increase the levels of reactive oxygen species (ROS), lipid ROS, MDA, and ferrous ions within H358 lung cancer cells, leading to a decrease in GSH, mitochondrial membrane potential (MMP) and changes in ferroptosis-related proteins in a dose-dependent manner. These findings were also confirmed in A549 lung cancer cells. In A549 cells, different concentrations of CuB induced the accumulation of intracellular lipid ROS, ferrous ions and changes in ferroptosis-related indicators in a concentration-dependent manner. Meanwhile, the cytotoxic effect induced by CuB in A549 cells was counteracted by ferroptosis inhibitors DFO and Fer-1. Through network pharmacology, we identified potential targets related to ferroptosis in NSCLC cells treated with CuB, with STAT3 targets showing high scores. Further experiments using molecular docking and cell thermal shift assay (CETSA) revealed that CuB interacts with the STAT3 protein. Western blot and immunofluorescence staining demonstrated that CuB inhibits the phosphorylation of STAT3 (P-STAT3) in H358 cells. Silencing STAT3 enhanced CuB-induced accumulation of lipid ROS and iron ions, as well as the expression of ferroptosis-related proteins. On the other hand, overexpression of STAT3 reversed the effects of CuB-induced ferroptosis. The results indicate that CuB has the capability to suppress STAT3 activation, resulting in ferroptosis, and could be a promising treatment choice for NSCLC.

Odontogenic carcinoma with dentinoid: case report and literature review of a rare entity.

BACKGROUND: Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of odontogenic lesions. Owing to the small number of reported cases, the clinicopathological characteristics, biological behavior, prognosis, and appropriate treatment strategies for OCD remain to be defined. Herein, we present an additional case of OCD with a focus on the differential diagnosis and review of the pertinent literature, in order to enable better recognition by oral clinicians and pathologists and further characterization of this entity. CASE PRESENTATION: This paper reports a case of OCD in the posterior mandible of a 22-year-old female. Radiography showed a well-defined unilocular radiolucency with radiopaque materials. The intraoperative frozen section pathology gave a non-committed diagnosis of odontogenic neoplasm with uncertain malignant potential. Then a partial mandibulectomy with free iliac crest bone graft and titanium implants was performed. Microscopically, the tumor consisted of sheets, islands, and cords of round to polygonal epithelial cells associated with an abundant dentinoid matrix. Immunohistochemically, the tumor cells were diffusely positive for CK19, p63, and ß-catenin (cytoplasmic and nuclear). No rearrangement of the EWSR1 gene was detected. The final diagnosis was OCD. There has been no evidence of recurrence or metastasis for 58 months after surgery. We also provide a literature review of OCD cases, including one case previously reported as ghost cell odontogenic carcinoma from our hospital. CONCLUSIONS: OCD is a locally aggressive low grade malignancy without apparent metastatic potential. Wide surgical excision with clear margins and long-term period follow-up to identify any possible recurrence or metastases are recommended. Histopathological examination is essential to conclude the diagnosis. Special care must be taken to distinguish OCD from ghost cell odontogenic carcinoma and clear cell odontogenic carcinoma, as misdiagnosis might lead to unnecessary overtreatment. Study of additional cases is required to further characterize the clinicopathological features and clarify the nosologic status and biological behavior of this tumor.

The antipyretic effect of the famous classical formula Qingwanzi Pills on a rabbit model and its serum metabolomic study.

Qingwanzi Pills (QP) were first mentioned in the "Puji Fang" of the Ming Dynasty, with a history of approximately 600 years. The formula consisted of Gypsum Fibrosum and Indigo Naturalis. It is a famous classical formula with antipyretic effects frequently utilized in ancient China, although our knowledge about the overall antipyretic mechanism of QP remains limited. Therefore, we replicated the fever model in New Zealand rabbits induced by lipopolysaccharide, performed the pharmacodynamic evaluation of QP, identified the differential metabolites among QP groups, and performed pathway enrichment analysis to comparatively analyze the effects of QP on fever-related metabolic pathways by ultra-performance liquid chromatography-mass spectrometry. The results showed that the antipyretic effect of QP was superior to that of each disassembled prescription, with Gypsum Fibrosum primarily contributing to the efficacy, followed by Indigo Naturalis and Junci Medulla. QP had an effective antipyretic effect, which was related to lowering the levels of TNF-α, IL-6, IL-1ß, and calcium in rabbit serum, lowering the levels of PGE2 and cAMP in rabbit cerebrospinal fluid, and increasing the level of calcium in rabbit cerebrospinal fluid. A total of 27 endogenous biomarkers were screened by serum metabolomics for the treatment of fever with QP. It is hypothesized that the antipyretic mechanism of QP may be related to regulating α-linolenic acid, sphingolipid, tryptophan, and bile acid metabolism. In summary, QP exhibited a significant antipyretic effect in rabbits with lipopolysaccharide-induced fever.

Research on dynamic characteristics of cutter breaking frozen soil and optimal drum rotation speed of the new shaft tunneling machine.

To improve the efficiency of frozen soil excavation, the new shaft tunneling machine was developed. The new shaft tunneling machine exerts pressure on the frozen soil through the cutter under the joint action of its own gravity, the drum rotational force and the inertia force, and the frozen soil is damaged. By unique way of breaking frozen soil to improve the efficiency of frozen soil excavation, the drum rotation speed is one of the factors affecting the performance of frozen soil excavation. This article applies SolidWorks software to establish the model of cutter breaking frozen soil, takes advantage of Hyper Mesh finite element software coupled with LS-DYNA solver to acquire the regular pattern of change in the force change, frozen soil stress-strain and specific energy of cutter crushing frozen soil, etc., which analyzes the destruction of frozen soil when the drum of the new shaft tunneling machine is rotating at the speed of 25-40 rpm. Combine with field test to investigate the mechanism of cutter breaking frozen soil under the optimal drum rotation speed. The investigation results demonstrate that: when frozen soil's self-bearing capacity is lower than the force of cutter, it breaks up and detaches from the soil body, and frozen soil undergoes tensile, compressive and shear damages. For this research, it is instructive for practical engineering.

Case Report: Giant left atrial cystic tumor: myxoma or intracardiac blood cyst?

Background: Primary cardiac tumors are uncommon, with the majority being benign myxomas. Cystic myxoma, a particularly rare type of benign cardiac tumor, demands cautious differential diagnosis from other cardiac tumors. Case summary: A 43-year-old male patient presenting with intermittent dyspnea was referred to our department for surgical evaluation. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) unveiled an intra-left atrial cyst, which was subsequently found to be blood-filled during a video-assisted microinvasive heart surgery. Pathological examination depicted a cyst wall filled with small stellate and fat spindle cells, along with a mucoid matrix, indicating a diagnosis of cystic myxoma. Conclusions: We herein presented a rare case of an adult patient with cystic myxoma, initially misdiagnosed as an intracardiac blood cyst (CBC) prior to surgery, and ultimately verified via pathological findings.

A novel risk score system based on immune subtypes for identifying optimal mRNA vaccination population in hepatocellular carcinoma.

PURPOSE: Although mRNA vaccines have shown certain clinical benefits in multiple malignancies, their therapeutic efficacies against hepatocellular carcinoma (HCC) remains uncertain. This study focused on establishing a novel risk score system based on immune subtypes so as to identify optimal HCC mRNA vaccination population. METHODS: GEPIA, cBioPortal and TIMER databases were utilized to identify candidate genes for mRNA vaccination in HCC. Subsequently, immune subtypes were constructed based on the candidate genes. According to the differential expressed genes among various immune subtypes, a risk score system was established using machine learning algorithm. Besides, multi-color immunofluorescence of tumor tissues from 72 HCC patients were applied to validate the feasibility and efficiency of the risk score system. RESULTS: Twelve overexpressed and mutated genes associated with poor survival and APCs infiltration were identified as potential candidate targets for mRNA vaccination. Three immune subtypes (e.g. IS1, IS2 and IS3) with distinct clinicopathological and molecular profiles were constructed according to the 12 candidate genes. Based on the immune subtype, a risk score system was developed, and according to the risk score from low to high, HCC patients were classified into four subgroups on average (e.g. RS1, RS2, RS3 and RS4). RS4 mainly overlapped with IS3, RS1 with IS2, and RS2+RS3 with IS1. ROC analysis also suggested the significant capacity of the risk score to distinguish between the three immune subtypes. Higher risk score exhibited robustly predictive ability for worse survival, which was further independently proved by multi-color immunofluorescence of HCC samples. Notably, RS4 tumors exhibited an increased immunosuppressive phenotype, higher expression of the twelve potential candidate targets and increased genome altered fraction, and therefore might benefit more from vaccination. CONCLUSIONS: This novel risk score system based on immune subtypes enabled the identification of RS4 tumor that, due to its highly immunosuppressive microenvironment, may benefit from HCC mRNA vaccination.

Effects of cognitive behavioral therapy in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes airflow blockage and breathing-related issues. This chronic disease impacts people worldwide. Substantial evidence supports the use of cognitive behavioral therapy (CBT) to help patients with chronic illnesses cope with worrisome and painful symptoms. However, the impact of CBT on COPD outcomes is less understood. OBJECTIVE: In this study, we systematically summarized the effects of CBT on lung function, anxiety and depressive symptoms, and quality of life of patients with COPD. METHODS: Six English-language and four Chinese-language databases were systematically searched for relevant randomized controlled trials published through April 15, 2023. Studies in which CBT was the only difference in treatment administered to experimental and control groups were included in the review. The studies' risk of bias was evaluated using the Cochrane Criteria. RESULTS: Sixteen studies (1887 participants) were included. The meta-analysis showed that CBT improved the percent-predicted forced expiratory volume in 1 second (FEV1%), forced vital capacity (FVC), FEV1/FVC ratio, maximal voluntary ventilation, peak expiratory flow, treatment compliance, and World Health Organization abbreviated quality of life, Self-rating Anxiety and Depression Scale, and St George's Respiratory Questionnaire scores compared with the control (all p < .05). CONCLUSION: This review demonstrated that CBT improves the lung function, anxiety and depressive symptoms, treatment compliance, and quality of life of patients with COPD and can be used widely in the clinical treatment of this disease.

High-Frequency Repetitive Transcranial Magnetic Stimulation on Overall Cognition in Patients With Poststroke Cognitive Impairment: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study is to comprehensively assess the recovery effects of high-frequency repetitive transcranial magnetic stimulation in patients with poststroke cognitive impairment. METHODS: Six English and four Chinese databases were searched for relevant studies published up to January 2022. Randomized controlled trials of patients with poststroke cognitive impairment treated with high-frequency repetitive transcranial magnetic stimulation were included. Included studies were assessed for the risk of bias through the Cochrane Intervention Systematic Review Manual 5.1.0. The meta-analysis was performed using RevMan 5.4 software. The PRISMA 2020 guidelines were followed. RESULTS: Sixty-one randomized controlled trials (4012 patients) were included. Montreal Cognitive Assessment Score, Mini-Mental State Examination score, event-related potential P300 (P300) amplitude, Loewenstein Occupational Therapy Cognitive Assessment score, and total effective rate of cognitive function were higher in the high-frequency repetitive transcranial magnetic stimulation group than in the control group at the end of the treatment period, and scores of Alzheimer Disease Assessment Scale-Cognitive Subscale and P300 latency were lower in the high-frequency repetitive transcranial magnetic stimulation group than in the control group. Fifty studies had selected the dorsolateral prefrontal cortex as the stimulation site for high-frequency repetitive transcranial magnetic stimulation. CONCLUSIONS: Compared with nonrepetitive transcranial magnetic stimulation or sham repetitive transcranial magnetic stimulation, high-frequency repetitive transcranial magnetic stimulation not only improves the overall cognitive function of poststroke cognitive impairment patients but also has better rehabilitation results.

Psoriasis comorbid with atherosclerosis meets in lipid metabolism.

Psoriasis (PSO) is a common skin disease affecting approximately 1%-3% of the population, and the incidence rate is increasing yearly. PSO is associated with a dramatically increased risk of cardiovascular disease, the most common of which is atherosclerosis (AS). In the past, inflammation was considered to be the triggering factor of the two comorbidities, but in recent years, studies have found that lipid metabolism disorders increase the probability of atherosclerosis in patients with psoriasis. In this review, we discuss epidemiological studies, clinical treatment methods, risk factors, and lipid metabolism of psoriasis and atherosclerosis comorbidities.

Corrigendum: Editorial: MSC-derived exosomes in tissue regeneration.

[This corrects the article DOI: 10.3389/fcell.2023.1293109.].

Study on Early Hydration Mechanism of Double-Liquid Grouting Material Modified by Composite Early Strength Agent.

To achieve an adjustable setting time and significantly improved early strength of a new type of sulphoaluminate cement-based double-liquid grouting material (SACDL), the effects of calcium formate, sodium sulfate, lithium carbonate, and a composite early strength agent on the setting hardening and early hydration behavior of SACDL paste were studied by means of setting time, fluidity, compressive strength, and viscosity tests. The results showed that the adsorption and osmosis of calcium formate, the complex decomposition of sodium sulfate, the precipitation polarization of lithium carbonate and the synergistic action of the composite early strength agent could accelerate the early hydration rate of SACDL, shorten the coagulation time, and improve the early strength of SACDL. The composite effect of 0.8% calcium formate and 0.5% sodium sulfate is the most significant in promoting coagulation and early strength; the initial setting time and final setting time of the slurry were shortened to 5 min and 10 min, respectively; and the 3 h compressive strength was capable of reaching 16.7 MPa, 31% higher than that of the blank group. In addition, X-ray diffraction and SEM morphology observation were used to study the composition of the hydration products and the evolution of the microstructure, which revealed the early hydration mechanism of SACDL under the synergistic effect of the composite early strength agent: (1) The solubility of tricalcium aluminate (C3A) and dihydrate gypsum (CaSO4·2H2O) increased under the low content composite early strength agent condition, which increased the ettringite (AFt) formation rate. HCOO- was able to penetrate the hydration layers of tricalcium silicate (C3S) and dicalcium silicate (C2S), accelerating the dissolution of C3S and C2S and promoting the early hydration of SACDL. (2) Under the condition of a high dosage of the composite early strength agent, the further increase in Ca2+ concentration promoted the crystallization nodules and precipitation of CH and accelerated the formation of calcium silicate hydrate (C-S-H) gel. C-S-H was filled between a large number of rod-like AFt crystals, thus making the structure more dense.

Dentinogenic ghost cell tumor revisited from a single institution in China with focus on adenoid ameloblastoma-like features.

OBJECTIVE: The present study aims to identify adenoid ameloblastoma (AdAM) from previously diagnosed cases of dentinogenic ghost cell tumor (DGCT), and gain insight to the possible relationship between AdAM and DGCT. METHODS: DGCT cases diagnosed between 2006 and 2022 were re-examined with focus on the AdAM-like features. RESULTS: A total of nine patients were included. Seven patients were males and two were females. The mean age was 38.0 ± 16.0 years. Five tumors occurred in the maxilla and four in the mandible, with a remarkable predilection for the posterior regions of both jaws. Microscopically, dentinoid material deposition was present in all cases. The ghost cells were absent in two cases. Rare ghost cells (<1%) were observed in three cases, and a higher proportion of ghost cells (5%-20%) were present in the remaining four cases. All cases showed prominent AdAM-like features, including duct-like structures, whorls/morules, and cribriform architecture. According to the diagnostic criteria proposed by the 2022 WHO classification, five cases without or with rare ghost cells were reclassified as AdAM. The other four cases including a higher proportion of ghost cells consisted of a mixture of DGCT and AdAM histopathologic patterns. CONCLUSION: Our results confirmed that the AdAM-like features had been largely overlooked in the diagnosis of DGCT at our institution in the past. Whilst a subset can now be more accurately classified as AdAM, some tumors showed overlapping morphological features between AdAM and DGCT, suggesting that the two may represent a spectrum of the same entity.

Akkermansia muciniphila Cell-Free Supernatant Improves Glucose and Lipid Metabolisms in Caenorhabditis elegans.

To explore the mechanism by which Akkermansia muciniphila cell-free supernatant improves glucose and lipid metabolisms in Caenorhabditis elegans, the present study used different dilution concentrations of Akkermansia muciniphila cell-free supernatant as an intervention for with Caenorhabditis elegans under a high-glucose diet. The changes in lifespan, exercise ability, level of free radicals, and characteristic indexes of glucose and lipid metabolisms were studied. Furthermore, the expression of key genes of glucose and lipid metabolisms was detected by qRT-PCR. The results showed that A. muciniphila cell-free supernatant significantly improved the movement ability, prolonged the lifespan, reduced the level of ROS, and alleviated oxidative damage in Caenorhabditis elegans. A. muciniphila cell-free supernatant supported resistance to increases in glucose and triglyceride induced by a high-glucose diet and downregulated the expression of key genes of glucose metabolism, such as gsy-1, pygl-1, pfk-1.1, and pyk-1, while upregulating the expression of key genes of lipid metabolism, such as acs-2, cpt-4, sbp-1, and tph-1, as well as down-regulating the expression of the fat-7 gene to inhibit fatty acid biosynthesis. These findings indicated that A. muciniphila cell-free supernatant, as a postbiotic, has the potential to prevent obesity and improve glucose metabolism disorders and other diseases.

Extramammary Paget disease of the buccal mucosa in an elderly patient.

OBJECTIVE: To report a rare case of oral extramammary Paget disease in an elderly patient. BACKGROUND: Extramammary Paget disease is a rare cutaneous malignancy, and oral mucosa involvement is extremely rare. MATERIAL AND METHOD: The patient was a 72-year-old man with a whitish plaque and areas of erosion on the right buccal mucosa. RESULTS: An incisional biopsy was performed, and the diagnosis was extramammary Paget disease. CONCLUSION: Both clinicians and pathologists should be aware of this disease to avoid misdiagnoses with other oral benign or malignant lesions.

Machine learning revealed ferroptosis features and ferroptosis-related gene-based immune microenvironment in lung adenocarcinoma.

Ferroptosis has been identified as a novel type of programmed cell death that has a major effect on the development of lung adenocarcinoma. Nevertheless, there has yet to be a clear set of therapeutic targets based on ferroptosis. This study seeks to employ machine learning methods to determine the regulators of ferroptosis in LUAD. 318 LUAD samples were investigated to determine three ferroptosis molecular phenotypes in LUAD, and then Boruta dimensionality reduction combined with principal component analysis was used to measure the ferroptosis regulation score (FRS) of patients. We additionally presented DeepFerr, a deep learning neural network model, which used the transcriptome map of 11 ferroptosis regulators to predict ferroptosis in LUAD. LASSO, SVM-RFE and elastic net were used to dissect the differential ferroptosis regulators, and the eight pivotal ferroptosis regulators have considerable ferroptosis prediction ability. It was established that RRM2 and AURKA are key suppressors of ferroptosis, and the depletion of RRM2 and AURKA caused an increase in ferroptosis in H358 cells. In addition, not only did they act as pro-proliferative factors that hindered immune infiltration in LUAD, but they were also essential for anti-PD1 therapy and chemotherapy. In summary, this research confirms the regulatory role of RRM2 and AURKA in ferroptosis, and could be useful in predicting individualized treatment for patients with LUAD.

GPX2 is a potential therapeutic target to induce cell apoptosis in lenvatinib against hepatocellular carcinoma.

INTRODUCTION: Lenvatinib has recently become available as the first-line therapy for advanced hepatocellular carcinoma (HCC), but its molecular mechanism in HCC remains largely unknown. OBJECTIVES: The current study aims to identify the molecular mechanisms of lenvatinib in HCC. METHODS: Gene expression microarrays, flow cytometry, western blot, qRT-PCR, immunohistochemistry and immunofluorescence were used to study the response of HCC cells to lenvatinib. Xenograft tumor of Huh7 cells was also established to detect the effect of lenvatinib in vivo. RESULTS: Herein, we found that lenvatinib could induce apoptosis via increasing reactive oxygen species (ROS) levels in HCC cells. Then, microarray analysis and qRT-PCR results confirmed that GPX2 was a vital target for lenvatinib against HCC. Loss and gain function of experiment showed that regulating GPX2 levels markedly affected the lenvatinib-induced ROS levels and apoptosis in HCC cells. In addition, analyses of The Cancer Genome Atlas database and the qRT-PCR results in our cohort both showed that GPX2 markedly overexpressed in tumor tissues and correlated with poor overall survival in HCC. Mechanistically, our findings further demonstrated that GPX2 was a downstream gene regulated by ß-catenin, while lenvatinib could prevent nuclear translocation of ß-catenin and further inhibit GPX2 expression in HCC cells. More importantly, the correlation of GPX2 expression with lenvatinib response was further analyzed in 22 HCC patients who received lenvatinib therapy, and the results showed that the objective response rate (ORR) in patients with low GPX2 expression was 44.4% (4/9), while the ORR in patients with high GPX2 levels was only 7.7% (1/13). CONCLUSION: Our findings indicated that GPX2 plays an important role in lenvatinib-induced HCC cell apoptosis, which might serve as a biomarker for instruction of lenvatinib therapy in HCC patients.

Epithelioid mesenchymal neoplasm with FUS::CREM gene fusion in the tongue: Report of a rare and challenging diagnosis.

FET (encompassing both EWSR1 and FUS) fusions with genes from the CREB family (CREB1, ATF1, and CREM) are involved in a variety of neoplasms. Recently, FET::CREB fusions were recognized in a group of malignant epithelioid neoplasm with a striking predilection to mesothelial-lined cavities and frequent cytokeratin immunoexpression. Herein, we report a rare mesenchymal neoplasm with epithelioid morphology and nonspecific immunoprofile harboring a FUS::CREM fusion arising in the oral tongue of a 53-year-old man. Histology showed a well-circumscribed tumor composed of epithelioid cells with eosinopohilic or clear cytoplasm with sparse stroma, accompanied by peripheral lymphoplasmacytic infiltrates. Immunohistochemically, an extensive panel revealed only patchy expression of synaptophysin and weak-to-moderate nuclear expression of TFE3, and negativity for other markers including cytokeratins, epithelial membrane antigen, p63/p40, vimentin, S100, smooth muscle actin, CD34, desmin, SOX10, glial fibrillary acidic protein, melan-A, HMB45, and CD68. A FUS::CREM gene fusion was detected by next generation sequencing at an outside institution, and subsequent fluorescence in situ hybridization analysis confirmed the presence of FUS gene rearrangement. The identification and analysis of additional cases should help to clarify the nosologic status and the biologic potential of this tumor.