Conjugation of substrate proteins with ubiquitin (Ub), a 76 amino acid protein, was discovered as the first major translational modification responsible for protein degradation. Ubiquitination occurs as a cascade among ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligases (E3) enzymes that transfer and covalently conjugate Ub to the lysine (Lys) residue and α-amino group in methionine (Met) residues of substrates. Following the initial conjugation, Ub itself then undergoes ubiquitination via its seven lysine residues (K6, K11, K27, K29, K33, K48, and K63) and N-terminal methionine (M1). These possible sites of Ub polymerization/assembly result in a significantly diverse and numerous set of linkage types and lengths, including homotypic, mixed and/or branched chains, which provoke distinct cellular responses via their proteolytic and non-proteolytic functions. We overview here the multiplicity of ubiquitin code with a particular focus on linkage-specific roles in biological processes, especially in the pathogenesis and progression of diseases such as cancer, neurodegeneration, and immune disorders. We will also discuss the possibility and ongoing efforts of modulating the ubiquitin code as a therapeutic strategy in drug development, including targeted protein degradation (TPD).

Cardiogenic shock (CS) is a critical condition marked by end-organ hypoperfusion and sustained hypotension, necessitating the use of inotropic or vasoactive agents for hemodynamic support. It is the leading cause of mortality in patients with acute myocardial infarction (AMI), exhibiting in-hospital mortality rates of 40% to 50% despite advances in treatment. Treatment strategies aim to restore hemodynamic stability and address the underlying cause through pharmacological agents and mechanical circulatory support devices. However, the persistently high mortality rates underline the challenges of a timely diagnosis, the limitations of current treatments, and the lack of a standardized multidisciplinary network of care. This review critically examines the existing literature on CS management, focusing on the efficacy, safety, and practical application of pharmacological interventions. By synthesizing evidence from recent studies, clinical guidelines, and expert consensus, our objective is to provide a useful, comprehensive, evidence-based framework to guide clinicians in the use of pharmacologic therapies tailored to the diverse presentations and stages of CS.

A vast range of neurological conditions impacting the central and peripheral nervous system are caused by ion channel dysfunctions, which are collectively referred to as channelopathies. These disorders, which are frequently autoimmune or genetic in nature, present as a variety of clinical syndromes, such as migraine, epilepsy, ataxia, neuropathic pain, and intermittent paralysis. The pathogenic mechanisms underlying these illnesses have been uncovered by recent developments in molecular genetics and electrophysiological research, opening up new avenues for accurate diagnosis and specialized treatment approaches. With an emphasis on important genetic variations and clinical manifestations, this study offers a targeted synthesis of channelopathies of the central and peripheral nervous system. By providing the most recent information on these complex disorders, this review aims to help physicians identify and treat channelopathies.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Early diagnosis and treatment of AD are of paramount importance, with the concept of biomarkers being intrinsically linked to diagnosis and therapy. Biomarkers are indices that can be objectively measured to indicate normal biological processes, pathological conditions, or responses to therapeutic interventions. In 2023, the National Institute on Aging and Alzheimer's Association released updated clinical diagnostic guidelines, refining the 2018 research framework. These guidelines categorize AD biomarkers into three types: core AD biomarkers, non-specific biomarkers of tissue response related to AD pathophysiology, and biomarkers for non-AD comorbidities, thus enhancing the amyloid/tau/x/neurodegeneration (ATX(N)) framework. This article aimed to provide a comprehensive overview of the advancements within the ATX(N) framework and the progress in the study of various biomarkers under this framework. It analyzes how biomarkers can facilitate early disease diagnosis, discusses the challenges of translating biomarkers into effective treatments, and explores their therapeutic prospects.

Background: Recurrent spontaneous abortion (RSA), also known as repeated miscarriage, refers to the consecutive loss of pregnancy three times or more before the fetus reaches viability. In this study, we aimed to investigate the impact of transforming growth factor β3 (TGF-β3), which plays a crucial role in immune dysregulation, on the imbalance of regulatory T cell (Treg) and T helper 17 (Th17) cells.

Methods: First, we isolated T cells from an RSA mouse model we established in-house. Tregs and Th17 cells were labeled by targeting forkhead box protein P3 (Foxp3) and retinoic-acid-receptor-γt (RORγt), respectively, and the levels of Tregs and Th17 were determined by flow cytometry. The expression levels of Foxp3, RORγt, TGF-β3, interleukin (IL)-10, and IL-17 in T cells were measured by means of reverse-transcription quantitative polymerase chain reaction (qRT-PCR) and Western blotting. The levels of interferon-γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-4 in mouse serum were quantified using enzyme-linked immunosorbent assay (ELISA). si-TGF-β3 was transfected into RSA mice, and the expression levels of IL-17 and CD25 were determined by flow cytometry, during which T cells were labeled with antibodies against IL-17 and CD25, respectively. Additionally, si-TGF-β3 or TGF-β3 interference therapy was administered to RSA mice, and the expression levels of IL-1β, tumor necrosis factor-α (TNF-α), IL-6, IFN-γ, GM-CSF, and IL-4 in mouse serum were measured using ELISA.

Results: In the RSA model, there was a significant decrease in the percentage of Treg cells, alongside an elevation of TGF-β3 mRNA (p < 0.05). The percentage of Th17 cells in RSA mice significantly increased and correlated positively with TGF-β3 levels. In RSA, the levels of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, IFN-γ, and GM-CSF increased, while those of anti-inflammatory cytokine IL-4 decreased (p < 0.05). Transfection of si-TGF-β3 into RSA mice reduced the percentage of Th17 cells and increased the percentage of Tregs and Treg/Th17 (p < 0.05). Increased levels of Th17-related markers and reduced levels of Tregs-related markers occurred following the administration of TGF-β3 to RSA mice (p < 0.05). Transfection of si-TGF-β3 into RSA mice also resulted in a decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines (p < 0.05), while TGF-β3 administration reversed these changes in RSA mice, indicating the role of TGF-β3 in modulating the inflammatory response during RSA.

Conclusions: Knockdown of TGF-β3 enhanced Treg/Th17 balance in RSA, suggesting TGF-β3 as a potential therapeutic target for RSA.

Background: Osteoarthritis (OA) is one of the most prevalent arthritis types globally, with the knee being particularly susceptible due to its frequent and strenuous use. Urolithin B (UB) exhibits various biological properties, with meniscal repair playing an important role in preventing knee OA. This study aimed to explore the impact of UB on meniscal regeneration and OA progression.

Methods: Initially, we explored the effect of UB on meniscal cells. Utilizing the cell counting kit (CCK)-8 assay, we determined the optimum concentration of UB treatment. Enzyme-linked immunosorbent assay (ELISA) was used for detecting inflammation-related interleukin-1beta (IL-1β). Real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was used for measuring the expression of extracellular matrix (ECM)-related proteins, ECM-degrading enzymes, and genes associated with joint formation in meniscal cells. Furthermore, 5-Bromo-2′-deoxyuridine (BrdU) staining was used to evaluate the proliferation of meniscal cells. Meniscal tissues were cultured in vitro, and western blot analysis was used to detect levels of proliferation-related markers such as proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF), as well as ECM protein collagen-1 (COL-1) and ECM degradation-related matrix metallopeptidase-13 (MMP-13). Mice were subjected to meniscus injury to establish a knee joint model of meniscus injury-induced osteoarthritis (MIOA) and to verify the effect of UB on meniscal cells in vivo. Pathological changes in knee joints were observed using hematoxylin-eosin (H&E) staining. Additionally, western blot was used to assess PCNA, VEGF, COL-1, and MMP-13 levels, while ELISA was used to detect inflammation-related tumor necrosis factor-alpha (TNF-α), IL-1β, IL-6, and interferon-gamma (IFN-γ) in mouse menisci.

Results: At concentrations up to 100 μM, UB exhibited non-toxicity and concomitantly decreased IL-1β in meniscal cells (p < 0.001). Moreover, UB increased the expression of ECM-related proteins (p < 0.001) and genes associated with joint formation (p < 0.001), while concurrently decreasing the expression of ECM-degrading enzymes (p < 0.001) in meniscal cells. UB promoted meniscal cell proliferation (p < 0.001). Additionally, UB increased PCNA, VEGF, and COL-1 while suppressing MMP-13 in menisci cultured in vitro (p < 0.001). Moreover, UB mitigated the pathological alterations observed in knee joints affected by meniscus injury. In murine models, MIOA led to decreased PCNA, VEGF, and COL-1 levels, alongside increased MMP-13, TNF-α, IL-1β, IL-6, and IFN-γ levels (p < 0.001), all of which were effectively reversed by UB treatment (p < 0.001).

Conclusion: UB effectively promotes meniscal regeneration and repair, while protecting against knee OA in mice, suggesting its potential role in clinical OA treatment.

Background: The role of tertiary lymphoid structures (TLSs) in stomach adenocarcinoma (STAD) remains unclear despite their known potential effects on tumor progression and prognosis.

Methods: Data were collected from 362 patients with STAD from The Cancer Genome Atlas (TCGA) database. Using single-sample genomic enrichment analysis, TLSs were quantified based on a 9-gene signature, and the patients were categorized into TLS-signature high (TLS-high) and TLS-signature low (TLS-low) groups. The association of TLS signature with prognosis, tumor microenvironment (TME) immune status, tumor mutation burden, and gene mutation status was evaluated. The GSE26253 cohort served as an external dataset to validate the prognostic predictive effect of the TLS signature in patients with STAD.

Results: The TLS-high group exhibited notably lower overall survival (OS) among male patients with STAD from the TCGA cohort (p = 0.01). Multivariate analysis revealed that the TLS signature was a significant independent negative predictor of OS in male patients with stage I–III STAD (hazard ratio (HR): 2.68; 95% confidence interval (CI): 1.19–6.00; p = 0.02). The TLS-high patients exhibited increased infiltration of immune cell subsets; however, cancer-immunity cycle analysis revealed both antitumor and protumor responses within the TME. Correlation analyses indicated that TLS was more strongly associated with immunosuppression-related cells than with antitumor immune cells. Furthermore, expressions of immunosuppressive cell-recruitment factors, immunosuppressive factors, and immune checkpoint receptors were higher in the TLS-high group than in the TLS-low group. Nonetheless, among male patients with stage I–III STAD who received adjuvant therapy, multivariate analysis identified TLS trait as a significant independent positive predictor of relapse-free survival in the GSE26253 cohort (HR: 0.61; 95% CI: 0.38–0.97; p = 0.04). Interaction of the TLS signature with adjuvant therapy exerted a significant positive effect on OS in these patients (HR: 0.41; 95% CI: 0.17–0.97; p = 0.04).

Conclusion: In the TCGA cohort, the TLS signature acted as an independent adverse prognostic factor for male patients with stage I–III STAD and was associated with immunosuppressive TME, which interacted to affect patient prognosis. However, adjuvant therapy may affect the prognostic predictive effect of TLS in male patients with stage I–III STAD.

Background: Exploring the pathological mechanism of colorectal cancer (CRC) onset and advancement is critical to clinical diagnosis and treatment. In this context, our study brings a novel perspective by investigating the role and regulatory mechanism of E74 Like ETS Transcription Factor 1 (ELF1) in CRC, a topic that has not been extensively explored.

Methods: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting (WB) assays were used to detect the expression of ELF1 in CRC cells. Sh-ELF1, ELF1 overexpresses lentivirus (Oe-ELF1), and Oe-Doublecortin Like Kinase 1 (DCLK1) were constructed and transfected into CRC cells. Transfection efficiency and the expression of stemness, as well as epithelial-mesenchymal transition (EMT)-related proteins were detected using RT-qPCR and WB assays. Cell proliferation and sphere-forming ability were detected using Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2′-deoxyuridine (EdU) staining, and sphere formation assay. Cell migration and invasion were detected using wound healing and transwell assay. The tube-forming ability of human umbilical vein endothelial cells (HUVEC) cells was detected using tubular formation experiments. To investigate the regulatory mechanism of ELF1, the crosstalk between ELF1 and downstream DCLK1 was predicated and verified using the JASPAR database, luciferase reporter gene, and Chromatin Immunoprecipitation (ChIP) assay.

Results: Results of the present study demonstrated that ELF1 expression was upregulated in CRC cells (p < 0.001). ELF1 silence significantly inhibited CRC cell proliferation, stemness, invasion, migration, and angiogenesis (p < 0.001). ELF1 silence also suppressed the expressions of Nanog Homeobox (Nanog), SRY-Box Transcription Factor 2 (Sox2), Octamer-Binding Transcription Factor 4 (OCT4), N-cadherin, and Vimentin while increasing the expression of E-cadherin (p < 0.001). Besides, ELF1 could positively regulate DCLK1 expression. However, the results of subsequent experiments revealed that DCLK1 overexpression partially offset the inhibitory effects of ELF1 knockdown on CRC cell proliferation, stemness, invasion, migration, and angiogenesis (p < 0.01).

Conclusion: In summary, our study provides compelling evidence that ELF1 up-regulates DCLK1 expression, thereby promoting the malignant progression and stemness of colorectal cancer. These findings significantly contribute to our understanding of the regulatory mechanisms in CRC and may have implications for future therapeutic strategies.

Background: Glucosamine-6-phosphate N-acetyltransferase 1 (GNPNAT1) is an enzyme involved in the hexosamine biosynthetic pathway, which is critical for glycosylation processes. In the context of non-small cell lung cancer (NSCLC), GNPNAT1 plays a significant role in modulating immune responses. The purpose of this study is to investigate the role of GNPNAT1 in regulating the efficacy of radiotherapy and resistance to natural killer (NK) cell-mediated cytotoxicity in patients with NSCLC.

Methods: To assess GNPNAT1's impact on radiotherapy efficacy, 122 lung cancer patients were categorized into radiosensitive and radioresistant groups. GNPNAT1 expression levels in cancerous tissues from both groups were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. This analysis was extended to various lung cancer cell lines (BEAS-2B, A549, LTEP-2, SPCA1, and H157) using the same molecular techniques. To investigate GNPNAT1's functional role in radioresistance, radioresistant A549 cells (A549R26-1) were established, and GNPNAT1 expression was genetically manipulated. Experimental groups included control, si-NC, si-GNPNAT1, Oe-NC, and Oe-GNPNAT1. Post-treatment, GNPNAT1 levels were measured via qRT-PCR and Western blotting. Cells were exposed to varying doses of radiation, and subsequent assessments included cell proliferation (Cell Counting Kit-8 (CCK-8) assay), radiosensitivity (plate cloning assays), and apoptosis rates (flow cytometry). Isolated and purified primary NK cells were co-cultured with lung cancer cells from each experimental group. The cytotoxicity of NK cells against lung cancer cells was assessed through lactate dehydrogenase (LDH) release and colony formation assays.

Results: Compared to the radiosensitive group, the radioresistant group exhibited significantly elevated GNPNAT1 expression levels (p < 0.05). The radioresistant cell line A549R26-1 demonstrated higher proliferation ability and lower apoptosis levels compared to its parental cell line, A549P. Subsequently, down-regulation of GNPNAT1 expression in A549R26-1 cells resulted in reduced proliferation, increased apoptosis, and weakened resistance to NK cell cytotoxicity. Conversely, up-regulation of GNPNAT1 expression in A549R26-1 cells following co-culture with NK cells led to increased proliferation and survival rates, and enhanced resistance to NK cell cytotoxicity. Notably, GNPNAT1 knockdown effectively attenuated the radioresistance of A549R26-1 cells.

Conclusion: Down-regulation of GNPNAT1 expression reduces the immune resistance of non-small cell lung cancer to radiotherapy and enhances susceptibility to NK cell cytotoxicity.

Background: Glioblastoma is an incurable and aggressive oncological disease of the brain. Recent studies have shown that transcranial non-invasive photobiomodulation is a promising new alternative method for suppression of glioblastoma growth. The lymphatic endothelium of the meningeal lymphatic vessels is an important target for the therapeutic effects of photobiomodulation. However, the functions of the meningeal lymphatic vessels decline with age. Therefore, it remains unknown whether photobiomodulation can be effective in adults and the elderly. To answer this question, this study examined the role of the meningeal lymphatic vessels and brain drainage in age-related differences in resistance to glioblastoma.

Methods: The studies were performed on 6- and 24-month-old rats using a model of fluorescent glioblastoma. Tumor progression was assessed using magnetic resonance imaging and the Fluor I in vivo fluorescence imaging system. Photobiomodulation was performed for 14 days for phototherapy of glioblastoma or once to study photoeffects on the brain's drainage. Brain drainage was studied by optical imaging of the lymphatic excretion of dye from the brain to the deep cervical lymph nodes, as well as by assessing the water content in brain tissues and the intracranial pressure. Histological and immunohistochemical methods were used to study apoptosis, proliferation and migration of CD8+ cells from the peripheral lymphatic system to glioblastoma.

Results: We clearly show that the network of the meningeal lymphatic vessels and brain drainage reduced in 24-month-old rats vs. 6-month-old animals (p < 0.001), which is accompanied by a decrease in resistance to the development of glioblastoma. Photobiomodulation significantly increases survival in 6-month-old (p < 0.001), but not in 24-month-old rats via an improvement of the functions of the meningeal lymphatic vessels, including a facilitating the traffic of protective CD8+ cells to glioblastoma (p < 0.001), reducing intracranial pressure and brain edema. The blockade of lymphatic communication between the peripheral and meningeal lymphatic systems completely suppresses the therapeutic effects of photobiomodulation in 6-month-old rats (p < 0.001).

Conclusion: Thus, photobiomodulation is an effective method of stimulation of brain drainage and immunity increasing resistance to glioblastoma progression in early but not in late ontogenesis due to the age-related decline in the functions of the meningeal lymphatic vessels.

Background: Depression represents a significant clinical concern for individuals diagnosed with non-small cell lung cancer (NSCLC) following surgical resection. This study aimed to investigate the potential of preoperative peripheral blood parameters, including the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR), as predictive indicators for the risk of developing depression within the initial 90-day postoperative period in NSCLC patients.

Methods: A prospective cohort study was conducted, enrolling 350 NSCLC patients, with 250 participants in the training set and 100 participants in the testing set. Participants were classified based on the presence or absence of depression 90 days after surgery. Preoperative blood parameters, including NLR, LMR, PLR, and inflammatory biomarkers, were measured. Statistical analyses, encompassing Logistics regression analysis and receiver operating characteristic (ROC) curve analysis, were performed to assess the significance and predictive value of these blood parameters. Multivariate predictive models were constructed based on the identified significant parameters.

Results: In the training set, statistically significant differences were observed between the non-depression and depression groups for NLR (4.35 ± 1.23 vs. 3.14 ± 0.82, t = 8.715, p < 0.001), LMR (3.84 ± 1.58 vs. 5.58 ± 1.23, t = 8.849, p < 0.001), PLR (187.46 ± 35.26 vs. 152.36 ± 32.46, t = 7.112, p < 0.001), and various blood parameters. Logistics regression analysis showed significant associations between NLR, LMR, PLR, and postoperative depression. ROC curve analysis indicated the predictive value of NLR [area under the curve (AUC) = 0.794], LMR (AUC = 0.800), and PLR (AUC = 0.766), with the multivariate model yielding an AUC of 0.931. These results were consistent in the testing set, where significant differences were observed between the non-depression and depression groups for NLR (4.23 ± 1.24 vs. 3.13 ± 0.75, t = 5.417, p < 0.001), LMR (3.17 ± 1.55 vs. 4.76 ± 1.22, t = 5.412, p < 0.001), PLR (189.46 ± 46.58 vs. 151.48 ± 34.26, t = 4.481, p < 0.001), and various blood parameters. The AUC values were 0.771, 0.791, and 0.755 for NLR, LMR, and PLR, respectively, while the multivariate model yielded an AUC of 0.928.

Conclusions: The study highlights the potential of preoperative peripheral blood NLR, LMR, and PLR as predictive indicators for the risk of postoperative 90-day depression in patients with NSCLC.

Clinical Trial Registration: Approval number: ChiCTR2300070375, https://www.chictr.org.cn/index.html.

Background: The relationship between hematocrit (HCT) levels and the occurrence of major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI) remains unexplored. A better understanding of this interplay may enhance the prognosis and management of AMI patients.

Methods: Between January 2021 and August 2022, clinical data were collected from patients diagnosed with AMI at 10 tertiary healthcare institutions in China. A total of 1946 eligible participants were included and divided into three groups based on sex-specific tertiles of HCT levels upon admission: 648 patients with low HCT levels, 649 patients with intermediate HCT levels, and 649 patients with high HCT levels. Follow-up approaches included hospital outpatient visits, inpatient stays, and telephone calls for 180 days. The primary endpoint was the occurrence of MACEs. Influential factors, including general information, admission status, and supplementary examination results that differed across the cohorts, were analyzed. Cox regression analysis was employed to evaluate the 180-day MACE rates and HCT levels in patients with AMI. To assess the reliability of the findings, three sensitivity analyses and subgroup analyses were performed.

Results: During this time, 136 individuals in the low HCT group, 77 in the intermediate HCT group, and 73 in the high HCT group experienced endpoint events. With all covariates controlled, the Cox regression analysis indicated that the low HCT group had a higher risk of MACEs compared to the intermediate HCT group [hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.07–1.95, p = 0.017]. The low HCT group also presented a higher risk of acute coronary syndrome (HR = 1.57, 95% CI = 1.06–2.32, p = 0.024). However, the high and intermediate HCT groups exhibited comparable prognoses for AMI. The limited cubic spline plot revealed that HCT values between 41.58% and 45.36% implied a protective effect against MACEs. These results were further verified by sensitivity analysis, and the subgroup analysis showed no variable interaction.

Conclusions: Our findings indicate that low HCT levels in patients with AMI increase the incidence of MACEs within 180 days, offering new insights into the prognosis and management of AMI patients.

Clinical Trial Registration: ChiCTR2200066456.

Background: Traditional Chinese medicines exhibit tremendous beneficial effects on the control of hyperlipidemia and hyperlipidemia-associated disorders. In the present study, we investigated the effects of four Coreopsis tinctoria Nutt. extracts, including luteolin, marein, naringenin (NGN) and chlorogenic acid (CQA), on lipid accumulation and oxidative stress induced by oleic acid (OA) in HepG2 cells.

Methods: Oleic acid was employed to create a high-lipid milieu in a cellular setting in vitro using HepG2 cells. After treatment by luteolin, marein, NGN, and CQA, cell counting kit-8 assay was used for measuring cell viability. Lipid accumulation, lipid metabolism and oxidative stress were examined by means of enzyme-linked immunosorbent assay, Oil red O staining, quantitative real-time polymerase chain reaction (qRT-PCR) and 2′,7′-dichlorodihydro fluorescein diacetate assays. Western blot and qRT-PCR assays were applied to determine the expression of genes and proteins, respectively.

Results: In OA-treated HepG2 cells, the administration of the four active flavonoids of Coreopsis tinctoria Nutt. (luteolin, marein, NGN and CQA) enhanced cell viability (p < 0.05 or p < 0.01); reduced lactate dehydrogenase releasing, lipid deposition and production of triglyceride, total cholesterol and low-density lipoprotein-cholesterol (p < 0.05 or p < 0.01); and elevated high-density lipoprotein-cholesterol production (p < 0.05 or p < 0.01 or p < 0.001). Moreover, after luteolin, marein, NGN or CQA treatment, the expression of lipid metabolism-related genes including 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), low-density lipoprotein receptor (LDLR) and apical sodium-dependent bile acid transporter (ASBT) was downregulated (p < 0.01 or p < 0.001) but the expression of cytochrome P450 family 7 subfamily A member 1 (CYP7A1) was upregulated (p < 0.05 or p < 0.01 or p < 0.001) in OA-treated HepG2 cells. Similarly, luteolin, marein, NGN or CQA treatment greatly enhanced the anti-oxidant activities (p < 0.05 or p < 0.01 or p < 0.001) and decreased reactive oxygen species production (p < 0.01 or p < 0.001) in OA-treated HepG2 cells. Sterol regulatory element-binding protein, a major transcription factor that moderates the biosynthesis of fatty acid, cholesterol and triglyceride, was also inhibited after luteolin, marein, NGN or CQA treatment (p < 0.05 or p < 0.01 or p < 0.001).

Conclusion: These findings demonstrated that luteolin, marein, NGN or CQA can effectively reduce OA-induced oxidative stress and lipid accumulation, corroborating their potential in hyperlipidemia treatment.

Background: The retromolar canal (RMC) is an extension of the mandibular canal located in the distal region of the mandibular third molar. Accurately detecting the RMC using conventional two-dimensional images is challenging, potentially leading to anesthetic failure and sensory disorders. This study aims to explore the clinical application of a radiomic model based on panoramic radiographs in detecting the RMC.

Methods: A retrospective collection of cone beam computed tomography (CBCT) and panoramic radiographs was conducted on 800 patients, covering 1555 hemimandibles. CBCT images served as the gold standard for confirming the presence of RMC. A dataset comprising 846 retromolar regions was established for model training and testing, with an 8:2 ratio. On the panoramic radiographs, the retromolar regions were delineated as the regions of interest, and radiomic features were extracted and selected. Support vector machine (SVM), logistic regression (LR), k-nearest neighbors (KNN), and multilayer perceptron (MLP) were employed to construct detection models for the RMC. The performance of these algorithms was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA), and the area under the receiver operating characteristics curve (AUC) values were compared with those of a dentist and a radiologist.

Results: The RMC was identified in 423 (27.2%) out of 1555 hemimandibles on CBCT images. The four algorithms, particularly SVM and MLP, demonstrated outstanding classification abilities in detecting the RMC, with AUC values ranging from 0.831 to 0.895 in the training set and from 0.719 to 0.808 in the testing set. These results significantly surpassed those of the dentist and radiologist (p < 0.05).

Conclusion: Radiomics based on panoramic radiographs exhibit a high detection capability for the RMC, emphasizing its considerable clinical application value.

Background: Angiotensin II (Ang II) and its receptor, Angiotensin II receptor type 1 (AGTR1), have been implicated in the proliferation of cancer cells across various tumor types. This study aims to examine the impact of Ang II and AGTR1 on esophageal squamous cell carcinoma (ESCC) cells.

Methods: The clonogenicity and proliferation of tumor cells were evaluated through Clone Formation and Cell Counting Kit-8 (CCK-8) assays. Cell migration and invasion were determined utilizing Transwell assays. Flow cytometry was employed to analyze the cell cycle. Additionally, to investigate the expressions of genes associated with cell growth, migration, infiltration, and Janus kinase-signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathways, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were utilized.

Results: In the current study, it was observed that increasing the concentration of Ang II significantly augmented the proliferation of ESCC cells. However, with the addition of its inhibitor losartan, the proliferative activity of ESCC cells was significantly reduced with the increase of losartan concentration (p < 0.05). The inhibition of AGTR1 also markedly reduced the proliferative activity of ESCC cells, counteracting the effect induced by Ang II treatment (p < 0.05). Additionally, Ang II was found to stimulate the migration and invasion of ESCC cells, facilitate the transition of these cells from the first gap (G1) to the synthesis (S) phase, and impede apoptosis (p < 0.05). However, treatment with losartan and AGTR1 inhibition significantly diminished the number of migratory and invasive cells, inhibited the transition from G1 to S phase, and promoted apoptosis in ESCC cells (p < 0.05). Regarding the mechanism, our research team found that Ang II and AGTR1 can enhance the proliferation and invasion of ESCC cells and inhibit their apoptosis via the JAK/STAT3 signaling pathway. Nevertheless, the AGTR1 blocker, losartan, effectively obstructed this process.

Conclusion: The activation of the JAK/STAT3 signaling pathway by Ang II and AGTR1 promotes the advancement of ESCC tumors. Consequently, targeting Ang II and AGTR1 could potentially emerge as a promising strategy for ESCC treatment.