Biological Behavior Research Articles

Flavonoids attenuate inflammation of HGF and HBMSC while modulating the osteogenic differentiation based on microfluidic chip

BackgroundWhen inflammation occurs in periodontal tissues, a dynamic cellular crosstalk interacts between gingival fibroblasts and bone marrow mesenchymal stem cells (BMSCs), which plays a crucial role in the biological behaviour and differentiation of the cells. Recently, flavonoids are increasingly recognized for their therapeutic potential in modulating inflammation and osteogenic differentiation. Owing to their varied molecular structures and mechanisms, there are more needs that flavonoid compounds should be identified by extensive screening. However, current drug research mostly relies on static, single-type cell cultures. In this study, an innovative bionic microfluidic chip system tailored for both soft and hard tissues was developed to screen for flavonoids suitable for treating periodontitis.MethodsThis study developed a microfluidic system that bionically simulates the soft and hard structures of periodontal tissues. Live/dead staining, reactive oxygen species (ROS) staining, and RT-qPCR analysis were employed. These techniques evaluated the effects of flavonoid compounds on the levels of inflammatory factors and ROS contents in HGF and HBMSC under LPS stimulation. Additionally, the impact of these compounds on osteogenic induction in HBMSC and the exploration of the underlying mechanisms were assessed.ResultsThe microfluidic chip used in this study features dual chambers separated by a porous membrane, allowing cellular signal communication via bioactive factors secreted by cells in both layers under perfusion. The inflammatory response within the chip under LPS stimulation was lower compared to individual static cultures of HGF and HBMSC. The selected flavonoids-myricetin, catechin, and quercetin-significantly reduced cellular inflammation, decreased ROS levels, and enhanced osteogenic differentiation of BMSCs. Additionally, fisetin, silybin, and icariside II also demonstrated favorable outcomes in reducing inflammation, lowering ROS levels, and promoting osteogenic differentiation through the Wnt/β-catenin pathway.ConclusionsThe bionic microfluidic chip system provides enhanced capabilities for drug screening and evaluation, delivering a more precise assessment of drug efficacy and safety compared to traditional in vitro methods. This study demonstrates the efficacy of flavonoids in influencing osteogenic processes in BMSCs primarily through the Wnt/β-catenin pathway. These results uncover the potential of flavonoids as therapeutic medicine for treating periodontitis, meriting further research and development.Graphical

Diverse Pharmacological Potential of different Substituted Pyrazole Derivatives.

The chemistry of heterocyclic compounds has been a topic of research interest. Some five-membered heterocyclic compounds have been the subject of extensive research due to their different types of pharmacological effects. The five-membered nitrogen-containing heterocyclic compounds pyrazole, pyrazoline, and pyrazolone derivatives have a lot of interest in the fields of medical and agricultural chemistry due to their diverse spectrum of therapeutic activities. Various substituted pyrazole, pyrazoline, and pyrazolone compounds exhibited diverse pharmacological effects like Anti-microbial, anti-inflammatory, anti-tubercular, anti-fungal, anti-malarial, anti-diabetic, diuretic, anti-depressant, anticonvulsant, antioxidant, anti-leishmanial, antidiabetic, and antiviral, etc. In recent decades, the synthesis of numerous pyrazole, pyrazoline, and pyrazolone derivatives by different synthetic methods as well as research into their chemical and biological behavior have become more important. This review focuses on synthetic methods of the pyrazole, pyrazoline, and pyrazolone derivatives, which have significant biological properties and a variety of applications.

Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance.

Early-onset breast cancer is known for its aggressive clinical characteristics and high prevalence in East Asian countries, but a comprehensive understanding of its molecular features is still lacking. In this study, we conducted a proteogenomic analysis of 126 treatment-naïve primary tumor tissues obtained from Korean patients with young breast cancer (YBC) aged ≤40 years. By integrating genomic, transcriptomic, and proteomic data, we identified five distinct functional subgroups that accurately represented the clinical characteristics and biological behaviors of patients with YBC. Our integrated approach could be used to determine the proteogenomic status of HER2, enhancing its clinical significance and prognostic value. Furthermore, we present a proteome-based homologous recombination deficiency (HRD) analysis that has the potential to overcome the limitations of conventional genomic HRD tests, facilitating the identification of new patient groups requiring targeted HR deficiency treatments. Additionally, we demonstrated that protein-RNA correlations can be used to predict the late recurrence of hormone receptor-positive breast cancer. Within each molecular subtype of breast cancer, we identified functionally significant protein groups whose differential abundance was closely correlated with the clinical progression of breast cancer. Furthermore, we derived a recurrence predictive index capable of predicting late recurrence, specifically in luminal subtypes, which plays a crucial role in guiding decisions on treatment durations for YBC patients. These findings improve the stratification and clinical implications for patients with YBC by contributing to the optimal adjuvant treatment and duration for favorable clinical outcomes.

Alendronate sodium induces G1 phase arrest and apoptosis in human umbilical vein endothelial cells by inhibiting ROS-mediated ERK1/2 signaling

Bisphosphonates are potent bone resorption inhibitors, among which alendronate sodium (ALN) is commonly prescribed for most osteoporosis patients, but long-term application of ALN can cause bisphosphonate-related osteonecrosis of jaw (BRONJ), the pathogenesis of which remains unclear. Previous studies have suggested that bisphosphonates cause jaw ischemia by affecting the biological behavior of vascular endothelial cells, leading to BRONJ. However, the impacts of ALN on vascular endothelial cells and its mechanism remain unclear. The purpose of this work is to assess the influence of ALN on human umbilical vein endothelial cells (HUVECs) and clarify the molecular pathways involved. We found that high concentration of ALN induced G1 phase arrest in HUVECs, demonstrated by downregulation of Cyclin D1 and Cyclin D3. Moreover, high concentration of ALN treatment showed pro-apoptotic effect on HUVECs, demonstrated by increased levels of the cleaved caspase-3, the cleaved PARP and Bax, along with decreased levels of anti-apoptotic protein Bcl-2. Further experiments showed that ERK1/2 phosphorylation was decreased. Additionally, ALN provoked the build-up of reactive oxygen species (ROS) in HUVECs, leading to ERK1/2 pathway suppression. N-acetyl-L-cysteine (NAC), a ROS scavenger, efficiently promoted the ERK1/2 phosphorylation and mitigated the G1 phase arrest and apoptosis triggered by ALN in HUVECs. PD0325901, an inhibitor of ERK1/2 that diminishes the ERK1/2 phosphorylation enhanced the ALN-induced G1 phase arrest and apoptosis in HUVECs. These findings show that ALN induces G1 phase arrest and apoptosis through ROS-mediated ERK1/2 pathway inhibition in HUVECs, providing novel insights into the pathogenic process, prevention and treatment of BRONJ in individuals receiving extended use of ALN.

DTL promotes the growth and migration of melanoma cells through the ERK/E2F1/BUB1 axis

Melanoma is the most dangerous form of skin cancer. Hence, a better understanding of molecular mechanisms in melanoma pathogenesis is urgently needed, which provides a new insight into the therapy of melanoma. DTL gene is screened out in melanoma pathogenesis by integrated bioinformatics analysis, and its expression is validated in the tissue and cell samples of melanoma. Forced DTL expression facilitates the proliferation, invasion, migration and EMT of melanoma cells, while DTL knockdown suppresses the biological behavior of melanoma cells. In addition, DTL promotes the malignancy of melanoma in vivo. Mechanistically, BUB1 is the crucial downstream target of DTL. Reduced DTL expression suppresses BUB1 expression, while enhanced DTL expression induces BUB1 upregulation. Rescue experiments showed that growing and migrating of melanoma cells induced by DTL are partially impaired by BUB1 inhibition. In addition, the expression of phosphorylated ERK (p-ERK) and the downstream transcription factor E2F1 are reduced when DTL expression is blocked. Meanwhile, BUB1 levels are decreased when the expression of p-ERK or E2F1 is repressed. Notably, the growth and migration of melanoma cells by inhibition of ERK and knockdown of E2F1 was rescued by overexpressing BUB1. DTL gene may be a prognosis marker and represent a unique potential target for melanoma patients. DTL supports the biologically malignant activity of melanoma cells via the ERK/E2F1/BUB1 axis.

The role of lncRNA binding to RNA‑binding proteins to regulate mRNA stability in cancer progression and drug resistance mechanisms (Review).

Cancer is a disease that poses a serious threat to human health, the occurrence and development of which involves complex molecular mechanisms. Long non‑coding RNAs (lncRNAs) and RNA‑binding proteins (RBPs) are important regulatory molecules within cells, which have garnered extensive attention in cancer research in recent years. The binding of lncRNAs and RBPs plays a crucial role in the post‑transcriptional regulation of mRNA, affecting the synthesis of proteins related to cancer by regulating the stability of mRNA. This, in turn, regulates the malignant biological behaviors of tumor cells, such as proliferation and metastasis, and serves an important role in therapeutic resistance. The present study reviewed the role of lncRNA‑RBP interactions in the regulation of mRNA stability in various malignant tumors, with a focus on the molecular mechanisms underlying this regulatory interaction. The aim of the present review was to gain a deeper understanding of these molecular mechanisms to provide new strategies and insights for the precise treatment of cancer.

Trifolirhizin targets PTK6 to induce autophagy and exerts antitumor effects in nasopharyngeal carcinoma.

Trifolirhizin, a natural flavonoid glycoside, has been proved to exert antitumor activities in various human malignant tumors. PTK6 was identified as a direct target of trifolirhizin based on public database SuperPred (https://prediction.charite.de/). Overexpressed PTK6 in a variety of tumors is closely associated with the malignant development of tumors. Herein, this present research was formulated to elaborate the effects of trifolirhizin on the biological behaviors of nasopharyngeal carcinoma (NPC) cells and to probe into the intrinsic mechanisms. The current study firstly elucidated the tumor-inhibiting functions of trifolirhizin in NPC malignant progression from the perspective of targeting inhibition of PTK6. In this work, CCK-8 for cell viability, EdU staining for cell proliferation, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining for cell apoptosis and immunofluorescence staining for LC3 expression were performed. Besides, levels of proliferation-related, apoptosis-related and autophagy-related proteins were detected by western blot analysis. Moreover, molecular docking of trifolirhizin with PTK6 was conducted to seek the compound-protein binding potential. It was demonstrated that trifolirhizin treatment inhibited the proliferation and promoted the apoptosis of NPC cells as well as strengthened autophagy in NPC cells. Furthermore, it was verified that trifolirhizin targeted PTK6 and negatively regulated PTK6 expression. The suppressive effects of trifolirhizin on the malignant behaviors of NPC cells and the enhancing effect of trifolirhizin on autophagy in NPC cells were partly abolished upon upregulation of PTK6. To conclude, findings suggested that trifolirhizin may downregulate PTK6 expression to induce autophagy and exert the antitumor activities in NPC.

Clinicopathological analysis of hybrid carcinomas of the salivary glands: A systematic review.

Hybrid carcinomas (HC) are the association of two or more malignant neoplasms arising within the same topographical area. The present study is a systematic review of HC of the salivary glands. This study aimed to assess HC clinicopathological features and molecular profile. Observational studies, case series, and case reports were included. PubMed, Scopus, EMBASE, Lilacs, Web of Science, and gray literature were searched until June 2024. A total of 18 articles including 34 patients were included. HC of the salivary glands is presented as a painless mass affecting mainly the parotid gland of adults with a preference for male patients. Histologically, adenoid cystic carcinoma and epithelial-myoepithelial carcinoma were the most prevalent association, being surgical excision with radiotherapy the most common treatment. It's seen that the most aggressive component might guide the patient's treatment and prognosis. Further molecular studies are necessary to determine if HC are distinct entities or biologically identical to the individual neoplasms. In conclusion, this systematic review may contribute to a better understanding of this rare lesion, their biological behavior, treatments employed, and the outcome of these patients.

Coregulation between parents and elementary school-aged children in response to challenge and in association with child outcomes: A systematic review.

Parent-child coregulation, the active dyadic adaptation of biological states, behaviors, and emotions, is an important developmental process. Especially in challenging situations, children need coregulatory support from their parents, which supports the formation of their self-regulation skills. While research has established that coregulation occurs in various contexts across the developmental period, less is known about what constitutes coregulation in terms of child adjustment and the contextual factors that affect coregulation. This systematic review examined what constitutes parent-child coregulation in response to an experimentally induced challenge and in association with child socioemotional outcomes. Systematic searches were conducted in Web of Science, APA PsycInfo, and PubMed, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Fourteen full-text, peer-reviewed, empirical journal articles that were available in English were included. Children were between the ages of 3 and 12 (Mage = 5.37 years, 44%-100% male, 6.3%-90% White). Findings indicate that behavioral and emotional coregulation in response to challenge is positively associated with better child self-regulation. Coregulation associated with positive child outcomes seems to be characterized by high flexibility and dyadic synchrony in mutually responsive and engaged states. Findings regarding physiological coregulation suggest that high levels of physiological synchrony can be maladaptive for child outcomes in the presence of risk (e.g., poverty, maltreatment). In addition, this review highlighted the current ambiguity surrounding the diverse terminologies and concepts used to measure coregulation. The findings of this review reveal a significant link between parent-child coregulation and child socioemotional outcomes, while supporting the idea that contextual factors need to be considered to understand its significance. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Switch/Sucrose Non-Fermentable (SWI/SNF) Complex—Partial Loss in Sinonasal Squamous Cell Carcinoma: A High-Grade Morphology Impact and Progression

Sinonasal carcinomas are aggressive neoplasms that present a high morbidity and mortality rate with an unfavorable prognosis. This group of tumors exhibits morphological and genetic diversity. Genetic and epigenetic alterations in these neoplasms are the current targets for diagnosis and treatment. The most common type of cancer originating in the sinonasal tract is sinonasal squamous cell carcinomas (SNSCCs), which present different histological patterns and variable histological aggressiveness. A significant number of alterations have been reported in sinonasal tumors, including deficiencies in the Switch/Sucrose non-fermentable (SWI/SNF) chromatin remodeling complex. In the sinonasal tract, deficiencies of the subunits SMARCB1/INI1, SMARCA4/BRG1, and SMARCA2 have been noted in carcinomas, adenocarcinomas, and soft tissue tumors with a distinctive high-grade morphology and a fatal prognosis. Objective: The objective of this study is to identify the status of the SWI/SNF complex using immunohistochemistry in sinonasal squamous cell carcinomas and their association with morphology and survival. Methods: A total of 103 sinonasal carcinomas with different grades of squamous differentiation were analyzed; the selection was based on those cases with high-grade morphology. The carcinomas were then evaluated immunohistochemically for SMARCB1 and SMARCA4 proteins. Their expression was compared with the biological behavior and survival of the patients. Results: Among the SNSCCs, 47% corresponded to the non-keratinizing squamous cell carcinoma (NKSCC) type with high-grade characteristics, 40% were keratinizing squamous cell carcinomas (KSCCs), 9% were SMARCB1-deficient carcinomas, and 4% were SMARCA4-deficient carcinomas. Mosaic expression for SMARCB1 (NKSCC—33%; KSCC—21.9%) and SMARCA4 (NKSCC—14.6%; KSCC—12.2%) was identified, showing an impact on tumor size and progression. Conclusions: We identified that that the partial loss (mosaic expression) of SMARCB1 in SNSCCs is associated with high-grade malignant characteristics and a negative effect on patient survival; meanwhile, SMARCA4-mosaic expression in SNSCCs is associated with high-grade malignant characteristics and an increase in tumor size concerning the intact SMARCA4.

Colloidal Quantum Dots‐Based Photoelectrochemical‐Type Optoelectronic Synapse

AbstractCurrent artificial neuromorphic systems are mainly constructed using solid‐state optoelectronic synaptic devices, limiting their potential artificial intelligence applications in liquid medium. Here, colloidal CuInGaSe/ZnSe quantum dots (QDs) with environment‐benign feature and broad visible light absorption are prepared to fabricate a photoelectrochemical (PEC)‐type optoelectronic synaptic device operating in aqueous electrolyte, enabling unique biological synaptic behaviors including paired‐pulse facilitation (PPF), short‐term plasticity (STP), long‐term plasticity (LTP) and learning‐forgetting‐relearning process when simulated by optical pulses with various wavelength, pulse number, frequency, power density, and applied voltage. These results demonstrate the feasibility of building PEC‐type optoelectronic synapses using colloidal QDs, paving the way to realize available optoelectronic synaptic devices for prospective underwater artificial intelligence technology.

Artificial Intelligence in Prostate Cancer Diagnosis

Prostate cancer (PCa) is a cancer with a broad spectrum of biological behavior and it is a heterogeneous nature. In order to prevent overdiagnosis and overtreatment, and to detect clinically significant PCa, standardized scoring and grading systems are used in imaging and pathological examinations. However, reproducibility and agreement between readers in these diagnostic stages, which require experience, are low. Promising results have been achieved by integrating artificial intelligence (AI)-based applications into the diagnosis and management of PCa. In radiological and pathological imaging, computer-aided diagnostic tools have increased clinical efficiency and achieved diagnostic accuracy comparable to that of experienced healthcare professionals. This review provides an overview of AI applications used in radiological imaging, prostate biopsy, and histopathological examination in the diagnosis of PCa.

Hydrogel-Based Network Metamaterials with Biological Tissue-like Poisson's Ratio Behavior and Stress Response.

Soft network metamaterials are widely used in fields such as flexible electronics, tissue engineering, and biomedicine due to their superior properties including low density, high stretchability, and high breathability. However, the prediction and customization of the nonlinear mechanical behavior of soft network metamaterials remain a challenging problem. In this study, a family of hydrogel-based network metamaterials with biological tissue-like mechanical properties are developed based on a machine learning-driven optimization design method. Numerical and experimental results explain the relationship between the mechanical properties of the designed metamaterials and their microstructural features and stretching ratios. The results indicate that the hydrogel-based network metamaterials exhibit J-shaped stress-deformation (σ-λ) behavior similar to biological tissues. This phenomenon arises from the transition of the deformation mode of metamaterials from bending-dominated to stretching-dominated as the stretching ratio increases. Based on the proposed design scheme, the Poisson's ratio of metamaterials can be adjusted within a remarkably wide range of -1.06 to 1.34. Furthermore, through optimizing the design parameters of the metamaterial, the customization of network metamaterials with biological tissue-like zero Poisson's ratio behavior and stress response is achieved. The potential applications of hydrogel-based network metamaterials are demonstrated through artificial skin and LED integrated device. This research offers novel insights into predicting, designing, and fabricating the mechanical behavior of soft network metamaterials.

Application of Artificial Intelligence in Prediction of Ki-67 Index in Meningiomas: A Systematic Review and Meta-Analysis.

The Ki-67 index is a histopathological marker that has been reported to be a crucial factor in the biological behavior and prognosis of meningiomas. Several studies have developed artificial intelligence (AI) models to predict the Ki-67 based on radiomics. In this study, we aimed to perform a systematic review and meta-analysis of AI models that predicted the Ki-67 index in meningioma. Literature records were retrieved on April 27th, 2024, using the relevant key terms without filters in PubMed, Embase, Scopus, and Web of Science. Records were screened according to the eligibility criteria, and the data from included studies were extracted. The quality assessment was performed using the QUADAS-2 tool. The meta-analysis, sensitivity analysis, and meta-regression were conducted using R software. Our study included six studies. The mean Ki-67 ranged from 2.7 ± 2.97 to 4.8 ± 40.3. Of six studies, five utilized an ML method. The most used AI method was the least absolute shrinkage and selection operator (LASSO). The AUC and ACC ranged from 0.83 to 0.99 and 0.81 to 0.95, respectively. AI models demonstrated a pooled sensitivity of 87.5% (95% CI: 75.2%, 94.2%), a specificity of 86.9% (95% CI: 75.8%, 93.4%), and a diagnostic odds ratio (DOR) of 40.02 (95% CI: 13.5, 156.4). The summary receiver operating characteristic SROC curve indicated an AUC of 0.931 for the prediction of Ki-67 index status in intracranial meningiomas. AI models have demonstrated promising performance for predicting the Ki-67 index in meningiomas and can optimize the treatment strategy.

Metastatic Adenoid Cystic Carcinoma at the Base of the Tongue and Duplicate Breast Cancer Diagnosed During Restaging.

Adenoid cystic carcinoma (AdCC) is a rare malignant tumor that primarily affects the salivary glands but can also occur in other organs. Low incidence and unpredictable clinical behavior make AdCC one of the most difficult head and neck tumors to treat. We present the case of a 54-year-old woman with AdCC localized at the base of the tongue, following radical surgical and oncological therapy. Due to advances in palliative oncological treatment, there is a more than five-year survival period before the progression of metastatic disease. Considering the rare occurrence of this disease, a literature search was also conducted, and therapy options are discussed. Ensuring a sufficient extent of the surgical procedure is still a challenge, and most specialists agree that subsequent postoperative radiotherapy reduces the risk of local recurrence. The effective dose of radiotherapy to the area of the primary tumor and lymph nodes is not clearly defined. The distinct biological behavior of AdCC results in varying sensitivity to chemotherapy or radiotherapy compared to treatments commonly used for head and neck squamous cell carcinomas. Treatment recommendations for these rarer tumors are based mainly on case reports and small clinical trials. The acquired therapeutic experience can contribute to prolonging the survival period of patients and improving their prognosis and quality of life.

Integrated analysis of bulk and single-cell RNA sequencing reveals the impact of nicotinamide and tryptophan metabolism on glioma prognosis and immunotherapy sensitivity

BackgroundNicotinamide and tryptophan metabolism play important roles in regulating tumor synthesis metabolism and signal transduction functions. However, their comprehensive impact on the prognosis and the tumor immune microenvironment of glioma is still unclear. The purpose of this study was to investigate the association of nicotinamide and tryptophan metabolism with prognosis and immune status of gliomas and to develop relevant models for predicting prognosis and sensitivity to immunotherapy in gliomas.MethodsBulk and single-cell transcriptome data from TCGA, CGGA and GSE159416 were obtained for this study. Gliomas were classified based on nicotinamide and tryptophan metabolism, and PPI network associated with differentially expressed genes was established. The core genes were identified and the risk model was established by machine learning techniques, including univariate Cox regression and LASSO regression. Then the risk model was validated with data from the CGGA. Finally, the effects of genes in the risk model on the biological behavior of gliomas were verified by in vitro experiments.ResultsThe high nicotinamide and tryptophan metabolism is associated with poor prognosis and high levels of immune cell infiltration in glioma. Seven of the core genes related to nicotinamide and tryptophan metabolism were used to construct a risk model, and the model has good predictive ability for prognosis, immune microenvironment, and response to immune checkpoint therapy of glioma. We also confirmed that high expression of TGFBI can lead to an increased level of migration, invasion, and EMT of glioma cells, and the aforementioned effect of TGFBI can be reduced by FAK inhibitor PF-573,228.ConclusionsOur study evaluated the effects of nicotinamide and tryptophan metabolism on the prognosis and tumor immune microenvironment of glioma, which can help predict the prognosis and sensitivity to immunotherapy of glioma.

Integrated Care in Specialized Networks: Leveraging Early Referrals to Reduce Local Recurrence in Soft Tissue Sarcoma

This study evaluated the impact of care pathways on the incidence of local recurrence (LR) in patients with soft tissue sarcomas (STS) and identified factors predictive of LR. It compared outcomes between patients managed entirely within a comprehensive care pathway (CCP) at the Swiss Sarcoma Network (SSN) and those who experienced fragmented care pathways (FCPs), where initial treatment occurred outside specialized centers. This prospective study utilized real-world-time data from the SSN-Sarconnector, capturing quality indicators through weekly Multidisciplinary Team/Sarcoma-Board (MDT/SB) meetings. The overall incidence of LR was 17.6% (n = 68/386), higher than rates typically reported in sarcoma center-based studies due to the inclusion of patients with prior inadequate management from real-world referrals. In a univariable logistic regression analysis, the FCP was significantly associated with higher LR rates, unplanned “whoops” resections (25.4%, n = 96), and positive surgical margins, emphasizing the detrimental impact of suboptimal initial management outside of specialized centers. Multivariable analysis confirmed that the FCP (aOR 2.7, 95% CI [1.41, 5.12], p = 0.003), tumor size (aOR 1.49, 95% CI [1.1, 2.02], p = 0.01), and biological behavior (aOR 5.84 95% CI [1.8, 18.86], p = 0.0003) are independent predictors of LR. Notably, patients referred to sarcoma centers after an initial FCP presented with inadequately managed disease, such as incomplete resections and unplanned surgeries, leading to increased complexity of subsequent treatments. These findings underscore the critical role of referral patterns on sarcoma center outcomes, highlighting the significant disparity in LR rates between institutions. The need for improved education and standardized early referral strategies at the spoke level is paramount to optimize patient outcomes and reduce the burden of LR. Enhanced spoke-level education and standardized referral protocols are critical to ensuring effective initial management and optimizing patient outcomes within specialized sarcoma networks like the SSN.

Clinical characteristics of renal anastomotic hemangioma.

In this editorial, we comment on the article by Chen and Cai. We focus on renal anastomotic hemangioma, which is a rare benign hemangiomatous disease. This disease has unique clinical characteristics. Its biological behavior is benign, but its imaging results are similar to those of renal cancer. Renal anastomotic hemangioma is easy to misdiagnose and can lead to unnecessary radical nephrectomy. Therefore, urologists need a better understanding of this disease. We believe that patients with renal anastomotic hemangioma should receive individualized diagnosis and treatment to avoid overtreatment.

Dysregulated inclusion of BOLA3 exon 3 promoted by HNRNPC accelerates the progression of esophageal squamous cell carcinoma.

Dysregulated RNA splicing events produce transcripts that facilitate esophageal squamous cell carcinoma (ESCC) progression, but how this splicing process is abnormally regulated remains elusive. Here, we unveiled a novel alternative splicing axis of BOLA3 transcripts and its regulator HNRNPC in ESCC. The long-form BOLA3 (BOLA3-L) containing exon 3 exhibited high expression levels in ESCC and was associated with poor prognosis. Functional assays demonstrated the protumorigenic function of BOLA3-L in ESCC cells. Additionally, HNRNPC bound to BOLA3 mRNA and promoted BOLA3 exon 3 inclusion forming BOLA3-L. High HNRNPC expression was positively correlated with the presence of BOLA3-L and associated with an unfavorable prognosis. HNRNPC knockdown effectively suppressed the malignant biological behavior of ESCC cells, which were significantly rescued by BOLA3-L overexpression. Moreover, BOLA3-L played a significant role in mitochondrial structural and functional stability. E2F7 acted as a key transcription factor that promoted the upregulation of HNRNPC and inclusion of BOLA3 exon 3. Our findings provided novel insights into how alternative splicing contributes to ESCC progression.

Immune checkpoint inhibitor therapy for primary neuroendocrine carcinoma of the gallbladder: A case report and literature review.

Gallbladder neuroendocrine carcinoma (GNEC) is indeed a relatively rare malignant tumor of the gallbladder with neuroendocrine differentiation and the ability to produce and secrete a number of neurotransmitters and hormones, characteristics that make its clinical presentation and biological behavior likely to be different from those of other types of gallbladder cancer. Current treatment mostly relies on surgery and adjuvant chemotherapy and radiotherapy. We report a 53-year-old middle-aged male patient who underwent radical surgery for gallbladder malignancy after a diagnosis of neuroendocrine carcinoma of the gallbladder. Diagnosis of neuroendocrine carcinoma of the gallbladder based on the return of pathologic findings. After local progression of postoperative chemotherapy with the first-line regimen of etoposide + cisplatin, an immune checkpoint inhibitor (traplizumab) + FOLIFIRI (fluorouracil + calcium folinate + irinotecan) regimen was used. The patient achieved 20 months of clinical survival and ultimately died of myelosuppression. The use of immune checkpoint inhibitors may become an effective tool in the treatment of neuroendocrine carcinoma of the gallbladder.