Disrupting Notch signaling related HES1 in myeloid cells reinvigorates antitumor T cell responses.

Background: Tumor-associated macrophages (TAMs) are immunosuppressive cells within the tumor microenvironment (TME) that hinder anti-tumor immunity. Notch signaling is a pathway crucial for TAM differentiation and function. Here, we investigate the role of HES1, a downstream target of Notch signaling, in TAM-mediated immunosuppression and explore its potential as a target for cancer immunotherapy.

Interleukin-13 Receptor Subunit Alpha 2 Induces Chemokine Expression and Macrophage Polarization to Promote Inflammation and Fibrosis.

Purpose: Interleukin-13 (IL-13) is a known mediator of radiation-induced lung injury (RILI). IL-13Rα2 has an accepted role in antagonizing IL-13 signaling by acting as a decoy receptor. We sought to understand the role of IL-13Rα2 in the progression of RILI.

Prognostic significance of tertiary lymphoid structures in gastric neuroendocrine carcinoma with association to delta-like ligand 3 and neuroendocrine expressions.

Background: Gastric neuroendocrine carcinomas (NECs) are rare cancers with highly aggressive behavior. Although tertiary lymphoid structures (TLSs) are well-known prognostic factors in various cancers, their role in gastric NECs remain unexplored. Unique immunohistochemical subtypes of pulmonary NECs have been discovered, however, their feasibility in gastric NECs is unknown.

Glypican-3 deficiency in liver cancer upregulates MAPK/ERK pathway but decreases cell proliferation.

Glypican-3 (GPC3) is overexpressed in hepatocellular carcinomas and hepatoblastomas and represents an important therapeutic target but the biologic importance of GPC3 in liver cancer is unclear. To date, there are limited data characterizing the biological implications of GPC3 knockout (KO) in liver cancers that intrinsically express this target. Here, we report on the development and characterization of GPC3-KO liver cancer cell lines and compare to them to parental lines.

Single-Nucleus RNA Sequencing Reveals Loss of Distal Convoluted Tubule 1 Renal Tubules in HIV Viral Protein R Transgenic Mice.

Although hyponatremia and salt wasting are common in patients with HIV/AIDS, the understanding of their contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the distal tubules and on the expression level of the Slc12a3 gene, encoding the sodium-chloride cotransporter (which is responsible for sodium reabsorption in distal nephron segments), single-nucleus RNA sequencing was performed on kidney cortices from three wild-type (WT) and three Vpr transgenic (Vpr Tg) mice.

Developing a comprehensive molecular subgrouping model for cervical cancer using machine learning.

This study developed a molecular classification model for cervical cancer using machine learning, integrating prognosis related biomarkers with clinical features. Analyzing 281 specimens, 27 biomarkers were identified, associated with recurrence and treatment response. The model identified four molecular subgroups: group 1 (OALO) with Overexpression of ATP5H and LOw risk; group 2 (LASIM) with low expression of ATP5H and SCP, indicating InterMediate risk; group 3 (LASNIM) characterized by Low expression of ATP5H, SCP, and NANOG, also at InterMediate risk; and group 4 (LASONH), with Low expression of ATP5H, and SCP, Over expression of NANOG, indicating High risk, and potentially aggressive disease.

Application of Brain Injury Guidelines at a Pediatric Level 1 Trauma Center predicts reliability, safety, and improved resource utilization.

Purpose: Brain Injury Guidelines (BIG) have been established to guide management related to TBI in adults. Here, BIG criteria were applied to pediatric TBI patients to evaluate reliability, safety, and resource utilization.

Methods: A retrospective study was performed on all pediatric TBI patients aged 18 years or younger from January 2012 to July 2023 at a Level 1 Pediatric Trauma Center.

Socioeconomic Disparities in Pediatric Traumatic Brain Injury Transfer Patterns: An Analysis of Area Deprivation Index and Clinical Outcomes.

Background: Traumatic brain injury (TBI) poses a significant health burden, particularly among pediatric populations, leading to long-term cognitive, physical, and psychosocial impairments. Timely transfer to specialized trauma centers is crucial for optimal management, yet the influence of socioeconomic factors, such as the Area Deprivation Index (ADI), on transfer patterns remains understudied.

Methods: A retrospective study was conducted on pediatric TBI patients presenting to a Level I Pediatric Trauma Center between January 2012 and July 2023.

Single-Cell Transcriptional Signatures of Glomerular Disease in Transgenic Mice with APOL1 Variants.

Key Points: Apolipoprotein L1 (APOL1)-G1 induced kidney disease in the two APOL1 transgenic mouse models, HIV-associated nephropathy and IFN- administration. Glomerular single-nuclear RNA-sequencing identified genes differentially expressed among mice with APOL1-G1 and G0 variants at single-cell resolution.

Background: Apolipoprotein L1 () high-risk variants contribute to kidney disease among individuals with African ancestry.

Non-Invasive Vagal Nerve Stimulation Pre-Treatment Reduces Neurological Dysfunction After Closed Head Injury in Mice.

Non-invasive vagus nerve stimulation (nVNS) has recently been suggested as a potential therapy for traumatic brain injury (TBI). We previously demonstrated that nVNS inhibits cortical spreading depolarization, the electrophysiological event underlying migraine aura, and is relevant to TBI. Our past work also suggests a role for interleukin-1 beta (IL-1β) in cognitive deficits after closed head injury (CHI) in mice.

Ascitic autotaxin as a potential prognostic, diagnostic, and therapeutic target for epithelial ovarian cancer.

Background: Malignant ascites contributes to the metastatic process by facilitating the multifocal dissemination of ovarian tumour cells onto the peritoneal surface. However, the prognostic and diagnostic relevance of ascitic fluid remains largely unknown. Herein, we investigated the potential clinical value and therapeutic utility of ascitic autotaxin (ATX) in epithelial ovarian cancer (EOC).

Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) occurs due to the accumulation of fat in the liver, leading to fatal liver diseases such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Elucidation of the molecular mechanisms underlying NAFLD is critical for its prevention and therapy. Here, we observed that deubiquitinase USP15 expression was upregulated in the livers of mice fed a high-fat diet (HFD) and liver biopsies of patients with NAFLD or NASH.

Nectin-4 as a Predictive Marker for Poor Prognosis of Endometrial Cancer with Mismatch Repair Impairment.

The adhesion molecule Nectin-4 is a new potential therapeutic target for different types of cancer; however, little is known about its diagnosis significance in endometrial cancer (EC). We found that Nectin-4 expression was significantly higher in EC tissues than in nonadjacent normal tissue. The area under the receiver operating characteristic curve value of 0.

VGLL3 expression is associated with macrophage infiltration and predicts poor prognosis in epithelial ovarian cancer.

Background/objective: High-grade serous ovarian carcinoma (HGSOC) is the most common histologic type of epithelial ovarian cancer (EOC). Due to its poor survival outcomes, it is essential to identify novel biomarkers and therapeutic targets. The hippo pathway is crucial in various cancers, including gynaecological cancers.

TRPV1 inhibition overcomes cisplatin resistance by blocking autophagy-mediated hyperactivation of EGFR signaling pathway.

Cisplatin resistance along with chemotherapy-induced neuropathic pain is an important cause of treatment failure for many cancer types and represents an unmet clinical need. Therefore, future studies should provide evidence regarding the mechanisms of potential targets that can overcome the resistance as well as alleviate pain. Here, we show that the emergence of cisplatin resistance is highly associated with EGFR hyperactivation, and that EGFR hyperactivation is arisen by a transcriptional increase in the pain-generating channel, TRPV1, via NANOG.

Selective ablation of TRA-1-60 pluripotent stem cells suppresses tumor growth of prostate cancer.

TRA-1-60 (TRA) is an established transcription factor of embryonic signaling and a well-known marker of pluripotency. It has been implicated in tumorigenesis and metastases, is not expressed in differentiated cells, which makes it an appealing biomarker for immunopositron emission tomography (immunoPET) imaging and radiopharmaceutical therapy (RPT). Herein, we explored the clinical implications of TRA in prostate cancer (PCa), examined the potential of TRA-targeted PET to specifically image TRA cancer stem cells (CSCs) and assessed response to the selective ablation of PCa CSCs using TRA-targeted RPT.

APOL1 kidney risk variants in glomerular diseases modeled in transgenic mice.

high-risk variants partially explain the high kidney disease prevalence among African ancestry individuals. Many mechanisms have been reported in cell culture models, but few have been demonstrated in mouse models. Here we characterize two models: (1) HIV-associated nephropathy (HIVAN) Tg26 mice crossed with bacterial artificial chromosome (BAC)/APOL1 transgenic mice and (2) interferon-γ administered to BAC/APOL1 mice.

High ATP6V1B1 expression is associated with poor prognosis and platinum‑based chemotherapy resistance in epithelial ovarian cancer.

The vacuolar ATPase H+ transporting V1 subunit B1 (ATP6V1B1) belongs to the family of ATP6Vs, which functions to transport hydrogen ions. The expression of ATP6V1B1 and associated clinicopathological features have been linked to various cancers; however, its role in epithelial ovarian cancer (EOC) has remained to be explored. The present study aimed to unveil the function, molecular mechanisms and clinical significance of ATP6V1B1 in EOC.

Prognostic value of β-Arrestins in combination with glucocorticoid receptor in epithelial ovarian cancer.

Hormones may be key factors driving cancer development, and epidemiological findings suggest that steroid hormones play a crucial role in ovarian tumorigenesis. We demonstrated that high glucocorticoid receptor (GR) expression is associated with a poor prognosis of epithelial ovarian cancer. Recent studies have shown that the GR affects β-arrestin expression, and vice versa.

Histopathology and SARS-CoV-2 Cellular Localization in Eye Tissues of COVID-19 Autopsies.

Ophthalmic manifestations and tissue tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in association with coronavirus disease 2019 (COVID-19), but the pathology and cellular localization of SARS-CoV-2 are not well characterized. The objective of this study was to evaluate macroscopic and microscopic changes and investigate cellular localization of SARS-CoV-2 across ocular tissues at autopsy. Ocular tissues were obtained from 25 patients with COVID-19 at autopsy.