Comparative proteomic analysis between tumor tissues and intratumoral exosomes from lung adenocarcinoma patients identifies PAFAH1B3 as an exosomal protein key for initiating metastasis in lung adenocarcinoma.

Mounting evidence strongly indicates that exosomes are pivotal in the advancement of cancer, yet the overarching profile of exosomal proteins and their contribution to lung adenocarcinoma (LUAD) progression remain underexplored. In our investigation, we isolated exosomes from treatment-naive LUAD (n = 20) and paired normal adjacent tissues (NATs), and conducted integrated proteomic on the acquired exosomes and source tissues to ascertain origin characteristics and potential therapeutic targets of the exosomal proteins in LUAD. The omics data revealed the overall landscape of exosomal proteins from tissues in LUAD, underscoring the profound linkage between exosomal proteins and tumor metastasis.

AKR1B1-dependent fructose metabolism enhances malignancy of cancer cells.

Fructose metabolism has emerged as a significant contributor to cancer cell proliferation, yet the underlying mechanisms and sources of fructose for cancer cells remain incompletely understood. In this study, we demonstrate that cancer cells can convert glucose into fructose through a process called the AKR1B1-mediated polyol pathway. Inhibiting the endogenous production of fructose through AKR1B1 deletion dramatically suppressed glycolysis, resulting in reduced cancer cell migration, inhibited growth, and the induction of apoptosis and cell cycle arrest.

The chronic consumption of dietary fructose promotes the gut Clostridium species imbalance and bile acid alterations in developing nonalcoholic fatty liver disease.

Excessive fructose intake is associated with the rising prevalence of nonalcoholic fatty liver disease (NAFLD). The gut microbiome (GM) and bile acids (BAs) are involved in the pathogenesis of NAFLD, but the impact of fructose on their cross-talk is unclear. In this study, adult male C57BL/6J mice were fed a normal diet with tap water (ND) or with 4% fructose in the drinking water (Fru), 60% high-fat diet with tap water (HF) or with 4% fructose solution (HFF) for 12 weeks.

Active post-transcriptional regulation and ACLY-mediated acetyl-CoA synthesis as a pivotal target of Shuang-Huang-Sheng-Bai formula for lung adenocarcinoma treatment.

Background: New therapeutic approaches are required to improve the outcomes of lung cancer (LC), a leading cause of cancer-related deaths worldwide. Chinese herbal medicine formulae widely used in China provide a unique opportunity for improving LC treatment, and the Shuang-Huang-Sheng-Bai (SHSB) formula is a typical example. However, the underlying mechanisms of action remains unclear.

Exosomal lncRNA HOTAIR promotes osteoclast differentiation by targeting TGF-β/PTHrP/RANKL pathway.

Bone tissue is a common metastatic site of lung cancer, and bone metastasis is characterized by abnormal differentiation and malfunction of osteoclast, and the roles of exosomes derived from lung cancer have attracted much attention. In our study, we found that the level of HOTAIR expression in A549 and H1299 exosomes was higher than those of normal lung fibrocytes. Overexpression of HOTAIR in A549 and H1299 exosomes promoted osteoclast differentiation.

A new quantitative method for pseudouridine and uridine in human serum and its clinical application in acute myeloid leukemia.

Pseudouridine, a C-C glycosidic isomer of uridine, is derived from uridine via isomerization, and pseudouridylation is the most common post-transcriptional modification. Our previous study shows pseudouridine may serve an important role in acute myeloid leukemia (AML). The clinical value of pseudouridine and uridine is hampered by the lack of a quantitative methods with high sensitivity, specificity, and stability.

New Metabolic Alterations and A Predictive Marker Pipecolic Acid in Sera for Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey.

Bile Acid-Microbiome Interaction Promotes Gastric Carcinogenesis.

Bile reflux gastritis (BRG) is associated with the development of gastric cancer (GC), but the specific mechanism remains elusive. Here, a comprehensive study is conducted to explore the roles of refluxed bile acids (BAs) and microbiome in gastric carcinogenesis. The results show that conjugated BAs, interleukin 6 (IL-6), lipopolysaccharide (LPS), and the relative abundance of LPS-producing bacteria are increased significantly in the gastric juice of both BRG and GC patients.

Transcriptome-scale spatial gene expression in rat arcuate nucleus during puberty.

Background: A variety of neurons in hypothalamus undergo a complicated regulation on transcription activity of multiple genes for hypothalamic-pituitary-gonadal axis activation during pubertal development. Identification of puberty-associated cell composition and characterization of the unique transcriptional signatures across different cells are beneficial to isolation of specific neurons and advanced understanding of their functions.

Methods: The hypothalamus of female Sprague-Dawley rats in postnatal day-25, 35 and 45 were used to define the dynamic spatial atlas of gene expression in the arcuate nucleus (ARC) by 10× Genomics Visium platform.

Oleanolic acid blocks the purine salvage pathway for cancer therapy by inactivating SOD1 and stimulating lysosomal proteolysis.

Metabolic reprogramming is a core hallmark of cancer and is key for tumorigenesis and tumor progression. Investigation of metabolic perturbation by anti-cancer compounds would allow a thorough understanding of the underlying mechanisms of these agents and identification of new anti-cancer targets. Here, we demonstrated that the administration of oleanolic acid (OA) rapidly altered cancer metabolism, particularly suppressing the purine salvage pathway (PSP).

A multi-omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment-naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC.

Metabolic Profiling Revealed Prediction Biomarkers for Infantile Hemangioma in Umbilical Cord Blood Sera: A Prospective Study.

Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence.

GLUT3 induced by AMPK/CREB1 axis is key for withstanding energy stress and augments the efficacy of current colorectal cancer therapies.

Cancer cells are usually characterized by hyperactive glucose metabolism, which can often lead to glucose scarcity; thus, alternative pathways to rewire cancer metabolism are required. Here, we demonstrated that GLUT3 was highly expressed in colorectal cancer (CRC) and negatively linked to CRC patient outcomes, whereas GLUT1 was not associated with CRC prognosis. Under glucose-limiting conditions, GLUT3 expedited CRC cell growth by accelerating glucose input and fuelling nucleotide synthesis.

Increased levels of conjugated bile acids are associated with human bile reflux gastritis.

Bile acids (BAs) play essential roles in facilitating lipid digestion and absorption in the intestine. Gastric BAs were attributed to abnormal refluxing from duodenal compartments and correlated with the occurrence of gastric inflammation and carcinogenesis. However, the differences in gastric BAs between physiologically compromised and healthy individuals have not been fully investigated.

The CRL3 E3 ubiquitin ligase complex targets TNFAIP1 for degradation to suppress cancer cell migration.

Tumor necrosis factor alpha-induced protein 1 (TNFAIP1) modulates a plethora of important biological processes, including tumorigenesis and cancer cell migration. However, the regulatory mechanism of TNFAIP1 degradation remains largely elusive. In the present study, with a label-free quantitative proteomic approach, TNFAIP1 was identified as a novel ubiquitin target of the Cullin-RING E3 ubiquitin ligase (CRL) complex.

GLUT5-mediated fructose utilization drives lung cancer growth by stimulating fatty acid synthesis and AMPK/mTORC1 signaling.

Lung cancer (LC) is a leading cause of cancer-related deaths worldwide. Its rapid growth requires hyperactive catabolism of principal metabolic fuels. It is unclear whether fructose, an abundant sugar in current diets, is essential for LC.

Effective targeting of the ubiquitin-like modifier NEDD8 for lung adenocarcinoma treatment.

Protein neddylation, a process of conjugating neural precursor cell expressed, developmentally downregulated 8 (NEDD8) to substrates, plays a tumor-promoting role in lung carcinogenesis. Our previous study showed MLN4924, an inhibitor of NEDD8 activating enzyme (E1), significantly inhibits the growth of multiple cancer cells. However, resistance can develop to MLN4924 by mutation.

An essential role for GLUT5-mediated fructose utilization in exacerbating the malignancy of clear cell renal cell carcinoma.

Fructose is an important alternative carbon source for several tumors, and GLUT5 is the major fructose transporter which mediates most of fructose uptake in cells. So far, it is unclear whether GLUT5-mediated fructose utilization is important for clear cell renal cell carcinoma (ccRCC). Here, we demonstrated that GLUT5 was highly expressed in a panel of ccRCC cell lines.

Low CLL-1 Expression Is a Novel Adverse Predictor in 123 Patients with De Novo CD34 Acute Myeloid Leukemia.

Recent reports state that C-type lectin-like molecule-1 (CLL-1) in acute myeloid leukemia (AML) is expressed primarily on myeloid cells, but there is still no investigation about its prognostic significance on leukemic blast compartment. Hence, this study aimed to evaluate the prognostic value of CLL-1 in 123 patients with de novo CD34 Non-M3 AML. Multiparameter flow cytometry was used to assess the expression of CLL-1 on immature compartment in AML and control groups.