The Warburg effect is known as the hyperactive glycolysis that provides the energy needed for rapid growth and proliferation in most tumor cells even under the condition of sufficient oxygen. This metabolic pattern can lead to a large accumulation of lactic acid and intracellular acidification, which can affect the growth of tumor cells and lead to cell death. Proton-coupled monocarboxylate transporters (MCTs) belong to the SLC16A gene family, which consists of 14 members. MCT1-4 promotes the passive transport of monocarboxylate (e.g., lactate, pyruvate, and ketone bodies) and proton transport across membranes. MCT1-4-mediated lactate shuttling between glycolytic tumor cells or cancer-associated fibroblasts and oxidative tumor cells plays an important role in the metabolic reprogramming of energy, lipids, and amino acids and maintains the survival of tumor cells. In addition, MCT-mediated lactate signaling can promote tumor angiogenesis, immune suppression and multidrug resistance, migration and metastasis, and ferroptosis resistance and autophagy, which is conducive to the development of tumor cells and avoid death. Although there are certain challenges, the study of targeted drugs against these transporters shows great promise and may form new anticancer treatment options.

Background: The high prevalence of kidney stones in adults worldwide has prompted research into potential interventions, one of which involves exploring the consumption of antioxidants that may confer protective effects. However, the relationship between the composite dietary antioxidant index (CDAI), a crucial measure used to assess an individual’s overall antioxidant capacity from daily dietary intake, and kidney stones remains unclear. Therefore, we conducted cross-sectional analysis to examine the association between CDAI and kidney stone prevalence.Methods: The analysis was conducted utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. Antioxidant intake was derived from two 24-h dietary recalls surveys, while CDAI, a comprehensive measure that includes antioxidants like vitamins A, C, and E, zinc, selenium, and carotenoids, was calculated. Multivariate logistic regression and restricted cubic spline (RCS) regression were utilized to examine the association between CDAI and the prevalence of kidney stones.Results: The study included a total of 28,516 participants, with 2,748 individuals having a history of kidney stones. The median of CDAI was −0.01 (−2.02, 2.37). Individuals in the fourth quartile of CDAI exhibited a significantly lower prevalence of kidney stones compared to those in the first quartile (Odds Ratio [OR] = 0.769 [0.633–0.935]), even after adjusting for potential confounding factors (including age, sex, race, education level, poverty income ratio, smoking status, drinking status, body mass index (BMI), energy intake levels, physical activity level, serum calcium concentration, estimated glomerular filtration rate (eGFR), hypertension, diabetes and supplement use). The RCS analysis revealed a non-linear relationship between CDAI and kidney stone prevalence, with inflection points identified at 0.06 (p for non-linearity = 0.039). Subgroup analysis demonstrated consistent CDAI-kidney stone prevalence associations across all subsets. Furthermore, a significant inverse correlation was observed between CDAI and inflammatory markers.Conclusion: This study provides evidence supporting a reciprocal correlation between adult dietary antioxidant intake, as measured by CDAI, and kidney stone prevalence. These findings emphasize the potential benefits of consuming dietary antioxidants in lowering the risk of kidney stone formation.

The kidney is a vital organ responsible for water and sodium metabolism, while the primary function of amiloride is to promote the excretion of water and sodium. We investigated amiloride enhanced the sunitinib sensitivity in RCC. We found both sunitinib and amiloride displayed cytotoxicity and exerted the synergy effect in RCC cells in vivo and in vitro arrays. Protein expression profiles were screened via MS/TMT, revealing that FN3K was upregulated in the sunitinib group, and rescued in amiloride and the combination administration. Exogenous FN3K could promote proliferation, invasion and metastasis and decrease the sensitivity of Caki-1 cells to sunitinib, also, exogenous FN3K up-regulated VEGFR2 expression and activated AKT/mTOR signal pathway. More FN3K and VEGFR2 accumulated in R-Caki-1 cells and rescued by amiloride treatment. Co-IP and IF confirmed the interaction between FN3K and VEGFR2. In conclusion, FN3K depletion mediated VEGFR2 disruption promotes amiloride synergized the anti-RCC activity of sunitinib.

Although recombinant human TNF‑related apoptosis‑inducing ligand (TRAIL) protein exhibits antitumor activity in a number of lung and liver cancer cells and tumor‑bearing animals, TRAIL resistance has substantially restricted its clinical application. Pyrroline‑5‑carboxylate reductase 1 (PYCR1) is a key enzyme in the regulation of proline synthesis. PYCR1 is highly expressed in various types of malignant tumor, in which it has been implicated in 5‑fluorouracil resistance. However, the possible relationship between PYCR1 and TRAIL resistance remains unclear. In the present study, both reverse transcription‑quantitative PCR and western blotting were performed. The results indicated that H1299 cells had higher PYCR1 expression levels and were less sensitive to TRAIL compared with the TRAIL‑sensitive cell line, H460. PYCR1 knockdown in H1299 cells increased TRAIL sensitivity, increased the localization of death receptors (DRs) on the cell surface and activated Caspase‑3/8. By contrast, overexpression of PYCR1 in H1299 cells decreased TRAIL sensitivity, reduced the distribution of DRs on the cell surface and suppressed the activation of Caspase‑3/8. Taken together, these results suggested that PYCR1 promoted TRAIL resistance in the non‑small cell lung cancer cell line, H1299, by preventing redistribution of DRs to the plasma membrane. This in turn inhibited TRAIL‑mediated cell apoptosis by reducing the activation of Caspase‑3/8.

Background: Nasopharyngeal carcinoma (NPC) is a type of malignant tumors commonly found in Southeast Asia and China, with insidious onset and clinical symptoms. N6-methyladenosine (m6A) modification significantly contributes to tumorigenesis and progression by altering RNA secondary structure and influencing RNA-protein binding at the transcriptome level. However, the mechanism and role of abnormal m6A modification in nasopharyngeal carcinoma remain unclear.Methods: Nasopharyngeal Carcinoma tissues from 3 patients and non-cancerous nasopharyngeal tissues from 3 individuals, all from Fujian Cancer Hospital, were sequenced for m6A methylation. These were combined with transcriptome sequencing data from 192 nasopharyngeal cancer tissues. Genes linked to prognosis were discovered using differential analysis and univariate Cox regression. Subsequently, a prognostic model associated with m6A was developed through the application of LASSO regression analysis. The model’s accuracy was verified using both internal transcriptome databases and external databases. An extensive evaluation of the tumor’s immune microenvironment and signaling pathways was performed, analyzing both transcriptomic and single-cell data.Results: The m6A methylation sequencing analysis revealed 194 genes with varying expression levels, many of which are predominantly associated with immune pathways. By integrating transcriptome sequencing data, 19 m6A-modified genes were found to be upregulated in tumor tissues, leading to the development of a three-gene (EME1, WNT4, SHISA2) risk prognosis model. The group with lower risk exhibited notable enrichment in pathways related to immunity, displaying traits like enhanced survival rates, stronger immune profiles, and increased responsiveness to immunotherapy when compared to the higher-risk group. Single-cell analysis revealed that malignant cells exhibited the highest risk score levels compared to immune cells, with a high-risk score indicating worse biological behavior. The three hub genes demonstrated significant correlation with m6A modification regulators, and MeRIP-RT-PCR confirmed the occurrence of m6A methylation in these genes within nasopharyngeal carcinoma cells.Conclusions: A prognostic model for nasopharyngeal carcinoma risk based on m6A modification genes was developed, and its prognostic value was confirmed through self-assessment data. The study highlighted the crucial impact of m6A modification on the immune landscape of nasopharyngeal cancer.