Unveiling the role of RAC3 in the growth and invasion of cisplatin-resistant bladder cancer cells.

Bladder cancer is one of the most prevalent cancers worldwide, and its morbidity and mortality rates have been increasing over the years. However, how RAC family small GTPase 3 (RAC3) affects the proliferation, migration and invasion of cisplatin-resistant bladder cancer cells remains unclear. Bioinformatics techniques were used to investigate the expression of RAC3 in bladder cancer tissues. Influences of RAC3 in the grade, stage, distant metastasis, and survival rate of bladder cancer were also examined. Analysis of the relationship between RAC3 expression and the immune microenvironment (TIME), genomic mutations, and stemness index. In normal bladder cancer cells (T24, 5637, and BIU-87) and cisplatin-resistant bladder cancer cells (BIU-87-DDP), the expression of RAC3 was detected separately with Western blotting. Plasmid transfection was used to overexpress or silence the expression of RAC3 in bladder cancer cells resistant to cisplatin (BIU-87-DDP). By adding activators and inhibitors, the activities of the JNK/MAPK signalling pathway were altered. Cell viability, invasion, and its level of apoptosis were measured in vitro using CCK-8, transwell, and flow cytometry. The bioinformatics analyses found RAC3 levels were elevated in bladder cancer tissues and were associated with a poor prognosis in bladder cancer. RAC3 in BIU-87-DDP cells expressed a higher level than normal bladder cancer cells. RAC3 overexpression promoted BIU-87-DDP proliferation. The growth of BIU-87-DDP cells slowed after the knockdown of RAC3, and RAC3 may have had an impact on the activation of the JNK/MAPK pathway.

CS-NO suppresses inhibits glycolysis and gastric cancer progression through regulating YAP/TAZ signaling pathway.

CONTEXT: Gastric cancer (GC) is a significant contributor to global mortality and is recognized for its elevated prevalence and fatality rates. Nitric Oxide (NO) plays a role in multiple aspects of cancer metastasis and progression. CS-NO is a polysaccharide-based biomaterial with NO-releasing properties that shows promising therapeutic potential. Nonetheless, the action mechanism of CS-NO in GC is still largely unclear. METHODS: The present study employed various experimental techniques, including CCK-8 assay, colony formation assay, EdU staining, and transwell assays, to evaluate the proliferation, migration, and invasion of GC cells. Additionally, ELISA was utilized to measure glucose uptake, lactate production, and cellular ATP levels in GC cells. In vivo investigations on nude mice were conducted to validate the in vitro results. OBJECTIVE: The present study aimed to examine the potential anti-tumor properties of CS-NO on GC through in vitro and in vivo investigations, while also exploring the underlying mechanisms involved. RESULTS: Our data suggested that CS-NO might prevent GC cell invasion and migration. Decreased expressions of GLUT1, HK2, and LDHA further demonstrated that CS-NO significantly suppressed aerobic glycolysis in GC cells. The administration of CS-NO resulted in a significant reduction of YAP and TAZ levels in GC cells. Our data further show that CS-NO treatment could inhibit GC cancer growth in mice, consistent with the significant decrease in Ki67, GLUT1 and YAP expression levels. DISCUSSION AND CONCLUSION: These findings could reveal the good effects of CS-NO therapy on inhibiting GC.

Associations Between Life's Essential 8 and Abdominal Aortic Calcification Among Middle-Aged and Elderly Populations.

BACKGROUND: Abdominal aortic calcification (AAC) is an independent risk factor for cardiovascular disease. We aim to examine the associations between Life's Essential 8 (LE8), the recently updated measurement of cardiovascular health (CVH), and AAC among participants aged ≥40 years. METHODS AND RESULTS: This population-based cross-sectional study used data from the National Health and Nutrition Examination Survey in 2013 to 2014. AAC (AAC score>0) and severe AAC (AAC score>6) were quantified by the Kauppila score system. Multiple linear, multivariable logistic, and restricted cubic spline models were used to assess the associations. A total of 2369 participants were included with a mean AAC score of 1.41 (0.13). Participants in the high-cardiovascular-health group had lower AAC scores, lower prevalence of AAC, and lower prevalence of severe AAC. After the adjustment of potential confounders (age, sex, race and ethnicity, education levels, marital status, poverty income ratio, estimated glomerular filtration rate, serum creatinine, serum uric acid, serum phosphorus, and serum total calcium), higher cardiovascular health was significantly associated with lower risk of AAC. Meanwhile, elevated nicotine exposure score, blood glucose score, and blood pressure score within the LE8 components were significantly associated with lower risk of AAC. Also, nonlinear dose-response relationships were observed. Subgroup analyses (age strata, sex, poverty income ratio, education levels, marital status) indicated the inverse associations of LE8 and AAC were generally similar in different populations. CONCLUSIONS: LE8 was negatively and nonlinearly related to the risk of AAC among middle-aged and older populations. Meanwhile, LE8 components should prioritize higher scores for nicotine exposure, blood glucose, and blood pressure evaluations.

Olfactory Proteins and Their Expression Profiles in the Eucalyptus Pest Endoclita signifier Larvae.

Endoclita signifier Walker (Lepidoptera: Hepialidae), a polyphagous insect, has become a new wood-boring pest in Eucalyptus plantations in southern China since 2007, which represents a typical example of native insect adaptation to an exotic host. After the third instar, larvae move from soil to standing trees and damage the plants with a wormhole. Although females disperse to lay eggs, larvae can accurately find eucalyptus in a mingled forest of eight species, which leads us to hypothesize that the larval olfactory system contributes to its host selection. Herein, we investigated the transcriptomes of the head and tegument of E. signifer larvae and explored the expression profiles of olfactory proteins. We identified 15 odorant-binding proteins (OBPs), including seven general OBPs (GOPBs), six chemosensory proteins (CSPs), two odorant receptors (ORs), one gustatory receptor (GR), 14 ionotropic receptors (IRs), and one sensory neuron membrane protein (SNMP). Expression profiles indicated that all olfactory proteins, except for EsigCSP1, were expressed in the head, and most were also detected in non-olfactory tissues, especially thorax tegument. Furthermore, EsigOBP2, EsigOBP8, EsigGOBP1, EsigGOBP2, EsigGOBP5, EsigCSP3, EsigCSP5, and EsigOR1 were expressed most strongly in the head; moreover, EsigCSP3 expressed abundantly in the head. EsigGR1 exhibited the highest expression among all tissues. Besides phylogenetic analysis shows that EsigGOBP7 probably is the pheromone-binding protein (PBP) of E. signifier. This study provides the molecular basis for future study of chemosensation in E. signifier larvae. EsigCSP3 and EsigGR1, which have unique expression patterns, might be factors that govern the host choice of larvae and worth further exploration.