Diverse roles of aldolase enzymes in cancer development, drug resistance and therapeutic approaches as moonlighting enzymes.

Aldolase enzymes, particularly ALDOA, ALDOB, and ALDOC, play a crucial role in the development and progression of cancer. While the aldolase family is mainly known for its involvement in the glycolysis pathway, these enzymes also have various pathological and physiological functions through distinct signaling pathways such as Wnt/ß-catenin, EGFR/MAPK, Akt, and HIF-1α. This has garnered increased attention in recent years and shed light on other sides of this enzyme. Potential therapeutic strategies targeting aldolases include using siRNA, inhibitors like naphthol AS-E phosphate and TX-2098, and natural compounds such as HDPS-4II and L-carnosine. Additionally, anticancer peptides derived from ALDOA, like P04, can potentially increase cancer cells' sensitivity to chemotherapy. Aldolases also affect cancer drug resistance by different approaches, making them good therapeutic targets. In this review, we extensively explore the role of aldolase enzymes in various types of cancers in proliferation, invasion, migration, and drug resistance; we also significantly explore the possible treatment considering aldolase function.

[Artesunate alleviates hypoxic-ischemic brain damage in neonatal rats by inhibiting NLRP3 inflammasome activation and inflammatory cytokine secretion].

Objective To investigate the protective effect of artesunate on hypoxic-ischemic brain damage (HIBD) and its mechanism in neonatal rats. Methods 7-day-old neonatal SD rats were randomly divided into sham operation group, model group, artesunate 5 mg/kg group, artesunate 10 mg/kg group, artesunate 20 mg/kg group and dexamethasone 6 mg/kg group, with 18 rats in each group. HIBD models were established in groups except for the sham operation group. The sham operation group only needed to separate the left common carotid artery without ligation and nitrogen-oxygen mixed gas ventilation. Each group was injected with drug intraperitoneally right after surgery and the rats in the sham operation group and the model group were injected with an equal volume of normal saline (once a day for a total of 5 times). One hour after the last injection, the rats in each group were scored for neurological defects. After the rats were sacrificed, the brain water content was measured and the pathological changes of the brain tissues of rats were observed. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) was used to detect the neuronal cell apoptosis, and ELISA was applied to detect the levels of IL-1ß, IL-6 and TNF-α in brain tissues and peripheral blood of each group of rats. Western blot analysis was adopted to detect the protein expression levels of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 in the rats brain tissues of each group. Results Compared with the model group, the neurological deficit score was decreased; the pathological damage of brain tissues was relieved; the brain water content was significantly reduced; the apoptosis number of hippocampal neurons was decreased significantly; the levels of IL-1ß, IL-6 and TNF-α in brain tissues and peripheral blood were significantly reduced; the protein expression levels of NLRP3, ASC and caspase-1 were significantly lowered in the middle-dose and high-dose artesunate groups and the dexamethasone group. Conclusion Artesunate can improve the neurological function, relieve the brain damage, and alleviate the brain edema in neonatal rats with HIBD. It can protect the HIBD, which may be related to the inhibition of NLRP3 inflammasome activation and reduction of inflammatory cytokine secretion.

Diagnostic challenges and good treatment outcomes in pediatric paraganglioma of the abdomen: A case report.

RATIONALE: Paraganglioma is a catecholamine-producing neuroendocrine tumor. Management of paraganglioma including its diagnosis is difficult, because it has no characteristic symptoms and many diseases can manifest as headache and high blood pressure. Herein, we report a rare case of paraganglioma of the abdomen with headache and initial normal blood pressure. PATIENT CONCERNS: A 9-year-old Chinese girl was hospitalized because of intermittent headache persisting for more than 9 months and recurrent headache for 15 days, accompanied by weight loss, impaired heat tolerance, and otherwise normal blood pressure. DIAGNOSES: We eventually diagnosed paraganglioma. INTERVENTIONS: Her paroxysmal hypertension subsided over 1 month after surgical removal of the tumor. LESSONS: Intermittent headache and normal hypertension as the initial symptoms of paraganglioma can easily lead to misdiagnosis as another disease (e.g., renal artery stenosis, primary hyperaldosteronism, Takayasu's arteritis), and its differential diagnosis is difficult. When a patient presents with intermittent hypertension, clinicians should consider a diagnosis of paraganglioma. The comprehensive use of ultrasonography, computed tomography (including enhanced computed tomography and 3D reconstruction), magnetic resonance imaging, and plasma catecholamine measurement can aid the diagnosis of paraganglioma.