Thymoquinone affects hypoxia-inducible factor-1αexpression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways

BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination degradation.CONCLUSION The regulatory mechanism of TQ on HIF-1αprotein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90;Secondly,TQ reduced the initial expression of HIF-1αprotein by inhibiting the PI3K/AKT/mTOR pathway.

Current status of drug therapy for alveolar echinococcosis

Alveolar echinococcosis(AE)is a chronic zoonotic parasitic disease caused by infection with Echinococcus multilocularis.AE is associated with a high mortality rate and poses a significant threat to human health.The primary treatment for AE is surgical resection of the lesions;however,owing to its long incubation period and insidious disease progression,many patients are diagnosed only after the onset of complications such as liver cirrhosis,jaundice,and portal hypertension,which preclude curative surgical intervention.For patients who are unwilling or unable to undergo surgery,lifelong administration of anti-AE medications is necessary.Benzimidazole compounds,such as albendazole and mebendazole,are the current mainstays of treatment,offering good efficacy.Nevertheless,these medications primarily inhibit parasite proliferation rather than eradicate the infection,and their long-term use can lead to significant drug-related toxic effects.Consequently,there is an urgent need to develop new therapeutic strategies that convey better efficacy and reduce the adverse effects associated with current treatments.Recent advancements in AE therapy include novel synthetic compounds such as antiviral agents,antibiotics,antineoplastic agents,immunosuppressants,and antiangiogenic agents,as well as natural compounds derived from traditional Chinese and Tibetan medicine.These new drugs show promising clinical potential because they interfere with parasitic metabolic pathways and cellular structures.This review aims to discuss recent research on AE drug therapy,including mechanisms of action,dosing regimens,signalling pathways,and therapeutic outcomes,with a goal of providing new insights and directions for the development of anti-AE drugs and summarizing current advancements in AE pharmacotherapy.

Retroperitoneal cavernous hemangioma misdiagnosed as lymphatic cyst:A case report and review of the literature

BACKGROUND Primary abdominal and retroperitoneal cavernous hemangioma is a vascular tumor and rarely seen in the clinic.Due to the lack of specific imaging features,retroperitoneal cavernous hemangioma cannot be diagnosed accurately.Some symptoms may develop with the enlargement of lesion volume or the occurrence of complications such as rupture or oppression.We report here a special case who was admitted with chronic abdominal pain.Admission examination suggested a retroperitoneal lymphatic duct cyst.Laparoscopic resection of the retroperitoneal mass was performed,and histological examination confirmed retroperitoneal cavernous hemangioma.CASE SUMMARY The patient was a 43-year-old Tibetan woman with intermittent left lower abdominal pain and discomfort 3 years ago.Ultrasonography revealed a cystic mass in the retroperitoneum with clear boundaries,internal septa,and no blood flow signal.Computed tomography(CT)and magnetic resonance imaging(MRI)showed an irregular space-occupying mass in the retroperitoneum,and retroperitoneal lymphatic cyst was considered.Plain CT scanning showed multiple cystlike hypo-intense shadows in the retroperitoneum,partially fused into a mass,and no obvious enhancement was found on enhanced scanning.MRI showed multiple irregular clump-like long T1 and long T2 signal shadows above the pancreas,within which linear short T2 signal shadows were seen.Diffusionweighted imaging sequence showed hypo-signal shadows,without obvious enhancement on enhanced scanning.Ultrasound,CT,and MRI all suggested the possibility of retroperitoneal lymphatic cyst.However,the patient was finally diagnosed with retroperitoneal cavernous hemangioma by pathological examination.CONCLUSION Retroperitoneal cavernous hemangioma is a benign lesion,and it is difficult to make a diagnosis preoperatively.Surgical resection may be the only treatment,which not only allows histopathological confirmation as a diagnostic purpose and excludes any risk of malignancy,but also avoids invasion of adjacent tissues,oppression,and other complications as a therapeutic goal.