整合素α6靶向自组装促凋亡纳米多肽对中枢神经系统急性淋巴细胞白血病的靶向治疗

There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression.The targeted peptide D(RWYD)(abbreviated RD),with nanomolar affinity to integrinα6 was identified by peptide scanning techniques such as alanine scanning,truncation,and D-substitution.Herein,we developed a therapeutic nanoparticle based on the integrinα6-targeted peptide for treating CNS-ALL.The self-assembled proapoptotic nanopeptide_(D)(RWYD)-_(D)(KLAKLAK)_(2)-G_(D)(FFY)(abbreviated RD-KLA-Gffy)contains the integrinα6-targeted peptide RD,the well-known proapoptotic peptide_(D)(KLAKLAK)_(2)(abbreviated KLA),and the self-assembling tetrapeptide GD(FFY)(abbreviated Gffy).The functional mechanism of RD-KLA-Gffy is clarified using different experiments.Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis,thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity.Moreover,the combined use of RD-KLA-Gffy and methotrexate(MTX)shows a potent antitumor effect in treating CNS-ALL,indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX,which shows promise for application in CNS-ALL therapy.

Combined sevoflurane-dexmedetomidine and nerve blockade on post-surgical serum oxidative stress biomarker levels in thyroid cancer patients

BACKGROUND The incidence of thyroid cancer is increasing annually.Clinical routine thyroid surgery can be performed under a cervical plexus block,but cannot mediate the stress response during the surgery.If thyroid surgery is performed under nerve block,an inappropriate level of blockade may occur.Similarly,the stress response caused by surgery is more serious than that caused by conventional anesthesia.Therefore,it is important to combine blockade with more effective anesthesia methods.AIM To investigate the effects of combining sevoflurane-dexmedetomidine inhalation general anesthesia with the cervical plexus nerve block on the post-surgical levels of the serum oxidative stress biomarkers levels in thyroid cancer patients.METHODS We enrolled 96 thyroid cancer patients admitted to the hospital between January 2019 and December 2020.Participants were divided into a control group(n=47)and an experimental group(n=49).The experimental group received a combination of inhaled sevoflurane-dexmedetomidine and cervical plexus block,while the control group received conventional general anesthesia.The groups were compared for serum levels of monocyte chemotactic protein-1(MCP-1)and glutathione peroxidase(GSH-Px)before and after surgery,and the adrenocorticotropic hormone(ACTH)and norepinephrine(NE)levels at 1 and 12 h postsurgery.The Bispectral index(BIS)and the incidence of anesthesia side effects were also compared.RESULTS Following surgery,MCP-1 was significantly lower in the experimental group compared to the control group,whereas GSH-Px was significantly higher than that in the control group(P<0.001).The serum ACTH and NE levels were significantly lower in the experimental group than those the control group at 1 and 12 h post-surgery(P<0.001).BIS was significantly lower in the experimental group than that in the control group at 20 minutes into the operation,but the direction of the difference was reversed at eye opening(P<0.001).The incidence of side effects was 10.20%(5/49)and 12.76%(6/47)in the experimental and control groups,respectively,the difference being non-significant.CONCLUSION Sevoflurane-dexmedetomidine inhalation general anesthesia combined with cervical plexus nerve block can reduce the postoperative stress and inflammatory responses in thyroid cancer patients,while maintaining high anesthesia effectiveness and safety.