Growth hormone promotes the reconstruction of injured axons in the hypothalamo-neurohypophyseal system

Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.

Targeting the ferroptosis crosstalk:novel alternative strategies for the treatment of major depressive disorder

Depression is a major contributor to poor global health and disability,with a recently increasing incidence.Although drug therapy is commonly used to treat depression,conventional antidepressant drugs have several disadvantages,including slow onset,low response rates and severe adverse effects.Therefore,developing effective therapies for depression remains challenging.Although various aetiological theories of depression exist,the underlying mechanisms of depression are complex,and further research is crucial.Moreover,oxidative stress(OS)-induced lipid peroxidation has been demonstrated to trigger ferroptosis.Both OS and ferroptosis are pivotal mechanisms implicated in the pathogenesis of neurological disorders,and investigation of the mediators involved in these processes has emerged as a prominent and active research direction.One previous study revealed that regulatory proteins involved in ferroptosis are implicated in the pathogenesis of depression,and antidepressant drugs could reverse depressive symptoms by inhibiting ferroptosis in vivo,suggesting an important role of ferroptosis in the pathogenesis of depression.Hence,our current comprehensive review offers an up-to-date perspective on the intricate mechanisms involved,specifically concerning ferroptosis and OS in the context of depression,along with promising prospects for using molecular mediators to target ferroptosis.We delineate the key targets of molecular mediators involved in OS and ferroptosis implicated in depression,most notably reactive oxygen species and iron overload.Considering the pivotal role of OS-induced ferroptosis in the pathogenesis of neurological disorders,delving deeper into the underlying subsequent mechanisms will contribute significantly to the identification of novel therapeutic targets for depression.

Induced pluripotent stem cells as a potential therapeutic source for corneal epithelial stem cells

Corneal blindness caused by limbal stem cell deficiency(LSCD) is one of the most common debilitating eye disorders. Thus far, the most effective treatment for LSCD is corneal transplantation, which is often hindered by the shortage of donors. Pluripotent stem cell technology including embryonic stem cells(ESCs) and induced pluripotent stem cells(iPSCs) have opened new avenues for treating this disease. iPSCs-derived corneal epithelial cells provide an autologous and unlimited source of cells for the treatment of LSCD. On the other hand, iPSCs of LSCD patients can be used for iPSCs-corneal disease model and new drug discovery. However, prior to clinical trial, the efficacy and safety of these cells in patients with LSCD should be proved. Here we focused on the current status of iPSCs-derived corneal epithelial cells used for cell therapy as well as for corneal disease modeling. The challenges and potential of iPSCs-derived corneal epithelial cells as a choice for clinical treatment in corneal disease were also discussed.

Crosstalk between glioblastoma and tumor microenvironment drives proneural–mesenchymal transition through ligand-receptor interactions

Glioblastoma(GBM)is the most common intrinsic and aggressive primary brain tumor in adults,with a median survival of approximately 15 months.GBM heterogeneity is considered responsible for the treatment resistance and unfavorable prognosis.Proneural-mesenchymal transition(PMT)represents GBM malignant progression and recurrence,which might be a breakthrough to understand GBM heterogeneity and overcome treatment resistance.PMT is a complicated process influenced by crosstalk between GBM and tumor microenvironment,depending on intricate ligand-receptor interactions.In this review,we summarize the autocrine and paracrine pathways in the GBM microenvironment and related ligand-receptor interactions inducing PMT.We also discuss the current therapies targeting the PMT-related autocrine and paracrine pathways.Together,this review offers a comprehensive understanding of the failure of GBM-targeted therapy and ideas for future tendencies of GBM treatment.

内侧杏仁核的神经调节素1信号通路调控青春期社会隔离导致的自闭样行为

Autistic spectrum disorder(ASD),characterized by impairments in social interaction and repetitive behaviors,is a complex neurodevelopmental brain disorder that is reportedly increasing in prevalence globally[1].It is widely accepted that genetic and environmental factors alone or in combination cause ASD[2].

Glioma cell membrane camouflaged cinobufotalin delivery system for combinatorial orthotopic glioblastoma therapy

Glioblastoma(GBM)belongs to the deadliest primary malignancies with high mortality rate and poor prognosis.Over the past decades,less progress has been made to treat GBM,owing largely to the lack of effective chemotherapeutics and poor drug accumulation in the glioma tissue.In order to address this issue,we present an efficient biomimetic nanocomposite(Cu_(2−x)Se-CB@MEM,CCM),consisting of Cu_(2−x)Se nanoparticle core modified by cinobufotalin(CB),a toad venom extract,which is camouflaged with glioma cell Ln229 membrane.It is demonstrated that CB can decrease the protein activity of inosine monophosphate dehydrogenase 1(IMPDH1),a key target correlated with prognosis,through intermolecular hydrogen bonding with amino acid residues ARG-105 and ASP-77.The glioma cell membrane-camouflage endows the CCM with blood-brain barrier penetration and homology tumor-targeted ability.The optimized cinobufotalin based chemotherapy combining with the near-infrared-II(NIR-II)irradiation shows outstanding inhibition effect to glioma cells,by blocking cell cycle and inducing apoptosis.In vivo mice bearing orthotopic Ln229 GBM treated with CCM+NIR-II(CCM+L)have significantly suppressed tumor growth and extended survival,without side effect.The glioma cell membrane camouflaged nanocomposite of Cu_(2−x)Se and cinobufotalin with its significant anti-glioma property and well biosafety will provide novel alternatives for clinical treatment of GBM.

Factor analysis and subtyping significance of CTNNB1 gene mutation detection in adamantinomatous craniopharyngioma

Craniopharyngioma(CP)is a rare,histologically benign tumor located in the sellar region which is defined as a grade I tumor by the World Health Organization(WHO)classification.1 There are mainly two different clinicopathological subtypes of CP,the adamantinomatous CP(ACP)and the papillary CP(PCP).1 Although both variations have distinct histomorphological characteristics,an accurate diagnosis might be difficult to make,especially in tiny and/or fragmented specimens.Furthermore,there is a continuous scientific dispute about the occurrence of mixed forms and the cell of origin of these tumors.