Mitochondria-Targetable Near-Infrared Fluorescent Probe for Visualization of Hydrogen Peroxide in Lung Injury, Liver Injury, and Tumor Models.

Hydrogen peroxide (H2O2) overexpressed in mitochondria has been regarded as a key biomarker in the pathological processes of various diseases. However, there is currently a lack of suitable mitochondria-targetable near-infrared (NIR) probes for the visualization of H2O2 in multiple diseases, such as PM2.5 exposure-induced lung injury, hepatic ischemia-reperfusion injury (HIRI), nonalcoholic fatty liver (NAFL), hepatic fibrosis (HF), and malignant tumor tissues containing clinical cancer patient samples. Herein, we conceived a novel NIR fluorescent probe (HCy-H2O2) by introducing pentafluorobenzenesulfonyl as a H2O2 sensing unit into the NIR hemicyanine platform. HCy-H2O2 exhibits good sensitivity and selectivity toward H2O2, accompanied by a remarkable "turn-on" fluorescence signal at 720 nm. Meanwhile, HCy-H2O2 has stable mitochondria-targetable ability and permits monitoring of the up-generated H2O2 level during mitophagy. Furthermore, using HCy-H2O2, we have successfully observed an overproduced mitochondrial H2O2 in ambient PM2.5 exposure-induced lung injury, HIRI, NAFL, and HF models through NIR fluorescence imaging. Significantly, the visualization of H2O2 has been achieved in both tumor-bear mice as well as surgical specimens of cancer patients, making HCy-H2O2 a promising tool for cancer diagnosis and imaging-guided surgery.

Combined simultaneous transsphenoidal and transcranial regimen improves surgical outcomes in complex giant pituitary adenomas: A longitudinal retrospective cohort study.

BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. MATERIALS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients (298 [46.1%] women, mean age: 48.5 ± 14.0 years) with complex GPAs, 91 were in the combined group and 556 were in the non-combined group. Compared with the non-combined regimen, the combined regimen was associated with a higher probability of gross total resection (50.5% vs. 40.6%, odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.30-3.63, P = 0.003). The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h (P < 0.001) and higher surgical costs of 22,000 CNY (approximate 3,000 USD, P = 0.022) compared with the non-combined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.

Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs.

Background and Objective: Non-functioning pituitary neuroendocrine tumors (NF-PitNETs) represent a heterogeneous tumor type that lacks effective medical treatment. MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. In this study, we measured the expression levels and role of MDM2 in non-functioning PitNET patients' combined clinical features and investigated the effect of etoposide on the cell bioactivity of the GT1-1 cell line in vivo and in vitro. Methods: RT-PCR and immunochemistry measured the expression levels and role of MDM2 in 103 NF-PitNET patients' combined clinical features. Cell proliferation, migration, colony and apoptosis experiments measured the effect of etoposide on the GT1-1 cell line in vivo and in vitro. Results: There was more invasive behavior (p = 0.013) in patients with high MDM2, who were also younger (p = 0.007), were more frequently female (p = 0.049) and had larger tumor sizes (p = 0.018) compared with patients with low MDM2. Patients with high p53 were younger (p = 0.017) and had larger tumor sizes (p = 0.034) compared with patients with low p53. Univariate (p = 0.018) and multivariate (p = 0.023) Cox regression analysis showed that MDM2 was the independent factor for invasive behavior in NF-PitNET patients. Log-rank analysis showed that the average progression-free survival (PFS) time in the low MDM2 patients was longer than that in the high MDM2 patients (p = 0.044). Functional studies indicated that etoposide inhibited cell proliferation and cell migration and induced apoptosis in p53 independence in GT1-1 cells. Furthermore, etoposide significantly inhibited the growth of GT1-1-xenograft in BALB/c nude mice. The tumor growth inhibition rate of etoposide was 67.4 ± 4.6% after 14 d of treatment, which suggested the anti-tumor activity of etoposide. Conclusions: MDM2 played the role of tumorigenesis of NF-PitNET in a p53 independence manner, and an MDM2 inhibitor could be a potential choice for the treatment of NF-PitNET patients.

Endoscopy-assisted high anterior cervical approach in craniovertebral junction (CVJ).

Background: Surgical procedures in the craniovertebral junction (CVJ) suffer from specific challenges due to the proximity between the cranium and spine containing the critical neurovascular structures and the brainstem, respectively. Owing to the complex transitional zone, it is highly challenging for classic surgical approaches to practically acquire the additional exposure to neurovascular structures of the CVJ. Inspired by these facts, we explore the feasibility of an endoscopy-assisted high anterior cervical approach in the CVJ. Methods: To explore the feasibility of an endoscopy-assisted approach, we quantitatively assessed the surgical corridor and extent of exposure of the CVJ in 6 cadaveric specimens using 0° and 30° endoscopes. Results: The applied endoscopes provided adequate exposure to neurovascular structures and the brainstem in the CVJ. Notably, the resection of the anterior arch of C1 is avoided in minimal anterior clivectomy. Further, improved exposure of the CVJ is obtained after removing the odontoid. Conclusion: An endoscope-assisted high anterior cervical approach in the CVJ significantly preserved the cervical spine stability while minimalizing the risk of neurovascular injury within the surgical corridor.

Integrated analysis of competitive endogenous ribose nucleic acids (ceRNAs)-related regulatory networks in invasive and non-invasive non-functioning pituitary adenomas (NFPAs).

Background: This study aims to identify the differentially expressed (DE) non-coding ribose nucleic acids (ncRNAs), messenger RNA (mRNA) expression profiles, and competitive endogenous RNA (ceRNA)-related regulatory networks in invasive and non-invasive nonfunctioning pituitary adenomas (NFPAs). Methods: A full-transcriptome sequencing of invasive and non-invasive NFPAs is carried out to evaluate the expression profiles of circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNA expression profiles. Results: The screening criteria resulted in 118 DEcircRNAs (88 up-regulated and 30 down-regulated), 105 DElncRNAs (68 up-regulated and 37 down-regulated), 43 DEmiRNAs (22 up-regulated and 21 down-regulated), and 268 DEmRNAs (194 up-regulated and 74 down-regulated). Accordingly, a ceRNA regulatory network related to invasive NFPA is constructed. Further, the Gene Ontology and Kyoto Encylopedia of Genes and Genomes analyses showed that circRNAs and lncRNAs in the network are related to chromatin remodeling, participating in the Janus kinase/signal transducer and activator of transcription (JAK-STAT) and calcium signaling pathways. Hsa-miR-1248 showed exceptional connectivity in the ceRNA regulatory network, which could be closely related to the invasiveness of NFPAs. Conclusions: Together, these findings clarified the regulatory mechanisms of invasive and non-invasive NFPAs, providing innovative research avenues and therapeutic targets for invasive NFPAs.

Rutin induces apoptosis via P53 up-regulation in human glioma CHME cells.

BACKGROUND: Flavonoids, despite having low nutritional value, have numerous biological activities and extremely beneficial health effects. This study investigated the anticancer activity of rutin in human glioma CHME cells. METHODS: Cytotoxicity was determined through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Protein expression was determined through Western blotting. Apoptosis was detected using annexin V/propidium iodide (PI) and fluorescence microscopy. RESULTS: Rutin induced maximum cytotoxicity in CHME cells, as revealed through MTT assays. Cell death induced by rutin was due to apoptosis via P53 up-regulation. Rutin induced nuclear condensation, fragmentation, and membrane blebbing, as determined through 4',6-diamidino-2-phenylindole (DAPI) staining. Furthermore, rutin increased reactive oxygen species (ROS) levels and caused a loss of mitochondrial membrane potential, activating the intrinsic apoptotic pathway in CHME cells. The induction of apoptosis by rutin was further confirmed by the release of cytochrome c, up-regulation of BAX, and down-regulation of BCL, activated caspase 9, and caspase 3. The knockdown of P53 reversed rutin-induced apoptosis in a concentration-dependent manner. CONCLUSIONS: Rutin plays an important role in the induction of apoptosis in CHME cells. Based on these data, rutin should be further investigated as an anticancer agent in human glioma CHME cells.

[Comparative analysis of neuroendoscope-assisted microsurgery and microscope treatment for small acoustic neuroma].

OBJECTIVE: To explore the outcomes of surgery for the treatment of small acoustic neuroma by the neuroendoscope-assisted microsurgery and microscope. METHODS: From 2008 to 2013, 42 patients with small acoustic neuroma underwent neuroendoscope-assisted microsurgery (n = 20) and microscopic tumoural resection (n = 22). Neurophysiological monitoring, 30-degree rigid neuroendoscope and microscope were employed intra-operatively. For the endoscope group, facial nerve and inner acoustic meatus could be visualized distinctly in each aspect, as for the microscope group, microscopic operation could be accomplished directly. The damage extents of facial nerve and inner acoustic meatus were compared between two groups. RESULTS: Total removal of acoustic neuroma and conservation of facial nerve were achieved in all patients. For the neuroendoscope-assisted group, the postoperative facial functions were Grade I (n = 6), Grade II (n = 10) and Grade III (n = 4). Internal acoustic canal was drilled 2-3 mm in 4 patients and no drilling in others. For the microscope group, Grade I (n = 5), Grade II (n = 6), Grade III (n = 8) and Grade III-IV (n = 3). Internal acoustic canal was drilled at least 3 mm in 12 patients and no drilling in others. No complication such as cerebrospinal fluid leakage occurred during the follow-ups. CONCLUSION: Endosocopic operation of acoustic neuroma surgery is superior to microscopic operation in terms of magnification, illumination, wide-angel and angulation. And the former procedure may yield better outcomes through alleviating the damage of facial nerve and decreasing the drilling degree of inner acoustic meatus.