Targeting NAD+: is it a common strategy to delay heart aging?

Heart aging is the main susceptible factor to coronary heart disease and significantly increases the risk of heart failure, especially when the aging heart is suffering from ischemia-reperfusion injury. Numerous studies with NAD+ supplementations have suggested its use in anti-aging treatment. However, systematic reviews regarding the overall role of NAD+ in cardiac aging are scarce. The relationship between NAD+ signaling and heart aging has yet to be clarified. This review comprehensively summarizes the current studies on the role of NAD+ signaling in delaying heart aging from the following aspects: the influence of NAD+ supplementations on the aging heart; the relationship and cross-talks between NAD+ signaling and other cardiac aging-related signaling pathways; Importantly, the therapeutic potential of targeting NAD+ in delaying heart aging will be discussed. In brief, NAD+ plays a vital role in delaying heart aging. However, the abnormalities such as altered glucose and lipid metabolism, oxidative stress, and calcium overload could also interfere with NAD+ function in the heart. Therefore, the specific physiopathology of the aging heart should be considered before applying NAD+ supplementations. We believe that this article will help augment our understanding of heart aging mechanisms. In the meantime, it provides invaluable insights into possible therapeutic strategies for preventing age-related heart diseases in clinical settings.

Effect of neoadjuvant iodine-125 brachytherapy upon resection of glioma.

BACKGROUND: A more extensive surgical resection of glioma contributes to improved overall survival (OS) and progression-free survival (PFS). However, some patients miss the chance of surgical resection when the tumor involves critical structures. PURPOSE: The present study aimed to assess the feasibility of neoadjuvant 125I brachytherapy followed by total gross resection for initially inoperable glioma. METHODS: Six patients diagnosed with inoperable glioma due to invasion of eloquent areas, bihemispheric diffusion, or large tumor volume received 125I brachytherapy. Surgical resection was performed when the tumor shrank, allowing a safe resection, assessed by the neurosurgeons. Patients were followed up after surgery. RESULTS: Shrinkage of the tumor after adjuvant 125I brachytherapy enabled a total gross resection of all six patients. Four patients were still alive at the last follow-up, with the longest survival time of more than 50 months, two of which returned to everyday life with a KPS of 100. Another two patients had neurological injuries with KPSs of 80 and 50, respectively. One patient with grade II glioma died 34 months, and another with grade IV glioma died 40 months after the combined therapy. CONCLUSIONS: In the present study, the results demonstrated that 125I brachytherapy enabled a complete resection of patients with initially unresectable gliomas. 125I brachytherapy may offer a proper neoadjuvant therapy method for glioma.

Permanent iodine-125 brachytherapy for patients with progressive or recurrent high-grade gliomas.

BACKGROUND: The prognosis of patients with progressive or recurrent high-grade gliomas (HGGs) after surgery remains poor. Iodine-125 brachytherapy is emerging as a salvage method for the treatment of gliomas. This study aimed to investigate whether permanent iodine-125 brachytherapy could be used as an effective therapeutic method even without radiotherapy and/or chemotherapy for progressive or recurrent HGG after gross total resection. METHODS: Between March 2004 and August 2016, 58 patients with progressive or recurrent HGG after gross total resection were included in this study. Twenty-nine patients underwent radiotherapy and/or chemotherapy and then permanent iodine-125 brachytherapy (SRCI group). Twenty-nine patients underwent permanent iodine-125 brachytherapy alone (SI group). Follow-up was carried out at 1, 3, and 6 months and then at 1, 2, 3, and 5 years after iodine-125 implantation. The median overall survival (OS) and progression-free survival (PFS), procedure-related complications and clinical outcomes were evaluated. RESULTS: No procedure-related fatal events happened. The temporary morbidity rate was 11.9%. The median OS and PFS for patients in the SI group were 22 and 8 months compared with 21 and 7 months in the SRCI group. No significant differences were found. Age and Karnofsky Performance Status (KPS) were independent prognostic factors for OS. Age, KPS and histology were independent prognostic factors for PFS. CONCLUSIONS: Permanent iodine-125 brachytherapy could be used as an effective therapeutic method even without radiotherapy and/or chemotherapy for progressive or recurrent HGG after gross total resection.

Dosimetry verification of 3D-printed individual template based on CT-MRI fusion for radioactive 125I seed implantation in recurrent high-grade gliomas.

PURPOSE: To verify the accuracy and efficacy of three-dimensional printing individual template (3D-PIT) with computed tomography-magnetic resonance imaging (CT-MRI) fusion for radioactive iodine-125 (125I) seed implantation in high-grade brain gliomas. MATERIAL AND METHODS: Between June 2017 and June 2018, 16 patients with recurrent high-grade gliomas (rHGG) underwent radioactive seed implantation with 3D-PIT. The prescribed dose was 120-140 Gy. We compared the dose distribution of the postoperative plan with the preoperative plan. Dose parameters included D90, V100, V200, conformity index (CI), and external index of the target volume (EI). Local control and early complications were also analyzed. RESULTS: Sixteen treatment areas were reported in our study. Median gross tumor volume (preoperative) of patients was 64.2 cm3, median needle number was 8, and median number of implanted 125I seeds was 60. For postoperative plans, the median D90, V100, and V200 was 152.1 Gy, 96.8%, and 49.1%, respectively, and 151.7 Gy, 97.0%, and 48.9%, respectively, in preoperative plans. Comparing with the preplanned cases, the dose of the target volume was slightly higher; the high-dose area of the target volume was larger in postoperative cases, but the difference was not statistically significant (p > 0.05). Actual dose conformity of the target volume was greater than preplanned, and the difference was not statistically significant (p > 0.05). Local control was 81.25% and 75% at 3 and 6 months after implantation, respectively. No serious early toxicities were observed. CONCLUSIONS: 3D-PIT based on the CT-MRI fusion images can result in good accuracy for positioning and dose distribution in radioactive seed implantation for treatment of rHGG.

Recurrent gliomas: comparison of computed tomography (CT)-guided 125I seed implantation therapy and traditional radiochemotherapy.

BACKGROUND: Primary brain tumors have always been associated with high morbidity and mortality. Glioma is the most common type of malignant brain tumors,with a high probability of recurrence after surgical excision and with poor prognosis.The purpose of this study was to compare the therapeutic efficacy of computed tomography (CT)-guided interstitial (125)I seed implantation with traditional radiochemotherapy for treatment of recurrent gliomas. RESULTS: The response rate at 1, 3, 6 and 12 months after (125)I seed implantation was 68.6, 74.3, 77.1 and 62.8% respectively, which was significantly higher than the group treated with the conventional chemoradiation protocol (p < 0.05). Patients exposed to (125)I seed implantation had a median survival of 29.0 months, whereas the median survival of those treated with traditional radiochemotherapy was 19.0 months. The difference observed between the two groups was significant. There were no severe complications or mortality associated with either treatment, except for one case of intracerebral hemorrhage around the tumor area in the (125)I seed implants group. METHODS: From November 2002 to May 2010, 73 consecutive patients with recurrent gliomas were treated with CT-guided (125)I seed implantation (35 cases) or traditional radiochemotherapy (38 cases). Patients were followed up after treatment and the therapeutic effect was evaluated by comparing the response and survival rates of the two groups. In particular, patients treated with (125)I seed implantation were monitored for adverse side effects. CONCLUSIONS: CT-guided (125)I seed implantation is safe and well-tolerated and more importantly, shows superior efficacy compared with conventional radiochemotherapy. This suggests that CT-guided (125)I seed implantation could be an alternative approach for recurrent gliomas.