Meningioma genomics: a therapeutic challenge for clinicians.

Meningiomas are amongst the most commonly encountered intracranial tumors. The majority of these tumors arise intracranially, and the remaining incidents occur along the spinal cord. Meningiomas tend to grow gradually, with many tumors arising in inaccessible locations. Such sporadic behavior poses a therapeutic challenge to clinicians, causing incomplete tumor resections that often lead to recurrence. Therefore, ongoing research seeks to find alternative systematic treatments for meningiomas, with gene-based therapeutics of high interest. Subsequently, genetic studies characterized frequent somatic mutations in NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA. These genes are communally exhibited in 80% of sporadic meningiomas. In addition, other genes such as the DUSP family, the NR4 family, CMKOR, and FOSL2, have been identified as key players in spinal meningiomas. In this perspective, we aim to investigate current genetic-based studies, with the ongoing research mainly focused on the above NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA genes and their involved pathways. In addition, this perspective can serve as a potential cornerstone for future genetic analyses of meningioma cases.

Effect of Phase Change Material Cooling Vests on Body Thermoregulation and Thermal Comfort of Patients With Paraplegia: A Human Subject Experimental Study.

STUDY DESIGN: Randomized experimental study. OBJECTIVE: Compared to able-bodied people, patients with paraplegia due to thoracic spinal cord injury (SCI) are at an increased risk of heat illnesses during exercise due to impaired thermoregulatory responses. To overcome this limitation, we investigated the performance of three phase change material (PCM) cooling vests of different melting temperatures (Eijsvogels, #49) and coverage area of the trunk. METHODS: Sixteen participants were divided into three groups according to their injury level. All were tested for V20 full vest (20°C Tm, 75% coverage). Mid-thoracic and high-thoracic groups were tested for V14 vest (14°C Tm, 75% coverage). The mid-thoracic group was tested for V20 half vest (20°C Tm, 50% coverage). The participants performed a 30-min arm-crank exercise followed by a recovery period inside a controlled hot climatic chamber. The heart rate, segmental skin (Tskin), and core temperature (Tcore) values were recorded, and subjective questionnaires were taken. RESULTS: Compared to no vest (NV) test, all the vests showed an effective decrease in Tskin values of the trunk. However, the decrease in Tskin was not enough to induce a significant decrease in Tcore in all three groups. Mid-thoracic and low-thoracic groups showed a reduction in the increasing Tcore by the end of the exercise and recovery period. Finally, the level of thermal comfort was enhanced for the three groups. CONCLUSION: The effectiveness of cooling vests for persons with paraplegia is dependent on injury level and thus the ratio of sensate to insensate skin. Future studies necessitate the investigation of the cooling effects of PCM vests at a lower Tm with a larger sample size.

Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization.

INTRODUCTION: Triple negative breast cancer is an aggressive disorder which accounts for at least 15% of breast cancer diagnosis and a high percentage of breast cancer morbidity, hence intensive research efforts are focused on the development of effective therapies to overcome the disease. Thymoquinone (TQ), the bioactive constituent of Nigella sativa, exhibits anticancer activity, yet its translation to the clinic is hindered by its poor bioavailability and lack of quantification method in blood and tissues. To overcome these limitations, cubosomes were utilized for the encapsulation and delivery of this anticancer molecule. METHODS: Thymoquinone loaded cubosomes were prepared through the emulsification homogenization method. The physicochemical characteristics, including particle size, zeta potential, morphology and entrapment efficiency, were studied. Moreover, the in vitro antitumor activity was tested on breast cancer cell lines (MCF-7 and MDA-MB-231) and compared to non-tumorigenic cell line (MCF-10A). Subcellular localization, cellular uptake and apoptotic effects of the formulations were assessed. RESULTS: The results revealed that the TQ loaded cubosomal formulation exhibited a mean particle size of 98.0 ± 4.10 nm with narrow unimodal distribution. The high entrapment efficiency (96.60 ± 3.58%) and zeta potential (31.50 ±4.20 mV) conceived the effectiveness of this nanosystem for TQ encapsulation. Cell viability in both breast cancer cell lines demonstrated a dose-dependent decrease in response to treatment with free TQ or TQ-loaded cubosomes, with enhanced antitumor activity upon treating with the latter formulation. A significant increase in apoptotic bodies and cleaved caspase 3 was observed upon treatment of MDA-MB-231 cells with either TQ or TQ-loaded cubosomes. Localization and trafficking studies unveiled that cubosomes accumulate in the cytoplasm of the studied breast cancer cell lines. DISCUSSION: Our results show that thymoquinone encapsulation in cubosomal nanoparticles provides a promising anticancer drug delivery system with the ability to label, detect and subsequently trace it within the human cells.