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.

Gold Nanoparticles Conjugated with Dendrigraft Poly-L-lysine and Folate-Targeted Poly(ethylene glycol) for siRNA Delivery to Prostate cancer.

Dendrigraft Poly-L-Lysine (d-PLL) coated gold nanoparticles (AuNPs) were synthesized by reducing Tetrachloroauric acid with ascorbic acid in the presence of d-PLL. AuNPs-d-PLL formed a stable colloidal solution that absorbs light at a maximum wavelength (λmax) centered at 570 nm as demonstrated by UV-visible (UV-Vis) spectroscopy. From Scanning Electron Microscopy (SEM) analysis, AuNPs-d-PLL were spherical in shape with a mean diameter of 128 ± 47 nm. Dynamic Light scattering (DLS) analysis of the colloidal solution exhibited one size distribution with a hydrodynamic diameter of about 131 nm (size distribution by intensity). Zeta potential (ξ) measurements revealed positively charged AuNPs-d-PLL with ξ about 32 mV, an indicator of high stability in an aqueous solution. The AuNPs-d-PLL was successfully modified with either thiolated poly (ethylene glycol) SH-PEG-OCH3 (Mw 5400 g mol-1) or folic acid-modified thiolated poly (ethylene glycol) SH-PEG-FA of similar molecular weight as demonstrated via DLS and Zeta potential measurements. Complexation of PEGylated AuNPs-d-PLL with siRNA was confirmed by DLS and gel electrophoresis. Finally, we analyzed the functionalization of our nanocomplexes with folic acid via targeted cellular uptake to prostate cancer cells using flow cytometry and LSM imaging. Our findings implicate the broader applicability of folate-PEGylated AuNPs in siRNA-based therapeutics against prostate cancer and perhaps other types of cancer.

D2B-Functionalized Gold Nanoparticles: Promising Vehicles for Targeted Drug Delivery to Prostate Cancer.

Despite the multitude of therapeutic agents available to treat prostate cancer (PC), there are still no effective and safe measures to treat the tumor. It remains a challenge to develop a simple approach to target PC with specific antibodies. In our study, D2B monoclonal antibodies against a prostate-specific membrane antigen (PSMA) were used. We investigated the functionalization of gold nanoparticles (AuNPs) with D2B to generate favorable physicochemical and biological properties that mediate specific binding to PC. For this purpose, AuNPs with a size of about 25 nm were synthesized in water using sodium citrate as a reducing and stabilizing agent and then coated with D2B. Major physicochemical properties of naked and D2B-coated AuNPs were investigated by ultraviolet-visible (UV-vis) spectroscopy, dynamic light scattering (DLS), and zeta potential measurements. The successful binding of D2B to AuNPs-citrate caused a 15 nm red shift in the UV-vis. This was assessed by DLS as an increase in zeta potential from ∼-45 to ∼-23 mV and in the size of AuNPs from ∼25 to ∼63 nm. Scanning electron microscopy confirmed the size shift of AuNPs, which was detected as an exterior organic layer of D2Bs surrounding each AuNP. Even at high exposure levels of the bioconjugates, PSMA-PC-3 cells exhibited minimal cytotoxicity. The specific and dose-dependent binding of AuNPs-D2B to PC-3-PSMA cells was validated by flow cytometry analysis. Our data provide effective drug delivery systems in PC theranostics.

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.

Role of connexins in spinal cord injury: An update.

Connexins (Cxs) are a family of transmembrane proteins that assemble into groups of six, forming what is known as a connexon or a hemichannel. Connexins are named based on their molecular weight, e.g. Cx43 is the connexin protein that weighs 43 kDa. Two hemichannels, each from a different cell, can link up end-to-end forming a gap junction. In the nervous system, gap junctions facilitate metabolite exchange between neighboring cells, in addition to electrical and chemical impulses. Many animal studies have been conducted to investigate the role of different types of Cxs in spinal cord injury (SCI) - most notably Cx43 - and the potential for targeting them with inhibitors. In this review, the authors discuss these studies and provide an update on recent connexin specific pharmacological agents that may potentially pave the way for the use of connexin inhibition in the management of SCI in humans, if more translational studies are done.