Comprehensive review of mechanisms of pathogenesis involved in Alzheimer's disease and potential therapeutic strategies.

Cancer is a leading cause of death and poor quality of life globally. Even though several strategies are devised to reduce deaths, reduce chronic pain and improve the quality of life, there remains a shortfall in the adequacies of these cancer therapies. Among the cardinal steps towards ensuring optimal cancer treatment are early detection of cancer cells and drug application with high specificity to reduce toxicities. Due to increased systemic toxicities and refractoriness with conventional cancer diagnostic and therapeutic tools, other strategies including nanotechnology are being employed to improve diagnosis and mitigate disease severity. Over the years, immunotherapeutic agents based on nanotechnology have been used for several cancer types to reduce the invasiveness of cancerous cells while sparing healthy cells at the target site. Nanomaterials including carbon nanotubes, polymeric micelles and liposomes have been used in cancer drug design where they have shown considerable pharmacokinetic and pharmacodynamic benefits in cancer diagnosis and treatment. In this review, we outline the commonly used nanomaterials which are employed in cancer diagnosis and therapy. We have highlighted the suitability of these nanomaterials for cancer management based on their physicochemical and biological properties. We further reviewed the challenges that are associated with the various nanomaterials which limit their uses and hamper their translatability into the clinical setting in certain cancer types.

/pdf/application-of-nanotechnology-in-cancer-diagnosis-and-4fmop5mjmr.pdf

Application of Nanotechnology in Cancer Diagnosis and Therapy - A Mini-Review.

Nanoparticles are zero-dimensional nanomaterials and, based on their nature, they can be categorized into organic, inorganic, and composites nanoparticles. Due to their unique physical and chemical properties, nanoparticles are extensively used in a variety of fields, including medicine, pharmaceutics, and food industry. Although they have the potential to improve the diagnosis and treatment of brain diseases, it is fundamentally important to develop standardized toxicological studies, which can prevent the induction of neurotoxic effects. The focus of this review is to emphasize both the beneficial and negative effects of nanoparticles on brain health.

https://www.mdpi.com/2077-0383/7/12/490/pdf

Impact of Nanoparticles on Brain Health: An Up to Date Overview.

The field of nanotechnology, through which nanomaterials are designed, characterized, produced, and applied, is rapidly emerging in various fields, including energy, electronics, food and agriculture, environmental science, cosmetics, and medicine. The most common biomedical applications of nanomaterials involve drug delivery, bioimaging, and gene and cancer therapy. Since they possess unique properties which are different than bulk materials, toxic effects and long-term impacts on organisms are not completely known. Therefore, the purpose of this review is to emphasize the main neurotoxic effects induced by nanoparticles, liposomes, dendrimers, carbon nanotubes, and quantum dots, as well as the key neurotoxicology assays to evaluate them.

https://www.mdpi.com/2079-4991/9/1/96/pdf

Neurotoxicity of Nanomaterials: An Up-to-Date Overview.

Tissue plasminogen activator (tPA) is the only FDA approved thrombolytic drug for acute ischemic stroke but concerns regarding its limitations remain. Here, we developed a new strategy by incorporating tPA into porous magnetic iron oxide (Fe3O4)-microrods (tPA-MRs) for targeted thrombolytic therapy in ischemic stroke induced by distal middle cerebral artery occlusion. We showed that intra-arterial injection of tPA-MRs could target the cerebral blood clot in vivo under the guidance of an external magnet, where tPA was subsequently released at the site of embolism. When applied with an external rotating magnetic field, rotating tPA-MRs significantly improved not only the mass transport of the tPA-clot reaction, but also mechanically disrupted the clot network, which thus increased clot interaction and penetration of tPA. Importantly, intravenously injected MRs could be discharged from the kidney, and the function of liver and kidney were not damaged at different durations after administration of tPA-MRs. Ou...

Tissue Plasminogen Activator-Porous Magnetic Microrods for Targeted Thrombolytic Therapy after Ischemic Stroke

Background Traumatic brain injury (TBI) refers to temporary or permanent damage to brain function caused by penetrating objects or blunt force trauma. TBI activates inflammasome-mediated pathways and other cell death pathways to remove inactive and damaged cells, however, they are also harmful to the central nervous system. The newly discovered cell death pattern termed pyroptosis has become an area of interest. It mainly relies on caspase-1-mediated pathways, leading to cell death. Methods Our research focus is VX765, a known caspase-1 inhibitor which may offer neuroprotection after the process of TBI. We established a controlled cortical impact (CCI) mouse model and then controlled the degree of pyroptosis in TBI with VX765. The effects of caspase-1 inhibition on inflammatory response, pyroptosis, blood-brain barrier (BBB), apoptosis, and microglia activation, in addition to neurological deficits, were investigated. Results We found that TBI led to NOD-like receptors (NLRs) as well as absent in melanoma 2 (AIM2) inflammasome-mediated pyroptosis in the damaged cerebral cortex. VX765 curbed the expressions of indispensable inflammatory subunits (caspase-1 as well as key downstream proinflammatory cytokines such as interleukin- (IL-) 1β and IL-18). It also inhibited gasdermin D (GSDMD) cleavage and apoptosis-associated spot-like protein (ASC) oligomerization in the injured cortex. In addition to the above, VX765 also inhibited the inflammatory activity of the high-mobility cassette -1/Toll-like receptor 4/nuclear factor-kappa B (HMGB1/TLR4/NF-kappa B) pathway. By inhibiting pyroptosis and inflammatory mediator expression, we demonstrated that VX765 can decrease blood-brain barrier (BBB) leakage, apoptosis, and microglia polarization to exhibit its neuroprotective effects. Conclusion In conclusion, VX765 can counteract neurological damage after TBI by reducing pyroptosis and HMGB1/TLR4/NF-κB pathway activities. VX765 may have a good therapeutic effect on TBI.

https://downloads.hindawi.com/journals/omcl/2020/7879629.pdf

VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-κB Pathways to Improve Functional Outcomes in TBI Mice

Nanomaterial applications for neurological diseases and central nervous system injury.

Dear Editor, Giant serpentine aneurysms (GSAs) were first reported in 1977 [9] and have been defined as giant, partially thrombosed aneurysms with ectatic vascular channels that run through the aneurysm [1]. They are particularly uncommon and represent a particular technical challenge in treatment. The pathogenesis and natural history of GSAs are still unclear. With their large size, dependent distal vessels, and unidentifiable neck, the management of these giant serpentine aneurysms poses difficult therapeutic issues. A giant serpentine aneurysm is usually a giant (>2.5 cm) and partially thrombosed aneurysm with serpiginous ectatic vascular channels that have an in-flow and out-flow pathway [3, 4, 7, 9]. Histopathologically, GSAs are large masses with a 1to 4-mm-thick fibrous walls that contain small vessels, hemosiderin, with or without calcification [2]. As reported, the majority of GSAs are located in the middle cerebral artery (MCA) circulation and usually present with symptoms of intracranial mass effect rather than hemorrhage [1]. A 38-year-old woman was admitted to our department with a history of intermittent severe headaches accompanied by nausea and vomiting. Physical and neurological examinations at the time of admission yielded no unusual findings. A T1weighted magnetic resonance image (MRI) showed a large right frontotemporal mass of complex signal representing variable degrees of hemoglobin degradation products (Fig. 1a). This lesion measured 4 × 5 × 4 cm and produced a mass effect with compression of the lateral ventricle and a shift of the midline. T2-weighted MRI shows the edema surrounding the lesion (Fig. 1b). Postgadolinium MRI shows the homogeneous enhancement in the periphery of the lesion and the flow void signal (Fig. 1c). Based on its appearance on MRI, the lesion was suspected to be a tumor accompanied by hemorrhage. The patient underwent a right frontotemporal craniotomy. Upon opening the dura, the lesion could be visualized in the enlarged Sylvian fissure. However, a giant MCA aneurysm was identified after the exposure of the lesion. The subsequent intraoperative cerebral angiography demonstrated tortuous ectatic vascular channel arising from the region of right MCA and ultimately supplying the distal arterial territory of MCA (Fig. 1d). The serpiginous lumen extended throughout a thrombosed portion of the aneurysm and filled extremely slowly. Direct surgical clipping was not pursued, as no identifiable aneurysm neck could be found. Bypass surgery was not performed at that time because we were unsure whether distal revascularization would be necessary, as preoperative evaluation including assessment of distal collateral flow via BTO, functional MR image, or Wada testing, was not done. A secondary surgery was planned but the patient refused to undergo surgery. Follow-up MR image obtained 3 months later shows that a large thrombosed aneurysm remains in the right frontotemporal region. MR image obtained 1 year after presentation showed significant minimization of the size of both the thrombosed aneurysm and the mass effect (Fig. 1e). Three years after the initial diagnosis, MRI study demonstrated large resorption of the lesion (Fig. 1f). CT angiography follow-up 3 years later did not show any residual portion of the giant serpentine aneurysm (Fig. 1g). The CT perfusion image showed a slight perfusion deficit in the right distal MCA Lijie Huang and Linhui Ruan contributed equally to this work.

Spontaneous resorption of giant serpentine aneurysm arising from middle cerebral artery.

Resveratrol Attenuates Endoplasmic Reticulum Stress-Induced Cell Death and Results in Functional Improvement after Traumatic Brain Injury in Mice

Current concepts in the management of spinal multiple myeloma: a single centre experience

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