Solid Lipid Curcumin Particles Induce More DNA Fragmentation and Cell Death in Cultured Human Glioblastoma Cells than Does Natural Curcumin

Despite recent advancements in cancer therapies, glioblastoma multiforme (GBM) remains largely incurable. Curcumin (Cur), a natural polyphenol, has potent anticancer effects against several malignancies, including metastatic brain tumors. However, its limited bioavailability reduces its efficiency for treating GBM. Recently, we have shown that solid lipid Cur particles (SLCPs) have greater bioavailability and brain tissue penetration. The present study compares the efficiency of cell death by Cur and/or SLCPs in cultured GBM cells derived from human (U-87MG) and mouse (GL261) tissues. Several cell viability and cell death assays and marker proteins (MTT assay, annexin-V staining, TUNEL staining, comet assay, DNA gel electrophoresis, and Western blot) were investigated following the treatment of Cur and/or SLCP (25 μM) for 24–72 h. Relative to Cur, the use of SLCP increased cell death and DNA fragmentation, produced longer DNA tails, and induced more fragmented nuclear lobes. In addition, cultured GBM cells had increased levels of caspase-3, Bax, and p53, with decreases in Bcl2, c-Myc, and both total Akt, as well as phosphorylated Akt, when SLCP, rather Cur, was used. Our in vitro work suggests that the use of SLCP may be a promising strategy for reversing or preventing GBM growth, as compared to using Cur

Acute and Post-Acute Neurological Complications of COVID-19

Coronavirus disease 2019 (COVID-19) is an emerging global health emergency caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The global outbreak of SARS-CoV-2 infection has been declared a global pandemic by the World Health Organization (WHO). The clinical presentation of SARS-CoV-2 infection depends on the severity of the disease and may range from an asymptomatic infection to a severe and lethal illness. Fever, cough, and shortness of breath are among the most common symptoms associated with SARS-CoV-2 infection. Accumulating evidence indicates that COVID-19 patients commonly develop neurological symptoms, such as headache, altered mental status, anosmia, and myalgia. In this comprehensive literature review, we have summarized the most common neurological complications and reported neurological case studies associated with COVID-19, and neurological side effects associated with COVID-19 treatments. Additionally, the post-acute COVID-19 syndrome and long-term neurological complications were discussed. We also explained the proposed mechanisms that are involved in the pathogenesis of these neurological complications

Pharmacological Approaches in Neurofibromatosis Type 1-Associated Nervous System Tumors

Neurofibromatosis type 1 is an autosomal dominant genetic disease and a common tumor predisposition syndrome that affects 1 in 3000 to 4000 patients in the USA. Although studies have been conducted to better understand and manage this disease, the underlying pathogenesis of neurofibromatosis type 1 has not been completely elucidated, and this disease is still associated with significant morbidity and mortality. Treatment options are limited to surgery with chemotherapy for tumors in cases of malignant transformation. In this review, we summarize the advances in the development of targeted pharmacological interventions for neurofibromatosis type 1 and related conditions

Curcumin and Solid Lipid Curcumin Particles Induce Autophagy, but Inhibit Mitophagy and the PI3K-Akt/mTOR Pathway in Cultured Glioblastoma Cells

Autophagy and the (PI3K-Akt/mTOR) signaling pathway play significant roles in glioblastoma multiforme (GBM) cell death and survival. Curcumin (Cur) has been reported to prevent several cancers, including GBM. However, the poor solubility and limited bioavailability of natural Cur limits its application in preventing GBM growth. Previously, we have shown the greater apoptotic and anti-carcinogenic effects of solid lipid Cur particles (SLCP) than natural Cur in cultured GBM cells. Here, we compared the autophagic responses on cultured U-87MG, GL261, F98, C6-glioma, and N2a cells after treatment with Cur or SLCP (25 µM for 24 h). Different autophagy, mitophagy, and chaperone-mediated autophagy (CMA) markers, along with the PI3K-AKkt/mTOR signaling pathway, and the number of autophagy vacuoles were investigated after treatment with Cur and or SLCP. We observed increased levels of autophagy and decreased levels of mitophagy markers, along with inhibition of the PI3K-Akt/mTOR pathway after treatments with Cur or SLCP. Cell survival markers were downregulated, and cell death markers were upregulated after these treatments. We found greater effects in the case of SCLP-treated cells in comparison to Cur. Given that fewer effects were observed on C-6 glioma and N2a cells. Our results suggest that SLCP could be a safe and effective means of therapeutically modulating autophagy in GBM cells

Management of Phantom Limb Pain through Thalamotomy of the Centro-Median Nucleus

Background: Phantom limb syndrome is defined as the perception of intense pain or other sensations that are secondary to a neural lesion in a limb that does not exist. It can be treated using pharmacological and surgical interventions. Most medications are prescribed to improve patients’ lives; however, the response rate is low. In this case report, we present a case of phantom limb syndrome in a 42-year-old female with a history of transradial amputation of the left thoracic limb due to an accidental compression one year before. The patient underwent placement of a deep brain stimulator at the ventral posteromedial nucleus (VPM) on the right side and removal secondary to loss of battery. The patient continued to have a burning pain throughout the limb with a sensation of still having the limb, which was subsequently diagnosed as phantom limb syndrome. After a thorough discussion with the patient, a right stereotactic centro-median thalamotomy was offered. An immediate response was reported with a reduction in pain severity on the visual analogue scale (VAS) from a value of 9–10 preoperative to a value of 2 postoperative, with no postoperative complications. Although phantom limb pain is one of the most difficult to treat conditions, centro-median thalamotomy may provide an effective stereotactic treatment procedure with adequate outcomes

Management of Phantom Limb Pain through Thalamotomy of the Centro-Median Nucleus

Background: Phantom limb syndrome is defined as the perception of intense pain or other sensations that are secondary to a neural lesion in a limb that does not exist. It can be treated using pharmacological and surgical interventions. Most medications are prescribed to improve patients’ lives; however, the response rate is low. In this case report, we present a case of phantom limb syndrome in a 42-year-old female with a history of transradial amputation of the left thoracic limb due to an accidental compression one year before. The patient underwent placement of a deep brain stimulator at the ventral posteromedial nucleus (VPM) on the right side and removal secondary to loss of battery. The patient continued to have a burning pain throughout the limb with a sensation of still having the limb, which was subsequently diagnosed as phantom limb syndrome. After a thorough discussion with the patient, a right stereotactic centro-median thalamotomy was offered. An immediate response was reported with a reduction in pain severity on the visual analogue scale (VAS) from a value of 9–10 preoperative to a value of 2 postoperative, with no postoperative complications. Although phantom limb pain is one of the most difficult to treat conditions, centro-median thalamotomy may provide an effective stereotactic treatment procedure with adequate outcomes

Boosting Ensemble Learning for Freeway Crash Classification under Varying Traffic Conditions: A Hyperparameter Optimization Approach

Freeway crashes represent a significant and persistent threat to road safety, resulting in both loss of life and extensive property damage. Effectively addressing this critical issue requires a comprehensive understanding of the factors contributing to these incidents and the ability to accurately predict crash severity under different traffic conditions. This study aims to improve the accuracy of crash classification by incorporating key traffic-related variables such as braking, weather conditions, and speed. To validate the effectiveness of proposed model, we utilize real-world crash data from Flint, Michigan. To achieve the objective, we employ an innovative Boosting Ensemble Learning approach, leveraging five advanced ensemble learning models: Gradient Boosting, Cat Boost, XGBoost, LightGBM, and SGD. Through the application of hyperparameter optimization techniques, we further enhance the performance of these models, improving their predictive capabilities. Our evaluation results demonstrated the effectiveness of our approach, with Gradient Boosting algorithms achieving an accuracy rate of up to 96% in crash classification. This research provides valuable insights into the potential of using Boosting Ensemble Learning as a tool for accurately and efficiently classifying freeway crashes across a spectrum of traffic conditions. Additionally, it sheds light on the nuanced variations in crash mechanisms observed when employing diverse ensemble learning models. The findings of this study underscore the significance of hyperparameter optimization as a critical factor in elevating the predictive precision of freeway crashes

Induced Pluripotent Stem Cell-Derived Neural Stem Cell Transplantations Reduced Behavioral Deficits and Ameliorated Neuropathological Changes in YAC128 Mouse Model of Huntington's Disease

Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by neuronal loss and motor dysfunction. Although there is no effective treatment, stem cell transplantation offers a promising therapeutic strategy, but the safety and efficacy of this approach needs to be optimized. The purpose of this study was to test the potential of intra-striatal transplantation of induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) for treating HD. For this purpose, we developed mouse adenovirus-generated iPSCs, differentiated them into neural stem cells in vitro, labeled them with Hoechst, and transplanted them bilaterally into striata of 10-month old wild type (WT) and HD YAC128 mice. We assessed the efficiency of these transplanted iPS-NSCs to reduce motor deficits in YAC128 mice by testing them on an accelerating rotarod task at 1 day prior to transplantation, and then weekly for 10 weeks. Our results showed an amelioration of locomotor deficits in YAC128 mice that received iPS-NSC transplantations. Following testing, the mice were sacrificed, and their brains were analyzed using immunohistochemistry and Western blot (WB). The results from our histological examinations revealed no signs of tumors and evidence that many iPS-NSCs survived and differentiated into region-specific neurons (medium spiny neurons) in both WT and HD mice, as confirmed by co-labeling of Hoechst-labeled transplanted cells with NeuN and DARPP-32. Also, counts of Hoechst-labeled cells revealed that a higher proportion were co-labeled with DARPP-32 and NeuN in HD-, compared to WT- mice, suggesting a dissimilar differentiation pattern in HD mice. Whereas significant decreases were found in counts of NeuN- and DARPP-32-labeled cells, and for neuronal density measures in striata of HD vehicle controls, such decrements were not observed in the iPS-NSCs-transplanted-HD mice. WB analysis showed increase of BDNF and TrkB levels in striata of transplanted HD mice compared to HD vehicle controls. Collectively, our data suggest that iPS-NSCs may provide an effective option for neuronal replacement therapy in HD