Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects.

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aß deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.

Does dual antiplatelet therapy increase the risk of haematoma enlargement in the acute stage? A retrospective study of the use of stent-assisted coiling versus coiling alone or balloon-assisted coiling for the treatment of ruptured intracranial aneurysms combined with intracranial haematoma.

This study aims to identify the efficacy and safety of stent-assisted coiling (SAC) treatment of ruptured intracranial aneurysms (RIAs) combined with intracranial haematoma (ICH) compared to coiling alone or balloon-assisted coiling (non-SAC). A retrospective analysis of 54 consecutive patients receiving endovascular therapy from 2014 to 2020 was performed. The data collected included baseline characteristics, angiographic results, perioperative complications, immediate aneurysm occlusion, clinical outcomes, follow-up at discharge and after 6 months, hospitalisation costs, and inpatient length of stay. Patients were categorised into the SAC group and the non-SAC group. Univariate and multivariate logistic regression analyses were used to identify risk factors related to clinical outcomes. Of the 54 patients harbouring RIAs with ICH, 22 (40.74%) and 32 (59.26%) patients were subject to SAC and non-SAC treatments, respectively. Postoperative rebleeding (1 [4.5%] and 3 [9.3%] in SAC and non-SAC groups, respectively, p > 0.05) and Hunt-Hess grade (IV-V) lesions (13.6% vs. 40.6%, p = 0.067) did not differ between the two groups. In total, 10 (45.5%) patients treated with SAC received a Fisher scale score of 0-3 compared with 6 (18.8%) patients treated with non-SAC methods (p = 0.035). Compared with the non-SAC group (7/21.9%), the rate of wide-necked aneurysms was increased in the SAC group (11/50%) (p = 0.031). No differences in poor outcomes (mRS > 2) were noted between the SAC and non-SAC groups (p > 0.05). Multivariate analysis revealed that ischaemic complication events (p = 0.016) represent the only independent risk factor for adverse outcomes, and a trend towards unfavourable clinical outcomes was noted for patients who smoke (p = 0.087). SAC is a safe and efficient treatment for RIAs combined with ICH when dual antiplatelet therapy (DAPT) is used in the perioperative period. In addition, SAC should be preferentially used in wide-neck RIAs. Ischaemic complications are a risk factor for poor clinical outcomes. Given the small sample size and retrospective bias of this study, these findings should be further verified in a study with a larger sample size or a randomised controlled trial (RCT).

Pre-metastatic niche: from revealing the molecular and cellular mechanisms to the clinical applications in breast cancer metastasis.

Breast cancer (BC) is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths in women worldwide. Metastasis is a major contributor to high cancer mortality and is usually the endpoint of a series of sequential and dynamic events. One of the critical events is forming a pre-metastatic niche (PMN) that occurs before macroscopic tumor cell invasion and provides a suitable environment for tumor cells to colonize and progress into metastases. Due to the unique characteristics of PMN in cancer metastasis, developing therapies to target PMN may bring new advantages in preventing cancer metastasis at an early stage. Various biological molecules, cells, and signaling pathways are altered in BC, regulating the functions of distinctive immune cells and stromal remodeling, inducing angiogenesis, and effect metabolic reprogramming and organotropism to promote PMN formation. In this review, we elucidate the multifaceted mechanisms contributing to the development of PMN in BC, discuss the characteristics of PMN, and highlight the significance of PMN in providing potential diagnostic and therapeutic strategies for BC metastasis, which may bring promising insights and foundations for future studies.

HOTAIR/miR-203/CAV1 Crosstalk Influences Proliferation, Migration, and Invasion in the Breast Cancer Cell.

In recent years, malignant breast cancer metastasis has caused a great increase in mortality. Research on the genetic and molecular mechanisms of malignant breast cancer has continued to deepen, and targeted therapy has become the general trend. Among them, competing endogenous RNA (ceRNA)-related molecules have received much attention. Homeobox transcript antisense RNA (HOTAIR) has been reported to function extensively as a ceRNA in breast cancer. Notably, miR-203 and Caveolin 1 (CAV1) have also been found to play a role in breast cancer. However, the relationship between the three remains unclear. In this study, we present a new mechanic through bioinformatics tool and basic experiments: the HOTAIR/miR-203/CAV1 axis, which complemented the role network of HOTAIR as a ceRNA, thus, it will provide a novel potential idea for breast cancer research and therapy.

Mechanical Thrombectomy for M2 Segment Occlusion in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: The safety and benefit of mechanical thrombectomy (MT) in the treatment of acute ischemic stroke (AIS) patients with M2 segment middle cerebral artery occlusions remain uncertain. OBJECTIVE: To investigate the benefit of mechanical thrombectomy for M2 occlusion compared with M1 occlusion in patients with AIS. METHODS: The PubMed, Embase, and Cochrane Library databases were searched from inception to April 2021 to identify relevant articles. The main results comprised 90-day functional independence (modified Rankin Score from 0-2), successful recanalization (thrombectomy in cerebral infarction [TICI] 2b/3), mortality, and rates of symptomatic intracerebral hemorrhage after using modern thrombectomy devices. Odds ratios (ORs) were generated for binary variants. ReviewManager 5.3 software was used. RESULTS: Ultimately, a total of 14 trials were included, with 3454 participants enrolled. MT for M2 occlusion had a higher rate of 3-month functional independence than M1 occlusion, but the difference was nonsignificant (OR: 1.19, 95% confidence interval [CI]: 0.98 to 1.46). The TICI2b/3 scores (OR: 0.71, 95% CI: 0.58-0.88) in M2 occlusion were remarkably lower than those in M1. The mortality and symptomatic intracerebral hemorrhage rates were comparable between the 2 groups. When comparing M2 and M1 occlusions, we found that there was no significant difference between stent retriever and aspiration in the modified Rankin Score (0-2) after AIS, but aspiration exerted an eminently higher recanalization rate with regard to TICI2b/3 (OR: 0.77, 95% CI: 0.61-0.96). CONCLUSIONS: Compared with M1 occlusion, patients with M2 occlusion treated by MT demonstrated similar clinical outcomes in this study. Moreover, there was no difference between stent retriever and aspiration in treating M2 occlusion in terms of functional independence at 90 days. However, aspiration exerted a conspicuously higher recanalization rate in M2 occlusion than in M1 occlusion.