Sierra Haile, Benjamin C. Balzer, Emily Egan
et al.
This article focuses on current and emerging therapeutics for CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). CADASIL is an inherited vascular disease that impairs blood flow in the small cerebral vessels of the brain, leading to strokes and other neurological deficits. The disease is caused by a mutation in the NOTCH3 gene located on chromosome 19. NOTCH3 encodes a transmembrane receptor expressed on vascular smooth muscle cells. In CADASIL, mutations in the NOTCH3 gene lead to the accumulation and deposition of the receptor, affecting the number of cysteine residues in its extracellular domain. These mutations result in the loss or gain of a cysteine residue within the epidermal growth factor-like repeat (EGFr) domains of the NOTCH protein. Beyond traditional symptomatic treatments for stroke, this work highlights advances in disease modifying approaches including gene editing, cell therapies, and immune-based interventions aimed at altering the course of CADASIL. It also examines ongoing clinical trials and recent patents related to these novel strategies. In addition to summarizing diagnostic methods and molecular mechanisms, the article emphasizes the translational potential of current research and the experimental models driving therapeutic development. The goal is to offer a comprehensive overview of CADASIL and emerging interventions that hold promise for improving long-term outcomes.
Sarah Zaidan, Syamsudin Abdillah, Nur Arfian
et al.
The purpose of this study was to obtain natural drugs from brown seaweed (Sargassum crassifolium) as antiatherosclerosis candidates through the study of hypolipidemic mechanisms of action. Modeling of dyslipidemia rats was carried out by feeding high-fat (HFF) and doses of crude fucoidan 100. 200. 400mg / KgBB. in both treatments measured blood lipid profile levels taken from the orbital sinuses. HE's histopathology. mRNA expression. immunohistochemistry (IHC) with parameters VCAM-1. ICAM-1. and MCP-1 were performed on adipose tissue. as well as liver. Total cholesterol values 51.07-225.2. triglycerides 30.43-115.73. HDL 13.1-24.86 mg/dl and LDL 20.22-189.68 mg/dl. In the treatment of crude fucoidan obtained the result of p value < α (0.05. Histopathological features of adipose tissue after administration of HFF for 60 days resulted in an increase in adipose cell size. and the liver experienced structural damage and inflammation. but after 21 days of treatment the morphological picture of adipose tissue was similar to normal morphology and the liver also decreased in severity and inflammation. The results of histochemical staining after treatment showed a positive staining part on MCP-1. The result of p value < α (0.05) of mRNA expression for administration of 3 treatment doses. A dyslipidemic mouse model with HFF administration for 60 days succeeded in becoming a dyslipidemic rat. and crude fucoidan had hypolipidemic activity. Doses of 100. 200. and 400 mg/KgBB crude fucoidan showed improvement in adipose and liver morphological features of severity and inflammation of dyslipidemic rats and decreased mRNA expression.
Christof A. Bertram, Taryn A. Donovan, Alexander Bartel
One of the most relevant prognostication tests for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review is to scholarly analyze the methods and prognostic relevance of histologically measuring mitotic activity in canine tumors. A total of 137 articles that correlated the mitotic activity in canine tumors with patient outcome were identified through a systematic (PubMed and Scopus) and manual (Google Scholar) literature search and eligibility screening process. These studies determined the mitotic count (MC, number of mitotic figures per tumor area) in 126 instances, presumably the mitotic count (method not specified) in 6 instances and the mitotic index (MI, proportion of mitotic figures per tumor cells) in 5 instances. A particularly high risk of bias was identified in the available details of the MC methods and statistical analysis, which often did not quantify the prognostic discriminative ability of the MC and only reported p-values. A significant association of the MC with survival was found in 72/109 (66%) studies. However, survival was evaluated by at least three studies in only 7 tumor types/groups, of which a prognostic relevance is apparent for mast cell tumors of the skin, cutaneous melanoma and soft tissue sarcoma of the skin. None of the studies on the MI found a prognostic relevance. Further studies on the MC and MI with standardized methods are needed to prove the prognostic benefit of this test for further tumor types.
Background: Bladder cancer is the 10th most common cancer worldwide, and its prevalence is increasing, especially in developing countries. Objective: In the present study, we employed gene expression profiles from the GSE163209 data set in the GEO database to identify potential molecular and genetic markers in BC patients. Methods: The data set comprised 217 samples, with 113 stage Ta tumor tissue samples and 104 stage T1 tumor tissue samples. The top 766 genes were chosen. P.value<0.0001 and |logFC|=1 was used to change the cutoff criteria for defining DEGs. Moreover, the MCODE plugin and cytoHubba plugin were employed to produce a module and detect 20 hub genes in these DEGs. We used GO and KEGG pathway enrichment analyses to get a better understanding of these DEGs. Results: The KEGG pathway enrichment results indicated that the top genes were mainly involved: Systemic lupus erythematosus, Alcoholism, and Viral carcinogenesis. SLE activation in the renal glomeruli could explain the connection between this disease's route and bladder cancer, and according to our results and previous researches, heavy alcohol intake can increase the risk of BC in males and particular populations. Conclusion: According to our hub genes, we can consider CDK1 and NDC80 as bladder cancer biomarkers. Not much research has been done on the effect of this gene on bladder cancer.
Neural interfaces using biocompatible scaffolds provide crucial properties for the functional repair of nerve injuries and neurodegenerative diseases, including cell adhesion, structural support, and mass transport. Neural stimulation has also been found to be effective in promoting neural regeneration. This work provides a new strategy to integrate photoacoustic (PA) neural stimulation into hydrogel scaffolds using a nanocomposite hydrogel approach. Specifically, polyethylene glycol (PEG)-functionalized carbon nanotubes (CNT), highly efficient photoacoustic agents, are embedded into silk fibroin to form biocompatible and soft photoacoustic materials. We show that these photoacoustic functional scaffolds enable non-genetic activation of neurons with a spatial precision defined by the area of light illumination, promoting neuron regeneration. These CNT/silk scaffolds offered reliable and repeatable photoacoustic neural stimulation. 94% of photoacoustic stimulated neurons exhibit a fluorescence change larger than 10% in calcium imaging in the light illuminated area. The on-demand photoacoustic stimulation increased neurite outgrowth by 1.74-fold in a dorsal root ganglion model, when compared to the unstimulated group. We also confirmed that photoacoustic neural stimulation promoted neurite outgrowth by impacting the brain-derived neurotrophic factor (BDNF) pathway. As a multifunctional neural scaffold, CNT/silk scaffolds demonstrated non-genetic PA neural stimulation functions and promoted neurite outgrowth, providing a new method for non-pharmacological neural regeneration.
Abstract In statistical modeling, we strive to specify models that resemble data collected in studies or observed from processes. Consequently, distributional specification and parameter estimation are central to parametric models. Graphical procedures, such as the quantile–quantile (Q–Q) plot, are arguably the most widely used method of distributional assessment, though critics find their interpretation to be overly subjective. Formal goodness of fit tests are available and are quite powerful, but only indicate whether there is a lack of fit, not why there is lack of fit. In this article, we explore the use of the lineup protocol to inject rigor into graphical distributional assessment and compare its power to that of formal distributional tests. We find that lineup tests are considerably more powerful than traditional tests of normality. A further investigation into the design of Q–Q plots shows that de-trended Q–Q plots are more powerful than the standard approach as long as the plot preserves distances in x and y to be the same. While we focus on diagnosing nonnormality, our approach is general and can be directly extended to the assessment of other distributions.
The generating function of partitions with repeated (resp. distinct) parts such that each odd part is less than twice the smallest part is shown to be the third order mock theta function ω(q) (resp. ν(−q)). Similar results for partitions with the corresponding restriction on each even part are also obtained, one of which involves the third order mock theta function ϕ(q). Congruences for the smallest parts partition function(s) associated to such partitions are obtained. Two analogues of the partition-theoretic interpretation of Euler’s pentagonal number theorem are also obtained.
We propose the notion of q-characters for finite-dimensional representations of quantum affine algebras. It is motivated by our theory of deformed W-algebras. We show that the q-characters give rise to a homomorphism from the Grothendieck ring of representations of a quantum affine algebra to a polynomial ring. We conjecture that the image of this homomorphism is equal to the intersection of certain "screening operators". We also discuss the connection between q-characters and Bethe Ansatz.