[Abnormalities in signal transduction of Purkinje cells in spinocerebellar ataxias: a review].

Spinocerebellar ataxias (SCAs) are a group of autosomal dominant neurodegenerative diseases that have been currently identified with numerous subtypes exhibiting genetic heterogeneity and clinical variability. Purkinje neuronal degeneration and cerebellar atrophy are common pathological features among most SCA subtypes. The physiological functions of Purkinje cells are regulated by multiple factors, and their dysfunction in signal transduction may lead to abnormal cerebellar motor control. This review summarizes the abnormalities in voltage-gated ionic channels, intracellular calcium signaling, and glutamate signaling transduction of Purkinje cells in SCAs, aiming to provide a theoretical basis for further understanding the common pathogenesis of SCAs and developing specific treatments.

Review of covalent organic frameworks for enzyme immobilization: Strategies, applications, and prospects.

Efficient enzyme immobilization systems offer a promising approach for improving enzyme stability and recyclability, reducing enzyme contamination in products, and expanding the applications of enzymes in the biomedical field. Covalent organic frameworks (COFs) possess high surface areas, ordered channels, optional building blocks, highly tunable porosity, stable mechanical properties, and abundant functional groups, making them ideal candidates for enzyme immobilization. Various COF-enzyme composites have been successfully synthesized, with performances that surpass those of free enzymes in numerous ways. This review aims to provide an overview of current enzyme immobilization strategies using COFs, highlighting the characteristics of each method and recent research applications. The future opportunities and challenges of enzyme immobilization technology using COFs are also discussed.

TMT proteomics analysis of a pseudocereal crop, quinoa (Chenopodium quinoa Willd.), during seed maturation.

Quinoa (Chenopodium quinoa Willd.), an Andean native crop, is increasingly popular around the world due to its high nutritional content and stress tolerance. The production and the popularity of this strategic global food are greatly restricted by many limiting factors, such as seed pre-harvest sprouting, bitter saponin, etc. To solve these problems, the underlying mechanism of seed maturation in quinoa needs to be investigated. In this study, based on the investigation of morphological characteristics, a quantitative analysis of its global proteome was conducted using the combinational proteomics of tandem mass tag (TMT) labeling and parallel reaction monitoring (PRM). The proteome changes related to quinoa seed maturation conversion were monitored to aid its genetic improvement. Typical changes of morphological characteristics were discovered during seed maturation, including mean grain diameter, mean grain thickness, mean hundred-grain weight, palea, episperm color, etc. With TMT proteomics analysis, 581 differentially accumulated proteins (DAPs) were identified. Functional classification analysis and Gene Ontology enrichment analysis showed that most DAPs involved in photosynthesis were downregulated, indicating low levels of photosynthesis. DAPs that participated in glycolysis, such as glyceraldehyde-3-phosphate dehydrogenase, pyruvate decarboxylase, and alcohol dehydrogenase, were upregulated to fulfill the increasing requirement of energy consumption during maturation conversion. The storage proteins, such as globulins, legumins, vicilins, and oleosin, were also increased significantly during maturation conversion. Protein-protein interaction analysis and function annotation revealed that the upregulation of oleosin, oil body-associated proteins, and acyl-coenzyme A oxidase 2 resulted in the accumulation of oil in quinoa seeds. The downregulation of ß-amyrin 28-oxidase was observed, indicating the decreasing saponin content, during maturation, which makes the quinoa "sweet". By the PRM and qRT-PCR analysis, the expression patterns of most selected DAPs were consistent with the result of TMT proteomics. Our study enhanced the understanding of the maturation conversion in quinoa. This might be the first and most important step toward the genetic improvement of quinoa.

Experimental research on surface acoustic wave microfluidic atomization for drug delivery.

This paper demonstrates that surface acoustic wave (SAW) atomization can produce suitable aerosol concentration and size distribution for efficient inhaled lung drug delivery and is a potential atomization device for asthma treatment. Using the SAW device, we present comprehensive experimental results exploring the complexity of the acoustic atomization process and the influence of input power, device frequency, and liquid flow rate on aerosol size distribution. It is hoped that these studies will explain the mechanism of SAW atomization aerosol generation and how they can be controlled. The insights from the high-speed flow visualization studies reveal that it is possible by setting the input power above 4.17 W, thus allowing atomization to occur from a relatively thin film, forming dense, monodisperse aerosols. Moreover, we found that the aerosol droplet size can be effectively changed by adjusting the input power and liquid flow rate to change the film conditions. In this work, we proposed a method to realize drug atomization by a microfluidic channel. A SU-8 flow channel was prepared on the surface of a piezoelectric substrate by photolithography technology. Combined with the silicon dioxide coating process and PDMS process closed microfluidic channel was prepared, and continuous drug atomization was provided to improve the deposition efficiency of drug atomization by microfluidic.

A covalent organic framework with a self-contained light source for photodynamic therapy.

External light-independent antitumor PDT is successfully realized with a covalent organic framework (COF)-based host-guest nanosystem. Its highly effective antitumor behavior is fully demonstrated by both H2O2-overexpressed 4T1 and H2O2-less expressed HCT116 and MCF-7 xenograft models.

Influence of Waterproof Films on the Atomization Behavior of Surface Acoustic Waves.

One of the reasons why commercial application of surface acoustic wave (SAW) atomization is not possible is due to the condensation of aerosol droplets generated during atomization, which drip on the interdigitated transducer (IDT), thereby causing electrodes to short-circuit. In order to solve this problem, a SU-8-2002 film coating on an IDT is proposed in this paper. The waterproof performance of the film coating was tested on a surface acoustic wave (SAW) device several times. The experimental results reveal that the film coating was robust. The experiment also investigated the effects of the SU-8-2002 film on atomization behavior and heating.

Long Non-Coding RNA: Dual Effects on Breast Cancer Metastasis and Clinical Applications.

As a highly heterogeneous malignancy, breast cancer (BC) has become the most significant threat to female health. Distant metastasis and therapy resistance of BC are responsible for most of the cases of mortality and recurrence. Distant metastasis relies on an array of processes, such as cell proliferation, epithelial-to-mesenchymal transition (EMT), mesenchymal-to-epithelial transition (MET), and angiogenesis. Long non-coding RNA (lncRNA) refers to a class of non-coding RNA with a length of over 200 nucleotides. Currently, a rising number of studies have managed to investigate the association between BC and lncRNA. In this study, we summarized how lncRNA has dual effects in BC metastasis by regulating invasion, migration, and distant metastasis of BC cells. We also emphasize that lncRNA has crucial regulatory effects in the stemness and angiogenesis of BC. Clinically, some lncRNAs can regulate chemotherapy sensitivity in BC patients and may function as novel biomarkers to diagnose or predict prognosis for BC patients. The exact impact on clinical relevance deserves further study. This review can be an approach to understanding the dual effects of lncRNAs in BC, thereby linking lncRNAs to quasi-personalized treatment in the future.

miR-29a Negatively Affects Glucose-Stimulated Insulin Secretion and MIN6 Cell Proliferation via Cdc42/ß-Catenin Signaling.

BACKGROUND: Diabetes is a progressive metabolic disease characterized by hyperglycemia. Functional impairment of islet ß cells can occur to varying degrees. This impairment can initially be compensated for by proliferation and metabolic changes of ß cells. Cell division control protein 42 (Cdc42) and the microRNA (miRNA) miR-29 have important roles in ß-cell proliferation and glucose-stimulated insulin secretion (GSIS), which we further explored using the mouse insulinoma cell line MIN6. METHODS: Upregulation and downregulation of miR-29a and Cdc42 were accomplished using transient transfection. miR-29a and Cdc42 expression was detected by real-time PCR and western blotting. MIN6 proliferation was detected using a cell counting kit assay. GSIS under high-glucose (20.0 mM) or basal-glucose (5.0 mM) stimulation was detected by enzyme-linked immunosorbent assay. The miR-29a binding site in the Cdc42 mRNA 3'-untranslated region (UTR) was determined using bioinformatics and luciferase reporter assays. RESULTS: miR-29a overexpression inhibited proliferation (P < 0.01) and GSIS under high-glucose stimulation (P < 0.01). Cdc42 overexpression promoted proliferation (P < 0.05) and GSIS under high-glucose stimulation (P < 0.05). miR-29a overexpression decreased Cdc42 expression (P < 0.01), whereas miR-29a downregulation increased Cdc42 expression (P < 0.01). The results showed that the Cdc42 mRNA 3'-UTR is a direct target of miR-29a in vitro. Additionally, Cdc42 reversed miR-29a-mediated inhibition of proliferation and GSIS (P < 0.01). Furthermore, miR-29a inhibited ß-catenin expression (P < 0.01), whereas Cdc42 promoted ß-catenin expression (P < 0.01). CONCLUSION: By negatively regulating Cdc42 and the downstream molecule ß-catenin, miR-29a inhibits MIN6 proliferation and insulin secretion.

[The role of Bmal1 in neuronal radial migration and axonal projection of the embryonic mouse cerebral cortex].

Normal development of the cerebral cortex is a basis for the formation and function of mammalian brains. During this process, the radial migration of cortical neurons, as well as the axon projection into specific layers, are the most important steps regulated by some transcription factors, but the underlying molecular mechanisms are still obscure. BMAL1 (brain and muscle Arnt-like protein 1) is a newly identified transcription factor that plays important roles in the circadian rhythms. It was recently found to regulate the proliferation of hippocampal neuronal progenitor/precursor cells (NPCs), implicating Bmal1 in the brain development. Here we employed both RT-RCR and real-time PCR to explore the expression pattern of the Bmal1 gene in the developing brain. We found BMAl1 is enriched in the brain cortex during the perinatal stages and peaked in P3 mouse brains. Combined with in utero electroporation and interference with RNAi, we found that reducing the expression level of Bmal1 in neurons, the radial migration of embryonic cortical neurons was largely delayed, in a gene dose-effect pattern. Moreover, reducing the level of Bmal1 expression in mouse brains, the axonal projection in the corpus callosum was also disrupted from ipsilateral to the lateral cerebral hemisphere. These findings indicate that BMAL1 is essential for the radial migration of neurons in the cerebral cortex and the axonal projection of the corpus callosum, providing insights into the molecular mechanisms of cerebral cortex development.

Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment.

Human breast cancer is one of the most frequent cancer diseases and causes of death among female population worldwide. It appears at a high incidence and has a high malignancy, mortality, recurrence rate and poor prognosis. Caveolin-1 (Cav1) is the main component of caveolae and participates in various biological events. More and more experimental studies have shown that Cav1 plays a critical role in the progression of breast cancer including cell proliferation, apoptosis, autophagy, invasion, migration and breast cancer metastasis. Besides, Cav1 has been found to be involved in chemotherapeutics and radiotherapy resistance, which are still the principal problems encountered in clinical breast cancer treatment. In addition, stromal Cav1 may be a potential indicator for breast cancer patients' prognosis. In the current review, we cover the state-of-the-art study, development and progress on Cav1 and breast cancer, altogether describing the role of Cav1 in breast cancer progression and application in clinical treatment, in the hope of providing a basis for further research and promoting CAV1 gene as a potential target to diagnose and treat aggressive breast cancers.

Cdc42 Promotes ADSC-Derived IPC Induction, Proliferation, And Insulin Secretion Via Wnt/ß-Catenin Signaling.

PURPOSE: Type 1 diabetes mellitus (T1DM) is characterized by irreversible islet ß cell destruction. Accumulative evidence indicated that Cdc42 and Wnt/ß-catenin signaling both play a critical role in the pathogenesis and development of T1DM. Further, bio-molecular mechanisms in adipose-derived mesenchymal stem cells (ADSCs)-derived insulin-producing cells (IPCs) remain largely unknown. Our aim was to investigate the underlying mechanism of Cdc42/Wnt/ß-catenin pathway in ADSC-derived IPCs, which may provide new insights into the therapeutic strategy for T1DM patients. METHODS: ADSC induction was accomplished with DMSO under high-glucose condition. ML141 (Cdc42 inhibitor) and Wnt-3a (Wnt signaling activator) were administered to ADSCs from day 2 until the induction finished. Morphological changes were determined by an inverted microscope. Dithizone staining was employed to evaluate the induction of ADSC-derived IPCs. qPCR and Western blotting were employed to measure the mRNA and protein expression level of islet cell development-related genes and Wnt signaling-related genes. The proliferation ability of ADSC-derived IPCs was also detected with a cell counting kit (CCK) assay. The expression and secretion of Insulin were detected with immunofluorescence test and enzyme-linked immunosorbent assay (ELISA) respectively. RESULTS: During induction, morphological characters of ADSCs changed into spindle and round shape, and formed islet-line cell clusters, with brown dithizone-stained cytoplasm. Expression levels of islet cell development-related genes were up-regulated in ADSC-derived IPCs. Wnt-3a promoted Wnt signaling markers and islet cell development-related gene expression at mRNA and protein levels, while ML141 played a negative effect. Wnt-3a promoted ADSC-derived IPC proliferation and glucose-stimulated insulin secretion (GSIS), while ML141 played a negative effect. CONCLUSION: Our research demonstrated that DMSO and high-glucose condition can induce ADSCs into IPCs, and Wnt signaling promotes the induction. Cdc42 may promote IPC induction, IPC proliferation and insulin secretion via Wnt/ß-catenin pathway, meaning that Cdc42 may be regarded as a potential target in the treatment of T1DM.

Effectiveness of dynamic contrast-enhanced magnetic resonance imaging in evaluating clinical responses to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Use of neoadjuvant chemotherapy necessitates assessment of response to cytotoxic drugs. The aim of this research was to investigate the effectiveness of dynamic contrast-enhanced magnetic resonance imaging (MRI) for evaluating clinical responses to neoadjuvant chemotherapy in breast cancer patients. METHODS: We examined patients receiving neoadjuvant chemotherapy for primary breast cancer between October 2007 and September 2008. Dynamic contrast-enhanced MRI was used to examine breast tumors prior to and after neoadjuvant chemotherapy. The MRI examination assessed tumors using Response Evaluation Criteria in Solid Tumors (RECIST). The Miller-Payne grading system was used as a histopathological examination to assess the effect of the treatment. We examined the relationship between the results of RECIST and histopathological criteria. In addition, we used time-signal intensity curves (MRI T-SI) to further evaluate the effects of neoadjuvant chemotherapy on tumor response. RESULTS: MRI examination of patients completing four three-week anthracycline-taxanes chemotherapy treatment revealed that no patients had complete responses (CR), 58 patients had partial responses (PR), 29 patients had stable disease (SD), and four with progressive disease (PD). The effectiveness of neoadjuvant chemotherapy (CR + PR) was 63.7% (58/91). The postoperative histopathological evaluations revealed the following: seven G5 (pCR) cases (7.7%), 39 G4 cases (42.9%), 16 G3 cases (17.6%), 23 G2 cases (25.3%), and six G1 cases (6.6%). The effectiveness (G5 + G4 + G3) was 68.1% (62/91). MRI T-SI standards classified 53 responding cases, 29 stable cases, and nine progressing cases. These results indicated that the treatment was 58.2% effective (53/91) overall. CONCLUSIONS: Dynamic contrast-enhanced MRI and histopathological standards were highly correlated. Importantly, MRI T-SI evaluation was found to be useful in assessing the clinical effectiveness of neoadjuvant chemotherapy.