A Review of the Research Applications of Centipeda minima.

Centipeda minima is a traditional Chinese medicine with wide applications and diverse pharmacological effects. Scholars have conducted extensive studies on its relevant clinical applications, especially its remarkable efficacy in cancer treatment. This paper thoroughly investigates the chemical composition and identification, pharmacological effects, and toxicity, along with the safety of Centipeda minima, so as to lay the foundation for corresponding clinical applications and product development. Furthermore, as global scholars have conducted extensive research on such clinical applications and made significant progress, the future development and utilization of Centipeda minima's active ingredients to create novel drugs are of great clinical significance.

Association of CYP46 gene polymorphism with sporadic Alzheimer's disease in Chinese Han populations: a meta-analysis.

It is well known that genetic variants play an important role in the pathogenesis of Alzheimer's disease (AD). Recently, several studies have found that an intronic single-nucleotide polymorphism (SNP) in cholesterol 24S-hydroxylase (CYP46) gene was associated with sporadic AD (SAD). Within the CYP46 gene, the most well-studied SNP that has been found to be associated with an increased risk for SAD in Caucasians is the intronic SNP rs754203. Subsequently, other researchers have attempted to validate this finding in Chinese Han populations. However, these studies have produced both negative and positive results. To derive a more precise estimation for whether an association exists between rs754203 and SAD in the Chinese Han population, we performed the present meta-analysis of six case-control studies published up to July 2012 by searching the Medline, AlzGene, CNKI, and Wan Fang databases. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for four genetic models (allelic model: T vs. C; additive model: TT vs. CC; recessive model: TT + TC vs. CC; dominant model: TC + CC vs. TT) in the six studies, which included a total of 1187 cases and 1283 controls. The statistical analysis showed no significant differences in rs754203 between patients and controls for any of the four genetic models (p > 0.05 for each model). In conclusion, despite several limitations, this meta-analysis indicates that the CYP46 gene SNP rs754203 is not significantly associated with SAD susceptibility in Chinese Han populations.

Pyridine nucleotide-disulphide oxidoreductase domain 2 (PYROXD2): Role in mitochondrial function.

Pyridine Nucleotide-Disulphide Oxidoreductase Domain 2 (PYROXD2), a Hepatitis B virus X protein (HBx)-interacting protein, is significantly down-regulated in hepatocellular carcinoma (HCC), however its exact biological function remains unclear. The aim of this study is to investigate the subcellular localization and biological function of PYROXD2 in hepatic cells. The results showed that PYROXD2 was imported to the mitochondrial inner membrane/matrix by Tom40 and Tim23, but not Mia40. PYROXD2 151-230aa might be the mitochondrial targeting sequence. PYROXD2 interacted with complex IV subunit COX5B. Knockout of PYROXD2 decreased MMP, intracellular ROS, complex IV activity, cell proliferation, ATP content and mtDNA copy number, but increased mtROS levels and the number of immature mitochondria. In summary, our data illustrated that PYROXD2 localizes to the mitochondrial inner membrane/matrix, and it plays important roles in regulating mitochondrial function.

Myeloid zinc finger 1 protein is a key transcription stimulating factor of PYROXD2 promoter.

Previous studies revealed that PYROXD2 was more highly expressed in normal liver tissue and liver cell lines than in cancer tissue and cancer cell lines, which indicated that decreased PYROXD2 expression may be involved in hepatocarcinogenesis. To identify the mechanisms which regulate PYROXD2 gene transcription, we constructed a series of luciferase reporter plasmids and used them to perform luciferase­based reporter assays with HepG2, Sk-hep1, L02 and 293T cells with the purpose of characterizing the PYROXD2 reporter region. Our results revealed that the transcription factor myeloid zinc finger 1 (MZF1) is necessary for PYROXD2 gene transcription and that it functions as a trans-activator. DNA binding assays revealed that the MZF1 protein binds to the cis-element TGGGGA located in the -320/-312 region of the PYROXD2 promoter. This promoter had a significantly enhanced activity when the MZF1 protein was overexpressed and a significantly decreased activity when the MZF1 protein expression was silenced. However, MZF1 gene expression was not significantly correlated with PYROXD2 protein expression in the samples of resected tumor tissues, which revealed that the PYROXD2 promoter transcription activity was determined by the aggregated effect of numerous transcription factors. This finding may be helpful in understanding the underlying mechanism which regulates the PYROXD2 expression.

Molecular signal networks and regulating mechanisms of the unfolded protein response.

Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum (ER). One of the primary mechanisms is the unfolded protein response (UPR). In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein (BiP) interacts with the three sensors (protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1α (IRE1α)). Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR)-phospholipase C-γ (PLCγ)-mammalian target of rapamycin complex 1 (mTORC1) pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IRE1α also can be activated by activated RAC-alpha serine/threonine-protein kinase (AKT). A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species (ROS), Ca2+ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase (JNK), signal transducer and activator of transcription 3 (STAT3), and P38, when cellular damage exceeds the capacity of this adaptive response.