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Despite mounting evidence linking Acute Myocardial Infarction (AMI) to Alzheimer's disease (AD), the shared mechanism of these two conditions' occurrence remains unclear. This research aims to delve deeper into the molecular process of the occurrence of the two diseases. We retrieved the gene expression profiles of AD (GSE5281) and AMI (GSE66360) from the Gene Expression Omnibus database. Then, a total of 22 common differentially expressed genes (DEGs) including one downregulated gene and 21 upregulated genes were chosen for further analysis. Following the discovery of the common DEGs between AMI and AD, we performed protein–protein interaction analysis and hub gene identification analysis. Next, ten important hub genes were identified. Additionally, the key genes were identified by the least absolute shrinkage and selection operator and support vector machine‐recursive feature elimination and multivariable logistic regression analysis. The BCL6 was identified to be the most connected with AMI and AD. Finally, the BCL6 gene was validated in the GSE40680 (AMI) and GSE122063 (AD) datasets. Our research indicates that AMI and AD share a comparable pathophysiology. The Hub genes, especially BCL6, were essential in developing AMI and AD. In addition, these hub genes and shared pathways can offer fresh perspectives for additional mechanism investigation. [ABSTRACT FROM AUTHOR]

Abstract Spermidine/spermine N1-acetyltransferase (SSAT) is a catabolic regulator of polyamines, ubiquitous molecules essential for cell proliferation and differentiation. In this study, the molecular characterization of the SSAT1 gene of the Sichuan white goose was analyzed, as well as its expression profiles in various follicles and tissues. The open reading frame of the SSAT1 cDNA (GenBank No. KM925008) is 516 bp in length and encodes a 171-amino acid protein with a putative molecular weight of 20 kDa. The predicted SSAT1 protein is highly conserved with those of other species, especially Gallus gallus. SSAT1 mRNA was ubiquitously expressed in all the examined tissues. The highest level of SSAT1 mRNA expression was found in the pineal gland (P<0.05), and was 12-fold greater than in the heart. The level of SSAT1 mRNA expression was relatively lower in preovulatory follicles, while it was higher in postovulatory follicles (POFs), particularly in POF1. Furthermore, as postovulatory follicles degenerated, SSAT1 expression gradually decreased. Our findings suggest that SSAT1 might play important roles in mediating the physiological function of the pineal gland and regulating the regression of POFs. [ABSTRACT FROM AUTHOR]

Background. Thyroid associated ophthalmopathy (TAO) is an autoimmune disease, which involves inflammation and tissue remodeling. Pentraxin-3 (PTX3) is a component of innate immune system and recently implicated in autoimmunity. This observation may indicate that PTX3 participates in the inflammatory process of TAO. Methods. All studies were performed on TAO patients and healthy controls (45: 28 in total). RNA-seq was used to detect differential gene expression of orbital adipose-connective tissue. Quantitative PCR was performed to verify the results. PTX3 protein in orbital adipose-connective tissues was visualized by immunohistochemistry (IHC). PTX3 concentration in serum was determined by enzyme-linked immunosorbent assay (ELISA). Results. RNA-seq showed 1.86-log⁡2FC higher PTX3 expression in the orbital adipose-connective tissues from TAO group than controls (FDR = 0.0059). qPCR confirmed the difference (5.59-fold increase, p=0.0012). The presence of PTX3 protein was demonstrated. Orbital adipose tissue from healthy controls showed weak staining for PTX3 while tissue from TAO group was strongly positive. Serum PTX3 concentration was significantly elevated in patients when compared to the control group (1.9-fold increase; p<0.0001). Conclusions. Patients with TAO showed increased presence of PTX3 in orbital tissue and serum, which may suggest a potential relationship of PTX3 and TAO. [ABSTRACT FROM AUTHOR]

An increasing number of studies suggest that ornithine decarboxylase antizyme 1 (OAZ1), which is regarded as a tumor suppressor gene, regulates follicular development, ovulation, and steroidogenesis. The granulosa cells in the ovary play a critical role in these ovarian functions. However, the action of OAZ1 mediating physiological functions of granulosa cells is obscure. OAZ1 knockdown in granulosa cells of geese was carried out in the current study. The effect of OAZ1 knockdown on polyamine metabolism, cell proliferation, apoptosis, and hormone receptor transcription of primary granulosa cells in geese was measured. The viability of granulosa cells transfected with the shRNA OAZ1 at 48 h was significantly higher than the control (p<0.05). The level of putrescine and spermidine in granulosa cells down-regulating OAZ1 was 7.04- and 2.11- fold higher compared with the control, respectively (p<0.05). The CCND1, SMAD1, and BCL-2 mRNA expression levels in granulosa cells down-regulating OAZ1 were each significantly higher than the control, respectively (p<0.05), whereas the PCNA and CASPASE 3 expression levels were significantly lower than the control (p<0.05). The estradiol concentration, ER and LHR mRNA expression levels were significantly lower in granulosa cells down-regulating OAZ1 compared with the control (p<0.05). Taken together, our results indicated that OAZ1 knockdown elevated the putrescine and spermidine contents and enhanced granulosa cell viability and inhibited ER and LHR transcriptions of granulosa cells in geese. [ABSTRACT FROM AUTHOR]

In the long history of traditional Chinese medicine, Panax notoginseng has been used as a key herb for the treatment of blood diseases. Brain microvessels support adequate blood circulation to maintain normal physiological function, therefore, brain microcirculation disorder is an important therapeutic target for various brain diseases. However, the role of Xueshuantong (XST) injection composed of saponins from P. Notoginseng (PNS) in the amelioration of cerebral microcirculation disorder is unclear. Cerebral microcirculation disorder and inflammation play a vital role in stroke. Capillary endothelial cells and adjacent tight junctions are fundamental to the structure and function of cerebrovascule. XST injection has been used clinically in the treatment of stroke, but no studies have reported its indication in cerebral microcirculation disorder. This study is to explore the action and mechanism of XST injection in the alleviation of cerebral microcirculation disorder in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. MCAO/R rats and LPS-induced bEnd.3 cells were employed for the investigation of effect and mechanism of XST injection. Brain damages were evaluated by neurobehavioral assessment, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin staining (H&E), and Nissl staining. Morphology and density changes of cerebral microvessels were monitored by immunohistochemistry. Cell permeability was detected by measurement of trans-endothelial electrical resistance (TEER) and sodium fluorescein (NaF) leakage. The mRNA and protein expressions of inflammatory cytokines, tight junction proteins, adhesion molecules, Janus kinase 2 (JAK2), signal transducer and activator of transcription-3 (STAT3), inhibitor of NF-κB (IκB), nuclear factor-κB (NF-κB) and c-jun N-terminal kinase (JNK) in brain microvessels and lipopolysaccharide (LPS)-induced bEnd.3 cells were measured by real-time PCR and Western blot, respectively. XST injection at 48 mg/kg significantly improved the neurological damage, inflammatory infiltration, and microvessel morphology, and increased microvessel density in brain of MCAO/R rats. The endothelial permeability was significantly mitigated by XST injection in LPS-induced bEnd.3 cells. Meanwhile, the tight junction proteins such as zona occludens 1 (ZO-1) and occludin were elevated remarkably in brain microvessel of MCAO/R rats and LPS-induced bEnd.3 cells. Moreover, the expression of inflammatory mediators including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), cycloocygenases 2 (COX-2), vascular cellular adhesion molecule-1 (VCAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 were inhibited by XST injection. In addition, XST injection suppressed the phosphorylation of JAK2, STAT3, IκB, NF-κB and JNK, which could be abolished by anisomycin, the JNK agonist. XST injection improved cerebral microvescular structure damage and dysfunction in MCAO/R rats through inhibiting inflammation activated by JNK mediated JAK2/STAT3 and NF-κB signaling pathways. The novel findings may provide theoretical basis for the clinical application in the treatment of cerebral microcirculation disorder. MCAO/R promotes microvascular endothelial cell activation and release of inflammatory mediators such as IL-1β, IL-6, TNF-α, VCAM-1 and MMP-9, and induces cerebral microcirculation disorder in rats. XST injection improves cerebral microvescular structure damage and dysfunction in MCAO/R rats through inhibiting inflammation activated by JNK mediated JAK2/STAT3 and NF-κB signaling pathways. [Display omitted] • XST injection improves cerebral microcirculation disorder in MCAO/R rats. • XST injection suppresses inflammatory response of the cerebral endothelial cells in MCAO/R rats. • XST injection inhibits the activation of JAK2/STAT3 and NF-κB signaling pathways by deactivation of JNK. [ABSTRACT FROM AUTHOR]

Berberine (BBR) is a compound derived from Chinese herbal medicine, known for its anticancer properties through multiple signaling pathways. However, whether BBR can inhibit tumor growth by participating in ferroptosis remains unconfirmed. In this study, we demonstrated that berberine synergistically inhibited NSCLC in combination with multiple ferroptosis inducers, and this combination synergistically down-regulated the mRNA and protein expression of SLC7A11, GPX4, and NRF2, resulting in ferroptosis accompanied by significant depletion of GSH, and aberrant accumulation of reactive oxygen species and malondialdehyde. In a lung cancer allograft model, the combination treatment exhibited enhanced anticancer effects compared to using either drug alone. Notably, p53 is critical in determining the ferroptosis sensitivity. We found that the combination treatment did not elicit a synergistic anticancer effect in cells with a p53 mutation or with exogenous expression of mutant p53. These findings provide insight into the mechanism by which combination induces ferroptosis and the regulatory role of p53 in this process. It may guide the development of new strategies for treating NSCLC, offering great medical potential for personal diagnosis and treatment. [Display omitted] • Berberine enhances NSCLC inhibition with ferroptosis inducers. • Combo treatment downregulates SLC7A11, GPX4, NRF2, induces ferroptosis via GSH depletion, ROS accumulation. • Combo treatment enhances anticancer effects in lung cancer allograft model. • Mutant p53 or p53 mutation abolishes synergistic anticancer effect. [ABSTRACT FROM AUTHOR]

Antizyme inhibitor 1 (Azin1) plays critical roles in various cellular pathways, including ornithine decarboxylase regulation, polyamine anabolism and uptake and cell proliferation. However, the molecular characteristics of the AZIN1 gene and its expression profile in goose tissues and ovarian follicles have not been reported. In this study, the AZIN1 cDNA of the Sichuan white goose ( Anser cygnoides ) was cloned, and analyzed for its phylogenetic and physiochemical properties. The expression profile of AZIN1 mRNA in geese tissues and ovarian follicles were examined using quantitative real-time PCR. The results showed that the open reading frame of the AZIN1 cDNA is 1353 bp in length, encoding a 450 amino acid protein with a molecular weight of 50 kDa. Out of all tissues examined, AZIN1 expression was highest in the adrenal gland and lowest in breast muscle. There was also a high expression of AZIN1 in the cerebellum and isthmus of oviduct. With follicular development, AZIN1 gene expression gradually increased, and its expression in F1 was significantly higher than in F5 ( P < 0.05). AZIN1 expression was also significantly higher in the POF1 than in the other follicles ( P < 0.05), and there was a low mRNA expression of AZIN1 in atretic follicles. The results of AZIN1 expression profiling in ovarian follicles suggest that AZIN1 may play an important role in the progression of follicular development, potentially through regulating polyamine levels. [ABSTRACT FROM AUTHOR]