Daleymchugh5914

Ginkgo biloba L. is one of the oldest trees on earth, and its leaves have been used since ages as herbal medicine to treat cerebrovascular disorders. It is worth noting that in addition to the widely concerned flavonoids and terpenoids, it also contains various thus far neglected biflavonoids. In fact, biflavonoids are flavonoids consisting of apigenin or its derivatives as monomeric scaffold, and are linked via C-C or C-O-C bond.

Based on the structural similarity of flavonoids, we hypothesized that biflavonoids may play a potential role in the treatment of cerebrovascular diseases. Here, we describe the effectiveness and underlying mechanisms for prevention and treatment of atherosclerosis (AS) by biflavonoids.

Four main biflavonoids in Ginkgo biloba leaves were screened by oleic acid-induced lipid production in HepG2 cells. The non-covalent effects of biflavonoids on the potential targets of atherosclerosis were screened by reverse targeting and molecular dynamics simulation. The interactions between1-S phase, which significantly inhibited abnormal cell growth which closely related to the occurrence and development of atherosclerosis. Biflavonoids could be a promising natural medicine for the treatment of atherosclerosis.

Rhein, an anthraquinone compound, displays extensive antifibrotic effects; however, its potential mechanisms are not fully understood. In this study, we explored the underlying molecular mechanism of action of rhein.

An integrated network pharmacology and cell metabolomics approach was developed based on network pharmacology and bioinformatics method, and then successfully applied to speculate the potential targets of rhein and construct a rhein-target-metabolic enzyme-metabolite network. Thereafter, the antifibrotic mechanism of rhein was validated in TGF-β- and oleic acid- induced HK-2 and NRK-52E cells in vitro as well as a unilateral ischemia-reperfusion injury Sprague-Dawley rat model.

Based on the construction of the rhein-target-metabolic enzyme-metabolite network, we found that rhein played an antifibrotic role through the PPAR-α-CPT1A-l-palmitoyl-carnitine axis. In vitro experiments demonstrated that rhein effectively activated the expression of PPARα and its downstream proteins (CPT1A and ACOX1) to alleviate lipid accumulation and fibrosis development. In vivo experiments indicated that rhein attenuated renal fibrosis mainly by activating the fatty acid oxidation pathway and improving lipid metabolism.

Taken together, our findings reveal that rhein is a novel agonist of PPARα, which contributes to its renoprotection through the regulation of the PPARα-CPT1A axis. Moreover, our study provides a novel insight into an integrated network pharmacology-metabolomics strategy for uncovering the pharmacological mechanisms of drugs from the system perspective.

Taken together, our findings reveal that rhein is a novel agonist of PPARα, which contributes to its renoprotection through the regulation of the PPARα-CPT1A axis. Moreover, our study provides a novel insight into an integrated network pharmacology-metabolomics strategy for uncovering the pharmacological mechanisms of drugs from the system perspective.

A growing percentage of the US population is over the age of 65, and geriatrics account for a large portion of trauma admissions, expected to reach nearly 40% by 2050. Cognitive status is important for operative management, especially in elderly populations. This study aims to investigate preoperative and postoperative cognitive function assessment tools in geriatric patients following acute trauma and associated outcomes, including functional status, postdischarge disposition, mortality, and hospital length of stay (H-LOS).

A literature search was conducted using Medline/PubMed, Google Scholar, Embase, JAMA Networks, and Cochrane databases for studies investigating the use of cognitive assessment tools for geriatric patients with acute trauma. The last literature search was conducted on November 13,2021.

Ten studies were included in this review, of which five focused on preoperative cognitive assessment and five focused on postoperative. The evidence suggests patients with preoperative cognitive impairt and effective at detecting cognitive impairment in the acute trauma setting and allow clinicians to address preoperative or postoperative cognitive impairments to improve patient outcomes.The most of embryo losses occur before the day 16 after artificial insemination, but there is no low cost and easy operation that can detect pregnancy with high accuracy within three weeks post-insemination in cattle. In this study, blood samples were collected at day 18 of the estrous cycle, and days 18, 25 and 35 of pregnancy, and relative levels of interferon stimulated genes (ISGs), Toll-like receptor (TLRs), complement components, early pregnancy factor (EPF) and pregnancy-associated plasma protein A (PAPPA) proteins were analyzed through Western blot. In addition, a colloidal gold immunochromatographic test strip was developed using the selected antibody, and the test was used for early pregnancy diagnosis. The results showed that there were changes in relative levels of plasma ISGs, TLRs, complement components, EPF and PAPPA proteins during early pregnancy in cattle, and complement component 1q (C1q) could be used as an ideal marker to develop a colloidal gold immunochromatographic test strip for early pregnancy diagnosis. Pemrametostat inhibitor In addition, the accuracy of pregnancy diagnosis by this test strip was 91.67% (11/12) for pregnant cows and 80% (8/10) nonpregnant cows at day 18 after insemination. In conclusion, the changes in plasma ISGs, TLRs, complement components, EPF and PAPPA proteins may be related to the maternal systemic immune modulation during early pregnancy, and a colloidal gold immunochromatographic test strip was developed for early pregnancy diagnosis using C1q as the ideal marker in cows. However, this colloidal gold immunochromatographic test strip needs further studies to improve the accuracy.RNA-seq technology can be used for the detection of miRNA transcripts in tissues and cells at specific periods and under specific treatment conditions, which can easily and effectively screen out differential transcripts. The purpose of this study was to compare miRNA expression in porcine cumulus cells before and after oocyte maturation, and to investigate the mechanism whereby cumulus cells may influence oocyte maturation. To that aim, cumulus cells surrounding GV- and MII-stage oocytes were isolated, and their differences in miRNA expression were examined using miRNA-seq. 143 differentially expressed miRNAs were identified, among which miR-101 was selected and further verified by qPCR. Moreover, miR-101 was found to target HAS2 through target gene prediction, luciferase-based co-transfection and cumulus cells transfection. Transfection of COCs with miR-101 mimics or inhibitor revealed that the miR-101 could inhibit oocyte IVM by regulating the expanding of CCSs, but had no effect on the embryo development competence. These findings demonstrated that miR-101 regulated oocyte maturation in vitro via targeting HAS2 in porcine cumulus cells.The Fc region of a monoclonal antibody (mAb) can play a crucial role in its biodistribution and therapeutic activity. The chimeric mAb, chDAB4 (APOMAB®), which binds to dead tumor cells after DNA-damaging anticancer treatment, has been studied pre-clinically in both diagnostic and therapeutic applications in cancer. Given that macrophages contribute to the tumor accumulation of chDAB4 and its potency as an antibody drug conjugate in vivo, we next wanted to determine whether the Fc region of the chDAB4 mAb also contributed. We found that, regardless of prior labeling with chDAB4, dead EL4 lymphoma or Lewis Lung (LL2) tumor cells were phagocytosed equally by wild-type or Fcγ knock-down macrophage cell lines. A similar result was seen with bone marrow-derived macrophages from wild-type, Fcγ knock-out (KO) and NOTAM mice that express Fcγ but lack immunoreceptor tyrosine-based activation motif (ITAM) signaling. Among EL4 tumor-bearing wild-type, Fcγ KO or NOTAM mice, no differences were observed in post-chemotherapy uptake of 89Zr-labeled chDAB4. Similarly, no differences were observed between LL2 tumor-bearing wild-type and Fcγ KO mice in post-chemotherapy uptake of 89Zr-chDAB4. Also, the post-chemotherapy activity of a chDAB4-antibody drug conjugate (ADC) directed against LL2 tumors did not differ among tumor-bearing wild-type, Fcγ KO and NOTAM mice, nor did the proportions and characteristics of the LL2 tumor immune cell infiltrates differ significantly among these mice. In conclusion, Fc-FcγR interactions are not essential for the diagnostic or therapeutic applications of chDAB4 conjugates because the tumor-associated macrophages, which engulf the chDAB4-labelled dead cells, respond to endogenous 'eat me' signals rather than depend on functional FcγR expression for phagocytosis.With the development in tumor immunology, people are gradually understanding the complexity and diversity of the tumor microenvironment immune status and its important effect on tumors. Tumor-associated macrophages (TAMs), an important part of the tumor immune microenvironment, have a double effect on tumor growth and metastasis. Many studies have focused on lung cancer, especially non-small cell lung cancer and other "hot tumors" with typical inflammatory characteristics. The polarization and infiltration of TAMs is an important mechanism in the occurrence and development of malignant tumors, such as lung cancer, and in the tumor immune microenvironment. Therapeutic drugs designed for these reasons are key to targeting TAMs in the treatment of lung cancer. A large number of reports have suggested that natural compounds have a strong potential of affecting immunity by targeting the polarization and infiltration of TAMs to improve the immune microenvironment of lung cancer and exert a natural antitumor effect. This paper discusses the infiltration and polarization effects of natural compounds on lung cancer TAMs, provides a detailed classification and systematic review of natural compounds, and summarizes the bias of different kinds of natural compounds by affecting their antitumor mechanism of TAMs, with the aim of providing new perspectives and potential therapeutic drugs for targeted macrophages in the treatment of lung cancer.Gestational Diabetes Mellitus (GDM) has an effect on the health of pregnant women and fetuses. Procyanidins (PA) is a flavonoid with anti-diabetic activity, but its effects and mechanisms on GDM have not been defined. Herein, we studied further the functions and mechanisms of PA on insulin resistance (IR) in GDM mice, as well as on postpartum and offspring mice. GDM mice model was built by feeding a high-fat-high-sucrose diet, and PA intervention (27.8 mg/kg/d) was performed from 4 weeks before pregnancy to delivery. Intestinal flora deficient (IFD) mice model was established by broad spectrum antibiotics. PA decreased the gestational weight gain, and the levels of fasting blood glucose, insulin, homeostasis model of assessment for IR index, yet increased the levels of HOMA for insulin sensitivity index. Interestingly, in IFD mice the effect of PA on improving IR was significantly weakened. PA inhibited inflammation by decreasing the levels of IL-6, TNF-α, IL-17 and CRP, which also been blocked in the IFD mice.