Sternatkins2227

Hyperuricemia may occur when there is an excess of uric acid in the blood. Hyperuricemia may result from increased production or decreased excretion of uric acid. Elevated uric acid levels are a risk factor for gout, and various risk factors, including some medications, alcohol consumption, kidney disease, high blood pressure, hypothyroidism, and pesticide exposure, as well as obesity, are associated with an elevated risk of hyperuricemia. Although the mechanisms underlying the pathogenesis of hyperuricemia are complex, previously reported studies have revealed that hyperuricemia is involved in a variety of biological processes and signaling pathways. In this review, we summarize common comorbidities related to hyperuricemia and describe an update of epidemiology, pathogenesis, and therapeutic options of hyperuricemia. This systematic review highlights the epidemiology and risk factors of hyperuricemia. Moreover, we discuss genetic studies on hyperuricemia to uncover current status and advances in the pathogenesis of hyperuricemia. Additionally, we conclude with a reflection on the underlying mechanisms of hyperuricemia and present the alternative drug strategies for the treatment of hyperuricemia to offer more effective clinical interventions.Leukocyte immunoglobulin (Ig)-like receptor B4 (LILRB4) is a member of leukocyte Ig-like receptors (LILRs), which associate with membrane adaptors to signal through multiple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Under physiological conditions, LILRB4 plays a very important role in the function of the immune system through its expression on various immune cells, such as T cells and plasma cells. Under pathological conditions, LILRB4 affects the processes of various diseases, such as the transformation and infiltration of tumors and leukemias, through various signaling pathways. Differential expression of LILRB4 is present in a variety of immune system diseases, such as Kawasaki disease, systemic lupus erythematosus (SLE), and sepsis. Recent studies have shown that LILRB4 also plays a role in mental illness. The important role of LILRB4 in the immune system and its differential expression in a variety of diseases make LILRB4 a potential prophylactic and therapeutic target for a variety of diseases.This study aims to reveal the biological relevancy between melanosis coli (MC) with colon cancer by analyzing the proteomics differences of tissues of melanosis coli, colon cancer, and normal ones to probe into the causes and development mechanisms of MC from the perspective of biomolecules. Fourteen differential protein spots were found in the study after using two-dimensional gel electrophoresis (2-DE) and bio-mass spectrometry (MALDI-TOF/TOF-MS). Specifically, six and eight differential protein spots in the melanosis coli tissues were detected, respectively, compared with the normal tissues and colon cancer tissues. Eight kinds of proteins, including keratin 8 (KRT8), keratin 18 (KRT18), fibrinogen beta chain isoform 2 preproprotein (FGB), catalase (CAT), 26s protease regulatory subunit 10b (PSMC6), isoform 1 of tropomyosin alpha-4 chain (TPM4), carbonic anhydrase 1 (CA1), isoform of prelammin-A/C (LMNA), were retrieved through the mass spectral database, which could be deemed as associated proteins of MC and colon cancer. The different expressions in the disease tissues indicate that these proteins may be connected with the carcinogenesis of MC as well as the malignant proliferation, development, differentiation, and diffusion of cancer cells.Follicle stimulating hormone (FSH) and its receptor (FSHR) play an important role in human metabolic diseases and cancer. Evidence showed that FSHR is not only distributed in ovary and testis but also in other cells or organs such as osteoclast, adipocytes, liver, pituitary cancer and so forth. Moreover, FSH is associated with lipogenesis, inflammation, insulin sensitivity, thermogenesis, skeletal metabolism, osteogenesis and ovarian cancer, all of which have been confirmed closely related to metabolic diseases or metabolic-related cancer. Therefore, FSH and FSHR may be potential therapeutic targets for metabolic diseases and metabolic-related cancer. Epidemiological researches revealed close relationship between FSH/FSHR and metabolic diseases or cancer. Experimental studies elucidated the underlying mechanism both in vivo and in vitro. We reviewed the recent researches and present an integrated framework of FSH/FSHR and metabolic diseases and cancer, which provides potential targets for the treatments of metabolic diseases and cancer.Colorectal cancer (CRC) is one of the most common malignancies. The current treatments of metastatic colorectal cancer (mCRC) are ineffective and the bottleneck problem. It is of significance to explore effective new therapeutic strategies to eradicate mCRC. Photothermal therapy (PTT) is an emerging technology for tumor therapy, with the potential in the treatment of mCRC. In this review, the current treatment approaches to mCRC including surgery, radiotherapy, chemotherapy interventional therapy, biotherapy, and photothermal therapy are reviewed. In addition, we will focus on the various kinds of nanomaterials used in PTT for the treatment of CRC both in vitro and in vivo models. In conclusion, we will summarize the combined application of PTT with other theranostic methods, and propose future research directions of PTT in the treatment of CRC.Sitagliptin, an inhibitor of the dipeptidyl peptidase IV (DPP4), has been implicated in the regulation of type 2 diabetes. However, the role and mechanism of sitagliptin administration in total body irradiation (TBI)- induced hematopoietic cells injury are unclear. In this study, we demonstrated that sitagliptin had therapeutic effects on hematopoietic damage, which protected mice from 7.5 Gy TBI-induced death, increased the numbers and colony formation ability of hematopoietic cells. These therapeutic effects might be attributed to the inhibition of NOX4-mediated oxidative stress in hematopoietic cells, and the alleviation of inflammation was also helpful. PF-9366 clinical trial Therefore, sitagliptin has potential as an effective radiotherapeutic agent for ameliorating TBI-induced hematopoietic injury.Aging is an important risk factor in the occurrence of many chronic diseases. Senescence and exhaustion of adult stem cells are considered as a hallmark of aging in organisms. In this study, a senescent human amniotic mesenchymal stem cell (hAMSC) model subjected to oxidative stress was established in vitro using hydrogen peroxide. We investigated the effects of ganoderic acid D (GA-D), a natural triterpenoid compound produced from Ganoderma lucidum, on hAMSC senescence. GA-D significantly inhibited β-galactosidase (a senescence-associated marker) formation, in a dose-dependent manner, with doses ranging from 0.1 μM to 10 μM, without inducing cytotoxic side-effects. Furthermore, GA-D markedly inhibited the generation of reactive oxygen species (ROS) and the expression of p21 and p16 proteins, relieved the cell cycle arrest, and enhanced telomerase activity in senescent hAMSCs. Furthermore, GA-D upregulated the expression of phosphorylated protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK), peroxidase III (PRDX3), and nuclear factor-erythroid 2-related factor (NRF2) and promoted intranuclear transfer of NRF2 in senescent cells. The PERK inhibitor GSK2656157 and/or the NRF2 inhibitor ML385 suppressed the PERK/NRF2 signaling, which was activated by GA-D. They induced a rebound for the generation of ROS and β-galactosidase-positive cells and attenuated the differentiation capacity. These findings suggest that GA-D retards hAMSC senescence through activation of the PERK/NRF2 signaling pathway and may be a promising candidate for the discovery of antiaging agents.Oxidative stress on retinal pigment epithelial (RPE) cells has been confirmed to play a crucial role in the development and progression of age-related macular degeneration (AMD) or other retinal degenerative diseases. Tribulus terrestris (TT) is a Chinese traditional herb medicine, which has been used for the treatment of ocular diseases for many centuries. In this study, we investigated the underlying mechanisms of TT and examined its ability to protect and restore the human retinal pigment epithelial cells (ARPE-19) against H2O2-induced oxidative stress. Our data show that 200 μg/mL of ethanol extract of Tribulus terrestris (EE-TT) significantly increased the cell viability and prevented the apoptosis of H2O2-treated ARPE-19 cells through the regulation of Bcl2, Bax, cleaved caspase-3, and caspase-9. Treatment with EE-TT also significantly decreased the upregulated reactive oxygen species (ROS) activities and increased the downregulated superoxide dismutase (SOD) activities induced by H2O2 in ARPE-19 cells. Additionally, H2O2 at 1 mM significantly decreased the mRNA expression levels of Nrf2, CAT, SOD1, SOD2, HO-1, GST-pi, NQO1, and GLCM in ARPE-19 cells; however, treatment with EE-TT reversed the downregulated mRNA expression levels of all these genes induced by H2O2. Furthermore, treatment with 200 μg/mL EE-TT alone for 24 h significantly increased Nrf2, HO-1, NQO1, and GCLM mRNA expressions in ARPE-19 cells when compared with untreated control cells. Pretreatment with the inhibitor of PI3K/Akt signaling (LY294002) completely blocked these EE-TT-upregulated mRNA expressions and abolished the improvement of cell viability in H2O2-treated ARPE-19 cells. These findings all suggest that Tribulus terrestris has significant antioxidant effects on oxidative stressed ARPE-19 cells through regulating PI3K/Akt-Nrf2 signaling pathway.

Constitutive nuclear factor kappa B (NF

B) activation has been shown to exacerbate during myocardial ischemia/reperfusion (I/R) injury. We recently showed that miR-181c-5p exacerbated cardiomyocytes injury and apoptosis by directly targeting the 3'-untranslated region of protein tyrosine phosphatase nonreceptor type 4 (PTPN4). However, whether miR-181c-5p mediates cardiac I/R injury through NF

B-mediated inflammation is unknown. Thus, the present study aimed to investigate the role of miR-181c-5p during myocardial I/R injury and explore its mechanism in relation to inflammation in H9C2 cardiomyocytes.

In hypoxia/reoxygenation (H/R, 6 h hypoxia followed by 6 h reoxygenation)-stimulated H9C2 cardiomyocytes or postischemic myocardium of rat, the expression of miR-181c-5p was significantly upregulated, which was concomitant increased NF

B activity when compared to the nonhypoxic or nonischemic control groups. This is indicative that miR-181c-5p may be involved in NF

B-mediated inflammation during myocardianti-inflammatory effects in H9C2 cardiomyocytes during H/R injury.

It is concluded that miR-181c-5p may exacerbate myocardial I/R injury and NF

B-mediated inflammation

PTPN4, and that targeting miR-181c-5p/PTPN4/NF

B signalling may represent a novel strategy to combat myocardial I/R injury.

It is concluded that miR-181c-5p may exacerbate myocardial I/R injury and NFκB-mediated inflammation via PTPN4, and that targeting miR-181c-5p/PTPN4/NFκB signalling may represent a novel strategy to combat myocardial I/R injury.