The amyloid hypothesis of Alzheimer's disease has long been the predominant theory, suggesting that Alzheimer's disease is caused by the accumulation of amyloid beta protein (Aβ) in the brain, ...leading to neuronal toxicity in the central nervous system (CNS). Because of breakthroughs in molecular medicine, the amyloid pathway is thought to be central to the pathophysiology of Alzheimer's disease (AD). Currently, it is believed that altered biochemistry of the Aβ cycle remains a central biological feature of AD and is a promising target for treatment. This review provides an overview of the process of amyloid formation, explaining the transition from amyloid precursor protein to amyloid beta protein. Moreover, we also reveal the relationship between autophagy, cerebral blood flow, ACHE, expression of LRP1, and amyloidosis. In addition, we discuss the detailed pathogenesis of amyloidosis, including oxidative damage, tau protein, NFTs, and neuronal damage. Finally, we list some ways to treat AD in terms of decreasing the accumulation of Aβ in the brain.
Brain ischemia and reperfusion (I/R) is one of the most severe clinical manifestations of ischemic stroke, placing a significant burden on both individuals and society. The only FDA-approved clinical ...treatment for ischemic stroke is tissue plasminogen activator (t-PA), which rapidly restores cerebral blood flow but can have severe side effects. The complex pathological process of brain I/R has been well-established in the past few years, including energy metabolism disorders, cellular acidosis, doubling of the synthesis or release of excitotoxic amino acids, intracellular calcium homeostasis, free radical production, and activation of apoptotic genes. Recently, accumulating evidence has shown that NO may be strongly related to brain I/R and involved in complex pathological processes. This review focuses on the role of endogenous NO in pathological processes in brain I/R, including neuronal cell death and blood brain barrier disruption, to explore how NO impacts specific signaling cascades and contributes to brain I/R injury. Moreover, NO can rapidly react with superoxide to produce peroxynitrite, which may also mediate brain I/R injury, which is discussed here. Finally, we reveal several therapeutic approaches strongly associated with NO and discuss their potential as a clinical treatment for ischemic stroke.
Pyroptosis is a pro-inflammatory type of regulated cell death (RCD) characterized by gasdermin protein-mediated membrane pore formation, cell swelling, and rapid lysis. Recent studies have suggested ...that pyroptosis is closely related to atherosclerosis (AS). Previous studies reported that pyroptosis involving endothelial cells (ECs), macrophages, and smooth muscle cells (SMCs) plays an important role in the formation and development of AS. Pyroptosis not only causes local inflammation but also amplifies the inflammatory response and it aggravates plaque instability, leading to plaque rupture and thrombosis, eventually resulting in acute cardiovascular events. In this review, we clarified some novel pathways and mechanics and presented some potential drugs.
Nitric oxide (NO), a free radical, plays a critical role in a wide range of physiological and pathological processes. Due to its pleiotropic function, it has been widely investigated in various types ...of cancers and is strongly associated with cancer development. Mounting pieces of evidence show that NO regulates various cancer-related events, which mainly depends on phosphorylating the key proteins in several signaling pathways. However, phosphorylation of proteins modulated by NO signaling pathway may lead to different effects in different types of cancer, which is complex and remains unclear. Therefore, in this review, we focus on the effect of protein phosphorylation modulated by NO signaling pathway in different types of cancers including breast cancer, lung cancer, prostate cancer, colon cancer, gastric cancer, pancreatic cancer, ovarian cancer, and neuroblastoma. Phosphorylation of key proteins, including p38 MAPK, ERK, PI3K, STAT3, and p53, modified by NO in various signaling pathways affects different cancer-related processes including cell apoptosis, proliferation, angiogenesis, metastasis, and several cancer therapies. Our review links the NO signaling pathway to protein phosphorylation in cancer development and provides new insight into potential targets and cancer therapy.
Rheumatoid arthritis, a chronic autoimmune disease with complex etiology, is characterized by excessive proliferation of synovial cells, massive production of inflammatory cells and cartilage ...destruction. Studies have shown that mitochondrial dysfunction plays an important role in promoting the occurrence of RA. Mitochondria with normal structure and function are essential for the normal survival of chondrocytes and synovial cells. Once mitochondrial function is destroyed, it will affect the survival, activation and differentiation of immune cells and non-immune cells involved in the pathogenesis of RA, thus leading to the occurrence of RA. However, the mechanism of mitochondrial dysfunction in RA remains unclear. This article reviews the method of mitochondrial dysfunction leading to RA, the effects of mitochondrial dysfunction on immune cells, the etiology of mitochondrial dysfunction in RA, and the pathology of mitochondrial dysfunction in RA. We also outline some drugs that can exert therapeutic effects on RA which are associated with modulating mitochondrial activity. The understanding and summary of mitochondrial dysfunction in RA may provide new research directions for pathological intervention and prevention of RA.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by autoimmunity, synovial inflammation and joint destruction. Pannus formation in the synovial cavity can cause ...irreversible damage to the joint and cartilage and eventually permanent disability. Current conventional treatments for RA have limitations regarding efficacy, safety and cost. microRNA (miRNA) is a type of non-coding RNA (ncRNA) that regulates gene expression at the post-transcriptional level. The dysregulation of miRNA has been observed in RA patients and implicated in the pathogenesis of RA. miRNAs have emerged as potential biomarkers or therapeutic agents. In this review, we explore the role of miRNAs in various aspects of RA pathophysiology, including immune cell imbalance, the proliferation and invasion of fibroblast-like synovial (FLS) cell, the dysregulation of inflammatory signaling and disturbance in angiogenesis. We delve into the regulatory effects of miRNAs on Treg/Th17 and M1/M2 polarization, the activation of the NF-κB/NLRP3 signaling pathway, neovascular formation, energy metabolism induced by FLS-cell-induced energy metabolism, apoptosis, osteogenesis and mobility. These findings shed light on the potential applications of miRNAs as diagnostic or therapeutic biomarkers for RA management. Furthermore, there are some strategies to regulate miRNA expression levels by utilizing miRNA mimics or exosomes and to hinder miRNA activity via competitive endogenous RNA (ceRNA) network-based antagonists. We conclude that miRNAs offer a promising avenue for RA therapy with unlimited potential.
Hepatic injury is a major event in liver surgery such as liver transplantation and it always leads to hepatic cell apoptosis. Nitric oxide (NO) is a key signaling regulation molecule. Many ...researchers have shown that increased NO level can influence liver cell apoptosis by promoting or inhibiting the relative signaling pathways that are involved in the caspase family, Bax/Bcl‐2, mitochondria, oxidative stress, death receptors, and mitogen‐activated protein kinases. Elucidating the relationships between NO and hepatic cell apoptosis is necessary for ameliorating prognosis of liver surgery. This article reviews the newest research progress in the relationships between higher NO levels and hepatic cell apoptosis in liver injury.
Abstract Background Extensive experimental and clinical studies have shown that ischemic preconditioning (IP) can produce protective effects during hepatic ischemia reperfusion (I/R) injury. Our ...recent studies indicate that rat liver I/R injury is related to an abnormal increase in leukotriene (LT) C4 production. However, the mechanisms underlying IP actions on LTC4 generation during hepatic I/R injury remain to be explored. Methods We randomly divided adult male Sprague-Dawley rats into sham (control), I/R, and IP groups ( n = 6). We subjected rat liver to 60 min partial hepatic ischemia followed by 5 h reperfusion with saline administered intravenously. We detected protein expression of LTC4 synthase (LTC4S) with Western blot, and measured LTC4 synthesis enzymes' activities and content by reverse-phase high-performance liquid chromatography. We assessed tissue injury using serum aspartate aminotransferase and aspartate aminotransferase activities and histologic changes. We examined liver tissue glutathione levels by a biochemical method. Results Ischemic preconditioning markedly decreased LTC4 content, reduced LTC4S protein expressions, and inhibited LTC4 synthesis enzymes' activities in rat liver compared with the I/R group ( P < 0.05). We also observed a decline in serum alanine aminotransferase and aspartate aminotransferase activities ( P < 0.05), together with hepatic tissue glutathione elevation ( P < 0.05) in the IP groups. Positive expression of LTC4S on hepatocytes and sinusoidal endothelial cells in the IP group was significantly lower than that in the I/R group. Conclusions These findings demonstrate that reduced LTC4 production by IP treatment during hepatic I/R injury could partially result from the down-regulation of LTC4S protein expression and the depression of LTC4 synthesis enzyme activity. They suggest that the beneficial effects of IP may be involved in repression of LTC4 generation during hepatic I/R injury.
Thromboangiitis obliterans (TAO) or Buerger's disease is a non atherosclerotic, segmentar inflammatory vasculitis that is incurable at present. Shenfu injection (SFI), a traditional Chinese ...formulation, have been confirmed to produce protective influences on several organs and limb during ischemia and reperfusion (IR) injury in rats. However, the effects of SFI on TAO remain unclear.
Adult male Sprague Dawley rats were randomly divided into sham operated group, TAO model group, SFI 2.5mg/kg (low dose), 5mg/kg (medium dose) and 10mg/kg (high dose) groups (n=8). Rats were intravenously administered SFI 2.5, 5 and 10mg/kg or saline once per day for 15 days. TAO model was prepared by injecting sodium laurate into the femoral artery of rats. Then we examined the changes of pathological signs, pathologic grading of thrombus, the indexes of hematology, the contents of thromboxane B2 (TXB2), 6-keto-prostaglandin Flα (6-K-PGF1α) in plasma following SFI or saline treatment.
More pathological signs of lesions, higher grades of pathological thrombosis, increased blood platelet counts, the increase in the TXB2 and TXB2/6-K-PGF1α ratio, as well as the decrease of 6-K-PGF1α in TAO model group were shown in present experiments; SFI treatment significantly improved the pathological signs of lesions induced by sodium laurate injection, reduced the numbers of thrombus formation, blood platelet counts, the TXB2 and TXB2/6-K-PGF1α ratio but increased the 6-K-PGF1α compared with TAO model group. However, there were no significant alterations in the counts of red blood cell, leucocyte and neutrophil among these groups.
Our preliminary findings first indicated that SFI can produce significant therapeutic effects on experimental Buerger's disease model rats in a dose independent manner. The underlying mechanisms may be due to its modifying hematology, inhibiting platelet aggregation and enhancing anti-thrombotic function of vessel endothelia.
Cancer is one of the most prevalent diseases worldwide, and poses a threat to human health. Noncoding RNAs (ncRNAs) constitute most transcripts, but they cannot be translated into proteins. Studies ...have shown that ncRNAs can act as tumor suppressors or oncogenes. This review describes the role of several ncRNAs in various cancers, including microRNAs (miRNAs) such as the miR-34 family, let-7, miR-17-92 cluster, miR-210, and long noncoding RNAs (lncRNAs) such as HOX transcript antisense intergenic RNA (HOTAIR), Metastasis associated lung adenocarcinoma transcript 1 (MALAT1), H19, NF-κB-interacting lncRNA (NKILA), as well as circular RNAs (circRNAs) and untranslated regions (UTRs), highlighting their effects on cancer growth, invasion, metastasis, angiogenesis, and apoptosis. They function as tumor suppressors or oncogenes that interfere with different axes and pathways, including p53 and IL-6, which are involved in the progression of cancer. The characteristic expression of some ncRNAs in cancer also allows them to be used as biomarkers for early diagnosis and therapeutic candidates. There is a complex network of interactions between ncRNAs, with some lncRNAs and circRNAs acting as competitive endogenous RNAs (ceRNAs) to decoy miRNAs and repress their expression. The ceRNA network is a part of the ncRNA network and numerous ncRNAs work as nodes or hubs in the network, and disruption of their interactions can cause cancer development. Therefore, the balance and stabilization of this network are important for cancer diagnosis and treatment.
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