The remodeling of phospholipid includes two processes: deacylation and reacylation. It realizes the conversion of nascent phospholipids to mature phospholipids by changing the length and types of fatty acids at specific sites of phospholipids, which is a key step in phospholipid metabolism. Phospholipids are not only the basic components of biological membranes, but also participate in the transduction of many molecular signals in cells. Therefore, phospholipid remodeling disorders can affect the structure and function of cell membranes, as well as the activity of membrane proteins, causing a series of intricate signaling cascades, and finally lead to many pathological changes including neurodegeneration. This paper reviews the basic process of phospholipid remodeling and the involvement of its key enzymes, calcium independent group VIA phospholipase A₂ (iPLA₂β), peroxiredoxin 6 (PRDX6), calcium independent group VIB phospholipase A₂ (iPLA₂γ) as well as acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) in the pathology of Parkinson's disease. The mutations in the gene encoding iPLA₂β, PLA2G6, have been widely reported to be directly related to hereditary Parkinson disease-14 (PARK14). Here we focus on the molecular mechanism of iPLA₂β in the development of Parkinson's disease, mainly involving phospholipid fatty acid metabolism disorders, mitochondrial physiology abnormalities and α-synuclein aggregate formation and other aspects, which will help to understand the role of phospholipid remodeling in Parkinson's disease, and provide new clues for the development of new Parkinson's disease diagnosis and treatment strategies.

Ferroptosis is a novel cell death mode proposed in recent years, which is characterized by intracellular iron-dependent lipid peroxidation. Its mechanisms include lipid peroxidation, iron accumulation and the imbalance of antioxidant system. The crosstalk between ferroptosis and asthma is gradually deepening. Elucidating the specific mechanism of ferroptosis in regulating asthma is helpful to broaden the understanding of the pathology of asthma. This paper expounds the role of ferroptosis in airway epithelial cells in the occurrence and development of asthma from three perspectives: lipid peroxidation, iron accumulation and the imbalance of antioxidant system, hoping to find new targets and strategies for asthma treatment.

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the conversion of heme to CO, biliverdin, and iron, which together protect cells from oxidative and inflammatory damage and play an important role in maintaining cell homeostasis. In recent years, HO-1 has also been found to have antiviral biological effects, and the induced expression of HO-1 inhibits the replication of various viruses such as hepatitis C virus, hepatitis B virus, human immunodeficiency virus, dengue virus, ebolavirus, influenza A virus, Zika virus, severe acute respiratory syndrome coronavirus 2, human respiratory syncytial virus, hepatitis A virus and enterovirus 71. The inhibitory effect of HO-1 on these viruses involves three mechanisms, including direct inhibition of virus replication by HO-1 and its downstream products, enhancement of type I interferon responses in host cell, and attenuation of inflammatory damage caused by viral infection. This review focuses on the recent advances in the antiviral effect of HO-1 and its mechanism, which is expected to provide evidence for HO-1 as a potential target for antiviral therapy.

As a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases, HER3 is an aberrantly activator of the PI3K/AKT pathway. Studies have indicated that HER3 is related to the progression of a variety of tumor types such as breast cancer, non-small cell lung cancer (NSCLC), ovary cancer and colon cancer, and in acquired resistance to EGFR and HER2 therapies. However, the attempts to target HER3 with neutralizing antibodies are not ideal previously. This is most likely due to the fact that the antibodies targeting HER3 fail to completely block the heterodimerization of HER3 and other receptors. Antibody-drug conjugates (ADCs) can specifically bind to target cells and exert the highly cytotoxicity effect on cancer cells through chemical drugs. ADCs have been widely used in clinical cancer therapies. We analyzed and optimized the structure of the antigen-antibody complex between HER3 and antibody LmAb3 by computer-aided molecular simulation technology, and the key sites involved in antigen binding in LmAb3 were predicted by distance geometry and computer graphics technology. Then a novel anti-HER3 antibody FD001 was obtained by point mutation technology. The affinity measurement by ForteBio results showed that the affinity of FD001 is much higher than LmAb3, the K_D values of FD001 and LmAb3 with HER3 were 1.48E-11 and 2.46E-10, respectively. Antibody drug conjugate FD001-DM1 is obtained by coupling FD001 to DM1 [emtansine, N²'-deacetyl-N²'-(3-mercapto-1-oxopropyl)-maytansine] by lysine coupling technology. The results of cell cytotoxicity experiments showed that FD001-DM1 could effectively inhibit the proliferation of HER3-positive HT-29 colon cancer cells, with EC₅₀ value of 33.62 nmol·L^-1. The in vivo xenografts therapy results showed that the tumor volume of the FD001-DM1 treatment group was about 25% of that of the control group, and there was no significant weight reduction of the mice. These results reveal that FD001-DM1 had good in vivo and in vitro anti-tumor activity with high safety, which may provide effective help for further exploration of HER3-targeted ADCs drugs. The mice in this study were used and treated in accordance with international laboratory animal care and use guidelines and approved by the Animal Ethics Committee of the Military Cognitive and Brain Science Institute of the Military Medical Research Institute.

There is a broad and urgent need for the clinical application of anticancer nanomedicine in tumor therapy, but the complex biological barrier in solid tumors has always been the main obstacle to infiltrating nanomedicine into the tumor. The traditional design of nanomedicine based on enhanced permeability and retention (EPR) effect still has some limitations in tumor permeability, it is urgent to find other design theories. Therefore, this review summarizes two novel strategies, active transcytosis and immune cell-mediated tumor penetration, for promoting tumor penetration of anticancer nanomedicine.

The aim of this study was to establish an efficient and stable mouse model of hyperuricemic nephropathy (HN) by testing different modes of administration of potassium oxonate (PO) combined with hypoxanthine (Hx). Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guangdong Pharmaceutical University. Male C57BL/6 mice were randomly divided into a control group, a PO+Hx group (i.g.; 100 mg·kg^-1·d^-1 and 500 mg·kg^-1·d^-1, respectively), and a PO+Hx group (i.p.; 100 mg·kg^-1·d^-1, and 500 mg·kg^-1·d^-1). This HN model was induced by combination of PO and Hx administration once daily for 21 days. The results of serum biochemistry showed that the levels of serum creatinine and 24 h albuminuria were increased compared with the normal group in intragastric administration of PO combined with Hx (P < 0.05), but there was no significant difference in serum uric acid and hepatic levels of xanthine oxidase. The maximum value of serum uric acid and creatinine was 349.3 μmol·L^-1 and 26.4 μmol·L^-1, respectively, in mice injected with PO combined with Hx. The levels of liver xanthine oxidase and 24 h albuminuria were significantly increased in mice injected with PO combined with Hx (P < 0.01). Pathological data showed that renal tubules were dilated, the epithelial cells of renal tubules were disordered, and the production of collagen fibers, reactive oxygen species (ROS) and lipid peroxidase 4-hydroxynonenal (4-HNE) were slightly increased after intragastric administration of PO combined with Hx mice. Obvious infiltration of inflammatory cells and large area of collagen deposition, with a large amount of ROS and the lipid peroxide 4-HNE were produced in mice injected with PO combined with Hx. Western blot analysis showed that the expression of fibronectin (FN) and urate transporter 1 (URAT1) was increased after intragastric administration of PO combined with Hx in mice and further increased in mice injected with PO combined with Hx. This study demonstrates that injection with 100 mg·kg^-1 potassium oxonate combined with 500 mg·kg^-1 hypoxanthine establishes a stable and efficient mouse HN model.

Mitochondrial oxidative stress has been recognized as a preliminary and critical factor that aggravates the pathological cascade of Alzheimer's disease, which induces the production of β-amyloid protein, upregulates the expression of phosphorylated tau protein and triggers oxidative damage to lipids, proteins and mitochondrial deoxyribonucleic acid. Central neurons are more vulnerable to oxidative stress than non-neuronal cells due to their high oxygen demand, abundant unsaturated fatty acids and antioxidant enzymes deficiency. On this account, this review introduces the causes of mitochondrial oxidative stress, and analyzes the important role of mitochondrial oxidative stress in the pathogenesis of Alzheimer's disease. Meanwhile, the review focuses on the design and intervention strategies of drug delivery systems targeting mitochondrial oxidative stress in neurons, aiming to provide new ideas for the prevention and treatment of Alzheimer's disease.

The ethyl acetate part of the alcoholic extract of Cordia dichotoma fruits was purified by a combination of normal-phase silica gel column chromatography, Sephadex LH-20 gel column chromatography and semi-preparative HPLC, and the structure was identified by modern spectroscopic techniques (UV, IR, MS, NMR). A total of 10 compounds were isolated and identified as cordilide (1), (S)-2-hydroxy-3-(4′-hydroxyphenyl) propanoic acid (2), vanillic acid (3), p-coumaric acid (4), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-1-one (5), benzoic acid (6), p-hydroxypropiophenone (7), p-hydroxyacetophenone (8), 5′-methoxyevofolin B (9) and vanillin (10). Among them, compound 1 is a pair of new phenylpropanoid enantiomers, and compounds 3, 6, 8 and 9 were isolated for the first time from the genus.

The pathogenesis of heart failure is a complex progression and associated with abnormal regulation of many signaling pathways. As a cofactor of hemoglobin, myoglobin, oxidative respiratory chain, DNA synthase and other important proteins, iron plays an indispensable role in myocardial energy metabolism. Recently, a large number of studies have shown that heart failure is related to the disorder of iron metabolism. Both iron deficiency and iron overload can lead to the development of a variety of cardiomyopathy, and even progress to heart failure. Iron metabolism could be a key target for the diagnosis, prevention and treatment of heart failure. Here, we review the basic process of iron metabolism and its mechanism in heart failure, expecting to provide new clues and evidence for the treatment of heart failure.

Oxygen is vital for life. Redox stress is important in cell signal transduction, mediating many physiological and pathological processes such as aging, neurodegenerative diseases, metabolic diseases and tumors. Redox homeostasis maintainance is critical for promoting life health. In this paper, the lasting challenges during antioxidant research and development and the beyond main reasons were analyzed: including insufficient understanding of the physiological function of redox stress; excessive antioxidant, causing reductive stress; antioxidant strategies lacking specificity. Here the author proposed that cells and the body own precise redox nature, therefore, redox intervention strategies such as anti-oxidation should consider the "5R" principle, i.e. right species, right time, right place, right level, right target. Precision redox regulation is the future direction and precise redox medicine development is opening.