Ferroptosis is a cell death path for the abnormal accumulation of iron dependent reactive oxygen species, which leads to the dysregulation of redox homeostasis. As a new type of cancer treatments, ferroptosis has attracted extensive attention of researchers. With the development of nanoscience, various functional nanomaterials can produce H₂O₂, exhaust glutathione, and gather Fenton reaction catalysts in tumor site. Therefore, these nanomaterials can play a stronger role in tumor inhibition in coordination with the ferroptosis-inducing agents. Firstly, this paper introduced the mechanism of ferroptosis and the feasibility of ferroptosis-inducing strategy in cancer therapy. Secondly, we summarized the construction strategies of the ferroptosis-inducing nanomedicines for cancer therapy, including accelerating intracellular Fenton reaction, inhibiting the activity of glutathione peroxidase 4, and increasing the exogenous delivery of lipid peroxides. In addition, we also discussed the combination therapy based on ferroptosis, including the combination of ferroptosis with traditional therapy strategies (combined with apoptosis-inducing drugs, immunotherapy and gene therapy) and external energy (including ultrasound therapy and photodynamic therapy). Finally, the expectations and challenges of ferroptosis-inducing nanomedicines for cancer therapy in the future were discussed.

Glucose-6-phosphate dehydrogenase, a key enzyme in the pentose phosphate pathway, plays an important role in plant resistance. In this study, three full length cDNAs of G6PDH genes, namely AsG6PDH1, AsG6PDH2 and AsG6PDH3 were cloned from Aquilaria sinensis for the first time. The open reading frames (ORF) of AsG6PDH1, AsG6PDH2 and AsG6PDH3 were 1 809, 1 767 and 1 548 bp, respectively, encoding proteins of 602, 588 and 516 amino acid residues, respectively, with predicted molecular masses of 68.02, 67.02, 59.35 kDa, respectively. The three AsG6PDHs proteins shared high sequence identity with the G6PDH proteins of various plants, and possessed three conserved sequences found in G6PDH proteins. The phylogenic analysis showed that AsG6PDH1 and AsG6PDH2 were grouped in the plastidic cluster, while AsG6PDH3 was classified into the cytosolic cluster. Expression analysis indicated that AsG6PDH1 and AsG6PDH2 were primarily observed in root, while AsG6PDH3 was primarily observed in stem. The expression of AsG6PDH1, AsG6PDH2 and AsG6PDH3 was induced by salt, drought, low temperature and CdCl₂ treatments, while the content of AsG6PDH1 and AsG6PDH2 was most significantly increased by drought stress, and the transcript level of AsG6PDH3 was most significantly induced by metal stress. Furthermore, G6PDH activity was stimulated under salt, drought, low temperature and CdCl₂ treatments, and G6PDH activity was remarkably increased under drought stress. These results provide valuable insights into the role of AsG6PDHs in plant defense and the mechanism of agarwood formation.

Cisplatin is one of the most commonly used chemotherapeutic drugs in clinic and has good therapeutic effect on various cancers, but the development of drug resistance limits its clinical treatment. The development of cisplatin resistance is caused by many factors, including the decrease of intracellular cisplatin accumulation, the inactivation of cisplatin by mercaptan proteins, the increase of DNA damage repair, apoptosis inhibition, tumor microenvironment and cancer stem cells. In recent years, traditional Chinese medicine (TCM) has been favored for its remarkable effect of reversing cisplatin resistance. This review will explore the mechanisms of cisplatin resistance and the combined modality treatment strategy of TCM to reverse cisplatin resistance, hoping to provide reference for clinical and scientific research.

The treatment plan for chronic pain often proceeds from a single drug to drug combination therapy. Sinomenine and ligustrazine, natural alkaline substances derived from traditional Chinese medicines, are expected to provide a new choice for combination analgesic therapy strategies. Here we establish a microdialysis sampling and HPLC-MS/MS quantification method for sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rat blood and brain extracellular fluid. Blood and brain microdialysis probes were implanted in the jugular vein toward the right atrium and left corpus striatum zone (AP +0.2 mm, ML 3.0 mm, DV 3.5 mm) in rats. The blood and brain microdialysis probes were perfused with citric acid buffer solution and Ringer's solution, respectively. Blood and brain extracellular fluid microdialysate were collected at intervals of 20 min at a perfusion rate of 1.5 μL·min^-1, and continuously collected for 24 h after administration. The liquid chromatographic separation used a C18-reversed phase chromatographic column (HSS T3 2.5 μm, 2.1 mm×50 mm), the mobile phase was methanol/water (containing 0.05‰ formic acid), and gradient elution was carried out at a flow rate of 0.3 mL·min^-1. Mass spectrometric detection used an electrospray ion source, positive ion mode and multi-reaction monitoring method. The selected quantitative ions for sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin, amitriptyline and internal standard naloxone were 330/181, 137/80, 172/154, 152/110, 160/142, 278/233 and 328/310 respectively. The specificity, linear range, matrix effect, accuracy, precision, stability and probe recovery were investigated and confirmed to be suitable for the determination of the above drugs in rat blood and brain extracellular fluid microdialysate. The calculated in vivo recovery of microdialysis probes ranged from 19.38% to 25.88%. After intravenous administration of sinomenine (50 mg·kg^-1), ligustrazine (50 mg·kg^-1), gabapentin (50 mg·kg^-1), paracetamol (50 mg·kg^-1), pregabalin (50 mg·kg^-1) and amitriptyline (40 mg·kg^-1) to rats, the peak concentration in the blood microdialysate was in the range of 0.2-10 μg·mL^-1. Drug concentrations could also be detected in brain extracellular fluid microdialysate, however with lower levels (peak concentration:0.1-6 μg·mL^-1) than those of blood microdialysates at each time point. In conclusion, this method can be applied to microdialysis sampling and quantification of sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rats. The method will promote research in identifying herb-drug pharmacokinetic interactions, as well as safety concerns in combination-therapy strategies.

To identify an effective structural modification strategy for improving the antitumor activity of fluoroquinolones, sixteen new 1-cyclopropyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-arylidene-2, 3-dihydroquinolin-4(1H)-ones compounds (4a-4p), were designed and synthesized by a condensation reaction of dihydroquinolin-4-one (3) and aromatic aldehydes, based on the structure of ciprofloxacin (1). Their structures were characterized by elemental analysis and spectral data, and anti-cell proliferative activities against Hep-3B, Capan-1 and HL60 cell lines were measured by an MTT assay. Preliminary pharmacological results indicated that the synthesized target compounds had greater potency than ciprofloxacin (1). SAR revealed that the halophenyl compounds such as fluorophenyl (4h, 4i), chlorophenyl (4j, 4k) or bromophenyl compounds (4l, 4m) and aromatic heterocyclic compounds such as furanly (4n) or pyridyl compounds (4o, 4p) demonstrated better activity than the control compounds, and the IC₅₀ values of the chlorophenyl compounds 4j and 4k against Capan-1 cell growth were comparable to that of doxorubicin. Thus, a 3-arylidene as an isostere of the C-3 carboxylic acid group appears to be beneficial in improving the antitumor activity of fluoroquinolone. Furthermore, an α, β-unsaturated ketone fragment used as a potential bioisostere of C-3 carboxylic acid group may warrant further study.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and cartilage destruction. An imbalance in macrophage polarization is closely related to the occurrence and development of RA, including a central role for M1 macrophages in promoting inflammation and bone destruction in the cytokine network environment of RA. It is a remarkable fact that the abnormal immune-microenvironment in RA patients promotes the metabolic reprogramming of macrophages, which disrupts the dynamic balance of M1/M2 by regulating the polarization of macrophages, leading to a persistent tissue inflammation. Using drugs to inhibit M1 macrophage polarization or induce M2 macrophage polarization is expected to be an ideal strategy for drug development for RA treatment. This review summarizes the effects of metabolic reprogramming of macrophages on polarization phenotype and the metabolism-related signaling pathways in the RA microenvironment, and provides references for the development of RA drugs that can target macrophage metabolism.

Breast cancer is the most common malignant tumor in women worldwide. In breast cancer tumor tissues, a variety of targets related to the occurrence and development of breast cancer have been observed, and many drugs have been used in clinical applications for these targets. However, most of these drugs are small molecule inhibitors. With the long-term use of these drugs, acquired drug resistance often occurs in breast cancer patients. To overcome the drug resistance, the development of more efficient drugs is highly desirable in the treatment of breast cancer. Proteolysis targeting chimera (PROTAC) technology is a new kind of targeted protein degradation technology, which has shown broad prospect of applications in the field of drug development. The use of PROTAC technology to target the degradation of relevant targets in breast cancer has become a feasible strategy for breast cancer treatment.

In scientific research, it is often needed to knock in, knock out, knock down, or overexpress a specific gene in model organisms or specific types of cells to achieve precise regulation of experimental independent variables. In this case, various transgenic mice are required. The cyclization recombinase (Cre) can directly interact with different loxP (locus X over P1) DNA sequences without any cofactors to perform specific gene knock-in or knock-out at specific targets. Because of its advantages of simple action principles, high spatial specificity, and high reorganization efficiency, the Cre-loxP system is widely used in scientific research. Furthermore, the CreERT2 system (mutant of the fusion protein of Cre and estrogen receptor ligand binding domain) and the tetracycline (Tet)-on/off system, derived from the Cre-loxP system, have made the recombination of the target gene occur in temporal-specificity on the basis of spatial-specificity. This dual specificity of time and space is indispensable for research in specific directions such as fear memory and engram cells on the basis of reducing the impacts on experimental animals. Therefore, these derived systems have broad application prospects.

Metabonomics techniques were used to investigate the mechanism and metabolic pathways of total extract of Amygdalus mongolicus against renal fibrosis in rats. Rats were randomly divided into a model group (MOD), a sham surgery group (SDG), a benazepril hydrochloride-treated group (BHT) and three groups treated with the total extract of Amygdalus mongolicus:low-dose group (TOT-L), middle-dose group (TOT-M) and high-dose group (TOT-H), with 10 rats in each group. The rats were given intragastric administration for 3 weeks and kidney and blood samples were taken. Pharmacodynamic studies and ultra performance liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC-Q-TOF/MS) analysis were used to show that the total extract of Amygdalus mongolicus has an anti-fibrotic effect in rats. Compared with the MOD group, rats in the TOT-L, TOT-M and TOT-H groups showed a reversal in 67, 69, and 70 biomarkers, respectively, and shared 62 biomarkers. Reversal was observed for 7 key biomarkers related to renal fibrosis, including S-adenosy-L-methioninamine, ornithine, diketogulonic acid, and others, and changes in 5 metabolic pathways, including arginine and proline metabolism, pentose and glucuronate interconversions. These results give evidence of the metabolic pathways and the mechanism of action of Amygdalus mongolicus to prevent renal fibrosis in rats. The animal experiments were approved by the Medical Ethics Committee of Baotou Medical College (No. 20190314).

This study was designed to investigate the effect of dihydromyricetin (DHM) on inducing apoptosis of ovarian cancer cells A2780 through endoplasmic reticulum stress (ERS) pathway and the mechanisms involved in vitro and in vivo. A2780 cells were treated with different concentrations of DHM, and the protein expression levels of glucose-regulated protein 78 (GRP78) which is related to ERS increased, apoptotic proteins C/EBP-homologous protein (CHOP), and cysteinyl aspartate specific proteinase-12 (caspase-12) elevated. After pretreatment with ERS inhibitor, 4-phenyl butyric acid (4-PBA), following the intervention with DHM, the A2780 cell viability decreased and apoptotic rate increased. All animal welfare and experimental procedures were approved by the Animal Ethics Committee of Chongqing Medical University. Intraperitoneal injection of DHM suspension into nude mice with ovarian cancer could significantly inhibit the growth of transplanted tumor in vivo, increase the protein expression levels of GRP78, CHOP, and caspase-3. Moreover, swollen and broken endoplasmic reticulum could be observed in tumor tissues, suggesting that DHM intervention induces apoptosis mediated by ERS. The results indicated that DHM could induce apoptosis of ovarian cancer cells and inhibit the growth of transplanted tumors in nude mice, which might be related to the activation of ERS pathway.