Photothermal therapy (PTT) has attracted significant attention due to minimal side effects and high treatment specificity. However, it often requires very high temperature to achieve complete tumor ablation under a single PTT. Such high temperature brings obvious thermal damage and inflammatory response to the body, affecting the therapeutic effect. In recent years, nitric oxide (NO) has been used to significantly inhibit tumor growth and enhance the sensitivity of tumor cells of temperature and drugs, thus enhancing the therapeutic effect. However, compounds as NO donors often have some disadvantages such as poor biocompatibility and untargeted delivery, etc., therefore, this medical application based on NO therapy is limited. In conclusion, the organic combination of NO donors and photothermal agents (PTAs) is expected to overcome the shortcomings of single therapy and achieve the antitumor effect of "1 + 1 > 2". In view of the rapid development of NO combining with PTT in tumor therapy, this review firstly introduces the antitumor mechanisms of different types of NO donors. Then the treatment strategy based on NO combined with PTT is discussed. Finally, the prospects and challenges of this combination therapy strategy in the clinical treatment of cancer are discussed.

Liquid-phase microextraction is a novel pretreatment technique for biological samples developed on the basis of liquid-phase extraction technology, which is simple, rapid, economical, and environmentally friendly, and has been widely used in the analysis of biological matrix samples such as blood, urine, and saliva. In this paper, we review the basic principles of the main modes of liquid-phase microextraction techniques, i.e., single-drop microextraction, dispersive liquid-liquid microextraction, and hollow-fiber liquid-phase microextraction, and the progress of their applications in biological sample pretreatment by reviewing the literature in the past five years, with a view to providing technical support and reference for sample pretreatment in the fields of in vivo drug analysis, pharmacokinetic studies and new drug development.

An open reading frame (ORF) of isopentenyl-diphosphate delta isomerase gene (FuIPI) was cloned from Fritillaria unibracteata Hsiao et K. C. Hsia. (F. unibracteata). Furthermore, the bioinformatics and functional analyses of FuIPI were performed in this study. The result showed that, the ORF of FuIPI gene was 825 bp, encoding a polypeptide of 274 amino acids in length, with a relative molecular mass of about 31 kD and a theoretical isoelectric point of 5.61. Sequence analysis showed that FuIPI contained conserved structural domains and key residues involved in the catalyzing process. The phylogenetic analysis exhibited that FuIPI was closely related to IPIs of Dendrobium officinale and Musa acuminate. Real-time PCR analysis showed that FuIPI was distributed in different tissues of F. unibracteata, but had the highest transcriptional level in leaves, followed by stems, bulbs, and flowers. Furthermore, the FuIPI protein was successfully expressed in Escherichia coli BL21(DE3). The purified FuIPI protein successfully catalyzed the conversion from isopentenyl diphosphate (IPP) to dimethylallyl pyrophosphate (DMAPP). The above results provided a theoretical basis for further investigation of the molecular role of FuIPI in the biosynthesis of alkaloids.

Cocrystal separation technology is a technology that utilizes coformers to selectively form cocrystals with target compounds and separate them from mixed systems. Our study used puerarin (PUE), daidzein (DDZ), and genistein (GEN) as model drugs, which have similar structures and are the main isoflavones in Pueraria lobata root. The separation and purification processes in the modern traditional Chinese medicine (TCM) of these three components use conventional column chromatography, recrystallization, and other technologies, which have the issues of lengthy separation cycles, high solvent consumption, and inefficient preparation. Different with existing separation technology, our team used the early-found cocrystal separation method to design a step-by-step extraction and separation experiment of GEN-PUE-DDZ ternary mixture. Caffeine and L-proline were added to the mixed system in turn, GEN-caffeine cocrystal and PUE-proline cocrystal were prepared by suspension method. The cocrystals precipitated out of the solution. The purities of the GEN-caffeine cocrystal and the PUE-proline cocrystal could achieve 93% (the purity of GEN) and 99% (the purity of PUE). Besides, the purity of DDZ could also be increased by 6.76 times. This study proposed a simple operating, low cost and wide application range separation method different from the traditional separation method and realized the separation of structurally similar chemical components in TCM, laying a foundation for the application of cocrystal technology in the separation and refining of TCM.

Polysaccharides is one of the main bioactive components of Cordyceps species, because of the potential clinical value with stronger anti-tumor, such as anti-neuroblastoma, anti-melanoma, anti-lung cancer, anti-colon cancer and so on, its have received widespread attention in biomedical field and increasing research in last decades. According to structural elucidation, this review gives a systematic literature overview on antitumor mechanism of Cordyceps species-derived polysaccharides from three aspects, including inhibition of tumor cell growth, enhancement of immunomodulatory activity and reduction of tumor metastasis. Finally, it also puts forward some scientific problems for follow up research.

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Epimedii Folium is a traditional non-toxic Chinese herbal medicine. However, liver injury caused by Chinese herb preparations, including Epimedii Folium, is frequently reported over the years. Based on ancient and modern literature, this paper systematically summarized and analyzed the safe application of Epimedii Folium from the perspectives of varieties, processing methods, clinical adverse reactions, pharmacological effects and toxic mechanism. Combined with our team work, we build the comprehensive prevention and control system "human-drug-application", for the safe and rational application of Epimedii Folium. This study is expected to provide support for scientific evaluation and precise prevention and control of the safety risk of Epimedii Folium.

Seven compounds were isolated from Onychium japonicum by macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography and semi-preparative HPLC. Their structures were identified by NMR, MS and other spectroscopic methods as onychone A (1), quercetin (2), quercetin-3-O-α-L-rhamnoside (3), kaempferol-7-O-β-D-glucopyranoside (4), kaempferol-3-O-α-L-rhamnopyranoside (5), (-)-prunin (6), and norathyriol (7). Compound 1 is a novel macrocyclic flavonoid, and all the others are reported from this plant for the first time. In vitro cytotoxic activities of compounds 1-7 were evaluated by MTS testing with five cancer cell lines. Compound 7 exhibited weak cytotoxicity against tumor cell lines A549, SMMC-7721, and SW480.

To investigate the mechanism by which Schisandra Chinensis mediates the phenotypic transformation of microglia via microRNA-124 (miR-124)-based regulation of the Toll-like receptor 4 (TLR4) pathway, a model was established using lipopolysaccharide (LPS) stimulation of BV2 cells. Cells were treated with different doses of Schisandra Chinensis extract (SCE). MiR-124 inhibitors and negative control sequences (NC inhibitor) were transfected into LPS-induced BV2 cells and treated with SCE. The MTT assay was used for cell activity detection; an NO kit was used to measure NO release; ELISA kits were used to measure the levels of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). Microglia markers, including ionized calcium binding adapter molecule-1 (IBA-1) and arginase-1 (Arg-1), and the nuclear translocation of nuclear factor-kappa B (NF-κB) were evaluated by immunofluorescent staining. NF-κB p65, IBA-1, Arg-1, TLR4, myeloid differentiation primary factor 88 (MyD88), inhibitor of nuclear factor-kappa B kinases-α (IKK-α), IL-10, TNF-α were detected by immunoblot. SCE at concentrations ranging from 31.25 to 250 μg·mL^-1 had no significant effect on cell activity. SCE treatment significantly inhibited NO release induced by LPS (P < 0.001, P < 0.01), increased the level of IL-10 (P < 0.05), and decreased the level of TNF-α (P < 0.001). In addition, SCE significantly reduced the expression of TNF-α, IBA-1, TLR4, and MyD88 (P < 0.01, P < 0.001) and elevated the expression of IL-10, Arg-1, NF-κB P65 and IKK-α (P < 0.001, P < 0.01, P < 0.05). SCE treatment could also promote the expression of miR-124 (P < 0.01). However, transfection with the miR-124 inhibitor increased TNF-α (P < 0.001), decreased the level of IL-10 (P < 0.05), increased the mRNA level and the protein expression of TNF-α and IBA-1 (P < 0.05, P < 0.01, P < 0.001), and decreased the mRNA level and protein expression of IL-10 and Arg-1 (P < 0.001, P < 0.01). In addition, the inhibition of TLR4 and MyD88 was attenuated. In conclusion, SCE appears to inhibit the activation of TLR4 signaling pathway by upregulating miR-124 so as to inhibit microglia M1 polarization and promote microglia M2 polarization.

In this study, a series of 18 histone deacetylases inhibitors (HDACis), derived from our in-house anti-cancer trans-β-arylacryl 1, 2, 3, 4-tetrahydroisoquinoline-based scaffold, were designed, synthesized, and antitumor evaluated. HDAC1 inhibitory activity assay showed that compounds 13d-13f and 13m-13o demonstrated attractive enzymatic activity with IC₅₀ at single-digit nanomolar or subnanomolar level.In addition, 13o exerted superior anti-proliferative activity (A549, IC₅₀ = 0.89 μmol·L^-1; HCT116, IC₅₀ = 0.49 μmol·L^-1) to that of vorinostat (SAHA).Besides, 13e, with the most potent HDAC1 enzymatic activity (IC₅₀ = 3.8 nmol·L^-1), also displayed attractive cellular activity (A549, IC₅₀ = 1.74 μmol·L^-1; HCT116, IC₅₀ = 2.43 μmol·L^-1). The Western blot analysis illustrated that 13e treatment increased the acetylation of H3 and α-tubulin in a dose-dependent manner in A549 cells. In summary, 13e and 13o deserve further functional investigation.