Hepatic selective insulin resistance refers to that insulin fails to suppress hepatic glucose production but continues to promote hepatic lipogenesis in insulin resistance. Therefore, type 2 diabetes mellitus is characterized with dyslipidemia apart from hyperglycemia. This review highlights the roles and molecular mechanisms of the key hepatic lipogenesis factors such as sterol regulatory factor binding protein 1c (SREBP1c), mammalian rapamycin target complex 1 (mTORC1), endoplasmic reticulum stress (ER stress), FoxO1, lipid synthesis substrate, etc.

Xiaoshuan Tongluo formula is effective in treating mental retardation and speech astringency caused by cerebral thrombosis, but its mechanism remains unclear. In this investigation, by collecting the chemical constituents from Xiaoshuan Tongluo formula and the targets related to stroke, we obtained 1 251 constituents from the formula and 10 drug targets related with stroke. We established 18 prediction models of compound-target interaction for 10 stroke-related targets, using molecular docking method and machine learning methods includes Naive Bayesian and recursive partitioning based on the input of molecular fingerprints and molecular descriptors. Using these models, we predicted the active chemical constituents from Xiaoshuan Tongluo formula and their drug targets, 153 potential active constituents were discovered, 22 among them could interact with at least two drug targets related with stroke. On this basis, the chemical constituent-target network was constructed using network construction software, and then the important metabolic pathways of the targets were identified by using Gene-Ontology (GO) enrichment analysis, such as blood coagulation, positive regulation of angiogenesis, positive regulation of ion transport and so on. On this basis, a target-pathway network was constructed. In conclusion, using machine learning, molecular docking, virtual screening, data mining and network construction, this study explored and partially revealed the active chemical constituents and chemical constituent-target-pathway network action mechanism of Xiaoshuan Tongluo formula against stroke, which will provide important information for its further study.

Depression is a common mental illness with mood disorders as the main clinical feature. In recent years numerous studies have shown that mitochondrial function and structure are abnormal in patients with depression, and changes in mitochondrial ultrastructure can lead to energy metabolism disorders in the body. It is suggested that 'mitochondrial energy metabolism disorder' may be the pathogenesis of depression. This paper reviews the intrinsic association of mitochondrial energy metabolism with depression and notes potential mechanisms from the standpoint of mitochondrial structure and function on the molecular level. We provide a reference for understanding the pathogenesis of depression and identifying the possible targets of antidepressant drugs.

The property of medicine is the "identity card" of traditional Chinese medicine (TCM), and the key to crack the theory of property of TCM. Based on molecular thermodynamics, the effects of interaction between TCM and organs in vitro were studied from the perspective of micro-energy release and absorption in order to construct a new idea of characterizing meridian theory. Scutellaria baicalensis, for example, application of isothermal titration calorimetry (ITC) were used to determine the energy changes during the interaction of Scutellaria baicalensis and its main active ingredient baicalin with brain, heart, lung, spleen and kidney in vitro, comparison including the association constant (K_a) and disassociation constant (K_d), combined with thermodynamic parameters, such as stoichiometry ratio (n), enthalpy change (ΔH), entropy change (ΔS), Gibbs free energy (ΔG), it is found that the interaction intensity between Scutellaria baicalensis and lung is significantly stronger than that of other organs, which is consistent with the theory of the return of Scutellaria baicalensis in ancient books. In addition, baicalin, the main active ingredient, showed the same action pattern as Scutellaria baicalensis. The thermodynamic parameters analysis showed that the action was a weak bond-induced spontaneous chemical binding reaction driven by both entropy and enthalpy. The results of specific curl measurement further proved the interaction between baicalin and lung, and were consistent with the results of ITC titration, indicating that ITC could be used to characterize the meridian tropism of TCM. Therefore, based on ITC, it is scientific and feasible to characterize the meridian of TCM by the energy change of the interaction between the decoction of TCM and its active components and the in vitro tissues respectively. This experiment provides a new idea for the discussion of meridian of TCM.

Following small molecules and monoclonal antibodies, oligonucleotides are expected to overcome the rare and refractory human diseases. It has been attracted the attention of the pharmaceutical industry since the approval of six oligonucleotides in recent years because of their unique mechanism of regulating disease gene transcription at the RNA level. As a new class of drug molecules, oligonucleotides are highly polar, charged, and need to be improved by means of chemical modification and drug delivery systems. And therefore, they have different clinical pharmacology properties compared with chemical molecules and monoclonal antibodies, which pose new challenges for early clinical development. This paper reviews the characteristics of oligonucleotides from the perspective of technological development, mechanism of action, human pharmacokinetics, efficacy and safety.

Uranium[U(Ⅵ)] in the blood is known to form stable complexes with apotransferrin (apo-Tf), which plays an important role in mediating the cytotoxicity induced by U(Ⅵ) transported to cells. The present study aimed to establish an new in vitro screening model of U(Ⅵ) decorporation agents through exploring the capability of chelating agents competing with U(Ⅵ) binding to apo-transferrin based on enzyme-linked immunosorbent assay (ELISA). The optimal concentrations of apo-Tf coated antigen, Tf antibody, secondary antibody and U(Ⅵ) treatment were achieved and the stability and reproducibility of this method were validated by methodology study. Using this model, the ability of four chelating agents to mobilize the U(Ⅵ) binding to apo-Tf was evaluated, and the rank of competitiveness was catechol-3, 6-bis(methyleiminodiacetic acid) (CBMIDA) ≈ Tiron > apo-Tf > DTPA-CaNa₃ ≈ DTPA-ZnNa₃. The efficacy of these chelating agents in removal of U(Ⅵ) was tested by animal experiments. The results showed that immediate administration of CBMIDA or Tiron after injection of U(Ⅵ) in mice significantly promoted urinary U(Ⅵ) excretion and reduced U(Ⅵ) accumulation in kidneys and femurs, while DTPA-CaNa₃ and DTPA-ZnNa₃ have no obvious effects as compared to U(Ⅵ)-exposed mice alone, which was consistent with the results of competitive ELISA method. The animal experiments conform to the rules of the Animal Research Ethics Committee of School of Pharmacy of Fudan University. These results show that the new proposed method is rapid, simple and convenient with good reproducibility and has the potential to be used for in vitro screening of U(Ⅵ) decorporation agents.

The resonance light scattering (RLS) spectral characteristics of the interaction between rose Bengal and mexiletine hydrochloride in the presence of cetylpyridinium bromide were investigated. A dual-wavelength resonance light scattering (DWO-RLS) method for the determination of mexiletine hydrochloride in drugs was established. In a weakly acidic solution, rose Bengal interacts with mexiletine hydrochloride and cetylpyridinium bromide to form a red ternary ion association complex, which led to a significantly enhanced resonance light scattering signal and produced two strong characteristic scattering peaks at 372 nm and 596 nm. In these two wavelengths the mass concentration of mexiletine hydrochloride was in the range of 0.004 to 0.65 mg·L^-1 and had a good linear relationship with the resonance light scattering enhancement intensity (ΔI_RLS), with detection limits of 0.003 2 mg·L^-1 (372 nm) and 0.003 8 mg·L^-1 (596 nm), respectively. When measured by the dual-wavelength resonance light scattering (DWO-RLS) technique, the detection limit was lower, only 0.001 8 mg·L^-1. When the DWO-RLS method was applied to the determination of mexiletine hydrochloride in commercially available mexiletine hydrochloride tablets, and the recovery was 98.5%-103%, and the relative standard deviation was 2.0%-2.7%.

Four alkaloids were isolated from the total alkaloids of the twigs and leaves of Alstonia yunnanensis (Apocynaceae) by using silica gel, ODS, Sephadex LH-20, and HPLC chromatography. Structures were determined by physical, chemical and spectroscopic methods and identified as N₄-methylpseudoakuammigine (1), pseudoakuammigine (2), vinorine (3), picraline (4). Among them, compound 1 is a new monoterpenoid indole alkaloid.

To determine the relationship between the effect of wuzhi capsules on the blood concentration of tacrolimus as compared to diltiazem and with regard to cytochrome P450 (CYP)3A5 gene polymorphisms, 170 patients who underwent renal transplantation from November 2014 to March 2018 and used tacrolimus combined with diltiazem 30 mg bid were selected in this study retrospectively. Patients were divided into an observation group (105 patients) and a control group (65 patients) according to whether they used wuzhi capsules after the operation. The polymorphisms of CYP3A5*3 were determined and the effect of wuzhi capsules on the blood concentration of tacrolimus, as compared with that of diltiazem was determined in patients with different CYP3A5*3 genotypes. This study complies with relevant ethical norms. The results show that compared with diltiazem, an increase of tacrolimus C₀/D was significantly correlated with the patient's CYP3A5*3 genotype in both the self-control and the control group. CYP3A5 expressers in the observation group were able to increase the tacrolimus C₀/D by about 76.8% by replacing the wuzhi capsules with diltiazem, but this effect was not observed in CYP3A5 non-expressers. In CYP3A5 expressers wuzhi capsules had a greater ability relative to diltiazem to increase the blood concentration of tacrolimus.

Cerebral malaria (CM) is the deadliest complication of Plasmodium falciparum infection and even with effective anti-malarial treatment the mortality of children can be as high as 18%; up to one-third of CM survivors are left with neurological and cognitive deficits. The pathophysiology of CM is not completely understood, but mechanical obstruction and immunopathology are its mainstream theories. Adjuvant therapy aims to improve clinical outcomes and/or reduce mortality, as well as preventing long-term neurocognitive deficits. Improving survival and reducing neurological damage to survivors are new goals for new antimalarials and adjuvant therapies. Herein, we discussed what is known about the disease mechanism of CM and systematically summarize the progress of adjuvant therapy research in protecting the vascular endothelium, reducing adhesion formation, regulating immune balance, interfering with malarial metabolism, protecting nerves, improving nitric oxide bioavailability, improving energy metabolism and alleviating inflammation, with the aim of exploiting this understanding to reduce the neurological damage to children with CM. This work also highlights some preclinical studies which may be candidate strategies in future clinical trials.