Pyroptosis is a form of inflammatory programmed cell death pathway. In vitro and in vivo studies have shown that pyroptosis contributes to the development of macrovascular complications of diabetes, mainly through activating inflammasomes and caspase-1/4/5/11, cleaving gasdermin D (GSDMD), releasing interleukin-18 (IL-18), IL-1β and other inflammatory cytokines. In recent years, the effect of systemic chronic inflammation caused by pyroptosis through inflammatory cascade reaction on macrovascular complications of diabetes has received long-term attention. This article reviews studies of pyroptosis in macrovascular complications of diabetes and the related drugs to provide promising thought for treating macrovascular complications of diabetes in clinical.

Liver fibrosis is characterized by scarring of liver tissue, which is an intermediate pathological process of chronic liver disease developing into liver cancer. Its mechanism involves multiple signal pathways, and its reversibility is a current research hotspot. Bone marrow mesenchymal stem cells (BMSCs) are adult stem cells with multi-differentiation potential. They have ability to differentiate into liver-like cells in vivo and in vitro to perform normal liver cell functions. Modern pharmacological experimental studies have shown that the use of BMSCs alone or in combination with active factors, Chinese medicine or Chinese medicine monomers, genetic modification and other methods can promote their proliferation, differentiation, and migration, improve the therapeutic effect, and play a role in improving liver fibrosis. By summarizing the existing literature, the therapeutic mechanism of BMSCs in improving liver fibrosis is reviewed from the aspects of the pathogenesis of liver fibrosis, the improvement mechanism of liver fibrosis, the biological characteristics of BMSCs and its improvement mechanism, so as to provide reference for the later development of BMSCs cell therapy.

This study aimed to research the antitumor activity and mechanisms of caffeic acid phenethyl ester derivative PEC01 in mouse G422 glioma. MTT assay, flow cytometry (FCM) and Transwell migration assay were used to detect the effects of PEC01 on proliferation, apoptosis, and migration of G422 cells respectively. Mouse subcutaneously transplanted G422 tumor model was used to analyse the effect of PEC01 on the growth of glioma in vivo. Animal welfare and experimental procedure are in accordance with the regulations of the Animal Ethics Committee of institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. Western blot was used to detect the protein levels of epidermal growth factor receptor (EGFR), Src and their downstream signaling pathways in G422 cells and tumor issue. The results showed that PEC01 inhibited proliferation of G422 cells in a time- and dose-dependent manner, with IC₅₀ of (9.02 ± 0.36) μmol·L^-1 at 96 h. PEC01 significantly induced early apoptosis and late apoptosis of G422 cells at 10.0 and 20.0 μmol·L^-1 concentrations for 96 h. Scratch healing rate of G422 cells reduced after treated with different concentrations (0.625-5.0 μmol·L^-1) of PEC01 for 12-48 h in scratch healing assay. The number of transmembrane G422 cells decreased in groups treated with PEC01 for 8 h compared with DMSO group. The average tumor weight of groups treated with 30.0 and 60.0 mg·kg^-1 PEC01 was significantly reduced in G422 insubcutaneously transplanted tumor model, and the inhibition rate of tumor weight was 72.29% and 59.44%, respectively. Protein levels of EGFR, Src, c-myc and hypoxia-inducible factor 1-alpha (HIF-1α) decreased significantly in G422 cells and tumor tissue. The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway related proteins were down-regulated. Related proteins of invasion, metastasis and cell cyclin were significantly down-regulated. PEC01 can suppress the growth of G422 glioma in vitro and in vivo. The antitumor activity of PEC01 in mouse subcutaneously transplanted G422 tumor model might be related to the blockcade of PI3K/Akt/mTOR and MAPK/ERK signaling pathways.

This study investigated the effect of morin, an active ingredient of the family Moraceae, on collagen-induced arthritis (CIA) in mice, and explored the underlying mechanism from the perspective of recovering immune balance. The collagen was used to induce model of CIA in mice, morin was administered by gavage, and arthritis index (AI) score, imaging and histopathological changes of the paws and ankle joints, and the levels of proinflammatory factors, proinflammatory mediators as well as the IgG class antibodies in serum were detected. In addition, the frequencies of T helper 17 (Th17) and regulatory T (Treg) cells and the levels of relevant transcription factors and functional factors in lymph nodes/spleen as well as the levels of interleukin-17A (IL-17A) and IL-10 in serum were determined. The results showed that oral administration of morin significantly reduced the AI score, improved joint swelling and bone damage, reduced the pathological score, and down-regulated the levels of proinflammatory factors [tumor necrosis factor-‍α (TNF-‍α), IL-6 and IL-1β], proinflammatory mediators [prostaglandin E₂ (PGE₂), matrix metalloproteinase-13 (MMP-13) and nitric oxide (NO)] and IgG class antibodies (IgG and IgG2a) in serum. Moreover, the percentage of Th17 cells, the expressions of Th17-specific transcription factor retinoic acid-related orphan receptor γt (RORγt) and functional factors IL-17A, IL-21 and IL-22 in lymph nodes/spleen, as well as the level of IL-17A in serum were down-regulated, while the percentage of Treg cells, the expressions of Treg-specific transcription factor forkhead box P3 (Foxp3) and functional factors IL-10 and transforming growth factor-‍β (TGF-‍β) in lymph nodes/spleen, as well as the level of IL-10 in serum were up-regulated. All animal treatments were approved by the Animal Ethics Committee of China Pharmaceutical University and strictly followed the welfare regulations of laboratory animals of China Pharmaceutical University. This study indicates the therapeutic effect of morin on mice with CIA, and the mechanism is associated with the improvement of Th17/Treg imbalance, which provides a theoretical basis for the clinical application of morin.

Viral infections pose a persistent threat to human health and life. The rapid emergence of drug-resistant strains and the outbreak of new viruses require researchers to develop innovative strategies to accelerate the development of more antiviral drugs towards novel targets to meet the clinical needs. This paper selects typical research cases and reviews the novel targets and strategies of antiviral drugs in recent years from the perspective of medicinal chemistry.

To explore the protective effects and pharmacophore of verbascoside against oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal cells injury, we used OGD/R-induced PC12 cells as a neuronal injury model. We investigated the neuroprotective effects of verbascoside and its structural fragments (caffeic acid 3, 4-dihydroxyphenethyl ester, caffeic acid, and 3, 4-dihydroxyphenylethanol) by MTT and crystal violet staining analysis. Moreover, we studied the protection of verbascoside and its structural fragments on mitochondria by Hoechst33258 staining, JC-1 staining and transmission electron microscope analysis. The neuroprotective mechanisms of verbascoside and its major active fragment caffeic acid were investigated by detecting B cell lymphoma 2 (Bcl 2)/Bcl 2 associated X protein (Bax)-dependent mitochondrial cysteinyl aspartate specific proteinase 3 (caspase 3)/poly ADP-ribose polymerase (PARP) apoptosis pathway by Western blot. The results showed that verbascoside, caffeic acid 3, 4-dihydroxyphenethyl ester and caffeic acid significantly improved cell viability and maintained normal PC12 cells morphology. These compounds also significantly reversed OGD/R-induced PC12 cells apoptosis, inhibited cell mitochondria depolarization, and maintained normal mitochondria structure. Furthermore, verbascoside and its major active fragment caffeic acid markedly inhibited the cleavage of mitochondrial apoptotic proteins caspase 3 and PARP, down-regulated Bax, and increased Bcl 2 expression. These results indicate that verbascoside protects OGD/R-induced neuronal cells injury via mitochondrial caspase 3/PARP apoptosis pathway, and caffeic acid may function as the major pharmacophore structure.

Recombinant human granulocyte colony stimulating factor (rhG-CSF) has been in clinical use for the adjuvant therapy of cancer patients with neutropenia caused by radiotherapy/chemotherapy. However, it does have some drawbacks such as poor stability and short half-life, and needs to be administered repeatedly, which is easy to cause adverse reactions such as drug tolerance and immune rejection. Therefore, it is necessary to develop long-acting rhG-CSF to improve its clinical efficacy. In this review, we summarize the research progress on the development of long-acting rhG-CSF using the strategies such as PEGylation, fusion protein and new dosage forms in recent years, and discuss its future development trend.

The success of new drug discovery in 2021 can be affirmative, although the whole world is still suffering from COVID-19 pandemic. 50 new drugs were approved by the FDA's Center for Drug Evaluation and Research (CDER) last year. Among them, 27 were defined as first-in-class drugs, accounting for the highest number in the past decade. Notably, small molecule drugs still occupy a dominant position in first-in-class drugs with 15 drugs approved. Some of them were regarded as milestones for the drug discovery including sotorasib, a first small molecular covalent inhibitor targeting the "undruggable" target of the KRAS G12C; asciminib, a first small molecular allosteric inhibitor targeting the allosteric pocket of BCR-ABL1; belzutifan, a first small molecular inhibitor to inhibit HIF-2α; and vericiguat, a first small molecular sGC agonist for the treatment of chronic heart failure (CHF). First-in-class drugs rely on the discovery of novel targets and biological mechanisms, thus requiring different drug design approaches and being important guidance. In this review, we expect to provide research ideas and methods for more first-in-class drugs based on the research background, development process and therapeutic application of 3 first-in-class small molecule drugs in 2021.

The heat shock protein 20 (Hsp20) gene family plays an important role in regulating the stress response and plant development. The characteristics of Hsp20 in Cannabis sativa (CsHsp20), however, are still unclear. We systematically analyzed the CsHsp20 family based on the whole-genome and transcriptome database of Cannabis sativa using a series of bioinformatical tools. A total of 35 CsHsp20 genes (CsHsp20-1-CsHsp20-35) were identified in Cannabis sativa; they distribute onto 9 chromosomes and belong to 10 subfamilies, each with similar protein motifs. The promoter region of the CsHsp20 genes contains a variety of hormone-responsive and stress-responsive cis-elements, indicating that CsHsp20 genes are involved in plant growth and development and various stress responses. Protein interaction analysis showed that CsHsp20 proteins interacted with other members of the Hsp family and were regulated by transcription factors Hop and HSFA2. Transcriptome data showed that the expression levels of CsHsp20 genes were different among different tissues of Cannabis sativa and across different developmental stages. CsHsp20 genes were highly expressed mainly in hemp seed and its maturation stage, suggesting that CsHsp20 gene family members regulate the growth and development of hemp seed. Our research lays a foundation for the studying the function of CsHsp20 gene family and the directional cultivation of high-quality non-psychoactive medicinal cannabis.

Inflammatory bowel disease (IBD) is a disease characterized by chronic and progressive inflammation of the intestinal tract, which seriously affects the quality of life of patients because it is difficult to cure and easy to recur. As the main organ of substance absorption, the changes of intestinal drug transporters will lead to changes in the behavior of endogenous and exogenous substances in vivo. Changes in the expression and function of a variety of drug transporters have also been observed in intestinal inflammatory tissues of patients with IBD. This paper reviews the changes of intestinal drug transporters in IBD and its related mechanisms, which provides a theoretical basis for finding new strategies for the treatment of IBD and clinical rational drug use.