Pulmonary fibrosis (PF) is a chronic respiratory inflammation disease that threatens human health. The topical immune microenvironment of lung tissue regulates progression of fibrosis. In this study, the efficacy and molecular mechanism of suplatast tosilate (ST) against PF were observed. ST is a T helper 2 (Th2) cytokine inhibitor for clinical treatment of bronchial asthma. But whether it can be applied to therapy of chronic PF and the biomechanism of ST inhibiting Th2 cytokine release are not clear. Using in vivo and in vitro experiments, we found that ST can significantly suppress the pathogenesis of chronic PF induced by multiple bleomycin injury, improve the lung function, and decrease the deposition of collagen in lung tissue. In addition, ST decreases Th2 cytokine releasing through restraining Th2 cell differentiation in the meantime, but did not influence the T helper 1 (Th1) cell differentiation and Th1 cytokine releasing. Further studies showed that ST inhibits Th2 cell differentiation by down-regulating GATA-binding protein 3 (GATA3) expression and activity through inhibiting the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and mammalian target of rapamycin (mTOR). The excessive expression of GATA3 in lungs can reverse the anti-PF effect of ST. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Our research not only clarifies the pharmacological mechanism of ST, but also provides a new selection for clinical anti-PF drug therapy.

Hepatic fibrosis is a common pathological link of multiple chronic liver diseases, and further causes cirrhosis and even liver cancer. Tibetan medicine possessed significant and unique clinical effects in the prevention and treatment of hepatic fibrosis through unique medication methods such as single prescription, time synergy, and dialectical combination prescription. Pharmacological experimental studies have shown that a variety of Tibetan medicine formulas and herbs have anti-fibrotic effects, and their main pharmacological action mechanism involves inhibiting lipid peroxidation, reducing liver stellate cell activation and proliferation, regulating collagen metabolism, etc. This review summarizes the research progress of the clinical application and pharmacodynamic mechanism of Tibetan medicine in the prevention and treatment of liver fibrosis, aiming to provide a reference for the development of clinical use and innovative drugs discovery of Tibetan medicine against hepatic fibrosis.

With the increasing drug resistance of bacteria, especially Gram-negative bacteria, the infection of drug-resistant bacteria has become one of the most challengeable clinical problems. The siderophore-antibiotic conjugates based on the "Trojan horse" strategy can penetrate the extracellular membrane of Gram-negative bacteria by active transport, and they are expected to become a powerful weapon for clinical anti-infection treatment. This review describes the drug design strategies of siderophore-antibiotic conjugates reported in recent years, and focuses on the use of different types of antibiotics in this strategy.

Chaihu Shugan San (CHSGS), a classic traditional Chinese medicinal formula, has been widely used in clinics for emotional disease. Here the protective effect and possible mechanisms of Chaihu Shugan San in stress-induced liver injury were investigated. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University, in compliance with the Institutional Animal Care Guidelines. Mice were administered CHSGS for 7 days and subjected to 18-h acute stress before being killed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) levels in serum were measured with commercial kits. Histomorphology of the liver was analyzed by hematoxylin-eosin staining and immunohistochemistry. Glutathione (GSH) content, 4-hydroxynonenal (4-HNE), brain and muscle Arnt-like protein-1 (BMAL1) and arachidonate 15-lipoxygenase (ALOX15) protein were detected by LC-MS and Western blot, respectively. The results showed that CHSGS ameliorated acute stress-induced liver damage by reducing ALT and AST levels in serum and inflammatory infiltration in liver tissue. Network pharmacology analysis showed that CHSGS was associated with lipid peroxidation. Further analysis confirmed that MDA and 4-HNE levels declined and GSH level increased in livers of stressed mice after CHSGS administration. CHSGS also lowered BMAL1 expression, a pivotal factor in circadian rhythm, in livers of stressed mice. In conclusion, CHSGS ameliorated stress-induced liver injury by repressing lipid peroxidation and regulating circadian rhythm. Our studies implicate that CHSGS is promising as a therapy for stress-induced liver injury, and lay foundation for designing novel prophylactic and therapeutic strategies for stress-induced liver injury.

Liver fibrosis is a common scarring response to virtually all forms of chronic liver injury and is characterized by excessive accumulation of extracellular matrix. Excessive activation of hepatic stellate cells (HSCs) is a key step in liver fibrogenesis. The withanolide extract of Physalis angulata (WEP) is a physalin-type withanolide enriched partition from Physalis angulata. In this study, liver fibrosis mice models were established by CCl₄ and bile duct ligation (BDL) in vivo. Transforming growth factor-β1 (TGF-β1) was given in vitro to induce activation of human hepatic stellate cells LX-2 and treated with WEP at different concentrations. All animal experiments in this paper have been approved by the Ethics Committee of China Pharmaceutical University. The in vivo results showed that, compared with the CCl₄ or BDL group, WEP could reduce collagen deposition and liver damage, and reduce the levels of aspartate transaminase (AST) and alanine transaminase (ALT) in serum. In vitro, WEP had no significant cytotoxicity to LX-2 cells, but significantly reduced the mRNA and protein expressions of fibrotic markers collagen type Ⅰ α 1 chain (COL1A1) and α-smooth muscle actin (α-SMA) and inhibited the activation of hepatic stellate cells. In addition, WEP inhibited the expression of yes-associated protein (YAP) and the phosphorylation level of Smad family member 2 (Smad2) in vivo and in vitro. In conclusion, WEP can inhibit hepatic stellate cells activation via regulating the YAP and TGF-β-Smad pathways, and shows promising anti-fibrosis activity in vitro and in vivo.

Cardiac fibrosis is a vital pathological feature of various cardiovascular diseases, including myocardial infarction and heart failure. However, there have been few clinical interventions to treat cardiac fibrosis. Noncoding RNAs (ncRNAs) are a class of RNAs that do not encode proteins. ncRNAs participate in various cellular biological processes and regulate gene expression at transcription, post-transcription and epigenetic levels. Recent studies demonstrate that ncRNAs participate in the regulation of cardiac fibrosis by affecting the proliferation and transition of cardiac fibroblasts. ncRNAs can be used as potential intervention targets and biomarkers for cardiac fibrosis, provide new strategies and approach for treating and preventing fibrosis associated cardiovascular diseases. This review summarizes the function and mechanisms of ncRNAs in cardiac fibrosis.

Glycosylation abnormalities are common in all stages of tumor development, and sialic acid (SA) modified polysaccharides have been found highly expressed on many different types of tumor cells. These highly sialylated tumor cells promote the formation of tumor immunosuppressive environment and help tumor cells gain metastatic potential by interacting with SA binding receptors Siglecs/selectins expressed on peripheral immune cells or endothelial cells. Related theoretical studies have promoted the development of tumor therapeutic strategies by targeting SA-binding receptors, mainly including specific antibodies trastuzumab (Mylotarg) or polysaccharides that block the interaction between Siglecs/selectins and its ligands, as well as nano-based drug delivery systems modified with SA and its derivatives. This article reviews the specific mechanisms of how SA-binding receptor Siglecs/selectins-mediated interactions contribute to tumor development and metastasis, and tumor therapeutic strategies by targeting SA-binding receptors, as well as makes a rational evaluation and reflection on these therapeutic strategies.

The development of mass spectrometry and proteomics significantly advanced our understanding of post-translational methylation of proteins. In recent years, a large number of proteins containing the methylation recognition domain have been identified. Protein methylation mainly occurs on lysine and arginine residues. Both lysine and arginine have three different methylation states. Lysine can be mono-methylated, di-methylated, and tri-methylated, while the arginine residue can be modified as mono-methylation, symmetrical di-methylation, and asymmetrical di-methylation. Methylation recognition domains can accurately identify lysine or arginine with different state of methylation, transfer methylation signals, and perform functions in a variety of cellular processes, including gene expression regulation, RNA splicing and translation, cell cycle regulation, etc. In recent years, researchers have found that the abnormalities of these recognition proteins are also closely related to the genesis and development of tumors. Therefore, these methylation recognition proteins were considered as potential drug targets for small molecule intervention. In this review, we summarized the researches on the recognition domains of protein methylation as well as their inhibitors, hoping to provide the basis for further drug development in this field.

Clearance reflects the speed of extraction and elimination of drug molecules from systemic circulation. Reducing the clearance of compounds using structure modification strategy could lead to good pharmacokinetic and pharmacodynamic properties. Herein, the concept of clearance, as well as several prediction methods of in vivo clearance are introduced. The strategies of reducing drug clearance are reviewed. These methods include reducing hepatic metabolic clearance through reducing lipophilicity, blocking metabolic site, scaffold modification and increasing steric hindrance; reducing biliary or renal excretion clearance through increasing lipophilicity, reducing polar surface area and bioisosterism. In addition, the influence of spatial configuration on drug clearance is also summarized.

The MIKC-type MADS-box gene family plays an important role in flower development in plants. This study identifies members of the MIKC-type gene family in Cannabis sativa L. at the genome level, with the chromosomal location and linkage, evolutionary relationships, and identification of conserved motifs determined using bioinformatics tools. The results show that C. sativa contains 39 members of the MIKC-type MADS-box gene family (named CsMADS1-CsMADS39) unevenly distributed on nine chromosomes. The encoded proteins range in length from 146 to 503 amino acids, and the theoretical isoelectric points range from 5.19 to 10.12. Molecular weights range from 16 739.35 to 57 070.56 Da. The subcellular location of CsMADS genes is mainly in the nucleus. The result of conserved domain analysis showed that all genes contain the MADS conserved domain. The analysis of GO showed that all genes were annotated to 331 GO terms, which were clustered by molecular function. A phylogenetic tree showed that CsMADS genes could be divided into 14 subclasses, according to ABCDE homologous gene model; CsMADS genes are clustered with SQUA/AP1, AP3, PI, GGM13, AG, SEP/AGL2 subfamilies in Arabidopsis. There are abundant cis-acting elements in the upstream promoter region of CsMADS genes, mainly light regulatory elements. The results of real-time fluorescent quantitative PCR showed that some CsMADS genes are highly expressed in flowers and bracts, with tissue-specific expression. This study identified and analyzed the MIKC-type MADS-box gene family in C. sativa at the genome level, and provides a theoretical basis for further exploration of the function of MIKC-type genes and their role in regulating the growth and development of medicinally important hemp.