As an essential amino acid, tryptophan (Trp) has various physiological functions and is of great significance in the metabolic process of tumors. In the human body, tryptophan is mainly transformed through kynurenine metabolic pathway, which not only promotes the inherent malignant properties of tumor cells, but also leads to immune-suppressive tumor microenvironment. Changes in tryptophan metabolism often occur in tumors, accompanied by abnormal gene expression of tryptophan-related enzymes, among which indoleamine 2, 3-bioxygenase (IDO)-related gene expression and tryptophan 2, 3-dioxygenase (TDO)-related gene changes are the most significant. A large number of clinical trials on IDO inhibitors, TDO inhibitors and combination therapy have been carried out. This paper reviewed the tryptophan metabolic pathway, regulation of IDO (TDO), kynurenine (KYN) and other related genes in tumor cells, and outlined the development of therapeutic schedule targeting tryptophan-related genes. The new progress provides new ideas for the further exploration of tumor treatment options.

In recent years, the oceans have provided an important source of highly promising new anti-tumor drugs for innovation and screening, with approximately 56% of biologically active compounds being discovered to have anti-tumor effects each year. In this study, we classified and summarized the approved drugs of marine origin in terms of anti-tumor therapy, and firstly, we briefly overviewed the role of the immune system in cancer pathogenesis and discussed the current dilemma of cancer immunotherapy and highlighted the main anti-tumor targets of marine drugs. Further, with a focus on tumor immunity, we classified and outlined the history of currently approved marine original drugs by species origin, structural features, relevant pathways, and clinical application and therapy. Lastly, the limitations of current marine drug research were discussed, as well as prospects and trends in new drug development.

WRKY, a class of conserved transcription factors in plants, plays important roles in plant growth, development and secondary metabolism. In the present study, 65 WRKY members were identified from de novo transcriptome sequencing data of three different tissues (root, stems and leaves) of Baphicacanthus cusia. BcWRKY proteins contained from 221 to 706 amino acids and the isoelectric point is from 4.68 to 9.68. Molecular weights range from 25 711.8 to 75 475 Da. The main secondary structures of BcWRKYs protein are random coil. A subcellular localization prediction indicated that the putative BcWRKY proteins were enriched in the nuclear region. Phylogenetic analysis showed that BcWRKYs could be categorized into three groups and five subgroups (Group IIa, Group IIb, Group IIc, Group IId and Group IIe) in Group II. Structural analysis found that all BcWRKY proteins contained a highly conserved motif WRKYGQK. Finally, the transcriptional profiles of ten BcWRKY genes highly expressed in root, stem and leaf tissues under abscisic acid (ABA), methyl jasmonate (MeJA), or salicylic acid (SA) treatment were systematically investigated using qRT-PCR analysis. Results showed that a total of ten BcWRKY genes were differentially expressed in response to ABA, MeJA, and SA treatment. This work would be provided a basis for further elucidating the molecular mechanism of WRKY transcription factors in the biosynthesis of indole alkaloids in B. cusia.

In this study, a novel oral drug delivery system based on linolenic acid-modified chitosan (CS-LA) micelle was developed to improve the oral bioavailability of doxorubicin (DOX), which was proven by its in vivo intestinal absorption in rats. The DOX-loaded CS-LA micelles (CS-LA@DOX) were prepared by the dialysis method. The synthesized micelle material was identified by proton nuclear magnetic resonance spectroscopy (¹H-NMR) and Fourier transform infrared spectroscopy (FT-IR). A series of the micelle properties, including particle size distribution, zeta potential, encapsulation efficiency (EE), drug loading (DL), micromorphology, polymorphy, and critical micelle concentration (CMC) were characterized or tested. The in vitro release of micelles was observed by the dialysis method, and the absorption-promoting effect of micelles was investigated by intestinal circulation experiments in rats. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guilin Medical University. The results of ¹H-NMR and FT-IR showed that CS and LA were covalently bound via an amide linkage. The DOX encapsulated in the micelle core was in an amorphous state. The as-prepared micelles in the transmission electron microscope (TEM) image showed regular spherical shapes and uniform sizes with a series of excellent characteristics including (119.2 ± 2.1) nm of mean particle size [polymer dispersity index (PDI), 0.190 ± 0.08], +12.1 mV of zeta potential, (70.23 ± 0.74) % of EE, (8.77 ± 0.02) % of DL and 51.75 μg·mL^-1 of CMC. Compared with the reference, DOX hydrochloride, the proposed micelle drug delivery system showed an obvious sustained-release effect in vitro release; and enhanced drug absorption in the small intestine of rats.

CDKs proteins are a kind of cell cycle protein-dependent kinases, which serve as important roles in controlling cell division and transcriptional stages. Among them, CDK9, as a key regulator responsible for the transcriptional elongation of cells, drives the development of various malignant cells and is considered as an important target in the field of anti-tumor drug development. However, the CDK family proteins feature high conservativeness and similarity in structure, leading to the poor selectivity and severe side effects for traditional small-molecular CDK9 inhibitors, which has limited their clinical applications. In view of this, there is an urgent need to investigate CDK9 targets through a novel strategy. The PROTAC is an emerging drug discovery strategy that the degrader could specifically recognize the target protein through indirect linkage with ubiquitin ligases and ultimately eliminate the target protein through the ubiquitination degradation system. This paper provides a brief overview of the structure and function of CDK9 protein, its relationship with the poor prognosis of clinical diseases, as well as the currently reported small molecular inhibitors. The latest research progress on the targeted degradation of CDK9 protein based on PROTAC technology is highlighted. Finally, the development prospects of this target protein in this novel technology field are summarized and prospected, aiming to provide a reference for the development of antitumor drugs in this direction.

Chronic kidney disease (CKD) is a progressive disease with many complications (eg, cardiovascular disease and acidosis and anemia) and high morbidity and mortality occurs in the population. There is no cure for this disease, current treatments including renin-angiotensin-aldosterone pathway inhibitors and sodium-glucose co-transporter 2 inhibitors can only delay the progression to end-stage renal disease. With the identification of more key factors and mechanisms in CKD development, new potential therapeutic approaches for CKD can be developed. This review summarizes the mainstays of therapy and strategies for CKD and related comorbidities to support the development of novel treatments.

Anemoside B4 (B4), a main triterpenoid saponin from a traditional Chinese medicine plant, Pulsatilla chinensis, is a novel anti-inflammatory agent for protection from acute lung injury. We investigated the pulmonary availability and anti-inflammatory efficacy of B4 after intratracheal and intravenous dosing with a view to evaluating the suitability of inhalation delivery. All animal studies were performed under the guidelines approved by the Animal Care and Use Committee of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences (Approval No: SLXD-20181113046). In vitro evaluation of the aerodynamic characteristics and droplet size distribution showed that the aerosols generated by a commercially available nebulizer were well deposited in the respiratory tract. Following intratracheal administration, B4 underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 103%. Compared to intravenous delivery, intratracheal administration dramatically increased the drug availability in lung tissue of rats by more than 1 000-fold, leading to improved and prolonged concentrations of B4 in lung tissue up to 48 h. In addition, the intratracheal administration of B4 resulted in dose-dependent and prolonged anti-inflammatory efficacy in a lipopolysaccharide (LPS)-induced lung injury model in mice. The present results demonstrate that inhalation delivery of B4 is a promising approach to treat pulmonary inflammation with once-daily dosing.

The bone marrow microenvironment, also known as the bone marrow niche, plays a critical role in maintaining the functions of hematopoietic stem cells. Under physiological conditions, various bone marrow cells regulate each other to sustain hematopoietic homeostasis. However, bone marrow cells gain abnormal function under pathological conditions to cause and promote the occurrence of leukemia and induce drug resistance. Recent findings indicate that abnormal proliferation and differentiation are not the sole reason to cause leukemia. Different types of bone marrow cells also induce intercellular adhesion, abnormally secrete cytokines and chemokines, accelerating leukemia's progress. This article reviews the multiple signaling pathways that regulate the formation and progress of leukemia bone marrow niche, such as C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 signaling pathway, et al. It emphasizes that targeting leukemia bone marrow niche is a vital strategy for improving the leukemia treatment.

Ten compounds were isolated from the 95% ethanol extract of the whole plant of Gerbera piloselloides by silica gel column chromatography, MCI column chromatography and semi-preparative HPLC methods. Their structures were identified on the basis of physicochemical properties, spectral data (UV, IR, MS and NMR), circular dichroism (CD) spectra and single crystal X-ray diffraction analysis as 3′R-gerpilosecoumarin A (1a), 3′S-gerpilosecoumarin A (1b), gymnastone (2), gerberinside (3), divaricataester C (4), luteolin (5), caffeic acid methyl ester (6), ethyl chlorogenate (7), 6-(β-D-glucopyranosyloxy)-7-methoxy-5-benzoranpropanoic acid methyl ester (8) and glucozaluzanin C (9). Among them, new compounds 1a and 1b were new compounds and optical enantiomers, which were obtained by chiral resolution, and their absolute configurations were determined by quantum chemical calculation ECD. Compounds 1 and 1a/1b significantly increased the survival of IEC-6 in rat small intestinal crypt epithelial cells after LPS injury.

Innate immune system, a non-specific defense system formed after birth, is body's first line of defense against pathogens. Innate immunity also plays a key role in the tumor immunosurveillance. With the clinical success of cancer immunotherapy, the regulatory mechanism of innate immune cells in antitumor response has begun to draw increasing attention. Recently, it has been recognized that metabolic regulation plays a vital role in innate immunity, in particular in the tumor microenvironment where the metabolic reprogramming in cancer increases the complexity of immunometabolism yet also provides therapeutic vulnerabilities. This review summarizes the recent progress in understanding the metabolic regulation of the innate immune response. We discuss how metabolites of glucose, amino acids, lipid and nucleotide metabolism regulate the function of innate immune cells. We pay the special attention to the metabolic crosstalk between immune cells or tumor-immune cells in the tumor microenvironment. With the review, we hope to get a better understanding of metabolic regulation of antitumor immunity and provide basis for metabolism-targeted immunotherapy.