Comparison of Plasma Metabolites From Patients With Non-Small Cell Lung Cancer by Erlotinib Treatment and Skin Rash.

Erlotinib is a necessary anticancer treatment for non-small cell lung cancer (NSCLC) patients yet it causes severe side effects such as skin rash. In this study, researchers compared the untargeted compound profiles before and after erlotinib administration to observe changes in blood metabolites in NSCLC patients. The levels of 1005 substances changed after taking erlotinib. The levels of 306 and 699 metabolites were found to have increased and decreased, respectively. We found 5539 substances with peak area differences based on the presence of skin rash. Carbohydrate, amino acid, and vitamin metabolic pathways were altered in response to the onset of erlotinib-induced skin rash. Finally, this study proposed using plasma metabolites to identify biomarker(s) induced by erlotinib, as well as target molecule(s), for the treatment of dermatological toxic effects.

Scoping review of the medicinal effects of Eupolyphaga sinensis Walker and the underlying mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Eupolyphaga sinensis Walker (ES) is an insect widely used in traditional East Asian medicine known to exhibit clinical effects on various pathological conditions. Overall, ES is a useful medicinal insect that can treat various diseases, including cancer and immune diseases. However, further mechanistic studies based on its therapeutic effects in clinical settings are required. AIM OF THE STUDY: We aimed to evaluate the current research landscape and diseases associated with ES to synthesize the clinical value of ES based on the associated diseases and underlying therapeutic mechanisms. MATERIALS AND METHODS: Embase and PubMed databases were searched for experimental studies that evaluated the therapeutic efficacy or underlying mechanisms of ES until May 2021. The evidence for each study was summarized using a narrative synthesis approach. Studies on extracted or dried whole ES and ES-derived compounds were quantitatively analyzed by year and disease type. Meanwhile, the overall research trend was confirmed for studies on ES-containing prescriptions by visualizing the disease type analysis. RESULTS: A total of 151 studies were identified, of which 51 were included in our review. There were 14 studies on extracted or dried whole ES, 15 on ES-derived compounds, and 22 on ES-containing prescriptions. ES was most commonly used for cancer-related diseases, followed by those related to endocrine function and immunity. ES regulates the cell cycle, tumor suppressor genes and proteins, immune-related biomarkers, and antioxidant molecules. CONCLUSIONS: Overall, ES is a beneficial medicinal insect that can treat various diseases, including cancer and immune diseases. However, further mechanistic studies based on its therapeutic effects in clinical settings are required.

3D Cell Printing of Tissue/Organ-Mimicking Constructs for Therapeutic and Drug Testing Applications.

The development of artificial tissue/organs with the functional maturity of their native equivalents is one of the long-awaited panaceas for the medical and pharmaceutical industries. Advanced 3D cell-printing technology and various functional bioinks are promising technologies in the field of tissue engineering that have enabled the fabrication of complex 3D living tissue/organs. Various requirements for these tissues, including a complex and large-volume structure, tissue-specific microenvironments, and functional vasculatures, have been addressed to develop engineered tissue/organs with native relevance. Functional tissue/organ constructs have been developed that satisfy such criteria and may facilitate both in vivo replenishment of damaged tissue and the development of reliable in vitro testing platforms for drug development. This review describes key developments in technologies and materials for engineering 3D cell-printed constructs for therapeutic and drug testing applications.

Thiostrepton: A Novel Therapeutic Drug Candidate for Mycobacterium abscessus Infection.

Mycobacterium abscessus is a rapid-growing, multidrug-resistant, non-tuberculous mycobacterial species responsible for a variety of human infections, such as cutaneous and pulmonary infections. M. abscessus infections are very difficult to eradicate due to the natural and acquired multidrug resistance profiles of M. abscessus. Thus, there is an urgent need for the development of effective drugs or regimens against M. abscessus infections. Here, we report the activity of a US Food and Drug Administration approved drug, thiostrepton, against M. abscessus. We found that thiostrepton significantly inhibited the growth of M. abscessus wild-type strains, subspecies, clinical isolates, and drug-resistant mutants in vitro and in macrophages. In addition, treatment of macrophages with thiostrepton significantly decreased proinflammatory cytokine production in a dose-dependent manner, suggesting an inhibitory effect of thiostrepton on inflammation induced during M. abscessus infection. We further showed that thiostrepton exhibits antimicrobial effects in vivo using a zebrafish model of M. abscessus infection.

Suppression of influenza B virus replication by sakuranetin and mode of its action.

This study aimed to investigate in vitro the anti-influenza B/Lee/40 virus effect of sakuranetin and mode of its action. The sakuranetin exhibited potent antiviral activity against influenza B/Lee/40 virus, reducing the formation of a visible cytopathic effect, with a 50% inhibitory concentration (IC50 ) of 7.21 µg/ml and no cytotoxicity at a concentration of 100 µg/ml, and the derived therapeutic index (TI) was >13.87. Oseltamivir showed weak anti-influenza B/Lee/40 virus activity with IC50 of 80.74 µg/ml, 50% cytotoxicity concentration of >100 µg/ml, and TI of >1.24. Sakuranetin also showed effective inhibitory effects when added at the viral attachment, entry, and postentry steps. Moreover, sakuranetin effectively inactivated influenza B/Lee/40 virus infection in dose- and temperature-dependent manners. Sakuranetin indicated an inhibitory effect in viral RNA synthesis in the presence of 100 µg/ml of sakuranetin. Overall, this research revealed that sakuranetin could inhibit influenza B/Lee/40 virus replication and that sakuranetin may be involved in the virus attachment, entry, and postentry. Therefore, sakuranetin is a good candidate for a chemopreventive agent for influenza virus-related diseases.

Capsosiphon fulvescens extracts improve obesity-associated metabolic disorders and hepatic steatosis in high-fat diet-induced obese mice.

Herbal dietary supplements have attracted more and more attention owing to their relative effectiveness in obesity -related metabolic disorders and diseases. This study investigated the therapeutic effects and underlying mechanisms of Capsosiphon fulvescens (CF) extracts on obesity, their associated metabolic disorders and hepatic steatosis in high-fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed with normal, HFD/Vehicle and HFD/CF (orally 300 mg/kg/day for CF). After 12 weeks, CF blocked HFD-induced body weight, food intake, liver weight, hepatic triglyceride (TG), fat mass (weight of abdominal subcutaneous fat and epididymal adipose tissue) and biochemical parameters (total cohlesterol, glucose, TG, creatinine, high-density lipoproteins cholesterol and low-density lipoprotein cholesterol) of serum. CF also had improved serum levels of adiponectin, leptin and insulin-like growth factor-1 in HFD/CF mice. Moreover, CF ameliorated the hepatic steatosis-reducing size of white adipose tissue. These results indicate that CF have anti-obesity effects and are effective for reducing metabolic risk and hepatic steatosis.

Mycobacterium marinum infection in Drosophila melanogaster for antimycobacterial activity assessment.

OBJECTIVES: The major advantages of Drosophila melanogaster are a well-characterized immune system and high degree of susceptibility to tuberculosis caused by Mycobacterium marinum. The D. melanogaster-M. marinum infection model is gaining momentum as a screening tool because it is genetically amenable, low priced, rapid, technically convenient and ethically acceptable. In this context, the aim of this study was to develop a new, effective D. melanogaster-M. marinum in vivo efficacy model for antimycobacterial drug discovery. METHODS: D. melanogaster were challenged with intra-abdominal injections of M. marinum and infected flies were fed with a fly medium containing isoniazid, rifampicin, ethambutol, pyrazinamide, amikacin, dinitrobenzamide or ampicillin dissolved in DMSO at different concentrations (0, 100 and 500 mg/L). Bacterial dissemination in flies was monitored by fluorescence microscopy/cfu counts and a fly survival curve was plotted. RESULTS: The D. melanogaster-M. marinum model allowed assessment of the effectiveness of antibiotic treatment not only with conventional drugs, but also with newly discovered antimycobacterial agents. Rifampicin, dinitrobenzamide, amikacin and isoniazid effectively extended the life span of infected flies and ethambutol showed slightly improved survival. However, M. marinum infection was not cured by ampicillin or pyrazinamide. CONCLUSIONS: This D. melanogaster-M. marinum infection/curing methodology may be valuable in the rapid evaluation of the activity of new antimycobacterial agents in drug discovery.