EXCLI Journal最新文献

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer related deaths globally. Despite advancements in treatment, drug resistance and adverse side effects have spurred the search for novel therapeutic strategies. This study aimed to investigate how the Emblica officinalis can inhibit key targets involved in HCC progression. Screening of the reported compounds based on ADMET profile and identification of protein targets was done using the literature survey. Protein targets were divided into four major categories including inflammatory, angiogenic, anti-apoptotic as well as proliferative targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to reveal the functional roles of genes. The STRING database was used to analyze the protein-protein interactions (PPI) of target genes. Docking was employed to predict the binding affinity of compounds with target proteins. Subsequently, MD simulation was conducted to assess the stability and dynamics of protein-ligand complexes. A total of 22 active compounds with 25 protein targets have been identified. These targets have a major role in controlling biological processes such as apoptosis, signaling and cellular interactions. KEGG pathway analysis showed that cancer, atherosclerosis, PI3K-Akt, EGFR tyrosine kinase inhibitor resistance and MAPK signaling pathways are mainly involved. Molecular docking by Mcule platform demonstrated that emblicanin A, punigluconin, penta-o-galloylglucose and quercetin showed higher binding energy affinities with BCL2, BCL2L1, c-Met, HSP70, EGFR, FGFR1, PTGS2 and TNFα. MD simulation revealed conformational changes, flexibility, interactions and compactness of protein-ligand complex. The stable protein binding interactions suggest the potential of compounds to inhibit the functions of target proteins. These results suggest that compounds derived from E. officinalis may have the therapeutic potential for treating HCC. See also the graphical abstract(Fig. 1).

Fluorophore-coupled bile acids (BA) represent an important tool for intravital analysis of BA flux in animal models of cholestatic diseases. However, addition of a fluorophore to a BA may alter transport properties. We developed and validated a 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole-coupled taurocholic acid (3β-NBD-TCA) as a probe for intravital analysis of BA homeostasis. We compared transport of 3β-NBD-TCA to [3H]-TCA in HEK293 cells stably expressing the mouse hepatic or renal BA carriers mNtcp or mAsbt, respectively. We also studied distribution kinetics intravitally in livers and kidneys of anesthetized wildtype and mOatp1a/1b cluster knockout mice (OatpKO) with and without administration of the Ntcp inhibitor Myrcludex B and the ASBT inhibitor AS0369. In vitro, 3β-NBD-TCA and [3H]-TCA showed comparable concentration- and time-dependent transport via mNtcp and mAsbt as well as similar inhibition kinetics for Myrcludex B and AS0369. Intravital analysis in the livers of wildtype and OatpKO mice revealed contribution of both mNtcp and mOatp1a/1b in the 3β-NBD-TCA uptake from the sinusoidal blood into hepatocytes. Combined deletion of mOatp1a/1b and inhibition of mNtcp by Myrcludex B blocked the uptake of 3β-NBD-TCA from sinusoidal blood into hepatocytes. This led to an increase of 3β-NBD-TCA signal in the systemic circulation including renal capillaries, followed by strong enrichment in a subpopulation of proximal renal tubular epithelial cells (TEC). The enrichment of 3β-NBD-TCA in TEC was strongly reduced by the systemic ASBT inhibitor AS0369. NBD-coupled TCA has similar transport kinetics as [3H]-TCA and can be used as a tool to study hepatorenal BA transport. See also the graphical abstract(Fig. 1).

The emergence of checkpoint inhibitors targeting the PD-1/PD-L1 axis marks a paradigm shift in cancer therapy, offering a novel avenue for enhancing patient outcomes. This review examines the structural and functional dynamics of PD-1 and PD-L1 while exploring the clinical implications of current PD-1/PD-L1 monoclonal antibodies. Highlighting recent advancements, this paper delves into the promising results from combination therapies that present a multifaceted attack on tumor progression. Despite the success observed across various cancer types, challenges such as immune resistance remain. Future considerations are discussed with an emphasis on the need for further clinical studies, aiming to refine and broaden the curative potential of PD-1/PD-L1 inhibitors in oncology. This review postulates that ongoing research and innovative approaches could significantly enhance cancer care, making immunotherapy an even more central strategy in the fight against cancer. See also the graphical abstract(Fig. 1).

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Its treatment is complicated due to the development of resistance to conventional chemotherapy and targeted therapy. Deoxybouvardin and related cyclic hexapeptides reportedly exhibit antitumor activities, but their mechanisms of action remain unclear. This study aimed to investigate the anticancer mechanisms of deoxybouvardin glucoside (DBG), a glucosidic form of deoxybouvardin from Rubia species, in gefitinib (GEF)-sensitive and -resistant NSCLC HCC827 cells. The effects of DBG treatment on cell proliferation were evaluated using a viability assay. The inhibitory effects of DBG treatment on the activities and phosphorylation of the protein kinases epidermal growth factor receptor (EGFR), MET, and AKTs were assessed using in vitro kinase assay and western blot, respectively. DBG treatment inhibited the growth of HCC827 cells in a concentration- and time-dependent manner. Results of in vitro kinase assay and western blotting showed that DBG treatment significantly inhibited the activities and phosphorylation of the protein kinases EGFR, MET, and AKT. Prediction using molecular docking showed that DBG is located in the ATP-binding pockets of these kinases, supporting the kinase inhibition by DBG treatment. Moreover, DBG treatment induced reactive oxygen species (ROS) generation and cell cycle arrest in the cells. The induction of apoptosis by DBG through caspase activation was confirmed by Z-VAD-FMK treatment. In summary, DBG treatment inhibited the growth of GEF-sensitive and -resistant NSCLC cells by targeting EGFR, MET, and AKTs. Moreover, it induced apoptosis by inducing ROS generation and caspase activation. These results indicate that DBG is a potential therapeutic agent for the treatment of GEF-resistant NSCLC. See also the graphical abstract(Fig. 1).

The main treatments for cancer are radiotherapy and chemotherapy, but they can generate side effects such as fatigue, myelosuppression, and radiodermatitis. The Multinational Association of Supportive Care in Cancer already recommends the use of laser for radiodermatitis in breast cancer patients. However, in relation to head and neck cancer patients, there is a lack of studies clearly demonstrating clinical effects and identifying the best light parameters for the treatment of radiodermatitis. This study reports on three oncological patients with radiodermatitis treated with light-based therapies to show clinical improvements in lesion grades and to discuss the effects of laser and its parameters. A retrospective report of three head and neck cancer patients with radiodermatitis, treated with photobiomodulation and photodynamic therapy at an outpatient health clinical facility. The Visual Analog Scale, Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG) Scale, and the clinical characteristics of lesions were evaluated before and after a photobiomodulation plus photodynamic therapy protocol. Improvements were observed in cases with RTOG grade III with just 4 treatment sessions required for complete healing of the lesions. The patient with RTOG grade IV required antibiotic therapy, temporary suspension of radiotherapy, and more than 4 light sessions to achieve improvements. None of the patients showed worsening of the lesions, necrosis, or infection after treatment with no adverse effects. Head and neck cancer patients with radiodermatitis treated with phototherapy obtained good results in wound healing and pain relief in a short period. These case reports embody the easy-to-apply implementation of a light protocol in a health facility based on previous scientific evidence with positive results and no short-term side effects. In light of the negative impact on quality of life caused by radiodermatitis, health teams should be encouraged to design research study protocols involving light-based therapies.

Bloodborne pathogens (BBPs) pose formidable challenges in the realm of infectious diseases, representing significant risks to both human and animal health worldwide. The review paper provides a thorough examination of bloodborne pathogens, highlighting the serious worldwide threat they pose and the effects they have on animal and human health. It addresses the potential dangers of exposure that healthcare workers confront, which have affected 3 million people annually, and investigates the many pathways by which these viruses can spread. The limitations of traditional detection techniques like PCR and ELISA have been criticized, which has led to the investigation of new detection methods driven by advances in sensor technology. The objective is to increase the amount of knowledge that is available regarding bloodborne infections as well as effective strategies for their management and detection. This review provides a thorough overview of common bloodborne infections, including their patterns of transmission, and detection techniques.