Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP) compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines—IL-1β, IL-6, TNF-α, but up-regulation of the anti-inflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.

The communication between hepatocellular carcinoma (HCC) cells and their microenvironment is an essential mechanism supporting or preventing tumor development and progression. Recent evidence has identified extracellular vesicles (EVs) as one of the mechanisms mediating paracrine signaling between cells. Exosomes, the most described class of EVs, deliver proteins, mRNAs, noncoding RNAs, DNA, and lipids to recipient cells, also at remote distances. MicroRNAs (miRNAs), as part of the non-coding RNA exosomal cargo, have an important role in regulating cellular pathways in targeted cells, regulating several processes related to tumor progression invasion and metastasis, such as angiogenesis, immune-escape, epithelial-to-mesenchymal transition, invasion, and multi-drug resistance. Accumulating evidence suggests exosomal miRNAs as relevant players in the dynamic crosstalk among cancerous, immune, and stromal cells in establishing the tumorigenic microenvironment. In addition, they sustain the metastasic niche formation at distant sites. In this review, we summarized the recent findings on the role of the exosome-derived miRNAs in the cross-communication between tumor cells and different hepatic resident cells, with a focus on the molecular mechanisms responsible for the cell re-programming. In addition, we describe the clinical implication derived from the exosomal miRNA-driven immunomodulation to the current immunotherapy strategies and the molecular aspects influencing the resistance to therapeutic agents.

The purpose of this study was to fabricate chitosan/poly(vinyl alcohol)/Ag nanoparticles (CPA) gels with microwave-assistance for skin applications. Microwave irradiation was employed to reduce silver ions to silver nanoparticles and to crosslink chitosan (CS) with polyvinyl alcohol (PVA). The presence of silver nanoparticles in CPA gels matrix was examined using UV-Vis spectroscopy, transmission electron microscopy, and X-ray diffraction. The interaction of CS and PVA was analysed by Fourier transform infrared spectroscopy. The release of silver ions was determined by atomic absorption spectrometry. The antimicrobial properties of CPA gels againstP. aeruginosaandS. aureuswere investigated using agar diffusion method. Finally, the biocompatibility and wound-healing ability of the gels were studied using fibroblast cells (in vitro) and mice models (in vivo). In conclusion, the results showed that CPA gels were successfully fabricated using microwave irradiation method. These gels can be applied to heal an open wound thanks to their antibacterial activity and biocompatibility.

Xeroderma pigmentosum (XP) group D, a severe disease often typified by extreme sun sensitivity, can be caused by ERCC2 mutations. ERCC2 encodes an adenosine triphosphate (ATP)-dependent DNA helicase, namely XP group D protein (XPD). The XPD, one of ten subunits of the transcription factor TFIIH, plays a critical role in the nucleotide-excision repair (NER) pathway. Mutations in XPD that affect the NER pathway can lead to neurological degeneration and skin cancer, which are the most common causes of death in XP patients. Here, we present detailed phenotypic information on a Vietnamese family in which four members were affected by XP with extreme sun sensitivity. Genomic analysis revealed a compound heterozygous mutation of ERCC2 that affected family members and single heterozygous mutations in unaffected family members. We identified a novel, nonsense mutation in one allele of ERCC2 (c.1354C > T, p.Q452X) and a known missense mutation in the other allele (c.2048G > A, p.R683Q). Fibroblasts isolated from the compound heterozygous subject also failed to recover from UV-driven DNA damage, thus recapitulating aspects of XP syndrome in vitro. We describe a novel ERCC2 variant that leads to the breakdown of the NER pathway across generations of a family presenting with severe XP.

Heart failure (HF) is a complex and multifactorial syndrome with high morbidity and mortality rates worldwide. Accumulative evidence suggests that microRNAs (miRNAs) play critical roles in maintaining cardiac homeostasis. The dysregulation of various miRNAs has been reported in different studies on failing human hearts. However, little is known about their circulatory profile. In this study, comprehensive miRNA profiling was performed by next-generation sequencing for plasma samples of 24 HF and 24 age and sex-matched, non-HF patients. A total of 1391 miRNAs were detected, of which 228 miRNAs and 261 miRNAs were commonly expressed in the HF and non-HF groups, respectively. Eight miRNAs (hsa-let-7b-3p, hsa-miR-92b-5p, hsa-miR-145-3p, hsa-miR-206, hsa-miR-664a-5p, hsa-miR-1307-5p, hsa-miR-1908-5p, and hsa-miR-3074-5p) were found to be dysregulated between HF and non-HF patients. The expression of another seven miRNAs (hsa-miR-589-5p, hsa-miR-30b-5p, hsa-miR-654-3p, hsa-miR-1292-5p, hsa-miR-659-5p, hsa-miR-548d-5p, and hsa-miR-7847-3p) was frequently observed in HF patients but not in non-HF cases. Subsequent analyses of target gene prediction and associated pathways revealed the enrichment of pathways related to vascular development, the cell cycle, and transcriptional activity. These data reveal the expression profile and the dysregulation of circulating miRNAs in our patients with HF.