rich experimental basis for further anti-inflammation research of SWHD and sets the foundation for the development of a viral inflammation drug of traditional Chinese medicine. V.ETHNOPHARMACOLOGICAL RELEVANCE In this study, we compare the traditional medicinal knowledge and associated spiritual practices of healers with that of non-healers, to understand the relevance of healers in contemporary times. Given that Brunei Darussalam is well-known for its forest cover, the study also aims to understand the number of species collected from the forests, compared to those from human influenced habitats. MATERIALS AND METHODS A total of six specialist healers from Belait, Tutong, Dusun and Iban communities, and seven non-healers who had personal experience in self-medication using medicinal plants participated in the study. We identified the specialist healers through purposive sampling, on the basis of their reputation in the locality, while the non-healers were those experienced in self-medication, recommended by the healers. Informants were interviewed at their residences, followed by collection trips to the plant habitats. We classified the total recorded ailments into 15 disease categorm were the most targeted group with 67 species used. All medicinal uses with more than one citation were recorded from healers. Medicinal uses cited by healers also had greater correspondence with prior published reports from Brunei Darussalam. Healers believe that combining medicinal plants can produce a synergistic effect. Our study found that traditional knowledge related to healing practices is mostly transmitted vertically from parents to children. We also show that a ritual gift (pikaras) and invocations characteristic of the beliefs of the healers play an important role in facilitating healing. CONCLUSION Our study adds further evidence to prior studies that the medicinal plants and healing practices in the Kiudang region could be considered as disturbance pharmacopoeia. Healers with their knowledge on both therapeutic and spiritual aspects of healing continue to play an important role in local healthcare. Peroxisomes are highly dynamic subcellular compartments with important functions in lipid and ROS metabolism. Impaired peroxisomal function can lead to severe metabolic disorders with developmental defects and neurological abnormalities. Recently, a new group of disorders has been identified, characterised by defects in the membrane dynamics and division of peroxisomes rather than by loss of metabolic functions. However, the contribution of impaired peroxisome plasticity to the pathophysiology of those disorders is not well understood. Mitochondrial fission factor (MFF) is a key component of both the peroxisomal and mitochondrial division machinery. Patients with MFF deficiency present with developmental and neurological abnormalities. Peroxisomes (and mitochondria) in patient fibroblasts are highly elongated as a result of impaired organelle division. The majority of studies into MFF-deficiency have focused on mitochondrial dysfunction, but the contribution of peroxisomal alterations to the pathophysiology is largely unknown. Here, we show that MFF deficiency does not cause alterations to overall peroxisomal biochemical function. However, loss of MFF results in reduced import-competency of the peroxisomal compartment and leads to the accumulation of pre-peroxisomal membrane structures. We show that peroxisomes in MFF-deficient cells display alterations in peroxisomal redox state and intra-peroxisomal pH. Removal of elongated peroxisomes through induction of autophagic processes is not impaired. A mathematical model describing key processes involved in peroxisome dynamics sheds further light into the physical processes disturbed in MFF-deficient cells. https://www.selleckchem.com/products/didox.html The consequences of our findings for the pathophysiology of MFF-deficiency and related disorders with impaired peroxisome plasticity are discussed. V.Cardiotoxicity is a highly relevant, because often life-threatening, adverse effect of doxorubicin (Doxo)-based anticancer therapy. Here, we investigated the Doxo-response of cardiovascular stem/progenitor cells employing a mouse embryonic stem cell (mESC)-based in vitro differentiation model. Endothelial progenitor cells revealed a pronounced Doxo sensitivity as compared to mESC, differentiated endothelial-like (EC), and cardiomyocyte-like cells (CM) and CM progenitors, which rests on the activation of senescence. Doxo treatment of EC progenitors altered protein expression of individual endothelial markers, actin cytoskeleton morphology, mRNA expression of genes related to mitochondrial functions, autophagy, apoptosis, and DNA repair as well as mitochondrial DNA content, respiration and ATP production in the surviving differentiated EC progeny. By contrast, LDL uptake, ATP-stimulated Ca2+ release, and cytokine-stimulated ICAM-1 expression remained unaffected by the anthracycline treatment. Thus, exposure of EC progenitors to Doxo elicits isolated and persistent dysfunctions in the surviving EC progeny. In conclusion, we suggest that Doxo-induced injury of EC progenitors adds to anthracycline-induced cardiotoxicity, making this cell-type a preferential target for pharmacoprotective and regenerative strategies. V.Although anaplastic lymphoma kinase (ALK) inhibitors have good clinical efficacy, the inevitable development of drug resistance is the most common obstacle to their clinical application. There is an urgent need to develop more effective and selective ALK inhibitors to overcome the problem of drug resistance. Here, we screened a series of ALK inhibitors and found that ZX-29 displayed potent cytotoxic activity against ALK rearrangement non-small cell lung cancer (NSCLC) NCI-H2228 cells. Then, we investigated the antitumor effects of ZX-29. We demonstrated that ZX-29 time- and dose-dependently inhibited the viability of NCI-H2228 cells, induced cell cycle arrest in the G1 phase, and then they subsequently progressed into cell death. The type of cell death induced by ZX-29 was apoptosis through endoplasmic reticulum (ER) stress. Interestingly, ZX-29 induced protective autophagy, and inhibiting autophagy could enhance the antitumor effect of ZX-29. Furthermore, ZX-29 suppressed tumor growth in a mouse xenograft model.