Reduced susceptibility in Burkholderia pseudomallei during carbapenem therapy may lead to treatment failure. We isolated a clinical strain that had developed reduced susceptibility to carbapenems while on treatment. After reviewing the patient's clinical notes, the initial isolate (BUPS01/14) was exposed to carbapenem in vitro to mimic the clinical scenario. The stability of susceptibility of the carbapenem-exposed strain (BUPS01/14R) was examined by serial subculture in antibiotic-free broth. Biochemical and morphological comparison was performed by the VITEK® system and electron microscopy. MICs increased 32-fold following carbapenem exposure and became stable in the antibiotic-free environment. On electron microscopic examination, the BUPS01/14R cells were smoother and less wrinkled compared to BUPS01/14 cells. This report highlights a potential anti-melioidosis treatment failure due to the emergence of resistance while on carbapenem monotherapy. Further study of this strain is necessary to understand the mechanism of resistance at a molecular level.
Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R (IC50= 192 μg/mL) compared to K562 (500 μg/ mL) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.
Understanding metabolite changes and underlying metabolic pathways that may be affected in target plants following essential oils (EOs) exposure is of great importance. In this study, a gas chromatography-mass spectrometry (GC/MS) based metabolomics approach was used to determine the metabolite changes in lettuce (Lactuca sativa L.) shoot and root after exposure to different concentrations of W. trilobata EO. Multivariate analyses of principal component analysis (PCA) and orthogonal partial least-discriminant analysis (OPLS-DA) corroborated that shoot and root of lettuce responded differently to W. trilobata EO. In EO-exposed shoot samples, an increase in the levels of malic acid, glutamine, serine, lactose and α-glucopyranose affected important metabolism pathways such as glycolysis, fructose and mannose metabolism and galactose metabolism. The findings suggest that lettuce may be up-regulating these metabolites to increase tolerance against W. trilobata EO. In EO-exposed root samples, changes in fatty acid biosynthesis, elongation, degradation, phenylalanine, tyrosine and tryptophan metabolism were linked to a decrease in lyxose, palmitic acid, octadecanoic acid, aspartic acid, phenylalanine and myo-inositol. These results indicate that W. trilobata EO could cause alterations in fatty acid compositions and lead to inhibition of roots growth. Together, these findings provide insight into the metabolic responses of lettuce upon W. trilobata EO exposure, as well as potential mechanisms of action of W. trilobata EO as bio-herbicides.
Hyperglycemia, a distinguishing feature of diabetes mellitus that might cause a diabetic foot ulcer (DFU), is an endocrine disorder that affects an extremely high percentage of people. Having a comprehensive understanding of the molecular mechanisms underlying the pathophysiology of diabetic wound healing can help researchers and developers design effective therapeutic strategies to treat the wound healing process in diabetes patients. Using nanoscaffolds and nanotherapeutics with dimensions ranging from 1 to 100 nm represents a state-of-the-art and viable therapeutic strategy for accelerating the wound healing process in diabetic patients, particularly those with DFU. Nanoparticles can interact with biological constituents and infiltrate wound sites owing to their reduced diameter and enhanced surface area. Furthermore, it is noteworthy that they promote the processes of vascularization, cellular proliferation, cell signaling, cell-to-cell interactions, and the formation of biomolecules that are essential for effective wound healing. Nanomaterials possess the ability to effectively transport and deliver various pharmacological agents, such as nucleic acids, growth factors, antioxidants, and antibiotics, to specific tissues, where they can be continuously released and affect the wound healing process in DFU. The present article elucidates the ongoing endeavors in the field of nanoparticle-mediated therapies for the management of DFU.