Refractory Transformed Chronic Lymphocytic Leukemia

Keloid is a unique refractory syndrome characterized by a proliferation disorder of the fibroblasts. Recently, photodynamic therapy (PDT) has become a promising technique to modulate fibroblasts. However, use of the photosensitizer Phenalen-1-one (Ph1) in PDT for keloid remains to be explored.

This study investigated the efficacy of Ph1-PDT in the in vitro and in vivo models of keloid.

Cell viability was assessed with a Cell Counting Kit-8 (CCK-8) analysis in keloid fibroblasts. The migrated and invaded keloid fibroblasts after Ph1-PDT were detected using scratch and matrigel invasion assays in vitro. Flow cytometry measured the apoptosis changes. The protein concentrations and the mRNA expression of inflammatory modulators (interleukin 8 (IL-8) and IL-1β) were determined using enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR) methods, respectively. Nude mice were used to perform the transplantation of keloid grafts. Western blot analysis measured the protein expression of CD31, CD34, tumor growth factor β1 (TGF-β1), and collagen 1 in keloid fibroblasts and grafts.

Our results revealed that Ph1-PDT significantly suppressed cell viability, migration and invasion, and enhanced the rate of cell apoptosis and caspase-3 expression in keloid fibroblasts. Moreover, in the nude mice model, Ph1-PDT decreased the volume of the graft and attenuated the vessel density by inhibiting the expression of vessel density biomarkers (CD31 and CD34) in keloid grafts. Furthermore, Ph1-PDT significantly inactivated the inflammatory mediators in keloid grafts. In addition, Ph1-PDT considerably attenuated the development of keloids by inhibiting TGF-β1 and collagen 1 proteins in keloid fibroblasts and grafts.

Ph1-PDT may suppress keloid progression by reducing vessel formation and inflammation, and promoting fibroblast apoptosis, suggesting a potential therapy method for keloid.

Fibromyalgia is a refractory syndrome characterized by chronic wayward pain and complex co-morbid psychological trepidation. The current treatments have a limited role and proper clinical benefits are far from satisfactory. Naturally occurring coumarins such as osthole are known to have analgesic and anti-inflammatory activities. Therefore, the current investigation was designed to explore the potential of natural coumarin esculetin (2.5, 5, and 10 mg/kg) in mitigating reserpine-induced fibromyalgia in Swiss albino mice. Esculetin is a 6,7 dihydroxy-coumarin obtained from various plant sources such as Aesculus hippocastanum L, Ceratostigma willmottianum, Citrus limonia, etc. Reserpine (0.5 mg/kg/day s.c.) treatment for first 3 days, significantly altered the behavior of mice as evidenced by reduced paw withdrawal threshold in pressure application measurement (PAM) test and electronic von-Frey (eVF) test, increased immobility time in forced swim test (FST), increased latency to reach the platform in Morris water maze (MWM) test and reduced number of square crossed in the open field test (OFT). These behavioral deficits with reserpine treatment were integrated with a reduced level of serotonin (5-HT), reduced glutathione (GSH), along with an increase in monoamine oxidase-A (MAO-A) activity, pro-inflammatory cytokines (IL-1β, TNF-α), thiobarbituric acid reactive substances (TBARS) and glutamate level. Esculetin (10 mg/kg/day i.p) treatment for 5 days, significantly abrogated reserpine induced behavioral and biochemical alterations. Whereas, no significant improvement was observed with lower doses of esculetin i.e. 2.5 and 5 mg/kg.