Narrowband ultraviolet B response in cutaneous T-cell lymphoma is characterized by increased bacterial diversity and reduced Staphylococcus aureus and Staphylococcus lugdunensis.

Skin microbiota have been linked to disease activity in cutaneous T-cell lymphoma (CTCL). As the skin microbiome has been shown to change after exposure to narrowband ultraviolet B (nbUVB) phototherapy, a common treatment modality used for CTCL, we performed a longitudinal analysis of the skin microbiome in CTCL patients treated with nbUVB. 16S V4 rRNA gene amplicon sequencing for genus-level taxonomic resolution, tuf2 amplicon next generation sequencing for staphylococcal speciation, and bioinformatics were performed on DNA extracted from skin swabs taken from lesional and non-lesional skin of 25 CTCL patients receiving nbUVB and 15 CTCL patients not receiving nbUVB from the same geographical region. Disease responsiveness to nbUVB was determined using the modified Severity Weighted Assessment Tool: 14 (56%) patients responded to nbUVB while 11 (44%) patients had progressive disease. Microbial α-diversity increased in nbUVB-responders after phototherapy. The relative abundance of Staphylococcus, Corynebacterium, Acinetobacter, Streptococcus, and Anaerococcus differentiated nbUVB responders and non-responders after treatment (q<0.05). Microbial signatures of nbUVB-treated patients demonstrated significant post-exposure depletion of S. aureus (q=0.024) and S. lugdunensis (q=0.004) relative abundances. Before nbUVB, responder lesional skin harboured higher levels of S. capitis (q=0.028) and S. warneri (q=0.026) than non-responder lesional skin. S. capitis relative abundance increased in the lesional skin of responders (q=0.05) after phototherapy; a similar upward trend was observed in non-responders (q=0.09). Post-treatment skin of responders exhibited significantly reduced S. aureus (q=0.008) and significantly increased S. hominis (q=0.006), S. pettenkoferi (q=0.021), and S. warneri (q=0.029) relative abundances compared to that of no-nbUVB patients. Staphylococcus species abundance was more similar between non-responders and no-nbUVB patients than between responders and no-nbUVB patients. In sum, the skin microbiome of CTCL patients who respond to nbUVB is different from that of non-responders and untreated patients, and is characterized by shifts in S. aureus and S. lugdunensis. Non-responsiveness to phototherapy may reflect more aggressive disease at baseline.

In Vitro and In Vivo Medicinal Value of Culinary-Medicinal Lung Oyster Mushroom Pleurotus pulmonarius var. stechangii (Agaricomycetes).

Pleurotus pulmonarius var. stechangii is a culinary-medicinal mushroom commonly cultivated in subtropical countries in Asia. In this study, the in vitro antixanthine oxidase, antihyperglycemic, and in vivo anti-inflammatory activities of a methanol extract (ME) of P. pulmonarius var. stechangii fruiting bodies were evaluated. The xanthine oxidase inhibitory activity of the ME of P. pulmonarius var. stechangii was lower than that of allopurinol, a xanthine oxidase inhibitor used as a positive control. Eleven phenolic compounds were identified from the fruiting bodies of P. pulmonarius var. stechangii by HPLC analysis. The inhibitory effects of ME on α-amylase and α-glucosidase were moderate and lower than that of acarbose, a positive control. The ME inhibited the production of nitric oxide (NO) and nitric oxide synthases (iNOS) protein expression in lipopolysaccharide-induced RAW 264.7 macrophages. It also exhibited an inhibitory effect on carrageenan-induced hind paw edema in a rat model. Taken together, our experimental results demonstrated that the fruiting bodies of P. pulmonarius var. stechangii might be a good natural source to promote human health through its antixanthine oxidase, antihyperglycemia, and anti-inflammatory activities.

Evaluation of Anticholinesterase and Inflammation Inhibitory Activity of Medicinal Mushroom Phellinus pini (Basidiomycetes) Fruiting Bodies.

Phellinus pini, a medicinal mushroom, has been used as folk medicine in Asian countries for treating ailments such as cancer and gastrointestinal diseases. In this study we evaluated in vitro the antidementia and anti-inflammatory activities of Ph. Pini fruiting bodies. Eleven phenol compounds were detected by high-performance liquid chromatography analysis. Acetylcholinesterase and butyrylcholinesterase inhibitory effects of a methanol extract and a hot water extract were moderate and comparable with those of galanthamine, the standard drug used to treat the early stages of Alzheimer's disease. The methanol extract had a neuroprotective effect against glutamate-induced cytotoxicity on PC-12 cells at concentration ranging from 20 to 40 µg/mL. The mushroom extracts also inhibited the production of nitric oxide and the expression of inducible nitric oxide synthase in lipopolysaccharide-induced RAW 264.7 macrophages, and they significantly inhibited in vivo carrageenan-induced hind-paw edema in rats. Therefore, it is suggested that Ph. Pini fruiting bodies possess anticholinesterase and anti-inflammatory effects.

In Vitro Antioxidant, Anti-Diabetes, Anti-Dementia, and Inflammation Inhibitory Effect of Trametes pubescens Fruiting Body Extracts.

Trametes pubescens, white rot fungus, has been used for folk medicine in Asian countries to treat ailments such as cancer and gastrointestinal diseases. This study was initiated to evaluate the in vitro antioxidant, anti-diabetes, anti-dementia, and anti-inflammatory activities of T. pubescens fruiting bodies. The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging activities of T. pubescens methanol (ME) and hot water (HWE) extracts (2.0 mg/mL) were comparable to butylated hydroxytoluene (BHT), the positive control. However, the chelating effects of ME and HWE were significantly higher than that of BHT. The HWE (6 mg/mL) also showed comparable reducing power to BHT. Eleven phenol compounds were detected by high performance liquid chromatography (HPLC) analysis. The α-amylase and α-glucosidase inhibitory activities of the ME and HWE of the mushroom were lower than Acarbose, the standard reference; however, the inhibitory effects of the mushroom extracts at 2.0 mg/mL were moderate. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory effects of ME and HWE were moderate and comparable with galanthamine, the standard drug to treat early stages of Alzheimer's disease (AD). The ME had a neuroprotective effect against glutamate-induced PC-12 cell cytotoxicity at the concentration range of 2-40 µg/mL. The mushroom extracts also showed inflammation inhibitory activities such as production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced murine macrophage-like cell lines (RAW 264.7) and significantly suppressed the carrageenan-induced rat paw-edema. Therefore, fruiting body extracts of T. pubescens demonstrated antioxidant related anti-diabetes, anti-dementia and anti-inflammatory activities.

Activation of GILZ gene by photoactivated 8-methoxypsoralen: potential role of immunoregulatory dendritic cells in extracorporeal photochemotherapy.

Extracorporeal photochemotherapy (ECP) is a widely used method for either immunization against cutaneous T cell lymphoma or immunosuppression of graft-versus-host disease and organ transplant rejection (OTR). Leukapheresed blood is routed through a chamber, in which 8-methoxypsoralen is activated by ultraviolet energy (PUVA), thereby causing DNA crosslinks in processed leukocytes. Return of ECP-processed mononuclear leukocytes to the patient then modulates aberrant T cell immunity. Since interaction with the ECP flow chamber induces monocyte-to-dendritic antigen presenting cell (DC) maturation, we examined the possibility that PUVA may direct the most heavily exposed monocytes to differentiate into tolerogenic DC, while the least exposed DC might remain immunogenic. Expression of the glucocorticoid-induced leucine zipper (GILZ) gene is a distinguishing marker of tolerogenic DC. We report that PUVA directly stimulates GILZ expression. PUVA-exposed DC up-regulated GILZ, down-regulated costimulatory CD80 and CD86, became resistant to Toll-like receptor-induced maturation, increased IL-10 production and decreased IL-12p70 production, all features of immunosuppressive DC. Knockdown of GILZ with siRNA reduced IL-10 and increased IL-12p70 production, demonstrating that GILZ is critical for this profile. PUVA-induction of GILZ expression by DC may help explain how ECP suppresses GVHD and OTR. Conversely, those ECP-processed monocytes minimally exposed to PUVA may mediate ECP's immunogenic effects.