High α-diversity of skin microbiome and mycobiome in Japanese patients with vitiligo.

BACKGROUND: Vitiligo is an acquired pigmentary disorder characterized by depigmented patches on the skin that majorly impact patients' quality of life. Although its etiology involves genetic and environmental factors, the role of microorganisms as environmental factors in vitiligo pathology remains under-researched. OBJECTIVES: Our study explored the presence of characteristic bacterial and fungal flora in vitiligo-affected skin and investigated their potential roles in vitiligo pathogenesis. METHODS: We sequenced bacterial 16S rRNA and the fungal ITS1 region from skin swabs collected at frequently affected sites, namely the forehead and back, of patients with vitiligo. We analyzed bacterial and fungal flora in lesional and non-lesional areas of patients with vitiligo compared with corresponding sites in age- and sex-matched healthy subjects. RESULTS: Our findings revealed elevated α-diversity in both bacterial and fungal flora within vitiligo lesions compared with healthy controls. Notably, bacterial flora exhibited a distinctive composition in patients with vitiligo, and the proportional representation of Enterococcus was inversely correlated with the degree of vitiligo progression. Gammaproteobacteria, Staphylococcus spp., and Corynebacterium spp. were more abundant in vitiligo patients, with notable Staphylococcus spp. prevalence during the stable phase on the forehead. Conversely, the proportion of Malassezia sympodialis was lower and that of Malassezia globosa was higher in the progressive phase on the back of vitiligo patients. CONCLUSION: Our study identified some characteristic bacterial and fungal groups associated with vitiligo activity and prognosis, highlighting the potential roles of microorganisms in pathogenesis and offering insights into personalized disease-management approaches.

The potential value of thallium-201 scintigraphy in the diagnosis of squamous cell carcinoma arising from extensive pyoderma.

Squamous cell carcinoma (SCC) arises from a variety of premalignant conditions, including pyoderma. However, an accurate diagnosis of SCC is sometimes challenging due to indistinguishable inflammatory lesions. Here, we present a case of SCC arising from extensive pyoderma, which was successfully diagnosed by taking advantage of thallium-201 scintigraphy. A 49-year-old man presented with an elevated tumor on his right buttock. Computed tomography (CT) and enhanced magnetic resonance imaging (MRI) identified the tumor, but many indistinguishable lesions were also found around the tumor. Histopathology revealed an atypical proliferation of keratinocytes with cancer pearls inside the tumor nests, while histopathology of nodules around the tumor revealed inflammatory tissues. Positron emission tomography CT (PET/CT) revealed an accumulation of 2-deoxy-2-[18 F]-D-glucose at the axillae and inguinal nodes, and at subcutaneous tissues in addition to the tumor. From the CT, enhanced MRI, and PET/CT analyses it was impossible to differentiate many scattered subcutaneous nodules on the trunk from SCCs. However, thallium-201 scintigraphy identified only the tumor and found no accumulation in other nodules. This finding suggests that thallium-201 scintigraphy is useful for the diagnosis of SCC by excluding false-positive signals detected by other imaging technologies.

Prognosis after steroid pulse therapy and seasonal effect in acquired idiopathic generalized anhidrosis.

Acquired idiopathic generalized anhidrosis is a rare disease with unknown etiology. Sudden loss of sweating function adversely affects young patients' quality of life. Although systemic corticosteroid therapy is the most frequently reported treatment for the disease, its effectiveness is controversial because of the risk of recurrence. To assist clinical decision-making regarding whether to use steroids, we investigated the treatment responsiveness and recurrence rates in patients undergoing steroid pulse therapy and explored factors affecting these rates. We retrospectively collected data of 124 patients who received steroid pulse therapy to calculate the rate of responsiveness to the therapy. We also conducted a time-to-event analysis in a cohort of 57 patients who responded to steroid pulse therapy to estimate the recurrence rate after the therapy. As a result, the response and recurrence rates were 73% and 48%, respectively. Recurrence occurred within 1 year in most patients. The overall effectiveness of steroid pulse therapy was estimated to be 57% considering the recurrence rate. A delay from onset to treatment and younger age appeared to be negative factors for effectiveness. Moreover, we found a significant seasonal effect on both treatment and recurrence: autumn was the worst season for acquired idiopathic generalized anhidrosis in Japan. Our study revealed that steroid pulse therapy can be expected to be effective in half of treated patients. We recommend starting the therapy promptly after the diagnosis; however, it is also worth considering the season for treatment planning.

Success of rechallenging dabrafenib and trametinib combination therapy after trametinib-induced rhabdomyolysis: a case report.

The mitogen-activated protein kinase pathway regulates cell growth and differentiation and is activated by BRAF mutations. BRAF mutations are present in about 40-50% of cutaneous melanomas. More than 90% of BRAF mutations are the V600E type. BRAF inhibitor (dabrafenib or vemurafenib) and MEK inhibitor (trametinib or cobimetinib) combination therapies are effective for BRAF-mutant advanced melanomas. A variety of side effects have been observed with combination therapy including pyrexia, fatigue, nausea, and vomiting. Rhabdomyolysis is one of the most severe adverse events, but it is very rare. Only two cases of rhabdomyolysis have been reported in clinical trials. A 41-year-old Japanese woman with cutaneous melanoma was started on a combination of dabrafenib and trametinib therapy after failure of immune checkpoint therapy. One month later, she complained of myalgia and fatigue and was shifted to our hospital. She was diagnosed with trametinib-induced rhabdomyolysis and showed improvement only with a high volume of fluid infusion. We stopped combination therapy, but there were no useful treatment options for her. After resuming dabrafenib, followed by trametinib, she did not have any problems. This is the first case of a patient with metastatic cutaneous melanoma who could recommence combination therapy after trametinib-associated rhabdomyolysis. We assume that not all patients experience recurrence of rhabdomyolysis in trametinib-induced rhabdomyolysis. As few cases have been reported, more information is needed. We have to evaluate safety carefully if rechallenging combination therapy.

Six new cycloartane glycosides from cimicifuga rhizome.

Three new 15-hydroxy-trinor type (1-3), a new tetranor type (4), and two new 3,15,23,24-tetrahydroxy-16-oxo type cycloartane glycosides (5, 6) were isolated from the rhizome of Cimicifuga heracleifolia KOMAROV. Their structures were determined by the use of the 2D-NMR techniques and chemical evidence.

Dolabellane diterpene and three cycloartane glycosides from Thalictrum squarrosum.

A new dolabellane diterpene glycoside, named squoside A, and three new cycloartane glycosides, named squarrosides V, VI, and VII, have been isolated from the dried aerial parts of Thalictrum squarrosum (Ranunculaceae). Their structures were determined by two dimensional (2D) NMR spectroscopic analysis and chemical evidence.

Four new ent-kaurane diterpenoids from the fruits of Annona cherimola.

Four new ent-kaurane diterpenoids (16R)-ent-kauran-17,19-diol (1), (16R)-17-hydroxy-ent-kauran-19-oic acid (2), (16S)-17-hydroxy-ent-kauran-19-oic acid (3), and (16R)-17-dimethoxy-ent-kauran-19-oic acid (4) have been isolated from the fresh fruits of Annona cherimola together with eight known compounds. Their structures are determined on the basis of spectroscopic data and optical rotation.

Two new cycloartane glycosides from the underground parts of Aquilegia vulgaris.

Two new cycloartane glycosides, named aquilegiosides K and L, have been isolated from the dried underground parts of Aquilegia vulgaris. Their structures were determined by two dimensional (2D) NMR spectroscopic analysis and chemical evidence.

Two labdane diterpene and megastigmane glycosides from Aquilegia hybrida.

Two new labdane diterpene glycosides, named aquosides A and B, and a new megastigmane glycoside, named aquoside C, have been isolated from the air-dried aerial parts of Aquilegia hybrida together with three known compounds comprising a phenolic glycoside and two flavone C-glycosides. Their structures were determined on the basis of spectroscopic data and chemical evidence.

Three new 15,16-seco-cycloartane glycosides from Cimicifuga Rhizome.

Three new 15,16-seco-cycloartane glycosides, which were constructed by a C-C bond cleavage in the D ring, have been isolated from Cimicifuga Rhizome for the first time. Their structures were determined by the use of 2D NMR techniques and chemical evidence.

Four new triterpene glycosides from Nigella damascena.

Four new triterpene glycosides, named nigellosides A, B, C, and D, were from the air-dried aerial parts of Nigella damascena L. (Ranunculaceae), and the structures were elucidated on the basis of spectroscopic data including 2D NMR spectra and chemical evidence. Their chemical structures have been characterized as 3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl gypsogenin 28-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl gypsogenin 28-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl hederagenin 28-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, and 3-O-beta-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyl hederagenin 28-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester.

Two new 15-deoxycimigenol-type and three new 24-epi-cimigenol-type glycosides from Cimicifuga Rhizome.

Two new 15-deoxycimigenol-type (1, 2) and three new 24-epi-cimigenol-type glycosides (3-5) were isolated from Cimicifuga Rhizome, and the structures were elucidated on the basis of spectroscopic data including 2D NMR spectra and chemical evidence. The two new 15-deoxycimigenol-type glycosides were the first cimigenol-type glycosides lacking a hydroxyl group at C-15.

Steroidal glycosides from the fruits of Solanum abutiloides.

Four steroidal glycosides, named abutilosides L, M and N, these being 22S,25S-epoxy-furost-5-ene type glycosides, and abutiloside O, a 20-22 seco-type steroidal glycoside, were isolated from the fresh fruits of Solanum abutiloides. Their structures were determined by 2D NMR spectroscopic analysis and chemical evidence.

Two new 15,16-seco-cycloartane glycosides from Cimicifuga rhizome.

Two new 15,16-seco-cycloartane glycosides (1, 2) were isolated from Cimicifuga Rhizome. Their structures were determined by spectroscopic analysis.

Two new tetranor-cycloartane glycosides from cimicifuga rhizome.

Two new tetranor-cycloartane glycosides (1, 2) were isolated from Cimicifuga Rhizome. Their structures were determined by spectroscopic analysis. These compounds suggested the existence of a biogenetic pathway into C-23 lactone-type cycloartane glycosides.

Four new cycloartane glycosides from Aquilegia vulgaris.

Four new cycloartane glycosides, named aquilegiosides G-J, were isolated from the dried aerial parts of Aquilegia vulgaris. Their structures were determined by spectroscopic analysis and chemical evidence.

Four new cycloartane glycosides from Aquilegia vulgaris and their immunosuppressive activities in mouse allogeneic mixed lymphocyte reaction.

Four new cycloartane glycosides, named aquilegiosides C-F, were isolated from the dried aerial parts of Aquilegia vulgaris. Their structures were determined by two dimensional (2D) NMR spectroscopic analysis and chemical evidence. Aquilegiosides C-F suppressed the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte reaction with IC(50), ranging from 3.7x10(-5) to 2.2x10(-4) M.

Three cycloartane glycosides from Cimicifuga rhizome and their immunosuppressive activities in mouse allogeneic mixed lymphocyte reaction.

One known (1) and two new cycloartane triglycosides, 20S,22R,23S,24R-16beta,23;22,25-diepoxy-cycloartane-3beta,23,24-triol 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranoside (2) and 20S,22R,23S,24R-16beta,23;22,25-diepoxy-cycloartane-3beta,23,24-triol 3-O-(6-O-trans-isoferuloyl-beta-D-glucopyranosyl)-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranoside (3), were isolated from a commercial Cimicifuga Rhizome. Their structures were determined by two dimensional (2D) NMR spectroscopic analysis and chemical evidence. These compounds suppressed the proliferation of lymphocytes in mouse allogeneic mixed lymphocyte reaction.