Gut and Cutaneous Microbiome Featuring Abundance of Lactobacillus reuteri Protected Against Psoriasis-Like Inflammation in Mice.

BACKGROUND: Psoriasis is a chronic autoinflammatory skin disease, and its aetiology remains incompletely understood. Recently, gut microbial dysbiosis is found to be tightly associated with psoriasis. OBJECTIVE: We sought to reveal the causal role of gut microbiota dysbiosis in psoriasis pathogenesis and investigate the protective effect of healthy commensal bacteria against imiquimod -induced psoriasis-like skin response. METHODS: By using fecal microbial transplantation (FMT), 16S rRNA gene-based taxonomic profiling and Lactobacillus supplement, we have assessed the effect of FMT from healthy individuals on psoriasis-like skin inflammation and associated immune disorders in imiquimod-induced psoriasis mice. RESULTS: Here, by using psoriasis mice humanized with the stools from healthy donors and psoriasis patients, the imiquimod-induced psoriasis in mice with psoriasis patient stool was found to be significantly aggravated as compared to the mice with healthy donor stools. Further analysis showed fecal microbiota of healthy individuals protected against Treg/Th17 imbalance in psoriasis. Moreover, we found the gut and skin microbiome in mice receipted with gut microbiota of healthy individuals (HD) differed from those of mice receipted with gut microbiota of psoriasis patients (PSD). 16S rRNA sequencing revealed that Lactobacillus reuteri was greatly enriched in fecal and cutaneous microbiome of HD mice as compared to PSD mice. Intriguingly, supplement with Lactobacillus reuteri was sufficient to increase the expression of anti-inflammatory gene IL-10, reduce Th17 cells counts and confer resistance to imiquimod-induced inflammation on the mice with gut microbiota dysbiosis. CONCLUSION: Our results suggested that the gut microbiota dysbiosis is the potential causal factor for psoriasis and the gut microbiota may serve as promising therapy target for psoriasis patients.

What is the most relevent factor causing pain during ALA-PDT? A multi-center, open clinical pain score research trial of actinic keratosis, acne and condylomata acuminata.

BACKGROUND: To date, it has been reported that the intrinsic factors(lesions location, lesions area, disease tynpes) and extrinsic factors(fluence rate) contribute to the pain during 5-aminolevulinic acid photodynamic therapy (ALA-PDT). But there are few studies on pain during ALA-PDT and lack of sufficient clinical evidence related to the pain intensity. OBJECTIVE: To investigate pain intensity and its relative factors during ALA-PDT and to provide clinical implication. METHODS: The pain numeric rating scale (PNRS) score was used to evaluate the patients' pain intensity at different times during ALA-PDT irradiation from 0 to 10 min during treatment. Gender, age, lesions location, lesions area, ALA concentration and fluence rate were recored. RESULTS: The trial enrolled 274 patients in total, including 118 acne patients (in face), 30 actinic keratosis(AK)patients(in face), 126 Condylomatata acuminate patients(in genitalia). The average pain score in PDT was highest in the patients with actinic keratosis(7.3 ± 0.7), and that of condylomata acuminata was the lowest (4.5 ± 1.1) (p < 0.05). The highest pain score in patients with AK, acne and condylomata acuminata was 8, 6 and 6 respectively which occurred at 4 min, 4 min and 6 min respectively. The pain score of males was higher compared with females in all of the three diseases (p < 0.05). The pain score of facial diseases (5.6 ± 1.2) was higher than that of the genitalia (4.5 ± 1.1) (p < 0.05). The lesions area was positively correlated with the pain score (p < 0.05). In facial diseases, the pain score of patients with high fluence rate (7.3 ± 0.7) was higher than patients with low fluence rate (5.1 ± 0.9) (p < 0.05). CONCLUSIONS: Intrinsic and extrinsic factors both correlate with pain during PDT. Intrinsic factors are difficult to change, so extrinsic factors are the key point to control. We can reduce the fluence rate and extend the treatment time, relieving pain intensity while still ensuring equivalent efficacy.

Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells.

Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC50 values of CD20-SA-NPs were reduced to 5.7 and 2.6 µg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg-1·d-1, iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.

Evaluation of the otolith function using c/oVEMPs in patients with Ménière's disease.

BACKGROUND: Cervical and ocular vestibular evoked myogenic potentials (c/oVEMPs) reflect otolith function. Up-to-date, there are no published reports on the systemic evaluation of otolith function in Ménière's Disease (MD) nor are there any reports on the differences in VEMPs between patients with early and late stage MD. The aim of this study was to evaluate the difference in c/oVEMPs between patients with MD and normal controls, as well as between patients with early and late stage MD. METHODS: Thirty patients with unilateral MD and thirty healthy subjects (as normal controls) were prospectively enrolled. c/oVEMPs using 500 Hz tone-burst stimuli were performed. VEMP tests were repeated 3 times on each subject to ensure reliability and reproducibility of responses. VEMPs were defined as present or absent. Abnormal VEMP was defined by lack of VEMP response. RESULTS: In the control group, abnormal cVEMPs and oVEMPs responses were detected in 6.67 and 3.34 % respectively. In MD patients (20 with early stage MD [ES-MD], 10 with late stage MD [LS-MD]), abnormal cVEMPs and oVEMPs responses were detected in 40 and 16.7 % respectively. More patients with MD showed abnormal responses in c/oVEMPs as compared to the control group (p < 0.05). cVEMPs was more often abnormal as compared to oVEMPs in MD patients (p < 0.05). There was a significant difference in abnormal cVEMP responses between ES-MD patients (25 %) and LS-MD patients (70 %) (p < 0.05). Difference in abnormal oVEMP responses (ES-MD, 5 %; LS-MD, 40 %) was significant (p < 0.05). CONCLUSION: An increased occurrence of abnormal c/oVEMP recordings appeared in MD patients, possibly as a result of hydrops of the otolith. cVEMPs were more often abnormal in MD patients as compared to oVEMPs, suggesting that saccular dysfunction may be more common than utricular dysfunction. Furthermore, o/cVEMP abnormalities in the LS-MD group were significantly higher than those in the ES-MD group, suggesting the trend that otolith damage is gradually increasing with the aggravation of cochlear injury in MD.

Degree of sigmoid sinus compression and the symptom relief using magnetic resonance angiography in venous pulsating tinnitus.

OBJECTIVES: To show that mechanical compression of sigmoid sinus is effective for treatment of pulsatile tinnitus caused by sigmoid sinus enlargement, and to evaluate the relationship between the compression degree of sigmoid sinus and the tinnitus symptom relief using magnetic resonance angiography. METHODS: Medical records of twenty-four patients who were diagnosed with venous tinnitus caused by sigmoid sinus enlargement and underwent mechanical compression of sigmoid sinus were reviewed between April 2009 and May 2013. All these patients received computed tomography and magnetic resonance venography study before undergoing surgery and were followed for at least 4 months. RESULTS: Twenty-three patients felt relief from tinnitus three months after the surgery, and the cross-sectional area of the sigmoid sinus on the tinnitus side was compressed approximately by half (46%-69%) after the surgery. There were 4 patients whose tinnitus suddenly disappeared while lying on the operating table before operation, which may be a result of the patient's emotional tension or postural changes from standing. One of the four patients felt no relief from tinnitus after the surgery, with the cross-sectional area of the sigmoid sinus only compressed by 30%. And two patients of them had a recurrence of tinnitus about 6 months after the surgery. Seven patients had sigmoid sinus diverticula, and tinnitus would not disappear merely by eliminating the diverticulum until by compressing the sigmoid sinus to certain degree. There were 3 minor complications, including aural fullness, head fullness and hyperacusis. The preoperative low frequency conductive and sensorineural hearing loss of 7 subjects subsided. CONCLUSION: Mechanical compression of sigmoid sinus is an effective treatment for pulsatile tinnitus caused by sigmoid sinus enlargement, even if it might be accompanied by sigmoid sinus diverticulum. A compression degree of sigmoid sinus about 54% is adequate for the relief of tinnitus symptom. Cases in which patients' tinnitus suddenly disappeared before the surgery might be excluded to improve the efficacy of surgery.

[Effect of sigmoid sinus plasty in sigmoid sinus original pulsatile tinnitus].

OBJECTIVE: To discuss the diagnosis and management of venous original pulsatile tinnitus associated with sigmoid sinus. METHODS: A retrospective study was conducted on 12 patients who were diagnosed with venous original pulsatile tinnitus associated with sigmoid sinus, and treated with sigmoid sinus constriction surgery. The diagnostic evidences for venous original pulsatile tinnitus associated with sigmoid sinus were re-evaluated, the pulsatile tinnitus improvements and MRV study results before and after surgeries associated with sigmoid sinus were compared. RESULTS: Eleven patients got relief of tinnitus within three months after the surgeries, while one patient had no relief. There were ten patients underwent MRV study, the cross-sectional area of the sigmoid sinus in the healthy side was about two times in the tinnitus side. Constriction sigmoid sinus was performed on the twelve patients. The cross-sectional area of the sigmoid sinus of relieved tinnitus patients were compressed by forty-six percent to eighty-three percent. None of the cases complained of any serious complications. CONCLUSIONS: Sigmoid sinus constriction is an available therapy for pulsatile tinnitus at present. More cases and longer follow-up are necessary to evaluate its treatment effect accurately.

Narrow-band UVB radiation promotes dendrite formation by activating Rac1 in B16 melanoma cells.

Melanocytes are found scattered throughout the basal layer of the epidermis. Following hormone or ultraviolet (UV) light stimulation, the melanin pigments contained in melanocytes are transferred through the dendrites to the surrounding keratinocytes to protect against UV light damage or carcinogenesis. This has been considered as a morphological indicator of melanocytes and melanoma cells. Small GTPases of the Rho family have been implicated in the regulation of actin reorganization underlying dendrite formation in melanocytes and melanoma cells. It has been proven that ultraviolet light plays a pivotal role in melanocyte dendrite formation; however, the molecular mechanism underlying this process has not been fully elucidated. The effect of small GTPases, such as Rac1 and RhoA, on the morphology of B16 melanoma cells treated with narrow-band UVB radiation was investigated. The morphological changes were observed under a phase contrast microscope and the F-actin microfilament of the cytoskeleton was observed under a laser scanning confocal microscope. The pull-down assay was performed to detect the activity of the small GTPases Rac1 and RhoA. The morphological changes were evident, with globular cell bodies and increased numbers of tree branch-like dendrites. The cytoskeletal F-actin appeared disassembled following narrow-band UVB irradiation of B16 melanoma cells. Treatment of B16 melanoma cells with narrow-band UVB radiation resulted in the activation of Rac1 in a time-dependent manner. In conclusion, the present study may provide a novel method through which narrow-band UVB radiation may be used to promote dendrite formation by activating the Rac1 signaling pathway, resulting in F-actin rearrangement in B16 melanoma cells.

Cutaneous neuroendocrine carcinoma of the external auditory canal: a case report and review of the literature.

Cutaneous neuroendocrine carcinoma (cNEC) is rarely seen in the external ear. In this paper, we newly describe a patient with cNEC in his right external auditory canal, followed by a further discussion on the clinical features, diagnosis, and treatments of cNEC of the external ear. A review of the literature showed that cNEC of the external auditory canal generally presents as asymptomatic and that pathology yields the most confirmative diagnosis. A wide resection with adjuvant radiotherapy and chemotherapy is recommended. The overall prognosis of this condition is poor.

Assessment of middle ear effusion and audiological characteristics in young children with adenoid hypertrophy.

BACKGROUND: Otitis media with effusion is a highly concurrent disease in young children with adenoid hypertrophy. The aim of this study was to assess the middle ear effusion and audiological characteristics in children with adenoid hypertrophy and compare the various assessment methods. METHODS: Two hundred and seven candidates who were to undergo adenoidectomy were analyzed using otoscopy, tympanometry, air-conduction auditory steady-state responses (AC-ASSR), and computerized tomography (CT) before adenoidectomy. RESULTS: About 73.4% (304/414) of ears were confirmed to have middle ear effusion (MEE) by otoscopy; 75.4% (312/414) of ears revealed MEE by CT. CT scan correctly predicted all the myringotomy results, giving 100% accuracy on the diagnosis of MEE. Additionally, CT revealed two children with inner ear malformations. Type B tracing tympanogram provided a sensitivity of 91.7% and a specificity of 92.2%. Type C tympanogram with peak pressure < -200 daPa indicated effusion; type C tympanogram having acoustic stapedius reflex could exclude MEE. We excluded the AC-ASSR results of the 4 ears with malformation; 54.4% (223/410) of ears were confirmed of hearing loss. Furthermore, 5.2% (16/310) of the ears with MEE suffered from severe to profound hearing loss. The average threshold level in the 0.25 kHz frequency of children was found to have poorer hearing thresholds than those in the 0.5, 1, 2, and 4 kHz (P < 0.001) frequencies; 29.7% (92/310) of ears with MEE were regarded as normal hearing level. About 55.8% (173/310) of ears with MEE were classified as having slight-mild hearing loss. CONCLUSIONS: The practitioners should pay much attention to the middle ear condition and be aware of a possible development of severe to profound hearing loss during the course of MEE in young children with adenoid hypertrophy. CT scan is good for the assessment of MEE before ventilation tube insertion.

Frequency perception and cell injury in the semicircular canal caused by gentamicin.

OBJECTIVE: The frequency characteristics of the vestibular organ have gained notice in recent years, but the morphologic basis was unknown. This study investigated the gentamicin-induced damage of frequency-selective perception of the horizontal semicircular canal and its morphologic basis. METHODS: Eighty guinea pigs were randomly divided into four groups, one control group and three experimental groups. The experimental animals received gentamicin subcutaneously for 1 to 3 weeks. Short-latency vestibular evoked potentials evoked by 0.5 and 10 Hz step rotation stimuli following drug administration were recorded, and then the crista ampullaris of the horizontal semicircular canals was investigated by scanning and transmission electron microscopy. RESULTS: Damage to hair cells of the crista ampullaris is concentrated at the apex area first and then extends to the peripheral area of the vestibular crista ampullaris when the gentamicin administration time increased. When only the hair cells at the apex area are damaged, the high-frequency (10 Hz) rotation perception of the crista ampullaris of the horizontal semicircular canal was injured, but perceptions to 0.5 Hz step rotation stimulation remained normal. CONCLUSION: Gentamicin mainly affects the high-frequency perception function of the crista ampullaris of the horizontal semicircular canal. The hair cells at the central apex area of the crista ampullaris might be responsible for high-frequency rotation perception function.