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BACKGROUND: Gut microbiome colonization during early life is significant for immunological and physiological development. Maternal microbiome is associated with proper development of infants. The aim of this study was to determine the gut microbiome profiles among Thai healthy pregnant women and its associated factors. METHODS: A multicenter, open trial prospective study was performed at three hospitals in Northern, Central, and Northeastern regions of Thailand. Thai healthy pregnant women attending antenatal clinics were recruited. Fecal samples of subjects at the third trimester of pregnancy were collected with sterilized techniques. The gut microbiome profiles and bacterial diversity were assessed using 16Ss RNA gene sequencing. Demographic data, dietary intake, and anthropometric data were recorded and analyzed. RESULTS: There were 86 healthy pregnant women. The dominant of gut microbiome profiles were Bacteroidetes and Firmicutes. Pregnant women in the Central region had significantly higher of Ruminococcaceae and Lachnospiraceae than those in other regions (p < 0.001). Pregnant women in the Northern region significantly consumed more glutinous rice than those in other regions (p < 0.001). Glutinous rice intake was positively correlated with Bacteroidetes (rho = 0.405, p = 0.01) and negatively correlated with Firmicutes (rho = - 0.440, p = 0.001). Alpha diversity was not correlated with pre-pregnancy body mass index (BMI) or gestational weight gain. CONCLUSIONS: The gut microbiome profiles mainly found in Thai healthy pregnant women were Bacteroidetes and Firmicutes. The gut microbiome profiles in pregnant women found in this study possibly depended on dietary patterns. Glutinous rice with high amylopectin is probably related to abundance of Bacteroidetes.
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Dieta , Microbioma Gastrointestinal , Mujeres Embarazadas , Adulto , Bacterias/clasificación , Estudios de Cohortes , Encuestas sobre Dietas , Femenino , Alimentos/clasificación , Humanos , Oryza/microbiología , Embarazo , Tercer Trimestre del Embarazo , Estudios Prospectivos , Tailandia/etnologíaRESUMEN
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here. METHODS: Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography-mass spectrometry. RESULTS: In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α-diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces). CONCLUSION: LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α-diversity that may contribute to the metabolic changes.
ANTECEDENTES: La gastrectomía vertical laparoscópica (laparoscopic sleeve gastrectomy, LSG) es un tratamiento bien establecido para la obesidad grave y la diabetes tipo 2. Aunque la microbiota intestinal se ha vinculado con la eficacia de LSG, los mecanismos subyacentes siguen siendo poco conocidos. En este estudio se evaluó el efecto de LSG en la obesidad mórbida sobre la microbiota del intestino y de los ácidos biliares (bile acids, BA). MÉTODOS: Tras la aprobación del Comité ético y la obtención del consentimiento informado, los sujetos con obesidad grave que eran candidatos para LSG fueron incluidos en el estudio y seguidos durante 6 meses después de la operación. Se evaluaron la composición y abundancia de la microbiota y BA en las heces mediante secuenciación del gen 16S rRNA, PCR cuantitativa y cromatografía líquida-espectrometría de masas. RESULTADOS: En total, 28 pacientes con una mediana (rango) del IMC de 43,9 kg/m2 (35,0-61,9) fueron reclutados y a los 6 meses tras una LSG, consiguieron una pérdida del exceso de peso de 47,3% (20,7-95,1) y mejoría de las enfermedades metabólicas acompañada de una alteración en la comunidad microbiana fecal. El aumento en la diversidad α y abundancia de especies taxonómicas específicas como Rikenellaceae y Christensenellaceae, se asociaba fuertemente con niveles fecales reducidos de BA. Estos cambios se asociaban de manera positiva y significativa con la pérdida del exceso de peso y las alteraciones metabólicas. Sin embargo, el número total de bacterias fecales en los pacientes fue inferior al de los sujetos sanos (10,84 log10 células/g heces (9,46-11,35)) antes de la operación (10,26 log10 células/g heces (9,44-10,91)) y después de la misma (10,42 log10 células/g heces (9,57-10,96)). CONCLUSIÓN: LSG se asoció con menos BA fecal y mayor abundancia de especies bacterianas específicas y diversidad α lo que puede contribuir a los cambios metabólicos.
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Ácidos y Sales Biliares/análisis , Heces/química , Gastrectomía/métodos , Laparoscopía/estadística & datos numéricos , Obesidad Mórbida/cirugía , Adulto , Carga Bacteriana , Biodiversidad , Diabetes Mellitus Tipo 2/microbiología , Heces/microbiología , Femenino , Microbioma Gastrointestinal/genética , Humanos , Concentración de Iones de Hidrógeno , Masculino , Obesidad Mórbida/microbiología , ARN Ribosómico 16S/genéticaRESUMEN
Poultry is an important high-quality food and protein source for humans. However, chicken is considered a primary source of foodborne diseases, especially Salmonella Enteritidis infection. Reducing Salmonella contamination in live poultry will thus lower the risk to consumers. Our previous studies reported that Lactobacillus reuteri KUB-AC5 can produce a substance with antimicrobial activity against pathogenic bacteria, especially Salmonella. In vivo testing revealed that this strain greatly influenced the ileal microbiota by improving chicken gastrointestinal health and inhibiting certain pathogenic bacteria. However, its activity against Salmonella in chicken is unknown. This study investigated the effects of the probiotic L. reuteri KUB-AC5 at various concentrations against Salmonella and the microbiota status in the gastrointestinal tract of broiler chickens. Four treatments groups were used: negative-control group (no Salmonella challenge), positive-control group (Salmonella challenge), and 5 or 7 log cfu probiotic supplementation to Salmonella-challenged chickens. The resultant microbial diversities at the growing and finisher stages were not significantly different among the groups (P>0.05). However, a high dosage of KUB-AC5 maintained similar microbial diversity in Salmonella-challenged chickens as observed in the non-challenged group in the early stage. The exposure Salmonella can affect the microbial diversity that consequently contributes to the disease progression in chicken. Low and high dosages of KUB-AC5 eliminated S. Enteritidis from the ileum and caecum at 14, 21 and 35 days of age. A high-dose of KUB-AC5 also enhanced Lactobacillaceae levels in the growing stage in both the ileum and caecum and suppressed Enterobacteriaceae levels in the finisher stage on day 35, whereas these effects were not observed in the low dose of KUB-AC5 or control groups. These results support the potential value of high-dose L. reuteri KUB-AC5 supplementation for three days after hatching in preventing Salmonella infection in chickens.
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Pollos/microbiología , Limosilactobacillus reuteri/fisiología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/prevención & control , Probióticos/administración & dosificación , Salmonelosis Animal/microbiología , Salmonelosis Animal/prevención & control , Alimentación Animal/análisis , Animales , Biodiversidad , Ciego/microbiología , Pollos/crecimiento & desarrollo , Aditivos Alimentarios/metabolismo , Íleon/microbiología , Masculino , Salmonella enteritidis/fisiologíaRESUMEN
AIMS: To clarify the effects of Lactobacillus gasseri CP2305 (CP2305) on quality of life and clinical symptoms and its functional mechanisms in patients with irritable bowel syndrome (IBS). METHODS AND RESULTS: After the patients were administered CP2305 daily for 4 weeks, the IBS-severity index score was significantly improved compared with that of the placebo group, and this improvement was accompanied by a reduction in health-related worry and changes in intestinal microbiota. The gene expression profiling of the peripheral blood leucocytes showed that CP2305 treatment significantly up-regulated genes related to eukaryotic initiation factor 2 (EIF2) signalling. Eighty-two genes were down-regulated in IBS patients compared with healthy controls. The expression of 23 of these genes exhibited a CP2305-dependent increase associated with an improvement in IBS severity. The majority of the restored genes were related to EIF2 signalling. CONCLUSIONS: CP2305 administration is a potential candidate therapeutic option for patients with IBS. SIGNIFICANCE AND IMPACT OF THE STUDY: Although probiotics have been proposed to benefit IBS patients, objective clinical evidence and elucidation of the functional mechanism remain insufficient. Our study demonstrated that CP2305 administration beneficially influences IBS patients in both subjective and objective evaluations, and gene expression profiling provided insights into the functional mechanism.
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Síndrome del Colon Irritable/tratamiento farmacológico , Lactobacillus gasseri/fisiología , Probióticos/administración & dosificación , Adulto , Femenino , Humanos , Síndrome del Colon Irritable/genética , Síndrome del Colon Irritable/metabolismo , Masculino , Persona de Mediana Edad , Calidad de Vida , Resultado del TratamientoRESUMEN
AIMS: Axonal aggregates of phosphorylated (p-) transactive response DNA-binding protein 43 kDa (TDP-43) in sporadic amyotrophic lateral sclerosis (sALS) were examined in relation to propagation of the protein in the nervous system. METHODS: Brains and spinal cords of Japanese patients with sALS and control subjects were examined immunohistochemically using formalin-fixed paraffin-embedded specimens with special reference to the topographical distribution, microscopic features, presynaptic aggregates, and correlation between the aggregates in axons and the clinical course. RESULTS: (i) Aggregates of p-TDP-43 were frequently present in axons of the hypoglossal and facial nerve fibres and the spinal anterior horn cells. (ii) Aggregates of p-TDP-43 in the axons showed two characteristic microscopic features - dash-like granuloreticular aggregates (GRAs) and massive aggregates (MAs). (iii) MAs were surrounded by p-neurofilaments, but p-neurofilament immunnoreactivity decreased at the inside of axons with GRAs. (iv) Patients showing MAs and GRAs had a relatively shorter clinical course than patients without the aggregates. (v) Some neurones in the red nucleus in patients were surrounded by synapses containing p- and p-independent (i)-TDP-43, and almost all neurones had lost their nuclear TDP-43 immunoreactivity; 17% of those neurones in the red nucleus also had TDP-43-immunopositive neuronal cytoplasmic inclusions, but no postsynaptic p-TDP-43 deposition was evident. CONCLUSIONS: There are two types of axonal p-TDP-43 aggregates, MAs and GRAs, located predominantly in the facial and hypoglossal nuclei and anterior horn cells. These aggregates may influence the function of neurones, and presynaptic aggregates of the protein induce loss of p-i-TDP-43 in the nuclei of postsynaptic neurones.
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Esclerosis Amiotrófica Lateral/patología , Axones/patología , Proteínas de Unión al ADN/metabolismo , Cuerpos de Inclusión/patología , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/metabolismo , Pueblo Asiatico , Axones/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Femenino , Humanos , Cuerpos de Inclusión/metabolismo , Masculino , Persona de Mediana Edad , Médula Espinal/metabolismo , Médula Espinal/patologíaRESUMEN
Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel ß3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.
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Apoptosis/efectos de los fármacos , Endometriosis/tratamiento farmacológico , Terapia Molecular Dirigida/métodos , Péptidos/farmacología , Secuencia de Aminoácidos , Animales , Canales Catiónicos Regulados por Nucleótidos Cíclicos/metabolismo , Proteínas de Unión al ADN/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Endometriosis/patología , Endometrio/patología , Células Epiteliales/metabolismo , Femenino , Humanos , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Papio , Biblioteca de Péptidos , Péptidos/metabolismo , Enfermedades Peritoneales/tratamiento farmacológico , Enfermedades Peritoneales/patologíaRESUMEN
AIM: The use of sentinel node biopsy (SNB) has not been established for cutaneous squamous cell carcinoma (SCC), and its clinical significance has not been clarified. We investigated the usefulness of and indication criteria for SNB for cutaneous SCC. MATERIALS AND METHODS: Twenty-six patients with high-risk cutaneous SCC that had undergone SNB were retrospectively reviewed. SNB was performed with either the dye method or a combined dye and radioisotope method. RESULTS: Of the 26 patients, recurrence or metastasis was observed in 5 cases (19.2%). Six cases (23.1%) were sentinel node (SN) metastasis-positive. All cases that were SN metastasis-negative survived, and 4 of 6 SN metastasis-positive (66.7%) cases died of the original disease. The 3-year survival rates of all cases, SN metastasis-negative cases, and SN metastasis-positive cases were 82.2%, 100%, and 20.8%, respectively. Tumour thickness was a significant risk factor for SN metastasis (p = 0.049). Recurrence occurred in 4 of 7 cases involving external genitalia, 3 of which died. The 3-year survival rates of external genitalia and nongenital cases were 47.6% and 94.1%, respectively (p = 0.016). CONCLUSIONS: SNB aided the early discovery and treatment of latent lymph node metastasis and helped predict whether SN metastasis had occurred, and therefore helped predict patient prognosis. These results suggest that thickness of the primary lesion is an indication criterion for the use of SNB in cases of cutaneous SCC. SNB should be considered in cases where tumour thickness is ≥2 mm and actively performed in cases ≥5 mm.
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Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Colorantes , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Organotecnecio , Pronóstico , Cintigrafía , Radiofármacos , Estudios Retrospectivos , Colorantes de Rosanilina , Carga TumoralRESUMEN
BACKGROUND: Psoriasis affecting sites such as the hands, feet and nails can be particularly difficult to treat. There are limited data on the efficacy of biological agents to treat these specific localizations. OBJECTIVE: This analysis of a phase 2 regimen-finding study evaluated the efficacy of secukinumab in subjects with moderate-to-severe psoriasis and non-pustular involvement of the hands, feet and/or nails. METHODS: Subjects were randomized (1 : 2 : 2 : 1) to one of three subcutaneous secukinumab 150-mg induction regimens [Single (Week 0), Monthly (Weeks 0, 4, 8), Early (Weeks 0, 1, 2, 4)] or placebo. In the subgroup (n = 131) with hand and/or foot psoriasis [baseline 5-point hand/foot Investigator's Global Assessment (IGA) score ≥2], efficacy was assessed as percentage of subjects achieving an IGA response [a score of 0 (clear) or 1 (minimal) and an improvement of ≥2 points on the 5-point hand/foot scale vs. baseline] at Week 12. In the subgroup (n = 304) with fingernail psoriasis (baseline composite score ≥1), efficacy was assessed as mean percentage change from baseline to Week 12 in a composite score. RESULTS: At Week 12, a markedly higher percentage of subjects with hand and/or foot psoriasis achieved an IGA response with the Early regimen vs. placebo (54.3% vs. 19.2%, P = 0.005). The composite fingernail score improved with the Early and Monthly regimens, but worsened with placebo [percentage mean change from baseline (SE): -19.1% (6.12) and -10.6% (7.06) vs. 14.4% (11.92); P = 0.010 vs. placebo for Early, P = 0.027 for Monthly). Secukinumab was well tolerated. CONCLUSION: Secukinumab demonstrated a beneficial effect on psoriasis of the hands/feet/nails in this short-term assessment.
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Anticuerpos Monoclonales/uso terapéutico , Pie/patología , Mano/patología , Uñas/patología , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Método Doble Ciego , Humanos , Placebos , Psoriasis/patologíaRESUMEN
BACKGROUND: O-linked ß-N-acetylglucosamine (O-GlcNAc) is a glycan essential for fundamental cellular processes such as transcription/translation, nuclear transport, protein stability and protein-protein interactions. However, the role of O-GlcNAc in prostate cancer progression of patients remains poorly unknown. Here we investigated the clinicopathological significance of O-GlcNAc expression level in prostate cancer. METHODS: O-GlcNAc expression level in prostate cancer cells was determined by immunohistochemistry of prostate biopsy specimens obtained from 56 patients later treated with hormone deprivation therapy comparing with adjacent normal prostate glands in the same sections. Overall survival was determined by the Kaplan-Meier and Cox proportional hazards methods with univariate and multivariate models. The effects of reduced O-GlcNAc expression level on proliferation and invasion of prostate cancer LNCaP cells were examined using small interfering RNA (siRNA) targeting O-GlcNAc transferase (OGT), the enzyme responsible for O-GlcNAc biosynthesis. RESULTS: Defining cancer cells showing stronger cytoplasmic staining than normal prostate glands as overexpression of O-GlcNAc, 39% of prostate cancer patients were categorized as overexpression. The Kaplan-Meier and Cox proportional hazards methods with univariate model analysis revealed that O-GlcNAc overexpression was associated with overall survival (P=0.0012 for the Kaplan-Meier and P=0.0021 for Cox univariate hazard model analysis). Furthermore, O-GlcNAc was the only item in which a significant difference was observed at overall survival by multivariate analysis (P=0.0475). Finally, siRNA-mediated OGT knockdown in LNCaP cells resulted in decreased expression of O-GlcNAc and promoted decreased proliferation and tumor cell invasion compared with control siRNA-transfected LNCaP cells. CONCLUSIONS: These results indicate that O-GlcNAc expression level in prostate cancer cells is associated with poor prognosis of prostate cancer patients and likely enhances tumor cell proliferation and invasion.
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Acetilglucosamina/metabolismo , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/mortalidad , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Proliferación Celular , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , N-Acetilglucosaminiltransferasas/genética , N-Acetilglucosaminiltransferasas/metabolismo , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patologíaRESUMEN
BACKGROUND: Herpes zoster (HZ), a reactivation of varicella zoster virus manifested by skin blisters and neuralgia, can lead to postherpetic neuralgia in 10-20% of affected subjects. METHOD: In this study, a cohort of 764 patients with HZ was treated with 1500 mg/day of famciclovir for 7 days, and zoster-associated pain (ZAP) was monitored monthly thereafter for up to 12 months until pain resolution was achieved. Patients were questioned monthly by telephone, and pain was recorded using a numerical rating scale (NRS, 0-10). KEY RESULTS: A total of 751 of 764 (98.3%) patients completed follow-up. The percentage of patients with ZAP was 12.4% at day 90, 7.1% at 6 months and 4.0% at 1 year. After the third month, the NRS were 3 or less in most of the remaining patients with ZAP. Stratified analysis revealed significant persistence of ZAP in patients aged ≥50 years and in those aged ≥65 years, and in patients with either moderate-to-severe skin symptoms or severe pain at the initial consultation.Stratified analyses unexpectedly showed patients who commenced famciclovir at 0-2 days after onset of the eruption had a higher prevalence of ZAP at day 90 than those treated at 3-5 days or ≥6 days after rash onset (P = 0.0164, log-rank test). On further analysis, a higher proportion of patients (45.4%) treated at 0-2 days had moderate to severe symptoms compared with those treated at 3-5 days (40.5%) or ≥6 days (37.0%) (P = 0.0987, Cochran-Armitage test). CONCLUSION & INFERENCE: This study, with an exceptionally high follow-up rate, revealed several new findings, including the influence of disease severity on the delay between the onset of symptoms and seeking medical attention. Six adverse drug reactions were reported in five of 721 patients in the safety analysis, including two severe cases of vomiting and convulsions.
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2-Aminopurina/análogos & derivados , Antivirales/uso terapéutico , Herpes Zóster/complicaciones , Inmunocompetencia , Dolor/etiología , 2-Aminopurina/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Estudios de Cohortes , Famciclovir , Femenino , Estudios de Seguimiento , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/inmunología , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Adulto JovenRESUMEN
Wasp sting is a relatively common arthropod assault, but is sometimes fatal because of anaphylaxis. Rhabdomyolysis is a serious condition, with destruction of striated muscles, and can be induced by various causes such as drugs, heart attacks, CRASH syndrome, and viper bites. Mass envenomation by multiple wasp stings can also cause rhabdomyolysis followed by acute renal failure, although it is extremely rare. We herein report a case who had an anaphylaxis-like reaction and rhabdomyolysis due to multiple wasp stings.
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BACKGROUND: Psoriasis is a chronic inflammatory skin disease of unknown aetiology, and an active form of vitamin D(3) (1α,25-dihydroxyvitamin D(3)) and its analogues (VD3As) are widely used topical reagents for psoriasis treatment. Besides their well-known calcium homeostasis functions, VD3As have been shown to have various immune-modulating effects including the induction of thymic stromal lymphopoietin (TSLP), a master cytokine for inducing Th2 inflammation, in mouse models, but not yet in human psoriasis. VD3As also have been shown to induce cathelicidin, an antimicrobial peptide and strong inducer of innate immunity. Cathelicidin is overexpressed in psoriatic skin lesions; however, its role in this disease seems as yet inconclusive. OBJECTIVES: To clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the modulation of expression patterns of related cytokines in human psoriatic lesions. METHODS: Skin biopsy samples from psoriatic lesions with or without VD3A treatment were subjected to immunohistochemical staining and quantitative reverse transcription-polymerase chain reaction analyses to measure the expression levels of various cytokines. RESULTS: Significantly higher levels of TSLP, thymus and activation-related chemokine and CCR4 expression were observed in VD3A+ skin samples than in VD3A- samples. In contrast, significantly lower levels of interleukin (IL)-12/23 p40, IL-1α, IL-1ß and tumour necrosis factor (TNF)-α expression were observed in the VD3A+ samples than in the VD3A- samples. Expression of cathelicidin was elevated in VD3A+ samples. CONCLUSIONS: Topical VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression of IL-12/23 p40, IL-1α, IL-1ß and TNF-α, thereby ameliorating psoriatic plaques.
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Péptidos Catiónicos Antimicrobianos/biosíntesis , Colecalciferol/análogos & derivados , Citocinas/biosíntesis , Fármacos Dermatológicos/administración & dosificación , Psoriasis/metabolismo , Administración Cutánea , Adulto , Anciano , Western Blotting , Calcitriol/administración & dosificación , Calcitriol/análogos & derivados , Dihidroxicolecalciferoles/administración & dosificación , Quimioterapia Combinada , Femenino , Humanos , Interleucinas/metabolismo , Masculino , Persona de Mediana Edad , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/metabolismo , Catelicidinas , Linfopoyetina del Estroma TímicoRESUMEN
AIMS: To identify and characterize novel bacteriocins from Weissella hellenica QU 13. METHODS AND RESULTS: Weissella hellenica QU 13, isolated from a barrel used to make Japanese pickles, produced two novel bacteriocins termed weissellicin Y and weissellicin M. The primary structures of weissellicins Y and M were determined, and their molecular masses were determined to be 4925·12 and 4968·40 Da, respectively. Analysis of the DNA sequence encoding the bacteriocins revealed that they were synthesized and secreted without N-terminal extensions such as leader sequences or sec signal peptides. Weissellicin M showed significantly high and characteristic homology with enterocins L50A and L50B, produced by Enterococcus faecium L50, while weissellicin Y showed no homology with any other known bacteriocins. Both bacteriocins showed broad antimicrobial spectra, with especially high antimicrobial activity against species, which contaminate pickles, such as Bacillus coagulans, and weissellicin M showed relatively higher activity than weissellicin Y. Furthermore, the stability of weissellicin M against pH and heat was distinctively higher than that of weissellicin Y. CONCLUSIONS: Weissella hellenica QU 13 produced two novel leaderless bacteriocins, weissellicin Y and weissellicin M, and weissellicin M exhibited remarkable potency that could be employed by pickle-producing industry. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report, which represents a complete identification and characterization of novel leaderless bacteriocins from Weissella genus.
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Bacteriocinas/química , Bacteriocinas/genética , Weissella/química , Weissella/fisiología , Secuencia de Aminoácidos , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Bacteriocinas/aislamiento & purificación , Secuencia de Bases , Orden Génico , Calor , Concentración de Iones de Hidrógeno , Espectrometría de Masas , Datos de Secuencia Molecular , Alineación de Secuencia , Weissella/genética , Weissella/aislamiento & purificaciónRESUMEN
The probiotic strain Lactobacillus reuteri KUB-AC5, which was originally isolated from chicken intestine, was fed to newborn broiler chicks for the first week post-hatch. The growth and ileum microbiota of the chickens were carefully monitored for 6 wk. The inclusion of 5 log cfu/g of feed statistically increased the BW gain in the first week compared with that of the control group, but this effect did not continue thereafter. Significant effects on host feed consumption and the feed-to-growth conversion ratio were not detected. The total amount and composition of ileum bacteria were investigated by quantitative PCR and pyrosequencing of the 16S rRNA gene (rDNA), respectively, and were compared between the control and the probiotic-treated groups. The amount of total bacterial 16S rDNA in ileum samples at d 42 was 5 times higher in the probiotic group than in the control, whereas no significant difference was observed at d 21. A composition analysis revealed the establishment of lactobacilli-enriched microbiota in the probiotic-treated chickens at d 42. At this point, the population level and species diversity of lactobacilli were significantly enhanced compared with those of the control group. In addition, Actinobacteria, mainly genera Corynebacterium and Dietzia, were also statistically higher in the probiotic group. However, Proteobacteria, including those of the family Campylobacterales and some other nonbeneficial bacterial groups, were decreased in the probiotic group at the growing stage. Therefore, with probiotic supplementation, it was demonstrated that Lactobacillus reuteri KUB-AC5 in the early post-hatching period had a delayed effect on ileum microbiota, which resulted in the enrichment of potentially beneficial lactobacilli and the suppression of Proteobacteria, including nonbeneficial bacterial groups.
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Alimentación Animal/análisis , Pollos/crecimiento & desarrollo , Pollos/microbiología , Íleon/microbiología , Limosilactobacillus reuteri/clasificación , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Limosilactobacillus reuteri/genética , Masculino , Probióticos/farmacologíaAsunto(s)
Anciano , Humanos , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/uso terapéutico , Nocturia/tratamiento farmacológico , Quinuclidinas/uso terapéutico , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Tetrahidroisoquinolinas/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Nocturia/complicaciones , Encuestas y Cuestionarios , Trastornos del Sueño-Vigilia/complicaciones , Vejiga Urinaria Hiperactiva/complicaciones , Incontinencia Urinaria de Urgencia/complicaciones , Incontinencia Urinaria de Urgencia/tratamiento farmacológicoRESUMEN
BACKGROUND: Laminin-5 (Ln5), a heterotrimer composed of three chains (α3, ß3, and γ2), is a major component of the basement membrane in most adult tissues. One of the chains, Ln5-γ2, is a marker of invasive tumours because it is frequently expressed as a monomer in malignant tumours. Recent studies from our laboratories detected higher levels of Ln5-γ2 expression in basal cell carcinoma (BCC) than in trichoblastoma. Furthermore, Ln5-γ2 overexpression tended to correlate with aggressiveness in BCC. METHODS: In this study, we compared the expression of Ln5-γ2 in invasive squamous cell carcinoma (SCC, n = 62) of the skin to that in preinvasive Bowen's disease (BD, n = 51), followed by analysis of the role of Ln5-γ2 in cancer invasion in vitro. RESULTS: Immunohistochemically, the proportion of SCC cases (86%) strongly positive for Ln5-γ2 expression was higher than that of BD (16%). Real-time RT-PCR showed Ln5-γ2 overexpression in SCC cell line, A431, compared with normal keratinocyte cell line, HaCaT. Ln5-γ2 monomer and proteolytically cleaved, biologically active fragments of Ln5-γ2 were identified in SCC tumour extracts. In in vitro raft cultures, which simulate in vivo conditions, Ln5-γ2 siRNA significantly suppressed epidermal growth factor (EGF)-stimulated A431 cell invasion. CONCLUSION: Our results indicate that Ln5-γ2 has a role in cutaneous SCC invasion.
Asunto(s)
Carcinoma de Células Escamosas/metabolismo , Laminina/metabolismo , Neoplasias Cutáneas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Bowen/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Cutáneas/patologíaAsunto(s)
Moléculas de Adhesión Celular/inmunología , Conjuntiva/inmunología , Penfigoide Benigno de la Membrana Mucosa/inmunología , Antiinfecciosos/uso terapéutico , Antiinflamatorios/uso terapéutico , Vesícula/tratamiento farmacológico , Vesícula/inmunología , Dapsona/uso terapéutico , Femenino , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Persona de Mediana Edad , Penfigoide Benigno de la Membrana Mucosa/tratamiento farmacológico , Prednisolona/uso terapéutico , Resultado del Tratamiento , KalininaRESUMEN
There is a large individual deviation for men, which may be caused by a difference in personality characteristics, in sexual interest in response to sexual stimuli. In this study, we investigate whether attention to the sexual region in a video depends on the personality characteristics of men, assessing this with an eye-tracking system. The study included 30 healthy males with a normal psychological state, who viewed a sexual video in which the sexual region had been designated. Visual attention was measured across the designated region according to gaze duration. Ten types of personality characteristics were evaluated as a T-score by a questionnaire. By Pearson's correlation coefficient, the relations between gaze duration at the sexual region and T-scores of paranoia, psychasthenia and social introversion were found to be statistically significant. By multivariate stepwise regression analysis, only social introversion was negatively associated with the sexual region. Even normal variation of personality characteristics can affect the viewing period of the sexual region. This is the first report showing that subjects with a high degree of paranoia, psychasthenia and particularly social introversion have a tendency to view the sexual region for a shorter duration.