Cellulamides: A New Family of Marine-Sourced Linear Peptides from the Underexplored Cellulosimicrobium Genus.

Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B (1 and 2), two novel linear peptides obtained from the culture of the macroalga-associated Cellulosimicrobium funkei CT-R177. The host of this microorganism, the Chlorophyta Codium tomentosum, was collected in the northern Portuguese coast and, in the scope of a bioprospecting study focused on its associated actinobacterial community, strain CT-R177 was isolated, taxonomically identified, and screened for the production of antimicrobial and anticancer compounds. Dereplication of a crude extract of this strain using LC-HRMS(/MS) analysis unveiled a putative novel natural product, cellulamide A (1), that was isolated following mass spectrometry-guided fractionation. An additional analog, cellulamide B (2) was obtained during the chromatographic process and chemically characterized. The chemical structures of the novel linear peptides, including their absolute configurations, were elucidated using a combination of HRMS, 1D/2D NMR spectroscopy, and Marfey's analysis. Cellulamide A (1) was subjected to a set of bioactivity screenings, but no significant biological activity was observed. The cellulamides represent the first family of natural products reported from the Actinomycetota genus Cellulosimicrobium, showcasing not only the potential of less-explored taxa but also of host-associated marine strains for novel chemistry discovery.

Decylprodigiosin: a new member of the prodigiosin family isolated from a seaweed-associated Streptomyces.

Bioprospecting actinobacterial secondary metabolism from untapped marine sources may lead to the discovery of biotechnologically-relevant compounds. While studying the diversity and bioactive potential of Actinomycetota associated with Codium tomentosum, a green seaweed collected in the northern Portuguese cost, strain CT-F61, identified as Streptomyces violaceoruber, was isolated. Its extracts displayed a strong anticancer activity on breast carcinoma T-47D and colorectal carcinoma HCT116 cells, being effective as well against a panel of human and fish pathogenic bacteria. Following a bioactivity-guided isolation pipeline, a new analogue of the red-pigmented family of the antibiotics prodigiosins, decylprodigiosin (1), was identified and chemically characterized. Despite this family of natural products being well-known for a long time, we report a new analogue and the first evidence for prodigiosins being produced by a seaweed-associated actinomycete.

Streptomyces profundus sp. nov., a novel marine actinobacterium isolated from deep-sea sediment of Madeira Archipelago, Portugal.

A novel strain, MA3_2.13T, was isolated from deep-sea sediment of Madeira Archipelago, Portugal, and characterized using a polyphasic approach. This strain produced dark brown soluble pigments, bronwish black substrate mycelia and an aerial mycelium with yellowish white spores, when grown on GYM 50SW agar. The main respiratory quinones were MK-10(H4), MK-10(H6) and MK-10(H8). Diphosphatidylglycerol, phosphatidylethanolamine, three unidentified phospholipids and two glycophospholipids were identified as the main phospholipids. The major cellular fatty acids were iso-C16 : 1, iso-C16 : 0, anteiso-C17 : 1 and anteiso-C17 : 0. Phylogenetic analyses based on 16S rRNA gene showed that strain MA3_2.13T is a member of the genus Streptomyces and was most closely related to Streptomyces triticirhizae NEAU-YY642T (NR_180032.1; 16S rRNA gene similarity 97.9 %), Streptomyces sedi YIM 65188T (NR_044582.1; 16S rRNA gene similarity 97.4 %), Streptomyces mimosae 3MP-10T (NR_170412.1; 16S rRNA gene similarity 97.3 %) and Streptomyces zhaozhouensis NEAU-LZS-5T (NR_133874.1; 16S rRNA gene similarity 97.0 %). Genome pairwise comparisons with closest related type strains retrieved values below the threshold for species delineation suggesting that strain MA3_2.13T represents a new branch within the genus Streptomyces. Based on these results, strain MA3_2.13T (=DSM 115980T=LMG 33094T) is proposed as the type strain of a novel species of the genus Streptomyces, for which the name Streptomyces profundus sp. nov. is proposed.

A análise morfométrica para avaliar a taxa de progressão da fibrose hepática na hepatite C crônica após o transplante renal: uma série de casos / Morphometric analysis to evaluate hepatic fibrosis progression rate in chronic hepatites C after kidney transplantation: a case serie study

O verdadeiro papel do transplante renal na progressão da fibrose hepática causada pelo vírus da hepatite C ainda é imprevisível. A avaliação histológica do fígado é a melhor forma para estimar a evolução da fibrose, embora a análise semiquantitativa traz limitações importantes. Objetivo: aplicar um ensaio morfométrico quantitativo sobre a progressão da fibrose hepática em pacientes renais crônicos com hepatite C. Métodos: trinta pacientes foram inicialmente avaliados, mas apenas sete foram incluídos. Eles foram submetidos à primeira biópsia perto da data do transplante e a segunda biópsia, pelo menos, quatro anos mais tarde. A terapia imunossupressora adotada em todos os casos foi a azatioprina e micofenolato. A taxa de progressão da fibrose (FPR) foi calculada antes e após a data da cirurgia de cada paciente, de acordo com a classificação de Metavir pontuação e análise morfométrica. Resultados: a FPR calculada pelo escore Metavir não mostrou diferença estatística entre pré e pós-transplante (p = 0,9). A FPR calculada pela análise morfométrica foi de 0,58 ± 0,78 antes do transplante e 3,0 ± 3,3 após a cirurgia, com significância estatística entre estes valores (p = 0,0026). Conclusão: na amostra avaliada, a progressão da fibrose hepática foi documentada e quantificada apenas pela análise morfométrica, que é uma abordagem promissora para avaliação histológica desses pacientes.

The real role of renal transplantation in hepatic fibrosis progression caused by hepatitis C virus is still unpredictable. Histological evaluation of the liver is the best form to estimate fibrosis evolution, although semiquantitative analysis carries important limitations. Objective: to apply a morphometric quantitative assay on hepatic fibrosis progression in renal recipients with hepatits C. Methods: thirty patients were initially evaluated, but only seven were included. They underwent the first biopsy near the transplantation date and the second biopsy at least 4 years later. The immunosuppressant therapy adopted in all cases was azatioprine and micofenolate. Fibrosis progression rate (FPR) was calculated before and after the surgery date in each patient according to Metavir score and morphometric analysis. Results: the FPR calculated by Metavir score showed no statistical difference between pre- and post-transplantation (p=0.9). The FPR calculated by the morphometric analysis was 0.58 ± 0.78 before transplantation and 3.0 ± 3.3 after the surgery, with statistical signifycance between these values (p=0.0026). Conclusion: in the sample assessed, the progression of hepatic fibrosis was documented and quantified only by the morphometric analysis, which is as a promising approach to histological evaluation of these patients.

As deficiências auditivas relacionadas às alteraçöes do DNA mitocondrial / Hearing loss related to mitochondrial DNA changes

A deficiência auditiva é sintoma comum que pode apresentar várias etiologias, entre elas as causadas por alteraçöes genéticas. As mutaçöes genéticas podem ocorrer em genes nucleares e mitocondriais. A mitocôndria, uma organela intracelular, tem o seu próprio genoma (DNA), que é uma molécula circular e é transmitido exclusivamente pela mäe. As mutaçöes do DNA mitocondrial säo transmitidas pela linhagem materna, mas podem ocorrer mutaçöes espontâneas. O fenótipo, ou expressäo clínica, da mutaçäo mitocondrial vai depender da quantidade de DNA mitocondrial mutante existente na célula, situaçäo conhecida como heteroplasmia. A mitocôndria tem a funçäo de disponibilizar energia para as células sob a forma de ATP (trifosfato de adenosina). Os órgäos que requerem grande quantidade de energia säo mais comumente acometidos em casos de mutaçöes do DNA mitocondrial, como células nervosas, musculares, endócrinas, ópticas e auditivas. Como a cóclea é grande consumidora de energia, uma mutaçäo no DNA mitocondrial de células ciliadas causa deficiência auditiva do tipo neurossensorial, bilateral, simétrica e progressiva. As deficiências auditivas causadas por mutaçöes no DNA mitocondrial correspondem a 0,5 por cento a 1 por cento de todas as deficiências auditivas de origem genética. Foi realizada uma extensa revisäo bibliográfica, a fim de estudar as deficiências auditivas causadas por alteraçöes no DNA mitocondrial. A deficiência auditiva pode se apresentar na forma isolada (forma näo sindrômica), como nos casos de hiper-sensibilidade aos antibióticos aminoglicosídeos e presbiacusia, ou associada a outras doenças (forma sindrômica), como na síndrome de Kearns-Sayre e diabete e surdez de herança materna

Paralisia laríngea na infância / Vocal Fold Paralysis in Children

A paralisia laríngea na infância apresenta-se de forma bastante distinta da forma como ela se apresenta nos adultos, devido às menores dimensões laríngeas e as etiologias mais relacionadas a malformações congênitas ou traumatismos de parto ou peri-natais. É a segunda causa mais freqüente de estridor no lactente, sendo imperativo um diagnóstico adequado e precoce, para garantir a patência da via aérea e evitar aspiração. Objetivo: Relatar a experiência do serviço no diagnóstico e tratamento deste problema, que constitui um desafio ao laringologista, e discutir as dificuldades comparando-as àquelas descritas na literatura mundial. Material e método: No período de julho de 1994 a fevereiro de 2000, foram diagnosticadas e acompanhadas 17 crianças (sete meninos e 10 meninas, com média de idade de 8,4 anos) com paralisia das pregas vocais em nosso Serviço. O diagnóstico foi feito pela história clínica e o exame nasofibrolaringoscópico. Resultados: Oito pacientes apresentavam paralisia unilateral; e nove, bilateral. A principal causa foi relacionada à correção cirúrgica de malformação cardíaca (40%), seguida de alterações congênitas ou adquiridas do sistema nervoso central (SNC) (30%). Na maioria, as crianças foram tratadas conservadoramente, sendo que três dos quatro casos submetidos à cirurgia laríngea somente foram assim tratados após no mínimo um ano de evolução. Quatro casos apresentaram regressão espontânea parcial ou total da paralisia após 15 meses de seguimento em média. O tempo médio de seguimento foi de 3,1 anos. Discussão e conclusões: As fibras ópticas flexíveis viabilizaram o diagnóstico não invasivo das paralisias laríngeas na infância e possibilitaram seu acompanhamento. Sempre que possível, evitamos intervenção cirúrgica nas crianças antes de seis meses a um ano de evolução, devido à chance de regressão espontânea.

Vocal fold (VF) paralysis in childhood presents in a distinctly from that of adults mostly because of the smaller size of the infantile larynx, but also because the causes are frequently related to congenital abnormalities or birth traumas. It is the second most common cause of stridor in childhood, thus it must be diagnosed and treated early and adequately to secure the airway and feeding. Objectives: Report the authors' experience in the diagnosis and treatment of children with uni or bilateral vocal fold paralysis comparing the difficulties encoutered to those reported in literature. Material and methods: Seventeen children (seven boys and 10 girls) were diagnosed and treated for VF paralysis from July,1994 to February, 2000. Diagnosis was made based on history and fibreoptic examination of the larynx and upper airways. Results: Eight patients presented unilateral VF paralysis and nine had bilateral paralysis. Paralysis was mostly secondary to surgical correction of congenital heart deformities (40%) followed closely by congenital or acquired central nervous system abnormalities (30%). The majority of children were treated conservatively. Three of the four patients who eventually were submitted to laryngeal surgery were only operated after a 1-year follow-up period. Four cases resolved spontaneously after a mean 15-month follow-up period. The average follow-up period was 3,1 years. Discussion and conclusions: Flexible endoscopy has made possible a non-invasive diagnosis and follow-up of laryngeal VF paralysis in children. Whenever possible conservative or reversible treatment should be augmented in order to allow spontaneous recovery of the vocal fold paralysis.

Síndrome de Woakes: a propósito de dois casos / Woake's Syndrome: a propos two cases

A Síndrome de Woakes foi descrita pela primeira vez em 1885, sendo caracterizada por uma etmoidite deformante, com alargamento da pirâmide nasal devido à polipose nasal desde a infância, aplasia do seio frontal, bronquiectasia e discrinia (produçäo, de muco altamente viscoso). Os autores relatam dois casos e suas possíveis variaçös clínicas