Unearthing a Cryptic Biosynthetic Gene Cluster for the Piperazic Acid-Bearing Depsipeptide Diperamycin in the Ant-Dweller Streptomyces sp. CS113.

Piperazic acid is a cyclic nonproteinogenic amino acid that contains a hydrazine N-N bond formed by a piperazate synthase (KtzT-like). This amino acid, found in bioactive natural products synthesized by non-ribosomal peptide synthetases (NRPSs), confers conformational constraint to peptides, an important feature for their biological activities. Genome mining of Streptomyces strains has been revealed as a strategy to identify biosynthetic gene clusters (BGCs) for potentially active compounds. Moreover, the isolation of new strains from underexplored habitats or associated with other organisms has allowed to uncover new BGCs for unknown compounds. The in-house "Carlos Sialer (CS)" strain collection consists of seventy-one Streptomyces strains isolated from the cuticle of leaf-cutting ants of the tribe Attini. Genomes from twelve of these strains have been sequenced and mined using bioinformatics tools, highlighting their potential to encode secondary metabolites. In this work, we have screened in silico those genomes, using KtzT as a hook to identify BGCs encoding piperazic acid-containing compounds. This resulted in uncovering the new BGC dpn in Streptomyces sp. CS113, which encodes the biosynthesis of the hybrid polyketide-depsipeptide diperamycin. Analysis of the diperamycin polyketide synthase (PKS) and NRPS reveals their functional similarity to those from the aurantimycin A biosynthetic pathway. Experimental proof linking the dpn BGC to its encoded compound was achieved by determining the growth conditions for the expression of the cluster and by inactivating the NRPS encoding gene dpnS2 and the piperazate synthase gene dpnZ. The identity of diperamycin was confirmed by High-Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR) and by analysis of the domain composition of modules from the DpnP PKS and DpnS NRPS. The identification of the dpn BGC expands the number of BGCs that have been confirmed to encode the relatively scarcely represented BGCs for depsipeptides of the azinothricin family of compounds and will facilitate the generation of new-to-nature analogues by combinatorial biosynthesis.

17ß-hydroxysteroid dehydrogenase type 1 improves survival in serous epithelial ovarian tumors.

The incidence of ovarian cancer has been epidemiologically related to female reproductive events and hormone replacement therapy after menopause. This highlights the importance of evaluating the role of sexual steroid hormones in ovarian cancer by the expression of enzymes related to steroid hormone biosynthesis in the tumor cells. This study was aimed to evaluate the presence of 17ß-hydroxysteroid dehydrogenase type 1 (17ß-HSD1), aromatase and estrogen receptor alpha (ERα) in the tumor cells and their association with the overall survival in 111 patients diagnosed with primary ovarian tumors. Positive immunoreactivity for 17ß-HSD1 was observed in 74% of the tumors. In the same samples, aromatase and ERα revealed 66% and 47% positivity, respectively. No association was observed of 17ß-HSD1 expression with the histological subtypes and clinical stages of the tumor. The overall survival of patients was improved in 17ß-HSD1-positive group in Kaplan-Meier analysis (P = 0.028), and 17ß-HSD1 expression had a protective effect from multivariate proportional regression evaluation (HR = 0.44; 95% CI 0.24-0.9; P = 0.040). The improved survival was observed in serous epithelial tumors but not in nonserous ovarian tumors. The expression of 17ß-HSD1 in the cells of the serous epithelial ovarian tumors was associated with an improved overall survival, whereas aromatase and ERα were not related to a better survival. The evaluation of hazard risk factors demonstrated that age and clinical stage showed worse prognosis, and 17ß-HSD1 expression displayed a protective effect with a better survival outcome in patients of epithelial ovarian tumors.

Identification of the Biosynthetic Gene Cluster of New Piperazic Acid-Containing Lipopeptides with Cytotoxic Activity in the Genome of Marine Streptomyces PHM034.

Three novel lipopeptides, PM130391 (1), PM130392 (2), and PM140293 (3) were obtained from cultures of Streptomyces tuirus PHM034 isolated from a marine sediment. Structural elucidation of the three compounds showed they belong to the nonribosomal peptides family, and they all contain an acylated alanine, three piperazic acids, a methylated glycine, and an N-hydroxylated alanine. The difference between the three compounds resides in the acyl chain bound to the alanine residue. All three compounds showed cytotoxic activity against human cancer cell lines. Genome sequence and bioinformatics analysis allowed the identification of the gene cluster responsible for the biosynthesis. Inactivation of a nonribosomal peptide synthase of this cluster abolished the biosynthesis of the three compounds, thus demonstrating the involvement of this cluster in the biosynthesis of these lipopeptides.

Determinación de transgenicidad y verificación en el etiquetado de alimentos industrializados de maíz en centros de expendio de Lima metropolitana

Introducción. El consumo de alimentos transgénicos constituye un riesgo potencial para la salud. Sin embargo, en el Perú se carece de información actualizada y confiable sobre la presencia de transgénicos en los alimentos y sobre los datos pertinentes en su etiquetado; de igual manera sobre los alimentos que consumen los animales de abasto, cuyos productos van a ser ingeridos por el humano. Objetivo. Determinar la transgenicidad, mediante la detección del promotor 35S, en productos alimenticios industrializados de maíz para consumo humano y animal, que se comercializan en Lima y verificar sí en el etiquetado se menciona si contiene o no secuencias transgénicas. Métodos. Se analizaron 30 muestras de alimentos para consumo humano y 10 para consumo de animales de abasto; y se revisó el etiquetado. Para la extracción del ADN se utilizó el kit Dneasy Mericon Food, para la detección del P35S el método Real Time-PCR empleando el kit Mericon Screen 35S y para determinar la concentración de copias el kit Mericon Quant Mon 810. Resultados. Se detectó el P35S en el 66,66% de las muestras para consumo humano, y en el 90,00% de las muestras para consumo animal. En el etiquetado del 100% de las muestras para consumo humano y animal no se menciona si contiene o no componentes transgénicos. Conclusiones. La detección de contenido transgénico en la mayoría de los alimentos industrializados de maíz para humanos y animales evidencian la necesidad de su mención en el etiquetado y de la implementación de una política exigente en bioseguridad alimentaria.

Introduction. Consumption of transgenic foods constitutes a potential health risk. However, in Peru there is a lack of updated and reliable information on the presence of transgenics in food and on the relevant data on their labeling; in the same way about the food consumed by animals for supply, whose products are going to be ingested by humans. Objetive. To determine the transgenicity, through the detection of the 35S promoter, in industrialized corn food products for human and animal consumption, which are marketed in Lima and to verify if the labeling mentions whether or not it contains transgenic sequences. Methods. 30 food samples for human consumption and 10 for consumption by animals for production were analyzed; and the labeling was revised. The Dneasy Mericon Food kit was used for DNA extraction, the Real Time-PCR method for P35S detection using the Mericon Screen 35S kit, and the Mericon Quant Mon 810 kit to determine the copy concentration. Results. P35S was detected in 66,66% of the samples for human consumption, and in 90.00% of the samples for animal consumption. The labeling of 100% of the samples for human and animal consumption does not mention whether or not it contains transgenic components. Conclusions. The detection of transgenic content in the majority of industrialized corn foods for humans and animals demonstrates the need to mention them on the label and the implementation of a demanding policy on food biosafety.

The Volatile Organic Compounds of Streptomyces spp.: An In-Depth Analysis of Their Antifungal Properties.

The study of volatile organic compounds (VOCs) has expanded because of the growing need to search for new bioactive compounds that could be used as therapeutic alternatives. These small molecules serve as signals to establish interactions with other nearby organisms in the environment. In this work, we evaluated the antifungal effect of VOCs produced by different Streptomyces spp. This study was performed using VOC chamber devices that allow for the free exchange of VOCs without physical contact between microorganisms or the diffusible compounds they produce. Antifungal activity was tested against Escovopsis weberi, a fungal pathogen that affects ant nest stability, and the results showed that Streptomyces spp. CS014, CS057, CS131, CS147, CS159, CS207, and CS227 inhibit or reduce the fungal growth with their emitted VOCs. A GS-MS analysis of volatiles produced and captured by activated charcoal suggested that these Streptomyces strains synthesize several antifungal VOCs, many of them produced because of the presence of E. weberi, with the accumulation of various VOCs determining the growth inhibition effect.

Co-Expression of Transcriptional Regulators and Housekeeping Genes in Streptomyces spp.: A Strategy to Optimize Metabolite Production.

The search for novel bioactive compounds to overcome resistance to current therapeutics has become of utmost importance. Streptomyces spp. are one of the main sources of bioactive compounds currently used in medicine. In this work, five different global transcriptional regulators and five housekeeping genes, known to induce the activation or overproduction of secondary metabolites in Streptomyces coelicolor, were cloned in two separated constructs and expressed in 12 different strains of Streptomyces spp. from the in-house CS collection. These recombinant plasmids were also inserted into streptomycin and rifampicin resistant Streptomyces strains (mutations known to enhance secondary metabolism in Streptomyces). Different media with diverse carbon and nitrogen sources were selected to assess the strains' metabolite production. Cultures were then extracted with different organic solvents and analysed to search for changes in their production profiles. An overproduction of metabolites already known to be produced by the biosynthesis wild-type strains was observed such as germicidin by CS113, collismycins by CS149 and CS014, or colibrimycins by CS147. Additionally, the activation of some compounds such as alteramides in CS090a pSETxkBMRRH and CS065a pSETxkDCABA or inhibition of the biosynthesis of chromomycins in CS065a in pSETxkDCABA when grown in SM10 was demonstrated. Therefore, these genetic constructs are a relatively simple tool to manipulate Streptomyces metabolism and explore their wide secondary metabolites production potential.

Uncovering the Cryptic Gene Cluster ahb for 3-amino-4-hydroxybenzoate Derived Ahbamycins, by Searching SARP Regulator Encoding Genes in the Streptomyces argillaceus Genome.

Genome mining using standard bioinformatics tools has allowed for the uncovering of hidden biosynthesis gene clusters for specialized metabolites in Streptomyces genomes. In this work, we have used an alternative approach consisting in seeking "Streptomyces Antibiotic Regulatory Proteins" (SARP) encoding genes and analyzing their surrounding DNA region to unearth cryptic gene clusters that cannot be identified using standard bioinformatics tools. This strategy has allowed the unveiling of the new ahb cluster in Streptomyces argillaceus, which had not been retrieved before using antiSMASH. The ahb cluster is highly preserved in other Streptomyces strains, which suggests a role for their encoding compounds in specific environmental conditions. By combining overexpression of three regulatory genes and generation of different mutants, we were able to activate the ahb cluster, and to identify and chemically characterize the encoded compounds that we have named ahbamycins (AHBs). These constitute a new family of metabolites derived from 3-amino-4-hydroxybenzoate (3,4-AHBA) known for having antibiotic and antitumor activity. Additionally, by overexpressing three genes of the cluster (ahbH, ahbI, and ahbL2) for the synthesis and activation of 3,4-AHBA, a new hybrid compound, AHB18, was identified which had been produced from a metabolic crosstalk between the AHB and the argimycin P pathways. The identification of this new BGC opens the possibility to generate new compounds by combinatorial biosynthesis.

Volatile Compounds in Actinomycete Communities: A New Tool for Biosynthetic Gene Cluster Activation, Cooperative Growth Promotion, and Drug Discovery.

The increasing appearance of multiresistant pathogens, as well as emerging diseases, has highlighted the need for new strategies to discover natural compounds that can be used as therapeutic alternatives, especially in the genus Streptomyces, which is one of the largest producers of bioactive metabolites. In recent years, the study of volatile compounds (VOCs) has raised interest because of the variety of their biological properties in addition to their involvement in cell communication. In this work, we analyze the implications of VOCs as mediating molecules capable of inducing the activation of biosynthetic pathways of bioactive compounds in surrounding Actinomycetes. For this purpose, several strains of Streptomyces were co-cultured in chamber devices that allowed VOC exchange while avoiding physical contact. In several of those strains, secondary metabolism was activated by VOCs emitted by companion strains, resulting in increased antibiotic production and synthesis of new VOCs. This study shows a novel strategy to exploit the metabolic potential of Actinomycetes as well as emphasizes the importance of studying the interactions between different microorganisms sharing the same ecological niche.

Combinatorial biosynthesis yields novel hybrid argimycin P alkaloids with diverse scaffolds in Streptomyces argillaceus.

Coelimycin P1 and argimycins P are two types of polyketide alkaloids produced by Streptomyces coelicolor and Streptomyces argillaceus, respectively. Their biosynthesis pathways share some early steps that render very similar aminated polyketide chains, diverging the pathways afterwards. By expressing the putative isomerase cpkE and/or the putative epoxidase/dehydrogenase cpkD from the coelimycin P1 gene cluster into S. argillaceus wild type and in argimycin mutant strains, five novel hybrid argimycins were generated. Chemical characterization of those compounds revealed that four of them show unprecedented scaffolds (quinolizidine and pyranopyridine) never found before in the argimycin family of compounds. One of these compounds (argimycin DM104) shows improved antibiotic activity. Noticeable, biosynthesis of these quinolizidine argimycins results from a hybrid pathway created by combining enzymes from two different pathways, which utilizes an aminated polyketide chain as precursor instead of lysine as it occurs for other quinolizidines.

Perspectives from leadership and frontline staff on telehealth transitions in the Los Angeles safety net during the COVID-19 pandemic and beyond.

Objectives: The start of the COVID-19 pandemic led the Los Angeles safety net health system to dramatically reduce in-person visits and transition abruptly to telehealth/telemedicine services to deliver clinical care (remote telephone and video visits). However, safety net patients and the settings that serve them face a "digital divide" that could impact effective implementation of such digital care. The study objective was to examine attitudes and perspectives of leadership and frontline staff regarding telehealth integration in the Los Angeles safety net, with a focus on telemedicine video visits. Methods: This qualitative study took place in the Los Angeles County Department of Health Services (LAC DHS), the second-largest safety net health system in the US. This system disproportionately serves the uninsured, Medicaid, racial/ethnic minority, low-income, and Limited English Proficient (LEP) patient populations of Los Angeles County. Staff and leadership personnel from each of the five major LAC DHS hospital center clinics, and community-based clinics from the LAC DHS Ambulatory Care Network (ACN) were individually interviewed (video or phone calls), and discussions were recorded. Interview guides were based on the Consolidated Framework for Implementation Research (CFIR), and included questions about the video visit technology platform and its usability, staff resources, clinic needs, and facilitators and barriers to general telehealth implementation and use. Interviews were analyzed for summary of major themes. Results: Twenty semi-structured interviews were conducted in August to October 2020. Participants included LAC DHS physicians, nurses, medical assistants, and physical therapists with clinical and/or administrative roles. Narrative themes surrounding telehealth implementation, with video visits as the case study, were identified and then categorized at the patient, clinic (including provider), and health system levels. Conclusions: Patient, clinic, and health system level factors must be considered when disseminating telehealth services across the safety net. Participant discussions illustrated how multilevel facilitators and barriers influenced the feasibility of video visits and other telehealth encounters. Future research should explore proposed solutions from frontline stakeholders as testable interventions towards advancing equity in telehealth implementation: from patient training and support, to standardized workflows that leverage the expertise of multidisciplinary teams.

Biosynthesis of Largimycins in Streptomyces argillaceus Involves Transient ß-Alkylation and Cryptic Halogenation Steps Unprecedented in the Leinamycin Family.

Largimycins A1 and A2 are key members of a recently identified family of hybrid nonribosomal peptide polyketides belonging to the scarcely represented group of antitumor leinamycins. They are encoded by the gene cluster lrg of Streptomyces argillaceus. This cluster contains a halogenase gene and two sets of genes for the biosynthesis and incorporation of ß branches at C3 and C9. Noticeably, largimycins A1 and A2 are nonhalogenated compounds and only contain a ß branch at C3. By generating mutants in those genes and characterizing chemically their accumulated compounds, we could confirm the existence of a chlorination step at C19, the introduction of an acetyl-derived olefinic exomethylene group at C9, and a propionyl-derived ß branch at C3 in the biosynthesis pathway. Since the olefinic exomethylene group and the chlorine atom are absent in the final products, those biosynthetic steps can be considered cryptic in the overall pathway but essential to generating keto and epoxide functionalities at C9 and C18/C19, respectively. We propose that chlorination at C19 is utilized as an activation strategy that creates the precursor halohydrin to finally yield the epoxy functionality at C18/C19. This represents a novel strategy to create such functionalities and extends the small number of natural product biosynthetic pathways that include a cryptic chlorination step.

In Vitro Antifungal Activity of Ibrexafungerp (SCY-078) Against Contemporary Blood Isolates From Medically Relevant Species of Candida: A European Study.

Background: Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis. Objective: The aim of this study was to assess the in vitro activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of Candida. Methods: Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163 Candida albicans, 108 Candida parapsilosis, 60 Candida glabrata, 40 Candida tropicalis, 29 Candida krusei, 20 Candida orthopsilosis, 6 Candida guilliermondii, 2 Candida famata, 2 Candida lusitaniae, and 1 isolate each of Candida bracarensis, Candida catenulata, Candida dubliniensis, and Candida kefyr. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22 Candida auris from different clinical specimens were evaluated. Results: Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for C. albicans (geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for C. tropicalis (geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC50s (mg/L) against Candida spp. were 0.125/0.06 for C. albicans, 0.5/0.5 for C. parapsilosis, 0.25/0.25 for C. glabrata, 0.5/0.5 for C. tropicalis, 1/1 for C. krusei, 4/2 for C. orthopsilosis, and 0.5/0.5 for C. auris. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%) C. parapsilosis, 4 (5%) C. glabrata, and 1 (2.5%) C. tropicalis. Conclusion: Ibrexafungerp showed a potent in vitro activity against Candida.

In vitro refolding of the structural protein VP1 of parvovirus B19 produces virus-like particles with functional VP1 unique region.

Virus-like particles (VLPs) from Parvovirus B19 (B19V) can be obtained by the self-assembly of the structural proteins VP1 and VP2. It is possible to produce B19V VLPs either from VP2 or a mixture of VP1 and VP2, through its heterologous expression in eukaryotic cells. The difference between VP1 and VP2 protein is a tract of 227 residues located at the N-terminal region of VP1, known as the VP1 unique region (VP1u). This region is critical for B19V infection, including tropism, cell internalization, and lysosomal scape through its phospholipase 2A activity. Herein, we report the in vitro self-assembly of VP1 to form VLPs. These species have phospholipase activity, suggesting that the phospholipase domain is correctly folded. Furthermore, VP1 and VP2 were co-assembled to produce hybrid VLPs which were able to bind and internalize in the non-permissive HepG2 cells, another evidence of the functionality of the in vitro refolded VP1u.

Electronic Health Literacy among Linguistically Diverse Patients in the Los Angeles County Safety Net Health System.

BACKGROUND: Electronic health (eHealth) literacy may affect telehealth uptake, yet few studies have evaluated eHealth literacy in underserved populations. OBJECTIVE: The objective of this study was to describe technology access and use patterns as well as eHealth literacy levels among English-speaking and LEP patients in a Los Angeles safety net health system. METHODS: Patients, aged ≥18 years with a diagnosis of diabetes mellitus and/or hypertension, and their caregivers were recruited from three primary care safety-net clinics in Los Angeles County (California) between June - July 2017. Participants' electronic health literacy was assessed by the eHealth Literacy Scale (eHEALS); participants were also asked about technology access and use. We examined these measures in English-speaking and limited English proficient (LEP) Spanish-speaking patients. RESULTS: A total of 71 participants (62 patients and 9 caregivers) completed the questionnaire. The mean age of the respondents was 56 years old. More than half of participants used a phone that could connect to the Internet (67%). The mean score for 10 eHEALS items was in the moderate range (26/50 points). There was no difference in mean eHEALS between language groups. However, 47% of Spanish-speaking participants "agreed/strongly agreed" that they knew how to use the Internet to answer their health questions, compared to 68% of English-speaking participants (P<.05). CONCLUSIONS: In this sample of patients from a diverse safety net population, perceived skills and confidence in engaging with electronic health systems were low, particularly among LEP Spanish-speakers, despite moderate levels of electronic health literacy. More studies are needed among diverse patient populations to better assess eHealth literacy and patients' digital readiness, and to examine how these patient metrics directly impact telehealth utilization.

Social networks: A quality tool for health dissemination?

BACKGROUND: Social networks are integrated in our lives and, amongst other functions, they are a means of dissemination. There are numerous social network accounts dedicated to health that could be used as an educational resource. The aim of this study was to evaluate the quality of accounts dedicated to health in different social networks, assessing their content and didactic and technological effectiveness and accessibility. MATERIALS AND METHODS: Observational cross-sectional descriptive study in which an analysis of social networks related to health was carried out from April to June 2021 in Spain. Twenty-eight accounts were analysed using a mixed qualitative-quantitative methodology. Content analysis of the speeches disseminated through the selected accounts was performed. In addition, the quality of the accounts was assessed with the Instrumento de Evaluación de Recursos Educativos Digitales (#IE_RED) (Digital Educational Resources Evaluation Instrument [#IE_RED]). RESULTS: Four categories were identified according to the content: student-focused profiles, specific professionals' profiles, current health issues and profiles promoting a healthy lifestyle. In addition, the quality of the accounts obtained a score that indicates they meet the requirements to be validated as a good educational digital resource but could be improved. Instagram social network accounts and those managed by nurses scored significantly higher. CONCLUSIONS: The analysed accounts were revealed as a quality tool for health dissemination, with varied content and applicable to teaching. Their use could be applied both to the training of health professionals and to the promotion of the population's health.

Colibrimycins, Novel Halogenated Hybrid Polyketide Synthase-Nonribosomal Peptide Synthetase (PKS-NRPS) Compounds Produced by Streptomyces sp. Strain CS147.

The improvement of genome sequencing techniques has brought to light the biosynthetic potential of actinomycetes due to the large number of gene clusters they present compared to the number of known compounds. Genome mining is a recent strategy in the search for novel bioactive compounds, which involves the analysis of sequenced genomes to identify uncharacterized natural product biosynthetic gene clusters, many of which are cryptic or silent under laboratory conditions, and to develop experimental approaches to identify their products. Owing to the importance of halogenation in terms of structural diversity, bioavailability, and bioactivity, searching for new halogenated bioactive compounds has become an interesting issue in the field of natural product discovery. Following this purpose, a screening for halogenase coding genes was performed on 12 Streptomyces strains isolated from fungus-growing ants of the Attini tribe. Using the bioinformatics tools antiSMASH and BLAST, six halogenase coding genes were identified. Some of these genes were located within biosynthetic gene clusters (BGCs), which were studied by construction of several mutants for the identification of the putative halogenated compounds produced. The comparison of the metabolite production profile of wild-type strains and their corresponding mutants by ultrahigh-performance liquid chromatography-UV and high-performance liquid chromatography-mass spectrometry allowed us the identification of a novel family of halogenated compounds in Streptomyces sp. strain CS147, designated colibrimycins. IMPORTANCE Genome mining has proven its usefulness in the search for novel bioactive compounds produced by microorganisms, and halogenases comprise an interesting starting point. In this work, we have identified a new halogenase coding gene that led to the discovery of novel lipopetide nonribosomal peptide synthetase/polyketide synthase (NRPS/PKS)-derived natural products, the colibrimycins, produced by Streptomyces sp. strain CS147, isolated from the Attini ant niche. Some colibrimycins display an unusual α-ketoamide moiety in the peptide structure. Although its biosynthetic origin remains unknown, its presence might be related to a hypothetical inhibition of virus proteases, and, together with the presence of the halogenase, it represents a feature to be incorporated in the arsenal of structural modifications available for combinatorial biosynthesis.

A Multidisciplinary Approach to Unraveling the Natural Product Biosynthetic Potential of a Streptomyces Strain Collection Isolated from Leaf-Cutting Ants.

The rapid emergence of bacterial resistance to antibiotics has urged the need to find novel bioactive compounds against resistant microorganisms. For that purpose, different strategies are being followed, one of them being exploring secondary metabolite production in microorganisms from uncommon sources. In this work, we have analyzed the genome of 12 Streptomyces sp. strains of the CS collection isolated from the surface of leaf-cutting ants of the Attini tribe and compared them to four Streptomyces model species and Pseudonocardia sp. Ae150A_Ps1, which shares the ecological niche with those of the CS collection. We used a combination of phylogenetics, bioinformatics and dereplication analysis to study the biosynthetic potential of our strains. 51.5% of the biosynthetic gene clusters (BGCs) predicted by antiSMASH were unknown and over half of them were strain-specific, making this strain collection an interesting source of putative novel compounds.

Clinical outcomes of combined Preserflo Microshunt implantation and cataract surgery in open-angle glaucoma patients.

To assess the effectiveness and safety of the Preserflo Microshunt (PMS) implantation combined with cataract surgery in open-angle glaucoma (OAG) patients. Retrospective, open-label study conducted on insufficiently controlled OAG patients, who underwent a PMS implant procedure with mitomycin-C 0.2%, either alone or in combination with cataract surgery, and were followed for at least 12 months. Success was defined as an intraocular pressure (IOP) ≤ 18 mmHg and a reduction of at least 20% without (complete) or with (qualified) hypotensive medication. Fifty-eight eyes were included in the study, 35 eyes underwent PMS alone and 23 underwent PMS + Phaco. In the overall study sample, mean IOP was significantly lowered from 21.5 ± 3.3 mmHg at baseline to 14.6 ± 3.5 mmHg at month 12 (p < 0.0001). The IOP was significantly reduced in both groups; p < 0.0001 each, respectively. Ocular hypotensive medication was significantly reduced (p < 0.0001) in both groups. No significant differences were observed in IOP lowering or medication reduction between groups. At month 12, 62.1% eyes were considered as complete success and 82.8% eyes as qualified success. The most common adverse events were device close-to-endothelium, conjunctival fibrosis, and wound leakage. PMS, either alone or in combination with phacoemulsification, may be considered as a valuable option for treating OAG patients.

Simultaneous expression of steroid sulfatase and androgen receptor reduced overall survival of patients with epithelial ovarian tumors.

BACKGROUND: Ovarian cancer is usually diagnosed at an advanced stage due to its early asymptomatic course and late-stage non-specific symptoms. This highlights the importance of researching the molecular mechanisms involved in ovarian carcinogenesis as well as the discovery of novel prognostic markers that could help improve the survival outcome of patients. The aim of this study was to evaluate the expression of the steroid sulfatase (STS) in 154 samples of primary ovarian tumors. This protein is crucial in the intracellular conversion of sulfated steroid hormones to active steroid hormones. The presence of STS, 3ß-HSD, and 17ß-HSD1 result in the production of testosterone which act through the androgen receptor (AR) in the tumor cell. The presence of STS and AR in epithelial ovarian tumors and their association to the overall survival of patients was evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: Immunoreactivity for STS was detected in 65% of the tumors and no association was observed with histological subtypes and clinical stages of the tumor. The STS expression in the tumors exhibiting immunoreactive AR resulted in a reduced survival (log-rank test, p = 0.032) and a risk factor in univariate and multivariate analysis, HR = 3.46, CI95% 1.00-11.92, p = 0.049 and HR = 5.92, CI95% 1.34-26.09, p = 0.019, respectively. CONCLUSIONS: These findings suggest that the intracellular synthesis of testosterone acting through its receptor can promote tumor growth and progression. Moreover, the simultaneous expression of STS and AR constitutes an independent predictor of poor prognosis in epithelial ovarian tumors.