Predictors of Endocrine Resistance in a Cohort of Mexican Breast Cancer Patients.

Purpose This study aimed to determine the prevalence of endocrine resistance in a cohort of Hispanic Mexican breast cancer (BC) patients receiving care at Instituto Nacional de Cancerología (INCan). Additionally, the clinical-pathological factors associated with endocrine resistance were identified, and their impact on patient survival was explored. Methods A retrospective analysis of 200 BC patients who attended INCan between 2012 and 2016 with estrogen receptor (ER) and progesterone receptor (PR) positive tumors was made. Endocrine resistance was defined according to the International Consensus Guidelines for Advance Breast Cancer 2 definition. Their clinicopathological characteristics were analyzed to determine the association with endocrine resistance presence. We used sensitivity analyses and multivariate-adjusted logistic regressions, Kaplan-Meier curves, and multivariate-adjusted Cox regressions. P -value < 0.05 was considered as statistically significant. Results Endocrine resistance was observed in 32.5% of patients included in this study. The distinction between hormone resistance and sensitivity was influenced by tumor size and node status. It had a mean diameter of 7.15 cm in endocrine resistance cases compared to 5.71 cm in non-endocrine, with N3 status present in 20% of endocrine resistance cases versus only 2.2% in non-endocrine (p-value < 0.001). The clinical stage exhibited a strong association with endocrine resistance (Risk Ratio [RR] 4.39, 95% confidence interval [95%CI] 1.50, 11.43). Furthermore, endocrine resistance significantly impacted mortality during the follow-up, with a Hazard Ratio [HR] of 23.7 (95%CI 5.20, 108.42) in multivariable-adjusted models. However, a complete pathological response reduced the endocrine resistance risk, as demonstrated by a Risk Ratio (RR) of 0.15 (95% CI 0.03, 0.75). Conclusions Advanced clinical stage at diagnosis predicted endocrine resistance in Hispanic Mexican BC patients. Complete pathologic response in locally advanced disease patients was also a key predictor of endocrine resistance. These results indicated that endocrine resistance was a critical factor in BC during follow-up.

Antivirulence and antipathogenic activity of Mayan herbal remedies against Pseudomonas aeruginosa.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yucatan Peninsula has a privileged wealth of vascular plants with which various Mayan herbal formulations have been developed. However, studies on their antipathogenic and antivirulence properties are scarce. AIM OF THE STUDY: Identify antivirulence properties in Mayan herbal remedies and determine their antipathogenic capacity in burn wounds infected with Pseudomonas aeruginosa. MATERIALS AND METHODS: An ethnobotanical study was conducted in Mayan communities in central and southern Quintana Roo, Mexico. Furthermore, the antipathogenic capacity of three Mayan herbal remedies was analyzed using an animal model of thermal damage and P. aeruginosa infection. Antivirulence properties were determined by inhibiting phenotypes regulated by quorum sensing (pyocyanin, biofilm, and swarming) and by the secretion of the ExoU toxin. The chemical composition of the most active herbal remedy was analyzed using molecular network analysis. RESULTS: It was found that topical administration of the remedy called "herbal soap" (HS) for eleven days maintained 100% survival of the animals, reduced establishment of the bacteria in the burn and prevented its systemic dispersion. Although no curative effect was recorded on tissue damaged by HS treatment, its herbal composition strongly reduced swarming and ExoU secretion. Through analysis of Molecular Networks, it was possible to carry out a global study of its chemical components, and identify the family of oxindole monoterpenoid alkaloids and carboline and tetrahydropyrididole alkaloids. In addition, flavonols, flavan-3-ols, and quinic acid derivatives were detected. CONCLUSIONS: The antipathogenic and antivirulence capacity of ancient Mayan remedies makes them a potential resource for developing new antibacterial therapies to treat burns infected by P. aeruginosa.

Association between Gross Motor Competence and Physical Fitness in Chilean Children Aged 4 to 6 Years.

The preschool period is considered critical for the development of motor competence, but as far as we know, no studies have investigated the association between motor competence and physical fitness in Chilean children. The aim of this study was to analyse the association between gross motor competence and physical fitness, controlling for possible confounding factors. A cross-sectional study was conducted with a sample of 144 preschool children (56.25% girls) with an average age of 5.3 years (4 to 6 years) from the Araucanía region, Chile. Motor competence was measured using the Children's Movement Assessment Battery, 2nd Edition (MABC-2). Regarding physical fitness, the components of cardiorespiratory fitness, lower body muscle strength and speed/agility were evaluated using the Battery to Assess FITness in PREschool (PREFIT). Partial correlation models and analysis of variance (ANCOVA) were used to assess differences in physical fitness between motor competence categories, controlling for age and body mass index. The mean fitness scores for cardiorespiratory fitness, lower body muscle strength and speed/agility components were significantly higher in children with higher gross motor competence. In terms of effect size, large values were found for the lower body strength component in model 1 for boys and in model 2 for the total samples of girls and boys. The results of this study suggest that good levels of gross motor competence are associated with better physical fitness levels.

Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Syndrome: A Case Report and Review of Literature.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant genetic disorder of the small arteries that causes ischemic vascular events, subcortical dementia, behavioral changes, and migraine-like headaches. It is caused by a mutation in the NOTCH3 gene; this disease was first described in 1955 by van Bogaert. We present a 29-year-old woman who presented to the neurology department. She has no history of chronic degenerative diseases. She has been complaining of migraine-like headaches for the past six months. She has cognitive impairment with arithmetic and executive function deficits on neurological examination. Blood biometry and blood chemistry are within normal parameters in her laboratory studies. A viral panel and immunological profile were also performed and were not reactive. A lumbar puncture was performed, and the composition of the cerebrospinal fluid was within normal limits. An MRI was performed, which showed bilateral and symmetric white matter hyperintensities consistent with CADASIL syndrome. There is no specific treatment. Management of these patients is based on symptom control. Neurological sequelae have an important impact on the quality of life and mortality of these patients. For this reason, pharmacological preventive therapies have been sought with controversial evidence.

Kynurenine 3-monooxygenase limits de novo NAD+ synthesis through dietary tryptophan in renal proximal tubule epithelial cell models.

Nicotinamide adenine dinucleotide (NAD+) is a pivotal coenzyme, essential for cellular reactions, metabolism, and mitochondrial function. Depletion of kidney NAD+ levels and reduced de novo NAD+ synthesis through the tryptophan-kynurenine pathway are linked to acute kidney injury (AKI), whereas augmenting NAD+ shows promise in reducing AKI. We investigated de novo NAD+ biosynthesis using in vitro, ex vivo, and in vivo models to understand its role in AKI. Two-dimensional (2-D) cultures of human primary renal proximal tubule epithelial cells (RPTECs) and HK-2 cells showed limited de novo NAD+ synthesis, likely due to low pathway enzyme gene expression. Using three-dimensional (3-D) spheroid culture model improved the expression of tubular-specific markers and enzymes involved in de novo NAD+ synthesis. However, de novo NAD+ synthesis remained elusive in the 3-D spheroid culture, regardless of injury conditions. Further investigation revealed that 3-D cultured cells could not metabolize tryptophan (Trp) beyond kynurenine (KYN). Intriguingly, supplementation of 3-hydroxyanthranilic acid into RPTEC spheroids was readily incorporated into NAD+. In a human precision-cut kidney slice (PCKS) ex vivo model, de novo NAD+ synthesis was limited due to substantially downregulated kynurenine 3-monooxygenase (KMO), which is responsible for KYN to 3-hydroxykynurenine conversion. KMO overexpression in RPTEC 3-D spheroids successfully reinstated de novo NAD+ synthesis from Trp. In addition, in vivo study demonstrated that de novo NAD+ synthesis is intact in the kidney of the healthy adult mice. Our findings highlight disrupted tryptophan-kynurenine NAD+ synthesis in in vitro cellular models and an ex vivo kidney model, primarily attributed to KMO downregulation.NEW & NOTEWORTHY Nicotinamide adenine dinucleotide (NAD+) is essential in regulating mitochondrial function. Reduced NAD+ synthesis through the de novo pathway is associated with acute kidney injury (AKI). Our study reveals a disruption in de novo NAD+ synthesis in proximal tubular models, but not in vivo, attributed to downregulation of enzyme kynurenine 3-monooxygenase (KMO). These findings highlight a crucial role of KMO in governing de novo NAD+ biosynthesis within the kidney, shedding light on potential AKI interventions.

Design and Characterization of Ocular Inserts Loaded with Dexamethasone for the Treatment of Inflammatory Ophthalmic Disease.

The short precorneal residence time of ophthalmic drops is associated with their low absorption; therefore, the development of ocular inserts capable of prolonging and controlling the ophthalmic release of drugs is an interesting option in the design and development of these drugs. A surface response design was developed, specifically the Central Composite Design (CCD), to produce ophthalmic films loaded with Dexamethasone (DEX) by the solvent evaporation method having experimental levels of different concentrations of previously selected polymers (PVP K-30 and Eudragit RS100.). Once optimization of the formulation was obtained, the in vivo test was continued. The optimal formulation obtained a thickness of 0.265 ± 0.095 mm, pH of 7.11 ± 0.04, tensile strength of 15.50 ± 3.94 gF, humidity (%) of 22.54 ± 1.7, mucoadhesion strength of 16.89 ± 3.46 gF, chemical content (%) of 98.19 ± 1.124, release of (%) 13,510.71, and swelling of 0.0403 ± 0.023 g; furthermore, in the in vivo testing the number and residence time of PMN cells were lower compared to the Ophthalmic Drops. The present study confirms the potential use of polymeric systems using PVPK30 and ERS100 as a new strategy of controlled release of ophthalmic drugs by controlling and prolonging the release of DEX at the affected site by decreasing the systemic effects of the drug.

Enhanced oxidative stress resistance in Ustilago maydis and its implications on the virulence.

The phytopathogenic fungus Ustilago maydis causes corn smut by suppressing host plant defenses, including the oxidative burst response. While many studies have investigated how U. maydis responds to oxidative stress during infection, the consequences of heightened resistance to oxidative stress on virulence remain understudied. This study aimed to identify the effects on virulence in U. maydis strains exhibiting enhanced resistance to hydrogen peroxide (H2O2).To achieve this, we exposed U. maydis SG200 to 20 escalating H2O2 shocks, resulting in an adapted strain resistant to concentrations as high as 60 mM of H2O2, a lethal dose for the initial strain. Genetic analysis of the adapted strain revealed five nucleotide substitutions, two minor copy number variants, and a large amplification event on chromosome nine (1-149 kb) encompassing the sole catalase gene. Overexpressing catalase increased resistance to H2O2; however, this resistance was lower than that observed in the adapted strain. Additionally, virulence was reduced in both strains with enhanced H2O2 resistance.In summary, enhanced H2O2 resistance, achieved through either continuous exposure to the oxidative agent or through catalase overexpression, decreased virulence. This suggests that the response to the oxidative stress burst in U. maydis is optimal and that increasing the resistance to H2O2 does not translate into increased virulence. These findings illuminate the intricate relationship between oxidative stress resistance and virulence in U. maydis, offering insights into its infection mechanisms.

Role of SLC5A8 as a Tumor Suppressor in Cervical Cancer.

BACKGROUND: The SLC5A8 gene is silenced in various types of cancer, including cervical cancer; we recently demonstrated that the SLC5A8 gene is also silenced in cervical cancer by hypermethylation of the CpG island in the gene promoter. This study aims to analyze whether SLC5A8 could be a tumor suppressor in cervical cancer. METHODS: After ectopic expressing SLC5A8 in the HeLa cell line, we evaluated its effects on cell behavior both in vitro and in vivo by Confocal immunofluorescence, cell proliferation, migration assays, and xenograft transplants. RESULTS: Overexpression of SLC5A8 in the HeLa cell line decreased its proliferation by arresting cancer cells in the G1 phase and inhibiting cellular migration. Furthermore, we observed that pyruvate increased the SLC5A8 effect, inducing S-phase arrest and inhibiting the entry into mitosis. SLC5A8 decreased tumor growth in xenograft transplants, significantly reducing the volume and tumor weight at 35 days of analysis. CONCLUSIONS: In summary, our results indicate that SLC5A8 has a role as a tumor suppressor in cervical cancer.

Synergistic Effect of Retinoic Acid and Lactoferrin in the Maintenance of Gut Homeostasis.

Lactoferrin (LF) is a glycoprotein that binds to iron ions (Fe2+) and other metallic ions, such as Mg2+, Zn2+, and Cu2+, and has antibacterial and immunomodulatory properties. The antibacterial properties of LF are due to its ability to sequester iron. The immunomodulatory capability of LF promotes homeostasis in the enteric environment, acting directly on the beneficial microbiota. LF can modulate antigen-presenting cell (APC) biology, including migration and cell activation. Nonetheless, some gut microbiota strains produce toxic metabolites, and APCs are responsible for initiating the process that inhibits the inflammatory response against them. Thus, eliminating harmful strains lowers the risk of inducing chronic inflammation, and consequently, metabolic disease, which can progress to type 2 diabetes mellitus (T2DM). LF and retinoic acid (RA) exhibit immunomodulatory properties such as decreasing cytokine production, thus modifying the inflammatory response. Their activities have been observed both in vitro and in vivo. The combined, simultaneous effect of these molecules has not been studied; however, the synergistic effect of LF and RA may be employed for enhancing the secretion of humoral factors, such as IgA. We speculate that the combination of LF and RA could be a potential prophylactic alternative for the treatment of metabolic dysregulations such as T2DM. The present review focuses on the importance of a healthy diet for a balanced gut and describes how probiotics and prebiotics with immunomodulatory activity as well as inductors of differentiation and cell proliferation could be acquired directly from the diet or indirectly through the oral administration of formulations aimed to maintain gut health or restore a eubiotic state in an intestinal environment that has been dysregulated by external factors such as stress and a high-fat diet.

The Effects of a Physical Activity Intervention on Adiposity, Physical Fitness and Motor Competence: A School-Based, Non-Randomized Controlled Trial.

Evidence suggests that early physical activity interventions are a means of preventing childhood obesity and are more effective when delivered in a school setting and based on the ecological model. Therefore, the present study aims to determine the effect of a multicomponent intervention based on the ecological model on adiposity, physical fitness and motor competence in children aged 4 to 5 years. METHODS: This study is a non-randomized controlled trial involving 173 children from Chile. The intervention was based on an ecological model and consisted of a physical activity program with three simultaneous parts, affecting intra- and interpersonal dimensions. The adiposity index, body mass index and waist circumference were measured. For physical fitness, muscle strength in the lower part, speed/agility and cardiorespiratory fitness were measured. Motor competence was assessed using catching, aiming and dynamic and static balance tests. RESULTS: After the intervention, there was no reduction in adiposity indices; in the intervention group, body mass index increased significantly with a high effect size. The intervention group showed significant differences in physical fitness in the components of muscle strength in the lower part (p = 0.000) and speed/agility (p = 0.002). For motor competence, the intervention group showed significant improvements in most components. CONCLUSIONS: The multicomponent intervention did not reduce adiposity indices; however, it caused significant improvements in the physical fitness and motor competence components, so it seems prudent to continue implementing it, given the benefits that adequate levels of motor competence and physical fitness bring to children's health, both in the short and long term.

Effect of Salmonella pathogenicity island 1 and 2 (SPI-1 and SPI-2) deletion on intestinal colonization and systemic dissemination in chickens.

Salmonella's virulence genes are located in two regions known as Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2). SPI-1 allows the bacteria to invade the intestine, while SPI-2 is important for intracellular survival and replication, although it is also necessary for intestinal disease. The aim of this study was to evaluate the effect of the deletion of SPI-1 or SPI-2 genes on the intestinal and systemic salmonellosis using the avian model. Groups of chickens were orally infected with 1010 Colony-Forming Units (CFU) of S. Typhimurium SL1344 WT strain, as well as mutants ∆SPI-1 or ∆SPI-2. At different times post-infection, 5 chickens from each group were euthanized and examined postmortem. Cecum and liver were taken from each chicken for determination of CFU's, histopathological analysis and immunochemistry. Bacterial colonies were recovered from the liver and cecum samples infected with WT strain, while in the cultures from the organs infected with the mutant strains no colonies were recovered or were drastically affected in the ability to survive. In histopathological analysis, the WT strain produced lesions in liver and ceca, and it was detected by immunohistochemistry throughout the course of the infection. On the other hand, organs of chickens infected with ∆SPI-1 or ∆SPI-2 showed attenuated lesions and the immunohistochemistry revealed less bacteria compared to the WT strain. Taken together, our results show the importance of SPI-1 and SPI-2 genes for the complete intestinal and systemic disease in an in vivo avian model.

Synthesis, antibiofilm activity and molecular docking of N-acylhomoserine lactones containing cinammic moieties.

We prepared a series of cinnamoyl-containing furanones by an affordable and short synthesis. The nineteen compounds hold a variety of substituents including electron-donating, electron-withdrawing, bulky and meta-substituted phenyls, as well as heterocyclic rings. Compounds showed antibiofilm activity in S. aureus, K. pneumoniae and, more pronounced, against P. aeruginosa. The disruption of quorum sensing (QS) was tested using the violacein test and molecular docking predicted the antagonism of LasR as a plausible mechanism of action. The trimethoxylated and diene derivatives showed the best antibiofilm and anti-QS properties, thus becoming candidates for further modifications.

Harnessing the Reactivity of Duclauxin toward Obtaining hPTP1B1-400 Inhibitors.

Duclauxin (1) from Talaromyces sp. IQ-313 was reported as a putative allosteric modulator of human recombinant protein tyrosine phosphatase 1B (400 amino acids) (hPTP1B1-400), a validated target for the treatment of type II diabetes. Based on these findings, a one-strain-many-compound (OSMAC) experiment on the IQ-313 strain generated derivatives 5a, 6, and 7. Moreover, a one-/two-step semisynthetic approach guided by docking toward hPTP1B1-400 produced 38 analogs, a series (A) incorporating a lactam functionalization at C-1 (8a-15a, 36a, and 37a) and a series (B) containing a lactam at C-1 and an extra unsaturation between C-7 and C-8 (5b, 11b-37b). In vitro evaluation and structure-activity relationship (SAR) analysis revealed that analogs from the B series are up to 10-fold more active than 1 and derivatives from the A series. Furthermore, duclauxin (1) and 36b were assessed for their potential acute toxicity, estimating their LD50 to be higher than 300 mg/kg. Moreover, 36b significantly reduced glycemia in an insulin tolerance test in mice, suggesting that its mechanism of action is through the PTP1B inhibition.

Association of SLC12A1 and GLUR4 Ion Transporters with Neoadjuvant Chemoresistance in Luminal Locally Advanced Breast Cancer.

Chemoresistance to standard neoadjuvant treatment commonly occurs in locally advanced breast cancer, particularly in the luminal subtype, which is hormone receptor-positive and represents the most common subtype of breast cancer associated with the worst outcomes. Identifying the genes associated with chemoresistance is crucial for understanding the underlying mechanisms and discovering effective treatments. In this study, we aimed to identify genes linked to neoadjuvant chemotherapy resistance in 62 retrospectively included patients with luminal breast cancer. Whole RNA sequencing of 12 patient biopsies revealed 269 differentially expressed genes in chemoresistant patients. We further validated eight highly correlated genes associated with resistance. Among these, solute carrier family 12 member 1 (SLC12A1) and glutamate ionotropic AMPA type subunit 4 (GRIA4), both implicated in ion transport, showed the strongest association with chemoresistance. Notably, SLC12A1 expression was downregulated, while protein levels of glutamate receptor 4 (GLUR4), encoded by GRIA4, were elevated in patients with a worse prognosis. Our results suggest a potential link between SLC12A1 gene expression and GLUR4 protein levels with chemoresistance in luminal breast cancer. In particular, GLUR4 protein could serve as a potential target for drug intervention to overcome chemoresistance.

Aquiluscidin, a Cathelicidin from Crotalus aquilus, and the Vcn-23 Derivative Peptide, Have Anti-Microbial Activity against Gram-Negative and Gram-Positive Bacteria.

Anti-microbial peptides play a vital role in the defense mechanisms of various organisms performing functions that range from the elimination of microorganisms, through diverse mechanisms, to the modulation of the immune response, providing protection to the host. Among these peptides, cathelicidins, a well-studied family of anti-microbial peptides, are found in various animal species, including reptiles. Due to the rise in anti-microbial resistance, these compounds have been suggested as potential candidates for developing new drugs. In this study, we identified and characterized a cathelicidin-like peptide called Aquiluscidin (Aq-CATH) from transcripts obtained from the skin and oral mucosa of the Querétaro's dark rattlesnake, Crotalus aquilus. The cDNA was cloned, sequenced, and yielded a 566-base-pair sequence. Using bioinformatics, we predicted that the peptide precursor contains a signal peptide, a 101-amino-acid conserved cathelin domain, an anionic region, and a 34-amino-acid mature peptide in the C-terminal region. Aq-CATH and a derived 23-amino-acid peptide (Vcn-23) were synthesized, and their anti-microbial activity was evaluated against various species of bacteria in in vitro assays. The minimal inhibitory concentrations against bacteria ranged from 2 to 8 µg/mL for both peptides. Furthermore, at concentrations of up to 50 µM, they exhibited no significant hemolytic activity (<2.3% and <1.2% for Aquiluscidin and Vcn-23, respectively) against rat erythrocytes and displayed no significant cytotoxic activity at low concentrations (>65% cell viability at 25 µM). Finally, this study represents the first identification of an antimicrobial peptide in Crotalus aquilus, which belongs to the cathelicidin family and exhibits the characteristic features of these peptides. Both Aq-CATH and its derived molecule, Vcn-23, displayed remarkable inhibitory activity against all tested bacteria, highlighting their potential as promising candidates for further antimicrobial research.

Molecular mechanisms of resveratrol as chemo and radiosensitizer in cancer.

One of the primary diseases that cause death worldwide is cancer. Cancer cells can be intrinsically resistant or acquire resistance to therapies and drugs used for cancer treatment through multiple mechanisms of action that favor cell survival and proliferation, becoming one of the leading causes of treatment failure against cancer. A promising strategy to overcome chemoresistance and radioresistance is the co-administration of anticancer agents and natural compounds with anticancer properties, such as the polyphenolic compound resveratrol (RSV). RSV has been reported to be able to sensitize cancer cells to chemotherapeutic agents and radiotherapy, promoting cancer cell death. This review describes the reported molecular mechanisms by which RSV sensitizes tumor cells to radiotherapy and chemotherapy treatment.

Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells.

The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) after their transfection into the Saos-2 cell line (null p53) as compared with p53WT transfected cells. The associations between these miRNAs and the signaling pathways in which they might participate were identified with miRPath Software V3.0. QRT-PCR was employed to validate the miRNA profiles. We observed that p53 mutants have an overall negative effect on miRNA expression. In the global expression profile of the human miRNome regulated by the p53R273C mutant, 72 miRNAs were underexpressed and 35 overexpressed; in the p53R175H miRNAs profile, our results showed the downregulation of 93 and upregulation of 10 miRNAs; and in the miRNAs expression profile regulated by the p53R248Q mutant, we found 167 decreased and 6 increased miRNAs compared with p53WT. However, we found overexpression of some miRNAs, like miR-182-5p, in association with processes such as cell migration and invasion. In addition, we explored whether the induction of cell migration and invasion by the p53R48Q mutant was dependent on miR-182-5p because we found overexpression of miR-182-5p, which is associated with processes such as cell migration and invasion. Inhibition of mutant p53R248Q and miR-182-5p increased FOXF2-MTSS1 levels and decreased cell migration and invasion. In summary, our results suggest that p53 mutants increase the expression of miR-182-5p, and this miRNA is necessary for the p53R248Q mutant to induce cell migration and invasion in a cancer cell model.

Integrating Taxonomic and Chemical Diversity of Mangrove-Associated Ascomycetes to Discover or Repurpose Bioactive Natural Products.

Natural product reisolation is a bottleneck when discovering new bioactive chemical entities from nature. To overcome this issue, multi-informative approaches integrating several layers of data have been applied with promising results. In this study, integration of taxonomy, nontargeted metabolomics, and bioactivity information resulted in the selection of Scytalidium sp. IQ-074 and Diaporthe sp. IQ-053 to isolate new natural products active against hPTP1B1-400 and repurpose others as antibiotics. Strain IQ-074 was selected based on the hypothesis that investigating poorly studied and highly metabolic taxa could lead to the isolation of new chemical entities. A chemical investigation of IQ-074 resulted in the isolation of papyracillic acid A (14), 7-deoxypapyracillic acid A (15a and 15b), and linear polyketides scytalpolyols A-D (16-19). Compound 17 inhibited hPTP1B1-400 with a half-maximal inhibitory concentration of 27.0 ± 1.7 µM. Diaporthe sp. IQ-053 was selected based on its antibacterial properties against pathogenic strains. Its chemical investigation yielded dothiorelones A (20) and I (21), cytosporones B (22) and C (23), pestalotiopsone B (24), and diaporthalasin (25). Compounds 22 and 25 inhibited the growth of Staphylococcus aureus and Staphylococcus epidermidis 42R and moderately inhibited the growth of Acinetobacter baumannii A564, a pandrug-resistant bacterium.

Clinical and ultrasonographic findings associated with testicular infiltration in pediatric patients with leukemia.

BACKGROUND: Testicular infiltration is infrequent in pediatric patients with leukemia and can be confused with other testicular conditions. OBJECTIVE: To analyze the presence of clinical and radiological features suggestive of testicular disease and its histological association with leukemia infiltration. METHOD: Retrospective and analytical observational study that included patients with diagnosis of leukemia who underwent biopsy for suspected testicular infiltration. The relationship with the variables analyzed were diagnosis, reason for taking the biopsy, ultrasound findings, stage of treatment, induration, increased volume and pain, with testicular infiltration. RESULTS: Eighteen patients were included; 11 of them with microlithiasis, of which one 1 reported infiltration (odds ratio: 0.075; p = 0.026), no association was found between ultrasound findings and the presence of infiltration. Clinical findings were significantly associated with positive biopsies. CONCLUSIONS: No risk association was found with the ultrasound findings such as microlithiasis and hypoechoic imaging. The clinically evident testicular disease (testicular enlargement and testicular induration) has a significant statistic association with the presence of leukemia infiltration.

ANTECEDENTES: La infiltración testicular en pacientes pediátricos con leucemia es infrecuente y puede ser confundida con otros padecimientos testiculares. OBJETIVO: Analizar la presencia de características clínicas y radiológicas sugestivas de enfermedad testicular y su asociación histológica con infiltración por leucemia. MÉTODO: Estudio observacional retrospectivo y analítico que incluyó a los pacientes con diagnóstico de leucemia sometidos a biopsia por sospecha de infiltración testicular. Se analizó la relación con las variables diagnóstico de base, motivo de toma de biopsia, hallazgos ultrasonográficos, etapa del tratamiento, induración, aumento de volumen y dolor, con infiltración a testículo. RESULTADOS: Se incluyeron 18 pacientes; de ellos, 11 con microlitiasis, de los cuales solo uno reportado con infiltración (odds ratio: 0.075; p = 0.026). No se encontró una asociación entre los hallazgos ultrasonográficos y la presencia de infiltración. Los hallazgos clínicos se asociaron significativamente con biopsias positivas. CONCLUSIONES: No se encontró una asociación de riesgo con los hallazgos por ultrasonido, como microlitiasis e imágenes hipoecogénicas. La enfermedad testicular clínicamente evidente (incremento de volumen e induración testicular) tiene una asociación estadísticamente significativa con la presencia de infiltración por leucemia.