Computer-made peptide RQ18 acts as a dual antifungal and antibiofilm peptide though membrane-associated mechanisms of action.

The spread of fungi resistant to conventional drugs has become a threatening problem. In this context, antimicrobial peptides (AMPs) have been considered as one of the main alternatives for controlling fungal infections. Here, we report the antifungal and antibiofilm activity and some clues about peptide RQ18's mechanism of action against Candida and Cryptococcus. This peptide inhibited yeast growth from 2.5 µM and killed all Candida tropicalis cells within 2 h incubation. Moreover, it showed a synergistic effect with antifungal agent the amphotericin b. RQ18 reduced biofilm formation and promoted C. tropicalis mature biofilms eradication. RQ18's mechanism of action involves fungal cell membrane damage, which was confirmed by the results of RQ18 in the presence of free ergosterol in the medium and fluorescence microscopy by Sytox green. No toxic effects were observed in murine macrophage cell lines and Galleria mellonella larvae, suggesting fungal target selectivity. Therefore, peptide RQ18 represents a promising strategy as a dual antifungal and antibiofilm agent that contributes to infection control without damaging mammalian cells.

Hepatic venous reconstruction of the left lateral segment with emphasis on anomalous hepatic vein in pediatric liver transplantation.

Left lateral segment grafts have become a suitable option in pediatric liver transplantation (PLT). The correlation between hepatic vein (HV) reconstruction and outcome is relevant when assessing the safe use of these grafts. We retrospectively reviewed the medical records prospectively collected from a pediatric living donor liver transplantation database and conducted a comparative analysis of the different left lateral segment graft types according to HV reconstruction. Donor, recipient, and intraoperative variables were analyzed. Post-transplant outcomes included vascular complications such as hepatic vein outflow obstruction, early (≤30 d) and late (>30 d) PVT, hepatic artery thrombosis, and graft survival. From February 2017 to August 2021, 303 PLTs were performed. According to venous anatomy, the distribution of the left lateral segment was as follows: single HV (type I) in 174 (57.4%), close HVs, simple venoplasty for reconstruction (type II) in 97 (32.01%), anomalous hepatic vein (AHV) with a distance between the HVs orifices that allowed simple venoplasty (type IIIA) in 25 (8.26%) and AHV with a distance between the HVs orifices requiring homologous venous graft interposition (type IIIB) in 07 (2.31%) grafts. Type IIIB grafts came from male donors ( p =0.04) and had a higher mean donor height ( p =0.008), a higher mean graft weight, and a higher graft-to-recipient weight ratio, both p =0.002. The median follow-up time was 41.4 months. The overall cumulative graft survival was 96.3%, and comparative graft survival showed no difference (log-rank p =0.61). No hepatic vein outflow obstructions were observed in this cohort study. There was no statistically significant difference in the post-transplant outcomes between the graft types. The venous reconstruction of the AHV with homologous venous graft interposition had similar outcomes in the short and long term.

Prevalence of Mollicutes among men who have sex with men and transgender women aged 15 to 19 years in Salvador, North-eastern Brazil.

BACKGROUND: Some species of Mollicutes have been associated with different pathologies of the urogenital tract in humans, with a high prevalence among adult men who have sex with men (MSM) and transgender women (TGW). However, few studies have been performed to investigate its prevalence among adolescents. In this study, we estimated the initial prevalence of Mycoplasma genitalium (MG), Mycoplasma hominis (MH), Ureaplasma urealyticum (UU), and Ureaplasma parvum (UP); the rate of misdiagnosis at different anatomical sites; and the associated factors with positive tests for Mollicutes among MSM and TGW aged 15 to 19 years enrolled in the PrEP1519 study. METHODS: PrEP-1519 is the first study to investigate the effectiveness of pre-exposure prophylaxis for human immunodeficiency virus among adolescent MSM and TGW aged 15 to 19 in Latin America. Oral, anal, and urethral swabs were taken from 246 adolescents upon enrolment in the study to detect MG, MH, UU, and UP by quantitative polymerase chain reaction (qPCR). Bivariate and multivariate analyses were conducted by Poisson regression and 95% confidence intervals (95% CI) were estimated. RESULTS: The prevalence of Mollicutes was 32.1%. UU was the most prevalent species (20.7%), followed by MH (13.4%), MG (5.7%), and UP (3.2%); 67.3% of the positive samples would have been missed if only urethral samples had been taken. Receptive anal sex (prevalence ratio [PR] = 1.79; 95% CI = 1.07-3.01) and clinical suspicion of sexually transmitted infection (PR = 1.62; 95% CI = 1.01-2.61) were factors associated with the detection of Mollicutes in general. Group sex (PR = 1.98; 95% CI = 1.12-3.50) and receptive anal sex (PR = 2.36; 95% CI = 0.95-5.86) were associated with the detection of Mycoplasma spp. No sociodemographic, clinical, or behavioural variable was significantly associated with the detection of Ureaplasma spp. CONCLUSIONS: A high prevalence of Mollicutes was observed among adolescent MSM and TGW, especially at extragenital sites. Further research is required to understand the epidemiological profile of high-risk adolescents in different regions and contexts, and to investigate the pathogenesis of Mollicutes in the oral and anal mucosa before routine screening can be recommended in clinical practice.

Prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis infections among adolescent men who have sex with men and transgender women in Salvador, Northeast Brazil.

Adolescent men who have sex with men (AMSM) and transgender women (ATGW) enrolled as part of the PrEP1519 study between April 2019 and February 2021 in Salvador were tested for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections.We performed real-time polymerase chain reaction using oropharyngeal, anal, and urethral swabs; assessed factors associated with NG and CT infections using multivariable Poisson regression analysis with robust variance; and estimated the prevalence ratios (PRs) and 95% confidence intervals (95% CIs). In total, 246 participants were included in the analyses (median age: 18.8; IQR: 18.2-19.4 years). The overall oropharyngeal, anal, and urethral prevalence rates of NG were 17.9%, 9.4%, 7.6%, and 1.9%, respectively. For CT, the overall, oropharyngeal, anal, and urethral prevalence rates were 5.9%, 1.2%, 2.4%, and 1.9%, respectively. A low level of education, clinical suspicion of STI (and coinfection with Mycoplasma hominis were associated with NG infection. The prevalence of NG and CT, especially extragenital infections, was high in AMSM and ATGW. These findings highlight the need for testing samples from multiple anatomical sites among adolescents at a higher risk of STI acquisition, implementation of school-based strategies, provision of sexual health education, and reduction in barriers to care.

Liver transplantation for hilar inflammatory myofibroblastic tumor: Case report and review of the literature.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) of the liver are rare neoplasms. These tumors are difficult to distinguish from other neoplasms by radiological examination, have uncertain evolution, and there is no consensus on the treatment of these lesions. Hilar tumors can involve the portal vein, hepatic artery, bile duct, and spread to the branches of the portal triad, causing obstructive symptoms, occlusive phlebitis, and portal hypertension. Thus, liver transplantation (LT) is an excellent alternative for locally advanced hilar tumors, since it ensures complete tumor resection with free margins. METHODS/RESULTS: We present a literature review and a case report showing a 3-year-old boy with liver IMT invading the hepatic hilum and inferior vena cava, who underwent a successful living donor liver transplantation that required portal vein and vena cava replacement. CONCLUSION: The incidence of hilar IMTs is low and there is no well-established standard treatment. Liver transplantation for a hilar tumor with vascular invasion was acceptable in this case because the radically of the surgery was the key for the cure, and because the tumor was benign in nature.

Anterior hepatic resection: A simple and safe technique for reducing the antero-posterior diameter of the liver graft for small pediatric recipients.

BACKGROUND: The techniques involved in neonatal and infantile transplantation require approaches that can sculpt a left lateral segment (LLS) to the right shape and size and avoid large-for-size syndrome. The aim of this article is to describe the anterior hepatic resection (AHR) of the LLS in pediatric LDLT. METHODS: A retrospective anatomical study of preoperative image studies, description of the technique for AHR, and short-term results. RESULTS: The AHR was performed in eight cases. All donors were male, with average age, BW, and BMI of 28.3 ± 5.9 years, 74.2 ± 9.3 kg, and 24.3 ± 2.6 kg/m2, respectively. Donors were discharged at an average of 3.6 ± 0.8 days. The median recipient age and BW at transplantation were 6.9 (2.7 to 11) months and 5.9 (3.9 to 8) kg, respectively, and the recipient-to-donor body weight ratio (RDBW) was <0.1 in all but one case. The mean percentage reduction in graft weight and in the antero-posterior diameter were 33.2% ± 5.5% and 38.3% ± 12.6%, respectively. The average (SD) GRWR was 4.8% ± 1.7% before all the resections and 3.5% ± 1.0% after the procedures. Seven patients were primarily closed. CONCLUSION: After LLS resection, a nonanatomical anterior resection of the LLS was accomplished without hilar vascular dissection to segments II/III. The final liver graft allowed primary abdominal wall closure in all but one patient, with meaningful adjustments in GRWR. AHR proved to be simple, safe, reproducible, and effective in the presented case series.

In vitro immunogenic profile of recombinant SARS-CoV2 S1-RBD peptide in murine macrophage and microglial cells.

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can infect common mice inducing significant pathological lung lesions and inflammatory responses. This substantially mimics coronavirus disease 19 (COVID-19) infection and pathogenesis in humans. OBJECTIVES: To characterise the effects of recombinant SARS-CoV-2 S1 receptor-binding domain (RBD) peptide in murine macrophage and microglial cells' immune activation compared with classical PAMPs in vitro. METHODS: Murine RAW 264.7 macrophages and BV2 microglial cells were exposed to increasing concentrations of the RBD peptide (0.01, 0.05, and 0.1 µg/mL), Lipopolysaccharide (LPS) and Poly(I:C) and evaluated after two and 24 h for significant markers of macrophage activation. We determined the effects of RBD peptide on cell viability, cleaved caspase 3 expressions, and nuclear morphometry analysis. FINDINGS: In RAW cells, RBD peptide was cytotoxic, but not for BV2 cells. RAW cells presented increased arginase activity and IL-10 production; however, BV2 cells expressed iNOS and IL-6 after RBD peptide exposure. In addition, RAW cells increased cleaved-caspase-3, apoptosis, and mitotic catastrophe after RBD peptide stimulation but not BV2 cells. CONCLUSION: RBD peptide exposure has different effects depending on the cell line, exposure time, and concentration. This study brings new evidence about the immunogenic profile of RBD in macrophage and microglial cells, advancing the understanding of SARS-Cov2 immuno- and neuropathology.

Usefulness of serum sodium levels as a novel marker for predicting acute appendicitis severity: a retrospective cohort study.

BACKGROUND: Early and accurate preoperative diagnosis of complicated appendicitis mandates the identification of new markers. The aim of this study is to determine whether preoperative serum sodium levels are useful for predicting the severity of acute appendicitis. METHODS: We retrospectively analyzed 475 patients who underwent emergency appendectomies between January 2018 and February 2023 in a general hospital in Brazil. The patients were divided into 2 groups: complicated (n = 254) and uncomplicated (n = 221). Hyponatremia was defined as serum sodium levels < 136 mEq/L. The primary outcome was to evaluate if hyponatremia is associated with complicated appendicitis. RESULTS: The patients had a median age of 22 years, and the median serum sodium level was 137 mEq/L in patients with complicated appendicitis and 139 mEq/L in uncomplicated appendicitis (P < 0.001). The analysis of the receiver operating characteristic curve used as the best cutoff value of serum sodium of 136 mEq/L with a sensitivity of 45.7%, specificity of 86.4%, positive predictive value of 79.5%, and negative predictive value of 58.1% for the diagnosis of complicated AA. Of the 254 patients with complicated appendicitis, 84 (33.1%) had serum sodium levels below 136 mEq/L, while only 12 (5.4%) patients with uncomplicated appendicitis had values ​​below this cutoff. Patients with hyponatremia were 5 times more likely to develop complicated appendicitis. (odds ratio: 5.35; 95% confidence interval: 3.39-8.45) CONCLUSIONS: Preoperative serum sodium levels are a useful tool for predicting the severity of acute appendicitis. Due to its low cost and wide availability, it has become an extremely relevant marker.

Investigating Effects of IR-780 in Animal Models of B16-F10 Melanoma: New Approach in Lung Metastasis.

IR-780 is a fluorescent marker, photostable and non-toxic, and is widely used in tumor targeting; however, studies on the impact of IR-780 in animal models of B16-F10 melanoma are scarce in the literature. Therefore, this study aims to analyze behavior of this marker in melanoma cells using in vitro and in vivo analyses with fluorescence microscopy to conduct an analysis of cell culture, and an in vivo imaging system for an analysis of cell culture, tumor targeting on animals, and organ examination. In vitro analysis showed that B16-F10 cells at a concentration of 2 × 105 cells.plate-1 allowed a better visualization using 20 µM of IR-780. Furthermore, the location of IR-780 accumulation was confirmed by its fluorescence microscopy. Through in vivo studies, fluorescence was not observed in subcutaneous nodules, and it was found that animals that received intraperitoneal injection of B16-F10 cells presented ascites and did not absorb IR-780. Additionally, animals exhibiting lung metastasis showed fluorescence in ex vivo lung images. Therefore, use of the IR-780 marker for evaluating the progression of tumor growth did not demonstrate efficiency; however, it was effective in diagnosing pulmonary metastatic tumors. Although this marker presented limitations, results of evaluating pulmonary involvement through ex vivo fluorescence imaging were determined based on intensity of fluorescence.

Intestinal complications are common in patients with acquired diaphragmatic hernia after pediatric living donor liver transplantation.

BACKGROUND: Acquired diaphragmatic hernia (DH) following liver transplantation (LT) is usually considered a surgical emergency. Interplay of contributing elements determines its occurrence but, in children, LT with partial liver grafts seems to be the most important causative factor. METHODS: This retrospective study describes the clinical scenario and outcomes of 11 patients with acquired DH following LDLT. RESULTS: During the study period, 1109 primary pediatric LDLT were performed (0.8% DH). The median age and BW of the recipients with DH at transplantation were 17 months and 11.1 kg, respectively; 63.7% of the cases had a weight/age Z-score of less than -2 at transplantation. The median interval between transplantation and diagnosis of DH was 114 days (32-538 days). A total of 6 (54.5%) of the patients had bowel obstruction due to bowel migration into the hemithorax. Ten defects were right-sided. Three patients required enterectomy and enterorrhaphy. Two patients required a new bilioenteric anastomosis, and one of them had complete necrosis of the Roux-in-Y limb. The patient with left-side DH presented gastroesophageal perforation. CONCLUSION: Most defects necessitate primary closure as the first treatment, and recurrence is rare. The associated problems encountered, especially related to intestinal complications, can determine increased morbidity following DH repair. Early diagnosis and intervention are required for achieving better outcomes.

Staphylococcus aureus Exfoliative Toxin E, Oligomeric State and Flip of P186: Implications for Its Action Mechanism.

Staphylococcal exfoliative toxins (ETs) are glutamyl endopeptidases that specifically cleave the Glu381-Gly382 bond in the ectodomains of desmoglein 1 (Dsg1) via complex action mechanisms. To date, four ETs have been identified in different Staphylococcus aureus strains and ETE is the most recently characterized. The unusual properties of ETs have been attributed to a unique structural feature, i.e., the 180° flip of the carbonyl oxygen (O) of the nonconserved residue 192/186 (ETA/ETE numbering), not conducive to the oxyanion hole formation. We report the crystal structure of ETE determined at 1.61 Å resolution, in which P186(O) adopts two conformations displaying a 180° rotation. This finding, together with free energy calculations, supports the existence of a dynamic transition between the conformations under the tested conditions. Moreover, enzymatic assays showed no significant differences in the esterolytic efficiency of ETE and ETE/P186G, a mutant predicted to possess a functional oxyanion hole, thus downplaying the influence of the flip on the activity. Finally, we observed the formation of ETE homodimers in solution and the predicted homodimeric structure revealed the participation of a characteristic nonconserved loop in the interface and the partial occlusion of the protein active site, suggesting that monomerization is required for enzymatic activity.

Effect of levodopa/carbidopa on stress response in zebrafish.

The dopaminergic system of zebrafish is complex and the numerous pathways and receptors in the central nervous system (CNS) are being extensively studied. A critical factor for the synthesis, activation and release of catecholamines (CAs) is the presence of tyrosine hydroxylase, an enzyme which converts L-tyrosine into levodopa. Levodopa thus is the intermediary in the synthesis of dopamine (DA) and norepinephrine (NE) and promotes its release; therefore, CAs play an important role in the CNS with hormonal functions. Here, we use levodopa/carbidopa to clarify the involvement of the dopaminergic pathway in the stress response in zebrafish submitted to an acute stress challenge. Acute stress was induced by chasing fish with a net for 2 min and assessed by measuring whole-body cortisol levels. Two experiments were carried out, the first with exposure to levodopa/carbidopa and the second with exposure to AMPT and levodopa/carbidopa. Levodopa/carbidopa balances the stress response through its action on the zebrafish hypothalamic-pituitary-adrenal (HPA) axis. Changes in cortisol levels suggest that DA was related to the balance of the stress response and that NE decreased this response. These effects were specific to stress since levodopa/carbidopa did not induce changes in cortisol in non-stressed fish.

Enantioselective Heck-Matsuda Reactions: From Curiosity to a Game-Changing Methodology.

The enantioselective palladium-catalyzed Heck arylation of olefins using arenediazonium salts is one of the last features in the evolution of a synthetic method known as the Heck-Matsuda reaction. This personal account highlights the development of the enantioselective Heck-Matsuda reaction in its initial stages, the challenges faced along the way, and the interesting findings that opened new synthetic opportunities, mainly from our laboratory, featuring the Heck-Matsuda reaction as a central player in the synthesis of bioactive and functional molecules.

Pediatric liver transplantation activity in a high-volume program during the COVID-19 pandemic in Brazil.

BACKGROUND: The impact of the COVID pandemic on liver transplant (LT) programs varied among countries. Few data are available about that impact in pediatric liver transplant (PLT) programs. This study aimed at comparing the data of our program in Brazil (2019 vs. 2020). METHODS: Retrospective cohort study. RESULTS: One hundred and seventy-four PLT were performed in the period (93% living donors). Patients were divided into two groups according to the LT date: pre-COVID-19 period (march/2019-February/2020) and COVID-19 period (March/2020-February 2021). In the pre-COVID-19 period, 97 LTs were performed, and 77 LTs were performed in the COVID-19 period. Patients in the COVID-19 period were younger (10.9 months vs. 16 months, p 0.009), had higher PELD scores (15 vs. 14, p 0.04), more ascites (66.2 vs. 51.5%, p 0.03), and more frequently hospitalized before LT (27.3 vs. 17.5%). However, there was no difference in post-LT complications, retransplantation nor survival rates. Six (6.2%) patients from pre-COVID-19 period were COVID positive at a median of 15.5 months (14-17.5), and 6 (7.8%) patients from COVID-19 period were COVID positive at a median of 3 months (20 days-6 months) from LT. There was neither mortality nor complications in those patients. Four (33%) were hospitalized, and one had prolonged intubation. Four (33%) were asymptomatic, 4 (33%) had upper airways symptoms, and the remaining had gastrointestinal symptoms. CONCLUSION: Overall, PLT was not affected during COVID-19 period. Even though patients from COVID-19 period were sicker, there was no significant impact in LT outcomes. All the recipients who tested positive for COVID had a favorable outcome.

Effects of purslane supplementation on C-reactive protein levels and biomarkers of oxidative stress as marks for metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.

The antioxidant and antiinflammatory properties of purslane (Portulaca oleracea L.) are known in preclinical studies but further examination is needed to expand their potential into the clinical scenario. A systematic review and meta-analysis of randomized controlled trials were performed to elucidate the effects of purslane supplementation on C-reactive protein (CRP) levels and biomarkers of oxidative stress in metabolic syndrome, its related complications, and other diseases. PubMed/MEDLINE, Web of Science, SCOPUS, and Embase were the databases searched. Heterogeneity was examined using the I-squared (I2 ) statistic, in which the source of heterogeneity was determined if the I2 -value was >50%. After all the screening processes, 10 studies met the eligibility criteria and were analyzed. Following purslane supplementation, CRP levels decreased significantly (weighted mean difference [WMD]: -0.33 mg/dl, 95% confidence interval [CI]: -0.66, -0.004, p = .047) but with significant heterogeneity (I2  = 87.4%, p = .001). Purslane supplementation did not significantly change serum levels of malondialdehyde (MDA) (WMD: -0.353 µm/L; 95% CI: -0.920, 0.213; I2  = 50.7%), total antioxidant capacity (TAC) (WMD: 0.090 mm/L, 95% CI: -0.081, 0.262; I2  = 47.1%), and superoxide dismutase (SOD) (WMD: 6.54 U/ml, 95% CI: -22.150, 35.236; I2  = 70.7%). Thus, this meta-analysis showed a positive effect of purslane supplementation as a tool to decrease CRP levels, but not to MDA, TAC, and SOD levels.

Pool-based exercise for amelioration of pain in adults with fibromyalgia syndrome: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of pool-based exercises on pain symptomatology among adults with fibromyalgia syndrome. METHODS: A systematic review and meta-analysis were carried out using PRISMA guidelines. Database search was conducted by two independent reviewers. For meta-analysis, the visual analogue scale (VAS) score for pain was used as the primary outcome and the Fibromyalgia Impact Questionnaire (FIQ) score was utilized as the secondary outcome. RESULTS: A total of 42 out of 292 potentially eligible studies were selected for being read in full by reviewers, 14 of which were included in meta-analysis, being 10 of them used in sensitivity analysis of either the primary or secondary outcome. Data pooled from 10 randomized controlled trials (n = 508) revealed that patients who underwent pool-based exercises exhibited a significantly lower mean in VAS score as compared to controls (SMD = -0.27, 95% CI: -0.45 to -0.09). Regarding FIQ scores, data from 10 randomized controlled trials were pooled (n = 578) and a lower mean score was also shown in the group that underwent a pool-based exercise program (SMD = -0.29, 95% CI: -0.49 to -0.09). Limitations of this study include the small sample size and moderate dropout rates in currently available clinical trials. CONCLUSION: Pool-based exercise may provide some additional benefit for pain relief in adults with fibromyalgia as compared to either land-based or no physical exercise. IMPLICATIONS OF KEY FINDINGS: Collectively, these findings suggest that pool-based exercise deserves further attention as a potential adjuvant therapeutic option for adults with fibromyalgia. PROSPERO registration number: CRD42019136755.

Adepamycin: design, synthesis and biological properties of a new peptide with antimicrobial properties.

Antimicrobial peptides (AMP) are molecules with a broad spectrum of activities that have been identified in most living organisms. In addition, synthetic AMPs designed from natural polypeptides have been largely investigated. Here, we designed a novel AMP using the amino acid sequence of a plant trypsin inhibitor from Adenanthera pavonina seeds (ApTI) as a template. The 176 amino acid residues ApTI sequence was cleaved in silico using the Collection of Antimicrobial Peptides (CAMPR3), through the sliding-window method. Further improvements in AMP structure were carried out, resulting in adepamycin, an AMP designed from ApTI. Adepamycin showed antimicrobial activity from 0.9 to 3.6 µM against Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Moreover, this peptide also displayed activity against Candida albicans and Candida tropicalis. No toxic effects were observed on healthy human cells. Studies on the mechanism of action of adepamycin were carried out using an E. coli and C. tropicalis. Adepamycin triggers membrane disturbances, leading to intracellular nucleic acids release in E. coli. For C. tropicalis, an initial interference with the plasma membrane integrity is followed by the formation of intracellular reactive oxygen species (ROS), leading to apoptosis. Structurally, adepamycin was submitted to circular dichroism spectroscopy, molecular modeling and molecular dynamics simulations, revealing an environment-dependent α-helical structure in the presence of 2,2,2- trifluoroethanol (TFE) and in contact with mimetic vesicles/membranes. Therefore, adepamycin represents a novel lytic AMP with dual antibacterial and antifungal properties.

Development of a novel anti-biofilm peptide derived from profilin of Spodoptera frugiperda.

Candida yeast infections are the fourth leading cause of death worldwide. Peptides with antimicrobial activity are a promising alternative treatment for such infections. Here, the antifungal activity of a new antimicrobial peptide-PEP-IA18-was evaluated against Candida species. PEP-IA18 was designed from the primary sequence of profilin, a protein from Spodoptera frugiperda, and displayed potent activity against Candida albicans and Candida tropicalis, showing a minimum inhibitory concentration (MIC) of 2.5 µM. Furthermore, the mechanism of action of PEP-IA18 involved interaction with the cell membrane (ergosterol complexation). Treatment at MIC and/or 10 × MIC significantly reduced biofilm formation and viability. PEP-IA18 showed low toxicity toward human fibroblasts and only revealed hemolytic activity at high concentrations. Thus, PEP-IA18 exhibited antifungal and anti-biofilm properties with potential applicability in the treatment of infections caused by Candida species.

Non-Leishmania Parasite in Fatal Visceral Leishmaniasis-Like Disease, Brazil.

Through whole-genome sequencing analysis, we identified non-Leishmania parasites isolated from a man with a fatal visceral leishmaniasis-like illness in Brazil. The parasites infected mice and reproduced the patient's clinical manifestations. Molecular epidemiologic studies are needed to ascertain whether a new infectious disease is emerging that can be confused with leishmaniasis.

Biochemical characterization of a Kunitz inhibitor from Inga edulis seeds with antifungal activity against Candida spp.

We describe the characterization of IETI, the first trypsin inhibitor purified from Inga edulis, a tree widely distributed in Brazil. Two-step chromatography was used to purify IETI, a protein composed of a single peptide chain of 19,685.10 Da. Amino-terminal sequencing revealed that IETI shows homology with the Kunitz family, as substantiated by its physical-chemical features, such as its thermal (up to 70 °C) and wide-range pH stability (from 2 to 10), and the value of its dissociation constant (6.2 nM). IETI contains a single reactive site for trypsin, maintained by a disulfide bridge; in the presence of DTT, its inhibitory activity was reduced in a time- and concentration-dependent manner. IETI presented activity against Candida ssp., including C. buinensis and C. tropicalis. IETI inhibitory activity triggered yeast membrane permeability, affecting cell viability, thus providing support for the use of IETI in further studies for the control of fungal infections.