Altered blood microbiome in patients with HCV-related Child-Pugh class B cirrhosis.

BACKGROUND: Altered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis). METHODS: We conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis. RESULTS: Patients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001). CONCLUSIONS: Blood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A.

Antifouling activity and ecotoxicological profile of the cyanobacterial oxadiazine nocuolin A.

Pursuing effective and biocompatible natural compounds to supplant current biocidal antifouling (AF) technologies remains crucial and challenging. Among natural products hosts, cyanobacteria are recognized as producers of bioactive secondary metabolites that are underexplored in terms of anti-biofilm and AF potential. Nocuolin A, a natural oxadiazine previously isolated and known to be produced by different cyanobacterial strains, has demonstrated bioactive potential, particularly against tumor cell lines. Considering this potential and its exquisite chemical structure, here nocuolin A was investigated as a potential natural AF agent through an integrative approach including AF bioactivity testing across distinct levels of biological organization, mode of action assessment, ecotoxicity evaluation, and ecological risk predictions. Nocuolin A was found to inhibit the settlement of mussel (Mytilus galloprovincialis) plantigrades (EC50 = 3.905 µM) while showing no toxicity to this biofouling species (LC50 > 100 µM). Additionally, while exhibiting no inhibitory activity against the growth of five marine biofilm-forming bacterial strains, it significantly suppressed the growth of the marine biofilm-forming diatom Navicula sp. (EC50 = 1.561 µM), and had a lethal effect on this diatom species (>3.1 µM). The AF targets of nocuolin A on mussel plantigrades revealed no correlation with acetylcholinesterase and tyrosinase metabolic processes; however, proteins involved in oxidative stress, muscle regulation, and energy production were highlighted. The results also provide insights into the ecological risk of nocuolin A, including its ecotoxicity against Artemia salina nauplii (LC50 = 2.480 µM), Amphibalanus amphitrite nauplii (LC50 = 0.0162 µM), and Danio rerio embryos (LC50 = 0.0584 µM). When matching these results with simulated environmental values, nocuolin A was deemed a considerable threat to the ecosystems. While this research highlights the AF activity of nocuolin A, it also emphasizes the potential adverse environmental impact when applied in preventive coatings.

Unveiling the Differentiation Potential of Ovarian Theca Interna Cells from Multipotent Stem Cell-like Cells.

RESEARCH QUESTION: Theca interna cells (TICs) are an indispensable cell source for ovarian follicle development and steroidogenesis. Recent studies have identified theca stem cells (TSCs) in both humans and animals. Interestingly, TSCs express mesenchymal stem cell (MSC)-related markers and can differentiate into mesenchymal lineages. MSCs are promising for tissue engineering and regenerative medicine due to their self-renewal and differentiation abilities. Therefore, this study investigated the potential origin of TICs from MSCs. DESIGN: Whole ovaries from postmenopausal organ donors were obtained, and their cortex was cryopreserved prior to the isolation of stromal cells. These isolated cells were differentiated in vitro to TICs using cell media enriched with various growth factors and hormones. Immunocytochemistry, an enzyme-linked immunosorbent assay, flow cytometry, and reverse transcription-quantitative polymerase chain were employed at different timepoints. Data were analyzed using one-way ANOVA. RESULTS: Immunocytochemistry showed an increase in TIC markers from day 0 to day 8 and a significant rise in MSC-like markers on day 2. This corresponds with rising androstenedione levels from day 2 to day 13. Flow cytometry identified a decreasing MSC-like cell population from day 2 onwards. The CD13+ cell population and its gene expression increased significantly over time. NGFR and PDGFRA expression was induced on days 0 and 2, respectively, compared to day 13. CONCLUSIONS: This study offers insights into MSC-like cells as the potential origin of TICs. Differentiating TICs from these widely accessible MSCs holds potential significance for toxicity studies and investigating TIC-related disorders like polycystic ovary syndrome (PCOS).

Longer ICU stay and invasive mechanical ventilation accelerate telomere shortening in COVID-19 patients 1 year after recovery.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.

Anticancer Activity of Benzo[a]phenoxazine Compounds Promoting Lysosomal Dysfunction.

Specific cancer therapy remains a problem to be solved. Breast and colorectal cancer are among the cancers with the highest prevalence and mortality rates. Although there are some therapeutic options, there are still few effective agents for those cancers, which constitutes a clinical problem that requires further research efforts. Lysosomes play an important role in cancer cells' survival, and targeting lysosomes has gained increased interest. In recent years, our team has been synthetizing and testing novel benzo[a]phenoxazine derivatives, as they have been shown to possess potent pharmacological activities. Here, we investigated the anticancer activity of three of the most potent derivatives from our library, C9, A36, and A42, on colorectal- and breast-cancer-derived cell lines, and compared this with the effect on non-neoplastic cell lines. We observed that the three compounds were selective for the cancer cells, namely the RKO colorectal cancer cell line and the MCF7 breast cancer cell line. In both models, the compounds reduced cell proliferation, cell survival, and cell migration, accumulated on the lysosome, and induced cell death accompanied by lysosomal membrane permeabilization (LMP), increasing the intracellular pH and ROS accumulation. Our results demonstrated that these compounds specifically target lysosomes from cancer cells, making them promising candidates as LMP inducers for cancer therapy.

Fecal calprotectin as an inflammatory biomarker in small bowel Crohn disease.

Background: Small bowel capsule endoscopy (SBCE) is an essential tool for evaluation of small bowel (SB) Crohn disease (CD). Fecal calprotectin (FC) represents an important biomarker of intestinal inflammation, widely used in ulcerative colitis and CD. Our aim was to evaluate the role of FC for diagnosing inflammatory activity in patients with isolated SB CD and how it correlates with SBCE findings. Methods: This is a retrospective study conducted in a tertiary inflammatory bowel disease referral center that included patients with SB CD who underwent SBCE between January 2017 and February 2023. FC value was obtained from the closest stool examination to SBCE. Results: One hundred ninety-six patients were included: 123 were women (63%) with a mean age of 44.2 years. In the SBCE, 127 (65%) patients had a Lewis Score ≥135 and, among the 94 patients with FC >200 µg/g, 23 had LS <135, 36 had LS between 135 and 790, and 35 had LS ≥790. FC levels were predictive of endoscopic lesions in SBCE, with significant correlation between FC level and total LS (Pearson correlation coefficient 0.43, P<.001). The sensitivity and specificity were calculated for each cut-off value being respectively 78% and 45% for FC = 100 µg/g, 69% and 59% for FC = 150 µg/g and 67% and 67% for FC = 200 µg/g. Conclusion: FC showed moderate correlation with endoscopic findings in SBCE in SB CD. It is, therefore, a reasonable marker for predicting significant inflammatory lesions in SBCE; however, none of the cut-off had a high sensitivity or specificity.

Rituximab as a treatment for refractory immune thrombocytopenia during pregnancy.

Immune thrombocytopenia (ITP) is most common in women during their reproductive years. When a low platelet count occurs for the first time during pregnancy, the differential diagnosis includes pregnancy-specific conditions. Although ITP is the most common cause of thrombocytopenia early in pregnancy, pregnancy-related thrombocytopenia develops mainly in late gestation. As maternal and neonatal outcomes are usually favourable, ITP per se is not a contraindication for pregnancy. We report the case with a literature review of patient with ITP, whose diagnosis was established in early pregnancy. This condition was refractory to first-line treatments, such as high-dose steroids and intravenous immunoglobulin and other splenectomy-sparing approaches, as rituximab, having the control been reached on the third trimester after splenectomy. Although not effective in this case, we still believe that rituximab should be considered before surgery during pregnancy.

Long-term storage stability of PGL-I coated ELISA plates for anti-Mycobacterium leprae IgM detection.

The assessment of ELISA plates coated with phenolic glycolipid-I/PGL-I revealed excellent stability during eight years of storage at room temperature, promoting consistent IgM antibody detection in multibacillary leprosy patients. These stable, standardized plates can significantly contribute to efficient leprosy serology research and support its widespread distribution and use in endemic countries.

Practices developed by nurses in primary health care in southern Brazil.

OBJECTIVE: To understand the practices developed by nurses in primary care in southern Brazil. METHOD: Qualitative study, with data collection via online interviews, conducted between October 2020 and May 2021, and recorded. 174 nurses from 24 municipalities in southern Brazil participated. Data analysis used inductive thematic analysis. RESULTS: The activity that stood out among nurses was the nurse consultation, for all age groups and health conditions, especially when dealing with chronic disease, prenatal care, attention to women and children, mental health, home visits, and the management of the nursing team and the health unit. FINAL CONSIDERATIONS: This study demonstrated that an excess of responsibilities associated to care and management, added to a lack of balance in the activities common to the team make it difficult for nurses to develop clinical practices.

miRNome profiling of extracellular vesicles in severe COVID-19 patients and identification of predictors of mortality.

BACKGROUND: Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. METHODS: A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. RESULTS: Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. CONCLUSION: : This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.

Clinical practice guidelines of foot care practice for patients with type 2 diabetes: A scoping review using self-care model.

BACKGROUND: Type 2 diabetes can lead to severe foot complications, making self-care education, guided by clinical guidelines, crucial. However, fragmented and dispersed recommendations challenge effective implementation of these guidelines. Bringing together recommendations and presenting them according to a self-care model can provide a solid framework and facilitate the interpretation of results. AIMS: to map the international guidelines that provide recommendations to nurses to enable people with type 2 diabetes for foot self-care and synthesize the recommendations according to the key concepts of the middle-range theory of self-care for chronic diseases. DESIGN: A scoping review was undertaken, using the methodological guidance of the Joanna Briggs Institute. DATA SOURCES: Databases were searched between September 2022 and June 2023, including PubMed, CINAHL, PsycINFO, Scopus, Web of Science Core Collection, ProQuest Dissertations and Theses Global, guideline websites and related professional association websites. The databases were chosen for their comprehensive coverage of the area. METHODS: Eligible articles included guidance documents providing foot care recommendations for diabetes, published or updated between 2013 and 2023. Two reviewers summarized the recommendations presented in at least two guidelines according to the key concepts of the self-care model. The PRISMA-ScR checklist was used. RESULTS: Seventeen guidelines were included. In total, we synthesized 175 recommendations. The recommendations were framed in three dimensions and their respective categories: Self-care maintenance (education for prevention, control of risk factors, daily foot care, footwear, and socks), Self-care monitoring (foot inspection, detection of signs of infection, and detection of other diabetes-related foot disease complications), and Self-care management (responses to signs and symptoms, foot wound care, follow-up with health professionals, and health services). CONCLUSIONS: The main aspect of foot care revolves around daily care, including cleaning, moisturizing, nail care, selecting appropriate footwear, and regular inspection of both feet and footwear.

Efficacy of the bumped kinase inhibitor BKI-1708 against the cyst-forming apicomplexan parasites Toxoplasma gondii and Neospora caninum in vitro and in experimentally infected mice.

Toxoplasma gondii and Neospora caninum are major worldwide morbidity-causing pathogens. Bumped kinase inhibitors (BKIs) are a compound class that has been optimized to target the apicomplexan calcium-dependent protein kinase 1 (CDPK1) - and several members of this class have proven to be safe and highly active in vitro and in vivo. BKI-1708 is based on a 5-aminopyrazole-4-carboxamide scaffold, and exhibited in vitro IC50 values of 120 nM for T. gondii and 480 nM for N. caninum ß-galactosidase expressing strains, and did not affect human foreskin fibroblast (HFF) viability at concentrations up to 25 µM. Electron microscopy established that exposure of tachyzoite-infected fibroblasts to 2.5 µM BKI-1708 in vitro induced the formation of multinucleated schizont-like complexes (MNCs), characterized by continued nuclear division and harboring newly formed intracellular zoites that lack the outer plasma membrane. These zoites were unable to finalize cytokinesis to form infective tachyzoites. BKI-1708 did not affect zebrafish (Danio rerio) embryo development during the first 96 h following egg hatching at concentrations up to 2 µM. Treatments of mice with BKI-1708 at 20 mg/kg/day during five consecutive days resulted in drug plasma levels ranging from 0.14 to 4.95 µM. In vivo efficacy of BKI-1708 was evaluated by oral application of 20 mg/kg/day from day 9-13 of pregnancy in mice experimentally infected with N. caninum (NcSpain-7) tachyzoites or T. gondii (TgShSp1) oocysts. This resulted in significantly decreased cerebral parasite loads and reduced vertical transmission in both models without drug-induced pregnancy interference.

Production of antigens expressed in Nicotiana benthamiana plant and Escherichia coli for the SARS-CoV-2 IgG antibody detection by ELISA.

The recent COVID-19 pandemic disclosed a critical shortage of diagnostic kits worldwide, emphasizing the urgency of utilizing all resources available for the development and production of diagnostic tests. Different heterologous protein expression systems can be employed for antigen production. This study assessed novel SARS-CoV-2 proteins produced by a transient expression system in Nicotiana benthamiana utilizing an infectious clone vector based on pepper ringspot virus (PepRSV). These proteins included the truncated S1-N protein (spike protein N-terminus residues 12-316) and antigen N (nucleocapsid residues 37-402). Two other distinct SARS-CoV-2 antigens expressed in Escherichia coli were evaluated: QCoV9 chimeric antigen protein (spike protein residues 449-711 and nucleocapsid protein residues 160-406) and QCoV7 truncated antigen (nucleocapsid residues 37-402). ELISAs using the four antigens individually and the same panel of samples were performed for the detection of anti-SARS-CoV-2 IgG antibodies. Sensitivity was evaluated using 816 samples from 351 COVID-19 patients hospitalized between 5 and 65 days after symptoms onset; specificity was tested using 195 samples collected before 2018, from domiciliary contacts of leprosy patients. Our findings demonstrated consistent test sensitivity, ranging from 85 % to 88 % with specificity of 97.5 %, regardless of the SARS-CoV2 antigen and the expression system used for production. Our results highlight the potential of plant expression systems as useful alternative platforms to produce recombinant antigens and for the development of diagnostic tests, particularly in resource-constrained settings.

Bartter Syndrome Presenting as Arginine-Vasopressin Resistance: A Report of 2 Cases.

BACKGROUND Bartter syndrome is a rare, inherited salt-wasting tubulopathy caused by mutations in 1 of 6 genes that express ion transport channels in the thick ascending limb of nephrons. Excessive prostaglandin E2 and associated hyperreninemic hyperaldosteronism occurs, causing polyhydramnios, polyuria, prematurity, failure to thrive, and characteristic physical features. Hypokalemia, hypochloremic metabolic alkalosis, and, depending on the affected gene, hypercalciuria and nephrocalcinosis are hallmarks of Bartter syndrome. CASE REPORT A 9-month-old male infant, born prematurely due to polyhydramnios, presented in the Emergency Department with dehydration due to incoercible vomiting and significant polyuria. A 6-year-old male infant with a previous history of prematurity due to polyhydramnios was referred to the Pediatric Endocrinology Department due to short stature and notable polydipsia and polyuria. Considering these marked symptoms, both cases triggered suspicion and started workup for arginine-vasopressin insufficiency/resistance. However, during the investigations, a broader clinical revision revealed that both had dysmorphic physical features (triangularly shaped face, prominent forehead, protruding ears, drooping mouth), poor growth, impaired weight gain, and typical biochemical findings (hypokalemic metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism) of Bartter syndrome. Genetic testing confirmed the diagnosis of Bartter syndrome types 1 and type 2, respectively, and this diagnosis allowed proper treatment and significant clinical improvements, personalized follow-up, and genetic counseling for parents desiring further healthy pregnancies. CONCLUSIONS Here, we present clinical and follow-up findings of 2 patients with Bartter syndrome types 1 and 2 discovered upon a broader clinical revision of suspected arginine-vasopressin insufficiency/resistance. We also review pertinent data on diagnosis and management of this challenging syndrome.

Canine Leishmaniosis Associated with Acute Pleural Effusion and Sudden Death in a Dog.

A two-year-old female crossbreed dog, previously a stray with no known owner, was adopted and subsequently spayed. The dog exhibited weight loss over a period of two months and died suddenly during a leashed walk. Upon necropsy, enlargement of the submandibular, prescapular, and popliteal lymph nodes was noted. The intrathoracic cavity contained a substantial volume of yellowish-white fluid. Lymph nodes in the mediastinal and ventral thoracic centers were also enlarged, hemorrhagic, and friable. Microscopic examination revealed significant architectural changes in the lymph nodes, characterized by a pronounced cellular infiltrate consisting of lymphocytes and histiocytes, along with macrophages containing intracytoplasmic Leishmania amastigotes. Immunohistochemical analysis of the lymph nodes confirmed positive staining for Leishmania amastigotes. This case represents the first report of canine leishmaniasis associated with acute pleural effusion and sudden death.

The fungicide cymoxanil impairs respiration in Saccharomyces cerevisiae via cytochrome c oxidase inhibition.

Cymoxanil (CYM) is a widely used synthetic acetamide fungicide, but its biochemical mode of action remains elusive. Since CYM inhibits cell growth, biomass production, and respiration in Saccharomyces cerevisiae, we used this model to characterize the effect of CYM on mitochondria. We found it inhibits oxygen consumption in both whole cells and isolated mitochondria, specifically inhibiting cytochrome c oxidase (CcO) activity during oxidative phosphorylation. Based on molecular docking, we propose that CYM blocks the interaction of cytochrome c with CcO, hampering electron transfer and inhibiting CcO catalytic activity. Although other targets cannot be excluded, our data offer valuable insights into the mode of action of CYM that will be instrumental in driving informed management of the use of this fungicide.

Hypertensive disorders during pregnancy as a major cause of preterm birth and adverse perinatal outcomes: findings from a Brazilian National Survey.

OBJECTIVE: This study aimed to evaluate the prevalence of hypertensive disorders during pregnancy among Brazilian women with preterm births and to compare the epidemiological characteristics and perinatal outcomes among preterm births of women with and without hypertension. METHODS: This was a secondary cross-sectional analysis of the Brazilian Multicenter Study on Preterm Birth. During the study period, all women with preterm births were included and further split into two groups according to the occurrence of any hypertensive disorder during pregnancy. Prevalence ratios were calculated for each variable. Maternal characteristics, prenatal care, and gestational and perinatal outcomes were compared between the two groups using χ2 and t-tests. RESULTS: A total of 4,150 women with preterm births were included, and 1,169 (28.2%) were identified as having hypertensive disorders. Advanced maternal age (prevalence ratio (PR) 2.49) and obesity (PR= 2.64) were more common in the hypertensive group. The gestational outcomes were worse in women with hypertension. Early preterm births were also more frequent in women with hypertension. CONCLUSION: Hypertensive disorders of pregnancy were frequent among women with preterm births, and provider-initiated preterm births were the leading causes of premature births in this group. The factors significantly associated with hypertensive disorders among women with preterm births were obesity, excessive weight gain, and higher maternal age.

In vitro and in vivo activities of a trithiolato-diRuthenium complex conjugated with sulfadoxine against the apicomplexan parasite Toxoplasma gondii.

Organometallic compounds, including Ruthenium complexes, have been widely developed as anti-cancer chemotherapeutics, but have also attracted much interest as potential anti-parasitic drugs. Recently hybrid drugs composed of organometallic Ruthenium moieties that were complexed to different antimicrobial agents were synthesized. One of these compounds, a trithiolato-diRuthenium complex (RU) conjugated to sulfadoxine (SDX), inhibited proliferation of Toxoplasma gondii tachyzoites grown in human foreskin fibroblast (HFF) monolayers with an IC50 < 150 nM, while SDX and the non-modified RU complex applied either individually or as an equimolar mixture were much less potent. In addition, conjugation of SDX to RU lead to decreased HFF cytotoxicity. RU-SDX did not impair the in vitro proliferation of murine splenocytes at concentrations ranging from 0.1 to 0.5 µM but had an impact at 2 µM, and induced zebrafish embryotoxicity at 20 µM, but not at 2 or 0.2 µM. RU-SDX acted parasitostatic but not parasiticidal, and induced transient ultrastructural changes in the mitochondrial matrix of tachyzoites early during treatment. While other compounds that target the mitochondrion such as the uncouplers FCCP and CCCP and another trithiolato-Ruthenium complex conjugated to adenine affected the mitochondrial membrane potential, no such effect was detected for RU-SDX. Evaluation of the in vivo efficacy of RU-SDX in a murine T. gondii oocyst infection model comprised of non-pregnant outbred CD1 mice showed no effects on the cerebral parasite burden, but reduced parasite load in the eyes and in heart tissue.

Bee Venom-Loaded Niosomes as Innovative Platforms for Cancer Treatment: Development and Therapeutical Efficacy and Safety Evaluation.

Despite past efforts towards therapeutical innovation, cancer remains a highly incident and lethal disease, with current treatments lacking efficiency and leading to severe side effects. Hence, it is imperative to develop new, more efficient, and safer therapies. Bee venom has proven to have multiple and synergistic bioactivities, including antitumor effects. Nevertheless, some toxic effects have been associated with its administration. To tackle these issues, in this work, bee venom-loaded niosomes were developed, for cancer treatment. The vesicles had a small (150 nm) and homogeneous (polydispersity index of 0.162) particle size, and revealed good therapeutic efficacy in in vitro gastric, colorectal, breast, lung, and cervical cancer models (inhibitory concentrations between 12.37 ng/mL and 14.72 ng/mL). Additionally, they also revealed substantial anti-inflammatory activity (inhibitory concentration of 28.98 ng/mL), effects complementary to direct antitumor activity. Niosome safety was also assessed, both in vitro (skin, liver, and kidney cells) and ex vivo (hen's egg chorioallantoic membrane), and results showed that compound encapsulation increased its safety. Hence, small, and homogeneous bee venom-loaded niosomes were successfully developed, with substantial anticancer and anti-inflammatory effects, making them potentially promising primary or adjuvant cancer therapies. Future research should focus on evaluating the potential of the developed platform in in vivo models.

Working towards the development of vaccines and chemotherapeutics against neosporosis-With all of its ups and downs-Looking ahead.

Neospora caninum is an apicomplexan and obligatory intracellular parasite, which is the leading cause of reproductive failure in cattle and affects other farm and domestic animals, but also induces neuromuscular disease in dogs of all ages. In cattle, neosporosis is an important health problem, and has a considerable economic impact. To date there is no protective vaccine or chemotherapeutic treatment on the market. Immuno-prophylaxis has long been considered as the best control measure. Proteins involved in host cell interaction and invasion, as well as antigens mediating inflammatory responses have been the most frequently assessed vaccine targets. However, despite considerable efforts no effective vaccine has been introduced to the market to date. The development of effective compounds to limit the effects of vertical transmission of N. caninum tachyzoites has emerged as an alternative or addition to vaccination, provided suitable targets and safe and efficacious drugs can be identified. Additionally, the combination of both treatment strategies might be interesting to further increase protectivity against N. caninum infections and to decrease the duration of treatment and the risk of potential drug resistance. Well-established and standardized animal infection models are key factors for the evaluation of promising vaccine and compound candidates. The vast majority of experimental animal experiments concerning neosporosis have been performed in mice, although in recent years the numbers of experimental studies in cattle and sheep have increased. In this review, we discuss the recent findings concerning the progress in drug and vaccine development against N. caninum infections in mice and ruminants.