Release of immunomodulatory peptides at bacterial membrane interfaces as a novel strategy to fight microorganisms.

Cationic and amphiphilic peptides can be used as homing devices to accumulate conjugated antibiotics to bacteria-enriched sites and promote efficient microbial killing. However, just as important as tackling bacterial infections, is the modulation of the immune response in this complex microenvironment. In the present report, we designed a peptide chimaera called Chim2, formed by a membrane-active module, an enzyme hydrolysis site and a formyl peptide receptor 2 (FPR2) agonist. This molecule was designed to adsorb onto bacterial membranes, promote their lysis, and upon hydrolysis by local enzymes, release the FPR2 agonist sequence for activation and recruitment of immune cells. We synthesized the isolated peptide modules of Chim2 and characterized their biological activities independently and as a single polypeptide chain. We conducted antimicrobial assays, along with other tests aiming at the analyses of the cellular and immunological responses. In addition, assays using vesicles as models of eukaryotic and prokaryotic membranes were conducted and solution structures of Chim2 were generated by 1H NMR. Chim2 is antimicrobial, adsorbs preferentially to negatively charged vesicles while adopting an α-helix structure and exposes its disorganized tail to the solvent, which facilitates hydrolysis by tryptase-like enzymes, allowing the release of the FPR2 agonist fragment. This fragment was shown to induce accumulation of the cellular activation marker, lipid bodies, in mouse macrophages and the release of immunomodulatory interleukins. In conclusion, these data demonstrate that peptides with antimicrobial and immunomodulatory activities can be considered for further development as drugs.

Cross-reactive immunity against SARS-CoV-2 N protein in Central and West Africa precedes the COVID-19 pandemic.

Early predictions forecasted large numbers of severe acute respiratory syndrome coronavirus (SARS-CoV-2) cases and associated deaths in Africa. To date, Africa has been relatively spared. Various hypotheses were postulated to explain the lower than anticipated impact on public health in Africa. However, the contribution of pre-existing immunity is yet to be investigated. In this study, the presence of antibodies against SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in pre-pandemic samples from Africa, Europe, South and North America was examined by ELISA. The protective efficacy of N specific antibodies isolated from Central African donors was tested by in vitro neutralization and in a mouse model of SARS-CoV-2 infection. Antibodies against SARS-CoV-2 S and N proteins were rare in all populations except in Gabon and Senegal where N specific antibodies were prevalent. However, these antibodies failed to neutralize the virus either in vitro or in vivo. Overall, this study indicates that cross-reactive immunity against SARS-CoV-2 N protein was present in Africa prior to the pandemic. However, this pre-existing humoral immunity does not impact viral fitness in rodents suggesting that other human immune defense mechanisms could be involved. In Africa, seroprevalence studies using the N protein are over-estimating SARS-CoV-2 circulation.

Dietary inflammatory index and its relationship with gut microbiota in individuals with intestinal constipation: a cross-sectional study.

OBJECTIVE: To determine whether there is an association between the inflammatory potential of the diet, measured by the dietary inflammatory index (DII®), and the composition of intestinal microbiota in adults with functional constipation (FC). METHODS: A cross-sectional study was carried out with 68 adults with FC. Energy-adjusted DII (E-DII) was calculated from data obtained from food surveys, serum inflammation markers were measured and the composition of the intestinal microbiota was evaluated using the 16S rRNA gene sequencing method. Participants were assigned into two groups: anti-inflammatory diet (AD: E-DII < 0) and pro-inflammatory diet (PD: E-DII ≥ 0). Associations of E-DII scores with microbial diversity and composition were examined using differences between the E-DII groups and linear and hierarchical regression. RESULTS: E- DII was inversely correlated with relative abundance of Hungatella spp. and Bacteroides fragilis and positively correlated with Bacteroides thetaiotaomicron and Bacteroides caccae (p < 0.05). B. fragilis was positively correlated with IL-10. The AD group had higher relative abundances for the genus Blautia and Hungatella, lower abundances of Bacteroides thetaiotamicron and Bacteroides spp. (p < 0.05), as well as higher frequency of evacuation (p = 0.02) and lower use of laxatives (p = 0.05). The AD group showed a reduction in the abundance of Desulfovibrio spp. and Butyrivibrio, Butyrivibrio crossotus, Bacteroides clarus, Bacteroides coprophilus and Bacteroides intestinalis (all p < 0.05). The greater abundance of Bacteroides clarus increased the individual's chance of performing a manual evacuation maneuver. CONCLUSION: Therefore, the results of this study demonstrated that the inflammatory potential of the diet is associated with the gut microbiota in individuals with FC.

Effect of n-3 long-chain polyunsaturated fatty acid intake on the eicosanoid profile in individuals with obesity and overweight: a systematic review and meta-analysis of clinical trials.

Dietary n-3 polyunsaturated fatty acids (PUFAs) present beneficial effects on counteracting inflammation status, displaying a critical anti-inflammatory role and maintaining physiological homeostasis in obesity. The primary objective of this systematic review was to evaluate the effect of n-3 PUFAs intake on the eicosanoid profile of people with obesity and overweight. The search strategy on Embase, Scopus, PubMed, Web of Science, Cochrane Library, Google Scholar and ProQuest was undertaken until November 2019 and updated January 2021. The effect size of n-3 PUFAs on prostaglandins was estimated by Glass's, type 1 in a random-effect model for the meta-analysis. Seven clinical trials met the eligible criteria and a total of 610 subjects were included in this systematic review, and four of seven studies were included in meta-analysis. The intake of n-3 PUFAs promoted an overall reduction in serum pro-inflammatory eicosanoids. Additionally, n-3 PUFAs intake significantly decreased the arachidonic acid COX-derived PG eicosanoid group levels (Glass's Δ -0⋅35; CI -0⋅62, -0⋅07, I 2 31⋅48). Subgroup analyses showed a higher effect on periods up to 8 weeks (Glass's Δ -0⋅51; CI -0⋅76, -0⋅27) and doses higher than 0⋅5 g of n-3 PUFAs (Glass's Δ -0⋅46; CI -0⋅72, -0⋅27). Dietary n-3 PUFAs intake contributes to reduce pro-inflammatory eicosanoids of people with obesity and overweight. Subgroup's analysis showed that n-3 PUFAs can reduce the overall arachidonic acid COX-derived PG when adequate dose and period are matched.

A multiple-strain probiotic product provides a better enzymatic antioxidant response in individuals with constipation in a double-blind randomized controlled trial.

OBJECTIVES: Probiotics may have beneficial effects on intestinal dysbiosis. However, the effects of probiotics on redox and inflammatory responses in intestinal constipation remain unknown. The aim of this study was to investigate the effect of a multiple-strain probiotic on the redox and inflammatory responses in individuals with intestinal constipation. METHODS: A randomized, double-blind, placebo controlled clinical trial was conducted with individuals diagnosed with constipation (defined according to the Rome IV criteria). The participants were randomized into two groups to receive either a probiotic capsule (PC; n = 25) containing probiotic strains or to receive a control capsule (CC; n = 20) containing a matching placebo for 30 d. In the baseline and at the end of the study, biomarkers of the redox (malondialdehyde, carbonylated protein, antioxidant enzymes, and ferric-reducing antioxidant power) and inflammatory responses, and Rome IV criteria for constipation were analyzed. RESULTS: The consumption of a multiple-strain probiotic attenuated the reduction of glutathione peroxidase (PC = -9.41 and CC = -19.60; P = 0.041) and glutathione-s-transferase activity (PC = -3.28 and CC = -12.08, P < 0.0001) in erythrocytes and marginally improved the symptom of feeling incomplete defecation in ≥25% of bowel movements, compared with the placebo group. No changes were observed in total antioxidant capacity, oxidative damage, and levels of inflammatory markers in the serum. CONCLUSIONS: Our data suggested that a multiple-strain probiotic may provide a better enzymatic antioxidant response and partially alleviate the feeling of incomplete defecation in ≥25% of bowel movements in individuals with intestinal constipation.

Synergistic Antitumor Efficacy of Magnetohyperthermia and Poly(lactic-co-glycolic acid)-Encapsulated Selol in Ehrlich Breast Adenocarcinoma Treatment in Elderly Swiss Mice.

Nanobiotechnology strategies for cancer treatments are currently being tested with increasing interest, except in elderly groups. It is well established that breast cancer incidence increases with age and that traditional therapies usually generate severe adverse effects, especially for elderly groups. To investigate if the benefits of nanotechnology could be extended to treating cancer in this group, citrate-coated maghemite nanoparticles (NpCit) were used for magnetohyperthermia (MHT) in combination with the administration of PLGA-Selol nanocapsule (NcSel), a formulation with antioxidant and antitumor activity. The combined therapies significantly inhibited breast Ehrlich tumor growth and prevented metastases to the lymph nodes, liver and lungs until 45 days after tumor induction, a better result than the group undergoing conventional drug treatment. The levels of TNF-α, associated with poor prognosis in Ehrlich tumor, were also normalized. Therefore, the results evidenced the potential use of these therapies for future clinical trials in elderly breast cancer patients.

Granzyme a in Chikungunya and other arboviral infections

Granzyme A (GzmA) is secreted by cytotoxic lymphocytes and has traditionally been viewed as a mediator of cell death. However, a growing body of data suggests the physiological role of GzmA is promotion of inflammation. Here, we show that GzmA is significantly elevated in the sera of chikungunya virus (CHIKV) patients and that GzmA levels correlated with viral loads and disease scores in these patients. Serum GzmA levels were also elevated in CHIKV mouse models, with NK cells the likely source. Infection of mice deficient in type I interferon responses with CHIKV, Zika virus, or dengue virus resulted in high levels of circulating GzmA. We also show that subcutaneous injection of enzymically active recombinant mouse GzmA was able to mediate inflammation, both locally at the injection site as well as at a distant site. Protease activated receptors (PARs) may represent targets for GzmA, and we show that treatment with PAR antagonist ameliorated GzmA- and CHIKV-mediated inflammation.

Granzyme a in Chikungunya and other arboviral infections

Granzyme A (GzmA) is secreted by cytotoxic lymphocytes and has traditionally been viewed as a mediator of cell death. However, a growing body of data suggests the physiological role of GzmA is promotion of inflammation. Here, we show that GzmA is significantly elevated in the sera of chikungunya virus (CHIKV) patients and that GzmA levels correlated with viral loads and disease scores in these patients. Serum GzmA levels were also elevated in CHIKV mouse models, with NK cells the likely source. Infection of mice deficient in type I interferon responses with CHIKV, Zika virus, or dengue virus resulted in high levels of circulating GzmA. We also show that subcutaneous injection of enzymically active recombinant mouse GzmA was able to mediate inflammation, both locally at the injection site as well as at a distant site. Protease activated receptors (PARs) may represent targets for GzmA, and we show that treatment with PAR antagonist ameliorated GzmA- and CHIKV-mediated inflammation.

Intragenic antimicrobial peptides (IAPs) from human proteins with potent antimicrobial and anti-inflammatory activity.

Following the treads of our previous works on the unveiling of bioactive peptides encrypted in plant proteins from diverse species, the present manuscript reports the occurrence of four proof-of-concept intragenic antimicrobial peptides in human proteins, named Hs IAPs. These IAPs were prospected using the software Kamal, synthesized by solid phase chemistry, and had their interactions with model phospholipid vesicles investigated by differential scanning calorimetry and circular dichroism. Their antimicrobial activity against bacteria, yeasts and filamentous fungi was determined, along with their cytotoxicity towards erythrocytes. Our data demonstrates that Hs IAPs are capable to bind model membranes while attaining α-helical structure, and to inhibit the growth of microorganisms at concentrations as low as 1µM. Hs02, a novel sixteen residue long internal peptide (KWAVRIIRKFIKGFIS-NH2) derived from the unconventional myosin 1h protein, was further investigated in its capacity to inhibit lipopolysaccharide-induced release of TNF-α in murine macrophages. Hs02 presented potent anti-inflammatory activity, inhibiting the release of TNF-α in LPS-primed cells at the lowest assayed concentration, 0.1 µM. A three-dimensional solution structure of Hs02 bound to DPC micelles was determined by Nuclear Magnetic Resonance. Our work exemplifies how the human genome can be mined for molecules with biotechnological potential in human health and demonstrates that IAPs are actual alternatives to antimicrobial peptides as pharmaceutical agents or in their many other putative applications.

Zika-Induced Male Infertility in Mice Is Potentially Reversible and Preventable by Deoxyribonucleic Acid Immunization.

Background: Zika virus (ZIKV) infection has been associated with prolonged viral excretion in human semen and causes testicular atrophy and infertility in 10-week-old immunodeficient mice. Methods: Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 × 105 plaque-forming units at 13 weeks of age. On day 28 postinfection, testes and epididymides were collected in some mice for histological and functional analyses, whereas others were mated with naive female wild-type C57BL/6J. Results: Although all mice challenged with ZIKV developed viremia, most of them were asymptomatic, showed no weight loss, and survived infection. On day 28 postinfection, none of the unvaccinated, infected mice (9 of 9) exhibited abnormal spermatozoa counts or motility. However, 33% (3 of 9) and 36% (4 of 11) of mated males from this group were infertile, from 2 independent studies. Contrarily, males from the noninfected and the vaccinated, infected groups were all fertile. On days 75 and 207 postinfection, partial recovery of fertility was observed in 66% (2 of 3) of the previously infertile males. Conclusions: This study reports the effects of ZIKV infection on male fertility in a sublethal, immunodeficient mouse model and the efficacy of GLS-5700 vaccination in preventing male infertility.

Granzyme A in Chikungunya and Other Arboviral Infections.

Granzyme A (GzmA) is secreted by cytotoxic lymphocytes and has traditionally been viewed as a mediator of cell death. However, a growing body of data suggests the physiological role of GzmA is promotion of inflammation. Here, we show that GzmA is significantly elevated in the sera of chikungunya virus (CHIKV) patients and that GzmA levels correlated with viral loads and disease scores in these patients. Serum GzmA levels were also elevated in CHIKV mouse models, with NK cells the likely source. Infection of mice deficient in type I interferon responses with CHIKV, Zika virus, or dengue virus resulted in high levels of circulating GzmA. We also show that subcutaneous injection of enzymically active recombinant mouse GzmA was able to mediate inflammation, both locally at the injection site as well as at a distant site. Protease activated receptors (PARs) may represent targets for GzmA, and we show that treatment with PAR antagonist ameliorated GzmA- and CHIKV-mediated inflammation.

Zika Virus Vaccines: Challenges and Perspectives.

Zika virus is an arbovirus that has rapidly spread within the Americas since 2014, presenting a variety of clinical manifestations and neurological complications resulting in congenital malformation, microcephaly, and possibly, in male infertility. These significant clinical manifestations have led investigators to develop several candidate vaccines specific to Zika virus. In this review we describe relevant targets for the development of vaccines specific for Zika virus, the development status of various vaccine candidates and their different platforms, as well as their clinical progression.

Schistosomal Lipids Activate Human Eosinophils via Toll-Like Receptor 2 and PGD2 Receptors: 15-LO Role in Cytokine Secretion.

Parasite-derived lipids may play important roles in host-pathogen interactions and immune evasion mechanisms. Remarkable accumulation of eosinophils is a characteristic feature of inflammation associated with parasitic disease, especially caused by helminthes. Infiltrating eosinophils are implicated in the pathogenesis of helminth infection by virtue of their capacity to release an array of tissue-damaging and immunoregulatory mediators. However, the mechanisms involved in the activation of human eosinophils by parasite-derived molecules are not clear. Here we investigated the effects and mechanisms of schistosomal lipids-induced activation of human eosinophils. Our results showed that stimulation of human eosinophils in vitro with total lipid extracts from adult worms of S. mansoni induced direct activation of human eosinophils, eliciting lipid droplet biogenesis, synthesis of leukotriene (LT) C4 and eoxin (EX) C4 (14,15 LTC4) and secretion of eosinophil pre-formed TGFß. We demonstrated that main eosinophil activating components within S. mansoni lipid extract are schistosomal-derived lysophosphatidylcholine (LPC) and prostaglandin (PG)D2. Moreover, TLR2 is up-regulated in human eosinophils upon stimulation with schistosomal lipids and pre-treatment with anti-TLR2 inhibited both schistosomal lipids- and LPC-, but not PGD2-, induced lipid droplet biogenesis and EXC4 synthesis within eosinophils, indicating that TLR2 mediates LPC-driven human eosinophil activation. By employing PGD2 receptor antagonists, we demonstrated that DP1 receptors are also involved in various parameters of human eosinophil activation induced by schistosomal lipids, but not by schistosomal LPC. In addition, schistosomal lipids and their active components PGD2 and LPC, triggered 15-LO dependent production of EXC4 and secretion of TGFß. Taken together, our results showed that schistosomal lipids contain at least two components-LPC and PGD2-that are capable of direct activation of human eosinophils acting on distinct eosinophil-expressed receptors, noticeably TLR2 as well as DP1, trigger human eosinophil activation characterized by production/secretion of pro-inflammatory and immunoregulatory mediators.

The effects of EPA and DHA enriched fish oil on nutritional and immunological markers of treatment naïve breast cancer patients: a randomized double-blind controlled trial.

BACKGROUND: We evaluated the effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids enriched fish oil (FO) on nutritional and immunological parameters of treatment naïve breast cancer patients. METHODS: In a randomized double blind controlled trial, the FO group (FG) patients were supplemented with 2 g/ day of FO concentrate containing 1.8 g of n-3 fatty acids during 30 days. The placebo group (PG) received 2 g/ day of mineral oil. At baseline and after the intervention, plasma levels of n-3 fatty acids, dietary intake, weight, body composition, biochemical and immunological markers were assessed. RESULTS: At the end of the intervention period, no between group differences were observed regarding anthropometric parameters. There was a significant increase in the plasma phospholipid EPA (p = 0.004), DHA (p = 0.007) of the FG patients. In FG patients the percentages of peripheral blood CD4+ T lymphocytes and serum high sensitivity C-reactive protein (hsCRP) levels were maintained while in PG patients there was a significant increase in hsCRP (p = 0.024). We also observed a significant reduction in the percentage of CD4+ T lymphocytes in the peripheral blood (p = 0.042) of PG patients. No changes in serum proinflammatory cytokine and prostaglandin E2 levels were observed. CONCLUSIONS: Supplementation of newly diagnosed breast cancer patients with EPA and DHA led to a significant change in the composition of plasma fatty acids, maintained the level of CD4+ T cells and serum levels of hsCRP, suggestive of a beneficial effect on the immune system and less active inflammatory response. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC): RBR-2b2hqh. Registered 29 April 2013, retrospectively registered.

Revealing a Novel Otubain-Like Enzyme from Leishmania infantum with Deubiquitinating Activity toward K48-Linked Substrate.

Deubiquitinating enzymes (DUBs) play an important role in regulating a variety of eukaryotic processes. In this context, exploring the role of deubiquitination in Leishmania infantum could be a promising alternative to search new therapeutic targets for leishmaniasis. Here we present the first characterization of a DUB from L. infantum, otubain (OtuLi), and its localization within parasite. The recombinant OtuLi (rOtuLi) showed improved activity on lysine 48 (K48)-linked over K63-linked tetra-ubiquitin (Ub) and site-directed mutations on amino acids close to the catalytic site (F82) or involved in Ub interaction (L265 and F182) caused structural changes as shown by molecular dynamics, resulting in a reduction or loss of enzyme activity, respectively. Furthermore, rOtuLi stimulates lipid droplet biogenesis (an inflammatory marker) and induces IL-6 and TNF-α secretion in peritoneal macrophages, both proinflammatory cytokines. Our findings suggest that OtuLi is a cytoplasmic enzyme with K48-linked substrate specificity that could play a part in proinflammatory response in stimulated murine macrophages.

Mycobacterium tuberculosis Prolyl Oligopeptidase Induces In vitro Secretion of Proinflammatory Cytokines by Peritoneal Macrophages.

Tuberculosis (TB) is a disease that leads to death over 1 million people per year worldwide and the biological mediators of this pathology are poorly established, preventing the implementation of effective therapies to improve outcomes in TB. Host-bacterium interaction is a key step to TB establishment and the proteases produced by these microorganisms seem to facilitate bacteria invasion, migration and host immune response evasion. We presented, for the first time, the identification, biochemical characterization, molecular dynamics (MDs) and immunomodulatory properties of a prolyl oligopeptidase (POP) from Mycobacterium tuberculosis (POPMt). POP is a serine protease that hydrolyzes substrates with high specificity for proline residues and has already been characterized as virulence factor in infectious diseases. POPMt reveals catalytic activity upon N-Suc-Gly-Pro-Leu-Gly-Pro-AMC, a recognized POP substrate, with optimal activity at pH 7.5 and 37°C. The enzyme presents KM and Kcat/KM values of 108 µM and 21.838 mM-1 s-1, respectively. MDs showed that POPMt structure is similar to that of others POPs, which consists of a cylindrical architecture divided into an α/ß hydrolase catalytic domain and a ß-propeller domain. Finally, POPMt was capable of triggering in vitro secretion of proinflammatory cytokines by peritoneal macrophages, an event dependent on POPMt intact structure. Our data suggests that POPMt may contribute to an inflammatory response during M. tuberculosis infection.

Differences in the modulation of reactive species, lipid bodies, cyclooxygenase-2, 5-lipoxygenase and PPAR-γ in cerebral malaria-susceptible and resistant mice.

Proinflammatory responses are associated with the severity of cerebral malaria. NO, H2O2, eicosanoid and PPAR-γ are involved in proinflammatory responses, but regulation of these factors is unclear in malaria. This work aimed to compare the expression of eicosanoid-forming-enzymes in cerebral malaria-susceptible CBA and C57BL/6 and -resistant BALB/c mice. Mice were infected with Plasmodium berghei ANKA, and the survival rates and parasitemia curves were assessed. On the sixth day post-infection, cyclooxygenase-2 and 5-lipoxygenase in brain sections were assessed by immunohistochemistry, and, NO, H2O2, lipid bodies, and PPAR-γ expression were assessed in peritoneal macrophages. The C57BL/6 had more severe disease with a lower survival time, higher parasitemia and lower production of plasmodicidal NO and H2O2 molecules than BALB/c. Enhanced COX-2 and 5-LOX expression were observed in brain tissue cells and vessels from C57BL/6 mice, and these mice expressed higher constitutive PPAR-γ levels. There was no translocation of PPAR-γ from cytoplasm to nucleus in macrophages from these mice. CBA mice had enhanced COX-2 expression in brain tissue cells and vessels and also lacked PPAR-γ cytoplasm-to-nucleus translocation. The resistant BALB/c mice presented higher survival time, lower parasitemia and higher NO and H2O2 production on the sixth day post-infection. These mice did not express either COX-2 or 5-LOX in brain tissue cells and vessels. Our data showed that besides the high parasite burden and lack of microbicidal molecules, an imbalance with high COX-2 and 5-LOX eicosanoid expression and a lack of regulatory PPAR-γ cytoplasm-to-nucleus translocation in macrophages were observed in mice that develop cerebral malaria.

Schistosomal-derived lysophosphatidylcholine triggers M2 polarization of macrophages through PPARγ dependent mechanisms.

Mansonic schistosomiasis is a disease caused by the trematode Schistosoma mansoni, endemic to tropical countries. S. mansoni infection induces the formation of granulomas and potent polarization of Th2-type immune response. There is great interest in understanding the mechanisms used by this parasite that causes a modulation of the immune system. Recent studies from our group demonstrated that lipids of S. mansoni, including lysophosphatidylcholine (LPC) have immunomodulatory activity. In the present study, our aim was to investigate the role of lipids derived from S. mansoni in the activation and polarization of macrophages and to characterize the mechanisms involved in this process. Peritoneal macrophages obtained from wild type C57BL/6mice or bone marrow derived macrophages were stimulated in vitro with lipids extracted from adult worms of S. mansoni. We demonstrated that total schistosomal-derived lipids as well as purified LPC induced alternatively activated macrophages/M2 profile observed by increased expression of arginase-1, mannose receptor, Chi3l3, TGFß and production of IL-10 and PGE2 24h after stimulation. The involvement of the nuclear receptor PPARγ in macrophage response against LPC was investigated. Through Western blot and immunofluorescence confocal microscopy we demonstrated that schistosomal-derived LPC induces increased expression of PPARγ in macrophages. The LPC-induced increased expression of arginase-1 were significantly inhibited by the PPAR-γ antagonist GW9662. Together, these results demonstrate an immunomodulatory role of schistosomal-derived LPC in activating macrophages to a profile of the type M2 through PPARγ-dependent mechanisms, indicating a novel pathway for macrophage polarization triggered by parasite-derived LPC with potential implications to disease pathogenesis.

Carbon dots (C-dots) from cow manure with impressive subcellular selectivity tuned by simple chemical modification.

Improved cellular selectivity for nucleoli staining was achieved by simple chemical modification of carbon dots (C-dots) synthesized from waste carbon sources such as cow manure (or from glucose). The C-dots were characterized and functionalized (amine-passivated) with ethylenediamine, affording amide bonds that resulted in bright green fluorescence. The new modified C-dots were successfully applied as selective live-cell fluorescence imaging probes with impressive subcellular selectivity and the ability to selectively stain nucleoli in breast cancer cell lineages (MCF-7). The C-dots were also tested in four other cellular models and showed the same cellular selection in live-cell imaging experiments.

Clavanin A improves outcome of complications from different bacterial infections.

The rapid increase in the incidence of multidrug-resistant infections today has led to enormous interest in antimicrobial peptides (AMPs) as suitable compounds for developing unusual antibiotics. In this study, clavanin A, an antimicrobial peptide previously isolated from the marine tunicate Styela clava, was selected as a purposeful molecule that could be used in controlling infection and further synthesized. Clavanin A was in vitro evaluated against Staphylococcus aureus and Escherichia coli as well as toward L929 mouse fibroblasts and skin primary cells (SPCs). Moreover, this peptide was challenged here in an in vivo wound and sepsis model, and the immune response was also analyzed. Despite displaying clear in vitro antimicrobial activity toward Gram-positive and -negative bacteria, clavanin A showed no cytotoxic activities against mammalian cells, and in acute toxicity tests, no adverse reaction was observed at any of the concentrations. Moreover, clavanin A significantly reduced the S. aureus CFU in an experimental wound model. This peptide also reduced the mortality of mice infected with E. coli and S. aureus by 80% compared with that of control animals (treated with phosphate-buffered saline [PBS]): these data suggest that clavanin A prevents the start of sepsis and thereby reduces mortality. These data suggest that clavanin A is an AMP that could improve the development of novel peptide-based strategies for the treatment of wound and sepsis infections.