Ancient genomes reveal insights into ritual life at Chichén Itzá.

The ancient city of Chichén Itzá in Yucatán, Mexico, was one of the largest and most influential Maya settlements during the Late and Terminal Classic periods (AD 600-1000) and it remains one of the most intensively studied archaeological sites in Mesoamerica1-4. However, many questions about the social and cultural use of its ceremonial spaces, as well as its population's genetic ties to other Mesoamerican groups, remain unanswered2. Here we present genome-wide data obtained from 64 subadult individuals dating to around AD 500-900 that were found in a subterranean mass burial near the Sacred Cenote (sinkhole) in the ceremonial centre of Chichén Itzá. Genetic analyses showed that all analysed individuals were male and several individuals were closely related, including two pairs of monozygotic twins. Twins feature prominently in Mayan and broader Mesoamerican mythology, where they embody qualities of duality among deities and heroes5, but until now they had not been identified in ancient Mayan mortuary contexts. Genetic comparison to present-day people in the region shows genetic continuity with the ancient inhabitants of Chichén Itzá, except at certain genetic loci related to human immunity, including the human leukocyte antigen complex, suggesting signals of adaptation due to infectious diseases introduced to the region during the colonial period.

Models in vivo and in vitro for the study of acute and chronic inflammatory activity: A comprehensive review.

Inflammatory conditions are among the principal causes of morbidity worldwide, and their treatment continues to be a challenge, given the restricted availability of effective and safe drugs. Thus, the identification of new compounds with biological activity that can be used for the treatment of inflammatory disorders is an essential field in medical and health research, in order to improve the health and quality of life of patients suffering from these diseases. Evaluation of the anti-inflammatory activity of drugs requires the implementation of models that accurately depict the biochemical and/or physiological responses that characterize human inflammation; for this reason, several in vitro and in vivo models have been developed, providing a platform for discovering novel or repurposed compounds. For this reason, in the present review we have selected twelve commonly used models for the evaluation of the anti-inflammatory effect, and extensively describes the difference between in vivo and in vitro models of inflammation, highlighting their advantages and limitations. On the other hand, the inflammatory mechanisms involved in them, the methods employed for their establishment, and the different parameters assessed to determine the anti-inflammatory activity of a given compound are extensively discussed. We expect to provide a comprehensive guide for the improved selection of a suitable model for the preclinical evaluation of plausible anti-inflammatory agents.

Activation of murine macrophages by membrane proteins from Tritrichomonas foetus grown on iron- and calcium-rich conditions.

Tritrichomonas foetus is a protozoan parasite that causes a venereal disease in cattle limiting reproduction by abortions and sterility. The immune response against this parasite is poorly understood. Since the iron and calcium ions are important regulators of the microenvironment of the urogenital tract in cattle, we decided to evaluate the role of these divalent cations on the antigenicity of membrane proteins of T. foetus on macrophage activation as one of the first inflammatory responses towards this pathogen. Colorimetric methods and ELISA were used to detect the nitric oxide and oxygen peroxide production and expression of cytokines in culture supernatant from macrophage incubated with membrane proteins from T. foetus cultured in iron- and calcium-rich conditions. qRT-PCR assays were used to evaluate the transcript expression of genes involved in the inflammatory response on the macrophages. The membrane proteins used for in vitro stimulation caused the up-regulation of the iNOS and NOX-2 genes as well as the generation of NO and H2 O2 in murine macrophages on a dependent way of the metal concentrations. Additionally, after stimulation, macrophages showed a considerable rise in pro-inflammatory cytokines and a downregulation of anti-inflammatory cytokines, as well as up-regulation in the transcription of the TLR4 and MyD88 genes. These data suggest that membrane proteins of T. foetus induced by iron and calcium can activate an inflammatory specific macrophage response via TLR4/MyD88 signalling pathway.

Exposure of Tritrichomonas foetus to sublethal doses of metronidazole induces a specific proinflammatory response in murine macrophages.

Tritrichomonas foetus is a flagellated parasite that primarily infects the reproductive tissues of livestock, causing bovine trichomoniasis. The cytoplasmic membrane of T. foetus contains various compounds that contribute to adherence, colonization, and pathogenicity. Metronidazole (MTZ) is the main treatment for trichomoniasis, but the emergence of drug-resistant strains is a concern due to improper use and dosing. T. foetus infection induces inflammation, and macrophages are key players in the immune response. However, our understanding of the host's immune response to T. foetus is limited, and the specific mechanisms underlying these responses are not well understood. This study aimed to investigate the impact of T. foetus surface proteins from trophozoites cultured under different sublethal MTZ conditions (MTZ-treated T. foetus MPs) on macrophage activation. By analyzing cytokine levels and gene expression in murine macrophages, we demonstrated that MTZ-treated T. foetus MPs induce a specific proinflammatory response. MTZ-treated T. foetus MPs-exposed macrophages exhibited a higher NO and H2 O2 production and overexpression of iNOS and NOX-2 genes in comparison to untreated T. foetus. Additionally, MTZ-treated T. foetus MPs triggered a significant induction of the proinflammatory cytokines IL-1ß, IL-6, TNF-α, and IFN-γ, as well as the overexpression of the TLR4, MyD88, and NF-κB genes on murine macrophages. The study aimed to unravel the immunological response and potential proinflammatory pathways involved in T. foetus infection and MTZ stress. Understanding the immune responses and mechanisms through which T. foetus surface proteins activate macrophages can contribute to the development of new therapeutic strategies for controlling bovine trichomoniasis.

Epigenetic Factors and ncRNAs in Testicular Cancer.

Testicular cancer is the most prevalent tumor among males aged 15 to 35, resulting in a significant number of newly diagnosed cases and fatalities annually. Non-coding RNAs (ncRNAs) have emerged as key regulators in various cellular processes and pathologies, including testicular cancer. Their involvement in gene regulation, coding, decoding, and overall gene expression control suggests their potential as targets for alternative treatment approaches for this type of cancer. Furthermore, epigenetic modifications, such as histone modifications, DNA methylation, and the regulation by microRNA (miRNA), have been implicated in testicular tumor progression and treatment response. Epigenetics may also offer critical insights for prognostic evaluation and targeted therapies in patients with testicular germ cell tumors (TGCT). This comprehensive review aims to present the latest discoveries regarding the involvement of some proteins and ncRNAs, mainly miRNAs and lncRNA, in the epigenetic aspect of testicular cancer, emphasizing their relevance in pathogenesis and their potential, given the fact that their specific expression holds promise for prognostic evaluation and targeted therapies.

Detection of rotavirus and norovirus among children with acute gastroenteritis in Merida and Chihuahua cities, Mexico.

INTRODUCTION: Infantile acute gastroenteritis (AGE) is a leading cause of morbidity and mortality, particularly in developing countries. The most frequent etiological agents of viral gastroenteritis in children are adenovirus, astrovirus, rotavirus, and norovirus, the last two, leading causes. Thus, the aim of this study was to identify the presence of these two viruses in children with AGE, from two cities located in the Southeast and the Northwest regions of México. METHODOLOGY: HuNoVs were detected and characterized by RT-PCR and sequencing, while RVs were detected by RNA electrophoresis. RESULTS: The presence of RV and HuNoV was evaluated in 81 stool samples; 37 were collected between April and July 2013 from patients with acute diarrhea in Merida, and 44 were collected between January and June 2017 in Chihuahua, who attended health services. Despite vaccination, RV resulted in the predominant viruses detected, with 30.8% (25/81) positivity, while HuNoV infection was present in 8.6% (7/81) of the stool samples; GII strains were identified circulating in the Southeast, while GI strains were identified in the Northwest. Moreover, co-infections with both viruses were detected at a prevalence rate of 2.4% (2/81). CONCLUSIONS: The circulation of RV and HuNoV in the country is continuous and should be constantly monitored due to their impact on public health.

Natural marine products as antiprotozoal agents against amitochondrial parasites.

The goal of this work is to compile and discuss molecules of marine origin reported in the scientific literature with anti-parasitic activity against Trichomonas, Giardia, and Entamoeba, parasites responsible for diseases that are major global health problems, and Microsporidial parasites as an emerging problem. The presented data correspond to metabolites with anti-parasitic activity in human beings that have been isolated by chromatographic techniques from marine sources and structurally elucidated by spectroscopic and spectrometric procedures. We also highlight some semi-synthetic derivatives that have been successful in enhancing the activity of original compounds. The biological oceanic reservoir offers the possibility to discover new biologically active molecules as lead compounds to develop new drug candidates. The molecular variety is extensive and must be correctly explored and managed. Also, it will be necessary to take some actions to preserve the source species from extinction or overharvest (e.g., by cryopreservation of coral spermatozoa, oocytes, embryos, and larvae) and coordinate appropriate exploitation to increase the chemical knowledge of the natural products generated in the oceans. Additional initiatives such as the total synthesis of complex natural products and their derivatives can help to prevent overharvest of the marine ecosystems and at the same time contribute to the discovery of new molecules.

In Vitro Activation of Macrophages by an MHC Class II-restricted Trichomonas Vaginalis TvZIP8-derived Synthetic Peptide.

BACKGROUND: Macrophages play an important role in the inflammatory response towards pathogens and their effector functions depend on the mode of activation which is mediated by recognition of pathogen-associated molecular patterns, as peptides. Trichomonas vaginalis provokes an inflammatory response in the host in which macrophages are the first line of defense. This study aimed to analyze the effect of a specific peptide derived from the transporter TvZIP8 of T. vaginalis on the activation of macrophages. METHODS: An in silico approach based on computational prediction of epitopes was applied to detect potential murine MHC class II-restricted peptides from TvZIP8 that can activate macrophages and the immunomodulatory activity was evaluated by in vitro stimulation of murine macrophages. RESULTS: Based on binding scores, one peptide denominated TvZIP8-pep was selected for further analysis. In vitro stimulation with synthetic TvZIP8-pep triggered on murine macrophages the NO and H2O2 production and an overexpression of iNOS and NOX-2 genes. Also, a significant increase of pro-inflammatory cytokines: IL-1ß, IL-6, and TNF-α, as well as, overexpression of the TLR4, MyD88, and NF-κB genes and NF-κB activation were observed on macrophages after stimulation with TvZIP8-pep in vitro. Moreover, higher levels of IFN-γ were detected in co-cultures using CD4 + T cells with TvZIP8-pep-stimulated macrophages. CONCLUSION: These results support the potential of TvZIP8 as a promising antigen to stimulates a specific macrophage response against T. vaginalis, but further analyses are required to evaluate their possible potential as a novel antigen for immunodiagnosis and/or vaccine against trichomoniasis.

Lupeol acetate isolated from Chrysophyllum cainito L. fruit as a template for the synthesis of N-alkyl-arylsulfonamide derivatives and their synergistic effects with metronidazole against Trichomonas vaginalis.

Pentacyclic triterpenes are found in a great variety of natural products and constitute an organic template for the development of new derivative compounds with therapeutic applications. In the present work, lupeol acetate isolated from Chrysophyllum cainito L. fruit was used as a template for the synthesis of novel N-alkyl-arylsulfonamide derivatives, and their synergistic effects with metronidazole against strains of Trichomonas vaginalis were tested. A library of 18 derivatives was synthesized. Ten compounds exhibited an IC50 < 100 µM against a metronidazole-sensitive strain of T. vaginalis. Only seven of these compounds (12, 15, 18-22) also showed activity against metronidazole-resistant strains. The compounds 20 (N-cyclohexyl-p-chlorobenzenesulfonamidolupeol acetate) and 22 (N-cyclohexyl-p-nitrobenzenesulfonamidolupeol acetate) exhibited a similar IC50 against both susceptible and resistant T. vaginalis strains and enhanced the efficacy of metronidazole in a partial and total synergistic way, respectively. These data provided evidence of the trichomonicidal effect of N-alkyl-arylsulfonamide derivatives of lupeol acetate, representing highly promising novel antiparasitic agents.

Pharmacological activities of Asclepias curassavica L. (Apocynaceae) aerial parts.

ETHNOPHARMACOLOGICAL RELEVANCE: Asclepias curassavica L. (Apocynaceae) is a perennial shrub used in the folk treatment of parasitism, pain, and inflammation. AIM OF THE STUDY: This work assessed the antiparasitic, anti-inflammatory, antinociceptive, and sedative effects of an ethanol extract from the aerial parts of Asclepias curassavica (ACE). MATERIALS AND METHODS: The antiparasitic activity against Trichomonas vaginalis was evaluated using the trypan blue exclusion test. The in vitro anti-inflammatory actions of ACE (1-200 µg/ml) were analyzed using LPS-stimulated primary murine macrophages. The in vivo pharmacological activity of ACE (50-200 mg/kg p.o.) was evaluated using animal models of inflammation (TPA-induced ear edema test and carrageenan-induced paw edema test) and nociception (acetic acid-induced writhing test, formalin-induced licking test, and hot plate test). RESULTS: ACE showed poor antiparasitic effects against Trichomonas vaginalis (IC50 = 302 µg/ml). ACE increased the production of IL-10 in both in vitro assays (EC50 = 3.2 pg/ml) and in vivo assays (ED50 = 111 mg/kg). ACE showed good antinociceptive actions (ED50 = 158 mg/kg in phase 1 and ED50 = 83 mg/kg in phase 2) in the formalin test. Pre-treatment with naloxone blocked the antinociceptive response induced by ACE. In addition, ACE did not induce sedative effects or motor coordination deficits in mice. CONCLUSION: Findings showed that the anti-inflammatory activity of ACE is associated with increasing levels of IL-10 in both in vitro and in vivo assays, whereas the antinociceptive effect is associated with the participation of the opioidergic system, without inducing sedation or motor coordination impairment.

Anti-inflammatory effects of Chrysophyllum cainito fruit extract in lipopolysaccharide-stimulated mouse peritoneal macrophages.

The present paper sought to investigate the in vitro and in vivo anti-inflammatory effects of the methanolic extract (ME), hexane-ethyl acetate fraction E (FE) found in Chrysophyllum cainito fruits (CCF), as well the lupeol acetate (LA) obtained from FE on lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. The macrophages were treated with ME, FE or LA at various concentrations and the viability of cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. Production of pro-inflammatory (IL-1ß, IL-6, and TNF-α) and anti-inflammatory (IL-10) cytokines, as well as the nitric oxide (NO) and hydrogen peroxide (H2O2) levels was determined using macrophages treated with ME, FE or LA at various concentrations and stimulated with LPS as an in vitro model. Afterwards, we evaluated the anti-inflammatory effects in vivo using the TPA-induced ear edema and carrageenan-induced paw edema tests in mice and production of inflammatory mediators was estimated in serum samples. The results showed that the ME, FE and LA from fruits, FE and LA were able to trigger an inhibition in NO and H2O2 levels, as well as IL-1ß, IL-6, and TNF-α released by macrophages in a concentration-dependent manner. LA from C. cainito fruits was found to significantly attenuate carrageenan-induced paw edema and TPA-induced ear edema. Therefore, the results suggest ME, FE and LA isolated from C. cainito fruits have anti-inflammatory effects on macrophages without affecting cell viability.

Clinical relevance of lipid panel and aminotransferases in the context of hepatic steatosis and fibrosis as measured by transient elastography (FibroScan®).

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease and is associated with various co-morbidities. Transient elastography (FibroScan®) is a non-invasive method to detect NAFLD using the controlled attenuation parameter (CAP). We aimed to evaluate the association of the lipid panel and aminotransferases concentrations with the presence or absence of steatosis and fibrosis. METHODS: One hundred and five patients with NAFLD were included. Hepatic steatosis was quantified by CAP (dB/m) and liver stiffness by Kilopascals (kPa), these values were then analyzed against patient lipid panel and serum concentrations of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). A correlation and multiple regression were used. Mann-Whitney U test was used as non-parametric analysis. RESULTS: We observed an association between hepatic steatosis and total cholesterol (B = 0.021, p = 0.038, Exp (B) = 1.021, I.C = 1.001-1.041) as well as serum triglycerides (B = 0.017, p = 0.006, Exp (B) = 1.018 and I.C = 1.005-1.030). Similarly, we found an association between significant hepatic fibrosis and lower concentrations of total cholesterol (B = -0.019, p = 0.005, Exp (B) = 0.982 I.C = 0.969-0.995) and elevated AST (B = 0.042, p = 3.25 × 10-4, Exp (B) = 1.043 I.C = 1.019-1.068) independent of age, gender and BMI. CONCLUSIONS: Our results suggest that, total cholesterol and triglyceride concentrations positively correlate with hepatic steatosis while significant hepatic fibrosis is associated with lower total cholesterol and higher AST concentrations.

Antitrichomonal activity and docking analysis of thiazole derivatives as TvMP50 protease inhibitors.

Trichomoniasis, caused by the protozoan Trichomonas vaginalis, is the most prevalent non-viral sexually transmitted infection that affects over 170 million people worldwide. The only type of drug recommended for the therapeutic control of trichomoniasis is the 5-nitroimidazoles, although there have been reports of some undesirable side effects and clinical resistance. Hence, the need for the search for new tricomonicidal agents is necessary. In a previous work, we demonstrated that two 2-amino-4-aryl thiazole derivatives (ATZ-1 and ATZ-2) possess a portent antigiardial effect. In the current paper, we investigated the in vitro antitrichomonal activity of these thiazole compounds. Both ATZ-1 and ATZ-2 reduced the viability and growth of parasites in a dose-dependent manner, with an IC50 value of 0.15 µg/mL and 0.18 µg/mL, respectively. Furthermore, both thiazole compounds were able to decrease the proteolytic activity in T. vaginalis trophozoites compared with untreated parasites. Interestingly, a full proteolytic inhibition profile was observed in the 50-kDa region which was associated with the decreased expression of the gene that codes for the trichomonad protease TvMP50. The docking simulations predicted strong interactions of the thiazole compounds in the TvMP50 protease's active site, suggesting a possible role as protease inhibitors. Our results demonstrate the potential of 2-amino-4-aryl thiazole derivatives as trichomonicidal compounds and could be, mechanistically, involved in the inhibition of key trichomonad proteases.

Antinociceptive and anti-inflammatory effects of Cuphea aequipetala Cav (Lythraceae).

Cuphea aequipetala Cav (Lythraceae) is an herb used in folk treatment for pain and inflammation. The aim of this study was to evaluate the antinociceptive and anti-inflammatory actions of an ethanol extract from the leaves and stem of Cuphea aequipetala (CAE). The antinociceptive actions of CAE (10-200 mg/kg p.o.) were assessed with the acetic acid-induced writhing, hot plate, and formalin tests. The possible mechanism of action of CAE was evaluated using inhibitors. The effects of CAE on motor coordination were assessed by the rotarod test. The in vitro anti-inflammatory actions of CAE were evaluated using LPS-stimulated primary murine macrophages, and the in vivo anti-inflammatory actions were assessed by the TPA-induced ear oedema and the carrageenan-induced paw oedema tests. The production of inflammatory mediators was estimated from both in vitro and in vivo assays. CAE showed antinociception (ED50 = 90 mg/kg) in the acetic acid test and in the second phase of the formalin test (ED50 = 158 mg/kg). Pretreatment with glibenclamide or L-NAME partially reversed the antinociception shown by the plant extract. CAE (50-200 mg/kg) did not affect motor coordination in mice. CAE increased the production of IL-10 in LPS-stimulated macrophages (EC50 = 10 pg/ml) and, in the carrageenan-induced paw oedema test (threefold increase). In conclusion, CAE induced antinociceptive effects without affecting motor coordination, probably due to the involvement of nitric oxide and ATP-sensitive K+ channels. CAE also exerts in vitro and in vivo anti-inflammatory effects by increasing the release of IL-10.

High expression levels of circulating microRNA-122 and microRNA-222 are associated with obesity in children with Mayan ethnicity.

OBJECTIVES: High expression levels (HELs) of microRNA-122 (miR-122) or microRNA-222 (miR-222) have been associated with insulin resistance (IR), which leads to the development of obesity. The association between HELs of circulating miR-122 and miR-222 and the risk of obesity was evaluated in Mexican school-aged children, where childhood obesity is the primary cause of morbidity. METHODS: Anthropometric data, biochemical parameters, and caloric intake were obtained in 50 children with obesity and 49 children with normal weight. The expression of circulating miR-122 and miR-222 was measured by quantitative real-time polymerase chain reaction amplification. Data were analyzed using Student t test, Pearson correlation coefficient, associations with chi-square, and multiple linear and logistic regressions with SPSS software v.23. RESULTS: The mean relative expression for miR-122 and miR-222 was 0.33 and 5.65, respectively, for children with obesity and 0.22 and 3.16, respectively, for children with normal weight. The expression of miR-122 and miR-222 was 1.47 and 1.78-fold higher, respectively, in children with obesity (P = 0.001 and P = 0.025). HELs of both miR-122 and miR-222 were associated with body mass index (BMI), waist to height ratio (WHR), fat percentage, serum high-density lipid levels, triglycerides (TGs), and metabolic index (MI) (P < .001). CONCLUSIONS: The HELs of circulating miR-122 conferred a 3.85-fold increase in the risk for obesity, whereas the HELs of both miR-122 and miR-222 conferred a 3.11-fold increase in the risk for obesity, which were also associated with higher anthropometric or biochemical parameters, such as BMI, WHR, fat percentage, serum high-density lipid levels, TGs, and MI, in Mayan children.

In vitro and in vivo anti-inflammatory effects of an ethanol extract from the aerial parts of Eryngium carlinae F. Delaroche (Apiaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Eryngium carlinae F. Delaroche (Apiaceae) is an herb used in folk medicine as a diuretic, analgesic, and anti-inflammatory agent. AIM OF THE STUDY: This work assessed the diuretic, antinociceptive, and anti-inflammatory actions of an ethanol extract from the leaves and stems of Eryngium carlinae (ECE). These ethnomedicinal properties of ECE were scientifically validated using in vitro and in vivo assays. MATERIALS AND METHODS: The antinociceptive and diuretic actions of ECE (10-200 mg/kg p.o.) were assessed with the acetic acid-induced writhing test and by using metabolic cages to house mice, respectively. The in vitro anti-inflammatory actions of ECE (1-500 µg/ml) were evaluated using LPS-stimulated primary murine macrophages, and the in vivo anti-inflammatory actions were assessed using the TPA-induced ear edema test (2 mg/ear) and carrageenan-induced paw edema test (50-200 mg/kg p.o.). The production of inflammatory mediators was estimated using in vitro and in vivo assays. RESULTS: ECE lacked antinociceptive and diuretic effects. ECE increased the production of IL-10 in LPS-stimulated macrophages (EC50 = 37.8 pg/ml) and the carrageenan-induced paw edema test (ED50 = 82.6 mg/kg). ECE showed similar in vivo anti-inflammatory actions compared to those observed with indomethacin. CONCLUSION: ECE exerts in vitro and in vivo anti-inflammatory effects by increasing the release of IL-10.

Matrix metalloproteinases deregulation in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons that results in progressive paralysis and muscular atrophy. There are many molecules and genes involved in neuromuscular degeneration in ALS; among these, matrix metalloproteinases (MMPs). MMPs play an important role in the pathology of ALS, and MMP-1, 2, 3, and 9 might serve as disease progression markers. Tissue inhibitors of metalloproteinases (TIMPS) might also function as progression markers in ALS because they participate in regulating the proteolytic activity of MMPs. Moreover, a diversity of genes also plays a role in the pathogenesis of ALS; most MMPs-coding genes present variants related to the pathological proteolytic activity. This short review, however, will focus on the role of matrix metalloproteinases in ALS.

In silico analysis of putative metal response elements (MREs) in the zinc-responsive genes from Trichomonas vaginalis and the identification of novel palindromic MRE-like motif.

Zinc is an essential micronutrient that plays an important role as a co-factor to several proteins, including zinc-responsive transcription factors. Trichomonas vaginalis is able to survive in the presence of high zinc concentrations in the male urogenital tract. Several genes in T. vaginalis have been shown to respond to changes in zinc concentrations, however, the zinc-dependent mechanism remains undetermined. Recently, we identified in T. vaginalis the zinc finger protein, TvZNF1, which is an ortholog of the mammal metal transcription factor (MTF1). We searched for several of the zinc-responsive genes in T. vaginalis to determine whether if they contain metal response elements (MRE), cis-acting DNA elements that specifically bind MTF1. Six highly conserved over-represented sequence motifs (TvMREs), which share similarity with other eukaryotic MREs, were identified in the zinc-responsive genes in T. vaginalis. We also demonstrated that some of the TvMREs assemble as divalent complexes either as two closely spaced TvMREs or as two overlapping TvMREs forming a palindromic-like sequence: TGCC(N3)GGCA. Electrophoretic mobility shift assays were used to detect the zinc-dependent binding of TvZNF1 and nuclear proteins from T. vaginalis to this specific palindromic motif. Our results support a novel mechanism used by T. vaginalis for the transcriptional regulation of associated zinc-responsive genes through a MTF1/MRE-like system.

Immunosuppressive effects of protein derivatives from Mucuna pruriens on a streptozotocin-induced type 1 diabetes murine model.

Type 1 diabetes is an autoimmune disease induced by abnormal insulin secretions from ß-cells in pancreas. The present study aimed to investigate the immunosuppressive effects from protein derivatives of Mucuna pruriens on a murine model of Type 1 diabetes. Hydrolyzate and five peptide fractions with different molecular weight were administered orally by 14 days, followed T1D murine model was built by intraperitoneal injection of streptozotocin over 5 days. The mice weight, blood glucose levels, anti-insulin, and anti-pancreatic islet ß-cells antibodies, pro-inflammatory cytokines as tumor necrosis factor alpha and interleukin-6 were determined in four times (0, 15, 30, and 45 day). Mice were sacrificed and pancreatic tissues samples were obtained and staining with hematoxylin and eosin to determine the degree of damage. The study demonstrated immunosuppressive activity in four of the six treatment groups: (a) T1D PPH, (b) T1D F 5-10 kDa, (c) T1D F 3-5 kDa, and (d) T1D F 1-3 kDa. PRACTICAL APPLICATIONS: Due to the high content of native protein in seeds of Mucuna pruriens, studies have reported potential in the elaboration of hydrolysates and peptides with biological activity. These protein derivatives could help in the treatment of immunological disorders that are observed in several chronic non-communicable disease and inflammatory diseases, such as T1D. Activated macrophages and lymphoplasmacytic infiltrate plays a crucial role in the initiation and maintenance of T1D; therefore, several studies has focused to reduce the effector functions of this cells for diminishing the clinical manifestations in inmmunocompromised patients. Thus, this study indicates the potential application of hydrolyzate and peptide fractions of M. pruriens in functional foods and dietary supplements could be developed for the treatment of inflammatory and chronic non-communicable diseases.

Anti-inflammatory and diuretic effects of the diterpene ent-dihydrotucumanoic acid.

Gymnosperma glutinosum (Spreng) Less (Asteraceae) is a shrub used in traditional medicine for the treatment of inflammatory and renal diseases. The ent-dihydrotucumanoic acid (DTA) is a diterpene obtained from G. glutinosum. This study evaluated the antioxidant, genotoxic, and diuretic properties of DTA, as well as its in vitro and in vivo anti-inflammatory actions. The antioxidant actions of DTA were assessed with the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assays, the genotoxic action was assessed with the comet assay, and the diuretic effects of DTA were assessed using metabolic cages. The anti-inflammatory actions were evaluated using primary murine peritoneal macrophages stimulated with LPS and the λ-carrageenan-induced hind paw edema test. DTA lacked antioxidant (IC50 > 25,000 µg/mL) activity in the ABTS, FRAP, and DPPH assays. DTA at 500-1,000 µg/mL showed moderate genotoxicity. In LPS-stimulated macrophages, DTA showed IC50 values of 74.85 µg/mL (TNF-α) and 58.12 µg/mL (NO), whereas the maximum inhibition of IL-6 (24%) and IL-1ß (36%) was recorded at 200 µg/mL. DTA induced in vivo anti-inflammatory effects with ED50 = 124.3 mg/kg. The in vitro anti-inflammatory activity of DTA seems to be associated with the decrease in the release of TNF-α and NO. DTA promoted the excretion of urine (ED50 = 86.9 mg/kg), Na+ (ED50 = 66.7 mg/kg), and K+ (ED50 = 8.6 mg/kg). The coadministration of DTA with L-NAME decreased the urinary excretion shown by DTA alone. Therefore, the diuretic activity is probably associated with the participation of nitric oxide synthase. In conclusion, DTA exerted anti-inflammatory and diuretic effects, but lacked antioxidant effects.