Antiparasitic effects of ethanolic extracts of Piper arboreum and Jatropha gossypiifolia leaves on cercariae and adult worms of Schistosoma mansoni

Parasitology ◽  
2020 ◽  
Vol 147 (14) ◽  
pp. 1689-1699
Author(s):  
Rayan Rubens da Silva Alves ◽  
João Gustavo Mendes Rodrigues ◽  
Andrea Teles-Reis ◽  
Ranielly Araújo Nogueira ◽  
Irlla Correia Lima Licá ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
High Performance ◽  
Treatment Strategies ◽  
Biologically Active ◽  
Internal Damage ◽  
Chemical Screening ◽  
Ethanolic Extracts ◽  
New Treatment ◽  
Jatropha Gossypiifolia

AbstractNew treatment strategies for schistosomiasis should be evaluated, since resistant strains to the only available drug, Praziquantel, have already been described. Thus, we demonstrated antiparasitic effects of ethanolic extracts of Jatropha gossypiifolia and Piper arboreum on cercariae and adult worms of Schistosoma mansoni. The bioassays were performed at 0–10 000 μg mL−1 concentration for 0–72 h. Adult worms were stained with carmine to assess external and internal damage. The chemical screening was performed using high-performance liquid chromatography. P. arboreum displayed the best cercaricidal effect, with a 100% reduction in viability in just 60 min. The extract of J. gossypiifolia was more effective against adult worms, with 100% viability reduction of male and female worms after 12 and 24 h, respectively. P. arboreum and J. gossypiifolia were equally effective in inhibiting the oviposition of S. mansoni (93% reduction) and causing damage to internal and external structures in adult worms. Flavonoids were identified in both the extracts and phenolic compounds and amides only in P. arboreum. Thus, for the first time, it was proven that ethanolic extracts of P. arboreum and J. gossypiifolia leaves are biologically active against cercariae and adult worms of S. mansoni in vitro.

Phytochemical, Analytical and Medicinal Studies of Holoptelea integrifolia Roxb. Planch - A Review

2019 ◽  
Vol 5 (4) ◽  
pp. 270-277 ◽  
Author(s):  
Vijay Kumar ◽  
Simranjeet Singh ◽  
Ragini Bhadouria ◽  
Ravindra Singh ◽  
Om Prakash
Keyword(s):  
Liquid Chromatography ◽  
Thin Layer ◽  
Thin Layer Chromatography ◽  
High Performance ◽  
Biologically Active ◽  
Toxicological Studies ◽  
Wide Range ◽  
Layer Chromatography

Holoptelea integrifolia Roxb. Planch (HI) has been used to treat various ailments including obesity, osteoarthritis, arthritis, inflammation, anemia, diabetes etc. To review the major phytochemicals and medicinal properties of HI, exhaustive bibliographic research was designed by means of various scientific search engines and databases. Only 12 phytochemicals have been reported including biologically active compounds like betulin, betulinic acid, epifriedlin, octacosanol, Friedlin, Holoptelin-A and Holoptelin-B. Analytical methods including the Thin Layer Chromatography (TLC), High-Performance Thin Layer Chromatography (HPTLC), High-Performance Liquid Chromatography (HPLC) and Liquid Chromatography With Mass Spectral (LC-MS) analysis have been used to analyze the HI. From medicinal potency point of view, these phytochemicals have a wide range of pharmacological activities such as antioxidant, antibacterial, anti-inflammatory, and anti-tumor. In the current review, it has been noticed that the mechanism of action of HI with biomolecules has not been fully explored. Pharmacology and toxicological studies are very few. This seems a huge literature gap to be fulfilled through the detailed in-vivo and in-vitro studies.

scholarly journals “Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

2021 ◽  
Vol 22 (4) ◽  
pp. 1824
Author(s):  
Matthias Mietsch ◽  
Rabea Hinkel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Cardiac Cells ◽  
Aging Effects ◽  
Beneficial Effects ◽  
Micro Rnas ◽  
New Treatment

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.

scholarly journals Metabolic Modeling of Clostridium difficile Associated Dysbiosis of the Gut Microbiota

Processes ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 97 ◽  
Author(s):  
Poonam Phalak ◽  
Michael Henson
Keyword(s):  
Clostridium Difficile ◽  
Treatment Strategies ◽  
E Coli ◽  
Biofilm Model ◽  
Commensal Species ◽  
Species Abundances ◽  
New Treatment ◽  
Biofilm Development

Recent in vitro experiments have demonstrated the ability of the pathogen Clostridium difficile and commensal gut bacteria to form biofilms on surfaces, and biofilm development in vivo is likely. Various studies have reported that 3%–15% of healthy adults are asymptomatically colonized with C. difficile, with commensal species providing resistance against C. difficile pathogenic colonization. C. difficile infection (CDI) is observed at a higher rate in immunocompromised patients previously treated with broad spectrum antibiotics that disrupt the commensal microbiota and reduce competition for available nutrients, resulting in imbalance among commensal species and dysbiosis conducive to C. difficile propagation. To investigate the metabolic interactions of C. difficile with commensal species from the three dominant phyla in the human gut, we developed a multispecies biofilm model by combining genome-scale metabolic reconstructions of C. difficile, Bacteroides thetaiotaomicron from the phylum Bacteroidetes, Faecalibacterium prausnitzii from the phylum Firmicutes, and Escherichia coli from the phylum Proteobacteria. The biofilm model was used to identify gut nutrient conditions that resulted in C. difficile-associated dysbiosis characterized by large increases in C. difficile and E. coli abundances and large decreases in F. prausnitzii abundance. We tuned the model to produce species abundances and short-chain fatty acid levels consistent with available data for healthy individuals. The model predicted that experimentally-observed host-microbiota perturbations resulting in decreased carbohydrate/increased amino acid levels and/or increased primary bile acid levels would induce large increases in C. difficile abundance and decreases in F. prausnitzii abundance. By adding the experimentally-observed perturbation of increased host nitrate secretion, the model also was able to predict increased E. coli abundance associated with C. difficile dysbiosis. In addition to rationalizing known connections between nutrient levels and disease progression, the model generated hypotheses for future testing and has the capability to support the development of new treatment strategies for C. difficile gut infections.

scholarly journals The Nutritional Value of Non-Traditional Gluten-Free Flakes and Their Antioxidant Activity

Antioxidants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 565
Author(s):  
Kristýna Šťastná ◽  
Martina Mrázková ◽  
Daniela Sumczynski ◽  
Betül Cındık ◽  
Erkan Yalçın
Keyword(s):  
Antioxidant Activity ◽  
High Performance ◽  
Sugar Content ◽  
Chenopodium Quinoa ◽  
Biologically Active ◽  
Eragrostis Tef ◽  
Total Phenolic ◽  
Phenolic Antioxidants ◽  
In Vitro Digestibility

Nowadays, there is a growing interest for foods with a lower sugar content and rich in fiber and biologically active substances. The main purpose of this study was to prepare flakes from non-traditional pigmented cereals (Oryza sativa, Chenopodium quinoa, and Eragrostis tef) and to analyze their fibre, sugar, and in vitro digestibility values. Regarding phenolic antioxidants (soluble, soluble conjugated, and insoluble bound fractions), their content and antioxidant activity were measured using spectrophotometry and high performance liquid chromatography (HPLC) methods. Hydrothermally treated grains resulted in flakes with higher total dietary fibre contents (11.1–24.4%), quinoa and teff flakes were rich in maltose (up to 42.0 mg/g). Non-traditional flakes had lower in vitro digestibility, but conversely, they exhibited the highest phenolic contents corresponding with the highest antioxidant activity values (up to 2.33 mg Gallic acid equivalent/g of total phenolic content and 1.59 mg Trolox equivalent/g for 2,2-diphenyl-1-picrylhydrazyl (DPPH) in case of brown teff). Among free phenolics, the main contributors to an antioxidant activity were p-coumaric, o-coumaric, and gallic acids (r > 0.8186); among the soluble conjugated fractions, they were epigallocatechin, epicatechin, caffeic, and vanillic acids (r > 0.5935); while caffeic, protocatechuic, and ferulic acids (r > 0.5751) were the main contributors among the insoluble bound phenolics.

Proteomic analysis of extracellular vesicles from medullospheres reveals a role for iron in the cancer progression of medulloblastoma

2019 ◽  
pp. 1-12
Author(s):  
Maja Larsen ◽  
Matthias Kuhlmann Kuhlmann ◽  
Michael Hvam ◽  
Kenneth Howard
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Early Stage ◽  
Cell Communication ◽  
Treatment Strategies ◽  
Iron Chelators ◽  
High Morbidity ◽  
New Treatment ◽  
Stem Cell Populations

Background: Medulloblastoma (MB) is the most common malignant childhood brain tumor with the propensity todisseminate at an early stage, and is associated with high morbidity. New treatment strategies are needed toimprove cure rates and to reduce life-long cognitive and functional deficits associated with current therapies.Extracellular Vesicles (EVs) are important players in cell-to-cell communication in health and diseases. A clearerunderstanding of cell-to-cell communication in tumors can be achieved by studying EV secretion inmedullospheres. This can reveal subtle modifications induced by the passage from adherent to non-adherentgrowth, as spheres may account for the adaptation of tumor cells to the mutated environment.Methods: Formation of medullospheres from MB cell lines stabilized in adherent conditions was obtained throughculture conditioning based on low attachment flasks and specialized medium. EVs collected by ultracentrifugation,in adherent conditions and as spheres, were subjected to electron microscopy, NanoSight measurements andproteomics.Results: Interestingly, iron carrier proteins were only found in EVs shed by CSC-enriched tumor cell population ofspheres. We used iron chelators when culturing MB cell lines as spheres. Iron chelators induced a decrease innumber/size of spheres and in stem cell populations able to initiate in vitro spheres formation.Conclusions: This work suggests a not yet identified role of iron metabolism in MB progression and invasion andopens the possibility to use chelators as adjuvants in anti-tumoral chemotherapy.

Analysis of immunoreactive and biologically active human parathyroid hormone-peptides by high-performance-liquid-chromatography

1984 ◽  
Vol 107 (1) ◽  
pp. 60-69 ◽  
Author(s):  
T. Schettler ◽  
B. Aufm' Kolk ◽  
M.J. Atkinson ◽  
H. Radeke ◽  
C. Enters ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Parathyroid Adenoma ◽  
High Performance ◽  
Biologically Active ◽  
Peptide Sequence ◽  
Human Parathyroid Hormone ◽  
Healthy Individuals ◽  
In Vitro Bioassay

Abstract. A combination of high-performance-liquidchromatography (HPLC), sensitive radioimmunoassays and a homologous in vitro bioassay was used to characterise human parathyroid hormone (hPTH)-peptides in human parathyroid adenoma and plasma. Chromatography of several synthetic hPTH-peptides allows the calibration of the HPLC column. On the basis of sequence hydrophobicity the elution position of peptides can be predicted. A model for the determination of the minimal peptide sequence of each peptide has been developed which based on immunological and physicochemical properties allows the characterisation of unknown hPTH-peptides. Using this technique the heterogeneity of circulating hPTH-peptides in human plasma has been examined. Plasma extracts from healthy individuals, osteoporotic, hyperparathyroid and pseudohyperparathyroid patients were investigated. A uniform pattern in the heterogeneity of hPTH-peptides was detected. Using parathyroid adenoma as reference disease specific changes were characterised.

scholarly journals Synthesis, Characterization of Pyrano-[2,3-c]-Pyrazoles Derivatives and Determination of Their Antioxidant Activities

2021 ◽  
Vol 15 (3) ◽  
pp. 175-194
Author(s):  
Boutaina Addoum ◽  
◽  
Bouchra El khalfi ◽  
Mohamed Idiken ◽  
Souraya Sakoui ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Performance ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Model Organism ◽  
Biologically Active ◽  
Strong Activity ◽  
Nitrative Stress

Background: Antioxidants are developed to assist the immune system and overcome oxidative stress, the aggression of cellular constituents due to imbalance between reactive oxygen species and the inner antioxidant system. The main objective of this study was to search for new and potent antioxidants to protect humans against diseases associated with oxidative stress. Methods: In this study, three pyrano-[2,3-c]-pyrazole derivatives were synthesized via Multicomponent Reaction (MCR) approach and were characterized, using a melting point, High-Performance Liquid Chromatography (HPLC), and spectroscopic analyses (IR; 1H-NMR; 13C-NMR). All of the generated compounds were screened for their antioxidant properties in vivo, using ciliate “Tetrahymena” as a model organism exposed to oxidative and nitrative stress. They were then studied in vitro by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. Results: The results demonstrated that the three compounds (5a, b, c) are biologically active and possess potent antioxidant activities, especially the 5a and 5b derivatives. On the other hand, the in vitro bioassays revealed that the 5a derivative possessed a significant antioxidant activity much greater than ascorbic acid. Accordingly, the in silico data are consistent with the experimental data. Conclusion: These findings confirmed the potent antioxidant property of the synthesized compounds, providing us with new inspiration and challenges to design a library of pharmaceutical compounds with strong activity and low toxicity in the future.

scholarly journals Downregulation of METTL7B Inhibits Proliferation of Human Clear Cell Renal Cancer Cells In Vivo and In Vitro

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Li ◽  
Shi Xu ◽  
Naixiong Peng ◽  
Zejian Zhang ◽  
Hua He ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Clear Cell ◽  
Tnm Classification ◽  
Treatment Strategies ◽  
Tumor Formation ◽  
Cell Renal Cell Carcinoma ◽  
Functional Studies ◽  
New Treatment

Clear cell renal cell carcinoma (ccRCC) is the most aggressive urologic tumor, and its incidence and diagonosis have been continuously increasing. Identifying novel molecular biomarker for inhibiting the progression of ccRCC will facilitate developing new treatment strategies. Although methyltransferase-like 7B (METTL7B) was identified as a Golgi-associated methyltransferase, the function and mechanism of METTL7B in ccRCC development and progression has not been explored. METTL7B expression were significantly upregulated in ccRCC tissues (n = 60), which significantly associated with TNM classification, tumor size, lymph node metastasis, and poor prognosis for ccRCC patients. Functional studies showed downregulation of METTL7B inhibited cell proliferation, migration in vitro, and xenograft tumor formation in vivo. In addition, METTL7B knockdown promoted cell cycle arrest at G0/G1phase and induced cellular apoptosis. Taken together, downregulation of METTL7B inhibits ccRCC cell proliferation and tumorigenesis in vivo and in vitro. These findings provide a rationale for using METTL7B as a potential therapeutic target in ccRCC patients.

scholarly journals MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Calvin VanOpstall ◽  
Srikanth Perike ◽  
Hannah Brechka ◽  
Marc Gillard ◽  
Sophia Lamperis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Treatment Strategies ◽  
Human Prostate ◽  
Protein Activity ◽  
Prostate Epithelial Cells ◽  
New Treatment ◽  
Hox Protein

The molecular roles of HOX transcriptional activity in human prostate epithelial cells remain unclear, impeding the implementation of new treatment strategies for cancer prevention and therapy. MEIS proteins are transcription factors that bind and direct HOX protein activity. MEIS proteins are putative tumor suppressors that are frequently silenced in aggressive forms of prostate cancer. Here we show that MEIS1 expression is sufficient to decrease proliferation and metastasis of prostate cancer cells in vitro and in vivo murine xenograft models. HOXB13 deletion demonstrates that the tumor-suppressive activity of MEIS1 is dependent on HOXB13. Integration of ChIP-seq and RNA-seq data revealed direct and HOXB13-dependent regulation of proteoglycans including decorin (DCN) as a mechanism of MEIS1-driven tumor suppression. These results define and underscore the importance of MEIS1-HOXB13 transcriptional regulation in suppressing prostate cancer progression and provide a mechanistic framework for the investigation of HOXB13 mutants and oncogenic cofactors when MEIS1/2 are silenced.

scholarly journals Antileishmanial Efficacy and Pharmacokinetics of DB766-Azole Combinations

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
April C. Joice ◽  
Sihyung Yang ◽  
Abdelbasset A. Farahat ◽  
Heidi Meeds ◽  
Mei Feng ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Treatment Strategies ◽  
Parasite Burden ◽  
Pharmacokinetic Analysis ◽  
Content Type ◽  
New Treatment ◽  
Almost All

ABSTRACT Given the limitations of current antileishmanial drugs and the utility of oral combination therapy for other infections, developing an oral combination against visceral leishmaniasis should be a high priority. In vitro combination studies with DB766 and antifungal azoles against intracellular Leishmania donovani showed that posaconazole and ketoconazole, but not fluconazole, enhanced DB766 potency. Pharmacokinetic analysis of DB766-azole combinations in uninfected Swiss Webster mice revealed that DB766 exposure was increased by higher posaconazole and ketoconazole doses, while DB766 decreased ketoconazole exposure. In L. donovani-infected BALB/c mice, DB766-posaconazole combinations given orally for 5 days were more effective than DB766 or posaconazole alone. For example, 81% ± 1% (means ± standard errors) inhibition of liver parasite burden was observed for 37.5 mg/kg of body weight DB766 plus 15 mg/kg posaconazole, while 37.5 mg/kg DB766 and 15 mg/kg posaconazole administered as monotherapy gave 40% ± 5% and 21% ± 3% inhibition, respectively. Combination index (CI) analysis indicated that synergy or moderate synergy was observed in six of nine combined dose groups, while the other three were nearly additive. Liver concentrations of DB766 and posaconazole increased in almost all combination groups compared to monotherapy groups, although many increases were not statistically significant. For DB766-ketoconazole combinations evaluated in this model, two were antagonistic, one displayed synergy, and one was nearly additive. These data indicate that the efficacy of DB766-posaconazole and DB766-ketoconazole combinations in vivo is influenced in part by the pharmacokinetics of the combination, and that the former combination deserves further consideration in developing new treatment strategies against visceral leishmaniasis.

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