Characterization and functional analysis of the proteins Prohibitin 1 and 2 in Trypanosoma cruzi

Background Chagas disease is the third most important neglected tropical disease. There is no vaccine available, and only two drugs are generally prescribed for the treatment, both of which with a wide range of side effects. Our study of T. cruzi PHBs revealed a pleiotropic function in different stages of the parasite, participating actively in the transformation of the non-infective replicative epimastigote form into metacyclic trypomastigotes and also in the multiplication of intracellular amastigotes. Methodology/principal findings To obtain and confirm our results, we applied several tools and techniques such as electron microscopy, immuno-electron microscopy, bioinformatics analysis and molecular biology. We transfected T. cruzi clones with the PHB genes, in order to overexpress the proteins and performed a CRISPR/Cas9 disruption to obtain partially silenced PHB1 parasites or completely silenced PHB2 parasites. The function of these proteins was also studied in the biology of the parasite, specifically in the transformation rate from non-infective forms to the metacyclic infective forms, and in their capacity of intracellular multiplication. Conclusion/significance This research expands our understanding of the functions of PHBs in the life cycle of the parasite. It also highlights the protective role of prohibitins against ROS and reveals that the absence of PHB2 has a lethal effect on the parasite, a fact that could support the consideration of this protein as a possible target for therapeutic action.

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Albizia chinensis bark extract ameliorates the genotoxic effect of cyclophosphamide

Bulletin of the National Research Centre ◽

10.1186/s42269-020-00422-9 ◽

2020 ◽

Vol 44 (1) ◽

Author(s):

Marian Nabil ◽

Entesar E. Hassan ◽

Neven S. Ghaly ◽

Fawzia A. Aly ◽

Farouk R. Melek ◽

...

Keyword(s):

Folk Medicine ◽

Inhibitory Effect ◽

Protective Role ◽

Bark Extract ◽

Repeated Treatment ◽

Mouse Bone Marrow ◽

Sperm Abnormalities ◽

Wide Range ◽

Different Doses

Abstract Background The genus Albizia (Leguminoseae) is used in folk medicine for the treatment of a wide range of ailments. Recently, saponins from plant origin have attracted much attention. Saponins are recorded to have a broad range of biological and pharmacological activities. This study was performed to evaluate the protective role of Albizia chinensis bark methanolic extract (MEAC) against the genotoxicity induced by cyclophosphamide (CP) using different mutagenic parameters. Results The results showed that MEAC induced an inhibitory effect against chromosomal aberrations of CP in mouse bone marrow and spermatocytes. Such effect was found to be significant (p < 0.01) with a dose of 100 mg/kg treated once for 24 h and also after repeated treatment at a dose of 25 mg/kg for 7 days. In sperm abnormalities, the protective effect of Albizia extract showed a dose-related relationship. Different doses of MEAC (25, 50, and 100 mg/kg) significantly (p < 0.01) ameliorated sperm abnormalities induced by CP dose-dependently. The percentage of sperm abnormalities was decreased to 5.14 ± 0.72 in the group of animals treated with CP plus MEAC (100 mg/kg) indicating an inhibitory effect of about 50%. Conclusion MEAC at the doses examined was non-genotoxic compared to control (negative) and exhibited a protective role against CP genotoxicity.

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Recent Updates on Research Models and Tools to Study Virus–Host Interactions at the Placenta

Viruses ◽

10.3390/v12010005 ◽

2019 ◽

Vol 12 (1) ◽

pp. 5 ◽

Cited By ~ 5

Author(s):

Jae Kyung Lee ◽

Soo-Jin Oh ◽

Hosun Park ◽

Ok Sarah Shin

Keyword(s):

Viral Infections ◽

Protective Role ◽

Biological Mechanisms ◽

Cellular Targets ◽

Host Interactions ◽

Wide Range ◽

Hofbauer Cells ◽

Maternal Fetal Transmission ◽

Immunological Barrier

The placenta is a unique mixed organ, composed of both maternal and fetal tissues, that is formed only during pregnancy and serves as the key physiological and immunological barrier preventing maternal–fetal transmission of pathogens. Several viruses can circumvent this physical barrier and enter the fetal compartment, resulting in miscarriage, preterm birth, and birth defects, including microcephaly. The mechanisms underlying viral strategies to evade the protective role of placenta are poorly understood. Here, we reviewed the role of trophoblasts and Hofbauer cells in the placenta and have highlighted characteristics of vertical and perinatal infections caused by a wide range of viruses. Moreover, we explored current progress and future opportunities in cellular targets, pathogenesis, and underlying biological mechanisms of congenital viral infections, as well as novel research models and tools to study the placenta.

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Protective Effects of Anti-depressant Citalopram Against Abnormal APP Processing and Amyloid Beta-induced Mitochondrial Dynamics, Biogenesis, Mitophagy and Synaptic Toxicities in Alzheimer’s Disease

Human Molecular Genetics ◽

10.1093/hmg/ddab054 ◽

2021 ◽

Author(s):

Arubala P Reddy ◽

Xiangling Yin ◽

Neha Sawant ◽

P Hemachandra Reddy

Keyword(s):

Electron Microscopy ◽

Alzheimer’S Disease ◽

Transmission Electron Microscopy ◽

Mitochondrial Dynamics ◽

Mitochondrial Fission ◽

Protective Role ◽

Mrna Levels ◽

Ht22 Cells ◽

Transmission Electron

Abstract The purpose of this study is to study the neuroprotective role of selective serotonin reuptake inhibitor (SSRI), citalopram against Alzheimer’s disease (ad). Multiple SSRIs, including citalopram are reported to treat patients with depression, anxiety, and ad. However, their protective cellular mechanisms have not been studied completely. In the current study, we investigated the protective role of citalopram against impaired mitochondrial dynamics, defective mitochondrial biogenesis, defective mitophagy, and synaptic dysfunction in immortalized mouse primary hippocampal cells (HT22) expressing mutant APP (SWI/IND) mutations. Using quantitative RT-PCR, immunoblotting, biochemical methods and transmission electron microscopy methods, we assessed mutant full-length APP/C-terminal fragments and Aβ levels and mRNA and protein levels of mitochondrial dynamics, biogenesis, mitophagy, and synaptic genes in mAPP-HT22 cells and mAPP-HT22 cells treated with citalopram. Increased levels of mRNA levels of mitochondrial fission genes, decreased levels of fusion biogenesis, autophagy, mitophagy and synaptic genes were found in mAPP-HT22 cells relative to WT-HT22 cells. However, in mAPP-HT22 cells treated with citalopram compared to mAPP-HT22 cells, revealed reduced levels of the mitochondrial fission genes, increased fusion, biogenesis, autophagy, mitophagy, and synaptic genes. Our protein data agrees with mRNA levels. Transmission electron microscopy revealed significantly increased mitochondrial numbers and reduced mitochondrial length in mAPP-HT22 cells; these were reversed in citalopram treated mAPP-HT22 cells. Cell survival rates were increased in citalopram treated mAPP-HT22 relative to citalopram-untreated mAPP-HT22. Further, mAPP and C-terminal fragments were also reduced in citalopram treated cells. These findings suggest that citalopram reduces mutant APP and Aβ and mitochondrial toxicities and may have a protective role of mutant APP and Aβ-induced injuries in patients with depression, anxiety, and ad.

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Child Maltreatment and Resilience: The Promotive and Protective Role of Future Orientation

10.31219/osf.io/35edp ◽

2019 ◽

Author(s):

Zehua Cui ◽

Assaf Oshri ◽

Sihong Liu ◽

Emilie Smith ◽

Steven M. Kogan

Keyword(s):

Child Maltreatment ◽

Behavioral Problems ◽

Future Orientation ◽

Protective Role ◽

Emotional And Behavioral Problems ◽

Positive Development ◽

Delinquent Behaviors ◽

Youth Delinquency ◽

Wide Range

Maltreatment is associated with risk for a wide range of socio-emotional and behavioral problems in adolescence. Despite this risk, many maltreated youth adjust well through the process of resilience. Extant research demonstrates that future orientation is linked to reduced risks for maladjustment in adolescence. Few studies, however, have tested the protective and promotive role of future orientation using positive and negative developmental outcomes among maltreated youth. The present study aimed to investigate the promotive and moderating role of future orientation among a longitudinal sample of maltreated and demographically comparable non-maltreated youth (N = 1,354, 51.5% female, 53.2% African American). Data collected from Time 1 (Mage = 4.56, SDage = .70) to Time 8 (Mage = 18.514, SDage = .615) were used. Compared to the non-maltreated youth, maltreated youth showed increased delinquent behaviors and reduced self-esteem. In addition, future orientation significantly predicted higher levels of social competence and attenuated the adverse effects of maltreatment on youth delinquency and substance use. The findings highlight the role of future orientation in the development of resilience among maltreated youth, bearing significant contributions to prevention and intervention programs designed to protect youth against risks linked to child maltreatment and promote their positive development.

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RFX1: a promising therapeutic arsenal against cancer

Cancer Cell International ◽

10.1186/s12935-021-01952-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Joby Issac ◽

Pooja S. Raveendran ◽

Ani V. Das

Keyword(s):

Protein Interactions ◽

Target Genes ◽

Cellular Proliferation ◽

Protein Protein Interactions ◽

Oncogenic Potential ◽

Cellular Processes ◽

Wide Range ◽

Induced Apoptosis ◽

Pleiotropic Function

AbstractRegulatory factor X1 (RFX1) is an evolutionary conserved transcriptional factor that influences a wide range of cellular processes such as cell cycle, cell proliferation, differentiation, and apoptosis, by regulating a number of target genes that are involved in such processes. On a closer look, these target genes also play a key role in tumorigenesis and associated events. Such observations paved the way for further studies evaluating the role of RFX1 in cancer. These studies were indispensable due to the failure of conventional chemotherapeutic drugs to target key cellular hallmarks such as cancer stemness, cellular plasticity, enhanced drug efflux, de-regulated DNA repair machinery, and altered pathways evading apoptosis. In this review, we compile significant evidence for the tumor-suppressive activities of RFX1 while also analyzing its oncogenic potential in some cancers. RFX1 induction decreased cellular proliferation, modulated the immune system, induced apoptosis, reduced chemoresistance, and sensitized cancer stem cells for chemotherapy. Thus, our review discusses the pleiotropic function of RFX1 in multitudinous gene regulations, decisive protein–protein interactions, and also its role in regulating key cell signaling events in cancer. Elucidation of these regulatory mechanisms can be further utilized for RFX1 targeted therapy.

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Fine structure of the giant cells induced by Meloidogyne javanica in lima bean

Canadian Journal of Botany ◽

10.1139/b84-065 ◽

1984 ◽

Vol 62 (3) ◽

pp. 429-436 ◽

Cited By ~ 4

Author(s):

F. Fattah ◽

J. M. Webster

Keyword(s):

Electron Microscopy ◽

Fine Structure ◽

Light And Electron Microscopy ◽

Lima Bean ◽

Meloidogyne Javanica ◽

Giant Cells ◽

Egg Laying ◽

Phaseolus Lunatus ◽

Wide Range

Giant cells associated with egg-laying females of Meloidogyne javanica in lima bean, Phaseolus lunatus cv. L-136, were examined by light and electron microscopy. These giant cells have characteristics that are typical of nematode-induced giant cells in a wide range of hosts, but they differ in that they (i) are less closely associated with xylem vessels, (ii) contain a very large number of plastids which are devoid of starch grains, and (iii) contain several different forms of cytoplasmic crystals. One form of the crystal is associated with a large number of "spiny" vesicles. The possible role of these features, especially the crystals, in the giant cell response of lima bean is discussed.

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Role of Quercetin in chemoprevention against wide range of carcinogens and mutagens

International Journal of Drug Delivery ◽

10.5138/09750215.2040 ◽

2017 ◽

Vol 9 (1) ◽

pp. 09

Author(s):

Savithiri Shivakumar ◽

Yasodha Lakshmi Tadakaluru ◽

Raja Ratna Reddy Yakkanti ◽

Sannidhi Ranga Suresh ◽

Pasula Chandra Sekhar

Keyword(s):

Alkylating Agents ◽

Antioxidant Properties ◽

Metabolic Activation ◽

Protective Role ◽

Clinical Activity ◽

Wide Range ◽

Cyp1a Activity

Quercetin is a ubiquitous plant flavoniod with significant pharmacological and clinical activity. In this study we determined to demonstrate the protective role of quercetin against range of mutagens and carcinogens in a combination of in vitro and in vivo studies via different mechanisms. Quercetin demonstrated significant protective role against sodium azide, benzo(a)pyrene, cyclophosphamide monohydrate, methyl methane sulphonate and etoposide compared to other mutagens. Quercetin is effective in both in vitro and in vivo test conditions and also in the presence as well as in the absence of metabolic activation system (Rat liver S9). Auto oxidation, antioxidant properties, inhibition of pro-mutagens metabolism by CYP1A activity and multiple antimutagenic and adaptive response, mechanisms of quercetin may account for its protective role in cancer prevention. In conclusion, the results clearly indicate that quercetin plays a significant role against mutagens that act by direct DNA binding (form DNA adducts), pro-mutagens and alkylating agents with free radical generation; which could be the rationale for its potent anticancer activity against particular cancer types.

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Potentiation of complement regulator factor H protects human endothelial cells from complement attack in aHUS sera

Blood Advances ◽

10.1182/bloodadvances.2018025692 ◽

2019 ◽

Vol 3 (4) ◽

pp. 621-632 ◽

Cited By ~ 5

Author(s):

Richard B. Pouw ◽

Mieke C. Brouwer ◽

Marlon de Gast ◽

Anna E. van Beek ◽

Lambertus P. van den Heuvel ◽

...

Keyword(s):

Endothelial Cells ◽

Complement Activation ◽

Protective Role ◽

Human Cells ◽

Factor H ◽

Human Endothelial Cells ◽

Complement Regulation ◽

Wide Range ◽

Complement Regulator

Abstract Mutations in the gene encoding for complement regulator factor H (FH) severely disrupt its normal function to protect human cells from unwanted complement activation, resulting in diseases such as atypical hemolytic uremic syndrome (aHUS). aHUS presents with severe hemolytic anemia, thrombocytopenia, and renal disease, leading to end-stage renal failure. Treatment of severe complement-mediated disease, such as aHUS, by inhibiting the terminal complement pathway, has proven to be successful but at the same time fails to preserve the protective role of complement against pathogens. To improve complement regulation on human cells without interfering with antimicrobial activity, we identified an anti-FH monoclonal antibody (mAb) that induced increased FH-mediated protection of primary human endothelial cells from complement, while preserving the complement-mediated killing of bacteria. Moreover, this FH-activating mAb restored complement regulation in sera from aHUS patients carrying various heterozygous mutations in FH known to impair FH function and dysregulate complement activation. Our data suggest that FH normally circulates in a less active conformation and can become more active, allowing enhanced complement regulation on human cells. Antibody-mediated potentiation of FH may serve as a highly effective approach to inhibit unwanted complement activation on human cells in a wide range of hematological diseases while preserving the protective role of complement against pathogens.

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Protective Role of Passively Transferred Maternal Cytokines against Bordetella pertussis Infection in Newborn Piglets

Infection and Immunity ◽

10.1128/iai.01063-16 ◽

2017 ◽

Vol 85 (4) ◽

Cited By ~ 11

Author(s):

Shokrollah Elahi ◽

David R. Thompson ◽

Jill Van Kessel ◽

Lorne A. Babiuk ◽

Volker Gerdts

Keyword(s):

Bordetella Pertussis ◽

Immune Cell ◽

Protective Role ◽

Cell Mediated Immunity ◽

Pertussis Infection ◽

Necrosis Factor Alpha ◽

Specific Antibodies ◽

Newborn Piglets ◽

Wide Range

ABSTRACT Maternal vaccination represents a potential strategy to protect both the mother and the offspring against life-threatening infections. This protective role has mainly been associated with antibodies, but the role of cell-mediated immunity, in particular passively transferred cytokines, is not well understood. Here, using a pertussis model, we have demonstrated that immunization of pregnant sows with heat-inactivated bacteria leads to induction of a wide range of cytokines (e.g., tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], interleukin-6 [IL-6], IL-8, and IL-12/IL-23p40) in addition to pertussis-specific antibodies. These cytokines can be detected in the sera and colostrum/milk of vaccinated sows and subsequently were detected at significant levels in the serum and bronchoalveolar lavage fluid of piglets born to vaccinated sows together with pertussis-specific antibodies. In contrast, active vaccination of newborn piglets with heat-inactivated bacteria induced high levels of specific IgG and IgA but no cytokines. Although the levels of antibodies in vaccinated piglets were comparable to those of passively transferred antibodies, no protection against Bordetella pertussis infection was observed. Thus, our results demonstrate that a combination of passively transferred cytokines and antibodies is crucial for disease protection. The presence of passively transferred cytokines/antibodies influences the cytokine secretion ability of splenocytes in the neonate, which provides novel evidence that maternal immunization can influence the newborn's cytokine milieu and may impact immune cell differentiation (e.g., Th1/Th2 phenotype). Therefore, these maternally derived cytokines may play an essential role both as mediators of early defense against infections and possibly as modulators of the immune repertoire of the offspring.

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Recent Applications of High Resolution Electron Microscopy to Crystalline Arrays of Virus Particles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100070199 ◽

1978 ◽

Vol 36 (3) ◽

pp. 470-482 ◽

Cited By ~ 1

Author(s):

R.W. Horne

Keyword(s):

Electron Microscopy ◽

Image Processing ◽

Analytical Techniques ◽

Staining Technique ◽

High Resolution Electron Microscopy ◽

Optical Diffraction ◽

Full Potential ◽

Virus Particles ◽

Resolution Electron ◽

Wide Range

The technique of surrounding virus particles with a neutralised electron dense stain was described at the Fourth International Congress on Electron Microscopy, Berlin 1958 (see Home & Brenner, 1960, p. 625). For many years the negative staining technique in one form or another, has been applied to a wide range of biological materials. However, the full potential of the method has only recently been explored following the development and applications of optical diffraction and computer image analytical techniques to electron micrographs (cf. De Hosier & Klug, 1968; Markham 1968; Crowther et al., 1970; Home & Markham, 1973; Klug & Berger, 1974; Crowther & Klug, 1975). These image processing procedures have allowed a more precise and quantitative approach to be made concerning the interpretation, measurement and reconstruction of repeating features in certain biological systems.

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