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  • 1
    Online Resource
    Online Resource
    Hematological Changes in Whole Blood Stored in Blood Bags Containing CPDA-1 Over a Period of 28 Days
    Nepal Journals Online (JOL) ; 2023
    In:  Med Phoenix Vol. 7, No. 2 ( 2023-01-06), p. 42-46
    Details
    In: Med Phoenix, Nepal Journals Online (JOL), Vol. 7, No. 2 ( 2023-01-06), p. 42-46
    Abstract: Introduction: Blood storage is needed to ensure a readily available and safe blood supply. During blood storage in blood bank, biochemical and physical properties of RBCs are altered because of storage conditions. In normal conditions in the body circulation, these do not occur as optimum pH, temperature, nutrient concentration and waste products removal are maintained. The aim of this study was to observe the changes in whole blood stored in blood bags containing CPDA-1 over a period of 28 days. Materials and Methods:  This was a hospital based observational study conducted in Blood Bank, National Medical College and Teaching Hospital (NMCTH), Birgunj. A total of 450 ml blood was drawn from 50 healthy volunteer donors into blood bags containing CPDA–1 anticoagulant and placed on the quarantine shelf of the blood bank refrigerator maintained at 2-8o centigrade. The blood bags were screened for HCV, HBsAg, syphillis and HIV. Ten milliliters blood was withdrawn from the blood bags on 1st, 7th, 14th, 21st, and 28th day and tested for hematological parameters using Yumizen H550 (HORIBA) fully automated hematology analyzer. Results: At the end of 28 days, whole blood storage in CPDA-1 revealed significant decrease in WBC (T = 4.79, p 〈 0.01) and platelets count (T=180.09, p 〈 0.01). Hematocrit increased significantly after 21 days of storage (T = 40.86, p 〈 0.01).  MCHC and MCH also demonstrated significant increase during the storage period (T = 37.32, p 〈 0.01) and (T = 29.38, p 〈 0.01), respectively. Conclusion:  WBC and platelets are significantly altered (decreased) when stored in blood bags containing CPDA- 1 after one week period. The study recommends   whole blood transfusion before seventh day of donation in order to avoid the adverse outcome of hematological changes in stored blood. In case it has to be used beyond one week, then it should be leukodepleted before storage.
    Type of Medium: Online Resource
    ISSN: 2631-1992 , 2392-425X
    URL: Article
    DOI: 10.3126/medphoenix.v7i2.50939
    Language: Unknown
    Publisher: Nepal Journals Online (JOL)
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    Iron Deficiency in Anemic Patients: Study in a Tertiary Care Centre
    Nepal Journals Online (JOL) ; 2022
    In:  Med Phoenix Vol. 6, No. 2 ( 2022-02-16), p. 21-24
    Details
    In: Med Phoenix, Nepal Journals Online (JOL), Vol. 6, No. 2 ( 2022-02-16), p. 21-24
    Abstract: Introduction Anemia is a clinical abnormality characterized by a reduction in hemoglobin concentration below the normal for age and sex. It can be of different types, the most common being iron deficiency anemia which affects mostly pregnant and lactating females and growing children in the developing world. Materials and Methods This was a hospital-based observational study conducted at National Medical College and Teaching Hospital, Pathology Department, Birgunj, Nepal. Patients above the age of 10 years of both sexes (male and females) having anemia ( males having hemoglobin level 〈 13 gm/dl and females having hemoglobin level 〈 12 gm/dl ) were included. After a detailed history, preliminary blood tests including complete blood counts, peripheral smear, and reticulocytes count were done. In patients suspected (microcytic hypochromic blood picture and normal reticulocytes count )  to have iron deficiency anemia, serum ferritin was done to confirm the diagnosis. Patients under the age of 10 years and those patients having blood malignancies (acute or chronic leukemia) were excluded from the study. Results Sixty anemic patients were found to have iron deficiency. Females were affected more (66%) with iron deficiency anemia than males (34%). There were two peaks (30% and 21%) in age groups 10 – 20 years and 61 – 70 years. Complete blood counts revealed a significant decrease in the value of red cell indices like mean corpuscular volume in 70% patients (Normal MCV 80 to 100 fl) and mean corpuscular hemoglobin in 72% patients (Normal MCH 27 to 33 pg ).  On peripheral smear, it was seen that most of the patients (72%) had microcytic hypochromic blood pictures. Iron deficiency anemia was more common in rural areas. Conclusion Iron deficiency anemia was the most common type of anemia. It is more common in females and the prevalence is more in rural areas.
    Type of Medium: Online Resource
    ISSN: 2631-1992 , 2392-425X
    URL: Article
    DOI: 10.3126/medphoenix.v6i2.37070
    Language: Unknown
    Publisher: Nepal Journals Online (JOL)
    Publication Date: 2022
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  • 3
    Online Resource
    Online Resource
    Study of Breast Lesions in a Tertiary Care Centre : A Retrospective Study
    Nepal Journals Online (JOL) ; 2017
    In:  Med Phoenix Vol. 2, No. 1 ( 2017-10-13), p. 48-51
    Details
    In: Med Phoenix, Nepal Journals Online (JOL), Vol. 2, No. 1 ( 2017-10-13), p. 48-51
    Abstract: Background: To study the prevalence of various type of breast lesions in a tertiary care centre.Methods : The period of study was one year , from 1st January 2015 to 31st December 2015. Patients with breast lesions who came to department of pathology for Fine needle aspiration cytology were included in the study. There were 55 patients who came to the department for Fine needle aspiration cytology during one year period. Information pertaining to patients were taken from the medical record section and department of pathology of National medical college.Results: Out of 55 cases 17 patients (9.35%) were diagnosed with fibroadenosis, which was the highest followed by fibroadenoma (12 cases- 6.6%). Ductal hyperplasia was the least diagnosed disorder which was seen in only one patient (0.5%). Carcinoma of breast was diagnosed in three patients (1.65%). There were three (1.65%) male patients with breast lesions who were diagnosed with gynaecomastia.Conclusion: This study revealed that fibroadenosis was the most common disorder among the patients who came for fine needle aspiration cytology of the breast.Med Phoenix Vol.2(1) July 2017, 48-51
    Type of Medium: Online Resource
    ISSN: 2631-1992 , 2392-425X
    URL: Article
    DOI: 10.3126/medphoenix.v2i1.18387
    Language: Unknown
    Publisher: Nepal Journals Online (JOL)
    Publication Date: 2017
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  • 4
    Online Resource
    Online Resource
    Involvement of Cathepsins Protein in Mycobacterial Infection and Its Future Prospect as a Therapeutic Target
    Springer Science and Business Media LLC ; 2022
    In:  International Journal of Peptide Research and Therapeutics Vol. 28, No. 2 ( 2022-03)
    Details
    In: International Journal of Peptide Research and Therapeutics, Springer Science and Business Media LLC, Vol. 28, No. 2 ( 2022-03)
    Type of Medium: Online Resource
    ISSN: 1573-3149 , 1573-3904
    URL: Article
    DOI: 10.1007/s10989-022-10385-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2192632-3
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  • 5
    Online Resource
    Online Resource
    Pathogen induced subversion of NAD+ metabolism mediating host cell death: a target for development of chemotherapeutics
    Springer Science and Business Media LLC ; 2021
    In:  Cell Death Discovery Vol. 7, No. 1 ( 2021-01-13)
    Details
    In: Cell Death Discovery, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2021-01-13)
    Abstract: Hijacking of host metabolic status by a pathogen for its regulated dissemination from the host is prerequisite for the propagation of infection. M. tuberculosis secretes an NAD + -glycohydrolase, TNT, to induce host necroptosis by hydrolyzing Nicotinamide adenine dinucleotide (NAD + ). Herein, we expressed TNT in macrophages and erythrocytes; the host cells for M. tuberculosis and the malaria parasite respectively, and found that it reduced the NAD + levels and thereby induced necroptosis and eryptosis resulting in premature dissemination of pathogen. Targeting TNT in M. tuberculosis or induced eryptosis in malaria parasite interferes with pathogen dissemination and reduction in the propagation of infection. Building upon our discovery that inhibition of pathogen-mediated host NAD + modulation is a way forward for regulation of infection, we synthesized and screened some novel compounds that showed inhibition of NAD + -glycohydrolase activity and pathogen infection in the nanomolar range. Overall this study highlights the fundamental importance of pathogen-mediated modulation of host NAD + homeostasis for its infection propagation and novel inhibitors as leads for host-targeted therapeutics.
    Type of Medium: Online Resource
    ISSN: 2058-7716
    URL: Article
    DOI: 10.1038/s41420-020-00366-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2842546-7
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  • 6
    Online Resource
    Online Resource
    Table_9.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular and Infection Microbiology Vol. 12 ( 2022-9-29)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 12 ( 2022-9-29)
    Abstract: Post-translational modifications (PTMs) including phosphorylation and palmitoylation have emerged as crucial biomolecular events that govern many cellular processes including functioning of motility- and invasion-associated proteins during Plasmodium falciparum invasion. However, no study has ever focused on understanding the possibility of a crosstalk between these two molecular events and its direct impact on preinvasion- and invasion-associated protein–protein interaction (PPI) network-based molecular machinery. Here, we used an integrated in silico analysis to enrich two different catalogues of proteins: (i) the first group defines the cumulative pool of phosphorylated and palmitoylated proteins, and (ii) the second group represents a common set of proteins predicted to have both phosphorylation and palmitoylation. Subsequent PPI analysis identified an important protein cluster comprising myosin A tail interacting protein (MTIP) as one of the hub proteins of the glideosome motor complex in P. falciparum , predicted to have dual modification with the possibility of a crosstalk between the same. Our findings suggested that blocking palmitoylation led to reduced phosphorylation and blocking phosphorylation led to abrogated palmitoylation of MTIP. As a result of the crosstalk between these biomolecular events, MTIP’s interaction with myosin A was found to be abrogated. Next, the crosstalk between phosphorylation and palmitoylation was confirmed at a global proteome level by click chemistry and the phenotypic effect of this crosstalk was observed via synergistic inhibition in P. falciparum invasion using checkerboard assay and isobologram method. Overall, our findings revealed, for the first time, an interdependence between two PTM types, their possible crosstalk, and its direct impact on MTIP-mediated invasion via glideosome assembly protein myosin A in P. falciparum . These insights can be exploited for futuristic drug discovery platforms targeting parasite molecular machinery for developing novel antimalarial therapeutics.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    URL: Article
    URL: Article
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    URL: Article
    URL: Article
    URL: Article
    URL: Article
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    URL: Article
    DOI: 10.3389/fcimb.2022.924424
    DOI: 10.3389/fcimb.2022.924424.s001
    DOI: 10.3389/fcimb.2022.924424.s002
    DOI: 10.3389/fcimb.2022.924424.s003
    DOI: 10.3389/fcimb.2022.924424.s004
    DOI: 10.3389/fcimb.2022.924424.s005
    DOI: 10.3389/fcimb.2022.924424.s006
    DOI: 10.3389/fcimb.2022.924424.s007
    DOI: 10.3389/fcimb.2022.924424.s008
    DOI: 10.3389/fcimb.2022.924424.s009
    DOI: 10.3389/fcimb.2022.924424.s010
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2619676-1
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  • 7
    Online Resource
    Online Resource
    Human Cyclophilin B forms part of a multi-protein complex during erythrocyte invasion by Plasmodium falciparum
    Springer Science and Business Media LLC ; 2017
    In:  Nature Communications Vol. 8, No. 1 ( 2017-11-16)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2017-11-16)
    Abstract: Invasion of human erythrocytes by Plasmodium falciparum merozoites involves multiple interactions between host receptors and their merozoite ligands. Here we report human Cyclophilin B as a receptor for PfRhopH3 during merozoite invasion. Localization and binding studies show that Cyclophilin B is present on the erythrocytes and binds strongly to merozoites. We demonstrate that PfRhopH3 binds to the RBCs and their treatment with Cyclosporin A prevents merozoite invasion. We also show a multi-protein complex involving Cyclophilin B and Basigin, as well as PfRhopH3 and PfRh5 that aids the invasion. Furthermore, we report identification of a de novo peptide CDP3 that binds Cyclophilin B and blocks invasion by up to 80%. Collectively, our data provide evidence of compounded interactions between host receptors and merozoite surface proteins and paves the way for developing peptide and small-molecules that inhibit the protein−protein interactions, individually or in toto, leading to abrogation of the invasion process.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-017-01638-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2553671-0
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  • 8
    Online Resource
    Online Resource
    Targeting Artemisinin-Resistant Malaria by Repurposing the Anti-Hepatitis C Virus Drug Alisporivir
    American Society for Microbiology ; 2022
    In:  Antimicrobial Agents and Chemotherapy Vol. 66, No. 12 ( 2022-12-20)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 66, No. 12 ( 2022-12-20)
    Abstract: The emergence of Plasmodium falciparum resistance raises an urgent need to find new antimalarial drugs. Here, we report the rational repurposing of the anti-hepatitis C virus drug, alisporivir, a nonimmunosuppressive analog of cyclosporin A, against artemisinin-resistant strains of P. falciparum . In silico docking studies and molecular dynamic simulation predicted strong interaction of alisporivir with Pf Cyclophilin 19B, confirmed through biophysical assays with a K d value of 354.3 nM. Alisporivir showed potent antimalarial activity against chloroquine-resistant ( Pf RKL-9 with resistance index [Ri] 2.14 ± 0.23) and artemisinin-resistant ( Pf Kelch13 R539T with Ri 1.15 ± 0.04) parasites. The Ri is defined as the ratio between the IC 50 values of the resistant line to that of the sensitive line. To further investigate the mechanism involved, we analyzed the expression level of Pf Cyclophilin 19B in artemisinin-resistant P. falciparum ( Pf Kelch13 R539T ). Semiquantitative real-time transcript, Western blot, and immunofluorescence analyses confirmed the overexpression of Pf Cyclophilin 19B in Pf Kelch13 R539T . A 50% inhibitory concentration in the nanomolar range, together with the targeting of Pf Cyclophilin 19B, suggests that alisporivir can be used in combination with artemisinin. Since artemisinin resistance slows the clearance of ring-stage parasites, we performed a ring survival assay on artemisinin-resistant strain Pf Kelch13 R539T and found significant decrease in parasite survival with alisporivir. Alisporivir was found to act synergistically with dihydroartemisinin and increase its efficacy. Furthermore, alisporivir exhibited antimalarial activity in vivo . Altogether, with the rational target-based Repurposing of alisporivir against malaria, our results support the hypothesis that targeting resistance mechanisms is a viable approach toward dealing with drug-resistant parasite.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/aac.00392-22
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 9
    Online Resource
    Online Resource
    DataSheet_1.doc
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular and Infection Microbiology Vol. 12 ( 2022-6-6)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 12 ( 2022-6-6)
    Abstract: SUMOylation is one of the post-translational modifications that have recently been described as a key regulator of various cellular, nuclear, metabolic, and immunological processes. The process of SUMOylation involves the modification of one or more lysine residues of target proteins by conjugation of a ubiquitin-like, small polypeptide known as SUMO for their degradation, stability, transcriptional regulation, cellular localization, and transport. Herein, for the first time, we report the involvement of the host SUMOylation pathway in the process of infection of Leishmania donovani , a causative agent of visceral leishmaniasis. Our data revealed that infection of L. donovani to the host macrophages leads to upregulation of SUMOylation pathway genes and downregulation of a deSUMOylating gene, SENP1. Further, to confirm the effect of the host SUMOylation on the growth of Leishmania , the genes associated with the SUMOylation pathway were silenced and parasite load was analyzed. The knockdown of the SUMOylation pathway led to a reduction in parasitic load, suggesting the role of the host SUMOylation pathway in the disease progression and parasite survival. Owing to the effect of the SUMOylation pathway in autophagy, we further investigated the status of host autophagy to gain mechanistic insights into how SUMOylation mediates the regulation of growth of L. donovani . Knockdown of genes of host SUMOylation pathway led to the reduction of the expression levels of host autophagy markers while promoting autophagosome–lysosome fusion, suggesting SUMOylation-mediated autophagy in terms of autophagy initiation and autophagy maturation during parasite survival. The levels of reactive oxygen species (ROS) generation, nitric oxide (NO) production, and pro-inflammatory cytokines were also elevated upon the knockdown of genes of the host SUMOylation pathway during L. donovani infection. This indicates the involvement of the SUMOylation pathway in the modulation of protective immune responses and thus favoring parasite survival. Taken together, the results of this study indicate the hijacking of the host SUMOylation pathway by L. donovani toward the suppression of host immune responses and facilitation of host autophagy to potentially facilitate its survival. Targeting of SUMOylation pathway can provide a starting point for the design and development of novel therapeutic interventions to combat leishmaniasis.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    DOI: 10.3389/fcimb.2022.878136
    DOI: 10.3389/fcimb.2022.878136.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2619676-1
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