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  1. Article ; Online: Post-mortem dissection of COVID-19: a pathogenic role for macrophages?

    Velu, Prasad P / Lucas, Christopher D / Conway Morris, Andrew

    Intensive care medicine

    2021  Volume 47, Issue 11, Page(s) 1322–1325

    MeSH term(s) Autopsy ; COVID-19 ; Dissection ; Humans ; Macrophages ; SARS-CoV-2
    Language English
    Publishing date 2021-09-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80387-x
    ISSN 1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
    ISSN (online) 1432-1238
    ISSN 0340-0964 ; 0342-4642 ; 0935-1701
    DOI 10.1007/s00134-021-06509-9
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  2. Article ; Online: Variation in grain zinc and iron concentrations, grain yield and associated traits of biofortified bread wheat genotypes in Nepal

    Dhruba Bahadur Thapa / Subedi, Mahesh / Yadav, Rajendra Prasad / Joshi, Bishnu Prasad / Adhikari, Bhim Nath / Shrestha, Keshav Prasad / Magar, Prem Bahadur / Pant, Khem / Gurung, Suk Bahadur / Ghimire, Sapana / Gautam, Nutan Raj / Acharya, Nav Raj / Sapkota, Manoj / Vinod Kumar Mishra / Joshi, Arun Kumar / Singh, Ravi P. / Velu, Govindan

    Frontiers in Plant Science

    2023  

    Abstract: Wheat (Triticum aestivum L.) is one of the major staples in Nepal providing the bulk of food calories and at least 30% of Fe and Zn intake and 20% of dietary energy and protein consumption; thus, it is essential to improve its nutritional quality. To ... ...

    Abstract Wheat (Triticum aestivum L.) is one of the major staples in Nepal providing the bulk of food calories and at least 30% of Fe and Zn intake and 20% of dietary energy and protein consumption; thus, it is essential to improve its nutritional quality. To select high-yielding genotypes with elevated grain zinc and iron concentration, the sixth, seventh, eighth, and ninth HarvestPlus Yield Trials (HPYTs) were conducted across diverse locations in Nepal for four consecutive years: 2015–16, 2016–17, 2017–18, and 2018–19, using 47 biofortified and 3 non-biofortified CIMMYT-bred, bread wheat genotypes: Baj#1, Kachu#1, and WK1204 (local check). Genotypic and spatial variations were found in agro-morphological traits; grain yield and its components; and the grain zinc and iron concentration of tested genotypes. Grain zinc concentration was highest in Khumaltar and lowest in Kabre. Likewise, grain iron concentration was highest in Doti and lowest in Surkhet. Most of the biofortified genotypes were superior for grain yield and for grain zinc and iron concentration to the non-biofortified checks. Combined analyses across environments showed moderate to high heritability for both Zn (0.48–0.81) and Fe (0.46–0.79) except a low heritability for Fe observed for 7th HPYT (0.15). Grain yield was positively correlated with the number of tillers per m2, while negatively correlated with days to heading and maturity, grain iron, grain weight per spike, and thousand grain weight. The grain zinc and iron concentration were positively correlated, suggesting that the simultaneous improvement of both micronutrients is possible through wheat breeding. Extensive testing of CIMMYT derived high Zn wheat lines in Nepal led to the release of five biofortified wheat varieties in 2020 with superior yield, better disease resistance, and 30–40% increased grain Zn and adaptable to a range of wheat growing regions in the country – from the hotter lowland, or Terai, regions to the dry mid- and high-elevation areas.
    Keywords biofortification ; wheat ; grain ; yields ; zinc ; iron
    Language English
    Publishing date 2023-01-12T16:01:25Z
    Publisher Frontiers Media
    Publishing country fr
    Document type Article ; Online
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  3. Article ; Online: Honokiol inhibits the growth of head and neck squamous cell carcinoma by targeting epidermal growth factor receptor.

    Singh, Tripti / Gupta, Nirzari A / Xu, Su / Prasad, Ram / Velu, Sadanandan E / Katiyar, Santosh K

    Oncotarget

    2015  Volume 6, Issue 25, Page(s) 21268–21282

    Abstract: ... gavage (100 mg/kg body weight) significantly (P < 0.01-0.001) inhibited the growth of SCC-1 and FaDu ...

    Abstract Here, we report the chemotherapeutic effect of honokiol, a phytochemical from Magnolia plant, on human head and neck squamous cell carcinoma (HNSCC). Treatment of HNSCC cell lines from different sub-sites, SCC-1 (oral cavity), SCC-5 (larynx), OSC-19 (tongue) and FaDu (pharynx) with honokiol inhibited their cell viability, which was associated with the: (i) induction of apoptosis, (ii) correction of dysregulatory cell cycle proteins of G0/G1 phase. Honokiol decreased the expression levels of epidermal growth factor receptor (EGFR), mTOR and their downstream signaling molecules. Treatment of FaDu and SCC-1 cell lines with rapamycin, an inhibitor of mTOR pathway, also reduced cell viability of HNSCC cells. Administration of honokiol by oral gavage (100 mg/kg body weight) significantly (P < 0.01-0.001) inhibited the growth of SCC-1 and FaDu xenografts in athymic nude mice, which was associated with: (i) inhibition of tumor cell proliferation, (ii) induction of apoptosis, (iii) reduced expressions of cyclins and Cdks, and (iv) inhibition of EGFR signaling pathway. Molecular docking analysis of honokiol in EGFR binding site indicated that the chemotherapeutic effect of honokiol against HNSCC is mediated through its firm binding with EGFR, which is better than that of gefitinib, a commonly used drug for HNSCC treatment.
    MeSH term(s) Animals ; Antineoplastic Agents, Phytogenic/therapeutic use ; Apoptosis ; Binding Sites ; Biphenyl Compounds/pharmacology ; Carcinoma, Squamous Cell/drug therapy ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation ; Cell Separation ; Cell Survival ; Dose-Response Relationship, Drug ; Female ; Flow Cytometry ; Head and Neck Neoplasms/drug therapy ; Humans ; Lignans/pharmacology ; Magnolia/chemistry ; Mice ; Mice, Nude ; Molecular Docking Simulation ; Phytotherapy/methods ; Plant Extracts/chemistry ; Receptor, Epidermal Growth Factor/chemistry ; Receptor, Epidermal Growth Factor/metabolism ; Signal Transduction ; Sirolimus/chemistry
    Chemical Substances Antineoplastic Agents, Phytogenic ; Biphenyl Compounds ; Lignans ; Plant Extracts ; honokiol (11513CCO0N) ; EGFR protein, human (EC 2.7.10.1) ; Receptor, Epidermal Growth Factor (EC 2.7.10.1) ; Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2015-08-28
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.4178
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  4. Article ; Online: The BRICS (Bronchiectasis Radiologically Indexed CT Score): A Multicenter Study Score for Use in Idiopathic and Postinfective Bronchiectasis.

    Bedi, Pallavi / Chalmers, James D / Goeminne, Pieter C / Mai, Cindy / Saravanamuthu, Pira / Velu, Prasad Palani / Cartlidge, Manjit K / Loebinger, Michael R / Jacob, Joe / Kamal, Faisal / Schembri, Nicola / Aliberti, Stefano / Hill, Uta / Harrison, Mike / Johnson, Christopher / Screaton, Nicholas / Haworth, Charles / Polverino, Eva / Rosales, Edmundo /
    Torres, Antoni / Benegas, Michael N / Rossi, Adriano G / Patel, Dilip / Hill, Adam T

    Chest

    2017  Volume 153, Issue 5, Page(s) 1177–1186

    Abstract: Objectives: The goal of this study was to develop a simplified radiological score that could assess clinical disease severity in bronchiectasis.: Methods: The Bronchiectasis Radiologically Indexed CT Score (BRICS) was devised based on a multivariable ...

    Abstract Objectives: The goal of this study was to develop a simplified radiological score that could assess clinical disease severity in bronchiectasis.
    Methods: The Bronchiectasis Radiologically Indexed CT Score (BRICS) was devised based on a multivariable analysis of the Bhalla score and its ability in predicting clinical parameters of severity. The score was then externally validated in six centers in 302 patients.
    Results: A total of 184 high-resolution CT scans were scored for the validation cohort. In a multiple logistic regression model, disease severity markers significantly associated with the Bhalla score were percent predicted FEV
    Conclusions: A simplified CT scoring system can be used as an adjunct to clinical parameters to predict disease severity in patients with idiopathic and postinfective bronchiectasis.
    MeSH term(s) Aged ; Bronchiectasis/diagnosis ; Bronchiectasis/etiology ; Cohort Studies ; Female ; Hospitalization ; Humans ; Logistic Models ; Male ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Respiratory Function Tests ; Severity of Illness Index ; Tomography, X-Ray Computed
    Language English
    Publishing date 2017-12-13
    Publishing country United States
    Document type Journal Article ; Multicenter Study
    ZDB-ID 1032552-9
    ISSN 1931-3543 ; 0012-3692
    ISSN (online) 1931-3543
    ISSN 0012-3692
    DOI 10.1016/j.chest.2017.11.033
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    Ui III Zs.45: Show issues Location:
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  5. Article ; Online: Inhibition of rapamycin-induced AKT activation elicits differential antitumor response in head and neck cancers.

    Radhakrishnan, Padhma / Baraneedharan, Ulaganathan / Veluchamy, Subhadra / Dhandapani, Muthu / Pinto, Dency D / Thiyagarajan, Saravanan / Thayakumar, Allen / Prasath, Arun / A, Kamal / Velu, Ayyappan / Jain, Misti / Brijwani, Nilesh / Narayanan, Prasad / Kekatpure, Vikram D / Majumder, Biswanath / Majumder, Pradip K

    Cancer research

    2013  Volume 73, Issue 3, Page(s) 1118–1127

    Abstract: The PI3K/AKT/mTOR pathway is an important signaling axis that is perturbed in majority of cancers. Biomarkers such as pS6RP, GLUT1, and tumor FDG uptake are being evaluated in patient stratification for mTOR pathway inhibitors. In the absence of a clear ... ...

    Abstract The PI3K/AKT/mTOR pathway is an important signaling axis that is perturbed in majority of cancers. Biomarkers such as pS6RP, GLUT1, and tumor FDG uptake are being evaluated in patient stratification for mTOR pathway inhibitors. In the absence of a clear understanding of the underlying mechanisms in tumor signaling, the biomarker strategy for patient stratification is of limited use. Here, we show that no discernible correlation exists between FDG uptake and the corresponding Ki67, GLUT1, pS6RP expression in tumor biopsies from patients with head and neck cancer. Correlation between GLUT1 and pS6RP levels in tumors was observed but elevated pS6RP was noticed even in the absence of concomitant AKT activation, suggesting that other downstream molecules of PI3K/AKT and/or other pathways upstream of mTOR are active in these tumors. Using an ex vivo platform, we identified putative responders to rapamycin, an mTOR inhibitor in these tumors. However, rapamycin did not induce antitumor effect in the majority of tumors with activated mTOR, potentially attributable to the observation that rapamycin induces feedback activation of AKT. Accordingly, treatment of these tumors with an AKT inhibitor and rapamycin uniformly resulted in abrogation of mTOR inhibition-induced AKT activation in all tumors but failed to induce antitumor response in a subset. Phosphoproteomic profiling of tumors resistant to dual AKT/mTOR inhibitors revealed differential activation of multiple pathways involved in proliferation and survival. Collectively, our results suggest that, in addition to biomarker-based segregation, functional assessment of a patient's tumor before treatment with mTOR/AKT inhibitors may be useful for patient stratification.
    MeSH term(s) Adult ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Female ; Glucose Transporter Type 1/analysis ; Head and Neck Neoplasms/drug therapy ; Head and Neck Neoplasms/pathology ; Humans ; Male ; Middle Aged ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors ; Proto-Oncogene Proteins c-akt/metabolism ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/physiology
    Chemical Substances Glucose Transporter Type 1 ; SLC2A1 protein, human ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2013-02-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-12-2545
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  6. Article: Relationship between T-lymphocyte cytokine levels and sero-response to hepatitis B vaccines.

    Velu, Vijayakumar / Saravanan, Shanmugam / Nandakumar, Subhadra / Shankar, Esaki-Muthu / Vengatesan, Appasamy / Jadhav, Suresh-Sakharam / Kulkarni, Prasad-Suryakant / Thyagarajan, Sadras-Panchatcharam

    World journal of gastroenterology

    2008  Volume 14, Issue 22, Page(s) 3534–3540

    Abstract: ... with recombinant HBsAg and were compared with respective antibody titers.: Results: A significant decrease (P ... P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response ...

    Abstract Aim: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders.
    Methods: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-gamma, IL-2, TNF-alpha, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers.
    Results: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-gamma, TNF-alpha and IL-10 in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response.
    Conclusion: Our findings suggest that unresponsiveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.
    MeSH term(s) Adult ; Antibody Formation/drug effects ; Antibody Formation/immunology ; Cells, Cultured ; Cytokines/metabolism ; Hepatitis B Surface Antigens/pharmacology ; Hepatitis B Vaccines/immunology ; Hepatitis B Vaccines/pharmacology ; Hepatitis B virus/immunology ; Humans ; Interferon-gamma/metabolism ; Interleukin-10/metabolism ; Interleukin-12/metabolism ; Interleukin-2/metabolism ; Interleukin-4/metabolism ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/metabolism ; Th1 Cells/cytology ; Th1 Cells/metabolism ; Th2 Cells/cytology ; Th2 Cells/metabolism ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Cytokines ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines ; Interleukin-2 ; Tumor Necrosis Factor-alpha ; Interleukin-10 (130068-27-8) ; Interleukin-12 (187348-17-0) ; Interleukin-4 (207137-56-2) ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2008-06-20
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2185929-2
    ISSN 2219-2840 ; 1007-9327
    ISSN (online) 2219-2840
    ISSN 1007-9327
    DOI 10.3748/wjg.14.3534
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    Zs.A 6039: Show issues Location:
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  7. Article ; Online: Relationship between T-lymphocyte cytokine levels and sero-response to hepatitis B vaccines

    Vijayakumar Velu, Shanmugam Saravanan, Subhadra Nandakumar, Esaki Muthu Shankar, Appasamy Vengatesan, Suresh Sakharam Jadhav, Prasad Suryakant Kulkarni, Sadras Panchatcharam Thyagarajan

    World Journal of Gastroenterology, Vol 14, Iss 22, Pp 3534-

    2008  Volume 3540

    Abstract: ... with recombinant HBsAg and were compared with respective antibody titers.RESULTS: A significant decrease (P = 0.001 ... response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and ...

    Abstract AIM: To investigate the cellular defects by analyzing the (Th1/Th2) cytokine levels in vaccine responders and non-responders.METHODS: Peripheral blood mononuclear cell (PBMC) from responders and non-responders were stimulated with or with out recombinant HBsAg or PHA. Broad spectrum of cytokines viz (Th1) IFN-γ, IL-2, TNF-α, IL-12 and (Th2) IL-10, IL-4 were measured after in vitro stimulation with recombinant HBsAg and were compared with respective antibody titers.RESULTS: A significant decrease (P = 0.001) in Th1 and Th2 cytokines namely, IL-2, INF-γ, TNF-α and IL-10 in non-responders was observed. The level of IL-4 was not significant between the three groups. Furthermore, despite a strong Th1 and Th2 cytokine response, the level of IL-12 was elevated in high-responders compared to other groups (P = 0.001) and demonstrated a positive correlation with anti-HBs titers and Th1 cytokine response.CONCLUSION: Our findings suggest that unresponsiveness to recombinant hepatitis B vaccines (rHB) is multifactorial, including specific failure of antigen presentation or the lack of both T helper Th1 and Th2 response.
    Keywords Hepatitis B vaccine ; Cytokines ; Humoral response ; T cell response ; Adult vaccines ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 610
    Language English
    Publishing date 2008-06-01T00:00:00Z
    Publisher Baishideng Publishing Group Co. Limited
    Document type Article ; Online
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  8. Article ; Online: Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic stroke: a multicentric, randomized trial.

    Prasad, Kameshwar / Sharma, Alka / Garg, Ajay / Mohanty, Sujata / Bhatnagar, Shinjini / Johri, Sharat / Singh, Kunwar Karni / Nair, Velu / Sarkar, Ravi Shankar / Gorthi, Sankar Prasad / Hassan, Kaukab Maqbool / Prabhakar, Sudesh / Marwaha, Neelam / Khandelwal, Niranjan / Misra, Usha Kant / Kalita, Jayantee / Nityanand, Soniya

    Stroke

    2014  Volume 45, Issue 12, Page(s) 3618–3624

    Abstract: ... arm and control arm in the Barthel Index score (63.1 versus 63.6; P=0.92), modified Rankin scale shift ... analysis (P=0.53) or score >3 (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change ... in infarct volume (-11.1 versus -7.36; P=0.63) at day 180. Adverse events were also similar in the 2 arms ...

    Abstract Background and purpose: Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke.
    Methods: This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of (18)fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days.
    Results: Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6; P=0.92), modified Rankin scale shift analysis (P=0.53) or score >3 (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change in infarct volume (-11.1 versus -7.36; P=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of (18)fluorodeoxyglucose uptake.
    Conclusions: With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome.
    Clinical trial registration: URLs: http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.
    MeSH term(s) Aged ; Bone Marrow Transplantation/methods ; Female ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Recovery of Function ; Stroke/pathology ; Stroke/surgery
    Language English
    Publishing date 2014-12
    Publishing country United States
    Document type Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 80381-9
    ISSN 1524-4628 ; 0039-2499 ; 0749-7954
    ISSN (online) 1524-4628
    ISSN 0039-2499 ; 0749-7954
    DOI 10.1161/STROKEAHA.114.007028
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