المؤلفون: Alaa M. Altaie, Mohammad G. Mohammad, Mohamed I. Madkour, Mohammed Amjed AlSaegh, Manju Nidagodu Jayakumar, Aghila Rani K.G., A. R. Samsudin, Rabih Halwani, Rifat A. Hamoudi, Sameh S. M. Soliman

المصدر: Scientific Reports, Vol 13, Iss 1, Pp 1-14 (2023)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Recently, 1-nonadecene and l-lactic acid were identified as unique metabolites in radicular cysts and periapical granuloma, respectively. However, the biological roles of these metabolites were unknown. Therefore, we aimed to investigate the inflammatory and mesenchymal-epithelial transition (MET) effects of 1-nonadecene, and the inflammatory and collagen precipitation effects of l-lactic acid on both periodontal ligament fibroblasts (PdLFs) and peripheral blood mononuclear cells (PBMCs). PdLFs and PBMCs were treated with 1-nonadecene and l-lactic acid. Cytokines’ expression was measured using quantitative real-time polymerase chain reaction (qRT-PCR). E-cadherin, N-cadherin, and macrophage polarization markers were measured using flow cytometry. The collagen, matrix metalloproteinase (MMP)-1, and released cytokines were measured using collagen assay, western blot, and Luminex assay, respectively. In PdLFs, 1-nonadecene enhances inflammation through the upregulation of some inflammatory cytokines including IL-1β, IL-6, IL-12A, monocyte chemoattractant protein (MCP)-1, and platelet-derived growth factor (PDGF) α. 1-Nonadecene also induced MET through the upregulation of E-cadherin and the downregulation of N-cadherin in PdLFs. 1-Nonadecene polarized macrophages to a pro-inflammatory phenotype and suppressed their cytokines’ release. l-lactic acid exerted a differential impact on the inflammation and proliferation markers. Intriguingly, l-lactic acid induced fibrosis-like effects by enhancing collagen synthesis, while inhibiting MMP-1 release in PdLFs. These results provide a deeper understanding of 1-nonadecene and l-lactic acid’s roles in modulating the microenvironment of the periapical area. Consequently, further clinical investigation can be employed for target therapy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/c3dbf986d5c74df1a277d9782ef547b8Test

المؤلفون: Fatma Al Qutami, Walaa AlHalabi, Aswathy Vijayakumar, Surendra Singh Rawat, Abubakr H. Mossa, Manju Nidagodu Jayakumar, Baila Samreen, Mahmood Y. Hachim

المصدر: Cancers, Vol 16, Iss 4, p 747 (2024)

مصطلحات موضوعية: neutrophiles, triple-negative breast cancer, TNBC, NETosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Breast cancer (BC) is one of the most common types of cancer in women in the United Arab Emirates. Immunogenic tumours, such as triple-negative breast cancer (TNBC), show increased neutrophil infiltration, which is associated with poor prognosis and limited efficacy of immunotherapy. This study aims to investigate in vitro the bidirectional effect of neutrophils on metastatic TNBC (MDA-MB-231) compared to less-metastatic luminal breast cancer (MCF-7) cell lines. We found that BC cells or their conditioned medium (CM) reduced the viability of neutrophil-like cells (HL60). This was supported by increased cellular stress and NETosis in differentiated HL60 cells (dHL60) upon exposure to MDA-MB-231 compared to MCF-7-CM using nucleic acid staining essays. Flow cytometry showed comparable expression of inflammatory markers by polymorphonuclear cells (PMN) when treated with MDA-MB-231-CM and standard polarizing cocktails. Furthermore, MDA-MB-231-CM triggered an inflammatory pattern with evidence of stronger adhesion (CD62L) and degranulation (CD11b and CD66b) phenotypes. The proinflammatory polarization of dHL60 by MDA-MB-231-CM was additionally confirmed by the elevated CD54 expression, myeloperoxidase, and CD11b protein levels, which matched an increased transwell migratory capacity. In conclusion, BC might use neutrophils to their benefit through NETosis and complement system activation, which makes this crosstalk a potential mechanism for understanding tumour progression.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/16/4/747Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/954f3bb5102246ff884ad064c0709fe1Test

المؤلفون: Fakhira Saif Alketbi, Amir Ali Khan, Muhammad Tehsil Gul, Muhammad Nasir Khan Khattak, Manju Nidagodu Jayakumar, A R Samsudin

المصدر: Advances in Biomedical and Health Sciences, Vol 2, Iss 2, Pp 62-71 (2023)

مصطلحات موضوعية: differentiation, epigenetic modifiers, human dental pulp stem cells, neural progenitor cells, Medicine

الوصف: Background: Human dental pulp stem cells (HDPSCs) may be differentiated into neural lineages. The main aim of the study was to assess the DNA demethylation and histone deacetylation inhibition on the differentiation of HDPSCs into neural progenitor-like cells (NPCs). Methods: HDPSCs were treated with 5-aza2′-deoxycytidine (AZA), DNA methylation inhibitor, and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) for 3 and 5 days followed by their differentiation into NPCs. The efficiency of the differentiation was evaluated by apoptosis, cellular proliferation, and relative expression of Nestin among the NPCs derived with the different treatments. Results: Five-day treatment of AZA was crucial for the more efficient demethylation of the HDPSCs. Analysis of the proliferation, apoptosis, and relative expression of the Nestin indicated that the AZA and SAHA neither enhance nor inhibit the differentiation of the HDPSCs into NPCs. Howevere, the expression of Nestin decreased at day 7 in NPCs derived with SAHAH treatment compared with NPCs derived with AZA treatmement. However, there was no difference in Nestin expression in any treatment-derived NPCs compared with control NPCs. All of the NPCs derived from all of the groups were able to differentiate into terminal neurons. Conclusion: Neither DNA demethylation nor the histone deacetylation has any main effects on proliferation and apoptosis during the differentiation of HDPSCs into NPCs. The only significant effect of the treatments was on the size of the NPCs at day 7; the SAHAH treatment had the smallest NPCs.

وصف الملف: electronic resource

العلاقة: http://www.abhsjournal.net/article.asp?issn=2773-1545;year=2023;volume=2;issue=2;spage=62;epage=71;aulast=AlketbiTest; https://doaj.org/toc/2773-1545Test; https://doaj.org/toc/2773-1553Test

الوصول الحر: https://doaj.org/article/b49e2d80a7ab42b49ff7b8fb044e281bTest

المؤلفون: Sakina Eqbal Hussain Tayabally, Amir Ali Khan, Sallam Hasan Abdallah, Muhammad Nasir Khan Khattak, Manju Nidagodu Jayakumar, A.B. Rani Samsudin

المصدر: Saudi Journal of Biological Sciences, Vol 29, Iss 4, Pp 2674-2682 (2022)

مصطلحات موضوعية: Human dental pulp stem cells, 2D cell culture, 3D cell culture, Col-Tgel, Biology (General), QH301-705.5

الوصف: Human dental pulp stem cells (HDPSCs) have great potential to be used in regenerative medicine. To use these stem cells effectively for this purpose, they should be grown in a 3D cell culture that mimics their natural niches instead of a 2D conventional cell culture. The aim of this study was to grow the HDPSCs in the 3D cell culture created by Transglutaminase-crosslinked collagen hydrogels (Col-Tgel) in two different strengths to find a suitable 3D cell culture environment for these stem cells. Two stiffness of the 3D Col-Tgel were used to grow the HDPSCs: soft and medium matrix with strength of 0.9–1.5 kPa and 14–20 kPa, respectively. HDPSCs express markers similar to MSCs, therefore seven such markers were analyzed in the HDPSCs during their growth in the 2D and in the 3D soft and medium Col-Tgel. The CD105 and CD90 markers were significantly (p

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1319562X21010792Test; https://doaj.org/toc/1319-562XTest

الوصول الحر: https://doaj.org/article/daca09edca4c4db6995524b21273ba21Test

المؤلفون: Waad Kheder, Amal Bouzid, Thenmozhi Venkatachalam, Iman M. Talaat, Noha Mousaad Elemam, Tom Kalathil Raju, Soumya Sheela, Manju Nidagodu Jayakumar, Azzam A. Maghazachi, Abdul Rani Samsudin, Rifat Hamoudi

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 14, p 11644 (2023)

مصطلحات موضوعية: dental implants, peri-implantitis, titanium, lymphocytes, macrophage polarization, IL-1β, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Titanium dental implants are one of the modalities to replace missing teeth. The release of titanium particles from the implant’s surface may modulate the immune cells, resulting in implant failure. However, little is known about the immune microenvironment that plays a role in peri-implant inflammation as a consequence of titanium particles. In this study, the peri-implant gingival tissues were collected from patients with failed implants, successful implants and no implants, and then a whole transcriptome analysis was performed. The gene set enrichment analysis confirmed that macrophage M1/M2 polarization and lymphocyte proliferation were differentially expressed between the study groups. The functional clustering and pathway analysis of the differentially expressed genes between the failed implants and successful implants versus no implants revealed that the immune response pathways were the most common in both comparisons, implying the critical role of infiltrating immune cells in the peri-implant tissues. The H&E and IHC staining confirmed the presence of titanium particles and immune cells in the tissue samples, with an increase in the infiltration of lymphocytes and macrophages in the failed implant samples. The in vitro validation showed a significant increase in the level of IL-1β, IL-8 and IL-18 expression by macrophages. Our findings showed evidence that titanium particles modulate lymphocyte and macrophage polarization in peri-implant gingival tissues, which can help in the understanding of the imbalance in osteoblast–osteoclast activity and failure of dental implant osseointegration.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/14/11644Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/694e6cb7c8a34cb6b3dae5f7e836e992Test

المؤلفون: Dali Vilma Francis, Manju Nidagodu Jayakumar, Hafiz Ahmad, Trupti Gokhale

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 12, p 9998 (2023)

مصطلحات موضوعية: antimicrobial activity, metal oxides, CuO nanoparticle, ZnO nanoparticle, WO3 nanoparticle, synergistic action, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: The rising prevalence of antibiotic-resistance is currently a grave issue; hence, novel antimicrobial agents are being explored and developed to address infections resulting from multiple drug-resistant pathogens. Biogenic CuO, ZnO, and WO3 nanoparticles can be considered as such agents. Clinical isolates of E. coli, S. aureus, methicillin-resistant S. aureus (MRSA), and Candida albicans from oral and vaginal samples were treated with single and combination metal nanoparticles incubated under dark and light conditions to understand the synergistic effect of the nanoparticles and their photocatalytic antimicrobial activity. Biogenic CuO and ZnO nanoparticles exhibited significant antimicrobial effects under dark incubation which did not alter on photoactivation. However, photoactivated WO3 nanoparticles significantly reduced the number of viable cells by 75% for all the test organisms, thus proving to be a promising antimicrobial agent. Combinations of CuO, ZnO, and WO3 nanoparticles demonstrated synergistic action as a significant increase in their antimicrobial property (>90%) was observed compared to the action of single elemental nanoparticles. The mechanism of the antimicrobial action of metal nanoparticles both in combination and in isolation was assessed with respect to lipid peroxidation due to ROS (reactive oxygen species) generation by measuring malondialdehyde (MDA) production, and the damage to cell integrity using live/dead staining and quantitating with the use of flow cytometry and fluorescence microscopy.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/12/9998Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/9790c55ad7ba450fa284dea394eb38bcTest

المؤلفون: Jibran Sualeh Muhammad, Maha Guimei, Manju Nidagodu Jayakumar, Jasmin Shafarin, Aisha Saleh Janeeh, Rola AbuJabal, Mohamed Ahmed Eladl, Anu Vinod Ranade, Amjad Ali, Mawieh Hamad

المصدر: Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 1, Pp 68-79 (2021)

مصطلحات موضوعية: Epigenetics, DNA methylation, Estrogen, Yes-associated protein-1 gene, Carcinogenesis, Breast cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Increased expression of Yes-associated protein-1 (YAP1) was shown to correlate with reduced survival in breast cancer (BC) patients. However, the exact mechanism of YAP1 regulation in BC cells remains ambiguous. Genomic sequence search showed that the promoter region of the YAP1 gene contains CpG Islands, hence the likelihood of epigenetic regulation by DNA methylation. To address this possibility, the effect of estrogen (17β estradiol; E2) on YAP1 gene expression and YAP1 promoter methylation status was evaluated in BC cells. The functional consequences of E2 treatment in control and YAP1-silenced BC cells were also investigated. Our data showed that E2 modulates YAP1 expression by hypomethylation of its promoter region via downregulation of DNA methyltransferase 3B (DNMT3B); an effect that seems to facilitate tumor progression in BC cells. Although the effect of E2 on YAP1 expression was estrogen receptor (ER) dependent, E2 treatment also upregulated YAP1 expression in MDA-MB231 and SKBR3 cells, which are known ER-negative BC cell lines but expresses ERα. Functionally, E2 treatment resulted in increased cell proliferation, decreased apoptosis, cell cycle arrest, and autophagic flux in MCF7 cells. The knockdown of the YAP1 gene reversed these carcinogenic effects of E2 and inhibited E2-induced autophagy. Lastly, we showed that YAP1 is highly expressed and hypomethylated in human BC tissues and that increased YAP1 expression correlates negatively with DNMT3B expression but strongly associated with ER expression. Our data provide the basis for considering screening of YAP1 expression and its promoter methylation status in the diagnosis and prognosis of BC.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1476558620301706Test; https://doaj.org/toc/1476-5586Test

الوصول الحر: https://doaj.org/article/3afad80d63294086be6b013c6f2fd0a5Test

المؤلفون: Abdul Wahid Ansari, Fatemeh Saheb Sharif-Askari, Manju Nidagodu Jayakumar, Abdul Khader Mohammed, Narjes Saheb Sharif-Askari, Thenmozhi Venkatachalam, Bassam Mahboub, Reinhold E. Schmidt, Rifat Akram Hamoudi, Rabih Halwani, Qutayba Hamid

المصدر: Frontiers in Immunology, Vol 11 (2020)

مصطلحات موضوعية: azithromycin, CD4+ helper T cells, anti-inflammatory, CCR4, CXCR3, IFN-γ, Immunologic diseases. Allergy, RC581-607

الوصف: In addition to their antibiotic activities, azithromycin (AZM) exhibits anti-inflammatory effects in various respiratory diseases. One of the potent anti-inflammatory mechanisms is through inhibition of CD4+ helper T (Th) cell effector function. However, their impact on specific Th subset is obscure. Herein, we demonstrate the cellular basis of phenotypic and functional alterations associated with Th subsets following AZM treatment in vitro. Using well-characterized Th subset specific chemokine receptors, we report significant suppression of T cell receptor (TCR)-stimulated hyperactivated CCR4+CXCR3+ (Th0) expansion compared to CCR4-CXCR3+ (Th1-like) and CCR4+CXCR3- (Th2-like) cells. Interestingly, this effect was associated with diminished cell proliferation. Furthermore, AZM significantly inhibited the inflammatory cytokines IFN-γ and IL-4 production, CCR4 and CXCR3 receptor expression, and viability of Th0, Th1-like, and Th2-like subsets. Our findings suggest that AZM differentially affects TCR-activated Th subsets phenotype and function, and CCR4 and CXCR3 downregulation and suppressed Th0 subset expansion could potentially influence their trafficking and differentiation into cytokine-producing effector cells.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fimmu.2020.556579/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/3c8891d47075420995b56217e3aa0f09Test

المؤلفون: Nour Z. Atwany, Seyedeh-Khadijeh Hashemi, Manju Nidagodu Jayakumar, Mitzi Nagarkatti, Prakash Nagarkatti, Mona Rushdi Hassuneh

المصدر: Biology, Vol 9, Iss 8, p 211 (2020)

مصطلحات موضوعية: human, Foxp3 induction, CD4+CD25+ regulatory T cells, natural molecules, mixed lymphocyte reaction (MLR), Biology (General), QH301-705.5

الوصف: Regulatory T cells (Tregs) are key players in the regulation of inflammatory responses. In this study, two natural molecules, namely, sparteine sulfate (SS) and harpagoside (Harp), were investigated for their ability to induce Tregs in human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from healthy volunteers and grown in the presence or absence of ConA, with TGF-beta, SS or Harp. Expression of the mRNA of FoxP3, TGF-beta, IL-10 and GAPDH was assessed via q-PCR. The expression of Treg markers including CD4, CD25, CD127 and FoxP3 was measured via flow cytometry. The secretion of IL-10 and TGF-beta by cultured cells was assessed by ELISA. Furthermore, the suppressive role of SS and Harp on PBMCs in vitro was tested via allogeneic mixed lymphocyte reaction (MLR). Data obtained show that both compounds increased the expression of FoxP3, TGF-beta and IL-10 mRNA in resting PBMCs but to a lesser extent in activated cells. Moreover, they significantly increased the percent of CD4+CD25+FoxP3+CD127− Tregs in activated and naïve PBMCs. Functionally, both compounds caused a significant reduction in the stimulation index in allogeneic MLR. Together, our data demonstrate for the first time that SS and Harp can induce human Tregs in vitro and therefore have great potential as anti-inflammatory agents.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2079-7737/9/8/211Test; https://doaj.org/toc/2079-7737Test

الوصول الحر: https://doaj.org/article/4f8ef0c0531e411bb1dec6e9ef0bc4d0Test

المؤلفون: Gokhale, Dali Vilma Francis, Manju Nidagodu Jayakumar, Hafiz Ahmad, Trupti

المصدر: International Journal of Molecular Sciences; Volume 24; Issue 12; Pages: 9998

مصطلحات موضوعية: antimicrobial activity, metal oxides, CuO nanoparticle, ZnO nanoparticle, WO3 nanoparticle, synergistic action, lipid peroxidation, flow cytometry

الوصف: The rising prevalence of antibiotic-resistance is currently a grave issue; hence, novel antimicrobial agents are being explored and developed to address infections resulting from multiple drug-resistant pathogens. Biogenic CuO, ZnO, and WO3 nanoparticles can be considered as such agents. Clinical isolates of E. coli, S. aureus, methicillin-resistant S. aureus (MRSA), and Candida albicans from oral and vaginal samples were treated with single and combination metal nanoparticles incubated under dark and light conditions to understand the synergistic effect of the nanoparticles and their photocatalytic antimicrobial activity. Biogenic CuO and ZnO nanoparticles exhibited significant antimicrobial effects under dark incubation which did not alter on photoactivation. However, photoactivated WO3 nanoparticles significantly reduced the number of viable cells by 75% for all the test organisms, thus proving to be a promising antimicrobial agent. Combinations of CuO, ZnO, and WO3 nanoparticles demonstrated synergistic action as a significant increase in their antimicrobial property (>90%) was observed compared to the action of single elemental nanoparticles. The mechanism of the antimicrobial action of metal nanoparticles both in combination and in isolation was assessed with respect to lipid peroxidation due to ROS (reactive oxygen species) generation by measuring malondialdehyde (MDA) production, and the damage to cell integrity using live/dead staining and quantitating with the use of flow cytometry and fluorescence microscopy.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=multidiscipl::d4a43b9f27bbc1a12060e3417ec678dbTest