Stimulation of cell responses and bone ingrowth into macro-microporous implants of nano-bioglass/polyetheretherketone composite and enhanced antibacterial activity by release of hinokitiol

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4+ and CD8+ memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4+CD45RA−CCR7− phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8+, but not CD4+, T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.

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Stimulation of autologous proliferative and cytotoxic T-cell responses by “leukemic dendritic cells” derived from blast cells in acute myeloid leukemia

Blood ◽

10.1182/blood.v97.9.2764 ◽

2001 ◽

Vol 97 (9) ◽

pp. 2764-2771 ◽

Cited By ~ 77

Author(s):

Beth D. Harrison ◽

Julie A. Adams ◽

Mark Briggs ◽

Michelle L. Brereton ◽

John A. Liu Yin

Keyword(s):

T Cells ◽

Acute Myeloid Leukemia ◽

Dendritic Cells ◽

T Cell ◽

Myeloid Leukemia ◽

T Cell Responses ◽

Cell Responses ◽

Antigen Presenting ◽

Acute Myeloid ◽

Stimulation Of

Abstract Effective presentation of tumor antigens is fundamental to strategies aimed at enrolling the immune system in eradication of residual disease after conventional treatments. Myeloid malignancies provide a unique opportunity to derive dendritic cells (DCs), functioning antigen-presenting cells, from the malignant cells themselves. These may then co-express leukemic antigens together with appropriate secondary signals and be used to generate a specific, antileukemic immune response. In this study, blasts from 40 patients with acute myeloid leukemia (AML) were cultured with combinations of granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor α, and development to DCs was assessed. After culture, cells from 24 samples exhibited morphological and immunophenotypic features of DCs, including expression of major histocompatibility complex class II, CD1a, CD83, and CD86, and were potent stimulators in an allogeneic mixed lymphocyte reaction (MLR). Stimulation of autologous T-cell responses was assessed by the proliferative response of autologous T cells to the leukemic DCs and by demonstration of the induction of specific, autologous, antileukemic cytotoxicity. Of 17 samples, 11 were effective stimulators in the autologous MLR, and low, but consistent, autologous, antileukemic cytotoxicity was induced in 8 of 11 cases (mean, 27%; range, 17%-37%). This study indicates that cells with enhanced antigen-presenting ability can be generated from AML blasts, that these cells can effectively prime autologous cytotoxic T cells in vitro, and that they may be used as potential vaccines in the immunotherapy of AML.

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Acellular Pertussis Vaccines and Pertussis Resurgence: Revise or Replace?

mBio ◽

10.1128/mbio.01339-14 ◽

2014 ◽

Vol 5 (3) ◽

Cited By ~ 28

Author(s):

Clara Maria Ausiello ◽

Antonio Cassone

Keyword(s):

Immune Responses ◽

Whooping Cough ◽

Experimental Models ◽

Adaptive Immune Responses ◽

Content Type ◽

Antigenic Composition ◽

Cell Responses ◽

Adaptive Immune ◽

Antibody Levels ◽

Stimulation Of

ABSTRACTThe resurgence of pertussis (whooping cough) in countries with high vaccination coverage is alarming and invites reconsideration of the use of current acellular pertussis (aP) vaccines, which have largely replaced the old, reactogenic, whole-cell pertussis (wP) vaccine. Some drawbacks of these vaccines in terms of limited antigenic composition and early waning of antibody levels could be anticipated by the results of in-trial or postlicensure human investigations of B- and T-cell responses in aP versus wP vaccine recipients or unvaccinated, infected children. Recent data in experimental models, including primates, suggest that generation of vaccines capable of a potent, though regulated, stimulation of innate immunity driving effective, persistent adaptive immune responses againstBordetella pertussisinfection should be privileged. Adjuvants that skew Th1/Th17 responses or new wP (detoxified or attenuated) vaccines should be explored. Nonetheless, the high merits of the current aP vaccines in persuading people to resume vaccination against pertussis should not be forgotten.

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Wound healing activity of Conyza canadensis (L.) Cronquist

Science and Technology Development Journal - Natural Sciences ◽

10.32508/stdjns.v1it5.533 ◽

2018 ◽

Vol 1 (T5) ◽

pp. 35-40

Author(s):

To Dinh Le ◽

Nga Thi Hoang ◽

Nhan Thi Thanh Nguyen ◽

Thuoc Linh Tran ◽

Thao Thi Phuong Dang

Keyword(s):

Wound Healing ◽

Antibacterial Activity ◽

Ethyl Acetate ◽

National Park ◽

Ethanolic Extract ◽

Ethyl Acetate Fraction ◽

Conyza Canadensis ◽

Keratinocyte Proliferation ◽

Wound Healing Activity ◽

Stimulation Of

Conyza canadensis (L.) Cronquist (CCL) has been used by K’Ho minority in Bidoup Nui Ba national park, Lam Dong province, Vietnam as one of wound healing remedies. However, the scientific proof of treatment is still unclear. This study aimed to evaluate this wound healing potential of CCL. CCL power was extracted by ethanol and then partitioned consecutively with petroleum ether, ethyl acetate and water. Wound healing potential was evaluated by antibacterial activity, stimulation of fibroblast and keratinocyte proliferation. Agar-well diffusion was used in the antibacterial tests and the results showed that CCL had antibacterial activity against 02 dermatitis bacteria (Pseudomonas aeruginosa, Staphylococcus aureus) and 02 opportunistic infection bacteria (Escherichia coli, Enterococcus faecalis). Moreover, our results illustrated that CCL stimulated the fibroblast and keratinocyte proliferation compared to the control. Particularly, the fibroblast division increased 1.6 times at 31.25 µg/mL when treated by ethanolic extract, while ethyl acetate fraction showed 1.7 times increase at 10 µg/mL in keratinocyte proliferation compared to the control. Taken together, our study contributed scientific base of CCL in the wound healing.

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pH regulation and response to AVP in A10 cells differ markedly in the presence vs. absence of CO2-HCO3-

AJP Cell Physiology ◽

10.1152/ajpcell.1990.259.3.c471 ◽

1990 ◽

Vol 259 (3) ◽

pp. C471-C483 ◽

Cited By ~ 23

Author(s):

D. Kikeri ◽

M. L. Zeidel ◽

B. J. Ballermann ◽

B. M. Brenner ◽

S. C. Hebert

Keyword(s):

Steady State ◽

Ph Regulation ◽

Disulfonic Acid ◽

Potential Contribution ◽

Vasoactive Agents ◽

Cell Responses ◽

Extrusion Mechanism ◽

Acid Extrusion ◽

Ambient Co2 ◽

Stimulation Of

The fluorescent pH-sensitive dye 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) was used to determine the effect of ambient CO2-HCO3- on the regulation of intracellular pH (pHi) and the pHi response to arginine vasopressin (AVP) in A10 vascular smooth muscle (VSM) cells. Steady-state pHi averaged 7.04 +/- 0.02 in the absence and 7.25 +/- 0.01 in the presence of CO2-HCO3-. In the absence of CO2-HCO3-, virtually all (greater than 96%) of the acid extrusion from acidification occurred by amiloride-sensitive Na(+)-H+ exchange. However, in the presence of CO2-HCO3-, acid extrusion after acidification occurred by both Na(+)-H+ exchange and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-sensitive Na(+)-dependent Cl(-)-HCO3- exchange. In CO2-HCO3(-)-containing media, amiloride-sensitive Na(+)-H+ exchange mediated 85% of acid extrusion at a pHi of 6.48, but the DIDS-sensitive acid extrusion mechanism (NA(+)-dependent Cl(-)-HCO3- exchange) was the dominant acid extrusion mechanism at a pHi of 6.94. Base exited A10 cells by a DIDS-sensitive process consistent with Na(+)-independent Cl(-)-HCO3- exchange. Both amiloride- and DIDS-sensitive processes regulated steady-state pHi in CO2-HCO3-. AVP (10(-7) M) alkalinized steady-state pHi in the absence of CO2-HCO3- (delta pHi = 0.08 +/- 0.01 pH units) by stimulating Na(+)-H+ exchange; however, AVP did not alter pHi of untreated cells in CO2-HCO3- (delta pHi = -0.01 +/- 0.01 pH units) because of concomitant stimulation of Na(+)-independent Cl(-)-HCO3-exchange. We conclude that the steady-state pHi, the mechanisms of pHi regulation, and the pHi response to AVP in A10 cells are critically influenced by the presence of extracellular CO2-HCO3-. Thus the potential contribution of pHi changes to VSM cell responses to vasoactive agents should be evaluated in the presence of CO2-HCO3-.

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Virus-Based Immunotherapy of Glioblastoma

Cancers ◽

10.3390/cancers11020186 ◽

2019 ◽

Vol 11 (2) ◽

pp. 186 ◽

Cited By ~ 32

Author(s):

Miika Martikainen ◽

Magnus Essand

Keyword(s):

Immune Responses ◽

Oncolytic Virus ◽

Early Stage ◽

Primary Brain Tumor ◽

Oncolytic Viruses ◽

Preclinical Models ◽

Adjuvant Effect ◽

Cell Responses ◽

Near Future ◽

Stimulation Of

Glioblastoma (GBM) is the most common type of primary brain tumor in adults. Despite recent advances in cancer therapy, including the breakthrough of immunotherapy, the prognosis of GBM patients remains dismal. One of the new promising ways to therapeutically tackle the immunosuppressive GBM microenvironment is the use of engineered viruses that kill tumor cells via direct oncolysis and via stimulation of antitumor immune responses. In this review, we focus on recently published results of phase I/II clinical trials with different oncolytic viruses and the new interesting findings in preclinical models. From syngeneic preclinical GBM models, it seems evident that oncolytic virus-mediated destruction of GBM tissue coupled with strong adjuvant effect, provided by the robust stimulation of innate antiviral immune responses and adaptive anti-tumor T cell responses, can be harnessed as potent immunotherapy against GBM. Although clinical testing of oncolytic viruses against GBM is at an early stage, the promising results from these trials give hope for the effective treatment of GBM in the near future.

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