IL-21 enhances influenza vaccine responses in aged macaques with suppressed SIV infection.

Natural aging and HIV infection are associated with chronic low-grade systemic inflammation, immune senescence, and impaired antibody responses to vaccines such as the influenza (flu) vaccine. We investigated the role of IL-21, a CD4+ T follicular helper cell (Tfh) regulator, on flu vaccine antibody response in nonhuman primates (NHPs) in the context of age and controlled SIV mac239 infection. Three doses of the flu vaccine with or without IL-21-IgFc were administered at 3-month intervals in aged SIV+ NHPs following virus suppression with antiretroviral therapy. IL-21-treated animals demonstrated higher day 14-postboost antibody responses, which associated with expanded CD4+ T central memory cells and peripheral Tfh-expressing (pTfh-expressing) T cell immunoreceptor with Ig and ITIM domains (TIGIT), expanded activated memory B cells, and contracted CD11b+ monocytes. Draining lymph node (LN) tissue from IL-21-treated animals revealed direct association between LN follicle Tfh density and frequency of circulating TIGIT+ pTfh cells. We conclude that IL-21 enhances flu vaccine-induced antibody responses in SIV+ aged rhesus macaques (RMs), acting as an adjuvant modulating LN germinal center activity. A strategy to supplement IL-21 in aging could be a valuable addition in the toolbox for improving vaccine responses in an aging HIV+ population

3-D Nanofibrous Electrospun Multilayered Construct is an Alternative ECM Mimicking Scaffold

Abstract Extra cellular matrix (ECM) is a natural cell environment, possesses complicated nano-and macroarchitecture. Mimicking this three-dimensional (3-D) web is a challenge in the modern tissue engineering. This study examined the application of a novel 3-D construct, produced by multilayered organization of electrospun nanofiber membranes, for human bone marrow-derived mesenchymal stem cells (hMSCs) support. The hMSCs were seeded on an electrospun scaffold composed of poly e-caproloactone (PCL) and collagen (COL) (1:1), and cultured in a dynamic flow bioreactor prior to in vivo implantation. Cell viability after seeding was analyzed by AlamarBlue TM Assay. At the various stages of experiment, cell morphology was examined by histology, scanning electron microscopy (SEM) and confocal microscopy

Effect of Quinoa Seeds (Chenopodium quinoa) in Diet on some Biochemical Parameters and Essential Elements in Blood of High Fructose-Fed Rats

The effect of Chenopodium quinoa seeds on lipid profile, glucose level, protein metabolism and selected essential elements (Na, K, Ca, Mg) level was determined in high—fructose fed male Wistar rats. Fructose decreased significantly LDL [42%, p < 0.01] and activity of alkaline phosphatase [20%, p < 0.05], and increased triglycerides level [86%, p < 0.01]. The analysis of blood of rats fed quinoa indicated, that these seeds effectively reduced serum total cholesterol [26%, p < 0.05], LDL [57%, p < 0.008] and triglycerides [11%, p < 0.05] when compared to the control group. Quinoa seeds also significantly reduced the level of glucose [10%, p < 0.01] and plasma total protein level [16%, p < 0.001]. Fructose significantly decreased HDL [15%, p < 0.05] level in control group but when the quinoa seeds were added into the diet the decrease of HDL level was inhibited. Quinoa seeds did not prevent any adverse effect of increasing triglyceride level caused by fructose. It was shown in this study that quinoa seeds can reduce most of the adverse effects exerted by fructose on lipid profile and glucose level

Opioids exacerbate inflammation in people with well-controlled HIV

IntroductionPeople with HIV (PWH) are known to have underlying inflammation and immune activation despite virologic control. Substance use including opioid dependence is common in this population and is associated with increased morbidity and reduced lifespan. The primary objective of the present study termed opioid immunity study (OPIS), was to investigate the impact of chronic opioids in PWH.MethodsThe study recruited people with and without HIV who had opioid use disorder (OUD). Study participants (n=221) were categorized into four groups: HIV+OP+, n=34; HIV-OP+, n=66; HIV+OP-, n=55 and HIV-OP-, n=62 as controls. PWH were virally suppressed on ART and those with OUD were followed in a syringe exchange program with confirmation of OP use by urine drug screening. A composite cytokine score was developed for 20 plasma cytokines that are linked to inflammation. Cellular markers of immune activation (IA), exhaustion, and senescence were determined in CD4 and CD8 T cells. Regression models were constructed to examine the relationships of HIV status and opioid use, controlling for other confounding factors.ResultsHIV+OP+ participants exhibited highest inflammatory cytokines and cellular IA, followed by HIV-OP+ for inflammation and HIV+OP- for IA. Inflammation was found to be driven more by opioid use than HIV positivity while IA was driven more by HIV than opioid use. In people with OUD, expression of CD38 on CD28-CD57+ senescent-like T cells was elevated and correlated positively with inflammation.DiscussionGiven the association of inflammation with a multitude of adverse health outcomes, our findings merit further investigations to understand the mechanistic pathways involved

The Schneiderian membrane contains osteoprogenitor cells: in vivo and in vitro study

Recent studies successfully demonstrated induction of new bone formation in the maxillary sinus by mucosal membrane lifting without the use of any graft material. The aim of this work was to test the osteogenic potential of human maxillary sinus Schneiderian membrane (hMSSM) using both in vitro and in vivo assays. Samples of hMSSM were used for establishment of cell cultures and for histological studies. Flow cytometry analysis was performed on P(0), P(1), and P(2) cultures using established mesenchymal progenitor cell markers (CD 105, CD 146, CD 71, CD 73, CD 166), and the ability of hMSSM cells to undergo osteogenic differentiation in culture was analyzed using relevant in vitro assays. Results showed that hMSSM cells could be induced to express alkaline phosphatase, bone morphogenic protein-2, osteopontin, osteonectin, and osteocalcin and to mineralize their extracellular matrix. Inherent osteogenic potential of hMSSM-derived cells was further proven by in vivo experiments, which demonstrated the formation of histology-proven bone at ectopic sites following transplantation of hMSSM-derived cells in conjunction with an osteoconductive scaffold. This study provides the biological background for understanding the observed clinical phenomena in sinus lifting. Our results show that a genuine osteogenic potential is associated with the hMSSM and can contribute to development of successful sinus augmentation techniques

IL-21-IgFc immunotherapy alters transcriptional landscape of lymph node cells leading to enhanced flu vaccine response in aging and SIV infection.

Aging people living with HIV (PWH) frequently manifest impaired antibody (Ab) responses to seasonal flu vaccination which has been attributed to ongoing inflammation and immune activation. We have recently reported a similar scenario in old simian immunodeficiency virus (SIV) infected rhesus macaques (RM) with controlled viremia and have been able to compensate for this deficiency by immunotherapy with interleukin (IL)-21-IgFc. To understand the underlying mechanisms of IL-21-induced immunomodulation leading to enhanced flu vaccine response in aging and SIV, we have investigated draining lymph node (LN) cells of IL-21-treated and -untreated animals at postvaccination. We observed IL-21-induced proliferation of flu-specific LN memory CD4 T cells, expansion of B cells expressing IL-21 receptor (IL-21R), and modest expansion of T follicular helper cells (Tfh) co-expressing T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and DNAX accessory molecule (DNAM-1). Transcriptional analysis of LN cells of IL-21-treated animals revealed significant inhibition of germinal center (GC) Tfh and B-cell interferon signaling pathways along with enhanced B-cell development and antigen presentation pathways. We conclude that IL-21 treatment at the time of flu vaccination in aging SIV-infected animals modulates the inductive LN GC activity, to reverse SIV-associated LN Tfh and B-cell dysfunction. IL-21 is a potential candidate molecule for immunotherapy to enhance flu vaccine responses in aging PWH who have deficient antibody responses