Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. ...However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel.
Gene expression databases were searched (http://genomics.senescence.info/genes including GenAge, AnAge, LongevityMap, CellAge, DrugAge, Digital Aging Atlas) to identify genes regulated in aging, longevity, and age-related diseases with a focus on secreted factors or molecules detectable in body fluids as potential frailty biomarkers. Factors broadly expressed, related to several "hallmark of aging" pathways as well as used or predicted as biomarkers in other disease settings, particularly age-related pathologies, were identified. This set of biomarkers was further expanded according to the expertise and experience of the authors. In the next step, biomarkers were assigned to six "hallmark of aging" pathways, namely (1) inflammation, (2) mitochondria and apoptosis, (3) calcium homeostasis, (4) fibrosis, (5) NMJ (neuromuscular junction) and neurons, (6) cytoskeleton and hormones, or (7) other principles and an extensive literature search was performed for each candidate to explore their potential and priority as frailty biomarkers.
A total of 44 markers were evaluated in the seven categories listed above, and 19 were awarded a high priority score, 22 identified as medium priority and three were low priority. In each category high and medium priority markers were identified.
Biomarker panels for frailty would be of high value and better than single markers. Based on our search we would propose a core panel of frailty biomarkers consisting of (1) CXCL10 (C-X-C motif chemokine ligand 10), IL-6 (interleukin 6), CX3CL1 (C-X3-C motif chemokine ligand 1), (2) GDF15 (growth differentiation factor 15), FNDC5 (fibronectin type III domain containing 5), vimentin (VIM), (3) regucalcin (RGN/SMP30), calreticulin, (4) PLAU (plasminogen activator, urokinase), AGT (angiotensinogen), (5) BDNF (brain derived neurotrophic factor), progranulin (PGRN), (6) α-klotho (KL), FGF23 (fibroblast growth factor 23), FGF21, leptin (LEP), (7) miRNA (micro Ribonucleic acid) panel (to be further defined), AHCY (adenosylhomocysteinase) and KRT18 (keratin 18). An expanded panel would also include (1) pentraxin (PTX3), sVCAM/ICAM (soluble vascular cell adhesion molecule 1/Intercellular adhesion molecule 1), defensin α, (2) APP (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) S100B (S100 calcium binding protein B), (4) TGFβ (transforming growth factor beta), PAI-1 (plasminogen activator inhibitor 1), TGM2 (transglutaminase 2), (5) sRAGE (soluble receptor for advanced glycosylation end products), HMGB1 (high mobility group box 1), C3/C1Q (complement factor 3/1Q), ST2 (Interleukin 1 receptor like 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (RETN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and frail cohorts in order to ascertain their diagnostic, prognostic and therapeutic potential.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Vascular aging, characterized by structural and functional alterations of the vascular wall, is a hallmark of aging and is tightly related to the development of cardiovascular mortality and ...age-associated vascular pathologies. Over the last years, extensive and ongoing research has highlighted several sophisticated molecular mechanisms that are involved in the pathophysiology of vascular aging. A more thorough understanding of these mechanisms could help to provide a new insight into the complex biology of this non-reversible vascular process and direct future interventions to improve longevity. In this review, we discuss the role of the most important molecular pathways involved in vascular ageing including oxidative stress, vascular inflammation, extracellular matrix metalloproteinases activity, epigenetic regulation, telomere shortening, senescence and autophagy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Schools must cooperate with parents to be effective. "Families are critical to children's educational success" as Sheldon (2018, vii), declared. The history of cooperation with parents is quite old. ...One effective way of cooperating with parents is home visits. The impacts of home visits on school-parent cooperation and student outcomes have been revealed in the researches. Since home visits are mostly an out-of-school activity, they are made with the dedication and personal efforts of the teachers. This study aims at revealing the opinions of teachers and principals about home visiting practices in Turkish primary and secondary schools. This is a qualitative research. The study group consists of 12 secondary schools and 10 primary schools in Sivas city center. So, the questionnaires developed by the researchers were distributed to the determined schools. The survey forms were distributed to volunteer teachers and principals. 102 survey forms from teachers and 41 principals were evaluated in accordance with the research purpose. The data obtained from the research were analyzed by content analysis method. The results show that both principals and teachers believe the positive effects of home visits and they find home visits necessary to build an effective school environment. However, they have some reservations of home visit practices.
It is well recognized that obesity increases the risk of various cancers, including breast malignancies in postmenopausal women. Furthermore, obesity may adversely affect tumor progression, ...metastasis, and overall prognosis in both pre- and postmenopausal women with breast cancer. However, the precise mechanism(s) through which obesity acts is/are still elusive and this relationship has been the subject of much investigation and speculation. Recently, adipose tissue and its associated cytokine-like proteins, adipokines, particularly leptin and adiponectin, have been investigated as mediators for the association of obesity with breast cancer. Higher circulating levels of leptin found in obese subjects could be a growth-enhancing factor as supported by
in vitro
and preclinical studies, whereas low adiponectin levels in obese women may be permissive for leptin’s growth-promoting effects. These speculations are supported by
in vitro
studies which indicate that leptin promotes human breast cancer cell proliferation while adiponectin exhibits anti-proliferative actions. Further, estrogen and its receptors have a definite impact on the response of human breast cancer cell lines to leptin and adiponectin. More in-depth studies are needed to provide additional and precise links between the
in vivo
development of breast cancer and the balance of adiponectin and leptin.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Inner ear involvement (IED) is a rare local complication of the very common acute otitis media (AOM). The most beneficial treatment for IED remains a matter of debate. The aim of this study is to ...analyze different treatment modalities based on hearing outcomes to contribute to the discussion of therapy for IED in AOM. This retrospective study includes 112 adult patients diagnosed with AOM with IED between 2000 and 2020. Patients either received conservative (systemic antibiotic and systemic steroid therapy), interventional (conservative plus myringotomy and tympanic tube) or operative (interventional plus antrotomy) treatment. Pre- and post-treatment pure tone audiometry was performed. The hearing outcome was compared, and hearing recovery was analyzed based on modified Siegel's criteria. The pre-treatment pure tone average (PTA) was significantly (
< 0.05) higher in the operative group than in the other groups. All treatment modalities led to a significant hearing improvement (
< 0.001). The pre- and post-treatment hearing loss was predominantly observed in high frequencies 2-4 kHz. The operative group showed the highest rate of complete hearing recovery. While all treatment modalities led to a significant improvement in hearing, the operative group showed the most beneficial hearing results in patients with high pre-treatment hearing loss. It remains to be shown if the findings in patients with high pre-treatment hearing loss can be generalized to patients with mild or moderate pre-treatment hearing loss.
Blood is a vital reservoir housing numerous disease-related metabolites and cellular components. Thus, it is also of interest for cancer diagnosis. Surface-enhanced Raman spectroscopy (SERS) is ...widely used for molecular detection due to its very high sensitivity and multiplexing properties. Its real potential for cancer diagnosis is not yet clear. In this study, using silver nanoparticles (AgNPs) as substrates, a number of experimental parameters and scenarios were tested to disclose the potential for this technique for cancer diagnosis. The discrimination of serum samples from cancer patients, healthy individuals and patients with chronic diseases was successfully demonstrated with over 90% diagnostic accuracies. Moreover, the SERS spectra of the blood serum samples obtained from cancer patients before and after tumor removal were compared. It was found that the spectral pattern for serum from cancer patients evolved into the spectral pattern observed with serum from healthy individuals after the removal of tumors. The data strongly suggests that the technique has a tremendous potential for cancer detection and screening bringing the possibility of early detection onto the table.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose/Background/Objectives
Tissue transglutaminase (TG2) is a highly expressed protein especially in endothelial cells. TG2 has several functions including transamidation activity which is ...important in several processes such as extracellular matrix remodeling
1
. TG2 activity takes place in aortic stiffness regulation and atherosclerotic plaque formation
2
. One of the most effective implementation for atheroprone state and general cardiovascular health is calorie restriction (CR). In addition, lipid accumulation and subsequent metabolic disorders can be regulated by CR and longer lifespan can be achieved
3
. In this study we aimed to determine the effect of different CR application types on liver TG2 levels of female mice fed up to 82 weeks old age.
Methods
For this purpose, female MMTV-TGF-
a
mice fed with different dietary regimes;
ad libitum
(AL), chronic CR (%15 restriction of AL group), intermittent CR (3 weeks AL (ICR-ReFeed)+1 week %60 restriction of AL (ICR-Restricted), between 10-week to 82-week old. Liver tissue was isolated at 10-week old (AL mice as baseline), 50 and 82 weeks. Then, liver tissue samples were homogenized for western blotting. Analysis made by ImageLab software and Glyceraldehyde-3-Phosphate Dehydrogenase used as housekeeping gene.
Results
TG2 levels were increased in CCR and ICR-R groups, decreased in ICR-RF compared to AL group. In addition, 82-week old AL mice had higher level of TG2 than 10-week old.
Conclusion
These results may provide future perspectives about TG2 levels depending on feeding protocols and ageing in kidney. TG2 levels in arteries of the same groups will be examined in further studies.
Point‐of‐care diagnosis is crucial to control the spreading of viral infections. Here, universal‐modifiable probe‐gated silica nanoparticles (SNPs) based lateral flow assay (LFA) is developed in the ...interest of the rapid and early detection of viral infections. The most superior advantage of the rapid assay is its utility in detecting various sides of the virus directly from the human swab samples and its adaptability to detect various types of viruses. For this purpose, a high concentration of fluorescein and rhodamine B as a reporting material was loaded into SNPs with excellent loading capacity and measured using standard curve, 4.19 μmol ⋅ g−1 and 1.23 μmol ⋅ g−1, respectively. As a model organism, severe acute respiratory syndrome coronavirus‐2 (CoV‐2) infections were selected by targeting its nonstructural (NSP9, NSP12) and envelope (E) genes as target sites of the virus. We showed that NSP12‐gated SNPs‐based LFA significantly outperformed detection of viral infection in 15 minutes from 0.73 pg ⋅ mL−1 synthetic viral solution and with a dilution of 1 : 103 of unprocessed human samples with an increasing test line intensity compared to steady state (n=12). Compared to the RT‐qPCR method, the sensitivity, specificity, and accuracy of NSP12‐gated SNPs were calculated as 100 %, 83 %, and 92 %, respectively. Finally, this modifiable nanoparticle system is a high‐performance sensing technique that could take advantage of upcoming point‐of‐care testing markets for viral infection detections.
Here, universal‐modifiable probe‐gated silica nanoparticles (SNPs) based lateral flow assay (LFA) is developed in the interest of the rapid and early detection of viral infections. The most superior advantage of the rapid assay is its utility in detecting various sides of the virus directly from the human swab samples and its adaptability to detect various types of viruses. The NSP12, NSP9, and E gene targets of CoV‐2 were used as detection targets.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Diagnostic biomarkers based on epigenetic changes such as DNA methylation are promising tools for early cancer diagnosis. However, there are significant difficulties in directly and specifically ...detecting methylated DNA regions. Here, we report an electrochemical sensing system based on magnetic nanoparticles that enable a quantitative and selective analysis of the methylated septin9 (mSEPT9) gene, which is considered a diagnostic marker in early stage colorectal cancer (CRC). Methylation levels of SEPT9 in CRC samples were successfully followed by the selective recognition ability of a related peptide nucleic acid (PNA) after hybridization with DNA fragments in human patients’ serums and plasma (n = 10). Moreover, this system was also adapted into a point-of-care (POC) device for a one-step detection platform. The detection of mSEPT9 demonstrated a limit of detection (LOD) value of 0.37% and interference-free measurement in the presence of branched-chain amino acid transaminase 1 (BCAT1) and SRY box transcription factor 21 antisense divergent transcript 1 (SOX21-AS1). The currently proposed functional platform has substantial prospects in translational applications of early CRC detection.
Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. ...Inflammatory cytokines alter calcium (Ca2+) signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3) and CD38-cyclic ADP-ribose (CD38/cADPR) are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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