scholarly journals Hearing loss in Alzheimer Disease is associated with altered serum lipidomic biomarker profiles

2020 ◽  
Author(s):  
Daniel A. Llano ◽  
Lina K. Issa ◽  
Priya Devanarayan ◽  
Viswanath Devanarayan ◽  
Keyword(s):  
Hearing Loss ◽  
Alzheimer Disease ◽  
Antioxidant Properties ◽  
Normal Subjects ◽  
Serum Levels ◽  
Pathological State ◽  
Inverse Association ◽  
Strong Inverse Association ◽  
Potential Factors ◽  
Metabolic Biomarkers

AbstractRecent data have found that aging-related hearing loss (ARHL) is associated with the development of Alzheimer Disease (AD). However, the nature of the relationship between these two disorders is not clear. There are multiple potential factors that link ARHL and AD, and previous investigators have speculated that shared metabolic dysregulation may underlie the propensity to develop both disorders. Here, we investigate the distribution of serum lipidomic biomarkers in AD subjects with or without hearing loss in a publicly available dataset. Serum levels of 349 known lipids from 16 lipid classes were measured in 185 AD patients. Using previously defined co-regulated sets of lipids, both age- and sex-adjusted, we found that lipid sets enriched in phosphatidylcholine and phosphatidylethanolamine showed a strong inverse association with hearing loss. Examination of biochemical classes confirmed these relationships and revealed that serum phosphatidylcholine levels were significantly lower in AD subjects with hearing loss. A similar relationship was not found in normal subjects. These data suggest that a synergistic relationship may exist between AD, hearing loss and metabolic biomarkers, such that in the context of a pathological state such as AD, alterations in serum metabolic profiles are associated with hearing loss. These data also point to a potential role for phosphatidylcholine, a molecule with antioxidant properties, in the underlying pathophysiology of ARHL in the context of AD, which has implications for our understanding and potential treatment of both disorders.

scholarly journals Hearing Loss in Alzheimer’s Disease Is Associated with Altered Serum Lipidomic Biomarker Profiles

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2556
Author(s):  
Daniel Llano ◽  
Lina Issa ◽  
Priya Devanarayan ◽  
Viswanath Devanarayan ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hearing Loss ◽  
Antioxidant Properties ◽  
Normal Subjects ◽  
Serum Levels ◽  
Pathological State ◽  
Inverse Association ◽  
Strong Inverse Association ◽  
Potential Factors

Recent data have found that aging-related hearing loss (ARHL) is associated with the development of Alzheimer’s Disease (AD). However, the nature of the relationship between these two disorders is not clear. There are multiple potential factors that link ARHL and AD, and previous investigators have speculated that shared metabolic dysregulation may underlie the propensity to develop both disorders. Here, we investigate the distribution of serum lipidomic biomarkers in AD subjects with or without hearing loss in a publicly available dataset. Serum levels of 349 known lipids from 16 lipid classes were measured in 185 AD patients. Using previously defined co-regulated sets of lipids, both age- and sex-adjusted, we found that lipid sets enriched in phosphatidylcholine and phosphatidylethanolamine showed a strong inverse association with hearing loss. Examination of biochemical classes confirmed these relationships and revealed that serum phosphatidylcholine levels were significantly lower in AD subjects with hearing loss. A similar relationship was not found in normal subjects. These data suggest that a synergistic relationship may exist between AD, hearing loss and metabolic biomarkers, such that in the context of a pathological state such as AD, alterations in serum metabolic profiles are associated with hearing loss. These data also point to a potential role for phosphatidylcholine, a molecule with antioxidant properties, in the underlying pathophysiology of ARHL in the context of AD, which has implications for our understanding and potential treatment of both disorders.

scholarly journals Reported Hearing Loss in Alzheimer’s Disease Is Associated With Loss of Brainstem and Cerebellar Volume

2021 ◽  
Vol 15 ◽  
Author(s):  
Daniel A. Llano ◽  
Susanna S. Kwok ◽  
Viswanath Devanarayan ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hearing Loss ◽  
Normal Subjects ◽  
Neural Substrates ◽  
Epidemiological Studies ◽  
Brain Regions ◽  
Pathological State ◽  
Brain Volumes ◽  
The Relationship

Multiple epidemiological studies have revealed an association between presbycusis and Alzheimer’s Disease (AD). Unfortunately, the neurobiological underpinnings of this relationship are not clear. It is possible that the two disorders share a common, as yet unidentified, risk factor, or that hearing loss may independently accelerate AD pathology. Here, we examined the relationship between reported hearing loss and brain volumes in normal, mild cognitive impairment (MCI) and AD subjects using a publicly available database. We found that among subjects with AD, individuals that reported hearing loss had smaller brainstem and cerebellar volumes in both hemispheres than individuals without hearing loss. In addition, we found that these brain volumes diminish in size more rapidly among normal subjects with reported hearing loss and that there was a significant interaction between cognitive diagnosis and the relationship between reported hearing loss and these brain volumes. These data suggest that hearing loss is linked to brainstem and cerebellar pathology, but only in the context of the pathological state of AD. We hypothesize that the presence of AD-related pathology in both the brainstem and cerebellum creates vulnerabilities in these brain regions to auditory deafferentation-related atrophy. These data have implications for our understanding of the potential neural substrates for interactions between hearing loss and AD.

Is Brain-Derived Neurotrophic Factor: A Common Link Between Neurodegenerative Disorders and Cancer?

2019 ◽  
Vol 16 (4) ◽  
pp. 344-352
Author(s):  
Radhika Khosla ◽  
Avijit Banik ◽  
Sushant Kaushal ◽  
Priya Battu ◽  
Deepti Gupta ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurotrophic Factor ◽  
Animal Studies ◽  
Neurodegenerative Disorder ◽  
Indirect Evidence ◽  
Brain Derived Neurotrophic Factor ◽  
Common Disease ◽  
Inverse Association ◽  
Bdnf Expression ◽  
Strong Inverse Association

Background: Cancer is a common disease caused by the excessive proliferation of cells, and neurodegenerative diseases are the disorders caused due to the degeneration of neurons. Both can be considered as diseases caused by the dysregulation of cell cycle events. A recent data suggests that there is a strong inverse association between cancer and neurodegenerative disorders. There is indirect evidence to postulate Brain-derived Neurotrophic Factor (BDNF) as a potential molecular link in this association. Discussion: The BDNF levels are found to be downregulated in many neurodegenerative disorders and are found to be upregulated in various kinds of cancers. The lower level of BDNF in Alzheimer’s and Parkinson’s disease has been found to be related to cognitive and other neuropsychological impairments, whereas, its higher levels are associated with the tumour growth and metastasis and poor survival rate in the cancer patients. Conclusion: In this review, we propose that variance in BDNF levels is critical in determining the course of cellular pathophysiology and the development of cancer or neurodegenerative disorder. We further propose that an alternative therapeutic strategy that can modulate BDNF expression, can rescue or prevent above said pathophysiological course. Larger studies that examine this link through animal studies are imperative to understand the putative biochemical and molecular link to wellness and disease.

scholarly journals IGF-1 Haploinsufficiency Causes Age-Related Chronic Cochlear Inflammation and Increases Noise-Induced Hearing Loss

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1686
Author(s):  
Adelaida M. Celaya ◽  
Lourdes Rodríguez-de la Rosa ◽  
Jose M. Bermúdez-Muñoz ◽  
José M. Zubeldia ◽  
Carlos Romá-Mateo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inflammatory Cytokines ◽  
Noise Exposure ◽  
Sensorineural Deafness ◽  
Serum Levels ◽  
Genetic Syndromes ◽  
Expression Ratio ◽  
Postnatal Maturation ◽  
Age Related ◽  
Underlying Mechanisms

Insulin-like growth factor 1 (IGF-1) deficiency is an ultrarare syndromic human sensorineural deafness. Accordingly, IGF-1 is essential for the postnatal maturation of the cochlea and the correct wiring of hearing in mice. Less severe decreases in human IGF-1 levels have been associated with other hearing loss rare genetic syndromes, as well as with age-related hearing loss (ARHL). However, the underlying mechanisms linking IGF-1 haploinsufficiency with auditory pathology and ARHL have not been studied. Igf1-heterozygous mice express less Igf1 transcription and have 40% lower IGF-1 serum levels than wild-type mice. Along with ageing, IGF-1 levels decreased concomitantly with the increased expression of inflammatory cytokines, Tgfb1 and Il1b, but there was no associated hearing loss. However, noise exposure of these mice caused increased injury to sensory hair cells and irreversible hearing loss. Concomitantly, there was a significant alteration in the expression ratio of pro- and anti-inflammatory cytokines in Igf1+/− mice. Unbalanced inflammation led to the activation of the stress kinase JNK and the failure to activate AKT. Our data show that IGF-1 haploinsufficiency causes a chronic subclinical proinflammatory age-associated state and, consequently, greater susceptibility to stressors. This work provides the molecular bases to further understand hearing disorders linked to IGF-1 deficiency.

scholarly journals Dietary Factors and Prevention: Risk of End-Stage Kidney Disease by Fruit and Vegetable Consumption

2021 ◽  
pp. 1-12
Author(s):  
Tanushree Banerjee ◽  
Juan Jesus Carrero ◽  
Charles McCulloch ◽  
Nilka Rios Burrows ◽  
Karen R. Siegel ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Risk Model ◽  
Vegetable Consumption ◽  
Dietary Factors ◽  
Inverse Association ◽  
Fruit And Vegetable ◽  
End Stage Kidney Disease ◽  
Strong Inverse Association ◽  
End Stage

<b><i>Background:</i></b> The association between fruit and vegetable (FV) intake and the risk of end-stage kidney disease (ESKD) has not been examined in the general population and fully explored in chronic kidney disease (CKD). We prospectively evaluated this relationship in US representative sample of adults and evaluated consistency by the presence or absence, and severity, of CKD. <b><i>Methods:</i></b> We used data from the Third National Health and Nutrition Examination Survey (1988–1994) linked with the US Renal Data System, including 14,725 adults aged ≥20 years and with follow-up for ESKD through 2008. Daily FV intake was ascertained using a food frequency questionnaire. We examined the association between selected categories of FV intake and ESKD using a Fine Gray competing risk model adjusting for sociodemographics, lifestyle, clinical and nutritional factors, estimated glomerular filtration rate, and albuminuria. We evaluated whether risk varied in individuals with severe versus any CKD. <b><i>Results:</i></b> 230 participants (1.5%) developed ESKD during follow-up. In the adjusted model, compared to highest intake, those in lowest categories of FV intake had a higher risk of ESKD, for &#x3c;2 times/day (1.45 [1.24–1.68], 2 to &#x3c;3 times/day (1.40 [1.18–1.61]), 3 to &#x3c;4 times/day (1.25 [1.04–1.46]), and 4 to &#x3c;6 times/day (1.14 [0.97–1.31]). There was suggestion of heterogeneity (<i>p</i> for interaction = 0.03) with possible stronger inverse association in patients with CKD than those without CKD. After stratification, we obtained similar strong inverse association when we examined ESKD incidence across intake of FVs in participants with CKD stages 1–4 (<i>n</i> = 5,346) and specifically in those with CKD stages 3–4 (<i>n</i> = 1,084). <b><i>Conclusions:</i></b> Low intake of FVs was associated with higher risk of ESKD in US adults with and without CKD, supporting an emerging body of literature on the potential benefits of plant-rich diets for prevention of ESKD.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

Relationship between Serum Tryptophan and Tryptophan Metabolite Levels after Tryptophan Ingestion in Normal Subjects and Age-Related Cataract Patients

1995 ◽  
Vol 89 (6) ◽  
pp. 591-599 ◽  
Author(s):  
Roger J. W. Truscott ◽  
Anthony J. Elderfield
Keyword(s):  
Anthranilic Acid ◽  
Kynurenic Acid ◽  
Normal Subjects ◽  
Serum Levels ◽  
Xanthurenic Acid ◽  
Control Subjects ◽  
Age Related ◽  
Hydroxyanthranilic Acid ◽  
And Control ◽  
Cataract Patients

1. Cataract is the single major cause of blindness worldwide; however, the reasons for the development of this condition remain unknown. It has been suggested that the essential amino acid tryptophan may be implicated in the aetiology but definitive evidence has been lacking. 2. The serum levels of tryptophan and seven of its metabolites have been measured in both cataract patients and control subjects, after administration of tryptophan, in order to determine the typical response profile and to discover whether differences could be found in tryptophan metabolism in the two groups. 3. Tryptophan, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, 5-hydroxyanthranilic acid, 5-hydroxytryptophan and anthranilic acid were measured by HPLC with dual electrochemical and programmable wavelength fluorescence detection. Fasting cataract patients (n = 42) and control subjects (n = 37) were given an oral dose of l-tryptophan and sera were sampled at 0, 1, 2, 4 and 6 h. 4. Statistically significant differences in the distribution of data between the two groups were observed. The responses of kynurenine and 5-hydroxyanthranilic acid were higher in cataract patients, but those of kynurenic acid and total tryptophan were lower than in control subjects. No statistically significant differences in free tryptophan, anthranilic acid, 3-hydroxyanthranilic acid, xanthurenic acid or 5-hydroxytryptophan levels were noted. 5. We conclude that there is a major subgroup of age-related cataract patients with a dysfunction in the metabolism of tryptophan. This may be related to the onset of cataract. The mechanism remains to be established but may operate via the action of tryptophan metabolites, such as 5-hydroxyanthranilic acid, which become reactive towards protein upon oxidation.

Serum LH and FSH Responses to Synthetic LH-RH in Normal Infants, Children and Patients With Turner's Syndrome

PEDIATRICS ◽  
1974 ◽  
Vol 54 (4) ◽  
pp. 470-475
Author(s):  
Selzo Suwa ◽  
Hatae Maesaka ◽  
Ichiro Matsui
Keyword(s):  
Normal Subjects ◽  
Serum Levels ◽  
Young Female ◽  
Normal Female ◽  
Turner's Syndrome ◽  
Turner’S Syndrome ◽  
Normal Children ◽  
Serum Lh ◽  
Female Children ◽  
Lh Rh

Effects of LH-RH on LH and FSH release were studied in 26 normal children and six patients with Turner's syndrome (two of them showed 45 x karyotype and the others were mosaics). Synthetic LH-RH (2µg/kg of body weight) was given intramuscularly after an overnight fast. The increase of serum FSH level was significantly greater in normal female infants than male infants. A similar tendency was observed in normal female children aged 2 to 9 years. No sex difference was observed in the LH response to LH-RH in all the normal subjects Studied. The response of FSH release to LH-RH was significantly greater than that of LH in female infants and young female children. The responsiveness of LH to LH-RH gradually increased with advancing age. Basal serum levels of FSH rather than LH were high in the patients with Turner's syndrome. Again a much greater increase of serum FSH than of LH was noted after the administration of LH-RH to patients with Turner's syndrome.

Abstract P137: Association Of Equol Producing Capacity With Aortic Calcification In Middle-aged Japanese Men

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Xiao Zhang ◽  
Akira Fujiyoshi ◽  
Aya Kadota ◽  
Vasudha Ahuja ◽  
Abhishek Vishnu ◽  
...  
Keyword(s):  
Serum Levels ◽  
Population Based ◽  
Aortic Calcification ◽  
Inverse Association ◽  
Middle Aged ◽  
Cross Sectional ◽  
Japanese Men ◽  
The Us ◽  
Multivariable Analyses ◽  
20 Nm

Background: Soy isoflavones (ISFs) are regularly consumed in Japan and other Asian countries where some studies showed a significant inverse association of ISFs intake with incident coronary heart disease (CHD). However, a US randomized clinical trial did not find ISFs as anti-atherogenic. This discrepancy may be due to the higher capacity of people in Japan than in the US to produce equol, a metabolite of ISF by the gut microbiome. Equol may have greater anti-atherogenic properties than ISFs. It is unknown whether equol producers (EP), people who produce equol after consuming ISF, have lower aortic calcification (AC), a biomarker of atherosclerosis, as compared to non-EP. Aim: To determine the association between equol producing status and AC in Japanese men. Method: This cross-sectional, population-based study included 302 Japanese men aged 40-49, free of CHD. EP was defined as participants with serum levels of equol ≥20 nM. AC was measured in the entire aorta and quantified by the Agatston method. The presence of AC was defined as AC score ≥10. We analyzed the association between equol producing status and AC using the Tobit and the logistic regressions. Result: We observed 125 participants as EP. In multivariable analyses, EP had non-significantly lower AC score by 147 (95% confidence interval (CI): -386, 92) units and an odds ratio of 0.71 (95% CI: 0.40, 1.26) for the AC presence as compared to non-EP. As significant interaction of equol producing status with age was present, we stratified the analyses by the median age. In men aged 45-49 years, EP had non-significantly lower AC score by 246 units and a non-significant 0.62 times the odds of AC presence as compared to non-EP; the corresponding values in men aged 40-44 were 12 units and 0.91 times (Table). Such an association was not observed with serum ISFs (data not shown). Conclusion: Japanese middle-aged men who were EP had non-significantly lower AC than non-EP and such association was stronger in men aged 45-49 than 40-44 years. Further study with much larger sample size is warranted.

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