- The role of hydrogen sulfide in the progression mechanisms of non-alcoholic steatohepatitis and chronic kidney disease. [Journal Article]
- WLWiad Lek 2018; 71(3 pt 1):474-478
- CONCLUSIONS: Conclusions: A significant increase in the synthesis of collagen and glycoproteins (fibronectin) in patients with NASH, which was observed on the background of obesity, was established, which is accompanied by an ineffective resorption of newly formed collagen due to inhibition of collagenolysis against activation of proteinase inhibitors (α2-MG).
- Disrupted reward and cognitive control networks contribute to anhedonia in depression. [Journal Article]
- JPJ Psychiatr Res 2018 May 12; 103:61-68
- Neuroimaging studies have identified that anhedonia, a core feature of major depressive disorder (MDD), is associated with dysfunction in reward and cognitive control processing. However, it is still...
Neuroimaging studies have identified that anhedonia, a core feature of major depressive disorder (MDD), is associated with dysfunction in reward and cognitive control processing. However, it is still not clear how the reward network (β-network) and the cognitive control network (δ-network) are linked to biased anhedonia in MDD patients. Sixty-eight MDD patients and 64 cognitively normal (CN) subjects underwent a resting-state functional magnetic resonance imaging scan. A 2*2 ANCOVA analysis was used to explore the differences in the nucleus accumbens-based, voxelwise functional connectivity (FC) between the groups. Then, the β- and δ-networks were constructed, and the FC intensities were compared within and between theβ- and δ-networks across all subjects. Multiple linear regression analyses were also employed to investigate the relationships between the neural features of the β- and δ-networks and anhedonia in MDD patients. Compared to the CN subjects, the MDD patients showed synergistic functional decoupling in both the β- and δ-networks, as well as decreased FC intensities in the intra- and inter- β- and δ-networks. In addition, the FC in both the β- and δ-networks was significantly correlated with anhedonia severity in the MDD patients. Importantly, the integrated neural features of the β- and δ-networks could more precisely predict anhedonic symptoms. These findings initially demonstrated that the imbalance between β- and δ-network activity successfully predicted anhedonia severity and suggested that the neural features of both the β- and δ-networks could represent a fundamental mechanism that underlies anhedonia in MDD patients.
- Beneficial and Paradoxical Roles of Selenium at Nutritional Levels of Intake in Healthspan and Longevity. [Review]
- FRFree Radic Biol Med 2018 May 18
- Accumulation of genome and macromolecule damage is a hallmark of aging, age-associated degeneration, and genome instability syndromes. Although processes of aging are irreversible, they can be modula...
Accumulation of genome and macromolecule damage is a hallmark of aging, age-associated degeneration, and genome instability syndromes. Although processes of aging are irreversible, they can be modulated by genome maintenance pathways and environmental factors such as diet. Selenium (Se) confers its physiological functions mainly through selenoproteins, but Se compounds and other proteins that incorporate Se nonspecifically also impact optimal health. Bruce Ames proposed that the aging process could be mitigated by a subset of low-hierarchy selenoproteins whose levels are preferentially reduced in response to Se deficiency. Consistent with this notion, results from two selenotranscriptomic studies collectively implicate three low-hierarchy selenoproteins in age or senescence. Experimental evidence generally supports beneficial roles of selenoproteins in the protection against damage accumulation and redox imbalance, but some selenoproteins have also been reported to unexpectedly display harmful functions under sporadic conditions. While longevity and healthspan are usually thought to be projected in parallel, emerging evidence suggests a trade-off between longevity promotion and healthspan deterioration with damage accumulation. We propose that longevity promotion under conditions of Se deficiency may be attributed to 1) stress-response hormesis, an advantageous event of resistance to toxic chemicals at low doses; 2) reduced expression of selenoproteins with paradoxical functions to a lesser extent. In particular, selenoprotein H is an evolutionally conserved nuclear selenoprotein postulated to confer Se functions in redox regulation, genome maintenance, and senescence. This review highlights the need to pinpoint roles of specific selenoproteins and Se compounds in healthspan and lifespan for a better understanding of Se contribution at nutritional levels of intake to healthy aging.
- A certain role of SOD/CAT imbalance in pathogenesis of autism spectrum disorders. [Journal Article]
- FRFree Radic Biol Med 2018 May 18
- The real impact of reactive oxygen species, antioxidant enzymes, mitochondrial dysfunction and chronic inflammation on the development of autism spectrum disorders (ASD) remains unclear, and even con...
The real impact of reactive oxygen species, antioxidant enzymes, mitochondrial dysfunction and chronic inflammation on the development of autism spectrum disorders (ASD) remains unclear, and even controversial. In this study we compared the plasma levels of antioxidant enzymes and their cofactors, markers of oxidative damage, and the respiratory burst in peripheral blood polymorphonuclear leukocytes (PMNL) as surrogate marker of chronic inflammation obtained from 10 children (4-10 year old) who met DSM-5 criteria and their siblings. We demonstrated diminished superoxide dismutase (SOD) and enhanced catalase (CAT) activities resulting in a markedly decreased SOD/CAT ratio and enhanced carbonyl content in the plasma of ASD patients. A strong correlation was present between SOD and CAT activities in the control group, which was not noted in ASD patients. Moreover, in autistic patients, we observed negative correlation between SOD activity on one side, and carbonyl content in plasma, 8-Hydroxy-2-deoxyguanosin content in urine, and respiratory burst intensity in PMNL on the other side. At the same time, low SOD level in autistic children was positively correlated with the magnesium content in the packed RBCs, which might indicate the involvement of the mitochondrial MnSOD in ASD pathogenesis, and therefore the consequent partaking of mitochondrial dysfunction in the development of ASD. Altogether, these results indicate that decreased antioxidant capacity and increased oxidative stress in ASD patients may have functional consequence in terms of increased superoxide leakage, oxidative protein damage, chronic inflammatory response, and, finally, neuronal cell abnormal functioning or death.
- 'He should feel your pain': Patient insights on patient-provider communication in Rwanda. [Journal Article]
- AJAfr J Prim Health Care Fam Med 2018 Apr 16; 10(1):e1-e11
- CONCLUSIONS: The expressed preferences, including those of patients with limited literacy, aligned well with the patient-centred care model. There were indications of a power imbalance weighing on the provider's side. Although patients with limited literacy were reliant on providers for decision-making, they were ready to be more involved in the care, suggesting a potential for improved patient involvement even for patients with paternalistic care preferences. These patients' insights can impact policies and curricula to optimise clinical practice. Generated knowledge will contribute to the indispensable yet underdeveloped field of health communication in sub-Saharan Africa. Findings call for more inclusion of patient perspectives in the patient-provider encounter. This could require more training of professionals and research on the topic, both in Rwanda and in other regions.
- Altered white matter connectivity associated with visual hallucinations following occipital stroke. [Journal Article]
- BBBrain Behav 2018 May 21; :e01010
- CONCLUSIONS: Cortical remapping and the disruption of communication between visual cortices and remote regions are consistent with our previous functional magnetic resonance imaging (fMRI) data showing imbalanced functional activity of the same regions in this patient (Rafique et al, 2016, Neurology, 87, 1493-1500). Long-term adaptive and disruptive changes in white matter connectivity may account for the rare nature of cases presenting with chronic and continuous visual hallucinations.
- Modulation of serine/threonine phosphatases by melatonin: therapeutic approaches in neurodegenerative diseases. [Review]
- BJBr J Pharmacol 2018 May 20
- Melatonin is an endogenous hormone produced by the pineal gland as well as many other tissues and organs. The natural decline in melatonin levels with aging strongly contributes to the development of...
Melatonin is an endogenous hormone produced by the pineal gland as well as many other tissues and organs. The natural decline in melatonin levels with aging strongly contributes to the development of neurodegenerative disorders. Neurodegenerative diseases share common mechanisms of toxicity such as proteinopathy, mitochondrial dysfunction, metal dyshomeostasis, oxidative stress, neuroinflammation, and an imbalance in the phosphorylation/dephosphorylation ratio. Several reports have proved the usefulness of melatonin in counteracting the events that lead to a neurodegenerative scenario. In this review we have focused on highlighting the fact that melatonin could rectify the altered phosphorylation/dephosphorylation rate found in some neurodegenerative diseases by influencing the activity of phosphoprotein phosphatases. We analyze whether melatonin offers any protective activity towards these enzymes through a direct interaction.
- Sex-dependent association of circulating sex steroids and pituitary hormones with treatment-free survival in chronic lymphocytic leukemia patients. [Journal Article]
- AHAnn Hematol 2018 May 21
- Chronic lymphocytic leukemia (CLL) is not considered a hormone-regulated cancer although sex is a recognized risk factor with men more frequently diagnosed and developing progressive disease. We hypo...
Chronic lymphocytic leukemia (CLL) is not considered a hormone-regulated cancer although sex is a recognized risk factor with men more frequently diagnosed and developing progressive disease. We hypothesized that variable hormonal exposure may have a sexually dimorphic influence on treatment-free survival (TFS). In 156 CLL cases, we quantitatively profiled 29 circulating steroids (progesterone, adrenal precursors, androgens, estrogens, and catechol estrogens) as well as luteinizing hormone (LH) and follicle-stimulating hormone. Median TFS was shorter for men than that for women (80.7 vs. 135.0 months, P = 0.033). Circulating hormone profiles in CLL patients were significantly different from those of healthy donors. In male CLL cases, higher LH levels were associated with shorter TFS (adjusted hazard ratio (HRadj) 2.11; P = 0.004). In female CLL cases, high levels of the potent androgens testosterone and dihydrotestosterone and the sum of methoxy estrogens were associated with an improved TFS with HRadj values of 0.24 (P = 0.007), 0.54 (P = 0.023), and 0.31 (P = 0.034), respectively. Reduced TFS was observed for women with CLL exhibiting high expression of the steroid-inactivating UGT2B17 enzyme. This study is the first to establish a link between the outcome of CLL patients, sex steroids, and pituitary hormones, revealing a sex-specific hormonal imbalance associated with disease progression.
- Molecular genetics and metabolism, special edition: Diagnosis, diagnosis and prognosis of Mucopolysaccharidosis IVA. [Review]
- MGMol Genet Metab 2018 May 15
- Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an autosomal recessive disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to th...
Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an autosomal recessive disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to the accumulation of specific glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS), which are mainly synthesized in the cartilage. Therefore, the substrates are stored primarily in the cartilage and its extracellular matrix (ECM), leading to a direct impact on bone development and successive systemic skeletal spondylepiphyseal dysplasia. The skeletal-related symptoms for MPS IVA include short stature with short neck and trunk, odontoid hypoplasia, spinal cord compression, tracheal obstruction, obstructive airway, pectus carinatum, restrictive lung, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. The degree of imbalance of growth in bone and other organs and tissues largely contributes to unique skeletal dysplasia and clinical severity. Diagnosis of MPS IVA needs clinical, radiographic, and laboratory testing to make a complete conclusion. To diagnose MPS IVA, total urinary GAG analysis which has been used is problematic since the values overlap with those in age-matched controls. Currently, urinary and blood KS and C6S, the enzyme activity of GALNS, and GALNS molecular analysis are used for diagnosis and prognosis of clinical phenotype in MPS IVA. MPS IVA can be diagnosed with unique characters although this disorder relates closely to other disorders in some characteristics. In this review article, we comprehensively describe clinical, radiographic, biochemical, and molecular diagnosis and clinical assessment tests for MPS IVA. We also compare MPS IVA to other closely related disorders to differentiate MPS IVA. Overall, imbalance of growth in MPS IVA patients underlies unique skeletal manifestations leading to a critical indicator for diagnosis.
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- Bisphenol A-Induced Endocrinotoxicity and Male Reprotoxicopathy is Modulated by the Dietary Iron Deficiency. [Journal Article]
- EMEndocr Metab Immune Disord Drug Targets 2018 May 20
- CONCLUSIONS: These results suggest that iron deficiency has no generalized effect on hormonal levels in BPA-treated animals and trends indicate a more remarkable effect in male animals at hormonal and tissue effect levels.