Biochemical and cellular mechanisms of aging and degenerative disease: Excessive, poor-quality caloric intake may deplete essential nutrients and interfere with cellular processes to produce degenerative damage

2008 ◽  
Vol 70 (4) ◽  
pp. 768-775 ◽  
Author(s):  
Gary E. Moore
Keyword(s):  
Caloric Intake ◽  
Poor Quality ◽  
Degenerative Disease ◽  
Cellular Mechanisms ◽  
Essential Nutrients ◽  
Cellular Processes

scholarly journals Maternal Uterine Vascular Remodeling During Pregnancy

Physiology ◽  
2009 ◽  
Vol 24 (1) ◽  
pp. 58-71 ◽  
Author(s):  
George Osol ◽  
Maurizio Mandala
Keyword(s):  
Extracellular Matrix ◽  
Blood Flow ◽  
Vascular Remodeling ◽  
Normal Pregnancy ◽  
Uterine Blood Flow ◽  
Growth And Remodeling ◽  
Cellular Mechanisms ◽  
Cellular Processes ◽  
Uteroplacental Blood Flow ◽  
Uterine Circulation

Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

Abstract 497: Cholesterol and Toll-like Receptor Signaling Are Important Regulators of Macrophage Interactions with Atherosclerotic Lipoprotein Aggregates

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Harvey F Chin ◽  
Abigail Haka ◽  
Frederick R Maxfield
Keyword(s):  
Molecular Mechanisms ◽  
Atherosclerotic Plaques ◽  
Cholesteryl Esters ◽  
Cellular Mechanisms ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Atherosclerotic Plaque Formation ◽  
Subendothelial Space ◽  
Morphological Responses ◽  
Cytoskeletal Rearrangements

Macrophages encounter deposits of aggregated low-density lipoproteins (agLDL) in the subendothelial space of blood vessels during the first stages of atherosclerotic plaque formation. Notably, current models for the mechanism of macrophage internalization of cholesterol in early atherosclerotic plaques are incomplete due to the lack of attention paid to the unique cellular mechanisms that are required for macrophages to degrade aggregates of LDL in particular, which can comprise >90% of the LDL in atherosclerotic plaques. In fact, internalization of cholesterol from cholesteryl esters in agLDL involves the development of intriguing cellular processes in which extracellular acidic compartments, lysosomal synapses (LSs), are formed whereby agLDL is partially degraded prior to internalization. This process requires extensive cytoskeletal rearrangements and secretion of lysosomal enzymes responsible for hydrolysis of cholesteryl esters from the agLDL. Subsequent delivery of free cholesterol from agLDL to the macrophage plasma membrane is central for development of the LS. Nonetheless, the molecular mechanism underlying initiation and propagation of the LS are currently largely unknown. This research proposal aims to elucidate the molecular mechanisms of LS formation and the role that cholesterol plays in eliciting these morphological responses to agLDL. Fluorescence microscopy assays were used to identify activation of TLR4 and downstream signaling involving PI3K and Akt as important events leading to LS formation. Furthermore, morphological responses of macrophages to cholesterol overloading require overlapping signaling pathways, indicating the role of interplay of cholesterol and TLR4 signaling in development of this novel macrophage interaction with aggregated LDL found in plaques. Identification of specific molecular pathways involved in this process will not only contribute to the basic understanding of one of the primary cellular processes contributing to atherosclerosis, one of the primary causes of heart disease, but also provide tangible molecular targets for the ultimate development of therapies.

scholarly journals Molecular and Clinical Insights into the Invasive Capacity of Glioblastoma Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Carlos Velásquez ◽  
Sheila Mansouri ◽  
Carla Mora ◽  
Farshad Nassiri ◽  
Suganth Suppiah ◽  
...  
Keyword(s):  
Treatment Resistance ◽  
Host Cells ◽  
Cellular Mechanisms ◽  
Poor Overall Survival ◽  
Cellular Processes ◽  
New Therapeutic Approaches ◽  
Invasive Capacity ◽  
Molecular Machinery ◽  
The Impact ◽  
Infiltrative Tumor

The invasive capacity of GBM is one of the key tumoral features associated with treatment resistance, recurrence, and poor overall survival. The molecular machinery underlying GBM invasiveness comprises an intricate network of signaling pathways and interactions with the extracellular matrix and host cells. Among them, PI3k/Akt, Wnt, Hedgehog, and NFkB play a crucial role in the cellular processes related to invasion. A better understanding of these pathways could potentially help in developing new therapeutic approaches with better outcomes. Nevertheless, despite significant advances made over the last decade on these molecular and cellular mechanisms, they have not been translated into the clinical practice. Moreover, targeting the infiltrative tumor and its significance regarding outcome is still a major clinical challenge. For instance, the pre- and intraoperative methods used to identify the infiltrative tumor are limited when trying to accurately define the tumor boundaries and the burden of tumor cells in the infiltrated parenchyma. Besides, the impact of treating the infiltrative tumor remains unclear. Here we aim to highlight the molecular and clinical hallmarks of invasion in GBM.

scholarly journals Impact of the severity of restrictive spirometric pattern on nutrition, physical activity, and quality of life: results from a nationally representative database

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sung Jun Chung ◽  
Hwan Il Kim ◽  
Bumhee Yang ◽  
Taehee Kim ◽  
Yun Su Sim ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
General Health ◽  
Multivariable Analysis ◽  
Caloric Intake ◽  
Health Problems ◽  
Poor Quality ◽  
Five Dimensions ◽  
The Impact

AbstractThe general disease burden associated with the restrictive spirometric pattern (RSP) is substantial. However, the impact of RSP by its severity on general health problems and quality of life has not been well elucidated. This study aimed to analyse nutrition, physical activity, and quality of life in subjects who participated in the Korea National Health and Nutrition Examination Survey 2007–2016 according to severity of RSP. Participants were classified as subjects with normal spirometry, those with mild-to-moderate RSP, and those with severe RSP. Poor quality of life was defined as 25th percentile value on the EuroQoL five dimensions (Eq5D) questionnaire index, i.e., 0.90. This study included 23,615 subjects composed of 20,742 with normal spirometry, 2758 with mild-to-moderate RSP, and 115 with severe RSP. The subjects with severe RSP were more likely to have attained lower education levels, had a lower total caloric intake, had less physical activity, had experienced a higher prevalence of comorbidities, and poorer quality of life than those with normal spirometry (P < 0.001 for all). In multivariable analysis, subjects with a mild-to-moderate RSP and severe RSP were more likely to show decreased total calories (coefficient for change in calorie = − 56.6 kcal and − 286.7 kcal, respectively) than those with normal spirometry; subjects with mild-to-moderate RSP and those with severe RSP were 1.26 times and 1.96 times more likely, respectively, to have a poorer quality of life than those with normal spirometry. Additionally, subjects with mild-to-moderate RSP and those with severe RSP were 0.84 times and 0.36 times less likely, respectively, to have high-intensity physical activity than those with normal spirometry in univariable analysis. The trends of a poorer quality of life and physical activity were only significant in the male subgroups. In conclusion, our study revealed that the severity of general health problems and quality of life reductions are correlated with the severity of RSP, especially in males.

scholarly journals Vitamin D Signaling in Myogenesis: Potential for Treatment of Sarcopenia

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Akira Wagatsuma ◽  
Kunihiro Sakuma
Keyword(s):  
Vitamin D ◽  
Current Knowledge ◽  
Poor Quality ◽  
Valuable Insight ◽  
Cellular Mechanisms ◽  
Life And Death ◽  
Nutritional Strategy ◽  
Proliferation And Differentiation ◽  
Vitamin D Signaling

Muscle mass and strength progressively decrease with age, which results in a condition known as sarcopenia. Sarcopenia would lead to physical disability, poor quality of life, and death. Therefore, much is expected of an effective intervention for sarcopenia. Epidemiologic, clinical, and laboratory evidence suggest an effect of vitamin D on muscle function. However, the precise molecular and cellular mechanisms remain to be elucidated. Recent studies suggest that vitamin D receptor (VDR) might be expressed in muscle fibers and vitamin D signaling via VDR plays a role in the regulation of myoblast proliferation and differentiation. Understanding how vitamin D signaling contributes to myogenesis will provide a valuable insight into an effective nutritional strategy to moderate sarcopenia. Here we will summarize the current knowledge about the effect of vitamin D on skeletal muscle and myogenic cells and discuss the potential for treatment of sarcopenia.

scholarly journals Colonic Epithelial miR-31 Associates with the Development of Crohn’s Phenotypes

2018 ◽  
Author(s):  
Benjamin P. Keith ◽  
Jasmine B. Barrow ◽  
Takahiko Toyonaga ◽  
Nevzat Kazgan ◽  
Michelle Hoffner O’Connor ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Cell Types ◽  
Adult Patients ◽  
Small Rna Sequencing ◽  
Cellular Mechanisms ◽  
Cellular Processes ◽  
Treatment Naïve ◽  
History Of ◽  
Mucosa Cell ◽  
Ileal Disease

AbstractCrohn’s disease (CD) is highly heterogeneous, due in large part to variability in cellular processes that underlie the natural history of CD, thereby confounding effective therapy. There is a critical need to advance understanding of the cellular mechanisms that drive CD heterogeneity. In this study, small RNA-sequencing and microRNA profiling in the colon revealed two distinct molecular subtypes, each with different clinical associations, in both adult and treatment-naïve pediatric CD patients. Notably, we found that microRNA-31 (miR-31) expression by itself can stratify patients into these two subtypes. Through detailed analysis of several colonic mucosa cell types from adult patients, we found that differential levels of miR-31 are particularly pronounced in epithelial cells. We generated patient crypt-derived epithelial colonoids and showed that miR-31 expression differences preserved in this ex-vivo system. In adult patients, low colonic miR-31 expression levels at the time of surgery are associated with post-operative recurrence of ileal disease. In pediatric patients, lower miR-31 expression at the time of diagnosis is associated with the future development of fibrostenotic ileal CD requiring surgery. These findings represent an important step forward in designing more effective clinical trials and developing personalized therapies for CD.

scholarly journals Causes, management and complications of severe adult dehydration in the emergency room

2021 ◽  
Vol 8 (2) ◽  
pp. 943
Author(s):  
Abdulrahman Mohammad Ghafouri ◽  
Shurouq Hamzah Arkoubi ◽  
Talal Maqboul Al-Amri ◽  
Afaf Matar Alshamari ◽  
Mohammed Ali Alqahtani ◽  
...  
Keyword(s):  
Emergency Room ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Skin Diseases ◽  
Caloric Intake ◽  
Fluid Administration ◽  
Renal Protection ◽  
Cellular Processes ◽  
Main Challenge ◽  
Uncontrolled Diabetes

This literature review aims to highlight the possible causes, complications, and management of this event from previously published studies discussing dehydration in critically-ill patients admitted to the emergency room (ER). In general, the administration of fluids has been used in the ER for critically-ill patients for many purposes. These include the optimization and adjustment of body fluids and electrolytes, increase renal protection against contrast, enhance uric acid, globins, caloric intake, and as an adjuvant to ameliorate the potentiality of certain medications or to dilute them. Many etiologies have been accused to cause dehydration in critically-ill patients. These include the fasting strategy that patients are obliged to whenever undergoing a surgical operation. Kidney, heart, and liver injuries have also been associated with patients’ dehydration. Old age and the presence of other co-morbidities diabetes insipidus and uncontrolled diabetes can also aggravate the condition. Mental affection is the main complication that patients with severe dehydration might complain about. Other complications might include aggravation of heart failure, and skin diseases, and deterioration of the kidney functions and other cellular processes that require adequate nourishment for their daily normal functions. Mortality is also a serious common complication, especially within elderly patients. Although the management of dehydration can be easily achieved by fluid administration, fluid overload can aggravate the underlying complications and develop others. Therefore, the main challenge here would be to frequently monitor patients during fluid administration and resuscitation to prevent this side effect.

scholarly journals Proteomic Landscape of Adeno-Associated Virus (AAV)-Producing HEK293 Cells

2021 ◽  
Vol 22 (21) ◽  
pp. 11499
Author(s):  
Lisa Strasser ◽  
Stefano Boi ◽  
Felipe Guapo ◽  
Nicholas Donohue ◽  
Niall Barron ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Host Cell ◽  
Reversed Phase ◽  
Hek293 Cells ◽  
Label Free ◽  
Cellular Mechanisms ◽  
Adeno Associated Virus ◽  
Cellular Processes ◽  
Cell Productivity ◽  
Product Manufacturing

Adeno-associated viral (AAV) vectors are widely used for gene therapy, providing treatment for diseases caused by absent or defective genes. Despite the success of gene therapy, AAV manufacturing is still challenging, with production yields being limited. With increased patient demand, improvements in host cell productivity through various engineering strategies will be necessary. Here, we study the host cell proteome of AAV5-producing HEK293 cells using reversed phase nano-liquid chromatography and tandem mass spectrometry (RPLC-MS/MS). Relative label-free quantitation (LFQ) was performed, allowing a comparison of transfected vs. untransfected cells. Gene ontology enrichment and pathway analysis revealed differential expression of proteins involved in fundamental cellular processes such as metabolism, proliferation, and cell death. Furthermore, changes in expression of proteins involved in endocytosis and lysosomal degradation were observed. Our data provides highly valuable insights into cellular mechanisms involved during recombinant AAV production by HEK293 cells, thus potentially enabling further improvements of gene therapy product manufacturing.

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