Smad7 attenuates TGF-β-mediated aging-related hypofunction of submandibular glands

2021 ◽  
pp. 153537022199343
Author(s):  
Minqi Hu ◽  
Wei Liu ◽  
Pingchuan Ma ◽  
Yingyi Wu ◽  
Honglin Li ◽  
...  
Keyword(s):  
Submandibular Gland ◽  
Interstitial Fibrosis ◽  
Treatment Strategies ◽  
Lymphocytic Infiltration ◽  
The Elderly ◽  
Salivary Flow ◽  
Pathological Process ◽  
Submandibular Glands ◽  
Restoration Strategies

Submandibular glands have essential functions in taste, mastication, swallowing, and digestion. Submandibular gland hypofunction is prevalent in the elderly, impairing the patients’ quality of life. Current clinical treatment strategies have not decelerated or reversed the pathological process of submandibular gland hypofunction. Therefore, novel restoration strategies should be explored. However, studies on the mechanism of aging-related submandibular gland hypofunction remain very limited. The role of the TGF-β/Smad pathway in fibrosis has been studied in other organs. Therefore, this study aimed to elucidate the role of TGF-β/Smad signaling in the aging-related submandibular gland hypofunction. The results showed that Smad7 knockout in mice decreased the salivary flow rate. H&E, Masson trichrome, and immunohistochemistry staining of MCP-1 and α-SMA showed that Smad7 knockout in mice resulted in lymphocytic infiltration, acinar cell atrophy, and interstitial fibrosis. The Western blotting of collagen I and III also confirmed extensive fibrosis. We then found that Smad7 depletion resulted in the TGF-β-mediated fibrosis via mir-21, mir-29, and np_5318, and NFκB-driven inflammation activation. This study confirmed the inhibitory role of Smad7 in the aging-related submandibular gland hypofunction. Therefore, it provided a promising treatment target for aging-related dysfunction and sialadenitis of submandibular gland.

Effect of pregestational sialoadenectomy of nursing mothers on eyelid opening of pups

1985 ◽  
Vol 249 (3) ◽  
pp. R285-R289
Author(s):  
S. Okamoto ◽  
T. Oka
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Submandibular Gland ◽  
Mammary Glands ◽  
Submandibular Glands ◽  
Nursing Mothers ◽  
Pregnant Mice ◽  
Epidermal Growth

The eyelid opening of pups born to and nursed by normal mice occurred by the 15th day of birth, whereas pregestational sialoadenectomy (removal of submandibular glands) of nursing mice delayed eyelid opening of their pups by as much as 5 days. Parotidectomy, however, had no effect on eyelid opening. Cross-foster nursing experiments indicated that the cause for delayed eyelid opening of pups was to be found in sialoadenectomized mothers, not their pups. Sialoadenectomized mothers had underdeveloped mammary glands that produced approximately 50% less milk than controls, and the amount of epidermal growth factor in their milk was similarly reduced. When epidermal growth factor, a polypeptide produced by the submandibular gland, was injected daily at a dose of 5 micrograms into sialoadenectomized pregnant mice, the eyelid opening of the pups nursed by their mothers occurred normally. These results are discussed with regard to the possible role of the submandibular gland and epidermal growth factor in neonatal eyelid opening.

Oxidative stress as a common pathway to chronic tubulointerstitial injury in kidney allografts

2007 ◽  
Vol 293 (2) ◽  
pp. F445-F455 ◽  
Author(s):  
Arjang Djamali
Keyword(s):  
Oxidative Stress ◽  
Interstitial Fibrosis ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Common Mechanism ◽  
Placebo Control ◽  
Tubulointerstitial Injury ◽  
Tubular Atrophy ◽  
Mesenchymal Transition

A major challenge for kidney transplantation is to dissect out the identifiable causes of chronic allograft tubulointerstitial fibrosis and to develop cause-specific treatment strategies. There has been a recent interest in the role of oxidative stress (OS) as a mediator of injury in chronic allograft tubular atrophy (TA) and interstitial fibrosis (IF). A review of the literature and data from my laboratory studying chronic allograft TA/IF in rat, rhesus monkey, and human kidneys suggests that OS is increased in graft-infiltrating macrophages, activated myofibroblasts, interstitium, and areas of tubular injury. Chronic allograft OS may be induced by inflammation, abnormal tissue oxygenation, immunosuppressant drugs, and comorbid clinical conditions including diabetes, hypertension, proteinuria, anemia, and dyslipidemia. Moreover, OS-induced chronic TA/IF is associated with signaling pathways including inflammation, apoptosis, hypoxia, and epithelial-to-mesenchymal transition. Most of these injury pathways participate in a self-perpetuating cycle with OS. In conclusion, evidence suggests that OS is a common mechanism of injury in chronic allograft TA/IF. However, most available data demonstrate a correlation and no causal relationship. Furthermore, the extent to which TA/IF is dependent on OS is unknown. These questions may be answered by prospective randomized placebo-control trials examining the role of select antioxidants in the prevention of chronic allograft TA/IF.

The role of ubiquitin proteasomal system and autophagy-lysosome pathway in Alzheimer’s disease

2017 ◽  
Vol 28 (8) ◽  
Author(s):  
Yuan Zhang ◽  
Xu Chen ◽  
Yanfang Zhao ◽  
Murugavel Ponnusamy ◽  
Ying Liu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Degradation ◽  
Molecular Chaperones ◽  
Elderly Population ◽  
Neurodegenerative Disorder ◽  
The Elderly ◽  
Pathological Process ◽  
Β Amyloid

AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly population. AD is associated with the buildup of β-amyloid and tau, which aggregate into extracellular plaques and neurofibrillary tangles. Although the exact mechanism of pathological process of AD is unclear, the dysfunction of protein degradation mechanisms has been proposed to play an important role in AD. The cellular degradation of abnormal or misfolded proteins consists of three different mechanisms: the ubiquitin proteasomal system (UPS), autophagy-lysosomal pathway (ALP), and interaction of molecular chaperones with UPS or ALP. Any disturbance to these systems causes proteins to accumulate, resulting in pathological process of AD. In this review, we summarize the knowledge of protein degradation pathways in the pathogenesis of AD in light of the current literature. In the future, the regulation UPS or ALP machineries could be the cornerstones of the treatment of AD.

scholarly journals Acetabular fractures in the elderly: modern challenges and the role of conservative management

2021 ◽  
Author(s):  
Kunal Mohan ◽  
James M. Broderick ◽  
Hasnain Raza ◽  
Brendan O’Daly ◽  
Michael Leonard
Keyword(s):  
Conservative Management ◽  
Young Patients ◽  
Treatment Strategies ◽  
The Elderly ◽  
High Energy ◽  
Acetabular Fractures ◽  
Individualized Approach ◽  
Vulnerable Patient ◽  
Vulnerable Patient Group

Abstract Introduction  The incidence of acetabular fractures in the elderly population is ever increasing. While management of acetabular fractures in young patients following high-energy trauma is well described, treatment of the elderly patient subgroup is complex and requires a unique, individualized approach. A variety of treatment strategies including operative and non-operative approaches exists to manage this vulnerable patient group. Conservative management of acetabular fractures in the elderly continues to play an important role in treatment of both stable fracture patterns and those medically unfit for surgery. Aim  This review assessing the current literature was undertaken with the purpose of summarising the challenges of management in this at-risk cohort as well as quantifying the role and outcomes following conservative management in the elderly.  Conclusion Our recommendation is that conservative management of acetabular fractures in the elderly can be considered as a treatment option on a case-by-case basis accounting for patient, injury, and surgical factors. If it is to be pursued, we advise a multidisciplinary approach focused on early mobility, minimisation of risk and regular follow-up to optimise patient outcomes.

scholarly journals Potential Application of Ixeris dentata in the Prevention and Treatment of Aging-Induced Dry Mouth

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1989 ◽  
Author(s):  
Kashi Bhattarai ◽  
Hwa-Young Lee ◽  
Seung-Hyun Kim ◽  
Jong-Sug Park ◽  
Hyung-Ryong Kim ◽  
...  
Keyword(s):  
Submandibular Gland ◽  
The Elderly ◽  
Salivary Flow ◽  
Treated Group ◽  
Dry Mouth ◽  
Aquaporin 5 ◽  
Aging Rats ◽  
Gland Weight ◽  
Oral Dryness ◽  
Ixeris Dentata

Dry mouth is a common complaint among the elderly population. The aim of this study was to investigate the effect of Ixeris dentata (IXD) extract on aging-induced dry mouth. We used young (two months) and aged (20 months) SD rats in our study. Using water as the vehicle, IXD extract (25, 50, and 100 mg/kg) was given via oral gavage to the young and aged rats for eight weeks. We found that the salivary flow rate relative to the submandibular gland weight was differently influenced by IXD extract treatment. IXD extract augmented the submandibular gland acinar cells, which are depleted during aging. In addition, the decreased salivary alpha-amylase, inositol triphosphate receptor, and aquaporin-5 in the aging rats were upregulated by IXD treatment. Free radical-induced oxidative stress in the aging rats was also alleviated in the IXD-treated group. The formation of high molecular weight complexes of protein disulfide isomerase, decreased expression of an ER chaperone (GRP78), and increased ER stress response (ATF-4, CHOP and p-JNK) in aging rats was regulated with IXD treatment, and eventually increased salivary secretions from the aging submandibular glands. These are the first data to suggest that IXD extract might ameliorate aging-associated oral dryness by regulating the ER environment.

Prospective Memory Development Across the Lifespan

2020 ◽  
Vol 25 (3) ◽  
pp. 162-173 ◽  
Author(s):  
Sascha Zuber ◽  
Matthias Kliegel
Keyword(s):  
Prospective Memory ◽  
Healthy Aging ◽  
Present Model ◽  
Current Knowledge ◽  
Well Being ◽  
The Elderly ◽  
Cognitive Factors ◽  
Everyday Functioning ◽  
Integrative Framework

Abstract. Prospective Memory (PM; i.e., the ability to remember to perform planned tasks) represents a key proxy of healthy aging, as it relates to older adults’ everyday functioning, autonomy, and personal well-being. The current review illustrates how PM performance develops across the lifespan and how multiple cognitive and non-cognitive factors influence this trajectory. Further, a new, integrative framework is presented, detailing how those processes interplay in retrieving and executing delayed intentions. Specifically, while most previous models have focused on memory processes, the present model focuses on the role of executive functioning in PM and its development across the lifespan. Finally, a practical outlook is presented, suggesting how the current knowledge can be applied in geriatrics and geropsychology to promote healthy aging by maintaining prospective abilities in the elderly.

HUBUNGAN PERAN FAMILY CAREGIVER TERHADAP QUALITAS HIDUP LANSIA

2019 ◽  
Vol 11 (1) ◽  
pp. 51-56
Author(s):  
RIANI PRADARA JATI ◽  
Sekar Farah Nabila
Keyword(s):  
Quality Of Life ◽  
Family Caregiver ◽  
Random Sampling ◽  
Simple Random Sampling ◽  
The Elderly ◽  
Chi Square ◽  
The Poor ◽  
The Family

  Penempatan peran yang baik bagi Family Caregiver sangatlah membantu lansia dalam meningkatkah qualitas hidupnya, meningkatkan motivasi dalam menjalankan hidup Penelitian ini bertujuan Mengetahui hubungan peran Family Caregiver dalam pemenuhan qualitas hidup bagi lansia di Kelurahan Langenharjo Kabupaten Kendal. DesainPenelitianDeskriptifKorelasional menggunakan pendekatan Krosectional,tehnikSamplingStratified Simple Random Sampling dengan karakteristik heterogen, dari populasi mempunyai hak yang sama untuk diseleksi sebagai sampel teknik undianPengambilan data dengan menggunakan kuesioner yang telah diuji validitas dan reliabilitasnya. Uji statistik Chi-square, dengan taraf signifikasi 5%jumlah sampel pada penelitian ini 70 sampel pada Family Caregiver dari 213 populasi yang ada. Hasil penelitian dari 70 responden didapatkan Peran Family Caregiver tidak baik dengan qualitas hidup tidak baik 33 (47,1%), sedangkan Peran Family Caregiver kurang baik dengan qualitas hidup lansia baik 3 (4,3%). Untuk distribusi Peran Family Caregiver kurang baik dengan qualitas hidup lansia tidak baik sebanyak 6 responden (8,6%) sedangkan untuk distribusi Peran Family Caregiver kurang baik dengan qualitas hidup lansia baik sebanyak 23 responden (32,9%). Terakhir, untuk distribusi Peran Family Caregiver baik dengan qualitas hidup lansia tidak baik didapatkan hasil 2 responden (2, 9%) sedangkan untuk distribusi Peran Family Caregiver baik dengan qualitas hidup lansia baik didapatkan hasil 3 responden (4,3%)Menunjukkan nilai ρ value 0,001 (ρ < 0,05) berarti ada hubungan antara dukungan keluarga dengan kepatuhan lansia dalam keikutsertaan posyandu lansia. Disarankan kepada semua Family Cregiver lansia untuk mampu memahami pentingnya perhatian, dukungan bagi lansia dalammeningkatkan qualitas hidup yang lebih baik bagi lansia.   Kata kunci : Peran family caregiver, qualitas hidup, lansia.   ABSTRACT Placement of a good role for Family Caregiver is very helpful for the elderly to improve their quality of life, increase motivation in living life Research Objective: To know the relationship between the role of Family Caregiver in fulfilling quality of life for the elderly in Langenharjo Village, Kendal Regency. Descriptive Correlational Research Design uses a cross sectional approach, Sampling Stratified Simple Random Sampling technique with heterogeneous characteristics, from the population has the same right to be selected as a sample lottery technique Retrieving data using a questionnaire that has been tested for validity and reliability. Test Chi-square statistics, with a significance level of 5% the number of samples in this study 70 samples on the Family Caregiver from 213 populations. Results of the Study Of 70 respondents found the role of Family Caregiver was not good with poor quality of life 33 (47.1%) , while the role of the Family Caregiver is not good with the quality of life of a good elderly 3 (4.3%). For the distribution of the role of Family Caregiver is not good with the quality of life of the poor family as many as 6 respondents (8.6%) while for the distribution of the Role of Family Caregiver is not good with the quality of life of good elderly as many as 23 respondents (32.9%). Finally, the distribution of the Role of Family Caregiver with good quality of life for the poor is obtained by 2 respondents (2, 9%), while the distribution of the Role of Family Caregiver with good quality of life for the elderly is obtained by 3 respondents (4.3%). 0.001 (ρ <0.05) means that there is a relationship between family support and the compliance of the elderly in the participation of the elderly posyandu. It is recommended to all elderly Cregiver families to be able to understand the importance of attention, support for the elderly in improving the quality of life better for the elderly   Keywords: Role of Family Caregiver, Quality of Life, Elderly

Galectin-3 in Heart Failure – Linking Fibrosis, Remodelling and Progression

2010 ◽  
Vol 6 (2) ◽  
pp. 33 ◽  
Author(s):  
Christopher R deFilippi ◽  
G Michael Felker ◽  
◽  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Risk Stratification ◽  
Cardiac Fibrosis ◽  
The Elderly ◽  
Preserved Ejection Fraction ◽  
Heart Failure Patients ◽  
Large Populations ◽  
Galectin 3

For many with heart failure, including the elderly and those with a preserved ejection fraction, both risk stratification and treatment are challenging. For these large populations and others there is increasing recognition of the role of cardiac fibrosis in the pathophysiology of heart failure. Galectin-3 is a novel biomarker of fibrosis and cardiac remodelling that represents an intriguing link between inflammation and fibrosis. In this article we review the biology of galectin-3, recent clinical research and its application in the management of heart failure patients.

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