The First Thousand Days: Kidney Health and Beyond

The global burden of chronic kidney disease (CKD) is rising. A superior strategy to advance global kidney health is required to prevent and treat CKD early. Kidney development can be impacted during the first 1000 days of life by numerous factors, including malnutrition, maternal illness, exposure to chemicals, substance abuse, medication use, infection, and exogenous stress. In the current review, we summarize environmental risk factors reported thus far in clinical and experimental studies relating to the programming of kidney disease, and systematize the knowledge on common mechanisms underlying renal programming. The aim of this review is to discuss the primary and secondary prevention actions for enhancing kidney health from pregnancy to age 2. The final task is to address the potential interventions to target renal programming through updating animal studies. Together, we can enhance the future of global kidney health in the first 1000 days of life.

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Adverse Impact of Environmental Chemicals on Developmental Origins of Kidney Disease and Hypertension

Frontiers in Endocrinology ◽

10.3389/fendo.2021.745716 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chien-Ning Hsu ◽

You-Lin Tain

Keyword(s):

Kidney Disease ◽

Animal Studies ◽

Kidney Development ◽

Renin Angiotensin System ◽

Chemical Exposure ◽

Environmental Chemicals ◽

Developmental Origins ◽

Environmental Chemical ◽

Pregnancy And Lactation ◽

Exposure During Pregnancy

Chronic kidney disease (CKD) and hypertension are becoming a global health challenge, despite developments in pharmacotherapy. Both diseases can begin in early life by so-called “developmental origins of health and disease” (DOHaD). Environmental chemical exposure during pregnancy can affect kidney development, resulting in renal programming. Here, we focus on environmental chemicals that pregnant mothers are likely to be exposed, including dioxins, bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAH), heavy metals, and air pollution. We summarize current human evidence and animal models that supports the link between prenatal exposure to environmental chemicals and developmental origins of kidney disease and hypertension, with an emphasis on common mechanisms. These include oxidative stress, renin-angiotensin system, reduced nephron numbers, and aryl hydrocarbon receptor signaling pathway. Urgent action is required to identify toxic chemicals in the environment, avoid harmful chemicals exposure during pregnancy and lactation, and continue to discover other potentially harmful chemicals. Innovation is also needed to identify kidney disease and hypertension in the earliest stage, as well as translating effective reprogramming interventions from animal studies into clinical practice. Toward DOHaD approach, prohibiting toxic chemical exposure and better understanding of underlying mechanisms, we have the potential to reduce global burden of kidney disease and hypertension.

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Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

Cancer Cell International ◽

10.1186/s12935-021-01906-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Marjan Talebi ◽

Mohsen Talebi ◽

Tahereh Farkhondeh ◽

Jesus Simal-Gandara ◽

Dalia M. Kopustinskiene ◽

...

Keyword(s):

Blood Cells ◽

Molecular Mechanisms ◽

Web Of Science ◽

Experimental Studies ◽

Protective Effects ◽

Pharmacological Activities ◽

Current Review ◽

Mesh Terms ◽

Online Databases ◽

Anti Cancer

AbstractChrysin has been shown to exert several beneficial pharmacological activities. Chrysin has anti-cancer, anti-viral, anti-diabetic, neuroprotective, cardioprotective, hepatoprotective, and renoprotective as well as gastrointestinal, respiratory, reproductive, ocular, and skin protective effects through modulating signaling pathway involved in apoptosis, oxidative stress, and inflammation. In the current review, we discussed the emerging cellular and molecular mechanisms underlying therapeutic indications of chrysin in various cancers. Online databases comprising Scopus, PubMed, Embase, ProQuest, Science Direct, Web of Science, and the search engine Google Scholar were searched for available and eligible research articles. The search was conducted by using MeSH terms and keywords in title, abstract, and keywords. In conclusion, experimental studies indicated that chrysin could ameliorate cancers of the breast, gastrointestinal tract, liver and hepatocytes, bladder, male and female reproductive systems, choroid, respiratory tract, thyroid, skin, eye, brain, blood cells, leukemia, osteoblast, and lymph. However, more studies are needed to enhance the bioavailability of chrysin and evaluate this agent in clinical trial studies. Graphic abstract

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The Nephroprotective Properties of Extracellular Vesicles in Experimental Models of Chronic Kidney Disease: a Systematic Review

Stem Cell Reviews and Reports ◽

10.1007/s12015-021-10189-9 ◽

2021 ◽

Author(s):

Natalia Nowak ◽

Masayuki Yamanouchi ◽

Eiichiro Satake

Keyword(s):

Systematic Review ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Interstitial Fibrosis ◽

Cell Damage ◽

Meta Analysis ◽

Experimental Studies ◽

Extracellular Vesicle ◽

Experimental Models ◽

Preclinical Research

AbstractExtracellular vesicle (EV)-based therapy was hypothesized as a promising regenerative approach which has led to intensive research of EVs in various pathologies. In this study, we performed a comprehensive systematic review of the current experimental evidence regarding the protective properties of EVs in chronic kidney disease (CKD). We evaluated the EV-based experiments, EV characteristics, and effector molecules with their involvement in CKD pathways. Including all animal records with available creatinine or urea data, we performed a stratified univariable meta-analysis to assess the determinants of EV-based therapy effectiveness. We identified 35 interventional studies that assessed nephroprotective role of EVs and catalogued them according to their involvement in CKD mechanism. Systematic assessment of these studies suggested that EVs had consistently improved glomerulosclerosis, interstitial fibrosis, and cell damage, among different CKD models. Moreover, EV-based therapy reduced the progression of renal decline in CKD. The stratified analyses showed that the disease model, administered dose, and time of therapeutic intervention were potential predictors of therapeutic efficacy. Together, EV therapy is a promising approach for CKD progression in experimental studies. Further standardisation of EV-methods, continuous improvement of the study quality, and better understanding of the determinants of EV effectiveness will facilitate preclinical research, and may help development of clinical trials in people with CKD. Graphical Abstract

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Epigenetic mechanisms involved in intrauterine growth restriction and aberrant kidney development and function

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174420001257 ◽

2020 ◽

pp. 1-11

Author(s):

Thu N. A. Doan ◽

Jessica F. Briffa ◽

Aaron L. Phillips ◽

Shalem Y. Leemaqz ◽

Rachel A. Burton ◽

...

Keyword(s):

Kidney Disease ◽

Intrauterine Growth Restriction ◽

Kidney Development ◽

Dna Methyltransferases ◽

Growth Restriction ◽

Epigenetic Mechanisms ◽

Specific Expression ◽

Maternal Line ◽

Intrauterine Growth ◽

Increased Risk

Abstract Intrauterine growth restriction (IUGR) due to uteroplacental insufficiency results in a placenta that is unable to provide adequate nutrients and oxygen to the fetus. These growth-restricted babies have an increased risk of hypertension and chronic kidney disease later in life. In rats, both male and female growth-restricted offspring have nephron deficits but only males develop kidney dysfunction and high blood pressure. In addition, there is transgenerational transmission of nephron deficits and hypertension risk. Therefore, epigenetic mechanisms may explain the sex-specific programming and multigenerational transmission of IUGR-related phenotypes. Expression of DNA methyltransferases (Dnmt1and Dnmt3a) and imprinted genes (Peg3, Snrpn, Kcnq1, and Cdkn1c) were investigated in kidney tissues of sham and IUGR rats in F1 (embryonic day 20 (E20) and postnatal day 1 (PN1)) and F2 (6 and 12 months of age, paternal and maternal lines) generations (n = 6–13/group). In comparison to sham offspring, F1 IUGR rats had a 19% decrease in Dnmt3a expression at E20 (P < 0.05), with decreased Cdkn1c (19%, P < 0.05) and increased Kcnq1 (1.6-fold, P < 0.01) at PN1. There was a sex-specific difference in Cdkn1c and Snrpn expression at E20, with 29% and 34% higher expression in IUGR males compared to females, respectively (P < 0.05). Peg3 sex-specific expression was lost in the F2 IUGR offspring, only in the maternal line. These findings suggest that epigenetic mechanisms may be altered in renal embryonic and/or fetal development in growth-restricted offspring, which could alter kidney function, predisposing these offspring to kidney disease later in life.

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Living well with kidney disease by patient and care-partner empowerment: kidney health for everyone everywhere

Clinical and Experimental Nephrology ◽

10.1007/s10157-021-02044-5 ◽

2021 ◽

Author(s):

Kamyar Kalantar-Zadeh ◽

◽

Philip Kam-Tao Li ◽

Ekamol Tantisattamo ◽

Latha Kumaraswami ◽

...

Keyword(s):

Kidney Disease ◽

Living Well ◽

Kidney Health

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Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol

Biomolecules ◽

10.3390/biom9030099 ◽

2019 ◽

Vol 9 (3) ◽

pp. 99 ◽

Cited By ~ 16

Author(s):

Danja J. Den Hartogh ◽

Evangelia Tsiani

Keyword(s):

Insulin Resistance ◽

Animal Studies ◽

Citrus Fruit ◽

Epidemiological Studies ◽

Personal Health ◽

Current Review ◽

Vegetables And Fruits

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.

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Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression

International Journal of Molecular Sciences ◽

10.3390/ijms22073571 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3571

Author(s):

Bonglee Kim ◽

Ji-Eon Park ◽

Eunji Im ◽

Yongmin Cho ◽

Jinjoo Lee ◽

...

Keyword(s):

Cancer Progression ◽

Animal Studies ◽

Molecular Mechanisms ◽

Future Research ◽

Clinical Implications ◽

Research Perspectives ◽

Current Review ◽

Gold Silver ◽

Significant Efficacy ◽

Rapid Clearance

Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil® (liposome-encapsulated doxorubicin), Abraxane® (albumin-bound paclitaxel), and Oncaspar® (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.

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Interventions to optimize medication use in nursing homes: a narrative review

European Geriatric Medicine ◽

10.1007/s41999-021-00477-5 ◽

2021 ◽

Author(s):

Anne Spinewine ◽

Perrine Evrard ◽

Carmel Hughes

Keyword(s):

Nursing Homes ◽

Large Scale ◽

Adverse Drug Events ◽

Experimental Studies ◽

Medication Use ◽

Nursing Home Residents ◽

Qualitative Studies ◽

Patient Centered ◽

Barriers And Enablers ◽

Specific Medication

Abstract Purpose Polypharmacy, medication errors and adverse drug events are frequent among nursing home residents. Errors can occur at any step of the medication use process. We aimed to review interventions aiming at optimization of any step of medication use in nursing homes. Methods We narratively reviewed quantitative as well as qualitative studies, observational and experimental studies that described interventions, their effects as well as barriers and enablers to implementation. We prioritized recent studies with relevant findings for the European setting. Results Many interventions led to improvements in medication use. However, because of outcome heterogeneity, comparison between interventions was difficult. Prescribing was the most studied aspect of medication use. At the micro-level, medication review, multidisciplinary work, and more recently, patient-centered care components dominated. At the macro-level, guidelines and legislation, mainly for specific medication classes (e.g., antipsychotics) were employed. Utilization of technology also helped improve medication administration. Several barriers and enablers were reported, at individual, organizational, and system levels. Conclusion Overall, existing interventions are effective in optimizing medication use. However there is a need for further European well-designed and large-scale evaluations of under-researched intervention components (e.g., health information technology, patient-centered approaches), specific medication classes (e.g., antithrombotic agents), and interventions targeting medication use aspects other than prescribing (e.g., monitoring). Further development and uptake of core outcome sets is required. Finally, qualitative studies on barriers and enablers for intervention implementation would enable theory-driven intervention design.

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