Implications of NAD+ boosters in translational medicine Kang, Baeki E.; Choi, Jun‐Yong; Stein, Sokrates ...
European journal of clinical investigation,
October 2020, 2020-10-00, 20201001, Letnik:
50, Številka:
10
Journal Article
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Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite in energy metabolism as well as a co‐substrate in biochemical reactions such as protein deacylation, protein ADP‐ribosylation and ...cyclic ADP‐ribose synthesis mediated by sirtuins, poly (ADP‐ribose) polymerases (PARPs) and CD38. In eukaryotic cells, NAD+ is synthesized through three distinct pathways, which offer different strategies to modulate the bioavailability of NAD+. The therapeutic potential of dietarily available NAD+ boosters preserving the NAD+ pool has been attracting attention after the discovery of declining NAD+ levels in ageing model organisms as well as in several age‐related diseases, including cardiometabolic and neurodegenerative diseases. Here, we review the recent advances in the biology of NAD+, including the salubrious effects of NAD+ boosters and discuss their future translational strategies.
In this paper, a simple and powerful method to control the induced handedness of helical nanofilaments (HNFs) is presented. The nanofilaments are formed by achiral bent-core liquid crystal molecules ...employing a cholesteric liquid crystal field obtained by doping a rod-like nematogen with a chiral dopant. Homochiral helical nanofilaments are formed in the nanophase-separated helical nanofilament/cholesteric phase from a mixture with a cholesteric phase. This cholesteric phase forms at a temperature higher than the temperature at which the helical nanofilament in a bent-core molecule appears. Under such conditions, the cholesteric liquid crystal field acts as a driving force in the nucleation of HNFs, realizing a perfectly homochiral domain consisting of identical helical nanofilament handedness.
Abstract
Background
Conducting a distinct comparison between the life expectancy (LE) and healthy life expectancy (HALE) of people with disabilities (PWDs) and the general population is necessary due ...to the various environmental and health conditions they encounter. Therefore, this study aimed to develop the life table for PWDs and calculate those of LE and HALE based on sex, severity, and disability types among the registered Korean PWDs.
Methods
We used aggregated data of registered PWDs from the Korea National Rehabilitation Center database between 2014 and 2018. Overall, 345,595 deaths were included among 12,627,428 registered PWDs. First, we calculated the LE for total PWDs and non-disabled people using a standard life table, extending the old age mortality among nine models. Subsequently, we calculated the LE for each type of disability using the relationship between the mortality of total PWDs and those of each type of disability. Finally, HALE was calculated using the Sullivan method for three types as follows: disability-free and perceived health (PH) using the National Survey, and hospitalized for ≥ 7 days using the Korea National Health Insurance System (NHIS) database.
Results
The calculated LE/HALE–NHIS (years) at registration in males and females were 81.32/73.32 and 87.38/75.58, 68.54/58.98 and 71.43/59.24, 73.87/65.43 and 78.25/67.51, and 61.53/50.48 and 62.41/49.72 years among non-disabled, total PWDs, mild disabled, and severe disabled, respectively. LE/HALE-NHIS was lowest and highest in respiratory dysfunction and hearing disabilities, respectively.
Conclusions
Males with disabilities had shorter LE and HALE at registration than females, except for those with severe disabilities, and there were variabilities in the LE based on the disability types.
Coronavirus disease 2019 (COVID-19) is pandemic and has caused illness to many people worldwide. This review aimed to summarize and analyze the herbal formulae provided by the guidelines for their ...pattern identifications (PIs) and compositions of herbs to treat patients with COVID-19.
We searched 7 data sources for eligible traditional medicine guidelines up to March 6, 2020 and found a total of 28 traditional medicine guidelines that provide treatment measures for COVID-19.
Of the 28 guidelines, there were 26 government-issued Chinese guidelines and 2 Korean guidelines. After standardizing the terminology of the PIs and herbal formulae, there were 8 PIs and 23 herbal formulae for the mild stage, 11 PIs and 31 herbal formulae for the moderate stage, 8 PIs and 21 herbal formulae for the severe stage, and 6 PIs and 23 herbal formulae for the recovery stage in the Chinese guidelines. In the Korean guidelines, there were 4 PIs and 15 herbal formulae for the mild stage, 3 PIs and 3 herbal formulae for the severe stage, and 2 PIs and 2 herbal formulae for the recovery stage. In the frequency analysis of herbs, Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum, Ephedrae Herba, and Gypsum Fibrosum were found to be the herbs with the high frequency of usage in the Chinese guidelines.
This review can be used as guidance for the traditional medicine treatment of COVID-19. Clinical evidence is needed in the future to evaluate the efficacy of traditional medicine.
•A high performance flexible thermoelectric generator (f-TEG) is developed.•Structural design guideline of the f-TEG for human body application is proposed.•The highest power (2.28 µW/cm2) using the ...f-TEG with no heatsink is achieved.•The efficiency of power management IC must be included for the f-TEG optimization.
Self-powered wearable electronic devices are expected to be one of the mainstream technologies for future portable electronic systems. As an energy harvester to power wearable electronic devices, a flexible thermoelectric generator (f-TEG) can utilize human body heat as the energy source, creating an ideal solution. The f-TEG can make conformal contact to the human skin and fully utilize body heat with minimal energy loss, while also being comfortable to wear. However, to maximize the power generated by an f-TEG attached to the human body, a careful thermal and structural design analysis of the f-TEG must be carried out. Here, we fabricated flexible thermoelectric generators (f-TEGs) with different device parameters and evaluated their power generating performance using an artificial arm, which was carefully designed to mimic a real human arm. We demonstrated the impact of the f-TEG device parameters on the power generation performance under various circumstances. The experimental results were compared with the theoretical model, and guidelines for an optimum device design in terms of maximizing the generated power density are also presented. Finally, we show that the optimum device structure varies when the efficiency of the power management IC (PMIC) is included in the analysis of the power generation system, which is practically important.
There is no registered regular doctor system in Korea, but people voluntarily select regular doctors for medical services. This study aims to study the ecology of medical care in Korea according to ...the presence and type of a regular doctor.
This study was conducted using Korean Health Panel survey in 2018. The proportion of people who had health problems and received medical care in various settings was analyzed per 1,000 people according to the following groups: without a regular doctor, having a clinic physician as a regular doctor, and having a hospital physician as a regular doctor. The adjusted odds ratio for usage of medical services was calculated.
Health problems and medical care use increased in the groups in this order: group without a regular doctor, group with a clinic physician as a regular doctor, the group with a hospital physician a regular doctor. Having a hospital physician as a regular doctor was associated with higher odds of inpatient care and emergency room visits, and having a clinic physician as a regular doctor was not associated with odds of inpatient care and emergency room visits when adjusting demographic and health-related variables.
Depending on whether having a regular doctor and a regular doctor's type, different ecology of medical care was observed. The position and role of a regular doctor in the context of the Korea health care system should be considered from the perspective of primary care.
Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC ...class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1− cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.
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•SARS-CoV-2-specific CD8+ T cells are effector memory cells in convalescents•CCR7+CD45RA+ cells are increased among SARS-CoV-2-specific cells in the late phase•SARS-CoV-2-specific CD8+ T cells have fewer IFN-γ+ cells than flu-specific cells•PD-1-expressing SARS-CoV-2-specific CD8+ T cells are not exhausted but functional
T cell responses have been demonstrated in COVID-19 patients, but ex vivo phenotypes and functions of SARS-CoV-2-specific T cells remain unclear. Rha et al. examined SARS-CoV-2-specific CD8+ T cells in acute and convalescent COVID-19 patients using MHC class I multimers, finding that PD-1-expressing SARS-CoV-2-specific CD8+ T cells are not exhausted but functional.
The specificity loop of Matrix Metalloproteinases (MMPs) is known to regulate recognition of their substrates, and the S1'-site surrounded by the loop is a unique place to address the selectivity of ...ligands toward each MMP. Molecular dynamics (MD) simulations of apo-MMP-13 and its complex forms with various ligands were conducted to identify the role of the specificity loop for the ligand binding to MMP-13. The MD simulations showed the dual role of T247 as a hydrogen bond donor to the ligand, as well as a contributor to the formation of the van der Waal surface area, with T245 and K249 on the S1'-site. The hydrophobic surface area mediated by T247 blocks the access of water molecules to the S1'-site of MMP-13 and stabilizes the ligand in the site. The F252 residue is flexible in order to search for the optimum location in the S1'-site of the apo-MMP-13, but once a ligand binds to the S1'-site, it can form offset π-π or edge-to-π stacking interactions with the ligand. Lastly, H222 and Y244 provide the offset π-π and π-CH(Cβ) interactions on each side of the phenyl ring of the ligand, and this sandwiched interaction could be critical for the ligand binding to MMP-13.
A nickel–zinc ferrite system, which is one of the well‐known versatile soft‐ferromagnetic oxides, was investigated in terms of magnetoelectric (ME) coupling at room temperature. Herein, we ...demonstrated that spin canting is manipulated through a composition‐induced structural transition from an inverse to a normal spinel structure, leading to modulation in the ME coupling. The ME coefficient was maximized at 60 at.% Zn substitution with a value of 0.1 mV/(Oe·cm), denoting ∼70% enhancement compared to that of the pure nickel ferrite. It was revealed that the interspin angle is enhanced along the octahedral site at up to ∼60 at.% Zn substitution, consistent with the composition level at the culmination of the ME coupling, evidenced by X‐ray diffraction profiles and magnetic hysteresis loops combined with density functional theory calculations. Given that this approach is based on a tractable fabrication method, this study is expected to be widely used in modulation of the ME coupling in spinel‐structured oxides.
Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress ...syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1β-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.
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