•Elevated serum γ-glutamyl transferase (GGT) activity signals oxidative stress.•Elevated serum GGT was associated with low jump power in adults aged ≥50 y.•Serum GGT levels showed a negative ...association with low handgrip strength.•The relationship persisted after adjustment for age, sex, lean mass, and body fat.•Serum GGT may act as a marker of muscle function.
Elevated serum γ-glutamyl transferase (GGT), a hepatic cholestasis or liver damage marker, has been associated with low lean mass and adiposity. However, whether serum GGT can predict muscle function in adults remains unclear. The aim of this study was to determine whether an elevated serum GGT is associated with low peak weight-corrected jump power (JP) and low handgrip strength (HGS).
This study included 662 individuals aged ≥50 y in the final cohort (women, 86%; mean age, 64.8 y). The primary outcome was low peak weight-corrected JP defined as <23.8 W/kg and <19W/kg in men and women, respectively, and the secondary outcome was low HGS (<28 kg in men; <18 kg in women).
Participants with low JP had a higher GGT level, older age, lower HGS, and higher body fat than those without low JP. Serum GGT showed a negative association with JP (adjusted β = –1.16, P = 0.005) and HGS (adjusted β = –0.92, P = 0.018). One log-unit increment in GGT was associated with elevated odds of low JP (adjusted odds ratio aOR 2.13, P = 0.002) after adjustment for age, sex, lean mass, and body fat percentage, particularly in individuals without hepatic steatosis (aOR, 2.30) versus those with hepatic steatosis (aOR, 0.80; Pinteraction = 0.020).
Elevated serum GGT was associated with low muscle function in adults independent of age, muscle mass, and adiposity, indicating that serum GGT may play a role as an independent marker of muscle function. <END ABSTRACT>
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Targeting the DNA damage response (DDR) pathway is an emerging therapeutic approach for leiomyosarcoma (LMS), and loss of RNase H2, a DDR pathway member, is a potentially actionable alteration for ...DDR targeted treatments. Therefore, we designed a protein and genomic based RNase H2 screening assay to determine its prevalence and prognostic significance. Using a selective RNase H2 antibody on a pan-tumor tissue microarray (TMA), RNase H2 loss was more common in LMS (11.5%, 9/78) than across all tumors (3.8%, 32/843). In a separate LMS cohort, RNase H2 deficiency was confirmed in uterine LMS (U-LMS, 21%, 23/108) and soft-tissue LMS (ST-LMS) (30%, 39/102). In the TCGA database, RNASEH2B homozygous deletions (HomDels) were found in 6% (5/80) of LMS cases, with a higher proportion in U-LMS (15%; 4/27) compared to ST-LMS (2%; 1/53). Using the SNiPDx targeted-NGS sequencing assay to detect biallelic loss of function in select DDR related genes, we found RNASEH2B HomDels in 54% (19/35) of U-LMS cases with RNase H2 loss by IHC, and 7% (3/43) HomDels in RNase H2 intact cases. No RNASEH2B HomDels were detected in ST-LMS. In U-LMS patient cohort (n = 109), no significant overall survival difference was seen in patients with RNase H2 loss versus intact, or RNASEH2B HomDel (n=12) vs Non-HomDel (n=37). The overall diagnostic accuracy, sensitivity, and specificity of RNase H2 IHC for detecting RNASEH2B HomDels in U-LMS was 76%, 93% and 71% respectively, and it is being developed for future predictive biomarker driven clinical trials targeting DDR in U-LMS.
Sodium‐ion batteries (SIBs) have emerged as a promising alternative to lithium‐ion batteries for large‐scale energy storage systems due to the abundance and low price of sodium. Until recently, the ...low theoretical capacities of intercalation‐type cathodes less than 250 mAh g−1 have limited the energy density of SIBs. On the other hand, iron oxyfluoride (FeOF) has a high theoretical capacity of ≈885 mAh g−1 as a conversion‐type cathode material for SIBs. However, FeOF suffers from poor cycling stability, rate capability, and low initial Coulombic efficiency caused by its low electrical conductivity and slow ionic diffusion kinetics. To solve these problems, doping aliovalent Ni2+ on FeOF electrodes is attempted to improve the electronic conductivity without using a carbon matrix. The ionic conductivity of FeOF is also enhanced due to the formation of oxygen defects in the FeOF crystal structure. The FeOF‐Ni1 electrode shows an excellent cycling performance with a reversible discharge capacity of 450.4 mAh g−1 at 100 mAh g−1 after 100 cycles with a fading rate of 0.20% per cycle. In addition, the FeOF‐Ni1//hard carbon full cell exhibited a high energy density of 876.9 Wh kg−1cathode with a good cycling stability.
Ni‐doped FeOF electrodes show the improved electrochemical performance as a cathode for sodium‐ion batteries. It is because doping FeOF with Ni2+ ions forms oxygen vacancies to maintain the charge balance and increases the electrical conductivity and ion diffusion of FeOF through the formation of oxygen vacancies to maintain the charge balance.
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•Family caregivers play a key role in providing home care for older adults with chronic disease.•Family caregivers are less likely to take care of their own health.•Physical activity can improve ...family caregivers’ physical and psychosocial health and decrease risk for the development of family caregivers’ illness.
This systematic review was conducted to analyze and capture the most recent trends in physical activity interventions for family caregivers of older adults with chronic disease as found in randomized clinical trials over the last 10 years (2010–2020). We used PubMed, CINAHL, Embase, PsycInfo, and the Cochrane Library. We synthesized participants’ demographics, physical activity interventions and family caregivers’ health outcomes. The Cochrane Collaboration Risk of Bias Tool was used to assess risk of bias of the included studies. Sixteen studies were included and most studies (n = 11) had a moderate risk of bias. Physical activity programs with mixed modes (e.g., aerobic and resistance exercise), mixed delivery methods (e.g., in-person and telephone) and mixed settings (e.g., supervised gym-based sessions and unsupervised home-based sessions) were used most frequently. Physical activity interventions significantly improved psychological health but had inconsistent effects on physical health. This review provides current trends and research findings that suggest types of physical activity interventions and components that improve family caregivers’ health and wellness.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
More than 17 million family caregivers (FCGs) provide care for older adults with chronic illness in the US. Caregiving for older adults with chronic disease places a considerable burden on ...FCGs and they tend to neglect their personal health. Generally, physical activity (PA) programs benefit the physical and psychological health of FCGs. However, no review of PA randomized clinical trials (RCTs) focused on FCGs of older adults with chronic disease. In this systematic review, we analyzed the most recent trends (2010-2020) in RCTs identifying the effects of PA in this population. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic databases (PubMed, CINAHL, Embase, PsycInfo, Cochrane Library) were searched for publications dated from 2010 to 2020. All studies included were appraised for quality using the Cochrane Collaboration Risk of Bias Tool. Of the resulting 16 studies, most studies (n=11) targeted FCGs of older adults with dementia or cancer. Most FCGs were non-Hispanic white. PA interventions with mixed modes (e.g., aerobic and resistance exercise), mixed delivery methods (e.g., in-person and telephone) and mixed settings (e.g., supervised gym- and unsupervised home sessions) were used most frequently. PA interventions significantly improved psychological health but had inconsistent effects on physical health. Tailored PA programs, designed based on FCGs’ goals, preferences and limitations, may improve upon physical health outcomes. Future PA studies should include samples of racially and ethnically diverse FCGs of older adults representing a broader range of chronic diseases.
The TRPM4 gene encodes a Ca2+-activated monovalent cation channel called transient receptor potential melastatin 4 (TRPM4) that is expressed in various tissues. Dysregulation or abnormal expression ...of TRPM4 has been linked to a range of diseases. We introduced the hemagglutinin (HA) tag into the extracellular S6 loop of TRPM4, resulting in an HA-tagged version called TRPM4-HA. This TRPM4-HA was developed to investigate the purification, localization, and function of TRPM4 in different physiological and pathological conditions. TRPM4-HA was successfully expressed in the intact cell membrane and exhibited similar electrophysiological properties, such as the current-voltage relationship, rapid desensitization, and current size, compared to the wild-type TRPM4. The presence of the TRPM4 inhibitor 9-phenanthrol did not affect these properties. Furthermore, a wound-healing assay showed that TRPM4-HA induced cell proliferation and migration, similar to the native TRPM4. Co-expression of protein tyrosine phosphatase, non-receptor type 6 (PTPN6 or SHP1) with TRPM4-HA led to the translocation of TRPM4-HA to the cytosol. To investigate the interaction between PTPN6 and tyrosine residues of TRPM4 in enhancing channel activity, we generated four mutants in which tyrosine (Y) residues were substituted with phenylalanine (F) at the N-terminus of TRPM4. The YF mutants displayed properties and functions similar to TRPM4-HA, except for the Y256F mutant, which showed resistance to 9-phenanthrol, suggesting that Y256 may be involved in the binding site for 9-phenanthrol. Overall, the creation of HA-tagged TRPM4 provides researchers with a valuable tool to study the role of TRPM4 in different conditions and its potential interactions with other proteins, such as PTPN6.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The TRPM4 gene encodes a Ca
-activated monovalent cation channel called transient receptor potential melastatin 4 (TRPM4) that is expressed in various tissues. Dysregulation or abnormal expression of ...TRPM4 has been linked to a range of diseases. We introduced the hemagglutinin (HA) tag into the extracellular S6 loop of TRPM4, resulting in an HA-tagged version called TRPM4-HA. This TRPM4-HA was developed to investigate the purification, localization, and function of TRPM4 in different physiological and pathological conditions. TRPM4-HA was successfully expressed in the intact cell membrane and exhibited similar electrophysiological properties, such as the current-voltage relationship, rapid desensitization, and current size, compared to the wild-type TRPM4. The presence of the TRPM4 inhibitor 9-phenanthrol did not affect these properties. Furthermore, a wound-healing assay showed that TRPM4-HA induced cell proliferation and migration, similar to the native TRPM4. Co-expression of protein tyrosine phosphatase, non-receptor type 6 (PTPN6 or SHP-1) with TRPM4-HA led to the translocation of TRPM4-HA to the cytosol. To investigate the interaction between PTPN6 and tyrosine residues of TRPM4 in enhancing channel activity, we generated four mutants in which tyrosine (Y) residues were substituted with phenylalanine (F) at the N-terminus of TRPM4. The YF mutants displayed properties and functions similar to TRPM4-HA, except for the Y256F mutant, which showed resistance to 9-phenanthrol, suggesting that Y256 may be involved in the binding site for 9-phenanthrol. Overall, the creation of HA-tagged TRPM4 provides researchers with a valuable tool to study the role of TRPM4 in different conditions and its potential interactions with other proteins, such as PTPN6.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Oxidative stress and inflammation are key factors responsible for progression of liver injury. A variety of functions of oyster hydrolysate (OH) are affected by their antioxidant and ...anti-inflammatory activities. However, little is known regarding the effects of OH on a liver injury model. This study was performed to evaluate the effects of OH on acute liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN) in mice. Experimental groups were divided into six groups as follows (each group, n=10): control (saline), LPS/D-GalN, LPS/D-GalN+OH (100 mg/kg), LPS/D-GalN+OH (200 mg/kg), LPS/D-GalN+OH (400 mg/kg), and LPS/D-GalN+silymarin (25 mg/kg, positive control). The experimental acute liver injury model was induced with LPS ($1{\mu}g/kg$) and D-GalN (400 mg/kg). We first analyzed antioxidant and anti-inflammatory activities in OH. OH showed high DPPH and ABTS radical scavenging activities and reduced ROS generation in Chang cells in a dose-dependent manner. In addition, OH showed anti-inflammatory activities, such as inhibition of cyclooxygenase-2 and 5-lipooxygenase. Treatment with OH down-regulated tumor necrosis factor $(TNF)-{\alpha}$, interleukin (IL)-6, and $IL-1{\alpha}$ expression levels in LPS-stimulated RAW264.7 cells. OH significantly reduced LPS/D-GalN-induced increases in the concentrations of alanine transaminase and aspartate aminotransferase in serum. In the LPS/D-GalN group, liver tissues exhibited apoptosis of hepatocytes with hemorrhages. These pathological alterations were ameliorated by OH treatment. Consistently, hepatic catalase activity was low in the LPS/D-GalN group compared to the control group, and catalase activity was significantly restored by OH treatment (P<0.05). Furthermore, OH markedly reduced the LPS/D-GalN-induced increase in $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 levels in liver tissue. Taken together, these results show that OH has hepatoprotective effects on LPS/D-GalN-induced acute liver injury via inhibition of oxidative stress and inflammation, suggesting that OH could be used as a health functional food and potential therapeutic agent for acute liver injury. 산화스트레스와 염증은 간 손상의 진행과정에 중요한 인자로 작용한다. 굴가수분해물의 항산화 및 항염증 활성은 지질대사, 혈압 및 혈당, 면역기능의 조절과 같은 다양한 기능에 관여한다. 그러나 급성 간 손상 모델에서 굴가수분해물의 효과를 확인한 연구 결과는 아직 확인된 바 없다. 본 연구는 LPS/D-GalN에 의해 유도된 급성 간 손상 생쥐 모델에서 굴가수분해물의 효과를 확인하기 위해 수행되었다. 실험군은 대조군(생리식염수), LPS/D-GalN 간 손상군, LPS/D-GalN과 굴가수분해물(100 mg/kg, 200 mg/kg, 400 mg/kg)의 병합투여군 및 LPS/D-GalN과 silymarin(25 mg/kg) 병합투여군으로 나누었다. 급성 간 손상 모델은 $1{\mu}g/kg$의 LPS와 400 mg/kg의 D-GalN으로 유도되었다. 먼저 시료의 항산화 및 항염증 활성을 분석한 결과 굴가수분해물은 농도 의존적으로 높은 DPPH 및 ABTS 라디칼 소거 활성을 보였으며, 인간 정상 간세포주(Chang)에서 과산화수소에 의한 세포 내 활성산소의 생성을 유의적으로 감소시켰다. 또한, 굴가수분해물은 농도 의존적으로 높은 COX-2 및 5-LOX 억제능을 보였으며, LPS에 의해 활성화된 생쥐 대식세포주 RAW264.7에서 발현되는 $TNF-{\alpha}$, IL-6 및 $IL-1{\beta}$의 염증성 사이토카인의 mRNA 발현률을 감소시켰다. 굴가수분해물 투여는 LPS/D-GalN에 의한 혈청 ALT 및 AST 증가를 유의적으로 감소시켰으며, 간 조직의 출혈 및 간세포의 자멸사를 감소시켰다. 또한, 간 균질의 $TNF-{\alpha}$, $IL-1{\beta}$ 및 IL-6 함량을 감소시켰으며, 감소한 catalase의 활성을 유의적으로 증가시켰다. 이상의 결과로부터 굴가수분해물은 간 보호 효과를 가지는 것으로 판단되며, 급성 간 손상의 예방 및 치료에 도움이 될 수 있는 시료로 활용될 수 있을 것으로 기대된다.
In our previous study, ...-glutamyl transpeptidase (GGT) isolated from Helicobacter pylori induced apoptosis of AGS cells. Here, we investigate Ca... effects on GGT-induced apoptosis. The GGT ...transiently and significantly increased intracellular Ca... concentration (Ca......) in AGS cells in a dose-dependent manner (P < 0.05). The GGT-induced Ca... increase resulted from Ca... influx and release through the phospholipase C - inositol 1,4,5-trisphosphate (PLC-IP3) pathway. The GGT-induced apoptosis was significantly reduced by treatment with U73122 (a PLC inhibitor) and xestospongin (an IP3 receptor antagonist) (P < 0.05). These results indicate that GGT could induce apoptosis of AGS cells by high levels of Ca...... (ProQuest: ... denotes formulae/symbols omitted.)
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