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1.
Sci Rep ; 14(1): 10631, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724633

ABSTRACT

Higher fat-to-muscle mass ratio (FMR) is reported to be a risk factor for various diseases, including type 2 diabetes and cardiovascular diseases, and mortality. Although this association suggests that reducing FMR may help to prevent certain diseases and mortality, the relationship between FMR and lifestyle factors is unclear. Therefore, we performed a cross-sectional study with the aim to elucidate this relationship. This cross-sectional study included 1518 healthy Japanese adults aged 30 to 64 years. We measured FMR in the whole body, arms, legs, and trunk and assessed various lifestyle factors. Then, we performed forced entry multiple regression analyses for FMR with the following variables: sex, age, physical activity, dietary intake, sleep quality, cigarette smoking, stress levels, and body mass index. As a result, whole-body and regional FMRs were correlated with female sex (ß = 0.71); age (ß = 0.06); physical activity (ß = - 0.07); dietary intake of protein (ß = - 0.12), carbohydrate (ß = 0.04), sodium (ß = 0.13), and fiber (ß = - 0.16); and body mass index (ß = 0.70). The results suggest that in the Japanese middle-aged population, low FMR is associated with certain lifestyle factors, i.e. higher physical activity and a diet with higher protein and fiber and lower carbohydrate and sodium, independent of age, sex, and body mass index.


Subject(s)
Dietary Carbohydrates , Dietary Fiber , Dietary Proteins , Exercise , Humans , Male , Female , Cross-Sectional Studies , Middle Aged , Adult , Exercise/physiology , Dietary Fiber/administration & dosage , Dietary Proteins/administration & dosage , Dietary Carbohydrates/administration & dosage , Body Mass Index , Japan , Muscle, Skeletal/physiology , Muscle, Skeletal/metabolism , Sodium, Dietary/administration & dosage , Adipose Tissue/metabolism , Body Composition , Life Style
2.
J Phys Ther Sci ; 36(5): 218-225, 2024 May.
Article in English | MEDLINE | ID: mdl-38694013

ABSTRACT

[Purpose] In gastric cancer patients, low muscle mass decreases overall survival and quality of life (QOL). Resistance exercise with leucine-enriched essential amino acid (LEAA) supplementation may prevent muscle mass loss. This study was aimed at determining whether resistance exercise with LEAA supplementation prevents muscle mass loss in post-gastrectomy patients. [Participant and Methods] We conducted a single-center, open-label, randomized controlled pilot trial. Ten participants who underwent gastrectomy were divided into two groups. The intervention group underwent resistance exercise at 70% of one repetition maximum and received a supplement of 3 g of LEAA twice daily for 15 days, while the control group received standard care. We compared changes in muscle mass, physical function (muscle strength and continuous walking distance), and QOL between the groups. [Results] We found good adherence and participation rates in both groups. We failed to detect a significant difference in muscle mass between the groups. The intervention group showed significant improvements in muscle strength and QOL, while the control group showed no significant changes. [Conclusion] We failed to detect a significant difference in muscle mass due to resistance exercise with LEAA supplementation in post-gastrectomy patients. However, resistance exercise with LEAA supplementation might be beneficial for muscle strength recovery and QOL improvements.

3.
Clin Psychopharmacol Neurosci ; 22(2): 354-363, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38627082

ABSTRACT

Objective: : Environmental deprivation, a type of childhood maltreatment, has been reported to constrain the cognitive developmental processes such as associative learning and implicit learning, which may lead to functional and morphological changes in the ventral pallidum (VP) and pessimism, a well-known cognitive feature of major depression. We examined whether neonatal isolation (NI) could influence the incidence of learned helplessness (LH) in a rat model mimicking the pessimism, and the number of vesicular glutamate transporter 2 (VGLUT2)-expressing VP cells and Penk-expressing VP cells. Methods: : The number of escape failures from foot-shocks in the LH test was measured to examine stress-induced depression-like behavior in rats. The number of VGLUT2-expressing VP cells and Penk-expressing VP cells was measured by immunohistochemistry. Results: : In NI rats compared with Sham rats, the incidence of LH in adulthood was increased and VGLUT2-expressing VP cells but not Penk-expressing VP cells in adulthood were decreased. VGLUT2-expressing VP cells were decreased only in the LH group of NI rats and significantly correlated with the escape latency in the LH test. Conclusion: : These findings suggest that the aberrant VP neuronal activity due to environmental deprivation early in life leads to pessimistic associative and implicit learning. Modulating VP neuronal activity could be a novel therapeutic and preventive strategy for the patients with this specific pathophysiology.

4.
Physiol Rep ; 12(7): e15991, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38605421

ABSTRACT

Skeletal muscle mass is critical for activities of daily living. Resistance training maintains or increases muscle mass, and various strategies maximize the training adaptation. Mesenchymal stem cells (MSCs) are multipotent cells with differential potency in skeletal muscle cells and the capacity to secrete growth factors. However, little is known regarding the effect of intramuscular injection of MSCs on basal muscle protein synthesis and catabolic systems after resistance training. Here, we measured changes in basal muscle protein synthesis, the ubiquitin-proteasome system, and autophagy-lysosome system-related factors after bouts of resistance exercise by intramuscular injection of MSCs. Mice performed three bouts of resistance exercise (each consisting of 50 maximal isometric contractions elicited by electrical stimulation) on the right gastrocnemius muscle every 48 h, and immediately after the first bout, mice were intramuscularly injected with either MSCs (2.0 × 106 cells) labeled with green fluorescence protein (GFP) or vehicle only placebo. Seventy-two hours after the third exercise bout, GFP was detected only in the muscle injected with MSCs with concomitant elevation of muscle protein synthesis. The injection of MSCs also increased protein ubiquitination. These results suggest that the intramuscular injection of MSCs augmented muscle protein turnover at the basal state after consecutive resistance exercise.


Subject(s)
Mesenchymal Stem Cells , Resistance Training , Humans , Male , Mice , Animals , Injections, Intramuscular , Muscle Proteins/metabolism , Activities of Daily Living , Muscle, Skeletal/metabolism , Mesenchymal Stem Cells/metabolism
5.
Cureus ; 16(3): e56241, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38618299

ABSTRACT

This study compared magnetic resonance imaging (MRI) findings of postmortem brain specimens with neuropathological findings to evaluate the value of postmortem MRI. Postmortem MRI was performed on five formalin-fixed whole brains with malignant tumors. Postmortem T2-weighted images detected all neuropathological abnormalities as high-signal regions but also showed histological tumor invasion in areas without edema. Tumor lesions with high necrosis and edema showed high signal intensity on T2-weighted images; in three cases, lesion enlargement was detected on the final prenatal imaging and postmortem MRI. Disease progression immediately before death may have contributed to this difference. In conclusion, the correlation between MRI and neuropathological findings facilitates understanding of the mechanisms responsible for MRI abnormalities. Increased free water due to edema, necrosis, and brain tissue injury can explain the increased signal intensity observed on T2-weighted images. Postmortem MRI may contribute to effective pathology by identifying subtle abnormalities prior to brain dissection.

6.
Cureus ; 16(2): e54503, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38516477

ABSTRACT

Prolactin-secreting pituitary neuroendocrine tumors (PitNETs) are more common in women. Male patients may also have few symptoms and have macroadenomas extending outside the sella turcica. This study aimed to report the results of cabergoline treatment in male patients with prolactin-secreting PitNET. The study included nine male patients aged 26-65 years (median, 46 years) diagnosed with prolactin-secreting PitNETs. The age at onset, prolactin values, tumor size, symptoms, and treatment were assessed. The mean prolactin value at the initial presentation was 2734.6 ng/mL, and the mean maximum tumor diameter was 40.4 mm. Visual field disturbance was the most common symptom (44.4%), followed by headaches (33.3%), asymptomatic symptoms (11.1%), and galactorrhea (11.1%). Eight patients responded to cabergoline treatment with normalization of prolactin levels and tumor shrinkage. One patient did not respond to the cabergoline treatment and required surgical intervention. There were no cases of cerebrospinal fluid leakage. Cabergoline was found to be an effective treatment for male prolactin-secreting PitNETs.

7.
Nat Plants ; 10(2): 206-218, 2024 02.
Article in English | MEDLINE | ID: mdl-38388723

ABSTRACT

Adjusting the microenvironment around the cell surface is critical to responding to external cues or endogenous signals and to maintaining cell activities. In plant cells, the plasma membrane is covered by the cell wall and scaffolded with cytoskeletal networks, which altogether compose the cell surface. It has long been known that these structures mutually interact, but the mechanisms that integrate the whole system are still obscure. Here we spotlight the brassinosteroid (BR) plant hormone receptor BRASSINOSTEROID INSENSITIVE1 (BRI1) since it represents an outstanding model for understanding cell surface signalling and regulation. We summarize how BRI1 activity and dynamics are controlled by plasma membrane components and their associated factors to fine-tune signalling. The downstream signals, in turn, manipulate cell surface structures by transcriptional and post-translational mechanisms. Moreover, the changes in these architectures impact BR signalling, resulting in a feedback loop formation. This Review discusses how BRI1 and BR signalling function as central hubs to integrate cell surface regulation.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Brassinosteroids/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Protein Kinases/metabolism , Cell Membrane/metabolism , Perception
8.
Langmuir ; 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38316021

ABSTRACT

Self-assembled materials have attracted attention and have been extensively studied because the reversibility of noncovalent interactions allows them to possess various properties, such as stimulus responsiveness and self-healing. Collagen model peptides have an amino acid sequence characteristic of the triple helix region of collagen and exhibit repeatable triple helix formation. Many studies of their applications have used homotrimers, and although some studies on heterotrimers have been reported, few have clarified the details. If the characteristics of heterotrimers can be revealed, they are expected to be applied as new self-assembled materials. In this study, we analyzed the detailed self-assembling properties of hetero- and homohelices formed by (proline-proline-glycine)10 (PPG)10 and (proline-hydroxyproline-glycine)10 (POG)10 to evaluate the potential of the helices for biomedical application. Fluorescein isothiocyanate-labeled (PPG)10 (F(PPG)10) and (POG)10 (F(POG)10) were synthesized to analyze the heterotriple helix formation using concentration quenching based on triple helix formation. When (PPG)10 was added to F(POG)10, the fluorescence intensity did not reach a plateau, while the fluorescence intensity reached about 100% in the other pairs such as (POG)10-F(POG)10, (PPG)10-F(PPG)10, and (POG)10-F(PPG)10. The critical triple helix formation concentration was 7 µM for the heterotrimer prepared under 1:2 mixing conditions of (PPG)10 and (POG)10, 320 µM for [(PPG)10]3, and 4 µM for [(POG)10]3, indicating that the triple helix formation concentration of the heterotrimer is almost half that of [(POG)10]3 but 45 times higher than [(PPG)10]3. Furthermore, the heterotrimer formed at 37 °C was stable after 5 days, which was the same as [(POG)10]3. These results suggest that heterotrimers have different association properties from homotrimers and are expected to be applied in nanotechnology and biomaterials as new self-assembled materials.

9.
ACS Omega ; 9(5): 5903-5910, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38343991

ABSTRACT

Calcium peroxide (CaO2) has recently attracted much attention as an oxygen-releasing biomaterial for tissue engineering. CaO2 has also been used in cancer therapies, such as photodynamic therapy. However, the uncontrollability of oxygen release after immersion in water is a challenge. Furthermore, the nanoscale surface chemistry of CaO2 on the oxygen release properties under cell culture conditions has not been taken into account in these applications. Herein, we report the stabilized amorphous calcium carbonate (ACC) nanocoating on CaO2 in a cell culture medium, which suppressed the reaction between CaO2 and water. Stabilized ACC was produced by the reaction between calcium hydroxide (Ca(OH)2) derived from CaO2 and sodium hydrogen carbonate (NaHCO3) including sodium dihydrogen phosphate (NaH2PO4) in a cell culture medium. In contrast, surface modification of CaO2 by calcium carbonate crystals was difficult due to the crystallization process via dissolution-reprecipitation. Strikingly, ACC-CaO2 showed pH-dependent oxygen release in a cell culture medium probably because of the dissolution of ACC under weak acidic condition. Since the environments in ischemic tissue and cancer are weakly acidic, our findings should be important for understanding and designing properties related to biomaterials and drugs using CaO2.

10.
Toxics ; 12(2)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38393216

ABSTRACT

Mechanically fibrillated cellulose nanofibers, known as fib-CNF (fiber length: 500 nm; diameter: 45 nm), are used in composites and as a natural thickener in foods. To evaluate their safety, we conducted a 28-day study in mice with inhalation exposure at 0.2 mg/body and oral administration of 400 mg/kg/day. Inhalation exposure to fib-CNF caused transient weight loss, changes in blood cell counts, and increased lung weights. These changes were attributed to adaptive responses. The oral administration of fib-CNF for 28 days resulted in no apparent toxic effects except for a slight decrease in platelet counts. The fib-CNF administration using the protocols studied appears to be safe in mice.

12.
Micromachines (Basel) ; 15(1)2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38258263

ABSTRACT

DNA microarrays have been applied for comprehensive genotyping, but remain a drawback in complicated operations. As a solution, we previously reported the solid-phase collateral cleavage (SPCC) system based on the clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 12 (CRISPR/Cas12). Surface-immobilized Cas12-CRISPR RNA (crRNA) can directly hybridize target double-stranded DNA (dsDNA) and subsequently produce a signal via the cleavage of single-stranded DNA (ssDNA) reporter immobilized on the same spot. Therefore, SPCC-based multiplex dsDNA detection can be performed easily. This study reports the miniaturization of SPCC-based spots patterned by a non-contact printer and its performance in comprehensive genotyping on a massively accumulated array. Initially, printing, immobilization, and washing processes of Cas12-crRNA were established to fabricate the non-contact-patterned SPCC-based sensor array. A target dsDNA concentration response was obtained based on the developed sensor array, even with a spot diameter of 0.64 ± 0.05 mm. Also, the limit of detection was 572 pM, 531 pM, and 3.04 nM with 40, 20, and 10 nL-printing of Cas12-crRNA, respectively. Furthermore, the sensor array specifically detected three dsDNA sequences in one-pot multiplexing; therefore, the feasibility of comprehensive genotyping was confirmed. These results demonstrate that our technology can be miniaturized as a CRISPR/Cas12-based microarray by using non-contact printing. In the future, the non-contact-patterned SPCC-based sensor array can be applied as an alternative tool to DNA microarrays.

13.
J Am Heart Assoc ; 13(1): e031219, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38158218

ABSTRACT

BACKGROUND: Ferroptosis, an iron-dependent form of regulated cell death, is a major cell death mode in myocardial ischemia reperfusion (I/R) injury, along with mitochondrial permeability transition-driven necrosis, which is inhibited by cyclosporine A (CsA). However, therapeutics targeting ferroptosis during myocardial I/R injury have not yet been developed. Hence, we aimed to investigate the therapeutic efficacy of deferasirox, an iron chelator, against hypoxia/reoxygenation-induced ferroptosis in cultured cardiomyocytes and myocardial I/R injury. METHODS AND RESULTS: The effects of deferasirox on hypoxia/reoxygenation-induced iron overload in the endoplasmic reticulum, lipid peroxidation, and ferroptosis were examined in cultured cardiomyocytes. In a mouse model of I/R injury, the infarct size and adverse cardiac remodeling were examined after treatment with deferasirox, CsA, or both in combination. Deferasirox suppressed hypoxia- or hypoxia/reoxygenation-induced iron overload in the endoplasmic reticulum, lipid peroxidation, and ferroptosis in cultured cardiomyocytes. Deferasirox treatment reduced iron levels in the endoplasmic reticulum and prevented increases in lipid peroxidation and ferroptosis in the I/R-injured myocardium 24 hours after I/R. Deferasirox and CsA independently reduced the infarct size after I/R injury to a similar degree, and combination therapy with deferasirox and CsA synergistically reduced the infarct size (infarct area/area at risk; control treatment: 64±2%; deferasirox treatment: 48±3%; CsA treatment: 48±4%; deferasirox+CsA treatment: 37±3%), thereby ameliorating adverse cardiac remodeling on day 14 after I/R. CONCLUSIONS: Combination therapy with deferasirox and CsA may be a clinically feasible and effective therapeutic approach for limiting I/R injury and ameliorating adverse cardiac remodeling after myocardial infarction.


Subject(s)
Ferroptosis , Iron Overload , Myocardial Infarction , Myocardial Ischemia , Myocardial Reperfusion Injury , Reperfusion Injury , Mice , Animals , Cyclosporine/pharmacology , Myocardial Reperfusion Injury/metabolism , Deferasirox/pharmacology , Deferasirox/metabolism , Deferasirox/therapeutic use , Ventricular Remodeling , Myocytes, Cardiac/metabolism , Myocardial Infarction/metabolism , Reperfusion Injury/metabolism , Iron/metabolism , Hypoxia/metabolism , Iron Overload/metabolism , Myocardial Ischemia/metabolism
14.
Physiol Rep ; 11(23): e15855, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38086691

ABSTRACT

TRPM8 agonist has been reported to promote osteogenic differentiation of mesenchymal stem cells (MSCs), therefore we evaluated whether cooling-induced activation of TRPM8 promotes myogenic differentiation of MSCs. We used 5-azacytidine as a myogenic differentiation inducer in murine bone marrow-derived MSCs. Addition of menthol, a TRPM8 agonist, to the differentiation induction medium significantly, increased the percentage of MyoD-positive cells, a specific marker of myogenic differentiation. We performed intracellular Ca2+ imaging experiments using fura-2 to confirm TRPM8 activation by cooling stimulation. The results confirmed that intracellular Ca2+ concentration ([Ca2+ ]i) increases due to TRPM8 activation, and TRPM8 antagonist inhibits increase in [Ca2+ ]i at medium temperatures below 19°C. We also examined the effect of cooling exposure time on myogenic differentiation of MSCs using an external cooling stimulus set at 17°C. The results showed that 60 min of cooling had an acceleratory effect on differentiation (2.18 ± 0.27 times). We observed that the TRPM8 antagonist counteracted the differentiation-promoting effect of the cooling. These results suggest that TRPM8 might modulate the multiple differentiation pathways of MSCs, and that cooling is an effective way of activating TRPM8, which regulates MSCs differentiation in vitro.


Subject(s)
Mesenchymal Stem Cells , TRPM Cation Channels , Mice , Animals , Osteogenesis , Mesenchymal Stem Cells/metabolism , Cell Differentiation , Cold Temperature , Azacitidine/metabolism , Azacitidine/pharmacology , TRPM Cation Channels/metabolism
15.
Nanomaterials (Basel) ; 13(22)2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37999268

ABSTRACT

Although regenerative medicine necessitates advanced three-dimensional (3D) scaffolds for organ and tissue applications, creating intricate structures across scales, from nano- to meso-like biological tissues, remains a challenge. Electrospinning of nanofibers offers promise due to its capacity to craft not only the dimensions and surfaces of individual fibers but also intricate attributes, such as anisotropy and porosity, across various materials. In this study, we used a 3D printer to design a mold with polylactic acid for gel modeling. This gel template, which was mounted on a metal wire, facilitated microfiber electrospinning. After spinning, these structures were treated with EDTA to remove the template and were then cleansed and dried, resulting in 3D microfibrous (3DMF) structures, with average fiber diameters of approximately 1 µm on the outer and inner surfaces. Notably, these structures matched their intended design dimensions without distortion or shrinkage, demonstrating the adaptability of this method for various template sizes. The cylindrical structures showed high elasticity and stretchability with an elastic modulus of 6.23 MPa. Furthermore, our method successfully mimicked complex biological tissue structures, such as the inner architecture of the voice box and the hollow partitioned structure of the heart's tricuspid valve. Achieving specific intricate shapes required multiple spinning sessions and subsequent assemblies. In essence, our approach holds potential for crafting artificial organs and forming the foundational materials for cell culture scaffolds, addressing the challenges of crafting intricate multiscale structures.

16.
Bioconjug Chem ; 34(10): 1754-1765, 2023 10 18.
Article in English | MEDLINE | ID: mdl-37782626

ABSTRACT

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 12 (Cas12) system is attracting interest for its potential as a next-generation nucleic acid detection tool. The system can recognize double-stranded DNA (dsDNA) based on Cas12-CRISPR RNA (crRNA) and induce signal transduction by collateral cleavage. This property is expected to simplify comprehensive genotyping. Here, we report a solid-phase collateral cleavage (SPCC) reaction by CRISPR/Cas12 and its application toward one-pot multiplex dsDNA detection with minimal operational steps. In the sensor, Cas12-crRNA and single-stranded DNA (ssDNA) are immobilized on the sensing surface and act as enzyme and reporter substrates, respectively. We also report a dual-target dsDNA sensor prepared by immobilizing Cas12-crRNA and a fluorophore-labeled ssDNA reporter on separate spots. When a spot captures a target dsDNA sequence, it cleaves the ssDNA reporter on the same spot and reduces its fluorescence by 42.1-57.3%. Crucially, spots targeting different sequences do not show a reduction in fluorescence, thus confirming the one-pot multiplex dsDNA detection by SPCC. Furthermore, the sequence specificity has a two-base resolution, and the detectable concentration for the target dsDNA is at least 10-9 M. In the future, the SPCC-based sensor array could achieve one-pot comprehensive genotyping by using an array spotter as a reagent-immobilizing method.


Subject(s)
CRISPR-Cas Systems , DNA , CRISPR-Cas Systems/genetics , DNA/genetics , RNA , DNA, Single-Stranded/genetics
18.
Biosensors (Basel) ; 13(8)2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37622905

ABSTRACT

The blood-brain barrier (BBB) is a selective barrier that controls the transport between the blood and neural tissue features and maintains brain homeostasis to protect the central nervous system (CNS). In vitro models can be useful to understand the role of the BBB in disease and assess the effects of drug delivery. Recently, we reported a 3D BBB model with perfusable microvasculature in a Transwell insert. It replicates several key features of the native BBB, as it showed size-selective permeability of different molecular weights of dextran, activity of the P-glycoprotein efflux pump, and functionality of receptor-mediated transcytosis (RMT), which is the most investigated pathway for the transportation of macromolecules through endothelial cells of the BBB. For quality control and permeability evaluation in commercial use, visualization and quantification of the 3D vascular lumen structures is absolutely crucial. Here, for the first time, we report a rapid, non-invasive optical coherence tomography (OCT)-based approach to quantify the microvessel network in the 3D in vitro BBB model. Briefly, we successfully obtained the 3D OCT images of the BBB model and further processed the images using three strategies: morphological imaging processing (MIP), random forest machine learning using the Trainable Weka Segmentation plugin (RF-TWS), and deep learning using pix2pix cGAN. The performance of these methods was evaluated by comparing their output images with manually selected ground truth images. It suggested that deep learning performed well on object identification of OCT images and its computation results of vessel counts and surface areas were close to the ground truth results. This study not only facilitates the permeability evaluation of the BBB model but also offers a rapid, non-invasive observational and quantitative approach for the increasing number of other 3D in vitro models.


Subject(s)
Blood-Brain Barrier , Deep Learning , Blood-Brain Barrier/diagnostic imaging , Endothelial Cells , Tomography, Optical Coherence , Microvessels/diagnostic imaging , Algorithms
19.
Circ Heart Fail ; 16(10): e010347, 2023 10.
Article in English | MEDLINE | ID: mdl-37522180

ABSTRACT

BACKGROUND: Cardiac autoantibodies (cAAbs) are involved in the progression of adverse cardiac remodeling in heart failure (HF). However, our understanding of cAAbs in HF is limited owing to the absence of relevant animal models. Herein, we aimed to establish and characterize a murine model of cAAb-positive HF after myocardial infarction (MI), thereby facilitating the development of therapeutics targeting cAAbs in post-MI HF. METHODS: MI was induced in BALB/c mice. Plasma cAAbs were evaluated using modified Western blot-based methods. Prognosis, cardiac function, inflammation, and fibrosis were compared between cAAb-positive and cAAb-negative MI mice. Rapamycin was used to inhibit cAAb production. RESULTS: Common cAAbs in BALB/c MI mice targeted cTnI (cardiac troponin I). Herein, 71% (24/34) and 44% (12/27) of the male and female MI mice, respectively, were positive for cAAbs against cTnI (cTnIAAb). Germinal centers were formed in the spleens and mediastinal lymph nodes of cTnIAAb-positive MI mice. cTnIAAb-positive MI mice showed progressive cardiac remodeling with a worse prognosis (P=0.014, by log-rank test), which was accompanied by cardiac inflammation, compared with that in cTnIAAb-negative MI mice. Rapamycin treatment during the first 7 days after MI suppressed cTnIAAb production (cTnIAAb positivity, 59% [29/49] and 7% [2/28] in MI mice treated with vehicle and rapamycin, respectively; P<0.001, by Pearson χ2 test), consequently improving the survival and ameliorating cardiac inflammation, cardiac remodeling, and HF in MI mice. CONCLUSIONS: The present post-MI HF model may accelerate our understanding of cTnIAAb and support the development of therapeutics against cTnIAAbs in post-MI HF.


Subject(s)
Heart Failure , Myocardial Infarction , Mice , Male , Female , Animals , Heart Failure/etiology , Heart Failure/complications , Myocardium/pathology , Troponin I , Disease Models, Animal , Autoantibodies , Ventricular Remodeling , Inflammation/pathology , Sirolimus
20.
Nutrients ; 15(9)2023 Apr 22.
Article in English | MEDLINE | ID: mdl-37432141

ABSTRACT

The aim of this study was to investigate the effects of increased dietary protein in daily-life settings in Japan for 6 months on the activities of daily living (ADL) in adults aged 75 or older at nutritional risk. The study was an open-label, exploratory, randomized controlled trial conducted at seven hospitals in Japan. The study participants were adults aged 75 or older who were hospitalized for treatable cancer, pneumonia, fractures, and/or urinary-tract infection at nutritional risk. The primary outcome was change in grip strength, skeletal muscle, and ADL indices (Barthel index, Lawton score). One hundred sixty-nine patients were randomly assigned to the intensive care (IC) or standard care (SC) group; the protein intake goals (g/kgw/day) were 1.5 for IC and 1.0 for SC. There was a significant improvement in grip strength only in the IC group (1.1 kg: 95% CI 0.1 to 2.1) (p = 0.02). While the skeletal muscle index and ADL indices were not significantly improved in either group, the improvement ratio tended to be greater in the IC group. There was no decrease in renal function in either group. Thus, intervention of increased dietary protein in daily-life settings for 6 months in adults aged 75 or older with treatable cancer, pneumonia, fractures, and/or urinary-tract infection and at nutritional risk may be effective in ameliorating loss of muscle strength.


Subject(s)
Activities of Daily Living , Fractures, Bone , Humans , Adult , Dietary Proteins , Research Design , Critical Care
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