Depletion and activation of microglia impact metabolic connectivity of the mouse brain.

AIM: We aimed to investigate the impact of microglial activity and microglial FDG uptake on metabolic connectivity, since microglial activation states determine FDG-PET alterations. Metabolic connectivity refers to a concept of interacting metabolic brain regions and receives growing interest in approaching complex cerebral metabolic networks in neurodegenerative diseases. However, underlying sources of metabolic connectivity remain to be elucidated. MATERIALS AND METHODS: We analyzed metabolic networks measured by interregional correlation coefficients (ICCs) of FDG-PET scans in WT mice and in mice with mutations in progranulin (Grn) or triggering receptor expressed on myeloid cells 2 (Trem2) knockouts (-/-) as well as in double mutant Grn-/-/Trem2-/- mice. We selected those rodent models as they represent opposite microglial signatures with disease associated microglia in Grn-/- mice and microglia locked in a homeostatic state in Trem2-/- mice; however, both resulting in lower glucose uptake of the brain. The direct influence of microglia on metabolic networks was further determined by microglia depletion using a CSF1R inhibitor in WT mice at two different ages. Within maps of global mean scaled regional FDG uptake, 24 pre-established volumes of interest were applied and assigned to either cortical or subcortical networks. ICCs of all region pairs were calculated and z-transformed prior to group comparisons. FDG uptake of neurons, microglia, and astrocytes was determined in Grn-/- and WT mice via assessment of single cell tracer uptake (scRadiotracing). RESULTS: Microglia depletion by CSF1R inhibition resulted in a strong decrease of metabolic connectivity defined by decrease of mean cortical ICCs in WT mice at both ages studied (6-7 m; p = 0.0148, 9-10 m; p = 0.0191), when compared to vehicle-treated age-matched WT mice. Grn-/-, Trem2-/- and Grn-/-/Trem2-/- mice all displayed reduced FDG-PET signals when compared to WT mice. However, when analyzing metabolic networks, a distinct increase of ICCs was observed in Grn-/- mice when compared to WT mice in cortical (p < 0.0001) and hippocampal (p < 0.0001) networks. In contrast, Trem2-/- mice did not show significant alterations in metabolic connectivity when compared to WT. Furthermore, the increased metabolic connectivity in Grn-/- mice was completely suppressed in Grn-/-/Trem2-/- mice. Grn-/- mice exhibited a severe loss of neuronal FDG uptake (- 61%, p < 0.0001) which shifted allocation of cellular brain FDG uptake to microglia (42% in Grn-/- vs. 22% in WT). CONCLUSIONS: Presence, absence, and activation of microglia have a strong impact on metabolic connectivity of the mouse brain. Enhanced metabolic connectivity is associated with increased microglial FDG allocation.

Improved blood pressure and flow-mediated dilatation via increased plasma adropin and nitrate/nitrite induced by high-intensity interval training in patients with type 2 diabetes.

NEW FINDINGS: What is the central question of this study? Exercise training increases adropin and nitrite/nitrate (NOx) plasma levels in middle-aged and older healthy people. We hypothesized that high-intensity interval training may improve blood pressure and flow-mediated dilatation through the effects of adropin and NOx in patients of this age with type 2 diabetes. What is the main finding and its importance? High-intensity interval training may be more effective than moderate-intensity continuous training in improving endothelial function, blood pressure and flow-mediated dilatation through its effects on adropin and NOx in patients with type 2 diabetes. ABSTRACT: Adropin is a newly identified bioactive protein that is important in energy hemostasis and vascular endothelial function. Lower levels of adropin in patients with type 2 diabetes are related to coronary atherosclerosis, characterized by impaired flow-mediated dilatation (FMD). The purpose of the present study was to investigate FMD and plasma levels of adropin and nitrite/nitrate (NOx) in patients with type 2 diabetes at baseline and follow-up after 12 weeks of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). Sixty-six persons with type 2 diabetes were divided into HIIT, MICT, and control groups. The HIIT group intervention was 12 intervals (1.5 min) at 85-90% maximal heart rate (HRmax ) separated by 2 min at 55-60% HRmax in three sessions per week for 12 weeks. MICT training consisted of 42 min of cycling at 70% HRmax . Before and after the intervention, FMD was recorded with high-resolution Doppler ultrasound. Plasma levels of adropin and NOx were measured by enzyme-linked immunosorbent assay. After training FMD was significantly higher in the MICT and HIIT groups compared to the control group (P < 0.05). Plasma levels of adropin and NOx were higher in both exercise groups, but the increase was greater in the HIIT group (P < 0.01). Peak oxygen consumption was increased after exercise training in both groups compared to the control group (P < 0.01). Percentage FMD showed a positive correlation with plasma levels of adropin and NOx (both P < 0.01), and a negative correlation with diastolic blood pressure (r = -0.530, P = 0.035) and systolic blood pressure (r = -0.606, P = 0.013) in the HIIT group. The results indicate that HIIT improved FMD whilst increasing adropin, NOx and peak oxygen consumption. Increased plasma levels of adropin may contribute, in part, to blood pressure reduction by increasing nitric oxide production.

Level of agreement in three-dimensional planimetric measurement of mitral valve area between transthoracic and transesophageal echocardiography.

BACKGROUND: Echocardiographic measurement of mitral valve area (MVA) is critical prior to percutaneous transmitral commissurotomy (PTMC). This study aimed to compare the agreement between transthoracic (TTE) and transesophageal echocardiography (TEE) in three-dimensional (3D) planimetric measurement of the MVA among patients with severe mitral stenosis. METHODS: MVA was measured with planimetry in 105 patients before undergoing PTMC. 3D reconstruction was applied to both TTE and TEE examinations. The MVA values from four different methods of 3D reconstruction were compared to the average values of 3D methods in TEE as the gold standard measurement method for the MVA in this study. The agreement levels between the two examinations were evaluated and analyzed for various reconstruction methods. RESULTS: The mean age was 49 ± 12 years for 28 men and 77 women who were enrolled. The image quality was graded as "excellent" in 57% of 3D images obtained by TTE, while it was graded as "excellent" in 81% of 3D images obtained by TEE. The ventricular zooming method in TTE with a bias of -0.006 ± 0.065 cm2 (P < 0.0001) had the highest agreement with the 3D-MVA in TEE. While 2D-TTE and 3D-TEE measurements of the MVA (R = 0.91; P < 0.0001) were significantly correlated, 2D-TTE overestimated the MVA by 0.19 cm2 . CONCLUSION: Although the quality of 3D images was significantly better in TEE than those in TTE, a good agreement existed between the measured 3D-TTE and 3D-TEE studies. We also demonstrated that 2D-TTE overestimated the MVA compare to 3D-TEE.

In vitro differentiation of menstrual blood stem cells into keratinocytes: A potential approach for management of wound healing.

The skin wounds caused by insults should be treated immediately to restore the functions and integrity. Recent studies suggest that stem cells-based therapies may be applicable in wound healing. Newly defined menstrual blood-derived stem cells (MenSCs) show high rate of cell proliferation and trans-differentiation potency to various cell types. However, MenSCs potential to generate keratinocyte for future therapeutic use of skin lesions has been remained to investigate. We cultivated MenSCs in the presence of isolated foreskin derived-keratinocytes using an indirect co-culture system and evaluated efficiency of this protocol to generate keratinocytes using immunofluorescent staining and Real Time PCR technique. Our results showed that differentiated keratinocytes express epidermal/keratinocytes lineage specific markers such as K14, p63, and involucrin at both mRNA and protein levels. Immunofluorescent staining showed the expression of involucrin and K14 in differentiated cells in contrast to undifferentiated cells. Moreover, mRNA expression levels of K14 (11.1 folds, p = 0.001), p63 (10.23 folds, p = 0.001), and involucrin (2.94 folds, p = 0.001) were higher in differentiated MenSCs compared to non-cocultured cells. Therefore, we firstly presented evidence about differentiation capability of MenSCs into epidermal/keratinocytes lineage. Considering the advantages of MenSCs such as great accessibility, these stem cells are promising for stem cells-based therapies of skin defects.

Assessment of protective effects of glucosamine and N-acetyl glucosamine against DNA damage induced by hydrogen peroxide in human lymphocytes.

The antigenotoxic activity of glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) in human peripheral lymphocytes exposed to oxidative stress was investigated. Human lymphocytes were treated with different concentrations of these aminosugars (0, 2.5, 5, 10, 20 and 40 mM) and 25 µM H2O2 simultaneously and evaluated by single cell gel electrophoresis technique (Comet assay). The single cells were analyzed using "TriTek Cometscore version 1.5" software and the data were presented as % DNA in tail. Both GlcN and GlcNAc at examined concentrations (2.5, 5, 10, 20 and 40 mM) did not reveal any genotoxicity compared to the vehicle control (PBS). Glucosamine at all concentrations (2.5, 5, 10, 20 and 40 mM) showed a significant protective activity (% DNA in tail ranging from 16.07 ± 0.85 to 5.47 ± 0.26, p < 0.001) against H2O2 induced DNA damage (% DNA in tail = 38 ± 0.65) while its N-acetylated analog only indicated a slight DNA protection at concentration of 40 mM (% DNA in tail = 33.4 ± 1.17, p < 0.01). We concluded that GlcN at tested concentrations exhibited potent antigenotoxic effect and its protection activity might be related to the presence of 2-NH2 moiety in its chemical backbone.

Machine learning assisted modelling of anaerobic digestion of waste activated sludge coupled with hydrothermal pre-treatment.

This study utilizes decision-tree-based models, including Random Forest, XGBoost, artificial neural networks (ANNs), support vector machine regressors, and K nearest neighbors algorithms, to predict sludge solubilization and methane yield in hydrothermal pretreatment (HTP) coupled with anaerobic digestion (AD) processes. Analyzing two decades of published research, we find that ANN models exhibit superior fitting accuracy for solubilization prediction, while decision-tree models excel in methane yield prediction. Pretreatment temperature is identified as pivotal among various variables, and heating time surprisingly emerges as equally significant as holding time for solubilization and surpasses it for methane yield. Contrary to prior expectations, the HTP method's impact on sludge solubilization and AD performance is minimal. This study underscores data-driven models' potential as resource-efficient tools for optimizing advanced AD processes with HTP. Notably, our research spans nearly two decades of lab, pilot, and full-scale studies, offering novel insights not previously explored.

Sildenafil-induced spinal cord infarction: a case report.

Spinal cord infarction is a rare condition, accounting for only a small percentage of strokes. It can be classified into cervical and thoracolumbar infarctions, with various factors contributing to its occurrence. Sildenafil, a phosphodiesterase type 5 inhibitor commonly used for erectile dysfunction, has been associated with cardiovascular side effects, including transient hypotension. In this case report, we present the unusual occurrence of spinal cord infarction in a 65-year-old man who had self-administered high doses of sildenafil without a doctor's prescription. The patient experienced severe radicular pain in the lumbar region and subsequent weakness in the lower limbs. Evaluation revealed an anterior spinal cord infarction in the thoracic region, confirmed by MRI imaging. After excluding other potential causes, it was concluded that the intake of sildenafil likely led to systemic hypotension, resulting in spinal cord infarction. This case highlights the importance of considering sildenafil as a possible contributor to spinal cord infarction, particularly when used at high doses. Further studies are needed to better understand the relationship between sildenafil and vascular complications, including spinal cord infarction.

Nutritional interventions for exercise-induced muscle damage: an umbrella review of systematic reviews and meta-analyses of randomized trials.

CONTEXT: Several meta-analyses have been conducted on the effect of nutritional interventions on various factors related to muscle damage. However, the strength of the evidence and its clinical significance are unclear. OBJECTIVES: This umbrella review aimed to provide an evidence-based overview of nutritional interventions for exercise-induced muscle damage (EIMD). DATA SOURCES: PubMed, Scopus, and ISI Web of Science were systematically searched up to May 2022. DATA EXTRACTION: Systematic reviews and meta-analyses of randomized controlled trials investigating nutritional interventions' effects on recovery following EIMD were included. The certainty of the evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Fifty-three randomized controlled trial meta-analyses were included, evaluating 24 nutritional interventions on 10 different outcomes. The results revealed a significant effect of hydroxymethylbutyrate (HMB) supplementation and l-carnitine supplementation for reducing postexercise creatine kinase; HMB supplementation for reducing lactate dehydrogenase; branched-chain amino acids and leaf extract supplementation for reducing the delayed onset of muscle soreness; and l-carnitine, curcumin, ginseng, polyphenols, and anthocyanins for reducing muscle soreness, all with moderate certainty of evidence. CONCLUSIONS: Supplementation with HMB, l-carnitine, branched-chain amino acids, curcumin, ginseng, leaf extract, polyphenols, and anthocyanins showed favorable effects on some EIMD-related outcomes. PROTOCOL REGISTRATION: PROSPERO registration no. CRD42022352565.

Community health workers (Behvarz) in primary health care: a qualitative inductive content analysis of challenges.

BACKGROUND: Behvarzs are the backbone of primary healthcare services in the Iranian health system and play a key role in providing efficient, responsive, and equitable services at the first level of service provision. This study aimed to identify the challenges of Behvarzs to provide a perspective for policymakers and managers to help them formulate future programs to enhance the efficiency of the health system. METHODS: Following a qualitative design, an inductive content analysis approach was used to analyse the data. The healthcare network of the Alborz province (Iran) was considered as the study context. A total of 27 interviews were conducted with policymakers, development managers, managers of Behavrz training centres, and Behvarz workers in 2020. All interviews were audio-taped and transcribed, followed by data analysis using MAXQDA ver. 10. RESULTS: Five themes were identified: service provision (scope of services, ambiguity of roles, non-compliance with the referral system, the quality of data entry, quality of services), access to equipment (quantity, quality), administrative issues (macro planning, micro planning), training (appropriateness of information, quality of training, recruiting related staff), perceived equity and fairness (balance between workload, income, and benefits, job satisfaction, job promotion). CONCLUSION: Occupational challenges affect the performance of Behvarzs in responding to society's needs because they not only play a major role in the health system, but also contribute to addressing the communication gap between local communities and high-level institutions, leading to the alignment of policy implementation. Therefore, strategies that emphasise the role of Behvarzs should be followed to promote community engagement.

Neurons on tape: Automated Tape Collecting Ultramicrotomy-mediated volume EM for targeting neuropathology.

In this chapter, we review Automated Tape Collecting Ultramicrotomy (ATUM), which, among other array tomography methods, substantially simplified large-scale volume electron microscopy (vEM) projects. vEM reveals biological structures at nanometer resolution in three dimensions and resolves ambiguities of two-dimensional representations. However, as the structures of interest-like disease hallmarks emerging from neuropathology-are often rare but the field of view is small, this can easily turn a vEM project into a needle in a haystack problem. One solution for this is correlated light and electron microscopy (CLEM), providing tissue context, dynamic and molecular features before switching to targeted vEM to hone in on the object's ultrastructure. This requires precise coordinate transfer between the two imaging modalities (e.g., by micro computed tomography), especially for block face vEM which relies on physical destruction of sections. With array tomography methods, serial ultrathin sections are collected into a tissue library, thus allowing storage of precious samples like human biopsies and enabling repetitive imaging at different resolution levels for an SEM-based search strategy. For this, ATUM has been developed to reliably collect serial ultrathin sections via a conveyor belt onto a plastic tape that is later mounted onto silicon wafers for serial scanning EM (SEM). The ATUM-SEM procedure is highly modular and can be divided into sample preparation, serial ultramicrotomy onto tape, mounting, serial image acquisition-after which the acquired image stacks can be used for analysis. Here, we describe the steps of this workflow and how ATUM-SEM enables targeting and high resolution imaging of specific structures. ATUM-SEM is widely applicable. To illustrate this, we exemplify the approach by reconstructions of focal pathology in an Alzheimer mouse model and CLEM of a specific cortical synapse.

Breast cancer metastasis to pituitary infandibulum.

Metastasis from breast cancer to other parts of the body is very common, but the spread of the tumor to pituitary gland, especially to infandibulum, is a rare presentation. At the time of pituitary metastasis, a majority of the patients have clinical and radiological evidence of the disease. It seems that the posterior area of the gland is the most common site of metastasis, probably due to highly rich blood supply through the hypophyseal artery. The present report introduces a case of a 55-years-old woman presented with diabetes insipidus resulting from metastasis of the tumor to pituitary infandibulum, which is a rare site for metastasis, without significant complaint resulting from metastasis to other part of the body, or other primary diseases. Further evaluation revealed that in spite of previous reports, which metastasis usually happens in end stage of cancer, the patients had primary breast cancer. In subsequent evaluations of the case, hypofunction of adenohypophysis was also detected.

A Method for Optimal Detection of Lung Cancer Based on Deep Learning Optimized by Marine Predators Algorithm.

Lung cancer is the uncontrolled growth of cells in the lung that are made up of two spongy organs located in the chest. These cells may penetrate outside the lungs in a process called metastasis and spread to tissues and organs in the body. In this paper, using image processing, deep learning, and metaheuristic, an optimal methodology is proposed for early detection of this cancer. Here, we design a new convolutional neural network for this purpose. Marine predators algorithm is also used for optimal arrangement and better network accuracy. The method finally applied to RIDER dataset, and the results are compared with some pretrained deep networks, including CNN ResNet-18, GoogLeNet, AlexNet, and VGG-19. Final results showed higher results of the proposed method toward the compared techniques. The results showed that the proposed MPA-based method with 93.4% accuracy, 98.4% sensitivity, and 97.1% specificity provides the highest efficiency with the least error (1.6) toward the other state of the art methods.

The Therapeutic Potential of MAPK/ERK Inhibitors in the Treatment of Colorectal Cancer.

The MAPK/ERK signaling pathway regulates cancer cell proliferation, apoptosis, inflammation, angiogenesis, metastasis and drug resistance. Mutations and up-regulation of components of the MAPK/ERK signaling pathway, as well as over-activation of this critical signaling pathway, are frequently observed in colorectal carcinomas. Targeting the MAPK/ERK signaling pathway, using specific pharmacological inhibitors, elicits potent anti-tumor effects, supporting the therapeutic potential of these inhibitors in the treatment of CRC. Several drugs have recently been developed for the inhibition of the MEK/ERK pathway in preclinical and clinical settings, such as MEK162 and MK-2206. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity for the treatment of this malignancy. This review summarizes the current knowledge on the role of the MAPK/ERK signaling pathway in the pathogenesis of CRC and the potential clinical value of synthetic inhibitors of this pathway in preventing CRC progression for a better understanding, and hence, better management of colorectal cancer.

Improved carotid intima-media thickness-induced high-intensity interval training associated with decreased serum levels of Dkk-1 and sclerostin in type 2 diabetes.

AIMS: Carotid intima-media thickness (cIMT) is a validated surrogate marker of atherosclerosis. Dickkopf-1 (Dkk-1) and sclerostin modulate wingless signaling, which is involved in atherosclerosis. The purpose of this study was to investigate whether 12 weeks of high-intensity interval training (HIIT) would improve cIMT and serum Dkk-1 and sclerostin levels in patients with type 2 diabetes. METHODS: Seventy-four sedentary patients with type 2 diabetes were randomly divided into HIIT and control groups. The HIIT group intervention was 6 intervals (4 min) at 85%-90% HRmax separated by 3 min at 45%-50% HRmax in 3 sessions/week for 12 weeks. Before and after the intervention, cIMT, artery diameter and wall/lm ratio were recorded with high-resolution ultrasound. Serum sclerostin and Dkk-1 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: cIMT decreased significantly in the HIIT group (0.83 ±â€¯0.17 baseline, 0.71 ±â€¯0.14 follow-up) compared to the control group (0.84 ±â€¯0.20 baseline, 0.85 ±â€¯0.19 follow-up) (P < .05). Dkk-1 and sclerostin decreased significantly after 12 weeks of HIIT (P < .01). In addition, VO2peak was increased in the HIIT group than the control group (by 6.2 mL/kg/min) (P < .05). There was a positive correlation between percent changes in cIMT and percent changes in Dkk-1 and sclerostin (both P < .01). Additionally, there were a negative correlation between percent changes VO2peak and cIMT (r = - 0.740, P = .003), Dkk-1 (r = - 0.844, P < .001) and sclerostin (r = - 0.575, P = .001) in HIIT group. CONCLUSION: Our results indicate that HIIT decreases cIMT, serum levels of Dkk-1 and sclerostin and improves VO2peak in patients with type 2 diabetes.

Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain.

An evolutionarily conserved function of glia is to provide metabolic and structural support for neurons. To identify molecules generated by glia and with vital functions for neurons, we used Drosophila melanogaster as a screening tool, and subsequently translated the findings to mice. We found that a cargo receptor operating in the secretory pathway of glia was essential to maintain axonal integrity by regulating iron buffering. Ferritin heavy chain was identified as the critical secretory cargo, required for the protection against iron-mediated ferroptotic axonal damage. In mice, ferritin heavy chain is highly expressed by oligodendrocytes and secreted by employing an unconventional secretion pathway involving extracellular vesicles. Disrupting the release of extracellular vesicles or the expression of ferritin heavy chain in oligodendrocytes causes neuronal loss and oxidative damage in mice. Our data point to a role of oligodendrocytes in providing an antioxidant defense system to support neurons against iron-mediated cytotoxicity.

Alendronate improves fasting plasma glucose and insulin sensitivity, and decreases insulin resistance in prediabetic osteopenic postmenopausal women: A randomized triple-blind clinical trial.

AIMS/INTRODUCTION: Postmenopausal women receive bisphosphonates for osteoporosis treatment. The effect of these medications on developing diabetes mellitus in prediabetic patients is yet to be investigated. We aimed to determine the effect of alendronate on plasma glucose, insulin indices of postmenopausal women with prediabetes and osteopenia. MATERIALS AND METHODS: The present triple-blind randomized controlled clinical trial included 60 postmenopausal women, aged 45-60 years. All patients were vitamin D sufficient. They were randomly enrolled in intervention (70 mg/week alendronate for 12 weeks) and control (placebo tablet per week for 12 weeks) groups. The morning 8-h fasting blood samples were collected at the baseline and follow-up visits to measure the fasting plasma glucose (mg/dL), insulin and hemoglobin A1c (HbA1c). Plasma glucose and insulin concentration were measured 30, 60 and 120 min after the glucose tolerance test. The Matsuda Index, homeostasis model assessment of insulin resistance, homeostasis model assessment of ß-cell function and the area under the curves of glucose and insulin were calculated. RESULTS: The mean (standard deviation) fasting plasma glucose (102.43 [1.46] mg/dL vs 94.23 [1.17] mg/dL, P = 0.001), 120-min insulin concentration (101.86 [15.70] mU/L vs 72.60 [11.36] mU/L, P = 0.026), HbA1c (5.60 [0.06]% vs 5.40 [0.05]%, P = 0.001), homeostasis model assessment of insulin resistance (3.57 [0.45] vs 2.62 [0.24], P = 0.021) and Matsuda Index (7.7 [0.41] vs 9.2 [0.4], P = 0.001) significantly improved in the alendronate-treated group. There were more statistically significant reductions in fasting plasma glucose (-8.2 [8.63] mg/dL vs -2.5 [14.26] mg/dL, P = 0.002) and HbA1c (-0.2 [0.23]% vs -0.09 [0.26]%, P = 0.015) observed in the alendronate-treated group than the placebo group during the study course, respectively. CONCLUSIONS: Administration of 70 mg/week alendronate improves fasting plasma glucose, HbA1c and insulin indices in postmenopausal women.

High-intensity interval training lowers blood pressure and improves apelin and NOx plasma levels in older treated hypertensive individuals.

Hypertension is the major risk factor for cardiovascular diseases and is one of the primary causes of morbidity and mortality worldwide. Apelin levels and NO bioavailability are impaired in older hypertensive patients. Exercise is an effective intervention for treating hypertension. Our purpose was to evaluate the effect of high-intensity interval training on blood pressure, apelin, and NOx plasma levels in older treated hypertensive individuals. Thirty treated hypertensive subjects (61.70 ± 5.78 years, 17 males, 13 females) were randomly divided into 6 weeks of high-intensity interval training (n = 15) and control (n = 15). The exercise training was conducted for three 35-min sessions a week (1.5-min interval at 85-90% of heart rate reserve [HRR] and 2 min active phase at 50-55% of HRR). Assessment of plasma apelin, nitrite/nitrate (NOx), and endothelin-1 (ET-1) was performed before and after the intervention. At the end of the study, apelin, and NOx plasma levels increased significantly in the high-intensity interval training (HIIT) group (P = 0.021, P = 0.003, respectively). Conversely, ET-1 plasma levels significantly decreased in the training group after the intervention (P = 0.015). Moreover, there was a positive correlation between the change of plasma apelin and change of plasma NOx (r = 0. 771, P = 0.0008). In addition, there was a negative correlation between the change of plasma ET-1, change of plasma apelin (r = - 0.595, P = 0.019), and variation of NOx (r = - 0.572, P = 0.025). This study indicates that, by increasing of apelin and NOx plasma levels, HIIT may be effective in reducing blood pressure.

Bilayer Amniotic Membrane/Nano-fibrous Fibroin Scaffold Promotes Differentiation Capability of Menstrual Blood Stem Cells into Keratinocyte-Like Cells.

The skin provides a dynamic barrier separating and protecting human body from the exterior world, and then immediate repair and rebuilding of the epidermal barrier is crucial after wound and injury. Wound healing without scars and complete regeneration of skin tissue still remain as a clinical challenge. The demand to engineer scaffolds that actively promote regeneration of damaged areas of the skin has been increased. In this study, menstrual blood-derived stem cells (MenSCs) have been induced to differentiate into keratinocytes-like cells in the presence of human foreskin-derived keratinocytes on a bilayer scaffold based on amniotic membrane and silk fibroin. Based on the findings, newly differentiated keratinocytes from MenSCs successfully expressed the keratinocytes specific markers at both mRNA and protein levels judged by real-time PCR and immunostaining techniques, respectively. We could show that the differentiated cells over bilayer composite scaffolds express the keratinocytes specific markers at higher levels when compared with those cultured in conventional 2D culture system. Based on these findings, bilayer amniotic membrane/nano-fibrous fibroin scaffold represents an efficient natural construct with broad applicability to generate keratinocytes from MenSCs for stem cell-based skin wounds healing and regeneration.

Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions.

The turnover of brain proteins is critical for organism survival, and its perturbations are linked to pathology. Nevertheless, protein lifetimes have been difficult to obtain in vivo. They are readily measured in vitro by feeding cells with isotopically labeled amino acids, followed by mass spectrometry analyses. In vivo proteins are generated from at least two sources: labeled amino acids from the diet, and non-labeled amino acids from the degradation of pre-existing proteins. This renders measurements difficult. Here we solved this problem rigorously with a workflow that combines mouse in vivo isotopic labeling, mass spectrometry, and mathematical modeling. We also established several independent approaches to test and validate the results. This enabled us to measure the accurate lifetimes of ~3500 brain proteins. The high precision of our data provided a large set of biologically significant observations, including pathway-, organelle-, organ-, or cell-specific effects, along with a comprehensive catalog of extremely long-lived proteins (ELLPs).

Safety concerns related to modular/prefabricated building construction.

The US construction industry annually experiences a relatively high rate of fatalities and injuries; therefore, improving safety practices should be considered a top priority for this industry. Modular/prefabricated building construction is a construction strategy that involves manufacturing of the whole building or some of its components off-site. This research focuses on the safety performance of the modular/prefabricated building construction sector during both manufacturing and on-site processes. This safety evaluation can serve as the starting point for improving the safety performance of this sector. Research was conducted based on Occupational Safety and Health Administration investigated accidents. The study found 125 accidents related to modular/prefabricated building construction. The details of each accident were closely examined to identify the types of injury and underlying causes. Out of 125 accidents, there were 48 fatalities (38.4%), 63 hospitalized injuries (50.4%), and 14 non-hospitalized injuries (11.2%). It was found that, the most common type of injury in modular/prefabricated construction was 'fracture', and the most common cause of accidents was 'fall'. The most frequent cause of cause (underlying and root cause) was 'unstable structure'. In this research, the accidents were also examined in terms of corresponding location, occupation, equipment as well as activities during which the accidents occurred. For improving safety records of the modular/prefabricated construction sector, this study recommends that future research be conducted on stabilizing structures during their lifting, storing, and permanent installation, securing fall protection systems during on-site assembly of components while working from heights, and developing training programmes and standards focused on modular/prefabricated construction.