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The aim of the present trial was to investigate the effect of two stretching programs, a dynamic and a static one, on the sprint ability of recreational volleyball players. The sample consisted of 27 male recreational volleyball players (age 21.6 ± 2.1 years, mean ± standard deviation, body mass 80.3 ± 8.9 kg, height 1.82 ± 0.06 m, body mass index 24.3 ± 2.5 kg.m-2, volleyball experience 7.7 ± 2.9 years). Participants were randomly divided into three groups: (a) the first performing dynamic stretching exercises three times per week, (b) the second following a static stretching protocol on the same frequency, and (c) the third being the control group, abstaining from any stretching protocol. The duration of the stretching exercise intervention period was 6 weeks, with all groups performing baseline and final field sprinting tests at 4.5 and 9 m. The post-test sprint times were faster in both the 4.5 (p = 0.027, η2 = 0.188) and 9 m tests (p < 0.001, η2 = 0.605) compared to the pre-test values. A large time × group interaction was shown in both the 4.5 (p = 0.007, η2 = 0.341) and 9 m tests (p = 0.004, η2 = 0.363) with the static and dynamic stretching groups being faster in the post-test than in the pre-test, whereas no change was found in the control group. The percentage change in the 4.5 m sprint time correlated with volleyball experience (r = -0.38, p = 0.050), i.e., the longer the volleyball experience, the larger the improvement in the 4.5 m sprint. Thus, it is concluded that both stretching techniques have a positive effect on the velocity of recreational male volleyball players, when performed at a frequency of three times per week for 6 weeks under the same conditions as defined in the study protocol.
High temperatures seriously limit plant growth and productivity. Investigating heat-responsive molecular mechanisms is important for breeding heat-tolerant crops. In this study, heat-responsive mechanisms in leaves from a heat-sensitive spinach (Spinacia oleracea L.) variety Sp73 were investigated using two-dimensional gel electrophoresis (2DE)-based and isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics approaches. In total, 257 heat-responsive proteins were identified in the spinach leaves. The abundance patterns of these proteins indicated that the photosynthesis process was inhibited, reactive oxygen species (ROS) scavenging pathways were initiated, and protein synthesis and turnover, carbohydrate and amino acid metabolism were promoted in the spinach Sp73 in response to high temperature. By comparing this with our previous results in the heat-tolerant spinach variety Sp75, we found that heat inhibited photosynthesis, as well as heat-enhanced ROS scavenging, stress defense pathways, carbohydrate and energy metabolism, and protein folding and turnover constituting a conservative strategy for spinach in response to heat stress. However, the heat-decreased biosynthesis of chlorophyll and carotenoid as well as soluble sugar content in the variety Sp73 was quite different from that in the variety Sp75, leading to a lower capability for photosynthetic adaptation and osmotic homeostasis in Sp73 under heat stress. Moreover, the heat-reduced activities of SOD and other heat-activated antioxidant enzymes in the heat-sensitive variety Sp73 were also different from the heat-tolerant variety Sp75, implying that the ROS scavenging strategy is critical for heat tolerance.
As is known, many antioxidants from plant extracts have been used as additives in skincare products to prevent skin damage following overexposure to environmental pollutants. 7,3',4'-trihydroxyisoflavone (734THIF), an isoflavone compound, possesses various biological activities, including antioxidant, antityrosinase, photodamage protection, and anticancer effects. Unfortunately, 734THIF has poor water solubility, which limits its skin penetration and absorption, and subsequently influences its biological activity. The aim of the present study was to investigate the mechanisms for the improvement in water solubility and skin penetration of 2-hydroxypropyl-β-cyclodextrin (HPBCD) inclusion complex with 734THIF (5-7HP). We also determined its photostability, antipollutant activity in HaCaT keratinocytes, and moisturizing effect in human subjects. Our results showed that 734THIF was embedded into the lipophilic inner cavity of HPBCD and its water solubility and skin penetration were thereby improved through amorphous transformation, surface area enhancement, and hydrogen bonding formation between 734THIF and HPBCD. In addition, 5-7HP inhibited PM-induced ROS generation and then downregulated ROS-mediated COX-2 and MMP9 production and AQP-3 consumption by inhibiting the phosphorylation of MAPKs. Consequently, we suggest that 5-7HP is a safe and photostable topical ingredient to enhance the skin penetration of 734THIF and skin hydration, and therefore 5-7HP may be used as an antipollutant additive in skin care products.
Insect bite hypersensitivity (IBH), which is a cutaneous allergic reaction to antigens from Culicoides spp., is the most prevalent skin disorder in horses. Misdiagnosis is possible, as IBH is usually diagnosed based on clinical signs. Our study is the first to employ IgE levels against several recombinant Culicoides spp. allergens as an objective, independent, and quantitative phenotype to improve the power to detect genetic variants that underlie IBH. Genotypes of 200 Shetland ponies, 127 Icelandic horses, and 223 Belgian Warmblood horses were analyzed while using a mixed model approach. No single-nucleotide polymorphism (SNP) passed the Bonferroni corrected significance threshold, but several regions were identified within and across breeds, which confirmed previously identified regions of interest and, in addition, identifying new regions of interest. Allergen-specific IgE levels are a continuous and objective phenotype that allow for more powerful analyses when compared to a case-control set-up, as more significant associations were obtained. However, the use of a higher density array seems necessary to fully employ the use of IgE levels as a phenotype. While these results still require validation in a large independent dataset, the use of allergen-specific IgE levels showed value as an objective and continuous phenotype that can deepen our understanding of the biology underlying IBH.
A dose of proanthocyanidins with satiating properties proved to be able to limit body weight increase several weeks after administration under exposure to a cafeteria diet. Here we describe some of the molecular targets and the duration of the effects. We treated rats with 500 mg grape seed proanthocyanidin extract (GSPE)/kg BW for ten days. Seven or seventeen weeks after the last GSPE dose, while animals were on a cafeteria diet, we used reverse transcriptase-polymerase chain reaction (RT-PCR) to measure the mRNA of the key energy metabolism enzymes from the liver, adipose depots and muscle. We found that a reduction in the expression of adipose Lpl might explain the lower amount of adipose tissue in rats seven weeks after the last GSPE dose. The liver showed increased expression of Cpt1a and Hmgs2 together with a reduction in Fasn and Dgat2. In addition, muscle showed a higher fatty oxidation (Oxct1 and Cpt1b mRNA). However, after seventeen weeks, there was a completely different gene expression pattern. At the conclusion of the study, seven weeks after the last GSPE administration there was a limitation in adipose accrual that might be mediated by an inhibition of the gene expression of the adipose tissue Lpl. Concomitantly there was an increase in fatty acid oxidation in liver and muscle.
Dengue, West Nile and Zika, closely related viruses of the Flaviviridae family, are an increasing global threat, due to the expansion of their mosquito vectors. They present a very similar viral particle with an outer lipid bilayer containing two viral proteins and, within it, the nucleocapsid core. This core is composed by the viral RNA complexed with multiple copies of the capsid protein, a crucial structural protein that mediates not only viral assembly, but also encapsidation, by interacting with host lipid systems. The capsid is a homodimeric protein that contains a disordered N-terminal region, an intermediate flexible fold section and a very stable conserved fold region. Since a better understanding of its structure can give light into its biological activity, here, first, we compared and analyzed relevant mosquito-borne Flavivirus capsid protein sequences and their predicted structures. Then, we studied the alternative conformations enabled by the N-terminal region. Finally, using dengue virus capsid protein as main model, we correlated the protein size, thermal stability and function with its structure/dynamics features. The findings suggest that the capsid protein interaction with host lipid systems leads to minor allosteric changes that may modulate the specific binding of the protein to the viral RNA. Such mechanism can be targeted in future drug development strategies, namely by using improved versions of pep14-23, a dengue virus capsid protein peptide inhibitor, previously developed by us. Such knowledge can yield promising advances against Zika, dengue and closely related Flavivirus.
Chronic inflammation contributes to the risk of osteoporosis and fracture. Dietary Inflammatory Index (DII), a novel method appraising the inflammatory potential of diet, has been utilized to examine the association between diet and bone health among postmenopausal women or the elderly. However, its relationship with bone density (BD) in lactating women has not been studied.
Internationally, acute homelessness is commonly associated with complex health and social care needs. While homelessness can be understood as an outcome of structural housing exclusion requiring housing led solutions, the health care issues faced by homeless people equally require attention. A substantive evidence base on the health needs of homeless people exists, but relatively little is known about what influences the self-rated health of homeless people. This article presents new evidence on whether drug use (alcohol consumption, ever having used drugs), health variables (visiting a hospital once in the last year, visiting the doctor in the last month, having a health card, sleeping difficulties, and having a disabling impairment) and sociodemographic characteristics are significantly associated with Self-Rated Health (SRH) among Spanish homeless people.
The role of calcineurin/NFAT signaling in ovarian cancer has been unknown. NFAT was significantly overexpressed in ovarian cancer tissues and that overexpression of NFAT was significantly associated with metastasis and poor prognosis on clinical tissue level. To investigate whether NFAT upstream protein, calcineurin (CN), affects the prognosis in various histological subtype of ovarian cancer (OC).
Women with dense breasts face a double risk for breast cancer; they are at a higher risk for development of breast cancer than those with less dense breasts, and there is a greater chance that mammography will miss detection of a cancer in dense breasts due to the masking effect of surrounding fibroglandular tissue. These women may be candidates for supplemental screening. In this study, a masking risk model that was previously developed is tested on a cohort of cancer-free women to assess potential efficiency of stratification.
Research reporting guidelines are increasingly commonplace and shown to improve the quality of published health research and health outcomes. Despite severe health inequities among Indigenous Peoples and the potential for research to address the causes, there is an extended legacy of health research exploiting Indigenous Peoples. This paper describes the development of the CONSolIDated critERtia for strengthening the reporting of health research involving Indigenous Peoples (CONSIDER) statement.
The MAPK/ERK signaling pathway is an essential regulator of numerous cell processes that are crucial for normal development as well as cancer progression. While much is known regarding MAPK/ERK signal conveyance from the cell membrane to the nucleus, the transcriptional and epigenetic mechanisms that govern gene expression downstream of MAPK signaling are not fully elucidated.
Ulcerative colitis (UC), a serious threat to public health, is one of the main forms of inflammatory bowel disease, whereas the molecular mechanisms underlying ulcerative colitis induced by inflammation still remain elusive. NPLR6 gene is previously shown to regulate intestinal homeostasis and regulate the colonic microbial ecology. Here, we report that microRNA-650 (miR-650) plays an important role in the pathogenesis of UC as an upstream regulator of NPLR6 gene. MiR-650 is proved overexpressed in the inflamed mucosa of patients with ulcerative colitis and the DSS induced colitis model mice by qRT-PCR. Over-expression of miR-650 leads to increased apoptosis of Caco-2 and IEC-6 cells, and the DSS-induced mice aggravation, while knock-down of miR-650 shows opposite effects. Through constructing luciferase reporter genes containing 3'-untranslated regions of NLRP6, we further demonstrate that miR-650 inhibits NLRP6 through binding to its 3'-untranslated regions. Overexpression of NLRP6 in Caco-2 and IEC-6 cells suppress the increase apoptosis induced by miR-650 overexpression. Overall, the findings of this study indicate the role of miR-650 in ulcerative colitis, which provides a new target for therapeutic treatment.
The use of Y-grafts for Fontan completion is hypothesized to offer more balanced hepatic flow distribution (HFD) and decreased energy losses. The purpose of this study was to evaluate the hemodynamic performance of Y-grafts over time using serial cardiac magnetic resonance data and to compare their performance with extracardiac Fontan connections.
Chronic non-malignant pain has a major impact on the well-being, mood and productivity of those affected. Opioids are increasingly prescribed to manage this type of pain, but with a risk of other disabling symptoms, when their effectiveness has been questioned. This trial is designed to implement and evaluate a patient-centred intervention targeting withdrawal of strong opioids in people with chronic pain.
Cervical spondylotic radiculopathy (CSR) is the most common pattern of cervical spondylosis, which is a serious and common degenerative disease. Both acupotomy and acupuncture have been widely used clinically to treat CSR in China with satisfied efficacy. However, there is no systematic review comparing the effectiveness of these two therapies. The aim of this study is to compare the therapeutic efficacy and safety between acupotomy and acupuncture for patients with CSR to provide evidence for clinical practice.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer derived from the malignant transformation of T-cell progenitors. Outcomes remain poor for T-ALL patients who have either primary resistance to standard-of-care chemotherapy or disease relapse. Notably, there are currently no targeted therapies available in T-ALL. This lack of next-generation therapies highlights the need for relevant preclinical disease modeling to identify and validate new targets and treatment approaches. Here, we adapted a spontaneously arising, genetically heterogeneous, thymic transplantation-based murine model of T-ALL, recapitulating key histopathological and genetic features of the human disease, to the preclinical testing of targeted and immune-directed therapies. Genetic engineering of the murine Notch1 locus aligned the spectrum of Notch1 mutations in the mouse model to that of human T-ALL and confirmed aberrant, recombination-activating gene (RAG)-mediated 5' Notch1 recombination events as the preferred pathway in murine T-ALL development. Testing of Notch1-targeting therapeutic antibodies demonstrated T-ALL sensitivity to different classes of Notch1 blockers based on Notch1 mutational status. In contrast, genetic ablation of Notch3 did not impact T-ALL development. The T-ALL model was further applied to the testing of immunotherapeutic agents in fully immunocompetent, syngeneic mice. In line with recent clinical experience in T-cell malignancies, programmed cell death 1 (PD-1) blockade alone lacked anti-tumor activity against murine T-ALL tumors. Overall, the unique features of the spontaneous T-ALL model coupled with genetic manipulations and the application to therapeutic testing in immunocompetent backgrounds will be of great utility for the preclinical evaluation of novel therapies against T-ALL.
The steadily increasing epidemic of obesity continues at alarming rates, is an important public health problem, and expression changes of S100A16 and 11 β-hydroxysteroid dehydrogenase type 1(11β-HSD1) is attributable to the adipocyte differentiation. In our previous study, we found that 11β-HSD1 protein expression increased in S100A16-overexpressed 3T3-L1 cell model. In order to further investigate the relationship between S100A16 and 11β-HSD1, and the molecular mechanisms of S100A16-induced adipogenesis, we constructed S100A16 transgenic and knockout mouse, and S100A16-overexpressed 3T3-L1 preadipocyte cell. Using S100A16 transgenic (S100A16Tg/+) mice fed with normal fat diet (NFD) and high fat diet (HFD) diet model, we evaluated the effect of S100A16 on adipogenesis, expression of 11β-HSD1, and RNA sequencing and quantification of gene expression. Using the 3T3-L1 cell model, we examined the effect of S100A16 and 11β-HSD1 on pre-adipocyte differentiation, and cell signaling events of 11β-HSD1 overexpression induced by S100A16. We found that when compared with C57BL/6 mice, overexpression of S100A16 under the condition of HFD increased lipid content in WAT and fat infiltration in hepatocytes, 11β-HSD1 protein expression increased along with S100A16. Elevated S100A16 and 11β-HSD1 expression promoted adipogenesis in 3T3-L1 cells. Overexpression of S100A16 inhibited the degradation of 11β-HSD1. We conclude that S100A16-induced adipogenesis is associated with up-regulation of 11β-HSD1.
Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of systems vaccinology provides detailed information on host responses to vaccination and has been successfully applied to study the molecular mechanisms of several vaccines. Long noncoding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from this analysis can be accessed easily. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of these lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children following immunization with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination.
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