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1.
PLoS One ; 19(5): e0300715, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38753625

RESUMO

With the onset of puberty, youth begin to choose their social environments and develop health-promoting habits, making it a vital period to study social and biological factors contextually. An important question is how pubertal development and behaviors such as physical activity and sleep may be differentially linked with youths' friendships. Cross-sectional statistical network models that account for interpersonal dependence were used to estimate associations between three measures of pubertal development and youth friendships at two large US schools drawn from the National Longitudinal Study of Adolescent to Adult Health. Whole-network models suggest that friendships are more likely between youth with similar levels of pubertal development, physical activity, and sleep. Sex-stratified models suggest that girls' friendships are more likely given a similar age at menarche. Attention to similar pubertal timing within friendship groups may offer inclusive opportunities for tailored developmental puberty education in ways that reduce stigma and improve health behaviors.


Assuntos
Comportamentos Relacionados com a Saúde , Puberdade , Humanos , Adolescente , Feminino , Puberdade/psicologia , Puberdade/fisiologia , Masculino , Estudos Transversais , Amigos/psicologia , Comportamento do Adolescente/psicologia , Estudos Longitudinais , Exercício Físico , Sono/fisiologia , Apoio Social , Rede Social
2.
Vaccines (Basel) ; 12(4)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38675812

RESUMO

Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear. In the current study, STAT1-/- mice were used to investigate the role of STAT1 in the tumorigenesis of a spontaneous HPV E6/E7-expressing oral tumor model. Subsequently, our candidate HPV DNA vaccine CRT/E7 was administered to determine whether the STAT1-/- host preserves a therapeutic-responsive tumor microenvironment. The results indicated that STAT1-/- induces robust tumorigenesis, yet a controlled tumor response was attained upon CRT/E7 vaccination. Characterizing this treatment effect, immunological analysis found a higher percentage of circulating CD4+ and CD8+ T cells and tumor-specific cytotoxic T cells. In addition, a reduction in exhaustive lymphocyte activity was observed. Further analysis of a whole-cell tumor challenge affirmed these findings, as spontaneous tumor growth was more rapid in STAT1-/- mice. In conclusion, STAT1 deletion accelerates tumorigenesis, but STAT1-/- mice maintains immunocompetency in CRT/E7 treatments.

3.
J Transl Med ; 22(1): 378, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649894

RESUMO

BACKGROUND: Bacteria-based cancer therapy have demonstrated innovative strategies to combat tumors. Recent studies have focused on gram-negative bacterial outer membrane vesicles (OMVs) as a novel cancer immunotherapy strategy due to its intrinsic properties as a versatile carrier. METHOD: Here, we developed an Human Papillomavirus (HPV)-associated E7 antigen displaying Salmonella-derived OMV vaccine, utilizing a Poly(L-arginine) cell penetrating peptide (CPP) to enhance HPV16 E7 (aa49-67) H-2 Db and OMV affinity, termed SOMV-9RE7. RESULTS: Due to OMV's intrinsic immunogenic properties, SOMV-9RE7 effectively activates adaptive immunity through antigen-presenting cell uptake and antigen cross-presentation. Vaccination of engineered OMVs shows immediate tumor suppression and recruitment of infiltrating tumor-reactive immune cells. CONCLUSION: The simplicity of the arginine coating strategy boasts the versatility of immuno-stimulating OMVs that can be broadly implemented to personalized bacterial immunotherapeutic applications.


Assuntos
Arginina , Vacinas Anticâncer , Proteínas E7 de Papillomavirus , Proteínas E7 de Papillomavirus/imunologia , Vacinas Anticâncer/imunologia , Humanos , Animais , Membrana Externa Bacteriana/imunologia , Camundongos Endogâmicos C57BL , Feminino
4.
J Ovarian Res ; 17(1): 19, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38225646

RESUMO

BACKGROUND: MUC16 is a heavily glycosylated cell surface mucin cleaved in the tumor microenvironment to shed CA125. CA125 is a serum biomarker expressed by > 95% of non-mucinous advanced stage epithelial ovarian cancers. MUC16/CA125 contributes to the evasion of anti-tumor immunity, peritoneal spread and promotes carcinogenesis; consequently, it has been targeted with antibody-based passive and active immunotherapy. However, vaccination against this self-antigen likely requires breaking B cell tolerance and may trigger autoimmune disease. Display of self-antigens on virus-like particles (VLPs), including those produced with human papillomavirus (HPV) L1, can efficiently break B cell tolerance. RESULTS: A 20 aa juxta-membrane peptide of the murine MUC16 (mMUC16) or human MUC16 (hMUC16) ectodomain was displayed either via genetic insertion into an immunodominant loop of HPV16 L1-VLPs between residues 136/137, or by chemical coupling using malemide to cysteine sulfhydryl groups on their surface. Female mice were vaccinated intramuscularly three times with either DNA expressing L1-MUC16 fusions via electroporation, or with alum-formulated VLP chemically-coupled to MUC16 peptides. Both regimens were well tolerated, and elicited MUC16-specific serum IgG, although titers were higher in mice vaccinated with MUC16-coupled VLP on alum as compared to L1-MUC16 DNA vaccination. Antibody responses to mMUC16-targeted vaccination cross-reacted with hMUC16 peptide, and vice versa; both were reactive with the surface of CA125+ OVCAR3 cells, but not SKOV3 that lack detectable CA125 expression. Interestingly, vaccination of mice with mMUC16 peptide mixed with VLP and alum elicited mMUC16-specific IgG, implying VLPs provide robust T help and that coupling may not be required to break tolerance to this epitope. CONCLUSION: Vaccination with VLP displaying the 20 aa juxta-membrane MUC16 ectodomain, which includes the membrane proximal cleavage site, is likely to be well tolerated and induce IgG targeting ovarian cancer cells, even after CA125 is shed.


Assuntos
Compostos de Alúmen , Neoplasias Ovarianas , Vacinas de Partículas Semelhantes a Vírus , Humanos , Feminino , Animais , Camundongos , Neoplasias Ovarianas/genética , Epitopos , Apoptose , Linhagem Celular Tumoral , Peptídeos , Imunoglobulina G , DNA , Antígeno Ca-125/genética , Microambiente Tumoral , Proteínas de Membrana/genética
5.
J Biomed Sci ; 31(1): 19, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287325

RESUMO

BACKGROUND: Previous research in FMS-like tyrosine kinase 3 ligands (FLT3L) has primarily focused on their potential to generate dendritic cells (DCs) from bone marrow progenitors, with a limited understanding of how these cells affect CD8 T cell function. In this study, we further investigated the in vivo role of FLT3L for the immunomodulatory capabilities of CD8 T cells. METHODS: Albumin-conjugated FLT3L (Alb-FLT3L) was generated and applied for translational medicine purposes; here it was used to treat naïve C57BL/6 and OT1 mice for CD8 T cell response analysis. Syngeneic B16ova and E.G7ova mouse models were employed for adoptive cell transfer to evaluate the effects of Alb-FLT3L preconditioning of CD8 T cells on tumor progression. To uncover the underlying mechanisms of Alb-FLT3L modulation, we conducted bulk RNA-seq analysis of the CD44high CD8 T cells. STAT1-deficient mice were used to elucidate the functional roles of Alb-FLT3L in the modulation of T cells. Finally, antibody blockade of type one interferon signaling and in vitro coculture of plasmacytoid DCs (pDCs) with naive CD8 T cells was performed to determine the role of pDCs in mediating regulation of CD44high CD8 T cells. RESULTS: CD44high CD8 T cells were enhanced in C57BL/6 mice administrated with Alb-FLT3L. These CD8 T cells exhibited virtual memory features and had greater proliferative and effective functions. Notably, the adoptive transfer of CD44high naïve CD8 T cells into C57BL/6 mice with B16ova tumors led to significant tumor regression. RNA-seq analysis of the CD44high naïve CD8 T cells revealed FLT3L to induce CD44high CD8 T cells in a JAK-STAT1 signaling pathway-dependent manner, as supported by results indicating a decreased ability of FLT3L to enhance CD8 T cell proliferation in STAT1-deficient mice as compared to wild-type control mice. Moreover, antibody blockade of type one interferon signaling restricted the generation of FLT3L-induced CD44high CD8 T cells, while CD44 expression was able to be induced in naïve CD8 T cells cocultured with pDCs derived from FLT3L-treated mice. This suggests the crucial role of pDCs in mediating FLT3L regulation of CD44high CD8 T cells. CONCLUSIONS: These findings provide critical insight and support the therapeutic potential of Alb-FLT3L as an immune modulator in preconditioning of naïve CD8 T cells for cancer immunotherapy.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Animais , Camundongos , Células Dendríticas , Interferons , Camundongos Endogâmicos C57BL , Neoplasias/metabolismo
6.
J Clin Invest ; 134(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37917174

RESUMO

Even with the prolific clinical use of next-generation cancer therapeutics, many tumors remain unresponsive or become refractory to therapy, creating a medical need. In cancer, DCs are indispensable for T cell activation, so there is a restriction on cytotoxic T cell immunity if DCs are not present in sufficient numbers in the tumor and draining lymph nodes to take up and present relevant cancer antigens. To address this bottleneck, we developed a therapeutic based on albumin fused with FMS-related tyrosine kinase 3 ligand (Alb-Flt3L) that demonstrated superior pharmacokinetic properties compared with Flt3L, including significantly longer half-life, accumulation in tumors and lymph nodes, and cross-presenting-DC expansion following a single injection. We demonstrated that Alb-Flt3L, in combination with standard-of-care chemotherapy and radiation therapy, serves as an in situ vaccination strategy capable of engendering polyclonal tumor neoantigen-specific immunity spontaneously. In addition, Alb-Flt3L-mediated tumor control synergized with immune checkpoint blockade delivered as anti-PD-L1. The mechanism of action of Alb-Flt3L treatment revealed a dependency on Batf3, type I IFNs, and plasmacytoid DCs. Finally, the ability of Alb-Flt3L to expand human DCs was explored in humanized mice. We observed significant expansion of human cross-presenting-DC subsets, supporting the notion that Alb-Flt3L could be used clinically to modulate human DC populations in future cancer therapeutic regimens.


Assuntos
Células Dendríticas , Neoplasias , Camundongos , Humanos , Animais , Proteínas de Membrana/metabolismo , Antígenos , Imunoterapia , Vacinação
7.
mBio ; 14(5): e0212123, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37791765

RESUMO

IMPORTANCE: Respectively, HPV16 and HPV18 cause 50% and 20% of cervical cancer cases globally. Viral proteins E6 and E7 are obligate drivers of oncogenic transformation. We recently developed a candidate therapeutic DNA vaccine, pBI-11, that targets HPV16 and HPV18 E6 and E7. Single-site intramuscular delivery of pBI-11 via a needle elicited therapeutic anti-tumor effects in mice and is now being tested in high-risk human papillomavirus+ head and neck cancer patients (NCT05799144). Needle-free biojectors such as the Tropis device show promise due to ease of administration, high patient acceptability, and the possibility of improved delivery. For example, vaccination of patients with the ZyCoV-D DNA vaccine using the Tropis device is effective against COVID19, well tolerated, and licensed. Here we show that split-dose, multi-site administration and intradermal delivery via the Tropis biojector increase the delivery of pBI-11 DNA vaccine, enhance HPV antigen-specific CD8+ T-cell responses, and improve anti-tumor therapeutic effects, suggesting its translational potential to treat HPV16/18 infection and disease.


Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Vacinas de DNA , Feminino , Humanos , Animais , Camundongos , Papillomavirus Humano 16/genética , Vacinas de DNA/genética , Vacinas de DNA/uso terapêutico , Papillomavirus Humano 18/genética , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genética , Neoplasias do Colo do Útero/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinação , Imunidade
8.
Ann Hum Biol ; 50(1): 152-160, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36636018

RESUMO

BACKGROUND: Leg volume (LV) is an important reference in nutrition, physiology in exercise, or clinical diagnosis. Therefore, how to evaluate LV easily and quickly with accuracy is important in these areas. AIM: To develop a simple anthropometric estimation formula with ease of use and good accuracy for leg volume (LV) of female labourers. SUBJECTS: One hundred and thirty female labourers (110 subjects for formula regression procedure and 20 subjects for the comparison phase) were recruited as subjects with no reported leg surgery history, trauma, or deformity. METHODS: A set of 3 D scanners was used to measure the range data of each subject's leg. RESULTS: The resultant LV estimation formula is LV = 0.215 × LL × CTH1.620 with R2 = 0.967, in which LL stands for leg length and CTH for circumference of thigh. Mean error of this LV estimation is 0.10% and much smaller than that of the previous study (25.11% with significant difference). CONCLUSION: An anthropometric estimation formula for female labourers' leg volume was developed in this study. Estimation mean error of this formula is much smaller than the one in the previous study. This formula is easy to use and shows good accuracy in estimating female labourers' leg volume.


Assuntos
Perna (Membro) , Coxa da Perna , Humanos , Feminino , Antropometria/métodos , Estado Nutricional , Nível de Saúde
9.
J Biomed Sci ; 29(1): 57, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35962391

RESUMO

BACKGROUND: For centuries, microbial-based agents have been investigated as a therapeutic modality for the treatment of cancer. In theory, these methods would be cheap to produce, broadly applicable in a wide array of cancer types, and could synergize with other cancer treatment strategies. We aimed to assess the efficacy of combining microbial-based therapy using Salmonella SL7207 with interleukin-2 (IL-2), a potent immunostimulatory agent, in the treatment of murine colon carcinoma. METHODS: Female BALB/c mice were implanted subcutaneously with CT26 tumors, a model of colon carcinoma. Mice bearing tumors were selected and administered Albumin-IL-2 (Alb-IL2), a fusion protein, for further analysis of anticancer effect. RESULTS: We demonstrated that Salmonella SL7207, a genetically modified strain of Salmonella enterica serovar Typhimurium, preferentially accumulates in the tumor microenvironment, potentiating it to stimulate localized innate immunity. We delivered IL-2 as a fusion protein, Alb-IL2, which we demonstrate to have preferential accumulation properties, bringing it to the tumor and secondary lymphoid organs. Treatment of tumor-bearing mice with Salmonella + Alb-IL2 leads to superior tumor control and enhanced overall survival compared to controls. When assessing immunological factors contributing to our observed tumor control, significantly enhanced T cell population with superior effector function was observed in mice treated with Salmonella + Alb-IL2. We confirmed that these T cells were indispensable to the observed tumor control through antibody-mediated T cell depletion experiments. CONCLUSIONS: These findings highlight the ability of Salmonella + Alb-IL2 to serve as a novel therapeutic approach to induce T cell-mediated antitumor immunity and exert long-term tumor control in a murine model of cancer.


Assuntos
Carcinoma , Neoplasias do Colo , Albuminas , Animais , Feminino , Interleucina-2 , Camundongos , Salmonella , Microambiente Tumoral
10.
Oncogene ; 41(20): 2833-2845, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35418692

RESUMO

Dysregulation of pericellular proteolysis is strongly implicated in cancer metastasis through alteration of cell invasion and the microenvironment. Matriptase-2 (MT-2) is a membrane-anchored serine protease which can suppress prostate cancer (PCa) cell invasion. In this study, we showed that MT-2 was down-regulated in PCa and could suppress PCa cell motility, tumor growth, and metastasis. Using microarray and biochemical analysis, we found that MT-2 shifted TGF-ß action towards its tumor suppressor function by repressing epithelial-to-mesenchymal transition (EMT) and promoting Smad2 phosphorylation and nuclear accumulation to upregulate two TGF-ß1 downstream effectors (p21 and PAI-1), culminating in hindrance of PCa cell motility and malignant growth. Mechanistically, MT-2 could dramatically up-regulate the expression of nuclear receptor NR4A3 via iron metabolism in PCa cells. MT-2-induced NR4A3 further coactivated Smad2 to activate p21 and PAI-1 expression. In addition, NR4A3 functioned as a suppressor of PCa and mediated MT-2 signaling to inhibit PCa tumorigenesis and metastasis. These results together indicate that NR4A3 sustains MT-2 signaling to suppress PCa cell invasion, tumor growth, and metastasis, and serves as a contextual factor for the TGF-ß/Smad2 signaling pathway in favor of tumor suppression via promoting p21 and PAI-1 expression.


Assuntos
Proteínas de Ligação a DNA , Proteínas de Membrana , Neoplasias da Próstata , Receptores de Esteroides , Receptores dos Hormônios Tireóideos , Serina Endopeptidases , Linhagem Celular Tumoral , Movimento Celular , Proteínas de Ligação a DNA/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Masculino , Proteínas de Membrana/metabolismo , Invasividade Neoplásica , Inibidor 1 de Ativador de Plasminogênio , Próstata/patologia , Neoplasias da Próstata/patologia , Receptores de Esteroides/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Serina Endopeptidases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral
11.
ACS Omega ; 7(5): 3917-3924, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35155888

RESUMO

A solid-state reaction method was used to synthesize Ca2+x MgSi2Eu0.025O7+x (x = 0-1.0) powders in the air atmosphere and in a reduction atmosphere (95% N2 + 5% H2) at 1350 °C and 4 h, and the reduction atmosphere was removed at 800 °C. Only the Ca2MgSi2O7 phase was found in the XRD pattern of the synthesized Ca2MgSi2Eu0.025O7 powder. The first important discovery was that when the x value of Ca2+x MgSi2Eu0.025O7+x powders was increased from 0.2 to 0.8, both Ca2MgSi2O7 and Ca3MgSi2O8 phases coexisted in the synthesized Ca2+x MgSi2Eu0.025O7+x powders, and the diffraction intensity of the Ca2MgSi2O7 (Ca3MgSi2O8) phase decreased (increased) with the x value. The second important discovery was that the Ca2MgSi2Eu0.025O7 phosphor exhibited stronger photoluminescence excitation (PLE), photoluminescence (PL), and decay curve properties than the Ca2.2MgSi2Eu0.025O7.2 phosphor, and the Ca3MgSi2Eu0.025O8 phosphor exhibited stronger PLE, PL, and decay curve properties than the Ca2+x MgSi2Eu0.025O7+x phosphors for x = 0.4, 0.6, and 0.8. For x = 0.2-0.8, the PL spectra of the Ca2+x MgSi2Eu0.025O7+x phosphors were a combination of the PL spectra of Ca2MgSi2Eu0.025O7 and Ca3MgSi2Eu0.025O8 phosphors. The third important discovery was that as the x value was increased, the maximum emission peak wavelengths of the Ca2+x MgSi2Eu0.025O7+x phosphors shifted to a lower value, the maximum emission intensity of the PL spectra increased, and the emission light changed from green and cyan to blue.

12.
Cancer Res ; 81(12): 3270-3282, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33771897

RESUMO

Current clinical trials of combined EGFR-tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) therapies show no additional effect. This raises questions regarding whether EGFR-TKIs attenuate ICB-enhanced CD8+ T lymphocyte function. Here we show that the EGFR-TKI afatinib suppresses CD8+ T lymphocyte proliferation, and we identify CAD, a key enzyme of de novo pyrimidine biosynthesis, to be a novel afatinib target. Afatinib reduced tumor-infiltrating lymphocyte numbers in Lewis lung carcinoma (LLC)-bearing mice. Early afatinib treatment inhibited CD8+ T lymphocyte proliferation in patients with non-small cell lung cancer, but their proliferation unexpectedly rebounded following long-term treatment. This suggests a transient immunomodulatory effect of afatinib on CD8+ T lymphocytes. Sequential treatment of afatinib with anti-PD1 immunotherapy substantially enhanced therapeutic efficacy in MC38 and LLC-bearing mice, while simultaneous combination therapy showed only marginal improvement over each single treatment. These results suggest that afatinib can suppress CD8+ T lymphocyte proliferation by targeting CAD, proposing a timing window for combined therapy that may prevent the dampening of ICB efficacy by EGFR-TKIs. SIGNIFICANCE: This study elucidates a mechanism of afatinib-mediated immunosuppression and provides new insights into treatment timing for combined targeted therapy and immunotherapy. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3270/F1.large.jpg.


Assuntos
Afatinib/farmacologia , Antineoplásicos Imunológicos/farmacologia , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxirribonucleases/antagonistas & inibidores , Agentes de Imunomodulação/farmacologia , Pirimidinas/biossíntese , Animais , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Lewis/imunologia , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Combinada , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/antagonistas & inibidores
13.
Artigo em Inglês | MEDLINE | ID: mdl-33498242

RESUMO

BACKGROUND: There are different types of hand motions in people's daily lives and working environments. However, testing duration increases as the types of hand motions increase to build a normative database. Long testing duration decreases the motivation of study participants. The purpose of this study is to propose models to predict pinch and press strength using grip strength. METHODS: One hundred ninety-eight healthy volunteers were recruited from the manufacturing industries in Central Taiwan. The five types of hand motions were grip, lateral pinch, palmar pinch, thumb press, and ball of thumb press. Stepwise multiple linear regression was used to explore the relationship between force type, gender, height, weight, age, and muscle strength. RESULTS: The prediction models developed according to the variable of the strength of the opposite hand are good for explaining variance (76.9-93.1%). Gender is the key demographic variable in the predicting models. Grip strength is not a good predictor of palmar pinch (adjusted-R2: 0.572-0.609), nor of thumb press and ball of thumb (adjusted-R2: 0.279-0.443). CONCLUSIONS: We recommend measuring the palmar pinch and ball of thumb strength and using them to predict the other two hand motions for convenience and time saving.


Assuntos
Mãos , Esforço Físico , Força da Mão , Humanos , Indústria Manufatureira , Taiwan
14.
Int J Occup Saf Ergon ; 27(4): 1207-1214, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31893965

RESUMO

The purpose of this study was to develop a body volume (BV) estimation equation for male laborers in Taiwan with body weight (W) and stature height (H) as initial estimators. A three-dimensional (3D) body scanner and a 3D foot scanner were used to measure the 3D range data of 100 male laborers in this study. Subjects' BV was extracted from the 3D body model, and H and W were used as independent variables in regression analysis. The results show that the final BV estimation equation is BV = 1122.927 × W0.972, with R2 = 0.949. Thirty extra male subjects were scanned to compare this BV estimation equation with those in previous studies. The results show that this BV estimation equation had the smallest absolute mean difference at 1.1458 L and the smallest standard error of the estimate at 2.48% in comparison.


Assuntos
Estatura , , Peso Corporal , Humanos , Masculino , Análise de Regressão , Taiwan
15.
Adapt Phys Activ Q ; 37(4): 404-422, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32998110

RESUMO

This study examined the effects of acute aerobic exercise on sustained attention and discriminatory ability of children with and without learning disabilities (LD). Fifty-one children with LD and 49 typically developing children were randomly assigned to exercise or control groups. The participants in the exercise groups performed a 30-min session of moderate-intensity aerobic exercise, whereas the control groups watched a running/exercise-related video. Neuropsychological tasks, the Daueraufmerksamkeit sustained attention test, and the determination tests were assessed before and after each treatment. Exercise significantly benefited performance in sustained attention and discriminatory ability, particularly in higher accuracy rate and shorter reaction time. In addition, the LD exercise group demonstrated greater improvement than the typically developing exercise group. The findings suggest that the acute aerobic exercise influenced the sustained attention and the discriminatory function in children with LD by enhancing regulation of mental states and allocation of attentional resources.


Assuntos
Cognição/fisiologia , Função Executiva/fisiologia , Exercício Físico/fisiologia , Deficiências da Aprendizagem , Adolescente , Atenção , Criança , Humanos , Testes Neuropsicológicos
16.
Oncogene ; 39(37): 5950-5963, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32778768

RESUMO

TMPRSS2 is an important membrane-anchored serine protease involved in human prostate cancer progression and metastasis. A serine protease physiologically often comes together with a cognate inhibitor for execution of proteolytically biologic function; however, TMPRSS2's cognate inhibitor is still elusive. To identify the cognate inhibitor of TMPRSS2, in this study, we applied co-immunoprecipitation and LC/MS/MS analysis and isolated hepatocyte growth factor activator inhibitors (HAIs) to be potential inhibitor candidates for TMPRSS2. Moreover, the recombinant HAI-2 proteins exhibited a better inhibitory effect on TMPRSS2 proteolytic activity than HAI-1, and recombinant HAI-2 proteins had a high affinity to form a complex with TMPRSS2. The immunofluorescence images further showed that TMPRSS2 was co-localized to HAI-2. Both KD1 and KD2 domain of HAI-2 showed comparable inhibitory effects on TMPRSS2 proteolytic activity. In addition, HAI-2 overexpression could suppress the induction effect of TMPRSS2 on pro-HGF activation, extracellular matrix degradation and prostate cancer cell invasion. We further determined that the expression levels of TMPRSS2 were inversely correlated with HAI-2 levels during prostate cancer progression. In orthotopic xenograft animal model, TMPRSS2 overexpression promoted prostate cancer metastasis, and HAI-2 overexpression efficiently blocked TMPRSS2-induced metastasis. In summary, the results together indicate that HAI-2 can function as a cognate inhibitor for TMPRSS2 in human prostate cancer cells and may serve as a potential factor to suppress TMPRSS2-mediated malignancy.


Assuntos
Glicoproteínas de Membrana/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Serina Endopeptidases/metabolismo , Animais , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Xenoenxertos , Humanos , Masculino , Glicoproteínas de Membrana/química , Invasividade Neoplásica , Neoplasias da Próstata/etiologia , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Mapeamento de Interação de Proteínas , Proteínas Secretadas Inibidoras de Proteinases/metabolismo , Proteólise
17.
Sci Rep ; 10(1): 11674, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669615

RESUMO

Stem cell activity and cell differentiation is robustly influenced by the nutrient availability in the gonads. The signal that connects nutrient availability to gonadal stem cell activity remains largely unknown. In this study, we show that tumor necrosis factor Eiger (Egr) is upregulated in testicular smooth muscles as a response to prolonged protein starvation in Drosophila testis. While Egr is not essential for starvation-induced changes in germline and somatic stem cell numbers, Egr and its receptor Grindelwald influence the recovery dynamics of somatic cyst stem cells (CySCs) upon protein refeeding. Moreover, Egr is also involved in the refeeding-induced, ectopic expression of the CySC self-renewal protein and the accumulation of early germ cells. Egr primarily acts through the Jun N-terminal kinase (JNK) signaling in Drosophila. We show that inhibition of JNK signaling in cyst cells suppresses the refeeding-induced abnormality in both somatic and germ cells. In conclusion, our study reveals both beneficial and detrimental effects of Egr upregulation in the recovery of stem cells and spermatogenesis from prolonged protein starvation.


Assuntos
Proteínas Alimentares/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas de Membrana/genética , Espermatozoides/metabolismo , Células-Tronco/metabolismo , Animais , Diferenciação Celular , Proteínas Alimentares/administração & dosagem , Proteínas de Drosophila/agonistas , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Ingestão de Alimentos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Homeostase/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Proteínas de Membrana/agonistas , Proteínas de Membrana/metabolismo , Espermatogênese/efeitos dos fármacos , Espermatogênese/genética , Espermatozoides/citologia , Espermatozoides/efeitos dos fármacos , Inanição/genética , Inanição/metabolismo , Nicho de Células-Tronco/genética , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Testículo/citologia , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-33383773

RESUMO

Objectives: The purpose of this study is to establish the norms of hand grip strength in the healthcare industry in Taiwan and propose models to predict the strength of hand movement by regression with demographic and anthropometric factors. Methods: This is a cross-sectional study with a stratified convenience sample of workers in healthcare service industries in central Taiwan. Three hundred twenty-nine healthy subjects were recruited. Strength of different hand movement were tested three times in both hands and rests were given between tests. Results: Female strength of these hand movement was 59.1% to 73.0% that in males (p < 0.001). In general, the hand strength of male workers in the healthcare industry was less than that of male workers in the manufacturing industry (p < 0.001). In the prediction model, sex and weight played important roles in predicting hand strength. Conclusions: The norms of different types of hand strength was investigated the first time in workers in the healthcare industry in Taiwan. The tasks performed by healthcare personnel vary widely, and this variable should be considered in a future prediction model.


Assuntos
Força da Mão , Pessoal de Saúde , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Taiwan , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-31783550

RESUMO

Background: The purpose of this study is to collect five types of maximum hand strength among workers in the manufacturing industry in Taiwan. Methods: This study is a cross sectional study with a stratified and convenient sample of workers on the production line in manufacturing industries in Central Taiwan. In total, we recruited 198 healthy subjects to participate in this study. Five types of hand strength were measured in both hands three times with 3 min rests between trials. Results: The strength of females for these five types of hand exertions were 52.0% to 67.6% of the strength of males (p < 0.001). For both genders, there was a main effect for the types of hand strength for the right hand (p < 0.001) and the left hand (p < 0.001). In general, the hand strength in U.S. and EU countries was 1.2 to 1.7 times greater than the strength among the three types of hand exertions in this study. Conclusion: These results can be used to evaluate the musculoskeletal burdens on the upper extremities in the manufacturing industry and could also be used for tool and job design and job modifications.


Assuntos
Força da Mão/fisiologia , Indústria Manufatureira , Saúde Ocupacional , Adulto , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Projetos Piloto , Taiwan , Extremidade Superior/fisiologia
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