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Cardiovascular disease (CVD), a global health concern, particularly coronary artery disease (CAD), poses a significant threat to well-being. Seeking safer and cost-effective diagnostic alternatives to invasive coronary angiography, noninvasive coronary computed tomography angiography (CCTA) gains prominence. This study employed OpenFOAM, an open-source Computational Fluid Dynamics (CFD) software, to analyze hemodynamic parameters in coronary arteries with serial stenoses. Patient-specific three-dimensional (3D) models from CCTA images offer insights into hemodynamic changes. OpenFOAM breaks away from traditional commercial software, validated against the FDA benchmark nozzle model for reliability. Applying this refined methodology to seventeen coronary arteries across nine patients, the study evaluates parameters like fractional flow reserve computed tomography simulation (FFRCTS), fluid velocity, and wall shear stress (WSS) over time. Findings include FFRCTS values exceeding 0.8 for grade 0 stenosis and falling below 0.5 for grade 5 stenosis. Central velocity remains nearly constant for grade 1 stenosis but increases 3.4-fold for grade 5 stenosis. This research innovates by utilizing OpenFOAM, departing from previous reliance on commercial software. Combining qualitative stenosis grading with quantitative FFRCTS and velocity measurements offers a more comprehensive assessment of coronary artery conditions. The study introduces 3D renderings of wall shear stress distribution across stenosis grades, providing an intuitive visualization of hemodynamic changes for valuable insights into coronary stenosis diagnosis.
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Vasos Coronarios , Hidrodinámica , Humanos , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Masculino , Estados Unidos , Programas Informáticos , United States Food and Drug Administration , Circulación Coronaria/fisiología , Angiografía Coronaria/métodos , Hemodinámica/fisiología , Femenino , Persona de Mediana Edad , Modelos Cardiovasculares , Angiografía por Tomografía Computarizada/métodos , Anciano , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Simulación por Computador , Reproducibilidad de los Resultados , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/fisiopatología , Velocidad del Flujo Sanguíneo/fisiologíaRESUMEN
Osteoporosis is a usual bone disease in aging populations, principally in postmenopausal women. Anti-resorptive and anabolic drugs have been applied to prevent and cure osteoporosis and are associated to a different of adverse effects. Du-Zhong is usually applied in Traditional Chinese Medicine to strengthen bone, regulate bone metabolism, and treat osteoporosis. Chlorogenic acid is a major polyphenol in Du-Zhong. In the current study, chlorogenic acid was found to enhance osteoblast proliferation and differentiation. Chlorogenic acid also inhibits the RANKL-induced osteoclastogenesis. Notably, ovariectomy significantly decreased bone volume and mechanical properties in the ovariectomized (OVX) rats. Administration of chlorogenic acid antagonized OVX-induced bone loss. Taken together, chlorogenic acid seems to be a hopeful molecule for the development of novel anti-osteoporosis treatment.
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Osteoclastos , Osteoporosis , Humanos , Ratas , Femenino , Animales , Ácido Clorogénico/farmacología , Ácido Clorogénico/uso terapéutico , Ácido Clorogénico/metabolismo , Osteogénesis , Osteoporosis/metabolismo , Osteoblastos/metabolismo , Diferenciación CelularRESUMEN
The study aimed to evaluate the impact of occupational noise on hearing loss among healthcare workers using audiometry. A longitudinal study was conducted with a six-month follow-up period in a hospital with 21 participants, divided into high-noise-exposure (HNE) and low-noise-exposure (LNE) groups. Mean noise levels were higher in the HNE group (70.4 ± 4.5 dBA), and hearing loss was measured using pure-tone audiometry at baseline and follow-up. The HNE group had significantly higher mean threshold levels at frequencies of 0.25 kHz, 0.5 kHz, 4.0 kHz, and an average of 0.5, 1, 2, and 4 kHz (all p-values < 0.05) after the follow-up period. After adjusting for confounding factors, the HNE group had significantly higher hearing loss levels at 0.25 kHz, 0.5 kHz, and average frequencies of 0.5, 1, 2, and 4 kHz compared to the LNE group at the second measurement. Occupational noise levels above 65 dBA over six months were found to cause significant threshold changes at frequencies of 0.25 kHz, 0.5 kHz, and an average of 0.5-4.0 kHz. This study highlights the risk of noise-induced hearing loss among healthcare workers and emphasizes the importance of implementing effective hearing conservation programs in the workplace. Regular monitoring and assessment of noise levels and hearing ability, along with proper use of personal protective equipment, are crucial steps in mitigating the impact of occupational noise exposure on the hearing health of healthcare workers.
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Pérdida Auditiva Provocada por Ruido , Ruido en el Ambiente de Trabajo , Enfermedades Profesionales , Exposición Profesional , Humanos , Estudios Longitudinales , Ruido en el Ambiente de Trabajo/efectos adversos , Pérdida Auditiva Provocada por Ruido/epidemiología , Personal de Hospital , AudiciónRESUMEN
Breast cancer stands as the predominant malignancy and primary cause of cancer-related mortality among females globally. Approximately 25% of breast cancers exhibit HER2 overexpression, imparting a more aggressive tumor phenotype and correlating with poor prognoses. Patients with metastatic breast cancer receiving HER2 tyrosine kinase inhibitors (HER2 TKIs), such as Lapatinib, develop acquired resistance within a year, posing a critical challenge in managing this disease. Here, we explore the potential of Artemisia argyi, a Chinese herbal medicine known for its anti-cancer properties, in mitigating HER2 TKI resistance in breast cancer. Analysis of the Cancer Genome Atlas (TCGA) revealed diminished expression of transmembrane serine protease 2 (TMPRSS2), a subfamily of membrane proteolytic enzymes, in breast cancer patients, correlating with unfavorable outcomes. Intriguingly, lapatinib-responsive patients exhibited higher TMPRSS2 expression. Our study unveiled that the compounds from Artemisia argyi, eriodictyol, and umbelliferone could inhibit the growth of lapatinib-resistant HER2-positive breast cancer cells. Mechanistically, they suppressed HER2 kinase activation by enhancing TMPRSS2 activity. Our findings propose TMPRSS2 as a critical determinant in lapatinib sensitivity, and Artemisia argyi emerges as a potential agent to overcome lapatinib via activating TMPRSS2 in HER2-positive breast cancer. This study not only unravels the molecular mechanisms driving cell death in HER2-positive breast cancer cells induced by Artemisia argyi but also lays the groundwork for developing novel inhibitors to enhance therapy outcomes.
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Artemisia , Neoplasias de la Mama , Resistencia a Antineoplásicos , Lapatinib , Extractos Vegetales , Receptor ErbB-2 , Serina Endopeptidasas , Lapatinib/farmacología , Lapatinib/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Humanos , Resistencia a Antineoplásicos/efectos de los fármacos , Artemisia/química , Femenino , Serina Endopeptidasas/metabolismo , Serina Endopeptidasas/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Línea Celular Tumoral , Extractos Vegetales/farmacología , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Artemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A. argyi and its constituents in reducing the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated in this study. RESULTS: Among the phytochemicals in A. argyi, eriodictyol and umbelliferone were identified to target transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) proteins, the essential factors for the cellular entry of SARS-CoV-2, in both FRET-based enzymatic assays and molecular docking analyses. These two ingredients of A. argyi suppressed the infection of ACE2-expressed HEK-293 T cells with lentiviral-based pseudo-particles (Vpp) expressing wild-type and variants of SARS-CoV-2 spike (S) protein (SARS-CoV-2 S-Vpp) via interrupting the interaction between S protein and cellular receptor ACE2 and reducing the expressions of ACE2 and TMPRSS2. Oral administration with umbelliferone efficiently prevented the SARS-CoV-2 S-Vpp-induced inflammation in the lung tissues of BALB/c mice. CONCLUSIONS: Eriodictyol and umbelliferone, the phytochemicals of Artemisia argyi, potentially suppress the cellular entry of SARS-CoV-2 by preventing the protein binding activity of the S protein to ACE2.
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Bacterial capsular polysaccharides provide protection against environmental stress and immune evasion from the host immune system, and are therefore considered to be attractive therapeutic targets for the development of anti-infectious reagents. Here, we focused on CapG, one of the key enzymes in the synthesis pathway of capsular polysaccharides type 5 (CP5) from the opportunistic pathogen Staphylococcus aureus. SaCapG catalyses the 2-epimerization of UDP-N-acetyl-D-talosamine (UDP-TalNAc) to UDP-N-acetyl-D-fucosamine (UDP-FucNAc), which is one of the nucleotide-activated precursors for the synthesis of the trisaccharide repeating units of CP5. Here, the cloning, expression and purification of recombinant SaCapG are reported. After extensive efforts, single crystals of SaCapG were successfully obtained which belonged to space group C2 and exhibited unit-cell parameters a = 302.91, b = 84.34, c = 145.09â Å, ß = 110.65°. The structure was solved by molecular replacement and was refined to 3.2â Å resolution. The asymmetric unit revealed a homohexameric assembly of SaCapG, which was consistent with gel-filtration analysis. Structural comparison with UDP-N-acetyl-D-glucosamine 2-epimerase from Methanocaldococcus jannaschii identified α2, the α2-α3 loop and α10 as a gate-regulated switch controlling substrate entry and/or product release.
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Polisacáridos Bacterianos , Staphylococcus aureus , Cristalografía por Rayos X , Polisacáridos Bacterianos/química , Methanocaldococcus , Uridina DifosfatoRESUMEN
Animal coronaviruses (CoVs) have been identified to be the origin of Severe Acute Respiratory Syndrome (SARS)-CoV, Middle East respiratory syndrome (MERS)-CoV, and probably SARS-CoV-2 that cause severe to fatal diseases in humans. Variations of zoonotic coronaviruses pose potential threats to global human beings. To overcome this problem, we focused on the main protease (Mpro), which is an evolutionary conserved viral protein among different coronaviruses. The broad-spectrum anti-coronaviral drug, GC376, was repurposed to target canine coronavirus (CCoV), which causes gastrointestinal infections in dogs. We found that GC376 can efficiently block the protease activity of CCoV Mpro and can thermodynamically stabilize its folding. The structure of CCoV Mpro in complex with GC376 was subsequently determined at 2.75 Å. GC376 reacts with the catalytic residue C144 of CCoV Mpro and forms an (R)- or (S)-configuration of hemithioacetal. A structural comparison of CCoV Mpro and other animal CoV Mpros with SARS-CoV-2 Mpro revealed three important structural determinants in a substrate-binding pocket that dictate entry and release of substrates. As compared with the conserved A141 of the S1 site and P188 of the S4 site in animal coronaviral Mpros, SARS-CoV-2 Mpro contains N142 and Q189 at equivalent positions which are considered to be more catalytically compatible. Furthermore, the conserved loop with residues 46-49 in animal coronaviral Mpros has been replaced by a stable α-helix in SARS-CoV-2 Mpro. In addition, the species-specific dimerization interface also influences the catalytic efficiency of CoV Mpros. Conclusively, the structural information of this study provides mechanistic insights into the ligand binding and dimerization of CoV Mpros among different species.
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COVID-19 , Péptido Hidrolasas , Animales , Proteasas 3C de Coronavirus , Dimerización , Perros , Endopeptidasas , Ligandos , Péptido Hidrolasas/química , SARS-CoV-2RESUMEN
BACKGROUND/AIM: The poor prognosis and chemoresistance of patients with triple-negative breast cancer (TNBC) urge the development of new therapeutic strategies. Snail mucus has shown its ability against inflammation, a process closely related to tumorigenesis, suggesting a potential anti-cancer activity. MATERIALS AND METHODS: The effect and mechanisms of snail mucus on cell viability were determined by IncuCyte Live-cell analysis and molecular biological methods. The anti-cancer fractions of snail mucus were isolated and identified by medium pressure liquid chromatography (MPLC) and nuclear magnetic resonance (NMR) spectrometry analysis. RESULTS: Snail mucus significantly decreased the viability of TNBC cells with relatively lower cytotoxicity to normal breast epithelial cells and enhanced their response to chemotherapy through activation of Fas signaling by suppressing nucleolin. Two peptide fractions have been identified as the anti-cancer ingredients of the snail mucus. CONCLUSION: Snail mucus can induce programmed cell death via the extrinsic apoptotic pathway and has therapeutic potential by achieving a chemo-sensitizing effect in TNBCs.
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Antineoplásicos/farmacología , Moco , Transducción de Señal/efectos de los fármacos , Caracoles , Neoplasias de la Mama Triple Negativas/metabolismo , Receptor fas/metabolismo , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Moco/química , Moco/metabolismo , Caracoles/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Vaccinium emarginatum Hayata is a medicinal plant that has been historically used in ethnopharmacy to treat diseases in Taiwan. The objective of this study is to evaluate the anti-cancer and anti-bacterial constitutes from the root nodule extract of V. emarginatum. The chemical composition of V. emarginatum fractions was analyzed by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and the chemical constitutes were isolated and structurally identified by nuclear magnetic resonance (NMR) spectroscopy. Bioassay-guided chromatography showed that the ethyl acetate (EA) fraction was bioactive on the hepatocellular carcinoma (HepG2). By LC-ESI-MS/MS analysis, twenty peaks of EA fraction were partially identified and the phytochemical investigation of the fractions led to the isolation and identification of protocatuchuic acid (1), epicatechin (2), catechin (3), procyanidin B3 (4), procyanidin A1 (5), hyperin (6), isoquercetin (7), quercetin (8), lupeol (9), beta-amyrin (10), and alpha-amyrin (11). Both procyanidin B3 and A1 exhibited anti-proliferative activity against HepG2 and gastric adenocarcinoma (AGS) cells at IC50 values between 38.4 and 41.1 µM and 79.4 and 83.8 µM, respectively. In addition, isoquercetin displayed the strongest anti-proliferative activity against the HepG2, lung carcinoma (A549), and AGS cell at 18.7, 24.6 and 68.5 µM, respectively. Among the triterpenoids, only lupeol showed the inhibitory activity against all tested tumor cell lines at IC50 values between 72.9 and 146.8 µM. Furthermore, procyanidins B3, A1 and isoquercetin displayed moderate anti-bacterial activity against Staphylococcus aureus. In conclusion, this study provides background information on the exploitation of V. emarginatum as a potential natural anti-cancer and anti-bacterial agent in pharmaceutical research.
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Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.
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Tratamiento Farmacológico de COVID-19 , Hesperidina/química , Hesperidina/farmacología , SARS-CoV-2/efectos de los fármacos , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , COVID-19/metabolismo , COVID-19/virología , Línea Celular Tumoral , Chlorocebus aethiops , Proteasas Similares a la Papaína de Coronavirus/química , Proteasas Similares a la Papaína de Coronavirus/metabolismo , Humanos , Simulación del Acoplamiento Molecular , SARS-CoV-2/metabolismo , Serina Endopeptidasas/química , Serina Endopeptidasas/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Células VeroRESUMEN
Smoker patients with non-small cell lung cancer (NSCLC) have poorer prognosis and survival than those without smoking history. However, the mechanisms underlying the low response rate of those patients to EGFR tyrosine kinase inhibitors (TKIs) are not well understood. Here we report that exposure to cigarette smoke extract enhances glycolysis and attenuates AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR; this in turn reduces the sensitivity of NSCLC cells with wild-type EGFR (EGFRWT) to EGFR TKI by repressing expression of liver kinase B1 (LKB1), a master kinase of the AMPK subfamily, via CpG island methylation. In addition, LKB1 expression is correlated positively with sensitivity to TKI in patients with NSCLC. Moreover, combined treatment of EGFR TKI with AMPK activators synergistically increases EGFR TKI sensitivity. Collectively, the current study suggests that LKB1 may serve as a marker to predict EGFR TKI sensitivity in smokers with NSCLC carrying EGFRWT and that the combination of EGFR TKI and AMPK activator may be a potentially effective therapeutic strategy against NSCLC with EGFRWT.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proteínas Serina-Treonina Quinasas/genética , Serina-Treonina Quinasas TOR/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Animales , Carcinoma de Pulmón de Células no Pequeñas/inducido químicamente , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Fumar Cigarrillos/efectos adversos , Islas de CpG/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Receptores ErbB/genética , Xenoinjertos , Humanos , Ratones , Mutación/genética , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Quinasas/genética , Transducción de Señal/efectos de los fármacos , Fumar/efectos adversosRESUMEN
Although dual EGFR/HER2 tyrosine kinase inhibitor lapatinib has provided effective clinical benefits for HER2-positive breast cancer patients, acquired resistance to this drug remains a major concern. Thus, the development of alternative therapeutic strategies is urgently needed for patients who failed lapatinib treatment. Proteasome inhibitors have been reported to possess high anti-tumor activity to breast cancer cells. Therefore, this study aims to examine whether and how proteasome inhibitor bortezomib can overcome lapatinib resistance. Treatments with several proteasome inhibitors, including Bortezomib, MG132, and proteasome inhibitor I (PSI), as well as the viabilities of both HER2-positive breast cancer cell lines and their lapatinib-resistant clones, were inhibited. Importantly, the expressions of ErbB family were downregulated at both transcriptional and translational levels. Also, our results further indicated that proteasome inhibitors decreased ErbB family expression through lysosomal degradation pathway in a heat shock protein 90 (HSP90)-dependent manner. In this study, our data supported a potential approach to overcome the acquired resistance of HER2-overexpressing breast cancer patients to lapatinib using proteasome inhibitors.
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Antineoplásicos/farmacología , Proteínas HSP90 de Choque Térmico/metabolismo , Lisosomas/metabolismo , Inhibidores de Proteasoma/farmacología , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Bortezomib/farmacología , Línea Celular Tumoral , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Proteolisis , Transducción de SeñalRESUMEN
Impaired growth factor production, angiogenic response, macrophage function, and collagen accumulation have been shown to delay wound healing. Delayed wound healing is a debilitating complication of diabetes that leads to significant morbidity. In this study, curcumin and Lithospermi radix (LR) extract, which are used in traditional Chinese herbal medicine, were added within nanofibrous membranes to improve wound healing in a streptozotocin (STZ)-induced diabetic rat model. Gelatin-based nanofibers, which were constructed with curcumin and LR extract at a flow rate of 0.1 mL/hour and an applied voltage of 20 kV, were electrospun onto chitosan scaffolds to produce bilayer nanofibrous scaffolds (GC/L/C). The wounds treated with GC/L/C exhibited a higher recovery rate and transforming growth factor-beta (TGF-ß) expression in Western blot assays. The decreased levels of pro-inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), provided evidence for the anti-inflammatory effects of GC/L/C treatment. Chronic wounds treated with GC/L/C achieved better performance with a 58 ± 7% increase in recovery rate on the seventh day. Based on its anti-inflammatory and wound-healing effects, the GC/L/C bilayer nanofibrous scaffolds can be potential materials for chronic wound treatment.
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Maspin is a tumor suppressor that stimulates apoptosis and inhibits metastasis in various cancer types, including hepatocellular carcinoma (HCC). Our previous study has demonstrated that HBx induced microRNA-7, 103, 107, and 21 expressions to suppress maspin expression, leading to metastasis, chemoresistance, and poor prognosis in HCC patients. However, it remains unclear how HBx elicits these microRNA expressions. HBx has been known to induce aberrant activation and nuclear translocation of inhibitor-κB kinase-α (IKKα) to promote HCC progression. In this study, our data further revealed that nuclear IKKα expression was inversely correlated with maspin expression in HBV-associated patients. Nuclear IKKα but not IKKß reduced maspin protein and mRNA expression, and inhibition of IKKα reverses HBx-mediated maspin downregulation and chemoresistance. In response to HBx overexpression, nuclear IKKα was further demonstrated to induce the gene expressions of microRNA-7, -103, -107, and -21 by directly targeting their promoters, thereby leading to maspin downregulation. These findings indicated nuclear IKKα as a critical regulator for HBx-mediated microRNA induction and maspin suppression, and suggest IKKα as a promising target to improve the therapeutic outcome of HCC patients.
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Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Virus de la Hepatitis B/fisiología , Quinasa I-kappa B/metabolismo , Neoplasias Hepáticas/genética , MicroARNs/metabolismo , Serpinas/metabolismo , Transactivadores/genética , Apoptosis , Biomarcadores de Tumor/metabolismo , Carcinogénesis/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Núcleo Celular/metabolismo , Progresión de la Enfermedad , Regulación hacia Abajo , Resistencia a Antineoplásicos/genética , Genes Supresores de Tumor , Células HEK293 , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Fosforilación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Serpinas/genética , Transducción de Señal , Transactivadores/metabolismo , Proteínas Reguladoras y Accesorias ViralesRESUMEN
The incidence of osteoporosis has increased among the elderly population. Establishing a model of bone remodeling for screening new drugs is critical to identify safe and effective treatments for osteoporosis. In this study, we established a platform to investigate the therapeutic effects of collagenous peptides extracted from scales of two kinds of fish, namely, sparidae and chanos. These peptides were prepared using seven concentrations of collagenous peptide: 100, 80, 60, 40, 20, 10 and 1 mg/ml. Experimental results indicated that collagenous peptides promoted the proliferation of osteoblasts and inhibited the proliferation of mature osteoclasts; the effective concentration of collagenous peptide-sparidae was 10 mg/ml and that of collagenous peptide-chanos was 40 mg/ml. These findings demonstrate that, to a certain extent, collagenous peptides extracted from fish scales can be used to prevent osteoporosis to assist bone remodeling.
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Colágeno/uso terapéutico , Proteínas de Peces/uso terapéutico , Osteoblastos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoporosis/prevención & control , Animales , Resorción Ósea/prevención & control , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colágeno/farmacología , Evaluación Preclínica de Medicamentos , Proteínas de Peces/farmacología , Humanos , PerciformesRESUMEN
Maspin suppresses tumor progression by promoting cell adhesion and apoptosis and by inhibiting cell motility. However, its role in tumorigenesis of hepatocellular carcinoma (HCC) remains unclear. The gene regulation of maspin and its relationship with HCC patient prognosis were investigated in this study. Maspin expression was specifically reduced in HBV-associated patients and correlated with their poor prognosis. Maspin downregulation in HCC cells was induced by HBx to promote their motility and resistance to anoikis and chemotherapy. HBx-dependent induction of microRNA-7, -107, and -21 was further demonstrated to directly target maspin mRNA, leading to its protein downregulation. Higher expressions of these microRNAs also correlated with maspin downregulation in HBV-associated patients, and were associated with their poor overall survival. These data not only provided new insights into the molecular mechanisms of maspin deficiency by HBx, but also indicated that downregulation of maspin by microRNAs confers HBx-mediated aggressiveness and chemoresistance in HCC.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroARNs/genética , Serpinas/genética , Transactivadores/genética , Regiones no Traducidas 3'/genética , Anoicis/efectos de los fármacos , Anoicis/genética , Antineoplásicos/farmacología , Western Blotting , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Células Hep G2 , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/metabolismo , Virus de la Hepatitis B/fisiología , Interacciones Huésped-Patógeno/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/virología , Masculino , Análisis Multivariante , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serpinas/metabolismo , Transactivadores/metabolismo , Proteínas Reguladoras y Accesorias ViralesRESUMEN
Acupuncture and electroacupuncture treatments of symptomatic carpal tunnel syndrome (CTS) may improve symptoms and aid nerve repair as well as improve sensory and motor functions. However, limited evidence is available regarding the effects of these treatments based on comprehensive evaluation methods. This research completed the treatment and evaluation of 26 patients with confirmed CTS. Participants were divided into two treatment groups based on a modified neurophysiological grading scale. Of the total number of participants, 15 received acupuncture and 11 received electroacupuncture on both upper limbs. Acupoints were PC-7 (Daling) and PC-6 (Neiguan) along the pericardial meridian compatible with the median nerve tract. The treatment program consisted of 24 sessions of 15 min duration over 6 weeks. After electroacupuncture treatments, symptom severity was evaluated using the short clinical questionnaire by Lo and Chiang, which indicated improvements in the respective symptom severity score. After the acupuncture treatment, grip strength in the major symptomatic side in CTS patients could be significantly increased. Electrophysiology evaluation likewise indicated a significant increase in the distal median motor amplitude of the palm-wrist segment. In addition, Tinel's sign significantly decreased in the major symptomatic side. Our findings indicated that electroacupuncture could improve symptomatology, while acupuncture could exert positive therapeutic effects for CTS patients, as evidenced by improved symptomatology, grip strength, electrophysiological function, and physical provocation sign.
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Terapia por Acupuntura , Síndrome del Túnel Carpiano/terapia , Electroacupuntura , Puntos de Acupuntura , Adulto , Síndrome del Túnel Carpiano/diagnóstico , Síndrome del Túnel Carpiano/fisiopatología , Electrodiagnóstico/métodos , Femenino , Fuerza de la Mano , Humanos , Masculino , Nervio Mediano/fisiopatología , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Hepatitis B virus- (HBV-) associated hepatocellular carcinoma (HCC) is the most common type of liver cancer. However, the underlying mechanism of HCC tumorigenesis is very complicated and HBV-encoded X protein (HBx) has been reported to play the most important role in this process. Activation of downstream signal pathways of epidermal growth factor receptor (EGFR) family is known to mediate HBx-dependent HCC tumor progression. Interestingly, HER2 (also known as ErbB2/Neu/EGFR2) is frequently overexpressed in HBx-expressing HCC patients and is associated with their poor prognosis. However, it remains unclear whether and how HBx regulates HER2 expression. In this study, our data showed that HBx expression increased HER2 protein level via enhancing its mRNA stability. The induction of RNA-binding protein HuR expression by HBx mediated the HER2 mRNA stabilization. Finally, the upregulated HER2 expression promoted the migration ability of HBx-expressing HCC cells. These findings deciphered the molecular mechanism of HBx-mediated HER2 upregulation in HBV-associated HCC.
Asunto(s)
Proteínas ELAV/metabolismo , Regulación Neoplásica de la Expresión Génica , Virus de la Hepatitis B/metabolismo , Neoplasias Hepáticas/metabolismo , Receptor ErbB-2/biosíntesis , Transactivadores/metabolismo , Células Hep G2 , Virus de la Hepatitis B/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Estabilidad del ARN/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Receptor ErbB-2/genética , Transactivadores/genética , Regulación hacia Arriba/genética , Proteínas Reguladoras y Accesorias ViralesRESUMEN
This study has two aims: [1] to evaluate the association between hOGG1 genotypic polymorphism and endometriosis risk, and [2] to investigate the joint effects of hOGG1 genotype and smoking habit on endometriosis susceptibility in Taiwan. For this purpose, the well-known polymorphic variants of hOGG1, codon 326, was genotyped and analyzed of its association with the risk of endometriosis. In total, 153 patients with endometriosis and 636 non-endometriosis healthy controls were recruited and genotyped. The methodology for genotyping is polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Pearson's Chi-square test was performed to compare the distributions of the genotypes between case and control groups. The results showed that the hOGG1 codon 326 genotypes were not differently distributed between the endometriosis and non-endometriosis control groups in both genotypic (P = 0.6212) and allelic (P = 0.4006) frequency analysis. We have further analyzed the genotypic-smoking joint effects on endometriosis risk and found an obvious interaction between hOGG1 codon 326 genotypes and smoking status. The hOGG1 codon 326 genotypes were increased in endometriosis risk only in the smoker groups (P = 0.0061), but not in the non-chewer group (P = 0.0648). Our results provide the evidence that the hOGG1 codon 326 genotype may have a joint effect with smoking on the development of endometriosis.
Asunto(s)
ADN Glicosilasas/genética , Endometriosis/genética , Fumar/efectos adversos , Adulto , Endometriosis/epidemiología , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Taiwán/epidemiologíaRESUMEN
Diet modification plays an important role in nephrolithiasis. Development of an easy, ready-to-use beverage such as a commercial juice drink to use as a preventive treatment for renal calculi formation would be widely welcomed. We previously developed a novel Drosophila model for the study of nephrolithiasis. It provides a new well-established drug discovery platform for this common disease. In our current study, we used the Drosophila model to investigate the preventive effects of various commercial juices as potential treatments for nephrolithiasis. Our results showed that apple, cranberry, orange, and pomegranate juices failed to reduce calcium oxalate (CaOx) crystal formation, whereas our positive control-potassium citrate (K-citrate)-significantly prevented CaOx crystal formation. Unlike the commercial fruit juices that were tested, the administration of K-citrate significantly ameliorated the ethylene glycol (EG)-induced life-span reduction in treated flies. These results indicate that EG-induced CaOx nephrolithiasis in Drosophila can be prevented by K-citrate, but not by commercial citrate-containing juices. However, the inhibitory capability of citrate-containing juices to reduce renal stone formation in humans requires further elucidation.