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Tourism development: A capacity dynamic
Get PDFThe internationally adopted definition of tourism prompts to develop a systemic dynamic approach of tourism development. The paper proposes to conceptualize tourism development as a system interlinking three agents: transport, domestic tourism activities and the visitor; generating three types of development tourism development dynamics. In a second step, it uses this framework to develop, with a minimalist set of hypotheses, a capacity-based model enabling to consider destination tourism development as a microfounded supply-driven systemic dynamic process. Through the lens of the model, exhaustion or asymmetric distribution of market power may halt destination tourism development. Using the modelโs framework, the structuring forces of the Tourism Area Life Cycle (TALC) are explained by the dual impact of capacity dynamics: accelerating by increasing arrivals, and at the same time decelerating by declining price elasticities
Lupeol Inhibits Stemness in Colon Cancer-Stem Like Cells and Promotes Chemosensitivity via Degrading β-Catenin
No full textObjective: Colon cancer stem-like cells (CSCs) are self-renewing and tumor-initiating. They are resistant to chemotherapy drugs, such as doxorubicin. The presence of this subpopulation leads to poor treatment outcomes, recurrence and metastasis in colon cancer. Therefore, current therapeutic strategies targeting stem cell self-renewal pathways are a reasonable approach for cancer prevention and treatment. In this study, we aimed to evaluate the potential antitumor effects of Lup-20(29)-en-3b-ol (lupeol) by targeting this subpopulation. Methods: CSCs were enriched by being cultured in serum-free medium, and the effects of lupeol on CSC malignancies were measured. These effects included proliferation, migration, invasion and tumor formation. The stemness hallmarks were measured by western blotting. The effects of lupeol on the chemosensitivity of CSCs were measured by detecting apoptosis. Results: We found that lupeol did not affect cell proliferation and viability but remarkably inhibited the invasion and tumor formation abilities of CSCs. When colon cancer cells were cultured in serum-free medium, lupeol inhibited sphere formation and decreased stemness hallmarks. Moreover, when lupeol was added to the formed spheres for 48 h, the spheres dissociated and tended to grow adherently. Additionally, only Nestin and β-catenin, but not Sox2, Oct4 (Octamer-binding transcription factor) or Nanog, were significantly decreased. These results demonstrate that lupeol disturbed stemness in colon cancer, potentially by regulating Nestin or β-catenin. Additionally, lupeol treatment or β-catenin inhibitor treatment significantly increased DOX (Doxorubicin)-induced apoptosis, demonstrating that lupeol increased chemosensitivity potentially by downregulating β-catenin in CSCs. Conclusions: Taken together, our results demonstrate that lupeol is a potential chemoagent that specifically targets CSCs in colon cancer
Neuroprotective Potential of Trachyspermum Ammi Essential Oil against Monosodium Glutamate Induced Excitotoxicity by Reducing Accumulation of β-Amyloid
No full textBackground: Present investigation evaluates the neuroprotective effect of Trachyspermum ammi essential oil (TAEO) against monosodium glutamate induced excitotoxicity. Methods: Glutamate excitotoxicity was induced in rats by administrating monosodium glutamate [MSG; 2 g/kg body weight, intraperitoneally (i.p.)] for seven days and further animals were grouped into the following groups along with respective treatments: Group 1: Normal healthy control animals without any treatment; Group 2: MSG-2 g/kg, intraperitoneally (i.p.)+vehicle treated disease control animals; Group 3: MSG-2 g/kg, intraperitoneally (i.p.)+TAEO 250 mg/kg orally; Group 4: MSG-2 g/kg, intraperitoneally (i.p.)+500 mg/kg; Group 5: MSG-2 g/kg, intraperitoneally (i.p.)+D-cycloserine 10 mg/kg, i.p. Effect of TAEO was estimated on motor and cognitive function, oxidative stress parameters and Acetylcholinesterase (AChE) activity in the brain tissue of excitotoxicity rat model. Moreover β-Amyloid deposition on the brain tissue was estimated using Congo Red staining. Results: There was significant improvement in motor and cognitive function in TAEO group in comparison with the negative control group, which was observed to be reversed in TAEO+N-methyl-D-aspartate (NMDA) treated agonist. Treatment with TAEO ameliorates the altered parameters of oxidative stress and activity of AChE in the brain tissue of excitotoxicity rats. β-Amyloid deposition was observed to be reduced in TAEO treated group as compared with negative control group. However, this effect of TAEO was reversed in the brain tissue of TAEO+NMDA agonist treated group. Conclusions: Hence, the data of the present study suggested that the TAEO treatment improves the motor and cognitive function in MSG-induced excitotoxicity in rat model by reducing oxidative stress and formation of β-Amyloid plaque by targeting NMDA receptor
SRPX2 Overexpression Promotes the Proliferation and Migration of Mouse Vascular Endothelial Progenitor Cells
No full textBackground: This study aimed to explore the molecular mechanism of Sushi repeat-containing protein X-linked 2 (SRPX2) overexpression in the growth of mouse vascular endothelial progenitor cells (EPCs). Methods: Lentiviral transfection was used to establish SRPX2 overexpression in the mouse EPC lines. Cell counting kit-8 (CCK8) and transwell assays were used to determine the role of SRPX2 overexpression in EPCs. Transcriptome sequencing of the SRPX2 overexpression (SRPX2 OE) and negative control (NC) groups was performed, followed by the screening of differentially expressed genes (DEGs). Protein-protein interaction (PPI) analysis was performed to screen potential hub genes. Furthermore, miRNAs and transcription factors (TFs) that regulated genes in the modules were predicted. The expression levels of genes were determined using real-time quantitative reverse transcription PCR (RT-qPCR). Results: SRPX2 overexpression promoted the proliferation and migration of EPCs. A total of 828 DEGs was identified. Five hub genes were screened using PPI analysis: Collagen type I alpha 2 chain (COL1A2), collagen type III alpha 1 chain (COL3A1), CX3-C motif chemokine receptor 1 (CX3CR1), insulin like growth factor binding protein 3 (IGFBP3), and sphingosine-1-phosphate receptor 3 (S1PR3). The RT-qPCR assay indicated that the expression levels of these genes were consistent with the results of the bioinformatics analysis. Moreover, miRNAs such as let-7e-5p, miR-29a-3p, and miR-29b-3p might be involved in the EPC proliferation. Conclusions: Our study suggested that SRPX2 overexpression could promote mouse EPC proliferation and migration, and the identified genes were considered as potential biomarkers for endothelial remodeling during angiogenesis
The Effect of Berberine on the PI3K/Akt/NF-kB Signaling Pathway in Colonic Tissues of Morphine-Induced Acute Constipation Mice
No full textBackground: Opioid-induced constipation not only directly affects the quality of life of patients, but also causes complications that seriously affect their health. This study aimed to observe the effect of berberine (BBR) on morphine (MP)-induced acute constipation in mice. Methods: The acute constipation model was tested by subcutaneous injection of MP at doses of 2, 5, or 10 mg/kg. According to the degree of constipation, MP (10 mg/kg) was selected as the MP dose for the MP-mediated model in the following experiment that included eight groups: Vehicle, MP, BBR (2 mg/kg), BBR (5 mg/kg), BBR (10 mg/kg), MP+BBR (2 mg/kg), MP+BBR (5 mg/kg), and MP+BBR (10 mg/kg). BBR was injected once intraperitoneally 30 minutes before a single injection of MP in each mouse. Defecation function, as reflected by accumulated fecal weight, fecal pellet number, and fecal water content, was measured over a 6-hour period. At the end of the experiment, colonic tissues of mice were extracted under general anesthesia. The expression of mRNA level of phosphatidylinositol 3-protein kinase (PI3K) and protein kinase B (Akt) was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). The expression levels of phosphorylated PI3K, Akt and nuclear factor kappa-B (NF-kB) and the total protein expression levels of PI3K, Akt, NF-kB, interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were detected by western blot assays. The ratio of phosphorylation levels of PI3K, Akt and NF-kB to total protein levels was calculated. The distribution of phosphorylated Akt (p-Akt) and p-NF-kB in colonic tissue was stained by immunohistochemistry and the mean intensity value was calculated. Results: Single administration of MP caused acute constipation in mice. BBR did not change defecation function compared with the blank group (p > 0.05). When BBR was used in combination with MP at doses 2, 5, and 10 mg/kg, no statistically significant differences from MP alone were observed (p > 0.05). Compared with the blank group, BBR caused no significant difference in the expression of PI3K and Akt at the mRNA level (p > 0.05). However, at the protein level, MP increased the relative expressions of p-PI3K, p-Akt, and p-NF-kB compared with the blank group (p < 0.05), and BBR completely reversed the activation (p < 0.05). Similar changes were observed in the expression of TNF-α and IL-6 that is downstream of NF-kB (p < 0.05). Conclusions: Though BBR did not affect MP-mediated constipation in mice, it ameliorated colonic inflammation by completely reversing MP-mediated activation of the PI3K/Akt/NF-kB signaling pathway
A Rapid Detection Method for Mycoplasma Pneumoniae through the Combination of Recombinase Polymerase Amplification and CRISPR-Cas12a
No full textBackground: There is a primary pathogen responsible for Mycoplasma pneumoniae pneumonia (MPP) in children called Mycoplasma pneumoniae (MP). Patients with mild symptoms usually complain of paroxysmal dry cough by stimulation and fever, while those with severe conditions may develop bronchopneumonia, pleural effusions, and lung abscesses, and even accompanied by lesions in the nervous system or urinary system. We aimed to develop a rapid detection method for MP adhesion protein P1 by merging recombinase polymerase amplification (RPA) and Clustered Regularly Interspaced Short Palindromic Repeats/associated proteins (CRISPR/Cas12a) gene editing. Methods: In this study, the sequence of P1 adhesion protein region (GenBank: AF290001.1) of MP was obtained from the national center of biotechnology information (NCBI) database. Five groups of primers and probes were designed using Primer Premier 5 software (Premier Canada Inc., Charlotte, NC, USA), and the best primers were selected. Furthermore, in the meantime, the corresponding real-time fluorescence quantitative polymerase chain reaction (RT-PCR) primers were designed for subsequent validation tests to determine the reagent proportion, reaction time, reaction temperature, and primer-probe concentration of the reaction system. Finally, diseased clinical samples (strong positive, medium positive, weak positive) and healthy clinical samples (1, 2, 3) were used to verify the optimized cutting system. Results: Through the experiments, we verified that the optimal reaction time for RPA at 37 °C was 30 min, and the best product was obtained by cleaving Cas12a-crRNA for 60 min, with a result fetched within 2 h. Conclusions: This method is not only fast and convenient in operation but also ensures the specificity, rapid efficiency and visualization of the test results without relying on instruments and professional personnel. It provides a solution to the subjective judgment of the culture test method and the difficulty of smear preparation
Effect of Acute Caffeine Supplementation on Dynamic Force Indicators at Different Training Moments in Paralympic Powerlifting
No full textBackground: Several reports have highlighted the beneficial impacts of caffeine on performance in various disciplines of Paralympic Powerlifting (PP), a sport renowned for its emphasis on maximal strength. Moreover, caffeine consumption within the context of PP has been found to be safe. Objective: To examine the effects of caffeine intake before, during, and after PP training sessions at national level in Brazil. Methods: Thirteen male PP athletes competing at national level (31.31 ± 10.13 years, 80.77 ± 22.66 kg) participated in the study. They were provided with either 9.0 mg/kg of Caffeine Anhydrous (CA) or Placebo (PL) and were evaluated using 45% of their one-repetition maximum (1RM) before and after training sessions, as well as 24 and 48 hours after sessions. Additionally, they performed five sets of five repetitions maximum (5x5), with assessments carried out during the first and fifth sets for all five repetitions. Evaluations focused on Mean Propulsive Velocity (MPV), Maximum Velocity (MaxV), and Power. Results: No significant differences were observed with 45% 1RM. However, at 80% 1RM, CA demonstrated significant improvement compared to PL during Set 1 and Set 5 (p < 0.05). Conclusions: CA exhibits promising ergogenic properties, enabling athletes to sustain training intensity throughout the session, even when working with heavier PP loads
Amygdalin Induced Mitochondria-Mediated Apoptosis of Hypopharyngeal Carcinoma
No full textPurpose: Amygdalin is a natural extract effective in cancer inhibition, though its effects on hypopharyngeal squamous cell carcinoma (HSCC) have not been investigated. This study aims to investigate the in vitro anti-hypopharyngeal carcinoma activity of amygdalin and its potential mechanism. Methods: The hypopharyngeal squamous cell carcinoma cell lines (FADU and TU212) were treated with amygdalin. The proliferation of hypopharyngeal carcinoma was tested by mitochondria targeting sequence (MTS) assay. Furthermore, Annexin V-fluorescein isothiocyanate/propidine iodide (Annexin V-FITC/PI) double staining, immunofluorescence and mitochondrial membrane potential (MMP) assays were taken to test apoptosis. Apoptotic mRNA transcript levels and protein expression were evaluated using real-time quantitative PCR (qPCR) and western blot (WB). Results: FADU and TU212 cells were treated with amygdalin. MTS assay showed that amygdalin inhibited the proliferation of hypopharyngeal carcinoma cells. Annexin V-FITC/PI double staining, immunofluorescence and MMP detection assays were carried out and confirmed that amygdalin induced apoptosis in hypopharyngeal carcinoma cells. In addition, qPCR and WB analysis suggested that amygdalin exerted a carcinogenic anti-hypopharyngeal effect by mediating the mitochondrial apoptosis pathway. Conclusions: Amygdalin can inhibit the proliferation of hypopharyngeal carcinoma cells and promote apoptosis of hypopharyngeal carcinoma cells by inducing the mitochondrial apoptosis pathway. Amygdalin is a potential chemotherapeutic agent for hypopharyngeal carcinoma
Diagnostic Value of Ultrasound Associated with Serum NLR, PLR, MLR and CA125 for Endometrial Carcinoma
No full textBackground: Overall mortality of endometrial carcinoma (EC) has been increasing. Therefore, the correct preoperative diagnosis and accurate staging of EC are of great significance. Objective: This study aims to explore the diagnostic value of ultrasound associated with serum ratios of neutrophils to lymphocytes (NLR), platelets to lymphocytes (PLR), monocytes to lymphocytes (MLR) and carbohydrate antigen 125 (CA125) for endometrial carcinoma (EC). Methods: From 2018 to 2020, 104 patients with suspected EC diagnosed by ultrasound from the Affiliated Hospital of Sichuan Medical College were enrolled. All patients were examined by routine ultrasound, serum tumor markers CA125 and serum levels of NLR, PLR and MLR before operation. The size, boundary, internal echo and internal blood flow of the focus were recorded in detail. The correlation between NLR, PLR, MLR, CA125 and the occurrence of EC was analyzed by logistic regression. The receiver operating curve (ROC) and area under curve (AUC) were employed to evaluate the sensitivity and specificity of NLR, PLR, MLR, CA125 associated with ultrasound for diagnosing EC. Results: Among the 104 suspected cases, 64 were EC patients. The growth site, lesion shape and lesion range of 50% of the cancer foci were shown more clearly than those before radiography. There was a significant difference between high and low levels of NLR for surgical and pathological stages, histological types and myometrial invasion depth (p < 0.05). There was a significant difference between high and low levels of PLR for surgical and pathological stages, histological types and cervical involvement (p < 0.05). There was a significant difference between high and low levels of CA125 for surgical and pathological stages, histological types and depth of myometrial invasion (p < 0.05). Elevated levels of NLR, PLR, and CA125 were independent predictors of EC based on multivariate logistic regression analysis. ROC curve analysis revealed that the AUC value of ultrasound examination combined with NLR, PLR, MLR and CA125 for EC diagnosis was higher than other indexes. Conclusions: The diagnostic value of NLR, PLR, MLR and CA125 associated with ultrasound for EC is higher than ultrasound alone
Platelet-Rich Plasma Reduces LPS-Stimulated Inflammatory Reaction in BV2 Cells by Blocking the TLR4-Mediated NF-κB/MAPKs Pathway
No full textBackground: The study was designed to decipher the impact of platelet-rich plasma (PRP) on lipopolysaccharide (LPS)-mediated inflammation in BV2 (A murine cell line has been generated by infecting primary microglial cell cultures with a v-raf/v-myc oncogene carrying retrovirus (J2)) microglia. Method: BV2 microglia activation was induced by lipopolysaccharide (LPS) to establish an in vitro model of neuroinflammation. After pretreatment with different concentrations of PRP, the apoptosis of BV2 microglia was determined by flow cytometry, terminal deoxynucleotidyl transferase fluorescence labeling (TUNEL) and JC-1 assay. The production level of nitric oxide (NO) was determined by Griess method, and the mRNA (messenger RNA) expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The contents of TNF-α, IL-1β, IL-6, and prostaglandin E2 (PGE2) cytokines were determined by enzyme-linked immunosorbent assay (ELISA). The phosphorylation of nuclear factor kappa-B (NF-κB/P65), inhibitor of NF-κB α (IκBα), c-Jun N-terminal kinase (JNK), extracellular signal-regulated MAP kinases 1/2 (ERK1/2), and p38 mitogen-activated protein kinases (p38 MAPKs) in the NF-κB/MAPKs pathway was analyzed by Western blot. The nuclear translocation of phosphorylated NF-κB/P65 subunits was evaluated by laser confocal microscopy. Results: PRP decreased LPS-stimulated apoptosis of BV2 microglia (p < 0.05). Moreover, PRP inhibited the mRNA levels of TNF-α, IL-1β, IL-6, iNOS, and COX-2 and the NO level (p < 0.05), in addition, PRP also reduced the production of inflammatory mediators including TNF-α, IL-1β, IL-6, and PGE2 (p < 0.05), inhibited the protein levels of p-NF-κB/P65, p-IκBα, p-JNK, p-ERK1/2, and p-p38 in the NF-κB/MAPKs pathway in LPS-induced BV2 microglia (p < 0.05), decreased the nuclear translocation of p-NF-κB/p65 subunit (p < 0.05). Particularly, PRP at a concentration of 10% showed the optimal the inhibition effects. Conclusions: PRP attenuates LPS-mediated inflammation in BV2 microglia by blocking the TLR4-NF-κB/MAPKs axis