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A series of ß-thioketiminate copper(I) complex trimers [LCuI]3 were synthesized by modifying the ligand framework with electron-withdrawing groups (F and Cl) or electron-donating groups (iPr and Me) at the N-aryl ring as well as with CF3 groups on the chelating backbone. This ligand modification significantly impacts the enhancement of Cuâ¯Cu short contacts, which can be rationalized by using steric and electronic factors of the chelated ligand. We observed that this intramolecular cuprophilicity among [LCuI]3 complexes is primarily governed by the size of N-aryl ortho-substituents. These findings were well supported by X-ray crystallography, Raman spectroscopy, and Mayer bond order analysis. The electronic effects induced by the ligand modification on the LCuI fragment were investigated using CO and 2,4,6-CNC6H2Me3 as probe molecules. Corroborated by the FTIR and CV measurements, our results reveal that the ß-thioketiminate SN chelators induce more pronounced changes in the electronic character of the LCuI fragment due to the presence of CF3 groups on the chelating backbone in comparison with the F or Cl substituents on the N-aryl ring.
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Extracellular vesicles (EVs) are functional substances secreted by microbes and host cells, and it has been discovered that they participate in the interactions between different microorganisms. Our recent findings indicate that Limosilactobacillus reuteri-derived EVs have the potential to improve the intestinal microbiota of Oplegnathus fasciatus fish and inhibit pathogenic bacteria. Previous research has reported that the host intestinal cells play a regulatory role in the intestinal microbiota. This suggested that to investigate the mechanisms through which L. reuteri-derived EVs regulate the intestinal microbiota, a system that excludes interference from host intestinal cells should be established. In this study, an in vitro cultured intestinal bacteria system, without host factors, was used to simulate the intestinal microbiota of O. fasciatus fish. After adding L. reuteri-derived EVs to the system, the changes in the microbiota were analyzed. The results showed that L. reuteri-derived EVs effectively reduced the abundance of Vibrio spp. In the results of the in vitro experiments, it was also observed that L. reuteri-derived EVs have the ability to inhibit Vibrio alginolyticus. We further sequenced the small RNA contained in L. reuteri-derived EVs and found that these small RNAs can interfere with genes (LysR, pirin, MIpA/OmpV, CatB, and aspartate-semialdehyde dehydrogenase) related to the growth of V. alginolyticus. Taken together, the results indicate that in the absence of host involvement, the small RNAs present in L. reuteri-derived EVs have the function of inhibiting pathogenic bacteria and exhibit the potential to regulate the intestinal microbiota.
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Aquaponics is an integrated food production system that intensively produces a diverse array of seafood and specialty crops in one closed-loop system, which is a potential solution to global challenges of food security. While current aquaponics systems are commonly operated with freshwater, marine aquaponics is an emerging opportunity to grow saltwater animals and plants. Although marine aquaponics can reduce the dependence on freshwater for food production, its environmental sustainability has not been systematically studied. This paper presents the first life cycle assessment (LCA) on a marine aquaponic production system growing shrimp and three halophytes. The system assessed covered from shrimp larvae nursery to grow-out. The effects of salinity, carbon/nitrogen (C/N) ratio and shrimp-to-plant stocking density ratio of aquaponics on its midpoint and endpoint environmental impacts were evaluated using a functional unit based on the economic value of the four products. Electricity use for aquaponic operation was the environmental hotspot, contributing â¼90 % to all the midpoint impacts. The system produced higher environmental impacts when operated at higher salinity, but lower C/N ratio and stocking density. Replacing fossil fuel with wind power for electricity generation can decrease the environmental impacts by 95-99 %. Variation in the shrimp price can change the impacts by up to 62 %. This study provides a useful tool to help marine aquaponic farmers improve their production from an environmental perspective, and can serve as groundwork for further assessing more marine aquaponic systems with different animal-plant combinations.
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Acuicultura , Productos Agrícolas , Animales , Hidroponía , Nitrógeno , Alimentos Marinos , Estadios del Ciclo de VidaRESUMEN
The underlying mechanism of colorectal cells developing into cancer cells has been extensively investigated, yet is still not fully delineated, resulting in the treatment of advanced colorectal cancer (CRC) remains regrettably an unmet need. Zinc Finger Protein 746/Parkin-interacting substrate (ZNF746/PARIS) has previously been identified to play a fundamental role on bladder cancer cell proliferation and metastasis that were effectively inhibited by melatonin (Mel). In this study, we utilized ex vivo/in vivo studies to verify whether the ZNF746 signaling was also crucial in CRC growth/invasion/migration. Tissue-bank specimens showed that the protein expression of ZNF746 was significantly increased in CRC than that of healthy colorectal tissues (p < 0.001). Additionally, in vitro study demonstrated that excessive expression of ZNF746 significantly inhibited mitochondrial activity via (1) interfering with the dynamic balance of mitochondrial fusion/fission and (2) inhibiting the protein expression of MFN1/MFN2/PGC1a (all p < 0.001). Furthermore, we identified that inhibition of ZNF746 protein expression significantly reduced the resistance of CRC cell lines to the anticancer drug of 5-FU (p < 0.001), whereas overexpression of ZNF746 significantly augmented resistance of CRC cells to 5-FU (all p < 0.001). Finally, using the cell culture method, we found that combined Mel and 5-FU was superior to merely one on promoting the CRC cell apoptosis (p < 0.001). Our results confirmed that ZNF746 signaling played a cardinal role of CRC cell proliferation/survival and combined Mel and 5-FU treatment attenuated the resistance of CRC cells to the drug mainly through suppressing this signaling.
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Neoplasias Colorrectales , Melatonina , Humanos , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Línea Celular Tumoral , Melatonina/farmacología , Melatonina/uso terapéutico , Dinámicas Mitocondriales , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Proliferación Celular , Resistencia a Antineoplásicos , Proteínas Represoras/metabolismoRESUMEN
This study discloses the nanoscale silicate platelet-supported nZnO (ZnONSP) applied as novel feed additives in aquaculture. The preparation of the nanohybrid (ZnO/NSP = 15/85, w/w) was characterized by UV-visible spectroscopy, powder X-ray diffraction and transmission electron microscope. The effects of ZnONSP on growth, zinc accumulation, stress response, immunity and resistance to Vibrio alginolyticus in white shrimp (Penaeus vannamei) were \demonstrated. To evaluate the safety of ZnONSP, shrimps (2.0 ± 0.3 g) were fed with ZnONSP containing diets (200, 400 and 800 mg/kg) for 56 days. Dietary ZnONSP did not affect the weight gain, specific growth rate, feed conversion ratio, survival rate, zinc accumulation, and the expression of heat shock protein 70 in tested shrimps. To examine the immunomodulatory effect of ZnONSP, shrimps (16.6 ± 2.4 g) were fed with the same experimental diets for 28 days. Dietary ZnONSP improved the immune responses of haemocyte in tested shrimps, including phagocytic rate, phagocytic index, respiratory burst, and phenoloxidase activity, and upregulated the expression of several genes, including lipopolysaccharide, ß-1,3-glucan binding protein, peroxinectin, penaeidin 2/3/4, lysozyme, crustin, anti-lipopolysaccharide factor, superoxide dismutase, glutathione peroxidase, clotting protein and α-2-macroglobulin. In the challenge experiment, shrimps (17.2 ± 1.8 g) were fed with ZnONSP containing diets (400 and 800 mg/kg) for 7 days and then infected with Vibrio alginolyticus. Notably, white shrimps that received ZnONSP (800 mg/kg) showed significantly improved Vibrio resistance, with a survival rate of 71.4 % at the end of 7-day observation. In conclusion, this study discovers that ZnONSP is a new type of immunomodulatory supplement that are effective on enhancing innate cellular and humoral immunities, and disease resistance in white shrimp.
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Inmunidad Innata , Penaeidae , Animales , Suplementos Dietéticos , Dieta/veterinaria , Resistencia a la Enfermedad , Vibrio alginolyticus/fisiología , Zinc/farmacologíaRESUMEN
In this study, a series of Al complexes bearing amidates, thioamidates, ureidates, and thioureidates were synthesized and their catalytic activity for ε-caprolactone (CL) polymerization was evaluated. SPr-Al exhibited a higher catalytic activity than OPr-Al (3.2 times as high for CL polymerization; [CL] : [SPr-Al] : [BnOH] = 100 : 0.5 : 2; [SPr-Al] = 10 mM, conv. = 93% after 14 min at 25 °C), and USCl-Al exhibited a higher catalytic activity than UCl-Al (4.6 times as high for CL polymerization; [CL] : [USCl-Al] : [BnOH] = 100 : 0.5 : 2; [USCl-Al] = 10 mM, conv. = 90% after 15 min at 25 °C). Regardless of whether aluminum amidates or ureidates were present, thioligands improved the polymerization rate of aluminum catalysts. Density functional theory calculations revealed that the eight-membered ring [SPr-AlOMe2]2 decomposed into the four-membered ring SPr-AlOMe2. However, [OPr-AlOMe2]2 did not decompose because of its strong bridging Al-O bond. The overall activation energy required for CL polymerization was lower when using [SPr-AlOMe2]2 (18.1 kcal mol-1) as a catalyst than when using [OPr-AlOMe2]2 (23.9 kcal mol-1). This is because the TS2a transition state of SPr-AlOMe2 had a more open coordination geometry with a small N-Al-S angle (72.91°) than did TS3c of [OPr-AlOMe2]2, the crowded highest-energy transition state of [OPr-AlOMe2]2 with a larger N-Al-O angle (99.63°).
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Two classes of ß-thioketiminate ligands, SN chelators (HL1 and HL2) and SNN chelators (HL3 and HL4), were prepared to understand their coordination behavior in copper(I) complex formation. The formation of these copper(I) complexes bearing ß-thioketiminate ligands and their corresponding adducts toward isocyanide, PPh3, and CO was investigated to address two important issues. First, whether the denticity governs the copper(I) thiolate species formation between SN chelators and SNN chelators. Second, how the length of the pendant pyridyl arm affects the coordination and reactivity behaviors of copper(I) complexes. Based on the characterization results, it was found that the denticity of SN chelators and SNN chelators led to different nuclearity of copper(I)-thiolate species. The coordination modes of the pendant pyridyl arm were confirmed by FTIR measurements, which allow us to conclude that the electron donating ability of the LCu fragment is in the order of SNN-chelator (SNN bound) > SNN-chelators (SN bound) > SN-chelator.
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Background and aim: We have previously reported that histamine H1 receptor antagonists facilitate electroacupuncture (EA) analgesia in experimental animals. In this pilot study, we sought to determine whether the histamine H1 receptor antagonist dexchlorpheniramine (DCPA) facilitates EA analgesia in healthy human subjects. Experimental procedure: Forty healthy subjects aged 20-30 years were randomly allocated to 1 of 4 groups: (1) sham EA at acupoints Zusanli (ST36) and Yanglingquan (GB34) (sham EA; n = 10); (2) EA at ST36 and GB34 (n = 10); (3) EA at ST36 and GB34 plus low-dose DCPA (2 mg, n = 10); (4) EA at ST36 and GB34 plus high-dose DCPA (4 mg, n = 10). Before and after acupuncture treatment, pain thresholds were determined by transcutaneous electrical stimuli on the glabrous skin of the left upper arm. Results: After the acupuncture session, subjects in the EA plus high-dose DCPA group had a significantly higher pain threshold elevation compared with the other 3 study groups. The change from baseline in pain threshold in the EA plus high-dose DCPA group was significantly greater than the change in pain threshold with EA only, indicating that DCPA 4 mg facilitated EA analgesia. Conclusion: The results suggest that combining H1 receptor antagonist treatment with EA appears to relieve pain to a greater extent compared with EA alone. This study is registered with ClinicalTrials.gov (https://clinicaltrials.gov/), number NCT03805035 (https://clinicaltrials.gov/ct2/show/NCT03805035).
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Background: Acupuncture or electroacupuncture (EA) appears to be a potential treatment in acute clinical traumatic brain injury (TBI); however, it remains uncertain whether acupuncture affects post-TBI histone deacetylase (HDAC) expression or impacts other biochemical/neurobiological events. Materials and methods: We used behavioral testing, Western blot, and immunohistochemistry analysis to evaluate the cellular and molecular effects of EA at LI4 and LI11 in both weight drop-impact acceleration (WD)- and controlled cortical impact (CCI)-induced TBI models. Results: Both WD- and CCI-induced TBI caused behavioral dysfunction, increased cortical levels of HDAC1 and HDAC3 isoforms, activated microglia and astrocytes, and decreased cortical levels of BDNF as well as its downstream mediators phosphorylated-Akt and phosphorylated-GSK-3ß. Application of EA reversed motor, sensorimotor, and learning/memory deficits. EA also restored overexpression of HDAC1 and HDAC3, and recovered downregulation of BDNF-associated signaling in the cortex of TBI mice. Conclusion: The results strongly suggest that acupuncture has multiple benefits against TBI-associated adverse behavioral and biochemical effects and that the underlying mechanisms are likely mediated by targeting HDAC overexpression and aberrant BDNF-associated Akt/GSK-3 signaling.
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BACKGROUND: No reports exist as to neuroprotective effects associated with topical activation of transient receptor potential melastatin 8 (TRPM8), a noted cold receptor. In the present study, we identified whether activating peripheral TRPM8 can be an adjuvant therapy for ischemic stroke. METHODS: Menthol, an agonist of TRPM8, was applied orally or topically to all paws or back of the mouse after middle cerebral artery occlusion (MCAO). We used Trpm8 gene knockout (Trpm8-/-) mice or TRPM8 antagonist and lidocaine to validate the roles of TRPM8 and peripheral nerve conduction in menthol against ischemic stroke. RESULTS: Application of menthol 16% to paw derma attenuated infarct volumes and ameliorated sensorimotor deficits in stroke mice induced by MCAO. The benefits of topically applied menthol were associated with reductions in oxidative stress, neuroinflammation and infiltration of monocytes and macrophages in ischemic brains. Antagonizing TRPM8 or Trpm8 knockout dulls the neuroprotective effects of topically application of menthol against MCAO. Immunohistochemistry analyses revealed significantly higher TRPM8 expression in skin tissue samples obtained from the paws compared with skin from the backs, which was reflected by significantly smaller infarct lesion volumes and better sensorimotor function in mice treated with menthol on the paws compared with the back. Blocking conduction of peripheral nerve in the four paws reversed the neuroprotective effects of topical menthol administrated to paws. On the other hand, oral menthol dosing did not assist with recovery from MCAO in our study. CONCLUSION: Our results suggested that activation of peripheral TRPM8 expressed in the derma tissue of limbs with sufficient concentration of menthol is beneficial to stroke recovery. Topical application of menthol on hands and feet could be a novel and simple-to-use therapeutic strategy for stroke patients.
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Accidente Cerebrovascular Isquémico , Mentol , Fármacos Neuroprotectores , Canales Catiónicos TRPM , Animales , Infarto/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Mentol/farmacología , Mentol/uso terapéutico , Ratones , Canales Catiónicos TRPM/genéticaRESUMEN
BACKGROUND: Neoadjuvant chemotherapy is commonly performed to reduce the size of tumors before partial mastectomy to improve the rate of breast-conservation. Few studies have been conducted to assess the neoadjuvant chemotherapy experience of women diagnosed with breast cancer and their responses to it. PURPOSE: To explore the experience of women diagnosed with breast cancer who received neoadjuvant chemotherapy and their responses to it. METHODS: The grounded theory was adopted as the methodology. Participants were recruited using purposive sampling. The data were collected using semi-structured, in-depth interviews and analyzed using open, axial, and selective coding. RESULTS: A total of 15 women newly diagnosed with breast cancer participated in this study, with information showing that the core category oscillated between the sizes of the tumor. The three categories included difficulty in coping with the physical response to chemotherapy, absence of role fulfillment, and uneasy emotions. The coping strategies used by the participants included: body and mind adjustment, hiding, family labor adjustment, and changing the pace of social life. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The participants experienced tremendous physical and psychological stress during their neoadjuvant chemotherapy, in which tumor response assessment served as a critical time point. Medical professionals, in addition to noting changes in women's physiological response, must pay attention to their psychological burden and provide emotional support and treatment information as needed.
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Neoplasias de la Mama , Terapia Neoadyuvante , Adaptación Psicológica , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/psicología , Femenino , Humanos , Mastectomía , Estrés PsicológicoRESUMEN
This study discussed the effects of two types of lactic acid bacteria, Lactobacillus reuteri (L. reuteri) and Pediococcus acidilactici (P. acidilactici), on the growth and nonspecific immunity of Penaeus vannamei (P. vannamei) and developed probiotic applications for shrimp cultivation. This study incorporated two types of lactic acid bacteria in shrimp feed through spraying. The shrimps were grouped according to the type and concentration of effective bacteria incorporated into their feed. This research was separated into 3 individual feeding treatment as control, L. reuteri (Lr groups) and P. acidilactici (Pa groups). The shrimp was feeding with 103, 105, and 107 cfu/feed (g) L. reuteri namely as Lr3, Lr5, and Lr7. The shrimp was feeding with 103, 105, and 107 cfu/feed (g) P. acidilactici were named Pa3, Pa5, and Pa7, respectively. Through 8 weeks of feeding, the results revealed that the use of shrimp feed incorporated with lactic acid bacteria did not cause negative effects on water quality. The testing items include ammonia-nitrogen concentration, nitrite-nitrogen concentration, and total vibrio count in the water. In addition, the lactic acid bacteria concentration in the water were in the range of 1.33 ± 0.58 × 101 to 9.77 ± 1.34 × 102 cfu/mL. Observations of the growth performance of the white shrimps after 8 weeks of feeding revealed that both bacteria were beneficial to shrimp growth. In particular, group Lr7 had the highest percentage weight gain (107.99 ± 3.92%), special growth rate (1.93 ± 0.07%), feed conversion ratio (3.34 ± 0.05), and survival rate (97.22 ± 4.81%). Furthermore, observations of the nonspecific immunity reactions of the white shrimps after 4 weeks of feeding indicated that on day 4, the total number of haemocyte in shrimps in groups Lr5, Lr7, Pa3, and Pa5 significantly increased. On days 1 and 4, the phenoloxidase activity and superoxide axion production rates of the Lr group and Ls group increased. This phenomenon was the most significant in group Lr7, and the effect continued until day 28. After day 7, the phagocytic rate of groups Lr5 and Lr7 significantly increased. In addition, Lr and Pa groups exhibited significant increases in the phagocytic index after days 4 and 14, respectively. This phenomenon was also the most significant in group Lr7.
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Limosilactobacillus reuteri , Pediococcus acidilactici , Penaeidae , Probióticos , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Inmunidad Innata , Nitrógeno/farmacología , Probióticos/farmacología , Calidad del AguaRESUMEN
pH is the major issue that concerns all producers in aquaponics, as the main three organisms (aquatic animal, plant, and microbes) have different preferences. Additional C is a potential approach to amend the growing environment and improve shrimp and plant growth, and microbe establishment. Aquaponics under saline conditions has, however, not been studied in detail in regard to the effect of pH and additional C. In this study, we evaluate the impact of pH and additional C on the growth of Pacific whiteleg shrimp and five edible plants (three halophytes and two glycophytes) in marine aquaponic systems using nutrient film technique (NFT). The results indicated that plants grow better in both pH 6.5 treatments; however, additional C improved the growth in pH 7.5 + C treatment and had similar yield to lower pH treatments. The results indicated both pH and additional C had little impact on shrimp growth. In conclusion, adding C can be a practical solution to the pH conundrum for marine aquaponics. Appling additional C was suggested for the operation of marine aquaponic food production system when the pH is high.
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Previous studies have shown that natural environments and leisure activities can reduce depression and increase well-being. Urban parks are important for the psychological well-being of middle-aged and older adults. However, it remains unknown whether the relationship between environmental perceptions, leisure activity, and well-being is affected by the quality of park environments. This study uses a cross-level framework to examine the effects of urban park quality on middle-aged and older adults' environmental perceptions, leisure activity, and well-being. The Neighborhood Green Space Tool was used to assess the environmental quality of 19 parks, and 380 individuals aged 55 years and older were interviewed in each park using an on-site questionnaire. The results reveal that the associations between environmental perception and well-being were moderated by the quality of park accessibility, amenities, and incivilities; the effect of environmental perception on depression was moderated by the quality of incivilities in parks; and the effect of frequency of leisure activities on depression was moderated by the quality of park accessibility.
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Actividades Recreativas , Parques Recreativos , Anciano , Ambiente , Planificación Ambiental , Humanos , Persona de Mediana Edad , Percepción , Características de la Residencia , Población UrbanaRESUMEN
Pruritus, or itch, is a frequent complaint amongst patients with cholestatic hepatobiliary disease and is difficult to manage, with many patients refractory to currently available antipruritic treatments. In this study, we examined whether manual acupuncture (MA) at particular acupoints represses deoxycholic acid (DCA)-induced scratching behavior and microglial activation and compared these effects with those induced by another pruritogen, 5'-guanidinonaltrindole (GNTI, a kappa opioid receptor antagonist). MA at Hegu (LI4) and Quchi (LI11) acupoints significantly attenuated DCA- and GNTI-induced scratching, whereas no such effects were observed at the bilateral Zusanli acupoints (ST36). Interestingly, GNTI-induced scratching was reduced similarly by both MA and electroacupuncture (EA) at the LI4 and LI11 acupoints. MA at non-acupoints did not affect scratching behavior. Intraperitoneal injection of minocycline (a microglial inhibitor) reduced GNTI- and DCA-induced scratching behavior. In Western blot analysis, subcutaneous DCA injection to the back of the neck increased spinal cord expression of ionized calcium-binding adapter molecule 1 (Iba1) and tumor necrosis factor-alpha (TNF-α) as compared with saline injection, while MA at LI4 and LI11 reduced these DCA-induced changes. Immunofluorescence confocal microcopy revealed that DCA-induced Iba1-positive cells with thicker processes emanated from the enlarged cell bodies, while this effect was attenuated by pretreatment with MA. It is concluded that microglia and TNF-α play important roles in the itching sensation and MA reduces DCA-induced scratching behavior by alleviating spinal microglial activation. MA may be an effective treatment for cholestatic pruritus.
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Terapia por Acupuntura , Ácidos y Sales Biliares/efectos adversos , Microglía/metabolismo , Prurito/terapia , Factor de Necrosis Tumoral alfa/fisiología , Animales , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Prurito/etiologíaRESUMEN
There is an interest in identifying Anaphase Promoting-Complex/Cyclosome (APC/C) inhibitors that lead to sensitivity to microtubule poisons as a strategy for targeting cancer cells. Using budding yeast Saccharomyces cerevisiae, peptides derived from the Mitotic Arrest Deficient 2 (Mad2)-binding motif of Cell Division Cycle 20 (Cdc20) were observed to inhibit both Cdc20- and CDC20 Homology 1 (Cdh1)-dependent APC/C activity. Over expression of peptides in vivo led to sensitivity to a microtubule poison and, in a recovery from a microtubule poison arrest, delayed degradation of yeast Securin protein Precocious Dissociation of Sisters 1 (Pds1). Peptides with mutations in the Cdc20 activating KILR-motif still bound APC/C, but lost the ability to inhibit APC/C in vitro and lost the ability to induce sensitivity to a microtubule poison in vivo. Thus, an APC/C binding and activation motif that promotes mitotic progression, namely the Cdc20 KILR-motif, can also function as an APC/C inhibitor when present in excess. Another activator for mitotic progression after recovery from microtubule poison is p31comet, where a yeast predicted open-reading frame YBR296C-A encoding a 39 amino acid predicted protein was identified by homology to p31comet, and named Tiny Yeast Comet 1 (TYC1). Tyc1 over expression resulted in sensitivity to microtubule poison. Tyc1 inhibited both APC/CCdc20 and APC/CCdh1 activities in vitro and bound to APC/C. A homologous peptide derived from human p31comet bound to and inhibited yeast APC/C demonstrating evolutionary retention of these biochemical activities. Cdc20 Mad2-binding motif peptides and Tyc1 disrupted the ability of the co-factors Cdc20 and Cdh1 to bind to APC/C, and co-over expression of both together in vivo resulted in an increased sensitivity to microtubule poison. We hypothesize that Cdc20 Mad2-binding motif peptides, Tyc1 and human hp31 peptide can serve as novel molecular tools for investigating APC/C inhibition that leads to sensitivity to microtubule poison in vivo.
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Ciclosoma-Complejo Promotor de la Anafase/antagonistas & inhibidores , Antineoplásicos/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Péptidos/farmacología , Ciclosoma-Complejo Promotor de la Anafase/metabolismo , Antineoplásicos/uso terapéutico , Proteínas Cdc20/metabolismo , Proteínas Cdh1/metabolismo , Pruebas de Enzimas , Inhibidores Enzimáticos/metabolismo , Humanos , Proteínas Mad2/metabolismo , Microtúbulos/efectos de los fármacos , Microtúbulos/metabolismo , Mitosis/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Péptidos/metabolismo , Péptidos/uso terapéutico , Dominios y Motivos de Interacción de Proteínas , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Moduladores de Tubulina/farmacología , Moduladores de Tubulina/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the hemostatic effect of spleen-invigorating, qi-replenishing and blood-containing formula on simvastatin-induced zebrafish hemorrhage model, and to compare with the effect of clearing heat and cooling blood formula. METHODS: Zebrafishes from breed A B line were treated with 0.5 µmol/L simvastatin for 24 hours to establish zebrafishes hemorrhage model. Under strict blinded experimental conditions, the above mentioned zebrafishes were then treated with experimental drug of different concentrations at the maximum non-lethal dose. The intervention effect of spleen-invigorating, qi-replenishing and blood-containing formula was comprehensively assessed by examining the main observational parameters, such as bleeding reduction rate and hemostasis rate while referring to additional parameters, such as blood flow, improvement rate of blood flow, velocity of movement, improvement rate of motion, which are characteristics of spleen qi deficiency. RESULTS: When the hemostatic effect of experimental drug B1 at the concentrations of 500 and 1 000 µg/ml, zebrafish bleeding rates were 30% and 15%, the hemostatic rate was 60% and 80%, respectively; when the experimental drug B2 at concentration of 500 and 1 000 µg/ml, Zebrafish bleeding rates were 45% and 40%, the hemostatic rate was 40% and 47%, respectively, showing that experimental drug B1 was superior to B2 in terms of decreasing bleeding rate and improving hemostatic effect in zebrafish. In the equal concentration, the experimental drug B1 was superior to B2 in terms of increasing and improving the blood flow of hemorrhagic zebrafish. Promotion and improvement of motion: in equal concentration, experimental drug B1 was superior to B2 in terms of promoting the motion velocity and increasing the improving rate of motion in zebrafish. CONCLUSION: The spleen-invigorating, qi-replenishing and blood-containing formula displays a good hemostatic effect on simvastatin-induced hemorrhage of zebrafish. It also boosts the blood flow and motion velocity in hemorrhagic zebrafish, therefore, providing an experimental basis for the treatment of syndrome of spleen failing to control blood by spleen-invigorating, qi-replenishing and blood-containing formula.
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Medicamentos Herbarios Chinos/uso terapéutico , Hemorragia/tratamiento farmacológico , Hemostáticos/uso terapéutico , Qi , Simvastatina/uso terapéutico , Bazo/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Pez CebraRESUMEN
Cancer-related fatigue (CRF) is a common and one of the most severe symptom in the period of onset, diagnosis, treatment and rehabilitation process of cancer. But there are no confirmed measures to relieve this problem at present. Traditional Chinese medical comprehensive therapy has its advantages in dealing with this condition. Based on the research status of CRF, the following problems have been analyzed and solved: the term of CRF has been defined and recommended, and the definition has been made clear; the disease mechanism is proposed, i.e. healthy qi has been impaired in the long-term disease duration, in the process of surgery, chemotherapy, radiotherapy and biology disturbing; it is clear that the clinical manifestations are related to six Chinese medicine patterns: decreased functioning of the Pi (Spleen) and Wei (Stomach), deficiency of the Pi with dampness retention, deficiency of the Xin (Heart) and Pi, disharmony between the Gan (Liver) and Pi, deficiency of the Pi and Shen (Kidney), and deficiency of the Fei (Lung) and Shen. Based on its severity, the mild patients are advised to have non-drug psychological intervention and sleep treatment in cooperation with appropriate exercise; diet therapy are recommended to moderate patients together with sleep treatment and acupuncture, severe patients are recommended to have herbal treatment based on pattern differentiation together with physiological sleep therapy.
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Fatiga/tratamiento farmacológico , Fatiga/etiología , Medicina Tradicional China , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , HumanosRESUMEN
OBJECTIVE: To observe the effects of Compound Zhebei Granule (, CZBG) combined with chemotherapy on surface markers of leukemia stem cell (LSC) in the bone marrow of patients with acute myeloid leukemia (AML). METHODS: Seventy-eight patients with AML received bone marrow aspiration and the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) cells were tested using flow cytometry method. A total of 24 refractory or relapsed AML patients were enrolled and treated with one cycle of standard chemotherapy combined with CZBG. Bone marrow samples were obtained before and after treatment, and the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) cells were examined by flflow cytometry. RESULTS: Compared with refractory or relapsed AML patients, patients achieved remission had a significant lower percentage of CD34(+) CD123(+) cells(P<0.01) and CD33(+) CD123(+) cells (P<0.01), indicating that controlling the LSC percentage may be important for patients with AML to achieve sustainable remission. Compared with those before treatment, the expression levels of CD34(+) CD123(+) were significantly decreased after CZBG combined with chemotherapy treatment (P<0.01). The percentages of CD34(+) CD123(+) cells and CD33(+) CD123(+) in patients achieving complete remission after CZBG combined with chemotherapy treatment were both significantly lower than those in patients with nonremission (P<0.01). CONCLUSION: CZBG combining chemotherapy could reduce the percentages of CD34(+) CD123(+) and CD33(+) CD123(+) LSC, which might improve the clinical efficacy of refractory or relapsed AML.
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Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Antígenos CD/metabolismo , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Inducción de RemisiónRESUMEN
This study was aimed to investigate the expression of biomarkers (PTEN, mTOR, NF-kB, CD44, PI3K) related with bone marrow cells in patients with acute myelogenous leukemia. The immunohistochemical method was used to detect the expression of PTEN, mTOR, NF-kB, CD44, PI3K in 20 patients. The AML patients were divided into remission group and non-remission group after calculating the percentage of leukemia cells in bone marrow. The results showed that by optical microscopy, the positive expression rates of PTEN, mTOR, NF-kB, CD44 and PI3K in remission group were 33.3%, 33.3%, 77.8%, 22.2%, 0, respectively; meanwhile, in non-remission group, the positive expression rates of above-menthioned biomarkers were 63.6%, 18.2, 90.9, 63.6%, 0, respectively. The percentage and mean OD for PTEN and CD44 were statistically different between the two groups (P < 0.05), but for mTOR, NF-kB and PI3K were not statistically differenly (P > 0.05). It is concluded that the high expression of PTEN and CD44 can be regarded as an important index for diagnosis and prognosis in acute myelogenous leukemia.