Adiponectin exhibits proliferative and anti-apoptotic effects on ovarian cancer cells via PI3K/Akt and Raf/MEK/ERK pathways

Purpose: To elucidate the effects and the underlying mechanism of adiponectin on human ovarian cancer cells.Methods: The level of adiponectin, adiponectin receptor-1, caspase-3 and bcl-2 in the serum and ascites of the patients were measured with enzyme-linked immunosorbent assay (ELISA), qPCR and Western blotting. The human ovarian cancer cell lines (Caov3 and SKOV3) were enumerated using 3-(4,5-dimethylthiazol-2-yl)-2,5-tetrazolium bromide (MTT) assay. Western blotting was also used to determine the levels of p-Akt, p-ERK and cyclin B.Results: Serum and ascite levels of adiponectin were significantly higher in ovarian cancer patients than in healthy patients (p < 0.05). Expression of adiponectin in the serum and ascites of patients in FIGO stage IV was remarkably higher than in earlier stages (p < 0.05). The proliferative effect of adiponectin on ovarian cells was dose-dependent. Adiponectin treatment significantly increased the expression of cyclin B in Caov3 and SKOV3, and reduced the levels of caspase-3 and bcl-2. Inhibitors of PI3K and MEK pathways significantly reduced the proliferation of attenuated Caov3 and SKOV3 by up-regulating cyclin B upon adiponectin treatment (p < 0.05), and thus alleviated the inhibitory effect of adiponectin on the expressions of caspase-3 and bcl-2.Conclusion: The findings demonstrate that adiponectin promotes proliferation of the cells via the PI3K/Akt and Raf/MEK/ERK pathways, and also provide new insights into ovarian cancer treatmment.Keywords: Adiponectin, Ovarian cancer, Proliferation, Apoptosis, PI3K/Akt pathwa

Newly identified colistin resistance genes, mcr-4 and mcr-5, from upper and lower alimentary tract of pigs and poultry in China

Antimicrobial resistance against colistin has emerged worldwide threatening the efficacy of one of the last-resort antimicrobials used for the treatment of Enterobacteriaceae. To investigate the presence of the recently identified colistin resistance genes (mcr-4, mcr-5) in China, we established PCRs to detect mcr-4 and mcr-5 on 213 anal and 1,339 nasal swabs from apparently healthy pigs (n = 1,454) in nine provinces, and 1,696 cloacal and 1,647 oropharyngeal samples from poultry (n = 1,836) at live-bird markets in 24 provinces of China. The prevalence of the mcr-4 in swine swabs (41.4%; 642/1,552) was significantly higher than in swabs from poultry (11.5%; 384/3,343). The mcr-4 gene was found in geese (49.5%, 54/109), chickens (17.2%, 257/1,498), pigeons (17.2%, 17/99) and ducks (15.4%, 20/130). In a similar trend, the prevalence of the mcr-5 in swine swabs (33.1%; 514/1552) was significantly higher than in swabs from poultry (5.6%; 187/3,343). The mcr-5 was identified in geese (17.4%, 19/109), chickens (9.9%, 148/1,498), ducks (7.7%, 10/130) and pigeons (3%, 3/99). The mcr-4 prevalence in the nasal swabs from pigs (59.2%, 58/98) was significantly higher than that in anal swabs (29.6%, 29/98) (P<0.001). Similarly, the mcr-5 prevalence in the nasal swabs from pigs (61.2%, 60/98) was significantly higher than in anal swabs (44.9%, 44/98) (P = 0.02), and significantly higher in oropharyngeal swabs (7.2%, 109/1,507) than in the cloacal swabs (3.7%, 56/1,507) (P<0.001). This study further confirms the presence of the mcr-4 and mcr-5 in animals and indicates these genes are prevalent and widespread in food producing animals (pig and poultry) in China. Future studies are needed to characterize the bacteria carrying the mcr-4 and mcr-5 and their locations on plasmids and/or the bacterial chromosomes, and determine co-resistances in the mcr-4 and mcr-5 positive strains

Low soil available phosphorus level reduces cotton fiber length via osmoregulation

IntroductionPhosphorus (P) deficiency hinders cotton (Gossypium hirustum L.) growth and development, seriously affecting lint yield and fiber quality. However, it is still unclear how P fertilizer affects fiber length.MethodsTherefore, a two-year (2019-2020) pool-culture experiment was conducted using the split-plot design, with two cotton cultivars (CCRI-79; low-P tolerant and SCRC-28; low-P sensitive) as the main plot. Three soil available phosphorus (AP) contents (P0: 3 ± 0.5, P1: 6 ± 0.5, and P2 (control) with 15 ± 0.5 mg kg−1) were applied to the plots, as the subplot, to investigate the impact of soil AP content on cotton fiber elongation and length. ResultsLow soil AP (P0 and P1) decreased the contents of the osmotically active solutes in the cotton fibers, including potassium ions (K+), malate, soluble sugar, and sucrose, by 2.2–10.2%, 14.4–47.3%, 8.7–24.5%, and 10.1–23.4%, respectively, inhibiting the vacuoles from facilitating fiber elongation through osmoregulation. Moreover, soil AP deficiency also reduced the activities of enzymes participated in fiber elongation (plasma membrane H+-ATPase (PM-H+-ATPase), vacuole membrane H+-ATPase (V-H+-ATPase), vacuole membrane H+-translocating inorganic pyrophosphatase (V-H+-PPase), and phosphoenolpyruvate carboxylase (PEPC)). The PM-H+-ATPase, V-H+-ATPase, V-H+-PPase, and PEPC were reduced by 8.4–33.0%, 7.0–33.8%, 14.1–38.4%, and 16.9–40.2%, respectively, inhibiting the transmembrane transport of the osmotically active solutes and acidified conditions for fiber cell wall, thus limiting the fiber elongation. Similarly, soil AP deficiency reduced the fiber length by 0.6–3.0 mm, mainly due to the 3.8–16.3% reduction of the maximum velocity of fiber elongation (VLmax). Additionally, the upper fruiting branch positions (FB10–11) had higher VLmax and longer fiber lengths under low soil AP. DiscussionCotton fibers with higher malate content and V-H+-ATPase and V-H+-PPase activities yielded longer fibers. And the malate and soluble sugar contents and V-H+-ATPase and PEPC activities in the SCRC-28's fiber were more sensitive to soil AP deficiency in contrast to those of CCRI-79, possibly explaining the SCRC-28 fiber length sensitivity to low soil AP

A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias

Patterns of attentional bias in antenatal depression: an eye-tracking study

IntroductionOne of the most common mental disorders in the perinatal period is depression, which is associated with impaired emotional functioning due to alterations in different cognitive aspects including thought and facial emotion recognition. These functional impairment may affect emerging maternal sensitivity and have lasting consequences for the dyadic relationship. The current study aimed to investigate the impact of depressive symptoms on the attention bias of infant stimuli during pregnancy.MethodsEighty-six pregnant women completed the Edinburgh Postnatal Depression Scale and an eye-tracking task comprising infant-related emotion images. All participants showed biased attention to infant-related images.ResultsFirst, compared to healthy pregnant women, pregnant women with depression symptoms initially directed their attention to infant-related stimuli more quickly (F (1, 84) = 6.175, p = 0.015, η2 = 0.068). Second, the two groups of pregnant women paid attention to the positive infant stimuli faster than the neutral infant stimuli, and the first fixation latency bias score was significantly smaller than that of the infant-related negative stimulus (p = 0.007). Third, compared with the neutral stimulus, the non-depression group showed a longer first gaze duration to the negative stimulus of infants (p = 0.019), while the depressive symptoms group did not show this difference.ConclusionWe speculate that structural and functional changes in affective motivation and cognitive-attention brain areas may induce these attentional bias patterns. These results provide suggestions for the implementation of clinical intervention programs to correct the attention bias of antenatal depressed women

Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157, a potential drug for treating various wounds, in rats and dogs

Body-protective compound (BPC) 157 demonstrates protective effects against damage to various organs and tissues. For future clinical applications, we had previously established a solid-phase synthesis process for BPC157, verified its biological activity in different wound models, and completed preclinical safety evaluations. This study aimed to investigate the pharmacokinetics, excretion, metabolism, and distribution profiles of BPC157. After a single intravenous (IV) administration, single intramuscular (IM) administrations at three doses in successive increments along with repeated IM administrations, the elimination half-life (t1/2) of prototype BPC157 was less than 30 min, and BPC157 showed linear pharmacokinetic characteristics in rats and beagle dogs at all doses. The mean absolute bioavailability of BPC157 following IM injection was approximately 14%–19% in rats and 45%–51% in beagle dogs. Using [3H]-labeled BPC157 and radioactivity examination, we proved that the main excretory pathways of BPC157 involved urine and bile. [3H]BPC157 was rapidly metabolized into a variety of small peptide fragments in vivo, thus forming single amino acids that entered normal amino acid metabolism and excretion pathways. In conclusion, this study provides the first analysis of the pharmacokinetics of BPC157, which will be helpful for its translation in the clinic

Leben und Zusammenleben der Sprachgruppen in Südtirol: Auswirkungen von Autonomie und Minderheitenschutz auf Schule und Bevölkerung

Effect of TP on Biochemical Indicators. (DOCX 14 kb

Molecular characterization of florfenicol and oxazolidinone resistance in Enterococcus isolates from animals in China

Florfenicol is widely used for the treatment of bacterial infections in domestic animals. The aim of this study was to analyze the molecular mechanisms of florfenicol and oxazolidinone resistance in Enterococcus isolates from anal feces of domestic animals. The minimum inhibitory concentration (MIC) levels were determined by the agar dilution method. Polymerase chain reaction (PCR) was performed to analyze the distribution of the resistance genes. Whole-genome sequencing and comparative plasmid analysis was conducted to analyze the resistance gene environment. A total of 351 non-duplicated enteric strains were obtained. Among these isolates, 22 Enterococcus isolates, including 19 Enterococcus. faecium and 3 Enterococcus. faecalis, were further studied. 31 florfenicol resistance genes (13 fexA, 3 fexB, 12 optrA, and 3 poxtA genes) were identified in 15 of the 19 E. faecium isolates, and no florfenicol or oxazolidinone resistance genes were identified in 3 E. faecalis isolates. Whole-genome sequencing of E. faecium P47, which had all four florfenicol and oxazolidinone resistance genes and high MIC levels for both florfenicol (256 mg/L) and linezolid (8 mg/L), revealed that it contained a chromosome and 3 plasmids (pP47-27, pP47-61, and pP47-180). The four florfenicol and oxazolidinone resistance genes were all related to the insertion sequences IS1216 and located on two smaller plasmids. The genes fexB and poxtA encoded in pP47-27, while fexA and optrA encoded in the conjugative plasmid pP47-61. Comparative analysis of homologous plasmids revealed that the sequences with high identities were plasmid sequences from various Enterococcus species except for the Tn6349 sequence from a Staphylococcus aureus chromosome (MH746818.1). The current study revealed that florfenicol and oxazolidinone resistance genes (fexA, fexB, poxtA, and optrA) were widely distributed in Enterococcus isolates from animal in China. The mobile genetic elements, including the insertion sequences and conjugative plasmid, played an important role in the horizontal transfer of florfenicol and oxazolidinone resistance

Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract – possible synergistic and resistance mechanisms

Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L-1), dihydroartemisinic acid (70.0±0.3 mg L-1), arteannuin B (1.3±0.0 mg L-1), isovitexin (105.0±7.2 mg L-1) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B’s potentiation of artemisinin

Research of Media Material Retrieval Scheme Based on XPath

Part 6: Information RetrievalInternational audienceWith more and more media materials appear on the internet, it comes a sharp problem of how to manage these resources and how to search them efficiently. We construct a management system of media material for the reliable wideband network. According to a detailed analysis of the characteristic of media material queries, we proposed a hierarchical indexing mechanism based on XPath language to discover the resources that match a given query. Our system permits users to locate data iteratively even using scarce information. The description of materials is mapped onto the DHT index. Our indexing scheme has good properties such as space efficient, good scalability and resilient to arbitrary linking