Complex effects of testosterone level on ectoparasite load in a ground squirrel: an experimental test for the immunocompetence handicap hypothesis.

BACKGROUND: The immunocompetence handicap hypothesis suggests that males with a higher testosterone level should be better at developing male secondary traits, but at a cost of suppressed immune performance. As a result, we should expect that males with an increased testosterone level also possess a higher parasite load. However, previous empirical studies aimed to test this prediction have generated mixed results. Meanwhile, the effect of testosterone level on parasite load in female hosts remains poorly known. METHODS: In this study, we tested this prediction by manipulating testosterone level in Daurian ground squirrels (Spermophilus dauricus), a medium-sized rodent widely distributed in northeast Asia. S. dauricus is an important host of ticks and fleas and often viewed as a considerable reservoir of plague. Live-trapped S. dauricus were injected with either tea oil (control group) or testosterone (treatment group) and then released. A total of 10 days later, the rodents were recaptured and checked for ectoparasites. Fecal samples were also collected to measure testosterone level of each individual. RESULTS: We found that testosterone manipulation and sex of hosts interacted to affect tick load. At the end of the experiment, male squirrels subjected to testosterone implantation had an averagely higher tick load than males from the control group. However, this pattern was not found in females. Moreover, testosterone manipulation did not significantly affect flea load in S. dauricus. CONCLUSIONS: Our results only lent limited support for the immunocompetence handicap hypothesis, suggesting that the role of testosterone on regulating parasite load is relatively complex, and may largely depend on parasite type and gender of hosts.

Effects of Involuntary and Voluntary Exercise in Combination with Acousto-Optic Stimulation on Adult Neurogenesis in an Alzheimer's Mouse Model.

Single-factor intervention, such as physical exercise and auditory and visual stimulation, plays a positive role on the prevention and treatment of Alzheimer's disease (AD); however, the therapeutic effects of single-factor intervention are limited. The beneficial effects of these multifactor combinations on AD and its molecular mechanism have yet to be elucidated. Here, we investigated the effect of multifactor intervention, voluntary wheel exercise, and involuntary treadmill running in combination with acousto-optic stimulation, on adult neurogenesis and behavioral phenotypes in a mouse model of AD. We found that 4 weeks of multifactor intervention can significantly increase the production of newborn cells (BrdU+ cells) and immature neurons (DCX+ cells) in the hippocampus and lateral ventricle of Aß oligomer-induced mice. Importantly, the multifactor intervention could promote BrdU+ cells to differentiate into neurons (BrdU+ DCX+ cells or BrdU+ NeuN+ cells) and astrocytes (BrdU+GFAP+ cells) in the hippocampus and ameliorate Aß oligomer-induced cognitive impairment and anxiety- and depression-like behaviors in mice evaluated by novel object recognition, Morris water maze tests, elevated zero maze, forced swimming test, and tail suspension test, respectively. Moreover, multifactor intervention could lead to an increase in the protein levels of PSD-95, SYP, DCX, NeuN, GFAP, Bcl-2, BDNF, TrkB, and pSer473-Akt and a decrease in the protein levels of BAX and caspase-9 in the hippocampal lysates of Aß oligomer-induced mice. Furthermore, sequencing analysis of serum metabolites revealed that aberrantly expressed metabolites modulated by multifactor intervention were highly enriched in the biological process associated with keeping neurons functioning and neurobehavioral function. Additionally, the intervention-mediated serum metabolites mainly participated in glutamate metabolism, glucose metabolism, and the tricarboxylic acid cycle in mice. Our findings suggest the potential of multifactor intervention as a non-invasive therapeutic strategy for AD to anti-Aß oligomer neurotoxicity.

Effects of involuntary treadmill running in combination with swimming on adult neurogenesis in an Alzheimer's mouse model.

Physical exercise plays a role on the prevention and treatment of Alzheimer's disease (AD), but the exercise mode and the mechanism for these positive effects is still ambiguous. Here, we investigated the effect of an aerobic interval exercise, running in combination with swimming, on behavioral dysfunction and associated adult neurogenesis in a mouse model of AD. We demonstrate that 4 weeks of the exercise could ameliorate Aß42 oligomer-induced cognitive impairment in mice utilizing Morris water maze tests. Additionally, the exercised Aß42 oligomer-induced mice exhibited a significant reduction of anxiety- and depression-like behaviors compared to the sedentary Aß42 oligomer-induced mice utilizing an Elevated zero maze and a Tail suspension test. Moreover, by utilizing 5'-bromodeoxyuridine (BrdU) as an exogenous cell tracer, we found that the exercised Aß42 oligomer-induced mice displayed a significant increase in newborn cells (BrdU+ cells), which differentiated into a majority of neurons (BrdU+ DCX+ cells or BrdU+NeuN+ cells) and a few of astrocytes (BrdU+GFAP+ cells). Likewise, the exercised Aß42 oligomer-induced mice also displayed the higher levels of NeuN, PSD95, synaptophysin, Bcl-2 and lower level of GFAP protein. Furthermore, alteration of serum metabolites in transgenic AD mice between the exercised and sedentary group were significantly associated with lipid metabolism, amino acid metabolism, and neurotransmitters. These findings suggest that combined aerobic interval exercise-mediated metabolites and proteins contributed to improving adult neurogenesis and behavioral performance after AD pathology, which might provide a promising therapeutic strategy for AD.

Enhanced expression of microtubule-associated protein 7 functioned as a contributor to cervical cancer cell migration and is predictive of adverse prognosis.

BACKGROUND: Cervical cancer (CC) is one of the most common female malignancies over the world. Microtubule-associated protein 7 (MAP7) belongs to the family of microtubule-associated proteins (MAPs) which involve in microtubule dynamics and are critical in several important cellular and intracellular activities. This study aimed to investigate the expression and potential role of MAP7 in CC. METHODS: The expression level of MAP7 in CC tissues and normal tissues were analyzed using the data obtained from The cancer genomes atlas (TCGA) and genotype-tissue expression (GTEx) databases. The prognostic value of MAP7 in patients with CC was analyzed by Kaplan-Meier analysis, Univariate and Multivariate analyses. Moreover, the influences of MAP7 expression alteration on the viability and motility of Caski, HeLa and C-33A cells was measured by CCK8 assay, colony formation assay, scratch assay, and transwell migration and invasion assays. Flow cytometry was conducted to determine cell apoptosis. Western blot was performed to evaluate the impact of MAP7 on the expression of apoptotic-related proteins as well as mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. In vivo tumorigenicity assay was performed to explore the influence of MAP7 on tumor growth. RESULTS: Up-regulation of MAP7 was observed in CC tissues and high MAP7 expression was positively correlated with worse prognosis. Multivariate analyses suggested that MAP7 expression can be served as an independent predictor for overall survival of patients with CC. Knockdown of MAP7 markedly suppressed Caski and HeLa cell viability, migration and invasion while notably induced cell apoptosis. Furthermore, depletion of MAP7 in Caski and HeLa cells elevated the expression levels of Active-caspase 3 and Bax, but declined the level of Bcl-2. Whilst, overexpression of MAP7 in C-33A cells presented the opposite outcomes. Additionally, knockdown of MAP7 significantly decreased the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) in Caski and HeLa cells, and overexpression of MAP7 increased their phosphorylation in C-33A cells, indicating that MAP7 may regulate the MAPK signaling pathway in CC cells. In vivo assays revealed that knockdown of MAP7 remarkably repressed the growth of CC tumors. CONCLUSION: The results of the present study suggest that MAP7 functions as a promoter during the occurrence and progression of CC, and that MAP7 may serve as a promising therapeutic target in CC.

Design, synthesis, and biological evaluations of phenylpropiolic acid derivatives as novel GPR40 agonists.

GPR40, also known as free fatty acid receptor 1 (FFAR1), is a member of G protein-coupled receptors (GPCR) family and has emerged as an attractive target for the treatment of type 2 diabetes mellitus. So far, most of the synthetic GPR40 agonists, including several drug candidates discontinued in clinical trials, were derived from the phenylpropionic acid scaffold. For discovering novel GPR40 agonists with diverse chemical structures, a series of phenylpropiolic acid derivatives were designed, synthesized, and evaluated under a battery of bioassays. Compound 9, the most potent compound in this series, exhibited submicromolar agonist activity and similar agonistic efficacy compared to that of TAK-875. In addition, compound 9 was able to dose-dependently amplify glucose-stimulated insulin secretion (GSIS) in pancreatic ß-cell line MIN6, which could be reversed by a selective GPR40 antagonist GW1100. In addition, compound 9 was found to have potent glucose-lowering effects during an oral glucose tolerance test in normal C57BL/6 mice.

Effect of N-Perfluorooctane on Hypoxia/Reoxygenation Injury in Human Umbilical Vein Endothelial Cells.

BACKGROUND: This study investigated the effect of n-perfluorooctane (PFC) on hypoxia/reoxygenation (H/R) injury in human umbilical vein endothelial cells (HUVECs). METHODS: In this study, the H/R models were prepared by chemical methods (using dithionite solution). The experimental groups included the control group, the PFC group with a culture volume ratio of 10%, the H/R model group, and treatment groups with various doses of PFC + H/R (i.e., 5%, 10%, or 20% PFC by volume). The cell counting kit-8 (CCK-8) method was used to assay cell viability. Colorimetric assays were used to estimate the leakage of lactate dehydrogenase (LDH) in the medium, the levels of intracellular malondialdehyde (MDA) and nitric oxide (NO), and the activity of superoxide dismutase (SOD). Western blot was used to analyze the expression of the apoptosis-related protein cystine aspartate proteolytic enzyme 3 (caspase-3). RESULTS: Compared with the control group, every detected index of 10% PFC group had no statistical significance (p > 0.05). Compared with the model group, 10% and 20% PFC treatment groups could increase cell viability A, decrease the content of NO and reduce caspase-3 expression (p < 0.05); Every PFC treatment group could significantly reduce the release of LDH and the contents of MDA, and also increase the activities of SOD (p < 0.01). CONCLUSIONS: PFC has a significant protective effect on HUVEC H/R injury, which may be related to the inhibition of oxidative stress and inflammation and further enhance cell antioxidant and anti-apoptotic characteristics.

Effects of cattle grazing on small mammal communities in the Hulunber meadow steppe.

Small mammals play important roles in many ecosystems, and understanding their response to disturbances such as cattle grazing is fundamental for developing sustainable land use strategies. However, how small mammals respond to cattle grazing remains controversial. A potential cause is that most of previous studies adopt rather simple experimental designs based solely on the presence/absence of grazing, and are thus unable to detect any complex relationships between diversity and grazing intensity. In this study, we conducted manipulated experiments in the Hulunber meadow steppe to survey small mammal community structures under four levels of grazing intensities. We found dramatic changes in species composition in native small mammal communities when grazing intensity reached intermediate levels (0.46 animal unit/ha). As grazing intensity increased, Spermophilus dauricus gradually became the single dominant species. Species richness and diversity of small mammals in ungrazed and lightly grazed (0.23 animal unit/ha) area were much higher than in intermediately and heavily grazed area. We did not detect a humped relationship between small mammal diversity and disturbance levels predicted by the intermediate disturbance hypothesis (IDH). Our study highlighted the necessity of conducting manipulated experiments under multiple grazing intensities.

Electrophysiological and behavioral responses of Diaphania glauculalis males to female sex pheromone.

The aim of this study is to identify the pheromone active component of female moths, Diaphania glauculalis, an important pest of Anthocephalus chinensis in China. The sex pheromone was extracted from sex pheromone gland extracts of virgin female moth of D. glauculalis using n-hexane, and the pheromone gland extracts of females were analyzed using coupled gas chromatography-electroantennogram detection (GC-EAD) and gas chromatography-mass spectrometry (GC-MS). The sex pheromone active components were based on the comparison the retention time and mass spectrum, with suitable synthetic compounds. (E)-11-hexadecenal (E11-16:Ald) and (E,E)-10,12-hexadecadienal (E10E12-16:Ald) were identified as the major sex pheromone components in the females. Their biological activities were evaluated in a series of electroantennogram (EAG) experiments and four-arm olfactometer assays using synthetic compounds. D. glauculalis males could be attracted by any single component, but a mixture of the E11-16:Ald and E10E12-16:Ald in a ratio of 5:5 elicited a substantial response, demonstrating that the binary blend is essential in male attraction. We therefore conclude that the aldehyde compounds, a mixture of E11-16:Ald and E10E12-16:Ald, comprise the sex pheromone components of D. glauculalis, which might be applied for insect field trapping.

Low-voltage direct-current stimulation is safe and promotes angiogenesis in rabbits with myocardial infarction.

This study evaluates safety and efficacy of low-voltage direct-current (DC) electrical stimulation of angiogenesis in rabbits with myocardial infarction (MI). Thirty Japanese rabbits were divided into treatment and control groups, and MI was induced by ligation of the left circumflex (LCX) artery. Two platinum electrodes were placed directly on the epicardium on either side of LCX artery. Low-voltage DC stimulation (4.0 V/cm, 30 min/day) was performed in the treatment group immediately after surgery until fourth week post-operatively. Cardio-electrophysiological, respiratory, hematological, blood biochemical, histopathological, immunohistochemical parameters, as well as capillary density at the marginal zone of myocardial infarct were compared between treatment and control groups. Capillary density in the treatment group (63.1 ± 2.2) was significantly higher (P < 0.01) than that in controls (45.4 ± 3.9). Overall mortality was 6.7%, and the prevalences of pneumothorax and intraoperative arrhythmia were 3.3 and 6.7%, respectively. Transient hypotension, anemia, leukocytosis, hypoxemia, and a slight increase in myocardial enzymes levels were observed in both groups. Regarding electrical stimulation, no adverse reactions except a minor infiltration of inflammatory cells and mild degeneration were observed in the myocardium. It was, therefore, concluded that low-voltage DC stimulation in the MI rabbits was not only safe but also effective in promoting angiogenesis in the myocardium.

[The first confirmed human case of avian influenza A (H5N1) in mainland, China].

OBJECTIVE: To ascertain the causation of a family cluster involving two undefined pneumonia cases, a 12-year-old girl and her brother, reported October, 2005 in Xiangtan county, Hunan province. METHODS: Information on epidemiology and clinical manifestation of the cases was collected from interviewing the keyman and referring to related medical records. The environment exposure of the cases to their households and the timeline of the illness were reproduced, using this information. Medical check-up was undergone among the close contacts of the cases and on sick/dead poultry. Throat swab of the cases were collected and tested by both RT-PCR and real-time PCR to detect viral nucleic acids of A/H5N1, and were then inoculated into special pathogen free (SPF) embryonated hens' eggs. Serum of the cases including acute and convalescent phases were also collected and tested by microneutralization and haemagglutination-inhibition (HI) assays to detect H5-specific antibodies. RESULTS: Both the girl and her brother developed fever 2 and 4 days after sudden deaths of chickens being raised in the same house. Both of them had developed pneumonia and the girl died from acute respiratory distress syndrome (ARDS) complicated with multi-organ failure. The boy survived and subsequently discharged from hospital. An eighth-day serum from the girl tested H5 antibody negative, while 4-fold and greater increased in antibody titers were detected in serum from the boy using microneutralization and HI assays in sequential acute and convalescent sera. Of 192 cases, only one doctor who cared for the girl during hospitalization had upper respiratory symptoms but tested negative for H5N1 by microneutralization assay. CONCLUSION: The boy was the first confirmed human case of avian influenza A (H5N1) in the mainland of China and his sister was diagnosed clinically. The most probable explanation of these two cases was that the transmission of H5N1 virus from infected poultry within the same household environment. No evidence of human-to-human transmission was noted in the family cluster.

[Study on a fatal pregnant woman died from by avian influenza (H5N1)].

OBJECTIVE: To ascertain the causation of a pregnant woman with undefined pneumonia reported from the People's Hospital of Tongling city in Anhui province on November 2005. METHODS: Epidemiological and clinical information of the case was collected from the keypersons close to the case and referring to the medical record. A medical observation was carried out on the close contacts of the case and sick or dead poultry. Tracheal aspirates being collected were tested by both RT-PCR and real-time PCR to detect viral nucleic acids of A/H5N1, and were inoculated into special pathogen free (SPF) embryonated hens' eggs. RESULTS: The pregnant woman was found to have been contacted with the sick/dead poultry directly on the 4th day before onset of illness. All the 122 close contacts were healthy after a 10-day medical observation. The major clinical features of the case were viral pneumonia with rapidly developed leukopenia and lymphopenia. The progress to acute respiratory distress syndrome and multiple organ dysfunction syndromes was found at clinical presentation. HA and NA gene of A/H5N1 virus were positive. The 8 gene fragments of A/Anhui/1/2005 (H5N1) isolated from the tracheal aspirates had not carried genes from a human virus through reassortment, and the receptor-binding site of the hemagglutinin was polybasic cleavage site. CONCLUSION: This was the first documented case of H5N1 infection in pregnant woman. The immunotolerant state of pregnancy might have predisposed to the fatal outcome of the patient.