Search

Authenticity has long been held as a virtue. However, is it beneficial for employees to be true to themselves in coworker interactions? Drawing on social penetration theory, we argue that a focal employee's exhibited authenticity at work helps the employee penetrate the interpersonal boundaries of an interacting coworker and as a result, the employee is more likely to be included in this coworker's social circles and receive help from the coworker. Accordingly, we propose a dyadic-level model and test this model in two survey studies using a round-robin design. The results of both studies consistently demonstrated that the focal employee's exhibited authenticity is positively related to help received from the coworker via inclusion in the coworker's social circle. Further, this positive indirect relationship is moderated by the coworker's perception of organizational politics, such that the relationship is weaker when the coworker's perception of organizational politics is high. These findings help advance the understanding of when and how employees can gain relational benefits from displaying authenticity at work. [ABSTRACT FROM AUTHOR]

A rapid and sensitive ultrahigh‐performance liquid chromatography–tandem mass spectrometry method was developed and validated for simultaneous determination of 15 bioactive ingredients in rat plasma and tissues after oral administration of Polygonum chinense Linn extract (PCE). After addition of internal standards (ISs; rutin and danshensu), plasma and tissue samples were pre‐treated by protein precipitation with acetonitrile–ethanol. The chromatographic separation was performed on an Agilent ZORBAX RRHD Eclipse Plus C18 column with gradient elution using a mobile phase composed of methanol and water (containing 0.2% acetic acid) at a flow rate of 0.3 mL min−1. Mass spectrometric detection was carried out using a mass spectrometer in both positive and negative ion electrospray ionization modes by multiple reaction monitoring. The method provided excellent linearity, and the lower limit of quantification range 0.5–30 ng mL−1 for all analytes. The intra‐ and inter‐day precision were less than 9.12% and the accuracy ranged from −4.02% to 6.32%, respectively. The mean extraction recovery and matrix effect of analytes and ISs ranged from 83.65% to 109.20%. The method was successfully applied to the pharmacokinetics and tissue distribution study of 15 ingredients of PCE in rats. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the effect of Shenfu injection in a rat model of ischemic heart failure and explore its mechanism. Methods: A rat model of ischemic heart failure after myocardial infarction was established by ligating the left anterior descending coronary artery. Forty-eight hours after surgery, the rats were intraperitoneally administered Shenfu injection for 7 weeks. Then, left ventricular fractional shortening and left ventricular ejection fraction were measured using transthoracic echocardiography, whereas heart rate and left ventricular end-diastolic pressure were measured using a MD3000 biosignal acquisition and processing system. The hearts and lungs of the rats were excised and weighed to measure the heart and lung weight indexes. In addition, cardiac histopathological changes were observed via hematoxylin–eosin and Masson's trichrome staining, and serum cardiac troponin content was detected using a cardiac troponin ELISA kit. Furthermore, matrix-assisted laser desorption/ionization–mass spectrometry imaging was used to detect the levels and distribution of small molecules in the hearts of rats with ischemic heart failure. Results: We found that Shenfu injection can significantly increase left ventricular fractional shortening and left ventricular ejection fraction in rats with ischemic heart failure and significantly reduce the left ventricular end-diastolic pressure, heart and lung weight indexes, and cardiac troponin content; improve cardiac tissue morphology; and reduce infarct size. In addition, the matrix-assisted laser desorption/ionization–mass spectrometry imaging results demonstrated that 22:6 phospholipids were predominately distributed in the non-infarct zone, whereas 20:4 phospholipids tended to concentrate in the infarct zone. Shenfu injection significantly reduced taurine, glutathione, and phospholipids levels in the hearts of rats with ischemic heart failure and primarily changed the distribution of these molecules in the non-infarct zone. Conclusion: Shenfu injection induced obvious myocardial protective effects in rats with ischemic heart failure by stimulating antioxidation and changing the phospholipid levels and distribution. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is a common acquired autoimmune disease, and thrombopoietin (TPO) is an important cytokine that regulates the production of megakaryocytes and platelets. We have identified a biologically active component, icaritin, from a Chinese herba epimedii extract. Icaritin promotes platelet production and regulates T cell polarization, but its mechanism is not clear. In this study, the BALB/c mouse model of ITP was established by injection of an antiplatelet antibody every other day for seven total times. The antiplatelet sera were derived from guinea pigs immunized with the platelets of BALB/c mice. Mice with ITP were treated with icaritin at low, moderate, or high doses of 4.73, 9.45, and 18.90 mg/kg, respectively, for fourteen consecutive days. The present study shows that icaritin can significantly increase peripheral blood platelet counts and thrombocytocrit, increase the TPO level in serum, attenuate splenomegaly, and reduce the abnormal proliferation of megakaryocytes in the spleen and bone marrow. Icaritin can also downregulate the expression of bone marrow TPO, myeloproliferative leukemia virus oncogene (MPL), and p-Stat3. Our results suggest that icaritin can significantly improve the health of mice with ITP via possible downregulation of p-Stat3 expression in the JAK2/Stat3 phosphorylation signaling pathway and regulation of bone marrow TPO/MPL metabolism. [ABSTRACT FROM AUTHOR]

Asthenozoospermia (AS), an important cause of male infertility, is characterized by reduced sperm motility. Among the aetiologies of AS, inflammation seems to be the main cause. DJ-1, a conserved protein product of the PARK7 gene, is associated with male infertility and plays a role in oxidative stress and inflammation. Although our previous studies showed that a reduction in DJ-1 was accompanied by mitochondrial dysfunction in the sperm of patients with AS, the specific mechanism underlying this association remained unclear. In this study, we found that compared to the patients without AS, the expression of mitochondrial protein nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3) was also significantly decreased in the sperm of patients with AS. Similarly, decreased expression of DJ-1 and NDUFS3 and reduced mitochondria complex I activity were evident in a rat model of AS. Moreover, we showed that the interaction between DJ-1 and NDUFS3 in rat testes was weakened by ORN treatment. These results suggest that the impaired mitochondrial activity could be due to the broken interaction between DJ-1 and NDUFS3 and that downregulation of DJ-1 in sperm and testes contributes to AS pathogenesis. [ABSTRACT FROM AUTHOR]

Perceivers remember own-race faces more accurately than other-race faces (i.e., Own-Race Bias). In the current experiments, we manipulated participants' attentional resources and social group membership to explore their influence on own and other-race face recognition memory. In Experiment 1, Chinese participants viewed own-race and Caucasian faces, and between-subjects we manipulated whether participants attention was divided during face encoding. We found that divided attention eliminated the Own-Race Bias in memory due to a reduction of memory accuracy for own-race faces, implicating that attention allocation plays a role in creating the bias. In Experiment 2, Chinese participants completed an ostensible personality test. Some participants were informed that their personality traits were most commonly found in Caucasian (i.e., other-race) individuals, resulting in these participants sharing a group membership with other-race targets. In contrast, other participants were not told anything about the personality test, resulting in the default own-race group membership. The participants encoded the faces for a subsequent recognition memory test either with or without performing a concurrent arithmetic distracting task. Results showed that other-race group membership and reducing attention during encoding independently eliminated the typical Own-Race Bias in face memory. The implications of these findings on perceptual-expertise and social-categorization models are discussed. [ABSTRACT FROM PUBLISHER]

Chlorotoxin (ClTx), originally isolated from scorpion venom of Leiurus quinquestriatus, is a 36-amino acid peptide and specifically binds to the brain gliomas and proliferating vascular endothelial cells. In this paper, it was first used to establish the ClTx-modified stealth liposomes (ClTx-LS) encapsulating levodopa (LD) for the targeting drug delivery against the Parkinson's disease (PD). After the DSPE-PEG-ClTx was synthesized and identified, the ClTx-LS system was prepared and characterized. Its targeting capability was studied in vitro and in vivo, and finally its anti-PD activity was evaluated, with non-modified liposomes (LS) as control. It was demonstrated through flow cytometry and confocal microscopy that ClTx modification highly facilitated the uptake of LS by brain microvascular endothelial cells in vitro. After intraperitoneal injection to mice, the active targeting system loaded with LD significantly increased the distribution of dopamine and dihydroxyphenyl acetic acid, the metabolites of LD, in the substantia nigra and striata. In the methyl-phenyl-tetrahydropyridine (MPTP)-induced PD mice model, LD-loaded ClTx-LS significantly attenuated the serious behavioral disorders and diminished the MPTP-induced loss of tyrosine hydroxylase-positive dopaminergic neurons. In conclusion, ClTx-modified LS might serve as a targeting delivery system to transport more drugs into the brain for a better PD therapy. [ABSTRACT FROM AUTHOR]

The article presents a study on acute nephrotoxicity of Cyclosporine A (CsA) by observing the plasma protein changes of treated wistar rats through two-dimensional (2D) gel electrophoresis. Among the CsA-treated rats, six spots indicating a stable and substantially different expressions were discovered by MALDI-TOF-MS and ESI-TOF-MS/MS, respectively. It notes that two induced proteins determined were &x03B1;-1-acid glycoprotein (AAG) and clusterin (CLUS), and haptoglobin (Hp) was inihibited.

Safflower (Carthamus tinctorius. L.), a Chinese materia medica, is widely used for the treatment of cardiovascular and cerebrovascular diseases, with flavonoids being the major active components. Multiple flavonoids in safflower bind to Parkinson's disease (PD)-related protein DJ-1. Safflower flavonoid extract (SAFE) improved behavioral indicators in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD; however, the underlying mechanisms remain unclear. We used a 6-OHDA-induced mouse model of PD and a primary neuron-astrocyte coculture system to determine the neuroprotective effects and mechanisms of SAFE. After three weeks of SAFE administration, behavioral indicators of PD mice were improved. SAFE regulated the levels of tyrosine hydroxylase (TH) and dopamine metabolism. It significantly inhibited the activation of astrocytes surrounding the substantia nigra and reduced Iba-1 protein level in the striatum of PD mice. SAFE reduced the plasma content of inflammatory factors and suppressed the activation of nod-like receptor protein 3 (NLRP3) inflammasome. In the coculture system, kaempferol 3-O-rutinoside and anhydrosafflor yellow B significantly improved neuronal survival, suppressed neuronal apoptosis, and reduced IL-1β and IL-10 levels in the medium. Thus, SAFE showed a significant anti-PD effect, which is mainly associated with flavonoid anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Thymoquinone is one of the main components present in Nigella sativa seeds and is known to have various biological functions in inflammation, oxidative stress, tumors, aging, and in lowering blood glucose levels. Few studies have focused on its neuroprotective effects and its regulation of small-molecule metabolites during cerebral ischemia reperfusion injury. In this study, transient middle cerebral occlusion (tMCAO) was used to establish the rat model of cerebral ischemia reperfusion injury. We investigated the effects of thymoquinone using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in a model of ischemia reperfusion injury to explore the changes in small-molecule metabolites in the brain. We found that that thymoquinone significantly improved neurobehavioral scores, reduced the cerebral infarct area, alleviated brain edema, and increased the number of normal neurons following injury. MALDI-MSI revealed that thymoquinone reduced abnormal accumulations of glucose, citric acid, succinate and potassium ions. Thymoquinone also increased the amount of energy-related molecules such as ADP, AMP, GMP, and creatine, antioxidants such as glutathione, ascorbic acid, and taurine, and other metabolism-related molecules such as glutamate, glutamine, aspartate, N-acetyl-L-aspartate, and sodium ions in damaged areas of the brain following cerebral ischemia reperfusion injury. In summary, based on the neuroprotective effect of thymoquinone on cerebral ischemia reperfusion injury, this study revealed the regulation of thymoquinone on energy metabolism and small-molecule substance metabolism. [ABSTRACT FROM AUTHOR]

Introduction: DJ‐1 mutation is a causative reason for familial Parkinson's disease (PD). Leucine166Proline (L166P) and C106S are two important DJ‐1 mutations. In this study, we established hydrogen peroxide (H2O2) induced L166P and C106S DJ‐1‐transfected neuroblastoma (SH‐SY5Y) cellular models of PD and investigated the effects of Cistanche extracts and key bioactive compounds, including acteoside, echinacoside, caffeic acid, and Cistanche total glycosides on these two models. Methods: After expressing FLAG‐tagged L166P and C106S DJ‐1 plasmids in Escherichia coli, the expressed plasmids were collected, treated with restriction enzyme, and identified using DNA electrophoresis. After purification, the L166P DJ‐1 and C106S DJ‐1 plasmids were separately transfected into SH‐SY5Y cells using liposomes. Transfected SH‐SY5Y cells were detected by western blotting and immunocytochemistry. Cell viability was determined using MTT assay. Results: Both western blotting and immunocytochemistry showed that L166P and C106S DJ‐1 were highly expressed in the transfected SH‐SY5Y cells. MTT assays showed that transfection with L166P or C106S DJ‐1 reduced the viability of SH‐SY5Y cells exposed to H2O2, as compared to untransfected SH‐SY5Y cells. In addition, Cistanche extracts and key bioactive compounds, including acteoside, echinacoside, caffeic acid, and Cistanche total glycosides, significantly inhibited the decreases of cell viability caused by H2O2 in L166P and C106S DJ‐1‐transfected SH‐SY5Y cells. Conclusions: These findings suggest that we successfully established sensitive and stable H2O2 induced L166P DJ‐1‐ and C106S DJ‐1‐transfected SH‐SY5Y cell models of PD and Cistanche extracts may thus be useful for treating PD. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) poses a serious threat to the quality of human life and health with an increasing incidence worldwide. Renal fibrosis is closely related to CKD and regarded as the final common pathophysiological pathway in most cases of end-stage renal diseases. Elucidating the mechanisms underlying renal fibrosis and developing novel therapeutic strategies are of great importance. Herein, matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) based on 1, 5-diaminonaphthalene hydrochloride was applied to the rat model of unilateral ureteral obstruction (UUO) to investigate metabolic changes during renal fibrosis. Among identified endogenous compounds, twenty-one metabolites involved in metabolic networks such as glycolysis, tricarboxylic acid (TCA) cycle, ATP metabolism, fatty acids metabolism, antioxidants, and metal ions underwent relatively obvious changes after 1 and 3 weeks of UUO. Unique distribution of the metabolites was obtained, and metabolic changes of kidneys during renal fibrosis were investigated simultaneously for the first time. These findings once again highlighted the promising potential of the organic salt matrix for application in small molecule in situ MSI and in the field of biomedical research. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Shenfu injection is a popular Chinese herbal formula that has been widely used in the treatment of shock in China. Aim of the study To investigate the effect of Shenfu injection on lipopolysaccharide (LPS)-induced septic shock in rabbits. Materials and methods We established a septic shock model in rabbits by administering an intravenous injection of 0.6 mg/kg LPS to anesthetized rabbit, and 15 min after LPS challenge, the rabbits were intravenously administered the Shenfu injection. In these in vivo experiments, the jugular vein of the rabbits was cannulated for LPS and drug administration, and the right common carotid artery was cannulated to record the mean arterial pressure (MAP) over a 6-h period. In addition, various serum biochemical parameters, including lactate dehydrogenase (LDH), aspartate aminotransferase (AST), glutamate transaminase (ALT), creatinine (Cre), and urea nitrogen (Urea), were measured at 0, 3, and 6 h. Serum LPS levels at 6 h were determined by the test kit. And histological changes in the heart, liver and kidney tissues were observed by HE staining. Furthermore, some related small molecules in the heart tissues were detected by MALDI-TOF-MSI. Results We found that Shenfu injection can increase the MAP, decrease the serum LPS, LDH and AST levels, and improve the tissue morphology of the heart, liver and kidney in rabbits with LPS-induced septic shock. In addition, Shenfu injection can increase the contents of ATP and taurine while reducing the content of AMP in the heart tissue during septic shock. Conclusions These results indicate that Shenfu injection exerts a protective effect on LPS-induced septic shock in rabbits. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Xiaoer Chaigui Tuire Oral Liquid (XCTOL) is a popular Chinese herbal formula. It is used to treat exogenous fever in children by inducing diaphoresis and clearing interior heat. Aim of the study To evaluate the acute and sub-chronic toxicity of XCTOL in mice and rats, respectively. Materials and methods In the acute toxicity study, mice were orally administered 100 g/kg body weight XCTOL three times a day. General behavior, adverse effects and mortality were recorded for 14 days after treatment. In the sub-chronic toxicity study, rats were orally administered 0, 20 or 80 g/kg XCTOL for 30 days. The rats were observed daily for clinical signs and mortality. Body weight changes were measured every three days, and relative organ weights, hematological parameters, urinalysis results, biochemical parameters and pathology were monitored at the end of treatment. After treatment, a 30-day withdrawal study was conducted. Results In the acute toxicity study, after the mice were administered with 300 g/kg (3×100 g/kg) XCTOL in the first day, no adverse effects or death were observed in the following 14 days. In the 30-day sub-chronic toxicity study, daily oral administration of 80 g/kg XCTOL resulted in significant body weight loss in both male and female rats. In the male rats, the red blood cell distribution width standard deviation (RDW-SD) and red blood cell distribution width coefficient of variability (RDW-CV) in the hematological test and total bilirubin (T-Bil) in the blood biochemistry test were significantly increased (RDW-SD, p <0.01; RDW-CV and T-Bil, p <0.05 vs. the control group). In the female rats, the specific gravity of the urinalysis was significantly increased ( p <0.05 vs. the control group). Pathological damage was not observed in the main organs in the 80 g/kg group. In the 20 g/kg group, the lymphocyte % (LYM%) was significantly increased ( p <0.05 the control group) in the female rats. Conclusions The maximum-tolerated dose of XCTOL was greater than 300 g/kg in mice. The no-observed-adverse-effect-level was between 20 and 80 g/kg body weight for 30 days in rats, which is 2.2–8.8 times higher, respectively, than the dose that has already been used in the clinical practice. Therefore, XCTOL at a dose less than 300 g/kg in one day or 20 g/kg per day for 30 days is considered safe. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is one of the common malignant tumors in clinic. In the current study, we aim to investigate the effects of PRMT4 on erastin-induced ferroptosis in NPC by cisplatin resistant. PRMT4 expression in patients with NPC by cisplatin was upregulated. PRMT4 upregulation promoted cell growth of erastin-induced ferroptosis in NPC cisplatin-resistant cells. PRMT4 downregulation reduced cell growth of erastin-induced ferroptosis in NPC cisplatin-resistant cells. PRMT4 promoted tumor volume in mice model of erastin-induced NPC by cisplatin. PRMT4 upregulation reduced erastin-induced ferroptosis in NPC cisplatin-resistant cells by mitochondrial damage. PRMT4 upregulation induced Nrf2 protein expression in model of erastin-induced NPC by cisplatin. Nrf2 reduced the effects of si-PRMT4 on cell growth of erastin-induced ferroptosis in NPC cisplatin-resistant cells. Nrf2 inhibitor reduced the effects of PRMT4 on cell growth of erastin-induced ferroptosis in NPC cisplatin-resistant cells. Nrf2 reduced the effects of si-PRMT4 on erastin-induced ferroptosis in NPC cisplatin-resistant cells by mitochondrial damage. PRMT4 protein interlinked with Nrf2 protein to decrease Nrf2 ubiquitination. Methylation increased PRMT4 DNA stability. Collectively, our data reveal that PRMT4 reduced erastin-induced ferroptosis in NPC cisplatin-resistant cells by Nrf2/GPX4 pathway, suggesting that targeting PRMT4 may present as a potential strategy against the development of NPC.

The gut microbiome has been considered to play an important role in inflammatory bowel disease (IBD). Our previous study reported that tacrolimus-altered gut microbiota elicited immunoregulatory effects in both colonic mucosa and circulation, contributing to an increased allograft survival rate in mice. Here, we aimed to observe the changes in the tacrolimus-induced microbiome in a dextran sulfate sodium (DSS)-induced colitis mouse model and explore the possibility and efficacy of combination therapy with tacrolimus and the microbiome on colitis. Mice were divided into the control, DSS, tacrolimus monotherapy and tacrolimus plus Lactobacillus plantarum 550 ( Lacto )-treated groups. The body weight, stool consistency, hematochezia and survival of mice were observed daily. Total RNA from colonic mucosa was extracted and subjected to transcriptome sequencing. Cecal contents were collected and the 16S rRNA sequencing was performed to characterize the gut microbiome and the ultrahigh- performance liquid chromatography-MS/MS (UHPLC-MS/MS) was used for targeted quantification of bile acids. The results confirmed that tacrolimus significantly ameliorated DSS-induced colitis in mice. Beneficial alterations of the gut microbiome characterized by a remarkable expansion of the genus Lactobacillus were induced by tacrolimus treatment. Oral supplementation with Lacto further improved the tacrolimus-mediated suppression of body weight loss in colitis, while the survival time of mice was further prolonged and the inflammation of colonic mucosa was obviously relieved. The immune and inflammation-related signaling pathways, including IFN-γ and IFN-α response, allograft rejection, IL2 STAT5 signaling and the inflammatory response pathways, were further downregulated in the tacrolimus plus Lacto cotreatment group. Cotreatment also improved the diversity of the gut microbiome and rescued the concentration of taurochenodeoxycholic acid (TCDCA) in colitis. The latter was positively correlated with the abundance of Lactobacillus but negatively related to the disease activity index score. Overall, our results indicated that Lactobacillus plantarum promoted the therapeutic effect of tacrolimus in experimental colitis, offering a promising strategy to combine tacrolimus and Lactobacillus in the treatment of colitis patients., Competing Interests: ZL and XP are employed by Technology Research Institute of Shuxi Condiments of Sichuan Cuisine Co. LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lv, Zhang, He, Liu, Shao, Lv, Pu, Wang and Liu.)

Dl-3-n-butylphthalide (NBP) has been widely used to treat ischemic stroke in China. To investigate the mechanisms underlying NBP activity, we established a permanent middle cerebral artery occlusion (pMCAO) rat model and injected the rats with 4 mg/kg/d NBP for nine days. We then assessed neuroinflammation, neovascularization and nerve regeneration within the brain. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry imaging (MALDI-TOF MSI) was used to determine the phospholipid distribution, while laser ablation-inductively coupled plasma mass spectrometry imaging (LA-ICP MSI) was used to measure Foxp3, Ki-67 and pCREB levels in the brain. Immunohistochemistry was used to investigate the expression of NLR family pyrin domain containing 3 (NLRP3) and its inflammatory products, caspase-1 and interleukin-1β, in brain tissues. NBP attenuated ischemic damage and ameliorated neurological deficits in rats with pMCAO. In the ischemic brain region, NBP reduced phosphatidylethanolamine (18:0), NLRP3, caspase-1 and interleukin-1β levels, but increased levels of Foxp3, Ki-67, pCREB and several phospholipids. In molecular docking analyses, NBP bound to NLRP3, interleukin-1β, caspase-1, Foxp3, and Ki-67. These results demonstrate that NBP reduces neuroinflammation in brain tissues and promotes nerve and blood vessel regeneration, thus protecting neuromorphology and function.

Asthenozoospermia (AS), defined as low-motility spermatozoa in the ejaculate, is a frequent cause of human male infertility. DJ-1 (also known as PARK7), a protein highly associated with male sterility, binds to the mitochondrial complex I subunit to protect mitochondrial function. However, its involvement in spermatogenesis has not been fully elucidated. Previously, the levels of DJ-1 were shown to be significantly decreased in testicular tissues of rats with ornidazole (ORN)-induced AS. Here, we used a rat model to investigate the localization and expression levels of DJ-1 and its interacting NDUFS3 and NDUFA4 mitochondrial complex I subunits, as well as AS-induced metabolic alterations in testicular tissues. ORN significantly reduced the levels of DJ-1 in the nucleus of secondary spermatocytes, while increasing the expression of NDUFS3 in the cytoplasm of primary spermatocytes. Further, NDUFA4 showed higher expression after treatment with ORN. The principal ORN-induced changes in metabolic small molecules related to the accumulation of glucose, glutamine, and N-acetyl aspartate, enhancement of purine pathway, increase of the phosphatidic acid (PA) (18:0/18:1), phosphatidylethanolamine (PE) (16:0/18:1), and PA (18:0/20:4) lipid metabolites, and imbalance in the concentrations of Na+ and K+. However, we did not observe any abnormalities of certain small metabolic molecules and metal ions in semen samples from patients with AS. In conclusion, these results suggest that DJ-1 deficiency in testicular tissues might be closely related to the localization of NDUFS3 and content of NDUFA4, thus causing abnormalities in the mitochondrial energy metabolism and multiple other metabolic pathways.

The extracellular space (ECS) is the space between the neurons and the capillaries in the brain. The volume fraction (α) and the tortuosity (λ) are the main parameters used to describe its characteristics. Thymoquinone has been proved to possess anti-oxidant and anti-inflammatory activity. In this study, we used a gadolinium-diethylenetriaminepentacetate (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) system to determine the effects of thymoquinone on ECS parameters in transient middle cerebral artery occlusion rats (tMCAO) to prove the neuroprotective effect of thymoquinone on brain tissue damage caused by ischemic stroke. Neurological examinations, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining and assaying of ECS parameters using MRI were performed 24 h after surgery. We found that thymoquinone could improve the behavioural performance by neurological examinations. TTC staining indicated that thymoquinone significantly decreased the percentage of hemi-cerebral infarction. Also, H&E staining showed that thymoquinone could inhibit the neuron necrosis in the hippocampal CA1 region. We found that thymoquinone treatment could inhibit the changes in ECS diffusion parameters, which might prove that thymoquinone might protect brain tissue damage caused by ischemic stroke. Thymoquinone can protect the brain against cerebral ischemia-reperfusion injury, effectively ameliorate abnormalities in characteristics of ECS and decrease cerebral infarction in tMCAO rats.

Chronic cerebral hypoperfusion is a pathological state that is associated with the cognitive impairments in vascular dementia. Oxiracetam is a nootropic drug that is commonly used to treat cognitive deficits of cerebrovascular origins. However, oxiracetam is currently used as a racemic mixture whose effective ingredient has not been identified to date. In this study, we first identified that (S)-oxiracetam, but not (R)-oxiracetam, was the effective ingredient that alleviated the impairments of spatial learning and memory by ameliorating neuron damage and white matter lesions, increasing the cerebral blood flow, and inhibiting astrocyte activation in chronic cerebral hypoperfused rats. Furthermore, using MALDI-MSI and LC-MS/MS, we demonstrated that (S)-oxiracetam regulated ATP metabolism, glutamine-glutamate and anti-oxidants in the cortex region of hypoperfused rats. Altogether, our results strongly suggest that (S)-oxiracetam alone could be a nootropic drug for the treatment of cognitive impairments caused by cerebral hypoperfusion.

Parkinson's disease (PD) is a major age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra par compacta (SNpc). Rotenone is a neurotoxin that is routinely used to model PD to aid in understanding the mechanisms of neuronal death. Safflower (Carthamus tinctorius. L.) has long been used to treat cerebrovascular diseases in China. This plant contains flavonoids, which have been reported to be effective in models of neurodegenerative disease. We previously reported that kaempferol derivatives from safflower could bind DJ-1, a protein associated with PD, and that a flavonoid extract from safflower exhibited neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD. In this study, a standardized safflower flavonoid extract (SAFE) was isolated from safflower and found to primarily contain flavonoids. The aim of the current study was to confirm the neuroprotective effects of SAFE in rotenone-induced Parkinson rats. The results showed that SAFE treatment increased body weight and improved rearing behavior and grip strength. SAFE (35 or 70 mg/kg/day) treatment reversed the decreased protein expression of tyrosine hydroxylase, dopamine transporter and DJ-1 and increased the levels of dopamine and its metabolite. In contrast, acetylcholine levels were decreased. SAFE treatment also led to partial inhibition of PD-associated changes in extracellular space diffusion parameters. These changes were detected using a magnetic resonance imaging (MRI) tracer-based method, which provides novel information regarding neuronal loss and astrocyte activation. Thus, our results indicate that SAFE represents a potential therapeutic herbal treatment for PD.

The dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) replicates many of the pathological hallmarks of Parkinson's disease (PD) in mice via selective destruction of dopamine neurons of the substantia nigra and striatum. Although MPTP has been widely used to study downstream effects following the degeneration of dopaminergic neurons, the underlying mechanisms of MPTP action remain poorly understood. To determine the underlying mechanisms of MPTP action at the protein level, a 2-DE-based proteomics approach was used to evaluate the changes in protein expression in substantia nigra and striatal tissue in C57BL/6 mice after MPTP administration. We identified nine proteins that were markedly altered and are likely to be involved in mitochondrial function, heat shock protein activity, and which contribute enzyme activities for energy metabolism and protein degradation., (Copyright © 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A 35 kDa protein was purified from rat spinal ganglia and sensory fibers. Combined direct trypsin digest and liquid chromatography ion trap mass spectrometry analysis, the 35 kDa protein was identified as annexin V. We then studied the distribution of serum antibodies to annexin V in patients with peripheral neuropathy. We found serum positive antibodies to annexin V only in some patients with immune-mediated neuropathy. This indicated that humoral immune responses to annexin V might play a role in the pathogenesis of autoimmune sensory neuropathy or sensory neuronopathy.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been employed to create a Parkinson's disease-like model in both rodents and primates based primarily on its ability to create a striatal dopamine deficit due to the loss of dopaminergic neurons in the substantia nigra compacta. The present study was carried out to determine the possible effects of phenylethanoid glycosides (PhGs) from Cistanches salsa (C. A. MEY, G. BECK) on attenuating the serious behavioral disorder and increasing dopamine (DA) levels in the striata of MPTP-lesioned C57 mice. MPTP (30 mg/kg i.p. for 4 d) induced serious behavioral disorders and significantly reduced striatal DA levels in C57 mice. In spontaneous motor activity and rotarod tests, obvious behavioral differences were seen between control and model groups. PhGs (10, 50 mg/kg) significantly increased the spontaneous movement number and latent period of mice on the rotating rod (p<0.01). Injections of MPTP 30 mg/kg for 4 d caused a significant reduction in DA, 3,4-dihydroxyphenyl acetic acid, and homovanillic acid in striata analyzed by HPLC-electrochemistry (p<0.01). The neurotoxic effects of MPTP were attenuated by pretreatment with PhGs (10, 50 mg/kg) in a dose-dependent fashion. The apparent neuroprotective effects of PhGs on nigral dopaminergic neurons were also confirmed by the results of immunohistochemical staining. The present in vivo data clearly demonstrate that PhGs can protect dopaminergic neurons against dopamine neurotoxicity induced by MPTP, as suggested by an earlier in vitro study. The neuroprotective effects of PhGs were the first reported for a natural product.