Innovative behaviour profile and its associated factors among nurses in China: a cross-sectional study based on latent profile analysis.

OBJECTIVES: This study aimed to investigate the current status of innovative behaviours among nurses in traditional Chinese medicine (TCM) hospitals using latent profile analysis, identify potential subgroups and their population characteristics and explore factors associated with different categories. DESIGN: Cross-sectional study. SETTING: Six TCM hospitals in Anhui, China. PARTICIPANTS: From 1 April 2023 to 31 July 2023, a total of 642 registered nurses with more than 1 year of work experience were recruited from the clinical departments of six TCM hospitals using a stratified cluster sampling method. 529 valid questionnaires were recovered, presenting a validity rate of 82.40%. PRIMARY AND SECONDARY OUTCOME MEASURES: Data were collected through online surveys containing a sociodemographic questionnaire, the Nurse Innovative Behaviour Scale, the Nurse Adversity Quotient Self-Evaluation Scale and the Conditions for Work Effectiveness Questionnaire-II. Latent profile analysis was performed to identify categorisation features of nurses' innovative behaviour in TCM hospitals. Multiple logistic regression analyses were used to investigate associated factors with profile membership. RESULTS: TCM hospital nurses' innovative behaviours were mainly classified into three types of latent profiles: low innovative behaviour (35.3%), moderate innovative behaviour (48.4%) and high innovative behaviour (16.3%). The results of multiple logistic regression analyses indicated that gender, monthly income, department, hospital level, position, nurse competency level, any training attended related to TCM knowledge and skills, adversity quotient level and structural empowerment level were the influencing factors for the potential profiles. CONCLUSIONS: The innovative behaviour of nurses in TCM hospitals can be classified into three categories. Studying the heterogeneity of the innovative behaviour of nurses in TCM hospitals and its associated factors provides evidence for nursing administrators and educators to develop individualised interventions based on each latent characteristic to improve the innovative behaviour of nurses in TCM hospitals. It is of great significance to the heritage and innovative development of TCM nursing.

Health characteristics and factors associated with transition shock in newly graduated registered nurses: a latent class analysis.

BACKGROUND: Transition shock occurs at a vulnerable time in newly graduated registered nurses' careers and has a clear impact on both newly graduated registered nurses' productivity and patient recovery outcomes. Identifying classification features of transition shock and targeting interventions to support newly graduated registered nurses is imperative. The study aimed to explore potential transition shock subgroups of newly graduated registered nurses and further explore the impact of population characteristics and two indices of health on transition shock. METHODS: A descriptive, cross-sectional design was conducted. An online questionnaire was sent via WeChat to newly graduated registered nurses who started work in 2021 at seven hospitals between August and November 2021, and 331 nurses filled out the questionnaire. Latent class analysis was used to identify the potential class of the transition shock of newly graduated registered nurses, and multinomial logistic regression analyses were used to determine the factors of potential classification. RESULTS: The study identified four classes of transition shock in newly graduated registered nurses, namely, "high transition shock", "physical fatigue-lack of knowledge", "development adaptation" and "low transition shock-worry" groups. Newly graduated registered nurses who urinated less than 4 times per day (OR = 0.051, 95% CI = 0.005-0.502) were likely to be in the "high transition shock" group. Newly graduated registered nurses who did not delay urination (OR = 4.267, 95% CI = 1.162-11.236) were more likely to belong to the "low transition shock-worry" group. Newly graduated registered nurses without sleep disturbance were more likely to be in the "physical fatigue - lack of knowledge" (OR = 3.109, 95% CI = 1.283-7.532), "development adaptation" (OR = 8.183, 95% CI = 2.447-27.066), and "low transition shock-worry" (OR = 8.749, 95% CI = 1.619-47.288) groups than in the 'high transition shock' group. CONCLUSIONS: This study highlights potential patterns of transition shock among newly graduated registered nurses. Two indices of health, namely, delayed urination and sleep disturbance, can predict the subgroups of newly graduated registered nurses with transition shock.

Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling.

Neurovascular coupling (NVC) is important for brain function and its dysfunction underlies many neuropathologies. Although cell-type specificity has been implicated in NVC, how active neural information is conveyed to the targeted arterioles in the brain remains poorly understood. Here, using two-photon focal optogenetics in the mouse cerebral cortex, we demonstrate that single glutamatergic axons dilate their innervating arterioles via synaptic-like transmission between neural-arteriolar smooth muscle cell junctions (NsMJs). The presynaptic parental-daughter bouton makes dual innervations on postsynaptic dendrites and on arteriolar smooth muscle cells (aSMCs), which express many types of neuromediator receptors, including a low level of glutamate NMDA receptor subunit 1 (Grin1). Disruption of NsMJ transmission by aSMC-specific knockout of GluN1 diminished optogenetic and whisker stimulation-caused functional hyperemia. Notably, the absence of GluN1 subunit in aSMCs reduced brain atrophy following cerebral ischemia by preventing Ca2+ overload in aSMCs during arteriolar constriction caused by the ischemia-induced spreading depolarization. Our findings reveal that NsMJ transmission drives NVC and open up a new avenue for studying stroke.

Resveratrol Modulates the Redox Response and Bile Acid Metabolism to Maintain the Cholesterol Homeostasis in Fish Megalobrama amblycephala Offered a High-Carbohydrate Diet.

This study aimed to characterize the effects of resveratrol on the redox balance, cholesterol homeostasis and bile acid metabolism of Megalobrama amblycephala offered a high-carbohydrate diet. Fish (35.0 ± 0.15 g) were fed four diets including one control diet (32% nitrogen-free extract), one high-carbohydrate diet (45% nitrogen-free extract, HC), and the HC diet supplemented with different levels (0.04%, HCR1; 0.08%, HCR2) of resveratrol for 12 weeks. The HC diet-induced redox imbalance is characterized by increased MDA content and decreased T-SOD and CAT activities in the liver. Resveratrol attenuated this by up-regulating the transcription of Cu/Zn-sod, and increasing the activities of T-SOD, CAT, and GPX. The HC diet enhanced the cholesterol synthesis, but decreased the bile acid synthesis via up-regulating both hmgcr and acat2, and down-regulating cyp7a1, thus resulting in excessive cholesterol accumulation. Resveratrol supplement decreased cholesterol synthesis, and increased cholesterol uptake in the liver by down-regulating both hmgcr and acat2, and up-regulating ldlr. It also increased bile acid synthesis and biliary excretion by up-regulating cyp7a1, and down-regulating mrp2, oatp1, and oatp4 in the hindgut, thereby decreasing cholesterol accumulation. In conclusion, resveratrol improves the cholesterol homeostasis of Megalobrama amblycephala fed a high-carbohydrate diet by modulating the redox response and bile acid metabolism.

Can DKI-MRI predict recurrence and invasion of peritumoral zone of hepatocellular carcinoma after transcatheter arterial chemoembolization?

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Transcatheter arterial chemoembolization (TACE) has been performed as a palliative treatment for patients with HCC. However, HCC is easy to recur after TACE. Magnetic resonance imaging (MRI) has clinical potential in evaluating the TACE treatment effect for patients with liver cancer. However, traditional MRI has some limitations. AIM: To explore the clinical potential of diffusion kurtosis imaging (DKI) in predicting recurrence and cellular invasion of the peritumoral liver zone of HCC after TACE. METHODS: Seventy-six patients with 82 HCC nodules were recruited in this study and underwent DKI after TACE. According to pathological examinations or the overall modified response evaluation criteria in solid tumors (mRECIST) criterion, 48 and 34 nodules were divided into true progression and pseudo-progression groups, respectively. The TACE-treated area, peritumoral liver zone, and far-tumoral zone were evaluated on DKI-derived metric maps. Non-parametric U test and receiver operating characteristic curve (ROC) analysis were used to evaluate the prediction performance of each DKI metric between the two groups. The independent t-test was used to compare each DKI metric between the peritumoral and far-tumoral zones of the true progression group. RESULTS: DKI metrics, including mean diffusivity (MD), axial diffusivity (DA), radial diffusivity (DR), axial kurtosis (KA), and anisotropy fraction of kurtosis (Fak), showed statistically different values between the true progression and pseudo-progression groups (P < 0.05). Among these, MD, DA, and DR values were higher in pseudo-progression lesions than in true progression lesions, whereas KA and FAk values were higher in true progression lesions than in pseudo-progression lesions. Moreover, for the true progression group, the peritumoral zone showed significantly different DA, DR, KA, and FAk values from the far-tumoral zone. Furthermore, MD values of the liver parenchyma (peritumoral and far-tumoral zones) were significantly lower in the true progression group than in the pseudo-progression group (P < 0.05). CONCLUSION: DKI has been demonstrated with robust performance in predicting the therapeutic response of HCC to TACE. Moreover, DKI might reveal cellular invasion of the peritumoral zone by molecular diffusion-restricted change.

Feed types affect the growth, nutrient utilization, digestive capabilities, and endocrine functions of Megalobrama amblycephala: a comparative study between pelleted and extruded feed.

Nowadays, both pelleted feed (PF) and extruded feed (EF) have been widely adopted in the aquaculture industry. However, limited information is available comparing their utilization efficiencies and meanwhile interpreting the underlying mechanisms. This study aimed to compare the utilization efficiencies of both PF and EF by blunt snout bream (Megalobrama amblycephala) based on growth performance, digestive capacities, and endocrine functions. Two feeds with identical formulas were prepared and named PF and EF. Fish were randomly distributed into two groups, including one that fed the PF continuously, and one that offered the EF continuously. The whole feeding trail lasted 8 weeks. The results showed that the protein efficiency (PER), retention of nitrogen and energy (NRE and ERE), viscera index (VSI), apparent digestibility of dry matter, protein, carbohydrate, and gross energy, whole-body crude protein and energy contents, intestinal enzymatic activities of protease, amylase, and Na+,K+-ATPase, intestinal villi length, crypt depth, muscular layer thickness, and the transcriptions of leptin (LEP) and cholecystokinin (CCK) of the EF group were all significantly higher than those of the PF group, while the opposite was true for feed intake and feed conversion ratio. These findings suggested that compared with PF, EF could improve the feed utilization and nutrient retention of blunt snout bream by enhancing the intestinal digestive and absorptive functions but reduce the feed intake through the stimulation of both LEP and CCK.

Improvements on sampling of point spread function in optical transfer function measurement.

Point spread function (PSF), which is the intensity distribution of optical system impulse response and usually acquired by imaging a single pinhole in experiment, can characterize the quality of optical imaging system. Faithful recording of the two-dimensional intensity distribution of PSF is key for accurate measurement of optical transfer function (OTF), however distortions in recorded PSF can be easily caused by a large sampling interval and the electronic noise of the detector. Under a given sampling interval, the position-phase difference between pixels and intensity signals can change the intensity distribution of acquired PSF remarkably, making the computed OTF or MTF (modulation transfer function) error prone. Aiming at problems existing in pinhole based MTF measurement methods, this paper developed a new method with underline physics similar to that of slanted edge method to realize sub-pixel sampling of PSF intensity by using accurate non-integer up-sampling matrix of separate binary pixels and applying random patterns shown on digital micro-mirror device (DMD) as target. Numerical simulations show that improvement on the discrete sampling of point spread function with this method is very helpful to improve anti-noise robustness and the accuracy of optical transfer function measurement.

Precise control of embolic stroke with magnetized red blood cells in mice.

Precise embolism control in immature brains can facilitate mechanistic studies of brain damage and repair after perinatal arterial ischemic stroke (PAIS), but it remains a technical challenge. Microhemorrhagic transformation is observed in one-third of infant patients who have suffered PAIS, but the underlying mechanism remains elusive. Building on an established approach that uses magnetic nanoparticles to induce PAIS, we develop a more advanced approach that utilizes magnetized erythrocytes to precisely manipulate de novo and in situ embolus formation and reperfusion in perinatal rodent brains. This approach grants spatiotemporal control of embolic stroke without any transarterial delivery of pre-formed emboli. Transmission electron microscopy revealed that erythrocytes rather than nanoparticles are the main material obstructing the vessels. Both approaches can induce microbleeds as an age-dependent complication; this complication can be prevented by microglia and macrophage depletion. Thus, this study provides an animal model mimicking perinatal embolic stroke and implies a potential therapeutic strategy for the treatment of perinatal stroke.

Molecular characterization of farnesoid X receptor alpha in Megalobrama amblycephala and its potential roles in high-carbohydrate diet-induced alterations of bile acid metabolism.

Farnesoid X receptorα (FXRα) plays a central role in maintaining the bile acid homeostasis in mammals, while relevant processes are still poorly interpreted in aquatic species. This study was conducted to characterize the fxrα gene in a cyprinidae species: blunt snout bream (Megalobrama amblycephala), and investigate its potential roles in bile acid metabolism. The Fxrα protein contains one DNA binding domain, one ligand binding domain, one His-Try "switch" and two modifies residues. A high degree of conservation (53.18-100.00 %) was observed in the Fxrα protein among most aquatic species and higher vertebrates. The transcription of fxrα was mainly observed in intestine, liver and kidney. Then fish (35.0 ± 0.15 g) were fed two diets containing 33 % and 45 % carbohydrate levels for 12weeks. High-carbohydrate diet significantly elevated the total cholesterol concentrations in plasma, liver and hindgut as well as the triglyceride concentrations in both liver and hindgut, but decreased the total bile acid concentrations in plasma, liver and hindgut. High dietary carbohydrate levels also significantly enhanced hepatic transcriptions of 3-hydroxy-3-methylglutaryl-CoA reductase (the rate-limiting enzyme in cholesterol synthesis), and those of fxrα (a bile acid receptor) and multidrug resistance associated protein 2 (a bile acid transporter) in hindgut. Furthermore, high dietary carbohydrate levels significantly decreased the transcriptions of cholesterol 7α-hydroxylase (the rate-limiting enzyme in bile acid synthesis) and organic anion-transporting polypeptides (a bile acid transporter) in liver as well as that of takeda G-protein-coupled bile acid receptor in hindgut. The results demonstrated that the fxrα gene of blunt snout bream is highly conserved compared with other vertebrates. Besides, high dietary carbohydrate levels increased total cholesterol concentrations, and up-regulated the transcription of fxrα, thus decreasing the biosynthesis and reabsorption of bile acids by mediating various target genes.

Carbonyl cyanide 3-chlorophenylhydrazone induced the imbalance of mitochondrial homeostasis in the liver of Megalobrama amblycephala: A dynamic study.

Carbonylcyanide-3-chlorophenylhydrazone (CCCP) is a protonophore, which causes uncoupling of proton gradient in the inner mitochondrial membrane, thus inhibiting the rate of ATP synthesis. However, this information is manly derived from mammals, while its effects on the mitochondrial homeostasis of aquatic animals are largely unknown. In this study, the mitochondrial homeostasis of a carp fish Megalobrama amblycephala was investigated systematically in a time-course manner by using CCCP. Fish was injected intraperitoneally with CCCP (1.8 mg/kg per body weight) and DMSO (control), respectively. The results showed that CCCP treatment induced hepatic mitochondrial oxidative stress, as was evidenced by the significantly increased MDA and PC contents coupled with the decreased SOD and MnSOD activities. Meanwhile, mitochondrial fission was up-regulated remarkably characterized by the increased transcriptions of Drp-1, Fis-1 and Mff. However, the opposite was true for mitochondrial fusion, as was indicative of the decreased transcriptions of Mfn-1, Mfn-2 and Opa-1. This consequently triggered mitophagy, as was supported by the accumulated mitochondrial autophagosomes and the increased protein levels of PINK1, Parkin, LC3-II and P62 accompanied by the increased LC3-II/LC3-I ratio. Mitochondrial biogenesis and function both decreased significantly addressed by the decreased activities of CS, SDH and complex I, IV and V, as well as the protein levels of PGC-1ß coupled with the decreased transcriptions of TFAM, COX-1, COX-2 and ATP-6. Unlikely, DMSO treatment exerted little influence. Overall, CCCP treatment resulted in the imbalance of mitochondrial homeostasis in Megalobrama amblycephala by promoting mitochondrial oxidative stress, fission and mitophagy, but depressing mitochondrial fusion, biogenesis and function.

Effect of α2­macroglobulin in the early stage of jaw osteoradionecrosis.

Advanced osteoradionecrosis (ORN) is one of the most serious complications in patients with head and neck cancer, resulting in poor prognosis. Numerous studies have therefore focused on the pathogenesis and interventions of ORN early stage. The present study aimed to investigate whether α2­macroglobulin (α2M) could prevent early­stage jaw osteoradionecrosis caused by radiotherapy (RT). Following local injection of α2M, a single dose of 30 Gy was delivered to rats for pathological exploration. For 28 days, the irradiated mandible and soft tissues were examined for potential changes. Furthermore, primary human bone marrow mesenchymal stem cells pretreated with α2M followed by 8 Gy irradiation (IR) were also used. Tartrate­resistant acid phosphatase assay, terminal uridine deoxynucleotidyl nick end labeling assay and immunohistochemical staining were performed on irradiated mandibular bone, tongue or buccal mucosa tissues from rats. Cell proliferation was assessed by evaluating the cell morphology by microscopy and by using the cell counting kit­8. Fluorescence staining, flow cytometry and western blotting were conducted to detect the reactive oxygen species level, cell apoptosis and protein expression of superoxide dismutase 2 (SOD2), heme oxygenase­1 (HO­1) and phosphorylated Akt following irradiation. The results demonstrated that α2M attenuated physical inflammation, osteoclasts number and fat vacuole accumulation in mandibular bone marrow and bone marrow cell apoptosis following IR in vivo. Furthermore, α2M pretreatment suppressed the expression of 8­hydroxy­2'­deoxyguanosine in mandibular bone and tongue paraffin embedded sections, which is a marker of oxidative damage, and increased SOD2 expression in mucosa and tongue paraffin embedded sections. The present study demonstrated the efficient regulation of antioxidative enzymes, including SOD2 and heme oxygenase­1, and reduction in oxidative damage by α2M. In addition, in vitro results confirmed that α2M may protect cells from apoptosis and suppress reactive oxygen species accumulation. Overall, the present study demonstrated that α2M treatment may exert some radioprotective effects in early­stage ORN via antioxidant mechanisms, and may therefore be considered as a potential alternative molecule in clinical prophylactic treatments.

Diffusion kurtosis imaging in liver: a preliminary reproducibility study in healthy volunteers.

OBJECTIVES: To systematically test the reproducibility of DKI technique in normal liver and report a complete set of DKI measurement data. MATERIALS AND METHODS: Thirty-two healthy volunteers were examined with liver DKI twice on the GE 3.0 T MRI scanner and reviewed by three professional experts. DKI-derived parameters fractional anisotropy of kurtosis (FAk), mean diffusivity (Md), axial diffusivity (Da), radial diffusivity (Dr), mean kurtosis (Mk), axial kurtosis (Ka), and radial kurtosis (Kr) in eight segments divided by Couinaud octagonal method were collected. Inter-class correlation coefficient (ICC) was used to assess the agreement between three experts. For each expert, the reproducibility of twice scans was evaluated by Bland-Altman method. Multivariate analysis of variance was to explore the regional distribution characteristics of DKI-derived parameters, and showed with box-plot graph. RESULTS: Using ICC analysis, except for FAk (ICC 0.312, 0.307), other DKI metric values showed high reproducibility (0.716 < ICC < 0.907) between three experts for each of two DKI measurements. With Bland-Altman method, liver segment 5 (S5) showed the best reproducibility between two DKI measurement, and the reproducibility of segment 4 (S4) was the worst. The reproducibility of the right lobe was significantly higher than the left lobe. The values of diffusion metrics (Md, Da, and Dr) and kurtosis metrics (Mk, Ka, and Kr) existed significantly difference between the right and left hepatic lobes. CONCLUSION: DKI has shown excellent reproducibility in liver imaging. The range of values for multiple DKI parameters, derived from the normal liver, was reported, and may provide data reference for further clinical DKI applications. Additionally, DKI technique is a non-invasive method to reflect the perfusion or structural differences between the left and right hepatic lobes from the molecular level.

Periodontitis and inflammatory bowel disease: a meta-analysis.

BACKGROUND: Periodontitis was reported to be associated with inflammatory bowel disease (IBD). However, the association between them has not been firmly established in the existing literature. Therefore, this meta-analysis was conducted to evaluate the relationship between periodontitis and IBD. METHODS: Electronic databases were searched for publications up to August 1, 2019 to include all eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated to determine the association between periodontal disease and IBD using a random or fixed effects model according to heterogeneity. RESULTS: Six eligible studies involving 599 IBD patients and 448 controls were included. The pooled OR between periodontitis and IBD was 3.17 (95% CI: 2.09-4.8) with no heterogeneity observed (I2 = 0.00%). The pooled ORs were 3.64 (95% CI: 2.33-5.67) and 5.37 (95% CI: 3.30-8.74) for the associations between periodontitis and the two sub-categories of IBD, Crohn' s disease and ulcerative colitis, respectively. CONCLUSIONS: The results demonstrated that periodontitis was significantly associated with IBD. However, the mechanisms underlying periodontitis and IBD development are undetermined. Further studies are needed to elucidate this relationship.

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma.

BACKGROUND: Immune-related genes (IRGs) were linked to the prognosis of head and neck squamous cell carcinoma (HNSCC). This study aimed to identify the effects of an immune-related gene signature (IRGS) that can predict the of HNSCC prognosis. METHODS: The expression data of 770 HNSCC patients from the TCGA database and the GEO database were used. To explore a predictive model, the Cox proportional hazards model was applied. The Kaplan-Meier survival analysis, as well as univariate and multivariate analyses were performed to evaluate the independent predictive value of IRGS. To explore biological functions of IRGS, enrichment analyses and pathway annotation for differentially expressed genes (DEGs) in different immune groups were applied, as well as the immune infiltration. RESULTS: A prognostic signature comprising 27 IRGs was generated. IRGS significantly stratified HNSCC patients into high and low immune risk groups in regard to overall survival in the training cohort (HR = 3.69, 95% CI 2.73-4.98, P < 0.001). Likewise, IRGS could be linked to the prognosis of HNSCC in patients of the validation cohort (HR = 1.84, 95% CI 1.21-2.81, P < 0.01). Even after adjusting for TNM stage, IRGS was maintained as an independent predictor in the multivariate analysis (HR = 3.62, 95% CI 2.58-5.09, P < 0.001), and in the validation cohort (HR = 1.73, 95% CI 1.12-2.67, P = 0.014). The IFN-α response, the IFN-γ response, IL-2/STAT5 signaling, and IL-6/JAK/STAT3 signaling were all negatively correlated with the immune risk (P < 0.01). Immune infiltration of the high-risk group was significantly lower than that of the low-risk group (P < 0.01). Most notably, the infiltration of CD8 T cells, memory-activated CD4 T cells, and regulatory T cells was strongly upregulated in the low immune risk groups, while memory resting CD4 T cell infiltration was downregulated (P < 0.01). CONCLUSION: Our analysis provides a comprehensive prognosis of the immune microenvironments and outcomes for different individuals. Further studies are needed to evaluate the clinical application of this signature.

Protective effects of α­2­macroglobulin on human bone marrow mesenchymal stem cells in radiation injury.

Osteoradionecrosis of the jaws (ORNJ) is a complication of oral and maxillofacial malignancy that arises following radiotherapy; progressive jaw necrosis severely decreases the quality of life of patients. Human bone marrow mesenchymal stem cells (hBMMSCs) are a cell type with self­renewal and pluripotent differentiation potential in the bone marrow stroma. These cells are associated with bone tissue regeneration and are one of the primary cell types affected by bone tissue radiation injury. α­2­macroglobulin (α2M) is a glycoprotein­rich macromolecule that interacts with cytokines, growth factors and hormones to serve a variety of biological roles. In addition, α2M possesses radio­protective effects. The aim of the present study was to investigate whether α2M has protective effects against radiation injury of hBMMSCs. Cell counting kit­8 and colony formation assays were used to monitor cell proliferation. Western blot analysis and reverse transcription­quantitative polymerase chain reaction were used to detect Beclin1, microtubule­associated protein 1A/1B, sex determining region Y, Nanog, runt­related transcription factor 2, osteoglycin and manganese superoxide dismutase expression. The formation of calcium nodules was evaluated by Alizarin red staining after osteogenic induction. Flow cytometric analysis of Annexin­V and propidium iodide double staining was used to detect changes in apoptosis rate. Alkaline phosphatase and superoxide dismutase activity were determined using colorimetric assays. Reactive oxygen species levels were detected using 2',7'­dichlorodihydrofluorescein diacetate. The results of the present study revealed that α2M increased the rate of proliferation, reduced autophagy, alleviated pluripotent differentiation injury, increased the osteogenic differentiation ability and decreased the rate of apoptosis in hBMMSCs following irradiation via an antioxidative pathway. In conclusion, α2M exhibited protective effects against radiation injury in hBMMSCs and may be considered a potential therapeutic agent for the prevention and treatment of ORNJ.

Deletion of Kir6.2/SUR1 potassium channels rescues diminishing of DA neurons via decreasing iron accumulation in PD.

ATP-sensitive potassium (K-ATP) channels express in the central nervous system extensively which coupling cell metabolism and cellular electrical activity. K-ATP channels in mature substantia nigra (SN) dopaminergic (DA) neurons are composed of inwardly rectifying potassium channel (Kir) subunit 6.2 and sulfonylurea receptor 1 (SUR1). Our previous study revealed that regulating K-ATP channel exerts the protective effect on DA neurons in a mouse model of Parkinson's disease (PD). However, the detailed mechanism underlying the role of Kir6.2/K-ATP remains unclear. In the present study, we found the deletion of Kir6.2 dramatically alleviated PD-like motor dysfunction of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD model. We further found that Kir6.2 knockout selectively restored the reduction of both DA neuronal number and dopamine transmitter level in the nigrostriatal of MPTP-treated PD mice. To gain some understanding on the molecular basis of this effect, we focused on the regulation of Kir6.2 deletion on iron metabolism which is tightly associated with DA neuron damage. We found that Kir6.2 knockout suppressed the excessive iron accumulation in MPTP-treated mouse midbrain and inhibited the upregulation of ferritin light chain (FTL), which is a main intracellular iron storage protein. We probed further and found out that the deletion of Kir6.2 inhibited the excessive production of FTL via IRP-IRE regulatory system, and thereby protecting SN DA neurons against MPTP challenge. Our findings suggest that Kir6.2 plays a crucial role in the pathogenesis of PD and regulating Kir6.2/K-ATP channel may be a promising strategy for PD treatment.

Role of dopamine D3 receptor in alleviating behavioural deficits in animal models of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a complicated psychiatric disorder, which occurs after exposure to a traumatic event. The main clinical manifestation of PTSD includes fear and stress dysregulation. In both animals and humans, dysregulation of dopamine function appears to be related to conditioned fear responses. Previous studies show that the dopamine D3 receptor (D3R) is involved in schizophrenia, autism, and substance use disorders and is related to emotional disorders. However, few studies have investigated the role of the D3R in the pathogenesis and aetiology of PTSD. In the current study, we have reported that D3R knockout (D3R-/-) mice displayed decreased freezing time of contextual fearing and anxiolytic effects following training sessions consisting of exposure to inescapable electric foot-shocks. Similarly, highly selective blockade of D3Rs by YQA14, a novel D3R antagonist, significantly ameliorated freezing and anxiogenic-like behaviours in the single-prolonged stress (SPS) model of PTSD in rats. And more, YQA14 selectively alleviated the symptoms of PTSD in WT mice but not in D3R-/- mice. In summary, this study demonstrates the anti-PTSD effects of blockade or knockout of the D3R, suggesting that the D3R might play an important role in the pathogenesis and aetiology of PTSD, and might be a potential target for the clinical management of PTSD.

Alpha-2-macroglobulin as a radioprotective agent: a review.

Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin (α2M) possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a non-selective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovic et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, anti-fibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of α2M. The lacunae in the existing knowledge and directions for future research are also addressed.

[Protective effects of hirudin on acute experimental intracerebral hemorrhage].

OBJECTIVE: To explore the protective effects of hirudin on acute experimental intracerebral hemorrhage (ICH) by observing the changes of histologic pathology and brain water content as well as GFAP-positive cells in the perihematomal brain regions. METHOD: The models of rat ICH were made with infusion of autologous blood into the right neucleus caudatus. The rats were divided randomly into control group, intracerebral hemorrhage group and treating group with hirudin. Brain water content was measured, and pathological and GFAP changes were observed. RESULT: The pathological impairation after ICH were gradually deteriorated and peaked at the third day. Brain water content after ICH was gradually increased and obviously after one day(P < 0.05) and peaked at the third day. GFAP-positive cells were gradually increased and peaked at the seventh day after ICH. In the treating groups, the pathological impairation and brain water content as well as the GFAP-positive cells were decreased as compared to those in the intracerebral hemorrhage group and the control group. And the positive correlation between GFAP-positive cell numbers and brain water content were shown by linear regression. CONCLUSION: The local administration of hirudin, a special inhibitor of thrombin, has protective effects within the first week after ICH.