Multiple low doses of erythropoietin delay the proliferation of hepatocytes but promote liver function in a rat model of subtotal hepatectomy.

PURPOSE: The impact of various doses of erythropoietin (EPO) on liver regeneration after partial hepatectomy (PH) in different animal models is still under debate. We investigated the impact of low doses of EPO on liver regeneration in a rat model of subtotal hepatectomy. METHODS: We established a 90 % PH rat model with perioperative injections of low-dose EPO (1,000 IU/kg). We analyzed survival and hepatocyte proliferation in animals treated with or without EPO and assessed liver function by blood ammonia measurement and the indocyanine green 15-min retention test. RESULTS: Low doses of EPO treatment improved the survival of rats after 90 % PH. Unexpectedly, during the first 24 h after the operation, liver regeneration in the EPO-treated rats was inhibited. DNA synthesis, cell proliferation, and the expression of cyclins and p-STAT3 peaked 48 h after PH, which was delayed by about 24 h vs. the control rats. Furthermore, EPO treatment increased the serum level of IL-6 and protected the hepatocytes from apoptosis. CONCLUSION: Low doses of EPO do not stimulate early hepatocyte proliferation in the regenerating liver, but contribute to liver protection by inducing IL-6 and inhibiting apoptosis.

Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice.

AIM: To evaluate the efficacy and safety of Entecavir (ETV) plus adefovir (ADV) for chronic hepatitis B (CHB) patients after multiple nucleos(t)ide analogue (NAs) failure treatment. METHODS: Hepatitis B e antigen (HBeAg)-positive patients who had a suboptimal response or developed resistance to two or more previous NAs treatments were included, and all subjects were treated with ETV in combination with ADV for ≥ 24 months. Complete virologic response (CVR) was defined as an undetectability of serum hepatitis B virus (HBV) DNA level during treatment. Safety assessment was based on the increasing of serum creatinine and creatine kinase levels. RESULTS: A total of 45 eligible patients were included. Twenty-five patients had been treated with lamivudine (LAM) or telbivudine (LdT) and developed genotypic resistance. Resistance to ADV was present in 18 patients and 4 patients had a suboptimal response to ETV. Two patients had a resistance to both LAM and ADV. The cumulative probabilities of CVR at 12 and 24 months of ETV + ADV treatment were 88.9% (40/45) and 97.8% (44/45), respectively. Although one patient failed to achieve CVR, its serum HBV DNA level decreased by 3.3 log copies/mL after 24 months of combination therapy. The cumulative probability of HBeAg seroconversion was 15.6% (7/45) and 26.7% (12/45) at 12 and 24 months of treatment, respectively. History of prior exposure to specific NAs did not make a difference to ETV + ADV treatment outcome. There were no significant adverse events related to ETV + ADV therapy observed in the study subjects. CONCLUSION: ETV + ADV can be used as an effective and safe rescue therapy in patients after multiple NA therapy failures, especially in the areas where tenofovir is not yet available.

Brain structure alterations and cognitive impairment following repetitive mild head impact: An in vivo MRI and behavioral study in rat.

Mild traumatic brain injury (mTBI) or concussion is a common health issue. Several people repeatedly experience head impact milder than that causing concussion. The present study aimed to confirm the effects of such repeated impact on the brain structure and cognitive abilities. Rat models were established by closed skull weight-drop injury. The animals were anesthetized, subjected to single (s)-sham, s-mTBI, repetitive (r)-sham, and r-mTBI, and recovery times were recorded. MRI, including T2-weighted and diffusion tensor imaging (DTI), as well as, neurological severity scores (mNSS) were assessed for the dynamics of the brain structure and neurological function. Morris water maze (MWM) was used to evaluate the cognitive function. The histological examination of r-mTBI rats revealed the basis of structural changes in the brain. There was no significant difference in the recovery time, MRI, mNSS, and MWM between the s-sham and the s-mTBI groups. Compared with r-sham, r-mTBI induced significant differences in the following aspects. The recovery time was prolonged and beam balance test (BBT) in mNSS increased from day 5. MWM performances were worse even after the BBT was recovered. The volumes of the cortex (CT), hippocampus (HP), and lateral ventricle had changed from day 5, which reached a maximum at day 14. Abnormal DTI parameters were observed in CT, corpus callosum, and HP. Histological analyses showed that both in CT and HP, neuron counts reduced at the end of the experiment. Altogether, these findings indicate that non-symptomatic head injury may result in brain atrophy and cognitive impairment when occurred repeatedly.

Cerebral vasospasm and corticospinal tract injury induced by a modified rat model of subarachnoid hemorrhage.

OBJECTIVE: Double-hemorrhage rat models of subarachnoid hemorrhages (SAH) are most effective at simulating delayed cerebral vasospasms (CVS). The present study modified the models to minimize additional trauma and investigated injury of the corticospinal tract (CST) using diffusion tensor imaging (DTI). METHODS: On the first day, 0.3ml of autologous arterial blood was collected by puncturing the caudal artery and injected into the cisterna magna via percutaneous puncture; and the operation was repeated on the third day. The diameters of the basilar artery (BA), middle cerebral artery (MCA), and anterior cerebral artery (ACA) were measured by magnetic resonance angiography on days 3, 5, 7, 9, and 11 post-SAH. Meanwhile, on days 3, 7, 11, 15 and 19, DTI was performed to evaluate the injury of the CST at cerebral peduncle (CP) and pyramidal tract (Py) by measuring fractional anisotropy (FA) value. RESULTS: Blood was deposited mainly in the basal cistern. Diameters of BA, MCA, and ACA were significantly reduced. FA value of the CP was lower in the SAH group than in the control group; but FA value of Py wasn't different between the two groups. CONCLUSION: This is a minimally-invasive and high performance rat model of SAH. Additionally, the occurrence of CVS is firm and the axons in CP are injured.

Diallyl trisufide protects against oxygen glucose deprivation -induced apoptosis by scavenging free radicals via the PI3K/Akt -mediated Nrf2/HO-1 signaling pathway in B35 neural cells.

Oxidative stress contributes to development of ischemic brain damage. Many antioxidants have been proven effective in ameliorating cerebral ischemia injury by inhibiting oxidative stress. DATS, an organosulfuric component of garlic oil, exhibits antioxidative effects. In present study, we used OGD model to investigate the neuroprotective effects of DATS and the mechanisms related to these effects. B35 neural cells exposed to OGD caused a decrease in cell viability and increases in the percentage of apoptotic cells and the level of intracellular cleaved caspase-3, all of which were markedly attenuated by DATS. Further, DATS treatment significantly increased Nrf2 expression and nuclear translocation, upregulated downstream gene HO-1 and inhibited intracellular ROS and MDA generation, all of which were markedly attenuated in cells transfected with Nrf2-specific siRNA. In addition, inhibition of PI3K/Akt signaling by PI3K-specific siRNA not only decreased the expression level of Nrf2 and HO-1 proteins, but also diminished the antioxidative and neuroprotective effect of DATS. Taken together, these results indicate that DATS protects B35 neural cells against OGD-induced cell injury by inhibiting ROS production via upregulating the PI3K/Akt-mediated Nrf2 pathway, which further activates HO-1. Based on our results, DATS may be a potential candidate for intervention in hypoxic-ischemic brain injuries such as stroke.

Analysis of protein-protein interaction network and functional modules on primary osteoporosis.

BACKGROUND: Primary osteoporosis is an age-related disease, and the main cause of this disease is the failure of bone homeostasis. Previous studies have shown that primary osteoporosis is associated with gene mutations.To explore the functional modules of the PPI (protein-protein interaction) network of differentially expressed genes (DEGs), and the related pathways participating in primary osteoporosis. METHODS: The gene expression profile of primary osteoporosis GSE35956 was downloaded from the GEO (Gene Expression Omnibus) database and included five MSC (mesenchymal stem cell) specimens of normal osseous tissue and five MSC specimens of osteoporosis. The DEGs between the two types of MSC specimens were identified by the samr package in R language. In addition, the functions and pathways of DEGs were enriched. Then the DEGs were mapped to String to acquire PPI pairs and the PPI network was constructed with by these PPI pairs. Topological properties of the network were calculated by Network Analyzer, and modules in the network were screened by Cluster ONE software. Subsequently, the fronting five modules whose P-value was less than 1.0e-05 were identified and function analysis was conducted. RESULTS: A total of 797 genes were filtered as DEGs from these ten specimens of GSE35956 with 660 up-regulated genes and 137 down-regulated genes. Meanwhile, up-regulated DEGs were mainly enriched in functions and pathways related to cell cycle and DNA replication. Furthermore, there were 4,135 PPI pairs and 377 nodes in the PPI network. Four modules were enriched in different pathways, including cell cycle and DNA replication pathway in module 2. CONCLUSIONS: In this paper, we explored the genes and pathways involved in primary osteoporosis based on gene expression profiles, and the present findings have the potential to be used clinically for the future treatment of primary osteoporosis.