Temporal coincidence of myasthenia gravis and Guillain Barré syndrome associated with Hashimoto thyroiditis.

Both myasthenia gravis (MG) and Guillain Barré syndrome (GBS) are autoimmune diseases leading to muscle weakness, while the temporal coincidence of MG and GBS is rare. Here, we report a case of MG and GBS, as well as Hashimoto's thyroiditis, for the first time. All these diseases were relieved by immunomodulatory therapy, which suggested abnormal regulation of the autoimmune system might be the cause in our case. In addition, MG was not diagnosed at first from the initial symptom of unilateral lateral rectus muscle palsy.

LncRNA LINC01857 promotes cell growth and diminishes apoptosis via PI3K/mTOR pathway and EMT process by regulating miR-141-3p/MAP4K4 axis in diffuse large B-cell lymphoma.

LINC01857 has been proven to be involved in glioma and breast cancer. However, the biological function of LINC01857 in diffuse large B-cell lymphoma (DLBCL) is poorly investigated. By accessing to the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEX), LINC01857 expression was found upregulated in both DLBCL tissues and cells. Cell proliferation and flow cytometry assays showed that LINC01857 promoted proliferation and cell cycle, but suppressed apoptosis in DLBCL cells. Bioinformatics analysis and luciferase reporter assay confirmed that LINC01857 may serve as a sponge for miR-141-3p and miR-141-3p may target MAP4K4. Mechanically, the regulatory action of miR-141-3p/MAP4K4 on DLBCL cellular behaviors was regulated by LINC01857. In addition, LINC01857 could increase the activity of PI3K/mTOR pathway and facilitate the EMT process in a miR-141-3p-mediated manner in DLBCL. Our data illustrated that the LINC01857/miR-141-3p/MAP4K4 might function as a promising therapeutic avenue for DLBCL treatment.

[The properties and research methods of pannexins].

The gene encoding pannexin is a new gap junction family member discovered in 2000. Recent studies indicated that pannexin protein can form hemichannel on the membrane or intercellular gap junction channel, which is involved in many physiological and pathological activities. Here, we make a review of the latest research progress on the expression and cellular localization, the channel properties and the research methods of pannexins in an attempt to provide some evidences and methodological references to further investigation on the physiological and pathological functions of pannexin.

Ischemic postconditioning protects against global cerebral ischemia/reperfusion-induced injury in rats.

BACKGROUND AND PURPOSE: Ischemic postconditioning has been found to decrease brain infarct area and spinal cord ischemic injury. In this study, we tested the hypothesis that ischemic postconditioning reduces global cerebral ischemia/reperfusion-induced structural and functional injury in rats. METHODS: Ten-minute global ischemia was induced by 4-vessel occlusion in male Sprague-Dawley rats. The animals underwent postconditioning consisting of 3 cycles of 15-second/15-second (Post-15/15), 30-second/30-second (Post-30/30), or 60-second/15-second (Post-60/15) reperfusion/reocclusion or 15-second/15-second reperfusion/reocclusion applied after a 45-second reperfusion (Post-45-15/15). RESULTS: Ten minutes of ischemia and 7 days of reperfusion destroyed 85.8% of CA1 hippocampal neurons and 64.1% of parietal cortical neurons. Three cycles of Post-15/15, Post-30/30, and Post-45-15/15 reperfusion/reocclusion markedly reduced neuronal loss after 7 days or 3 weeks of reperfusion and diminished the deficiency in spatial learning and memory. After reperfusion, a period of hyperperfusion followed by hypoperfusion was observed, both of which were blocked by postconditioning. The cytosolic level of cytochrome c increased significantly after 48 hours of reperfusion, and this was inhibited by Post-15/15, Post-30/30, and Post-45-15/15. However, 3 cycles of 60-second/15-second reperfusion/reocclusion failed to protect against neuronal damage, behavioral deficit, or cytochrome c translocation. CONCLUSIONS: Our data provide the first evidence that an appropriate ischemic postconditioning strategy has neuroprotective effects against global cerebral ischemia/reperfusion injury and a consequent behavioral deficit and that these protective effects are associated with its ability to improve disturbed cerebral blood flow and prevent cytochrome c translocation.

Genistein attenuates oxidative stress and neuronal damage following transient global cerebral ischemia in rat hippocampus.

Oxidative stress is believed to contribute to neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. The present study was undertaken to evaluate the possible antioxidant neuroprotective effect of genistein against neuronal death in hippocampal CA1 neurons following transient global cerebral ischemia in the rat. Transient global cerebral ischemia was induced in male Sprague-Dawley rats by four-vessel-occlusion for 10min. At various times of reperfusion, the histopathological changes and the levels of mitochondria-generated reactive oxygen species (ROS), malondialdehyde (MDA), cytosolic cytochrome c and caspase-3 activity in hippocampus were measured. We found extensive neuronal death in the CA1 region at day 5 after I/R. The ischemic changes were preceded by increases in ROS generation and MDA concentration and followed by increased cytosolic cytochrome c, and subsequently caspase-3 activation and apoptosis. Treatment with genistein (15mg/kg, i.p.) significantly attenuated ischemia-induced neuronal death. Genistein administration also decreased ROS generation, MDA concentration and the apoptotic indices. These results suggest that genistein protects neurons from transient global cerebral I/R injury in rat hippocampus by attenuating oxidative stress, lipid peroxidation and the signaling cascade leading to apoptotic cell death.

D-dimer >2.785 µg/ml and multiple infarcts ≥3 vascular territories are two characteristics of identifying cancer-associated ischemic stroke patients.

BACKGROUND: The patterns and mechanisms underlying stroke in cancer patients differ from those of the conventional etiology. In this study, we further investigated the characteristics distinguishing cancer-associated ischemic stroke (CAIS) and the relationship of D-dimer value with CAIS. METHODS: Sixty-one acute ischemic stroke patients with cancer (cancer group) and 76 stroke patients without cancer (control group) were recruited. Cerebrovascular distribution was divided into 3 circulations and 23 vascular territories, and acute multiple brain infarcts (AMBIs) were defined as discrete MRI diffusion-weighted imaging (DWI) lesions in >1 vascular territory. RESULTS: Cancer patients had higher average D-dimer and fibrinogen degradation product values, and fewer stroke risk factors. The numbers of infarct-affected vascular territories, AMBIs, and AMBIs in multiple circulations were significantly higher in the cancer group. Receiver operating characteristic analysis showed that the cutoff value of D-dimer was 2.785 µg/ml; and above features were particularly evident in cancer patients whose D-dimer values were >2.785 µg/ml, while those with D-dimer values ≤2.785 µg/ml were similar to controls. CONCLUSIONS: D-dimer >2.785 µg/ml may be an effective cutoff value and a sensitive index for identifying CAIS patients. AMBIs in ≥3 vascular territories and AMBIs in both the anterior and posterior circulations are two imaging characteristics of CAIS.

Inhibition of receptor-interacting protein 3 upregulation and nuclear translocation involved in Necrostatin-1 protection against hippocampal neuronal programmed necrosis induced by ischemia/reperfusion injury.

Receptor-interacting protein 3 (RIP3) is a key molecular switch in tumor necrosis factor-induced necroptosis requiring the formation of an RIP3-RIP1 complex. We have recently shown that hippocampal cornu ammonis 1 (CA1) neuronal death induced by 20-min global cerebral ischemia/reperfusion (I/R) injury is a form of programmed necrosis. However, the mechanism behind this process is still unclear and was studied here. Global cerebral ischemia was induced by the four-vessel occlusion method and Necrostatin-1 (Nec-1), a specific inhibitor of necroptosis, was administered by intracerebroventricular injection 1h before ischemia. Normally, in the hippocampal CA1 neurons, RIP1 and RIP3 are located in the cytoplasm. However, after I/R injury, RIP3 was upregulated and translocated to the nucleus while RIP1 was not affected. Nec-1 pretreatment prevented hippocampal CA1 neuronal death and I/R induced changes in RIP3. Decreased level of NAD+ in hippocampus and the release of cathepsin-B from lysosomes after I/R injury were also inhibited by Nec-1. Our data demonstrate that Nec-1 inhibits neuronal death by preventing RIP3 upregulation and nuclear translocation, as well as NAD+ depletion and cathepsin-B release. The nuclear translocation of RIP3 has not been reported previously, so this may be an important role for RIP3 during ischemic injury.

Antioxidant action of a Chrysanthemum morifolium extract protects rat brain against ischemia and reperfusion injury.

The present study evaluated the potential neuroprotective effect and underlying mechanism of the total flavones extracted from Chrysanthemum morifolium (TFCM) against ischemia/reperfusion (I/R) injury. An animal model of cerebral ischemia was established by occluding the right middle cerebral artery for 90 minutes followed by reperfusion for 22 hours. The neurobehavioral scores, infarct area, and hemispheric edema were evaluated. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and reactive oxygen species (ROS) level in brain were also measured. The results showed that pretreatment with TFCM significantly decreased the neurological deficit scores, percentage of infarction, and brain edema and attenuated the decrease in SOD activity, the elevation of MDA content, and the generation of ROS. In isolated brain mitochondria, Ca(2+)-induced swelling was attenuated by pretreatment with TFCM, and this effect was antagonized by atractyloside. These results showed that pretreatment with TFCM provides significant protection against cerebral I/R injury in rats by, at least in part, its antioxidant action and consequent inhibition of mitochondrial swelling.