LAMC1 attenuates neuronal apoptosis via FAK/PI3K/AKT signaling pathway after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The poor prognosis in patients with subarachnoid hemorrhage (SAH) is often attributed to neuronal apoptosis. Recent evidence suggests that Laminin subunit gamma 1 (LAMC1) is essential for cell survival and proliferation. However, the effects of LAMC1 on early brain injury after SAH and the underlying mechanisms are unknown. The current study aimed to reveal the anti-neuronal apoptotic effect and the potential mechanism of LAMC1 in the rat and in the in vitro SAH models. METHODS: The SAH model of Sprague-Dawley rats was established by endovascular perforation. Recombinant LAMC1 (rLAMC1) was administered intranasally 30 min after modeling. LAMC1 small interfering RNA (LAMC1 siRNA), focal adhesion kinase (FAK)-specific inhibitor Y15 and PI3K-specific inhibitor LY294002 were administered before SAH modeling to explore the neuroprotection mechanism of rLAMC1. HT22 cells were cultured and stimulated by oxyhemoglobin to establish an in vitro model of SAH. Subsequently, SAH grades, neurobehavioral tests, brain water content, blood-brain barrier permeability, western blotting, immunofluorescence, TUNEL, and Fluoro-Jade C staining were performed. RESULTS: The expression of endogenous LAMC1 was markedly decreased after SAH, both in vitro and in vivo. rLAMC1 significantly reduced the brain water content and blood-brain barrier permeability, improved short- and long-term neurobehavior, and decreased neuronal apoptosis. Furthermore, rLAMC1 treatment significantly increased the expression of p-FAK, p-PI3K, p-AKT, Bcl-XL, and Bcl-2 and decreased the expression of Bax and cleaved caspase -3. Conversely, knockdown of endogenous LAMC1 aggravated the neurological impairment, suppressed the expression of Bcl-XL and Bcl-2, and upregulated the expression of Bax and cleaved caspase-3. Additionally, the administration of Y15 and LY294002 abolished the protective roles of rLAMC1. In vitro, rLAMC1 significantly reduced neuronal apoptosis, and the protective effects were also abolished by Y15 and LY294002. CONCLUSION: Exogenous LAMC1 treatment improved neurological deficits after SAH in rats, and attenuated neuronal apoptosis in both in vitro and in vivo SAH models, at least partially through the FAK/PI3K/AKT pathway.

Lentinan-functionalized selenium nanoparticles induce apoptosis and cell cycle arrest in human colon carcinoma HCT-116 cells.

Selenium nanoparticles (SeNPs) have gained extensive attention for their excellent biological activity and low toxicity. However, SeNPs are extremely liable to aggregate into non-bioactive or gray elemental selenium, which limits their application in the biomedicine field. This study aimed to prepare stable SeNPs by using lentinan (LNT) as a template and evaluate its anti-colon cancer activity. The average particle diameter of obtained lentinan-selenium nanoparticles (LNT-SeNPs) was approximately 59 nm and presented zero-valent, amorphous, and spherical structures. The monodisperse SeNPs were stabilized by LNT through hydrogen bonding interactions. LNT-SeNPs solution remained highly stable at 4°C for at least 8 weeks. The stability of LNT-SeNPs solution sharply decreased under high temperature and strong acidic conditions. LNT-SeNPs showed no obvious cytotoxic effect on normal cells (IEC-6) but significantly inhibited the proliferation of five colon cancer cells (HCT-116, HT-29, Caco-2, SW620, and CT26). Among them, LNT-SeNPs exhibited the highest sensitivity toward HCT-116 cells with an IC50 value of 7.65 µM. Also, LNT-SeNPs displayed better cancer cell selectivity than sodium selenite and selenomethionine. Moreover, LNT-SeNPs promoted apoptosis of HCT-116 cells through activating mitochondria-mediated apoptotic pathway. Meanwhile, LNT-SeNPs induced cell cycle arrest at G0/G1 phase in HCT-116 cells via modulation of cell cycle regulatory proteins. The results of this study indicated that LNT-SeNPs possessed strong potential application in the treatment of colorectal cancer (CRC).

[The complications of traumatic optic neuropathy].

OBJECTIVE: To investigate the complications of traumatic optic neuropathy and to call the surgeons attention to precaution. METHOD: Retrospectively analysis of 122 cases patients with traumatic optic neuropathy and 3 cases were analyzed in detail including 1 case with purulent meningitis, another 1 case with internal carotid artery pseudoaneurysm and the other 1 case with internal carotid artery cavernous sinus fistula. RESULT: Most of the patients had the complications of orbital fracture, maxillofacial fracture, ocular and craniocerebral injury. A few of patients had other injuries all over the body. The case with purulent meningitis was cured with antibiotics. The case with internal carotid artery pseudoaneurysm was cured with neurosurgery. The visual acuity of the both cases were improved. The case with internal carotid artery cavernous sinus fistula died of severe hemorrhage. CONCLUSION: The patient with traumatic optic neuropathy has the possibility of severe cranial disorders, orbital fracture, maxillofacial fracture and injuries of viscera or limbs. It should be paid more attention and treated accordingly.

[Influence of the physical growth and neuropsychological characteristic in children with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To explore the influence of obstructive sleep apnea hypopnea syndrome (OSAHS) on physical growth and neuropsychological characteristic of children. METHOD: Eighty-two cases with OSAHS were examined by PSG, and divided to mild, moderate and severe group according to AHI, and 40 healthy children were selected as control group. Physical and mental development were evaluated on the basis of growth and neurodevelopmental assessments, respectively. Psychological behavior were assessed by Wechsler Intelligence Scale for Children Chinese Version and Achenbach Child Behavior checklist. RESULT: (1) The children of mild group were lower than the control group in the height and sitting height. The children of moderate and severe group were significantly lower than the control group in physical growth. (2) The children of mild group showed no difference compared with control group in Wechsler Intelligence Scale test. The moderate group were lower than control group in some test. Mean verbal IQ (VIQ), performance IQ (PIQ) and total scores in cognitive tests for severe groups were within the normal range, but lower than those of controls. (3) Melancholy, disobey, schizophreniform anxiety and offensive behavior were more common in male children with OSAHS than controls. While, offensive behavior, hyperactivity and aggressive behavior were more common in female children with OSAHS than controls. CONCLUSION: The physical growth and neuropsychological characteristic can be influenced by obstructive sleep apnea hypopnea syndrome in children, and treatment ought to be done as early in case of the severity of the disease is aggravated.

[Relationship between levels of intercellular adhesion molecule-1, interleukin-6 and airway hyperresponsiveness in patients with allergic rhinitis].

OBJECTIVE: To investigate the relation between levels of intercellular adhesion molecule-1, interleukin-6 and airway hyperresponsiveness in patients with allergic rhinitis. METHODS: Fifty-four patients with allergic rhinitis (AR) and 20 controls were included in the study. The levels of intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in nasal lavage fluid, gathered 1 hour after specific allergen nasal provocation test (SANPT), were detected by sandwich enzyme-linked immunosorbent assay (ELISA) technique. The pulmonary function (FEV1) and nonspecific bronchial provocation test were measured in 54 patients with AR, 36 patients with AR and bronchial asthma (BA) and 20 controls. At the same time, the correlation between levels of ICAM-1 and IL-6 in nasal lavage fluid and pulmonary function (FEV1) was studied. RESULTS: The levels of ICAM-1 and IL-6 in nasal lavage fluid from patients with AR were (272.75 +/- 32.25) pg/ml and (52.11 +/- 16.54) pg/ml, significantly higher than those the controls, which were (158.82 +/- 33.88) pg/ml and (25.64 +/- 10.14) pg/ml (P < 0.01). The pulmonary function (FEV1) in patients with AR and BA was (78.82 +/- 7.41)%. It was obviously lower than that in patients with AR [(83.90 +/- 4.87)%], much lower than that in normal controls [(90.25 +/- 4.69)%]. The difference among them was significant. In patients with AR, the positive percentage of bronchial provocation test was 64.81%, in patients with AR and BA, it was 83.33% in normal controls, it was 0. The differences among them had very significant meaning. The levels of ICAM-1 and IL-6 in nasal provocation fluid had closely negative correlation with pulmonary function (FEV1), r = -0.7071, -0.6248, P < 0.01. CONCLUSIONS: The close correlation was observed in upper and lower airway for allergic inflammation. The pulmonary function of patients with AR was lower, and 64. 8% of them had airway hyperresponsiveness, so that they had the potent possibility to have bronchial asthma.