Expression of AKT and p-AKT protein in lung adenocarcinoma and its correlation with PD-L1 protein and prognosis.

BACKGROUND: The PI3K/AKT/mTOR signaling pathway were significantly associated with EGFR mutation in lung adenocarcinoma (LUAD), but its correlation with PD-L1 protein and prognosis are not clear. The aim of this study was to evaluate the expression of AKT and phosphorylated AKT (p-AKT) in LUAD and its correlation with programmed death ligand-1 (PD-L1); and to analyze the factors affecting LUAD prognosis. METHODS: The expression of AKT, p-AKT, and PD-L1 was examined using immunohistochemistry in LUAD tissues from 110 patients who underwent surgical treatment. RESULTS: AKT protein expression was examined in 64.5% (71/110) of the LUAD samples, and p-AKT protein expression was examined in 44.5% (49/110) of the LUAD samples. The positive rate of PD-L1 at TC1/2/3 was 38.2% (42/110). AKT and p-AKT expression was significantly associated with epidermal growth factor receptor (EGFR) mutation (P=0.016, P=0.014 respectively). Pearson's correlation analysis indicated a negative correlation of p-AKT with PD-L1 protein (P=0.022). Out of the 62 patients with EGFR mutation, the expression of PD-L1 was negatively correlated with that of p-AKT protein (P=0.032). The expressions of AKT and p-AKT were not associated with prognosis. Multivariate analysis showed that tumor-node-metastasis (TNM) stage (P=0.013) and differentiation (P=0.046) were independent prognostic factors for overall survival. CONCLUSIONS: PI3K/AKT/mTOR in the downstream pathway of EGFR may negatively regulate the expression of PD-L1, which may partly explain why patients with EGFR mutation respond poorly to PD-1/PD-L1 inhibitors.

[Effects of sulfur plus resin-coated controlled release urea fertilizer on winter wheat dry matter accumulation and allocation and grain yield].

A field experiment was conducted to study the effects of sulfur plus resin-coated urea fertilizer on the winter wheat dry matter accumulation and allocation and grain yield. Four treatments were installed, i.e., sulfur plus resin-coated urea (SRCU), resin-coated urea (RCU), sulfur-amended conventional urea (SU), and conventional urea (U). The coated urea fertilizers were applied as basal, and the conventional urea fertilizers were 50% applied as basal and 50% applied as topdressing. There were no significant differences in the plant dry matter accumulation and grain yield between treatments RCU and U. Under the conditions the available S content in 0-20 cm soil layer was 43.2 mg x kg(-1) and the S application rate was 91.4 kg x hm(-2), treatments SRCU and SU had no significant differences in the dry matter accumulation and allocation after anthesis and the grain yield, but the amount of the assimilates after anthesis allocated in grain, the grain-filling rate at mid grain-filling stage, the 1000-grain weight, and the grain yield in the two treatments were significantly higher than those in treatment RCU. When the available S content in 0-20 cm soil layer was 105.1 mg x kg(-1) and the S application rate was 120 kg x hm(-2), the grain yield in treatment SRCU was significantly higher than that in treatment SU, but had no significant difference with that in treatments RCU and U. These results suggested that from the viewpoints of dry matter accumulation and allocation and grain yield, the nitrogen released from SRCU had the same regulation effect as the conventional urea 50% applied as basal and 50% applied as topdressing, while the regulation effect of the sulfur released from SRCU was controlled by the available S content in 0-20 cm soil layer. When the soil available S content was 43.2 mg x kg(-1), the released sulfur could promote the dry matter accumulation after anthesis and the grain-filling, and increase the grain yield significantly; when the soil available S content was 105.1 mg x kg(-1), the released sulfur from SRCU had no significant effect in increasing grain yield. Excessive S-amendment could even induce the decrease of grain yield.

Anti-neuroinflammatory and neurotrophic effects of combined therapy with annexin II and Reg-2 on injured spinal cord.

The present study was designed to investigate the neuroprotective effects of Ca(2+)-dependent phospholipid-binding protein annexin II and a secreted protein Reg-2 (regeneration gene protein 2) in spinal cord injury (SCI) model produced by contusion SCI at T(9) using the weight drop method. The agents were delivered intrathecally with Alzet miniosmotic pumps. We found that annexin II and Reg-2 remarkably reduced neuronal death, attenuated tissue damage and alleviated detrimental inflammation in vivo; meanwhile, a significant increase in white matter sparing and myelination area was observed. The propriospinal axons and long-distance supraspinal pathways were protected by the treatments as revealed by retrograde tracing. Basso Beattie Bresnahan locomotor rating scores also revealed a measurable behavioral improvement. However, no evident behavioral improvements in locomotor performance were achieved by the combined treatment with annexin II and Reg-2, compared with the separate treatment with annexin II and Reg-2.

The neuroprotective effects of Reg-2 following spinal cord transection injury.

This study was designed to elucidate the potential neuroprotective effects of Reg-2 (regeneration gene protein 2) in a rodent model of spinal cord transection injury at the ninth thoracic level. Reg-2 at 100 and 500 µg, recombinant rat ciliary neurotrophic factor, or vehicle were delivered intrathecally using Alzet miniosmotic pumps. We found that Reg-2 treatment significantly reduced neuronal death in the spinal cord. There was also an attenuation of inflammation at the injury site and an increase in white matter sparing and retained myelination. Retrograde tracing revealed that Reg-2 protected axons of long descending pathways at 6 weeks post-SCI, and the number of FluoroGold-labeled neurons in spinal and supraspinal regions was also significantly increased. Immunofluorescent staining confirmed that the spared white matter contained neurofilament-positive axons. Moreover, behavioral improvements were revealed by Basso Beattie Bresnahan locomotor rating scores and grid-walk analysis. These results suggest that Reg-2 might promote functional recovery by increasing axonal growth, inhibiting neuronal apoptosis, and attenuating spinal cord secondary injury after SCI.

Analysis of neuronal nitric oxide synthase expression and increasing astrogliosis in the brain of senescence-accelerated-prone 8 mice.

The senescence-accelerated mouse (SAM) is an autogenic senile murine model characterized by early cognitive impairment and age-related deterioration of learning and memory. The present study investigated the alternations of neuronal nitric oxide synthase (nNOS) expression in frontal cortex and hippocampus in the aging process of SAM-prone 8 (SAMP8) and SAM-resistant 1 (SAMR1) mice. The results demonstrated that the expression of nNOS was upregulated in the frontal cortex, but downregulated in the hippocampus in SAMP8. Further, age-related increases of astrogliosis were seen in the cortex and hippocampi of aged SAMP8 and SAMR1, as revealed by the expression of the astrocyte specific marker, glial fibrillary acidic protein (GFAP). Indeed, astrogliosis in aged SAMP8 was significantly greater than that of aged SAMR1. Our results suggest the possibility of a correlation between the downregulation of nitric oxide (NO) in the hippocampus and reported learning and memory deficits in SAMP8. However, the toxic effects of NO and age-related increases of astrogliosis, may have contributed to abnormal alterations in metabolism and neurochemical mechanisms in aged SAMP8.

[Alterations of glial fibrillary acidic protein expression and neural apoptosis in brain of rat offspring born by cesarean section].

OBJECTIVE: To study changes of glial fibrillary acidic protein (GFAP) expression and neural apoptosis in rat hippocampus and cortex of cesarean delivered offspring. METHODS: Thirty-eight pregnant SD rats were randomly allocated into 2 groups: 19 rats in vaginal delivery (VD) and 19 rats in cesarean section (CS). Forty-eight fetuses born by VD were kept intact, 40 fetuses were delivered by CS on day 21 of gestation. The fetal brain tissues were taken out on postnatal day 30 and 115, the expression profiles of GFAP in hippocampus and cortex were measured by immunohistochemical staining and western blot. Apoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. RESULTS: (1) The expression profiles of GFAP: on postnatal day 115, the mean number of GFAP-immunoreactive astrocytes of hippocampus 29.7 ± 10.9 in VD group was significantly lower than 36.2 ± 2.8 in CS group (P < 0.05). The average GFAP-positive cells in the cortex of frontal lobe of 23.2 ± 4.6 in VD group was significantly lower than 36.8 ± 5.9 in CS group (P < 0.01). Likewise, on postnatal day 30, the mean number of GFAP-immunoreactive astrocytes of frontal cortex of 27.8 ± 6.0 in VD group was remarkably lower than 39.4 ± 4.5 in CS group (P < 0.01). The average GFAP-positive cells in the hippocampus of 31.5 ± 3.5 in VD group were not significantly lower than 37.2 ± 7.0 in CS group (P > 0.05). The expression of GFAP was detected in hippocampus and frontal cortex by western blot, however, there was no significant different expression of GFAP between VD group and CS group. (2) Neuronal apoptosis: TUNEL staining results indicated that, on postnatal day 115, fewer apoptotic cells scattered in offspring hippocampus subregion were only shown in CS group, never in VD group. No TUNEL positive staining cells were labeled in hippocampal subregion in VD group, therefore significantly lower than that of CS group (P < 0.05). CONCLUSIONS: There were different influences of cesarean section on GFAP expression in hippocampus or cortex in different developmental stage of offspring. Cesarean section might increase GFAP expression in the hippocampus and frontal cortex, even trigger neuronal apoptosis of hippocampus region.

[Relationship between expression of vimentin, type IV collagen and fibronectin in human placenta and pregnancy induced hypertension].

OBJECTIVE: To elucidate the possible relationship between pregnancy-induced hypertension syndrome (PIH) and expression of vimentin, type IV collagen and fibronectin in human placenta. METHODS: Nineteen pregnant women (PIH group) and 15 normal pregnant women (control group) matched for age and gestation were recruited. The expression of vimentin, type IV collagen and fibronectin in the placenta of PIH patients and normal subjects was investigated using immunohistochemical perioxidase-antiperoxidase (PAP) staining technique combined with an analysis through a computer-aided microphotographic system and compared between the two groups. RESULTS: The average grey value difference (GVD) which indicated positive staining of vimentin was 30 +/- 7 in section images of the moderate and severe PIH group, significantly lower than that of normal control group, 42 +/- 6 and mild PIH group, 42 +/- 9 (P < 0.01). The average GVD of type IV collagen in moderate and severe PIH group was 70 +/- 6, significantly higher than 29 +/- 4 of control group and 30 +/- 5 of mild PIH group (P < 0.001). The average GVD of fibronectin in moderate and severe PIH group was 37 +/- 4, significantly higher than that in control group, 31 +/- 4 and mild PIH group, 32 +/- 6 (P < 0. 05). CONCLUSIONS: There is tight relationship between abnormal expression of placental vimentin, type IV collagen, fibronectin and pathogenesis of PIH. Furthermore, the severity of PIH is positively correlated with the abnormal expression levels of those proteins.