Comprehensive bioinformatic analysis of mind bomb 1 gene in stomach adenocarcinoma.

BACKGROUND: The carcinogenesis of stomach adenocarcinoma (STAD) involves many different molecules and multiple pathways, including the NOTCH signaling pathway. As a key factor that functions as a critical link in the NOTCH pathway, mind bomb 1 (MIB1) is upregulated in various tumors and has been reported to promote cell metastasis and invasion. However, studies on the role of MIB1 in STAD are limited. Here, we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number variation. AIM: To elucidate the relationship between MIB1 gene and gastric cancer (GC) and provide a new idea for the treatment of GC. METHODS: We identified mutations in the MIB1 gene by searching the cBioPortal database and then analyzed their relationship with the overall survival rate and disease-free survival rate using the Kaplan-Meier method. The Cancer Genome Atlas (TCGA) database provided transcript levels for MIB1 in STADs and normal tissues. As a method of distinguishing the STAD tissues from adjacent normal tissues, a receiver operating characteristic (ROC) curve was generated. Kaplan-Meier plotter was used to determine the effect of MIB1 expression on survival. Based on the LinkedOmics database, we were able to identify the coexpressed genes of the MIB1 gene, the top 50 positively correlated genes, and the top 50 negatively correlated genes. STRING was used to construct protein-protein interaction networks related to the MIB1 gene. An analysis of functional enrichment was carried out using the R package "Cluster Profiler". The relationships between mRNA expression of MIB1 and immune infiltrates were assessed by Tumor IMmune Estimation Resource (TIMER) and the "GSVA package" in R. RESULTS: According to the cBioPortal database, the MIB1 mutation rate in 287 patients in the TCGA dataset was approximately 6%. Kaplan-Meier survival analysis showed that patients with STAD in the mutated group had a worse prognosis than those in the unmutated group (P = 0.0156). There was a significant upregulation of MIB1 expression in STAD tissues compared to adjacent normal tissues. A high T stage was associated with increased MIB1 mRNA expression. The ROC curve analysis revealed 59.4% sensitivity and 85.6% specificity of MIB1 for differentiating STAD tissues from adjacent normal tissues at a truncation level of 2.248. Kaplan-Meier plotter indicated that patients with higher MIB1 levels had a worse prognosis than those with lower levels (26.4 mo vs 56.2 mo, P = 0.0330). A correlation analysis demonstrated an association between immune infiltrates and MIB1 mRNA expression. CONCLUSION: Upregulation of MIB1 expression is significantly associated with poor survival rate and immune infiltration in gastric adenocarcinoma. MIB1 may be a biomarker for the poor prognosis of STAD patients and a potential immunotherapeutic target.

Incidental finding of metastatic prostatic adenocarcinoma of cerebellopontine angle presenting as acoustic neuroma: A case report and review of literature.

INTRODUCTION: Brain metastases from carcinoma of prostate are rare and only few cases with brain metastases preceding the diagnosis of carcinoma of prostate have been reported in the literature. Lesions of brain metastasis from prostate cancer had a large variety of imaging presentations and it is very difficult to distinguish them from the other types of brain occupying lesions. We report one case of metastatic prostatic adenocarcinoma of cerebellopontine angle presenting as acoustic neuroma, as the first clinical evidence of metastatic carcinoma of the prostate. PRESENTATION OF CASE: The 57-year-old male presented to the neurology clinic complaining of dizziness accompanied by right tinnitus, he was proposed to be diagnosed with acoustic neuroma, and the tumor resection was performed later in our neurosurgery department. The postoperative histopathological and immunohistochemical (IHC) examinations revealed a cerebellar pontine angle metastatic adenocarcinoma, which was then confirmed as prostate cancer metastasis. The patient refused surgical castration and only agreed to conservative treatment. The patient's condition continued to deteriorate, and he died 12 months after the initial presentation. DISCUSSION: Brain metastasis is rare in prostate cancer, which accounts for only 0.2 % to 2 % of all brain metastases. Intracranial metastasis as the first clinical symptom of prostate cancer is extremely rare. In our article, we report the VIIIth and VIIth cranial nerves palsy for the first time, caused by brain metastases from prostate cancer, with symptoms similar to an acoustic neuroma. Prostate cancer most commonly spreads to the bones, including the skull, Cranial nerve palsy is caused by extensive invasion of the skull base. The serum PSA level is considered the most valuable tool to monitor the disease progression of patients with prostate cancer metastasis. A high PSA level significantly increases the tendency of prostate cancer to metastasize to the brain. A high Gleason score is believed to help determine the risk and likelihood of brain metastases in patients with prostatic carcinoma. CONCLUSION: In our case, we initially report the VIIIth and VIIth cranial nerve palsy, mimicking an acoustic neuroma, caused by metastatic prostate carcinoma. For early diagnosis, the prostate should not be neglected as a possible source of the metastases in male patients presenting with brain metastases. High prostate specific antigen (PSA) level and high Gleason score can be useful parameters for the prediction of brain metastasis from prostate cancer. The PSA should play a vital role in distinguishing metastatic prostate carcinoma in male patients.

Degranulation of mast cells induced by gastric cancer-derived adrenomedullin prompts gastric cancer progression.

Mast cells are prominent components of solid tumors and exhibit distinct phenotypes in different tumor microenvironments. However, their precise mechanism of communication in gastric cancer remains largely unclear. Here, we found that patients with GC showed a significantly higher mast cell infiltration in tumors. Mast cell levels increased with tumor progression and independently predicted reduced overall survival. Tumor-derived adrenomedullin (ADM) induced mast cell degranulation via PI3K-AKT signaling pathway, which effectively promoted the proliferation and inhibited the apoptosis of GC cells in vitro and contributed to the growth and progression of GC tumors in vivo, and the effect could be reversed by blocking interleukin (IL)-17A production from these mast cells. Our results illuminate a novel protumorigenic role and associated mechanism of mast cells in GC, and also provide functional evidence for these mast cells to prevent, and to treat this immunopathogenesis feature of GC.

The Synergistic Roles of the Chronic Prenatal and Offspring Stress Exposures in Impairing Offspring Learning and Memory.

In Alzheimer's disease (AD), extensive experimental studies have demonstrated a negative impact of chronic stress during various stages of life (including prenatal phase) on some aspects of AD pathology. Nevertheless, presently, few studies have been involved in the learning and memory impairments, as well as neuropathology elicited by the chronic prenatal stress (CPS) and the chronic offspring stress (COS) exposures simultaneously, particularly for the adult male APPswe/PS1dE9 murine offspring. Therefore, the aim of the present study was to investigate the influence of CPS on learning and memory impairments induced by COS in 6-month-old male APPswe/PS1dE9 offspring mice and the related mechanism. Our study firstly demonstrates that 14-day exposure to CPS could exacerbate the learning and memory impairments, as well as neuropathological damages in the CA3 regions of the hippocampus and cortex neurons, which is induced by the 28-day exposure to COS in 6-month-old male APPswe/PS1dE9 offspring mice. In addition, CPS could potentiate the production of AßPP, Aß42, and corticosterone in 6-month-old male APPswe/PS1dE9 offspring that also suffer COS. In conclusion, our novel findings strongly implicate the synergistic roles of the CPS and COS exposures in impairing offspring learning and memory. Moreover, CPS potentiating the production of Aß42 might be mediated by glucocorticoids through increasing the expression of APP and BACE1 gene.

Gradual and controlled decompression for brain swelling due to severe head injury.

Patients suffering from uncontrollable intracranial hypertension due to posttraumatic brain swelling (BS) generally either die or survive in an extremely disabled state. Decompressive craniectomy (DC) with dural augmentation may be the best method to assist these patients. However, the efficacy of DC on functional outcomes remains controversial. One of the factors contributing to poor outcomes could be intraoperative brain extrusion, which is an acute potential complication of DC. The authors have adopted a new surgical technique for traumatic BS that can prevent and control massive intraoperative BS (IOS). In the past 3 years, the authors have used a unique technique, called "gradual and controlled decompression", in the treatment of posttraumatic BS. This procedure consists of creating numerous small dural openings and removing clots; enlarging fenestration in the frontal and temporal basal regions to detect and treat brain contusion; making U-shaped, discontinuous, small dural incisions around the circumference of the craniotomy; and performing an augmentation duraplasty through the discontinuous small opening with dural prosthetic substances. This technique has been employed in 23 patients suffering from posttraumatic BS. In all cases, IOS was prevented and controlled through gradual stepwise decompression, and expanded duraplasty was performed successfully. This new surgical approach for posttraumatic BS can prevent severe extrusion of the brain through the craniotomy defect and allows the gradual and gentle release of the subdural space. Further clinical studies should be conducted to estimate the impact of this new technique on morbidity and mortality rates.

Characterization of a vacuolar zinc transporter OZT1 in rice (Oryza sativa L.).

The CDF family is a ubiquitous family that has been identified in prokaryotes, eukaryotes, and archaea. Members of this family are important heavy metal transporters that transport metal ions out of the cytoplasm. In this research, a full length cDNA named Oryza sativa Zn Transporter 1 (OZT1) that closely related to rat ZnT-2 (Zn Transporter 2) gene was isolated from rice. The OZT1 encoding a CDF family protein shares 28.2 % ~ 84.3 % of identities and 49.3 % ~ 90.9 % of similarities with other zinc transporters such as RnZnT-2, HsZnT-8, RnZnT-8 and AtMTP1. OZT1 was constitutively expressed in various rice tissues. The OZT1 expression was significantly induced both in the seedlings of japonica rice Nipponbare and indica rice IR26 in response to Zn(2+) and Cd(2+) treatments. Besides, OZT1 expression was also increased when exposed to other excess metals, such as Cu(2+), Fe(2+) and Mg(2+). Subcellular localization analysis indicated that OZT1 localized to vacuole. Heterologous expression of OZT1 in yeast increased tolerance to Zn(2+) and Cd(2+) stress but not the Mg(2+) stress. Together, OZT1 is a CDF family vacuolar zinc transporter conferring tolerance to Zn(2+) and Cd(2+) stress, which is important to transporting and homeostasis of Zn, Cd or other heavy metals in plants.

[Suppression effect of different stage antigens of Schistosoma japonicum on airway inflammation in a murine model of asthma].

OBJECTIVE: To investigate the effect of antigens of different stage Schistosoma japonicum on airway inflammation in a murine model of asthma. METHODS: 48 female BALB/c mice were randomly divided into eight groups. Mice in group A were given normal saline of equal volume as control. Group B was asthma model which was established by intraperitoneal and intranasal challenge with OVA. Mice in groups C, D and E were immunized with soluble egg antigen (SEA), soluble male worm antigen (SWA), and schistosomulum antigen (SSA) respectively 4 times in a week interval, followed by OVA sensitization as in group B 1 week after the final immunization. Mice in groups F, G, and H were immunized with SEA, SWA, and SSA respectively but sensitized and challenged with saline instead of OVA. 48 hours after asthma was induced, the mice were sacrificed. Leukocytes and eosinophils were counted in bronchoalveolar lavage fluid (BALF). The level of IL-5, IL-10 and IFN-gamma in BALF was detected. Pathologic changes in lung tissues were observed. RESULTS: Inflammation cells, especially eosinophils, appeared in airways of mice in groups B, C, D and E, but with much less number in groups C, D and E. No inflammation cells were seen in airways of group A mice. The number of leukocytes, eosinophils and level of IL-5 in BALF of group B [(98.4 +/- 16.1) x 10(4)/ml, (17.6 +/- 4.3) x 10(4)/ml, (197.9 +/- 36.5) pg/ml respectively] were significantly higher than those of group A [(8.2 +/- 1.1) x 10(4)/ml, (0.02 +/- 0.01) x 10(4)/ ml, (12.3 +/- 7.4) pg/ml], however the levels of IL-10 and IFN-gamma were significantly lower than that of group A (P < 0.05). The number of leukocytes, especially eosinophils, in BALF of groups C, D and E was significantly lower than that of group B. The level of IL-5 in BALF of groups C, D and E was significantly reduced, while that of IL-10 and IFN-gamma in BALF of the 3 groups was significantly higher than group B (P < 0.05). CONCLUSIONS: The immunization with S. japonicum antigens can effectively modulate the level of cytokines and inhibit the eosinophil infiltration and airway inflammation in asthmatic mice.

[Up-expression of PD-1-PD-L induced by immunization with SEA and SMWA of Schistosoma japonicum in mice].

OBJECTIVE: To explore the expression of PD-1-PD-L pathway of mice immunized with soluble egg antigen (SEA) or soluble male worm antigen (SMWA) of Schistosoma japonicum. METHODS: Eighteen BALB/c mice were randomly divided into three groups named as control group (A), SEA immunized group (B) and SMWA immunized group (C). Mice in groups B and C were subcutaneously immunized weekly with SEA (50 microg) and SMWA (50 microg) of S. japonicum respectively. After 4 times immunization, the expression of programmed death-1 (PD-1), programmed death-ligand1 (PD-L1) and PD-L2 in splenic cells was measured with flow cytometer. The expression of IL-4 and IFN-gamma in cultural suspension of splenic cells was detected by sandwich-ELISA after stimulation with ConA. RESULTS: The expression ratio of PD-1, PD-L1 and PD-L2 was extremely low in the control group, but increased after the immunization with SEA and SMWA. The expression ratio of PD-1 was (8.24 +/- 1.31)% in SEA immunized mice, higher than the mice immunized by SMWA [(6.08 +/- 1.28)%]. PD-L2 was much more elevated in SEA immunized mice [(5.26 +/- 1.73)%] while PD-L1 more significantly increased with SMWA immunization [(10.82 +/- 2.33)%]. In addition, the up-expression of PD-L1 was associated with the level of IFN-gamma and the expression of PD-L2 was associated with IL-4 secretion. CONCLUSION: The expression of PD-1-PDL was up-regulated in BALB/c mice immunized by SEA or SMWA of S. japonicum.

[Clinical experience of 70 cases of cerebral arteriovenous malformations embolization with Onyx, a novel liquid embolic agent].

OBJECTIVE: To report our clinical experience of using Onyx, a new liquid embolic agent, to treat cerebral arteriovenous malformations (AVMs) as well as its efficacy. METHODS: Seventy cases were placed with 6F sheath in the femoral artery after Seldinger puncture and 6F guiding catheter was introduced into the internal carotid artery or vertebral artery, then a microcatheter was navigated into the nidus of AVMs. Slow injection of Onyx under fluoroscopic control was performed to embolize cerebral AVMs using the "plug and push" technique. RESULTS: Thirteen AVM cases (18.6%) were totally occluded by Onyx and 5 cases of which didn't recurrence at 6-month after operation. Thirty-eight cases (54.3%) were subtotally occluded, while another 19 cases (27.1%) were partially embolized. Severe cerebral hemorrhage occurred in 4 cases, 2 of which had mild to severe hemiplegia after operation, and one died. Mild hemiplegia was also found in 1 case due to functional area embolization, and visual field deficit in 2 cases. CONCLUSIONS: Onyx has unique and distinctive superiority in treating cerebral AVMs. Nonetheless, the correct embolization technique should be learned to achieve good clinical results and avoid complications.

[Formation and hemodynamics of pseudoaneurysm after rupture and bleeding of aneurysm: an experiment with dogs].

OBJECTIVE: To study the process and mechanism of the formation of pseudoaneurysm after the rupture of aneurysm. METHODS: A model of aneurysm (AN) of the left common carotid artery (CCA) was made in 20 dogs. One to 2 weeks after the formation of AN, a localized hematoma connected with the AN was formed as a model of pseudoaneurysm after the rupture of true aneurysm (false aneurysm caused by the ruptured true aneurysm, T + F) was established. The models were examined by using color Doppler, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and digital subtraction angiographies (DSA) 1, 2, 3, 4, and 8 weeks after the operation in all the animals. By the end of experiment the models of AN were taken out to undergo pathological examination by light and electron microscopy. The blood flow velocity, pressure on the walls and shear stress in the true and false aneurysm were analyzed by simulation of computational fluid dynamics (CFD) on these animal models. RESULTS: Experimental models of T + F were successfully created in the 11 dogs. CCA was successfully occluded in 3 dogs, true aneurysm was occluded in 2, and true aneurysms without pseudoaneurysm were produced in 4. The blood flow in the pseudoaneurysm was very slow. The pressure and shear stress were very high in the ends distal to the aneurysms and not high around the boundary between the true and false aneurysms. CONCLUSION: The formation and growth of pseudoaneurysm are probably correlated with the pressure within the vessels. T + F should be positively and definitely treated by surgery to prevent them from rupture and bleeding.

Identification of a rice zinc finger protein whose expression is transiently induced by drought, cold but not by salinity and abscisic acid.

A C2H2-type zinc finger protein gene ZFP245 was cloned by RT-PCR approach from cold treated rice seedlings. ZFP245 is 712 bp in length and encodes a 24.5 KDa protein, which has 35% identity in amino acid with SCOF-1, a cold-inducible zinc finger protein from soybean. By database search, ZFP245 was mapped on chromosome 7 and clustered together with another C2H2 zinc finger gene. Tissue expression analysis showed that ZFP245 was constitutively expressed in various rice tissues including roots, stems, leaves and spikes. The semi-quantitative-RT-PCR assay revealed ZFP245 was strongly induced after 6 h exposure to cold and drought stresses, and then reduced to the baseline. However, ZFP245 was not regulated by high salt or abscisic acid treatment. The promoter sequence of 1017 nucleotides, upstream of ZFP245, was cloned directly by PCR approach. Sequence analysis revealed a CRT/DRE element was found within the ZFP245 promoter region. Taken together, ZFP245, as the first identified C2H2-type zinc finger protein involved in stress response in monocots probably plays a role as a transcription regulator in plant cold and drought responses through an ABA-independent pathway.