Down-regulation of Leucine-rich Repeats and Immunoglobulin-like Domain Proteins (LRIG1-3) in HP75 Pituitary Adenoma Cell Line

Three human leucine-rich repeats and immunoglobulin-like domains （LRIG） genes and proteins, named LRIG1-3, has been previously characterized and it was proposed that they may act as suppressors of tumor growth. The LRIG1 protein can inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor. Real-time reverse transcription-polymerase chain reaction （RT-PCR） is a recently developed technique for quantitative assessment of specific RNA levels. In the current study, it was demonstrated that LRIG1-3 and EGFR mRNA was detected in human pituitary adenoma cell lines and a normal pituitary sample, with differences in the expression levels. Compared to the normal pituitary samples, the expression of LRIG1-3 in HP75 cell line was lower, but the expression of EGFR in HP75 cell line was higher. The results are consistent with LRIG1-3 being tumour suppressor genes, and LRIG genes decreasing the expression of EGFR. The ratio of EGFR/LRIGl was increased at least 13-fold in HP75 cells compared with the normal pituitary cells, which was also the case for the ratio of EGFR/LRIG2 （14-fold increase in HP75） and EGFR/LRIG3 （11-fold increase in HP75）. Further studies were needed to elucidate the explicit role of LRIG genes as negative regulators of oncogenesis in human pituitary adenoma.

Does Lower Dose of Long-acting Triptorelin Maintain Pituitary Suppression and Produce Good Live Birth Rate in Long Down-regulation Protocol for In-vitro Fertilization?

The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone（Gn RH） agonist in Gn RH agonist long protocol for in vitro fertilization（IVF）/intracytoplasmic sperm injection（ICSI） were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with Gn RH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group（41.2% vs. 43.7%）. The mean luteinizing hormone（LH） level on follicle-stimulating hormone（FSH） starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin（h CG） administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group（12.90±5.82 vs. 13.52±6.97）. There was no significant difference in clinical pregnancy rate between the two groups（50.5% vs. 54.5%）. It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

Bisoprolol reverses down-regulation of potassium channel proteins in ventricular tissues of rabbits with heart failure

Remodeling of ion channels is an important mechanism of arrhythmia induced by heart failure （HF）. We investigated the expression of potassium channel encoding genes in the ventricles of rabbit established by volumeoverload operation followed with pressure-overload. The reversible effect of these changes with bisoprolol was also evaluated. The HF group exhibited left ventricular enlargement, systolic dysfunction, prolongation of corrected QT interval （QTc）, and increased plasma brain natriuretic peptide levels in the HF rabbits. Several potassium channel subunit encoding genes were consistently down-regulated in the HF rabbits. After bisoprolol treatment, heart function was improved significantly and QTc was shortened. Additionally, the mRNA expression of potassium channel subunit genes could be partially reversed. The down-regulated expression of potassium channel subunits Kv4.3, Kv1.4, KvLQT1, minK and Kir 2.1 may contribute to the prolongation of action potential duration in the heart of rabbits induced by volume combined with pressure overload HF. Bisoprolol could partially reverse these down-regulations and improve heart function.

Down-regulation of Hsp90 could change cell cycle distribution and increase drug sensitivity of tumor cells

AIM:To construct Hsp90 antisense RNA eukaryotic expression vector, transfect it into SGC7901 and SGC7901/VCR of MDR-type human gastric cancer cell lines, HCC7402 of human hepatic cancer and Ec109 of human esophageal cancer cell lines, and to study the cell cycle distribution of the gene transected cells and their response to chemotherapeutic drugs.METHODS:A 1.03kb cDNA sequence of Hsp90beta was obtained from the primary plasmid phHSP90 by EcoR I and BamH I nuclease digestion and was cloned to the EcoR I and BamH I site of the pcDNA by T4DNA ligase and an antisense orientation of Hsp90beta expression vector was constructed. The constructs were transfected with lipofectamine and positive clones were selected with G418. The expression of RNA was determined with dot blotting and RNase protection assay, and the expression of Hsp90 protein determined with western blot. Cell cycle distribution of the transfectants was analyzed with flow cytometry, and the drug sensitivity of the transfectants to Adriamycin (ADR), vincrinstine (VCR), mitomycin (MMC) and cyclophosphamide (CTX) with MTT and intracellular drug concentration of the transfectants was determined with flow cytometry.RESULTS:In EcoR I and BamH I restriction analysis, the size and the direction of the cloned sequence of Hsp90beta remained what had been designed and the gene constructs were named pcDNA-Hsp90.AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 cell clones all expressed Hsp90 anti-sense RNA. The expression of Hsp90 was down-regulated in AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 cell clones. Cell cycle distribution was changed differently. In AH-SGC7901/VCR and AH-Ec109 cells, G(1) phase cells were increased; S phase and G(2) phase cells were decreased as compared with their parental cell lines. In AH-SGC7901 cell, G(1)phase cells were decreased, G(2) phase cells increased and S phase cells were not changed, and in AH-HCC7402 cells G(1), S and G(2) phase cells remained unchanged as compared with their parental cell lines. The sensitivity of AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 to chemotherapeutic drugs, the sensitivity of AH-SGC7901/VCR to ADR, VCR, MMC and CTX the sensitivity of AH-HCC7402 to ADR and VCR, and the sensitivity of Ec109 to ADR, VCR and CTX all increased as compared with their parental cell lines. The mean fluorescence intensity of ADR in AH-SGC7901, AH-SGC7901/VCR, AH-HCC7402 and AH-Ec109 was also significantly elevated (P 【 0.05).CONCLUSION: Down-regulation of Hsp90 could change cell cycle distribution and increase the drug sensitivity of tumor cells.

Inactivated Sendai Virus Induces Apoptosis in Murine Melanoma Cells by IGF-1R Down-regulation

The mortality of cancer patients has considerably improved due to progress in surgery, chemotherapy and radiotherapy. However, some types of cancers, such as melanoma, remain refractory to conventional strategies. Although melanoma accounts for only 4% of all dermatological malignancies, it is responsible for 80% of mortalities from skin tumors[11. The reported survival rate of melanoma over 5 years is not yet encouraging due to its chemo-resistance and rapid metastasis. Therefore, it is necessary to develop new drugs with potent activity and weak side-effect against melanoma.

LncRNA LUCAT1 Activation Mediated by theDown-regulation of DNMT1 Is Involved inCell Apoptosis Induced by PM2.5

Particulate matter （PM）, which is a great environmental concern, has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer （IARC）;.Epidemiological and experimental studies have indicated that chronic exposure to PM, especially PM;(particles with an aerodynamic diameter less than

Down-regulation of glucocorticoid receptor mRNA by glucocorticoids in rats

The effect of glucocorticoids on the down-regulation of glucocorticoidreceptor (GR) mRNA was studied in intact rats.GR mRNA was characterized byNorthern blot hybridization and quantitated by dot blot hybridization using a hu-man GR cDNA fragment as a probe.Administration of hydrocortisone (F) inpolyvinyl alcohol (PVA) resulted in a rapid increase in plasma glucocorticoidswhich maintained at stress levels (20 to 40μg/dl) for about 3 d.HepaticGR mRNA decreased significantly to 73.5±6.3% of control values 6h followingF treatment,after which the decline of GR mRNA was gradual,reaching a mini-mum of 44.0±5.0% of control levels 3d after the treatment.The effect of F onthe down-regulation of hepatic GR mRNA lasted up to 11 d.In contrast,F treat-ment had no effect on GR mRNA in rat brain.These results are consistent withthe changes in GR in rats as reported previously,except that even though thehepatic cytosol GR decreased markedly,no significant changes in hepatic GRmRNA were found 1h after F treatment,strongly suggesting that thedown-regulation of GR by its ligands in vivo occurs at both transcriptional andposttranscriptional levels and is of tissue-specific fashion.

Maternal Lead Exposure Induces Down-regulation of Hippocampal Insulin-degrading Enzyme and Nerve Growth Factor Expression in Mouse Pups

Lead exposure is a known potential risk factor for neurodegenerative diseases such as Alzheimer’s disease （AD）. Exposure to lead during the critical phase of brain development has been linked with mental retardation and hypophrenia in later life.

Glypican 4 down-regulation in pluripotent stem cells as a potential strategy to improve differentiation and to impair tumorigenicity of cell transplants

Recent advances in stem cell technologies have opened new avenues for the treatment of a number of diseases still lacking effective therapeutic options.Cell transplantation has emerged as among the most promising clinical intervention for disorders such as injuries,diabetes,liver diseases, neurodegeneration and heart failure （Lee et al., 2013; Forbes and Rosenthal, 2014; Tabar and Studer, 2014）.

Clinical case discussions-Hypopituitarism and pituitary apoplexy caused by pituitary Adenomas

A case of“Hypopituitarism and pituitary apoplex induced by pituitary Adenomas”was collected in the Third Affiliated Hospital of Inner Mongolia medical University Geriatric Department.A rare and atypical disease as it is,delayed diagnosis and treatment is easily seen among those cases.Therefore,the paper aims to investigate the difference of clinical characteristics and treatment outcome of pituitary adenomas in elder patient through the case analysis.Clinically,patients with pituitary dysfunction may have life-threatening crisis so that timely diagnosis and aggressive treatment can be effective in reducing the pituitary crisis and reducing the misdiagnosis rate.

Bisecreting Pituitary Neuroendocrine Tumors: About 9 Cases at the Abass Ndao Hospital Center in Dakar

Introduction: Pituitary neuroendocrine tumor (PitNET) may present multisecreting forms. Identifying its forms helps to guide management. This management is a real challenge, given the limited resources in our regions. In view of advances in the management of these multisecreting pituitary neuroendocrine tumors and the lack of published data in Africa, and in Senegal particularly, this survey was carried out with the aim of describing the epidemiological, clinical and therapeutic aspects of multisecreting PitNETs. Patients and Method: It was a multicenter, retrospective, descriptive and analytical study carried out on files collected from 1st January 2008 to 31 December 2022 in the neurosurgery departments of the Fann and Principal hospitals in Dakar and the endocrinology department of the Abass Ndao hospital in Dakar. Results: Of the 242 patients treated for PitNET, 09 presented (the mean age of our patients was 41.7 ± 11 years) with bihormonal PitNET, i.e. a proportion of 3.71%. Two types of association were found: 08 tumors with GH (Growth Hormon) + PRL (prolactin) secretion and 01 PitNET with ACTH (Adreno Corticotropic Homon) + prolactin secretion. Clinically, gonadotropic insufficiency was found in all patients (100%). Dysmorphic syndrome was found in 6 patients (66.7%) and tumor syndrome in 7 patients (77.8%). Ophthalmological evaluation revealed a decrease in visual acuity in 66.6% of patients. All had macroadenomas, with extension noted in 02 patients. All patients underwent transsphenoidal surgery with complications such as transient diabetes insipidus (3 patients, 33.3%), followed by cerebrospinal fluid leaks (1 patient, 11.1%). Remission was noted in all 5 patients tested. A comparison between the different secretory forms did not reveal any significant difference in the frequency of postoperative complications. Conclusion: Despite the lack of immunohistochemistry, two types of association were found: ACTH-PRL and GH-PRL. All were macroadenomas, the majority with an associated tumor syndrome. The latter was significantly less frequent in bisecreting PitNETs compared with monosecreting and non-functional forms. However, there was no significant difference in the occurrence of post-operative complications between the three secretory forms of PitNETs.

Pituitary metastasis from lung adenocarcinoma

Pituitary tumor is a common neuroendocrine tumor,but there are also rare clinical metastases at this site,which are generally transferred from extrabellar tumors.Although the clinical incidence is low,the prognosis is poor.The purpose of this editorial is to discuss further the relevant knowledge of pituitary metas-tases and remind clinicians to prevent missed diagnosis and improve the prog-nosis of these patients.

miR-200b-3p accelerates progression of pituitary adenomas by negatively regulating expression of RECK

MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.

Pituitary metastasis from lung adenocarcinoma:A case report

BACKGROUND Pituitary gland metastasis is an unusual event,and pituitary metastasis from lung adenocarcinoma is extremely rare and associated with poor prognosis.To date,approximately 15 cases have been reported.CASE SUMMARY Here,we present the case of a 64-year-old woman with pituitary metastasis derived from lung adenocarcinoma,which was difficult to distinguish from other sellar tumors.The patient presented to the neurosurgery clinic with blurred vision and intermittent headache.During hospitalization,brain computed tomography(CT)and magnetic resonance imaging revealed a pituitary macroadenoma.Chest CT revealed irregular nodules in the basal segment of the lower lobe of the left lung,which were likely lung cancer.Positron emission tomography-CT revealed a carbohydrate metabolism tumor in the lungs and sellar region,which was considered malignant.Postoperative pathological examination of the sellar tumor revealed lung adenocarcinoma.CONCLUSION Excision of pituitary metastases combined with radiotherapy and chemotherapy should be a priority treatment for patients with pituitary metastasis.

Down-regulation of Notch-1 gene expression inhibits growth of TJ-905 glioblastoma

Objective To study the inhibitory effect of siRNA on glioblastoma (GBM) Notch-1 gene expression in addition to the growth of TJ-905 glioblastoma. Methods Three small interference RNAs (siRNAs) targeting Notch1 gene,named siRNA1,siRNA2,siRNA3,synthesized chemically in vitro with gene bank BLAST. TJ-905 cells were transfected twice with the siRNA by using Oligofectamine

Pituitary stalk interruption syndrome complicated with liver cirrhosis:A case report

BACKGROUND Pituitary stalk interruption syndrome(PSIS)is a rare disorder,often characterized by delayed growth and development,short stature,and hypogonadism as the main clinical manifestations.It is not clear whether PSIS can lead to liver cirrhosis.CASE SUMMARY This paper reported a case of liver cirrhosis of unknown origin.The patient was admitted to Beijing Ditan Hospital Affiliated to Capital Medical University in November 2023.The diagnosis of PSIS complicated with liver cirrhosis was established after a series of blood tests and pituitary magnetic resonance imaging examination.CONCLUSION We also reviewed the literature from both domestic and international sources to deepen the clinical understanding of PSIS in conjunction with liver cirrhosis among medical practitioners.

Pulsatile gonadotropin-releasing hormone therapy induces spermatogenesis in pituitary stalk interruption syndrome:A case report and review of the literature

BACKGROUND Pituitary stalk interruption syndrome(PSIS)is a rare anatomical defect of the pituitary gland falling under the spectrum of holoprosencephaly phenotypes.It is characterized by a deficiency in anterior pituitary hormones,such as growth hormone,gonadotropins,and thyroid hormones.Due to the syndrome's rarity and nonspecific manifestations,there is a lack of standardized treatment strategies.Consequently,early diagnosis through imaging and on-time intervention are crucial for improving patients’outcomes.CASE SUMMARY A 30-year-old man presented with absent secondary sexual characteristics and azoospermia.Laboratory evaluation revealed a deficiency in gonadotropins,while thyroid function was mostly within normal ranges.Magnetic resonance imaging of the pituitary gland showed pituitary stalk agenesis,hypoplasia of the anterior pituitary,and ectopic posterior pituitary,leading to the diagnosis of PSIS.Initially,the patient underwent 6 mo of gonadotropin therapy without significant changes in hormone levels and secondary sexual characteristics.Pulsatile gonadotropin-releasing hormone therapy was then administered,resulting in the detection of sperm in the semen analysis within 3 mo.After 6 mo,routine semen tests showed normal semen quality.The couple faced challenges in conceiving due to abstinence and underwent three cycles of artificial insemination,which was unsuccessful.They also attempted in vitro fertilization,but unfortunately,the woman experienced a miscarriage 10 wk after the embryo transfer.CONCLUSION Early detection,accurate diagnosis,and timely treatment are crucial in improving the quality of life and fertility of PSIS patients.

Clinical application of reserved gastric tube in neuroendoscopic endonasal surgery for pituitary tumor

BACKGROUND The neuroendoscopic approach has the advantages of a clear operative field,convenient tumor removal,and less damage,and is the development direction of modern neurosurgery.At present,transnasal surgery for sphenoidal pituitary tumor is widely used.But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts.AIM To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors.METHODS A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups,with 30 in each group.Experimental group:After anesthesia,a gastric tube was placed through the mouth under direct vision using a visual laryngoscope,and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection,during the operation,and when the patient recovered from anesthesia.Control group:Given the routine intraoperative care,no gastric tube was left.The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups;the scores of pharyngalgia after waking up,6 h post-operation,and 24 h postoperation.The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared.The hospitalization days of the two groups were statistically compared.RESULTS The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group,and the difference in the incidence of nausea was statistically significant(P<0.05).After the patient woke up,the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group,and the difference was statistically significant(P<0.05).The number of cases of postoperative cerebrospinal fluid leakage and intracranial infection was higher than that of the control group,but there was no statistically significant difference from the control group(P>0.05).The hospitalization days of the experimental group was lower than that of the control group,and the difference was statistically significant(P<0.05).CONCLUSION Reserving a gastric tube in the endoscopic endonasal resection of pituitary tumors,combined with intraoperative and postoperative gastrointestinal decompression,can effectively reduce the incidence of nausea,reduce the number of vomiting and aspiration in patients,and reduce the complications of sore throat The incidence rate shortened the hospitalization days of the patients.

无功能垂体大腺瘤神经内镜下经蝶窦切除术后垂体前叶功能减退发生风险预测模型构建与验证

目的构建预测无功能垂体大腺瘤(NFPMA)神经内镜下经蝶窦切除术后垂体前叶功能减退(HAP)发生风险的列线图模型,并验证该模型的效能。方法选择接受神经内镜下经蝶窦切除术的NFPMA患者103例,术后1年复查垂体前叶功能,HAP 38例(HAP组)、垂体前叶功能正常65例(NHAP组)。收集所有研究对象术前一般资料、实验室检查资料、临床症状、影像学资料、手术并发症以及术后病理资料,采用单因素和多因素Logistic回归模型分析NFPMA神经内镜下经蝶窦切除术后发生HAP的独立危险因素。根据其独立危险因素构建预测NFPMA神经内镜下经蝶窦切除术后HAP发生风险的列线图模型,并通过受试者工作特征(ROC)曲线验证该列线图模型的预测效能。结果基于单因素和多因素Logistic回归模型筛选出4个NFPMA神经内镜下经蝶窦切除术后发生HAP的独立危险因素:糖化血红蛋白(HbA1c)、垂体最大径、侵袭性评分、中枢性尿崩症,构建NFPMA神经内镜下经蝶窦切除术后HAP发生风险的Logictic回归方程:logit(P)=-6.309+0.333×HbA1c+0.817×垂体最大径+0.532×侵袭性评分+3.402×中枢性尿崩症(有=1,无=0),并通过R4.2.0软件构建其列线图模型;ROC曲线分析发现,该列线图模型预测NFPMA神经内镜下经蝶窦切除术后发生HAP的曲线下面积为0.842(95%CI:0.763~0.920),其预测敏感度为81.6%、特异度为76.9%。结论HbA1c、垂体最大径、侵袭性评分、中枢性尿崩症是NFPMA神经内镜下经蝶窦切除术后HAP发生的独立危险因素,基于上述独立危险因素构建的列线图模型可以较好地预测NFPMA神经内镜下经蝶窦切除术后HAP的发生风险。

Relationship Between Histopathology and Clinical Prognosis of Invasive Pituitary Adenoma

Objective: To study the relationship between histopathology and clinical prognosis of invasive pituitary adenoma subjected to transsphenoidal surgery. Methods: The enrolled were 82 patients with invasive pituitary adenomas undergoing transsphenoidal surgery during Jan. 2000 - May 2003 in our department with full MR imaging findings, pathology data and follow-up information. The follow-up duration was 5-30 months. Results: MR imaging findings of invasive pituitary adenoma included: depression of the sellar floor, involvement of sphenoid sinus and cavernous sinus, breakthrough of diaphragma sellae, encasement of internal carotid artery, etc. Pathological examination revealed that the invasion rate of dura in sella turcica was the highest among the structures around tumor. Pituitary adenoma apoplexy was found in 20 cases (24.4%). The total removal rate for PRL-secreting adenomas was significantly lower than that for non-secreting adenomas (P<0.01), but non-, GH-, ACTH-secreting adenomas had no significant differences. The recurrence rate of PRL-secreting adenomas was higher than that of non- and GH-secreting adenomas (P<0.05). Conclusion: Among invasive pituitary adenomas, the therapeutic effects of non-and GH-secreting pituitary adenomas are better than that of PRL-secreting adenomas. Invasive biological behaviors of invasive pituitary adenomas result in radical operation failure and postoperative recurrence.