A high-throughput screening campaign against PFKFB3 identified potential inhibitors with novel scaffolds.

The growth of solid tumors depends on tumor vascularization and the endothelial cells (ECs) that line the lumen of blood vessels. ECs generate a large fraction of ATP through glycolysis, and elevation of their glycolytic activity is associated with angiogenic behavior in solid tumors. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) positively regulates glycolysis via fructose-2/6-bisphosphate, the product of its kinase activity. Partial inhibition of glycolysis in tumor ECs by targeting PFKFB3 normalizes the otherwise abnormal tumor vessels, thereby reducing metastasis and improving the outcome of chemotherapy. Although a limited number of tool compounds exist, orally available PFKFB3 inhibitors are unavailable. In this study we conducted a high-throughput screening campaign against the kinase activity of PFKFB3, involving 250,240 chemical compounds. A total of 507 initial hits showing >50% inhibition at 20 µM were identified, 66 of them plus 1 analog from a similarity search consistently displayed low IC50 values (<10 µM). In vitro experiments yielded 22 nontoxic hits that suppressed the tube formation of primary human umbilical vein ECs at 10 µM. Of them, 15 exhibited binding affinity to PFKFB3 in surface plasmon resonance assays, including 3 (WNN0403-E003, WNN1352-H007 and WNN1542-F004) that passed the pan-assay interference compounds screening without warning flags. This study provides potential leads to the development of new PFKFB3 inhibitors.

GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH), as a severe form of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis. The pathogenesis of NASH is complex and multifactorial, obesity and type 2 diabetes mellitus (T2DM) have been implicated as major risk factors. Glucagon-like peptide-1 receptor (GLP-1R) is one of the most successful drug targets of T2DM and obesity, and its peptidic ligands have been proposed as potential therapeutic agents for NASH. In this article we provide an overview of the pathophysiology and management of NASH, with a special focus on the pharmacological effects and possible mechanisms of GLP-1 mimetics in treating NAFLD/NASH, including dual and triple agonists at GLP-1R, glucose-dependent insulinotropic polypeptide receptor or glucagon receptor.

Florid cystitis glandularis (intestinal type) with mucus extravasation: Two case reports and literature review.

Background: Cystitis glandularis is a common bladder epithelial lesion characterized by hyperplasia and metaplasia of the bladder mucosa epithelium. The pathogenesis of cystitis glandularis of the intestinal type is unknown and less common. When cystitis glandularis (intestinal type) is extremely severely differentiated, it is called florid cystitis glandularis (the occurrence is extremely rare). Case summary: Both patients were middle-aged men. In patient 1, the lesion was also seen in the posterior wall and was diagnosed more than 1 year ago as cystitis glandularis with urethral stricture. Patient 2 was examined for symptoms such as hematuria and was found to have an occupied bladder; both were treated surgically, and the postoperative pathology was diagnosed as florid cystitis glandularis (intestinal type), with mucus extravasation. Conclusion: The pathogenesis of cystitis glandularis (intestinal type) is unknown and less common. When cystitis glandularis of the intestinal type is extremely severely differentiated, we call it florid cystitis glandularis. It is more common in the bladder neck and trigone. The clinical manifestations are mainly symptoms of bladder irritation, or hematuria as the main complaint, which rarely leads to hydronephrosis. Imaging is nonspecific and the diagnosis depends on pathology. Surgical excision of the lesion is possible. Due to the malignant potential of cystitis glandularis of intestinal type, postoperative follow-up is required.

Case Report: Adrenal glands degenerated schwannoma: Report of three cases and literature review.

Background: Schwannoma is a benign tumor, of which degenerated schwannoma is a subtype. Retroperitoneal schwannomas are extremely rare, as they account for only 3% of retroperitoneal tumors.Degenerated schwannoma is a schwannoma subtype. However,degenerated schwannoma occurring in the adrenal glands is extremely rare. Case summary: Case 1: A 42-year-old man was referred to our hospital for further examination of a left adrenal mass that was incidentally discovered during a routine physical check-up.No significant abnormalities were found in laboratory tests results. Robotic-assisted laparoscopic excision of the left adrenal gland was performed under general anesthesia. Case 2: A 47-year-old man was admitted to the hospital because of a left adrenal mass found on a routine physical examination.The patient was previously in good health, and there was no family history of a similar disorder. Left-sided laparoscopic adrenalectomy was performed under general anaesthesia. Case 3: A 62-year-old woman with hypertension and diabetes mellitus was referred to our hospital after an incidentally found left adrenal mass.There was no family history of a similar disorder. Left-sided laparoscopic adrenalectomy was performed under general anaesthesia. None of the patients had a recurrence in our study during the postoperative follow-up. Conclusion: Degenerated schwannoma of the adrenal glands is very rare. The clinical presentations of degenerated schwannoma are nonspecific; a small number of patients do not have any symptoms, and the mass is only found incidentally during physical examination for any number of reasons. The preoperative diagnosis of adrenal degenerated schwannoma is difficult because the diagnosis must rely on pathological examination and immunohistochemistry assays. The management is surgical excision and regular follow-up.

Case Report: The ectopic pancreas in the adrenal glands: It was found due to elevated blood pressure and initially diagnosed as adrenal adenoma.

Background: The ectopic pancreas is a kind of congenital malformation formed during embryonic development, which has no anatomical relationship with the normal pancreas and is a rare solid disease. The ectopic pancreas in the adrenal glands is extremely rare. Case summary: A 32-year-old man was admitted to the hospital after experiencing elevated blood pressure for 2 years as well as dizziness and blurred vision for 2 weeks. He had an elevated blood pressure of 170/110 mmHg (1 mmHg = 0.133 kPa) on physical examination 2 years ago, without palpitations, chest pain, and chest tightness. Two weeks ago, he presented with dizziness and blurred vision. Blood renin and aldosterone levels were elevated. Plain CT and contrast-enhanced CT scan showed nodular thickening of the left adrenal and homogeneous enhancement, which was initially considered adrenal adenoma. The postoperative pathology supported the ectopic pancreas in the left adrenal. After 78 months of postoperative follow-up, no recurrence was observed, but his blood pressure remained persistently high. Conclusion: The ectopic pancreas occurring in the adrenal glands is extremely rare, has no specific clinical symptoms, and is mainly found for other reasons. It can easily be misdiagnosed as an adrenal adenoma. The final confirmation of the diagnosis still depends on the pathological biopsy. A great deal of reporting is still required for whether there is a correlation with elevated blood pressure.

Case report: High-grade endometrial stromal sarcoma with adrenal glands metastases: An unreported site of metastasis.

Background: Endometrial stromal sarcoma is a relatively rare malignant tumor that derives from the malignant transformation of primitive uterine mesenchymal cells. It can lead to distant metastases. High-grade endometrial stromal sarcoma is extremely rare. The adrenal glands are an unreported site of metastasis. Case summary: A 71-year-old woman with a diagnosis of endometrial stromal sarcoma 30 months ago. After receiving treatment with radiotherapy and chemotherapy, the patient was kept asymptomatic during the follow-up until 2 years later, when she complained of dyspnea. Pulmonary and right adrenal gland metastases were detected by 18F-FDG PET/CT. The right upper lobe mass was diagnosed as a high-grade endometrial stromal sarcoma metastasis after postoperative pathology. Due to the patient's high risk of surgery, as she had many underlying diseases, we performed adequate preoperative preparation. The physical examination revealed that a hard mass was palpable in the right renal area. The right adrenal mass was resected in our hospital. Immunohistochemistry showed ER (-), PR (-), CD10 (+), P16 (+), Ki-67 (50%). The final diagnosis on pathological examination was a high-grade ESS metastatic to the right adrenal gland. The patient continued treatment in other hospitals after surgical resection. After four months of postoperative follow-up, metastasis was detected again during a PET/CT examination at an outside hospital. Conclusion: Endometrial stromal sarcoma is rare, and the adrenal glands are an unreported site of metastasis. It has no specific clinical symptoms and mainly found for other reasons. The diagnosis still depends on pathology and immunohistochemistry. If there is no relevant past history, it is difficult to exclude a primary adrenal tumor.

Molecular Hydrogen Reduces Electromagnetic Pulse-Induced Male Rat Reproductive System Damage in a Rodent Model.

Infertility has got to be a broadly concerned social issue these days, in which the malefactor cannot be overlooked. Numerous studies have shown that electromagnetic pulse (EMP) radiation may have seriously damaging effects on reproductive health, through nonthermal effects and oxidative stress. Molecular hydrogen, a selective hydroxyl radical scavenger, explains the protective effects against many diseases closely associated with oxidative damage, such as ionizing radiation (IR). We sought to characterize the beneficial effects of molecular hydrogen on the male reproductive system in a rodent EMP exposure model. The 8-week-old male Sprague-Dawley rats were exposed to EMP (peak intensity 1000 kV/m, pulse edge 20 ns, pulse width 200 ns, 1 Hz, and 200 pulses), with or without hydrogen-rich water. The pathological structure of the testis, the rate of apoptosis of the testis, the serum testosterone level, the sperm parameters, and the activity of the antioxidant enzymes of the testis were measured. Then, transcriptomic and untargeted metabolomic analyses were applied to uncover the underlying mechanism. Exposure to EMP increased testicular apoptosis rate and apoptosis protein level, decreased sperm viability and motility, decreased serum testosterone levels, and diminished testicular antioxidant capacity. Molecular hydrogen-alleviated damage decreased the testicular apoptosis rate and apoptosis protein level, increased sperm motility, increased serum testosterone levels, and improved antioxidative capacity. Omics results showed that molecular hydrogen has a strong influence on metabolic pathways, and EMP affects mainly oxidative phosphorylation, TNF signaling pathways, and cytokine-receptor interactions. The mechanism of molecular hydrogen's effect may be related to the reversal of some metabolite levels. These observations warrant molecular hydrogen as an innovative approach for potential protection against EMP.

MiR-21 attenuates apoptosis-triggered by amyloid-ß via modulating PDCD4/ PI3K/AKT/GSK-3ß pathway in SH-SY5Y cells.

Alzheimer's disease (AD) remains the most common neurodegenerative disease with amyloid beta (Aß) formatted and accumulated. Recently, microRNAs have been identified as significant regulators in neurogenesis of the central nervous system (CNS). However, the biological role of miR-21 in AD remains unclear. The purpose of our study was to investigate the mechanism of miR-21 in AD. AD model was established using 20 µM Aß1-42 in SH-SY5Y cells. Aß1-42 can induce cell apoptosis via increasing Bax and decreasing Bcl-2 protein levels. Meanwhile, we observed that miR-21 was remarkably elevated by indicated Aß1-42 in vitro. Subsequently, miR-21 mimics were transfected into SH-SY5Y cells and it was found that miR-21 can inhibit cell apoptosis induced by Aß1-42. Programmed cell death protein 4 (PDCD4), an important tumor suppressor in various cancers has been reported to prevent AKT activation. The phosphatidylinositol 3-kinase (PI3K)/AKT/GSK-3ß pathway can release a survival signal to protect from multiple injuries. Interestingly, it was found that PDCD4 was involved in miR-21-repressed cell apoptosis in AD models. miR-21 mimics can increase the PI3K, AKT and GSK-3ß activity while PDCD4 ovexexpression inhibited their activity respectively. Moreover, knockdown of PDCD4 can rescue PI3K/AKT/GSK-3ß pathway in SH-SY5Y cells. Taken these together, it was suggested by our data that miR-21 can exert protective roles in AD, which might be dependent on PDCD4/PI3K/AKT/GSK-3ß signaling pathway in vitro.

[Distribution regarding tendency on personality disorder among college students in Shijiazhuang city].

OBJECTIVE: To survey the prevalence of tendency on tendency of personality disorder among college students. METHODS: By means of stratified cluster sampling, 498 students from 6 colleges in Shijiazhuang city and 204 students from 3 colleges in Beijing were studied through 'personality diagnostic questionnaire-revised UPDI'. RESULTS: The incidence rates on dependent personality (2.81%), histrionic personality (2.41%) and borderline personality (2.21%) were higher than obsessive-compulsive personality (0.40%) and schizoid personality (0.60%). The prevalence of personality disorder tendency was related to sex, major and years in college, blood type as well as their origins (from urban or rural). The overall incidence of personality disorder was 28.31% while the incidence rates of personality deviation and serious personality disorder tendency were 17.07% and 11.24% respectively. The incidence in males was higher than that in females. There appeared differences in dissociative personality, avoidant personality, paranoid personality, obsessive-compulsive personality, histrionic personality and narcissistic personality on people with different blood types. The scores of the city students were higher than that of the students from the rural areas regarding paranoid personality, dependent personality and narcissistic personality. Differences were also noticed between freshmen and students from other levels in the incidence rates on the tendency of avoidant personality disorder. CONCLUSION: There were different incidence rates on the tendency of personality disorder among college students that related to sex, level in college and the origins where they were from (urban or rural).