Super enhancer related gene ANP32B promotes the proliferation of acute myeloid leukemia by enhancing MYC through histone acetylation.

BACKGROUND: Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, and childhood AML accounts for about 20% of pediatric leukemia. ANP32B, an important nuclear protein associated with proliferation, has been found to regulate hematopoiesis and CML leukemogenesis by inhibiting p53 activity. However, recent study suggests that ANP32B exerts a suppressive effect on B-cell acute lymphoblastic leukemia (ALL) in mice by activating PU.1. Nevertheless, the precise underlying mechanism of ANP32B in AML remains elusive. RESULTS: Super enhancer related gene ANP32B was significantly upregulated in AML patients. The expression of ANP32B exhibited a negative correlation with overall survival. Knocking down ANP32B suppressed the proliferation of AML cell lines MV4-11 and Kasumi-1, along with downregulation of C-MYC expression. Additionally, it led to a significant decrease in H3K27ac levels in AML cell lines. In vivo experiments further demonstrated that ANP32B knockdown effectively inhibited tumor growth. CONCLUSIONS: ANP32B plays a significant role in promoting tumor proliferation in AML. The downregulation of ANP32B induces cell cycle arrest and promotes apoptosis in AML cell lines. Mechanistic analysis suggests that ANP32B may epigenetically regulate the expression of MYC through histone H3K27 acetylation. ANP32B could serve as a prognostic biomarker and potential therapeutic target for AML patients.

Prognostic factors of pancreatic tumors in children and adolescents: a population study based on the surveillance, epidemiology, and end results database.

PURPOSE: Pancreatic tumors in children are uncommon, and data is scarce. The purpose of this study is to examine the prognostic factors of pediatric pancreatic tumors in a population-based cohort. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all pediatric patients with pancreatic tumors diagnosed between 1975 and 2018. The overall survival (OS) rates were determined using a Kaplan-Meier analysis. The log-rank test was used for univariate survival analysis. Cox proportional-hazards regression was used to determine the variables related to OS. RESULTS: We identified 195 children with pancreatic tumors, with a median age at diagnosis of 16 years. Tumors were classified as neuroendocrine tumors (33.8%), solid pseudopapillary tumors (SPTs) (32.3%), pancreatoblastoma (11.3%), and others (22.6%). Of the patients, 30.3% had distant metastases, and 69.7% had surgery. Pancreatoblastomas were more common in younger children, whereas solid pseudopapillary tumors were more common in female patients. Overall 1-year, 3-year, and 5-year survival rates for all patients were 90.3%, 79.2%, and 77.7%, respectively. The Cox proportional hazard regression revealed that SEER stage and surgery were significant independent predictors of overall survival. CONCLUSIONS: Pancreatic tumors are rare in children, and overall survival is grim except for SPTs. SEER stage and surgery were determined to be the most relevant determinants of OS in our study.

Meckel's diverticulum mimicking acute appendicitis in children: a retrospective cohort study.

BACKGROUND: The aims of this study were to summarize the clinical presentation and histological results of 20 cases of complicated Meckel diverticulum (MD) who were presumed to have acute appendicitis before surgery, as well as to improve the diagnosis and treatment of complicated MD in children. MATERIALS AND METHODS: We retrospectively reviewed the records of 20 complicated MD admitted to our institution who were preoperatively diagnosed with acute appendicitis from January 2012 to January 2019. Patients were divided into the perforated MD group and the Meckel's diverticulitis group. Patient demographics, clinical manifestations, laboratory data, auxiliary examinations, surgical methods, and the result of heterotopic tissue were recorded. RESULTS: A total of 20 cases of complicated MD (perforated or diverticulitis) were identified. Children were aged from 3 to 13 years, with a mean age of 7.75 years (median 7.75; range, 1-13 years). Perforated Meckel's diverticulum occurred in 5 of 20 (25%) cases. For perforated MD versus diverticulitis, no significant differences were found between age, time to intervention, length of hospital stay, and distance from the ileo-cecal valve. Heterotopic tissue was confirmed on histopathology in 75% of all patients, including 10 cases of gastric mucosa, 3 cases of coexistent gastric mucosa and pancreatic tissue, and 2 cases of pancreatic tissue. All patients underwent diverticulectomy or partial ileal resection under laparoscopy or laparotomy; two cases combined with appendectomy owing to slight inflammation of the appendix. CONCLUSIONS: The most common presentation of symptomatic MD is painless rectal bleeding; however, it can present symptoms of acute abdomen mimicking acute appendicitis. The key point of diverticulectomy is to remove the ectopic mucosa completely.

Evaluation of career planning group counseling and its effectiveness for intern male nursing students.

OBJECTIVE: To investigate the influence of group counselling on the career planning and career maturity of male nursing students. METHOD: Sixty male nursing students were randomly selected from a specific-level first-class hospital in Hunan Province from July to August 2020 by using the convenience sampling method and were subsequently divided into the control group and the experimental group using the random number table method. The control group received routine pre-job training, including aspects concerning the hospital profile, nurse etiquette, nursing core systems, professional ethics, nursing emergency treatment and career prospects and planning. In the experimental group, career planning group counselling was added after the regular pre-service training (once a week) with each session lasting 2 h for a total of six training sessions. At six weeks and three months after the intervention, the career status evaluation scale and the college students' career maturity scale were used to compare the career planning and career maturity status of the two groups of male nursing students. RESULTS: After six weeks and three months of intervention, all the dimensions and total scores of both the career status evaluation scale and the career maturity scale in the experimental group were superior to those in the control group with statistically significant differences (all P < 0.05). The repeated measures of variance analysis indicated that the differences in the total score for career planning and the four dimensions in terms of intergroup effect, time effect and interaction effect between the two groups were statistically significant (P < 0.05). The intergroup effect, time effect and interaction effect of the total score for vocational maturity, career goal, career confidence, career value, career freedom and career reference of the two groups were statistically significant (P < 0.05), while the time effect of the relative dependency dimension was also statistically significant (P < 0.05). CONCLUSION: Group counselling can significantly improve the career planning and career maturity status of male nursing students and has a certain long-term effect.

Improving the diagnosis of common parotid tumors via the combination of CT image biomarkers and clinical parameters.

BACKGROUND: Our study aims to develop and validate diagnostic models of the common parotid tumors based on whole-volume CT textural image biomarkers (IBMs) in combination with clinical parameters at a single institution. METHODS: The study cohort was composed of 51 pleomorphic adenoma (PA) patients and 42 Warthin tumor (WT) patients. Clinical parameters and conventional image features were scored retrospectively and textural IBMs were extracted from CT images of arterial phase. Independent-samples t test or Chi-square test was used for evaluating the significance of the difference among clinical parameters, conventional CT image features, and textural IBMs. The diagnostic performance of univariate model and multivariate model was evaluated via receiver operating characteristic (ROC) curve and area under ROC curve (AUC). RESULTS: Significant differences were found in clinical parameters (age, gender, disease duration, smoking), conventional image features (site, maximum diameter, time-density curve, peripheral vessels sign) and textural IBMs (mean, uniformity, energy, entropy) between PA group and WT group (P<0.05). ROC analysis showed that clinical parameter (age) and quantitative textural IBMs (mean, energy, entropy) were able to categorize the patients into PA group and WT group, with the AUC of 0.784, 0.902, 0.910, 0.805, respectively. When IBMs were added in clinical model, the multivariate models including age-mean and age-energy performed significantly better than the univariate models with the improved AUC of 0.940, 0.944, respectively (P<0.001). CONCLUSIONS: Both clinical parameter and CT textural IBMs can be used for the preoperative, noninvasive diagnosis of parotid PA and WT. The diagnostic performance of textural IBM model was obviously better than that of clinical model and conventional image model in this study. While the multivariate model consisted of clinical parameter and textural IBM had the optimal diagnostic performance, which would contribute to the better selection of individualized surgery program.

May Measurement Month 2018: an analysis of blood pressure screening results from China.

To further improve awareness, treatment, and control of hypertension, the May Measurement Month (MMM) campaign continued in 2018 in China. Study subjects were adults aged 18 years or more, ideally those who had not their blood pressure (BP) measured for at least a year. Blood pressure was measured three times consecutively with a 1-min interval in the sitting position, using automated BP monitors in 288 342 participants and transmitted to a central database by a smartphone app. Questionnaire data were collected with the same app. After imputation, the overall proportion of hypertension was 29.8%. Of those with hypertension, the rates of awareness, treatment, and control were 62.3%, 57.3%, and 35.9%, respectively. In analysis based on linear regression models, both systolic and diastolic BP were higher with cigarette smoking, alcohol intake, and overweight and obesity. Our study results suggest that hypertension management is improving in comparison with the data in MMM 2017 and the nationwide survey in 2012-15, and several known lifestyle factors are key to hypertension management.

Colorectal Cancer Diagnostic Algorithm Based on Sub-Patch Weight Color Histogram in Combination of Improved Least Squares Support Vector Machine for Pathological Image.

In order to improve the diagnostic accuracy of colon cancer, a novel classification algorithm based on sub-patch weight color histogram and improved SVM is proposed, which has good approximation ability for complex pathological image. Our proposed algorithm combines wavelet kernel SVM with color histogram to classify pathological image. Firstly, the pathological image is divided into non-overlapping sub-patches, and the features of sub-patch histogram are extracted. Then, the global and local features are fused by the sub-patch weighting algorithm. Then, the RelicfF based forward selection algorithm is used to integrate color features and texture features so as to enhance the characterization capabilities of the tumor cell. Finally, Morlet wavelet kernel-based least squares support vector machine method is adopted to enhance the generalization ability of the model for small sample with non-linear and high-dimensional pattern classification problems. Experimental results show that the proposed pathological diagnostic algorithm can gain higher accuracy compared with existing comparison algorithms.

Correction to: Colorectal Cancer Diagnostic Algorithm Based on Sub-Patch Weight Color Histogram in Combination of Improved Least Squares Support Vector Machine for Pathological Image.

The original article unfortunately contained a mistake. The corresponding author's name should be corrected as "Yingsheng Cheng".

[Expression and significance of dishevelled proteins in the Wnt pathway in childhood acute lymphoblastic leukemia].

OBJECTIVE: To study the significance of dishevelled (DVL) proteins in the Wnt signaling pathway in the pathogenesis and prognosis of childhood acute lymphoblastic leukemia (ALL). METHODS: A total of 33 children with new-onset ALL were enrolled as the case group. According to the degree of risk, they were divided into 3 groups: low-risk (n=14), intermediate-risk (n=5) and high-risk (n=14). A total of 29 children with immune thrombocytopenia were enrolled as the control group. At diagnosis and on day 33 of induction therapy, 2 mL bone marrow samples were collected from the case and control groups, and qRT-PCR was used to measure the mRNA expression of DVL1, DVL2 and DVL3 in blood cells of bone marrow. RESULTS: The mRNA expression of DVL1, DVL2 and DVL3 in the case group in the incipient stage was significantly higher than that in the remission stage and the control group (P<0.05). Compared with the control group, the case group had a significant increase in the mRNA expression of DVL2 in the remission stage (P<0.05). The mRNA expression of DVL2 was significantly higher than that of DVL1 and DVL3 in both remission and incipient stages (P<0.05). The high- and intermediate-risk groups had significantly higher mRNA expression of DVL1 and DVL2 than the low-risk group (P<0.05). The mRNA expression of DVL2 was significantly higher than that of DVL1 and DVL3 in the low-, intermediate- and high-risk groups (P<0.05). CONCLUSIONS: The change in the expression of DVL, especially DVL2, in the Wnt signal pathway has certain significance in the pathogenesis and prognosis of childhood ALL.

SIRT1 plays a neuroprotective role in traumatic brain injury in rats via inhibiting the p38 MAPK pathway.

Traumatic brain injury (TBI) is a major cause of disability and death in patients who experience a traumatic injury. Mitochondrial dysfunction is one of the main factors contributing to secondary injury in TBI-associated brain damage. Evidence of compromised mitochondrial function after TBI has been, but the molecular mechanisms underlying the pathogenesis of TBI are not well understood. Silent information regulator family protein 1 (SIRT1), a member of the NAD+-dependent protein deacetylases, has been shown to exhibit neuroprotective activities in animal models of various pathologies, including ischemic brain injury, subarachnoid hemorrhage and several neurodegenerative diseases. In this study, we investigated whether SIRT1 also exert neuroprotective effect post-TBI, and further explored the possible regulatory mechanisms involved in TBI pathogenesis. A lateral fluid-percussion (LFP) brain injury model was established in rats to mimic the insults of TBI. The expression levels of SIRT1, p-p38, cleaved caspase-9 and cleaved caspase-3 were all markedly increased and reached a maximum at 12 h post-TBI. In addition, mitochondrial function was impaired, evidenced by the presence of swollen and irregularly shaped mitochondria with disrupted and poorly defined cristae, a relative increase of the percentage of neurons with low ΔΨm, the opening of mPTP, and a decrease in neuronal ATP content, especially at 12 h post-TBI. Pretreatment with the SIRT1 inhibitor sirtinol (10 mg/kg, ip) induced p-p38 activation, exacerbated mitochondrial damage, and promoted the activation of the mitochondrial apoptosis pathway. In contrast, pretreatment with the p38 inhibitor SB203580 (200 µg/kg, ip) significantly attenuated post-TBI-induced expression of both cleaved caspase-9 and cleaved caspase-3 and mitochondrial damage, whereas it had no effects on SIRT1 expression. Together, these results reveal that the 12 h after TBI may be a crucial time at which secondary damage occurs; the activation of SIRT1 expression and inhibition of the p38 MAPK pathway may play a neuroprotective role in preventing secondary damage post-TBI. For this reason, both SIRT1 and p38 are likely to be important targets to prevent secondary damage post-TBI.

Gene copy-number variations (CNVs) of complement C4 and C4A deficiency in genetic risk and pathogenesis of juvenile dermatomyositis.

OBJECTIVE: Complement-mediated vasculopathy of muscle and skin are clinical features of juvenile dermatomyositis (JDM). We assess gene copy-number variations (CNVs) for complement C4 and its isotypes, C4A and C4B, in genetic risks and pathogenesis of JDM. METHODS: The study population included 105 patients with JDM and 500 healthy European Americans. Gene copy-numbers (GCNs) for total C4, C4A, C4B and HLA-DRB1 genotypes were determined by Southern blots and qPCRs. Processed activation product C4d bound to erythrocytes (E-C4d) was measured by flow cytometry. Global gene-expression microarrays were performed in 19 patients with JDM and seven controls using PAXgene-blood RNA. Differential expression levels for selected genes were validated by qPCR. RESULTS: Significantly lower GCNs and differences in distribution of GCN groups for total C4 and C4A were observed in JDM versus controls. Lower GCN of C4A in JDM remained among HLA DR3-positive subjects (p=0.015). Homozygous or heterozygous C4A-deficiency was present in 40.0% of patients with JDM compared with 18.2% of controls (OR=3.00 (1.87 to 4.79), p=8.2×10(-6)). Patients with JDM had higher levels of E-C4d than controls (p=0.004). In JDM, C4A-deficient subjects had higher levels of E-C4d (p=0.0003) and higher frequency of elevated levels of multiple serum muscle enzymes at diagnosis (p=0.0025). Microarray profiling of blood RNA revealed upregulation of type I interferon-stimulated genes and lower abundance of transcripts for T-cell and chemokine function genes in JDM, but this was less prominent among C4A-deficient or DR3-positive patients. CONCLUSIONS: Complement C4A deficiency appears to be an important factor for the genetic risk and pathogenesis of JDM, particularly in patients with a DR3-positive background.

[Prenatal ultrasonic manifestation and clinical significance of fetal hemivertebra].

OBJECTIVE: To explore the manifestation and clinical significance of prenatal ultrasound diagnosis of fetal hemivertebra. METHODS: In the study, 27 fetals with hemivertebras (proven by post-natal X-ray, CT or MR) were examined by prenatal ultrasound and MR in Women & Children's Hospital, Ningbo, Zhejiang. Two-dimensional and three-dimensional prenatal ultrasonic manifestations were retrospective analyzed and compared with the prenatal MR diagnoses, the post-natal X-ray, CT, MR examinations. All the fetuses were carried out karyotype examinations. The full-term births recieved surgical treatment and the Cobb angle correction rate was calculated. RESULTS: The 27 cases of fetal ultrasound showed the morphological changes of the spine, with the involved segment only half of the vertebra, in which 9 cases were single hemivertebra and 18 cases multiple, 8 cases were no malformation and 19 cases other malformations, and 19 cases were induction of labor, and 8 cases of term delivery. Compared with postpartum X-ray and other imaging tests, the prenatal ultrasound accuracy rate was 92.5%, and prenatal MR 96.3%. In the 27 cases, the chromosome cultures of 25 cases were successful, in which the normal karyotype was 68.0% (17/25), and abnormal karyotype 32.0% (8/25) with multiple hemivertebra accounting for 47.1% (8/17). In 8 cases with posterior approach of hemivertebra resection, 6 patients were less than and equal to 3 years old, whose average Cobb angle correction rate was 38.02%, and 2 more than 3 years old, whose average Cobb angle correction rate was 24.98%. CONCLUSION: Fetal hemivertebra have typical sonographic manifestations. In diagnosis of fetal hemivertebra, the accuracy of prenatal ultrasound is close to that of MR, which has important clinical implications in diagnosis and overall assessment of fetal hemivertebra, and can also provide appropriate clinical genetic reference.

[Construction and identification of the Bifidobacterium expression system pGEX-TSOL18/B. longum of Taenia solium].

The TSOL18 gene of Taenia solium was synthesized and cloned into Escherichia coli-Bifidobacteria shuttle vector pGEX-1lambdaT. The recombinant plasmid pGEX-TSOL18 was transformed into Bifidobacterium longum with electroporation. The recombinant plasmid containing TSOL18 gene was identified by restriction endonuclease analysis, PCR and DNA sequencing. The length of synthesized TSOL18 gene was 393 bp. The results indicated that the Bifidobacteria expression system pGEX-TSOL18/B. longum was successfully constructed.

Prognostic factors of alveolar soft part sarcoma in children and adolescents: A population-based study.

PURPOSE: Alveolar Soft Part Sarcoma (ASPS) is an exceedingly rare and aggressive cancer in children. Our objective was to conduct a population-based cohort study to forecast overall survival (OS) in pediatric ASPS patients. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify all pediatric ASPS patients diagnosed between 1975 and 2019. Kaplan-Meier estimations were employed to construct survival curves based on various criteria. Survival curves were compared using the log-rank test. Cox proportional-hazards regression was utilized to determine variables associated with OS. Additionally, we constructed a nomogram to predict overall survival in pediatric ASPS patients. RESULTS: A total of 103 pediatric ASPS patients were identified. Predominantly, the tumors affected females (62.2 %), and most of them located in the extremities (53.4 %). The majority of patients underwent surgery (83.5 %). Survival rates declined with increasing tumor size, and patients with localized tumors exhibited significantly better prognoses than those with distant tumors. Surgery conferred superior survival outcomes compared to no surgery. Cox proportional hazard regression analysis identified SEER stage and surgery as important independent predictors of survival. CONCLUSIONS: Our study highlights SEER stage and surgery as key predictors of OS in pediatric ASPS, offering crucial epidemiological insights for clinical management.

Prognostic factors of adrenocortical carcinoma in children and adolescents: a population-based study.

PURPOSE: Adrenocortical carcinoma (ACC) is an uncommon adrenal gland endocrine tumor that has a poor prognosis in children. We aimed to conduct a population-based cohort study to predict overall survival (OS) in pediatric patients with ACC. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to conduct a retrospective cohort research on pediatric patients diagnosed with ACC between 1975 and 2018. We examined demographic characteristics, tumor stage and size, treatment options, and survival results. Kaplane-Meier estimations were used to generate survival curves based on several parameters. To compare survival curves, the log-rank test was applied.Cox proportional-hazards regression was used to determine the variables related with OS. In addition, we created a nomogram to predict overall survival in pediatric ACC patients. RESULTS: A total of 143 pediatric ACC patients were identified. Females were the most impacted (60.8%). Overall 1 year, 3 year, and 5 year survival rates were 75.0%, 57.6%, and 53.7% for all patients, respectively. In comparison to older patients (5-19 years), younger patients (≤ 4 years) were shown to have more positive characteristics, including a higher likelihood of local disease (29.4% vs. 14%, P < 0.001), tumors less than 10 cm (23.1% vs. 14.7%, P < 0.001), and improved overall survival (5 year OS 89.6% vs. 27.7%, P < 0.001). Age at diagnosis, SEER stage, and surgery were significant independent predictors of OS in this model, according to the results of Cox proportional hazard regression. After that, we developed a nomogram for predicting OS in children with ACC. Patients older than 4 years old had a higher chance of dying. Furthermore, the higher the SEER stage, the higher the risk of death. Patients who do not have surgery have a worse survival rate than those who do. CONCLUSIONS: Our study revealed that age at diagnosis, SEER stage, and surgery were found to be the most important predictors of the overall survival of pediatric ACC. These findings contribute to the existing body of knowledge and emphasize the importance of continued research to advance our understanding of pediatric ACC and improve patient care.

Double Balloon Combined with Oxytocin in Labor Induction: Analysis of Multivariate Factors Affecting the Efficacy of Cervical Ripening.

Objective: Labor induction during the late trimester of pregnancy is a common option of terminating pregnancy by inducing uterine contractions through medication or cervical mechanical dilation. However, there are few researches on the factors influencing the effectiveness of cervical ripening balloon combined with oxytocin in inducing labor. To explore factors affecting the efficacy of cervical ripening double balloon combined with oxytocin in labor induction. Methods: Using a convenient sampling method, this study retrospectively collected the clinical data of 230 pregnant women who underwent cervical ripening double balloon combined with oxytocin for labor induction in our hospital from September 2021 to August 2022. The included subjects were divided into a vaginal delivery group (n = 180) and a cesarean section group (n = 50) based on the delivery mode for comparing relevant indicators between the two groups. Results: The presence of acute chorioamnionitis (OR = 1.456, 95% CI: 1.257-2.112), fetal distress (OR = 1.371, 95% CI: 1.331-2.633), and the placement of cervical ripening balloon catheter for >12h (OR = 1.563, 95% CI: 1.231-3.263) were risk factors for successful application of cervical ripening double balloon combined with oxytocin for labor induction in pregnant women; while multi-gravidity (OR = 0.736, 95% CI: 0.455-0.875) was a protective factor. In addition, evaluation of the predictive value revealed that acute chorioamnionitis, fetal distress, the placement of cervical ripening balloon catheter for >12h, and gravidity all had certain predictive value for the failure of cervical ripening double balloon combined with oxytocin for labor induction, with the highest predictive value found through joint predictive (AUC: 0.931, 95% CI: 0.714-0.811). Conclusion: Cervical ripening double balloon combined with oxytocin for labor induction may have a high success rate in multigravida. Acute chorioamnionitis, fetal distress, and prolonged placement of the balloon may have a negative impact on the success rate of cervical ripening double balloon combined with oxytocin for labor induction.

Dexmedetomidine attenuates ferroptosis by Keap1-Nrf2/HO-1 pathway in LPS-induced acute kidney injury.

Previous research has demonstrated that Dexmedetomidine (DEX), an α2 adrenergic agonist commonly used for its sedative and analgesic properties, can attenuate lipopolysaccharide (LPS)-induced acute kidney injury (AKI). This study explores the possibility that DEX's protective effects in LPS-induced AKI are mediated through the inhibition of ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, and the activation of the antioxidant response through the Keap1/Nrf2/HO-1 signaling pathway. We induced AKI in 42 mice using LPS and divided them into six groups: saline control, LPS, LPS + DEX, LPS + Ferrostatin-1 (LPS + Fer-1; a ferroptosis inhibitor), LPS + DEX with α2-receptor antagonist Altipamizole (LPS + DEX + ATI), and LPS + DEX with Nrf2 inhibitor ML385 (LPS + DEX + ML385). After 24 h, we analyzed blood and kidney tissues. LPS exposure resulted in AKI, with increased serum creatinine, BUN, and cystatin C, and tubular damage, which DEX and Fer-1 ameliorated. However, Altipamizole and ML385 negated these improvements. The LPS group exhibited elevated oxidative stress markers and mitochondrial damage, reduced by DEX and Fer-1, but not when α2-adrenergic or Nrf2 pathways were blocked. Nrf2 and HO-1 expression declined in the LPS group, rebounded with LPS + DEX and LPS + Fer-1, and fell again with inhibitors; inversely, Keap1 expression varied. Our results demonstrate that DEX may protect against LPS-induced AKI, at least partially by regulating ferroptosis and the α2-adrenergic receptor/Keap1/Nrf2/HO-1 pathway, suggesting a potential therapeutic role for DEX in AKI management by modulating cell death and antioxidant defenses.

Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro.

BACKGROUND: Schistosomiasis is a relatively neglected parasitic disease that afflicts more than 250 million people worldwide, for which the control strategy relies mainly on mass treatment with the only available drug, praziquantel (PZQ). This approach is not sustainable and is a priority for developing novel drug candidates for the treatment and control of schistosomiasis. METHODOLOGYS/PRINCIPAL FINDINGS: In our previous study, we found that DW-3-15, a kind of PZQ derivative, could significantly downregulate the expression of the histone acetyltransferase of Schistosoma japonicum (SjHAT). In this study, several commercially available HAT inhibitors, A485, C646 and curcumin were screened in vitro to verify their antischistosomal activities against S. japonicum juveniles and adults. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of HAT inhibitors in vitro. Quantitative real-time PCR was employed to detect the mRNA level of SjHAT after treatment with different HAT inhibitors. Our results demonstrated that curcumin was the most effective inhibitor against both juveniles and adults of S. japonicum, and its schistosomicidal effects were time- and dose dependent. However, A485 and C646 had limited antischistosomal activity. Scanning electron microscopy demonstrated that in comparison with DW-3-15, curcumin caused similar tegumental changes in male adult worms. Furthermore, both curcumin and DW-3-15 significantly decreased the SjHAT mRNA level, and curcumin dose-dependently reduced the SjHAT expression level in female, male and juvenile worms. CONCLUSIONS: Among the three commercially available HATs, curcumin was the most potent against schistosomes. Both curcumin and our patent compound DW-3-15 markedly downregulated the expression of SjHAT, indicating that SjHAT may be a potential therapeutic target for developing novel antischistosomal drug candidates.

Abnormal function of EPHA2/p.R957P mutant in congenital cataract.

AIM: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. METHODS: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. RESULTS: A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. CONCLUSION: Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.