High miR-34a and miR-26b expressions inhibit prostate cancer cell OPCN-1 proliferation and enhances apoptosis

Purpose: To investigate the effects of miR-34a and miR-26b on the targeted genes, LEF1 and EphA2, and proliferation and apoptosis of OPCN-1.Methods: Sixty specimens of cancer tissue (CT) and equivalent tissue adjacent to tumors (TAT) were collected from prostate cancer patients. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the mRNA expression levels of miR-34a, miR-26b, LEF1, and EphA2 in the above tissues, while protein expression levels of LEF1 and EphA2 were evaluated by Western blot.Results: Compared with TAT, the expression levels of miR-26b and miR-34a in CT decreased significantly (p < 0.05), whereas the mRNA and protein expression levels of EphA2 and LEF1 in CT significantly increased (p < 0.05). TargetScanHuman7.2 assay data revealed that miR-26b targeted EphA2, while miR-34a targeted LEF1. MiR-26b MG showed decreased EphA2 mRNA and protein levels when compared with miR-26b-NC group after overexpression. The miR-34a MG exhibited decreased expression levels of LEF1 mRNA and protein compared with the miR-34a-NC group. Between 48 and 72 h, miR-26b MG grew more slowly than miR-26b-NC group; miR-34a MG also showed significantly slower growth than miR-34a-NC group. The miR-26b MG and miR-34a MG groups displayed higher apoptosis rate than miR-26b-NC and miR-34a-NC groups, respectively.Conclusion: High expressions of miR-34a and miR-26b targeted the inhibition of LEF1 and EphA2, respectively, indicating that they inhibit the proliferation, and also control the increased apoptosis rate of OPCN-1 cells. Hence, miR-34a and miR-26b are probable molecular targets for the development of new prostate cancer drugs

Cortical hierarchy disorganization in major depressive disorder and its association with suicidality

ObjectivesTo explore the suicide risk-specific disruption of cortical hierarchy in major depressive disorder (MDD) patients with diverse suicide risks.MethodsNinety-two MDD patients with diverse suicide risks and 38 matched controls underwent resting-state functional MRI. Connectome gradient analysis and stepwise functional connectivity (SFC) analysis were used to characterize the suicide risk-specific alterations of cortical hierarchy in MDD patients.ResultsRelative to controls, patients with suicide attempts (SA) had a prominent compression from the sensorimotor system; patients with suicide ideations (SI) had a prominent compression from the higher-level systems; non-suicide patients had a compression from both the sensorimotor system and higher-level systems, although it was less prominent relative to SA and SI patients. SFC analysis further validated this depolarization phenomenon.ConclusionThis study revealed MDD patients had suicide risk-specific disruptions of cortical hierarchy, which advance our understanding of the neuromechanisms of suicidality in MDD patients

Association between gut microbiota and pan-dermatological diseases: a bidirectional Mendelian randomization research

BackgroundGut microbiota has been associated with dermatological problems in earlier observational studies. However, it is unclear whether gut microbiota has a causal function in dermatological diseases.MethodsThirteen dermatological diseases were the subject of bidirectional Mendelian randomization (MR) research aimed at identifying potential causal links between gut microbiota and these diseases. Summary statistics for the Genome-Wide Association Study (GWAS) of gut microbiota and dermatological diseases were obtained from public datasets. With the goal of evaluating the causal estimates, five acknowledged MR approaches were utilized along with multiple testing corrections, with inverse variance weighted (IVW) regression serving as the main methodology. Regarding the taxa that were causally linked with dermatological diseases in the forward MR analysis, reverse MR was performed. A series of sensitivity analyses were conducted to test the robustness of the causal estimates.ResultsThe combined results of the five MR methods and sensitivity analysis showed 94 suggestive and five significant causal relationships. In particular, the genus Eubacterium_fissicatena_group increased the risk of developing psoriasis vulgaris (odds ratio [OR] = 1.32, pFDR = 4.36 × 10−3), family Bacteroidaceae (OR = 2.25, pFDR = 4.39 × 10−3), genus Allisonella (OR = 1.42, pFDR = 1.29 × 10−2), and genus Bacteroides (OR = 2.25, pFDR = 1.29 × 10−2) increased the risk of developing acne; and the genus Intestinibacter increased the risk of urticaria (OR = 1.30, pFDR = 9.13 × 10−3). A reverse MR study revealed insufficient evidence for a significant causal relationship. In addition, there was no discernible horizontal pleiotropy or heterogeneity.ConclusionThis study provides novel insights into the causality of gut microbiota in dermatological diseases and therapeutic or preventive paradigms for cutaneous conditions

Preparation, biological characterization and preliminary human imaging studies of 68Ga-DOTA-IBA

PurposeIn this study, DOTA-IBA was radiolabeled with 68Ga and we determined the optimum labelling conditions and assessed the biological properties of 68Ga-DOTA-IBA. We investigated the biodistribution of 68Ga-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility 68Ga-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of 177Lu/225Ac-DOTA-IBA.MethodsThe controlled variables method was used to assess the impact of variables on the radiochemical purity of 68Ga-DOTA-IBA. The biological properties of 68Ga-DOTA-IBA were investigated.68Ga-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for 68Ga-DOTA-IBA imaging and data were compared to 99mTc-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions.ResultsThe prepared 68Ga-DOTA-IBA had a radiochemical purity of >97% and demonstrated good biological properties with a good safety profile in normal mice. PET/CT imaging of the animals showed rapid blood clearance with high contrast between the bone and stroma. Human imaging showed that 68Ga-DOTA-IBA could detect more lesions compared to 99mTc-MDP and had a higher targeted to untargeted ratio.Conclusions68Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. 68Ga-DOTA-IBA has high radiochemical purity and is stable in vitro stability. It is rapidly cleared from the blood, has low toxicity and has strong targeting to the bone with long retention times. We also found that it is rapidly cleared in non-target tissues and has high contrast on whole-body bone imaging. 68Ga-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease

Clusters of spatial, temporal, and space-time distribution of hemorrhagic fever with renal syndrome in Liaoning Province, Northeastern China

<p>Abstract</p> <p>Background</p> <p>Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by Hantavirus, with characteristics of fever, hemorrhage, kidney damage, and hypotension. HFRS is recognized as a notifiable public health problem in China, and Liaoning Province is one of the most seriously affected areas with the most cases in China. It is necessary to investigate the spatial, temporal, and space-time distribution of confirmed cases of HFRS in Liaoning Province, China for future research into risk factors.</p> <p>Methods</p> <p>A cartogram map was constructed; spatial autocorrelation analysis and spatial, temporal, and space-time cluster analysis were conducted in Liaoning Province, China over the period 1988-2001.</p> <p>Results</p> <p>When the number of permutation test was set to 999, Moran's I was 0.3854, and was significant at significance level of 0.001. Spatial cluster analysis identified one most likely cluster and four secondary likely clusters. Temporal cluster analysis identified 1998-2001 as the most likely cluster. Space-time cluster analysis identified one most likely cluster and two secondary likely clusters.</p> <p>Conclusions</p> <p>Spatial, temporal, and space-time scan statistics may be useful in supervising the occurrence of HFRS in Liaoning Province, China. The result of this study can not only assist health departments to develop a better prevention strategy but also potentially increase the public health intervention's effectiveness.</p