CircMEF2C(2, 3) modulates proliferation and adipogenesis of porcine intramuscular preadipocytes by miR-383/671-3p/MEF2C axis.

Circular RNA is a special category of non-coding RNA that has emerged as epigenetic regulator of adipose tissue development. However, the mechanism governing intramuscular adipogenesis of circRNA remains largely uncharted. In this study, circMEF2C(2, 3), looped by MEF2C exons 2 and 3, was identified from the pig MEF2C gene. Expression of circMEF2C(2, 3) is upregulated in early stage of intramuscular adipogenesis and muscular tissue of lean pigs (DLY pig). Subsequently, overexpression or knockdown of circMEF2C(2, 3) reflected that it participates in promoting proliferation and inhibiting adipogenic differentiation in porcine intramuscular preadipocytes and murine C3H10T1/2 cells. Mechanically, circMEF2C(2, 3) competitively combined with miR-383 and miR-671-3p to the 3'-UTR of MEF2C, which maintains MEF2C expression in regulating proliferation and adipogenesis. In summary, circMEF2C(2, 3) is a key regulator in the proliferation and adipogenic differentiation of intramuscular adipogenesis, suggesting its potential as a multi-target strategy for adipose development and associated diseases.

Detection of Bartonella spp. in farmed deer (Artiodactyla: Cervidae) using multiplex assays in the Qinghai-Tibet Plateau, China.

In this study, we investigated the prevalence of Bartonella in deer from Qilian County, Qinghai Province, China. Blood samples were collected from 69 red deer, 40 white-lipped deer, and 27 sika deer. The detection of Bartonella spp. has been conducted. The overall prevalence of Bartonella was 33.6% (46/135). Species-specific prevalence was 50.72% in red deer (35/69), 20.00% in white-lipped deer (8/40), and 11.11% in sika deer (3/27). There were significant differences in the prevalence rates among the different species of deer. The amplicon sequence comparison revealed a high homology of the ruminant-associated Bartonella spp. Nanopore sequencing further confirmed the results. Bartonella reads were presented in each of the qPCR-positive samples. Phylogenetic analysis indicated that the Bartonella sequences detected in deer blood were closely related to ruminant-borne Bartonella spp. In summary, we reported the Bartonella prevalence of different deer species in Qinghai, and there were at least one species of ruminant-associated Bartonella, B. schoenbuchensis. IMPORTANCE: This is the first report about Bartonella infections in the deer population from China. We found that there were two species of Bartonella and an unidentified species of Bartonella among the unculturing strains carried by these deer populations. We first used Nanopore sequencing to detect Bartonella from deer blood samples and indicated that Nanopore sequencing is beneficial to detect pathogens due to its advantage of real-time and high sensitivity.

Associations between perceived and actual risk of HIV infection and HIV prevention services uptake among men who have sex with men in Shandong province, China: a cross-sectional study.

BACKGROUND: Associations between perceived and actual risk of HIV infection and HIV prevention services uptake are inconclusive. This study aimed to evaluate the discrepancy between the perceived and actual HIV risk, and quantify the associations between perceived and actual risk of HIV infection and three HIV prevention services utilization among men who have sex with men (MSM) in Shandong province, China. METHODS: A cross-sectional study was conducted in Shandong province in June 2021. Participants were eligible if they were born biologically male, aged 18 years or older, had negative or unknown HIV status, and had sex with men in the past year. Participants were recruited online. The discrepancy between their perceived and actual risk of HIV infection was evaluated by calculating the Kappa value. Bayesian model averaging was used to assess the associations between perceived and actual risk of HIV infection and HIV prevention services uptake. RESULTS: A total of 1136 MSM were recruited, most of them were 30 years old or younger (59.9%), single (79.5%), with at least college education level (74.7%). Most participants (97.4%) perceived that they had low risk of HIV infection, and 14.1% were assessed with high actual risk. The discrepancy between their perceived and actual risk of HIV infection was evaluated with a Kappa value of 0.076 (P < 0.001). HIV testing uptake had a weak association with perceived high HIV prevalence among social networks (aOR = 1.156, post probability = 0.547). The perceived high HIV prevalence among national MSM was positive related to willingness to use PrEP (aOR = 1.903, post probability = 0.943) and PEP (aOR = 1.737, post probability = 0.829). Perceived personal risk (aOR = 4.486, post probability = 0.994) and perceived HIV prevalence among social networks (aOR = 1.280, post probability = 0.572) were related to history of using PrEP. Perceived personal risk (aOR = 3.144, post probability = 0.952), actual risk (aOR = 1.890, post probability = 0.950), and perceived risk among social networks (aOR = 1.502, post probability = 0.786) were related to history of using PEP. CONCLUSIONS: There is discordance between perceived and actual personal risk of HIV infection among MSM in China. HIV risk assessment and education on HIV prevalence among MSM should be strengthened to assist high-risk populations aware their risk accurately and hence access HIV prevention services proactively.

Analysis of risk factors leading to anxiety and depression in patients with prostate cancer after castration and the construction of a risk prediction model.

BACKGROUND: Cancer patients often suffer from severe stress reactions psychologically, such as anxiety and depression. Prostate cancer (PC) is one of the common cancer types, with most patients diagnosed at advanced stages that cannot be treated by radical surgery and which are accompanied by complications such as bodily pain and bone metastasis. Therefore, attention should be given to the mental health status of PC patients as well as physical adverse events in the course of clinical treatment. AIM: To analyze the risk factors leading to anxiety and depression in PC patients after castration and build a risk prediction model. METHODS: A retrospective analysis was performed on the data of 120 PC cases treated in Xi'an People's Hospital between January 2019 and January 2022. The patient cohort was divided into a training group (n = 84) and a validation group (n = 36) at a ratio of 7:3. The patients' anxiety symptoms and depression levels were assessed 2 wk after surgery with the Self-Rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS), respectively. Logistic regression was used to analyze the risk factors affecting negative mood, and a risk prediction model was constructed. RESULTS: In the training group, 35 patients and 37 patients had an SAS score and an SDS score greater than or equal to 50, respectively. Based on the scores, we further subclassified patients into two groups: a bad mood group (n = 35) and an emotional stability group (n = 49). Multivariate logistic regression analysis showed that marital status, castration scheme, and postoperative Visual Analogue Scale (VAS) score were independent risk factors affecting a patient's bad mood (P < 0.05). In the training and validation groups, patients with adverse emotions exhibited significantly higher risk scores than emotionally stable patients (P < 0.0001). The area under the curve (AUC) of the risk prediction model for predicting bad mood in the training group was 0.743, the specificity was 70.96%, and the sensitivity was 66.03%, while in the validation group, the AUC, specificity, and sensitivity were 0.755, 66.67%, and 76.19%, respectively. The Hosmer-Lemeshow test showed a χ2 of 4.2856, a P value of 0.830, and a C-index of 0.773 (0.692-0.854). The calibration curve revealed that the predicted curve was basically consistent with the actual curve, and the calibration curve showed that the prediction model had good discrimination and accuracy. Decision curve analysis showed that the model had a high net profit. CONCLUSION: In PC patients, marital status, castration scheme, and postoperative pain (VAS) score are important factors affecting postoperative anxiety and depression. The logistic regression model can be used to successfully predict the risk of adverse psychological emotions.

Observational Study: Clinical characteristics and Survival Rates in Patients with Prostate Cancer with Normal Prostate-Specific Antigen Concentrations.

Objectives: This study aimed to explore the clinical characteristics of patients with prostate cancer with prostate-specific antigen (PSA) concentrations of less than 4 ng/mL (normal PSA) to provide clinical insights regarding diagnosis and treatment. Methods: We recruited 35 patients with prostate cancer with normal PSA who were admitted to Xi'an People's Hospital from January 2013 to January 2018, and further determined their clinical characteristics, serum PSA concentration, prostate volume, tumor pathology, surgical margins, seminal vesicle invasion, lymph node metastasis, Gleason score, TNM staging, risk classification, and survival, and described the patients' interventions and treatments. All patients and their families signed informed consent forms before enrollment. Results: In our study, we observed a 3-year survival rate of 77.14% for patients with prostate cancer and normal PSA concentrations. This outcome can be attributed to several clinical characteristics, including the absence of obvious clinical presentation, a high detection rate of seminal vesicle invasion, as well as high Gleason scores and risk levels. The primary outcome, 3-year survival rate, reflects the long-term prognosis of this specific patient subgroup. We also conducted correlation analyses to better understand the relationships between these clinical characteristics and patient survival.

Bartonella Prevalence and Genome Sequences in Rodents in Some Regions of Xinjiang, China.

In this study, we investigated Bartonella infection and its genetic diversity in rodents in Beitun, Xinjiang Uygur Autonomous Region, China. Small mammals were captured using snap traps at four sampling sites in 2018. Spleen and liver tissues were collected and cultured to isolate Bartonella strains. Whole-genome sequencing was performed on the strains identified as Bartonella by gltA gene PCR, and the average nucleotide identity (ANI) of the genomes was calculated by using FastANI v1.33. Phylogenetic trees were constructed for the samples positive for Bartonella spp. by the gltA PCR assay based on 1,290-bp gltA genes, 2,903-bp rpoB genes, and core-genome single nucleotide polymorphisms (SNPs). Among 66 rodents, 11 were positive for Bartonella, with an infection rate of 16.67%. The rodent infection rates in different tissues (χ2 = 2.133; P = 0.242), species (χ2 = 9.631; P = 0.141), and habitats (χ2 = 4.309; P = 0.312) did not show statistical differences. Bartonella spp. isolated from the rodents were phylogenetically divided into six clades (two different Bartonella species were detected in two rodents). By comparing phylogenetic trees based on gltA genes, rpoB genes, and SNPs, we found that the topological structures of several evolutionary trees are different. However, the Bartonella strains isolated in this study were clustered into six clusters in different phylogenetic trees. Broad distributions and high genetic diversity of Bartonella strains were observed among rodents in Beitun, Xinjiang. IMPORTANCE Rodent-borne Bartonella species have been associated with zoonotic diseases. Bartonella species such as Bartonella elizabethae, Bartonella grahamii, and Bartonella tribocorum can cause disease in humans. Humans can be infected by blood-sucking arthropods through the scratches and bites of an infected reservoir host or via contact with infectious rodents. Xinjiang is one of the provinces with the most abundant species of Bartonella in China, but there are few reports about the prevalence of Bartonella in the Beitun area. This research aims to investigate the occurrence and prevalence of Bartonella infection in rodents at these sampling sites and provide a basis for the prevention and control of rodent Bartonella species in Beitun and the surrounding areas of Xinjiang.

HMG20A Inhibit Adipogenesis by Transcriptional and Epigenetic Regulation of MEF2C Expression.

Obesity and its associated metabolic disease do serious harm to human health. The transcriptional cascade network with transcription factors as the core is the focus of current research on adipogenesis and its mechanism. Previous studies have found that HMG domain protein 20A (HMG20A) is highly expressed in the early stage of adipogenic differentiation of porcine intramuscular fat (IMF), which may be involved in regulating adipogenesis. In this study, HMG20A was found to play a key negative regulatory role in adipogenesis. Gain- and loss-of-function studies revealed that HMG20A inhibited the differentiation of SVF cells and C3H10T1/2 cells into mature adipocytes. RNA-seq was used to screen differentially expressed genes after HMG20A knockdown. qRT-PCR and ChIP-PCR confirmed that MEF2C was the real target of HMG20A, and HMG20A played a negative regulatory role through MEF2C. HMG20A binding protein LSD1 was found to alleviate the inhibitory effect of HMG20A on adipogenesis. Further studies showed that HMG20A could cooperate with LSD1 to increase the H3K4me2 of the MEF2C promoter and then increase the expression of MEF2C. Collectively, these findings highlight a role for HMG20A-dependent transcriptional and epigenetic regulation in adipogenesis.

Corrigendum: Tanshinone IIA Inhibits Epithelial-to-Mesenchymal Transition Through Hindering ß-Arrestin1 Mediated ß-Catenin Signaling Pathway in Colorectal Cancer.

[This corrects the article DOI: 10.3389/fphar.2020.586616.].

Jianpi Jiedu Recipe inhibits colorectal cancer liver metastasis via regulating ITGBL1-rich extracellular vesicles mediated activation of cancer-associated fibroblasts.

BACKGROUND: Extracellular vesicles (EVs) contribute greatly to the formation of pre-metastatic niche and tumor metastasis. Our previous study has revealed that tumor-derived ITGBL1 (integrin beta- like 1)-rich EVs activate fibroblasts through the NF-κB signaling to promote colorectal cancer (CRC) metastasis. Targeting ITGBL1-loaded EVs may be a new and effective therapy for treating CRC metastasis. Simultaneously, our preliminary clinical trial has demonstrated that Jianpi Jiedu Recipe (JPJDR) was an ideal alternative traditional Chinese medicine for the prevention and treatment of CRC metastasis. However, the underlying mechanism of JPJDR in the prevention of CRC metastasis is not clear. In this study, we will investigate the regulatory effect of JPJDR on ITGBL1 levels in CRC-derived EVs, and to detect how JPJDR regulate ITGBL1-rich EVs mediated activation of fibroblasts to inhibit CRC metastasis. METHODS: EVs derived from CRC cells with/without JPJDR treatment were obtained by ultracentrifugation, following by characterization with electron microscopy, LM10 nanoparticle characterization system and western blot. The migration and growth of CRC cells were tested by transwell assay, wound healing assay and colony formation assay. The effect of JPJDR on the fibroblasts-activation associated inflammatory factors including IL-6, IL-8 and α-SMA was detected by real-time PCR. The levels of IL-6, IL-8 and α-SMA in the cell culture supernatant were detected by ELISA. The protein expressions of TNFAIP3, ITGBL1, p-NF-κB, IκBα and ß-actin were detected by western blot. Liver metastasis model in mice was established by injecting MC38 single cell suspension into the spleen of mice to observe the effect of JPJDR on CRC liver metastasis. Immunohistochemistry were applied to detect the expression of ITGBL1 and TNFAIP3 in the liver metastatic tissues. Tissue immunofluorescence detection was performed to observe the regulatory effect of JPJDR on the ITGBL1-NF-κB signaling pathway. Cancer-associated fibroblasts (CAFs) in the liver metastatic tissues were sorted and characterized by platelet-derived growth factor receptor ß (PDGFRß) with flow cytometry, following by the detection of inflammatory factors including IL-6, IL-8 and α-SMA using real-time PCR. RESULTS: JPJDR reduced the ITGBL1 levels in CRC cells-derived EVs. JPJDR inhibited the migration and growth of CRC cells via regulating ITGBL1-rich EVs mediated fibroblasts activity. Mechanically, JPJDR decreased fibroblasts activation by regulating ITGBL1-rich EVs mediated TNFAIP3-NF-κB signaling. Further in vivo experiments demonstrated that JPJDR reduced CRC liver metastasis by regulating ITGBL1-rich EVs secretion from CRC and blocked the fibroblasts activation by regulating ITGBL1-TNFAIP3- NF-κB signaling. CONCLUSION: Our research demonstrated that JPJDR preventd CRC liver metastasis via down-regulating CRC-derived ITGBL1-loaded EVs mediated activation of CAFs, providing the experimental evidence for the clinical application of JPJDR in the prevention and treatment of CRC metastasis. More importantly, our study confirmed the great benefits of therapeutic targeting the EVs-mediated metastasis and warranted future clinical validation.

Ultra-compact VCSEL scanner for high power solid-state beam steering.

We demonstrate the lateral monolithic integration of a tunable first-order surface-grating loaded vertical-cavity surface-emitting laser (VCSEL) and slow-light waveguide with fan-beam steering and amplifier function. Shallow Bragg-grating formed on the surface of a VCSEL section enables the selection of a single slow-light mode, which can be coupled into the integrated long waveguide and amplified through pumping the amplifier above threshold. We obtained over 3W amplified slow-light power with single-mode operation and over 4W amplified quasi-single-mode power under pulsed current injection. To the best of our knowledge, this is the highest output power for single-mode VCSELs. Solid-state beam steering of the device is also demonstrated with 9° fan-beam steering range and 200 resolution points.

Bilateral inguinal lymphadenectomy using simultaneous double laparoscopies for penile cancer: A retrospective study.

OBJECTIVE: To assess the feasibility, safety, and efficiency of bilateral inguinal lymphadenectomy using simultaneous double laparoscopies for penile cancer. MATERIALS AND METHODS: We reviewed retrospectively the records of 65 patients who underwent inguinal lymph nodes dissection (ILND) for penile cancer from January 2012 to May 2019. Treatments included open ILND (OILND, 19 patients), video-endoscopic inguinal lymphadenectomy (VEIL) using single laparoscopy (S-VEIL, 24 patients), and VEIL using double laparoscopies (D-VEIL, 22 patients). We evaluated the peri-operative and short-term oncological outcomes of the three groups. RESULTS: The mean operative time of D-VEIL (105.91 ± 10.87 minutes) was significantly shorter than the other two groups, OILND shorter than S-VEIL (160.47 ± 13.74 minutes, 191.67 ± 17.80 minutes, respectively) (P < 0.001). Intraoperative blood loss in the S-VEIL and D-VEIL groups were 53.54 ± 8.78 and 48.41 ± 13.22 ml, respectively; they were significantly lower than that of the OILND group (99.74 ± 9.64 ml; P < 0.001). The numbers of unilateral and total lymph nodes harvested were similar in all groups. The complication rates in the S-VEIL group (4.2%) and the D-VEIL group (4.5%) were significantly lower than that in the OILND group (63.2%; P < 0.001). Compared with open surgery (13.53 ± 1.74 days for hospitalization; 11.37 ± 1.92 days for the left side of drain, 11.95 ± 1.84 days for the right side), the two VEIL groups had significantly shorter drainage tube residence time (7.42 ± 2.02 and 7.32 ± 1.52 days, respectively for the left side; 7.63 ± 1.81 and 7.27 ± 1.58 days, respectively for the right side), shorter postoperative hospitalization (9.46 ± 1.64 and 9.00 ± 1.83 days, respectively) (P < 0.001). There were no statistically significant differences in rates of regional recurrence and short-term survival among the three groups. CONCLUSION: Bilateral inguinal lymphadenectomy using double laparoscopies simultaneously can provide adequate oncological outcomes safely and efficiently, and carry significantly lower morbidity than OILND, at a median follow-up of 33.5 months. It is a more time-saving surgical approach for penile cancer patients who need bilateral ILND.

Naringenin Prevents Oxidative Stress and Inflammation in LPS-Induced Liver Injury through the Regulation of LncRNA-mRNA in Male Mice.

Inflammation accompanies hepatic dysfunction resulting from tissue oxidative damage. Naringenin (Nar), a natural flavanone, has known antioxidant and anti-inflammatory activities, but its mechanism of action in the regulation of liver dysfunction requires further investigation. In this study, the role of naringenin in lipopolysaccharide (LPS)-induced hepatic oxidative stress and inflammation was explored, as well as its mechanism by transcriptome sequencing. The results indicated that compared with the LPS group, Nar treatment caused a significant increase in the mRNA levels of antioxidant factors glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM), yet the expression of related inflammatory factors (MCP1, TNFα, IL-1ß and IL-6) showed less of an increase. RNA sequencing identified 36 differentially expressed lncRNAs and 603 differentially expressed mRNAs. KEGG enrichment analysis indicated that oxidative stress and inflammation pathways are meticulously linked with naringenin treatment. The Co-lncRNA-mRNA network was also constructed. Tissue expression profiles showed that lncRNA played a higher role in the liver. Subsequently, expression levels of inflammatory factors indicated that lncRNAs and target mRNAs were significantly reduced after naringenin treatment in mouse liver AML12 cells and obese mouse. These results suggest that naringenin helps to prevent liver dysfunction through the regulation of lncRNA-mRNA axis to reduce oxidative stress and inflammatory factors.

Mufangji Decoction and Its Active Ingredient Patchouli Alcohol Inhibit Tumor Growth through Regulating Akt/mTOR-Mediated Autophagy in Nonsmall-Cell Lung Cancer.

BACKGROUND: Nonsmall-cell lung cancer (NSCLC) is the main type of lung cancer, whose morbidity and mortality rank first among malignant tumors. More than 70% of NSCLC patients are diagnosed at locally advanced or advanced stage, missing the best operation period. Chemotherapy and targeted therapy are important means for the treatment of advanced NSCLC, but various side effects seriously affect the curative effect and the life quality of NSCLC patients. Our previous clinical practice has shown that Mufangji Decoction, a classic traditional Chinese medicine, has a significant curative effect in the treatment of NSCLC, but the specific mechanism is not clear. This study intends to explore the potential mechanism of Mufangji Decoction and its active ingredient patchouli alcohol against NSCLC and to provide a scientific basis for the prevention and treatment of NSCLC by traditional Chinese medicine. METHODS: The in vivo and in vitro experiments were performed to evaluate the antitumor effects and investigate the underlying mechanism of Mufangji Decoction and its active ingredient patchouli alcohol. Network pharmacology was applied to analyze the effective ingredients and potential targets or signaling pathways of Mufangji Decoction. RESULTS: Our current study shows that Mufangji Decoction can effectively inhibit the growth of subcutaneous transplantation of NSCLC. The following network pharmacological analysis and in vivo experiment suggest that patchouli alcohol is one of the main active ingredients of Mufangji Decoction and exerts antitumor effects. Further mechanism investigation reveals that the antitumor effect of patchouli alcohol is related to the induction of Akt/mTOR signaling pathway-mediated autophagy in NSCLC cells. CONCLUSION: Mufangji Decoction and its active ingredient patchouli alcohol might exert their antitumor effects in NSCLC partly through regulating Akt/mTOR-mediated autophagy, providing the evidence that traditional Chinese medicine might be a key approach for NSCLC treatment via targeting the Akt/mTOR signal axis.

[Quantitative analysis methods of white matter microstructure based on diffusion tensor imaging and its application in chronic pain research].

As the two essential components, the white matter and gray matter compose the central nervous system of the brain. Widely known that axons of neurons mainly form the white matter, and these formed nerve fibers are responsible for transmitting information among various brain regions to achieve the coordinated operation of the entire brain. Early research on the white matter could only be done by dissecting living animals or human cadavers, until Basser et al. proposed diffusion tensor imaging (DTI) technology in 1994, which could detect the diffusion characteristics of water in the brain in vivo noninvasively. Accordingly, this technology could be applied to investigate the diffusion movement of water in white matter to obtain the information of direction and micro-anatomy of white matter fiber bundles. With the advancement on the display and analysis of the anatomical structure of white matter fiber bundles, the exploration of microscopic pathological changes, and the assistance of clinical diagnosis and neurophysiological research, DTI technology has become one of the most popular topics in brain science research. Chronic pain refers to pain lasting more than three months, which not only seriously affects the patient's physical and social functions, but also dramatically reduces the quality of life. It was reported that long-term pain stimulation might cause pathological remodeling of the central nervous system, and abnormalities in white matter were found in imaging examinations of patients with chronic pain. This review introduces the quantitative analysis methods of white matter fiber bundle microstructure based on DTI and its application in chronic pain, and further discusses the application value of DTI technology on clinical research of chronic pain.

Posaconazole and fluconazole prophylaxis during induction therapy for pediatric acute lymphoblastic leukemia.

PURPOSE: To assess and compare the efficacy and safety of posaconazole with fluconazole for the prevention of invasive fungal infections in children who were undergoing induction therapy for acute lymphoblastic leukemia (ALL). To develop an approach to predict invasive fungal infections in ALL patients who accepted posaconazole prophylaxis. METHODS: This was a single-center, retrospective cohort study of patients with newly diagnosed ALL, comparing invasive fungal infections in patients who received no prophylaxis, posaconazole prophylaxis, or fluconazole prophylaxis during induction therapy. A propensity score-weighted logistic regression model was used to adjust for confounders. Hepatotoxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria. RESULTS: Out of the 155 ALL patients, 60 received no prophylaxis, 70 received posaconazole prophylaxis, and 25 received fluconazole prophylaxis. Posaconazole prophylaxis reduced the odds of invasive fungal infections by > 60%, prolonged infection-free survival significantly, and did not increase the risk of hepatotoxicity. Additionally, we found that the combination of age at diagnosis, clinically documented bacterial infection in the first 15 days of induction therapy, and absolute neutrophil count (ANC) curve enabled significant prediction of the susceptibility to infections after receiving posaconazole prophylaxis. CONCLUSIONS: Our findings supported using targeted prophylaxis with posaconazole in ALL children undergoing induction chemotherapy. Age, clinically documented bacterial infection and ANC are important predictors of invasive fungal infections in patients with posaconazole prophylaxis.

White matter characteristics between amygdala and prefrontal cortex underlie depressive tendency in end stage renal disease patients before the dialysis initiation.

Depression is one of the common incidental symptoms in end-stage renal disease (ESRD) patients, empirically overlooked. Reproducible results observed that altered interregional white matter (WM) connections between depression-related brain regions (thalamus, amygdala, and prefrontal cortex (PFC)) in the human brain were closely associated with depression. Whether the depressive tendency of ESRD patients is also association with the WM connections is remains unknown. To address this problem, 56 ESRD patients before dialysis initiation and 56 healthy controls (HCs) were scanned with diffusion tensor imaging. According to the diagnostic and statistical manual of mental disorders, ESRD patients were separated into with and without depressive tendency groups. Twenty-five essential metabolites were tested in ESRD. The tractography atlas-based analysis and multiple regression analysis were implemented to gain features which could map the depressive tendency variability across ESRD. For metabolites, the levels of thrombocytes and calcium have significant differences between with and without depressive tendency groups. For WM microstructure, depressive tendency ESRD patients had abnormal WM diffusion properties along the fiber tracts of the amygdala-PFC. Compared with the features which were extracted from the group-difference of WM or metabolites, only WM features combinations (1000 bootstrap samples; 5000 permutation tests) along the fiber tract of the amygdala-PFC was a significant predictor of either with or without depressive tendency. Our findings suggested that the advanced neuroprotection may be planned before dialysis initiation, and the WM characteristics of amygdala-PFC may be a potential neuromarkers for the early diagnosis of depressive tendency in ESRD patients before dialysis initiation.

miR-144-3p inhibits proliferation and invasion of bladder cancer T24 cells through targeted regulation of E2F3 / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the expression of miR144-3p in bladder cancer tissues and cells and its effect on the proliferation and invasion of T24 cells. Methods: A total of 36 cases of bladder cancer tissue specimens and 10 cases of normal bladder epithelial tissue specimens were collected from Tangdu Hospital of Air Force Medical University during February 2018 and December 2018. In addition, bladder cancer T24 cell line and normal urothelial cell line SV-HUC-1 were also collected for this study. The levels of miR144-3p in bladder cancer tissues and cells were detected by qPCR methods. The miR-144-3p mimics and miR-NC were transfected into T24 cells by LipofectamineTM 2000, respectively. The proliferation, cell cycle distribution and invasion abilities were detected by MTT, Flow cytometry and Transwell chamber methods, respectively. TargetScan software was used to predict the binding site between miR-144-3p and E2F3 (E2F transcription factor 3); Dual luciferase reporter gene assay was used to verify the relationship between miR-144-3p and E2F3; and WB was used to detect the expression levels of miR-144-3p and E2F3 in cells. Results: The expression of miR-144-3p was downregulated in bladder cancer tissues and cells (all P<0.01). In addition, the expression level of miR-144-3p in muscular invasive bladder cancer tissues was significantly lower than that in non-muscular invasive bladder cancer tissues (P<0.05). Dual luciferase reporter gene assay confirmed that there was a targeted relationship between miR-144-3p and E2F3. Overexpression of miR-144-3p inhibited the proliferation and invasion of T24 cells (all P<0.01) and downregulated the expression of E2F3 (P<0.01); upregulation of E2F3 could reverse the inhibitory effect of miR-144-3p overexpression on proliferation and invasion of T24 cells. Conclusion: miR-144-3p has low expression level in bladder cancer tissues. It inhibits proliferation and invasion of bladder cancer cells by downregulating E2F3.

Tanshinone IIA Inhibits Epithelial-to-Mesenchymal Transition Through Hindering ß-Arrestin1 Mediated ß-Catenin Signaling Pathway in Colorectal Cancer.

Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to be able to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the mechanisms of anti-metastatic effect of Tan IIA on CRC are not well explored. A number of studies indicate that epithelial-to-mesenchymal transition (EMT) plays an important role in CRC metastasis, and our previous studies demonstrate that ß-arrestin1could regulate EMT in CRC partly through ß-catenin signaling pathway. In this work, we investigate whether Tan IIA could regulate EMT in CRC through ß-arrestin1-mediated ß-catenin signaling pathway both in vivo and in vitro. Our results showed that Tan IIA inhibited lung metastases of CRC cells in vivo and extended the survival time of mice with CRC. In vitro, Tan IIA increased the expression of E-cadherin, decreased the expression of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found that the mechanism of action of Tan IIA in regulating EMT and metastasis is associated with the suppression of ß-arrestin1 expression, resulting in the increase of GSK-3ß expression, reduction of ß-catenin nuclear localization, thereby decreased the activity of ß-catenin signaling pathway. Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via ß-arrestin1-mediated ß-catenin signaling pathway and provided support for using Tan IIA as anti-metastatic agents in CRC.

MIR22HG regulates miR-486/PTEN axis in bladder cancer to promote cell proliferation.

The tumor suppressive role of MIR22HG has been studied in several types of cancer. We analyzed the TCGA dataset and found the down-regulation of MIR22HG in bladder cancer (BC). Bioinformatics analysis predicted the interaction between MIR22HG and miR-486. The direct interaction between MIR22HG and miR-486 was also confirmed by dual luciferase assay. However, overexpression of these two factors did not significantly affect the expression of each other. Interestingly, overexpression of MIR22HG led to up-regulated phosphatase and tensin homolog (PTEN), which is a target of miR-486. In cell proliferation assay, overexpression of MIR22HG and PTEN led to decreased rates of BC cell proliferation. Moreover, overexpression of miR-486 played an opposite role and attenuated the effects of overexpression of MIR22HG and PTEN. Therefore, MIR22HG regulates miR-486/PTEN axis to promote cell proliferation in BC.