Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma.

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a malignant renal tumor that is highly prone to metastasis and recurrence. The exact pathogenesis of this cancer is still not well understood. This study aimed to identify novel hub genes in renal clear cell carcinoma and determine their diagnostic and prognostic value. METHODS: Intersection genes were obtained from multiple databases, and protein-protein interaction analysis and functional enrichment analysis were performed to identify key pathways related to the intersection genes. Hub genes were identified using the cytoHubba plugin in Cytoscape. GEPIA and UALCAN were utilized to observe differences in mRNA and protein expression of hub genes between KIRC and adjacent normal tissues. The Wilcoxon rank sum test was used to analyze hub gene levels between paired KIRC and matched non-cancer samples. IHC results were obtained from the HPA online database, and according to the median gene expression level, they were divided into a high-expression group and a low-expression group. The correlation of these groups with the prognosis of KIRC patients was analyzed. Logistic regression and the Wilcoxon rank sum test were used to test the relationship between SLC34A1 level and clinicopathological features. The diagnostic value of SLC34A1 was evaluated by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Cox regression analysis was used to analyze the relationship between clinicopathological features, SLC34A1 expression, and KIRC survival rate. LinkedOmics was used to obtain the genes most related to SLC34A1 and their functional enrichment. Genetic mutations and methylation levels of SLC34A1 in KIRC were obtained from the cBioPortal website and the MethSurv website, respectively. RESULTS: Fifty-eight ccRCC differential genes were identified from six datasets, and they were mainly enriched in 10 functional items and 4 pathways. A total of 5 hub genes were identified. According to the GEPIA database analysis, low expression of SLC34A1, CASR, and ALDOB in tumors led to poor prognosis. Low expression of SLC34A1 mRNA was found to be related to clinicopathological features of patients. SLC34A1 expression in normal tissues could accurately identify tumors (AUC 0.776). SLC34A1 was also found to be an independent predictor of ccRCC in univariate and multivariate Cox analyses. The mutation rate of the SLC34A1 gene was 13%. Eight of the 10 DNA methylated CpG sites were associated with the prognosis of ccRCC. SLC34A1 expression in ccRCC was positively correlated with B cells, eosinophils, neutrophils, T cells, TFH, and Th17 cells, and negatively correlated with Tem, Tgd, and Th2 cells. CONCLUSION: The expression level of SLC34A1 in KIRC samples was found to be decreased, which predicted a decreased survival rate of KIRC. SLC34A1 may serve as a molecular prognostic marker and therapeutic target for KIRC patients.

Factors associated with balance impairments in the community-dwelling elderly in urban China.

BACKGROUND: Identification of factors relevant to balance performance impairments in the elderly population was critical for developing effective interventions and preventions. However, there have been very limited data available based on large scale studies. The present study identified factors that independently contributed to performance impairments in overall balance, domains of static balance, postural stability, and dynamic balance, and individual items. METHODS: A total of 1984 community-dwelling Chinese elderly from urban areas of Shanghai were recruited. Information on demographic characteristic, exercise, and health status were collected with a face-to-face interview. Balance performances were assessed on site by trained investigators based on the X16 balance testing scale. To identify the effectors, ordinal logistic regression analysis was applied for overall balance, static balance, postural stability, and dynamic balance. Binary logistic regression analysis was used for 16 items. RESULTS: The community-dwelling elderly residents were aged from 60 to 97 years old. With increases of age, risks of impairments in overall balance increased gradually (ORs from 1.26 to 3.20, all P < 0.01). In the elderly with overweight and obesity, there was higher proportion of balance impairments compared to the elderly with normal BMI (OR = 1.26, P < 0.001). Regular exercise every week was associated with reduced risks of balance impairments (ORs from 0.63 to 0.73, all P < 0.001). Presences with vision lesion (ORs from 1.28 to 1.59, all P < 0.001), moderate hearing impairment (OR = 1.54, P < 0.001), somesthesis dysfunction (ORs from 1.59 to 13.26, all P < 0.001), and cerebrovascular disease (OR = 1.45, P = 0.001) were related to increased risks of balance impairments. Likewise, age, exercise, vision, hearing, somesthesis, and cerebrovascular disease were significantly associated with static balance, postural stability, and dynamic balance. Both overweight and obesity and underweight were associated with higher proportions of dynamic balance impairments. Regular exercise was significantly related to reduced risks of impairments in 15 out of the 16 items. CONCLUSIONS: In the elderly, age, overweight and obesity, exercise, vision, hearing, somesthesia, and cerebrovascular disease were dominant factors associated with impairments in overall balance, domains of static balance, postural stability, and dynamic balance, and most individual items. TRIAL REGISTRATION: Not applicable.

AUP1 regulates lipid metabolism and induces lipid accumulation to accelerate the progression of renal clear cell carcinoma.

Lipid metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Lipid accumulation affects cellular energy homeostasis, biofilm synthesis, lipid signal transduction, and phenotypic transformation in ccRCC. Herein, a prognostic-related model was constructed, and the prognostic utility of AUP1, a lipid droplet-regulating very low-density lipoprotein assembly factor, in ccRCC was determined through multiparameter analysis. AUP1 expression was significantly higher in clinical samples than in normal tissues and was closely associated with the clinical stage. The inhibition of AUP1 expression impaired the proliferation, migration, and invasion of ACHN and A498 ccRCC cells in vitro and in vivo. RNA-seq analysis revealed that AUP1 inhibition can significantly reduce the contents of intracellular triglyceride and cholesterol and regulate cell growth by cell cycle arrest, promoting apoptosis and reversing epithelial-mesenchymal transition. AUP1 regulated the synthesis of cholesterol esters and fatty acids (FAs) in ccRCC cells by targeting sterol O-acyltransferase 1 and partially promoted the progression of ccRCC. AUP1 also induced lipid accumulation in ccRCC by promoting the de novo synthesis of FAs (inhibiting protein kinase AMP-activated catalytic subunit alpha 2), inhibiting the rate-limiting enzyme of FA ß oxidation (carnitine palmitoyltransferase 1A), regulating the key enzyme of lipolysis (monoglyceride lipase, MGLL), and inhibiting the lipid transporter StAR-related lipid transfer domain containing 5 (STARD5). However, it did not affect the intracellular cholesterol synthesis pathway. The differential expression and prognostic significance of MGLL and STARD5 in ccRCC should be further studied. AUP1 may serve as a new and effective potential target and prognostic marker for ccRCC.

circRNA_101277 Influences Cisplatin Resistance of Colorectal Cancer Cells by Modulating the miR-370/IL-6 Axis.

Background: Colorectal cancer (CRC) is among the most prevalent malignancies globally. Early detection of precancerous lesions through routine colonoscopy has led to a dramatic reduction in CRC-related incidence and mortality among those between the ages of 50 and 70. However, in those where the disease progresses to an advanced stage, chemotherapy remains the primary available treatment option, and the associated 5-year survival rate remains low. The identification of genes associated with CRC chemoresistance would thus be a beneficial approach to identifying novel treatments for this deadly disease. Methods: The expression of circRNA_101277, miR-370, and IL-6 was assessed via qRT-PCR. IL-6 levels were measured with a human IL-6 ELISA kit based on the provided protocols. CRC cellular proliferation and cisplatin IC50 values were quantified via MTT assays. Luciferase assays were used to detect circRNA_101277 and miR-370 binding sites or miR-370 and IL-6 binding sites. Results: circRNA_101277 was increased in CRC tissues compared with control samples. circRNA_101277 overexpression was evident in CRC cells, and knockdown of this circRNA suppressed cellular proliferation and cisplatin resistance in these cancer cells. At a mechanistic level, circRNA_101277 was found to function by sequestering miR-370, thereby upregulating the miR-370 target gene IL-6 and promoting cisplatin resistance via this miR-370/IL-6 axis. Conclusion: In summary, our data highlight circRNA_101277 as a novel driver of CRC cell cisplatin resistance that functions by sequestering miR-370 and thereby enhancing IL-6 expression. These findings suggest that this circRNA_101277/miR-370/IL-6 axis may represent a critical axis of chemoresistance in CRC that can be targeted to diagnose and/or treat this cancer.

Effectiveness of WeChat-group-based parental health education in preventing unintentional injuries among children aged 0-3: randomized controlled trial in Shanghai.

BACKGROUND: Unintentional injuries to children are a major public health problem. The online social media is a potential way to implement health education for caregivers in online communities. Using WeChat, a free and popular social media service in China, this study evaluated the effectiveness of social online community-based parental health education in preventing unintentional injuries in children aged 0-3. METHODS: We recruited 365 parents from two community health centers in Shanghai and allocated them into intervention and control groups randomly. Follow-up lasted for one year. The intervention group received and followed their WeChat group and a WeChat official account for dissemination of reliable medical information. The control group received only the WeChat group. RESULTS: Between the intervention and control groups, changes in unintentional injuries (OR = 1.71, 95% CI: 1.02-2.87, P = .04), preventability (ß = 0.344, 95% CI: 0.152-0.537, P < .001), daily supervision behavior (ß = 0.503, 95% CI: 0.036-0.970, P = .04), and behaviors for preventing specific injuries (ß = 2.198, 95% CI: 1.530-2.865, P < .001) were significantly different, and change in first-aid skills for treating a tracheal foreign body were nearly significant (P = .06). CONCLUSIONS: The WeChat-group-based parental health education can reduce the occurrence of unintentional child injuries by improving parents' skills, beliefs, and behaviors. Online social communities promote health education and reduce unintentional injuries among children. TRIAL REGISTRATION: ChiCTR1900020753. Registered on January 17, 2019.

Mechanisms Affecting Physical Aging and Swelling by Blending an Amphiphilic Component.

Polymer blending is a promising method to overcome stability obstacles induced by physical aging and swelling of implant scaffolds prepared from amorphous polymers in biomedical application, since it will not bring potential toxicity compared with chemical modification. However, the mechanism of polymer blending still remains unclearly explained in existing studies that fail to provide theoretical references in material R&D processes for stability improvement of the scaffold during ethylene oxide (EtO) sterilization, long-term storage, and clinical application. In this study, amphiphilic poly(ethylene glycol)-co-poly(lactic acid) (PELA) was blended with amorphous poly(lactic-co-glycolic acid) (PLGA) because of its good miscibility so as to adjust the glass transition temperature (Tg) and hydrophilicity of electrospun PLGA membranes. By characterizing the morphological stability and mechanical performance, the chain movement and the glass transition behavior of the polymer during the physical aging and swelling process were studied. This study revealed the modification mechanism of polymer blending at the molecular chain level, which will contribute to stability improvement and performance adjustment of implant scaffolds in biomedical application.

Environmental hazards increase the fall risk among residents of long-term care facilities: a prospective study in Shanghai, China.

BACKGROUND: Falls are one of the most common safety concerns in long-term care facilities (LTCFs). OBJECTIVE: To evaluate the associations between the environmental hazards and the fall risk in LTCF residents. DESIGN: Prospective study with 12-month follow-up. SETTING: Twenty-five LTCFs in a central district of Shanghai. SUBJECTS: A total of 739 older people participated and 605 were followed up for 1 year. METHODS: Environmental hazards were measured using a 75-item Environment Assessment Checklist, and the associations between environmental hazards and falls were analysed using univariate and multilevel logistic regressions. RESULTS: The incidence of falls was 0.291 per person with 11 items/LTCF of hazards on average. The most common hazard items were inadequate/inappropriate handrails (96% LTCFs; odds ratio (OR) for falls: 1.88 [95% confidence interval: 1.13-3.13]), unsafe floors (92% LTCFs; 2.50 [1.11-5.61]) and poor lighting (84% LTCFs; 2.01 [1.10-3.66]). Environmental hazards were most frequently distributed in bedrooms (96% LTCFs), shared toilets/showers (80% LTCFs) and individual toilets/showers (68%LTCFs) and accounted for 20% of the differences in falls occurrence among the LTCFs. After adjusting for individual intrinsic and fall-related behavioural factors, it is found that having more than eight environmental hazard items increased the fall risk among older residents (adjusted OR = 4.01 [1.37-11.73]). Environmental hazards and toilet visits at night showed significant associations with falls (adjusted OR = 5.97 [1.10-32.29]). CONCLUSIONS: The high prevalence of environmental hazards associated with falls highlights the urgency of improving environmental safety in LTCFs and the need of environmental safety policies, resource allocation and interventions in falls prevention.

Characteristics of balance performance in the Chinese elderly by age and gender.

BACKGROUND: Population aging has been an emerging public and health concern globally. Balance performance can be applied as an indicator of functional status and a predictor of health outcomes in the elderly. However, reference data of balance performance in the elderly generated from large scale studies have been very limited. In research and geriatric assessment settings, the age and gender specific data on balance performance are indispensable prerequisites for identifying subpopulation with and at risk of impairments and subsequently implementing targeted interventions in clinics and public health to improve their balance performance. METHODS: A total of 1984 elderly subjects aged 60 to 97 years from community settings in urban China were investigated. The balance performances together with 3 individual domains and 16 items were evaluated using the X16 balance testing scale. RESULTS: In the elderly, with age increases each item, individual domain, and overall balance performance scores decreased gradually. Meanwhile, individual variations of individual domains and overall balance performance were all increased over age. Relative to levels of 60- years, postural stability and overall balance performance decreased significantly since 65 years old, static balance and dynamic balance capacities started to decrease significantly since 70 years old. There was no significant difference in each balance domain and overall balance performance between men and women. Across age groups, portions of individuals able to perform task 4, 8 and 11 successfully were the lowest amongst their corresponding domains static balance, postural stability, and dynamic balance, respectively. Similar patterns were observed in both men and women. Balance performances were categorized into poor, fair, and good groups with scores of 0 to 10, 11 to 17, and 18 to 20, respectively. With increases of age, proportions with poor and fair balance capacities elevated stably. CONCLUSIONS: In the elderly, with advances in age, abilities of overall balance performance, individual domains of static balance, postural stability, and dynamic balance, and successful performances on specific tasks declined gradually and stably. The deterioration started to be obvious since 65-75 years. Men and women had similar patterns.

Teneligliptin prevents doxorubicin-induced inflammation and apoptosis in H9c2 cells.

Doxorubicin is a common chemotherapy treatment with numerous negative ramifications of use such as nephropathy and radiation-induced cardiotoxicity. Doxorubicin has been shown to cause overexpression of proinflammatory cytokines including MCP-1 and IL-1ß via activation of the NF-κB pathway. Furthermore, apoptosis marked by dysregulation of the Bax/Bcl-2 ratio and oxidative stress and the production of reactive oxygen species (ROS) are also exacerbated by doxorubicin administration. Teneligliptin is part of the wider dipeptidyl peptidase-4 (DPP-4) inhibitor family which has until recently been almost exclusively used to treat type 2 diabetes mellitus. DPP-4 inhibitors such as teneligliptin control the overexpression of glucagon-like peptidase 1 (GLP-1) which has the downstream effects of general insulin resistance and high blood sugar levels. Our findings indicate a significant protective effect of teneligliptin against the aftereffects of doxorubicin as a chemotherapy treatment. This protective effect includes but is not limited to the reduction of inflammation and the mitigation of dysregulated apoptosis, as evidenced by reduced expression of IL-1ß and MCP-1, inhibition of NF-κB activation, and improvement of the Bax/Bcl-2 ratio. The aim of the present study was to establish teneligliptin as a potentially useful agent for the treatment of radiation-induced cardiotoxicity, and our findings support this notion.

IL-36 s in the colorectal cancer: is interleukin 36 good or bad for the development of colorectal cancer?

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a major killer. Host immunity is important in tumorigenesis. Direct comparison among IL-36α, IL-36ß and IL-36γ in the prognosis of CRC is unclear. METHODS: CRC tissue arrays were generated from colorectostomy samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, IL-36α, IL-36ß and IL-36γ were determined, in comparison to non-cancer tissues. RESULTS: A significant association was observed between colonic IL-36α, IL-36ß or IL-36γ and the presence of cancer (with all P < 0.0001). Using ROC curve analysis, specificity and sensitivity of IL-36α, IL-36ß or IL-36γ were confirmed, with area under the curve (AUC) values of 0.68, 0.73 and 0.65, respectively. Significant differences in survival were observed between IL-36αhigh and IL-36αlow (P = 0.003) or IL-36γhigh and IL-36γlow (P = 0.03). Survival curves varied significantly when further stratification into sub-groups, on the basis of combined levels of expression of two isotypes of IL-36 was undertaken. A significant difference was observed when levels of IL-36α and IL-36ß were combined (P = 0.01), or a combination of IL-36α plus IL-36γ (P = 0.002). The sub-groups with a combination of IL-36αhigh plus IL-36ßhigh, or IL-36αhigh plus IL-36γlow exhibited the longest survival time among CRC patients. In contrast, the sub-groups of IL-36αlow plus IL-36ßhigh or IL-36αlow plus IL-36γhigh had the shortest overall survival. Using the log-rank test, IL-36αhigh expression significantly improved survival in patients with an invasion depth of T4 (P < 0.0001), lymph node metastasis (P = 0.04), TNM III-IV (P = 0.03) or with a right-sided colon tumour (P = 0.02). Similarly, IL-36γlow expression was significantly associated with improved survival in patients with no lymph node metastasis (P = 0.008), TNM I-II (P = 0.03) or with a left-sided colon tumour (P = 0.05). Multivariate analysis demonstrated that among IL-36α, IL-36ß and IL-36γ, only IL-36α (HR, 0.37; 95% CI, 0.16-0.87; P = 0.02) was an independent factor in survival, using Cox proportional hazards regression analysis. CONCLUSION: IL-36α or IL-36γ are reliable biomarkers in predicting the prognosis of CRC during the later or early stages of the disease, respectively. Combining IL-36α plus IL-36γ appears to more accurately predict the postoperative prognosis of CRC patients. Our data may be useful in the management of CRC.

Tripartite-motif family genes associated with cancer stem cells affect tumor progression and can assist in the clinical prognosis of kidney renal clear cell carcinoma.

Ubiquitination is presently a hot topic in the field of oncology. The tripartite-motif (TRIM) family of proteins represents one of the largest classes of putative single protein RING-finger E3 ubiquitin ligases, which play an essential role in the ubiquitination of proteins in the body. At the same time, research related to cancer stem cells (CSCs) is increasing in popularity in the field of oncology. CSCs are potentially chemically resistant and can be selectively enriched in patients receiving chemotherapy, ultimately leading to adverse outcomes, such as treatment failure and cancer recurrence. There is a close relationship between multiple TRIM family genes and CSCs. Accumulating evidence suggests that TRIM family proteins are expressed in diverse human cancers and act as regulators of oncoproteins or tumor suppressor proteins. In this study, we used biological information to explore the potential function of TRIM family genes related to CSCs in the development of pan-cancer. Kidney renal clear cell carcinoma (KIRC) is one of the deadliest malignant tumors in the world. Owing to its complex molecular and cellular heterogeneity, the effectiveness of existing KIRC-related risk prediction models is not satisfactory at present. Therefore, we focused on the potential role of these TRIM family genes in KIRC and used seven TRIM family genes to establish a prognostic risk model. This model includes TRIM16, TRIM32, TRIM24, TRIM8, TRIM27, PML, and TRIM11. In conclusion, this study provides further insight into the prognosis of KIRC, which may guide treatment.

Allicin suppresses growth and metastasis of gastric carcinoma: the key role of microRNA-383-5p-mediated inhibition of ERBB4 signaling.

Allicin is a natural product suppressing the progression of gastric carcinoma (GC). In the current study, the mechanism underlying the anti-GC effect of allicin was explored by focusing on the role of miR-383-5p/ERBB4 signaling. Two GC cell lines were treated with allicin and the effects on viability, apoptosis, migration, invasion, and miR-383-5p/ERBB4 activity in the cells were assessed. The interaction between allicin and miR-383-5p was further explored by inhibiting the miR-383-5p level. Allicin suppressed cell viability and induced apoptosis in both GC cell lines. The compound also inhibited migration and invasion of GC cells, which was associated with the up-regulation miR-383-5p and down-regulation of ERBB4. The inhibition of miR-383-5p by specific inhibitor blocked the anti-GC effect of allicin. Our results demonstrated that allicin contributed to the suppressed growth and metastasis potentials in GC cell lines. The effect was accompanied by an increased level of miR-383-5p and subsequent inhibition of ERBB4.

Falls and Fall-Related Consequences among Older People Living in Long-Term Care Facilities in a Megacity of China.

INTRODUCTION: Falls are currently the top safety problem in long-term care facilities (LTCFs) in China. Due to the increasing number of residents living in LTCFs, more evidence is needed to give a foundation for fall prevention. OBJECTIVE: This study aimed to explore the epidemiological characteristics of falls in LTCFs in central Shanghai. METHODS: The study was conducted in 21 LTCFs in a central district in Shanghai, with a capacity of 3,065 residents. A two-stage sampling method was applied in participant recruitment. Falls were recorded by LTCF staff over a 12-month period. Details of falls were obtained by face-to-face interviews. The χ2 test was used in data analyses. RESULTS: The incidence of falls was 13.5%; 64.0% falls resulted in injuries, with 32.0% involving fractures. Women had a significantly higher incidence of injurious falls than men (χ2 = 4.066, p = 0.044). Residents aged 80-89 years or in level 1 care had the highest incidence of falls with severe consequences. The incidence of falls was significantly higher at small- or medium-sized LTCFs, public LTCFs, and LTCFs with higher environmental risk levels compared to their counterparts. Most falls occurred when walking on a flat floor (28.9%) and rising up or sitting down (24.0%); 40.9% occurred during the night. Of those injured, 54.8% were treated in hospitals, and only 53.7% completely recovered. CONCLUSIONS: Though the average incidence of falls in LTCFs in Shanghai was relatively low, great variation was observed between LTCFs, and severe consequences occurred frequently. Fall prevention programmes should be evidence-based with applicable devices and individualized care services and supports. The roles of personal and institutional factors on falls warrant further study.

miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4.

BACKGROUND: miR-148-3p and miR-152-3p as the tumor suppressors have been reported in various cancer types. Our study is aimed to discuss the synergistic effect of miR-148-3p and miR-152-3p in prostate cancer (PCa). METHODS: Bioinformatics algorithm and luciferase reporter assays were used to verify whether miR-148-3p and 152-3p could bind with the 3'-untranslated region (3'-UTR) of Kruppel-like factor 4 (KLF4). PCa cell growth in vivo was analyzed using the mouse xenograft tumor model. RESULTS: miR-148-3p and miR-152-3p were reduced in PCa tumor tissues. Moreover, the protein expression of KLF4 was increased in PCa tissues. The 3'-UTR of KLF4 contained the conserved binding sites with miR-148-3p and miR-152-3p. The mimics or inhibitors of miR-148-3p and/or miR-152-3p could downregulated or upregulated KLF4 expression, respectively. miR-148-3p and miR-152-3p-induced PCa cell growth inhibition were observed both in vivo and in vitro. KLF4 overexpression had the ability to neutralize the antitumor effect of miR-148-3p/152-3p in vivo and in vitro. CONCLUSION: miR-148-3p/152-3p family could serve as tumor suppressors in PCa via repressing KLF4.

Spectroscopic and computational exploration of hypoxanthine riboside interacting with plasma albumin.

Hypoxanthine riboside (HXR) is a nucleoside essential for wobble base pairs to translate the genetic code. In this work, an absorption and luminescence study showed that HXR and human serum albumin (HSA) formed a new complex through hydrogen bonds and van der Waals forces at ground state. Fluorescence probe experiments indicated that HXR entered the first subdomain of domain II in HSA and was fixed by amino acid residues in site I defined by Sudlow, and after competing with a known site marker. The recognition interaction featured negative ΔHÏ´ , ΔSÏ´ and ΔGÏ´ thermodynamic parameters. Fluorescence and circular dichroism spectra described the polarity of residues and α-helix and ß-strand content changed because of HXR binding. The most rational structure for the HXR-HSA complex was recommended by the molecular docking method, in which the binding location, molecular orientation, adjacent amino acid residues, and hydrogen bonds were included. In addition, the influence of ß-cyclodextrin and some essential metal ions on the balance of the HSA-HXR system interaction was measured. The study gained comprehensive information on the transportation mechanism for HXR in blood, and was of great significance in understanding the theory of HXR biotransformation and in discussing its clinical in vivo half-life.

Long noncoding RNA SNHG16 contributes to the development of bladder cancer via regulating miR-98/STAT3/Wnt/ß-catenin pathway axis.

This study aimed to investigate the role and the possible mechanism of the long noncoding small nucleolar RNA host gene 16 (SNHG16) in bladder cancer development. The expression of SNHG16 in the tumor tissues and plasma of patients with bladder cancer as well as bladder cancer cell lines was detected. T24 cells were then transfected with sh-SNHG16 to further investigate the effects of suppression of SNHG16 on T24 cell proliferation, apoptosis, migration, and invasion. In addition, the regulatory relationships between SNHG16 and miR-98 as well as the target of miR-98 were explored. Besides, the association between SNHG16 and the Wnt/ß-catenin pathway was further elucidated. The SNHG16 expression was upregulated in the tumor tissues and plasma of patients with bladder cancer, as well as bladder cancer cells. Suppression of SNHG16 inhibited T24 cell proliferation, promoted apoptosis, and suppressed migration and invasion in vitro. In addition, SNHG16 negatively regulated miR-98 expression and regulated the malignant behaviors of T24 cells through sponging miR-98. Moreover, signal transducer and activator of transcription 3 (STAT3) was identified as a functional target of miR-98, and miR-98 regulated the malignant behaviors of bladder cancer cells by targeting STAT3. Besides, suppression of SNHG16 inhibited the activation of the Wnt/ß-catenin pathway, which was further regulated by miR-98 and STAT3, indicating that the effects of SNHG16/miR-98/STAT3 on T24 cells were achieved through the Wnt/ß-catenin pathway. Our findings reveal that long noncoding RNAs SNHG16 is upregulated in bladder cancer and contributes to the development of bladder cancer possibly via regulating the miR-98/STAT3/Wnt/ß-catenin pathway axis. The SNHG16/miR-98/STAT3/Wnt/ß-catenin pathway axis may provide a new strategy for bladder cancer treatment.

Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer.

BACKGROUND/AIMS: Although EpCAM+CD44+ cells exhibit more stem-like properties than did EpCAM-CD44- cells, the specificity of EpCAM combined with CD44 in defining CSCs needs further improvement. Lgr5 is used as a biomarker to isolate cancer stem cells (CSCs) in colorectal cancer. However, it remains unclear whether Lgr5, along with EpCAM and CD44, can further identify and define CSCs in colorectal cancer. METHODS: Lgr5+CD44+EpCAM+, Lgr5+CD44+EpCAM-, Lgr5+CD44-EpCAM+, Lgr5-CD44+EpCAM+, and Lgr5-CD44-EpCAM-cells were separately isolated using fluorescence-activated cell sorting (FACS). Colony formation, self-renewal, differentiation, and tumorigenic properties of these cells were investigated through in vitro experiments and in vivo tumor xenograft models. The expression of stemness genes and CSC- and epithelial-mesenchymal transition (EMT)-related genes, such as KLF4, Oct4, Sox2, Nanog, CD133, CD44, CD166, ALDH1, Lgr5, E-cadherin, ZO-1, Vimentin, Snail, Slug, and Twist, was examined using real-time PCR. RESULTS: Lgr5-positive subpopulations exhibited higher capacities for colony formation, self-renewal, differentiation, and tumorigenicity as well as higher expression of stemness genes and mesenchymal genes and lower expression of epithelial genes than did Lgr5-negative subpopulations. CONCLUSION: Our data revealed that tumorigenic cells were highly restricted to Lgr5-positive subpopulations. Most importantly, Lgr5+CD44+EpCAM+ cells exhibited more pronounced CSC-like traits than did any other subpopulation, indicating that Lgr5 combined with CD44 and EpCAM can further improve the stem-like traits of CSCs in colorectal cancer.

Study on the molecular recognition action of lamivudine by human serum albumin.

In this work, the interaction of an anti-HIV drug lamivudine and human serum albumin (HSA) was studied by multispectroscopic and molecular modeling methods. The fluorescence emission spectra showed that the fluorescence of HSA was quenched by lamivudine through static mechanism with HSA-lamivudine complex produced at ground state. According to the binding equilibriums observed at 4 different temperatures, the number of binding site, binding constant, enthalpy change, entropy change, and Gibbs free energy change of the interaction were calculated. The results indicated that there was only 1 main binding site under present concentration condition, and then, the location of this binding site was ascertained by molecular probe experiments using warfarin and ibuprofen as site markers. The interaction was a spontaneous and exothermic process. Hydrogen bonds and van der Waals force were the major power that fixed lamivudine on Sudlow's site I in subdomain IIA of HSA molecule. The distance between donor and acceptor was determined by Förster's nonradiative fluorescence resonance energy transfer theory. Circular dichroism spectra exhibited the alteration of HSA's secondary structures. Molecular modeling investigation revealed the structure of HSA-lamivudine complex, including the conformation of lamivudine in binding site, the amino residues close to lamivudine, and the interaction forces between receptor and ligand. The study may be beneficial to therapists in understanding the distribution of lamivudine in vivo and explaining its drug-resistant mechanism in clinical diagnosis.

Valproic acid sensitizes metformin-resistant human renal cell carcinoma cells by upregulating H3 acetylation and EMT reversal.

BACKGROUND: Metformin (Met) is a widely available diabetic drug and shows suppressed effects on renal cell carcinoma (RCC) metabolism and proliferation. Laboratory studies in RCC suggested that metformin has remarkable antitumor activities and seems to be a potential antitumor drug. But the facts that metformin may be not effective in reducing the risk of RCC in cancer clinical trials made it difficult to determine the benefits of metformin in RCC prevention and treatment. The mechanisms underlying the different conclusions between laboratory experiments and clinical analysis remains unclear. The goal of the present study was to determine whether long-term metformin use can induce resistance in RCC, whether metformin resistance could be used to explain the disaccord in laboratory and clinical studies, and whether the drug valproic acid (VPA), which inhibits histone deacetylase, exhibits synergistic cytotoxicity with metformin and can counteract the resistance of metformin in RCC. METHODS: We performed CCK8, transwell, wound healing assay, flow cytometry and western blotting to detect the regulations of proliferation, migration, cell cycle and apoptosis in 786-O, ACHN and metformin resistance 786-O (786-M-R) cells treated with VPA, metformin or a combination of two drugs. We used TGF-ß, SC79, LY294002, Rapamycin, protein kinase B (AKT) inhibitor to treat the 786-O or 786-M-R cells and detected the regulations in TGF-ß /pSMAD3 and AMPK/AKT pathways. RESULTS: 786-M-R was refractory to metformin-induced antitumor effects on proliferation, migration, cell cycle and cell apoptosis. AMPK/AKT pathways and TGF-ß/SMAD3 pathways showed low sensibilities in 786-M-R. The histone H3 acetylation diminished in the 786-M-R cells. However, the addition of VPA dramatically upregulated histone H3 acetylation, increased the sensibility of AKT and inhibited pSMAD3/SMAD4, letting the combination of VPA and metformin remarkably reappear the anti-tumour effects of metformin in 786-M-R cells. CONCLUSIONS: VPA not only exhibits synergistic cytotoxicity with metformin but also counteracts resistance to metformin in renal cell carcinoma cell. The re-sensitization to metformin induced by VPA in metformin-resistant cells may help treat renal cell carcinoma patients.

Evaluation of the reliability and validity for X16 balance testing scale for the elderly.

BACKGROUND: Balance performance is considered as an indicator of functional status in the elderly, a large scale population screening and evaluation in the community context followed by proper interventions would be of great significance at public health level. However, there has been no suitable balance testing scale available for large scale studies in the unique community context of urban China. METHODS: A balance scale named X16 balance testing scale was developed, which was composed of 3 domains and 16 items. A total of 1985 functionally independent and active community-dwelling elderly adults' balance abilities were tested using the X16 scale. The internal consistency, split-half reliability, content validity, construct validity, discriminant validity of X16 balance testing scale were evaluated. RESULTS: Factor analysis was performed to identify alternative factor structure. The Eigenvalues of factors 1, 2, and 3 were 8.53, 1.79, and 1.21, respectively, and their cumulative contribution to the total variance reached 72.0%. These 3 factors mainly represented domains static balance, postural stability, and dynamic balance. The Cronbach alpha coefficient for the scale was 0.933. The Spearman correlation coefficients between items and its corresponding domains were ranged from 0.538 to 0.964. The correlation coefficients between each item and its corresponding domain were higher than the coefficients between this item and other domains. With the increase of age, the scores of balance performance, domains static balance, postural stability, and dynamic balance in the elderly declined gradually (P < 0.001). With the increase of age, the proportion of the elderly with intact balance performance decreased gradually (P < 0.001). CONCLUSIONS: The reliability and validity of the X16 balance testing scale is both adequate and acceptable. Due to its simple and quick use features, it is practical to be used repeatedly and routinely especially in community setting and on large scale screening.