Concurrence of dermatomyositis and psoriasis: a case report and literature review.

Dermatomyositis (DM) is a type of inflammatory myopathy with unknown causes. It is characterized by distinct skin lesions, weakness in the muscles close to the body, and the potential to affect multiple organs. Additionally, it may be associated with the presence of malignancies. The development of DM is influenced by genetic susceptibility, autoimmune response, and various external factors like cancer, drugs, and infectious agents. Psoriasis is a chronic, recurring, inflammatory, and systemic condition. Scaly erythema or plaque is the typical skin manifestation. The etiology of psoriasis involves genetic, immune, environmental and other factors. It is uncommon for a patient to have both of these diseases simultaneously, although individuals with DM may occasionally exhibit symptoms similar to those of psoriasis. Our patient was diagnosed with psoriasis in his 50s because of scalp squamous plaques, but he did not receive standard treatment. Ten years later, he developed symptoms of muscle pain and limb weakness. He was diagnosed with psoriasis complicated with dermatomyositis in our department and received corresponding treatment. Moreover, we reviewed the relevant literature to evaluate similarities and differences in clinical manifestation and treatment to other cases.

Urolithin A exerts a protective effect on lipopolysaccharide-induced acute lung injury by regulating HMGB1-mediated MAPK and NF-κB signaling pathways.

Acute lung injury (ALI) is a severe inflammatory disorder that has a high morbidity and mortality rate. Urolithin A (UA) is reported to have anti-inflammatory and anti-oxidative effects in ALI. However, its molecular mechanisms in ALI remain to be explored. Mice and BEAS-2B cells were administrated with lipopolysaccharide (LPS) to mimic the ALI model in vivo and in vitro. Hematoxylin-eosin (HE) staining was used to detect the pathological injury of lung tissues. The levels of proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) and culture supernatant and the levels of oxidative stress markers in lung tissues were measured using ELISA. DCFH-DA probe was used to assess the reactive oxygen species (ROS) level. TUNEL staining and flow cytometry were performed to determine cell apoptosis. The key targets and pathways were confirmed by immunohistochemistry (IHC) and western blot. UA suppressed the pathologic damage, wet/dry weight ratio, and total protein and inflammatory cells in BALF. UA decreased neutrophil infiltration and proinflammatory cytokines production. UA reduced the level of malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in pulmonary tissues. UA also inhibited cell apoptosis in lung tissues by decreasing Bax expression and increasing Bcl-2 expression. In addition, UA suppressed LPS-induced inflammatory factor production, ROS level, and cell apoptosis in BEAS-2B. Importantly, UA decreased the expression of HMGB1 in LPS-treated mice and BEAS-2B cells. HMGB1 overexpression greatly abrogated the inhibition of UA on inflammation, ROS, and cell apoptosis in LPS-administrated BEAS-2B. Furthermore, UA treatment suppressed the phosphorylated levels of p38, JNK, ERK, and p65 in LPS-administrated mice and BEAS-2B cells. UA alleviated lung inflammation, oxidative stress, and apoptosis in ALI by targeting HMGB1 to inactivate the MAPK/NF-κB signaling, suggesting the potential of UA to treat ALI.

A survey on perceived medication guide reading and comprehension ease among US adults.

Medication guides (MGs) provide patients with important information about certain prescription drugs to help them take these drugs safely. We surveyed US residents about their perceptions of MG readability and understandability. We randomly sampled 5204 US residents (age 18+) from Ipsos's KnowledgePanel to complete a two-part survey. Only respondents who reported receiving an MG with their prescription drugs (n = 3852) completed part 2, which included two key items: How easy to [(1)read/(2)understand] are the MGs that you have received from a pharmacy along with your prescription medicines? (1 = Very easy, 5 = Very difficult; reverse-coded). Health literacy (HL) and demographic data were also collected. After weighting our data, we found that 85% of respondents who reported receiving an MG perceived this information as 'very easy' (27.3%), 'somewhat easy' (28.3%) or 'about average' (29.3%) to read. Eighty-seven percent of respondents who reported receiving an MG perceived it as 'very easy' (27.6%), 'somewhat easy' (30.2%) or 'about average' (29.5%) to understand. ANOVAs revealed higher average perceived MG reading and comprehension ease scores among respondents presumed to have adequate versus inadequate HL (ps ≤ 0.0006). Younger or less-educated respondents and non-Hispanic Blacks perceived MGs as easier to read and understand, on average, than their counterparts (ps ≤ 0.0001). Many of these relationships remained intact in models predicting perceived MG reading and comprehension ease (ps ≤ 0.001). Adjusted R2 values across models were small, however (≤0.06). Our findings suggest most US residents (18+) who received MGs perceived them to be 'about average' to 'very easy' to read and understand.

Examining health care access disparities in Hispanic populations with peripheral artery disease and diabetes.

INTRODUCTION: This study investigated disparities in health care access for Hispanic adults with diabetes and peripheral artery disease (PAD) who are at risk of lower-extremity amputation and other cardiovascular morbidities and mortalities. METHODS: We utilized the health care access survey data from the All of Us research program to examine adults (⩾ 18 years) with either diabetes and/or PAD. The primary associations evaluated were: could not afford medical care and delayed getting medical care in the past 12 months. Multivariable logistic regression models were used to assess the association of Hispanic ethnicity and survey responses, adjusting for age, sex, income, health insurance, and employment status. RESULTS: Among 24,104 participants, the mean age was 54.9 years and 67% were women. Of these, 8.2% were Hispanic adults. In multivariable analysis, Hispanic adults were more likely to be unable to afford seeing a health care provider, and receiving emergency care, follow-up care, and prescription medications (p < 0.05) than non-Hispanic adults. Furthermore, Hispanic adults were more likely to report being unable to afford medical care due to cost (odds ratios [OR] 1.72, 95% CI 1.50-1.99), more likely to purchase prescription drugs from another country (OR 2.20, 95% CI 1.69-2.86), and more likely to delay getting medical care due to work (OR 1.46, 95% CI 1.22-1.74) and child care (OR 1.80, 95% CI 1.35-2.39) issues than non-Hispanic White adults. CONCLUSION: The Hispanic population with diabetes and PAD faces substantial barriers in health care access, including a higher likelihood of delaying medical care and being unable to afford it.

Integrating Network Pharmacology and Experimental Validation to Elucidate the Mechanism of Yiqi Yangyin Decoction in Suppressing Non-Small-Cell Lung Cancer.

Yiqi Yangyin Decoction (YYD) is a classic traditional Chinese medicine (TCM) formulation to treat lung cancer in clinic. Nevertheless, the active ingredients, key targets, and molecular mechanisms for YYD are still poorly understood. This study is focused on elucidating the pharmacological mechanism of YYD in non-small-cell lung cancer (NSCLC) by using a combined network pharmacology approach and biological experiment validation. Online bioinformatics tools showed that 40 bioactive compounds and 229 putative targets of YYD were associated with anti-NSCLC activity. Protein-Protein Interaction (PPI) network demonstrated AKT1, SRC, JUN, TP53, and EGFR as the top five key targets for YYD against NSCLC. Through enrichment analysis, YYD was found to affect cell proliferation and apoptosis in NSCLC possibly by PI3K-AKT signaling. Molecular docking confirmed a strong binding between the main compounds (quercetin or luteolin) and EGFR. As demonstrated by CCK-8, EdU, and colony formation assays, we found a significant inhibition of YYD on cell proliferation. Moreover, YYD treatment induced cell cycle arrest by affecting p53, p21, and cyclin D1 expression. YYD administration enhanced apoptosis by changing the expression of cleaved caspase-3, Bax, and Bcl-2. Mechanistically, YYD resulted in a significant inactivation of EGFR-PI3K-AKT signaling. Furthermore, EGFR activator significantly reversed YYD-mediated proliferation inhibition and apoptosis. YYD also showed an inhibitory effect on tumor growth in mice. Together, YYD might target the EGFR-PI3K-AKT pathway to repress NSCLC progression.

Retraction Notice to: Silencing of Long Non-coding RNA RP1-93H18.6 Acts as a Tumor Suppressor in Cervical Cancer through the Blockade of the PI3K/Akt Axis.

[This retracts the article DOI: 10.1016/j.omtn.2019.10.041.].

Circ_0006006 facilitates non-small cell lung cancer progression by modulating miR-924/SRSF7 axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is an aggressive tumor with high mortality. Circular RNAs played crucial roles in the development of cancers, including NSCLC. In the present study, the action of circ_0006006 in NSCLC was investigated. METHODS: Using a real-time quantitative polymerase chain reaction, the relative gene expression was detected. The structure of circ_0006006 was identified using RNase R digestion and actinomycin D treatment. The functional role of circ_0006006 in cell proliferation, migration, invasion, apoptosis and angiogenesis was explored using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, colony formation, wound healing, transwell, flow cytometry and tube formation assays, respectively. Using western blotting, the relative proteins expression was measured. Dual-luciferase reporter and RNA immunoprecipitation assays were employed to verify the correlation between microRNA-924 (miR-924) and circ_0006006 or serine/arginine-rich splicing factor 7 (SRSF7). Xenograft tumor experiment was used to investigate the effect of circ_0006006 on tumor growth in vivo. An immunohistochemistry assay was performed to detect Ki-67, Bax, Bcl-2 and SRSF7 expression in tissues of mice. RESULTS: Circ_0006006 was increased in NSCLC tissues and cells. Loss-of-function assays demonstrated that circ_0006006 silencing repressed proliferative ability, cell migration and invasion, and angiogenesis, as well as promoted cell apoptosis, in A549 and H1299 cells. Follow-up mechanism experiments depicted that circ_0006006 sponged miR-924 and miR-924 inhibitor rescued the circ_0006006 knockdown-mediated inhibition effect on the progression of NSCLC. Additionally, the inhibition effect of circ_0006006 knockdown on SRSF7 expression was reversed by miR-924 inhibitor. Moreover, the suppressive effect of miR-924 on NSCLC progression was reversed by SRSF7 overexpression. Xenograft tumor experiment unveiled that circ_0006006 knockdown inhibited tumor growth in vivo. CONCLUSIONS: Circ_0006006 stimulated NSCLC progression by targeting miR-924 to regulate SRSF7 expression.

Long Non-Coding RNA THOR Depletion Inhibits Human Non-Small Cell Lung Cancer Cell Growth.

Long non-coding RNA (LncRNA) THOR (Lnc-THOR) is expressed in testis and multiple human malignancies. Lnc-THOR association with IGF2BP1 (IGF2 mRNA-binding protein 1) is essential for stabilization and transcription of IGF2BP1 targeted mRNAs. We tested its expression and potential functions in non-small cell lung cancer (NSCLC). In primary NSCLC cells and established cell lines, Lnc-THOR shRNA or CRISPR/Cas9-mediated knockout (KO) downregulated IGF2BP1 target mRNAs (IGF2, Gli1, Myc and SOX9), inhibiting cell viability, growth, proliferation, migration and invasion. Significant apoptosis activation was detected in Lnc-THOR-silenced/-KO NSCLC cells. Conversely, ectopic overexpression of Lnc-THOR upregulated IGF2BP1 mRNA targets and enhanced NSCLC cell proliferation, migration and invasion. RNA-immunoprecipitation and RNA pull-down assay results confirmed the direct binding between Lnc-THOR and IGF2BP1 protein in NSCLC cells. Lnc-THOR silencing and overexpression were ineffective in IGF2BP1-KO NSCLC cells. Forced IGF2BP1 overexpression failed to rescue Lnc-THOR-KO NSCLC cells. In vivo, intratumoral injection of Lnc-THOR shRNA adeno-associated virus potently inhibited A549 xenograft tumor growth in nude mice. At last we show that Lnc-THOR is overexpressed in multiple NSCLC tissues and established/primary NSCLC cells. Collectively, these results highlighted the ability of Lnc-THOR in promoting NSCLC cell growth by associating with IGF2BP1, suggesting that Lnc-THOR represents a promising therapeutic target of NSCLC.

circBTBD7 Promotes Immature Porcine Sertoli Cell Growth through Modulating miR-24-3p/MAPK7 Axis to Inactivate p38 MAPK Signaling Pathway.

Sertoli cells are the crucial coordinators to guarantee normal spermatogenesis and male fertility. Although circular RNAs (circRNAs) exhibit developmental-stage-specific expression in porcine testicular tissues and have been thought of as potential regulatory molecules in spermatogenesis, their functions and mechanisms of action remain largely unknown, especially in domestic animals. A novel circBTBD7 was identified from immature porcine Sertoli cells using reverse transcription PCR, Sanger sequencing, and fluorescence in situ hybridization assays. Functional assays illustrated that circBTBD7 overexpression promoted cell cycle progression and cell proliferation, as well as inhibited cell apoptosis in immature porcine Sertoli cells. Mechanistically, circBTBD7 acted as a sponge for the miR-24-3p and further facilitated its target mitogen-activated protein kinase 7 (MAPK7) gene. Overexpression of miR-24-3p impeded cell proliferation and induced cell apoptosis, which further attenuated the effects of circBTBD7 overexpression. siRNA-induced MAPK7 deficiency resulted in a similar effect to miR-24-3p overexpression, and further offset the effects of miR-24-3p inhibition. Both miR-24-3p overexpression and MAPK7 knockdown upregulated the p38 phosphorylation activity. The SB202190 induced the inhibition of p38 MAPK pathway and caused an opposite effect to that of miR-24-3p overexpression and MAPK7 knockdown. Collectively, circBTBD7 promotes immature porcine Sertoli cell growth through modulating the miR-24-3p/MAPK7 axis to inactivate the p38 MAPK signaling pathway. This study expanded our knowledge of noncoding RNAs in porcine normal spermatogenesis through deciding the fate of Sertoli cells.

Identification of circ_0058357 as a regulator in non-small cell lung cancer cells resistant to cisplatin by miR-361-3p/ABCC1 axis.

BACKGROUND: Drug resistance is a major clinical drawback behind the failure of chemotherapy in non-small cell lung cancer (NSCLC). In this study, we undertook to identify the precise role of circular RNA (circRNA) circ_0058357 in the functional properties of DDP-resistant NSCLC cells. METHODS: Circ_0058357, miR-361-3p and ATP-binding cassette (ABC) subfamily C member 1 (ABCC1) were quantified by qRT-PCR and western blot. Cell survival and viability were gauged by MTT assay. Cell proliferation, apoptosis, invasion and migration were measured by EdU, flow cytometry, transwell and wound-healing assays, respectively. The direct relationship between miR-361-3p and circ_0058357 or ABCC1 was validated by dual-luciferase reporter assay. RESULTS: Our data showed that circ_0058357 was highly expressed in DDP-resistant NSCLC tissues and cells. Inhibition of circ_0058357 repressed cell growth, invasion, migration, and promoted DDP sensitivity and cell apoptosis of H1299/DDP and A549/DDP cells in vitro. Moreover, inhibition of circ_0058357 diminished the growth of A549/DDP cells and sensitized them to the cytotoxic effect of DDP in vivo. Mechanistically, circ_0058357 contained a miR-361-3p binding site and miR-361-3p was identified as a molecular mediator of circ_0058357 regulation. MiR-361-3p suppressed ABCC1 expression by binding to ABCC1 3'UTR, and miR-361-3p-mediated inhibition of ABCC1 affected the growth, invasion, migration, apoptosis and DDP sensitivity of H1299/DDP and A549/DDP cells. Furthermore, circ_0058357 regulated ABCC1 expression by competitively binding to shared miR-361-3p. CONCLUSIONS: Our findings identified that inhibition of circ_0058357 suppresses the growth and metastasis of H1299/DDP and A549/DDP cells and sensitizes them to DDP therapy partially by targeting the miR-361-3p/ABCC1 axis.

miR-126 Controls the Apoptosis and Proliferation of Immature Porcine Sertoli Cells by Targeting the PIK3R2 Gene through the PI3K/AKT Signaling Pathway.

The quantity of Sertoli cells in the adult testis decides the daily gamete formation, and accumulating evidence indicates that epigenetic factors regulate the proliferation of Sertoli cells. Research on the function and regulatory mechanism of microRNAs (miRNAs) in Sertoli cells has not been comprehensive yet, especially on domestic animals. In this article, we report that miR-126 controls the proliferation and apoptosis of immature porcine Sertoli cells based on previous studies. Our results confirmed that miR-126 elevation promotes cell cycle progression, cell proliferation and represses cell apoptosis; on the contrary, the inhibitory effects of miR-126 result in the opposite. The phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) gene, a member of the PI3K family, was verified as a direct target of miR-126 using the dual-luciferase reporter analysis. miR-126 negatively regulated the mRNA and protein expression level of PIK3R2 in immature porcine Sertoli cells. siRNA-induced PIK3R2 inhibition caused similar effects as miR-126 overexpression and eliminated the influences of miR-126 knockdown in immature porcine Sertoli cells. In addition, both miR-126 overexpression and PIK3R2 inhibition elevated the phosphorylation of PI3K and AKT, whereas the miR-126 knockdown demonstrated the contrary result. In short, miR-126 controls the proliferation and apoptosis of immature porcine Sertoli cells by targeting the PIK3R2 gene through the PI3K/AKT signaling pathway. The research supplies a theoretical and practical foundation for exploring the functional parts of miR-126 in swine sperm by defining the destiny of immature Sertoli cells.

MiR-191 promotes the porcine immature Sertoli cell proliferation by targeting the BDNF gene through activating the PI3K/AKT signaling pathway.

The number of Sertoli cells in the testis is a major regulator on the sperm production capacity. MicroRNAs (miRNAs) participate in regulating the proliferation and apoptosis of porcine immature Sertoli cells. However, the functions and mechanisms of action of most identified miRNAs in porcine Sertoli cells remain largely unknown. In the present study, based on our previous results from an EdU-based high-content screening assay, we further studied the mechanism of action of miR-191 on the proliferation and apoptosis of porcine immature Sertoli cells through flow cytometry, Western blotting, and dual-luciferase activity analyses. The results demonstrated that overexpression of miR-191 promoted cell cycle progression from G1 phase to the S and G2 phases, enhanced cell proliferation, and inhibited apoptosis in the porcine immature Sertoli cells, whereasmiR-191 inhibition resulted in the opposite effects. The results from a luciferase reporter assay showed that miR-191 directly targeted the 3'-UTR of theBDNF gene. BDNF knockdown also promoted cell cycle progression to the S phase, cell proliferation and inhibited cell apoptosis, which were consistent with the effects of the miR-191overexpression. A co-transfection experiment showed that BDNF knockdown abolished the effects of miR-191 inhibition. Furthermore, both miR-191 overexpression and BDNFinhibition elevated the phosphorylation of PI3K and AKT, the key components of the PI3K/AKT signaling pathway, whereas BDNFinhibition offset the effects of the miR-191 knockdown. Overall, these data indicated that miR-191 promotes cell proliferation and inhibits apoptosis in porcine immature Sertoli cells by targeting theBDNF gene through activating the PI3K/AKT signaling pathway. This study provides a novel scientific basis for further investigation on the biological functions of miR-191 on porcine spermatogenesis.

NIH Funding of Researchers in Surgery: Decreased Career Development Awards Over Time.

BACKGROUND: Over time, NIH funding has become increasingly competitive. In addition, academic surgeons' research competes with time required for patient care, operating, and administrative work. Due to these competing interests for surgeons, we hypothesize that the percentage of NIH grants awarded to researchers from departments of surgery is decreasing. METHODS: The NIH Research Portfolio Online Reporting Tool was queried for the number and value of new and renewal R01 grants, and career development awards noting which surgery departments received awards from 1998 to -2018. Statistical analysis was performed using univariate and multivariable logistic regression. RESULTS: The number of career development awards granted to researchers from departments of surgery decreased significantly over time (P = 0.007) while new R01's and R01 renewal awards were stable. The number of grants awarded to researchers from all procedural departments were compared to non-procedural departments and again, career development awards decreased significantly (P = 0.005) over time but new R01's and R01 renewals stayed stable. Looking at the difference in average dollar amount received for new R01, renewal R01, or career development awards between department of surgery awardees and non-surgery over time, there was no significant difference. CONCLUSIONS: NIH funding is becoming increasingly competitive and surgeons have many competing interests. Our study found that there has been a significant decrease in career development awards to department of surgery awardees and procedural specialists. The decrease in receipt of these awards is particularly concerning given that they are meant to provide protected time for developing researchers and thus have potential consequences for future research.

Circulating miR-1246 Targeting UBE2C, TNNI3, TRAIP, UCHL1 Genes and Key Pathways as a Potential Biomarker for Lung Adenocarcinoma: Integrated Biological Network Analysis.

Analysis of circulating miRNAs (cmiRNAs) before surgical operation (BSO) and after the surgical operation (ASO) has been informative for lung adenocarcinoma (LUAD) diagnosis, progression, and outcomes of treatment. Thus, we performed a biological network analysis to identify the potential target genes (PTGs) of the overexpressed cmiRNA signatures from LUAD samples that had undergone surgical therapy. Differential expression (DE) analysis of microarray datasets, including cmiRNAs (GSE137140) and cmRNAs (GSE69732), was conducted using the Limma package. cmiR-1246 was predicted as a significantly upregulated cmiRNA of LUAD samples BSO and ASO. Then, 9802 miR-1246 target genes (TGs) were predicted using 12 TG prediction platforms (MiRWalk, miRDB, and TargetScan). Briefly, 425 highly expressed overlapping miRNA-1246 TGs were observed between the prediction platform and the cmiRNA dataset. ClueGO predicted cell projection morphogenesis, chemosensory behavior, and glycosaminoglycan binding, and the PI3K-Akt signaling pathways were enriched metabolic interactions regulating miRNA-1245 overlapping TGs in LUAD. Using 425 overlapping miR-1246 TGs, a protein-protein interaction network was constructed. Then, 12 PTGs of three different Walktrap modules were identified; among them, ubiquitin-conjugating enzyme E2C (UBE2C), troponin T1(TNNT1), T-cell receptor alpha locus interacting protein (TRAIP), and ubiquitin c-terminal hydrolase L1(UCHL1) were positively correlated with miR-1246, and the high expression of these genes was associated with better overall survival of LUAD. We conclude that PTGs of cmiRNA-1246 and key pathways, namely, ubiquitin-mediated proteolysis, glycosaminoglycan binding, the DNA metabolic process, and the PI3K-Akt-mTOR signaling pathway, the neurotrophin and cardiomyopathy signaling pathway, and the MAPK signaling pathway provide new insights on a noninvasive prognostic biomarker for LUAD.

miR-130a promotes immature porcine Sertoli cell growth by activating SMAD5 through the TGF-ß-PI3K/AKT signaling pathway.

Sertoli cells play vital roles in normal spermatogenesis, and microRNAs (miRNAs) participate in regulating Sertoli cell development. However, the functions and mechanisms of action of most identified miRNAs in porcine Sertoli cells remain largely unknown. Herein, we primarily explored the regulatory roles of miR-130a in immature porcine Sertoli cells using EdU-based high-content screening assay. The results demonstrated that 27 miRNAs have potential roles in the promotion of immature porcine Sertoli cell proliferation, and miR-130a was identified as a promising candidate. miR-130a promoted cell cycle progression and cell proliferation, whereas it impeded cell apoptosis in immature porcine Sertoli cells. It also contributed to Sertoli cell proliferation and testis development in vivo. A TMT-based proteomics approach revealed that miR-130a regulated the expression of 91 proteins and multiple pathways, including the TGF-ß and PI3K/AKT signaling. miR-130a did not directly target the 3'-UTR of SMAD5; however, it increased SMAD5 phosphorylation. Moreover, miR-130a enhanced TGF-ß signaling by activating SMAD5 protein, and TGF-ß signaling further activated the PI3K/AKT signaling pathway to promote cell proliferation and inhibit cell apoptosis in porcine immature Sertoli cells. Collectively, miR-130a promoted immature porcine Sertoli cell growth by activating SMAD5 through the TGF-ß-PI3K/AKT signaling pathway. This study, therefore, provides novel insights into the effects of miR-130a on porcine spermatogenesis through the regulation of immature Sertoli cell proliferation and apoptosis.

Silencing of Long Non-coding RNA RP1-93H18.6 Acts as a Tumor Suppressor in Cervical Cancer through the Blockade of the PI3K/Akt Axis.

Cervical cancer (CC) remains a distinct public health stumbling block worldwide. Increasing evidence has highlighted long non-coding RNAs (lncRNAs) as tumor-associated biological molecules. In this study, by means of altering the expression of lncRNA RP1-93H18.6 in CC cells, its ability to influence the biological activities of CC cells was evaluated. Differentially expressed lncRNAs were initially screened from the GEO database. A series of RP1-93H18.6 vectors, small interfering RNA (siRNA) against RP1-93H18.6, and LY294002 (an inhibitor for the phosphatidylinositol 3-kinase [PI3K]/Akt [serine/threonine kinase] axis) were introduced in a respective manner to treat the HeLa cells in order to analyze their effects on cellular activities in vitro. Nude mice with xenograft tumors were utilized in order to assess CC tumor growth and metastasis in vivo. lncRNA RP1-93H18.6 was highly expressed in CC, which could activate the P13K/Akt axis. RP1-93H18.6 vectors exposure increased cell viability, adhesion, migration, and invasion, which resulted in more cells arrested at the S stage and reduced apoptosis, while acting to promote tumor growth and metastasis. The siRNA against RP1-93H18.6 or LY294002 exposure was observed to attenuate the effects induced by RP1-93H18.6 vectors. This study suggests that suppression of lncRNA RP1-93H18.6 exerts potent inhibitory effects on the development and progression of CC via blockade of the PI3K/Akt axis.

LSD1 mediates microbial metabolite butyrate-induced thermogenesis in brown and white adipose tissue.

OBJECTIVE: The gut microbiota regulates thermogenesis to benefit metabolic homeostasis at least partially via its metabolite butyrate, and the underlying mechanisms of this regulation are still unclear. In this study, we aim to investigate the role of lysine specific demethylase (LSD1), a histone demethylase and important regulator of thermogenesis, in mediating gut microbial metabolite butyrate regulation of thermogenesis. METHODS: The antibiotic cocktail (ABX) was administrated to deplete gut microbiota. Adipose-specific LSD1 knockout mice (LSD1 aKO) were generated by crossing LSD1-lox/lox with adiponectin-cre mice and sodium butyrate and dietary fiber inulin was administrated through oral-gavage. Primary stromal vascular cells were isolated from adipose tissues and differentiated to adipocytes for studying butyrate effects on adipocyte thermogenesis. RESULTS: The antibiotic cocktail (ABX)-mediated depletion of the gut microbiota in mice downregulated the expression of LSD1 in both brown adipose tissue (BAT) and subcutaneous white adipose tissue (scWAT) in addition to uncoupling protein 1 (UCP1) and body temperature. Gavage of the microbial metabolite butyrate in ABX-treated mice reversed the thermogenic functional impairment and LSD1 expression. The adipose-specific ablation of LSD1 in mice attenuated the butyrate-mediated induction of thermogenesis and energy expenditure. Notably, our results showed that butyrate directly increased the expression of LSD1 and UCP1 as well as butyrate transporter monocarboxylate transporter 1 (MCT1) and catabolic enzyme acyl-CoA medium-chain synthetase 3 (ACSM3) in ex vivo cultured adipocytes. The inhibition of MCT1 blocked the effects of butyrate in adipocytes. Furthermore, the butyrate-mediated prevention of diet-induced obesity (DIO) through increased thermogenesis was attenuated in LSD1 aKO mice. Moreover, after gavaging HFD-fed mice with the dietary fiber inulin, a substrate of microbial fermentation that rapidly produces butyrate, thermogenesis in both BAT and scWAT was increased, and DIO was decreased; however, these beneficial metabolic effects were blocked in LSD1 aKO mice. CONCLUSIONS: Together, our results indicate that the microbial metabolite butyrate regulates thermogenesis in BAT and scWAT through the activation of LSD1.

Propionate promotes intestinal lipolysis and metabolic benefits via AMPK/LSD1 pathway in mice.

Dietary fibers and their microbial fermentation products short chain fatty acids promote metabolic benefits, but the underlying mechanisms are still unclear. Recent studies indicate that intestinal lipid handling is under regulatory control and has broad influence on whole body energy homeostasis. Here we reported that dietary inulin and propionate significantly decreased whole body fat mass without affecting food intake in mice fed with chow diet. Meanwhile, triglyceride (TG) content was decreased and lipolysis genes expressions, such as adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL) and lysosomal acid lipase (LAL) were elevated in the jejunum and ileum of inulin and propionate treated mice. In vitro studies on Caco-2 cells showed propionate directly induced enterocyte ATGL, HSL and LAL gene expressions and decreased TG content, via activation of phosphorylation of AMP-activated protein kinase (p-AMPK) and lysine specific demethylase 1 (LSD1). Moreover, inulin and propionate could increase intestinal lipolysis under high fat diet (HFD) fed condition which contributed to the prevention of HFD-induced obesity. Our study suggests dietary fiber inulin and its microbial fermentation product propionate can regulate metabolic homeostasis through regulating intestinal lipid handling, which could provide a novel therapeutic target for both prevention and treatment of obesity.

LncRNA LINC01305 silencing inhibits cell epithelial-mesenchymal transition in cervical cancer by inhibiting TNXB-mediated PI3K/Akt signalling pathway.

Cervical cancer (CC) remains one of the leading malignancies afflicting females worldwide, with its aetiology associated with long-term papillomavirus infection. Recent studies have shifted their focus and research attention to the relationship between long non-coding RNAs (lncRNAs) and CC therapeutic. Thus, the aim of the current study was to investigate the underlying mechanism of lncRNA LINC01305 on the cell invasion, migration and epithelial-mesenchymal transition (EMT) of CC cells via modulation of the PI3K/Akt signalling pathway by targeting tenascin-X B (TNXB). The expressions of LINC01305, TNXB, MMP2, MMP9, E-cadherin, vimentin, PI3K, Akt, p-PI3K, p-Akt and TNXB were detected in this study. After which, the cell invasion and migration abilities of the CC cells were determined respectively. Bioinformatics and the application of a dual luciferase reporter gene assay provided verification indicating that TNXB is the target gene of lncRNA LINC01305. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis methods revealed that the expressions of MMP2, MMP9, vimentin, PI3K, Akt, p-PI3K and p-Akt were decreased following the down-regulation of LncRNA LINC01305 or overexpression of TNXB. LncRNA LINC01305 silencing or TNXB overexpression was noted to decrease the migration and invasion of SiHa cells. Taken together, the key findings of the current study present evidence suggesting that lncRNA LINC01305 silencing suppresses EMT, invasion and migration via repressing the PI3K/Akt signalling pathway by means of targeting TNXB in CC cells, which ultimately provides novel insight and identification of potential therapeutic targets for CC.

Evaluation of daily ginger consumption for the prevention of chronic diseases in adults: A cross-sectional study.

OBJECTIVES: The aim of this study was to assess daily ginger consumption and explore its correlation with chronic diseases among adults and to analyze further how different levels of ginger intake affect the prevalence of chronic diseases. METHODS: We examined the prevalence rate of chronic diseases (diabetes, hypertension, coronary heart disease [CHD], hyperlipidemia, cerebrovascular disease, fatty liver, anemia, and tumor), as well as the daily ginger intake in a large cross-sectional study. In all, 4628 participants (1823 men and 2805 women) ages 18 to 77 y completed face-to-face dietary and health questionnaires. We extracted diagnoses and investigation results from the participants' health records. The association between the level of ginger intake (0-2 g/d, 2-4 g/d, and 4-6 g/d) and the prevalence of chronic diseases was analyzed by using χ2 statistical test and unconditional logistic model. RESULTS: Overall, daily ginger consumption was associated with decreased risk for hypertension (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.86-0.98) and CHD (OR, 0.87; 95% CI, 0.78-0.96) in adults ages ≥18 y. Differences were also observed in adults ages ≥40 y: hypertension (OR, 0.92; 95% CI, 0.87-0.99), CHD (OR, 0.87; 95% CI, 0.78-0.97). However, after 20 y, no association was seen for hypertension but there was still a difference between ginger consumption and CHD in adults ages ≥60 y (OR, 0.84; 95% CI, 0.73-0.96). Again, the probability of illness (hypertension or CHD) decreased when the level of daily ginger intake increased. CONCLUSIONS: These data indicate that ginger has a potential preventive property against some chronic diseases, especially hypertension and CHD, as well as its ability to reduce the probability of illness.