Efficacy and safety of over-the-scope-clips in the therapy of acute nonvariceal upper gastrointestinal bleeding: Meta-analysis.

BACKGROUND: Acute nonvariceal upper gastrointestinal bleeding (ANVUGIB) is a frequent life-threatening acute condition in gastroenterology associated with high morbidity and mortality. Over-the-scope-clip (OTSC) is a new endoscopic hemostasis technique, which is being used in ANVUGIB and is more effective. AIM: To summarize and analyze the effects of the OTSC in prevention of recurrent bleeding, clinical success rate, procedure time, hospital stay, and adverse events in the treatment of ANVUGIB, to evaluate whether OTSC can replace standard endoscopic therapy as a new generation of treatment for ANVUGIB. METHODS: The literature related to OTSC and standard therapy for ANVUGIB published before January 2023 was searched in PubMed, Web of Science, EMBASE, Cochrane, Google, and CNKI databases. Changes in recurrent bleeding (7 or 30 days), clinical results (clinical success rate, conversion rate to surgery, mortality), therapy time (procedure time, hospital stay), and adverse events in the OTSC intervention group were summarized and analyzed, and the MD or OR of 95%CI is calculated by Review Manager 5.3. RESULTS: This meta-analysis involved 11 studies with 1266 patients. Total risk of bias was moderate-to-high. For patients in the OTSC group, 7- and 30-days recurrent bleeding rates, as well as procedure time, hospital stay, and intensive care unit stay, were greatly inhibited. OTSC could significantly improve the clinical success rate of ANVUGIB. OTSC therapy did not cause serious adverse and was effective in reducing patient mortality. CONCLUSION: OTSC may provide more rapid and sustained hemostasis, and thus, promote recovery and reduce mortality in patients with ANVUGIB. In addition, the safety of OTSC is assured.

Influence of γ-PGA on greenhouse gas emissions and grain yield from paddy rice under different rice varieties.

BACKGROUND: Significant efforts have been devoted to assess the effects of the poly-gamma-glutamic acid (γ-PGA) on crop growth, yield and quality, soil water retention and fertilizer use efficiency. However, few studies have evaluated the effects of γ-PGA on greenhouse gas (GHG) emissions and grain yield from paddy fields with different rice varieties. METHODS: In the present study, a split-plot field experiment was performed to comprehensively evaluate the effects of γ-PGA concentrations (i.e., no application [P0] and 25.0 kg ha-1 of γ-PGA fermentation solution [P1]) and rice varieties (i.e., conventional rice [Huanghuazhan, H], red rice [Gangteyou 8024, R] and black rice [Black indica rice, B]) on the grain yield, GHG emissions, global warming potential (GWP), greenhouse gas intensity (GHGI), net ecosystem economic profit (NEEP) and carbon footprint (CF) during 2022 and 2023 rice-growing seasons in central China. RESULTS: Application of γ-PGA significantly affected the GHGs emissions, NEEP and CF. Compared with P0 treatments, P1 treatments significantly increased the NEEP by 1.2-11.2 %, and decreased the GWP by 12.9-35.4 %, the GHGI by 16.5-35.9 % and the CF by 13.8-26.2 % in 2022-2023. Application of γ-PGA showed a tendency to increase the yield. Under γ-PGA application condition, R treatment exhibited the lowest GWP, GHGI and CF, and the highest yield and NEEP compared with B and H treatments. CONCLUSION: Our results suggest that γ-PGA application is an ecological agricultural management to increase rice yield, reduce greenhouse gas emission and increase economic benefit, and its advantage is more significant for red rice than for other rice varieties.

Co-occurrence of Erdheim-Chester disease and clonally evolving acute myeloid leukemia with FLT3-ITD and PTPN11 mutations.

Erdheim-Chester disease (ECD) is a rare histiocytosis that tends to co-exist with other myeloid malignancies. Here, we use genetic and transcriptomic sequencing to delineate a case of co-occurring BRAFV600E-mutated ECD and acute myeloid leukemia (AML), followed by AML remission and relapse. The AML relapse involved the extinction of clones with KMT2A-AFDN and FLT3-ITD, and the predominance of PTPN11-mutated subclones with distinct transcriptomic features. This case report has highlighted the screening for other myeloid malignancies at the diagnosis of ECD and the clinical significance of PTPN11-mutated AML subclones that require meticulous monitoring.

Trends in confinement-induced cell migration and multi-omics analysis.

Cell migration is an essential manner of different cell lines that are involved in embryological development, immune responses, tumorigenesis, and metastasis in vivo. Physical confinement derived from crowded tissue microenvironments has pivotal effects on migratory behaviors. Distinct migration modes under a heterogeneous extracellular matrix (ECM) have been extensively studied, uncovering potential molecular mechanisms involving a series of biological processes. Significantly, multi-omics strategies have been launched to provide multi-angle views of complex biological phenomena, facilitating comprehensive insights into molecular regulatory networks during cell migration. In this review, we describe biomimetic devices developed to explore the migratory behaviors of cells induced by different types of confined microenvironments in vitro. We also discuss the results of multi-omics analysis of intrinsic molecular alterations and critical pathway dysregulations of cell migration under heterogeneous microenvironments, highlighting the significance of physical confinement-triggered intracellular signal transduction in order to regulate cellular behaviors. Finally, we discuss both the challenges and promise of mechanistic analysis in confinement-induced cell migration, promoting the development of early diagnosis and precision therapeutics.

Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration.

The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, the mechanism underlying this type of cell migration remains unclear. Here we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi-omics analyses and high-resolution live-cell imaging. We find that, upon VACV infection, the epithelial cells undergo epithelial-mesenchymal transition-like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV-hijacked RhoA signaling significantly alters cellular morphology and rearranges the actin cytoskeleton involving the depolymerization of robust actin stress fibers, leading-edge protrusion formation, and the rear-edge recontraction, which coordinates VACV-induced cell migration. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses.

Single-cell transcriptome analysis reveals stem cell-like subsets in the progression of Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia (WM) is an uncommon lymphoproliferative disorder, and the precise cellular landscape and the mechanisms of progression from IgM monoclonal gammopathy of undetermined significance (MGUS) to WM remain unclear. We performed single-cell RNA sequencing of CD19 + and CD19-CD38 + cells from healthy donors, IgM MGUS and WM patients. We found that samples from IgM MGUS and WM patients were composed of fewer early B-cell subsets and more T cells and NK cells than those from healthy controls. Compared with those of IgM MGUS patients, mature B cells of WM patients showed upregulation of HES1, GADD45B, NEAT1, DUSP22, RGS1, RGS16, and PIM1. We also identified a subpopulation of CD3 + CD19 + cells in IgM MGUS and WM patients, and trajectory analysis suggested that this subpopulation might be a stem cell-like subset. Further targeted gene sequencing of CD3 + CD19 + and CD3-CD19 + cells proved that MYD88 might be the early events in tumorigenesis according to variant allele fraction analysis. Additional subclonal hits such as CXCR4 and MAP2K1 mutations could be acquired during tumor progression. CXCL signaling, CCL signaling, IL2 signaling and TGFß signaling pathways were involved in communication between CD3 + CD19 + cells and other immune cells. Our findings reveal the composition of CD38 + immune microenvironment together with B cells and plasma cells in IgM MGUS and WM patients, and provide comprehensive insights into mechanisms of progression from IgM MGUS to WM. The rare CD3 + CD19 + cells might be cells with "stemness" feature.

PLEKHH2 binds ß-arrestin1 through its FERM domain, activates FAK/PI3K/AKT phosphorylation, and promotes the malignant phenotype of non-small cell lung cancer.

PLEKHH2 is an important FERM domain containing-protein. However, the role of PLEKHH2 in human solid tumors has not been reported yet. We report that PLEKHH2 showed enhanced cytoplasmic expression in non-small cell lung cancer (NSCLC). Its overexpression was positively correlated with high TNM stage, low differentiation, lymphatic node metastasis, and poor prognosis. In A549 and H1299 cells, high expression of PLEKHH2 significantly promoted cell proliferation, migration, invasion, and increased the expression of proliferation- and invasion-related proteins. It also enhanced the phosphorylation of FAK and promoted the activity of the PI3K/AKT pathway. Immunofluorescence and co-immunoprecipitation analyses were performed to elucidate the molecular mechanism underlying PLEKHH2-mediated regulation of proliferation and invasion in lung cancer cells. Upon transfection of full length PLEKHH2 or its FERM domain, we observed enhanced binding of PLEKHH2 to ß-arrestin1, whereas FAK- ß-arrestin1 binding was diminished and this led to an increase in FAK phosphorylation. PLEKHH2-mutant plasmids without the FERM domain could not effectively promote its binding to ß-arrestin1, activation of FAK phosphorylation, PI3K/AKT activation, or the malignant phenotype. Our findings suggested that PLEKHH2 is an important oncogene in NSCLC. PLEKHH2 binding to ß-arrestin1 through the FERM domain competitively inhibits ß-arrestin1 binding to FAK, which causes the dissociation of FAK from the FAK-ß-arrestin1 complex. Furthermore, the dissociation of FAK promotes its autophosphorylation, activates the PI3K/AKT signaling pathway, and subsequently promotes lung cancer cell proliferation, migration, and invasion. These results provide evidence for the potential use of PLEKHH2 inhibition as an anticancer therapy.

[Acupuncture for improving neuroinflammation in vascular dementia rats by regulating Th1/Th2 cells balance in peripheral blood].

OBJECTIVE: To observe the effect of acupuncture on the balance of T helper (Th) 1/Th2 cells in peripheral blood, inflammatory reaction and intracerebral neuroinflammation in vascular dementia (VD) rats, and to explore the mechanism of acupuncture for improving cognitive function in VD. METHODS: A total of 60 SPF Wistar rats were randomized into a normal group (n=12), a sham operation group (n=12) and an operation group (n=36). Bilateral common carotid artery occlusion was adopted to establish the VD model in rats of the operation group. The rats of successful modeling were randomized into a model group and an acupuncture group, 12 rats in each one. In the acupuncture group, Sanjiao acupuncture was applied at "Danzhong" (CV 17), "Zhongwan" (CV 12), "Qihai" (CV 6), "Xuehai" (SP 10) and "Zusanli" (ST 36), the needles were manipulated for 30 s at each acupoint, without retaining. The intervention was given once a day for 15 days, and there was 1-day rest on day 8. Morris water maze test was adopted to observe the ethology, flow cytometry was used to detect the ratio of Th1/Th2 in peripheral blood, and Luminex liquid chip technology was used to detect the levels of interleukin (IL)-4, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in serum and hippocampus. RESULTS: There were no significant differences in various indexes between the normal group and the sham operation group (P>0.05). Compared with the sham operation group, in the model group, the escape latency of hidden platform test and reversal platform test was prolonged (P<0.01), the residence time of the original platform quadrant was shortened and the number of crossing the original platform was reduced in probe test (P<0.01, P<0.05), the proportion of Th1 cells was increased, the proportion of Th2 cells was decreased and the ratio of Th1/Th2 cells was increased in peripheral blood (P<0.01), the levels of TNF-α and IFN-γ were increased, the levels of IL-4 and IL-10 were decreased in serum and hippocampus (P<0.05, P<0.01). Compared with the model group, in the acupuncture group, the escape latency of hidden platform test and reversal platform test was shortened (P<0.01), the residence time of the original platform quadrant of the probe test was prolonged (P<0.05), the proportion of Th1 cells was decreased, the proportion of Th2 cells was increased and the ratio of Th1 / Th2 cells was decreased in peripheral blood (P<0.05), the levels of TNF-α and IFN-γ were decreased, the levels of IL-4 and IL-10 were increased in serum and hippocampus (P<0.05, P<0.01). CONCLUSION: Acupuncture can improve the cognitive dysfunction and reduce the intracerebral neuroinflammation in VD rats, its mechanism may relate to the regulation of Th1/Th2 cells balance and reduce the inflammatory reaction in peripheral blood.

PTP-PEST Regulated Membranous/Cytoplasmic Translocation of p120ctn in the Lung Cancer Resistance to Tyrosine Kinase Inhibitor.

Our previous studies indicate that resistance induction using first-generation tyrosine kinase inhibitors (TKIs) in lung cancer is accompanied with p120-catenin (p120ctn) cytoplasmic translocation from the membrane. However, the molecular mechanism underlying p120ctn intracytoplasmic translocation has not yet been reported. We performed immunohistochemistry to detect the correlation of p120ctn distribution with protein tyrosine phosphatase non-receptor type 12 (PTP-PEST) and p120ctn Y335 phosphorylation levels in non-small cell lung cancer (NSCLC) patients. After resistance induction using first-generation TKIs in lung cancer cells, Western blotting and substrate trapping were used to assess PTP-PEST expression and its influence on p120ctn Y335 phosphorylation, as well as the role of p120ctn Y335 phosphorylation on the association of p120ctn with E-cadherin and p120ctn membrane/cytoplasm translocation. In 197 samples collected from NSCLC patients, cytoplasmic p120ctn and enhanced p120ctn Y335 phosphorylation were associated with decreased PTP-PEST. After resistance induction using gefitinib, decreased PTP-PEST expression was accompanied by enhanced phosphorylation of p120ctn Y335 and p120ctn translocated to the cytoplasm. In gefitinib-resistant cells, PTP-PEST overexpression restrained p120ctn Y335 phosphorylation and restored membrane p120ctn expression. PTP-PEST enhanced the interaction of p120ctn with E-cadherin and elevated p120ctn membrane expression. However, increased p120ctn-Y335F mutant had no effect on p120ctn interaction with E-cadherin and membrane/cytoplasm translocation compared with the control group. In conclusion, resistance to first-generation TKIs inhibited PTP-PEST expression, which promoted p120ctn-Y335 phosphorylation and reduced the interaction of p120ctn with E-cadherin, resulting in p120ctn cytoplasmic translocation.

Periodontitis aggravates renal inflammatory response in a mouse model of renal fibrosis.

OBJECTIVES: To assess the effects of periodontitis on renal interstitial fibrosis in a mouse model. MATERIALS AND METHODS: Thirty C57BL/6 male mice were divided into control, periodontitis (PD), unilateral ureteral ligation (UUO) and PD+UUO groups. Unilateral ureteral ligation was performed 6 days after periodontitis. After 2 weeks, all mice were sacrificed, and samples were collected for the assessment of gene expression, immune cells, biochemical indicators and renal pathology. RESULTS: Expression of tumour necrosis factor-α, interleukin-1ß, and Ly6G in the kidneys in the PD+UUO group was significantly greater than in the UUO group. The percentage of CD11b+ Ly6G+ cells was significantly higher in the PD+UUO than in the UUO group. Fibrotic areas in the kidneys in the PD+UUO group were slightly, but not significantly, greater than those in the UUO group. Kidneys from the PD+UUO group showed markedly higher gene expression of matrix metalloproteinase-9, but not α-smooth muscle actin or collagen I, than those in the UUO group. There were no significant differences in blood urea nitrogen, serum creatinine and uric acid between the PD+UUO and UUO groups. CONCLUSIONS: Periodontitis increases the renal inflammatory response without showing a significant influence on renal interstitial fibrosis or renal function in the UUO mouse model.

Integrated effects of microbial decomposing inoculant on greenhouse gas emissions, grain yield and economic profit from paddy fields under different water regimes.

Few studies have comprehensively evaluated the impacts of microbial decomposing inoculants on greenhouse gas emissions and economic profit from paddy fields under different water regimes. Here, this study evaluated the effects of microbial decomposing inoculant treatments (straw returning without or with microbial decomposing inoculants (S and SMD)) on rice yield, CH4 and N2O emissions, economic profit and net ecosystem economic profit (NEEP) from paddy fields under different water regimes (continuous flooding (CF) and alternate wetting and drying irrigation (AWD)) in central China with a two-year field experiment. Compared with S treatment, SMD treatment significantly increased the rice yield and crop water productivity by 6.6-7.2% and 5.6-7.9%, respectively. AWD treatment significantly enhanced the crop water productivity by 56.9-73.7% while did not affect rice yield relative to CF treatment. Regardless of water regimes, SMD treatment did not affect N2O emissions, but significantly increased CH4 emissions by 13.8-39.6% relative to S treatment, resulting in a remarkable enhancement of global warming potential by 13.5-32.5%. Compared with S treatment, SMD treatment improved the economic profit and NEEP. By contrast, AWD treatment significantly increased N2O emissions by 19.1-64.8% compared with CF treatment, but significantly reduced CH4 emissions by 35.3-79.1%. Accordingly, AWD treatment significantly decreased the global warming potential by 33.4-73.9% compared with CF treatment. In addition, AWD treatment resulted in 39.9-96.4% higher economic profit and 48.0-124.4% higher NEEP relative to CF treatment. In summary, AWD treatment is a sustainable water regime that can maintain rice yield, mitigate global warming potential, and increase economic income. However, regardless of water regimes, SMD treatment led to higher rice yield and economic profit, as well as higher global warming potential than S treatment, suggesting that other appropriate treatments of crop straw are needed to mitigate CH4 emissions while improving economic profit for rice sustainable production.

KCTD11 inhibits progression of lung cancer by binding to ß-catenin to regulate the activity of the Wnt and Hippo pathways.

KCTD11 has been reported to be a potential tumour suppressor in several tumour types. However, the expression of KCTD11 and its role has not been reported in human non-small cell lung cancer (NSCLC). Whether its potential molecular mechanism is related to its BTB domain is also unknown. The expression of KCTD11 in 139 NSCLC tissue samples was detected by immunohistochemistry, and its correlation with clinicopathological factors was analysed. The effect of KCTD11 on the biological behaviour of lung cancer cells was verified in vitro and in vivo. Its effect on the epithelial-mesenchymal transition(EMT)process and the Wnt/ß-catenin and Hippo/YAP pathways were observed by Western blot, dual-luciferase assay, RT-qPCR, immunofluorescence and immunoprecipitation. KCTD11 is under-expressed in lung cancer tissues and cells and was negatively correlated with the degree of differentiation, tumour-node-metastasis (TNM) stage and lymph node metastasis. Low KCTD11 expression was associated with poor prognosis. KCTD11 overexpression inhibited the proliferation and migration of lung cancer cells. Further studies indicated that KCTD11 inhibited the Wnt pathway, activated the Hippo pathway and inhibited EMT processes by inhibiting the nuclear translocation of ß-catenin and YAP. KCTD11 lost its stimulatory effect on the Hippo pathway after knock down of ß-catenin. These findings confirm that KCTD11 inhibits ß-catenin and YAP nuclear translocation as well as the malignant phenotype of lung cancer cells by interacting with ß-catenin. This provides an important experimental basis for the interaction between KCTD11, ß-catenin and YAP, further revealing the link between the Wnt and Hippo pathways.

Research Progress on the Mechanism Between Polycystic Ovary Syndrome and Abnormal Endometrium.

As a highly dynamic tissue, the endometrium is periodically shed in response to the secretion of estrogen and progesterone. After menarche, the endometrium of healthy women proliferates and differentiates under the action of steroid hormones (e.g., 17ß-estradiol and progesterone) that are secreted by the ovaries to provide appropriate conditions for embryo implantation. Polycystic ovary syndrome (PCOS), a prevalent endocrine and metabolic disorder in reproductive-aged women, is usually associated with multiple cysts within the ovaries and excess levels of androgen and is characterized by hirsutism, acne, menstrual irregularity, infertility, and increased risk of insulin resistance. Multiple factors, such as anovulation, endocrine-metabolic abnormalities, and inflammation, can disrupt the endometrium in PCOS patients and can lead to endometrial hyperplasia, pregnancy complications, or even cancer. Despite many recent studies, the relationship between PCOS and abnormal endometrial function is still not fully understood. In this review, we investigate the correlation of PCOS patient endometrium with anovulation, hyperandrogenemia, insulin resistance, progesterone resistance, and inflammatory cytokines, aiming to provide a theoretical basis for the treatment of disorders caused by endometrial dysfunction in PCOS patients.

Overexpression of Ubiquitin-Specific Protease15 (USP15) Promotes Tumor Growth and Inhibits Apoptosis and Correlated With Poor Disease-Free Survival in Hepatocellular Carcinoma.

USP15 is a member of ubiquitin-specific proteases (USPs, the largest subfamily of deubiquitinases) and functions as a stabilize factor of target proteins in reversible ubiquitiantion progression. Dysregulated expression of USP15 has been observed in various cancers. However the expression profile and regulatory mechanism of USP15 in hepatocellular carcinoma (HCC) remains largely elusive. To exam the USP15 expression changes in the progression of HCC, we performed IHC analysis to test USP15 expression in a series of cancer-prone diseases including 2 normal liver tissues, 6 liver cirrhosis, 16 primary liver lesions and 15 metastases of hepatocellular carcinoma. The expression of USP15 was upregulated in various liver diseases in compared with normal tissue significantly (p < 0.05). Although no significant different of USP15 expression were discovered between cirrhotic tissue and primary tissue, its expression in HCC metastatic tissue was upregulated. Subsequently, we test the USP15 expression profile in a cohort of 66 HCC patients. USP15 expression was positively correlated with the recurrence of HCC significantly (p = 0.004). HCC patients with high USP15 expression had shorter disease free survival time in compare with those with low USP15 expression (56.9% VS 26.7%, P = 0.012). Subsequently, Cox multivariate analyses of clinical factors associated with disease free survival were performed and USP15 expression (p = 0.008) together with tumor size (p = 0.034) were proved to be independent predict factors in HCC. Then, we silenced USP15 expression in HCC cells and the results showed that downregulated USP15 expression resulting proliferation inhibition and apoptosis induction. In conclusion, our results suppose USP15 to be a potential target in HCC.

Effect of shikonin on the proliferation and apoptosis of human ovarian cancer cell SKOV3: A protocol of systematic review and meta-analysis.

BACKGROUND: This study will investigate the effect of shikonin on the proliferation and apoptosis of human ovarian cancer cell SKOV3 (HOCC-SKOV3). METHODS: We will retrieve potential studies from inception to the March 1, 2020 in Cochrane Library, MEDLINE, EMBASE, Scopus, Cumulative Index to Nursing and Allied Health Literature, WANGFANG, and China National Knowledge In-frastructure. There are not restrictions related to the language and publication status. This study will include case-controlled studies (CCSs) or randomized controlled studies (RCSs) that examine the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3. Two researchers will independently identify literatures, extract data, and appraise study quality. Any disagreements will be resolved by discussion with another researcher. RevMan 5.3 software will be placed to perform statistical analysis. RESULTS: This study will summarize the present evidence to test the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3. CONCLUSION: It will provide evidence to investigate the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3, and will supply reference for further study.Systematic review registration: INPLASY202040146.

ANKHD1 promotes proliferation and invasion of non­small­cell lung cancer cells via regulating YAP oncoprotein expression and inactivating the Hippo pathway.

The ankyrin repeat and KH domain­containing 1 (ANKHD1) protein was recently reported to be a potential member of the Hippo signaling pathway. However, its role in human non­small­cell lung cancer (NSCLC) has not been extensively investigated. The aim of the present study was to examine the expression of ANKHD1 in primary human tissues and cells and determine whether it is correlated with the clinical characteristics of tumor growth. The biological functions of ANKHD1 were evaluated in vitro and in vivo. Yes­associated protein (YAP) expression and phosphorylation induced by ANKHD1 were evaluated by western blotting and immunoprecipitation. Marked upregulation of ANKHD1 protein expression was observed in NSCLC cells and tissues, which was associated with advanced pathological tumor­node­metastasis stage, lymph node metastasis and poor prognosis in patients with NSCLC. ANKHD1 overexpression also promoted the proliferation and invasion of NSCLC cells. ANKHD1 upregulation inactivated Hippo signaling via increasing YAP protein levels, as well as inhibiting YAP protein phosphorylation, whereas depletion of YAP abolished the effects of ANKHD1 on cell proliferation and invasion. Therefore, ANKHD1 may play an important role in NSCLC through regulating the YAP­dependent Hippo signaling pathway.

Down-regulation of miR-10b represses cell vitality in osteosarcoma and is inversely associated with prognosis via interacting with FAM46C: Running title: MiR-10b/FAM46C axis modulates OS progression.

The purpose of this exploration was to detect the biological effects of miR-10b/FAM46C pair on osteosarcoma (OS) development. By accessing to the Gene Expression Omnibus (GEO) database, we achieved expressional profiles of miR-10b and FAM46C. Kaplan-Meier method was applied to determine the overall survival rates of OS patients. MiR-10b mimic/inhibitor were utilized to alter miR-10b expression. Overexpression of FAM46C was induced by pcDNA3.1-FAM46C. QRT-PCR and western blot were conducted to assess the expression levels. Cell counting kit-8 (CCK-8) and transwell assays were employed to evaluate the proliferative, invasive and migratory properties of OS cells. Pearson correlation analysis was performed to confirm the association between miR-10b and FAM46C. Dual-luciferase reporter assay was conducted to determine the target of miR-10b. The overall survival of OS patients was inversely correlated with miR-10b expression. MiR-10b was increased in OS compared with normal controls. Depletion of miR-10b attenuated the proliferation, invasion and migration of MG-63 cells. FAM46C was considered as a target gene of miR-10b and inversely related with miR-10b. Overexpression of FAM46C could inhibit cell growth, invasion and migration in OS; furthermore, it also can enforced the miR-10b inhibitor-induced effects on cell behaviors of OS cells. Down-regulation of miR-10b played a suppressive effect on the cell activity in OS cells, which provides a novel insight into the advance of OS therapeutic therapies.

Rhodobacter sphaeroides Extract Lycogen™ Attenuates Testosterone-Induced Benign Prostate Hyperplasia in Rats.

Benign prostate hyperplasia (BPH) is one of the most common urological problems in mid-aged to elderly men. Risk factors of BPH include family history, obesity, type 2 diabetes, and high oxidative stress. The main medication classes for BPH management are alpha blockers and 5α-reductase inhibitors. However, these conventional medicines cause adverse effects. Lycogen™, extracted from Rhodobacter sphaeroides WL-APD911, is an anti-oxidant and anti-inflammatory compound. In this study, the effect of Lycogen™ was evaluated in rats with testosterone-induced benign prostate hyperplasia (BPH). Testosterone injections and Lycogen™ administration were carried out for 28 days, and body weights were recorded twice per week. The testosterone injection successfully induced a prostate enlargement. BPH-induced rats treated with different doses of Lycogen™ exhibited a significantly decreased prostate index (PI). Moreover, the Lycogen™ administration recovered the histological abnormalities observed in the prostate of BPH rats. In conclusion, these findings support a dose-dependent preventing effect of Lycogen™ on testosterone-induced BPH in rats and suggest that Lycogen™ may be favorable to the prevention and management of benign prostate hyperplasia.

Spermidine ameliorates the neuronal aging by improving the mitochondrial function in vitro.

Changes in mitochondrial structure and function are the initial factors of cell aging. Spermidine has an antiaging effect, but its effect on neuronal aging and mitochondrial mechanisms is unclear. In this study, mouse neuroblastoma (N2a) cells were treated with d­galactose (d­Gal) to establish cell aging to investigate the antiaging effect and mechanisms of spermidine. Changes in the cell cycle and ß-galactosidase activity were analyzed to evaluate the extent of cell aging. Stabilities of mitochondrial mRNA and mitochondrial membrane potential (MMP) were evaluated in the process of cell aging under different treatments. The mitochondrial function was also evaluated using the Seahorse Metabolic Analysis System combined with ATP production. The unfolded protein response (UPR) of the N2a cells was analyzed under different treatments. Results showed that spermidine pretreatment could delay the cell aging and could maintain the mitochondrial stability during d­Gal treatment. Spermidine increased the proportion of cells in the S phase and maintained the MMP. The oxygen utilization and ATP production in the N2a cells were reduced by d­Gal treatment but were partially rescued by the spermidine pretreatment. Spermidine ameliorated the N2a cell aging by promoting the autophagy and inhibiting the apoptosis except the UPR. These results showed that spermidine could ameliorate the N2a cell aging by maintaining the mitochondrial mRNA transcription, MMP and oxygen utilization during the d­Gal treatment.

Pulmonary Papillary Adenoma: Report of Two Cases.

Pulmonary papillary adenoma is a rare tumor. Two cases without any clinical symptoms were enrolled in our hospital. Both cases were incidentally detected in pulmonary area by imaging. Pathological examination revealed well-circumscribed nodules consisting of papillary growth of cuboidal to low columnar epithelial cells lining the surface of the fibrovascular stroma. Immunohistochemistry (IHC) staining showed that the lining cells were diffusely positive for TTF-1, CK, p63, CK7, and Napsin A. The Ki-67 proliferation index was approximately 2%. The morphological features and the IHC profile of the tumor were in agreement with that of pulmonary papillary adenoma. Both patients are doing well without recurrence or metastasis of the tumor.