Dietary phytoestrogen intake and ovarian cancer risk: a prospective study in the Prostate, Lung, Colorectal and Ovarian (PLCO) cohort.

Estrogen plays crucial roles in ovarian tumorigenesis. Phytoestrogens (PEs) are a type of daily dietary nutrients for humans and possess a mild estrogenic characteristic. This study aimed to assess the correlation of the consumption of dietary PEs with ovarian cancer risk using data in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Participants were enrolled in PLCO from 1993 to 2001. Hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to determine the association between the intake of PEs and ovarian cancer occurrence, which were calculated by the Cox proportional hazards regression analysis. Totally, 24,875 participants were identified upon completion of the initial dietary questionnaire (DQX). Furthermore, the analysis also included a total of 45,472 women who filled out the diet history questionnaire (DHQ). Overall, after adjustment for confounders, the dietary intake of total PEs was significantly associated with the risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.69, 95% CI: 0.50-0.95; P for trend = 0.066). Especially, individuals who consumed the highest quartile of isoflavones were found to have a decreased risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.68, 95% CI: 0.50-0.94; P for trend = 0.032). However, no such significant associations were observed for the DQX group. In summary, this study suggests that increased dietary intake of total PEs especially isoflavones was linked with a lower risk for developing ovarian cancer. More researches are necessary to validate the findings and explore the potential mechanisms.

Effect of prehabilitation on postoperative outcomes in the frail older people: A systematic review and meta-analysis.

OBJECTIVE: The study investigates the impact of preoperative rehabilitation on the surgical prognosis of frail older patients. METHOD: The effect sizes of all studies retrieved and included by the nine databases were analyzed and expressed as RR and WMD. RESULTS: 8 studies with 902 participants met the criteria for inclusion. A significant reduction in total complications (RR = 0.84, 95 % CI = 0.73 to 0.97, P = 0.021) and the 6MWT after surgery (WMD = 74.76, 95 % CI = 44.75 to 104.77, P = 0.000) was observed in the prehabilitation group. But it had no differences in mortality(RR = 1.89, 95 % CI = 0.75 to 4.72, P = 0.176), readmission rates(RR = 1.04, 95 % CI = 0.56 to 1.91, P = 0.906) and LOS(WMD = -0.24, 95 % CI = -1.00 to 0.52, P = 0.540). CONCLUSIONS: Prehabilitation had positive effect on postoperative complications and functional recovery in frail older patients.

Blocking exosomal secretion aggravated 1,4-benzoquinone-induced cytotoxicity.

Benzene exposure inhibits the hematopoietic system and leads to the occurrence of various types of leukemia. However, the mechanism underlying the hematotoxicity of benzene is still largely unclear. Emerging evidence has shown that exosomes are involved in toxic mechanisms of benzene. To understand the effect of 1,4-benzoquinone (PBQ; an active metabolite of benzene in bone marrow) on the exosomal release characteristics and role of exosomal secretion in PBQ-induced cytotoxicity. Exosomes were isolated from PBQ-treated HL-60 cells, purified by ultracentrifugation, and verified by transmission electron microscopy, nanoparticle tracking analysis and the presence of specific biomarkers. Our results showed that PBQ increased exosomal secretion in a dose-dependent manner, reaching a peak in 3 h at 10 µM PBQ treatment and then slowly decreasing in HL-60 cells. The exosomes contained miRNAs, which have been reported to be associated with benzene exposure or benzene poisoning. In particular, mir-34a-3p and mir-34A-5p were enriched in exosomes derived from PBQ-treated cells. In addition, the inhibition of exosomal release by GW4869 (an inhibitor of exosomal release) exacerbated PBQ-induced cytotoxicity, including increased intracellular reactive oxygen species levels, decreased mitochondrial membrane potential, and increased the apoptosis rate. Our findings illustrated that exosomes secretion plays an important role in antagonizing PBQ-induced cytotoxicity and maintaining cell homeostasis.

Idiopathic calcinosis cutis of the buttocks: A case report and review of the literature.

RATIONALE: Calcinosis cutis is a rare skin disease, and idiopathic cases are rarely reported. It is characterized by the deposition of insoluble calcium salts in the skin, subcutaneous tissue, superficial muscles, and tendon sheaths. However, no abnormal changes were found in the bone. In this article, we introduce a case of idiopathic calcinosis cutis of the buttocks with a long course and large lesion area. PATIENT CONCERNS: A 51-year-old male patient was admitted to the hospital with a chief complaint of 'Due to the discovery of hard nodules with pruritus in the buttocks for 32 years. The patient was a male who was 51 years old. He has been in good health and reported no history of surgery, trauma, infection, metabolic disease, tumor, or other diseases. There was no family history. It is worth noting that the patient has the occupation of driving trucks, which keeps him sedentary. DIAGNOSES: The accurate diagnosis of calcinosis cutis was confirmed by postoperative histopathological examination with many local calcifications and multinucleated giant cells in subcutaneous tissue. INTERVENTIONS: The patient underwent skin lesion excision and autologous skin grafting under general anesthesia. A medium-thickness skin graft from the left lateral thigh was transplanted into the hip operation area, and a bolus tie-over pressure dressing was applied. After the operation, the patient received anti-infection treatment and was advised to rest in the prone position to prevent extrusion of the operation area. OUTCOMES: The postoperative recovery was good, and there was no recurrence after 4 months of follow-up. LESSONS: The incidence rate of cutaneous calcinosis is not clear. This patient had a large lesion area, long onset time, an invasion of the fat layer, and the onset site was located in the sacrococcygeal region. It is necessary to choose appropriate treatment methods.

TUBA1C: a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression.

BACKGROUND: The lack of obvious symptoms of early gastric cancer (GC) as well as the absence of sensitive and specific biomarkers results in poor clinical outcomes. Tubulin is currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders, however, its mechanism of action in gastric cancer is still unclear. Tubulin alpha-1 C (TUBA1C) is a subtype of α-tubulin, high TUBA1C expression has been shown to be closely related to a poor prognosis in various cancers, this study, for the first time, revealed the mechanism of TUBA1C promotes malignant progression of gastric cancer in vitro and in vivo. METHODS: The expression of lncRNA EGFR-AS1 was detected in human GC cell lines by qRT-PCR. Mass spectrometry experiments following RNA pulldown assays found that EGFR-AS1 directly binds to TUBA1C, the CCK8, EdU, transwell, wound-healing, cell cycle assays and animal experiments were conducted to investigate the function of TUBA1C in GC. Combined with bioinformatics analyses, reveal interaction between Ki-67, E2F1, PCNA and TUBA1C by western blot. Rescue experiments furtherly demonstrated the relationship of EGFR-AS1and TUBA1C. RESULTS: TUBA1C was proved to be a direct target of EGFR-AS1, and TUBA1C promotes gastric cancer proliferation, migration and invasion by accelerating the progression of the cell cycle from the G1 phase to the S phase and activating the expression of oncogenes: Ki-67, E2F1 and PCNA. CONCLUSION: TUBA1C is a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression and could be a novel biomarker and therapeutic target for GC.

A retrospective study of 1064-nm Q-switched Nd:YAG laser therapy for acquired bilateral nevus of Ota-like macules.

BACKGROUND: The therapeutic efficacy of laser treatments for acquired bilateral nevus of Ota-like macules (ABNOM) varies among studies, and few studies have evaluated the factors affecting therapeutic effects. AIMS: To evaluate the efficacy and safety of 1064-nm Q-switched Nd:YAG laser (QSNYL) therapy for ABNOM and to identify the factors influencing the outcome. METHODS: A total of 110 patients with ABNOM were retrospectively evaluated and received two-to-nine treatment sessions. The effects of different factors on the therapeutic effect were analyzed on the basis of the number of treatments, age at first treatment, skin type, lesion color, affected area, number of lesion sites, and presence of concomitant melasma. RESULTS: The curative effect was positively correlated with the treatment time and negatively correlated with the increasing age at first treatment (p < 0.05). The curative effect was better in patients with skin type III than those with type IV ( p < 0.05) and in patients with a lesion area of less than 10 cm2 than those with a larger affected area (p < 0.05). Additionally, the treatment effect was poorer in patients with concomitant melasma (p < 0.05). The treatment effect was not significantly correlated with the lesion color or number of affected sites (p > 0.05). Eleven patients (10%) developed postinflammatory hyperpigmentation (PIH). CONCLUSIONS: Early and repeated QSNYL therapy achieved satisfactory results for ABNOM. The risk of PIH after laser treatment is highest among patients with older age, darker lesion color, and darker skin color. For patients with ABNOM with concurrent melasma, low-energy laser therapy is recommended to reduce the risk of melasma aggravation.

Preliminary study of the intranuclear function of Sma and Mad related protein 5 gene in Litopenaeus vannamei.

Litopenaeus vannamei Smad5 (LvSmad5) in cytoplasm has been proved to be involved in environmental stress response. As LvSmad5 could also locate in nucleus under specific stress, it was conjectured that LvSmad5 might participate in environmental stress response. While, the experimental evidence is still lacking. In this study, cytosolic LvSmad5 mutant or nuclear LvSmad5 mutant was expressed in Drosophila S2 cells, and then transcriptomic analysis of mentioned cells was performed using Illumina HiSeq based RNA-Seq, to reveal the function of LvSmad5 in nucleus. By comparing the two groups of cDNA libraries from S2 cells with cytosolic or nucleus LvSmad5 mutant, 86 differentially expressed genes as well as 765 differentially expressed transcripts were found. It was revealed that genes in the ER-stress response pathway, such as unfolded protein response and ER-associated degradation (ERAD) were enriched. Additionally, some kinds of metabolic reprogramming occurred in S2 cells with over-expressing nuclear LvSmad5, for significant changes in the expression of some metabolism-related genes. To test our infer that nuclear LvSmad5 was engaged in environmental stress response, homologous gene of Drosophila translocation in renal carcinoma on chromosome 8 in L.vannamei (LvTRC8) was chosen for further investigation. And studies about LvTRC8, a member of ERAD showed that it was induced by ER-stress or heat shock treatment. Suppressed the expression of LvTRC8 increased the cumulative mortality of shrimp upon stress. In some degree, these results support our speculation that nuclear LvSmad5 are involved in the environmental stress response of L. vannamei in fact.

Blocking exosomal secretion aggravates 1,4-benzoquinone-induced mitochondrial fission activated by the AMPK/MFF/Drp1 pathway in HL-60 cells.

There is in vivo and in vitro evidence that exposure to benzene or its metabolites could affect the mitochondrial function. However, the underlying molecular mechanism of mitochondrial damage remains to be elucidated. In this study, exposure of human promyelocytic leukemia cells (HL-60) to 1,4-benzoquinone (1,4-BQ; an active metabolite of benzene) increased the intracellular reactive oxygen species levels, decreased the mitochondrial membrane potential, adenosine triphosphate production and mitochondrial DNA (mtDNA) copy number, up-regulated the expression of mitochondrial fission proteins Drp1 and Fis1, and down-regulated the expression of mitochondrial fusion proteins Mfn2 and Opa1. Further study showed that 1,4-BQ mediated mitochondrial fission through activation of the AMP-activated protein kinase/mitochondrial fission factor/dynamin-related protein 1 pathway. Additionally, we also examined the role of exosomal secretion in mitochondrial damage under 1,4-BQ treatment. Results showed that 1,4-BQ increased the total protein level and mtDNA content in exosomes. Upon pre-treatment with the mitochondria-targeted antioxidant SS-31, there was attenuation of the mitochondrial damage induced by 1,4-BQ, accompanied by a change in the exosome release characteristics, while inhibition of exosomal secretion using GW4869 aggravated the 1,4-BQ-mediated mitochondrial fission. We concluded that exosomal secretion may serve as a self-protective mechanism of cells against 1,4-BQ-induced mitochondria damage and mitochondrial dynamics interference.

SNHG16/miR-485-5p/BMP7 axis modulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.

BACKGROUND: Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) is crucial for bone formation and its dysfunction is reported to be linked to osteoporosis (OP). The present study aimed to probe the function of the long non-coding RNA small nucleolar RNA host gene 16 (SNHG16) with respect to modulating the osteogenic differentiation of hBMSCs. METHODS: SNHG16 expression in hBMSCs obtained from OP patients was measured by a quantitative real-time polymerase chain reaction (qRT-PCR). Gain-of-function and loss-of-function models of SNHG16 were established with hBMSCs. The expression of OP-related genes (ALP, OCN and OPN) in hBMSCs was determined by qRT-PCR and western blotting. StarBase, TargetScan7.2, miRDB and PicTar databases were used to predict the binding sites between SNHG16 and miR-485-5p, miR-485-5p and 3'-UTR of bone morphogenetic protein 7 (BMP7), respectively. A dual-luciferase reporter assay was used to determine the regulatory relationships between SNHG16 and miR-485-5p, miR-485-5p and 3'-UTR of BMP7, respectively. RESULTS: SNHG16 was remarkably down-regulated in hBMSCs obtained from patients with OP. Overexpression of SNHG16 promoted the osteogenic differentiation of hBMSCs, whereas knockdown of SNHG16 suppressed it. Mechanistically, miR-485-5p is a target of SNHG16, and miR-485-5p can reverse the function of SNHG16. BMP7 is also identified as a target of miR-485-5p and can be indirectly modulated by SNHG16 in hBMSCs. CONCLUSIONS: SNHG16 promotes the osteogenic differentiation of hBMSCs via regulating the miR-485-5p/BMP7 axis and comprises a prospective therapy target for OP.

Preparative HPLC fraction of Hibiscus rosa-sinensis essential oil against biofilm forming Klebsiella pneumoniae.

Recent years Klebsiella pneumoniae (K. pneumoniae) biofilm formation (BF) is emerging thread worldwide. For tackling this problem, we have chosen Hibiscus rosa-. pneumoniae. The HPLC purified essential oils (EOs sinensis (H. rosa-sinensis) (HRS) to inhibit the BF K) of H. rosa-sinensis was performed against BF K. pneumoniae and showed concentration dependent biofilm inhibition. At the MBIC of EOs (90 µg/ml), the biofilm inhibition was showed at 92% against selected BF K. Pneumoniae. The biofilm metabolic assay, exopolysaccharide quantification and hydrophobicity index variation results exhibited with 88%, 92% and 89% reduction at 90 µg/mL was observed respectively. In addition, the morphological modification of MBIC treated K. pneumoniae was clearly viewed by scanning electron microscope (SEM). Overall, all the invitro experiments result were confirmed that the MBIC of H. rosa-sinensis EOs was very effective against BF K. pneumonia.

Assessment of the Therapeutic Effects of Fucoxanthin by Attenuating Inflammation in Ovalbumin-Induced Asthma in an Experimental Animal Model.

Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.

Benzoquinone induces ROS-dependent mitochondria-mediated apoptosis in HL-60 cells.

Benzene exposure affects the hematopoietic system and leads to the occurrence of various types of leukemia and hematotoxicity. It has been confirmed that active metabolites of benzene, including 1,4-benzoquinone (1,4-BQ), can induce reactive oxygen species (ROS) and apoptosis in the bone marrow, and recent studies have also suggested that benzene exposure can affect mitochondrial function in both experimental animals and cell lines. However, the potential relationship among ROS production, mitochondrial damages, and subsequent apoptosis following benzene exposure has not been well studied in detail. In the present study, we utilized HL-60 cells, a well-characterized human myeloid cell line, as an in vitro model and examined the effects of 1,4-BQ on intracellular ROS formation, mitochondria damage, and the occurrence of apoptotic events with or without using the ROS scavenger N-acetyl-l-cysteine (NAC). The results demonstrated that 1,4-BQ could dose-dependently induce production of ROS and mitochondrial damage as characterized by mitochondrial membrane potential disruption, mitochondrial ultrastructure alteration, and induced apoptosis and activated caspase-3 and caspase-9. Preincubation of HL-60 cells with NAC prior to 1,4-BQ treatment could block 1,4-BQ-induced production of ROS and the occurrence of apoptosis. These results demonstrated that 1,4-BQ induced apoptosis in HL-60 cells through a ROS-dependent mitochondrial-mediated pathway.

[mRNA expression and methylation status of p15 promoter in mouse bone marrow cells exposed to 1,4-benzoquinone].

OBJECTIVE: To detect the expression and the CpG island methylation status of tumor suppressor gene p15 after exposure to 1,4-benzoquinone (1,4-BQ) in primary cultivated C57BL/6J mouse bone marrow cells in vitro. METHODS: The mouse bone marrow cells were isolated in vitro. The effect of 0, 0.1, 1, 5, 10, 20, and 40 µmol/L 1,4-BQ on cell viability (CKK-8) was detected. 0, 0.1, 1, 10 µmol/L 1,4-BQ were used to intoxicate the mouse bone marrow cells for 24 h; Real-time PCR was employed to analyze the mRNA expression level of p15; The bisulfite sequencing PCR (BSP) was used to look into the methylation status of CpG islands in p15 promoter region. RESULTS: 1,4-BQ exhibited dose-dependent toxicity to mouse bone marrow cells, and the LC(50) was 8.3 µmol/L (95%CI: 4.6 - 10.6 µmol/L). The mRNA expression of p15 in 10 µmol/L group was only equivalent to 43% of control group. Compared with control group, the decrease of p15 mRNA expression in1 and 10 µmol/L concentration were obvious, and the differences had statistical significance (P < 0.05 or P < 0.01). BSP sequencing results were same between the exposure groups and control group, the 56 CpG sites on CpG islands remained in the state of unmethylated. CONCLUSION: mRNA expression of p15 gene decreases after exposure to 1,4-BQ, but the CpG islands methylation status in promoter is not affected, suggesting that methylation does not participate in 1,4-BQ-mediated p15 gene expression decrease, other effect mechanisms still need to be investigated.

Overexpression of SOX15 inhibits proliferation of NT2/D1 cells derived from a testicular embryonal cell carcinoma.

SOX (Sry-related HMG box) family proteins, which have an evolutionarily conserved DNA binding domain, have crucial roles in cell differentiation. However, their target genes remain enigmatic. Some members of the SOX family may have roles in regulation of cell proliferation. We established stable NT2/D1 cell lines overexpressing SOX15 (SOX15-NT2/D1), and a modified 3-(4,5-dime-thylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that the SOX15-NT2/D1 cells exhibited significantly slower growth than the controls. Flow cytometry analysis revealed that an increased fraction of the SOX15-NT2/D1 cells were in G1-G0. In addition, a microarray analysis identified 26 genes that were up-regulated in the SOX15-NT2/D1 cells, but none that were down-regulated genes. Among the up-regulated genes, IGFBP5, S100A4, ID2, FABP5, MTSS1, PDCD4 have been shown to be related to cell proliferation and/or the cell cycle.