Molecular genetics and research progress of uterine leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is a type of malignant soft-tissue tumor, which is developed from myometrium in the female reproductive system. This disease is difficult to be distinguished from benign uterine leiomyoma in the early stages, but it progresses aggressively and relentlessly. Hence, uLMS has a dismal prognosis and high rates of both misdiagnosis and missed diagnosis. Unfortunately, current studies of uLMS pathogenesis and disease biology are inadequate. uLMS disease models are also very limited, hindering the development of effective therapeutics. In this review, we focus on the pathological molecular biology of uLMS, and systematically review the molecular genetic features, epigenetic variants, experimental models, and clinical research progress of uLMS. We further discuss the development direction and potential needs of uLMS in the fields of tumor evolution, tumor microenvironment, and tumor therapy, with the aim of providing a better understanding of the pathobiological mechanism of uLMS and providing a reference for the development of potential diagnostic and therapeutic strategies.

Folic acid-mediated hollow Mn 3 O 4 nanocomposites for in vivo MRI/FLI monitoring the metastasis of gastric cancer.

BACKGROUND: Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric cancer metastasis. METHODS: In this paper, we constructed a new type of hollow Mn 3 O 4 nanocomposites, Mn 3 O 4 @HMSN-Cy7.5-FA, which had a size distribution of approximately 100 nm and showed good stability in different liquid environments. The in vitro magnetic resonance imaging (MRI) results show that the nanocomposite has good response effects to the acidic microenvironment of tumors. The acidic environment can significantly enhance the contrast of T 1 -weighted MRI. The cellular uptake and endocytosis results show that the nanocomposite has good targeting capabilities and exhibits good biosafety, both in vivo and in vitro. In a gastric cancer nude mouse orthotopic metastatic tumor model, with bioluminescence imaging's tumor location information, we realized in vivo MRI/fluorescence imaging (FLI) guided precise monitoring of the gastric cancer orthotopic and metastatic tumors with this nanocomposite. RESULTS: This report demonstrates that Mn 3 O 4 @HMSN-Cy7.5-FA nanocomposites is a promising nano-diagnostic platform for the precision diagnosis and therapy of gastric cancer metastasis in the future. CONCLUSIONS: In vivo MRI/FLI imaging results show that the nanocomposites can achieve accurate monitoring of gastric cancer tumors in situ and metastases. BLI's tumor location information further supports the good accuracy of MRI/FLI dual-modality imaging. The above results show that the MHCF NPs can serve as a good nano-diagnostic platform for precise in vivo monitoring of tumor metastasis. This nanocomposite provides more possibilities for the diagnosis and therapy of gastric cancer metastases.

Study on Green Nanofluid Profile Control and Displacement of Oil in a Low Permeability Reservoir.

Low permeability reservoirs are characterized by low permeability, small pore throat, strong heterogeneity, and poor injection-production ability. High shale content of the reservoir, strong pressure sensitivity, micropore undersaturation, and significant water-lock effect in water injection development lead to increased fluid seepage resistance. There is an urgent need to adopt physical and chemical methods to supplement energy and improve infiltration efficiency, thereby forming effective methods for increasing the production and efficiency. Aiming at the characteristics of ultralow permeability reservoirs, in this paper, a green and environmental friendly biobased profile control and displacement agent (Bio Nano30) has been developed using noncovalent supramolecular interaction. Physical simulation experiments illustrate the profile control and displacement mechanism of Bio-Nano30. Laboratory experiments and field applications show that good results have been achieved in oil well plugging removal, water well pressure reduction and injection increase, and well group profile control and oil displacement. This research has good application prospects in low permeability heterogeneous reservoirs.

[Cloning and expression analysis of U6 promoters in Panax quinquefolius].

The U6 promoter is an important element driving sgRNA transcription in the CRISPR/Cas9 system. Seven PqU6 promo-ter sequences were cloned from the gDNA of Panax quinquefolium, and the transcriptional activation ability of the seven promoters was studied. In this study, seven PqU6 promoter sequences with a length of about 1 300 bp were cloned from the adventitious roots of P. quinquefolium cultivated for 5 weeks. Bioinformatics tools were used to analyze the sequence characteristics of PqU6 promoters, and the fusion expression vectors of GUS gene driven by PqU6-P were constructed. Tobacco leaves were transformed by Agrobacterium tumefaciens-mediated method for activity detection. The seven PqU6 promoters were truncated from the 5'-end to reach 283, 287, 279, 289, 295, 289, and 283 bp, respectively. The vectors for detection of promoter activity were constructed with GUS as a reported gene and used to transform P. quinquefolium callus and tobacco leaves. The results showed that seven PqU6 promoter sequences(PqU6-1P to PqU6-7P) were cloned from the gDNA of P. quinquefolium, with the length ranged from 1 246 bp to 1 308 bp. Sequence comparison results showed that the seven PqU6 promoter sequences and the AtU6-P promoter all had USE and TATA boxes, which are essential elements affecting the transcriptional activity of the U6 promoter. The results of GUS staining and enzyme activity test showed that all the seven PqU6 promoters had transcriptional activity. The PqU6-7P with a length of 1 269 bp had the highest transcriptional activity, 1.31 times that of the positive control P-35S. When the seven PqU6 promoters were truncated from the 5'-end(PqU6-1PA to PqU6-7PA), their transcriptional activities were different in tobacco leaves and P. quinquefolium callus. The transcriptional activity of PqU6-7PA promoter(283 bp) was 1.59 times that of AtU6-P promoter(292 bp) when the recipient material was P. quinquefolium callus. The findings provide more ideal endogenous U6 promoters for CRISPR/Cas9 technology in ginseng and other medicinal plants.

Cobalt Ferrite-Gossypol Coordination Nanoagents with High Photothermal Conversion Efficiency Sensitizing Chemotherapy against Bcl-2 to Induce Tumor Apoptosis.

Gossypol is a chemotherapeutic drug that can inhibit the anti-apoptotic protein Bcl-2, but the existing gossypol-related nanocarriers cannot well solve the problem of chemotherapy resistance. Based on the observation that gossypol becomes black upon Fe3+ coordination, it is hypothesized that encasing gossypol in glyceryl monooleate (GMO) and making it coordinate cobalt ferrite will not only improve its photothermal conversion efficiency (PCE) but also help it enter tumor cells. As the drug loading content and drug encapsulation efficiency of gossypol are 10.67% (w/w) and 96.20%, the PCE of cobalt ferrite rises from 14.71% to 36.00%. The synergistic therapeutic effect finally induces tumor apoptosis with a tumor inhibition rate of 96.56%, which is 2.99 and 1.47 times higher than chemotherapy or photothermal therapy (PTT) alone. PTT generated by the GMO nanocarriers under the irradiation of 808 nm laser can weaken tumor hypoxia, thereby assisting gossypol to inhibit Bcl-2. In addition, the efficacy of nanocarriers is also evaluated through T2 -weighted magnetic resonance imaging. Observations of gossypol-induced apoptosis in tissue slices provide definitive proof of chemotherapy sensitization, indicating that such coordination nanocarriers can be used as an effective preclinical agent to enhance chemotherapy.

Stimulation phosphatidylinositol 3-kinase/protein kinase B signaling by Porphyromonas gingivalis lipopolysacch aride mediates interleukin-6 and interleukin-8 mRNA/protein expression in pulpal inflammation.

BACKGROUND/PURPOSE: The signaling mechanisms for Porphyromonas gingivalis lipopolysaccharide (PgLPS)-induced inflammation in human dental pulp cells are not fully clarified. This in vitro study aimed to evaluate the involvement of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in PgLPS-induced pulpal inflammation. METHODS: Human dental pulp cells (HDPCs) were challenged with PgLPS with or without pretreatment and coincubation with a PI3K/Akt inhibitor (LY294002). The gene or protein levels of PI3K, Akt, interleukin (IL)-6, IL-8, alkaline phosphatase (ALP), osteocalcin and osteonectin were analyzed by reverse transcription polymerase chain reaction (PCR), real-time PCR, western blotting, and immunofluorescent staining. In addition, an enzyme-linked immunosorbent assay was used to analyze IL-6 and IL-8 levels in culture medium. RESULTS: In response to 5 µg/ml PgLPS, IL-6, IL-8, and PI3K, but not Akt mRNA expression of HDPCs, was upregulated. IL-6, IL-8, PI3K, and p-Akt protein levels were stimulated by 10-50 µg/ml of PgLPS in HDPCs. PgLPS also induced IL-6 and IL-8 secretion at concentrations higher than 5 µg/ml. Pretreatment and co-incubation by LY294002 attenuated PgLPS-induced IL-6 and IL-8 mRNA expression in HDPCs. The mRNA expression of ALP, but not osteocalcin and osteonectin, was inhibited by higher concentrations of PgLPS in HDPCs. CONCLUSION: P. gingivalis contributes to pulpal inflammation in HDPCs by dysregulating PI3K/Akt signaling pathway to stimulate IL-6 and IL-8 mRNA/protein expression and secretion. These results are useful for understanding the pulpal inflammation and possible biomarkers of inflamed pulp diagnosis and treatment.

Antioxidant Activity, Functional Properties, and Cytoprotective Effects on HepG2 Cells of Tree Peony (Paeonia suffruticosa Andr.) Seed Protein Hydrolysate as Influenced by Molecular Weights Fractionation.

In recent years, plant protein hydrolysates have gained increased attention due to their superior antioxidant activity and potential to prevent several chronic diseases associated with oxidative stress. This study aimed to investigate the antioxidant activity, functional properties, and cytoprotective effects of the tree peony seed protein hydrolysate (TPSPH) with different molecular weights (MWs). The antioxidant activities were evaluated by DPPH, hydroxyl radicals scavenging, Fe2+ chelating, and inhibition of the ß-carotene oxidation abilities. The protective effects and mechanism against oxidative stress were determined using H2O2-stressed HepG2 cells. MW > 30 kDa of TPSPH showed the highest radical scavenging (DPPH IC50 = 0.04, hydroxyl IC50 = 0.89 mg/mL) and inhibition of ß-carotene oxidation (80.07% at 2.0 mg/mL) activity. Moreover, MW > 30 kDa possessed high hydrophobicity, emulsifying capacity, and abundant antioxidant amino acids (28.22% of hydrophobic amino acids and 8.3% of aromatic amino acids). MW 5−10 kDa exhibited more effective protection against H2O2-induced HepG2 cells, by reducing reactive oxygen species (ROS), malonaldehyde (MDA), lactate dehydrogenase (LDH), and activating antioxidant enzymes (superoxide dismutase and catalase). These results indicated the potential application of TPSPH as an antioxidant in food and functional foods.

Expression and the Prognostic Value of Biglycan in Gastric Cancer.

Background: Biglycan (BGN) is a family member of small leucine-rich repeat proteoglycans. High expression of BGN might enhance the invasion and metastasis in some types of tumors. Here, the prognostic significance of BGN was evaluated in gastric cancer. Material and Methods. Two independent Gene Expression Omnibus (GEO) gastric cancer microarray datasets (n = 64 and n = 432) were collected for this study. Kaplan-Meier analysis was applied to evaluate if BGN impacts the outcomes of gastric cancer. Protein-protein interaction (PPI) analysis was performed on gastric cancer-related genes and BGN targets, and those interactions with confidence interval (CI) ≥ 0.7 were chosen to construct a PPI network. The gene set enrichment analysis (GSEA) was used to explore BGN and cancer-related gene signatures. Gene Transcription Regulation Database (GTRD) and ALGGEN-PROMO predicted the transcription factor binding sites (TFBSs) of the BGN promoter. BGN protein level in gastric cancer tissue was determined by immunohistochemistry (IHC). Bioinformatic analysis predicted the putative TFs of BGN. Results: For gastric cancer, the mRNA expression level of BGN in tumor tissue was significantly higher than that in normal tissue. Kaplan-Meier analysis showed that higher expression of BGN mRNA was significantly associated with more reduced recurrence-free survival (RFS). GSEA results suggested that BGN was significantly enriched in gene signatures related to metastasis and poor prognosis, revealing that BGN might be associated with cell proliferation, poor differentiation, and high invasiveness of gastric cancer. Meanwhile, the putative TFs, including AR, E2F1, and TCF4, were predicted by bioinformatic analysis and also significantly correlated with expression of BGN in mRNA levels. Conclusion: High expression of BGN mRNA was significantly related to poor prognosis, which suggested that BGN was a potential prognostic biomarker and therapeutic target of gastric cancer.

Physicochemical, functional and antioxidant properties of mung bean protein enzymatic hydrolysates.

This study aimed to investigate physicochemical, functional and antioxidant properties of mung bean protein (MBP) enzymatic hydrolysates (MBPEHs) by alcalase, neutrase, protamex, flavourzyme and papain. Physicochemical properties were evaluated by SDS-PAGE, particle size distribution, FTIR, ultraviolet visible and fluorescence spectrophotometries. ABTS, hydroxyl scavenging, Fe2+ chelating activity were used to evaluate antioxidant activity. Enzymolysis with five proteases decreased average particle size, α-helix, ß-sheet, surface hydrophobicity of hydrolysates. Alcalase hydrolysate had the highest degree of hydrolysis (23.55%), absolute zeta potential (33.73 mV) and the lowest molecular weight (<10 kDa). Protamex and papain hydrolysates had higher foaming capacities, emulsification activity indexes, emulsion stability indexes (235.00%, 123.07 m2/g, 132.54 min; 200.10%, 105.39 m2/g, 190.67 min) than MBP (135.03%, 20.03 m2/g, 30.88 min). Alcalase hydrolysate demonstrated the lowest IC50 (mg/mL) in ABTS (0.12), hydroxyl (2.98), Fe2+ chelating (0.22). These results provide support for application of MBPEHs as foaming agent, emulsifier and antioxidant in food industry.

Dental technology of Taiwan during the Japanese colonial period.

Background/purpose: During the Japanese colonial period, the Taipei Hospital had already provided complete dental services with a fixed price per treatment. This study tried to compare the differences in the prices of various dental treatments between the Japanese colonial period and today. Materials and methods: This study used the "Dental Treatment Fees in the 27th Annual Report of Taipei Hospital (Taisho 12)" as the study materials to compare the differences in the prices of various dental treatments between the Japanese colonial period and today using the monthly salary of a novice elementary school teacher as an income benchmark. Results: A hundred years ago, the Taipei Hospital had already provided the dental treatments such as scaling and endodontic, operative dentistry, prosthodontic, and orthodontic treatments. Of these treatment items, the prices for prosthodontic and orthodontic treatments were more expensive. After a century of development, the costs of scaling and operative dentistry treatments dropped, while the costs of endodontic, prosthodontic, and orthodontic treatments increased. Conclusion: During the Japanese colonial period, Taiwan's dental treatment technology had already had the forms of modern dentistry with several dental specialties. At that time, the costs of dental treatments are quite expensive. Today's dental treatment items are more detailed and diverse. The health insurance system provides Taiwanese people with convenient and cheap general dental treatments such as scaling and treatments related to operative dentistry, endodontics, periodontics, and oral surgery. However, the costs of prosthodontic and orthodontic treatments increase and have to be paid by the patients themselves.

Influence of ultrasound treatment on the physicochemical and antioxidant properties of mung bean protein hydrolysate.

This study aimed to investigate influence of ultrasonic treatment on physicochemical and antioxidant properties of mung bean protein hydrolysate (MPH). Physicochemical properties of MPH were evaluated by Tricine-SDS-PAGE, particle size distribution, fourier transform infrared spectroscopy (FTIR) and fluorescence spectroscopy, among others. Radicals scavenging activities of ABTS, hydroxyl, superoxide anion, Fe2+ chelating ability and reducing power characterized antioxidant activities of MPH. MPH contained four bands of 25.6, 12.8, 10.6 and 4.9 kDa, in which 4.9 kDa was the most abundant. Ultrasonic treatment increased the contents of aromatic and hydrophobic amino acids in MPH. Ultrasonic treatment decreased the content of α-helix of MPH and increased ß-sheet and ß-turn compared to MPH. MPH-546 W (ultrasonic treatment 546 W, 20 min) had the lowest average particle size (290.13 nm), zeta potential (-36.37 mV) and surface hydrophobicity (367.95 A.U.). Antioxidant activities of ultrasonicated-MPH increased with the ultrasonic power, achieving the lowest IC50 (mg/mL) of 0.1087 (ABTS), 1.796 (hydroxyl), 1.003 (superoxide anion) and 0.185 (Fe2+ chelating ability) in 546 W power. These results indicated ultrasonic treatment would be a promising method to improve the antioxidant properties of MPH, which would broaden the application scope of MPH as bioactive components in the food industry.

Dental manpower and treated dental diseases in department of dentistry, Taipei Hospital (the predecessor of National Taiwan University Hospital) in 1923.

BACKGROUND/PURPOSE: In 1906, there was a dental treatment room established in the department of surgery of Taipei Hospital to introduce modern dental services to Taiwan. It is undoubtedly the earliest hospital dentistry in Taiwan. This study tried to assess the dental manpower and treated dental diseases in Taipei Hospital, and hence to explore the appearance of Taiwan's early hospital dentistry. MATERIALS AND METHODS: This study utilized the secondary data analysis to evaluate the dental manpower and treated dental diseases of dental outpatients in the 27th Annual Report of Taipei Hospital (Taisho 12th year or 1923). RESULTS: Our results found that there were 3 dentists and one dental technician in the dental department of Taipei Hospital in 1923. These 3 dentists totally treated 3 inpatients and 1759 outpatients with 4511 outpatient visits (1959 for male patients and 2552 for female patients) in that year. Dental caries and retained root were the two most common dental diseases in Japanese and Taiwanese dental outpatients, and followed in a descending order by missing tooth, pulp necrosis, and pulpitis for Japanese outpatients as well as pulpitis, suppurative periodontitis, and acute or chronic periodontitis for Taiwanese outpatients. CONCLUSION: We conclude that the dentistry of Taipei Hospital in 1923 does have a modern form of dentistry with 3 dentists and one dental technician. Its dental patients are mainly Japanese and minorly Taiwanese. Moreover, the treated dental diseases are mainly tooth diseases for Japanese outpatients and both tooth and periodontal diseases for Taiwanese outpatients.

Changes in stability and in vitro digestion of egg-protein stabilized emulsions and ß-carotene gels in the presence of sodium tripolyphosphate.

BACKGROUND: Egg proteins are effective emulsifiers and gelators in food systems. However, the physicochemical stability and control release properties of egg-protein stabilized emulsions and gels need to be further improved. The potential of sodium tripolyphosphate (St) to improve the functionality of egg proteins was evaluated. RESULTS: The emulsions with St had smaller particle sizes and higher zeta potential, leading to better physical stability. Furthermore, the oxidation stability increased with increasing St contents, possibly due to its metal chelating capacity and the improved emulsifying activity of whole-egg dispersions. Phosphate had a positive impact on the chemical stability of ß-carotene in whole-egg liquids and gels, decreasing the degradation during thermal treatment. The gel made with St was firm and broke down slowly, leading to a low rate of digestion and ß-carotene release in simulated gastric fluid. CONCLUSION: This study shows that St is useful to improve the egg proteins stabilized emulsions and gels, which is applicable in the development of emulsion-based food grade gel products. © 2021 Society of Chemical Industry.

Physicochemical properties and antioxidant activities of tree peony (Paeonia suffruticosa Andr.) seed protein hydrolysates obtained with different proteases.

The physicochemical and antioxidant properties of tree peony seed protein (TPSP) hydrolysates by Alcalase, Neutrase, Papain, Protamex, and Flavourzyme were investigated in this study. The physicochemical properties were characterized by SDS-PAGE, particle size distribution, fourier transform infrared and fluorescence spectroscopy etc. The antioxidant activities were determined by DPPH radical, ABTS radical, Fe2+ chelating, and reducing power. The results showed five proteases produced hydrolysates with a significantly reduced average particle size, α-helices, and surface hydrophobicity compared to TPSP. Alcalase and Neutrase hydrolysis enhanced the nutritional value of the hydrolysates. Alcalase hydrolysates possessed the highest degree of hydrolysis (27.97%) and lowest molecular weight (<13 kDa) with average particle size (231.33 nm). Alcalase hydrolysate displayed the highest radical scavenging (DPPH IC50 = 0.18 mg/mL, ABTS IC50 = 1.57 mg/mL), Fe2+ chelating activity (IC50 = 0.99 mg/mL), and reducing power (0.594). These results provide the fundamentals for TPSP hydrolysates as antioxidants to be employed in food industry or pharmaceutical industry.

C-phycocyanin Mitigates Cognitive Impairment in Doxorubicin-Induced Chemobrain: Impact on Neuroinflammation, Oxidative Stress, and Brain Mitochondrial and Synaptic Alterations.

Chemotherapy-induced cognitive impairment (CICI) is a common detrimental effect of cancer treatment, occurring in up to 75% of cancer patients. The widely utilized chemotherapeutic agent doxorubicin (DOX) has been implicated in cognitive decline, mostly via cytokine-induced neuroinflammatory and oxidative and mitochondrial damage to brain tissues. C-phycocyanin (CP) has previously been shown to have potent anti-inflammatory, antioxidant, and mitochondrial protective properties. Therefore, this present study was aimed to investigate the neuroprotective effects of CP against DOX-elicited cognitive impairment and explore the underlying mechanisms. CP treatment (50 mg/kg) significantly improved behavioral deficits in DOX-treated mice. Furthermore, CP suppressed DOX-induced neuroinflammation and oxidative stress, mitigated mitochondrial abnormalities, rescued dendritic spine loss, and increased synaptic density in the hippocampus of DOX-treated mice. Our results suggested that CP improves established DOX-induced cognitive deficits, which could be explained at least partly by inhibition of neuroinflammatory and oxidant stress and attenuation of mitochondrial and synaptic dysfunction.

Ribonuclease H2 Subunit A impacts invasiveness and chemoresistance resulting in poor survivability of breast cancer in ER dependent manner.

Ribonuclease H2 subunit A (RNASEH2A), a member of the RNase HII family, acts in DNA replication by mediating removal of lagging-strand Okazaki fragment RNA primers. We explored the roles of RNASEH2A in the prognosis of breast cancer, specifically in relation to proliferation, invasiveness, and sensitivity to cytotoxins of cells in the estrogen receptor (ER)-positive MCF-7 and the ER-negative MDA-MB-231 breast cancer cell lines. We collected 26 datasets from around the world, comprising 7815 accessible cases. In these datasets, we probed the association between expression of RNASEH2A and clinical parameters, primarily by inhibiting the expression of RNASEH2A with siRNAs. Such inhibition inhibited the growth and invasiveness of MCF-7 cells. Independent and pooled Kaplan-Meier and Cox analyses revealed that RNASEH2A overexpression was associated with aggressiveness and poor outcomes in a dose-dependent manner in breast cancers of ER-positive subtypes, but not with ER-negative subtypes. The prognostic performance of RNASEH2A mRNA in ER-positive breast cancer was comparable to that for other gene signatures, such as the 21-gene recurrence score. Overexpression of RNASEH2A was also positively associated with cancer cell resistance to chemotherapy; inhibition of RNASEH2A by siRNA enhanced the chemosensitivity in an in vitro study. Bioinformatic analyses indicated that the ER may modulate RNASEH2A action in mitosis, DNA repair, and differentiation through transcriptional regulation. RNASEH2A may be a useful prognostic and predictive biomarker in ER-positive breast cancer and may serve as a therapeutic target for the treatment of ER-positive breast cancer.

DEAD-box RNA Helicase 39 Promotes Invasiveness and Chemoresistance of ER-positive Breast Cancer.

Purpose: DDX39 is a DEAD-box RNA helicase that unwinds double-stranded RNA in an ATP-dependent manner. This study evaluated the prognostic and predictive significance of DDX39 in breast cancer (BC). Methods: The cellular proliferation, invasion, and drug cytotoxicity by DDX39 siRNA were evaluated in MCF7 (ER-positive) and MDA-MB-231 (ER-negative) cell lines. A total of 27 datasets (total 8110 accessible cases) with following-up information were collected from Asia, Europe, and North America to explore associations between DDX39 gene expression and clinical parameters of BC patients. Results: Down-regulation of DDX39 by siRNA significantly reduce the cell growth and invasion ability in MCF7 cells, but only slightly in MDA-MB-231 cells. The DDX39 mRNA level was elevated in breast adenocarcinoma compared with normal breast tissue (p<0.01). Higher DDX39 level was significantly correlated with larger tumor size (p<0.01) and poorer tumor differentiation (p<0.01). The prognostic significance of DDX39 for BC was assessed by pooled-analysis and meta-analysis. Kaplan-Meier analysis demonstrated that increased DDX39 mRNA expression was associated with poor outcomes significantly in a dose-dependent manner in ER-positive BC. The prognostic performance of DDX39 mRNA was comparable to 21-gene, 70-gene, and wound-response gene signatures, and it was superior to the TNM stage. Lower DDX39 expression was associated with reduced relative risk death on ER-positive BC with chemotherapy or radiotherapy. Inhibition of DDX39 by siRNA could significantly enhance the sensitivity of MCF-7 to doxorubicin. Conclusion: DDX39 may be a potential novel prognostic and predictive biomarker for BC patients with ER-positive status.

Activation of RAW264.7 macrophages by active fraction of Albizia julibrissin saponin via Ca2+-ERK1/2-CREB-lncRNA pathways.

The saponin active fraction from the stem bark of Albizia julibrissin (AJSAF) is an ideal vaccine adjuvant, but its mechanism of action remains unclear. The recent evidences indicate that long noncoding RNAs (lncRNAs) play essential roles in regulating the activation and function of macrophages. The current experiments were designed to investigate the effects of AJSAF on the activation of RAW264.7 macrophages and to explore its intracellular molecular mechanisms using a global gene expression microarray. AJSAF could significantly enhance phagocytic activity, induce reactive oxygen species (ROS), promote surface molecule expression, and up-regulate the mRNA and protein expression of cytokines and chemokines in RAW264.7 cells. AJSAF induced the differential expression of 223 mRNAs and 103 lncRNAs in RAW264.7 cells. Bioinformatics were used to predict the potential target mRNAs and function of up-regulated lncRNA A_30_P01018532 in RAW264.7 cells induced by AJSAF. The total 99 co-expressed mRNAs were classified as putative target genes of A_30_P01018532. A_30_P01018532 was associated with the inflammatory and immune response. AJSAF significantly increased the intracellular free Ca2+ levels and induced the phosphorylation of ERK1/2 and CREB in RAW264.7 cells. Moreover, Ca2+ chelator BAPTA-AM, ERK1/2 inhibitor PD98059 and CREB inhibitor KG-501 significantly inhibited the up-regulation of TNF-α, CCL2, CXCL2, CCL22, and A_30_P01018532 in RAW264.7 cells induced by AJSAF. These results suggested that AJSAF could activate RAW264.7 cells via Ca2+-ERK1/2-CREB pathways and that A_30_P01018532 might be an important regulator of mRNA expression in AJSAF-activated macrophage. This study may provide insights into the molecular mechanisms of action of AJSAF.

The potential role of tubeimosides in cancer prevention and treatment.

Natural compounds are important sources of anticancer drugs. Rhizoma Bolbostemmatis (Chinese name "Tu Bei Mu") is the dry tuber of Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae). It has long been widely used for treating various ailments including cancer in traditional Chinese medicine. Its major pharmacologically active components are the triterpenoid saponins tubeimosides (TBMs) including tubeimoside (TBM) I, II and III. Extensive researches have provided evidences of the anticancer activities of TBMs in different stages of carcinogenesis both in vitro and in vivo model. TBMs could inhibit cell growth and proliferation, induce cell differentiation, apoptosis, autophagy and, inhibit inflammation, and suppress angiogenesis, invasion and metastasis via various signaling pathways. They are effective in combination therapies, particularly at targeting drug-resistant cancer cells. This mini-review aims to summarize and analyze the current knowledge on the pre-clinical studies of anti-tumor effects, the underlying molecular mechanisms and discuss the prospects of the application of TBMs in cancer prevention and treatment. The potential of TBMs as pertinent candidates could be appropriately developed and designed into an efficacious anticancer drug.

Association of initial mucogingival status with clinical outcome of non-surgical periodontal therapy: A retrospective analysis of 204 patients.

BACKGROUND/PURPOSE: This study was conducted to evaluate the influence of mucogingival parameters, including keratinized mucosa (KM) and attached gingiva (AG), on the outcome of non-surgical periodontal therapy (NSPT). METHODS: A total of 204 non-smoking patients with generalized chronic periodontitis who received NSPT between 2012 and 2014 were included. The Mantel-Haenszel chi-square test was used to assess the associations between initial mucogingival parameters and initial clinical parameters on the buccal aspect, and the associations between initial mucogingival parameters and outcome clinical parameters on the buccal aspect of the sites with severe periodontal destruction. The generalized liner model was used to evaluate the contribution of initial clinical parameters to the outcome of NSPT. RESULTS: KM ≥ 3 mm was associated with greater probing pocket depth (PD), less gingival recession (REC), and less clinical attachment level (CAL), and AG < 1 mm was associated with greater PD, REC, and CAL before NSPT. At the sites with severe periodontal destruction, KM ≥ 3 mm was associated with greater PD reduction (0.25 ± 0.08 mm) and CAL gain (0.25 ± 0.09 mm), and AG < 1 mm was associated with greater CAL gain (0.15 ± 0.08 mm) after NSPT. Initial PD ≥ 7 mm and non-molar teeth showed greater contribution to the outcome of NSPT. CONCLUSION: Less AG (<1 mm) was associated with greater periodontal destruction at baseline. At the sites with severe periodontal destruction, greater KM (≥3 mm) and less AG (<1 mm) resulted in better outcomes of NSPT.