IRX5 suppresses osteogenic differentiation of hBMSCs by inhibiting protein synthesis.

In our previous study, IRX5 has been revealed a significant role in adipogenesis of hBMSCs. Considering the expansion of adipose tissue in bone marrow in aged and ovariectomy-related osteoporosis, the effect of IRX5 on the osteogenesis of BMSCs still needs to be elucidated. In vivo, models of aging-induced and ovariectomy-induced osteoporotic mice, and in vitro studies of IRX5 gene gain- and loss-of-function in hBMSCs were employed. Histology, immunofluorescence, qRT-PCR, and Western blot analysis were performed to detect the functions of IRX5 in hBMSCs osteogenic differentiation. RNA-seq, transmission electron microscopy, Seahorse mito-stress assay, and Surface Sensing of Translation assay were conducted to explore the effect of mammalian/mechanistic target of rapamycin (mTOR)-mediated ribosomal translation and mitochondrial functions in the regulation of hBMSCs differentiation by IRX5. As a result, elevated IRX5 protein expression levels were observed in the bone marrow of osteoporotic mice compared to normal mice. IRX5 overexpression attenuated osteogenic processes, whereas IRX5 knockdown resulted in enhanced osteogenesis in hBMSCs. RNA-seq and enrichment analysis unveiled that IRX5 overexpression exerted inhibitory effects on ribosomal translation and mitochondrial functions. Furthermore, the application of the mTOR activator, MHY1485, effectively reversed the inhibitory impact of IRX5 on osteogenesis and mitochondrial functions in hBMSCs. In summary, our findings suggest that IRX5 restricts mTOR-mediated ribosomal translation, consequently impairing mitochondrial OxPhos, which in turn results in osteogenic dysfunction of hBMSCs.

Association between pulp and periapical disease with type 2 diabetes: A bidirectional Mendelian randomization.

AIM: This current Mendelian randomization (MR) study aims to comprehensively explore the potential bidirectional link between pulp and periapical disease (PAP) with type 2 diabetes mellitus (T2DM). METHODOLOGY: Summary level data of European-based population genome-wide association studies (GWASs) were employed to undertake this MR study. With the selection of single nucleotide polymorphisms (SNPs) as the instrumental variable, the radial inverse-variance weighted (radial IVW) method with modified second-order weights was applied as the primary method. Additionally, a range of sensitivity analyses were conducted to investigate pleiotropy. Results from different sources of outcome were pooled by meta-analysis with the fixed model. RESULTS: The results of this MR analysis did not suggest a significant impact of pulp and periapical disease on type 2 diabetes (combined OR = 1.04, 95% CI: 1.00-1.07, p = .033) and vice versa (OR = 1.04, 95% CI: 0.96-1.14, p = .329). No significant pleiotropy was detected in the final model after the removal of outliers, demonstrating the reliability of the results in our primary analysis. CONCLUSIONS: With the limitations inherent in the present MR study, there is no significant evidence in either direction to suggest a causal association between pulp and periapical disease and type 2 diabetes mellitus.

Downregulation of Rab23 inhibits hepatocellular carcinoma by repressing SHH signaling pathway.

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumors and the third leading cause of cancer-related death worldwide. As an oncogene, Rab23 has been shown to be significantly related to the growth and migration of hepatocellular carcinoma in both in vitro and in vivo studies, but its underlying mechanism remains obscure. In the present study, we examined the effect of inhibiting Rab23 expression on the pathological progression of HCC. The correlation between liver Rab23 gene expression and survival probability in human HCC patients was analyzed using the TCGA database and CPTAC database. Rab23 knockdown hepatocellular carcinoma cell line was generated through lentiviral transduction, then we established a nude HCC xenograft model by subcutaneously implanting the transfected cells. The analysis of gene and protein expression was carried out using Western blot or RT-qPCR, respectively. Flow cytometry analysis was used to detect the level of apoptosis. The expression levels of key proteins involved in the Sonic Hedgehog (SHH) signaling pathway were assessed. The results showed that HCC patients with low levels of hepatic Rab23 mRNA and protein had a better survival tendency than those with higher levels of Rab23. Cell proliferations were reduced and apoptosis levels were increased after Knocking down Rab23 in HCC cell lines. Furthermore, in vivo studies have demonstrated that suppression of the Rab23 gene results in decreased tumor size, proliferation rate, and reduced levels of SHH-related proteins Smoothened and GLI-1. The above results suggest that Rab23 is involved in the pathological progression of HCC as an important regulator of the SHH signaling pathway, which also provides an important research basis for new therapeutic strategies for HCC.

Comparison of the pathological response to 2 or 4 cycles of neoadjuvant CAPOX in II/III rectal cancer patients with low/intermediate risks: study protocol for a prospective, non-inferior, randomized control trial (COPEC trial).

BACKGROUND: For patients with low- and intermediate-risk stage II/III rectal cancer, current studies have reached a consensus that preoperative radiotherapy may be dispensed with, and neoadjuvant chemotherapy (NCT) alone might achieve an accepted local control. Our previous phase II study has evidenced that the morphological response of NCT could be better judged at a relatively early stage. Low- and intermediate-risk stage II/III rectal cancer patients could achieve a high rate of tumor shrinkage and downgrade after only 4 cycles of NCT and obvious tumor morphological changes could be observed after 2 cycles of NCT. However, there is still a lack of more detailed stratification and evidence for pathological criteria. The aim of the present study (comparison of the pathological response to 2 or 4 cycles of neoadjuvant CAPOX in II/III rectal cancer patients with low/intermediate risks, COPEC trial) is to determine the pathological tumor regression grade (pTRG) rate of 2 or 4 cycles of NCT in low- and intermediate-risk stage II/III rectal cancer and verify the feasibility of early identification of chemotherapy-insensitive population. METHODS/DESIGN: This is a multicenter, prospective, non-inferior, randomized controlled trial (RCT) initiated by West China Hospital of Sichuan University and designed to be conducted in fourteen hospitals around China. Eligible patients will be centrally randomized into 2 or 4 cycles of CAPOX in a 1:1 ratio using the central automated randomization system offered by the O-trial online system ( https://plus.o-trial.com/ ) and accept total mesorectal excision after 2 or 4 cycles of CAPOX (oxaliplatin 130 mg/m2, once daily on day 1, every 21 days and capecitabine 1000 mg/m2, twice daily on days 1 to 14, every 21 days). The primary endpoint is the proportion of patients with pathological no-tumor regression (pTRG 3), which is determined postoperatively by each sub-center and verified by the primary center. DISCUSSION: COPEC trial is designed to verify that the preoperative CAPOX chemotherapy for low- and intermediate-risk stage II/III rectal cancer could achieve a good response judgment after 2 cycles and obtain the tumor pathological response rate after 2 cycles of CAPOX. We hope the COPEC trial could help in establishing a consensus standard of low- and intermediate-risk rectal cancer and the early identification of stage II/III rectal patients with low- and intermediate-risk who are poorly responding to NCT. TRIAL REGISTRATION: Clinicaltrial.gov NCT04922853. Registered on June 4, 2021.

The effect of pain-education nursing based on a mind map on postoperative pain score and quality of life in patients with colorectal cancer.

Mind mapping is a combination of images and logical thinking in the form of pictures and texts. It presents a natural expression process that conforms to the divergent thinking of the brain, helping patients understand memory. This study aimed to investigate the impact of pain-education nursing with the aid of mind maps on postoperative pain scores and quality of life in patients with colorectal cancer. The medical records of 100 colorectal cancer patients treated from July 2020 to July 2022 were selected as retrospective research participants and divided into control and observation groups. The control group received routine pain care, and the observation group was given pain-education nursing based on a mind map. The effects on quality of life, pain, negative emotions, and comfort after nursing were compared between the 2 groups. There was no significant difference in quality of-life scores between the 2 groups before the nursing intervention (P > .05). After nursing, the physical, emotional, cognitive, and social functions of patients in the observation group were significantly higher than those in the control group. However, the overall quality of life and financial difficulties of patients in the observation group were significantly lower than those in the control group (P < .05). The observation group's social, physical, and psychological comfort scores were significantly higher than those in the control group after nursing intervention (P < .05). After nursing, the observation group's visual analog scale scores at different times after the operation were significantly lower than those of the control group. The scores on the self-rating anxiety scale and self-rating depression scale in the observation group were significantly lower than those in the control group (P < .05). Pain-education nursing based on mind maps can effectively improve the daily living ability, pain symptoms, and quality of life of patients after colorectal cancer, and there is a reference value for post-nursing care of patients after colorectal cancer.

Functional liposome loaded curcumin for the treatment of Streptococcus mutans biofilm.

Introduction: Plaque biofilms, mainly formed by Streptococcus mutans (S. mutans), play an important role in the occurrence and development of dental caries. Antibiotic treatment is the traditional way to control plaque. However, problems such as poor drug penetration and antibiotic resistance have encouraged the search for alternative strategies. In this paper, we hope to avoid antibiotic resistance through the antibacterial effect of curcumin, a natural plant extract with photodynamic effects, on S. mutans. However, the clinical application of curcumin is limited due to its low water solubility, poor stability, high metabolic rate, fast clearance rate, and limited bioavailability. In recent years, liposomes have become a widely used drug carrier due to their numerous advantages, such as high drug loading efficiency, high stability in the biological environment, controlled release, biocompatibility, non-toxic, and biodegradability. So, we constructed a curcumin-loaded liposome (Cur@LP) to avoid the defect of curcumin. Methods: Cur@LP functioned with NHS can adhere to the surface of the S. mutans biofilm by condensation reaction. Liposome (LP) and Cur@LP was characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The cytotoxicity of Cur@LP was evaluated by CCK-8 assay and LDH assay. The adhesion of Cur@LP to S. mutans biofilm was observed by confocal laser scanning microscope (CLSM). The antibiofilm efficiency of Cur@LP were evaluated by crystal violet staining, CLSM, and scanning electron microscope (SEM). Results: The mean diameter of LP and Cur@LP were 206.67 ± 8.38 nm and 312 ± 18.78 nm respectively. The ζ-potential of LP and Cur@LP were ∼-19.3 mV and ∼-20.8 mV respectively. The encapsulation efficiency of Cur@LP was (42.61 ± 2.19) %, and curcumin was rapidly released up to ±21% at 2 h. Cur@LP has negligible cytotoxicity, and can effectively adhered to the S. mutans biofilm and inhibited its growth. Discussion: Curcumin has been widely studied in many fields such as cancer, which can be attributed to its antioxidant and anti-inflammatory effects. At present, there are few studies on the delivery of curcumin to S. mutans biofilm. In this study, we verified the adhesion and antibiofilm of Cur@LP to S. mutans biofilm. This biofilm removal strategy has the potential to be translated into the clinic.

Enhancing adhesive-dentin interface stability of primary teeth: From ethanol wet-bonding to plant-derived polyphenol application.

OBJECTIVES: To investigate whether the adhesive-dentin interface stability of primary teeth would be enhanced by epigallocatechin-3-gallate (EGCG) with ethanol wet-bonding. METHODS: Non-caries primary molars were sliced to achieve a flat dentin surface and etched then randomly distributed into five groups in accordance with different treatments: group 1, no treatment; group 2, applying absolute ethanol wet-bonding for 60 s; groups 3-5, applying 0.1%, 0.5%, and 1% (w/v) EGCG-incorporating ethanol wet-bonding (0.1%, 0.5%, and 1% EGCG) for 60 s. Singlebond universal adhesive was then applied followed by resin composite construction. Microtensile bond strength, fracture mode, and nanoleakage at adhesive-dentin interface were evaluated after 24 h of water storage or 10,000 times of thermocycling. Zymography of hybrid layer, biofilm formation of Streptococcus mutans by CLSM, FESEM, and MTT test, and cytotoxicity by CCK-8 assay were respectively assessed. RESULTS: Irrespective of thermocycling, the dentin bond strength was preserved with reduced nanoleakage in the 0.5% and 1% EGCG groups. Furthermore, the activity of endogenous proteases and the growth of Streptococcus mutans biofilm were inhibited after treatment with 0.5% and 1% EGCG/ethanol solutions (groups 4 and 5). CCK-8 results of the 0.1% and 0.5% EGCG groups showed acceptable biocompatibility. CONCLUSIONS: Treatment by EGCG/ethanol solutions effectively enhanced the bond stability of primary teeth at the adhesive-dentin interface. CLINICAL SIGNIFICANCE: Synergistic application of EGCG and ethanol wet-bonding suggesting a promising strategy to improve dentin bonding durability with bacterial biofilm inhibition, thus increasing resin-based restorations' service life in primary dentition.

A combination of transcriptome and methylation analyses reveals the role of lncRNA HOTAIRM1 in the proliferation and metastasis of breast cancer.

Background: DNA methylation status is strongly associated with the prognosis of breast invasive carcinoma (BRCA). Elucidating the mechanisms underlying DNA methylation coupled with determining its biological function is imperative to the effective development of treatment and prevention strategies for breast cancer. Methods: We retrieved transcriptome and DNA methylation profiles of BRCA patients from The Cancer Genome Atlas (TCGA) database, then applied the "limma" package in R software to identify differentially expressed genes (DEGs) and aberrantly methylated genes. Next, we used the "MethylMix" package to screen for methylation-driven genes, and performed univariate and multivariate Cox regression analyses to determine the prognostic value of the methylation-driven genes and clinical characteristics. We validated these findings in 51 breast cancer tissues alongside 51 corresponding normal tissues. Furthermore, we used cell experiments to clarify the biological function and underlying molecular mechanisms of HOTAIRM1 in vitro. Results: A total of 25 methylation-driven genes were identified in the dataset. Results from univariate and multivariate Cox regression showed that SYN2, HOTAIRM1, BCAS1, and ALDOC were significantly associated with patient prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) results showed that the expression levels of SYN2 and HOTAIRM1 were negatively correlated with BRCA stage, whereas those of BCAS1 and ALDOC were positively correlated with BRCA stage. Results from in vitro experiments showed that knockdown HOTAIRM1 expression promoted breast cancer cells proliferation, clone formation, and invasion. Up-regulation of HOTAIRM1 inhibited breast cancer cells proliferation, clone formation, and invasion. Conclusions: In summary, low HOTAIRM1 expression is a significant prognostic factor for the survival of BRCA patients and thus could be a potential therapeutic target for the treatment of BRCA.

Two new aspidosperma-type monoterpenoid indole alkaloids from Ervatamia officinalis.

Two new aspidosperma-type monoterpenoid indole alkaloids, 16-O-methylvoafinine (1) and 14,15-diepi-voafinidine (2) were isolated from the aerial parts of Ervatamia officinalis. Their structures were established by comprehensive spectroscopic analysis including 1D and 2D NMR, HR-ESI-MS, and electronic circular dichroism calculation. The isolated compounds were evaluated for cytotoxic activities against HepG2, MCF-7, and A549 cell lines by CCK-8 assay.

Molecular phylogenetic analyses based on the complete plastid genomes and nuclear sequences reveal Daphne (Thymelaeaceae) to be non-monophyletic as current circumscription.

The diverse members of the genus Daphne are prized for their fragrant flowers. Despite being promising ornamental plants in many countries, genetic information of Daphne is scarce. In this study, the plastomes of four species and one variety of Daphne were sequenced and analyzed. The plastomes were typical and contained a pair of inverted repeat (IR) regions that separated the large single-copy (LSC) region from the small single-copy (SSC) region. With a length ranging from 132,869 bp (D. genkwa) to 174,773 bp (D. championii), 106 to 141 genes were predicted. Comparative plastome analysis of the newly sequenced plastomes with four publicly available Daphne plastomes identified an expansion of the IRs, sequence variations, and mutational hotspots. Phylogenetic analyses indicated that the genus Daphne in its current circumscription is polyphyletic. Daphne genkwa was nested within the genus Wikstroemia, while D. championii was well resolved as sister to Edgeworthia. These findings concurred with results from our study that used nuclear ribosomal internal transcribed spacer sequence data. The conflicts on the molecular placement of D. championii and D. genkwa and the present taxonomic classification in Daphne suggest that a new intergeneric classification system of Daphneae warrants consideration.

Association between baseline LH/FSH and live-birth rate after fresh-embryo transfer in polycystic ovary syndrome women.

This study aimed to retrospectively analyse the effect of the baseline luteinising hormone/follicle-stimulating hormone ratio (bLH/FSH) on the live-birth rate per fresh-embryo transfer cycle (LBR/ET) in infertile women with polycystic ovary syndrome (PCOS) who received a fresh-embryo transfer. A total of 424 patients with PCOS who underwent the first cycle of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) fresh-embryo transfer at our hospital was enrolled. Univariate and multivariate logistic regression analyses, along with curve fitting and a threshold effect analysis, were performed. Baseline LH/FSH levels were a significant (P < 0.05) independent risk factor affecting live birth. In the first IVF/ICSI antagonist treatment cycles, LBR/ET after fresh-embryo transfer was relatively flat, until bLH/FSH was 1.0; thereafter, it started to decrease by 17% for every 0.1-unit bLH/FSH increase. Considering the decline in LBR/ET, it is recommended that PCOS women with bLH/FSH > 1.0 carefully consider fresh-embryo transfer during their first IVF/ICSI.

Characterization of mandarin fish (Siniperca chuatsi) IL-6 and IL-6 signal transducer and the association between their SNPs and resistance to ISKNV disease.

In fish, interleukin-6 (IL-6) is a very important immune-regulatory cytokine that plays a polyfunctional role in inflammation, metabolism, regeneration, and neural processes. IL-6 signal transducer (IL-6ST) is a specific receptor for IL-6 and expressed mainly in immune cells and hepatocytes. In this study, the complete cDNA and genomic DNA sequences of mandarin fish (Siniperca chuatsi) IL-6 and IL-6ST genes were identified and analyzed. Quantitative real-time PCR showed that IL-6 and IL-6ST were chiefly expressed in the immune organs. After challenge with infectious spleen and kidney necrosis virus (ISKNV), the expression levels of IL-6 were significantly up-regulated after 6 h and 24 h in the head kidney and spleen, respectively (p < 0.01), the peak value for both reached at 72 h, IL-6ST increased significantly after 120 h with a peak at 168 h in the head kidney (p < 0.01) and improved markedly at 168 h in the spleen (p < 0.01). Besides, IL-6 and IL-6ST have been identified 3 and 8 single nucleotide polymorphisms (SNPs), respectively. Statistical analysis showed that one SNP locus (1625C/T) in the coding region of IL-6 was significantly related to the resistance of mandarin fish against ISKNV. The 1625C→T locus in the coding region of IL-6 is a synonymous mutation; compared with the susceptible group, the frequency of allele T in the disease resistance group was significantly higher, which may be due to the rare codon produced by the mutation affecting translation. The involvement of IL-6 and IL-6ST in response to ISKNV infection in mandarin fish clearly indicate that the role of SNP markers in IL-6 was associated with the ISKNV resistance, which was demonstrated for the first time in our results. Thus, the current study may provide fundamental information for further breeding of mandarin fish with resistance to ISKNV infection.

A rapidly magnetically assembled stem cell microtissue with "hamburger" architecture and enhanced vascularization capacity.

With the development of magnetic manipulation technology based on magnetic nanoparticles (MNPs), scaffold-free microtissues can be constructed utilizing the magnetic attraction of MNP-labeled cells. The rapid in vitro construction and in vivo vascularization of microtissues with complex hierarchical architectures are of great importance to the viability and function of stem cell microtissues. Endothelial cells are indispensable for the formation of blood vessels and can be used in the prevascularization of engineered tissue constructs. Herein, safe and rapid magnetic labeling of cells was achieved by incubation with MNPs for 1 h, and ultrathick scaffold-free microtissues with different sophisticated architectures were rapidly assembled, layer by layer, in 5 min intervals. The in vivo transplantation results showed that in a stem cell microtissue with trisection architecture, the two separated human umbilical vein endothelial cell (HUVEC) layers would spontaneously extend to the stem cell layers and connect with each other to form a spatial network of functional blood vessels, which anastomosed with the host vasculature. The "hamburger" architecture of stem cell microtissues with separated HUVEC layers could promote vascularization and stem cell survival. This study will contribute to the construction and application of structural and functional tissues or organs in the future.

Injectable chitin hydrogels with self-healing property and biodegradability as stem cell carriers.

To meet the demands of various therapeutic tasks, injectable hydrogels with tunable mechanical properties and degradability are highly desired. Herein, we developed an injectable chitin hydrogel system with well-manipulated mechanical properties and degradability through dynamic acylhydrazone crosslinking catalyzed by 4-amino-DL-phenylalanine (Phe-NH2). The mechanical properties and degradability of the hydrogels could be easily adjusted by varying the solid content, while their gelation time could be maintained at a constant level (∼130 s) by altering Phe-NH2 content, thereby ensuring the good injectability of hydrogels. Moreover, the chitin hydrogels showed excellent self-healing capacity with a healing efficiency up to 95 %. Owing to their superior biocompatibility and biodegradability, the chitin hydrogels could support the proliferation and multi-potent differentiations of rat bone marrow-derived stem cells, serving as a beneficial 3D scaffold for stem cell encapsulation and delivery. This work provides a promising injectable delivery vehicle of therapeutic drugs or cells for tissue regenerative medicine.

A Marine Alkaloid, Ascomylactam A, Suppresses Lung Tumorigenesis via Inducing Cell Cycle G1/S Arrest through ROS/Akt/Rb Pathway.

Ascomylactam A was reported for the first time as a new 13-membered-ring macrocyclic alkaloid in 2019 from the mangrove endophytic fungus Didymella sp. CYSK-4 from the South China Sea. The aim of our study was to delineate the effects of ascomylactam A (AsA) on lung cancer cells and explore the antitumor molecular mechanisms underlying of AsA. In vitro, AsA markedly inhibited the cell proliferation with half-maximal inhibitory concentration (IC50) values from 4 to 8 µM on six lung cancer cell lines, respectively. In vivo, AsA suppressed the tumor growth of A549, NCI-H460 and NCI-H1975 xenografts significantly in mice. Furthermore, by analyses of the soft agar colony formation, 5-ethynyl-20-deoxyuridine (EdU) assay, reactive oxygen species (ROS) imaging, flow cytometry and Western blotting, AsA demonstrated the ability to induce cell cycle arrest in G1 and G1/S phases by increasing ROS generation and decreasing of Akt activity. Conversely, ROS inhibitors and overexpression of Akt could decrease cell growth inhibition and cell cycle arrest induced by AsA. Therefore, we believe that AsA blocks the cell cycle via an ROS-dependent Akt/Cyclin D1/Rb signaling pathway, which consequently leads to the observed antitumor effect both in vitro and in vivo. Our results suggest a novel leading compound for antitumor drug development.

Yes-associated protein promotes tumour necrosis factor α-treated cementoblast mineralization partly by inactivating NF-κB pathway.

Cementum regeneration, as one of the most difficult challenges of periodontal regeneration, is influenced by inflammatory factors. Inflammation may hamper or promote periodontal tissue repair under different circumstances, as it is found to do in dentin-pulp complex and bone tissue. Our team demonstrated that YAP promotes mineralization of OCCM, a cementoblast cell line. However, the effect of YAP on its mineralization under inflammatory microenvironment is unclear. In this study, cementogenesis in vitro was up-regulated after transient TNF-α treatment for 30 minutes. YAP expression also was increased by TNF-α treatment. YAP overexpression promoted OCCM mineralization after the cells were transiently treated with TNF-α because YAP overexpression inhibited NF-κB pathway activity, while YAP knockdown elevated it. The inhibited mineralization potential and activated NF-κB pathway activity by YAP knockdown also were partly rescued by the application of the NF-κB inhibitor Bay 11-7082. These results demonstrated that YAP plays a positive role in the mineralization of TNF-α transiently treated cementoblast, partly by inhibiting the NF-κB pathway activity.

Intra/Extracellular Lactic Acid Exhaustion for Synergistic Metabolic Therapy and Immunotherapy of Tumors.

Regulating the tumor microenvironment (TME) has been a promising strategy to improve antitumor therapy. Here, a red blood cell membrane (mRBC)-camouflaged hollow MnO2 (HMnO2 ) catalytic nanosystem embedded with lactate oxidase (LOX) and a glycolysis inhibitor (denoted as PMLR) is constructed for intra/extracellular lactic acid exhaustion as well as synergistic metabolic therapy and immunotherapy of tumor. Benefiting from the long-circulation property of the mRBC, the nanosystem can gradually accumulate in a tumor site through the enhanced permeability and retention (EPR) effect. The extracellular nanosystem consumes lactic acid in the TME by catalyzing its oxidation reaction via LOX. Meanwhile, the intracellular nanosystem releases the glycolysis inhibitor to cut off the source of lactic acid, as well as achieve antitumor metabolic therapy through the blockade of the adenosine triphosphate (ATP) supply. Both the extracellular and intracellular processes can be sensitized by O2 , which can be produced during the decomposition of endogenous H2 O2 catalyzed by the PMLR nanosystem. The results show that the PMLR nanosystem can ceaselessly remove lactic acid, and then lead to an immunocompetent TME. Moreover, this TME regulation strategy can effectively improve the antitumor effect of anti-PDL1 therapy without the employment of any immune agonists to avoid the autoimmunity.

Performing Data Mining And Integrative Analysis Of Biomarker in Breast Cancer Using Multiple Publicly Accessible Databases.

In recent years, emerging databases were designed to lower the barriers for approaching the intricate cancer genomic datasets, thereby, facilitating investigators to analyze and interpret genes, samples and clinical data across different types of cancer. Herein, we describe a practical operation procedure, taking ID1 (Inhibitor of DNA binding proteins 1) as an example, to characterize the expression patterns of biomarker and survival predictors of breast cancer based on pooled clinical datasets derived from online accessible databases, including ONCOMINE, bcGenExMiner v4.0 (Breast cancer gene-expression miner v4.0), GOBO (Gene expression-based Outcome for Breast cancer Online), HPA (The human protein atlas), and Kaplan-Meier plotter. The analysis began with querying the expression pattern of the gene of interest (e.g., ID1) in cancerous samples vs. normal samples. Then, the correlation analysis between ID1 and clinicopathological characteristics in breast cancer was performed. Next, the expression profiles of ID1 was stratified according to different subgroups. Finally, the association between ID1 expression and survival outcome was analyzed. The operation procedure simplifies the concept to integrate multidimensional data types at the gene level from different databases and test hypotheses regarding recurrence and genomic context of gene alteration events in breast cancer. This method can improve the credibility and representativeness of the conclusions, thereby, present informative perspective on a gene of interest.

NAC-loaded electrospun scaffolding system with dual compartments for the osteogenesis of rBMSCs in vitro.

PURPOSE: In this study, we aimed to develop a unique N-acetyl cysteine (NAC)-loaded polylactic-co-glycolic acid (PLGA) electrospun system with separate compartments for the promotion of osteogenesis. MATERIALS AND METHODS: We first prepared solutions of NAC-loaded mesoporous silica nanoparticles (MSNs), PLGA, and NAC in N, N-dimethylformamide and tetrahydrofuran for the construction of the electrospun system. We then fed solutions to a specific injector for electrospinning. The physical and chemical properties of the scaffold were characterized through scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. The release of NAC and Si from different PLGA scaffolds was estimated. The cell viability, cell growth, and osteogenic potential of rat bone marrow-derived stroma cell (rBMSCs) on different PLGA scaffolds were evaluated through MTT assay, live/dead staining, phalloidin staining, and Alizarin red staining. The expression levels of osteogenic-related markers were analyzed through real-time PCR (qRT-PCR). RESULTS: NAC was successfully loaded into MSNs. The addition of MSNs and NAC decreased the diameters of the electrospun fibers, increased the hydrophilicity and mechanical property of the PLGA scaffold. The release kinetic curve indicated that NAC was released from (PLGA + NAC)/(NAC@MSN) in a biphasic pattern, that featured an initial burst release stage and a later sustained release stage. This release pattern of NAC encapsulated on the (PLGA + NAC)/(NAC@MSN) scaffolds enabled to prolong the high concentrations of release of NAC, thus drastically affecting the osteogenic differentiation of rBMSCs. CONCLUSION: A PLGA electrospun scaffold was developed, and MSNs were used as separate nanocarriers for recharging NAC concentration, demonstrating the promising use of (PLGA + NAC)/(NAC@MSN) for bone tissue engineering.

Comparison of Gingival Troughing by Laser and Retraction Cord.

This study was aimed at comparing the most common two methods for gingival troughing: presaturated cord and lasers (including diode, Nd:YAG, and Er:YAG). A total of 108 anterior teeth (58 maxillary and 50 mandibular) in 50 patients were included in this study. Gingival treatment was carried out in the following four groups: presaturated cord, diode laser, Nd:YAG laser, and Er:YAG laser. The gingival width and gingival recession (GR) were measured at different times (at the time of treatment, after 1 week, and after 4 weeks). The presaturated cord resulted in significantly higher (P < .05) GR than lasers and narrower gingival sulci. Er:YAG laser resulted in the quickest and most uneventful wound healing when compared to diode and Nd:YAG lasers.