Mechanism of Smilax china L. in the treatment of intrauterine adhesions based on network pharmacology, molecular docking and experimental validation.

BACKGROUND: Smilax china L. (SCL) is a traditional herbal medicine for the potential treatment of intrauterine adhesion (IUA). However, the mechanisms of action have not yet been determined. In this study, we explored the effects and mechanisms of SCL in IUA by network pharmacology, molecular docking and molecular biology experiments. METHODS: Active ingredients and targets of SCL were acquired from TCMSP and SwissTargetPrediction. IUA-related targets were collected from the GeneCards, DisGeNET, OMIM and TTD databases. A protein‒protein interaction (PPI) network was constructed by Cytoscape 3.9.1 and analysed with CytoHubba and CytoNCA to identify the core targets. The DAVID tool was used for GO and KEGG enrichment analyses. Furthermore, molecular docking was employed to assess the interaction between the compounds and key targets. Finally, the mechanisms and targets of SCL in IUA were verified by cellular experiments and western blot. RESULTS: A total of 196 targets of SCL were identified, among which 93 were related to IUA. Topological and KEGG analyses results identified 15 core targets that were involved in multiple pathways, such as inflammation, apoptosis, and PI3K/AKT signalling pathways. Molecular docking results showed that the active compounds had good binding to the core targets. In vitro experiments showed that astilbin (AST), a major component of SCL, significantly reduced TGF-ß-induced overexpression of fibronectin (FN), activation of the PI3K/AKT signalling pathway and the expression of downstream factors (NF-κB and BCL2) in human endometrial stromal cells, suggesting that AST ameliorates IUA by mediating the PI3K/AKT/NF-κB and BCL2 proteins. CONCLUSIONS: AST, a major component of SCL, may be a potential therapeutic agent for IUA. Moreover, its mechanism is strongly associated with regulation of the PI3K/AKT signalling pathway and the downstream NF-κB and BCL2 proteins. This study will provide new strategies that utilize AST for the treatment of IUA.

Actinidia arguta Extract Containing Myo-Inositol Suppresses TNF-α-Induced VCAM-1 Expression and Monocyte Adhesion to Endothelial Cells via Inhibition of the PTEN/Akt/GSK-3ß and NF-κB Signaling Pathways.

The primary inflammatory process in atherosclerosis, a major contributor to cardiovascular disease, begins with monocyte adhering to vascular endothelial cells. Actinidia arguta (kiwiberry) is an edible fruit that contains various bioactive components. While A. arguta extract (AAE) has been recognized for its anti-inflammatory characteristics, its specific inhibitory effect on early atherogenic events has not been clarified. We used tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs) for an in vitro model. AAE effectively hindered the attachment of THP-1 monocytes and reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. Transcriptome analysis revealed that AAE treatment upregulated phosphatase and tensin homolog (PTEN), subsequently inhibiting phosphorylation of AKT and glycogen synthase kinase 3ß (GSK3ß) in HUVECs. AAE further hindered phosphorylation of AKT downstream of the nuclear factor kappa B (NF-κB) signaling pathway, leading to suppression of target gene expression. Oral administration of AAE suppressed TNF-α-stimulated VCAM-1 expression, monocyte-derived macrophage infiltration, and proinflammatory cytokine expression in C57BL/6 mouse aortas. Myo-inositol, identified as the major compound in AAE, played a key role in suppressing THP-1 monocyte adhesion in HUVECs. These findings suggest that AAE could serve as a nutraceutical for preventing atherosclerosis by inhibiting its initial pathogenesis.

Effect of Coenzyme Q10 Supplementation on Vascular Endothelial Function: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Coenzyme Q10 (CoQ10) has gained attention as a potential therapeutic agent for improving endothelial function. Several randomized clinical trials have investigated CoQ10 supplementation's effect on endothelial function. However, these studies have yielded conflicting results, therefore this systematic review and meta-analysis were conducted. AIM: This systematic review and meta-analysis were conducted to assess the effects of CoQ10 supplementation on endothelial factors. METHODS: A comprehensive search was done in numerous databases until July 19th, 2023. Quantitative data synthesis was performed using a random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis, and publication bias. RESULTS: 12 studies comprising 489 subjects were included in the meta-analysis. The results demonstrated significant increases in Flow Mediated Dilation (FMD) after CoQ10 supplementation (WMD: 1.45; 95% CI: 0.55 to 2.36; p < 0.02), but there is no increase in Vascular cell adhesion protein (VCAM), and Intercellular adhesion molecule (ICAM) following Q10 supplementation (VCAM: SMD: - 0.34; 95% CI: - 0.74 to - 0.06; p < 0.10) (ICAM: SMD: - 0.18; 95% CI: - 0.82 to 0.46; p < 0.57). The sensitivity analysis showed that the effect size was robust in FMD and VCAM. In meta-regression, changes in FMD percent were associated with the dose of supplementation (slope: 0.01; 95% CI: 0.004 to 0.03; p = 0.006). CONCLUSIONS: CoQ10 supplementation has a positive effect on FMD in a dose-dependent manner. Our findings show that CoQ10 has an effect on FMD after 8 weeks of consumption. Additional research is warranted to establish the relationship between CoQ10 supplementation and endothelial function.

Monochasma Savatieri Aqueous Extract inhibits Human Breast Cancer Cell Line Migration and Adhesion Without Generating Toxicity.

BACKGROUND: Monochasma savatieri, is a rare and endangered plant used to treat cancer in Chinese traditional medicine. OBJECTIVE: To evaluate the anti-cancer activity of M. savatieri aqueous extract by determining its cytotoxicity, anti-migratory, and anti-adhesion effects on breast cancer cells. METHODS: Cell viability, migration, adhesion, circularity, and cell cycle were evaluated by crystal violet (CV) staining, wound-healing, and transwell assays and flow cytometry in MCF7 and MDA-MB-231 cells. Caveolin-1, snail, vimentin and activated Erk and Akt expression were determined by western blot in MDA-MB-231 cells. Immunofluorescent assays confirmed caveolin-1 expression in MDA-MB-231 cells. RESULTS: Survival and cell cycle of MCF7 and MDA-MB-231 cells were not modified by doses up to 500 µg/mL of the extract. The extract inhibited cell migration and adhesion of MDA-MB-231 cells. When cells were exposed to the extract, there was a slight decrease in protein expression of factors related to epithelial-to-mesenchymal transition (snail and vimentin) and a strong decrease in the expression of the oncogenic membrane protein caveolin- 1. Furthermore, the levels of phosphorylated Erk and Akt were also decreased. The content of acteoside, a phenylpropanoid glycoside with reported anti-cancer activity present in M. savatieri, was almost 5 times as much as isoacteoside. CONCLUSION: M. savatieri possesses anti-cancer activity without exerting cytotoxicity on breast cancer cells. The extract exhibited anti-migratory and anti-adhesion effects on breast cancer cells by regulating Erk and Akt signaling pathways and the expression of caveolin-1. In addition, acteoside present in M. savatieri could be responsible for the observed effects.

Mircrofabricating double-sided polydimethylsiloxane (PDMS) artificial phylloplane for microbial food safety research.

Leafy green surface microbiology studies often experience significant variations in results due to the heterogeneous nature of leaf surfaces. To provide a precise and controllable substitute, we microfabricated double-sided artificial leafy green phylloplanes using polydimethylsiloxane (PDMS) with a vinyl-terminated polyethylene glycol chain-based hydrophobicity modifier (PDMS-PEG) to modify PDMS hydrophobicity. We further tested the properties and applications of these artificial leaves, by examining the function of epicuticular wax, growth and survival of E. coli O157:H7 87-23 on the surface, and removal of attached E. coli cells via sanitation. The double-sided PDMS-PDMS-PEG leaves well-replicated their natural counterparts in macroscopic and microscopic structure, hydrophobicity, and E. coli O157:H7 87-23 attachment. After depositing natural epicuticular wax onto artificial leaves, the leaf surface wetting ability decreased, while E. coli O157:H7 87-23 surface retention increased. The artificial leaves supplied with lettuce lysate or bacterial growth media supported E. coli O157:H7 87-23 growth and survival similarly to those on natural leaves. In the sanitation test, the artificial lettuce leaves also displayed patterns similar to those of natural leaves regarding sanitizer efficiency. Overall, this study showcased the microfabrication and applications of double-sided PDMS-PDMS-PEG leaves as a replicable and controllable platform for future leafy green food safety studies.

Combination Therapy of Bone Marrow Mesenchymal Stem Cell Transplantation and Electroacupuncture for the Repair of Intrauterine Adhesions in Rats: Mechanisms and Functional Recovery.

Transplantation of bone marrow mesenchymal stem cells (BMSCs) has demonstrated promising clinical utility in the treatment of endometrial injury and the restoration of fertility. However, since the efficacy of BMSCs after transplantation is not stable, it is very important to find effective ways to enhance the utilisation of BMSCs. Electroacupuncture (EA) has some positive effects on the chemotaxis of stem cells and diseases related to uterine injury. In this study, we established the intrauterine adhesion (IUA) model of the Sprague-Dawley rat using lipopolysaccharide infection and mechanical scratching. Phosphate-buffered saline, BMSCs alone, and BMSCs combined with EA were randomly administered to the rats. Fluorescent cell labelling showed the migration of transplanted BMSCs. H&E staining, Masson staining, Western blot, immunohistochemistry, ELISA, and qRT-PCR were utilised to detect changes in endometrial morphology and expressions of endometrial receptivity-related factors, endometrial pro-inflammatory factors, and fibrosis factors. Finally, we conducted a fertility test to measure the recovery of uterine function. The results showed that EA promoted transplanted BMSCs to migrate into the injured uterus by activating the SDF-1/CXCR4 axis. Endometrial morphology showed the most significant improvement in the BMSC + EA group. The expressions of endometrial pro-inflammatory factors and fibrosis indexes in the BMSC + EA group were lower than those in the model and BMSC groups. Further studies revealed that the expression of endometrial receptivity-related factors and the number of embryos implanted on day 8 of gestation increased in the BMSC + EA group compared with the model group and the BMSC group.

1,3,6-Trigalloylglucose: A Novel Potent Anti-Helicobacter pylori Adhesion Agent Derived from Aqueous Extracts of Terminalia chebula Retz.

1,3,6-Trigalloylglucose is a natural compound that can be extracted from the aqueous extracts of ripe fruit of Terminalia chebula Retz, commonly known as "Haritaki". The potential anti-Helicobacter pylori (HP) activity of this compound has not been extensively studied or confirmed in scientific research. This compound was isolated using a semi-preparative liquid chromatography (LC) system and identified through Ultra-high-performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). Its role was evaluated using Minimum inhibitory concentration (MIC) assay and minimum bactericidal concentration (MBC) assay, scanning electron microscope (SEM), inhibiting kinetics curves, urea fast test, Cell Counting Kit-8 (CCK-8) assay, Western blot, and Griess Reagent System. Results showed that this compound effectively inhibits the growth of HP strain ATCC 700392, damages the HP structure, and suppresses the Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Importantly, it exhibits selective antimicrobial activity without impacting normal epithelial cells GES-1. In vitro studies have revealed that 1,3,6-Trigalloylglucose acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, a critical step in HP infection. These findings underscore the potential of 1,3,6-Trigalloylglucose as a targeted therapeutic agent against HP infections.

Preparation and structural characterization of epoxidized soybean oils-based pressure sensitive adhesive grafted with tea polyphenol palmitate.

Vegetable oils-based pressure sensitive adhesives (PSAs) are green and sustainable but face unsatisfactory adhesion strengths and are prone to aging during storage and application due to the existence of residual double bonds and massive ester bonds. Nine common antioxidants (tea polyphenol palmitate (TPP), caffeic acid, ferulic acid, gallic acid, butylated hydroxytoluene, tertiary butylhydroquinone, butylated hydroxyanisole, propyl gallate, and tea polyphenols) were grafted into epoxidized soybean oils-PSA (ESO-PSA) system to enhance antiaging properties and adhesion strengths. Results showed ESO-PSAs grafted with caffeic acid, tertiary butylhydroquinone, butylated hydroxyanisole, propyl gallate, tea polyphenols, or TPP didn't occur failure with TPP having best performance. The optimal conditions were ESO reacted with 0.9 % TPP, 70 % rosin ester, and 7.0 % phosphoric acid at 50 °C for 5 min, under which peel strength and loop tack increased to 2.460 N/cm and 1.66 N, respectively, but peel strength residue reduced to 138.09 %, compared with control (0.407 N/cm, 0.43 N, and 1669.99 %). Differential scanning calorimetry and thermogravimetric results showed TPP grafting increased the glass transition temperature of ESO-PSA slightly but improved its thermal stability significantly. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance results showed TPP, phosphoric acid, and rosin ester all partially participated in the covalently crosslinking polymerization of ESO-PSAs and the rest existed in the network structures in the free form.

The mechanism of selenium regulating the permeability of vascular endothelial cells through selenoprotein O.

Vascular diseases, a leading cause of death in human, are strongly associated with pathological damage to blood vessels. The selenoprotein (Sel) have been reported to play important roles in vascular disease. However, the role of SelO in vascular disease has not been conclusively investigated. The present experiment was to investigate the regulatory mechanism of the effect of SelO on the permeability of vascular endothelial. The H.E staining, FITC-Dextran staining, Dil-AC-LDL staining and FITC-WGA staining showed that vascular structure was damaged, and intercellular junctions were disrupted with selenium (Se)-deficient. Immunohistochemistry, qPCR and Western blot revealed decreased expression of the adhesion plaque proteins vinculin, talin and paxillin, decreased expression of the vascular connectivity effector molecules connexin, claudin-1 and E-cadherin and increased expression of JAM-A and N-cadherin, as well as decreased expression of the ZO-1 signaling pathways ZO-1, Rock, rhoGEF, cingulin and MLC-2. In a screening of 24 Sel present in mice, SelO showed the most pronounced changes in vascular tissues, and a possible association between SelO and vascular intercellular junction effectors was determined using IBM SPSS Statistics 25. Silencing of SelO, vascular endothelial intercellular junction adverse effects present. The regulatory relationship between SelO and vascular endothelial intercellular junctions was determined. The results showed that Se deficiency lead to increased vascular endothelial permeability and vascular tissue damage by decreasing SelO expression, suggesting a possible role for SelO in regulating vascular endothelial permeability.

Vinorelbine Improves the Efficacy of Sorafenib against Hepatocellular Carcinoma: A Promising Therapeutic Approach.

Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. Despite the widespread adoption of sorafenib as the standard HCC treatment, its efficacy is constrained, frequently encountering resistance. To augment the effectiveness of sorafenib, this study investigated the synergy of sorafenib and vinorelbine using 22 HCC patient-derived xenograft (PDX) models. In this study, mice bearing HCC tumors were treated with the vehicle, sorafenib (15 mg/kg), vinorelbine (3 mg/kg), and sorafenib-vinorelbine combination (Sora/Vino). Rigorous monitoring of the tumor growth and side effects coupled with comprehensive histological and molecular analyses was conducted. The overall survival (OS) of mice bearing HCC orthotopic tumors was also assessed. Our data showed a notable 86.4% response rate to Sora/Vino, surpassing rates of 31.8% for sorafenib and 9.1% for vinorelbine monotherapies. Sora/Vino significantly inhibited tumor growth, prolonged OS of mice bearing HCC orthotopic tumors (p < 0.01), attenuated tumor cell proliferation and angiogenesis, and enhanced necrosis and apoptosis. The combination therapy effectively suppressed the focal adhesion kinase (FAK) pathway, which is a pivotal player in cell proliferation, tumor angiogenesis, survival, and metastasis. The noteworthy antitumor activity in 22 HCC PDX models positions Sora/Vino as a promising candidate for early-phase clinical trials, leveraging the established use of sorafenib and vinorelbine in HCC and other cancers.

A synergistic anti-bacterial and anti-adhesion activity of tea tree (Melaleuca alternifolia) and lemon eucalyptus tree (Eucalyptus citriodora Hook) essential oils on Legionella pneumophila.

Legionella pneumophila is a Gram-negative bacterial pathogen that colonizes natural and artificial water systems and has the ability to form a biofilm. The biofilm protects L. pneumophila from various environmental factors and makes it more resistant to chlorine-based disinfectants. This study investigated the anti-bacterial properties of tea tree (Melaleuca alternifolia (Maiden and Betche) Cheel) oil and lemon eucalyptus tree (Eucalyptus citriodora Hook) essential oils (EOs) and their synergistic, additive inhibitory and anti-adhesive effects against L. pneumophila biofilm formation on polystyrene. The minimum effective concentration (MEC) for tea tree is 12.8 mg ml-1 and for lemon eucalyptus tree EO 6.4 mg ml-1. In the checkerboard assay, different combinations of these two EO show synergistic and additive anti-microbial activity. The minimum anti-adhesive concentration (MAC) for tea tree is 12.8 mg ml-1 and for lemon eucalyptus tree EO 6.4 mg ml-1. A combination of 3.2 mg ml-1 tea tree EO and 0.8 mg ml-1 lemon eucalyptus tree EO showed the strongest anti-adhesive effect against L. pneumophila on polystyrene. The tested oils and their combination showed intriguing potential to inhibit L. pneumophila biofilm formation.

Effects of dried okra extract on lipid profile, renal function and some RAGE-related inflammatory genes expression in patients with diabetic nephropathy: A randomized controlled trial.

BACKGROUND: Diabetic nephropathy (DN) is a common complication of type 2 diabetes. Okra (Abelmoschus esculentus L) is reported to have anti-diabetic effects. The present study aimed to investigate the effects of dried okra extract (DOE) supplementation on lipid profile, renal function indices, and expression of inflammatory genes, as well as serum level of soluble Receptor for Advanced glycation end products (sRAGE) in patients with DN. METHODS: In this triple-blind randomized placebo-controlled clinical trial, 64 eligible patients with DN received either 125 mg of DOE or placebo daily along with DN-related nutritional recommendations for 10 weeks. Changes in kidney indices including proteinuria and estimated glomerular filtration rate (eGFR), lipid profile, serum SRAGE, as well as the expression of RAGE, ICAM-1, and IL-1 genes were measured over 10 weeks. RESULTS: After adjustment for the potential confounders, between-group analyses showed no significant differences in terms of lipid profile, kidney function indices, sRAGE, and RAGE-related inflammatory genes expression after 10 weeks. CONCLUSION: Daily 125 mg DOE along with nutritional recommendations on top of usual care did not lead to significant changes in renal function indices, lipid profile, and inflammatory genes expression in patients with DN.

Green Starch-Based Hydrogels with Excellent Injectability, Self-Healing, Adhesion, Photothermal Effect, and Antibacterial Activity for Promoting Wound Healing.

Hydrogel materials have proven valuable in wound healing, but improving the safety of these hydrogels is still challenging. Therefore, designing multifunctional natural polymeric-based hydrogels with excellent mechanical properties to replace toxic or potentially risky, refractory chemical polymer-based hydrogels such as polyacrylamide and polyethylene glycol is of particular significance. Here, a green starch-based hydrogel (Starch@Ca/CGC hydrogel) with injectability, self-healing, and instant adhesion was constructed by coordination interaction, electrostatic interaction, and intramolecular and intermolecular hydrogen bonds. Therein, natural bioactive small molecules gallic acid (GA) and carvacrol (CA) were coordinated with metal ions by the ultrasonic-triggered self-assembly and ionic cross-linking codriven strategy to prepare Cu-gallic acid-carvacrol nanospheres (CGC NPs), which conferred the hydrogel with near-infrared light (NIR)-controlled CA release and photothermal synergistic sterilization properties, as well as antioxidant and anti-infection capabilities. More importantly, the multifunctional hydrogel platforms could completely cover an irregular wound shape to prevent secondary injury and significantly accelerate wound healing under NIR with more skin appendages like hair follicles and blood vessels appearing. Therefore, it is expected that this starch-based hydrogel could serve as a competitive multifunctional dressing in the biomedical field, including bacteria-derived wound infection and other tissue repair.

Effect of the use of bromelain associated with bioactive glass-ceramic on dentin/adhesive interface.

OBJECTIVES: To evaluate the effect of bromelain associated with Biosilicate on the bond strength (BS) of a universal adhesive system to sound (SD) and caries-affected dentin (CAD), and on the proteolytic activity. MATERIALS AND METHODS: Cavities were prepared in 360 molars, half submitted to cariogenic challenge. Teeth were separated into groups (n=20): Control-No treatment; CHX-0.12% chlorhexidine; NaOCl-5% sodium hypochlorite; Br5%-5% bromelain; Br10%-10% bromelain; Bio-10% Biosilicate; NaOClBio-NaOCl+Bio; Br5%Bio-Br5%+Bio; Br10%Bio-Br10%+Bio. Following treatments, the adhesive system was applied, and cavities were restored. Samples were sectioned into sticks and stored at 37 °C for 24 h, 6 months, and 1 year. Microtensile BS (2-way ANOVA, Bonferroni's test, α=0.05), fracture patterns (SEM), and adhesive interfaces (TEM) were evaluated. Bacterial collagenase assay and in situ zymography were performed. RESULTS: In CAD, Br10% presented higher BS (p=0.0208) than Br5%Bio. Br5% presented higher BS (p=0.0033) after 6 months than after 24 h; and association of treatments, higher BS (p<0.05) after aging than after 24 h. Mixed fractures were the most prevalent. Association of treatments promoted a more uniform hybrid layer with embedded Bio particles. Experimental groups presented lower (p<0.0001) relative fluorescence units than Control. Bromelain, associated or not with Bio, showed collagenolytic degradation. CONCLUSIONS: Bromelain associated with Biosilicate did not affect the BS to SD. In CAD, Br5%Bio decreased immediate BS but had no long-term influence. This association decreased the proteolytic activity. CLINICAL RELEVANCE: Bromelain and Biosilicate may enhance the longevity of adhesive restorations by inhibiting endogenous proteases.

Massa intermedia in adults: incidence, dimension, location and clinical importance.

PURPOSE: This retrospective magnetic resonance imaging investigation aimed to obtain information related to the anatomy of the massa intermedia (MI) in an adult population. METHODS: The work conducted on MRI views of 1058 (539 males and 519 females) healthy adult samples aged with 48.93 ± 17.63 years. Initially, the presence or absence of MI was noted, and then if present, its numbers and location in the third ventricle were recorded. Its horizontal (HDMI) and vertical (VDMI) diameters were measured on MRI views, while the cross-sectional area (CSAMI) was calculated using its diameters. RESULTS: MI was missing in 2.6% (27 cases) of 1058 adult samples. Six subjects (0.6%) had a double MI. HDMI, VDMI and CSAMI were measured as 4.83 ± 1.01 mm, 4.86 ± 0.98 mm, and 19.11 ± 7.23 mm2, respectively. MI size did not show a significant alteration from 19 up to 49 years, but then its size distinctly decreased between 50 and 60 years. After age 60, MI dimension did not display an important change. MI was settled in the antero-superior quadrant in 929 cases (90.63% of 1025 subjects), in the postero-superior quadrant in 22 cases (2.15%), in the antero-inferior quadrant in 32 cases (3.12%), in the postero-inferior quadrant in 8 cases (0.78%), and in the central part in 34 cases (3.32%). CONCLUSIONS: The size, position and incidence of MI were not affected by sex, and its position and incidence were not affected by adult age periods. In adults, MI size demonstrated a significant decrease in the middle age.

The effect of supplementing the calcium phosphate cement containing poloxamer 407 on cellular activities.

Calcium phosphate cement (CPC) is generally used for bone repair and augmentation. Poloxamers are tri-block copolymers that are used as surfactants but have applications in drug and antibiotic delivery. However, their biological effects on bone regeneration systems remain unelucidated. Here, we aimed to understand how supplementing the prototype CPC with poloxamer would impact cellular activity and its function as a bone-grafting material. A novel CPC, modified beta-tricalcium phosphate (mß-TCP) powder, was developed through a planetary ball-milling process using a beta-tricalcium phosphate (ß-TCP). The mß-TCP dissolves rapidly and accelerates hydroxyapatite precipitation; successfully shortening the cement setting time and enhancing the strength. Furthermore, the addition of poloxamer 407 to mß-TCP could reduce the risk of leakage from bone defects and improve fracture toughness while maintaining mechanical properties. In this study, the poloxamer addition effects (0.05 and 0.1 g/mL) on the cellular activities of MC3T3-E1 cells cultured in vitro were investigated. The cell viability of mß-TCP containing poloxamer 407 was similar to that of mß-TCP. All specimens showed effective cell attachment and healthy polygonal extension of the cytoplasm firmly attached to hydroxyapatite (HA) crystals. Therefore, even with the addition of poloxamer to mß-TCP, it does not have a negative effect to osteoblast growth. These data demonstrated that the addition of poloxamer 407 to mß-TCP might be considered a potential therapeutic application for the repair and regeneration of bone defects.

Impact of dairy fat manipulation on endothelial function and lipid regulation in human aortic endothelial cells exposed to human plasma samples: an in vitro investigation from the RESET study.

PURPOSE: Longer-term intake of fatty acid (FA)-modified dairy products (SFA-reduced, MUFA-enriched) was reported to attenuate postprandial endothelial function in humans, relative to conventional (control) dairy. Thus, we performed an in vitro study in human aortic endothelial cells (HAEC) to investigate mechanisms underlying the effects observed in vivo. METHODS: This sub-study was conducted within the framework of the RESET study, a 12-week randomised controlled crossover trial with FA-modified and control dairy diets. HAEC were incubated for 24 h with post-intervention plasma samples from eleven adults (age: 57.5 ± 6.0 years; BMI: 25.7 ± 2.7 kg/m2) at moderate cardiovascular disease risk following representative sequential mixed meals. Markers of endothelial function and lipid regulation were assessed. RESULTS: Relative to control, HAEC incubation with plasma following the FA-modified treatment increased postprandial NOx production (P-interaction = 0.019), yet up-regulated relative E-selectin mRNA gene expression (P-interaction = 0.011). There was no impact on other genes measured. CONCLUSION: Incubation of HAEC with human plasma collected after longer-term dairy fat manipulation had a beneficial impact on postprandial NOx production. Further ex vivo research is needed to understand the impact of partial replacement of SFA with unsaturated fatty acids in dairy foods on pathways involved in endothelial function.

Sprayable tissue adhesive microparticle-magnetic nanoparticle composites for local cancer hyperthermia.

Incomplete removal of early-stage gastrointestinal cancers by endoscopic treatments often leads to recurrence induced by residual cancer cells. To completely remove or kill cancer tissues and cells and prevent recurrence, chemotherapy, radiotherapy, and hyperthermia using biomaterials with drugs or nanomaterials are usually administered following endoscopic treatments. However, there are few biomaterials that can be applied using endoscopic devices to locally kill cancer tissues and cells. We previously reported that decyl group-modified Alaska pollock gelatin-based microparticles (denoted C10MPs) can adhere to gastrointestinal tissues under wet conditions through the formation of a colloidal gel driven by hydrophobic interactions. In this study, we combined C10MPs with superparamagnetic iron oxide nanoparticles (SPIONs) to develop a sprayable heat-generating nanomaterial (denoted SP/C10MP) for local hyperthermia of gastrointestinal cancers. The rheological property, tissue adhesion strength, burst strength, and underwater stability of SP/C10MP were improved through decyl group modification and SPION addition. Moreover, SP/C10MP that adhered to gastrointestinal tissues formed a colloidal gel, which locally generated heat in response to an alternating magnetic field. SP/C10MP successfully killed cancer tissues and cells in colon cancer-bearing mouse models in vitro and in vivo. Therefore, SP/C10MP has the potential to locally kill residual cancer tissues and cells after endoscopic treatments.

Photobiomodulation therapy at 632 nm wavelength ameliorates intrauterine adhesion via activation of cAMP/PKA/CREB pathway.

Intrauterine adhesion (IUA), a major cause of uterine infertility, is pathologically characterized by endometrial fibrosis. Current treatments for IUA have poor efficacy with high recurrence rate, and restoring uterine functions is difficult. We aimed to determine the therapeutic efficacy of photobiomodulation (PBM) therapy on IUA and elucidate its underlying mechanisms. A rat IUA model was established via mechanical injury, and PBM was applied intrauterinely. The uterine structure and function were evaluated using ultrasonography, histology, and fertility tests. PBM therapy induced a thicker, more intact, and less fibrotic endometrium. PBM also partly recovered endometrial receptivity and fertility in IUA rats. A cellular fibrosis model was then established with human endometrial stromal cells (ESCs) cultured in the presence of TGF-ß1. PBM alleviated TGF-ß1-induced fibrosis and triggered cAMP/PKA/CREB signaling in ESCs. Pretreatment with the inhibitors targeting this pathway weakened PBM's protective efficacy in the IUA rats and ESCs. Therefore, we conclude that PBM improved endometrial fibrosis and fertility via activating cAMP/PKA/CREB signaling in IUA uterus. This study sheds more lights on the efficacy of PBM as a potential treatment for IUA.

Safflower Yellow Inhibits Progression of Hepatocellular Carcinoma by Modulating Immunological Tolerance via FAK Pathway.

OBJECTIVE: To explore the anti-tumor effect of safflower yellow (SY) against hepatocellular carcinoma (HCC) and the underlying potential mechanism. METHODS: An in vitro model was established by mixing Luc-Hepa1-6 cells and CD3+CD8+ T cells, followed by adding programmed cell death protein 1 (PD-1) antibody (Anti-mPD-1) with or without SY. The apoptosis was detected by flow cytometry and the level of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. The protein levels of programmed cell death 1 ligand 1 (PD-L1), chemokine ligand (CCL5), C-X-C motif chemokine ligand 10 (CXCL10) were measured by Western blot. An in situ animal model was established in mice followed by treatment with anti-mPD-1 with or without SY. Bioluminescence imaging was monitored with an AniView 100 imaging system. To establish the FAK-overexpressed Luc-Hepa1-6 cells, cells were transfected with adenovirus containing pcDNA3.1-FAK for 48 h. RESULTS: The fluorescence intensity, apoptotic rate, release of inflammatory cytokines, and CCL5/CXCL10 secretion were dramatically facilitated by anti-mPD-1 (P<0.01), accompanied by an inactivation of PD-1/PD-L1 axis, which were extremely further enhanced by SY (P<0.05 or P<0.01). Increased fluorescence intensity, elevated percentage of CD3+CD8+ T cells, facilitated release of inflammatory cytokines, inactivated PD-1/PD-L1 axis, and increased CCL5/CXCL10 secretion were observed in Anti-mPD-1 treated mice (P<0.01), which were markedly enhanced by SY (P<0.05 or P<0.01). Furthermore, the enhanced effects of SY on inhibiting tumor cell growth, facilitating apoptosis and inflammatory cytokine releasing, suppressing the PD-1/PD-L1 axis, and inducing the CCL5/CXCL10 secretion in Anti-mPD-1 treated mixture of Luc-Hepa1-6 cells and CD3+CD8+ T cells were abolished by FAK overexpression (P<0.01). CONCLUSION: SY inhibited the progression of HCC by mediating immunological tolerance through inhibiting FAK.