Pectin wrapped halloysite nanotube reinforced Polycaprolactone films for potential wound healing application.

The current research work focuses on preparing the polycaprolactone (PCL) based nanocomposite films embedded with surface modified Halloysite Nanotube (HNT). The avenue of the study is to unravel the applicability of polymer nanocomposites for wound healing. The flexible property of HNT was taken as the major force to accomplish the addition of biopolymer pectin onto its surface. Functionalization of HNT with pectin has certainly enhanced its binding nature with the polymer. The PCL nanocomposite films were characterized by several promising techniques such as FTIR, XRD, DSC-TGA, FESEM, TEM, AFM, and mechanical properties were too examined along. When compared to the plane PCL film, the nanocomposite films manifested favorable results in terms of mechanical and chemical properties. Additionally, biometric studies such as in-vitro swelling, enzymatic degradation, and hemolysis performed on the films gave extremely good results. The haemolytic percentage recorded for the films exhibited a steady decrease with increasing amount of nanofillers. The MTT assay showed cell proliferation and its increase as the embedded HNT is more in the matrix. Wound closure study performed on NIH3T3 cell line with 1, 3 and 5wt% of films has given a strong proof for the involvement of polymer and HNT in the healing procedure.

Ripe papaya pectins inhibit the proliferation of colon cancer spheroids and the formation of chemically induced aberrant crypts in rats colons.

Pectins are a class of soluble polysaccharides that can have anticancer properties through several mechanisms. This study aimed to characterize the molecular structure of water-soluble fractions (WSF) derived from ripe and unripe papayas and assess their biological effects in two models: the 3D colon cancer spheroids to measure cell viability and cytotoxicity, and the in vivo model to investigate the inhibition of preneoplastic lesions in rats. WSF yield was slightly higher in ripe papaya, and both samples mainly consisted of pectin. Both pectins inhibited the growth of colon cancer HT29 and HCT116 spheroids. Unripe pectin disturbed HT29/NIH3T3 spheroid formation, decreased HCT116 spheroid viability, and increased spheroid cytotoxicity. Ripe pectin had a more substantial effect on the reduction of spheroid viability for HT29 spheroids. Furthermore, in vivo experiments on a rat model revealed a decrease in aberrant crypt foci (ACF) formation for both pectins and increased apoptosis in colonocytes for ripe papaya pectins. The results suggest potential anticancer properties of papaya pectin, with ripe pectin showing a higher potency.

Isolation and structure elucidation of the compounds from Teucrium hyrcanicum L. and the investigation of cytotoxicity, antioxidant activity, and protective effect on hydrogen peroxide-induced oxidative stress.

BACKGROUND: Teucrium hyrcanicum L. (family Lamiaceae) is widely distributed in the North and Northwest of Iran. It has been used in the form of tea, tonic, and tincture for the treatment of various diseases such as cough, rheumatism, and fever. METHODS: In this study, the total phenolic and flavonoid contents, antioxidant and cytotoxic activities of methanol extract and different fractions of T. hyrcanicum were measured. Furthermore, the potential ability of T. hyrcanicum to protect against H2O2-induced oxidative stress was tested on the NIH3T3 cell line. Then, the isolation and structure elucidation of the compounds were performed on the most potent fractions. Finally, the quantification of isolated compounds in methanol extract (ME) was done by the HPLC method. Isolated phytochemicals were assessed for the cytotoxic and antioxidant activities. RESULTS: The results indicated that the methanol fraction (MF) had the highest amount of phenolic and flavonoid contents (69.36 mg GAE/g extract and 68.95 mg QE/g extract). The highest radical scavenging activities were observed from MF and ME (IC50 44.32 and 61.12 µg.ml-1, respectively). The best cytotoxicity was obtained by ethyl acetate fraction (EF) against A431 and MCF7 cell lines (IC50 values of 235.4and 326.6 µg.ml-1, respectively). The pretreatment with MF exerts the highest reduction in malondialdehyde (MDA) formation (IC50 2.51 µM, p < 0.001) compared to the H2O2 group (5.77 µM). Also, MF significantly inhibited H2O2-induced Glutathione (GSH) oxidation (p < 0.001). Furthermore, two phenolic compounds, acteoside and quercetin, were isolated and identified in MF and EF, respectively. The IC50 values of acteoside and quercetin in the DPPH assay were 7.19 and 5.56 µg.ml-1, respectively. Both quercetin and acteoside significantly reduced the MDA formation and inhibited GSH oxidation, which was comparable with BHA (as a standard antioxidant) (p < 0.05). Acteoside demonstrated significant cytotoxicity against all tested cell lines (IC50 = 32 to 145 µg.ml-1). The HPLC quantification of isolated compounds revealed that the quantity of acteoside and quercetin in ME were 93.31 and 16.87 µg.mg-1, respectively. CONCLUSION: The isolated compounds (quercetin and acteoside) had significant antioxidant activities and revealed a protective effect on H2O2-induced oxidative stress which was comparable with BHA.

Biosynthesis and characterization of selenium nanoparticles from Andrographis alata: Assessment of their potential antimicrobial, antidiabetic, anti-Alzheimer's and wound healing properties.

Recently, there has been a lot of focus on the environmentally friendly, specifically plant-based, synthesis of nanoparticles. The extract of leaves from Andrographis alata (A. alata) was used in the current work as a reducing agent to create selenium nanoparticles (SeNPs), which will be used in biological applications (antibacterial, antioxidant and antidiabetic, anti-Alzheimer's and wound healing properties). As part of detailed characterization, the UV-Vis spectra showed an absorption peak at 274 nm with a size in the range of 55-75 nm were shown in morphological investigations using EDS, DLS and SEM analysis to have crystalline spherical-shaped structures. Against several harmful bacterial strains, SeNPs demonstrated a remarkable antibacterial effectiveness. The minimum inhibitory concentration (MIC) of synthesized SeNPs completely prevented the development of various pathogens. Furthermore, bio-reduced SeNPs showed high cholinesterase inhibition efficacy and good antipotential Alzheimer's. According to the current research, treatment with biosynthesized SeNPs stimulates faster wound healing in NIH3T3 murine fibroblast cell lines without cytotoxicity. Different in vitro biological experiments also showed that, when compared with the extract of A. alata, bio-reduced SeNPs had considerable antibacterial, antioxidant effects, antidiabetic, anti-Alzheimer's and wound healing. In general, the findings demonstrate the efficacy and prospective therapeutic uses of SeNPs.

Assessing the effect of selenium on cyclin D1 level and nuclear factor kappa b activity in NIH/3T3 fibroblast cells at 2100 MHz electromagnetic field exposure.

Although there are numerous studies on the health impacts of electromagnetic field (EMF) of mobile phone operation frequency 2100 MHz, the published works present contradicting results. Long-term exposure to mobile phone frequencies has unclear health hazards. Therefore, it is important to investigate the molecular mechanism of possible biological effects in mobile phone exposure and to determine the corresponding biological markers. Towards this end, this study was designed to assess the effect of 200 nM selenium (Se) on cell viability% [trypan blue], cell cycle biomarker [cyclin D1] and the transcription factor [nuclear factor kappa b (NF-κB)] in NIH/3T3 fibroblast cells when exposed to 2100 MHz mobile phone frequency. When 2100 MHz EMF was exposed to NIH/3T3 fibroblast cells, the cell viability% was reduced, whereas cyclin D1 level and NF-kB activity increased. Also we show that Se supplementation decreases the effects of 2100 MHz EMF on these parameters. Although future studies will be required to investigate the biological effects of EMF emitted by mobile phones, the results obtained here provide an insight into the molecular mechanisms and specifically underlying selenium's protective effect against 2100 MHz EMF exposure.

Golden Buckwheat Extract-Loaded Injectable Hydrogel for Efficient Postsurgical Prevention of Local Tumor Recurrence Caused by Residual Tumor Cells.

To prevent local tumor recurrence caused by possible residual cancer cells after surgery, avoid toxicity of systemic chemotherapy and protect the fragile immune system of postsurgical patients, an increasing amount of attention has been paid to local anti-cancer drug delivery systems. In this paper, golden buckwheat was first applied to prevent post-operative tumor recurrence, which is a Chinese herb and possesses anti-tumor activity. Golden buckwheat extract-loaded gellan gum injectable hydrogels were fabricated via Ca2+ crosslinking for localized chemotherapy. Blank and/or drug-loaded hydrogels were characterized via FT-IR, TG, SEM, density functional theory, drug release and rheology studies to explore the interaction among gellan gum, Ca2+ and golden buckwheat extract (GBE). Blank hydrogels were non-toxic to NIH3T3 cells. Of significance, GBE and GBE-loaded hydrogel inhibited the proliferation of tumor cells (up to 90% inhibition rate in HepG2 cells). In vitro hemolysis assay showed that blank hydrogel and GBE-loaded hydrogel had good blood compatibility. When GBE-loaded hydrogel was applied to the incompletely resected tumor of mice bearing B16 tumor xenografts, it showed inhibition of tumor growth in vivo and induced the apoptosis of tumor cells. Taken together, gellan gum injectable hydrogel containing GBE is a potential local anticancer drug delivery system for the prevention of postsurgical tumor recurrence.

Development of κ-carrageenan-PEG/lecithin bioactive hydrogel membranes for antibacterial adhesion and painless detachment.

The issue of wound dressing adherence poses a substantial challenge in the field of wound care, with implications both clinically and economically. Overcoming this challenge requires the development of a hydrogel dressing that enables painless removal without causing any secondary damage. However, addressing this issue still remains a significant challenge that requires attention and further exploration. The present study is focused on the synthesis of hydrogel membranes based on κ-carrageenan (CG), polyethylene glycol (PEG), and soy lecithin (LC), which can provide superior antioxidant and antibacterial attachment properties with a tissue anti adhesion activity for allowing an easy removability without causing secondary damage. The (CG-PEG)/LC mass ratio was varied to fabricate hydrogel membranes via a facile approach of physical blending and solution casting. The physicochemical properties of (CG-PEG)/LC hydrogel membranes were studied by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and mechanical analyses. The membranes showed significantly enhanced mechanical properties with excellent flexibility and had high swelling capacity (˃1000 %), which would provide a moist condition for wound healing. The membranes also exhibited excellent free radical scavenging ability (>60 %). In addition, the (CG-PEG)/LC hydrogel membranes showed reduced peel strength 26.5 N/m as a result of weakening the hydrogel-gelatin interface during an in vitro gelatin peeling test. Moreover, the membrane showed superior antibacterial adhesion activity (>90 %) against both S. aureus and E. coli due to the presence of both PEG and LC. The results also suggested that the hydrogel membranes exhibit NIH3T3 cell antiadhesion property, making them promising material for easy detachment from the healed tissue without causing secondary damage. Thus, this novel combination of (CG-PEG)/LC hydrogel membranes have immense application potential as a biomaterial in the healthcare sector.

1-Tetracosanol isolated from the leaves of Eupatorium glandulosum, accelerates wound healing by expressing inflammatory cytokines and matrix metalloproteinase.

ETHNOPHARMACOLOGICAL RELEVANCE: The leave paste of the plant, Eupatorium glandulosum H. B & K, has been traditionally used to treat cuts and wounds by the tribal community of the Nilgiris district of Tamilnadu, India. AIM OF THE STUDY: The present study was carried out to investigate the wound healing potential of this plant extract and the compound, 1-Tetracosanol, isolated from the ethyl acetate fraction. MATERIALS AND METHODS: An in vitro study was designed to compare the viability, migration and apoptosis of the fresh methanolic extract fractions and 1-Tetracosanol using mouse fibroblast NIH3T3 cell lines and human keratinocytes HaCaT cell lines, respectively. 1-Tetracosanol was evaluated for its viability, migration, qPCR analysis, in silico, in vitro and in vivo. RESULTS: 1-Tetracosanol at the concentration of 800, 1600, 3200 µM has significant wound closure of 99% at 24 h. The compound when screened in silico against various wound healing markers, TNF-α, IL-12, IL-18, GM-CSF and MMP-9, revealed high binding energy of -5, 4.9 and -6.4 kcal/mol for TNF-α, IL-18 and MMP-9, respectively. Gene expression and the release of cytokines increased at an early stage of the wound repair. 1-Tetracosanol, at 2% gel showed 97.35 ± 2.06% wound closure at 21st day. CONCLUSION: 1-Tetracosanol is a good lead for drug development targeted towards wound healing activity and work in this direction is in progress.

Anti-cancer Effect and Active Phytochemicals of Houttuynia cordata Thunb. against Human Breast Cancer Cells.

BACKGROUND: Houttuynia cordata Thunb (HCT) is a medicinal herb used in Southeast Asia. Aim of this work: This study aimed at investigating the cytotoxicity of this plant extract and fractions towards human breast cancer MDA-MB-231 and MCF-7 cells. HCT's phytoactive compounds are determined. MATERIALS AND METHODS: Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The mode of cell death was measured by staining with annexin V-FITC and propidium iodide (PI) employing flow cytometry technique. The oxidative stress was measured by using 2',7'-dihydrodichlorofluorescein diacetate (DCFH-DA) and dihydroethidium (DHE+) fluorescent probes and using a fluorescence microplate reader. HCT phytochemicals were characterized by high performance liquid chromatography (HPLC). RESULTS: The proliferation of MDA-MB-231 and MCF-7 cells was dramatically decreased by the crude extract and individual fraction of HCT. Ethyl acetate was the solvent fraction with the highest toxicity against MCF-7 cells, followed by dichloromethane, crude, and hexane fractions, respectively, whereas in MDA-MB231 cells, dichloromethane, crude, hexane, and ethyl acetate fractions each had the strongest impact, respectively. The methanol fraction had no effect on either cell line up to 200 µg/ml. The extract and fractions were less harmful to the NIH3T3 normal murine fibroblast cell line. The mode of both cell death was apoptosis evidenced by the increase of cell population stained with annexin V-FITC and PI. The fluorescence probes of both DCFH-DA and DHE in MDA-MB-231 cell line were enhanced. Phenolic acids included chlorogenic acid (CA), gallic acid (GA), transcoumaric acid (TCA), vanillic acid (VA), and syringic acid (SA), as well as flavonoids like quercetin and rutin, were identified as the active phytochemicals in the crude and fractions by using HPLC method. CONCLUSION: MDA-MB-231cells underwent apoptosis via oxidative stress when induced with HCT hexane fraction. Phenolic acids and flavonoids were identified in HCT's extract and fractions.

Bromelain: a candidate to enhance wound healing after endonasal surgeries.

OBJECTIVE: In the present study, we investigated the topical bromelain's cytotoxic effects on mouse fibroblast NIH/3T3 cells via cell culture study. MATERIALS AND METHODS: In this cell culture study, Dulbecco's Modified Eagle Medium (DMEM) with fetal bovine serum (FBS, 10%) and penicillin/streptomycin (1%) was used as a cell growth medium for NIH/3T3 mouse fibroblast cells. MTT test was performed in 96-well plates seeded with NIH/3T3 cells 5x103/well and under standard cell culture conditions. Bromelain doses of 3.13 to 100 µM were administered to the wells and incubated for 24, 48, and 72 hours in the same cell culture conditions. For Confocal microscopic evaluation, NIH/3T3 cells were plated on cover slips in 6-well plates (105 cells/well) and treated with 100 µM concentration of bromelain for 24 h. Untreated cells were used as controls. RESULTS: MTT results showed that bromelain is not cytotoxic on mouse fibroblast NIH/3T3 cells. All three incubation times of 24, 48, and 72 hours bromelain initiated cell growth. A statistically significant rise in cell growth was detected in the only applied highest dose of 100 µM bromelain for all incubation times except for 24 hours. The nontoxic effect was further investigated by using confocal microscopy by applying the highest bromelain dose of 100 µM to NIH/3T3 mouse fibroblast cells. Confocal micrographs showed that bromelain did not change the morphology of mouse fibroblast cells at the incubation time of 24h. In untreated cells and bromelain-treated cells, the nucleus of NIH/3T3 cells was undamaged and compact, and the cytoskeleton was fusiform and non-fragmented. CONCLUSIONS: Bromelain is not cytotoxic on mouse fibroblast NIH/3T3 cells and enhances cell growth. If clinical trials will confirm this, it is possible that bromelain will be used topically in humans to enhance wound healing, in rhinosinusitis and chronic rhinosinusitis with nasal polyps and endonasal surgeries due to its anti-inflammatory effects.

Enhancing the Antioxidant, Antibacterial, and Wound Healing Effects of Melaleuca alternifolia Oil by Microencapsulating It in Chitosan-Sodium Alginate Microspheres.

In this study, antibacterial and antioxidant molecules-rich Melaleuca alternifolia oil (tea tree oil (TTO)) loaded chitosan (CS) based nanoemulsions (NEMs) were prepared and encapsulated by sodium alginate (SA) microsphere for antibacterial wound dressing. CS-TTO NEMs were prepared by oil-in-water emulsion technique, and the nanoparticle tracking analysis (NTA) confirmed that the CS-TTO NEMs had an average particle size of 89.5 nm. Further, the SA-CS-TTO microsphere was confirmed through SEM analysis with an average particle size of 0.76 ± 0.10 µm. The existence of TTO in CS NEMs and SA encapsulation was evidenced through FTIR analysis. The XRD spectrum proved the load of TTO and SA encapsulation with CS significantly decreased the crystalline properties of the CS-TTO and SA-CS-TTO microsphere. The stability of TTO was increased by the copolymer complex, as confirmed through thermal gravimetric analysis (TGA). Furthermore, TTO was released from the CS-SA complex in a sustained manner and significantly inhibited the bacterial pathogens observed under confocal laser scanning microscopy (CLSM). In addition, CS-TTO (100 µg/mL) showed antioxidant potential (>80%), thereby increasing the DPPH and ABTS free radicals scavenging ability of SA-CS-TTO microspheres. Moreover, CS and SA-CS-TTO microsphere exhibited negligible cytotoxicity and augmented the NIH3T3 cell proliferation confirmed in the in vitro scratch assay. This study concluded that the SA-CS-TTO microsphere could be an antibacterial and antioxidant wound dressing.

Polypropylene sulphide coating on magnetic nanoparticles as a novel platform for excellent biocompatible, stimuli-responsive smart magnetic nanocarriers for cancer therapeutics.

Magnetic nanoparticle (MNP) delivery systems are promising for targeted drug delivery, imaging, and chemo-hyperthermia of cancer; however, their uses remain limited primarily due to their toxicity associated with reactive oxygen species (ROS) generation, targeted delivery, and biodegradation. Attempts employing polymer coatings to minimize the toxicity, along with other challenges, have had limited success. We designed a novel yet generic 'one-for-all' polypropylene sulphide (PPS) coated magnetic nano-delivery system (80 ± 15 nm) as a multi-faceted approach for significant biocompatibility improvement, loading of multiple drugs, ROS-responsive delivery, and combined chemo-hyperthermia therapy for biomedical applications. Three distinct MNP systems (15 ± 1 nm) were fabricated, coated with PPS polymer, and investigated to validate our hypothesis and design. Simultaneous degradation of MNPs and PPS coatings with ROS-scavenging characteristics boosted the biocompatibility of MNPs 2-3 times towards non-cancerous fibroblasts (NIH3T3) and human epithelial cells (HEK293). In an alternating magnetic field, PPS-MNPs (MnFe) had the strongest heating characteristics (SAR value of 240 W g-1). PPS-MNP drug-loaded NPs were efficiently internalised into cells and released 80% of the drugs under tumor microenvironment-mimicking (pH 5-7, ROS) conditions, and demonstrated effective chemo-hyperthermia (45 °C) application for breast cancer cells with 95% cell death in combined treatment vs. 55% and 30% cell death in only hyperthermia and chemotherapy respectively.

Development of handheld induction heaters for magnetic fluid hyperthermia applications andin-vitroevaluation on ovarian and prostate cancer cell lines.

Objective:Magnetic fluid hyperthermia (MFH) is a still experimental technique found to have a potential application in the treatment of cancer. The method aims to reach around 41 °C-47 °C in the tumor site by exciting magnetic nanoparticles with an externally applied alternating magnetic field (AMF), where cell death is expected to occur. Applying AMFs with high spatial resolution is still a challenge. The AMFs from current and prospective MFH applicators cover relatively large areas; being not suitable for patients having metallic implants near the treatment area. Thus, there will be a clinical need for smaller magnetic field applicators. To this end, a laparoscopic induction heater (LIH) and a transrectal induction heater (TRIH) were developed.Methods:Miniature 'pancake' coils were wound and inserted into 3D printed enclosures. Ovarian (SKOV-3, A2780) and prostate (PC-3, LNCaP) cancer cell lines were used to evaluate the instruments' capabilities in killing cancer cellsin vitro, using Synomag®-D nanoparticles as the heat mediators. NIH3T3 normal cell lines were also used with both devices to observe if these cells tolerated the conditions applied.Results:Magnetic field intensities reached by the LIH and TRIH were 42.6 kA m-1at 326 kHz and 26.3 kA m-1at 303 kHz, respectively. Temperatures reached in the samples were 41 °C by the LIH and 43 °C by the TRIH. Both instruments successfully accomplished killing cancer cells, with minimal effects on normal cells.Conclusion:This work presents the first line of handheld medical induction heaters and have the potential to be a complement to existing cancer therapies.Significance:These instruments could enable the development of MFH modalities that will facilitate the clinical translation of this thermal treatment.

Polyetherimide- and folic acid-modified Fe3 O4 nanospheres for enhanced magnetic hyperthermia performance.

Recent studies have highlighted the development prospects of magnetic hyperthermia in cancer therapy. A few studies on the application of Fe3 O4 nanospheres for the magnetic hyperthermia of gynecological malignancies have achieved certain efficacy, but there was no visible progress currently. In this work, Fe3 O4 nanospheres modified with polyetherimide (PEI) and folic acid (FA) were synthesized using a hydrothermal method for possible utility in biocompatible and active tumor-targeting magnetic induction hyperthermia. The PEI- and FA-coated Fe3 O4 nanospheres showed high crystallinity, well-dispersed spherical structures and ideal Ms value. As a result, the designed Fe3 O4 @ PEI@FA nanospheres achieved higher specific absorption rate (SAR) values at 360 kHz and 308 Oe, as well as excellent biocompatibility in Hela, SKOV3, HEC-1-A and NIH3T3 cells. These nanospheres can be used as an optimal heating agent for the magnetic hyperthermia treatment of gynecological cancers.

UHPLC-MS/MS Studies and Antiproliferative Effects in Breast Cancer Cells of Mexican Sargassum.

BACKGROUND: Sargassum is a marine organism that, under specific conditions, drastically increases its population damaging the environment and risking other organisms. However, sargassum could represent a source of bioactive compounds to treat different diseases such as cancer. Thus, aqueous, ethanolic, and ethyl acetate extracts of sargassum from Playa del Carmen, Mexico, were subjected to metabolomic and antiproliferative assays in breast cancer cells. OBJECTIVE: To evaluate the biological effect of different extracts of sargassum, its toxicity over Artemia salina and its antiproliferative effect tested in MCF-7, MDA-MB-231, and NIH3T3 cell lines. Finally, using UHPLC-MS/MS to identify the metabolites in each extract to correlate them with its antiproliferative effect. METHODS: The sargassum sample collection was carried out in September at three different points in Playa del Carmen, Quintana Roo, Mexico. The aqueous, ethanolic, and ethyl acetate extracts of Mexican sargassum were obtained by evaporation of solvent and lyophilization. Then, these extracts were evaluated in the cytotoxicity bioassay of Artemia salina. Next, its antiproliferative effect was assessed in MCF-7, MDA-MB-231, and NIH3T3 cell lines. Using UHPLC-MS/MS, the metabolites present in each extract were identified. Finally, docking studies on sphingosine kinase 1 (PDB ID: 3VZB) of sphingosine were carried out. RESULTS: The extracts from sargassum showed a greater effect in the antiproliferative assays in cells than in cytotoxic assays in Artemia salina. The ethanolic extract obtained from sargassum showed the best antiproliferative activity in MCF7 and MDA-MB-231 cells. Despite its antiproliferative effect on NIH3T3 cells, an additional extract is required indicating that this extract has compounds that could have a better effect on cancer cells in fibroblast (NIH3T3). The UHPLC-MS/MS of ethanolic and the ethyl acetate extract showed that these extracts have compounds such as sphinganine C16, N, N-Dimethylsphingosine compound, and that it could be possible that the effect observed is due to their metabolites which could be ligands for the sphingosine kinase 1 as demonstrated by docking studies. CONCLUSION: The ethanolic extract obtained from sargassum has better antiproliferative activity, despite not having a cytotoxic effect in Artemia salina. The antiproliferative effect could be related to the sphinganine C16, N,NDimethylphingosine identified with more abundance by UHPLC-MS/MS. In addition, these metabolites could be targets of sphingosine kinase 1.

Curcumin encapsulated polylactic acid nanoparticles embedded in alginate/gelatin bioinks for in situ immunoregulation: Characterization and biological assessment.

Curcumin is a known naturally occurring anti-inflammatory agent derived from turmeric, and it is commonly used as a herbal food supplement. Here, in order to overcome the inherent hydrophobicity of curcumin (Cur), polylactic acid (PLA) nanoparticles (NPs) were synthesised using a solvent evaporation, and an oil-in-water emulsion method used to encapsulate curcumin. Polymeric NPs also offer the ability to control rate of drug release. The newly synthesised NPs were analysed using a scanning electron microscope (SEM), where results show the NPs range from 50 to 250 nm. NPs containing graded amounts of curcumin (0 %, 0.5 %, and 2 %) were added to cultures of NIH3T3 fibroblast cells for cytotoxicity evaluation using the Alamar Blue assay. Then, the curcumin NPs were incorporated into an alginate/gelatin solution, prior to crosslinking using a calcium chloride solution (200 nM). These hydrogels were then characterised with respect to their chemical, mechanical and rheological properties. Following hydrogel optimization, hydrogels loaded with NP containing 2 % curcumin were selected as a candidate as a bioink for three-dimensional (3D) printing. The biological assessment for these bioinks/hydrogels were conducted using THP-1 cells, a human monocytic cell line. Cell viability and immunomodulation were evaluated using lactate dehydrogenase (LHD) and a tumour necrosis factor alpha (TNF-α) enzyme-linked immunosorbent (ELISA) assay, respectively. Results show that the hydrogels were cytocompatible and supressed the production of TNF-α. These bioactive hydrogels are printable, supress immune cell activation and inflammation showing immense potential for the fabrication of tissue engineering constructs.

Cytotoxic Activity of Polyphenol Extracts from Three Oregano Species: Hedeoma patens, Lippia graveolens and Lippia palmeri, and Antiproliferative Potential of Lippia graveolens against Two Types of Breast Cancer Cell Lines (MDA-MB-231 and MCF-7).

Oregano infusions have traditionally been used to treat some diseases related to inflammation and cancer; also, some species have shown antiproliferative activity on cancer cell lines, for example, colon and liver, and this has been attributed to its phytochemical profile, mainly its phenolic compounds. This study aimed to evaluate the cytotoxicity and antiproliferative potential of the polyphenols-rich extracts (PRE) of the oregano species H. patens, L. graveolens, and L. palmeri on breast cancer cell lines. The PRE of the three oregano species were obtained from dried leaves. The extract was characterized by determining antioxidant activity, total phenols content, and identifying the profile of phenolic acids and flavonoids by chromatography UPLC-MS/MS. Furthermore, the cytotoxicity of the extracts was evaluated in vitro on a non-cancer cell line of fibroblast NIH3T3 and the antiproliferative potential on the breast cancer cell lines MDA-MB-231 and MCF-7. L. graveolens showed the highest antioxidant capacity and significantly inhibited the proliferation of MCF-7 and MDA-MB-231 cells at non-cytotoxic concentrations in normal cells, with a similar effect to that cisplatin in MDA-MB-231 cells. Therefore, the polyphenol-rich extract from L. graveolens showed the greatest potential to guide future research on the antiproliferative mechanism of action.

An Innovative Customized Biomimetic Hydrogel for Drug Screening Application Potential: Biocompatibility and Cell Invasion Ability.

The ability of Pluronic F127 (PF127) conjugated with tetrapeptide Gly-Arg-Gly-Asp (GRGD) as a sequence of Arg-Gly-Asp (RGD) peptide to form the investigated potential hydrogel (hereafter referred to as 3DG bioformer (3BE)) to produce spheroid, biocompatibility, and cell invasion ability, was assessed in this study. The fibroblast cell line (NIH 3T3), osteoblast cell line (MG-63), and human breast cancer cell line (MCF-7) were cultured in the 3BE hydrogel and commercial product (Matrigel) for comparison. The morphology of spheroid formation was evaluated via optical microscopy. The cell viability was observed through cell counting Kit-8 assay, and cell invasion was investigated via Boyden chamber assay. Analytical results indicated that 3BE exhibited lower spheroid formation than Matrigel. However, the 3BE appeared biocompatible to NIH 3T3, MG-63, and MCF-7 cells. Moreover, cell invasion ability and cell survival rate after invasion through the 3BE was displayed to be comparable to Matrigel. Thus, these findings demonstrate that the 3BE hydrogel has a great potential as an alternative to a three-dimensional cell culture for drug screening applications.

AgVI and Ag/ZnOVI nanostructures from Vateria indica (L.) exert antioxidant, antidiabetic, anti-inflammatory and cytotoxic efficacy on triple negative breast cancer cells in vitro.

Human triple-negative breast cancer (TNBC) being an aggressive cancer type accounts for about 15-20% of global breast cancer cases. In the present study, the cytotoxicity of pure silver (AgVI) and silver/zinc oxide (Ag/ZnOVI) nanostructures was evaluated against the TNBC cells. The nanostructures synthesized from a green route using Vateria indica (L.) fruit extract were characterized to scrutinize their formation, crystal phase, size, shape, and surface properties via FTIR, PXRD, FE-SEM coupled with EDS spectroscopy, and BET analysis. The results of the studies have unveiled the formation of 26.43 nm and 20.97 nm sized AgVI and Ag/ZnOVI nanostructures in their purest form. The in-vitro anticancer study performed on human TNBC cells [MDA-MB468] revealed the enhancement in the antiproliferative potentiality of bimetallic Ag/ZnOVI nanostructures from 66.99 ± 0.13 to 79.73 ± 0.23 in comparison to pure AgVI nanostructures. In addition to this, the greenish yellow-fluorescence observed in the TNBC nuclei during the AO-EB staining study manifested the early apoptosis. Furthermore, the anti-inflammatory and cytotoxicity study performed on the human RBC and normal NIH3T3 murine fibroblasts cells proved the biocompatibility and non-toxic nature of the synthesized nanostructures with membrane stabilization percentage up to 94.5 ± 0.001. Additionally, the antioxidant and antidiabetic studies carried out have corroborated the radical scavenging and α-amylase inhibition capability up to 85.87 ± 0.001 and 89.60 ± 0.002 % respectively. Thus the overall results of the study substantiate the superlative antioxidant, antidiabetic, and antiproliferative property of green synthesized AgVI and Ag/ZnOVI nanostructures with excellent biocompatibility.

Wound healing, anti-inflammatory and anti-melanogenic activities of ursane-type triterpenes from Semialarium mexicanum (Miers) Mennega.

ETHNO-PHARMACOLOGICAL RELEVANCE: The bark of Semialarium mexicanum commonly known as 'Cancerina' is used as an infusion in Central America and Mexico to treat various wound infections, as well as skin and vaginal ulcers. AIM OF THE STUDY: This study aimed to determine the wound healing, anti-inflammatory and anti-melanogenic activities of the aqueous extract of Semialarium mexicanum and to identify the compounds related to these activities. MATERIALS AND METHODS: A bio-guided isolation of the active compounds of Semialarium mexicanum was carried out, selecting the sub-extracts and fractions depending on their wound healing, anti-inflammatory and anti-melanogenic activities in the RAW 264.7, NIH/3T3 and B16-F10 cells. RESULTS: Three compounds were obtained and characterised by nuclear magnetic resonance and mass spectrometry. These compounds are (3ß)-3-Hydroxy-urs-12-en-28-oic acid (1), (3ß)-Urs-12-ene-3,28-diol (2) and (2α, 19α)-2,19-Dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Regarding the anti-inflammatory activity, the three compounds inhibited the production of NF-κB and NO, however, compound 3 was the most active with IC50 values of 8.15-8.19 µM and 8.94-9.14 µM, respectively, in all cell lines. The anti-melanogenic activity of these compounds was evaluated by the inhibition of tyrosinase and melanin in the B16-F10 cell line. The three compounds showed anti-melanogenic activity, however, compound 3 was the most active with an IC50 of 8.03 µM for the inhibition of tyrosinase production, and an IC50 of 8.53 µM for the inhibition of melanin production. Finally, concerning the wound healing activity, the three compounds presented proliferative activity in all the tested cell lines, however, compound 3 showed higher cell proliferation percentages than compounds 1 and 2 (88.89-89.60% compared to 64.92-65.71% and 71.53-71.99%, respectively). CONCLUSION: The wound healing, anti-inflammatory and anti-melanogenic activity of the aqueous extract of Semialarium mexicanum was tested and analysed in the present study, after having isolated three ursane-type triterpenes.