Myxoma Virus Combination Therapy Enhances Lenalidomide and Bortezomib Treatments for Multiple Myeloma.

This study aimed to explore the effectiveness and safety of Myxoma virus (MYXV) in MM cell lines and primary myeloma cells obtained from patients with multiple myeloma. Myeloma cells were isolated from MM patients and cultured. MYXV, lenalidomide, and bortezomib were used in MM cells. The cytotoxicity assay was investigated using WST-1. Apoptosis was assessed through flow cytometry with Annexin V/PI staining and caspase-9 concentrations using ELISA. To explore MYXV entry into MM cells, monoclonal antibodies were used. Moreover, to explore the mechanisms of MYXV entry into MM cells, we examined the level of GFP-labeled MYXV within the cells after blocking with monoclonal antibodies targeting BCMA, CD20, CD28, CD33, CD38, CD56, CD86, CD117, CD138, CD200, and CD307 in MM cells. The study demonstrated the effects of treating Myxoma virus with lenalidomide and bortezomib. The treatment resulted in reduced cell viability and increased caspase-9 expression. Only low-dose CD86 blockade showed a significant difference in MYXV entry into MM cells. The virus caused an increase in the rate of apoptosis in the cells, regardless of whether it was administered alone or in combination with drugs. The groups with the presence of the virus showed higher rates of early apoptosis. The Virus, Virus + Bortezomib, and Virus + Lenalidomide groups had significantly higher rates of early apoptosis (p < 0.001). However, the measurements of late apoptosis and necrosis showed variability. The addition of MYXV resulted in a statistically significant increase in early apoptosis in both newly diagnosed and refractory MM patients. Our results highlight that patient-based therapy should also be considered for the effective management of MM.

Validation of prognosis-based in vitro fertilization grant selection criteria.

Objective: To validate a prognosis-based scoring system for in vitro fertilization (IVF) grant allocation. Design: Retrospective cohort study. Setting: A 501(c)(3) nonprofit foundation that awards donated IVF cycles and grants to those with demonstrated financial need. In contrast to lottery-based or subjective allocation systems, applications are scored according to medical prognostic criteria in addition to personal characteristics. Patients: Grant recipients from 2015 to 2019. Interventions: None. Main outcome measures: Live birth rate (LBR) and cumulative LBR (CLBR) among grant recipients were compared with 2019 Society for Assisted Reproductive Technology (SART) national averages. Results: A total of 435 applications were reviewed, with 59 grants awarded for 51 autologous IVF cycles, 6 donor oocyte cycles, and 2 gestational carrier cycles, resulting in 39 live births after initial embryo transfer (LBR 61.9%) and 43 CLBRs (CLBR 72.9%). Among autologous cycles, the mean (±SD=3.9 years) age was 31.8 years, and LBR and CLBR were 62.8% and 68.6% vs. 28.2% and 37.1% among all autologous SART cycles, respectively. A subanalysis of grant recipients aged <35 years (n=39) revealed LBR and CLBR of 66.7% and 74.4% vs. 40.7% and 47.8% among autologous SART cycles aged <35 years, respectively. Conclusions: A scoring system incorporating medical criteria identified IVF grant applicants with a high likelihood of achieving a LB. Although most IVF grant programs select recipients through a lottery or personal characteristics, a prognosis-based scoring system should be considered to maximize LBR in a limited resource setting.

Understanding the effects of chitosan, chia mucilage, levan based composite coatings on the shelf life of sweet cherry.

Sweet cherry (Prunus avium L.) fruits are prone to quality and quantity loss in shelf-life conditions and cold storage due to their short post-harvest life. Until now efforts have been made to extend the shelf life of the sweet cherry. However, an efficient and commercially scalable process remains elusive. To contribute to this challenge, here in this study, biobased composite coatings consisting of chitosan, mucilage, and levan, were applied on sweet cherry fruits and tested for postharvest parameters in both market and cold storage conditions. Results demonstrated that the shelf life of sweet cherries can be extended until the 30th day while retaining important post-harvest properties like decreased weight loss, fungal deterioration, increased stem removal force, total flavonoid, l-ascorbic acid, and oxalic acid. Given the cost-effectiveness of the polymers used, the findings of this study indicate the feasibility of extending the shelf-life of sweet cherries on a larger scale.

Adsorption behavior of carboxy- and amine-terminated magnetic beads for patulin: Batch experiments in aqueous solution and apple juice.

Patulin (PAT) is a highly water soluble, heat resistant and toxic fungal metabolite mostly contaminating apple juice. Due to its serious health effects, its removal from foodstuffs is required to ensure food safety. In this study, carboxy- and amine-terminated iron oxide spheres (Fe3O4-COOH and Fe3O4-NH2) were investigated for their adsorbing capacity of PAT in both aqueous solution and apple juice, and evaluated for being an effective detoxifying agent for PAT. The physical and chemical properties of adsorbents were characterized by X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM). The maximum adsorption capacities Fe3O4-COOH and Fe3O4-NH2 for PAT obtained at 25 °C, pH 6 for 5 h were 0.206 mg/g and 0.104 mg/g, respectively. Best fitting adsorption isotherm and kinetics models of PAT adsorption process were Hill isotherm (Radj2 = 0.985) and pseudo-second kinetic models (Radj2 > 0.99) for carboxy groups and Langmuir isotherm (Radj2 = 0.974) and pseudo-second kinetic models (Radj2 > 0.99) for amine groups on the surface of adsorbents. These models with the experimental results confirmed the physical adsorption process, while thermodynamic analysis indicated that adsorption process was spontaneous and endothermic between PAT and both adsorbents. Reusability study showed the effective removal of PAT at four cycles by both adsorbents. This study indicated that carboxy- and amine-terminated magnetic spheres have promising potentials in PAT removal from both aqueous solution and apple juice without affecting quality parameters of juice.

A rapid responsive coumarin-naphthalene derivative for the detection of cyanide ions in cell culture.

Cyanide ion (CN-) is widely used in many industrial processes; however, it causes several diseases in humans. Therefore, rapid and accurate detection of CN- is very important and urgent. In this study, a CN- sensor (MH-2) which was capable of detecting CN- ions in living cell was developed. MH-2 gives a rapid color change, absorbance and fluorescence response to CN- in the presence of the anions tested in the working system. The binding ratio between the sensor and CN- was demonstrated by some spectrophotometric methods and the sensing mechanism was investigated by NMR titration experiments, suggesting that MH-2 gives response to CN- via the nucleophilic addition reaction. The fluorescence detection limit and the absorbance detection limit were calculated as 0.056 µM and 0.11 µM, respectively. Both of these detection limits are below the tolerable limit recommended by WHO for CN- in the drinking water (1.9 µM). MH-2 was also applied to living cells for bio-imaging and the results showed that the sensor penetrates the cells and can detect cyanide ions in living cells.

Release of nifedipine, furosemide, and niclosamide drugs from the biocompatible poly(HEMA) hydrogel structures.

The primary aim of this article was to improve the solubility and bioavailability of the drugs nifedipine, niclosamide, and furosemide due to their poor solubility and dissolution rate. Therefore, these drugs require improvement in solubility and dissolution rate in formulation development, especially in solid dosage forms such as hydrogels and capsules. Hydrogel structures were synthesized by using a biocompatible, nontoxic, and protective pure 2-hydroxy ethyl methacrylate (HEMA) monomer. These hydrogel structures were characterized by various techniques such as scanning electron microscopy and Fourier-transformed infrared spectroscopy. In the next step, drug molecules were loaded in the poly (HEMA) hydrogels. Drug releases of drug-loaded hydrogel structures were measured at certain time intervals and recorded cumulatively (%). The pH affinity, morphology, structure, drug release, swelling, and cytotoxic effect of the resulting materials were studied in detail. In addition to investigating the biocompatibility and cytotoxicity of the poly (HEMA) hydrogel, we evaluated an in vitro cytotoxicity assay on MCF-7and MIA PaCa-2 and HEK 293 cell lines with the hydrogel structure and confirmed cell viability of over 85%. These results suggest that our HEMA polymeric hydrogel is a material with biological importance and great pharmacological potential as a supporting material in the drug release of nifedipine, furosemide, niclosamide, and similar drug molecules.

Understanding the effects of copolymerized cellulose nanofibers and diatomite nanocomposite on blend chitosan films.

Chitosan films lack various important physicochemical properties and need to be supplemented with reinforcing agents to bridge the gap. Herein, we have produced chitosan composite films supplemented with copolymerized (with polyacrylonitrile monomers) cellulose nanofibers and diatomite nanocomposite at different concentrations. The incorporation of CNFs and diatomite enhanced the physicochemical properties of the films. The mechanical characteristics and hydrophobicity of the films were observed to be improved after incorporating the copolymerized CNFs/diatomite composite at different concentrations (CNFs: 1%, 2% and 5%; diatomite: 10% and 30%). The antioxidant activity gradually increased with an increasing concentration (1-5% and 10-30%) of copolymerized CNFs/diatomite composite in the chitosan matrix. Moreover, the water solubility decreased from 30% for chitosan control film (CH-0) to 21.06% for films containing 30% diatomite and 5% CNFs (CNFs-D30-5). The scanning electron micrographs showed an overall uniform distribution of copolymerized CNFs/diatomite composite in the chitosan matrix with punctual agglomerations.

A novel signal to image transformation and feature level fusion for multimodal emotion recognition.

Emotion is one of the most complex and difficult expression to be predicted. Nowadays, many recognition systems that use classification methods have focused on different types of emotion recognition problems. In this paper, we aimed to propose a multimodal fusion method between electroencephalography (EEG) and electrooculography (EOG) signals for emotion recognition. Therefore, before the feature extraction stage, we applied different angle-amplitude transformations to EEG-EOG signals. These transformations take arbitrary time domain signals and convert them two-dimensional images named as Angle-Amplitude Graph (AAG). Then, we extracted image-based features using a scale invariant feature transform method, fused these features originates basically from EEG-EOG and lastly classified with support vector machines. To verify the validity of these proposed methods, we performed experiments on the multimodal DEAP dataset which is a benchmark dataset widely used for emotion analysis with physiological signals. In the experiments, we applied the proposed emotion recognition procedures on the arousal-valence dimensions. We achieved (91.53%) accuracy for the arousal space and (90.31%) for the valence space after fusion. Experimental results showed that the combination of AAG image features belonging to EEG-EOG signals in the baseline angle amplitude transformation approaches enhanced the classification performance on the DEAP dataset.

Antibacterial, thermal decomposition and in vitro time release studies of chloramphenicol from novel PLA and PVA nanofiber mats.

The present investigation is the first report containing design and synthesis of novel calixarene derivatives (6-8) and their inclusion complexes (IC6-IC8) with Chloramphenicol (CAM). After synthesis, the antibiotic CAM, calixarene derivatives (6-8) and their inclusion complexes (IC6-IC8) were successfully incorporated into biodegradable PVA and/or PLA nanofiber skeleton by electrospinning. The obtained electrospun nanofibers were tested and compared for inhibition of bacterial growth towards multiple bacterial species (Escherichia coli, and Bacillus subtilis). Moreover, we evaluated thermal decomposition and release profile of CAM by spectrophotometric methods. The results suggested that CAM can be successfully encapsulated in nanofiber webs by inclusion complexation, and these fibers could be used as a part of new controlled release packaging system for food preservation.

Novel integrated sensing system of calixarene and rhodamine molecules for selective colorimetric and fluorometric detection of Hg2+ ions in living cells.

Three novel and facile calixarene derivatives (5, 6 and 7), which were appended with four rhodamine units at the upper rim of calixarene skeleton, were firstly prepared and evaluated for selective detection of metal ions in solution. Receptors (5) and (7) indicated immediate turn on fluorescence output toward Hg2+ ions over other most competitive metal ions with the ultralow detection limits, indicating their high efficiency and reliability. The binding response to Hg2+ ions in solution was also observed through a chromogenic change (from colorless to pale pink). Furthermore, in vitro and bio-imaging studies with MCF-7 or MIA PaCa-2 cell lines were also performed to investigate the use of receptors in biological systems in order to monitor of mercury ions. Results showed that new receptors (5) or (7) were cell permeable and suitable for real-time imaging of Hg2+ in living cells (MCF-7) or (MIA PaCa-2) without any damage to healthy cell lines (HEK 293).

Natural ß-chitin-protein complex film obtained from waste razor shells for transdermal capsaicin carrier.

In the literature, the produced ß-chitin samples are in powder or flake forms but there is no natural ß-chitin based film. Also, the commercially available transdermal patches are produced from synthetic polymers. In this regard, we produced natural ß-chitin-protein complex (CPC) film from the waste shells of Ensis spp. The obtained natural film was characterized by FTIR, TGA and SEM. Additionally, swelling, thickness, contact angle and antioxidant tests were done to learn more about the films. After production and characterization of the film, capsaicin, which is commonly used for pain relief was loaded into the film. The loading capacity was recorded as 5.79%. The kinetic models were studied in three different pH, then the results were fitted with Higuchi model with high correlation at pH 7.4. After considering all the obtained results, the capsaicin loaded CPC film may be an alternative candidate for transdermal patch instead of the synthetic ones.

GATA2 and Progesterone Receptor Interaction in Endometrial Stromal Cells Undergoing Decidualization.

The transcription factor GATA2 is important for endometrial stromal cell decidualization in early pregnancy. Progesterone receptor (PGR) is also critical during decidualization but its interaction with GATA2 in regulating genes and pathways necessary for decidualization in human endometrium are unclear. RNA-sequencing (RNA-seq) was performed to compare gene expression profiles (n = 3), and chromatin immunoprecipitation followed by sequencing (ChIP-seq) using an antibody against GATA2 (n = 2) was performed to examine binding to target genes in human endometrial stromal cells undergoing in vitro decidualization (IVD including estrogen, progestin, and 3',5'-cyclic AMP analogue) or vehicle treatment. We identified 1232 differentially expressed genes (DEGs) in IVD vs vehicle. GATA2 cistrome in IVD-treated cells was enriched with motifs for GATA, ATF, and JUN, and gene ontology analysis of GATA2 cistrome revealed pathways that regulate cholesterol storage, p38 mitogen-activated protein kinase, and the c-Jun N-terminal kinase cascades. Integration of RNA-seq and ChIP-seq data revealed that the PGR motif is highly enriched at GATA2 binding regions surrounding upregulated genes in IVD-treated cells. The integration of a mined public PGR cistrome in IVD-treated human endometrial cells with our GATA2 cistrome showed that GATA2 binding was significantly enhanced at PGR-binding regions in IVD vs vehicle. Interrogating 2 separate ChIP-seq data sets together with RNA-seq revealed integration of GATA2 and PGR action to coregulate biologic processes during decidualization of human endometrial stromal cells, specifically via WNT activation and stem cell differentiation pathways. These findings reveal the key pathways that are coactivated by GATA2 and PGR that may be therapeutic targets for supporting implantation and early pregnancy.

Recovery and Reusability of ApoUnaG Fluorescence Protein from the Unconjugated Bilirubin Complex Structure.

This study is the first report on the separation and reusability of ApoUnaG protein, indicating excellent fluorescence response with high affinity and specificity toward unconjugated bilirubin (UC-BR) molecules, from the UnaG-UC-BR complex structure. The fluorescence properties of the UnaG-UC-BR complex (holo-UnaG) are studied by addition of different metal ions to perform possible interactions with holo-UnaG through absorbance and emission spectra. After addition of metal ions, some changes with respect to the type of metal ions are observed in fluorescence intensity of the holo-UnaG. When compared to metal ions, an excellent quenching response is sighted in the presence of Cu2+ ions by binding with UC-BR in the UnaG-UC-BR complex structure. Obtained non-fluorescence holo-UnaG-Cu2+ complex mixture is passed through Ni-NTA agarose to remove the ingredients such as Cu2+, UC-BR and Cu2+-UC-BR coordination complex from holo-UnaG. From the obtained experiments, it is concluded that Cu2+ ion can be used as an agent for the recovery of ApoUnaG protein via binding with UC-BR molecules. Graphical Abstract Recovery and Reusability of ApoUnaG Fluorescence Protein from the Unconjugated Bilirubin Complex Structure.

Use of sea urchin spines with chitosan gel for biodegradable film production.

In recent years, the film production from natural polymers has considerably increased in food industry as an alternative to the petroleum based synthetic films. Chitosan is one of the most preferred biopolymers for bio-based film production, due to its biocompatibility, biodegradability, antioxidant activity and antimicrobial properties. Because of its hydrophilic properties, chitosan based films dissolve in water, limiting its uses in industry, to overcome this problem; we mixed 200 and 400 mg of the sea urchin spine powder (SUSP) with 20 mL chitosan gel respectively, to obtain a hydrophobic film. The chitosan films prepared with 200 mg SUSP showed a rise in the degree of contact angle from 70.2° to 107° providing hydrophobicity properties. On the other hand, addition of 400 mg of SUSP to chitosan film resulted in a contact angle of 96.1°. Moreover, the antioxidant activity and thermal stability of the films were increased in the presence of SUSP. Fourier Transform Infrared Spectrophotometry results proved the interactions between chitosan and SUSP. Chitosan films have smooth surface while SUSP blended films have rough surface morphology. These results demonstrated that SUSP is needed to improve the properties of chitosan films for usage in food industry.

Genome-wide estrogen receptor-α binding and action in human endometrial stromal cells.

OBJECTIVE: To investigate the gene targets of estradiol (E2)-estrogen receptor-α (ESR1) in human endometrial stromal cells. DESIGN: Basic science. SETTING: University research center. PATIENT(S): Premenopausal women with or without endometriosis. INTERVENTION(S): Primary cultures of human endometrial stromal cells from healthy endometrium, with or without small-interfering RNA (siRNA) knockdown of ESR1 expression, were treated with E2 or vehicle control. MAIN OUTCOME MEASURE(S): Genome-wide RNA expression by RNA sequencing was compared in endometrial stromal cells with or without siRNA knockdown of ESR1 in the presence or absence of E2. Genome-wide recruitment of ESR1 to chromatin was assessed by chromatin immunoprecipitation sequencing. Gene expression by real-time qualitative polymerase chain reaction of a potential E2-ESR1 target gene was determined in endometrial stromal cells and endometriotic stromal cells. RESULT(S): We identified several important pathways that are dependent on E2-ESR1 signaling in endometrial stromal cells, including progesterone signaling, cell-matrix adhesion, and cytoskeleton rearrangement, as well as paracrine signaling by members of the fibroblast growth factor family. We detected a total of 709 ESR1 target sites on chromatin. By integrating data on genome-wide transcriptomic changes and E2-ESR1 binding sites, we identified inositol polyphosphate phosphatase type II (INPP4B) as a candidate E2-mediated suppressor of proliferation in healthy endometrial cells. INPP4B was downregulated in endometriosis-derived stromal cells. CONCLUSION(S): E2-ESR1 activates genes involved in human endometrial stromal cell cycle regulation, progesterone response, and production of stromal growth factors. Understanding the direct role of estrogen on the endometrial stroma and identifying downstream targets of E2-ESR1 can inform the development of targeted therapies for endometriosis and diminished endometrial receptivity.

Correction to: An Application of a Schiff-Base Type Reaction in the Synthesis of a New Rhodamine-Based Hg(II)-Sensing Agent.

The original version of this article unfortunately contained a mistake. The presentation of Scheme 1 was incorrect as the word "modifified" should be written as "modified" and the abbreviation "CS-F" should be replaced by "AA-AR".

Diversity in a signal-to-image transformation approach for EEG-based motor imagery task classification.

Nowadays, motor imagery-based brain-computer interfaces (BCIs) have been developed rapidly. In these systems, electroencephalogram (EEG) signals are recorded when a subject is involved in the imagination of doing any motor imagery movement like the imagination of the right/left hands, etc. In this paper, we sought to validate and enhance our previously proposed angle-amplitude transformation (AAT) technique, which is a simple signal-to-image transformation approach for the classification of EEG and MEG signals. For this purpose, we diversified our previous method and proposed four new angle-amplitude graph (AAG) representation methods for AAT transformation. These modifications were made on some points such as using different left/right side changing points at a different distance. To confirm the validity of the proposed methods, we performed experiments on the BCI Competition III Dataset IIIa, which is a benchmark dataset widely used for EEG-based multi-class motor imagery tasks. The procedure of proposed methods can be summarized in a concise manner as follows: (i) convert EEG signals to AAG images by using the proposed AAT transformation approaches; (ii) extract image features by employing Scale Invariant Feature Transform (SIFT)-based Bag of Visual Word (BoW); and (iii) classify features with k-Nearest Neighbor (k NN) algorithm. Experimental results showed that the changes in the baseline AAT approaches enhanced the classification performance on Dataset IIIa with an accuracy of 96.50% for two-class problem (left/right hand movement imaginations) and 97.99% for four-class problem (left/right hand, foot and tongue movement imaginations). These achievements are mainly due to the help of effective enhancements on AAG image representations. Graphical Abstract The flow diagram of the proposed methodology.

Evaluation of Anticancer Activities of Novel Facile Synthesized Calix[n]arene Sulfonamide Analogs.

Here, new calixarene sulfonamide analogs were synthesized from the reaction of chlorosulfonated calix[n]arene (n: 4, 6, and 8) with N,N'-dimethylethylenediamine or ethylenediamine for the first time and an excellent calixarene sulfonamide analog showing potent and selective cytotoxic activity on some cancer cell lines were discovered. Cytotoxicity of the prepared calix[n]arene sulfonamide analogs towards both cancer and healthy cell lines was assessed by performing cell growth inhibition assays. In cytotoxicity assay results, it was observed that while sulfonamide analog based calix[4]arene (9) was not affecting the growth of epithelial cell lines (HEK), and it was especially effective on inhibiting the growth of some human cancer cell lines (MCF-7 and MIA PaCa-2). These results highlight that sulfonamide analog-based calix [4] arene (9) can be further studied as a potential anticancer agent.

An Application of a Schiff-Base Type Reaction in the Synthesis of a New Rhodamine-Based Hg(II)-Sensing Agent.

A facile synthesis procedure, whereby 9-Anthraldehyde (AA) is coupled to aminated rhodamine (AR) via a Schiff base-type reaction, is reported. The applicability and performance of the obtained material (AA-AR) as a sensing agent was studied towards 16 metal cations (i.e. Li+, Na+, Ag+, Ca2+, Ba2+, Co2+, Cs+, Cu2+, Mg2+, Hg2+, Mn2+, Pb2+, Ni2+, Sr2+, Zn2+, Al3+). Among the studied metals, an extraordinary selectivity was observed for Hg2+, and the observed selectivity was found not to be influenced by the presence of other cations and some common anions (i.e. Br-, Cl-, I-, HPO42-, H2PO4-, NO3-, NO2-, ClO4-, AcO-, HSO4-, SO42-, Cr2O7-, CO32-, OH- and HCO3-). The material, AA-AR, exhibited such a high selectivity and sensitivity towards Hg2+ that it could be detected even by naked eyes. The Hg2+-sensing property of AA-AR was found not to be limited to colorimetric detections so that a high fluorescent nature of the compound was also observed upon binding Hg2+ ion. The detection limit, which is correspondent to fluorescence emission intensity, was found as 0.87 µM. The underlying mechanism of sensing property was studied by using some spectroscopic techniques such as FT-IR, 1H-NMR, 13C-NMR, and UV-Vis. (Job-plot). In the final course of the experiments, the performance of AA-AR in cell-imaging was also studied, and even trace amounts of Hg2+ in living cells could be detected by the studied probe. Thus, the applicability of a new synthesis approach in producing a highly efficient new fluorescence sensor for the detection of Hg2+ ions is discussed in detail.