Search

A new series of 1-(acyl/aroyl)-3-(ciprofloxacinyl) thioureas (5a–o) was synthesized by the reaction of ciprofloxacin (4) in dry acetone with acyl isothiocyanate intermediate (3). The synthesized compounds were characterized by FT-IR, 1H-NMR, and 13C-NMR. Furthermore, the synthesized compounds were tested for inhibitory potential against carbonic anhydrase (CA-II) and 15 lipoxygenase (LOX) enzymes. The tested compounds exhibited maximum inhibition of CA-11 with moderate anti-inflammatory potential, at the same concentration, i.e. 100 µM, therefore, can be considered as the selective inhibitors of CA-II. Among the tested derivatives 5g showed remarkable inhibitory activity against CA enzyme with IC50 value of 0.97 ± 0.11 µM and this derivative exhibited approximately 40% inhibition of 15-LOX, indicating that compound has moderate anti-inflammatory properties. The molecular docking studies, density functional theory (DFT) calculations, and molecular dynamic (MD) simulation studies were performed to evaluate their binding affinities, stability, and chemical reactivity within the active pocket of the targeted enzymes. The docking analysis and MD simulation studies revealed that the most active inhibitor 5g showed important interactions within the binding pockets of CA-II and may be responsible for the inhibitory activity of the compound toward the targeted enzymes. Therefore, the screened derivatives provided an outstanding platform for further development of CA inhibitors.

Safiah Alhazmi,1 Maryam Alzahrani,1 Reem Farsi,1 Mona Alharbi,1 Khloud Algothmi,1 Najla Alburae,1 Magdah Ganash,1 Sheren Azhari,1 Fatemah Basingab,1 Asma Almuhammadi,1 Amany Alqosaibi,2 Heba Alkhatabi,3,4 Aisha Elaimi,3,4 Mohammed Jan,5 Hesham M Aldhalaan,6 Aziza Alrafiah,4 Aisha Alrofaidi1 1Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Biology, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia; 3Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Medical Laboratory Science, King Abdulaziz University, Jeddah, Saudi Arabia; 5College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 6Center for Autism Research at King Faisal Specialist Hospital & Research Center, Riyadh, Saudi ArabiaCorrespondence: Aziza Alrafiah, Department of Medical Laboratory Science, King Abdulaziz University, P.O Box 80200, Jeddah, 21589, Saudi Arabia, Tel +966 126401000 Ext. 23495, Fax +966 126401000 Ext. 21686, Email aalrafiah@kau.edu.saIntroduction: Autism spectrum disorder (ASD) is a developmental disorder that can cause substantial social, communication, and behavioral challenges. Genetic factors play a significant role in ASD, where the risk of ASD has been increased for unclear reasons. Twin studies have shown important evidence of both genetic and environmental contributions in ASD, where the level of contribution of these factors has not been proven yet. It has been suggested that copy number variation (CNV) duplication and the deletion of many genes in chromosome 22 (Ch22) may have a strong association with ASD. This study screened the CNVs in Ch22 in autistic Saudi children and assessed the candidate gene in the CNVs region of Ch22 that is most associated with ASD.Methods: This study included 15 autistic Saudi children as well as 4 healthy children as controls; DNA was extracted from samples and analyzed using array comparative genomic hybridization (aCGH) and DNA sequencing.Results: The aCGH detected (in only 6 autistic samples) deletion and duplication in many regions of Ch22, including some critical genes. Moreover, DNA sequencing determined a genetic mutation in the TBX1 gene sequence in autistic samples. This study, carried out using aCGH, found that six autistic patients had CNVs in Ch22, and DNA sequencing revealed mutations in the TBX1 gene in autistic samples but none in the control.Conclusion: CNV deletion and the duplication of the TBX1 gene could be related to ASD; therefore, this gene needs more analysis in terms of expression levels.Keywords: autism spectrum disorder, chromosome 22, copy number variations, Saudi autistic children, TBX1

Alpha-1-Acid glycoprotein 2 (AGP2) or orosomucoid 2 (ORM2) is a major plasma protein. AGP2 is a member of the immunocalin family, a lipocalin subfamily expressed mainly in hepatocytes and also in astrocytes and endothelial cells. The detailed physiological role of this protein has not yet been known, but some physiological activates have been related to this protein, including drug binding and immunomodulating effects. As it belongs to the positive acute phase proteins (APP), AGP2 increases during acute phase reactions and under certain pathological conditions such as unspecific inflammatory stimulation. AGP2 play a critical role in many diseases throughout its critical biological pathways. This literature review evaluates and discusses the contribution of AGP2 in different diseases, including several types of cancer, Rheumatoid Arthritis and Coronavirus Disease 2019 (COVID-19).

Algothmi K, Alqurashi A, Alrofaidi A, et al. Pharmgenomics Pers Med. 2022;15:131–142. The authors have advised affiliation 4 on page 131 is incorrect. The correct affiliation should read “Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia”. The authors apologize for this error.

Urinary tract infection is among the greatest prevalent infections, and it is also one of the most challenging diseases to treat because there are germs that are resistant to several drugs. Antibiotics are typically provided as the treatment; however, there is a disparity in the type of antibiotic that was being prescribed, the amount of the dosage, and the length of time that patients were required to take antibiotics, which led to the creation of multidrug-resistant infections. The objective of this research is to prescribe Fosfomycin treatment for the infection brought by the Escherichia coli bacterium and to determine whether or not it is effective. Throughout the course of this research, the antimicrobial drugs fosfomycin were factored in the equation at various points. The patients who had exhibited symptoms of urinary tract infection provided their urine for the purpose of giving a sample for the studies, which were carried out on them. The results of these studies showed that there were Fosfomycin antimicrobials that were successful in disrupting the E. coli bacteria, and the least inhibitory concentration (MIC) required for the pathogen to be vulnerable was quite low. In addition, administration of fosfomycin intravenously considerably lowers both the bacterial load and the inflammatory infiltration in the kidney and bladder, which helps to preserve the structural integrity of the kidney.

Khloud Algothmi,1 Amal Alqurashi,1 Aisha Alrofaidi,1 Mona Alharbi,1 Reem Farsi,1 Najla Alburae,1 Magdah Ganash,1 Sheren Azhari,1 Fatemah Basingab,1 Asma Almuhammadi,1 Amany Alqosaibi,2 Heba Alkhatabi,3,4 Aisha Elaimi,3,4 Mohammed Jan,5 Hesham Aldhalaan,6 Aziza Alrafiah,4 Safiah Alhazmi1 1Biological Sciences Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Biology, College of Science, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; 3King Abdulaziz University, Centre of Excellence in Genomic Medicine Research, Jeddah, Saudi Arabia; 4Medical LaboratorySciencesDepartment,Faculty of Applied Medical Sciences, Jeddah, Saudi Arabia; 5College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 6Center for Autism Research at King Faisal Specialist Hospital & Research Center (KFSH & RC), Riyadh, Saudi ArabiaCorrespondence: Aziza Alrafiah, P.O Box 80200, Jeddah, 21589, Saudi Arabia, Tel +966 126401000 Ext. 23495, Fax +966 126401000 Ext. 21686, Email aalrafiah@kau.edu.saBackground: DNA methylation (DNAm) is one of the main epigenetic mechanisms that affects gene expression without changing the underlying DNA sequence. Aberrant DNAm has an implication in different human diseases such as cancer, schizophrenia, and autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder that affects behavior, learning, and communication skills. Acyl-CoA synthetase family member 3 (ACSF3) encodes malonyl-CoA synthetase that is involved in the synthesis and oxidation of fatty acids. The dysregulation in such gene has been reported in combined malonic and methylmalonic aciduria associated with neurological symptoms such as memory problems, psychiatric diseases, and/or cognitive decline. This research aims to study DNAm in the transcription factor (TF) binding site of ACSF3 in Saudi autistic children. To determine whether the DNAm of the TF-binding site is a cause or a consequence of transcription regulation of ACSF3.Methods: RT-qPCR and DNA methylight qPCR were used to determine the expression and DNAm level in the promoter region of ACSF3, respectively. DNA and RNA were extracted from 19 cases of ASD children and 18 control samples from their healthy siblings.Results: The results showed a significant correlation between the gene expression of ACSF3 and specificity protein 1 (SP1) in 17 samples of ASD patients, where both genes were upregulated in 9 samples and downregulated in 8 samples.Conclusion: Although this study found no DNAm in the binding site of SP1 within the ACSF3 promoter, the indicated correlation highlights a possible role of ACSF3 and SP1 in ASD patients.Keywords: autism, DNA methylation, SP1, ACSF3, Saudi autistic children, DNAm

DNA methylation (DNAm) is one of the main epigenetic mechanisms that affects gene expression without changing the underlying DNA sequence. Aberrant DNAm has an implication in different human diseases such as cancer, schizophrenia, and autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder that affects behavior, learning, and communication skills. Acyl-CoA synthetase family member 3 (RT-qPCR and DNA methylight qPCR were used to determine the expression and DNAm level in the promoter region ofThe results showed a significant correlation between the gene expression ofAlthough this study found no DNAm in the binding site of

Urease is an amidohydrolase enzyme that is responsible for fatal morbidities in the human body, such as catheter encrustation, encephalopathy, peptic ulcers, hepatic coma, kidney stone formation, and many others. In recent years, scientists have devoted considerable efforts to the quest for efficient urease inhibitors. In the pharmaceutical chemistry, the thiourea skeleton plays a vital role. Thus, the present work focused on the development and discovery of novel urease inhibitors and reported the synthesis of a set of 1-aroyl-3-[3-chloro-2-methylphenyl] thiourea hybrids with aliphatic and aromatic side chains 4a–j. The compounds were characterized by different analytical techniques including FT-IR, 1H-NMR, and 13C-NMR, and were evaluated for in-vitro enzyme inhibitory activity against jack bean urease (JBU), where they were found to be potent anti-urease inhibitors and the inhibitory activity IC50 was found in the range of 0.0019 ± 0.0011 to 0.0532 ± 0.9951 μM as compared to the standard thiourea (IC50 = 4.7455 ± 0.0545 μM). Other studies included density functional theory (DFT), antioxidant radical scavenging assay, physicochemical properties (ADMET properties), molecular docking and molecular dynamics simulations. All compounds were found to be more active than the standard, with compound 4i exhibiting the greatest JBU enzyme inhibition (IC50 value of 0.0019 ± 0.0011 µM). The kinetics of enzyme inhibition revealed that compound 4i exhibited non-competitive inhibition with a Ki value of 0.0003 µM. The correlation between DFT experiments with a modest HOMO-LUMO energy gap and biological data was optimal. These recently identified urease enzyme inhibitors may serve as a starting point for future research and development.

Exosomes are small nanovesicles that carry bioactive molecules which can be delivered to neighbouring cells to modify their biological functions. Studies have showed that exosomes from ovarian cancer (OVCA) cells can alter the cell migration and proliferation of cells within the tumour microenvironment, an effect modulated by the invasiveness capacity of their originating cells. Using an OVCA cell line xenograph mouse model, we showed that exosomes derived from a high invasiveness capacity cell line (exo-SKOV-3) promoted metastasis in vivo compared with exosomes from a low invasiveness capacity cell line (exo-OVCAR-3). Analysis from anin vivo imaging system (IVIS) revealed that exo-SKOV-3 formed metastatic niches, whereas exo-OVCAR-3 formed colonies of clustered cells close to the site of injection. Interestingly, kinetic parameters showed that the half-maximal stimulatory time (ST50) of tumour growth with exo-OVCAR-3 (4.0 ± 0.31 weeks) was significantly lower compared with the ST50 in mice injected with exo-SKOV-3 (4.5 ± 0.32 weeks). However, the number of metastic nodes in mice injected with exo-SKOV-3 was higher compared with exo-OVCAR-3. Using a quantitative mass spectrometry approach (SWATH MS/MS) followed by bioinformatics analysis using the Ingenuity Pathway Analysis (IPA), we identified a total of 771 proteins. Furthermore, 40 of these proteins were differentially expressed in tumour tissues from mice injected with exo-SKOV-3 compared with exo-OVCAR-3, and associated with Wnt canonical pathway (β-catenin). Finally, we identified a set of proteins which had elevated expression in the circulating exosomes in association with tumour metastasis. These observations suggest that exosomal signalling plays an important role in OVCA metastasis.

Onions contain high antioxidants compounds that fight inflammation against many diseases. The purpose was to investigate some selected bioactive activities of onion varieties (Yellow, Red, Green, Leek, and Baby). Antioxidant assays and anti-inflammatory activities such as NO production with the addition of some bioactive components were determined and analyzed by using a spectrophotometer. Gas chromatography and mass spectrometry (GC–MS) was used for the volatile compounds, while an Atomic absorption spectrometer was used for mineral determinations. Red variety achieved the highest antioxidant activities. The total flavonoids were between (12.56 and 353.53 mg Quercetin/gin dry weight) (dw) and the total phenol was (8.75–25.73 mg/g dw). Leek, Yellow and Green extracts achieved highly anti-inflammatory values (3.71–4.01 μg/mL) followed by Red and Baby extracts, respectively. The highest contents of sodium, potassium, zinc, and calcium were established for Red onions. Furfuraldehyde, 5-Methyl-2-furfuraldehyde, 2-Methyl-2-pentenal, and 1-Propanethiol were the most predominant, followed by a minor abundance of the other compounds such as Dimethyl sulfide, Methyl allyl disulfide, Methyl-trans-propenyl-disulfide, and Methyl propyl disulfide. The results recommend that these varieties could act as sources of essential antioxidants and anti-inflammatories to decrease inflammation and oxidative stresses, especially red onions that recorded high activities.

White button mushroom or (Agaricus bisporus) is known as a healthy foodstuff with several nutrients, polyphenols, proteins, and dietary fibers. Mushrooms have a short shelf-life, approximately three to four days at commercial storage and about eight days under chilling conditions. In the current study, titanium dioxide nanoparticles and chitosan films were used as novel active coating materials with the addition of thymol and tween (T and T) as food preservatives to prolong mushroom shelf life up to 12 days. Chitosan, Chitosan-Nano, and Chitosan-Nano/TT were used as coating materials, while water was used as control. Chitosan-Nano/TT film reported the lowest peroxidase activity (0.005 U kg−1 FW) and the highest superoxide dismutase activity (4.033 U kg−1 FW), while catalase activity in Chitosan-Nano film was (0.45 U kg−1 FW). Chitosan-Nano film enhanced the reactive oxygen species production levels, DPPH radicals (74.70%), and malondialdehyde content (1.68 µmol kg−1FW). Chitosan-Nano/TT film preserved the respiration rates (O2 consumption −0.026 mmol s−1kg−1, CO2 production −0.004 mg CO2 kg−1s−1) and increased the phenolic contents (0.38 g kg−1). The results suggested that nano-coating films can increase the oxidation processes which enhanced the quality of the mushrooms.

In the current study, novel films with chitosan/nano/SiO2/nisin films and their antimicrobial application on cantaloupe fruit shelf-life have been studied. Novel films were prepared by the addition of 1% chitosan, 1% nano silicon dioxide, and 1% nisin and freeze-dried for the performance study. Physicochemical properties such as tensile strength, optical, and thermal properties with the performance characteristics of the novel films were measured. Coated and uncoated cantaloupes with various coating solutions were stored and chilled at 4 °C in a relative humidity of 70% for up to nine days. The microbial population measurements have been detected every three days. Results show that the fourier transform infrared intensity (FTIR) of nano/SiO2 and with the addition of nisin (nano/SiO2/n) were higher than chitosan (CH) film except in the wavenumber (3150–3750 cm−1) films peaks. Novel nanofilms enhanced tensile strength as well as optical and thermal properties. XRD analysis reported two distinct peak values of 32.08 and 45.99 to correspond to nano/SiO2/n film orientation (7095) and (3316), respectively. Zeta potential values and turbidity were increased, while nano/SiO2 films decreased the hydrophobicity of the film surface by 80.07°. The coating treatments with nano/SiO2 and nano/SiO2/n both reduced the yeast and mold counts 2.49 and 1.92 log CFU/g, respectively, on day nine. In summary, chitosan/nano/SiO2/n novel film improved the functional properties of coating films, and those bio-nanocomposites are effective in food packaging.

Agaricus bisporus is an edible fungus with a limited shelf life due to high moisture loss, browning, respiration, self-dissolve, lack of physical protection, rotting, and microbial attack. Mushrooms have been coated with nisin, nano-silica, and chitosan films in order to extend the shelf life, preserve quality and oxidation activities. The results showed that treating the mushrooms with chitosan and nano-silica (CH-AN-SILICA) increased superoxide dismutase activity (SOD—6.53 U kg−1), total phenolic content (TPC—0.39 g kg−1), and malondialdehyde content (MDA—1.63 µmol kg−1). CH-AN-SILICA treatment exhibited the highest scavenging against 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. While, CH-AN-SILICA with the addition of nisin as an antimicrobial agent preserved almost the reactive oxygen species such as hydroxyl radicals (OH—0.33 µmol g−1), superoxide anion (O2•−—0.271 mmol s−1 kg−1), and hydrogen peroxide (H2O2—21.54 µmol g−1). Besides, both CH-AN-SILICA and CH-AN-SILICA/N enhanced the catalase (CAT) activity and reduced the respiration rate. The results indicated that the combination of nisin, nano-silica, and chitosan coating films was effective in providing a longer storage life with acceptable quality in mushrooms.

Introduction Diabetes mellitus (DM) is considered to be a significant public health problem globally. According to the American Society of Retina Specialists, diabetic retinopathy (DR) is a complication of diabetes that causes damage to the blood vessels of the retina. In a Japanese study showed that HbA1c and fasting blood glucose values can be considered as predictors for the future development of DR. Thus, this study aimed to determine the prevalence and severity of DR among diabetic patients in Medina, Saudi Arabia, and to assess its relationship with HbA1c and other biomarkers. Methods This cross-sectional study was conducted at Prince Abdulaziz Bin Majed Diabetes Center and Charitable Healthcare Society in Medina, Saudi Arabia, in July 2018. The data were collected from direct interview questionnaires that were administered to 130 randomly selected diabetic subjects. The subjects' demographic information, eye disease history, medical backgrounds, and laboratory biomarkers were noted. Fundus examinations using a slit lamp were conducted by ophthalmic physicians to diagnose and grade DR. The data were analyzed using Statistical Package for Social Sciences (SPSS) (IBM Corp., Armonk, NY, USA). Results All 130 diabetic patients were examined for DR. DR was prevalent among 35 (26.9%) of the participants. According to the DR severity grading, 95 (73.1%) had no apparent DR, 11 (8.5%) had mild non-proliferative diabetic retinopathy (NPDR), 11 (8.5%) had moderate NPDR, 11 (8.5%) had severe NPDR, and only two (1.5%) had proliferative diabetic retinopathy (PDR). There was a significant association between the development of DR and HbA1c levels (p = 0.040). The duration of DM was also determined to be a significant risk factor for DR (p = 0.001). No other factors were found to have a significant association with DR. Conclusion Around one-third of the participants in our study had DR. HbA1c levels and duration of DM were established as important risk factors for DR. Screening is necessary, even in patients with good HbA1c levels, to avoid the late presentation of severe DR and to prevent blindness.

Mushrooms have limited shelf-life and it can be prolonged if suitable conditions and treatments are effectively applied. In this study, nanocomposite material and antimicrobial agents with a combination of chitosan were used as novel packaging material for mushroom preservation. The microbiological analysis, physicochemical properties, headspace gas analysis, and polyphenol oxidase activity (PPO) during cold storage were investigated. As compared with control, coated mushrooms with chitosan (CHS), and nano-titanium dioxide CHSTiO2 thymol + tween-80 CHSTiO2/TT80 coating treatment showed significantly (p &le, 0.05) lower respiration rate, microbial contaminations (4.27 log CFU/g), and (5.93 log CFU/g) for total yeast/mold and aerobic plate counts, respectively. The weight loss ratio was the lowest for CHSTiO2/TT80 (10.88% loss) followed by CHSTiO2 (11.76% loss). CHSTiO2/TT80 recorded a higher electrolyte leakage rate (25.84%) and acidity. While the lowest PPO activity was established for CHSTiO2 (17.09 U mg&minus, 1 Protein), while the lowest values for total soluble solid concentrations were reported for CHSTiO2/TT80 mushrooms (4.91%). These results indicated that CHSTiO2/TT80 coating treatment might delay the aging degree of white button mushrooms and be investigated as a novel packaging material for other food products in the future.

White button mushrooms are greatly high perishable and can deteriorate within a few days after harvesting due to physicomechanical damage, respiration, microbial growth of the delicate epidermal structure. For that reason, the present research work was applied to evaluate the effect of chitosan combination with nano-coating treatments on physicochemical parameters and microbial populations on button mushrooms at chilling storage. Nano coating with the addition of nisin 1% (CHSSN/M) established the minimum value for weight loss 12.18%, maintained firmness 11.55 N, and color index profile. Moreover, O2% rate of (CHSSN/M) mushrooms was the lowest at 1.78%; while the highest rate was reported for CO2 24.88% compared to the untreated samples (Control/M) on day 12. Both pH and total soluble solid concentrations increased during storage. Results reported that the (CHSS/M) mushroom significantly (P −1 Protein) compared with (Control/M) mushrooms that increased faster than the treated samples. (CHSSN/M) treatment was the most efficient in the reduction of yeast and mold, aerobic plate microorganisms (5.27–5.10 log CFU/g), respectively. The results established that nano-coating film might delay the aging degree and accompany by marked prolongation of postharvest mushroom freshness.

Introduction: Due to the diversity of reports and on the rates of medications errors (MEs) in Saudi Arabia, we performed the first meta-analysis to determine the rate of medications errors in Saudi Arabia using meta-analysis in the hospital settings. Methods: We conducted a systematic literature search through August 2019 using PubMed, EMBASE, CINAHL, PsycINFO, and Google Scholar to identify all observational studies conducted in hospital settings in Saudi Arabia that reported the rate of MEs. A random-effects models were used to calculate overall MEs, as well as prescribing, dispensing, and administration error rates. The I2 statistics were used to analyze heterogeneity. Results: Sixteen articles were included in this search. The total incidence of MEs in Saudi Arabia hospitals was estimated at 44.4%. Prescribing errors, dispensing errors, and adminstration errors incidents represent 40.2%, 28.2%, and 34.5% out of the total number of reported MEs, respectively. However, between-study heterogeneity was also generally found to be >90% (I-squared statistic). Conclusions: This study demonstrates the MEs common in health facilities. Additional efforts in the field are needed to improve medication management systems in order to prevent patient harm incidents.

Chemoresistance is one of the major obstacles in the treatment of cancer patients. It poses a fundamental challenge to the effectiveness of chemotherapy and is often linked to relapse in patients. Chemoresistant cells can be identified in different types of cancers; however, ovarian cancer has one of the highest rates of chemoresistance-related relapse (50% of patients within 5 years). Resistance in cells can either develop through prolonged cycles of treatment or through intrinsic pathways. Mechanistically, the problem of drug resistance is complex mainly because numerous factors are involved, such as overexpression of drug efflux pumps, drug inactivation, DNA repair mechanisms and alterations to and/or mutations in the drug target. Additionally, there is strong evidence that circulating miRNAs participate in the development of chemoresistance. Recently, miRNAs have been identified in exosomes, where they are encapsulated and hence protected from degradation. These miRNAs within exosomes (exo-miRNAs) can regulate the gene expression of target cells both locally and systemically. Exo-miRNAs play an important role in disease progression and can potentially facilitate chemoresistance in cancer cells. In addition, and from a diagnostic perspective, exo-miRNAs profiles may contribute to the development of predictive models to identify responder and non-responder chemotherapy. Such model may also be used for monitoring treatment response and disease progression. Exo-miRNAs may ultimately serve as both a predictive biomarker for cancer response to therapy and as a prognostic marker for the development of chemotherapy resistance. Therefore, this review examines the potential role of exo-miRNAs in chemotherapy in ovarian cancer.

Ovarian cancer has resulted in over 140 000 deaths reported annually worldwide. This is often attributed to cellular changes in the microenvironment, including increased migration of mesenchymal stem cells (MSCs) and endothelial cells (ECs) to facilitate metastasis. Recently, the ability of exosomes to communicate signals between cells (and promote cancer progression) has been established. In the present study, we explored the effect of exosomes on cells present in the tumour microenvironment. Exosomes were isolated from ovarian cancer cells with different invasive capacity (high = SKOV-3 and low = OVCAR-3) by differential and buoyant density centrifugation and characterised using nanoparticle tracking analysis (NTA), Western blot, and EM. Exosome secretion was positively correlated with invasiveness of releasing cells. Proteomic analyses identified common and unique proteins between exosomes from SKOV-3 and OVCAR-3 with gene ontology analyses revealing that these exosomes are involved in the regulation of cell migration. Since the tumour microenvironment contains multiple cell types, including MSCs and ECs, we examined the effect of these exosomes on MSC and EC migration. Exosomes promoted MSC and EC migration in a time- and concentration-dependent manner. The effect of exosomes isolated from SKOV-3 on cell migration was significantly higher compared with exosomes from OVCAR-3. Thus, we suggest that exosomes from ovarian cancer cells contain a specific set of proteins that are representative of its cell of origin and the invasive capacity.

Glutathione reductase (GR) is highly conserved among diverse taxa and has important biochemical functions. These functions may facilitate survival in harsh conditions, but the role of GR from the liver of the Arabian camel (Camelus dromedarius) is unknown. In this study, the mitochondrial glutathione reductase gene (Gsr) from C. dromedarius liver was cloned and highly expressed in Escherichia coli (Jm109) to gain insight into GR functions in the liver. After amplification of the cDNA encoding the functional unit of Gsr (1.2 kb), the products were cloned into the PGEM-T Easy and PET28a vectors. Gsr expression was confirmed using an immunoblotting technique (45 kDa). Recombinant GR was purified to homogeneity using Ni-NTA resins, with an overall yield of 7.23% and a specific activity of 0.3063 U/mg. The optimum pH of recombinant GR was 7 and the optimum temperature was 35 °C in 50 mM K3PO4 buffer. The Michaelis constant, Km, for the substrates glutathione disulfide (GSSG) and NADPH was 45.6 μM and 63.5 μM, respectively; moreover, maximal velocity (Vmax) values were 3.969 x 10-2 U/mg and 1.497 x 10-1 U/mg. This partial characterization of camel liver GR extends our insight into the ability of camels to cope with harsh environmental conditions.

Exosomes are small nanovesicles that carry bioactive molecules which can be delivered to neighbouring cells to modify their biological functions. Studies have showed that exosomes from ovarian cancer (OVCA) cells can alter the cell migration and proliferation of cells within the tumour microenvironment, an effect modulated by the invasiveness capacity of their originating cells. Using an OVCA cell line xenograph mouse model, we showed that exosomes derived from a high invasiveness capacity cell line (exo-SKOV-3) promoted metastasis

The prime objective of the research was to explore the coating effects of chitosan and nano-silicon dioxide with nisin as an antimicrobial agent on physicochemical properties, microbiological stability, and sensorial quality changes during the storage at 4 °C. The combination of nano-material and chitosan in addition to nisin was effective for reducing the postharvest attributes of fresh-cut cantaloupes in addition to the highest score in sensory evaluation. Chitosan coating treatment enhanced the microbiological quality 2.50 log CFU/g and 1.87 log CFU/g for aerobic counts and mold/yeasts populations, respectively. In a word, the combination of chitosan/nano-silica/nisin treatment was the best condition for fresh-cut cantaloupe shelf life extension by maintaining color, vitamin C 22.29 mg/100g, peroxidase activity 8.06 U/min.g, and other microbiological tests up to storage time of 8 days.

Carboplatin, administered as a single drug or in combination with paclitaxel, is the standard chemotherapy treatment for patients with ovarian cancer (OVCA). Recent evidence suggests that miRNAs associated with small extracellular vesicles (sEVs) participate in the development of chemoresistance. We studied the effect of carboplatin in a heterogeneity population of OVCA cells and their derived sEVs to identify mechanisms associated with chemoresistance. sEVs were quantified using an engineered superparamagnetic material, gold-loaded ferric oxide nanotubes and a screen-printed electrode. miR-21-3p, miR-21-5p, and miR-891-5p are enriched in sEVs, and they contribute to carboplatin resistance in OVCA. Using a quantitative MS/MS, miR-21-5p activates glycolysis and increases the expression of ATP-binding cassette family and a detoxification enzyme. miR-21-3p and miR-891-5p increase the expression of proteins involved in DNA repair mechanisms. Interestingly, the levels of miR-891-5p within sEVs are significantly higher in patients at risk of ovarian cancer relapse. Identification of miRNAs in sEVs also provides the opportunity to track them in biological fluids to potentially determine patient response to chemotherapy.