Effect of Solanum lycopersicum and Citrus limon-Derived Exosome-Like Vesicles on Chondrogenic Differentiation of Adipose-Derived Stem Cells.

Articular cartilage defect treatment is a very important problem because its therapeutic options are not successful enough. Due to the weak self-repairing capacity of the avascular cartilage, even minor damage can progress and cause joint damage leading to osteoarthritis. Although various treatment strategies have been developed to repair damaged cartilage, cell- and exosome-based therapies are promising. Plant extracts have been used for decades, and their effects on cartilage regeneration have been studied. Exosome-like vesicles, which are secreted by all living cells, are involved in cell-to-cell communication and cell homeostasis. The differentiation potential of exosome-like vesicles isolated from S. lycopersicum and C. limon, which are known to have anti-inflammatory and antioxidant properties, was investigated in the differentiation of human adipose-derived mesenchymal stem cells (hASCs) into chondrocytes. In order to obtain tomato-derived exosome-like vesicles (TELVs) and lemon-derived exosome-like vesicles (LELVs) Aquous Two- Phase system was performed. Characterisation of isolated vesicles based on size, shape were achived via Zetasizer, NTA FAME analysis, and SEM techniques. These results showed that TELVs and LELVs increased cell viability and did not show any toxic effects on stem cells. Although TELVs triggered chondrocyte formation, LELVs downregulated. The expression of ACAN, SOX9, and COMP, known as chondrocyte markers, was increased by TELV treatment. In addition, protein expression of the two most important proteins, COL2 and COLXI, found in the extracellular matrix of cartilage, increased. These findings suggest that TELVs can be used for cartilage regeneration, and may be a novel and promising treatment for osteoarthritis.

Evaluation of Fatty Acid Contents and Biological Activities of Jurinea turcica.

The fatty acid profile, antioxidant/antibacterial, and cytotoxic effects of the extracts obtained from Jurinea turcica B.Dogan& A.Duran have been evaluated for the first time in the current study. The fatty acid profile of ethanolic extracts was determined using the Soxhlet extractor by a gas chromatography-mass spectrometer. The antioxidant and antibacterial activities were measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferrous reduction tests and the disc diffusion technique. Additionally, the cytotoxicity and wound healing assays were performed on A549 cells. The highest amount of component in the leaf extract was docosanoic acid methyl ester, whereas abundant arachidonic acid methyl ester was mainly found in the flower extract. The IC50 values, the 50 % scavenging value for the DPPH radical, were 179.13 and 124.67 µg/mL for the leaf and flower extracts, respectively. IC50 values (the half-maximal inhibitory concentration) were 10.4 and 24.7 µg/mL for the flower and leaf extracts, respectively. The leaf extract showed more potent antibacterial activity on Enterococcus faecalis (17 mm) and Staphylococcus aureus (16 mm) bacteria than the flower extract. In conclusion, the extracts of J. turcica have anti-cancerogenic and antibacterial effects. Leaf extracts have antibacterial and anti-metastatic effects, while flower extracts show antioxidant, cytotoxic, and apoptotic properties in A549 cells.

e-Health Literacy Status of Individuals with Multiple Sclerosis in Turkey.

Background: This research aims to compare e-health literacy of technology users and nonusers in people with multiple sclerosis (MS) and to investigate whether there are correlations between age, duration of MS, gender, marital status, and e-health total scores. Methods: This descriptive study was carried out with a web-based questionnaire. The questionnaire was sent to 300 patients with MS who were registered at Istanbul University-Cerrahpasa Medical Faculty Neurology Department. Results: A total of 156 people (mean age: 35.33 ± 10.47 years) participated in the survey. Smartphone 98.1% (n = 153) was the mostly used device. Rate of using Google and recommended websites about MS was 94.25% (n = 145) and 73.9% (n = 113), respectively. e-Health literacy of both the tablet and recommended websites users significantly differed from that of nonusers (p = 0.007 for both). Participants' e-health literacy total score was found to weakly, but significantly, correlate with their age, marital status, and education level (rho: -0.161, p = 0.044; rho: 0.172, p = 0.032; rho: -0.192, p = 0.016, respectively). Conclusions: With developments in digital technologies, it is important to identify the access status of people with MS to improve daily clinical management and implement further motor and cognitive rehabilitation. Therefore, determining the health literacy of individuals with MS and providing education on this subject will reduce the information pollution.

Garlic Exosomes Promote Hair Growth Through the Wnt/ß-catenin Pathway and Growth Factors.

Background Exosomes are membrane-derived nanovesicles produced by cells and play an important role in intercellular communication. Objectives This study aimed to investigate the effects of garlic exosome (GE) on hair growth. Methods Forty-two Sprague-Dawley/Wistar albino rats were randomly divided into six groups: non-shaved control, shaved control, topical control, GE 2 mg, GE 4 mg, and topical GE. At the end of the experiment, the number of hair follicles, follicle diameter, and subcutaneous tissue thicknesses were measured histopathologically. The Wnt-1, ß-catenin, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), and collagen I levels were measured by the Western Blot method. Results The anagen follicle counts of the GE 2 mg, 4 mg, and topical GE groups were 66.57±15.49, 105.71±25.06, and 55.29±6.72, and were significantly higher than the control groups (p<0.01, p<0.001 and p<0.05, respectively). The follicle diameter of the GE 4 mg group was higher than the others (p<0.05). The Wnt-1, PDGF, VEGF, TGF-ß1, and collagen I levels of all GE groups, and the ß-catenin levels of the GE 4 mg and topical GE groups were significantly higher than the control groups (p<0.05). Conclusion GE induces hair growth in rats via the Wnt-1, ß-catenin, VEGF, PDGF, and TGF-ß1 signaling pathways.

Is it possible to predict Surgical Site Infection?

Introduction: Surgical site infection (SSI) is a widely seen postoperative complication that causes a decrease in life quality and an economic burden. In this study, we aim to find the predictive values of preoperative and postoperative neutrophile lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) values for SSI. Methods: In this retrospective study, 698 patients who had total abdominal hysterectomy operations with benign indications and confirmed histopathological results were accessed. In this study, the correlation of preoperative NLR, preoperative PLR, postoperative NLR, and postoperative PLR, with the occurrence of postoperative surgical site infection complications were examined. Results: The overall SSI rate was 9.46% (n = 66) with 30 days follow-up postoperatively. Preoperative NLR and PLR values of the patients who had SSIs were significantly lower than the control group (p < 0.05). Postoperative NLR and PLR values of the patients who had SSIs were significantly higher than control group (p < 0.05). In the patients who had postoperative SSIs, the increase of the values of postoperative NLR and PLR were significantly higher than the control group (p < 0.05). Conclusions: In our study, hematological markers of NLR and PLR were found to be independent and significant predictive markers for SSI.

Substituted phenethylamine-based ß-lactam derivatives: Antimicrobial, anticancer, and ß-lactamase inhibitory properties.

In this study, a series of novel ß-lactam derivatives were synthesized with yields ranging from 41 % to 91 %, and their antimicrobial activities were investigated against bacterial and fungal isolates that cause nosocomial infections. The results revealed that the novel ß-lactam derivatives, especially compound 19, showed antibacterial activities ranging from 0.98 to 250 µg/mL. In contrast, the compounds showed no antifungal activity against fungal isolates. Following that, biochemical (Nitrocefin) investigation of compounds with antibacterial activity was carried out, as well as their effects on the ß-lactamase enzyme. According to the results, the compounds inhibited the ß-lactamase enzyme against bacterial isolates. Furthermore, the anticancer activity and toxicity profiles of ß-lactam derivatives were also studied against colorectal cancer (Caco-2), the most common type of cancer, and non-human dermal fibroblast cell line. The results revealed that compound 19 was shown the best anticancer activity and lowest toxicity profile among other compounds. Therefore, these compounds, especially compound 19, could be useful in the treatment of colorectal cancer and related nosocomial infections. Furthermore, the potential of being an antibiotic can be put forward by investigating the resistant mechanism and further pharmacological studies.

The apoptotic effect of ozone therapy on mitochondrial activity of highly metastatic breast cancer cell line MDA-MB-231 using in vitro approaches.

Ozone (O3) gas is the triatomic state of oxygen and it is used as a disinfection agent due to its strong oxidizing effect, since its discovery in the mid-nineteenth century. Ozone therapy is also an alternative therapeutic approach for some diseases like circulatory disorders, AIDS, asthma, cardiovascular diseases, and certain types of cancer by increasing the oxygen levels in the blood by external addition of ozone to the body. In this study, the therapeutic potential of ozone therapy was examined by inhibiting the growth of breast cancer cells in a dose-dependent procedure. Ozone concentrations varying from 5 to 20 â€‹µg/ml were applied to the MDA-MB-231, human breast adenocarcinoma and HUVEC, human umbilical vein endothelium, cell lines, and MDA cells demonstrated an increased rate of death while its migration potential decreases. RT-PCR analysis showed mRNA expression levels of pro-apoptotic genes demonstrated higher folds in MDA cells after 10 â€‹µg/ml treatment. In the same context, Annexin V/PI and cell cycle analysis also concluded that ozone therapy causes apoptotic cell death on breast tumor cells. The use of ozone therapy for cancer treatment requires further and extensive research. However, this research has shown that ozone therapy is a promising source for cancer treatment in a way by inhibiting the proliferation of breast tumor cells.

Dysregulation of E-cadherin in pulmonary cell damage related with COPD contributes to emphysema.

Air pollution, especially at chronic exposure to high concentrations, is a respiratory risk factor for the development of chronic obstructive pulmonary disease (COPD). E-cadherin, a cell-cell adhesion protein, is involved in the integrity of the alveolar epithelium. Causes of E-cadherin decreases in emphysematous areas with pulmonary cell damage related to COPD are not well understood. We aimed to determine the molecules causing the decrease of E-cadherin and interactions between these molecules. In emphysematous and non-emphysematous areas of lungs from COPD patients (n = 35), levels of E-cadherin, HDACs, Snail, Zeb1, active-ß-catenin, p120ctn, and Kaiso were determined by using Western Blot. The interactions of HDAC1, HDAC2, and p120ctn with transcription co-activators and Kaiso were examined by co-immunoprecipitation experiments. The methylation status of the CDH1 promoter was investigated. E-cadherin, Zeb1, Kaiso, and active-ß-catenin were decreased in emphysema, while HDAC1, HDAC2, and p120ctn2 were increased. Snail, Zeb1, Twist, active-ß-catenin, Kaiso, and p120ctn co-precipitated with HDAC1 and HDAC2. E-cadherin, Kaiso, and active-ß-catenin co-precipitated with p120ctn. HDAC1-Snail and HDAC2-Kaiso interactions were increased in emphysema, but p120ctn-E-cadherin interaction was decreased. The results show that HDAC1-Snail and HDAC2-Kaiso interactions are capable of decreasing the E-cadherin in emphysema. The decreased interaction of p120ctn/E-cadherin leads to E-cadherin destruction. The decreased E-cadherin and its induced degradation in pneumocytes cause impaired repair and disintegrity of the epithelium. Approaches to suppress HDAC1-Snail and HDAC2-Kaiso interactions may help the protection of alveolar epithelial integrity by increasing the E-cadherin stability in pneumocytes.

Atorvastatin attenuates pulmonary fibrosis in mice and human lung fibroblasts, by the regulation of myofibroblast differentiation and apoptosis.

Statins have anti-inflammatory and antifibrotic effects in addition to cholesterol-lowering effect. We aimed to investigate the effect of atorvastatin (ATR) in fibrotic mouse lung and human lung fibroblasts (MRC5s). Pulmonary fibrosis was induced by a single dose of bleomycin by intratracheal instillation in adult mice. ATR was administered (20 mg/kg ip) to mice with healthy and pulmonary fibrosis for 10 days from Day 7 of the experiment. Mice were dissected on the 21st day. The levels of alpha-smooth muscle actin (α-SMA), pSMAD2/3, LOXL2, and p-Src were determined by Western blot analysis in the lungs. Furthermore, a group of MRC5 was differentiated into myofibroblasts by transforming growth factor-beta (TGF-ß). Another group of MRC5s was treated with 10 µM ATR at 24 h after TGF-ß stimulation. Cells were collected at 0, 24, 48, and 72 h. The effects of ATR on myofibroblast differentiation, apoptosis, and TGF-ß and Wnt/ß-catenin signaling activations were examined by Western blot analysis and flow cytometry in MRC5s. ATR attenuated pulmonary fibrosis by regulating myofibroblast differentiation and interstitial accumulation of collagen, by acting on LOXL2, p-Src, and pSMAD2/3 in mice lungs. Additionally, it blocked myofibroblast differentiation via reduced TGF-ß and Wnt/ß-catenin signaling and decreased α-SMA in MRC5s stimulated with TGF-ß. Moreover, ATR caused myofibroblast apoptosis via caspase-3 activation. ATR treatment attenuates pulmonary fibrosis in mice treated with bleomycin. It also inhibits fibroblast/myofibroblast activation, by both reducing myofibroblasts differentiation and inducing myofibroblast apoptosis.

COVID-19 Infodemic: A study on the Fragile Five countries.

During the COVID-19 pandemic, many rumors and conspiracy theories spread in various media outlets. The purpose of this study is to reveal the nature of the misinformation detected by fact check platforms that spread in the Fragile Five countries. To determine the themes of misinformation about COVID-19 and from which media it is disseminated are a possible way to prevent it. The data of the study were obtained from International Fact-checking Network's CoronaVirusFacts database. One thousand seven hundred thirty-four piece of misinformation collected by web scraping method during the period January 24, 2020 to November 14, 2020 and analyzed with MAXQDA Analytics Pro 2020. As a result of the research, it was found that rumors (96.3%) spread more in the Fragile Five countries than conspiracy theories (3.7%). While the main theme of the rumors is about illness (26.9%) and diagnosis-treatment (25%), conspiracy theories are mostly related to the cause of the disease (68.8%). 53.06% of misinformation was spread through the Facebook platform. 15.32% on Twitter; 13.34% on WhatsApp. Misinformation has been heavily false (85.12%) in both rumor and conspiracy theories. In the second place, misleading (10.09%) news spread.

Escape from COVID-19 pandemic to safe haven.

Gold, which is accepted as a safe haven by households, is known as an investment tool that is preferred especially in times of crisis and uncertainty. Especially in recent days, the uncertainty caused by the COVID-19 pandemic and the visible increase in Turkey's 5-year CDS data has led investors in Turkey to grams of gold, which is considered a safe haven. In this context, this study aims to test the long-term relationship between daily case-related deaths and Turkey's 5-year CDS data with gram gold prices in Turkish lira during the COVID-19 pandemic. The long-term relationship between the variables was tested with the autoregressive distributed lag bound test (ARDL bound test) applied to the daily data for the period March 17, 2020-April 11, 2020. For the application of ARDL bound test, the stationarity of the variables was tested with unit root tests such as augmented Dickey-Fuller test (ADF) and Phillips-Perron (PP). According to the ARDL bound test findings, there is a statistically significant and positive relationship between the number of case-related deaths and the gram gold prices in Turkish lira in the long run. However, it has been found that Turkey's 5-year CDS data does not have a significant long-term relationship with gram gold prices in Turkish lira.

Garlic (Allium sativum)-derived SEVs inhibit cancer cell proliferation and induce caspase mediated apoptosis.

As a key component of the cell-to-cell communication, small extracellular vesicles (SEVs) released from various sources are known to be affecting the physiological conditions of the target cells. Although it has been suggested that edible plant-derived nanoparticles contributes to the cross kingdom communication with the mammalian cells, the effect of these particles on cancer cell progression still needs a further exploration. Here, we isolated and then characterized garlic derived SEVs by nanoparticle tracking analysis, electron microscopy and SEV surface antibodies. In order to investigate anti-cancer property of garlic SEVs A498 human kidney carcinoma, A549 human lung carcinoma were used as cell models along with the normal human dermal fibroblast cell lines. Annexin V/pI staining and analysis of apoptotic mRNA and protein expression levels suggested that garlic SEVs induced apoptosis through activation of intrinsic pathway. Furthermore, angiogenic VEGF protein expression levels significantly decreased in response to SEVs treatment in cancer cells. Our results support that garlic derived SEVs could cause apoptotic cell death among cancer cells while normal cells remain unaffected with the treatment. This study revealed for the first time that plant SEVs possess anti-cancer affects by inducing caspase mediated apoptosis and provided a new alternative for cancer treatment.

Cold Denaturation of Proteins: Where Bioinformatics Meets Thermodynamics to Offer a Mechanistic Understanding: Pea Protein As a Case Study.

Protein structure can be altered with heat, but models which predict denaturation show that globular proteins also spontaneously unfold at low temperatures through cold denaturation. By an analysis of the primary structure of pea protein using bioinformatic modeling, a mechanism of pea protein cold denaturation is proposed. Pea protein is then fractionated into partially purified legumin and vicilin components, suspended in ethanol, and subjected to low temperatures (-10 to -20 °C). The structural characterizations of the purified fractions are conducted through FTIR, ζ potential, dynamic light scattering, and oil binding, and these are compared to the results of commercial protein isolates. The observed structural changes suggest that pea protein undergoes changes in structure as the result of low-temperature treatments, which could lead to innovative industrial processing techniques for functionalization by low-temperature processing.

Effect of long noncoding RNAs on epithelial-mesenchymal transition in A549 cells and fibrotic human lungs.

Long noncoding RNAs (LncRNAs) regulate epithelial-mesenchymal transition (EMT). EMT involves myofibroblast differentiation and pulmonary fibrosis (PF). We aimed to determine the expression profiles of HOTAIR, CARLo-5, and CD99P1 LncRNAs in EMT-mediated myofibroblast differentiation in A549 cells and fibrotic human lungs and to explain their roles. A group of A549s was stimulated with transforming growth factor ß (TGF-ß; 5 ng/ml) to induce EMT. The remaining A549s were incubated with 20 µM FH535 after 24 h of TGF-ß treatment to inhibit EMT. A549s were collected at 0, 24, 36, and 48 h. Expressions of three LncRNAs and protein/genes related to EMT, myofibroblast differentiation, and PF were assayed by quantitative reverse-transcription polymerase chain reaction and Western blot analysis in A549s and fibrotic human lungs. The targets of three LncRNAs were investigated by bioinformatics methods. TGF-ß stimulation resulted in increased expressions of three LncRNAs, ACTA2, COL1A1, SNAI1, CTNNB1, TCF4, LEF1, α-SMA, and active-ß-catenin, and decreased E-cadherin at 24, 36, and 48 h in A549s. FH535 treatment regressed these alterations. But it increased HOTAIR expression at 36 h and did not increase E-cadherin at 48 h. Fibrotic human lungs were characterized by increased expressions of HOTAIR, CARLo-5, CD99P1, and miR-214, decreased expressions of miR-148b, miR-218-1, miR-7-1, and the presence of CARLo-5 and CD99P1 in HDAC1-LncRNAs coprecipitation products, but not HOTAIR. Bioinformatic analysis showed the interactions of three LncRNAs with both proteins and at least 13 microRNAs related to EMT and PF. In conclusion, HOTAIR, CARLo-5, and CD99P1 can regulate EMT-mediated myofibroblast differentiation through interacting with proteins and miRNAs associated with EMT and PF. These LncRNAs can be considered as potential targets to decrease EMT for treating PF.

Impact of Prepartum Body Condition Score Loss on Metabolic Status During the Transition Period and Subsequent Fertility in Brown Swiss Dairy Cows.

INTRODUCTION: The objectives of this study were to determine the role of a fall in pre-calving body condition score (BCS) in postpartum metabolic status and reproductive outcomes, and gauge the indicativeness of blood metabolites during the transition period. MATERIAL AND METHODS: Cows were grouped based on BCS loss between days -14 ±3 and 0 relative to calving. Cows that lost no BCS were the BCS control group (BCS-C), cows that lost 0.25 BCS points the low BCS loss group (BCS-L), and those that lost 0.5 points or more the high BCS loss (BCS-H) group. Blood was taken on days -14 ±3, 3, 14, and 30 ±4 for determination of comprehensive metabolic panel biomarker levels. Beta-hydroxybutyric acid (BHBA) levels were quantified on postpartum examination days. Vaginal discharge scores, ovarian activity on day 30 ±4, and subsequent fertility parameters were evaluated. RESULTS: The BCS-H cows had lower mean Ca concentrations before calving and on day 3, when the group's BHBA and CK were higher (P < 0.05); on day 14 they had higher AST concentrations (P < 0.05). The BCS-L cows had greater bilirubin levels (P < 0.05). The BCS-H cows had lower cyclicity and higher endometritis rates. First service pregnancy rates were 50%, 50%, and 61.9%, open days 96.8, 95.75, and 89.2, and overall pregnancy rates 56.25%, 65%, and 80.95 % in the BCS-H, BCS-L, and BCS-C groups, respectively. CONCLUSION: Prepartum BCS loss of ≥ 0.5 points could be associated with Brown Swiss cow low Ca and BHBA concentrations early postpartum, and with subsequent uterine health and overall pregnancy rate. Prepartum Ca concentration might be a prognostic biomarker for postpartum metabolic status and reproductive outcomes.

The effects of atorvastatin on the kidney injury in mice with pulmonary fibrosis.

OBJECTIVES: The present study investigated the effects of atorvastatin on kidney injury in mice with pulmonary fibrosis (PF). METHODS: Adult mice were divided into four groups: mice treated with intratracheal bleomycin (I) and their controls (II), and mice treated with atorvastatin for 10 days after 7 days from bleomycin treatment (III) and their controls (IV). Mice were dissected on the 21st day. KEY FINDINGS: Mononuclear cell infiltrations, injured proximal tubule epithelium and p-c-Jun level increased, while cell proliferation and the levels of p-SMAD2, ELK1, p-ELK1, p-ATF2 and c-Jun decreased in the kidney tissue of mice with PF. The atorvastatin treatments to mice with PF resulted in significant increases at the TGF-ß activation, cell proliferation and kidney damage and decreases in the levels of p-SMAD2, p-ELK1, p-ATF2 and p-c-Jun, but not change the p-SMAD3, ELK1 and ATF2 in kidneys. CONCLUSIONS: The depletion of MAPK signals, rather than SMAD signalling, is effective in kidney damage of mice with PF. Atorvastatin did not regress kidney damage in these mice, whereas it increases the kidney injury. The c-Jun-mediated JNK signals could help kidney repair through cell proliferation. The treatment time and doses of atorvastatin should be optimized for regression of kidney damage.

Rheology, particle-size distribution, and stability of low-fat mayonnaise produced via double emulsions.

In this study, the effects of the double emulsification method on the rheological properties, particle size, and stability of low-fat mayonnaise were studied. Different water-phase-to-oil ratios (2:8 and 4:6) of primary emulsions and different stabilizer types (sodium caseinate, xanthan gum, and lecithin-whey protein concentrate) were used to produce double-emulsified mayonnaise. As a control sample, mayonnaise was prepared conventionally. Sodium caseinate was found to be the most efficient stabilizer. In the presence of sodium caseinate, the stability and apparent viscosity of double-emulsified mayonnaise increased but their particle sizes decreased. It was found that flow behavior of double-emulsified and conventionally prepared mayonnaise could be described by the power law model. The double-emulsified mayonnaise samples were not different from the control samples in terms of stability and particle size. In addition, using the double emulsion method, it was possible to reduce the oil content of mayonnaise to 36.6%.

Factors affecting cervical screening among Turkish women.

BACKGROUND: Cervical cancer is second most common cancer among women worldwide. OBJECTIVE: To determinate pap smear test rates and affecting factors among Turkish women. METHODS: This descriptive and cross-sectional questionnaire study covered 397 women consulting at Gynecology Outpatient Clinic of Birth and Children's Hospital in Ordu province, enrolled non-consecutively as volunteers after providing informed consent. Data for women who had a history of at least one pap smear in her history were compared with those having none. RESULTS: 24.7% of women had knowledge about the pap smear test and 11.8% of them had undergone at least one pap smear test. Higher mean age (p=0.000), high education level (p=0.013), duration of marriage (p=0.001), working outside home (p=0.000), use of contraceptive method (p=0.000), history of cancer in women's family or relatives (p=0.021), having a sexually transmitted disease history (p=0.042), positive attitude towards gynecologic examination of women (p=0.000) and considering oneself in a cervical cancer risk group (p=0.004) were positively associated with a pap smear test history. CONCLUSION: Since the rate of pap smear testing was very low, education of women about screening and protection against cervical cancer appears a high priority.