Centaurea behen leaf extract mediated green synthesized silver nanoparticles as antibacterial and removing agent of environmental pollutants with blood compatible and hemostatic effects.

The present study focused on evaluating the antibacterial properties, radical scavenging, and photocatalytic activities of Centaurea behen-mediated silver nanoparticles (Cb-AgNPs). The formation of Cb-AgNPs was approved by UV-Vis spectrometry, Fourier-transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy (SEM), energy dispersive X-ray and X-ray diffraction. The results showed that the obtained AgNPs have a maximum absorbance peak at 450 nm with spherical morphology and an average size of 13.03 ± 5.8 nm. The catalytic activity of the Cb-AgNPs was investigated using Safranin O (SO) solution as a cationic dye model. The Cb-AgNPs performed well in the removal of SO. The coupled physical adsorption/photocatalysis reaction calculated about 68% and 98% degradation of SO dye under solar irradiation. The Cb-AgNPs inhibited the growth of gram-negative or positive bacteria strains and had excellent DPPH radicals scavenging ability (100% in a concentration of 200 µg/ml) as well as a good effect on reducing coagulation time (at concentrations of 200 and 500 µg/mL reduced clotting time up to 3 min). Considering the fact that green synthesized Cb-AgNPs have antioxidant and antibacterial properties and have a good ability to reduce coagulation time, they can be used in wound dressings. As well as these NPs with good photocatalytic activity can be a suitable option for degrading organic pollutants.

The Combined Effect of Curcumin and Crocin on the Reduction of Inflammatory Responses in Arthritic Rats.

The present study evaluated the anti-arthritic impact of combined crocin and curcumin on Adjuvant Induced Arthritis (AIA) in rats. Arthritis model was induced in rats by injecting Complete Freund's adjuvant (CFA) into the right hind paw and was subsequently treated with crocin and curcumin. Evaluation of anti-arthritic activity was carried out using paw swelling, hematological parameters, biochemical parameters, inflammatory cytokines, and histopathology of rats. The results showed increased paw swelling, increased serum markers levels, including CRP, RF, ALP, ALT, and AST, and inflammatory cytokines (ILlß and TNFα) along with histology changes (cartilage and bone degradation) in arthritic rats when compared to the normal group. Crocin, curcumin and crocin + curcumin administration at different doses (especially combination at 40 mg/kg and 30 mg/kg respectively), as well as MTX revealed suitable therapeutic effect on AIA rats. Moreover, both phytochemicals and their combination at different doses showed effective anti-arthritic effects owing to their anti-inflammatory effects. Therefore, crocin and curcumin, either alone or in combination, can be a suitable treatment modality for rheumatoid arthritis .

Electrospun sandwich-structured of polycaprolactone/gelatin-based nanofibers with controlled release of ceftazidime for wound dressing.

In the present work, sandwich-like polycaprolactone/gelatin/polycaprolactone electrospun multilayered mats were implemented to control the release of ceftazidime (CTZ). The outer layers were made from polycaprolactone nanofibers (NFs), and CTZ-loaded gelatin provided an internal layer. The release profile of CTZ from mats was compared with monolayer gelatin mats and chemically cross-linked GEL mats. All the constructs were characterized using scanning electron microscopy (SEM), mechanical properties, viscosity, electrical conductivity, X-ray diffraction (XRD), and Fourier transform-infrared spectroscopy (FT-IR). In vitro cytotoxicity against normal fibroblasts as well as antibacterial activity of CTZ-loaded sandwich-like NFs were investigated by the MTT assay. The results showed that the drug release rate from the polycaprolactone/gelatin/polycaprolactone mat was slower than that of gelatin monolayer NFs, and the rate of release can be adjusted by changing the thickness of hydrophobic layers. The NFs exhibited high activity against Pseudomonas aeruginosa and Staphylococcus aureus, while no significant cytotoxicity was observed against human normal cells. Altogether, the final mat as a predominant antibacterial scaffold can be used for controlled drug release of antibacterial drugs as the wound healing dressings in tissue engineering.

Incidence Pattern and Geographical Distribution of Breast Cancer among Females Using Geographic Information System in Kermanshah Province, West Iran: First Data from A Population-Based Cancer Registry in Kermanshah.

Background: Breast cancer (BC) is the second most frequent cancer in females worldwide. In recent years, the incidence rates of BC have been increasing among Iranian women. This study aimed to examine the incidence of BC among females in Kermanshah province, west of Iran, based on the data taken from the Kermanshah Population-based Cancer Registry (KPCR) during 2014-2017. Methods: In this registry study, data were obtained from the KPCR, a high-quality cancer registry that collects data on various cancers using standard protocols all over Kermanshah province. The crude incidence rates (CRs) and age-standardized incidence rates (ASRs) of BC were determined per 105 person-years. Further, temporal trends were assessed using joinpoint regression analysis to describe the average annual percent change (AAPC) and 95% CIs. ArcGIS software was used to map the geographic distribution of BC incidence. Results: During 2014-2017, 1,177 new cases of BC were detected in Kermanshah province. Most of the females diagnosed with BC (cases/100,000, percentage) lived in Kermanshah county (900, 76%) compared to the other counties (277, 23%). The overall ASR of BC increased by 38.7 cases per 100,000 females-year (AAPC: 2.2; 95%CI 5.1-10.1; P=0.3). The lowest and highest ASRs were observed in 2015 (36.7/100,000) and 2017 (40.7/100,000), respectively. The maximum incidence of BC among females was reported in the age group 45-49 years. Conclusion: The BC trend for females increased from 2014 to 2017 in Kermanshah province across all age groups, especially in the age group 45-49 years. Thus, it is essential to take a series of effective health measures to prevent and control this cancer.

Nrf2 antioxidant pathway and apoptosis induction and inhibition of NF-κB-mediated inflammatory response in human prostate cancer PC3 cells by Brassica oleracea var. acephala: An in vitro study.

BACKGROUND: Brassica oleracea var. acephala is a good source of health-promoting biologically active compounds like phenolics, vitamins, and glucosinolates. METHODS AND RESULTS: This in vitro research was conducted to evaluate the apoptotic, antioxidant, anti-inflammatory, and antiproliferative properties of ethanolic extract of Brassica oleracea var. acephala (EEBO) in PC3 prostate cancer cells. The LC-MS/MS technique was applied to identify the biomolecules of EEBO. The MTT assay was used to evaluate the cytotoxic effects of EEBO on PC3 cells. Moreover, qRT-PCR was used to examine the expression levels of Nrf2, NQO1, HO-1, NF-κB, TNF-α, IL-6, BAX, and BCL-2 in PC3 cell line. MMP was predicted by Rhodamine 123 staining, and release of cytochrome c was detected by an ELISA kit. Further, apoptosis was quantified by DNA fragmentation assay. The Western blotting method was used to detect the protein expression levels, and The DPPH assay was applied to determine the antioxidant effect of EEBO. The formula and structure of 19 biomolecules were predicted by LC-MS/MS. EEBO exhibited scavenging activity for DPPH. The MTT test showed EEBO reduced the viability of PC3 cells. The mRNA and protein levels of NRF2 pathway genes and BAX were increased, but those of the NF-κB pathway genes and BCL-2 were decreased in the EEBO-treated cells. Moreover, EEBO led to the diminution of MMP and enhanced the release of cytochrome c and DNA fragmentation, which resulted in apoptosis. CONCLUSIONS: Molecular changes due to the anticancer impact of EEBO on PC3 were involved in the induction of Nrf2 antioxidant pathway and apoptosis and inhibition of inflammation.

Analysis of molecular resistance to azole and echinocandin in Candida species in patients with vulvovaginal candidiasis.

Background and Purpose: Vulvovaginal candidiasis (VVC) is considered the most common mucosal infection caused by Candida species. Azoles were considered the first-line treatment for VVC or recurrent vulvovaginal candidiasis (RVVC) in both healthy and immunocompromised populations. Recently, azole-resistant isolates, especially among non-albicans Candida samples have been encountered. This study aimed to evaluate the antifungal susceptibility profile of Candida spp. isolated from VVC or RVVC patients and assess the molecular resistance mechanism of Candida spp. to azole and echinocandin. Materials and Methods: Point mutation analysis was performed on the ERG11 and FKS candidate genes of azole- and caspofungin-resistant Candida albicans and Candida glabrata isolates. Real-time polymerase chain reaction was performed to gain insight into the differential expression of ERG11 mRNA. Results: Variations in the amino acid D116E were observed in fluconazole- and itraconazole-resistant C. albicans strains, and changes in amino acid E517Q were observed only in fluconazole-resistant C. albicans strains. No polymorphisms were observed in the complete sequence alignment of the ERG11 gene in one azole-resistant C. glabrata isolate. The mutation triggered the changes in the amino acid serine in the reference gene FKS1 by the leucine at position 642 (S642L) of the isolates. Conclusion: In patients with persistent or recurrent infection, the choice of an antifungal agent is often challenging and requires monitoring of the antifungal susceptibility of the colonizing strain. C. albicans and C. glabrata isolates can be resistant to azole and caspofungin antifungal agents without mutations in the ERG 11 and HS1 regions of the FKS1 gene.

Evaluation of the association between polymorphisms of PRM1 and PRM2 and the risk of male infertility: a systematic review, meta-analysis, and meta-regression.

Studies have reported the genetic gives rise to male infertility. The aim of the present meta-analysis was to evaluate the association between PRM1 (rs737008 and rs2301365) and PRM2 (rs1646022 and rs2070923) polymorphisms and susceptibility to male infertility. The association between PRM1 and PRM2 polymorphisms and the risk of male infertility was evaluated using specific search terms in the Web of Science, Cochrane Library, PubMed, and Scopus databases without language restriction until January 28, 2020. The association was determined by odds ratio (OR) and 95% confidence interval (CI) on five genetic models using Review Manager 5.3 software. The funnel plot analysis and sensitivity analysis were done by the Comprehensive Meta-analysis 2.0 software. Out of 261 records retrieved from the databases, 17 studies were analyzed in the meta-analysis, including the four PRM polymorphisms. The pooled results as OR (P-value) showed 0.96 (0.44), 1.04 (0.70), 0.94 (0.51), 0.94 (0.48), and 1.03 (0.72) for PRM1 rs737008 polymorphism and 1.67 (0.0007), 1.73 (0.06), 1.50 (0.007), 1.56 (0.004), and 1.62 (0.33) for PRM1 rs2301365 polymorphism in allele, homozygous, heterozygous, recessive, and dominant models, respectively. Moreover, the pooled results as OR (P-value) showed 1.19 (0.004), 1.15 (0.26), 1.08 (0.70), 1.05 (0.76), and 0.98 (0.82) for PRM2 rs1646022 and 0.88 (0.04), 0.84 (0.10), 1.05 (0.81), 0.90 (0.24), and 0.80 (0.02) for PRM2 rs2070923 in allele, homozygous, heterozygous, recessive, and dominant models, respectively. The results showed PRM1 rs2301365 and PRM2 rs1646022 polymorphisms were associated with an elevated risk of male infertility and PRM2 rs2070923 polymorphism had a protective role in infertile men.

Spherical Gold Nanoparticles: Small Interfering RNA Delivery in Regulation of the Tumor Necrosis Factor-Alpha Gene Expression.

Proinflammatory cytokines are signaling molecules that are expelled from immune cells like macrophages and other types of cells. Tumor necrosis factor-alpha (TNF-α) is overexpressed during inflammation caused by inflammatory diseases. Therefore, the regulation of TNF-α has a key role in inflammation. The use and target delivery of small interfering RNAs (siRNAs) provide many effectual treatment benefits in the regulation of gene expression in cells. In this study, we used siRNA nanoparticle conjugates in the regulation of gene expression and inflammation. We first prepared safe fusion ribonucleic acid interference carrier, spherical nucleic acid nanoparticle conjugates (SNA-NCs), to enhance the perforation of siRNA into the macrophages and their ability to target TNF-α gene regulation. Furthermore, the suppression of the TNF-α gene was monitored after curing macrophages by SNA-NCs. Gene expression was carried out by real-time polymerase chain reaction in cells and the levels of TNF-α were investigated by the enzyme-linked immunosorbent assay (ELISA) method. This study indicated that the SNA-NCs were safe and very stable. TNF-α siRNA could significantly regulate gene expression in cells to form SNA-NCs. The results indicated that TNF-α gene expression downregulated to 93.40% ± 1.45%, 66.06% ± 0.95%, and 35.76% ± 1.09% in the presence of 0.1, 1, and 10 nM siRNA, respectively. The proliferation of macrophages and subsequently expression of TNF-α were significant for the formation of inflammation. These findings showed that the use of SNA-NC siRNA might ameliorate the inflammatory disease by suppression of gene expression and functional activity of macrophage generation.

Using siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation in psoriasis.

Psoriasis is a T-cell-mediated skin disease with autoimmune nature that is generally not observed in animals, this lack of a relevant experimental animal model of psoriasis has hindered the investigation of pathogenesis of disease. Application and systemic delivery of small interfering RNAs offer many effective therapeutic advantages for gene regulation in the skin. In this study, we present an IMQ animal model of psoriasis and designed a safe fusion peptide carrier, spherical nucleic acid gold nanoparticles conjugate, to improve penetration of the siRNA into the cells and skin and their targeting ability to gene regulation. We evaluated the model of psoriasis and EGFR siRNA treatment (as spherical nucleic acid nanoparticles), phenotypically (signs of erythema, scaling, inflammation and thickening), microscopic evaluation of cell proliferation and immunohistochemically evaluation of CD3, CD4, and CD8 markers. Also, we monitored suppression of EGF&EGFR genes after treatment of A431 cells by SNA-NCs. The expression of genes was validated by qRT-PCR in human skin cells. The results showed that the SNA-NCs were stable and non-toxic. In vitro experiments indicated that EGF&EGFR siRNAs conjugated with spherical nucleic acid gold nanoparticles can significantly reduce gene expression in cells. In vivo experiments showed that the topical application of siRNAs delivered by SNA-NCs through the skin can significantly inhibit the proliferation of cells. Microscopic evaluation of mice back skin and immunohistochemistry process approved Inhibitory effect of SNA-NCs siRNA in the mouse model of psoriasis. Since the proliferation of T cells was crucial for the development of a psoriatic phenotype. These results demonstrate that topical application of SNA-NCs siRNA may improve psoriatic-like skin lesions by suppressing gene expression and functional activity of T cell production.

Antioxidant status in patients with psoriasis.

Psoriasis is a chronic inflammatory skin disease with an unknown aetiology that has been associated with abnormal plasma lipid metabolism and oxidative stress. There are controversial results in the previous studies investigating oxidant/antioxidant systems in psoriasis.The aim of this work was to evaluate the plasma levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total bilirubin (T. Bili), direct bilirubin (D. Bili), uric acid (UA), apolipoproteins (ApoA1 and ApoB), Lp(a) and activities of paraxonase 1 (PON1) in 100 patients with psoriasis and 100 controls, and to look for a correlation between these parameters in psoriasis.PON1, bilirubin and UA were measured spectrophotometrically, MDA by the high-performance liquid chromatography method, apolipoproteins and Lp(a) by immunoprecipitation assays, and lipid and other biochemical parameters were determined by routine laboratory methods.In patients with psoriasis, there was a significant decrease in PON1, SOD and CAT activities (P < 0.05) and an increase in MDA levels (P < 0.01). Also, the levels of bilirubin (total and direct) and UA were decreased in patients with psoriasis but were not significant (P > 0.05).These results suggest that psoriasis was in a state of oxidative stress and that the protective effects of high-density lipoprotein against atherosclerosis may be dependent on PON1 activity. Moreover, there is a negative correlation between antioxidant with Lp(a), apoB and MDA levels, suggesting that subjects with higher levels of Lp(a) and apoB and lower levels of antioxidant are more exposed to oxidative damage. These findings may explain in part the reported increase in cardiovascular mortality in psoriasis.

Serum lipid profile in psoriatic patients: correlation between vascular adhesion protein 1 and lipoprotein (a).

Psoriasis is a chronic inflammatory skin disease characterized by excessive cellular replication. Apolipoproteins are genetically determined molecule whose role has been implied in cardiovascular pathology. Vascular adhesion protein-1 (VAP-1) is an adhesion molecule with an enzymatic activity that partakes in the migration process of lymphocytes into sites of inflammation. Our purpose was to evaluate the plasma lipid profiles, apolipoproteins (A1, B) and Lp (a) and VAP-1 in order to compare the lipid profile in psoriatic patients with non-affected persons and correlation between VAP-1 and Lp (a). We determined serum concentrations of lipids, lipoproteins , apolipoproteins and VAP-1 in 90 patients with psoriasis and 90 age matched controls. Serum Lp (a), apo A1 and apo B were measured by immunoprecipitation assays, and the lipids and lipoproteins were measured by enzymatic methods.The VAP-1 were measured by ELISA method. The mean levels of total cholesterol, LDL, apo B and VAP-1 in patients with psoriasis were found to be significantly higher than those of healthy subjects (P<0.05. In psoriatic patients, elevation of VAP-1 correlated with elevation of Lp (a) (p = 0.025). This study shows that high serum lipid level and VAP-1, is significantly more common in psoriasis. This fact may be responsible for higher prevalence of cardiovascular accident in psoriatic patients.

Spectroscopic characterization of furosemide binding to human carbonic anhydrase II.

This study reports the interaction between furosemide and human carbonic anhydrase II (hCA II) using fluorescence, UV-vis and circular dichroism (CD) spectroscopy. Fluorescence data indicated that furosemide quenches the intrinsic fluorescence of the enzyme via a static mechanism and hydrogen bonding and van der Walls interactions play the major role in the drug binding. The binding average distance between furosemide and hCA II was estimated on the basis of the theory of Förster energy transfer. Decrease of protein surface hydrophobicity was also documented upon furosemide binding. Chemical modification of hCA II using N-bromosuccinimide indicated decrease of the number of accessible tryptophans in the presence of furosemide. CD results suggested the occurance of some alterations in α-helical content as well as tertiary structure of hCA II upon drug binding.