In silico design and mechanistic study of niosome-encapsulated curcumin against multidrug-resistant Staphylococcus aureus biofilms.

Curcumin, an important natural component of turmeric, has been known for a long time for its antimicrobial properties. This study aimed to investigate the anti-biofilm action of the niosome-encapsulated curcumin and explore the involved anti-biofilm mechanism. In silico investigations of ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) were first performed to predict the suitability of curcumin for pharmaceutical application. Curcumin showed low toxicity but at the same time, low solubility and low stability, which, in turn, might reduce its antimicrobial activity. To overcome these intrinsic limitations, curcumin was encapsulated using a biocompatible niosome system, and an encapsulation efficiency of 97% was achieved. The synthesized curcumin-containing niosomes had a spherical morphology with an average diameter of 178 nm. The niosomal curcumin was capable of reducing multi-drug resistant (MDR) Staphylococcus aureus biofilm 2-4-fold compared with the free curcumin. The encapsulated curcumin also demonstrated no significant cytotoxicity on the human foreskin fibroblasts. To understand the interaction between curcumin and S. aureus biofilm, several biofilm-related genes were analyzed for their expression. N-acetylglucosaminyl transferase (IcaD), a protein involved in the production of polysaccharide intercellular adhesion and known to play a function in biofilm development, was found to be downregulated by niosomal curcumin and showed high binding affinity (-8.3 kcal/mol) with curcumin based on molecular docking analysis. Our study suggests that the niosome-encapsulated curcumin is a promising approach for the treatment of MDR S. aureus biofilm and can be extended to biofilms caused by other pathogens.

Polyvinyl Alcohol (PVA)-Based Nanoniosome for Enhanced in vitro Delivery and Anticancer Activity of Thymol.

Introduction: There is an unmet need to develop potent therapeutics against cancer with minimal side effects and systemic toxicity. Thymol (TH) is an herbal medicine with anti-cancer properties that has been investigated scientifically. This study shows that TH induces apoptosis in cancerous cell lines such as MCF-7, AGS, and HepG2. Furthermore, this study reveals that TH can be encapsulated in a Polyvinyl alcohol (PVA)-coated niosome (Nio-TH/PVA) to enhance its stability and enable its controlled release as a model drug in the cancerous region. Materials and Methods: TH-loaded niosome (Nio-TH) was fabricated and optimized using Box-Behnken method and the size, polydispersity index (PDI) and entrapment efficiency (EE) were characterized by employing DLS, TEM and SEM, respectively. Additionally, in vitro drug release and kinetic studies were performed. Cytotoxicity, antiproliferative activity, and the mechanism were assessed by MTT assay, quantitative real-time PCR, flow cytometry, cell cycle, caspase activity evaluation, reactive oxygen species investigation, and cell migration assays. Results: This study demonstrated the exceptional stability of Nio-TH/PVA at 4 °C for two months and its pH-dependent release profile. It also showed its high toxicity on cancerous cell lines and high compatibility with HFF cells. It revealed the modulation of Caspase-3/Caspase-9, MMP-2/MMP-9 and Cyclin D/ Cyclin E genes by Nio-TH/PVA on the studied cell lines. It confirmed the induction of apoptosis by Nio-TH/PVA in flow cytometry, caspase activity, ROS level, and DAPI staining assays. It also verified the inhibition of metastasis by Nio-TH/PVA in migration assays. Conclusion: Overall, the results of this study revealed that Nio-TH/PVA may effectively transport hydrophobic drugs to cancer cells with a controlled-release profile to induce apoptosis while exhibiting no detectable side effects due to their biocompatibility with normal cells.

Encapsulation of Thymol in Gelatin Methacryloyl (GelMa)-Based Nanoniosome Enables Enhanced Antibiofilm Activity and Wound Healing.

Non-healing wounds impose huge cost on patients, healthcare, and society, which are further fortified by biofilm formation and antimicrobial resistance (AMR) problems. Here, Thymol, an herbal antimicrobial agent, is utilized to combat AMR. For efficient delivery of Thymol gelatin methacryloyl (GelMa), a hydrophilic polymeric hydrogel with excellent biocompatibility combined with niosome was used to encapsulate Thymol. After optimization of the niosomal Thymol (Nio-Thymol) in the company of GelMa (Nio-Thymol@GelMa) to achieve maximum entrapment efficiency, minimum size, and low polydispersity index, the Thymol release peaked at 60% and 42% from Nio-Thymol@GelMa in medium with pH values of 6.5 and 7.4 after 72 h, respectively. Furthermore, Nio-Thymol@GelMa demonstrated higher antibacterial and anti-biofilm activity than Nio-Thymol and free Thymol against both Gram-negative and Gram-positive bacteria. Interestingly, compared with other obtained formulations, Nio-Thymol@GelMa also led to greater enhancement of migration of human dermal fibroblasts in vitro, and higher upregulation of the expression of certain growth factors such as FGF-1, and matrix metalloproteinases such as MMP-2 and MMP-13. These results suggest that Nio-Thymol@GelMa can represent a potential drug preparation for Thymol to enhance the wound healing process and antibacterial efficacy.

Metabiotic extracted from Bifidobacterium bifidum modulates antioxidant capacity and inflammatory responses during peptic ulcer healing in male wistar rats: a preliminary study.

Background and Objectives: Peptic ulcer disease is a multifactorial disease that affects up to 10% of people. The use of natural product remedies has received much attention for its treatment. In this research, the healing effect of metabiotic extracted from Bifidobacterium bifidum was investigated. Materials and Methods: 45 male wistar rats were divided into 3 groups (Ctrl-, drug, and metabiotic), and stomach ulcers were induced by ethanol administration and treated by drug and metabiotic. The healing process was investigated on different days by histological analysis and qRT-PCR. Results: The metabiotic increased IL-8 and PDGF expression and stimulated the recruitment of polymorphonuclear cells to the wound site. It caused a faster onset of the inflammation phase followed by the proliferation phase. The metabiotic increased the expression of SOD and GPx genes and the antioxidant capacity of the wound. The increase in EGF expression led to faster re-epithelization, which was evident in the wound closure process. Conclusion: Metabiotic extracted from B. bifidum is a promising candidate for the treatment of PUD. It causes a faster onset of the inflammation phase. Improving the antioxidant status of the wound, causes a faster resolution of inflammation, which leads to the acceleration of the wound-healing process.

Biogenic synthesis of gold nanoparticles using Satureja rechingeri Jamzad: a potential anticancer agent against cisplatin-resistant A2780CP ovarian cancer cells.

Drug resistance of cancer cells is a major issue in cancer treatment. Plant-mediated nanoparticle synthesis has been applied in recent years to overcome this problem. In this study, the biogenic synthesis of AuNPs was explored using Satureja rechingeri Jamzad aqueous leaf extract, and their anticancer effects were evaluated in cisplatin-resistant A2780CP ovarian cancer cells. The chemical composition of S. rechingeri Jamzad was analyzed using gas chromatography-mass spectrometry. The characteristics of green-synthesized AuNPs were confirmed using XRD, FTIR, UV-visible spectroscopy, TEM, SEM, EDX, DLS, and zeta potential. The cytotoxic effects of AuNPs and S. rechingeri Jamzad aqueous extract on cisplatin-resistant A2780CP ovarian cancer cells were evaluated by MTT assay and flow cytometry. Real-time PCR analyzed gene expression. The chemical composition revealed that carvacrol (89%) was the main component of the S. rechingeri Jamzad extract. The average size of the spherical biosynthesized AuNPs was 15.1 ± 3.7 nm. The AuNPs and plant extract inhibited the growth of cisplatin-resistant ovarian cancer cells in a time- and dose-dependent manner. The apoptotic cell death was confirmed by flow cytometry and DAPI staining. The proapoptotic genes were upregulated, while anti-apoptotic and metastatic genes were downregulated. According to the cell cycle analysis, cancer cells were arrested in the G0/G1 phase. Considering the anticancer activity of the synthesized AuNPs using S. rechingeri Jamzad and the low side effects of AuNPs on normal cells, these AuNPs showed strong potential for use as biological agents in drug-resistant cancer cells treatment.

Niosomes-loaded selenium nanoparticles as a new approach for enhanced antibacterial, anti-biofilm, and anticancer activities.

Targeted drug delivery and increasing the biological activity of drugs is one of the recent challenges of pharmaceutical researchers. Niosomes are one of the new targeted drug delivery systems that enhances the biological properties of drugs. In this study, for the first time, the green synthesis of selenium nanoparticles (SeNPs), and its loading into niosome was carried out to increase the anti-bacterial and anti-cancer activity of SeNPs. Different formulations of noisome-loaded SeNPs were prepared, and the physical and chemical characteristics of the prepared niosomes were investigated. The antibacterial and anti-biofilm effects of synthesized niosomes loaded SeNPs and free SeNPs against standard pathogenic bacterial strains were studied, and also its anticancer activity was investigated against breast cancer cell lines. The expression level of apoptotic genes in breast cancer cell lines treated with niosome-loaded SeNPs and free SeNPs was measured. Also, to evaluate the biocompatibility of the synthesized niosomes, their cytotoxicity effects against the human foreskin fibroblasts normal cell line (HFF) were studied using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The results illustrated that the optimal formulation had an average size of 177.9 nm, a spherical shape, and an encapsulation efficiency of 37.58%. Also, the results revealed that the release rate of SeNPs from niosome-loaded SeNPs and free SeNPs was 61.26% and 100%, respectively, in 72 h. Also, our findings demonstrated that the niosome-loaded SeNPs have significant antibacterial, anti-biofilm, and anticancer effects compared to the free SeNPs. In addition, niosome-loaded SeNPs can upregulate the expression level of Bax, cas3, and cas9 apoptosis genes while the expression of the Bcl2 gene is down-regulated in all studied cell lines, significantly. Also, the results of the MTT test indicated that the free niosome has no significant cytotoxic effects against the HFF cell line which represents the biocompatibility of the synthesized niosomes. In general, based on the results of this study, it can be concluded that niosomes-loaded SeNPs have significant anti-microbial, anti-biofilm, and anti-cancer effects, which can be used as a suitable drug delivery system.

Glucomannan as a Dietary Supplement for Treatment of Breast Cancer in a Mouse Model.

Konjac glucomannan (KGM) is a water-soluble polysaccharide derived from the Amorphophallus's tuber and, as herbal medicine has shown, can suppress tumor growth or improve health. However, there has been no investigation into the effects of KGM on breast tumor-bearing mice. Therefore, in two cohort experiments, we assessed the effect of glucomannan at daily doses of 2 and 4 mg for 28 days as a dietary supplement and also glucomannan in combination with tumor lysate vaccine as an adjuvant. Tumor volume was monitored twice weekly. In addition, TNF-α cytokines and granzyme B (Gr-B) release were measured with ELISA kits, and IL-2, IL-4, IL-17, and IFN-γ were used as an index for cytotoxic T lymphocyte activity. Moreover, TGF-ß and Foxp3 gene expression were assessed in a real-time PCR test. The results show that glucomannan as a dietary supplement increased the IFN-γ cytokine and Th1 responses to suppress tumor growth. Glucomannan as a dietary supplement at the 4 mg dose increased the IL-4 cytokine response compared to control groups. In addition, cell lysate immunization with 2 or 4 mg of glucomannan suppressed tumor growth. As an adjuvant, glucomannan at both doses showed 41.53% and 52.10% tumor suppression compared with the PBS group. Furthermore, the administration of glucomannan as a dietary supplement or adjuvant reduced regulatory T cell response through decreasing TGF-ß and Foxp3 gene expression in the tumor microenvironment. In conclusion, glucomannan as a dietary supplement or adjuvant enhanced the immune responses of tumor-bearing mice and decreased immune response suppression in the tumor milieu, making it a potentially excellent therapeutic agent for lowering breast tumor growth.

Folate-Targeted Curcumin-Loaded Niosomes for Site-Specific Delivery in Breast Cancer Treatment: In Silico and In Vitro Study.

As the most common cancer in women, efforts have been made to develop novel nanomedicine-based therapeutics for breast cancer. In the present study, the in silico curcumin (Cur) properties were investigated, and we found some important drawbacks of Cur. To enhance cancer therapeutics of Cur, three different nonionic surfactants (span 20, 60, and 80) were used to prepare various Cur-loaded niosomes (Nio-Cur). Then, fabricated Nio-Cur were decorated with folic acid (FA) and polyethylene glycol (PEG) for breast cancer suppression. For PEG-FA@Nio-Cur, the gene expression levels of Bax and p53 were higher compared to free drug and Nio-Cur. With PEG-FA-decorated Nio-Cur, levels of Bcl2 were lower than the free drug and Nio-Cur. When MCF7 and 4T1 cell uptake tests of PEG-FA@Nio-Cur and Nio-Cur were investigated, the results showed that the PEG-FA-modified niosomes exhibited the most preponderant endocytosis. In vitro experiments demonstrate that PEG-FA@Nio-Cur is a promising strategy for the delivery of Cur in breast cancer therapy. Breast cancer cells absorbed the prepared nanoformulations and exhibited sustained drug release characteristics.

Coinfection of torque teno virus (TTV) and human papillomavirus (HPV) in cervical samples of women living in Tehran, Iran.

Background and Objectives: Torque Teno virus or transfusion-transmitted virus (TTV) is a non-enveloped virus with a single strand circular DNA genome that currently is classified in the Alphatorquevirus genus and the family of Anelloviridae. Unlike other DNA viruses, TTV has an extremely wide genomic diversity. This virus, based on previous studies, infects both healthy people, as well as those who have HCV and human papillomavirus (HPV). This study aimed to evaluate the coinfection of torque teno virus (TTV) and HPV in cervical samples from Iranian women. Materials and Methods: In this case-control study, the fresh cervical cytobrush specimens were collected from 150 women referred to Dena laboratory in Tehran. Viral DNA was extracted from samples. The HPV-DNA was detected and genotyped. Then, nested polymerase chain reaction (Nested PCR) was performed for TTV using specific primers. Results: Among 50 cervical specimens without HPV, 14 were TTV positive (28%); among 50 low-risk HPV cervical specimen, 23 were TTV positive (46%), and from 50 high-risk HPV cervical specimen, 48 were TTV positive (96%). There is a significantly higher prevalence of TTV virus in low-risk and high-risk papillomavirus-infected specimens than in healthy specimens (p 0.0001). Additionally, TTV is more prevalent in samples containing high-risk papillomaviruses than in samples with low-risk papillomaviruses (P = 0.048). Conclusion: The higher prevalence of TTV among people infected with papillomavirus than in non-infected people indicates that both viruses are transmitted by the same mechanism (sexual route). In addition, the prevalence of TTV in samples containing high-risk papillomavirus is significantly higher than that in samples containing low-risk papillomavirus. The presence of papillomaviruses, particularly high-risk types, may be associated with TTV proliferation, which requires further research in the future.

The Optimized Formulation of Tamoxifen-Loaded Niosomes Efficiently Induced Apoptosis and Cell Cycle Arrest in Breast Cancer Cells.

The aim, as proof of concept, was to optimize niosomal formulations of tamoxifen in terms of size, morphology, encapsulation efficiency, and release kinetics for further treatment of the breast cancer (BC). Different assays were carried out to evaluate the pro-apoptotic and cytotoxicity impact of tamoxifen-loaded niosomes in two BC cells, MDA-MB-231 and SKBR3. In this study, tamoxifen was loaded in niosomes after optimization in the formulation. The formulation of niosomes supported maximized drug entrapment and minimized their size. The novel formulation showed improvement in storage stability, and after 60 days only, small changes in size, polydispersity index, and drug entrapment were observed. Besides, a pH-dependent release pattern of formulated niosomes displayed slow release at physiological pH (7.4) and a considerable increase of release at acidic pH (5.4), making them a promising candidate for drug delivery in the BC treatment. The cytotoxicity study exhibited high biocompatibility with MCF10A healthy cells, while remarkable inhibitory effects were observed after treatment of cancerous lines, MDA-MB-231, and SKBR3 cells. The IC50 values for the tamoxifen-loaded niosomes were significantly less than other groups. Moreover, treatment with drug-loaded niosomes significantly changed the gene expression pattern of BC cells. Statistically significant down-regulation of cyclin D, cyclin E, VEGFR-1, MMP-2, and MMP-9 genes and up-regulation of caspase-3 and caspase-9 were observed. These results were in correlation with cell cycle arrest, lessoned migration capacity, and increased caspase activity and apoptosis induction in cancerous cells. Optimization in the formulation of tamoxifen-loaded niosomes can make them a novel candidate for drug delivery in BC treatment.

Improvement of hepatitis B vaccine to induce IFN-γ cytokine response: A new formulation.

Hepatitis B virus (HBV) infection is limited through vaccination against HBsAg formulated in the Alum adjuvant. However, this alum-formulated vaccine fails to be preventive in some cases, also known as non-responders. Recent studies have shown the immunomodulatory effect of α-tocopherol in various models. Here, we developed a new formulation for HBsAg using α-tocopherol, followed by assessment of immune responses. Experimental BALB/c mice were immunized with a commercial alum-based vaccine or the one formulated in α-tocopherol at different doses. Mice were immunized subcutaneously with 5 µg of HBsAg with different formulations three times with 2-week intervals. Specific total IgG, IgG1, and IgG2a isotypes of antibodies were measured by ELISA. Immunologic cytokines, such as IFN-γ, IL-4, IL-2, and TNF-α, were also evaluated through commercial ELISA kits. Our results showed that the new α-tocopherol-formulated vaccine had the ability to reinforce specific total IgG responses. Moreover, α-tocopherol in the HBsAg vaccine increased IFN-γ, IL-2, and TNF-α cytokines at higher concentrations; however, the vaccine suppressed IL-4 cytokine release. At a lower concentration of α-tocopherol, the IL-4 cytokine response increased without a positive effect on IFN-γ and TNF-α cytokine response. It seems that α-tocopherol can change the immune responses against HBsAg; however, the type of response depends on the dose of α-tocopherol used in the vaccine formulation.

Super Magnetic Niosomal Nanocarrier as a New Approach for Treatment of Breast Cancer: A Case Study on SK-BR-3 and MDA-MB-231 Cell Lines.

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe2O4 core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe2O4@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe2O4@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.

Anti-cancer & anti-metastasis properties of bioorganic-capped silver nanoparticles fabricated from Juniperus chinensis extract against lung cancer cells.

The current study evaluated the anti-cancer properties of bio-functionalized silver nanoparticles fabricated by Juniperus chinensis leaf extracts. The nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy, UV-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering, Zeta potential and X-ray spectroscopy. Further, this study elucidated the cellular and molecular mechanisms of nanoparticles for anti-proliferative and apoptotic effects on human lung cancer cells (A549) and compared them with commercial drug cisplatin. The size of the spherical nanoparticle was 12.96 nm with negative zeta potential. Up-regulation of caspase 3,9 and p53, Annexin V-FITC/PI, DAPI staining, and ROS production indicated the remarkable apoptotic effect of AgNPs compared to cisplatin. Moreover, down-regulation of MMP2/MMP9 scratch and matrigel assays revealed anti-metastatic properties of AgNPs. Cell cycle analysis and downregulation of cyclin D1 indicated cancer cell cessation in the G0/G1 phase. Overall, the results revealed that the green-synthetized AgNPs had anti-metastasis and anti-proliferation effects on lung cancer cells in comparison to cisplatin with lower side effects on the normal cell line.

Preparation, Optimization and In-Vitro Evaluation of Curcumin-Loaded Niosome@calcium Alginate Nanocarrier as a New Approach for Breast Cancer Treatment.

Cancer is one of the most common causes of mortality, and its various treatment methods can have many challenges for patients. As one of the most widely used cancer treatments, chemotherapy may result in diverse side effects. The lack of targeted drug delivery to tumor tissues can raise the possibility of damage to healthy tissues, with attendant dysfunction. In the present study, an optimum formulation of curcumin-loaded niosomes with a calcium alginate shell (AL-NioC) was developed and optimized by a three-level Box-Behnken design-in terms of dimension and drug loading efficiency. The niosomes were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering. The as-formulated niosomes showed excellent stability for up to 1 month at 4 °C. Additionally, the niosomal formulation demonstrated a pH-dependent release; a slow-release profile in physiological pH (7.4), and a more significant release rate at acidic conditions (pH = 3). Cytotoxicity studies showed high compatibility of AL-NioC toward normal MCF10A cells, while significant toxicity was observed in MDA-MB-231 and SKBR3 breast cancer cells. Gene expression studies of the cancer cells showed downregulation of Bcl2, cyclin D, and cyclin E genes, as well as upregulation of P53, Bax, caspase-3, and caspase-9 genes expression following the designed treatment. Flow cytometry studies confirmed a significant enhancement in the apoptosis rate in the presence of AL-NioC in both MDA-MB-231 and SKBR3 cells as compared to other samples. In general, the results of this study demonstrated that-thanks to its biocompatibility toward normal cells-the AL-NioC formulation can efficiently deliver hydrophobic drugs to target cancer cells while reducing side effects.

Ecofriendly Biomolecule-Capped Bifidobacterium bifidum-Manufactured Silver Nanoparticles and Efflux Pump Genes Expression Alteration in Klebsiella pneumoniae.

Background: Klebsiella pneumoniae is currently considered as an immediate threat to human health due to its various multidrug efflux pumps. Microbially synthesized silver nanoparticles (AgNPs) are an attractive and eco-friendly approach to prevent antibiotic resistance in bacteria. In the present study, we compared the inhibitory effect of both commercial and green AgNPs by Bifidobacterium bifidum on OxqAB efflux pump genes in ciprofloxacin-resistant strains of K. pneumoniae. Materials and Methods: AgNPs were characterized by ultraviolet-visible spectrophotometer, Fourier transform infrared spectroscopy, X-ray diffraction, zeta potential, transmission electron microscopy, and scanning electron microscopy. Antibiogram was used to identify resistant isolates and the effect of the biosynthesized AgNPs against OxqAB efflux pump strains was assessed by the minimum inhibitory concentration (MIC) method. The expression levels of oxqAB genes were evaluated using real-time polymerase chain reaction (PCR) followed by exposure to subMICs of the AgNPs. Results: PCR results showed that 25 strains had OxqAB efflux pump and the MIC method indicated that AgNPs had an inhibitory effect on all resistant strains with OxqAB efflux pump. The efficacy of the synthetic nanoparticles was assessed by comparing the antiefflux pump activity with commercial AgNPs. In ciprofloxacin-resistant isolates, the oxqAB genes expression levels reduced in the subMIC of both AgNPs, whereas biosynthesized AgNPs had greater bactericidal effects compared with the commercial AgNPs. Conclusions: Efflux pumps could be an attractive target for our biosynthesized AgNPs. The oxqAB genes expression levels reduced in subMIC of both AgNPs, whereas biosynthesized AgNPs had greater bactericidal effects than the commercial AgNPs.

Preparation and optimization of ciprofloxacin encapsulated niosomes: A new approach for enhanced antibacterial activity, biofilm inhibition and reduced antibiotic resistance in ciprofloxacin-resistant methicillin-resistance Staphylococcus aureus.

Ciprofloxacin is an alternative to vancomycin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. The objective of this study was to optimization of niosomes encapsulated ciprofloxacin and evaluate their antibacterial and anti-biofilm efficacies against ciprofloxacin-resistant methicillin-resistant S. aureus (CR-MRSA) strains. Formulation of niosomes encapsulated ciprofloxacin were optimized by changing the proportions of Tween 60, Span 60, and cholesterol. The optimized ciprofloxacin encapsulated niosomal formulations based on Span 60 and Tween 60 were prepared and characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The SEM and TEM results showed that the formulation of niosomes encapsulated ciprofloxacin were spherical with a size between 50 and 150 nm. The prepared niosomal formulations showed high storage stability up to 30 days with the slight change in size and drug entrapment during the storage, making them good candidates for drug delivery systems. Optimum niosome encapsulated ciprofloxacin enhanced antibacterial activity against CR-MRSA strains via reduction in minimum inhibitory concentration (MIC) value and inhibited significantly biofilm formation. Niosome encapsulated ciprofloxacin down-regulated the expression of icaB biofilm formation gene. Our results showed that encapsulating ciprofloxacin in niosomes is a promising approach to enhanced antibacterial activity, biofilm inhibition and reduced resistance to antibiotic in CR-MRSA strains.

A narrative literature review on traditional medicine options for treatment of corona virus disease 2019 (COVID-19).

Coronavirus disease 2019 (COVID-19) as a life-threatening disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is accounted as global public health concern. Treatment of COVID-19 is primarily supportive and the role of antiviral agents is yet to be established. However, there are no specific anti-COVID-19 drugs and vaccine until now. This review focuses on traditional medicine such as medicinal plant extracts as promising approaches against COVID-19. Chinese, Indian and Iranian traditional medicine, suggests some herbs for prevention, treatment and rehabilitation of the diseases including COVID-19. Although, inhibition of viral replication is considered as general mechanism of herbal extracts, however some studies demonstrated that traditional herbal extracts can interact with key viral proteins which are associated with virus virulence. Chinese, Indian and Iranian traditional medicine, suggests some herbs for prevention, treatment and rehabilitation of the diseases including COVID-19. However the beneficial effects of these traditional medicines and their clinical trials remained to be known. Herein, we reviewed the latest updates on traditional medicines proposed for treatment of COVID-19.

Niosomal delivery of simvastatin to MDA-MB-231 cancer cells.

OBJECTIVE: The objective of this study was to use nano-niosomal formulations to deliver simvastatin as a poor-water soluble drug into breast cancer cells. SIGNIFICANCE: Our study focused on the problem associated with poor water-soluble drugs which have significant biological activity in vivo. METHODS: Different niosomal formulations of simvastatin were prepared and characterized in terms of morphology, size, encapsulation efficiency (EE), and release kinetic. Antiproliferative activity and the mechanism were assessed by quantitative real-time PCR and flow cytometry. Moreover, confocal microscopy was employed to analyze the cell uptake of simvastatin loaded niosomes to the cancerous cells. RESULTS: Size, polydispersity index (PDI), and EE of the best formulation were obtained as 164.8 nm, 0.232, and 97%, respectively. The formulated simvastatin had a spherical shape and showed a slow release profile of the drug after 72 h. Stability data elucidated an increase in mean diameter and PDI which was lower for 4 °C than 25 °C. Confocal microscopy showed the localization of drug loaded niosomes in the cancer cells. The MTT assay revealed both free drug and drug loaded niosomes exhibited a dose-dependent cytotoxicity against breast cancer cells (MDA-MB-231 cells). Flow cytometry and qPCR analysis revealed drug loaded niosomes exert their cytotoxicity on cancerous cells via regulation of apoptotic and anti-apoptotic genes. CONCLUSION: The prepared niosomal simvastatin showed good physicochemical and biological properties than free drug. Our study suggests that niosomal delivery could be considered as a promising strategy for the delivery of poor water-soluble drugs to cancer cells.

Antibacterial, anti-efflux, anti-biofilm, anti-slime (exopolysaccharide) production and urease inhibitory efficacies of novel synthesized gold nanoparticles coated Anthemis atropatana extract against multidrug- resistant Klebsiella pneumoniae strains.

In this study, the antibacterial, anti-efflux, anti-biofilm, anti-slime (exopolysaccharide) production and urease inhibitory efficacies of green synthesized gold nanoparticles (AuNPs) coated Anthemis atropatana extract against multidrug- resistant (MDR) Klebsiella pneumoniae strains were evaluated. The green synthesized AuNPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffractometer (XRD), particle size distribution, zeta potential and Fourier-transform infrared spectroscopy (FTIR). Then, antibacterial, anti-slime (exopolysaccharide) production, anti-biofilm and anti-efflux activities of AuNPs were investigated using micro-dilation, Congored agar, microtiter plate and MIC of ethidium bromide methods, respectively. Subsequently, the expression of mrkA, wzm and acrB genes was evaluated using quantitative Real-Time PCR (qRT-PCR). The synthesized AuNPs exhibited antibacterial activity against MDR strains of K. pneumoniae (minimum inhibitory concentration (MIC) of 6.25-50 µg/ml), as well as showed significant anti-slime (exopolysaccharide) production, anti-biofilm and anti-efflux activities against MDR strains. AuNPs showed significant inhibition against jack-bean urease and down-regulated the expression of mrkA, wzm and acrB genes. Moreover, the in vitro cytotoxic activity confirmed by MTT assay on the HEK-293 normal cell line showed negligible cytotoxicity. Thus, the present study suggests the potential use of AuNPs in the development of novel therapeutics for the prevention of biofilm-associated K. pneumoniae infections.

Synthesis and characterization of alginate nanocarrier encapsulating Artemisia ciniformis extract and evaluation of the cytotoxicity and apoptosis induction in AGS cell line.

The aim of this study was to synthesize the alginate nanogel encapsulating Artemisia ciniformis extract and to evaluate its apoptotic effects on AGS gastric cancer cells. Characterization of the synthesized nanogel was confirmed by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Dynamic light scattering method (DLS), and Zeta potential. The cytotoxic effects and apoptosis induction of A. ciniformis extract, nanogel encapsulating A. ciniformis extract and alginate nanogel alone were evaluated in the AGS cell line using MTT assay, Annexin-FITC, DAPI staining, cell cycle analysis, and real-time PCR for 24, 48 and 72 h. Anti-proliferative activity and apoptosis induction were observed in the cells treated with alginate nanogel encapsulating A. ciniformis extract and free extract. The alginate nanogel encapsulating A. ciniformis extract had greater potential for the induction of apoptosis than free extract. Flow cytometric results of the cell cycle showed that synthesized nanogel encapsulating A. ciniformis extract could inhibit cell proliferation and arrest the cell cycle at the G0/G1 phase. Induction of apoptosis occurred in a time-, and dose-dependent manner. Expression levels of pro-apoptotic genes were up-regulated. Down-regulation of anti-apoptotic and metastatic genes were detected. It can be concluded that nanogel encapsulating A. ciniformis extract would be a potent anticancer agent against AGS gastric cancer cells.