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Globally, skin cancer is a main public health challenge whose incidence is continuously increasing. Given the limitations of conventional t herapies, new research and novel therapies may be promising for reducing skin cancer morbidity and mortality. Phytochemicals are attractive resources for new therapy design in cancer research due to their cost-effectiveness and lower side effects. In the present study, the anti-cancer activity of Oliveria decumbens (O.decumbens) extract was investigated on the human skin cancer A431 cell line A431. The aqueous extract of the O.decumbens plant was prepared using the traditional method. Then IC50 was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay under different concentrations of O. decumbens. Cell apoptosis was investigated by Annexin V-FITC/Propidium Iodide (PI) and flow cytometry. Cell cycle was investigated by PI staining and flow cytometry. Reactive oxygen species (ROS) production was analyzed by DCFH-DA (2', 7' -dichlorofluorescein-diacetate) staining and flowcytometry.IC50 for cell viability was determined 475 μg/ml. Cell cycle analyses showed G1 arrest in treated cells compared to control cell. Results also confirmed significant increase of apoptotic cells (8.2±%1, P<0.05) under IC50 concentration of the extract in comparison to the control group (2.5±0.99%). A significant increase in ROS level was observed in O.ecumbens treated cells compared to control cells (738± 170 vs 316±55 in the control group, P<0.05.).Overall, the present results indicate that O.decumbens extract can inhibit skin cancer cell proliferation via inhibition of cell cycle and apoptosis. It seems that ROS production plays a critical role in the anticancer effect of O. decumbens extract. Therefore, its potential option for future treatment of skin cancer should be considered. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common cancers among women and can be fatal if not diagnosed and treated on time. Various genetic and environmental factors play a significant role in the development and progression of BC. Within the body, different signaling pathways have been identified that contribute to cancer progression, or conversely, cancer prevention. Phosphatase and tensin homolog (PTEN) is one of the proteins that prevent cancer by inhibiting the oncogenic PI3K/Akt/mTOR signaling pathway. MicroRNAs (miRNAs) are molecules with about 18 to 28 base pairs, which regulate about 30% of human genes after transcription. miRNAs play a key role in the progression or prevention of cancer through different signaling pathway and mechanisms, e.g., apoptosis, angiogenesis, and proliferation. miRNAs, which are upstream mediators of PTEN, can reinforce or suppress the effect of PTEN signaling on BC cells, and suppressing the PTEN signaling, linked to weakness of the cancer cells to chemotherapeutic drugs. However, the precise mechanism and function of miRNAs on PTEN in BC are not yet fully understood. Therefore, in the present study, has been focused on miRNAs regulating PTEN function in BC., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Extracellular vesicles (EV) secreted from cancer cells are present in various biological fluids, carrying distinctly different cellular components compared to normal cells, and have great potential to be used as markers for disease initiation, progression, and response to treatment. This under-utilised tool provides insights into a better understanding of prostate cancer., Methods: EV from serum and urine of healthy men and castration-resistant prostate cancer (CRPC) patients were isolated and characterised by transmission electron microscopy, particle size analysis, and western blot. Proteomic and cholesterol liquid chromatography-mass spectrometry (LC-MS) analyses were conducted., Results: There was a successful enrichment of small EV/exosomes isolated from serum and urine. EV derived from biological fluids of CRPC patients had significant differences in composition when compared with those from healthy controls. Analysis of matched serum and urine samples from six prostate cancer patients revealed specific EV proteins common in both types of biological fluid for each patient., Conclusion: Some of the EV proteins identified from our analyses have potential to be used as CRPC markers. These markers may depict a pattern in cancer progression through non-invasive sample collection., (© 2022. The Author(s).)

In December 2019, a new infectious complication called CoronaVirus Infectious Disease-19, briefly COVID-19, caused by SARS-COV-2, is identified in Wuhan, China. It spread all over the world and became a pandemic. In many individuals who had suffered SARS-COV-2 infection, cytokine storm starts through cytokine overproduction and leads to Acute Respiratory Syndrome (ARS), organ failure, and death. According to the obtained evidence, Vitamin D (VitD) enhances the ACE2/Ang(1-7)/MasR pathway activity, and it also reduces cytokine storms and the ARS risk. Therefore, VitD intake may be beneficial for patients with SARS-COV-2 infection exposed to cytokine storm but do not suffer hypotension. In the present review, we have explained the effects of VitD on the renin-angiotensin system (RAS) function and angiotensin-converting enzyme2 (ACE2) expression. Furthermore, we have reviewed the biochemical and immunological effects of VitD on immune function in the underlying diseases and its role in the COVID-19 pandemic.

Fluorophores emitting in the near-infrared (NIR) wavelength region present optimal characteristics for photonics and especially bioimaging. Unfortunately, only few NIR fluorescent materials are known, and even fewer are biocompatible. For this reason, the scientific interest in designing NIR fluorophores is very high. Egyptian Blue (CaCuSi 4 O 10 , EB) is an NIR fluorescent layered silicate that can be exfoliated into fluorescent nanosheets (EB-NS). So far, its surface chemistry has not been tailored, but this is crucial for colloidal stability and biological targeting. Here, we demonstrate covalent surface functionalization of EB nanosheets (EBfunc) via Si-H activation using hydrosilanes with variable functionalities. In the first part of this work, EB-NS are grafted with the visible fluorescent pyrene (Pyr) moieties to demonstrate conjugation by colocalization of the Vis/NIR fluorescence on the (single) EB-NS level. Next, the same grafting procedure was repeated and validated with carboxyl group (COOH)-containing hydrosilanes. These groups serve as a generic handle for further (bio)functionalization of the EB-NS surface. In this way, folic acid (FA) could be conjugated to EB-NS, allowing the targeting of folic acid receptor-expressing cancer cells. These results highlight the potential of this surface chemistry approach to modify EB-NS, enabling targeted NIR imaging for biomedical applications.

Objects: Shortly after cancer is diagnosed, a phenomenon develops in cancer cells called multidrug resistance (MDR), in which cell sensitivity against anti-cancer drugs is significantly reduced. The present investigation aimed to assess the effects of nitazoxanide (NTZ), a safe drug, on LS174T/OXP-resistant cells., Methods: In the current in vitro research, the effects of NTZ and oxaliplatin (OXP) on the viability of LS174T and LS174T/OXP cell lines were evaluated through MTT assay. Then, the changes in expression levels of MDR1, MRP1, BCRP, and LRP genes and proteins were measured by RT-qPCR and western blotting methods, respectively. Lastly, the apoptosis status was assessed by annexin V-FITC/PI staining flow cytometry assay., Results: The IC50 values for cells resistant or sensitive to OXP were revealed (11567 nM vs. 1745 nM; p <0.05 for 24 h incubation, and 5161 nM vs. 882.2 nM; p <0.05 for 48 h incubation). Moreover, NTZ plus OXP led to a leftward shift in the cytotoxicity curve (2004 nM; p = 0.007). This co-treatment significantly decreased the expression of all genes and proteins ( p <0.05). Finally, the combination of NTZ and OXP induced a significant increase in apoptosis ( p <0.001)., Conclusion: The data showed that NTZ treatment could increase the sensitivity of LS174T/OXP cell line to the OXP cytotoxic effects. Thus, NTZ may be efficient in reducing drug resistance in clinics by means of the negative regulation of ATP-binding cassette (ABC) transporters. However, further studies are necessary to explain the exact mechanisms of NTZ., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Vitiligo is a chronic skin disease, which its etiopathogenesis is not fully understood. Numerous studies have suggested that oxidative stress may play a role in the pathophysiology of vitiligo. There are controversial reports as to the changes of serum trace elements, copper (Cu) and zinc (Zn) levels in vitiligo patients., Objectives: We evaluated the alterations in the level of serum Cu and Zn among a group of Iranian vitiligo patients., Methods: The levels of serum Cu and Zn were compared between 117 vitiligo patients and 137 healthy controls using atomic absorption spectrophotometry., Results: The mean Cu and Zn levels in the cases (113.57 ± 59.43 and 95.01 ± 58.95 μg/dl, respectively) were significantly lower than those of the controls (138.90 ± 38.14 and 121.83 ± 33.80 μg/dl, respectively) (P = 0.00). We also observed significantly lower serum Cu and Zn concentrations in young (< 50 years) than the elderly (≥ 50 years) patients (P = 0.00). The mean Cu and Zn levels in the patients with generalized vitiligo (111.63±54.18 and 93.11±59.33 μg/dl, respectively) were significantly lower than patients with localized vitiligo (120.74 ±71.64 and 98.69±58.63 μg/dl, respectively) and those in the control (P = 0.00). The serum Cu/Zn ratio obtained in the young and male patients was higher than those in their matched controls (P = 0.01)., Conclusions: The current study has shown that the disturbance of serum Cu and Zn levels is associated with vitiligo, and may play an important role in the disease development of Iranian patients., Competing Interests: Competing interests: None., (©2022 Khoshdel et al.)

Infection triggers a dynamic cascade of reciprocal events between host and pathogen wherein the host activates complex mechanisms to recognise and kill pathogens while the pathogen often adjusts its virulence and fitness to avoid eradication by the host. The interaction between the pathogen and the host results in large-scale changes in gene expression in both organisms. Dual RNA-seq, the simultaneous detection of host and pathogen transcripts, has become a leading approach to unravelling complex molecular interactions between the host and the pathogen and is particularly informative for intracellular organisms. The amount of in vitro and in vivo dual RNA-seq data is rapidly growing, which demands computational pipelines to effectively analyse such data. In particular, holistic, systems-level, and temporal analyses of dual RNA-seq data are essential to enable further insights into the host-pathogen transcriptional dynamics and potential interactions. Here, we developed an integrative network-driven bioinformatics pipeline, dRNASb , a systems biology-based computational pipeline to analyse temporal transcriptional clusters, incorporate molecular interaction networks (e.g. protein-protein interactions), identify topologically and functionally key transcripts in host and pathogen, and associate host and pathogen temporal transcriptome to decipher potential between-species interactions. The pipeline is applicable to various dual RNA-seq data from different species and experimental conditions. As a case study, we applied dRNASb to analyse temporal dual RNA-seq data of Salmonella -infected human cells, which enabled us to uncover genes contributing to the infection process and their potential functions and to identify putative associations between host and pathogen genes during infection. Overall, dRNASb has the potential to identify key genes involved in bacterial growth or host defence mechanisms for future uses as therapeutic targets.

Background: Multidrug resistance (MDR) is a major cause of unsuccessful cancer treatment in which drugs are not effective. Therefore, it is necessary to identify the critical mechanisms of the development of MDR and target those with novel compounds. Accordingly, the current study is the first to investigate the combination effect and molecular mechanism of nitazoxanide (NTZ) and oxaliplatin (OXP) on LS174T/OXP-resistant cells., Methods: The effect of NTZ on OXP cytotoxicity in LS174T and LS174T/OXP cell lines was evaluated by MTT assay. Changes in expression levels of MDR1, MRP1, CTNNB1, peptidylarginine deiminase (PAD)2, and PAD4 genes and proteins were evaluated by RT-qPCR and western blotting methods, respectively. Lastly, the apoptosis assay was performed by flow cytometer., Results: OXP resistant and sensitive cells were identified based on the IC50 values (11567 nM vs. 1745 nM, p<0.05 for 24 h treatment; and 5161 nM vs. 882 nM, p<0.05 for 48 h incubation). The combination of NTZ and OXP for 48 h led to a reduction in IC50 values in resistant cells (2154 nM, p<0.05). The effect of NTZ plus OXP significantly decreased the expression of MDR1 (p<0.001), MRP1 (p<0.05), and CTNNB1 (p<0.001), while PAD2 and PAD4 expression was significantly increased (p<0.001). This combination therapy enhanced the percentage of the sub-G1 population (apoptosed) compared to other groups., Conclusion: The results showed that NTZ leads to notable upregulation of PAD2 and PAD4, which can disrupt the Wnt/β-catenin signaling pathway and reverse the MDR by reducing MDR1 and MRP1 expression.

Because of global warming, desertification is increasing. One of the best strategies for combating desertification is reforestation of forests and biological operations of vegetation. However, events like soil salinity and dust storms, as the most important manifestations of desertification, prevent vegetation from settling in these areas. In this study, the effects of two halotolerant plant growth-promoting rhizobacterial strains, Bacillus pumilus HR and Zhihengliuella halotolerans SB, on physiological and nutritional status of the desert halophyte Haloxylon aphyllum under the stress of salinity (0, 300, and 600 mM NaCl) and dust (0 and 1.5 g m -2 month -1 ) were examined. Under dust application, the Z. halotolerans SB strain compared to the B. pumilus HR strain and the combination of these two bacterial strains improved the content of total chlorophyll (247 and 316%), carotenoid (94 and 107%), phosphorus (113 and 209%), magnesium (196 and 212%), and total dry biomass (13 and 28%) in H. aphyllum at salinity levels of 300 and 600 mM NaCl, respectively. Under conditions of combined application of dust and salinity, B. pumilus HR compared to Z. halotolerans SB and the combination of two strains at salinity levels of 300 and 600 mM NaCl, respectively, had better performance in increasing the content of iron (53 and 69%), calcium (38 and 161%), and seedling quality index (95 and 56%) in H. aphyllum . The results also showed that both bacterial strains and their combination were able to reduce the content of ascorbic acid, flavonoid, total phenol, proline, and malondialdehyde, and catalase activity, and ultimately improve the antioxidant capacity of H. aphyllum . This showed that the use of halotolerant rhizobacteria can stop the production of free radicals and thus prevent cell membrane damage and the formation of malondialdehyde under salinity and dust stress. The results of this study for the first time showed that halotolerant rhizobacteria can increase the seedling quality index of H. aphyllum under combined conditions of salinity and dust. The use of these bacteria can be useful in the optimal afforestation of H. aphyllum species in arid and semi-arid ecosystems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Najafi Zilaie, Mosleh Arani, Etesami and Dinarvand.)

Purpose: Despite the promising therapeutic effects of gene silencing with small interfering RNAs (siRNAs), the challenges associated with delivery of siRNAs to the tumor cells in vivo , has greatly limited its clinical application. To overcome these challenges, we employed gold nanoparticles modified with trimethyl chitosan (TMC) as an effective delivery carrier to improve the stability and cellular uptake of siRNAs against epidermal growth factor receptor (EGFR) that is implicated in breast cancer. Methods: AuNPs were prepared by the simple aqueous reduction of chloroauric acid (HAuCl 4 ) with ascorbic acid and coated with synthesized TMC. EGFR-siRNA was then complexed with the AuNPs-TMC via electrostatic interaction to make AuNPs-TMC/EGFR-siRNA with a w/w ratio of 10:1. Nanoparticles were assessed for physicochemical characteristics and in vitro cellular behavior on MCF-7 breast cancer cell line. Results: Spherical and positively charged AuNPs-TMC (67 nm, +45 mV) were successfully complexed with EGFR-siRNA (82 nm, +11 mV) which were able to retard the gene migration completely. Confocal microscopy and flow cytometry analysis demonstrated complete cellular uptake of Cy5 labeled AuNPs-TMC in the MCF-7 cells after 4 h incubation. MTT test after 48 h incubation showed that the AuNPs-TMC were safe but when combined with EGFR-siRNA exert significant cytotoxicity while the cell viability was about 50%. These nanocomplexes also showed a high gene expression knockdown (86%) of EGFR and also a high apoptosis rate (Q2 + Q3 = 18.5%) after 24 h incubation. Conclusion: This study suggests that the simply synthesized AuNPs-TMC are novel, effective, and promising nanocarriers for siRNA delivery, and AuNPs-TMC/EGFR-siRNA appears to be a potential therapeutic agent for breast cancer treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Baghani, Noroozi Heris, Khonsari, Dinarvand, Dinarvand and Atyabi.)

Objectives: One of the most important complications that lead to unsuccessful treatment of cancer is resistance against chemotherapy agents, so called multidrug resistance (MDR). Thus, identification of the novel medications with low side effects and high efficacy to reverse MDR is highly required. Accordingly, the current study was performed to investigate the molecular mechanism of MDR in LS174T and LS174T/Oxaliplatin (OXP) cell lines during treatment with Nitazoxanide (NTZ) in combination with OXP., Materials and Methods: In the present in vitro study, we evaluated the effects of NTZ on the cytotoxicity of OXP using Thiazolyl Blue Tetrazolium Blue (MTT) assay in LS174T and LS174T/OXP cell lines when treated with OXP and NTZ, alone or in combination, for 24 and 48 h incubation. Then, we assessed the changes in the expression level of CTNNB1, ABCB1, c-Myc, and cyclin D1 genes in different treated groups., Results: Exposure of LS174T/OXP cells to NTZ led to the elevation of cell sensitivity to OXP and induced caspase-3/7 activity, which results in apoptosis. Furthermore, NTZ downregulated Wnt/β-catenin signaling pathway through significant decrease of CTNNB1, c-Myc, ABCB1, and cyclin D1 genes and resulted in drug resistance reversal and inhibition of cell proliferation., Conclusion: These results indicate that Wnt/β-catenin pathway is important in developing cancer and MDR. In this regard, NTZ could reverse MDR in colorectal cancer (CRC) cells by downregulation of Wnt/β-catenin signaling pathway, suggesting that NTZ should be more considered in future studies as a potent adjuvant in CRC chemotherapy., Competing Interests: Conflict of Interest None., (Copyright © 2021. Published by Elsevier Inc.)

After its emergence in late 2019 SARS-CoV-2 was declared a pandemic by the World Health Organization on 11 March 2020 and has claimed more than 2.8 million lives. There has been a massive global effort to develop vaccines against SARS-CoV-2 and the rapid and low cost production of large quantities of vaccine is urgently needed to ensure adequate supply to both developed and developing countries. Virus-like particles (VLPs) are composed of viral antigens that self-assemble into structures that mimic the structure of native viruses but lack the viral genome. Thus they are not only a safer alternative to attenuated or inactivated vaccines but are also able to induce potent cellular and humoral immune responses and can be manufactured recombinantly in expression systems that do not require viral replication. VLPs have successfully been produced in bacteria, yeast, insect and mammalian cell cultures, each production platform with its own advantages and limitations. Plants offer a number of advantages in one production platform, including proper eukaryotic protein modification and assembly, increased safety, low cost, high scalability as well as rapid production speed, a critical factor needed to control outbreaks of potential pandemics. Plant-based VLP-based viral vaccines currently in clinical trials include, amongst others, Hepatitis B virus, Influenza virus and SARS-CoV-2 vaccines. Here we discuss the importance of plants as a next generation expression system for the fast, scalable and low cost production of VLP-based vaccines., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Drug similarity studies are driven by the hypothesis that similar drugs should display similar therapeutic actions and thus can potentially treat a similar constellation of diseases. Drug-drug similarity has been derived by variety of direct and indirect sources of evidence and frequently shown high predictive power in discovering validated repositioning candidates as well as other in-silico drug development applications. Yet, existing resources either have limited coverage or rely on an individual source of evidence, overlooking the wealth and diversity of drug-related data sources. Hence, there has been an unmet need for a comprehensive resource integrating diverse drug-related information to derive multi-evidenced drug-drug similarities. We addressed this resource gap by compiling heterogenous information for an exhaustive set of small-molecule drugs (total of 10 367 in the current version) and systematically integrated multiple sources of evidence to derive a multi-modal drug-drug similarity network. The resulting database, 'DrugSimDB' currently includes 238 635 drug pairs with significant aggregated similarity, complemented with an interactive user-friendly web interface (http://vafaeelab.com/drugSimDB.html), which not only enables database ease of access, search, filtration and export, but also provides a variety of complementary information on queried drugs and interactions. The integration approach can flexibly incorporate further drug information into the similarity network, providing an easily extendable platform. The database compilation and construction source-code has been well-documented and semi-automated for any-time upgrade to account for new drugs and up-to-date drug information., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Marine natural products (MNPs) have been an important and rich source for antimicrobial drug discovery and an effective alternative to control drug resistant infections. Herein, we report bioassay guided fractionation of marine extracts from sponges Lendenfeldia , Ircinia and Dysidea that led us to identify novel compounds with antimicrobial properties. Tertiary amines or quaternary amine salts: aniline 1 , benzylamine 2 , tertiary amine 3 and 4 , and quaternary amine salt 5 , along with three known compounds ( 6-8 ) were isolated from a crude extract and MeOH eluent marine extracts. The antibiotic activities of the compounds, and their isolation as natural products have not been reported before. Using tandem mass spectrometry (MS) analysis, potential structures of the bioactive fractions were assigned, leading to the hit validation of potential compounds through synthesis, and commercially available compounds. This method is a novel strategy to overcome insufficient quantities of pure material (NPs) for drug discovery and development which is a big challenge for pharmaceutical companies. The antibacterial screening of the marine extracts has shown several of the compounds exhibited potent in-vitro antibacterial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values between 15.6 to 62.5 microg mL -1 . Herein, we also report structure activity relationships of a diverse range of commercial structurally similar compounds. The structure-activity relationships (SAR) results demonstrate that modification of the amines through linear chain length, and inclusion of aromatic rings, modifies the observed antimicrobial activity. Several commercially available compounds, which are structurally related to the discovered molecules, showed broad-spectrum antimicrobial activity against different test pathogens with a MIC range of 50 to 0.01 µM. The results of cross-referencing antimicrobial activity and cytotoxicity establish that these compounds are promising potential molecules, with a favourable therapeutic index for antimicrobial drug development. Additionally, the SAR studies show that simplified analogues of the isolated compounds have increased bioactivity.

Background: Parkinson's disease (PD) is defined as a long-lasting, neurological illness. Low levels of serum lipid fractions are related with a high risk of PD. Current investigation was designed to evaluate the concentration blood lipid fractions in patients suffering from PD and compared with healthy subjects., Methods: This case-control study was conducted from February 2016 to September 2018 in Tabriz University of Medical Sciences, Tabriz, Iran. The present investigation consisted of 75 persons who had PD and 75 normal people. The blood levels of lipid fractions were measured by concentrations of total cholesterol (TC), serum triglycerides (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), and total cholesterol. The results were analyzed with SPSS software using Kolmogorov-Smirnov, chi-square, and student's t-test., Results: Serum level of TG was remarkably lower in patients with PD (111.92±8.75 mg/dL) compared with healthy subjects (123.64±9.97 mg/dL, P=0.008). Furthermore, we saw an important difference in the level of LDL-C (P=0.001) and TC (P=0.004) between the two groups. However, there was not any observed meaningful difference in the serum concentrations of HDL-C between the studied groups (P=0.135)., Conclusion: Our results showed that the serum concentration of TG, LDL-C, and TC are noticeably lower in the PD suffering patients. Further investigations are needed to provide comprehensive information on the participants' cognitive layout and subsequent actions., (Copyright © 2020, Babol University of Medical Sciences.)

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder. Oxidative stress is a main modulator in the advancement of PD. This investigation aimed to evaluate the relations between serum trace elements, vitamin C, ferritin, transferrin, Nitrite Oxide (NOx) and Peroxynitrite (PrN) concentrations and clinical parameters in patients with PD., Methods: Serum concentrations of variables were measured in 75 PD patients and 75 healthy subjects from Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran between Feb 2016 and Sep 2018. Receiver Operating Characteristic (ROC) analysis was performed to examine incremental diagnostic value of vitamin C, NOx, and PrN in the study groups., Results: Mean serum NOx (35.81±5.16 vs. 11.27±3.59 mol/L, P <0.001) and PrN (15.78±4.23 vs. 9.62±4.57 mol/L, P = 0.004) were markedly higher in patient group versus healthy individuals. Significant differences were also observed in the serum levels of vitamin C ( P <0.001), copper (Cu) ( P <0.001), Iron (Fe) ( P =0.003), and Zinc (Zn) ( P <0.001) between patients with PD and healthy subjects. Nevertheless, the serum levels of Se ( P =0.515), ferritin ( P =0.103), and transferrin ( P =0.372) were not statistically significant between the study groups. ROC analysis has revealed a diagnostic ability of serum vitamin C levels for PD with an area under ROC curve of ≥0.7 ( P <0.05) and relatively high sensitivity and specificity., Conclusion: Serum levels of NOx and PrN are significantly higher in patients with PD. In additions, serum vitamin C levels have a diagnostic value as a biomarker. Further studies are required with larger sample size to provide more detailed information about the cognitive profile of participants and the outcome measures., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests., (Copyright © 2021 Barmaki et al. Published by Tehran University of Medical Sciences.)

Background: Surgery and chemotherapy are the two most common treatments for cancers, including ovarian cancer. Although most ovarian cancers occur over the age of 45 yr, it may involve younger women and affect their reproductive ability., Objective: To assess the expression of Leucine-rich repeat-containing G-protein coupled receptor 5 ( LGR5 ), Forkhead Box O1 ( FOXO1 ), and miR-340 genes in the ovarian cancer tissues as well as ovarian cancer cell lines., Materials and Methods: In this case-control study, 30 ovarian cancer samples (with the average age of 37 ± 2.5 years) coupled with their non-tumor marginal tissue (as a control) were collected. Proliferated cell lines were treated with several concentrations of cisplatin, and the half maximal inhibitory concentration (IC50) of cisplatin was quantified by MTT-assay. After RNA extraction, cDNA synthesis and qRT-PCR were done. Finally, the results were analyzed., Results: While the expression levels of miR-340 and FOXO1 genes in tumor samples displayed a significant reduction (p ≤ 0.001), the LGR5 gene presented a significant increase in expression (p ≤ 0.0001). However, conversely, the expression levels of miR-340 and FOXO1 genes in cisplatin-sensitive cell lines, after 24, 48, and 72 hr of cisplatin treatment, indicated a significant increase (p ≤ 0.001) while the expression of LGR5 gene showed a significant decrease in the cisplatin-sensitive cell line (p < 0.05)., Conclusion: The LGR5 , FOXO1 , and miR-340 genes can be targeted for early diagnosis and more accurate treatment of ovarian cancer and may prevent some of the ovarian cancer complications such as infertility., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Khodadadian et al.)

Drug resistant bacteria have emerged, so robust methods are needed to evaluate combined activities of known antibiotics as well as new synthetic compounds as novel antimicrobial agents to treatment efficacy in severe bacterial infections. Marine natural products (MNPs) have become new strong leads in the drug discovery endeavor and an effective alternative to control infections. Herein, we report the bioassay guided fractionation of marine extracts from the sponges Lendenfeldia , Ircinia , and Dysidea that led us to identify novel compounds with antimicrobial properties. Chemical synthesis of predicted compounds and their analogs has confirmed that the proposed structures may encode novel chemical structures with promising antimicrobial activity against the medically important pathogens. Several of the synthetic analogs exhibited potent and broad spectrum in vitro antibacterial activity, especially against the Methicillin-resistant Staphylococcus aureus (MRSA) (MICs to 12.5 μM), Mycobacterium tuberculosis (MICs to 0.02 μM), uropathogenic Escherichia coli (MIC o 6.2 μM), and Pseudomonas aeruginosa (MIC to 3.1 μM). Checkerboard assay (CA) and time-kill studies (TKS) experiments analyzed with the a pharmacodynamic model, have potentials for in vitro evaluation of new and existing antimicrobials. In this study, CA and TKS were used to identify the potential benefits of an antibiotic combination (i.e., synthetic compounds, vancomycin, and rifampicin) for the treatment of MRSA and M. tuberculosis infections. CA experiments indicated that the association of compounds 1a and 2a with vancomycin and compound 3 with rifampicin combination have a synergistic effect against a MRSA and M. tuberculosis infections, respectively. Furthermore, the analysis of TKS uncovered bactericidal and time-dependent properties of the synthetic compounds that may be due to variations in hydrophobicity and mechanisms of action of the molecules tested. The results of cross-referencing antimicrobial activity, and toxicity, CA, and Time-Kill experiments establish that these synthetic compounds are promising potential leads, with a favorable therapeutic index for antimicrobial drug development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Dinarvand, Spain and Vafaee.)

Background: Parkinson's disease (PD) is a prevalent neurodegenerative illness. It has been believed that oxidative stress (OS) is an important factor in the advancement of PD. This investigation attempts to evaluate the relations between blood trace elements, ferritin, and transferrin concentrations as well as the levels of protein and gene expression of ceruloplasmin (CP), Nrf-2, and HO-1 in patients suffering PD., Methods: The serum concentrations of variables were assessed in 110 PD patients group and 110 normal subjects. Furthermore, we applied qRT-PCR as well as western blot (WB) analysis to measure the levels of gene and protein, respectively., Results: Considerable differences were detected in the serum concentrations of copper (Cu), iron (Fe), and zinc (Zn), when healthy and patient groups were compared. Nevertheless, the levels of Se, ferritin, and transferrin were not significantly different between the two groups. qRT-PCR and WB data analysis revealed significant differences of CP, Nrf-2, and HO-1at genes expression and protein levels when comparing the two PD patients and control groups., Conclusion: The results of the current work revealed that blood levels of Cu, Fe, and Zn were significantly higher in subjects who had PD. In addition, it was found that the levels of protein and gene expression CP, Nrf-2, and HO-1 were markedly higher in PD group than in non-PD subjects. Indeed, in this study, the results showed that the antioxidant content of the body can be linked to PD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

At the end of the year 2019, the novel coronavirus (2019-nCoV) was spreading in Wuhan, China, and the outbreak process has a high speed. It was recognized as a pandemic by the World Health Organization (WHO) on 11 March 2020. Coronaviruses are enveloped and single-stranded RNA that have several families including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The pathogenesis mechanism and disease outcomes of SARS and MERS are now clear to some extent, but little information is available for 2019-nCoV. This newly identified corona virus infection represents flu-like symptoms, but usually the first symptoms are fever and dry cough. There has been no specific treatment against 2019-nCoV up to now, and physicians only apply supportive therapy. In the present article, we made an attempt to review the behavior of the virus around the world, epidemiology, a pathway for influx into the host cells, clinical presentation, as well as the treatments currently in use and future approaches; nitazoxanide may be our dream drug. We hope that this review has a positive impact on public knowledge for helping to deal with the 2019-nCoV and move one step forward toward its treatment in the near future., (Copyright © 2020 IMSS. Published by Elsevier Inc. All rights reserved.)

Cells use biomolecules to convey information. For instance, neurons communicate by releasing chemicals called neurotransmitters, including several monoamines. The information transmitted by neurons is, in part, coded in the type and amount of neurotransmitter released, the spatial distribution of release sites, the frequency of release events, and the diffusion range of the neurotransmitter. Therefore, quantitative information about neurotransmitters at the (sub)cellular level with high spatiotemporal resolution is needed to understand how complex cellular networks function. So far, various analytical methods have been developed and used to detect neurotransmitter secretion from cells. However, each method has limitations with respect to chemical, temporal and spatial resolution. In this review, we focus on emerging methods for optical detection of neurotransmitter release and discuss fluorescent sensors/probes for monoamine neurotransmitters such as dopamine and serotonin. We focus on the latest advances in near infrared fluorescent carbon nanotube-based sensors and engineered fluorescent proteins for monoamine imaging, which provide high spatial and temporal resolution suitable for examining the release of monoamines from cells in cellular networks., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

RNA interference is one of the prosperous approaches for cancer treatment. However, small interfering RNA (siRNA) delivery to cancer cells has been faced with various challenges restricting their clinical application over the decades. Since ROR1 is an onco-embryonic gene overexpressed in many malignancies, suppression of ROR1 by siRNA can potentially fight cancer. Herein, a delivery system for ROR1 siRNA based on HIV-1 TAT peptide-capped gold nanoparticles (GNPs) was developed to treat breast cancer. Besides, we introduced a new feasible method for conjugating the peptide to the nanoparticles. Since the GNPs have high affinity to the sulfur, the findings demonstrated the peptide successfully conjugated to the nanoparticles via Au-S bonds. As positively charged nanoparticles showed high cellular uptake, we could use a low concentration of nanoparticles led to high efficient gene transfection with negligible cytotoxicity that was confirmed by flow cytometry, confocal microscopy, gel retardation, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Following transfection, downregulation of ROR1 and its targeted gene, CCND1, induced apoptosis in cancer cells. In conclusion, the reported capped GNPs could be potentially utilized for delivering negatively charged therapeutic agents in particular genes., (© 2019 Wiley Periodicals, Inc.)

Eco-friendly functional bionanocomposite films were prepared using sodium caseinate (SC) and guar gum (GG) as the polymer matrix and TiO 2 and cumin essential oil (CEO) as functional fillers. 0.2 vol% GG selected for the preparation of SC/GG composite film and various amount of TiO 2 and CEO (1 and 2 wt% based on SC) were incorporated into the SC/GG film either individually or in combination. The addition of TiO 2 and CEO significantly improved the water permeability and sensitivity properties and mechanical characteristics such as the strength (TS), stiffness (YM), and flexibility (EB) of the composite films. Also, the SC/GG films incorporated with TiO 2 and CEO exhibited remarkable antibacterial activity against both Gram-positive (L. monocytogenes and S. aureus) and Gram-negative (E. coli O157: H7 and S. enteritidis) bacteria. All the film properties were varied not only on the concentration of TiO 2 and CEO, but also increased synergistically when they were added together., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Various numbers of factors such as oxidative stress, neurotoxins, and pesticides have been implicated in its pathophysiology of Parkinson's disease (PD). Paraoxonas1 (PON1) metabolizes xenobiotics, including pesticides. Therefore, we surveyed the relationship between PON1 polymorphisms with its activities in the pathogenesis of Parkinson's disease.., Methods: We investigated polymorphisms of the PON1 (L55M and Q192R) by PCR-RFLP assays; we also measure the levels of PON1, TAC (total antioxidant capacity) and TOS (total oxidant status) with ELISA (Enzyme-linked immunosorbent assay) and spectrophotometric method for their activities., Results: Paraoxonase and arylesterase activity of PON1 as well as their concentrations were lower in patients with PD compared with control group, but from the view of the specific activity, it was not significant between two groups. In the compare of TAC, TOS, and OSI, the TOS and OSI were higher in the patients than controls, while patients had lower levels of TAC compared with controls. Serum PON1 concentrations and activities were higher in LL (comparison with LM and MM) and RR (comparison with QR and QQ) genotypes while we did not observe any significant differences in arylesterase levels among mentioned polymorphisms., Conclusion: In the current study, we reported associations between PON1 polymorphisms (55, 192) and enzyme activities in Parkinson's disease as there was a significant reduction in PON1 levels in patients with Parkinson compared with healthy. Taken together, paraoxonase enzyme in subjects with different genotypes could be a potential biomarker for determining the severity and prognosis of Parkinson. However, more studies are needed to clarify its clinical values. Key words: Parkinson's disease; paraoxonase1; Polymorphism.

Parkinson's disease (PD) is defined as a chronic neurodegenerative disorder which is diagnosed mostly by its clinical manifestations. Reactive oxygen species (ROS) are considered as key modulators in the development of PD. Despite the intensive investigations, antioxidant-dependent molecular mechanisms of initiation and development of PD are controversial. Free radicals cause serious damage and death of dopamine producing cells when antioxidant capacity of the cells is reduced against oxidative stress (OxS). Many intracellular reactions create ROS, including activation of NADPH oxidase (NOX), mitochondrial dysfunction, and hydrogen peroxide (H₂O₂) decomposition. On the contrary, natural antioxidants, vitamins, proteins, and antioxidant signaling pathways are major factors to neutralize ROS and its destructive effects. The functional role of nuclear factor E2-related factor 2, Heme oxygenase-1, and selenium against ROS-dependent initiation and progression of PD is elucidated. In this review, we collected multiple factors that play the main role in the initiation, development, and pathogenesis of PD and we discussed their function in the PD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Serotonin is an important neurotransmitter involved in various functions of the nervous, blood, and immune system. In general, detection of small biomolecules such as serotonin in real time with high spatial and temporal resolution remains challenging with conventional sensors and methods. In this work, we designed a near-infrared (nIR) fluorescent nanosensor (NIRSer) based on fluorescent single-walled carbon nanotubes (SWCNTs) to image the release of serotonin from human blood platelets in real time. The nanosensor consists of a nonbleaching SWCNT backbone, which is fluorescent in the beneficial nIR tissue transparency window (800-1700 nm) and a serotonin binding DNA aptamer. The fluorescence of the NIRSer sensor (995 nm emission wavelength for (6,5)-SWCNTs) increases in response to serotonin by a factor up to 1.8. It detects serotonin reversibly with a dissociation constant of 301 nM ± 138 nM and a dynamic linear range in the physiologically relevant region from 100 nM to 1 μM. As a proof of principle, we detected serotonin release patterns from activated platelets on the single-cell level. Imaging of the nanosensors around and under the platelets enabled us to locate hot spots of serotonin release and quantify the time delay (≈ 21-30 s) between stimulation and release in a population of platelets, highlighting the spatiotemporal resolution of this nanosensor approach. In summary, we report a nIR fluorescent nanosensor for the neurotransmitter serotonin and show its potential for imaging of chemical communication between cells.

Micheliolide (MCL) is a naturally derived anti-inflammatory agent. In the present investigation, we examined the protective potential of MCL against doxorubicin (DOX)-induced cardiotoxicity in mice. Mice were injected with a single 15-mg/kg intraperitoneal dose of DOX at day 1 and the study groups received daily 12.5, 25, and 50 mg/kg doses of MCL for 7 days. Cardiac histopathology, cardiac function, serum markers of cardiac injury, and tissue markers of inflammation, and oxidative stress were examined. MCL decreased serum levels of creatinine kinase MB (CK-MB) and cardiac troponin I (cTnI) levels, ameliorated cardiac tissue architecture, and improved cardiac stroke volume. Apart from reducing the activities of NF-kB p65 subunit, MCL attenuated the cardiac levels of PI3K, phosphorylated (p)-Akt, p-Bad, and caspase-3 levels and simultaneously elevated p-PTEN levels. While the gene expressions of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) were decreased, the tissue activities of superoxide dismutase (SOD) as well as gene expressions of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase-1 (NQO1) were increased after treatment with MCL. Furthermore, tissue levels of malondialdehyde (MDA) were also decreased. Collectively, these findings point to the protective effects of MCL against DOX-induced cardiotoxicity by regulating PI3K/Akt/NF-kB signaling pathway in mice.

miR-145 is a tumor suppressive miRNA which is abnormally reduced in different cancers. miR-145 overexpression reduces cancer migration, invasion, and cell adhesion. Increasing miR-145 level using suitable and efficient gene delivery systems could be valuable in cancer treatment. In this study, a redox-responsive miR-145 conjugated thiolated dextran (TD-miR) was prepared. Also, polyelectrolyte complexes (PECs) of TD-miR and chitosan were fabricated and decorated with anti nucleolin aptamer, AS1411 (apt-PEC). The size of the PECs was between 40-270 nm, and the zeta potential was varied according to the TD-miR to chitosan molar ratio. The outcomes of cellular studies indicated the excellence of the apt-PEC as a duel targeted delivery system and the PECs composed of chitosan 18 kDa with TD-miR to chitosan ratio of 5. TD-miR and the PECs are appropriate as the smart gene delivery systems which preserve and transfect the cargo and release it in cytoplasm., (Copyright © 2018. Published by Elsevier Ltd.)

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a well-characterized tumour-suppressor gene that is lost or mutated in about half of metastatic castration-resistant prostate cancers and in many other human cancers. The restoration of functional PTEN as a treatment for prostate cancer has, however, proven difficult. Here, we show that PTEN messenger RNA (mRNA) can be reintroduced into PTEN-null prostate cancer cells in vitro and in vivo via its encapsulation in polymer-lipid hybrid nanoparticles coated with a polyethylene glycol shell. The nanoparticles are stable in serum, elicit low toxicity and enable high PTEN mRNA transfection in prostate cancer cells. Moreover, significant inhibition of tumour growth is achieved when delivered systemically in multiple mouse models of prostate cancer. We also show that the restoration of PTEN function in PTEN-null prostate cancer cells inhibits the phosphatidylinositol 3-kinase (PI3K)-AKT pathway and enhances apoptosis. Our findings provide proof-of-principle evidence of the restoration of mRNA-based tumour suppression in vivo.

Recent insights into the nanomedicine have revealed that nanoplatforms enhance the efficacy of carrier in therapeutic applications. Here, multifunctional nanoplatforms were utilized in miRNA-101 delivery and NIR thermal therapy to induce apoptosis in breast cancer cells. Au nanorods (NRs) or nanospheres (NSs) covered with graphene oxide (GO) were prepared and functionalized with polyethylene glycol as a stabilizer and poly-L-arginine (P-L-Arg) as a targeting agent. In nanoplatforms, coupling Au@GO prepared stable structures with higher NIR reactivity. P-L-Arg substantially enhanced the cellular uptake and gene retardation of stuffs coated by them. However, rod-shape nanoplatforms indicated better performance in cellular uptake and gene transfection than spherical ones. NIR thermal therapy was implemented to improve gene release and in synergy with miRNA-101 activated the apoptotic pathway and decreased the viability of breast cancer cell (<20%). Briefly, presented delivery systems are potentially efficient in distinguishing cancer cells, miRNA internalization and controlling apoptosis of cancer cells., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is one of the most common diseases associated with neurodegenerative disorders. It affects 3% to 4% of the population over the age of 65 years. The neuropathological dominant symptoms of PD include the destruction of neurons in the substantia nigra, thus causing striatal dopamine deficiency and the presence of intracellular inclusions that contain aggregates of α‑synuclein. The premature form of PD is familial and is known as early onset PD (EOPD). It involves a small portion of patients with PD, displaying symptoms before the age of 60 years. Although individuals who are suffering from the EOPD may have genetic changes, the molecular mechanisms that differentiate between EOPD and late onset PD (LOPD) remain unclear. Owing to the complexity of discriminating between the different forms, treatment, and management of PD, the identification of biomarkers for early diagnosis seems necessary. For this purpose, many studies have been undertaken for the introduction of several biological molecules through various techniques as potential biomarkers. The main focus of these studies was on α-synuclein. However, there are other molecules that are potential biomarkers, such as microRNAs and peptoids. In this article, we tried to review some of these studies., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Influenza virus causes a highly contagious viral respiratory tract infection with potentially fatal outcomes in humans and animals. There is now widespread influenza virus resistance to commercial drugs due to the genetic diversity of virus. Therefore, new therapeutic formulation needs to be developed. Chitosan/siRNA nanoparticles were generated as a new therapeutic approach against influenza virus infections both in vitro and in vivo. Designed siRNA against influenza nucleoprotein was formulated in chitosan polymer as siRNA/chitosan nanoparticle complex. Particle size and zeta potential of the nanoparticles were measured by dynamic light scattering. The uptake of labeled siRNA into Vero cells was visualized using fluorescence microscopy. Nanoparticle-mediated knockdown of enhanced green fluorescent protein (EGFP) was analyzed and quantified by flow cytometry in Vero cells. Results of the in vitro study showed that chitosan/siRNA nanoparticle was efficiently uptaken by Vero cells, leading to inhibition of influenza virus replication. Furthermore, nasal delivery of siRNA by chitosan nanoparticle complex has antiviral effects and significantly protected BALB/c mice from a lethal influenza challenge. These findings suggest that chitosan nanoparticle equipped with siRNA is a promising system for controlling influenza virus infection.

Background: Treatment of the ischemic stroke has remained a major healthcare challenge. The phenolic compound, sesamol, has shown promising antioxidant and neuroprotective effects, however, fast clearance may negatively affect its efficiency. This, prompted us to incorporate sesamol into the nanostructured lipid carriers (S-NLCs) and evaluate its therapeutic potential in in vitro and in vivo models of ischemic stroke., Methods: S-NLCs formulations were prepared by high-pressure homogenization followed by physicochemical characterization, evaluation of the bioactivity of the optimal formulation in oxygen-glucose deprivation (OGD) and global cerebral ischemia/reperfusion (I/R) injury and implication of phosphatidylinositol 3-kinase (PI3K) pathway in this regard. Two- or three-way ANOVA, Mann-Whitney U test, and Student's t-test were used for data analysis., Results: Formation of S-NLCs which exhibited a controlled release profile, was confirmed by scanning electron microscope and differential scanning calorimetry. 1- and 8-h OGD followed by 24 h re-oxygenation significantly reduced PC12 cell viability, increased lactate dehydrogenase activity and the number of condensed nuclei, and induced oxidative stress as revealed by increased malondialdehyde level and decreased glutathione content and superoxide dismutase and catalase activities. Sesamol (80 and 100 μM) reduced the cytotoxicity, oxidative stress, and cellular damage only after 1-h OGD, while, S-NLCs (containing 80 and 100 μM of sesamol) were effective at both time points. Intravenous injections of S-NLCs (20 and 25 mg/kg) into rats markedly attenuated I/R-induced neurobehavioural deficits, cellular damage, and oxidative stress, while, free sesamol failed. Pre-treatment with PI3K inhibitor, LY294002, abolished the protective effects against OGD or I/R., Conclusions: S-NLCs improve the pharmacological profile of sesamol and provide longer lasting protective effects for this phenolic phytochemical. This nanoformulation by activating PI3K pathway may serve as a promising candidate for neuroprotection against the cerebral stroke or other neurodegenerative disorders. Sesamol-loaded NLCs, a promising nanoformulation against the ischemic stroke.

Objective: Parkinson's disease (PD) is a common neurodegenerative disease. Oxidative stress is considered as a key modulator in the development of PD. This study aimed to investigate associations between serum NOX1 (NADPH oxidase1), ferritin, selenium (Se), and uric acid (UA) levels and clinical parameters in patients with PD., Design and Methods: Serum levels of NOX1, ferritin, Se, and UA were measured in 40 PD patients and 40 healthy individuals. Receiver operating characteristic (ROC) analysis was performed to investigate incremental diagnostic value of each factor in the study groups., Results: Mean serum NOX1 levels were markedly higher in patient group (22.36±5.80ng/mL) versus healthy individuals (8.89±2.37ng/mL) (p<0.001). Significant differences were also observed in the serum concentrations of ferritin (p=0.005) and Se (p=0.001) between patients with PD and healthy individuals. However, the serum concentrations of UA were not statistically significant between the study groups (p=0.560). ROC analysis revealed a diagnostic ability of serum NOX1 and ferritin levels for PD with an area under ROC curve of ≥0.7 (p<0.05) and relatively high sensitivity and specificity. Combination of serum NOX1 and Se along with ferritin and UA levels increased the sensitivity up to 85%, specificity up to 97% and area under the ROC curve up to 0.94 (95% confidence interval (95% CI): 0.89 to 0.99, p<0.001)., Conclusion: Our findings indicated that serum concentrations of NOX1, ferritin, and Se are significantly higher in the patients with PD. Therefore, these factors can be considered as potential diagnostic biomarkers for diagnosis and monitoring of PD patients. Further studies are required with larger sample size to provide more detailed information about the cognitive profile of participants and the outcome measures., (Copyright © 2017. Published by Elsevier Inc.)

The aim of this study was obtain a model that maximizes growth and production of inulinase and invertase by Aspergillus niger ATCC 20611, employing response surface methodology (RSM). The RSM with a five-variable and three-level central composite design (CCD) was employed to optimize the medium composition. Results showed that the experimental data could be appropriately fitted into a second-order polynomial model with a coefficient of determination (R 2 ) more than 0.90 for all responses. This model adequately explained the data variation and represented the actual relationships between the parameters and responses. The pH and temperature value of the cultivation medium were the most significant variables and the effects of inoculum size and agitation speed were slightly lower. The intra-extracellular inulinase, invertase production and biomass content increased 10-32 fold in the optimized medium condition (pH 6.5, temperature 30°C, 6% (v/v), inoculum size and 150rpm agitation speed) by RSM compared with medium optimized through the one-factor-at-a-time method. The process development and intensification for simultaneous production of intra-extracellular inulinase (exo and endo inulinase) and invertase from A. niger could be used for industrial applications., (Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Saline municipal wastewater treatment is a challenging environmental issue in coastal cities, due to the discharge of saline water into the sewers. The present research article focuses on the phytoremediation of high saline municipal wastewater by Ruppia maritime , a widespread plant which can be found in saline medium such as traditional fish ponds, estuaries, tidal flats, salt pans, coastal paddy fields, coastal lagoons, marsh pools, and mangrove salt marshes in Khuzestan province, Iran. The experimental data was obtained using a pilot plant constructed in Chobeineh wastewater treatment plant in Ahvaz city, fed by activated sludge effluent in 3 levels of electrical conductivity (EC) (10, 15, 20 ms cm -1 ), during 45 days of the experiment. Chemical oxygen demand (COD), total nitrogen (TN), total phosphorus (TP) and total suspended solids (TSS) were daily monitored in blank and pilot study. The COD removal decreased from 83.26% to 72.39% by increasing the EC level from 10 to 20 ms cm -1 , respectively. The experimental data will practically be an appropriate source of information for environmental engineers to design a natural treatment scenario for saline wastewater treatment.

Small interfering RNA (siRNA) has established its reputation in the field of tissue engineering owing to its ability to silence the proteins that inhibit tissue regeneration. siRNA is capable of regulating cellular behavior during tissue regeneration processes. The concept of using siRNA technology in regenerative medicine derived from its ability to inhibit the expression of target genes involved in defective tissues and the possibility to induce the expression of tissue-inductive factors that improve the tissue regeneration process. To date, siRNA has been used as a suppressive biomolecule in different tissues, such as nervous tissue, bone, cartilage, heart, kidney, and liver. Moreover, various delivery systems have been applied in order to deliver siRNA to the target tissues. This review will provide an in-depth discussion on the development of siRNA and their delivery systems and mechanisms of action in different tissues., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Antibiotic resistance in bacteria incurs fitness cost, but compensatory mechanisms may ameliorate the cost and sustain the resistance even under antibiotics-free conditions. The aim of this study was to determine compensatory mechanisms of antibiotic resistance in H. pylori . Five strains of levofloxacin-sensitive H. pylori were induced in vitro to develop resistance. In addition, four pairs of metronidazole-sensitive and -resistant H. pylori strains were isolated from patients carrying dual H. pylori populations that consist of both sensitive and resistant phenotypes. Growth rate, virulence and biofilm-forming ability of the sensitive and resistant strains were compared to determine effects of compensatory response. Proteome profiles of paired sensitive and resistant strains were analyzed by liquid chromatography/mass spectrophotometry (LC/MS). Although there were no significant differences in growth rate between sensitive and resistant pairs, bacterial virulence (in terms of abilities to induce apoptosis and form biofilm) differs from pair to pair. These findings demonstrate the complex and strain-specific phenotypic changes in compensation for antibiotics resistance. Compensation for in vitro induced levofloxacin resistance involving mutations of gyrA and gyrB was functionally random. Furthermore, higher protein translation and non-functional protein degradation capabilities in naturally-occuring dual population metronidazole sensitive-resistant strains may be a possible alternative mechanism underlying resistance to metronidazole without mutations in rdxA and frxA . This may explain the lack of mutations in target genes in ~10% of metronidazole resistant strains.

Docetaxel acts through the inhibition of tubulin polymerization and reduction in the expression of BCL-2 gene. In this study, nanoparticles containing Docetaxel were prepared and their effects on the gene expression levels of BCL-2 and BAX genes were investigated. The drug was first conjugated to chitosan, and the nanoparticles were assembled in the presence of hyaluronic acid. Conjugations were confirmed by 1 H-NMR, and the obtained nanoparticles were characterized by dynamic light scattering and SEM. Cytotoxicity of the nanoparticles, cellular uptake, and cell death were evaluated. Finally, the effect of nanoparticles on the expression of BAX and BCL-2 genes in MCF-7 cells were investigated through real-time PCR. The results revealed that the prepared NPs had spherical shape with narrow size distribution of <200 nm with positive zeta potentials. In vitro cytotoxicity of Cs nanoparticles and free Docetaxel investigations revealed that increasing the treatment time with nanoparticles led to decrease in the rate of cell viability. BAX and BCL-2 gene expressions were decreased in nanoparticle-treated cells in comparison with intact cells, while the BAX/BCL-2 ratio was significantly elevated compared with free drug-treated cells after 72 h. Docetaxel-conjugated NPs may offer a promising treatment with low off-target toxicity for breast cancer., (© 2016 John Wiley & Sons A/S.)