Nucleolin-targeted doxorubicin and ICG co-loaded theranostic lipopolymersome for photothermal-chemotherapy of melanoma in vitro and in vivo.

Combination therapy using chemo-photothermal therapy (chemo-PTT) shows great efficacy toward tumor ablation in preclinical studies. Besides, lipopolymersomes as a hybrid nanocarriers, integrate advantages of liposomes and polymersomes in a single platform in order to provide tremendous biocompatibility, biodegradability, noteworthy loading efficacy for both hydrophobic and hydrophilic drugs with adjustable drug release and high stability. In this study, a multipurpose lipopolymersome was fabricated for guided chemotherapy-PTT and NIR-imaging of melanoma. A lipopolymerosomal hybrid nanovesicle consisting of equal molar ratio of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) diblock copolymer (molar ratio 1:1) was fabricated. The nanoparticulate system was prepared through film rehydration technique for encapsulation of doxorubicin (DOX) and indocyanine green (ICG) to form DOX-ICG-LP platform. At the next stage, AS1411 DNA aptamer was conjugated to the surface of lipopolymersome (Apt-DOX-ICG-LP) for selective delivery. The sizes of DOX-ICG-LP and Apt-DOX-ICG-LP were obtained through DLS analysis (61.0 ± 6 and 74 ± 5, respectively). Near Infrared-responsive release pattern of the prepared lipopolymersome was verified in vitro. The formulated platform showed efficient photothermal conversion, and superior stability with acceptable encapsulation efficiency. Consistent with the in vitro studies, NIR-responsive lipopolymersome exhibited significantly higher cellular toxicity for Chemo-PTT versus single anti-cancer treatment. Moreover, superlative tumor shrinkage with favorable survival profile were attained in B16F10 tumor-bearing mice received Apt-DOX-ICG-LP and irradiated with 808 nm laser compared to those treated with either DOX-ICG-LP or Apt-DOX-ICG-LP without laser irradiation. The diagnostic capability of Apt-DOX-ICG-LP was addressed using in vivo NIR imaging, 6 and 24 h post-intravenous administration. The results indicated desirable feature of an established targeted theranostic capability of Apt-DOX-ICG-LP for both diagnostics and dual chemo-PTT of melanoma.

Physicians' Perspectives with the E-prescribing System in Five Teaching Hospitals.

OBJECTIVES: Despite the evidence suggesting the potential of electronic prescribing (e-prescribing), this system also faces challenges that can lead to inefficiency and even failure. This study aimed to evaluate physicians' perspectives on the efficiency, effectiveness, opportunities, and challenges associated with the e-prescribing system. METHODS: In 2023, a descriptive analytics cross-sectional study was carried out. Due to the finite population size, all the physicians from five studied hospitals who agreed to participate in the study were included through the census method (n = 195). Data collection was conducted using a validated questionnaire. Data were analyzed using descriptive (mean, standard deviation, and frequency) and analytical (Pearson's correlation coefficient, two-sample t-test, one-way analysis of variance (ANOVA), and linear multiple regression model) statistics. RESULTS: The mean scores of efficiency and effectiveness were 47.47 ± 14.46 and 36.09 ± 10.67 out of 95 and 65, respectively. Removing the illegibility of the prescriptions (n = 22) was the most frequent opportunity and internet connectivity problem (n = 37) was the most frequent challenge associated with the e-prescribing system. There was a strong positive significant correlation between efficiency and effectiveness (r = 0.850, p < 0.01). Moreover, age was found to have a significant negative correlation with efficiency (B = -7.261, p = 0.004) and effectiveness (B = - 5.784, p = 0.002). CONCLUSION: Physicians believe that e-prescribing enhances the efficiency and effectiveness of their work. There are many opportunity and challenges to the use of e-prescription. Assessing the needs of physicians, actively participating and training them in the stages of design and implementation, and conducting regular evaluations of the e-prescribing system are crucial to overcome the challenges. Our finding offers insightful information about how doctors see the e-prescribing system at teaching hospitals and provide a basis for managers and policy makers at the local and national levels to support the implementation of this system and plan for improvement of its shortcomings.

Dual COX-2/15-LOX inhibitors: A new avenue in the prevention of cancer.

Dual cyclooxygenase 2/15-lipoxygenase inhibitors constitute a valuable alternative to classical non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 (cyclooxygenase-2) inhibitors for the treatment of inflammatory diseases, as well as preventing the cancer. Indeed, these latter present diverse side effects, which are reduced or absent in dual-acting agents. In this review, COX-2 and 15-LOX (15-lipoxygenase) pathways are first described in order to highlight the therapeutic interest of designing such compounds. Various structural families of dual inhibitors are illustrated. This study discloses various structural families of dual 15-LOX/COX-2 inhibitors, thus pave the way to design potentially-active anticancer agents with balanced dual inhibition of these enzymes.

Synthesis approaches of amphiphilic copolymers for spherical micelle preparation: application in drug delivery.

The formation of polymeric micelles in aqueous environments through the self-assembly of amphiphilic polymers can provide a versatile platform to increase the solubility and permeability of hydrophobic drugs and pave the way for their administration. In comparison to various self-assembly-based vehicles, polymeric micelles commonly have a smaller size, spherical morphology, and simpler scale up process. The use of polymer-based micelles for the encapsulation and carrying of therapeutics to the site of action triggered a line of research on the synthesis of various amphiphilic polymers in the past few decades. The extended knowledge on polymers includes biocompatible smart amphiphilic copolymers for the formation of micelles, therapeutics loading and response to external stimuli, micelles with a tunable drug release pattern, etc. Different strategies such as ring-opening polymerization, atom transfer radical polymerization, reversible addition-fragmentation chain-transfer, nitroxide mediated polymerization, and a combination of these methods were employed to synthesize copolymers with diverse compositions and topologies with the proficiency of self-assembly into well-defined micellar structures. The current review provides a summary of the important polymerization techniques and recent achievements in the field of drug delivery using micellar systems. This review proposes new visions for the design and synthesis of innovative potent amphiphilic polymers in order to benefit from their application in drug delivery fields.

Detection and Diagnosis of Bacterial Leaf Streak on Small Grain Cereals: From Laboratory to Field.

Bacterial leaf streak of small-grain cereals is an economically important disease of wheat and barley crops. The disease occurs in many countries across the globe, with particular importance in regions characterized by high precipitation or areas in which sprinkler irrigation is used. Three genetically distinct lineages of the Gram-negative bacterium Xanthomonas translucens (X. translucens pv. undulosa, X. translucens pv. translucens, and X. translucens pv. cerealis) are responsible for most of the bacterial leaf streak infections on wheat and barley crops. Considering the seedborne nature of the pathogens, they are included in the A2 (high-risk) list of quarantine organisms for some European countries; hence, they are under strict quarantine control and zero tolerance. Due to the taxonomic complexities within X. translucens, the exact geographic distribution of each pathovar has not yet been determined. In this mini review, we provide an updated overview of the detection and diagnosis of the bacterial leaf streak pathogens. First, a short history of the leaf streak pathogens is provided, followed by the symptomology and host range of the causal agents. Then, the utility of conventional methods and high-throughput molecular approaches in the precise detection and identification of the pathogens is explained. Finally, we highlight the role of quarantine inspections and early detection of the pathogen in combating the risk of bacterial leaf streak in the 21st century's small-grains cereals' industry.

Mesenchymal stem cells-derived exosomes as a promising new approach for the treatment of infertility caused by polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial metabolic and most common endocrine disorder that its prevalence, depending on different methods of evaluating PCOS traits, varies from 4% to 21%. Chronic low-grade inflammation and irregular apoptosis of granulosa cells play a crucial role in the pathogenesis of PCOS infertility. Mesenchymal stem cells (MSCs)-derived exosomes and extracellular vesicles (EVs) are lipid bilayer complexes that act as a means of intercellular transferring of proteins, lipids, DNA and different types of RNAs. It seems that this nanoparticles have therapeutic effects on the PCOS ovary such as regulating immunity response, anti-inflammatory (local and systemic) and suppress of granulosa cells (GCs) apoptosis. Although there are few studies demonstrating the effects of exosomes on PCOS and their exact mechanisms is still unknown, in the present study we reviewed the available studies of the functions of MSC-derived exosome, EVs and secretome on apoptosis of granulosa cells and inflammation in the ovary. Therefore, the novel cell-free therapeutic approaches for PCOS were suggested in this study.

Synthesis of block copolymers used in polymersome fabrication: Application in drug delivery.

Amphiphilic block copolymers are common materials used for the fabrication of various nanostructures with biomedical applications including nanocapsules, nanospheres, micelles and polymeric vesicles. According to the literature, polymersomes have several advantages compared to other nanostructures used as drug delivery systems comprising better stability, facile synthesis, prolonged circulation time, and passive/active targeting capability. Various types of nanoparticles are formed by varying the ratio of the hydrophobic/hydrophilic blocks. Changing hydrophobic/hydrophilic ratio of amphiphilic block copolymers has an impact on the structural characteristics of polymers such as changing molecular weight and surface functionalization of the block copolymer. Thus, polymerization strategies are an important factor that influences polymersomes quality. In this review, different polymerization strategies for the synthesis of block copolymers applied in polymersomes formation, are described.

Immunomodulatory Effects of Curcumin in Rheumatoid Arthritis: Evidence from Molecular Mechanisms to Clinical Outcomes.

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disorder characterized by the destruction of the joint and bone resorption. The production of pro-inflammatory cytokines and chemokines, dysregulated functions of three important subtypes of T helper (TH) cells including TH1, TH17, and regulator T (Treg) cells are major causes of the initiation and development of RA. Moreover, B cells as a source of the production of several autoantibodies play key roles in the pathogenesis of RA. The last decades have seen increasingly rapid advances in the field of immunopharmacology using natural origin compounds for the management of various inflammatory diseases. Curcumin, a main active polyphenol compound isolated from turmeric, curcuma longa, possesses a wide range of pharmacologic properties for the treatment of several diseases. This review comprehensively will assess beneficial immunomodulatory effects of curcumin on the production of pro-inflammatory cytokines and also dysregulated functions of immune cells including TH1, TH17, Treg, and B cells in RA. We also seek the clinical efficacy of curcumin for the treatment of RA in several recent clinical trials. In conclusion, curcumin has been found to ameliorate RA complications through modulating inflammatory and autoreactive responses in immune cells and synovial fibroblast cells via inhibiting the expression or function of pro-inflammatory mediators, such as nuclear factor-κB (NF-κB), activated protein-1 (AP-1), and mitogen-activated protein kinases (MAPKs). Of note, curcumin treatment without any adverse effects can attenuate the clinical symptoms of RA patients and, therefore, has therapeutic potential for the treatment of the diseases.

Mesenchymal Stem-Cell Derived Exosome Therapy as a Potential Future Approach for Treatment of Male Infertility Caused by Chlamydia Infection.

Some microbial sexually transmitted infections (STIs) have adverse effects on the reproductive tract, sperm function, and male fertility. Given that STIs are often asymptomatic and cause major complications such as urogenital inflammation, fibrosis, and scarring, optimal treatments should be performed to prevent the noxious effect of STIs on male fertility. Among STIs, Chlamydia trachomatis is the most common asymptomatic preventable bacterial STI. C. trachomatis can affect both sperm and the male reproductive tract. Recently, mesenchymal stem cells (MSCs) derived exosomes have been considered as a new therapeutic medicine due to their immunomodulatory, anti-inflammatory, anti-oxidant, and regenerative effects without consequences through the stem cell transplantation based therapies. Inflammation of the genital tract and sperm dysfunction are the consequences of the microbial infections, especially Chlamydia trachomatis. Exosome therapy as a noninvasive approach has shown promising results on the ability to regenerate the damaged sperm and treating asthenozoospermia. Recent experimental methods may be helpful in the novel treatments of male infertility. Thus, it is demonstrated that exosomes play an important role in preventing the consequences of infection, and thereby preventing inflammation, reducing cell damage, inhibiting fibrogenesis, and reducing scar formation. This review aimed to overview the studies about the potential therapeutic roles of MSCs-derived exosomes on sperm abnormalities and male infertility caused by STIs.

Self-assembled polymeric vesicles: Focus on polymersomes in cancer treatment.

The progress in advanced materials using nanoscale components can be conducted by an innovative idea involving combining nanotechnology approaches with supramolecular chemistry. This concept which is called self-assembly, is employed for formation of nanoscale self-assembled architectures with desirable properties. Self-assembly has emerged as a potent procedure for controlling the structure and characteristics of ensembles. Among self-assembled structures, polymersomes have revealed prodigious potential in drug delivery and development of smart nanomedicine due to their morphological similarities to cellular membranes and viral capsids. Moreover, their functional, tunable and stable membrane render them more advantageous to their lipid counter parts. Polymersomes have been used as different therapeutic carriers as drugs and imaging agents, as well as nanoreactors and artificial organelles. Here we review different basis of self-assembling polymersomes and their properties, the synthesis of various amphiphilic copolymers for vesicles preparation and potential applications of smart controlled release vesicles.

Electronic health record-based disease surveillance systems: A systematic literature review on challenges and solutions.

OBJECTIVE: Disease surveillance systems are expanding using electronic health records (EHRs). However, there are many challenges in this regard. In the present study, the solutions and challenges of implementing EHR-based disease surveillance systems (EHR-DS) have been reviewed. MATERIALS AND METHODS: We searched the related keywords in ProQuest, PubMed, Web of Science, Cochrane Library, Embase, and Scopus. Then, we assessed and selected articles using the inclusion and exclusion criteria and, finally, classified the identified solutions and challenges. RESULTS: Finally, 50 studies were included, and 52 unique solutions and 47 challenges were organized into 6 main themes (policy and regulatory, technical, management, standardization, financial, and data quality). The results indicate that due to the multifaceted nature of the challenges, the implementation of EHR-DS is not low cost and easy to implement and requires a variety of interventions. On the one hand, the most common challenges include the need to invest significant time and resources; the poor data quality in EHRs; difficulty in analyzing, cleaning, and accessing unstructured data; data privacy and security; and the lack of interoperability standards. On the other hand, the most common solutions are the use of natural language processing and machine learning algorithms for unstructured data; the use of appropriate technical solutions for data retrieval, extraction, identification, and visualization; the collaboration of health and clinical departments to access data; standardizing EHR content for public health; and using a unique health identifier for individuals. CONCLUSIONS: EHR systems have an important role in modernizing disease surveillance systems. However, there are many problems and challenges facing the development and implementation of EHR-DS that need to be appropriately addressed.

Correction to: Curcumin: a modulator of inflammatory signaling pathways in the immune system.

Unfortunately, the 4th author name was incorrectly published in the original article. The complete correct name is given below.

Curcumin: a modulator of inflammatory signaling pathways in the immune system.

Curcumin is a natural compound derived from the spice, turmeric, that has been extensively reported for its efficacy in controlling or treatment of several inflammatory diseases. There is a growing body of literature that recognizes the anti-inflammatory effects of curcumin in the immune system. On the other hand, the role of inflammatory signaling pathways has been highlighted in the pathogenesis of several inflammatory diseases, and signaling molecules involved in these pathways are considered as valuable targets for new treatment approaches. We aimed to provide a comprehensive overview of the modulatory effects of curcumin on inflammatory signaling pathways which leads to inhibition of inflammation in different types of immune cells and animal models. In this comprehensive review, we elaborate on how curcumin can effectively inhibit multiple signaling molecules involved in inflammation including NF-κB, JAKs/STATs, MAPKs, ß-catenin, and Notch-1.

Application of Ethics for Providing Telemedicine Services and Information Technology.

INTRODUCTION: Advanced technology has increased the use of telemedicine and Information Technology (IT) in treating or rehabilitating diseases. An increased use of technology increases the importance of the ethical issues involved. The need for keeping patients' information confidential and secure, controlling a number of therapists' inefficiency as well as raising the quality of healthcare services necessitates adequate heed to ethical issues in telemedicine provision. AIM: The goal of this review is gathering all articles that are published through 5 years until now (2012-2017) for detecting ethical issues for providing telemedicine services and Information technology. The reason of this time is improvement of telemedicine and technology through these years. This article is important for clinical practice and also to world, because of knowing ethical issues in telemedicine and technology are always important factors for physician and health providers. MATERIAL AND METHODS: the required data in this research were derived from published electronic sources and credible academic articles published in such databases as PubMed, Scopus and Science Direct. The following key words were searched for in separation and combination: tele-health, telemedicine, ethical issues in telemedicine. A total of 503 articles were found. After excluding the duplicates (n= 93), the titles and abstracts of 410 articles were skimmed according to the inclusion criteria. Finally, 64 articles remained. They were reviewed in full text and 36 articles were excluded. At the end, 28 articles were chosen which met our eligibility criteria and were included in this study. RESULTS: Ethics has been of a great significance in IT and telemedicine especially the Internet since there are more chances provided for accessing information. It is, however, accompanied by a threat to patients' personal information. Therefore, suggestions are made to investigate ethics in technology, to offer standards and guidelines to therapists. Due to the advancement in technology, access to information has become simpler than the past. This has prompted hackers to seize the opportunity. DISCUSSION: This research shows that the ethical issues in telemedicine can be investigated from several aspects like technology, doctor-patient relationship, data confidentiality and security, informed consent, patient's and family's satisfaction with telemedicine services. Following ethical issues in telemedicine is a primary aspect of high quality services. In other words, if therapists abide by ethical rules, they can provide better services for patients. Attention to ethical issues in telemedicine guarantees a safer use of the services.

Relationship Between Job Characteristics and Organizational Commitment: A Descriptive Analytical Study.

BACKGROUND: Many factors influence the organizational commitment of employees. One of these factors is job designing since it affects the attitude, beliefs, and feelings of the organization employees. OBJECTIVES: We aimed to determine the relationship between job characteristics and organizational commitment among the employees of hospitals. PATIENTS AND METHODS: In this descriptive and correlational study, 152 Iranian employees of the hospitals (physicians, nurses, and administrative staff) were selected through stratified random sampling. Data gathered using 3-part questionnaire of "demographic information", "job characteristics model," and "organizational commitment," in 2011. Study data were analyzed using SPSS v. 16. RESULTS: There was significant statistical correlation between organizational commitment and variables of educational level (P = 0.001) and job category (P = 0.001). Also, a direct and significant correlation existed between motivating potential score and job feedback on one hand and organizational commitment on the other hand (P = 0.014). CONCLUSIONS: According to the results, managers of the hospitals should increase staff's commitment through paying attention to proper job designing.

Queen sex pheromone of the slave-making ant, Polyergus breviceps.

Workers of the slave-making ant, Polyergus breviceps, raid nests of Formica ants and return with Formica pupae that mature into worker ants in the slave-makers' colony. These Formica workers then tend the Polyergus brood, workers, and reproductives. During raids in the mating season, winged virgin Polyergus queens accompany the workers in the raiding columns. During the raid, the virgin queens release a pheromone that attracts males that quickly mate with the queens. We report the identification, synthesis, and bioassay of the sex attractant pheromone of the queens as an approximately 1:6 ratio of (R)-3-ethyl-4-methylpentan-1-ol and methyl 6-methylsalicylate. The ants produce exclusively the (R)-enantiomer of the alcohol, and the (S)-enantiomer has no biological activity, neither inhibiting nor increasing attraction to blends of methyl 6-methylsalicylate with the (R)-enantiomer.

Ascorbic acid antagonizes nicotine-induced place preference and behavioral sensitization in mice.

In the present study, the influence of ascorbic acid on the nicotine-induced behavioral sensitization and conditioned place preference was investigated in mice. In the place preference paradigm, intraperitoneal (i.p.) nicotine (1 and 1.5 mg/kg, three drug sessions) but not ascorbic acid (1, 10, 100 and 1000 mg/kg) administration induced place preference. Ascorbic acid administration (10, 100 and 1000 mg/kg, i.p.) reduced both the acquisition and expression of nicotine-induced place conditioning. Locomotor sensitization in mice was produced by intraperitoneal injection of nicotine (0.25 mg/kg) for 7 consecutive days. On the 9th day of the experiments, activity of the mice was recorded after challenge with nicotine (0.1 mg/kg, i.p.). Ascorbic acid (10, 100 and 1000 mg/kg, i.p.) was injected 20 min before each injection of nicotine (acquisition of sensitization) or acutely 20 min before a challenge nicotine injection (expression of sensitization). It was shown that ascorbic acid attenuated the acquisition of nicotine sensitization in a dose-independent manner but the expression of nicotine-induced sensitization was not affected by ascorbic acid. In conclusion, it seems that ascorbic acid may interfere with nicotine-induced place preference and behavioral sensitization in mice.

Sex pheromone of queens of the slave-making ant, Polyergus breviceps.

The sex attractant pheromone produced in mandibular glands of queens of the slave-making ant Polyergus breviceps has been identified as a blend of methyl 6-methylsalicylate and 3-ethyl-4-methylpentanol. In field trials, each compound alone was completely unattractive to males, whereas blends of the two compounds attracted hundreds of males within a couple of hours.