Polysaccharide-based hydrogel enriched by epidermal growth factor peptide fragment for improving the wound healing process.

Wounds represent a "silent epidemic" in the global population that impact significantly people's quality of life and the economy of societies. Owing to the numerous therapies, the pursuit of a perfect wound dressing with superior performance for treating all sorts of wounds is still underway. Several studies have shown the potential of integrating restorative peptides into the scaffolds as potential therapeutic candidates for wound healing. So far, there is little information about the wound-healing effect of S-acetamidomethyl Cys 20-31-EGF peptide, a main fragment of epidermal growth factor. In this regard, the effectiveness of this peptide in the alginate-gum arabic polysaccharide hydrogel was evaluated as a wound dressing (AG-P). Physicochemical evaluation of the hydrogels demonstrated that the incorporation of the peptide compressed the hydrogel network due to the presence of hydrogen and electrostatic bonds without significant effect on the mechanical, viscoelastic properties, swelling and degradation rate of the hydrogel. The hydrogel could continuously release the peptide and prevent rapid attenuation of its concentration. Cellular assessment of AG-P by scratch test and CFSE cytoplasmic dye/flow cytometry technique encouraged the migration and proliferation of human fibroblast cells, respectively. The effect of the AG-P on the expression of IL-6, TNF-α, NF-kB1 and VEGF genes indicated that this hydrogel reduced inflammation, and significantly increased angiogenesis compared to the control group based on the Real-time PCR results. In vitro assessment indicated that this structure can promote efficient and faster wound regeneration by altering the microenvironment of the wound. The hydrogel showed interesting features to be more equipped with other therapeutic agents making it as suitable dressing for various type of the wounds.

Catalase-gold nanoaggregates manipulate the tumor microenvironment and enhance the effect of low-dose radiation therapy by reducing hypoxia.

Radiotherapy as a standard method for cancer treatment faces tumor recurrence and antitumoral unresponsiveness. Suppressive tumor microenvironment (TME) and hypoxia are significant challenges affecting efficacy of radiotherapy. Herein, a versatile method is introduced for the preparation of pH-sensitive catalase-gold cross-linked nanoaggregate (Au@CAT) having acceptable stability and selective activity in tumor microenvironment. Combining Au@CAT with low-dose radiotherapy enhanced radiotherapy effects via polarizing protumoral immune cells to the antitumoral landscape. This therapeutic approach also attenuated hypoxia, confirmed by downregulating hypoxia hallmarks, such as hypoxia-inducible factor α-subunits (HIF-α), vascular endothelial growth factor (VEGF), and EGF. Catalase stability against protease digestion was improved significantly in Au@CAT compared to the free catalase. Moreover, minimal toxicity of Au@CAT on normal cells and increased reactive oxygen species (ROS) were confirmed in vitro compared with radiotherapy. Using the nanoaggregates combined with radiotherapy led to a significant reduction of immunosuppressive infiltrating cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (T-regs) compared to the other groups. While, this combined therapy could significantly increase the frequency of CD8+ cells as well as M1 to M2 macrophages (MQs) ratio. The combination therapy also reduced the tumor size and increased survival rate in mice models of colorectal cancer (CRC). Our results indicate that this innovative nanocomposite could be an excellent system for catalase delivery, manipulating the TME and providing a potential therapeutic strategy for treating CRC.

Alginate/gum arabic-based biomimetic hydrogel enriched with immobilized nerve growth factor and carnosine improves diabetic wound regeneration.

Diabetic foot ulcers (DFUs) often remain untreated because they are difficult to heal, caused by reduced skin sensitivity and impaired blood vessel formation. In this study, we propose a novel approach to manage DFUs using a multifunctional hydrogel made from a combination of alginate and gum arabic. To enhance the healing properties of the hydrogel, we immobilized nerve growth factor (NGF), within specially designed mesoporous silica nanoparticles (MSN). The MSNs were then incorporated into the hydrogel along with carnosine (Car), which further improves the hydrogel's therapeutic properties. The hydrogel containing the immobilized NGF (SiNGF) could control the sustain release of NGF for >21 days, indicating that the target hydrogel (AG-Car/SiNGF) can serve as a suitable reservoir managing diabetic wound regeneration. In addition, Car was able to effectively reduce inflammation and significantly increase angiogenesis compared to the control group. Based on the histological results obtained from diabetic rats, the target hydrogel (AG-Car/SiNGF) reduced inflammation and improved re-epithelialization, angiogenesis, and collagen deposition. Specific staining also confirmed that AG-Car/SiNGF exhibited improved tissue neovascularization, transforming growth factor-beta (TGFß) expression, and nerve neurofilament. Overall, our research suggests that this newly developed composite system holds promise as a potential treatment for non-healing diabetic wounds.

Catalase application in cancer therapy: Simultaneous focusing on hypoxia attenuation and macrophage reprogramming.

The tumor microenvironment (TME), as an immunosuppressive milieu, has a critical role in tumor progression and increases resistance to the conventional treatments. Among the abundant immunosuppressive cells in the TME, tumor-associated macrophages (TAMs) could be a promising target for reprogramming and potentiating the local anti-tumor response. On the other hand, hypoxia is a major barrier in treating solid tumors, which aggravates the situation and alleviates the anti-tumor immune responses. Moreover, catalase and catalase-mimicking compounds can efficiently participate in the TAMs polarization and hypoxia attenuation in the TME. In this review, we will introduce a practical and novel approach which can simultaneously reduce hypoxia and polarize TAMs in the TME. Furthermore, catalase therapeutic effects in combination with cancer therapy methods will be fully discussed. This work aims to inspire readers to explore new avenues for designing and development of next-generation catalase-based formulations for cancer therapy.

The Situation of Small Molecules Targeting Key Proteins in combatting SARS-CoV-2: Synthesis, Metabolic Pathway, Mechanism of Action, and Potential Therapeutic Applications.

Due to the high mortality rate of the 2019 coronavirus disease (COVID-19) pandemic, there is an immediate need to discover drugs that can help before a vaccine becomes available. Given that the process of producing new drugs is so long, the strategy of repurposing existing drugs is one of the promising options for the urgent treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease. Although FDA has approved Remdesivir for the use in hospitalized adults and pediatric patients suffering from COVID-19, no fully effective and reliable drug has been yet identified worldwide to treat COVID-19 specifically. Thus, scientists are still trying to find antivirals specific to COVID-19. This work reviews the chemical structure, metabolic pathway, and mechanism of action of the existing drugs with potential therapeutic applications for COVID-19. Furthermore, we summarized the molecular docking stimulation of the medications related to key protein targets. These already established drugs could be further developed, and after their testing through clinical trials, they could be used as suitable therapeutic options for patients suffering from COVID-19.

Immunopathological similarities between COVID-19 and influenza: Investigating the consequences of Co-infection.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a global public health emergency since December 2019, and so far, more than 980,000 people (until September 24, 2020) around the world have died. SARS-CoV-2 mimics the influenza virus regarding methods and modes of transmission, clinical features, related immune responses, and seasonal coincidence. Accordingly, co-infection by these viruses is imaginable because some studies have reported several cases with SARS-CoV-2 and influenza virus co-infection. Given the importance of the mentioned co-infection and the coming influenza season, it is essential to recognize the similarities and differences between the symptoms, immunopathogenesis and treatment of SARS-CoV-2 and influenza virus. Therefore, we reviewed the virology, clinical features, and immunopathogenesis of both influenza virus and SARS-CoV-2 and evaluated outcomes in cases with SARS-CoV-2 and influenza virus co-infection.

Magnetic carnosine-based metal-organic framework nanoparticles: fabrication, characterization and application as arsenic adsorbent.

This study centers on the controllable synthesis, characterization, and application of a novel magnetic bio-metal-organic framework (Bio-MOF) for the adsorption and subsequent removal of arsenic from aqueous solutions. Zinc ions and carnosine (Car) were exploited to construct the Car-based MOF on the surface of magnetite (Fe3O4 NPs). The Magnetite precoating with Car led to an increase in the yield and the uniform formation of the magnetic MOF. The prepared magnetic Bio-MOF nanoparticles (Fe3O4-Car-MOF NPs) had semi-spherical shape with the size in the range of 35-77 nm, and the crystalline pattern of both magnetite and Car-based MOF. The NPs were employed as an adsorbent for arsenic (As) removal. The adsorption analyses revealed that all studied independent variables including pH, adsorbent dose, and initial arsenic concentration had a significant effect on the arsenic adsorption, and the adsorption data were well matched to the quadratic model. The predicted adsorption values were close to the experimental values confirming the validity of the suggested model. Furthermore, adsorbent dose and pH had a positive effect on arsenic removal, whereas arsenic concentration had a negative effect. The adsorption isotherm and kinetic studies both revealed that As adsorption fitted best to the Freundlich isotherm model. The maximum monolayer adsorption capacity (94.33 mg/g) was achieved at room temperature, pH of 8.5 and adsorbent dose of 0.4 g/L. Finally, the results demonstrated that the adsorbent could be efficiently applied for arsenic removal from aqueous environment.

Clinical and economical impacts of guideline implementation by the pharmaceutical care unit for high cost medications in a referral teaching hospital.

BACKGROUND: Irrational drug use is a global health challenge in all healthcare settings, such as hospitals. This study evaluated the impact of an intervention by the pharmaceutical care unit on the use pattern of high-value medications and their direct costs in a referral hospital. METHODS: This interventional, prospective study was carried out in clinical wards of Namazi Hospital (Shiraz University of Medical Sciences) during six months from May 2015 to October 2015. Clinical pharmacists completed the checklists for albumin, intravenous (IV) pantoprazole, and IV immune globulin (IVIG), as three high-cost medications. When ordering these medications, the physicians were asked to complete the checklists. Then, trained pharmacists examined the checklists, based on the clinical and paraclinical conditions. RESULTS: The total number of administered medications and their relative cost decreased by 50.76% through guideline implementation; the difference was significant (P <  0.001). In addition, the direct cost of albumin and IV pantoprazole significantly decreased (55.8% and 83.92%, respectively). In contrast, the direct cost of IVIG increased by 40.9%. After guideline implementation, the monthly direct cost of all three medications decreased by $77,720 (55.88%). The all-cause in-hospital mortality rate did not change significantly due to the intervention. The median length of hospital stay was six and seven days, respectively in the pre- and post-intervention periods. CONCLUSION: Based on the findings, implementation of guidelines by the pharmaceutical care unit caused a significant reduction in albumin and IV pantoprazole consumption and reduced their direct costs in a referral center in Iran.

Enhanced Delivery of Plasmid Encoding Interleukin-12 Gene by Diethylene Triamine Penta-Acetic Acid (DTPA)-Conjugated PEI Nanoparticles.

Recombinant therapeutic proteins have been considered as an efficient category of medications used for the treatment of various diseases. Despite their effectiveness, there are some reports on the systemic adverse effects of recombinant therapeutic proteins limiting their wide clinical applications. Among different cytokines used for cancer immunotherapy, interleukin-12 (IL-12) has shown great ability as a powerful antitumor and antiangiogenic agent. However, significant toxic reactions following the systemic administration of IL-12 have led researchers to seek for alternative approaches such as the delivery and local expression of the IL-12 gene inside the tumor tissues. In order to transfer the plasmid encoding IL-12 gene, the most extensively investigated polycationic polymer, polyethylenimine (PEI), was modified by diethylene triamine penta-acetic acid (DTPA) to modulate the hydrophobic-hydrophilic balance of the polymer as well as its toxicity. DTPA-conjugated PEI derivatives were able to form complexes in the size range around 100-180 nm with great condensation ability and protection of the plasmid against enzymatic degradation. The highest gene transfer ability was achieved by the DTPA-conjugated PEI at the conjugation degree of 0.1 % where the level of IL-12 production increased up to twofold compared with that of the unmodified PEI. Results of the present study demonstrated that modulation of the surface positive charge of PEI along with the improvement of the polymer hydrophobic balance could be considered as a successful strategy to develop safe and powerful nanocarriers.

DFT-based QSAR study of alkanols and alkanthiols using the conductor-like polarizable continuum model (CPCM).

The usefulness of the CPCM method, calculated at the level of the DFT theory using 6-311++G** basis set for QSAR study of anesthetic activity of alkanol(thiol)s was examined. Three classes of molecular descriptors including AIM, chemical and quantum chemical were used to model the relationships between the anesthetics activity and structural characteristics. Multiple linear regressions were performed to model the relationships between molecular descriptors and biological activity of these molecules using stepwise method and as variable selection tool. A multi-parametric equation containing four descriptors with good statistical qualities was obtained by multiple linear regression (MLR) using stepwise method.