Search Results (1,495)

Genetic constructs must be delivered selectively to target tissues and intracellular compartments at the necessary concentrations in order to achieve the maximum therapeutic effect in gene therapy. Development of targeted carriers for non-viral delivery of nucleic acids into cells, including those in muscle, which is one of the most challenging tissues to transfect in vivo, remains a topical issue. We have studied ternary complexes of plasmid DNA and an arginine–histidine-rich peptide-based carrier coated with a glutamate–histidine-rich polymer bearing skeletal muscle targeting peptide (SMTP) for the gene delivery to muscle tissue. The relaxation of the ternary complexes after polyanion treatment was assessed using the ethidium bromide displacement assay. The developed polyplexes were used to transfect C2C12 myoblasts in full-media conditions, followed by analysis of their toxic properties using the Alamar Blue assay and expression analysis of lacZ and GFP reporter genes. After delivering plasmids containing the GFP and lacZ genes into the femoral muscles of mdx mice, which are model of Duchenne muscular dystrophy, GFP fluorescence and β-galactosidase activity were detected. We observed that the modification of ternary polyplexes with 10 mol% of SMTP ligand resulted in a 2.3-fold increase in lacZ gene expression when compared to unmodified control polyplexes in vivo. Thus, we have demonstrated that the developed DNA/carrier complexes and SMTP-modified coating are nontoxic, are stable against polyanion-induced relaxation, and can provide targeted gene delivery to muscle cells and tissues. The results of this study are useful for a range of therapeutic applications, from immunization to amelioration of inherited neuromuscular diseases. Full article

This study focuses on the preparation and optimization of caffeic acid (CA)-loaded casein nanoparticles (CS NPs) via the Box–Behnken design (BBD) for potential applications in cancer treatment. CS NPs were loaded with CA as a promising anti-cancer molecule. Non-hazardous green materials were exploited for nanoparticle fabrication. The BBD was used, followed by a desirability function to select the optimum formulation. The BBD was adopted as it avoids the runs implemented in extreme conditions, hence making it suitable for proteins. CS NPs were characterized regarding particle size (PS), size distribution (PDI), zeta potential (ZP), drug entrapment, morphology using TEM, differential scanning calorimetry, molecular docking, in vitro release, and cytotoxicity studies. PS, PDI, and ZP had significant responses, while EE% was insignificant. The suggested models were quadratic with high fitting. Optimized NPs showed PS = 110.31 ± 1.02 nm, PDI = 0.331 ± 0.029, ZP = −23.94 ± 1.64 mV, and EE% = 95.4 ± 2.56%. Molecular modeling indicated hydrophobic and electrostatic interactions between CA and CS, accounting for the high EE%. Almost spherical particles were realized with a sustained CA release pattern. Optimized NPs effectively suppressed the growth of MCF-7 cell lines by scoring the lowest IC50 = 78.45 ± 1.7 µg/mL. A novel combination of bioinspired-derived materials was developed for use in breast cancer treatment. Full article

The gut is an intricate and diverse organ system for investigating visceral pattern generation. The gut made an early evolutionary breakthrough. There is evidence that the molecular mechanisms governing the development of gastrointestinal patterns are species-specific. Some have suggested using marine drugs to treat gastrointestinal disorders. The study, which used an integrated network pharmacology approach, aimed to find out how well fucoidan worked and what Fucus vesiculosus might be doing to help prevent digestive problems. Researchers gathered information on how potential bioactive components of brown seaweed and their associated targets interact with the disease gene targets of gastrointestinal disorders. We studied the signaling pathways linked to F. vesiculosus in the context of gut health treatments using a KEGG (Kyoto Encyclopedia of Genes and Genomes pathway) and GO (Gene ontology) enrichment analysis. We built and studied the protein–protein interaction (PPI) and compound-target networks using Cytoscape. PPI network analysis yielded a total of 44 important targets, including BCL2, ESR1, and STAT3. The KEGG enrichment analysis revealed a strong correlation between the signaling pathways used in the treatment and the prevention of gastrointestinal disorders. We docked significant genes with TNF, STAT3, BCL2, and ALB. Fucoxanthin and fucoidan possess beneficial properties for improving gut health by treating gastric-intestinal issues. This study showed that by controlling several targets and many pathways with multiple components, F. vesiculosus exhibited preventive effects against gastrointestinal disorders. Full article

Curcumin is a well-known and widely used substance of natural origin. It has also been found to be helpful in the treatment of liver diseases. Unfortunately, curcumin has very low bioavailability and a sensitivity to external agents. Improving these parameters is the subject of many studies. One way to overcome these problems may be to use Phosal^® Curcumin as a source of curcumin and encapsulate this dispersion into a nanoemulsion using different types and concentrations of surfactants and co-surfactants, thus manipulating the physicochemical parameters of the nanoemulsion. The present study aimed to develop curcumin-loaded nanoemulsions for intravenous administration and to investigate the effect of Kolliphor HS15 concentration on their critical quality attributes. Methods: Phosal^® Curcumin-loaded nanoemulsions with different concentrations of Kolliphor HS15 were prepared by high-pressure homogenization. The effect of Kolliphor HS15 on emulsion physicochemical properties such as mean droplet diameter (MDD), polydispersity index (PDI), zeta potential (ZP), osmolality (OSM), and pH, as well as encapsulation efficiency (EE) and retention rate (RR) of curcumin, were determined. Mid-term stability studies and short-term stress tests were conducted to evaluate the impact of Kolliphor HS15 on the critical quality attributes of the curcumin-loaded nanoemulsions stored under various conditions. Results: Five nanoemulsions with increasing Kolliphor HS15 concentrations were developed. Their MDD ranged from 85.2 ± 2.0 to 154.5 ± 5.1 nm, with a PDI from 0.18 ± 0.04 to 0.10 ± 0.01 and ZP from −15.6 ± 0.7 to −27.6 ± 3.4 mV. Depending on the concentration of Kolliphor HS15, the EE ranged from 58.42 ± 1.27 to 44.98 ± 0.97%. Conclusions: The studied parameters of the developed nanoemulsions meet the requirements for formulations for intravenous administration. Using the appropriate concentration of Kolliphor HS15 allows for a formulation that presents a protective effect against both curcumin and emulsion degradation. Full article

This paper presents the results of obtaining new cobalt and zinc complexes based on dicyanophenoxy-substituted carboxypthalocyanine. The original method of synthesis and isolation of the compound is shown; its spectroscopic and photophysical characteristics are studied. Studies show the absence of aggregation processes in organic media for solutions of complexes in working concentration ranges. This shows the possibility of the practical application of structures as catalysts. The high catalytic activity of cobalt complexes with dicyanophenoxy-substituted carboxyphthalocyanine ligand in the conversion reaction of sodium diethyldithiocarbamate to disulfiram, which is an active component of drugs for the treatment of alcohol dependence, is determined. Full article

Increasing the biological effectiveness of probiotic preparations requires the development of new stable forms in the gastrointestinal tract. Live bacteria immobilized on a sorbent belong to the latest, fourth generation of probiotics, which ensures a prolonged effect. This study is devoted to developing a new method of preparing active lactobacilli on a natural mineral carrier, a tuff containing zeolite of the clinoptilolite group, which is among the most common authigenic silicate minerals that occur in sedimentary rocks and is known as a safe ion-exchange and adsorbing detoxicant. Among the characterized lactobacilli, strains of L. plantarum, L. acidophilus, and L. crispatus possessed a high level of acid formation and stability in gastrointestinal fluids. The protective effect of the clinoptilolite-containing tuff was registered when the samples were incubated in gastric juice. The optimal technological conditions for immobilization and lyophilization were determined, and the preservation of the viability and probiotic properties of bacteria was confirmed during 8 months of storage. The release of bacteria from the carrier occurred gradually over 12 h. The data obtained show how promising the new preparation is, combining the ability to detoxify harmful intestinal metabolites and the prolonged release of probiotics. Full article

Free radicals are highly reactive compounds that lead to the onset of a variety of serious health conditions, known as “oxidative stress”. Antioxidants, on the other hand, act as defense mechanisms to fight the accumulation of free radicals and maintain cell homeostasis. Urtica dioica L. is a medicinal plant with unique antioxidant properties, mainly attributable to the presence of polar phenolic compounds. This study aimed to optimize the combination of determinant factors toward the maximum extraction of antioxidants from U. dioica L. Furthermore, it investigated the protective role of the extract on red blood cells that were exposed to oxidative stress. The extraction optimization was performed using Response Surface Methodology and the in vitro antioxidant activity of the extract was determined with Folin–Ciocalteu, FRAP, and DPPH assays. Based on the results, the highest value of antioxidant activity and polar phenolic compounds was recorded using 34% (v/v) ethanol as a solvent in an ultrasonic process carried out at 42 °C for 87 min. In addition, UV–Vis spectrum of the extract revealed the presence of chlorophylls, carotenoids, and flavonoid glycosides. This study also provided insight into the in vitro protective effect of the plant extract on red blood cells morphology under oxidative stress conditions. The findings highlighted the good predictability of the extraction model and the potential role of the extract as an antioxidant product. Full article

“Koji” is one of the most well-known probiotic microorganisms in Japan that contribute to the maintenance of human health. Although the beneficial effects of some probiotics on ulcer healing have been demonstrated, there have been no reports on the wound healing effects of koji to date. In the present study, we investigated the effects of “cha-koji”, green tea leaves fermented with Aspergillus luchuensis, on cutaneous wound healing, using a linear incision wound mouse model. Topical application of autoclave-sterilized cha-koji suspension on the dorsal incision wound area healed the wound significantly faster and, notably, with less scarring than did the green tea or the control distilled water treatment. Further in vitro experiments revealed that the accelerated effects of cha-koji could be attributed to its increased anti-bacterial activity, enhanced epidermal cell proliferation and migration, augmented expression of the anti-inflammatory cytokine transforming growth factor-β1, reduced expression of inflammatory cytokine interleukin-6 in macrophages, and decreased endoplasmic reticulum stress. In addition, we conducted a skin sensitizing potential test, which revealed that cha-koji had no adverse effects that posed a sensitizing risk. Thus, cha-koji may have a potent therapeutic effect on cutaneous wound healing, opening up a new avenue for its clinical application as a medical aid. Full article

Different reaction control methods for producing nano/microstructures of poly(butyl cyanoacrylate) (PBCA) have been studied, focusing on pH and monomer-to-initiator ratios. However, these methods often require multiple steps and reagents. In the synthesis of PBCA microparticles using three versions of micromixers designed with HH geometry and varying numbers of channels (4, 10, and 15), different synthesis formulations were investigated by varying monomer concentrations. PBCA microparticles synthesized with 19.2% (w/w) n-butyl cyanoacrylate (n-BCA) monomer, a residence time of 0.06 s, a flow rate of 78 mL·min⁻¹, and a phase ratio of 45/55 (W/O), exhibited an average diameter of 642.2 nm as determined by dynamic light scattering (DLS) analysis. In contrast, PBCA microparticles synthesized with 5.0% (w/w) n-BCA monomer, the same residence time of 0.06 s, a flow rate of 39 mL·min⁻¹, and a phase ratio of 20/80 (W/O), exhibited an average diameter of 74.73 µm according to laser diffraction particle size analysis. Polymer formation was confirmed by Fourier-transform infrared (FTIR) spectroscopy in both formulation and process conditions. These results indicate that the parameters for the production of microparticles with different monomer concentrations in the microfluidic system with HH geometry and 15 channels can be optimized for potential applications in cosmetics and pharmaceutical ingredients. Full article

Helianthemum nummularium (HN) and Helianthemum oelanticum subsp. incanum (HO) are plant species, among Cistaceae, that are highly distributed in the Mediterranean region. In the current study, extracts of the aerial parts from both species have been analyzed phytochemically. The non-polar extract analysis resulted in the identification of 15 compounds in each species, mainly terpene and fatty acid derivatives, through GC–MS. The methanolic extract analysis, conducted through UHPLC–MS/MS, led to the identification of 39 metabolites in HN and 29 in HO, respectively, the majority of which were phenolics. Among the identified compounds, several have also been isolated and structurally determined (from HN: rutin, linoleic acid, gallic acid, and isoquercetin, and from HO: quercetin-3-O-(2″-O-galloyl)-galactopyranoside, methyl gallate, catechin-3-O-glucopyranoside, and astragalin, while hyperoside, and cis- and trans-tiliroside have been determined in both species). Furthermore, the methanolic extracts of HN and HO displayed a high total phenolic content (177.2 mg GA/g extract and 150.6 mg GA/g extract, respectively) and considerable free-radical scavenging activity against the DPPH radical (94.6% and 94.0% DPPH inhibition, respectively). Antimicrobial testing showed stronger inhibition of HN against Gram (+) bacterial strains (MIC values 0.07–0.15 mg/mL), while both extracts exhibited low tyrosinase-inhibitory activity. Considering the lack of studies conducted on the chemistry and biological activities of the genus Helianthemum, the chemical characterization of extracts could contribute to new sources of bioactive metabolites to be explored and exploited for further potential applications such as food and/ or the cosmetic industry. Full article

Currently, there are various physical and mechanical agents that can cause skin wounds, which are still traditionally treated with plant extracts. It has been reported that the genus Tagetes has a wide range of biological properties, including antibacterial and wound healing activity. Likewise, Agave americana extract and Aloe vera gel have shown potential in the treatment of burn wounds and other skin conditions both in vitro and in vivo. In this study, the antibacterial and wound healing activities of each of these plants were investigated, as well as the possibility of enhancing these activities by combining them. First, the secondary metabolites of the extracts were quantified, the antibacterial activity was evaluated using the Kirby-Bauer method, and their cytotoxicity was measured in 3T3 and HaCaT cells using the sulforhodamine B assay. The results revealed that Tagetes nelsonii extract had a higher amount of secondary metabolites, which is why it exhibited antibacterial activity. Finally, the scratch assay showed that the individual extracts of T. nelsonii and A. americana demonstrated greater cell migration and proliferation starting from 12 h, as well as when using the combination of A. americana extract and A. vera gel, which almost completely closed the wound compared to the control. Full article

Chagas disease, caused by the parasitic protozoan Trypanosoma cruzi (T. cruzi), represents a worldwide public health issue. To date, there is no efficient treatment to combat this pathology, and the only drugs available are usually toxic to the patient. Through the enzyme trans-salidase, the parasite invades, infects, and multiplies intracellularly in the host cell. This protein has been considered an attractive target for developing or searching for compounds with potential trypanocidal activity. In this study, an in silico analysis was performed using a Food and Drug Administration-approved computational drug repositioning approach to identify compounds with anti-Chagas potential against two trans-sialidase proteins. Those compounds with potential inhibition were analyzed and selected through a molecular docking-based virtual screening. Forty-nine compounds were identified, of which forty-five are available on the market, and the rest were evaluated in silico. Our predicted results follow that these compounds are safe for human use and could be potential anti-trans-sialidase agents. Full article

Objectives: In this retrospective observational study, the aim is to establish how the implementation of the use of antimicrobial stewardship programs at the hospital and intensive care unit level in a Sucre Clinic in Sincelejo has had a significant impact on the improvement of the rational use of antibiotics, due to the alarming situation of increasing antibiotic resistance. Materials and methods: The methodology used was to analyze the Excel database of the Clinic in such a way as to compare the data from 2017, the period prior to the implementation of the antimicrobial stewardship program (ASP), with the subsequent evolution between the years 2018 and 2022, in relation to the institutional records of four antibiotics—ceftriaxone3, ciprofloxacin4, meropenem5, and vancomycin6, measured in defined daily dose (DDD). Results: According to the defined daily dose values obtained for the four antibiotics, a reduction in the defined daily dose was identified in the post-implementation period. On the other hand, considering the DDD reported by the World Health Organization for each of the antibiotics, significant differences were verified in comparison with those obtained in the clinic in the hospitalization and intensive care unit services. Conclusions: In conclusion, in the clinic, a reduction in the defined daily dose was verified in the period after the implementation of the antimicrobial stewardship program compared to the previous period, both in the hospitalization and intensive care unit, as well as having a mild-to-large effect with Cohen’s D. Full article

Background: Depression is a common mood disorder that manifests itself simultaneously with chronic diseases. It is especially common in patients diagnosed with cancer, and when neglected, it reduces the success of cancer treatment. The fact that breast cancer is the most common type of cancer in women shows that the treatment of depression in women with cancer is very important. As a result, cancer patients undergoing chemotherapy in oncology units also use antidepressants simultaneously. It is critical to correctly understand the interactions between drugs used in combination. Method: In this study, doses were prepared for MCF7 and MDAMB-231 cell lines by serial dilution from 1000 ng/mL to 1.95 ng/mL. Cell viability was calculated with the WST-1 kit by applying the prepared doses of capecitabine and sertraline alone. In the sertraline/capecitabine combination study, cell viability was examined in MDAMB-231 and MCF-7 cells by applying doses of 300, 100, 50, 25, 10 ng/mL. Combinations that showed selective cytotoxicity after the combination were analyzed with the CompuSyn program and the combination index (CI<1 = synergism) was calculated. Studies on caspase 3-8-9, DNA fragmentation and mTOR were continued using a combination that showed a synergistic effect. Result: It was determined that compared to drug use alone, the sertraline/capecitabine combination decreased cell viability. There is no significant difference in caspase-3,-8,-9 and DNA fragmentation in cancer cells, but there is a reduction in the level of mTOR. This suggests that the death mechanism may be autophagy. Docking studies with autophagy pathway-related proteins further support our results. It is noteworthy that the AKT1-sertraline complex had the best binding affinity among the target proteins (−9.1 kcal/mol). Full article

In recent years, an innovative approach has emerged in the field of toxicology for managing acute intoxications caused by lipophilic substances: intravenous lipid emulsions (ILEs). Through numerous experiments and case reports, the efficacy of lipid emulsions in counteracting toxicities induced by lipophilic agents, including a significant number of antiepileptic (AE) drugs, have become increasingly evident. Data spanning a 10-year period (2010–2020) were analyzed by searching through multiple scientific publication platforms like PubMed, Science Direct, Research Gate, and Springer Link. This study focused on reviewing relevant case reports detailing successful intravenous lipid emulsion (ILE) administration in patients with acute intoxications with antiepileptics, specifically examining the impact of fat emulsions on neurological status, Glasgow Coma Scale (GCS) scores, and corrected QT interval concerning hemodynamic instability. The typical symptoms of antiepileptic toxicity include central nervous system depression, ataxia, and nystagmus. Intravenous lipid emulsion application resulted in an increase in Glasgow Coma Scale scores and enhanced recovery from drug intoxication. This study provides a comprehensive overview of the potential utility of ILE as a component to antidote therapy in cases of acute AE poisoning involving neurotropic drugs. The process involves the engagement of various mechanisms of antitoxic activity. Full article