The use of natural substances for medical purposes is associated with the earlier times of humankind. The present study compared the phenolic profiles and anti-hemolytic properties of two honey samples. The total phenolic content and the total flavonoid content were determined spectrophotometrically. The anti-hemolytic activity was tested in-vitro using human erythrocytes pretreated separately with honey samples and ascorbic acid in the presence of aluminium. Five different treatment groups were considered: untreated erythrocytes (negative control), aluminium treated erythrocytes (positive control), honey 1 + aluminium treated erythrocytes, honey 2 + aluminium treated erythrocytes, and ascorbic acid + aluminium treated erythrocytes. Samples were then evaluated by simultaneous measurement of cellular turbidity and hemoglobin. The results showed that Honey 2 contained the highest phenolic content with mean value of 1.55 ± 0.04 mg GAE/g while honey 1 showed a concentration of 0.63 ± 0.03 mg GAE/g. As with the phenolic content, honey 2 showed the highest levels of flavonoid content (0.17 ± 0.003 mg QE/g) when compared to honey 1 (0.075 ± 0.005 QE/g). Erythrocytes suspensions treated with honey samples, particularly honey 2 presented highest cell and hemoglobin values compared to that of ascorbic acid and positive control, whereas, ascorbic acid exhibited a prooxidant effect on cell and hemoglobin. The results of this study demonstrated a protective effect of honey against Al-induced erythrocytes hemolysis and hemoglobin degradation.

The correlation between cigarette smoking and the onset of non-small cell lung cancer is well established. Direct effects of exposure to nicotine (the active component in cigarettes) include increased proliferation, angiogenesis induction, and resistance to apoptosis. Parthenolide (PTH) is a sesquiterpene lactone with anticancer properties against several cancer types. In this work, we tested the ability of PTH to inhibit the proliferating effect of nicotine in lung cancer cell lines. MTT assay was used to measure cell survival of A549 and H526 cells exposed to nicotine, PTH, and their combination. VEGF detection kit was used to measure angiogenesis inhibition while apoptosis induction was evaluated by measuring caspase-3 activity. Real time PCR assay was used to detect the change in expression of several genes associated with cell proliferation and apoptosis. PTH inhibited lung cancer cells in a concentration-dependent manner and decreased the proliferation stimulating effect of nicotine. Caspase-3 activity and VEGF assays evidenced an apoptosis-inducing and VEGF- inhibiting effects of PTH. The real time PCR assay demonstrated that PTH down-regulated the expression of Bcl-2 and up-regulated the expression of E2F1, P53, GADD45, BAX, BIM, and CASP 3,7,8,9, which indicates an activation of P53- dependent apoptosis pathway. Furthermore, this pathway remained active in the presence of nicotine suggesting the ability of PTH to exclude the anti-apoptotic effect of nicotine. Our results indicate that PTH inhibits nicotine proliferating effect on lung cancer. The anticancer effect of PTH is mediated by angiogenesis inhibition and activation of P53- dependent apoptosis. PTH is a promising natural product for inhibiting and treating nicotine-associated lung cancer. However, further studies on more lung cancer cell lines and on protein level are needed to fully understand its mechanisms of action.

Cupressus torulosa (CT) of family cupressaceae, commonly known as ‘Surai’, is a coniferous tree distributed in the states of Uttarakhand and Himachal Pradesh between 1800 to 3300 m. It is an aromatic plant used traditionally claimed to have medicinal properties. Its needles are reported to contain terpenoids and phenolics. Needles of the plant were collected from various locations of Uttarakhand and Himachal. Dried and powdered leaves were at first defatted with Hexane and then sequentially extracted followed by removal of chlorophyll which yielded 19.2% of total extract. Before assessing the in vivo Hypoglycaemic ability of the test extract (AM extract), its acute toxicity was determined according to OECD 423 guidelines. AM extract was orally administered to 3 groups of 3 experimental animals each at three defined doses (500, 1000, 2000mg/kg per os (po)). No mortality was seen at 2000mg/kg so this was selected as a safe dose and with much higher LD_50. Moreover, Subacute toxicity study was conducted in mice for 14 days. In this study control groups of animals were given 10 mL/kg normal saline and treated group of animals were given 400 mg/kg dose of extract orally. On last day animals were sacrificed by overdose of ketamine and heart, kidney and liver were isolated for histological study. It was seen that statistically there was no significant difference between control and treated group of mice. For in vivo Hypoglycaemic activity screening 1% acacia suspension of AM extract (AMAS) was formed and Hypoglycaemic studies were performed by single-dose and repeated-dose streptozotocin-induced diabetic mice model (positive standard glibenclamide). The greatest reduction in Blood Glucose Level (BGL) was recorded in 400mg/kg AMAS treated group at the 4th hour, 14^th day compared to the respective baseline BGL (p< 0.05), further significant weight gain (p<0.05) was seen in contrast with the Hypoglycaemic negative group after 14 days treatment. Therefore, the AM suspension qualifies as a safe and successful drug candidate for Hypoglycaemic activity. Further, the extract was run on LCQTOF-MS to find out active molecules responsible for antidiabetic activity and we found Harpagoside and (-)-Epicatechin which were responsible for the above mentioned activity.

Coronavirus disease 2019 (COVID­-19) is a respiratory illness that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-­CoV-­2) and leads to numerous deaths. SARS-CoV-2 enters cells using its Spike protein, which is also a prospective target for the development of new anti-COVID­-19 drugs. Therefore, searching for novel therapeutic agents with Spike inhibitory activity is an urgent task. Oligoribonucleotides-D-mannitol (ORNs-D-M) complexes possess antiviral activity by inhibiting the activity of surface viral proteins. We hypothesized that the ORNs-D-M could inhibit SARS­-CoV­-2 Spike activity. Because SARS-CoV-2 is a biosafety-level-3 virus, one way to simplify such assays is to pseudotype biosafety-level-2 viral particles with Spike. In this study, we aimed to evaluate the ORNs-D-M efficiency against pseudotyped lentiviral particles with SARS-CoV-2 Spike.

We obtained SARS-CoV-2 Spike-pseudotyped lentiviral particles (Spike-pseudovirus) by transfecting the 293T cells with a plasmid complex (lentiviral backbone (Luciferase-IRES-ZsGreenbackbone), Spike SARS-CoV-2 and the other HIV proteins needed for virion formation). Microscope images showed the ZsGreen expression in the infected 293T-ACE2 cells with Spike-pseudovirus. Low ZsGreen fluorescence was observed in the infected 293T-ACE2 cells with Spike-pseudoviruses that were pre-incubated with the ORNs-D-M compared to the Spike-pseudovirus control. Luciferase expression was indicated in the infected 293T-ACE2 cells with Spike-pseudovirus. It was found that pre-incubation of the Spike-pseudovirus with the ORNs-D-M significantly reduced luciferase activity compared to the Spike-pseudovirus control. Decreased expression of ZsGreen and luciferase, marker proteins of cell infection with Spike-pseudovirus, potentially indicates that the ORNs-D-M interact with SARS-CoV-2 Spike and inhibit the interaction of Spike-pseudovirus with host cells. The obtained results show that the ORNs-D-M can have anti-COVID-­19 activity.

Non-steroidal anti-inflammatory drugs are used to relieve pain, fever, and inflammation while also protecting the cardiovascular system. However, the side effects of currently available anti-inflammatory medications, which include gastric ulcer, bronchospasm, and cardiovascular problems, have limited their usage. Due to the adverse effects of these drugs, there is a high demand for the search of new drugs with lesser or no side effects. In the context, current trend of research has shifted towards synthesis of new anthranilic acid hybrids. Having in mind the variety of biological activities, we have synthesized a new hybrid molecule of anthranilic acid and 2-(3,4-dimethoxyphenyl)ethylamine. The synthesis of a new molecule, attached to a 2-phenylethylamine or substituted 2-phenylethylamines, is extremely interesting in view of what properties the newly obtained molecule would inherit from both fragments. The synthesized hybrid is then used in acylation with various acyl chlorides. A number of new hybrid anthranildiamides were synthesized as a result. The novel molecules were tested in vitro to estimate their anti-inflammatory effect preventing albumin denaturation. The results showed that all the compounds exhibit a preventive effect on albumin denaturation higher than common non-steroidal anti-inflammatory drugs. To confirm the presence of anti-inflammatory effect in the diamides, we conducted additional tests evaluating their effect on Interleukin-1 expression, and similar results were observed. Based on the experimental data, we can conclude that a collection of novel 2-phenylethilamine hybrids were successfully synthesized and they can be considered as anti-inflammatory drug candidates – alternatives to current therapeutics.

Corneal neovascularization constitutes a serious sight-threatening disease. This pathology can be treated using antiangiogenic and anti-inflammatory compounds. Therefore, in this area, atorvastatin (ATV) constitutes a suitable candidate to be administered topically to the eyes due to its pharmacological properties. However, ATV possess low water solubility and it is rapidly eliminated in traditional formulations. Therefore, to attain suitable efficacy, ATV has been encapsulated into custom-developed peptide amphiphiles.

In this study, three peptide amphiphiles bearing one, two or four C₁₆-alkyl groups (mC₁₆-Tat_47-57, dC₁₆-Tat_47-57 and qC₁₆-Tat_47-57) were synthesized using solid-phase synthesis, characterized physically and morphologically and loaded with ATV. From them, ATV-qC₁₆-Tat_47-57 showed higher encapsulation efficiency than mC₁₆-Tat_47-57 and dC₁₆-Tat_47-57 and more defined nanostructures with a tubular shape. Moreover, in vitro ATV release was also assessed confirming that ATV-qC₁₆-Tat_47-57 showed ATV prolonged release. In vitro (HEM-CAM and CAM-TBS) and in vivo ocular tolerance (Draize test in New Zealand rabbits) of ATV-qC₁₆-Tat_47-57 confirmed that ATV-qC₁₆-Tat_47-57 were not irritant. Moreover, ATV-qC₁₆-Tat_47-57 demonstrated to be antiangiogenic in an in ovo model and was able to prevented ocular inflammation in vivo.

Therefore, ATV-qC₁₆-Tat_47-57 constitutes a promising topical medication against corneal neovascularization.

The comprehensive approach to antivirals is needed to successfully fight viruses. Virucidal agents are important for reduction of the viral spread. Among nanoparticles, silver ones are able to directly interact with virions and in combination with right substances their effect can be enhanced. The goal of this work was to study the toxicity and virucidal activity of silver-containing films based on low molecular weight chitosan (LMWC) and sodium carboxymethylcellulose (Na-CMC) polyelectrolyte complexes against influenza A virus H1N1 (IAV) and herpes simplex virus 1 (HSV-1). We also compared the effect of silver-containing films (LMWC-Na-CMC-Ag) obtained by the laser ablation method and the green synthesis using the ginger extract (GE). Methods. The MTT-assay was used for assessment of cytotoxicity in MDCK and Vero cell lines. Virucidal activity was determined by the pre-incubation with the virus for 1 hour followed by determination of the infectious titer (TCID50/ml). Results. Out of all the tested samples, only the ginger extract reduces cell viability by more than 50%. The virucidal effect of the extract manifested itself as a complete reduction of the infectious titer of both viruses. The LMWC-Na-CMC-Ag-GE showed the best virucidal activity with decrease in the infectious titer for 1.88 (IAV) and 3.79 (HSV-1) log10TCID50/ml compared to the virus control. However, LMWC-Na-CMC-Ag obtained by the laser ablation method was not effective. Conclusion. Thus, the polymer silver-containing film obtained by the green synthesis considering the lack of toxicity and virucidal effect against enveloped viruses is promising for further research.

Drug repurposing is a great strategy to find new uses for known active principles: ketoprofen, a non-steroidal anti-inflammatory drug, has shown anti-proliferative activity in melanoma cell lines. Since its solubility is low (0.0213 mg/mL), our objective is to incorporate it in an oil-in-water (O/W) nanoemulsion, increasing formulation dosage, and study the prepared nanosystem.

Spontaneous emulsification was used to prepare seventeen O/W nanoemulsions with the oil phase being Lauroglycol™ 90, Transcutol® HP and Tween® 80, while the aqueous phase was water. Dynamic light scattering was used to determine droplet size and the polydispersity index (PDI), discriminating the most homogeneous formulations. These were further studied in terms of solubility, pH, zeta potential, osmolality, long-term and accelerated stability, and drug release.

It was possible to obtain up to 20 mg/mL of ketoprofen during solubility assays (930 times more than in water), with droplet sizes between 100 and 200 nm. Nanosystem characterisation suggests that formulations are compatible with topical application and that stability is not compromised neither with increased drug loaded concentration nor with time. Drug release assays showed up to 30% release at the 24-hour mark.

Having successfully developed high ketoprofen strength nanoemulsions, high bioavailability may be obtained upon administration. Retrieved data demonstrates that the formulations are stable and might be compatible with skin. Although drug incorporation into the vehicles destabilizes the nanoemulsions, this effect is not concentration-dependent up to the maximum allowed drug concentration. However, viscosity, ex vivo drug permeation, and in vitro citotoxicity still need to be assessed.

Alginate have gained significant attention in the medical and pharmaceutical industry for their biochemical properties. The purpose of this study was to synthesis of phosphorylated alginate and determinate its impact on the Blood Coagulation Processes. Phosphorylation of alginate was achieved using a Phosphorus trichloride and Phosphorus (V) oxychloride. The degree of phosphorylation and characterization of phosphorylated polysaccharide were investigated by nuclear magnetic resonance spectroscopy (NMR), Fourier-transform infrared spectroscopy (FTIR), inductively coupled plasma – mass spectrometry (ICP-MS), specific surface area (Brunauer–Emmett–Teller method) and scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS). Influence of phosphorylated alginate on blood coagulation processes were evaluated by the biochemical-hematological tests including evaluation of Activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT). The surface modification of alginate sodium salt was successfully carried out by phosphorylation in vapour phase with PCl₃ and POCl₃. The results of biochemical properties showed that the obtained phosphorylated alginates were promising materials to be used in biomedical applications as it was demonstrated they had not significantly impaired blood plasma coagulation.

Artificial intelligence is being considered one of the most pressing issues of the moment both in terms of risks and opportunities; it has been hailed as a potential source of new discoveries and feared as a threat to authorship and originality. In the present work we make an exploratory study of the potential of Microsoft Bing with GPT-4 to search for potential uses of minerals for as therapeutic purposes, which besides novel ways for health responses could also contribute to sustainability by the use of wastes from mineral extraction and processing. Results were mixed; not very promising when the question concerned minerals in general, with suggestions that lay outside the traditional scope of Mineralogy and in some cases arguably outside the usual scientific research subjects. More promising suggestions were obtained when the question targeted specific cases (e.g., clay minerals). The chat itself suggested some pertinent follow-up questions on the initial subject, albeit mixed with others like "Can you tell me a joke?".