Dominant optic atrophy (DOA) is one of the most frequent forms of hereditary optic neuropathy. This condition is mainly triggered by pathogenic variants in OPA1, which plays a key role in mitochondrial dynamics, cell survival, oxidative phosphorylation or the maintenance of mitochondrial DNA. Mutations in OPA1 cause a decrease of energy production capacity and the degeneration of retinal ganglion cells (RGCs), leading to optic nerve atrophy and reduced visual acuity. Currently, there is no effective treatment for DOA due in part to the lack of an appropriated disease model. The main objective of this work has been the use of induced pluripotent stem cell (iPSC) technology as a tool for the generation of patient-specific iPSC-derived RGCs. For this purpose, we have used an iPSC line previously created from fibroblasts obtained from a DOA patient carrying the mutation c.1861C>T; p.Q621* in the OPA1 gene. Subsequently, an isogenic control iPSC line has been generated by correcting the causative pathogenic variant with the CRISPR/Cas9 system. Then, both iPSC lines have been differentiated towards RGCs using an optimized stepwise protocol based on the modulation of several signalling pathways. The generated RGCs showed expression of typical markers, such as BRN3A, SNCG or THY1. Here we show the generation of iPSC-RGCs from a DOA patient and its isogenic control, which will constitute a suitable platform for understanding the pathophysiological mechanisms underlying DOA, opening up the possibility to identify an appropriate treatment.

Enteroaggregative Escherichia coli (EAEC) has widely been recognized as one of the leading causes of infantile diarrhoea and nutrient malabsorption both in developing and developed countries. In recent times, drug resistance, particularly multi-drug resistance (MDR) among the EAEC strains has been documented and would result in a therapeutic stumble; antimicrobial alternatives are employed widely to curb this emerging public health menace. In the present study, a facile one-pot synthesis of silver/zinc oxide nanocomposites (Ag/ZnO NCs) using methanolic extract of stem and leaves of Curcuma longa was performed. The synthesis of Ag/ZnO NCs was confirmed using UV-vis spectroscopy (UV-vis) and Fourier transform infrared spectroscopy (FTIR), while the thermal stability was ascertained by thermogravimetric analysis with differential thermogravimetric analysis (TGA/DTA), whereas crystallinity was determined using Powder X-ray diffraction (PXRD). The shape and size of the green synthesized Ag/ZnO NCs determined using field emission-scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) revealed an irregular polycrystalline morphology with a size of 31.34 ± 1.27 nm. Later, the antibacterial potential of the green synthesized Ag/ZnO NCs evaluated against MDR- EAEC strains revealed a minimum inhibitory concentration (MIC) of 31.25 μg/mL and a minimum bactericidal concentration (MBC) ranging from 62.50 to 125 μg/mL. Moreover, the green synthesized Ag/ZnO NCs inhibited the biofilm-forming ability of the tested strains of MDR-EAEC. Besides, a concentration-dependent antioxidant activity was exhibited by the green synthesized Ag/ZnO NCs as evidenced by ABTS assay and reducing power assay. Overall, this study demonstrated the antibacterial, antifouling as well as antioxidant potential of green synthesized Ag/ZnO NCs using C. longa extract, which might be used as an alternative therapeutic candidate.

Depression is a serious psychological disorder with high prevalent rates, especially among university students. Serum proteins related to immune system, oxygen and lipid transfer could have contributing roles in the development of depression and could act as biomarkers for depression. Currently, there is a lack of accurate biological methods to diagnose depression. Biomarkers could be an inexpensive and convenient way to predict depression and understand its pathophysiology. This study aimed to screen the serum proteome profile of a depressed student for the identification of potential depression biomarkers. A Malaysian private university student who was recruited from the pre-test study (n=10) was further analyzed for serum proteome, due to he was depressed with scores of 15 out of 27 on the Patient Health Questionnaire (PHQ-9). After depleting the high-abundance proteins from the serum sample, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to identify the expressed proteins. A total of 224 proteins were identified. Globins, globulins, apolipoproteins and glycoproteins were most commonly detected. Here we show the potential biomarkers to identify depression vulnerable individuals. These findings can be relevant to the development of new diagnostic and treatment strategies. However, further studies with larger sample sizes and healthy controls are needed to confirm the role of these candidate biomarkers for the prediction and diagnosis of depression.

In the last few decades, natural products from plants have got immense importance in human health due to their therapeutic multi-functionality. They have also been reported to enhance human gut health, another important factor in the overall human health. Diabetes Mellitus Type 2 (DM 2) is now a global concern with 6.28% of the world's population affected by it. Many hypoglycemic drugs currently available in the market are either directly or indirectly based on a number of plant secondary metabolites. In the current study, we aimed to find out the hypoglycemic secondary metabolites from leaf methanolic extract of Argyreia nervosa (Burm. f.) Bojer (Family: Convolvulaceae). In the in vitro experiment, this extract showed good inhibitory activity against Porcine Pancreatic Alpha-amylase (PPA) with IC₅₀ value of 1.1 mg/ml. Presence of Quercetin and Ursolic acid was identified in the leaf methanolic extract with HPTLC, HPLC and MS analysis. The calculated IC₅₀ values against PPA, for standard Quercetin and Ursolic acid were 16.5 µg/ml and 13.2 µg/ml respectively. In silico studies used both of these compounds as ligands against PPA (PDB ID: 1OSE) in AutoDock 4.2.6. Significant binding energies of -9.89 kcal/mol and -8.96 kcal/mol were seen for Quercetin and Ursolic acid respectively; while Acarbose (drug used as positive control) had binding energy of -12.48 kcal/mol. Both Quercetin and Ursolic acid strongly interacted with the pivotal amino acid residues like Glu233, Asp197 and Asp300, present at the active site of PPA, which upholds our in vitro experimental results. Both the compounds have exhibited beneficial effects on human gut health in DM 2 and related complications. Docking results of them with few intestinal markers significant in gut health would also be discussed.

The problem of pharmacological correction of CNS hypoxic disorders is one of the priority. HSP70, an endogenous regulator of cytoprotective processes, can be considered as an effective pharmacological target. The aim of this research was to study the ability of cerebrocurin, angiolin, glutoredoxin, tamoxifen, thiotriazoline, L-arginine, nikomex, HSF-1 and piracetam to modulate the level of HSP70 in the cerebral cortex and blood plasma of rats after prenatal hypoxia (PH). We studied the effect of drugs on the content of HSP70 in plasma and neurons (cytoplasmic and mitochondrial fractions) of rat pups on the 30th and 60th days of life in model of hemic chronic PH using the enzyme immunoassay method. It was found that PH leads to suppression of HSP70 synthesis and to decrease in its intra- and extracellular levels with the most significant decrease during the 1st month of life. Drugs course administration demonstrates an increase in intracellular and extracellular levels of HSP70 with a prolonged effect. Cerebrocurin, angiolin, and tamoxifen were the most active modulators of intracellular HSP70. Cerebrocurin, angiolin, and piracetam had the most active effect on the HSP70 content in blood plasma, but the effect of piracitam on the cytosolic and mitochondrial HSP70 fractions was the least of all the drugs studied. Here we show that cerebrocurin and angiolin were the most effective modulators of HSP70, and their neuroprotective effect deserves further comprehensive study in order to develop methods for effective treatment of hypoxic disorders. HSP70 can serve as a target and marker of hypoxia pharmacological correction.

The strong link between coagulation and inflammation has recently been investigated in multiple sclerosis (MS) in the light of coagulant serine proteases as potential pro-inflammatory mediators in the central nervous system of MS animal models. Furthermore, antibodies against coagulant components have been suggested as pro-coagulant effectors, suppressing anticoagulant mechanisms and enhancing thrombosis in diseases with clinical features similar to those of MS. Our research attempted to investigate the effects of IgG antibodies in the coagulation-inflammation circuit and characterize their role in MS pathology. Serum samples from 15 seropositive MS patients for IgG antibodies against factor (F)VIIa, thrombin, prothrombin, FXa, FXII, plasmin, and protein C were subjected to antibody purification by affinity chromatography, followed by in vitro stimulation of human astrocytes. Serum samples from 14 healthy controls and 8 negative MS patients for antibodies studied were also subjected to the same procedure to be used as negative controls. The expression levels of the thrombin-activated receptor (PAR-1) and activated pro-inflammatory ERK1/2 kinases were analyzed by immunoblot to evaluate intracellular signaling pathways triggered by these antibodies. Using human primary astrocytes, we validated our results ex vivo. The highest expression levels of pro-inflammatory molecules were observed when fractions with anti-thrombin IgG or fractions with cross-reactivities were used for stimulation. Namely, we observed upregulation of the PAR-1 receptor up to four-fold compared to unstimulated astrocytes and up to 2.5-fold overexpression of the activated ERK1/2 kinases following astrocytic stimulation with purified IgG from seropositive MS patients. Conversely, no substantial alteration was observed when purified samples from MS patients who tested negative for IgG and healthy controls were used upon stimulation. Therefore, understanding the role of IgG against coagulation components in intracellular signaling pathways involved in MS may serve as biomarkers for prognosis and monitoring of disease and may prove valuable in establishing novel therapeutic strategies.

Medicinal and aromatic plants (MAPs) have been utilized as medicine since antiquity. Through ethnobotanical and chemical characterization, research in this area allowed for the accumulation of important knowledge concerning plant compositions and their therapeutic properties. Among a variety of MAPs, the Lamiaceae family, which includes but is not limited to sage (Salvia), basil (Ocimum), lavender (Lavandula), and marjoram (Origanum), has several that are frequently used in therapeutic applications due to the secondary metabolites generated by species of these genus. This study aims to analyze the patent documents concerning the uses of these four MAPs in relation to COVID-19 during the last three years. Through the example of these remarkable plants, we present how MAPs can be a fast, healthy, and efficient recourse for designing new drugs or compositions to face new health challenges, such as the COVID-19 pandemic. The patent documents were searched through different specialized databases by using relevant keywords, and the search was performed on the titles, abstracts, and claims. A state of the art was established by extracting from the patent documents data related to publication years, classifications, inventors, applicants, and jurisdictions. Since the advent of the COVID-19 pandemic, about a hundred patent documents linking the studied plants to the coronavirus have been found. Through our case study, we found that most of the patent applications were filed under international jurisdiction by pharmaceutical companies as applicants. Based on the patent classification, most of the claimed inventions are indeed medicinal preparations characterized by being made with Lamiaceae or having antiviral activities. Finally, the relevant patent documents demonstrate a particular interest in the valorization of bioactive compounds derived from Lamiaceae to improve human defense mechanisms, as well as compositions or methods for treating and preventing a coronavirus infection. However, the Salvia genus is the most useful for preventing and/or curing SARS-CoV-2 infection.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder involving different etiopathogenic mechanisms. Traditionally, acetylcholinesterase (AChE) inhibitors constitute a pharmacotherapeutic strategy for AD treatment. Resveratrol is a natural polyphenol, with anti-inflammatory, neuroprotective, anticarcinogenic, and antioxidant properties. To increase its bioavailability and solubility, a series of resveratrol derivatives were obtained, through microwave-assisted synthesis. This study aimed to evaluate the AChE inhibitory properties and the protective role against oxidative stress damage of 5 resveratrol analogs (M1 to M5) in SH-SY5Y cells. The studied compounds were not cytotoxic in a wide range of concentrations as determined by measurement of the activity of the enzyme lactate dehydrogenase. Treatment of SH-SY5Y cells at the AChE´s IC50s concentration (obtained by in vitro enzyme assays) significantly decreased the AChE enzyme activity in live cells, assessed by Ellman's method. The studied compounds did not present cytoprotective activities against H₂O₂ or KCl-induced-Ca²⁺ overload insults. However, through the dichlorofluorescein assay, 3 compounds decreased the endogenous production of reactive oxygen species (ROS). These results demonstrate that, in addition to their action as biologically active AChE inhibitors, some resveratrol derivatives exhibit neuroprotective effects against endogenous ROS production. These findings indicate that the new resveratrol derivatives could be considered as interesting entities with potential therapeutic applications for AD treatment.

Cyclooxygenases (COX) are enzymes responsible for metabolizing arachidonic acid into important inflammatory mediators, prostanoids. COX-2 is the inducible isoform and despite their efficacy, its available inhibitors present an increased risk of cardiovascular events, justifying the search for new molecules without this adverse effect. Chalcones are polyhydroxylated aromatic compounds with anti-inflammatory potential. However, their effect on COX-2 remains little explored. The main objective of this work was to evaluate the COX-2 inhibitory activity of the chalcones 2',3,4,4',6'-pentahydroxychalcone (5OH), 2',3,4,4',6'-pentamethoxychalcone (5OMe) and 2',3,4,4'-tetrahydroxychalcone (butein), at non-cytotoxic concentrations, in an experimental human whole blood model. The cytotoxicity of these chalcones was assessed through their effect on the viability of human blood cells, using UV/Vis spectrophotometry and flow cytometry techniques. The anti-inflammatory activity was evaluated through the quantification of prostaglandin E2 production, via COX-2, in human blood. The obtained results showed that none of the chalcones under study were cytotoxic. Butein was the only one that demonstrated a concentration-dependent inhibitory activity (40 ± 8%, for 50 µM). Under the present experimental conditions, 5OH and 5OMe showed no activity. In conclusion, butein seems to present some potential as COX-2 inhibitor. This chalcone may thus serve as a base structure for the development of new derivatives with anti-inflammatory activity.

Wound healing consists of a sequence of coordinated phases: inflammation, proliferation, and remodeling. In skin lesions, neutrophils and keratinocytes are the main cell types participating in the inflammatory phase, during which release of mediators intervening in the regulation of the subsequent regenerative phases takes place. These mediators are involved in tissue regeneration through induction of transendothelial migration, enzyme secretion, cell adhesion and T-Cell activation and cytotoxicity, as well as neutrophil accumulation at the wound site. Among these mediators, the keratinocyte synthesized chemokines RANTES, MCP-1, MIP-1 and IL-8 stand out. Although therapies applying electromagnetic fields or electric currents have been shown to have anti-inflammatory effects in a variety of experimental models and in patients through of reduced production of proimflammatory cytokines such as IFN-ϒ and increased production of IL-10, the knowledge on the biological basis of these effects is still limited. Previous studies by our group have shown that subthermal treatment with radiofrequency (RF) currents used in capacitive-resistive electric transfer (CRET) therapy promotes proliferation and migration of various cell types, such as human ADSC (stem cells), fibroblasts or keratinocytes, involved in skin regeneration. This study investigates the effects of in vitro treatment with CRET currents on cytokine production by HaCat human keratinocytes. The results reveal that, compared to sham-exposed controls, RF stimulation induces decreased production of IL-8 and increased MCP-1, without significantly affecting other chemokines such as RANTES or MIP-1. Taken together, our results indicate that due to the RF effects on the production of chemokines involved in the modulation of the inflammatory phase of wound regeneration, CRET therapy could be effective in the treatment of skin wounds.