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The aim of this study was to identify the association between four selected inflammatory polymorphisms with the development of long-term post-COVID symptoms in subjects who had been hospitalized due to SARS-CoV-2 infection during the first wave of the pandemic. These polymorphisms were selected as they are associated with severe COVID-19 disease and cytokine storm, so they could be important to prognoses post-COVID. A total of 408 (48.5% female, age: 58.5 ± 14.0 years) previously hospitalized COVID-19 survivors participated. The three potential genotypes of the following four single-nucleotide polymorphisms, IL-6 rs1800796 , IL-10 rs1800896 , TNF-α rs1800629 , and IFITM3 rs12252 , were obtained from non-stimulated saliva samples of the participants. The participants were asked to self-report the presence of any post-COVID symptoms (defined as symptoms that had started no later than one month after SARS-CoV-2 acute infection) and whether the symptoms persisted at the time of the study. At the time of the study (mean: 15.6, SD: 5.6 months after discharge), 89.4% of patients reported at least one post-COVID symptom (mean number of symptoms: 3.0; SD: 1.7). Fatigue (69.3%), pain (40.9%), and memory loss (27.2%) were the most prevalent post-COVID symptoms in the total sample. Overall, no differences in the post-COVID symptoms depending on the IL-6 rs1800796 , IL-10 rs1800896 , TNF-α rs1800629 , and IFITM3 rs12252 genotypes were seen. The four SNPs assessed, albeit having been previously associated with inflammation and COVID-19 severity, did not cause a predisposition to the development of post-COVID symptoms in the previously hospitalized COVID-19 survivors.

Shigella flexneri is a facultative intracellular pathogen that causes shigellosis, a human diarrheal disease characterized by the destruction of the colonic epithelium. Novel antimicrobial compounds to treat infections are urgently needed due to the proliferation of bacterial antibiotic resistance and lack of new effective antimicrobials in the market. Our approach to find compounds that block the Shigella virulence pathway has three potential advantages: (i) resistance development should be minimized due to the lack of growth selection pressure, (ii) no resistance due to environmental antibiotic exposure should be developed since the virulence pathways are not activated outside of host infection, and (iii) the normal intestinal microbiota, which do not have the targeted virulence pathways, should be unharmed. We chose to utilize two phenotypic assays, inhibition of Shigella survival in macrophages and Shigella growth inhibition (minimum inhibitory concentration), to interrogate the 1.7 M compound screening collection subset of the GlaxoSmithKline drug discovery chemical library. A number of secondary assays on the hit compounds resulting from the primary screens were conducted, which, in combination with chemical, structural, and physical property analyses, narrowed the final hit list to 44 promising compounds for further drug discovery efforts. The rapid development of antibiotic resistance is a critical problem that has the potential of returning the world to a "pre-antibiotic" type of environment, where millions of people will die from previously treatable infections. One relatively newer approach to minimize the selection pressures for the development of resistance is to target virulence pathways. This is anticipated to eliminate any resistance selection pressure in environmental exposure to virulence-targeted antibiotics and will have the added benefit of not affecting the non-virulent microbiome. This paper describes the development and application of a simple, reproducible, and sensitive assay to interrogate an extensive chemical library in high-throughput screening format for activity against the survival of Shigella flexneri 2457T-nl in THP-1 macrophages. The ability to screen very large numbers of compounds in a reasonable time frame (~1.7 M compounds in ~8 months) distinguishes this assay as a powerful tool in further exploring new compounds with intracellular effect on S. flexneri or other pathogens with similar pathways of pathogenesis. The assay utilizes a luciferase reporter which is extremely rapid, simple, relatively inexpensive, and sensitive and possesses a broad linear range. The assay also utilized THP-1 cells that resemble primary monocytes and macrophages in morphology and differentiation properties. THP-1 cells have advantages over human primary monocytes or macrophages because they are highly plastic and their homogeneous genetic background minimizes the degree of variability in the cell phenotype (1). The intracellular and virulence-targeted selectivity of our methodology, determined via secondary screening, is an enormous advantage. Our main interest focuses on hits that are targeting virulence, and the most promising compounds with adequate physicochemical and drug metabolism and pharmacokinetic (DMPK) properties will be progressed to a suitable in vivo shigellosis model to evaluate the therapeutic potential of this approach. Additionally, compounds that act via a host-directed mechanism could be a promising source for further research given that it would allow a whole new, specific, and controlled approach to the treatment of diseases caused by some pathogenic bacteria., Competing Interests: The authors declare no conflict of interest.

Secamone afzelii (Roem. & Schult.) K. Schum (family Asclepiadaceae) is a creeping woody climber used to treat ailments in many traditional medicine systems. The present study aims to examine the antioxidant and enzyme inhibition activities of S. afzelii leaf using different compositions of methanol-water mixture as an extraction solvent. The extracts were characterized by HPLC-ESI-MS n in terms of chemical compounds. The in silico results show that compound 23 (quercitrin) has the higher docking scores among the selected substances and the MD simulation revealed that the interactions with the enzymatic pocket are stable over the simulation time and strongly involve the tyrosinase catalytic Cu atoms. All together the results showed that both 80% and 100% methanolic extracts contained significantly ( p < 0.05) the highest total phenolics content while the highest content of total flavonoids was significantly ( p < 0.05) extracted by 100% methanol. About 26 compounds were tentatively identified by HPLC-ESI-MS n and 6 of them were quantified using standards. Results showed that the extracts were rich in flavonoids with a relatively high abundance of two kaempferol glycosides comprising 60% of quantified compounds. The 100% and 80% methanol extracts recorded significantly ( p < 0.05) the highest total antioxidant, DPPH and ABTS activity as well as tyrosinase and ⍺-amylase inhibitory activities. The best significant ( p < 0.05) cholinesterase inhibitory activity and reducing capacity of Fe +++ and Cu ++ was recorded from the 80% methanolic extract while 100% ethanolic extract gave the highest significant ( p < 0.05) butyrylcholinesterase inhibitory activity. The best glucosidase activity was observed in the 50% and 80% methanolic extracts. Although the water extract displayed the least total phenolics and flavonoids content and consequently the lowest antioxidant and enzyme inhibition activity, it displayed significantly ( p < 0.05) the highest chelating power. In conclusion, these results demonstrated the richness of S. afzelii leaf as a potential source of bioactive compounds for the food industry, for the preparation of food supplements and functional foods.

Moringa oleifera has been reported to possess a high number of bioactive compounds; hence, several food supplements are commercially available based on it. This work aimed to analyze the phytochemical composition and antioxidant activity of commercial food supplements. The phenolic composition of methanolic extracts was determined by using high-performance liquid chromatography with diode-array and electrospray ionization mass spectrometric detection (HPLC-DAD-ESI-MS n ), and the antioxidant activity was assessed by ABTS ·+ and DPPH assays. Thirty-three compounds were identified, and all the main compounds were quantified, observing that the main contribution to the phenolic profile was due to kaempferol and quercetin glucosides. The antioxidant activity in both assays agreed with the phenolic content: the higher the phenolic levels, the higher the antioxidant activity. The obtained results were compared with those previously published regarding Moringa oleifera leaves to establish the potential benefits of food supplement consumption in the diet.

Cathissa reverchonii (formerly Ornithogalum reverchonii ) is a threatened species, constituting an endemism present in the south of Spain and northern Morocco. In Spain, it is only found in two disjoint populations in the region of Andalusia. The determination of its chemical composition and the influence that environmental factors have on it can contribute significantly to the development of appropriate protection and conservation plans. However, there are no previous reports about this species to date. Consequently, this research aimed to study the phenolic composition and antioxidant activity of C. reverchonii and to assess the influence of environmental factors on the phenolic profile and bioactivity. The vegetal material was collected in seven places inhabited by the two separate populations in Spain. The phenolic composition of methanolic extracts of the species was determined by HPLC-ESI-Q-TOF-MS, and the antioxidant activity was assessed by DPPH and ABTS assays. Fifteen compounds were characterized in the extracts of the aerial parts of C. reverchonii , revealing differences in the phytochemical profile between both populations analyzed, mainly in the saponin fraction. The main phenolics were flavone di- C -glucoside (lucenin-2), followed by a quercetin-di- C -glucoside. The composition of the extracts of C. reverchonii and their radical scavenging power were compared with those of other species of the genus Ornithogalum L., revealing significant differences between the latter and the genus Cathissa .

Objectives: BK polyomavirus is one of the main causes of chronic renal failure and ureteral stenosis in kidney transplant recipients, affecting approximately 15% of kidney transplant patients during the first year after transplant. The immunosuppressive treatment used in these recipients allows a reactivation of the virus by allowing infection, which can manifest from viruria, viremia, or nephropathy. The use of ureteral stents in renal transplant to prevent postoperative complications has been associated with an increase in BK polyomavirus nephropathy. Our objective was to describe associations between viruria and viremia and our reimplantation surgical technique and ureteral stenting., Materials and Methods: We conducted a retrospective review of 184 transplant recipients who were seen at our center between January 2013 and December 2016. To define possible risk factors from analysis of different variables, we categorized patients into 3 groups: patients who did not present with either viremia or viruria caused by BK virus, patients who presented with viremia, and patients who presented with viruria., Results: We found that 127 transplant recipients (69%) presented with neither BK viruria nor BK viremia, 11 recipients (6%) presented with BK viremia, and 46 recipients (25%) presented with BK viruria. No patient in the study had BK polyomavirus nephropathy., Conclusions: Our type of ureteral stenting has a low rate of BK viruria and BK viremia compared with other studies. In addition, with our technique, the ureteral stent removal procedure does not require an invasive endoscopic procedure, thereby avoiding the consequent economic and assistance inconvenience typically associated with an endoscopic procedure.

Background: The Tehuacán Valley, Mexico is a region with exceptionally high biocultural richness. Traditional knowledge in this region comprises information on nearly 1,600 plant species used by local peoples to satisfy their subsistence needs. Plant resources with higher cultural value are interchanged in traditional markets. We inventoried the edible plant species interchanged in regional markets documenting economic, cultural and ecological data and about their extraction and management in order to: (1) assess how commercialization and ecological aspects influence plant management, (2) identify which species are more vulnerable, and (3) analyze how local management contributes to decrease their risk. We hypothesized that scarcer plant species with higher economic value would be under higher pressure motivating more management actions than on more abundant plants with lower economic value. However, construction of management techniques is also influenced by the time-span the management responses have taken as well as biological and ecological aspects of the plant species that limit the implementation of management practices. Plant management mitigates risk, but its absence on plant species under high risk may favor local extinction., Methods: Six traditional markets were studied through 332 semi-structured interviews to local vendors about barter, commercialization, and management types of local edible plant species. We retrieved ethnobotanical information on plant management from ten communities in a workshop and sampled regional vegetation in a total of 98 sites to estimate distribution and abundance of plant species commercialized. Through Canonical Correspondence Analysis (CCA) we analyzed the amount of variation of management types that can be explained from socioeconomic and ecological information. A risk index was calculated relating distribution, abundance, economic value and management of plant resources to identify the most vulnerable species., Results: We recorded 122 edible plant species interchanged in the main regional markets. CCA explained significantly 24% of management variation, spatial distribution and plant parts used being particularly important in management decisions. The indeterminate 76% of variation suggests that management decisions depend on particular variables that are not explained by the ecological and socioeconomic factors studied and/or their high variation in the context at the regional scale. The risk index indicated that management was the factor that mostly influences decreasing of risk of interchanged plant species. We identified Clinopodium mexicanum, Pachycereus weberi, Dasylirion serratifolium, Disocorea sp., Ceiba aesculifolia, Neobuxbamia tetetzo, Lippia graveolens, Litsea glaucescens, L. neesiana, Jatropha neopauciflora, Agave potatorum and other agave species used for producing mescal among the more endangered plant species due to human pressure, their relative scarcity and limited or inexistent management., Conclusion: Spatial distribution and plant parts used are particularly meaningful factors determining risk and influencing management actions on edible plant species interchanged in the region. Limited or inexistent management may favor extinction of local populations under risk. Local management techniques synthesize knowledge and experiences crucial for designing sustainable management programs. Traditional management techniques supported by ecological information and environmental management approaches could make valuable contributions for sustainable use of plant species, particularly those becoming economically important more recently.