Mesenchymal Stem/Stromal Cells: BIOLOGICAL THREAT AGENT RICIN INTOXICATION OF THE LUNGS IS EFFECTIVELY TREATED BY MESENCURE, A PROFESSIONALIZED ALLOGENEIC MESENCHYMAL CELL THERAPY, PREFERABLY VIA THE SUBCUTANEOUS ROUTE

Background & Aim: Ricin is one of the most lethal toxins, particularly if inhaled, and is considered a biological threat agent due to its wide availability and ease of production. Pulmonary ricin intoxication manifests in ARDS, cytokine storm, immune infiltration, and severe edema. Passive immunization is the preferred measure against pulmonary ricinosis, but only if administered shortly after exposure. Despite their potential to remedy pulmonary injury and inflammation, mesenchymal cell (MSC) therapies were never investigated in ricinosis. Here, we report the potential for treating pulmonary ricinosis with MesenCure, a professionalized allogeneic MSC therapy shown to reduce the mortality of patients suffering from severe pulmonary manifestations of COVID by 68%. Methods, Results & Conclusion(s): Preliminary studies demonstrated positive MesenCure effects in a sub-lethal pulmonary ricinosis model in CD1 mice. This model is regarded as highly translational due to the broad heterogeneity of these outbred mice. Positive effects included a reduction in excess protein content of the bronchoalveolar lavage fluid (BALF) by 45% when MesenCure was injected intravenously (IV) at 125k cells/animal, 48h post-exposure (PE) and evaluated one day later (p<0.05, Fig. 1A). Moreover, we found up to 52% reduction in the excess BALF leukocytes, when MesenCure was injected IV, 24h PE using the same dose (p<0.05, Fig. 1B) or 6h PE using a double dose (p<0.01, Fig. 1C), and evaluated two days PE. Optimizing the dose and administration route further improved the therapeutic outcome of MesenCure applied 6h PE as assessed by weight loss. As shown in Fig. 1D-E, IV injection of 250k-500k MesenCure cells/animal slightly protected the intoxicated animals against weight loss (p for treatment x time interaction <0.01 or <0.05 for 250k and 500k cells/animal, respectively). Interestingly, one million cells IV resulted in a lesser effect (not shown), however when injected subcutaneously (SC), 1M cells were very effective (p<0.001, Fig. 1F), seemingly even more effective than 2M cells/animal SC (Fig. 1G). Surprisingly, 2M thawed cells/animal injected SC protected the animals against weight loss almost completely (p<0.0001, Fig. H). In conclusion, we provide evidence for the potential of SC MSCs, specifically MesenCure, for treating pulmonary ricinosis and possibly other forms of ARDS. In agreement with Giri and Galipeau (2020), we provide further evidence for the dependency of MSC outcomes on their specific state and administration route. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Optimization of high protein and zinc composite flour formulation with response surface methodology

Covid-19 pandemic had limited people's movement despite the demand to remain productive and maintain good health. Therefore, it was necessary to provide foods which are easy to distribute, durable, nutritious, and easily transformable to increase immunity. This research aims to develop a composite flour (TK) formula with optimal proportion of wheat flour (TT), snakehead fish flour (TIG), pumpkin flour (TBuL), and pumpkin seed flour (TBiL) which then enriched with zinc. The resulting TK is expected to be used as an ingredient for nutritious snacks containing high protein and zinc. The research was conducted in four stages, namely the making of each constituent flour, determining the best formulation with the Response Surface Methodology using Central Composite Design model, characterizing the physicochemical properties of TK and making meatballs, biscuits, and unting-unting from the TK. The three products were tested on experimental animals for their metabolic responses. The optimization of the formula resulted in three optimal formulations, namely formula A, B, and C with the proportion of TT:TIG:TBuL:TBiL respectively as follows 55:20:15:10;56.65:20:13.35:10;57.98:20:12.02:10. The most optimal formula of composite flour was formula A with the highest protein (26.12%) and zinc (18.06 mg/kg) content among other formulas. Then, zinc was added into Formula A using microencapsulation, and TK with protein content of 26.74% and zinc of 56.8 mg/kg were obtained. The histopatology observation on experimental animals showed that the three products made from TK did not cause necrosis of the liver or cell infiltration in the kidneys.

On the value of apricot kernel in modern medicine and its future development

Apricot kernels are one of the most regularly used traditional Chinese medicinal ingredients in Asia. The medical significance of apricot kernels is highlighted since Traditional Chinese Medicine (TCM) demonstrated its favourable impact when apricot kernels were used in the prevention and treatment of Corona Virus Disease 2019 (COVID-19). Furthermore, apricot kernels are high in fat, protein, dietary fibre, and specific amygdalin, making them a new form of dried fruit in comparison to almond kernels, with a bigger market opportunity. This paper systematically reviewed the active components of apricot kernels and their application in medicine, especially for molecular mechanisms of anti-tumors of amygdalin, providing scientific theoretical foundations for modern medicine treatment with COVID-19-induced lung disease, and for the development of high value-added apricot kernels.

The use of quantitative enzyme-linked immunosorbent assay for the determination of S-antigen concentration in whole-virion inactivated adsorbed coronavirus vaccines

The severe consequences and high mortality of COVID-19 prompted the development of a wide range of preventive vaccines. The first vaccines to be tested were developed in China and formulated as inactivated SARS-CoV-2 adsorbed on aluminium hydroxide. One of the quality indicators for inactivated adsorbed vaccines is the degree of adsorption, which can be used to control the content not only of non-adsorbed antigen, but also of specific antigen in one dose of a vaccine. The aim of the study was to investigate the possibility of desorbing SARS-CoV-2 antigen from formulated adsorbed vaccines and the possibility of measuring its concentration using the BioScan-SARS-CoV-2 (S) ELISA kit for SARS-CoV-2 S-protein content determination. Materials and methods: the study used four batches of BBIBP-CorV by CNBG, Sinopharm (China) and three batches of CoronaVac by Sinovac Biotech (China). The authors desorbed SARS-CoV-2 S antigen in accordance with monograph FS.3.3.1.0029.15 of the State Pharmacopoeia of the Russian Federation edition XIV (Ph. Rus.), and quantified it using the BioScan-SARS-CoV-2 (S) ELISA kit by Bioservice Biotechnology Co. Ltd. (Russia). Results: mean S-antigen concentrations in the desorbed samples ranged from 61 to 129 ng/mL for BBIBP-CorV and from 461 to 533 ng/mL for CoronaVac. Conclusions: the study demonstrated the possibility of specific SARS-CoV-2 antigen desorption from the surface of aluminium hydroxide using the Ph. Rus. method, as well as the possibility of S-antigen quantification in desorbed medicinal products and supernatants using the BioScan-SARS-CoV-2 (S) ELISA kit. The authors observed 3.6- to 8.7-fold difference between the S-antigen concentrations of the desorbed preparations by the two manufacturers.

Delta And Omicron Variants Of SARS-Cov-2 Do Not Stimulate ACE2 Conversion Of Ang II To Ang-(1-7)

The Spike domain of SARS-COV-2 binds ACE2 and induces peptidase internalization removing a key regulatory site within the renin-angiotensin system that may exacerbate the effects of SARS-COV-2. However, a recent study finds that an early Beta variant (D614G) of the SARS-COV-2 Spike protein and its receptor-binding domain (RBD) markedly stimulated ACE2 activity using fluorescent substrates. The more dominant forms of SARS-COV-2 include the Delta and Omicron variants and we determined whether these new variants activate ACE2. Delta (B.1.617.1) and Omicron (B.1.1.529) RBDs, and Beta Spike (B1.351) were incubated with human soluble ACE2 for 10 mins at 37degreeC followed by Ang II [2 muM] and 125I-Ang II [0.5 nM] for up to 20 mins, and the Ang-(1-7)/Ang II ratio quantified by HPLC-gamma detection. Ang-(1-7)/Ang II increased linearly over time and doubled with 10 ng of ACE2 (*P<0.01 vs 5 ng;N=4);however, the Delta or Omicron RBD proteins (1 muM) failed to stimulate ACE2 activity at any time point (A). Varying concentrations of the Delta or Omicron RBDs, as well as Spike protein also failed to stimulate ACE2 activity (5 ng), although 200 nM Omicron RBD was inhibitory (B). The newer Spike variants may not activate ACE2;however, the Spike D614G variant also failed to activate ACE2, which questions whether SARS-COV-2 enhances ACE2 activity to metabolize Ang II. We conclude that Delta and Omicron variants do not stimulate the metabolism of Ang II to Ang-(1-7). Moreover, alterations in circulating ACE2 activity in COVID-19 patients likely reflect changes in protein content through shedding of the peptidase, although the interaction of ACE2 autoantibodies to influence peptidase activity is also possible. (Figure Presented).

Effects of adding different silver carp fish pastes on the quality of lion's head meatballs

To clarify the most suitable fish paste for preparing lion's head meatballs, this study investigated the effect of adding 6 different silver carp fish pastes: fresh unwashed (group 1-1), fresh washed (group 1-2), frozen unwashed without antifreeze agent (group 2-1), frozen washed without antifreeze agent (group 2-2), frozen unwashed with antifreeze agent (group 3-1), and frozen washed with antifreeze agent (group 3-2) on the basic nutrients, color, texture properties, waterholding capacity, sensory and flavor properties, thiobarbituric acid reactive substance (TBARs) value, and total volatile basic nitrogen (TVB-N) content of pork/fish composite meatballs. The results showed that the contents of protein and fat in meatballs from groups 2-1 and 2-2 were lower than those in groups 3-1 and 3-2, and the contents of water, protein and fat were 61.68%, 11.32% and 19.41% for group 2-1, and 62.45%, 11.09% and 19.33% for group 2-2, respectively. The gel properties, hardness, elasticity, cohesion, and sensory quality of groups 3-1 and 3-2 were significantly higher than those of groups 2-1 and 2-2 (P < 0.05), but there was no significant difference compared with groups 1-1 and 1-2. The odor response value of groups 3 was lower than that of groups 1, and groups 3 had the highest sweetness value (3 039.66) and lowest bitterness value (534.59). The TBARs value and TVB-N content in groups 1-2, 2-2, and 3-2 (with washed fish paste) were significantly lower than those in groups 1-1, 2-1 and 3-1 (with unwashed fish paste) (P < 0.05). Since fresh fish paste is not easy to store and subject to spoilage, frozen washed fish paste with antifreeze agent can be used to produce composite meatballs.

Critically ill patients with and without SARS-CoV-2 better achieve energy and protein targets with a high-energy, high-protein peptide-based enteral tube feed;insights from a multicentre clinical audit performed during the COVID-19 pandemic

Meeting energy and protein requirements in critically ill patients is important for prognosis, yet difficult to achieve as a consequence of disease, management and/or altered nutritional intake[1]. Improvements in achieving energy and protein requirements with a high-energy, high-protein peptide-based tube feed were observed in community patients with impaired gastrointestinal function[2]. To establish whether this remained true in the critical care setting, where feeding intolerance is observed frequently in patients with[3] and without SARS-CoV-2[4], a retrospective multicentre audit was performed. Adults (> 18years) with or without SARS-CoV-2, admitted to critical care across 6 UK hospitals between May 2020 and December 2020, were retrospectively included if they received a peptide-based enteral tube feed (Nutrison Peptisorb Plus HEHP®, Nutricia Ltd), containing 1.5kcal/ml and 7.5g protein/100ml (herein referred to as HEHP). Data were collected from 15 critically ill patients (52±12y;87% male), with mean length of hospital stay being 26days (range: 7-49days). Of these, 10 were SARS-CoV-2 positive, with the remainder having pancreatitis (n=3), delayed gastric emptying (n=1) or unconfirmed diagnosis (n=1). HEHP was used second line (after whole protein) and indications (multiple were cited for some) for use included tolerance issues (n=10), elevated energy and protein requirements (n=5) or due to primary diagnosis (n=2). Estimated energy and protein intakes (% of requirements achieved) were recorded before and during use of HEHP. In addition, Dietitians were asked whether HEHP allowed patients to better meet their nutrient target Mean intake of HEHP was 2008±461kcal/day and 100±23g protein/day provided over a mean of 12days (range: 3-29days). The percentage of estimated energy and protein targets achieved increased albeit non significantly with the use of HEHP (from 76% before vs 87% during use of HEHP for both) and the direction of effect remained true regardless of SARS-CoV-2 status. Two thirds (67%, n=10 of 15) of Dietitians reported HEHP helped patients better meet their nutrient targets and 87% (n=13 of 15) of Dietitians perceived the high protein content of HEHP as beneficial for this patient group. Gastrointestinal tolerance (anecdotal reports) remained largely unchanged in approximately half of SARS-CoV-2 positive patients when using HEHP yet improved for others including non-SARS-CoV-2 patients. Enteral tube feeding in critically ill patients poses numerous difficulties, especially in SARS-CoV-2 positive patients. This audit in critically ill patients demonstrates that a high-energy, high-protein, peptide-based enteral tube feed can help complex patients better achieve energy and protein targets in patients with and without SARS-CoV-2. References 1.Pullen K, Colins R, Stone T et al. Are energy and protein requirements met in hospital? Clin Nutr 2017;31(2): 178-187. 2.Green B, Sorensen K, Phillips M et al. Complex Enterally Tube-Fed Community Patients Display Stable Tolerance, Improved Compliance and Better Achieve Energy and Protein Targets with a High-Energy, High-Protein Peptide-Based Enteral Tube Feed: Results from a Multi-Centre Pilot Study. Nutrients. 2020, 12, 3538. 3.Liu R, Paz M, Siraj L et al. Feeding intolerance in critically ill patients with COVID-19. Clin Nutr 2021. 4.Gungabissoon U, Hacquoil K, Bains C et al. Prevalence, Risk Factors, Clinical Consequences, and Treatment of Enteral Feed Intolerance During Critical Illness. J. Parenter. Enteral. Nutr. 2015, 39, 441–448.

New insights into perceptions of technology claims in greek-style yogurt: A view in the COVID-19 pandemic.

The Covid-19 pandemic has strongly impacted people's lives and the food industry. In this sense, food products claiming nutritional and health-promoting benefits due to the presence of bioactive peptides and probiotics, such as Greek-style yogurt, have been in demand. The objective of this work was to investigate, through word association, the perception of the consumers regarding the seven concepts related to Greek-style yogurt (traditional, ultra-creamy, zero fat, high content proteins, zero lactose, light and with no added sugars), in the context of social isolation due to Covid-19. In this online survey, 346 participants completed a questionnaire. The participants were divided according to health concerns (increased, not changed, or decreased) and eating habits (improved, not changed, or worsened) during the Covid-19 pandemic. Chi-square and prototypical analysis were used as statistical tests. During the Covid-19 pandemic, based on self-report, around 66% of the participants had their eating habits and their concerns about health changed. The general associations were related to the categories pleasure, health, creamy, pleasant texture, food restriction, and loss of sensory quality. 'Health' and 'pleasure' were negatively associated with the conceptualization of Greek-style yogurt. For the zero-fat, light, and sugar-free Greek-style yogurts, the terms creamy and ultra-creamy are sensory appealing to the consumers. In general, the price and concerns about health are factors that strongly influence the purchase intention of Greek-style yogurts. The yogurts were associated with sensory and non-sensory characteristics, which can be useful for marketing strategies for of different product concepts.

Infestation of pest of pulses legume grains Callosobruchus spp and substantial loss of dietary vegan protein

The current study is the reviews of the work done for pest infestation in different legume pulse grains Pulse grains have been found to have different susceptibility for the attack of pulse beetle. An insect has varied fecundity on different varieties of pulses. India is agriculture based country and agriculture is the key sector of Indian economy. Including many kharif and rabbi crops, pulses are cultivated in all parts of country. Pulse cultivation has its own significant place in agriculture as it has been considered as complimentary to cereal crop in many aspects and positioned as a second most important crop plant [1]. Study indicates 20-40% of dry matter of pulse grains is made up of beneficial dietary proteins [2]. Insufficiency of adequate amount of protein in diet may lead to protein energy malnutrition. Like poverty and hunger, to combat PEM is another great provocation for agriculture and nation. Pulse grains legumes are good source of protein and other nutrient materials. Crop plant of Arhar has its own advantage for agriculture. The leguminous plants are used in crop rotation to improve the fertility of soil as the root nodules harbor the nitrogen fixing bacteria;fixes atmospheric nitrogen to nitrogen compound about 72-350 kg/hectare/year . The current study emphasizes the different facts of pulse beetle and their infestation in arhar seed grains. About eight months of the year have been found to be susceptible for infestation;remarkable growth and development of pests continue during six months of the year. Arhar pulse grains are most suitable for pest infestation. Bold variety of arhar was identified to be the most preferred for maximum oviposition having larger and smooth surface area. Temperature suitable for oviposition was noticed between 28-370c. Developmental period was found to be of lesser duration and survival of adults was more in bold varieties as compared to the smaller variety. Developmental period was recorded as 24-30.3 days in bold legume grains and 26-32.3 days in smaller size grains. Survival of male and female insect pest was also different as male survived for 7-10.6 days and females for 8.3-12.6 days. Increased growth rate of insect population was there with the increase in temperature and humidity. Significant Weight loss, content loss and percent germination loss have been found in the pulse grains of both varieties in the current studies. Indian economy relies significantly on agriculture and loss and damage of complementary crop plant certainly affect it. At this point there is need to consider the condition of Mass poverty of India after pandemic covid -19 which has been ascertained after more than 45 years The outcome of pandemic recession is more than 2 fold increase in the number of poor from 60 million in a year to 134 million (Reports of downtoearth.org.in). Furthermore any rise in price would snatch the accessibility of the easily available protein diet from people living in indigence.

A Novel Ogremorphin Group of First-in-Class GPR68 Inhibitors Upregulate Endothelial Barrier Function and Rescue Bacterial Pathogens or Acidosis-Induced Inflammation in Lung Endothelium

Rationale: An increase in endothelial permeability resulting from the disruption of endothelial barrier and aggravated inflammatory responses are two major pathological hallmarks of various lung disorders including the current global pandemic COVID-19. Drugs that enable the preservation and restoration of endothelial function represent attractive therapeutic targets to treat endothelial dysfunction-derived cardiopulmonary diseases. A role of G protein-coupled receptors (GPCRs), especially a sub-family of proton-sensing GPCRs including GPR4 and GPR68, has been suggested in modulation of endothelial function. In this study, we analyzed the barrier protective and anti-inflammatory effects of two recently developed novel class of GPR68 inhibitors: ogremorphins OGM8345 and OGM-1.Methods: Transendothelial electrical resistance (TER) was monitored in human pulmonary arterial endothelial cells (HPAECs) to evaluate endothelial barrier function. Quantitative real time PCR and western blot analyses were performed to determine mRNA and protein expression of endothelial inflammation markers, respectively. Acidic pH (6.5) medium was used to induce acidosis, and luciferase-based Tango assay was employed to evaluate GPR68 activation. C57BL/6 mice were exposed to lipopolysaccharide (LPS from Escherichia coli) or heatkilled Staphylococcus aureus (HKSA), and vascular leak/inflammation was assessed by determining the extravasation of intravenously injected Evans blue tracer into lungs and total cells/protein count in bronchoalveolar lavage samples. Results: A robust dose-dependent increase in basal EC barrier function was observed with OGM8345 (1-5 μM) and OGM-1 (0.3-1.5 μM) evident by an 150-200% increase in TER values. Both inhibitors also effectively rescued LPS- and HKSA-induced EC hyperpermeability. RT-PCR analysis demonstrated that LPS or HKSA-induced upregulation of inflammatory cytokines/chemokines genes TNF-α, ICAM-1, VCAM-1, IL-6, IL-8, IL- 1β, and CXCL5 was significantly attenuated by OGMs. Consistently, both OGMs suppressed LPSand HKSA-induced protein expression of VCAM-1 and ICAM-1. In contrast, pharmacologic inhibition of GPR4 by NE 52-QQ57 failed to alleviate LPS or HKSA-induced EC barrier dysfunction and inflammation. Importantly, LPS, HKSA or acidosis stimulation resulted in increased GPR68 mRNA expression and GPR68 activity that was inhibited by OGMs. Intratracheal injection of LPS or HKSA in C57BL/6 mice caused vascular leak and lung inflammation that was attenuated by both OGMs as illustrated by reduced Evans blue accumulation in the lungs and significant inhibition of accumulation of inflammatory cells and protein content in bronchoalveolar lavage samples. Conclusion: These results establish a critical role of GPR68 in endothelial dysfunction and strongly suggest a therapeutic potential of GPR68-selective inhibitors in improving endothelial dysfunction caused by bacterial infections and acidosis associated with acute and chronic lung injury.

Phytochemical screening, GCMS profile, and in-silico properties of bioactive compounds in methanolic leaf extracts of Moringa oleifera

Plant Based Natural Products (PBNPs) have been subject of interest since ancient time due to their use in food, industrial and biomedical applications. Research attention has further augmented to explore their phytochemical composition, properties, and potential application in the post-COVID era. In the present study phytochemical screening has been carried out with Methanolic Leaf Extracts of Moringa oleifera (MLEMO) followed by Gas Chromatography-Mass Spectrometry (GCMS) analysis. Phytochemical analysis of MLEMO revealed the presence of Alkaloids, Carbohydrates, Coumarins, Flavonoids, Glycosides, Phenol, Proteins, Quinones, Saponins, Steroids, Tannins and Terpenoids. Further, GCMS analysis revealed the presence of 41 compounds of which Dihydroxyacetone;Monomethyl malonate;4H-Pyran-4-one,2,3-dihydro- 3,5-dihydroxy-6-methyl;1,3-Propanediol, 2-ethyl-2-(hydroxymethyl);Propanoic acid, 2- methyl-, octyl ester;3-Deoxy-d-mannoic lactone;Sorbitol;Inositol;Cyclohexanemethanol, alpha-methyl-4-(1-methylethyl), Hexadecanoic acid, Methyl palmitate;n-Hexadecanoic acid (Palmitic acid);9-Octadecenoic acid, methyl ester;Phytol;9,12,15-Octadecatrienoic acid;Octadecanoic acid;9-Octadecenamide were prominent. Most of the compounds in the list are bioactive and possess medicinal properties that are expected to serve as a baseline lead for the development of therapeutic agents.

Biological activities of Egyptian grape and mulberry by-products and their potential use as natural sources of food additives and nutraceuticals foods

Interest in the biological role of bioactive compounds present in plant by-products has increased over the last few years. This study aimed to investigate the nutritive value and biological activities of Egyptian Grape leaves (GL), Grape seeds (GS) and Mulberry leaves (ML), as well as investigate the impact of P-irradiation for improving the utilization of these plant by-products. The dose level 5.0 kGy showed highest the content of crude protein (24.42, 19.41 and 13.50 mg/100 g), as well as crude fiber (34.26 and 21.18 mg/100 g) for ML, GL and GS, respectively. Mulberry leaves has a highest content of protein and fiber at dose 5.0 kGy compared with GL and GS. The highest total phenolic content was found in GS (9.75 mg/g DW), followed by GL (7.32 mg/g DW) and the lowest in ML (5.97 mg/g DW). While ML had a higher total flavonoids content (5.61 mg/g DW) than GS (4.88 mg/g DW) and GL (2.86 mg/g DW). Total phenolic and flavonoid contents were significantly increased at 5.0 kGy. The highest level (83.25% and 80.24%) of scavenging activity (DPPH %) and inhibition activity of HCT 116 cells was recorded at 5.0 kGy by GS. All extracts irradiated at 5.0 kGy exhibited varying degrees of antibacterial activity against (Gram+ve and Gram-ve), the GS followed by GL then ML showed strong antibacterial activity with a diameter of inhibition zone of 26.2, 24.5 and 19.7 mm, against L. monocytoganes, respectively and 24.4, 21.4 and 17.2 against S. typhimurium, respectively. This study suggests that P-irradiation is an effective technique to enhance the recovery of phenolics and flavonoids from GL, GS and ML. Also in current study, antioxidant, antibacterial and anticancer activity has been suggested to appear a clear positive relationship with the total phenolic material. This study has proved that the Egyptian GL, GS and ML are rich sources of valuable phytochemicals and nutrients that can serve as a potential source of nutraceuticals and multifunctional food additives (antimicrobial, antioxidant, and anticancer). Phenolic compounds recovered from GL, GS and ML may have a potential role in fighting the COVID-19.

Chemical composition, biological activity and factors influencing the quality of Algerian bee-honey (Apis mellifera)

For centuries, honey, the main bee-hive product, has been widely used as an effective therapeutic agent against several health disorders, in addition to its extensive uses as a natural-healthy and energetic food. Further, bee-honey is a beneficial substance when we explore the many uses in medicine, including bacteria-and-virus killing such as Covid-19, body-protecting chemicals, anti-inflammatory, antioxidant, and anti-cancer activities. Honey is characterized by complex and variable chemical compositions depending on several fac-tors;botanical origin, climatic condition, bee health, and other stress factors, in particular, uncontrolled use of pesticides and adulteration in this product. Additionally, honey contains an important number of bioactive compounds (carbohydrates, lipids, amino acids, proteins, vitamins, and minerals) whose main roles are involved in medical therapies and wound healing. Thus, this review summarizes the literature about the chemical composition, biological activity, and factors affecting bee-honey production and quality.

Valsartan protects both cardiac and lung cells from sars-cov-2 infection

Background: Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) disease (COVID19) mainly affects the respiratory system, but cardiac complications occur very often. SARS-CoV-2 entry in host cells is mediated by the interaction between the viral Spike (S) glycoprotein and the host angiotensin-converting enzyme 2 (ACE2). The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) might influence the expression of ACE2 and viral infection, but not much is known about these interactions. Aim: To evaluate the effects of ACEIs and ARBs during active viraemia. Methods: We tested the ACEI Lisinopril (at 100nM and 500nM) and the ARB Valsartan (at 10uM and 50uM) for one week on two cell types: cardiomyocytes derived from hiPSC (hiPSC-CMs) as heart model and a lung epithelial cancer cell line (16HBE) as pulmonary model. The SARS-CoV-2 wild strain was inoculated in the two treated cell types for one hour. Cell viability was measured 72 hours after infection. Supernatants were collected and titrated to verify the presence of infectious virus using a micro-neutralization assay on VERO-E6 cells. Levels of ACE2 mRNA and protein content on cell lysates were quantified after each treatment by RT-qPCR and western blot, respectively. Results: ACEI and ARB at both concentrations affected the viability of neither hiPSC-CMs nor 16HBE cells in the absence of virus. Vice versa, viral infection significantly decreased viability of both hiPSC-CMs (-46%;p<0,01) and 16HBE (-19%;p<0,05). Viral titration revealed that SARSCoV-2 replicated in both cell lines and was actively released in supernatants. Importantly, pretreatment with Valsartan 50uM increased the viability of both hiPSC-CMs and 16HBE after infection, while Lisinopril and the lower dose of Valsartan had neutral effect. Of note, Valsartan 50uM treatment decrease ACE2 mRNA level in both hiPSC-CMs (-47%, p<0,01) and 16HBE (-37%, p<0,01). Also ACE2 protein levels were reduced in cell lysates of hiPSC-CMs and 16HBE treated with Valsartan 50uM. Conclusion: These data suggest that ACEIs and ARBs do not worsen the SARS-CoV-2 infection. On the contrary, Valsartan seems to be protective against SARS-CoV-2 infection, possibly by reducing ACE2 expression.

Development of experimental model of ARDS in SHR strain old rats

Introduction. ARDS (acute respiratory distress syndrome) is a direct cause of death due to lung lesions of various origins including SARS-CoV-2 infection. Most lung and respiratory diseases are characterized by inflammation, which in turn causes occlusions, mucous hypersecretion, shortness of breath, cough and other symptoms of airway inflammation. Understanding the pathological processes involved in the regulation of the immune response may lead to the discovery of new mechanisms that support or suppress inflammatory processes in the lungs and respiratory tract. Methods. In order to develop the experimental model of ARDS we used precision pulmonary hyperventilation and intratracheal administration of poly I:C, which reproduces the body's response to viral infection (mimic viral infection). The severity of ARDS was estimated by the following parameters: the ratio of wet lung weight to dry lung (wet/dry lung weight), extensibility, impedance, lung stiffness, protein level and the number of neutrophils in the bronchial lavage, the level of proinflammatory cytokines in lung tissue. Moreover, we provide a method of simultaneous registration of the lungs vagal nerve activation parameters due to ARDS induction. It is known that the lungs have a massive innervation of the peripheral nervous system and such innervation has a powerful effect on the cells of the immune system. Results. The biologically active substances of neurons affect the activity of immune cells, and the activity of the immune system affects the functioning of the nervous system. That is why the investigation of neuro-immune interaction has a great potential in studying ARDS. Evaluation of dynamic changes in respiratory function due to simulated ARDS showed a significant increase in such parameters as Newtonian resistance, tissue stiffness, static elongation, and a decrease in elasticity and tissue dumping, which is fully consistent with the pathogenesis of ARDS in patients. Analysis of the dry/wet lung ratio showed a two-fold increase in pulmonary edema, a severe, life-threatening condition that develops as a result of ARDS. Significant increase of the protein content and concentration of neutrophils in bronchopulmonary lavage indicates an increase in the permeability of the pulmonary capillaries due to ARDS. The real time PCR identified significant increase of proinflammatory chemokine Cxl2 concentration. Also we observed an increase of neutrophil-activating protein 3 cytokine Gro1, which stimulates the migration of neutrophils. Electrophysiological registration of the activity of the vagal nerve innervating the lungs showed a significant increase in the activity of nociceptive and mechanosensitive fibers, especially in the last stage of acute respiratory distress syndrome, which confirms the role of the nervous system in this pathology. Conclusion. As a result we obtained a model that reproduces ARDS most relevant to human pathological condition.