Biofabrication of Silver Nanoparticles Using Nostoc muscorum Lukesova 2/91: Optimization, Characterization, and Biological Applications.

Purpose: The biological synthesis of nanoparticles (NPs) has become a new methodology for the eco-friendly production of NPs with high scalability and biocompatibility. Cyanobacteria are one of the most widespread microorganisms on Earth and have been proven to be successful biofactories for synthesizing NPs. It is challenging to discover new microalgae with the potential to synthesize NPs of small size with high stability. Methods: Nostoc muscorum Lukesova 2/91 was isolated, purified, and identified morphologically and genetically using microscopy and DNA sequencing. Volatile biomolecules in aqueous algal extracts were assessed using gas chromatography-mass spectroscopy (GC-MS). Results: Data showed that the main biomolecules were fatty acids and their esters, followed by secondary metabolites. Algal extract was used to convert silver nitrate (AgNO3) into silver NPs under various optimized parameters. 1 mM of AgNO3, 1:1 (V/V ratio of algal extract to AgNO3), 25 °C, under light illumination, for 24 h, at pH 7.4 were the optimum conditions for NP production (Nos@AgNPs). Nos@AgNPs were characterized using UV-VIS spectroscopy, FTIR, TEM, SEM, EDx, mapping, and a Zetasizer. The wavelength of Nos@AgNPs was 401.4 nm and their shapes were cubic to oval, with an average diameter of 11.8 ± 0.5 nm. FTIR spectroscopy revealed that proteins/polysaccharides could be the main reductants, whereas these molecules and/or fatty acids could be stabilizers for NP synthesis. Nos@AgNPs (86.15%) was silver and had a hydrodynamic diameter of 10.7 nm with a potential charge of -19.7 mV. Antiproliferative and antimicrobial activities of Nos@AgNPs were evaluated. Nos@AgNPs exhibited significant inhibitory activity against lung, colon, and breast cancer cells and considerable biocidal activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. Conclusion: N. muscorum Lukesova 2/91 is an excellent source for the biofabrication of small and stable AgNPs with potent inhibitory effects against cancer and bacterial cells.

Planophila laetevirens-Mediated Synthesis of Silver Nanoparticles: Optimization, Characterization, and Anticancer and Antibacterial Potentials.

Algal-mediated synthesis of nanoparticles (NPs) opens the horizon for green and sustainable synthesis of NPs that can be used in many fields, such as medicine and industry. We extracellularly synthesized silver NPs (Ag-NPs) using the novel microalgae Planophila laetevirens under optimized conditions. The isolate was collected from freshwater/soil, purified, morphologically identified, and genetically identified using light, inverted light, scanning electron microscopy, and 18S rRNA sequencing. The phytochemicals in the algal extract were detected by GC-MS. Aqueous biomass extracts and cell-free media were used to reduce silver nitrate to Ag-NPs. To get small, uniformly shaped, and stable Ag-NPs, various abiotic parameters, including precursor concentration, the ratio between the reductant and precursor, temperature, time of temperature exposure, pH, illumination, and incubation time, were controlled during the synthesis of Ag-NPs. B-P@Ag-NPs and S-P@Ag-NPs (Ag-NPs synthesized using biomass and cell-free medium, respectively) were characterized using UV-vis spectroscopy, transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray analysis (EDX) and mapping, Fourier transform infrared (FTIR) spectroscopy, and a zeta sizer. S-P@Ag-NPs had a smaller size (10.8 ± 0.3 nm) than B-P@Ag-NPs (19.0 ± 0.6 nm), while their shapes were uniform quasispherical (S-P@Ag-NPs) and spherical to oval (B-P@Ag-NPs). EDX and mapping analyses demonstrated that Ag was the dominant element in the B-P@Ag-NP and S-P@Ag-NP samples, while FTIR revealed the presence of O-H, C-H, N-H, and C-O groups, indicating that polysaccharides and proteins acted as reductants, while polysaccharides/fatty acids acted as stabilizers during the synthesis of NPs. The hydrodynamic diameters of B-P@Ag-NPs and S-P@Ag-NPs were 37.7 and 28.3 nm, respectively, with negative charges on their surfaces, suggesting their colloidal stability. Anticancer activities against colon cancer (Sw620 and HT-29 cells), breast cancer (MDA-MB231 and MCF-7 cells), and normal human fibroblasts (HFs) were screened using the MTT assay. B-P@Ag-NPs and S-P@Ag-NPs had a greater antiproliferative effect against colon cancer than against breast cancer, with biocompatibility against HFs. The biocidal effects of the B-P@Ag-NPs and S-P@Ag-NPs were evaluated against Escherichia coli, Bacillus cereus, and Bacillus subtilis using agar well diffusion and resazurin dye assays. B-P@Ag-NPs and S-P@Ag-NPs caused higher growth inhibition of Gram-negative bacteria than of Gram-positive bacteria. B-P@Ag-NPs and S-P@Ag-NPs synthesized by P. laetevirens are promising antitumor and biocidal agents.

One-Step Phytofabrication Method of Silver and Gold Nanoparticles Using Haloxylon salicornicum for Anticancer, Antimicrobial, and Antioxidant Activities.

Among various routes of metallic nanoparticle (NPs) fabrication, phytosynthesis has significant advantages over other conventional approaches. Plant-mediated synthesis of NPs is a fast, one-step, ecobenign, and inexpensive method with high scalability. Herein, silver (Ag) and gold (Au)-NPs were extracellularly synthesized using aqueous Haloxylon salicornicum (H@Ag-, H@Au-NPs) leaf extracts. GC-MS was performed to analyze the chemical compositions of H. salicornicum extract. H@Ag- and H@Au-NPs were characterized via UV-Vis spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission and scanning electron microscopy, and Zetasizer. H@Ag- and H@Au-NPs have surface plasmon resonance at 435.5 and 530.3 nm, respectively. FTIR and GC-MS data suggest that secondary plant metabolites and hydrocarbons might be responsible for the reduction and stabilization of NPs. XRD demonstrated that both NPs have a crystalline nature. H@Ag-NPs have a uniform spherical shape, whereas H@Au-NPs are spherical with few oval and triangular shapes, and their average nanosizes were 19.1 ± 0.8 and 8.1 ± 0.3 nm, respectively. Hydrodynamic diameters of H@Ag-NPs and H@Au-NPs were 184.7 nm, 56.4, and 295.4 nm, and their potential charges were -24.0 and -24.4 mV, respectively. The inhibitory activity of 500 µg/mL H@Ag- and H@Au-NPs was tested against Sw480, Sw620, HCT-116, and Caco-2 colon cancer cell lines and two normal cell lines, including HFs and Vero. H@Ag-NPs revealed potent anticancer activity against all cancer cells at low concentrations. Sw480 was the most sensitive cell to H@Ag-NPs, whereas Sw620 was the least permeable one. These findings suggested that the antiproliferative activity of H@Ag-NPs is cell-response-dependent and may be influenced by a variety of factors, including the cellular metabolic state, which influences cellular charge and interactions with charged NPs. Although H@Au-NPs were smaller, their reactivity against cancer cells was weak, suggesting that the chemical properties, metal structure, quantity and chemistry of the functional groups on the NP surface may influence their reactivity. The biocidal activity of 1 mg/mL H@Ag- and H@Au-NPs against Staphylococcus aureus, Bacillus cereus, Escherichia coli and Klebsiella pneumoniae was assessed. H@Ag-NPs showed biocidal activity against Gram-positive bacteria compared to Gram-negative bacteria, whereas H@Au-NPs showed no inhibitory activity. FRAP and DPPH assays were used to determine the scavenging activity of the plant extracts and both NPs. H@Ag-NPs (1 mg/mL) had the greatest scavenging activity compared to tested drugs. These findings suggest that H@Ag-NPs are potent anticancer, antibacterial, and antioxidant agents, while H@Au-NPs may be used as a drug vehicle for pharmaceutical applications.

Immunohistochemical evidence of melatonin protection on lung tissue during chemotherapy / Evidencia inmunohistoquímica de la protección de la melatonina en el tejido pulmonar durante la quimioterapia

SUMMARY: The present study investigated the possible protective effects of melatonin on Bleomycin, Cisplatin and etoposide (BEP) chemotherapy regimens using immunohistochemistry. Forty male Wistar rats were divided into four groups of ten as; group 1 as untreated control; group 2 as BEP group which received the three cycles of 21 days' regimen each of 0.5¥ dose levels ofBEP (bleomycin 0.75 mg/kg, etoposide 7.5 mg/kg and cisplatin 1.5 mg/kg). Rats in the group 3 (MEL group) received 10 mg/kg/day melatonin once daily. Group 4 received the melatonin (30 min before the BEP injections) and BEP as in groups 2. Proliferating cell nuclear antigen (PCNA) staining was used to detect cell proliferation and caspase-3, caspase-9 and Caspase-8 were detected to investigate apoptosis. PCNA immunostaining in alveolar epithelium, alveolar macrophages and bronchus was weak to moderate in BEP group. However, diffuse and strong caspase immunoreactions for caspase-3, caspase 8- and caspase-9 were detected in the bronchioles epithelium, vascular endothelium, alveolar luminal macrophages in the BEP group. PCNA and caspase immunoreactivities in MEL and Mel + BEP groups were close to the control one. The surface are in the BEP group was significantly reduced as compared to the control one ((P0.05). It can be concluded that BEP regimen can affects negatively on lung tissue and melatonin inhibits lung tissue injuries during BEP chemotherapy.

El presente estudio investigó los posibles efectos protectores de la melatonina en los regímenes de quimioterapia con bleomicina, etopósido y cisplatino (BEP) mediante inmunohistoquímica. Cuarenta ratas Wistar macho se dividieron en cuatro grupos de diez: grupo 1, control sin tratar; grupo 2, quimioterapia con una dosis de 0,5x de BEP (0,75 mg/kg de bleomicina, 7,5 mg/ kg de etopósido y 1,5 mg/kg de cisplatino) con tres ciclos de 21 días cada uno. Las ratas del grupo 3 (grupo MEL) recibieron 10 mg/kg/día de melatonina una vez al día. El grupo 4 (Mel + BEP) recibió melatonina (30 minutos antes de las inyecciones de BEP) y BEP, como en los grupos 2. Se usó la tinción del antígeno nuclear de células en proliferación (PCNA) para detectar la proliferación celular y, caspasa- 3, caspasa-9 y caspasa-8 para investigar apoptosis. La inmunotinción de PCNA en el epitelio alveolar, los macrófagos alveolares y los bronquios varió de débil a moderada en el grupo BEP. Sin embargo, se detectaron inmunorreacciones difusas y fuertes para caspasa-3, caspasa 8- y caspasa-9 en el epitelio de los bronquiolos, endotelio vascular y macrófagos luminales alveolares. Las inmunorreactividades de PCNA y caspasa en los grupos MEL y Mel + BEP fueron similares a las del control. El área de superficie en el grupo BEP se redujo significativamente en comparación con el control (P0,05). Se puede concluir que la quimioterapia con BEP puede afectar negativamente al tejido pulmonar y la melatonina inhibe las lesiones durante la quimioterapia.

Green Synthesis of Hexagonal Silver Nanoparticles Using a Novel Microalgae Coelastrella aeroterrestrica Strain BA_Chlo4 and Resulting Anticancer, Antibacterial, and Antioxidant Activities.

Microalgae-mediated synthesis of nanoparticles (NPs) is an emerging nanobiotechnology that utilizes the biomolecular corona of microalgae as reducing and capping agents for NP fabrication. This study screened a novel microalgal strain for its potential to synthesize silver (Ag)-NPs and then assayed the biological activities of the NPs. Coelastrella aeroterrestrica strain BA_Chlo4 was isolated, purified, and morphologically and molecularly identified. Chemical composition of the algal extract was determined by GC-MS analysis. Ag-NPs were biosynthesized by C. aeroterrestrica BA_Chlo4 (C@Ag-NPs) and characterized using various techniques. Antiproliferative activity and the biocidal effect of C@Ag-NPs, C. aeroterrestrica algal extract, and chemically synthesized Ag-NPs (Ch@Ag-NPs) were explored, and the scavenging activity of C@Ag-NPs against free radicals was investigated. C@Ag-NPs were hexagonal, with a nanosize diameter of 14.5 ± 0.5 nm and a maximum wavelength at 404.5 nm. FTIR and GC-MS analysis demonstrated that proteins and polysaccharide acted as capping and reducing agents for C@Ag-NPs. X-ray diffraction, energy diffraction X-ray, and mapping confirmed the crystallinity and natural structure of C@Ag-NPs. The hydrodynamic diameter and charge of C@Ag-NPs was 28.5 nm and -33 mV, respectively. C@Ag-NPs showed significant anticancer activity towards malignant cells, with low toxicity against non-cancerous cells. In addition, C@Ag-NPs exhibited greater antioxidant activity and inhibitory effects against Gram-positive and -negative bacteria compared with the other tested treatments. These findings demonstrate, for first time, the potential of a novel strain of C. aeroterrestrica to synthesize Ag-NPs and the potent antioxidant, anticancer, and biocidal activities of these NPs.

An in-silico investigation of potential natural polyphenols for the targeting of COVID main protease inhibitor.

The deadliest recent pandemic outbreak of COVID-19 disease has severely damaged the socio-economic health of the people globally. Due to unavailability of any effective vaccine or treatment the human beings are still struggling to overcome the pandemic condition. In an attempt to discover anti-COVID molecule, we used in-silico approach and reported 160 natural polyphenols to identify the most promising druggable HITs that can further used for drug discovery process. The co-crystallized structure COVID protease enzyme (PDB id 6LU7) was used. HTVS, MD simulation, binding energy calculations and in-silico ADME calculation were done and analyzed. Depending upon the scores three compounds galangin, nalsudaldain and rhamnezine were identified and the docking score were found to be -7.704, -6.51, -4.212 respectively. These docked complexes were further subjected to MD simulation runs over a 100 ns time and the RMSD and RMSF values were determined. The RMSD values of three compounds were found to be 2.9 Å, 7.6 Å & 9.5 Å respectively and the lowest RMSF values suggested the steady stability of ligand-protein complexes. The binding free energies (ΔG) of compounds with protein were found to be -49.8, -56.45, -62.87 kJ/mole. Moreover, in-silico ADME calculations indicated the drug likeliness properties of these molecules. By considering all these in-silico results the identified HITs would be the most probable anti-COVID drug molecules that can be further taken in wet lab and can act as lead for development of newer inhibitor of COVID-19 main protease enzyme.

Design & discovery of small molecule COVID-19 inhibitor via dual approach based virtual screening and molecular simulation studies.

The emerged COVID-19 (SARS corona virus) pandemic leads to severe or fatal respiratory tract infections affecting millions of people worldwide since its outbreak. The situation needs the newer molecule to control the infections as the pandemic had very badly affected the health and socioeconomic conditions of human being. CoV-2 main protease is considered to be key enzyme by targeting which we can design or develop the drug candidate. The active fitting and binding of any molecule depends upon the shape and electrostatic properties of ligand complementary to the receptor site. In this study ZINC13 database, a drug like subset (13,195,609 molecules) was subjected to shape and electrostic based virtual screening (VROCS & EON software) and followed by molecular modelling studies using docking and molecular dynamics simulation. Further the drug ability of identified candidate was predicted by the SiteMap analysis. The best shape and electrostatic similarities were observed between ZINC19973962 and reference molecule. The Tamintoshape and Tanimotoelectrostatic was found to be 0.667 and 0.022 respectively. The molecule also displayed the identical binding pattern with docking score -7.964 and this interaction was further validated by the molecular dynamics simulations. The RMSD & RMSF values were found to be 1.5 Å and1.8 Å respectively suggesting the stability of complex and very low fluctuation in ligand-protein complex over the entire MD simulation run. SiteMap analysis showed the identical Dscore of reference and identified HIT that indicated the molecule ZINC19973962 would be the promising druggable candidate against COVID main protease enzyme and can be used as lead molecule for the development of anti-COVID molecule.

Algal-Derived Synthesis of Silver Nanoparticles Using the Unicellular ulvophyte sp. MBIC10591: Optimisation, Characterisation, and Biological Activities.

Algal-mediated synthesis of nanoparticles (NPs) is an eco-friendly alternative for producing NPs with potent physicochemical and biological properties. Microalgae represent an ideal bio-nanofactory because they contain several biomolecules acting as passivation and stabilising agents during the biogenesis of NPs. Herein, a novel microalgae sp. was isolated, purified, and identified using light and electron microscopy and 18s rRNA sequencing. The chemical components of their watery extract were assessed using GC-MS. Their dried biomass was used to synthesise silver (Ag) NPs with different optimisation parameters. Ag-NPs were physiochemically characterised, and their anticancer and antibacterial effects were examined. The data showed that the isolated strain was 99% similar to the unicellular ulvophyte sp. MBIC10591; it was ellipsoidal to spherical and had a large cup-shaped spongiomorph chloroplast. The optimum parameters for synthesising Ag-NPs by unicellular ulvophyte sp. MBIC10591 (Uv@Ag-NPs) were as follows: mixture of 1 mM of AgNO3 with an equal volume of algal extract, 100 °C for 1 h, and pH of 7 under illumination for 24 h. TEM, HRTEM, and SEM revealed that Uv@Ag-NPs are cubic to spherical, with an average nanosize of 12.1 ± 1.2 nm. EDx and mapping analysis showed that the sample had 79% of Ag, while FTIR revealed the existence of several functional groups on the NP surface derivatives from the algal extract. The Uv@Ag-NPs had a hydrodynamic diameter of 178.1 nm and a potential charge of -26.7 mV and showed marked antiproliferative activity against PC3, MDA-MB-231, T47D, and MCF-7, with IC50 values of 27.4, 20.3, 23.8, and 40 µg/mL, respectively, and moderate toxicity against HFs (IC50 of 13.3 µg/mL). Uv@Ag-NPs also showed marked biocidal activity against Gram-negative bacteria. Escherichia coli was the most sensitive bacteria to the NPs with an inhibition zone of 18.9 ± 0.03 mm. The current study reports, for the first time, the morphological appearance of the novel unicellular ulvophyte sp., MBIC10591, and its chemical composition and potential to synthesise Uv@Ag-NPs with smaller sizes and high stability to act as anti-tumour and microbial agents.

Lichens-A Potential Source for Nanoparticles Fabrication: A Review on Nanoparticles Biosynthesis and Their Prospective Applications.

Green synthesis of nanoparticles (NPs) is a safe, eco-friendly, and relatively inexpensive alternative to conventional routes of NPs production. These methods require natural resources such as cyanobacteria, algae, plants, fungi, lichens, and naturally extracted biomolecules such as pigments, vitamins, polysaccharides, proteins, and enzymes to reduce bulk materials (the target metal salts) into a nanoscale product. Synthesis of nanomaterials (NMs) using lichen extracts is a promising eco-friendly, simple, low-cost biological synthesis process. Lichens are groups of organisms including multiple types of fungi and algae that live in symbiosis. Until now, the fabrication of NPs using lichens has remained largely unexplored, although the role of lichens as natural factories for synthesizing NPs has been reported. Lichens have a potential reducible activity to fabricate different types of NMs, including metal and metal oxide NPs and bimetallic alloys and nanocomposites. These NPs exhibit promising catalytic and antidiabetic, antioxidant, and antimicrobial activities. To the best of our knowledge, this review provides, for the first time, an overview of the main published studies concerning the use of lichen for nanofabrication and the applications of these NMs in different sectors. Moreover, the possible mechanisms of biosynthesis are discussed, together with the various optimization factors influencing the biological synthesis and toxicity of NPs.

Exendin-4 Attenuates Remodeling in the Remote Myocardium of Rats After an Acute Myocardial Infarction by Activating ß-Arrestin-2, Protein Phosphatase 2A, and Glycogen Synthase Kinase-3 and Inhibiting ß-Catenin.

PURPOSE: This study tested if the protective anti-remodeling effect of GLP-1 agonist Exendin-4 after an acute myocardial infarction (MI) in rats involves inhibition of the Wnt1/ß-catenin signaling pathway. METHODS: Rats were divided into sham, sham + Exendin-4 (10 µg/day, i.p), MI, and MI + Exendin-4. MI was introduced to rats by permanent left anterior descending coronary artery (LAD) ligation. RESULTS: On day 7 post-infraction, MI rats showed LV dysfunction with higher serum levels of cardiac markers. Their remote myocardia showed increased mRNA and protein levels of collagen I/III with higher levels of reactive oxygen species (ROS) and inflammatory cytokines, as well as protein levels of Wnt1, phospho-Akt, transforming growth factor (TGF-ß1), Smad, phospho-Smad3, α-SMA, caspase-3, and Bax. They also showed higher protein levels of phospho-glycogen synthase kinase-3ß (p-GSK3ß), as well as total, phosphorylated, and nuclear ß-catenin with a concomitant decrease in the levels of cyclic adenosine monophosphate (cAMP), mRNA of manganese superoxide dismutase (MnSOD), and protein levels of Bcl-2, ß-arrestin-2, and protein phosphatase-2 (PP2A). Administration of Exendin-4 to MI rats reduced the infarct size and reversed the aforementioned signaling molecules without altering protein levels of TGF-1ß and Wnt1 or Akt activation. Interestingly, Exendin-4 increased mRNA levels of MnSOD, protein levels of ß-arrestin-2 and PP2A, and ß-catenin phosphorylation but reduced the phosphorylation of GSK3ß and Smad3, and total ß-catenin levels in the LV of control rats. CONCLUSION: Exendin-4 inhibits the remodeling in the remote myocardium of rats following acute MI by attenuating ß-catenin activation and activating ß-arrestin-2, PP2A, and GSK3ß. Graphical Abstract A graphical abstract that illustrates the mechanisms by which Exendin-4 inhibits cardiac remodeling in remote myocardium of left ventricle MI-induced rats. Mechanisms are assumed to occur in the cardiomyocytes and/or other resident cells such as fibroblast. Β-catenin activation and nuclear translocation are associated with increased synthesis of inflammatory cytokines and transforming growth factor ß-1 (TGF-ß1). GSK3ß is inhibited by phosphorylation at Ser9. Under normal conditions, ß-catenin is degraded in the cytoplasm by the active GSK3ß-dependent degradation complex (un-phosphorylated) which usually phosphorylates ß-catenin at Ser33/37/Thr41. After MI, TGF-ß1, and Wnt 1 levels are significantly increased, the overproduction of Wnt1 induces ß-catenin stabilization and nuclear translocation through increasing the phosphorylation of disheveled (DVL) protein which in turn phosphorylates and inhibits GSK3ß. TGF-ß1 stimulates the phosphorylation of Smad-3 and subsequent nuclear translocation to activate the transcription of collage 1/III and α-smooth muscle actin (α-SMA). Besides, TGF-ß1 stabilizes cytoplasmic ß-catenin levels indirectly by phosphorylation of Akt at Thr308-induced inhibition of GSK3ß by increasing phosphorylation of Ser9. Exendin-4, and possibly through G protein-coupled receptors (GPCRs), increases levels of cAMP and upregulates ß-arrestin-2 levels. Both can result in a positive inotropic effect. Besides, ß-arrestin-2 can stimulate PP2A to dephosphorylation Smad3 (inhibition) and GSK3ß (activation), thus reduces fibrosis and prevents the activation of ß-catenin and collagen deposition.

Exendin-4 Protects Against Myocardial Ischemia-Reperfusion Injury by Upregulation of SIRT1 and SIRT3 and Activation of AMPK.

This study evaluated if the cardioprotective effect of Exendin-4 against ischemia/reperfusion (I/R) injury in male rats involves modulation of AMPK and sirtuins. Adult male rats were divided into sham, sham + Exendin-4, I/R, I/R + Exendin-4, and I/R + Exendin-4 + EX-527, a sirt1 inhibitor. Exendin-4 reduced infarct size and preserved the function and structure of the left ventricles (LV) of I/R rats. It also inhibited oxidative stress and apoptosis and upregulated MnSOD and Bcl-2 in their infarcted myocardium. With no effect on SIRTs 2/6/7, Exendin-4 activated and upregulated mRNA and protein levels of SIRT1, increased levels of SIRT3 protein, activated AMPK, and reduced the acetylation of p53 and PGC-1α as well as the phosphorylation of FOXO-1. EX-527 completely abolished all beneficial effects of Exendin-4 in I/R-induced rats. In conclusion, Exendin-4 cardioprotective effect against I/R involves activation of SIRT1 and SIRT3. Graphical Abstract Exendin-4 could scavenge free radical directly, upregulate p53, and through upregulation of SIRT1 and stimulating SIRT1 nuclear accumulation. In addition, Exendin-4 also upregulates SIRT3 which plays an essential role in the upregulation of antioxidants, inhibition of reactive oxygen species (ROS) generation, and prevention of mitochondria damage. Accordingly, SIRT1 induces the deacetylation of PGC-1α and p53 and is able to bind p-FOXO-1. This results in inhibition of cardiomyocyte apoptosis through increasing Bcl-2 levels, activity, and levels of MnSOD; decreasing expression of Bax; decreasing cytochrome C release; and improving mitochondria biogenesis through upregulation of Mfn-2.

Kefir: A protective dietary supplementation against viral infection.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a recently discovered coronavirus termed 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2). Several scholars have tested antiviral drugs and compounds to overcome COVID-19. 'Kefir' is a fermented milk drink similar to a thin yogurt that is made from kefir grains. Kefir and its probiotic contents can modulate the immune system to suppress infections from viruses (e.g., Zika, hepatitis C, influenza, rotaviruses). The antiviral mechanisms of kefir involve enhancement of macrophage production, increasing phagocytosis, boosting production of cluster of differentiation-positive (CD4+), CD8+, immunoglobulin (Ig)G+ and IgA+ B cells, T cells, neutrophils, as well as cytokines (e.g., interleukin (IL)-2, IL-12, interferon gamma-γ). Kefir can act as an anti-inflammatory agent by reducing expression of IL-6, IL-1, TNF-α, and interferon-γ. Hence, kefir might be a significant inhibitor of the 'cytokine storm' that contributes to COVID-19. Here, we review several studies with a particular emphasis on the effect of kefir consumption and their microbial composition against viral infection, as well as discussing the further development of kefir as a protective supplementary dietary against SARS-CoV-2 infection via modulating the immune response.

Cyanobacteria - A Promising Platform in Green Nanotechnology: A Review on Nanoparticles Fabrication and Their Prospective Applications.

Green synthesis of nanoparticles (NPs) is a global ecofriendly method to develop and produce nanomaterials with unique biological, physical, and chemical properties. Recently, attention has shifted toward biological synthesis, owing to the disadvantages of physical and chemical synthesis, which include toxic yields, time and energy consumption, and high cost. Many natural sources are used in green fabrication processes, including yeasts, plants, fungi, actinomycetes, algae, and cyanobacteria. Cyanobacteria are among the most beneficial natural candidates used in the biosynthesis of NPs, due to their ability to accumulate heavy metals from their environment. They also contain a variety of bioactive compounds, such as pigments and enzymes, that may act as reducing and stabilizing agents. Cyanobacteria-mediated NPs have potential antibacterial, antifungal, antialgal, anticancer, and photocatalytic activities. The present review paper highlights the characteristics and applications in various fields of NPs produced by cyanobacteria-mediated synthesis.

Cadmium Chloride Induces Memory Deficits and Hippocampal Damage by Activating the JNK/p66Shc/NADPH Oxidase Axis.

This study investigated whether the mechanism underlying the neurotoxic effects of cadmium chloride (CdCl2) in rats involves p66Shc. This study comprised an initial in vivo experiment followed by an in vitro experiment. For the in vivo experiment, male rats were orally administered saline (vehicle) or CdCl2 (0.05 mg/kg) for 30 days. Thereafter, spatial and retention memory of rats were tested and their hippocampi were used for biochemical and molecular analyses. For the in vitro experiment, control or p66Shc-deficient hippocampal cells were treated with CdCl2 (25 µM) in the presence or absence of SP600125, a c-Jun N-terminal kinase (JNK) inhibitor. Cadmium chloride impaired the spatial learning and retention memory of rats; depleted levels of glutathione and manganese superoxide dismutase; increased reactive oxygen species (ROS), tumor necrosis factor α, and interleukin 6; and induced nuclear factor kappa B activation. Cadmium chloride also decreased the number of pyramidal cells in the CA1 region and induced severe damage to the mitochondria and endoplasmic reticulum of cells in the hippocampi of rats. Moreover, CdCl2 increased the total unphosphorylated p66Shc, phosphorylated (Ser36) p66Shc, phosphorylated JNK, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, cytochrome c, and cleaved caspase-3. A dose-response increase in cell death, ROS, DNA damage, p66Shc, and NADPH oxidase was also observed in cultured hippocampal cells treated with CdCl2. Of note, all of these biochemical changes were attenuated by silencing p66Shc or inhibiting JNK with SP600125. In conclusion, CdCl2 induces hippocampal ROS generation and apoptosis by promoting the JNK-mediated activation of p66Shc.

Oxidative Stress and Apoptotic Responses Elicited by Nostoc-Synthesized Silver Nanoparticles against Different Cancer Cell Lines.

Green nanoparticles represent a revolution in bionanotechnology, providing opportunities to fight life-threatening diseases, such as cancer, with less risk to the environment and to human health. Here, for the first time, we systematically investigated the anticancer activity and possible mechanism of novel silver nanoparticles (N-SNPs) synthesized by Nostoc Bahar M against the MCF-7 breast cancer cells, HCT-116 colorectal adenocarcinoma cells, and HepG2 liver cancer cells, using cell viability assays, morphological characterization with inverted light and transmission electron microscopy, antioxidants and enzymes (glutathione peroxidase (GPx), glutathione (GSH), adenosine triphosphatase (ATPase), and lactate dehydrogenase (LDH)), and western blotting (protein kinase B (Akt), phosphorylated-Akt (p-Akt), mammalian target of rapamycin (mTOR), B-cell lymphoma 2 (Bcl-2), tumor suppressor (p53), and caspase 3). N-SNPs decreased the viability of MCF-7, HCT-116, and HepG2 cells, with half-maximal inhibitory concentrations of 54, 56, and 80 µg/mL, respectively. They also significantly increased LDH leakage, enhanced oxidative stress via effects on antioxidative markers, and caused metabolic stress by significantly decreasing ATPase levels. N-SNPs caused extensive ultrastructural alterations in cell and nuclear structures, as well as in various organelles. Furthermore, N-SNPs triggered apoptosis via the activation of caspase 3 and p53, and suppressed the mTOR signaling pathway via downregulating apoptosis-evading proteins in MCF-7, HCT-116, and HepG2 cells. Ultrastructural analysis, together with biochemical and molecular analyses, revealed that N-SNPs enhanced apoptosis via the induction of oxidative stress and/or through direct interactions with cellular structures in all tested cells. The cytotoxicity of Nostoc-mediated SNPs represents a new strategy for cancer treatment via targeting various cell death pathways. However, the potential of N-SNPs to be usable and biocompatible anticancer drug will depend on their toxicity against normal cells.

Synthesis of Silver Nanoparticles Using a Novel Cyanobacteria Desertifilum sp. extract: Their Antibacterial and Cytotoxicity Effects.

BACKGROUND: The emergence of multi drug-resistant (MDR) bacterial infections and cancer has necessitated the development and discovery of alternative eco-safe antibacterial and anticancer agents. Biogenic fabrication of metallic nanoparticles is an emerging discipline for production of nanoproducts that exert potent anticancer and antibacterial activity, and do not suffer from the limitations inherent in physiochemical synthesis methods. METHODOLOGY: In this study, we isolated, purified, and characterized a novel cyanobacteria extract (Desertifilum IPPAS B-1220) to utilize in biofabrication of silver nanoparticles (D-SNPs). D-SNPs were produced by adding Desertifilum extract to silver nitrate solution under controlled conditions. Biofabrication of D-SNPs was confirmed using a UV-Vis spectrophotometer. The resultant D-SNPs were characterized using XRD, FTIR, SEM, and TEM. The toxicity of D-SNPs against five pathogenic bacteria and three cancer cell lines (MCF-7, HepG2, and Caco-2) was evaluated. RESULTS: Formation of D-SNPs was indicated by a color change from pale yellow to dark brown. The peak of the surface plasmon resonance of the D-SNPs was at 421 nm. The XRD detected the crystallinity of D-SNPs. FTIR showed that polysaccharides and proteins may have contributed to the biofabrication of D-SNPs. Under SEM and TEM, the D-SNPs were spherical with diameter ranges from 4.5 to 26 nm. The D-SNPs significantly suppressed the growth of five pathogenic bacteria, and exerted cytotoxic effects against MCF-7, HepG2, and Caco-2 cancer cells with IC50 values of 58, 32, and 90 µg/mL, respectively. CONCLUSION: These findings showed for the first time the potentiality of novel cyanobacteria strain Desertifilum IPPAS B-1220 to fabricate small SNPs that acted as potent anticancer and antibacterial material against different cancer cell lines and pathogenic bacterial strains. These findings encourage the researchers to focus on cyanobacteria in general and especially Desertifilum sp. IPPAS B-1220 for synthesizing different NPs that opening the window for new applications.

Kaempferol Protects Against Cadmium Chloride-Induced Memory Loss and Hippocampal Apoptosis by Increased Intracellular Glutathione Stores and Activation of PTEN/AMPK Induced Inhibition of Akt/mTOR Signaling.

This study investigated the protective effect of Kaempferol against CdCl2-induced hippocampal damage and memory deficit in rats and investigated if such effects involve modulating the activity of AMPK/PTEN/Akt/mTOR axis. Adult male rats (n = 12/group) were divided into control or CdCl2-treated rats received the vehicle of Kaempferol for consecutive 6 weeks. Also, hippocampal cells were treated with CdCl2 in the presence or absence of Kaempferol for 24 h with or without 1 h pre-incubation with compound C, an AMPK inhibitor or with bpV a PTEN inhibitor. Kaempferol improved the behavioral of CdCl2-treated rats, preserved hippocampus structure and reduced hippocampal levels of ROS and protein levels of Bax and cleaved caspase-3. In both control and CdCl2-treated rats, Kaempferol significantly increased hippocampal levels of GSH levels and protein levels of Nfr2, Bcl2 and synaptic proteins (SNAP-25, PSD-25, and synapsin). Concomitantly, it increased the activity of PTEN and AMPK and subsequently, decreased the activity of Akt and mTOR. In cultured cells, individual pharmacological inhibition of PTEN by bpv or AMPK of compound C (CC) partially prevented the stimulatory effect of Kaempferol on Akt/mTOR and its inhibitory effect on cell death whereas a combination of both inhibitors completely prevented this. Also, inhibition of PTEN alone completely abolished the inhibitory effect of Kaempferol by synaptic proteins, whereas inhibition of AMPK completely abolished its stimulatory effect of Nfr2. In conclusion, Kaempferol protects against CdCl2-induced memory deficits and hippocampal apoptosis by its antioxidant potential and inhibition of Akt/mTOR axis and requires the activation of PTEN and AMPK.

Biofabrication And Antitumor Activity Of Silver Nanoparticles Utilizing Novel Nostoc sp. Bahar M.

BACKGROUND: Over recent years, green chemistry procedures have been developed to synthesize nanoparticles in eco-friendlier and less expensive ways. These procedures use natural sources such as bacteria, fungi, yeast, plants, actinomycetes, algae, or cyanobacteria, or use biomolecules such as proteins, vitamins, or pigments instead of chemical materials to fabricate salt precursors into nanoparticles. METHODOLOGY: In the current investigation, we developed an effective, inexpensive, nontoxic method to synthesize silver nanoparticles (SNPs) using the cellular extract of a novel strain of cyanobacterium, Nostoc sp. Bahar M. SNPs were characterized using ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The antitumor properties of the biogenic SNPs were tested against Caco-2 cells using a cell proliferation assay and inverted light microscopy. RESULTS: The new strain Nostoc sp. Bahar M was able to fabricate small SNPs from silver nitrate through an eco-friendly and inexpensive biosynthesis process. SNPs synthesis was accompanied by a color transformation from pale yellow to dark brown. Ultraviolet spectroscopy showed an absorption peak at 403 nm, confirming SNPs formation. X-ray diffraction analysis indicated that the SNPs had a face-centered cubic crystalline structure. Fourier-transform infrared spectroscopy was used to identify a protein that may play an important role in SNPs biosynthesis. Scanning and transmission electron micrographs showed that the SNPs were uniformly distributed and spherical in shape, with an average diameter of 14.9 nm. Cytotoxicity assays showed that SNPs exhibited a significant dose-dependent cytotoxic activity against human colon cancer cells with an IC50 of 150 µg/mL. CONCLUSION: Nostoc sp. Bahar M provided an eco-friendly route for fabricating SNPs, which have cytotoxic activity toward Caco-2 cells.

Ginger extract ameliorates renal damage in high fat diet-induced obesity in rats: biochemical and ultrastructural study / El extracto de jengibre mejora el daño renal en la obesidad inducida por la dieta alta en grasas en ratas: estudio bioquímico y ultraestructural

Obesity is a modifiable risk factor for the development and progression of kidney disease. Obesity may harm kidneys in individuals without hypertension, diabetes, or pre-existing renal disease. Ginger, Zingiber officinale, has many beneficial pharmaceutical benefits. This study aimed to evaluate the Zingiber officinale protective effect against obesity complications which induced by high fat diet and caused renal dysfunctions. The study period was two months, and the experimental animals' groups were four, 80 Wistar rats were appropriated similarly 20 animals/group: control group; ginger extract group (GE); high-fat diet (HFD); and GE+HFD group. Body and fat weight, creatinine, leptin, TNF-α, total antioxidants, renal histopathological and ultrastructure were investigated. Rats in group of HFD showed a significant increase (P<0.05) in the body and fat weights, creatinine, leptin and TNF-α, and significant decrease (P<0.05) in total antioxidants (TAS). Ginger administration significantly showed the protective restoring the altered parameters. Furthermore, rats co-treated with ginger extract improved the histopathological and ultrastructural renal injury induced by obesity. The study concluded that the ginger extract used could suppress and decrease the renal damage induced by high-fat diet as it possesses potential medicinal values.

La obesidad es un factor de riesgo modificable para el desarrollo y la progresión de la enfermedad renal. La obesidad puede dañar los riñones en personas sin hipertensión, diabetes o enfermedad renal preexistente. El jengibre, Zingiber officinale, tiene muchos beneficios farmacéuticos. Este estudio tuvo como objetivo evaluar el efecto protector de Zingiber officinale en las complicaciones de la obesidad inducida por una dieta alta en grasas y las enfermedad renal. El período de estudio fue de dos meses, y los grupos de animales experimentales fueron cuatro, se asignaron 80 ratas Wistar de manera similar, 20 animales por grupo: grupo de control; grupo de extracto de jengibre (GE); dieta alta en grasas (DAG); y el grupo GE + DAG. Se evaluó el peso corporal y la grasa, creatinina, leptina, TNF-α, antioxidantes totales, histopatología renal y ultraestructura. Las ratas en el grupo de DAG mostraron un aumento significativo (P<0,05) en el peso corporal y de grasa, creatinina, leptina y TNF-a, y una disminución significativa (P<0,05) en los antioxidantes totales. La administración de jengibre mostró una protección significativa restaurando los parámetros alterados. Además, las ratas tratadas conjuntamente con extracto de jengibre mejoraron la lesión renal histopatológica y ultraestructural inducida por la obesidad. El estudio concluyó que el extracto de jengibre podría suprimir y disminuir el daño renal inducido por la dieta alta en grasas, ya que posee potenciales valores medicinales.

Suppressive effects of capsaicin against N-nitrosomethylurea-induced mammary tumorigenesis in rats.

Capsaicin, is commonly used in folk medicine to management oxidative stress in cells and might decrease the riskiness effects of cancers. The purpose of this study was to evaluate the suppressive activity of capsaicin against mammary carcinoma induced by N-nitrosomethylurea in rats. The study continued for 16 weeks. The sample consisted of 80 female rats which were divided equally into four groups and the following investigations were recorded: Body and gain weights, estradiol and progesterone, Carcinoembryonic Antigen, anti-oxidant enzymes, oxidative stress marker, histopathological and proliferating cell nuclear antigen immunohistochemical. N-nitrosomethylurea treated group displayed a significant decrease body weight and anti-oxidant enzymes. Also, subjects in this group displayed a significant increase estradiol, progesterone, CEA and Malondialdehyde. Additionally, the NMU exposure and capsaicin treated group significantly showed the protective potential of capsaicin in restoring the altered sexual hormones, antioxidants and other biochemical analyses. Rats treated with NMU and protected with capsaicin improved the histopathological changes induced by NMU and showed that the desquamation of most of the layers of carcinoma cells leaving one or two epithelial layers in some cases and in some instances. Animals treated with NMU immunostained for PCNA displayed the strong positive stained nuclei in most of the cells, but in capsaicin treated against the NMU effects immunostained for PCNA displayed that the positive stained nuclei was less than that detected in NMU group. To conclude, the results have clearly shown that capsaicin performs a very important defensive role during breast carcinogenesis and has the ability to act as a chemo-suppressive factor against NMU effects.