Postbiotics as potential promising tools for SARS-CoV-2 disease adjuvant therapy

The SARS-CoV-2 pandemic defines the global health tension of our time. There are several continuous efforts to find a definitive cure in this regard. According to some adverse effects and problems of customary SARS-CoV-2 disease therapies, bioactive compounds, for example probiotics-derived metabolites (postbiotics) have been accomplishing supreme importance by investigators for adjuvant cures in patients with SARS-CoV-2. Postbiotics inhibit angiotensin-converting enzyme 2 activity and stimulate the immune system. They also boost the SARS-CoV-2 disease treatment effectiveness and reduce its adverse effects in SARS-CoV-2 illness patients as a result of antiviral and anti-inflammatory effects. Furthermore, postbiotics having unique features such as high safety, high shelf life and stability to the gastrointestinal tract can be utilized as hopeful instruments for both adjuvant and inhibition strategies in SARS-CoV-2 patients with no earnest unfavourable adverse effects. The concept of postbiotics and their biocompatible characteristics are comprehensively discussed in the present review while highlighting the bilateral relationship between postbiotic biometabolites and respiratory tract infection with a special look at the potential biological role in the inactivation of SARS-CoV-2 and reduction of related inflammatory pathways.     

The tropical white rot fungus, <Emphasis Type="Italic">Lentinus squarrosulus</Emphasis> Mont.: lignocellulolytic enzymes activities and sugar release from cornstalks under solid state fermentation

Lentinus squarrosulus Mont., a high temperature tolerant white rot fungus that is found across sub-Saharan Africa and many parts of Asia, is attracting attention due to its rapid mycelia growth and potential for use in food and biodegradation. A solid state fermentation (SSF) experiment with L. squarrosulus (strain MBFBL 201) on cornstalks was conducted. The study evaluated lignocellulolytic enzymes activity, loss of organic matter (LOM), exopolysaccharide content, and the release of water soluble sugars from degraded substrate. The results showed that L. squarrosulus was able to degrade cornstalks significantly, with 58.8% LOM after 30 days of SSF. Maximum lignocellulolytic enzyme activities were obtained on day 6 of cultivation: laccase = 154.5 U/L, MnP = 13 U/L, peroxidase = 27.4 U/L, CMCase = 6.0 U/mL and xylanase = 14.5 U/mL. L. squarrosulus is a good producer of exopolysaccharides (3.0–5.13 mg/mL). Glucose and galactose were the most abundant sugars detected in the substrate during SSF, while fructose, xylose and trehalose, although detected on day zero of the experiment, were absent in treated substrates. The preference for hemicellulose over cellulose, combined with the high temperature tolerance and the very fast growth rate characteristics of L. squarrosulus could make it an ideal candidate for application in industrial pretreatment and biodelignification of lignocellulosic biomass.     

A comparative proteome approach to decipher the mechanism of rice adaptation to phosphorous deficiency

Mineral deficiency limits crop production in most soils and in Asia alone, about 50% of rice lands are phosphorous deficient. In an attempt to determine the mechanism of rice adaptation to phosphorous deficiency, changes in proteome patterns associated with phosphorous deficiency have been investigated. We analyzed the parental line Nipponbare in comparison to its near isogenic line (NIL6‐4) carrying a major phosphorous uptake QTL (Pup1) on chromosome 12. Using 2‐DE, the proteome pattern of roots grown under 1 and 100 μM phosphorous were compared. Out of 669 proteins reproducibly detected on root 2‐DE gels, 32 proteins showed significant changes in the two genotypes. Of them, 17 proteins showed different responses in two genotypes under stress condition. MS resulted in identification of 26 proteins involved in major phosphorous deficiency adaptation pathways including reactive oxygen scavenging, citric acid cycle, signal transduction, and plant defense responses as well as proteins with unknown function. Our results highlighted a coordinated response in NIL in response to phosphorous deficiency which may confer higher adaptation to nutrient deficiency.     

Proteomic signature of human embryonic stem cells

Human embryonic stem cells (hESC) represent a population of undifferentiated pluripotent cells with both self-renewal and multilineage differentiation characteristics. Proteomics provides a powerful approach for studying the characteristics of hESC and discovering molecular markers. We have analyzed proteome profiles of three hESC lines using 2-DE and MALDI TOF-TOF. Out of 844 spots analyzed with MALDI TOF-TOF, 685 proteins were identified of which 60 proteins were classified as the most abundant proteins on 2-D gels. A large number of proteins particularly high abundant ones were identified as chaperones, heat shock proteins, ubiquitin/proteasome, and oxidative stress responsive proteins underscoring the ability of these cells to resist oxidative stress and increase the life span. Several proteins involved in cell proliferation and differentiation were also among the highly expressed proteins. Although overall expression pattern of three hESC were similar, 54 spots changed quantitatively and 14 spots changed qualitatively among the hESC cell lines. Most of these proteins were identified as proteins involved in cell growth, metabolism and signal transduction, which may affect the self-renewal and pluripotency. To our knowledge, this study represents the first proteomic dataset for hESC and provides a better insight into the biology of hESC. Proteome maps of hESC are accessible at http://www.RoyanProteomics.ir.     

Anti-Inflammatory Activity of S. Marianum and N. Sativa Extracts on Macrophages

Background:Nigella sativa (N. sativa) and Silybum marianum (S. marianum) are used to regulate macrophage polarization in lipopolysaccharide-induced RAW 264.7 cells and thioglycollate-elicited peritoneal inflammation.Methods:Cytotoxicity assays and acute toxicity tests were performed to investigate the safe dose and toxicity of the prepared extracts. Also, nitric oxide production was determined by Griess assay on RAW264.7 and peritoneal macrophage supernatants. After RNA extraction from macrophages, real-time PCR was performed to measure the relative gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-β, and IL-10. Finally, regulatory T cells (Treg cells) were counted by flow cytometry.Results:S. marianum methanolic extract (SME), N. sativa ethanolic extract (NEE), and their mixture (SME+NEE) decreased NO levels significantly in RAW264.7 and peritoneal murine macrophages. N. sativa ethanolic extract significantly increased IL-10 gene expression and significantly decreased IL-6 and TNF-α expression in RAW264.7 cells. In mixture-treated peritoneal macrophages, IL-10 and TGF-β expression were significantly increased, while IL-6 and TNF-α were significantly decreased. Also, the percentage of Treg cells was significantly greater in the mixture-treated cells than in controls.Conclusion:These results suggest that an SME and NEE mixture has anti-inflammatory and immunomodulatory activities and may be useful in the treatment of diseases of immunopathologic origin characterized by macrophage hyperactivation.Key Words: Cytokine, Inflammation, Nigella sativa, Nitric oxide, Silybum marianum     

Differentiation of microfluidic-encapsulated trabecular meshwork mesenchymal stem cells into insulin producing cells and their impact on diabetic rats

Tissue and stem cell encapsulation andtransplantation were considered as promising tools in the treatment of patients with diabetes mellitus. The aim of this study was to evaluate the effect of microfluidic encapsulation on the differentiation of trabecular meshwork mesenchymal stem cells (TM-MSC), into insulin-producing cells (IPCs) both in vitro and in vivo. The presence of differentiated cells in microfibers (three dimensional [3D]) and tissue culture plates (TCPS; two dimensional [2D]) culture was evaluated by detecting mRNA and protein expression of pancreatic islet-specific markers as well as measuring insulin release of cells in response to glucose challenges. Finally, semi-differentiated cells in microfibers (3D) and 2D cultures were used to control the glucose level in diabetic rats. The results of this study showed that MSCs differentiated in alginate microfibers (fabricated by microfluidic device) express more Pdx-1 mRNA (1.938-fold, p-value: 0.0425) and Insulin mRNA (2.841-fold, p-value: 0.0001) compared with those cultured on TCPS. Furthermore, cell encapsulation in microfluidic derived microfibers decreased the level of blood glucose in diabetic rats. The approach used in this study showed the possibility of alginate microfibers as a matrix for differentiation of TM-MSCs (as a new source) into IPCs. In addition, it could minimize different steps in stem cell differentiation, handling, and encapsulation, which lead to loss of an unlimited number of cells.     

Cytokines as potential combination agents with PD-1/PD-L1 blockade for cancer treatment

Immunotherapy has caused a paradigm shift in the treatment of several malignancies, particularly the blockade of programmed death-1 (PD-1) and its specific receptor/ligand PD-L1 that have revolutionized the treatment of a variety of malignancies, but significant durable responses only occur in a small percentage of patients, and other patients failed to respond to the treatment. Even those who initially respond can ultimately relapse despite maintenance treatment, there is considerable potential for synergistic combinations of immunotherapy and chemotherapy agents with immune checkpoint inhibitors into conventional cancer treatments. The clinical experience in the use of cytokines in the clinical setting indicated the efficiency of cytokine therapy in cancer immunotherapy. Combinational approaches to enhancing PD-L1/PD-1 pathways blockade efficacy with several cytokines such as interleukin (IL)-2, IL-15, IL-21, IL-12, IL-10, and interferon-α (IFN-α) may result in additional benefits. In this review, the current state of knowledge about PD-1/PD-L1 inhibitors, the date in the literature to ascertain the combination of anti-PD-1/PD-L1 antibodies with cytokines is discussed. Finally, it is noteworthy that novel therapeutic approaches based on the efficient combination of recombinant cytokines with the PD-L1/PD-1 blockade therapy can enhance antitumor immune responses against various malignancies.