Proliferation Of Human Lymphocytes Research Articles

Biological Importance and Therapeutic Potential of Calycopterin From Dracocephalum kotschyi: An Overview of Current Scientific Research Work.

Dracocephalum kotschyi Boiss is an important medicinal plant of Asia, Europe and Iran. The therapeutic potential of Dracocephalum kotschyi has been mentioned in traditional as well as in modern medicine, mainly due to its therapeutic effectiveness against different types of human disorders and associated secondary complications. Calycopterin is a flavonoid class phytochemical commonly called 5,4-dihydroxy-3,6,7,8- tetramethoxyflavone, which has been isolated from Dracocephalum kotschyi. It is widely used for the treatment of human disorders and associated secondary complications. Medicinal importance and therapeutic potential of calycopterin was investigated in the present work through scientific data analysis of different research works. Scientific data on calycopterin published in different research articles were collected from PubMed, Google, Google Scholar, Science Direct, SpringerLink, and Scopus and analyzed in the present work. Further, scientific data was collected from books and book chapters. Analytical data on calycopterin was also collected and analyzed in the present work. Scientific data analysis of different research work revealed the biological importance and therapeutic potential of calycopterin. Calycopterin showed therapeutic effectiveness against different types of cancerous disorders, including human prostate cancer, breast cancer, cervical cancer, lymphocyte proliferation and hepatoblastoma cancer. Moreover, the biological effectiveness of calycopterin on neuroprotection and Pseudomonas aeruginosa has also been discussed in the present work with their pharmacokinetic parameters. Nevertheless, more scientific investigations must be conducted to explore the healthbeneficial aspects of calycopterin in medicine. Present work signified the biological importance and therapeutic potential of calycopterin for the treatment of human disorders and complications, including different types of cancerous disorders.

Intracellular Potassium in Cell Growth and Proliferation of Human Mesenchymal Stem Cells and Blood Lymphocytes

Many data show that K+ ions are essential for cell proliferation. In this brief review, we summarize our own studies and literature data that characterize the relationship between modulations of intracellular K+ content and the intensity of cell proliferation. Using flame emission assay we compared the transport of monovalent cations in transformed cells and in human mesenchymal stem cells in growing cultures, as well as during stress-induced cell cycle arrest and transition from monolayer (2D) to three-dimensional (3D) spheroids. A decrease in the intracellular content of K+ (evaluated as the ratio of the content of K+ in cells to the mass of cellular protein) associated with the accumulation of G1 cells in the population and accompanied by a stop in proliferation was revealed. The relationship between intracellular K+ and initiation of cell proliferation was further analyzed in human blood lymphocytes (HBL) as a model for the transition of cells from quiescence to proliferation. In HBL stimulated to proliferate, the content of K+ in cells increases during the transition G0/G1/S, accompanying the growth of small lymphocytes into blasts. Cellular water content, calculated from buoyant cell density, is higher in proliferating HBLs and in Jurkat leukemic T cells than in resting HBL. Available data suggest that intracellular K+ is important for successful cell proliferation as the main intracellular ion involved in the regulation of cell volume during the transition from quiescence to proliferation, and high K+ content and associated high water content in the cell are a characteristic feature of cell proliferation and transformation.

Immunological evaluation of herbal extracts commonly used for treatment of mental diseases during pregnancy

Nonpsychotic mental diseases (NMDs) affect approximately 15% of pregnant women in the US. Herbal preparations are perceived a safe alternative to placenta-crossing antidepressants or benzodiazepines in the treatment of nonpsychotic mental diseases. But are these drugs really safe for mother and foetus? This question is of great relevance to physicians and patients. Therefore, this study investigates the influence of St. John’s wort, valerian, hops, lavender, and California poppy and their compounds hyperforin and hypericin, protopine, valerenic acid, and valtrate, as well as linalool, on immune modulating effects in vitro. For this purpose a variety of methods was applied to assess the effects on viability and function of human primary lymphocytes. Viability was assessed via spectrometric assessment, flow cytometric detection of cell death markers and comet assay for possible genotoxicity. Functional assessment was conducted via flow cytometric assessment of proliferation, cell cycle and immunophenotyping. For California poppy, lavender, hops, and the compounds protopine and linalool, and valerenic acid, no effect was found on the viability, proliferation, and function of primary human lymphocytes. However, St. John’s wort and valerian inhibited the proliferation of primary human lymphocytes. Hyperforin, hypericin, and valtrate inhibited viability, induced apoptosis, and inhibited cell division. Calculated maximum concentration of compounds in the body fluid, as well as calculated concentrations based on pharmacokinetic data from the literature, were low and supported that the observed effects in vitro would probably have no relevance on patients. In-silico analyses comparing the structure of studied substances with the structure of relevant control substances and known immunosuppressants revealed structural similarities of hyperforin and valerenic acid to the glucocorticoids. Valtrate showed structural similarities to the T cells signaling modulating drugs.

Medicinal Importance and Pharmacological Activities of Sciadopitysin in the Medicine: Drug Target for Neuroprotection, Myocardial Infarction, Alzheimer’s Disease, Diabetes, and Related Complications

Backgrounds: Herbal medicines have been used in the medicine over the last three decades and demand of herbal drugs has been increasing in the modern medicine due to their health beneficial aspects and pharmacological activities. Herbal medicines were mainly derived from the plants and their derived products which have significant role in the traditional and modern system of medicine. Plant based products have been used in the preparation of numerous health product including some of the modern pharmaceutical preparation. Ginkgo biloba is one of the important medicinal plants of the herbal medicine, which contain significant amount of sciadopitysin. Methods: Biological importance and therapeutic benefit of sciadopitysin have been investigated in the present investigation through scientific data analysis of different scientific research work in order to know the therapeutic potential of sciadopitysin in the medicine. Pharmacological activities of sciadopitysin have been searched and analyzed in the present work through different literature databases. Modern analytical tools for the isolation and quantification of sciadopitysin have been also discussed in the present work to know the therapeutic value of sciadopitysin in the medicine. Results: Scientific data analysis of different research work revealed the biological importance and therapeutic benefit of sciadopitysin which is a biflavonoids class phytochemical found to be present in the Ginkgo biloba. Scientific data analysis of present work revealed the biological importance of sciadopitysin in the medicine for the treatments of human health complications against diabetes and its complications, osteoclastogenesis, myocardial infarction, Alzheimer’s disease, hepatic and renal toxicity, inflammatory disorders, osteoporosis, human skin disorders, lymphocyte proliferation and fungal diseases. Further scientific data analysis revealed the importance of standardization of plant materials and their derived products through sciadopitysin in the medicine. Conclusion: Scientific data analysis of collected research work revealed the biological importance of sciadopitysin in the medicine for their effectiveness against human health complications.

Comparative study on the impacts of visnagin and its methoxy derivative khellin on human lymphocyte proliferation and Th1/Th2 balance.

Visnagin is a phenolic and natural compound in turmeric and fenugreek, and its anti-inflammatory effect has been indicated. Therefore, this study aimed to investigate and compare the anti-inflammatory properties of visnagin and its methoxy derivative khellin on human lymphocytes. Human lymphocytes were treated with khellin, visnagin (10, 30, and 100µM), and dexamethasone (0.1mM) in the presence of phytohemagglutinin (PHA). The levels of cell proliferation, nitric oxide (NO), glutathione (GSH), malondialdehyde (MDA), and MDA/GSH ratio were measured using biochemistry methods. Furthermore, the mRNA levels of interferon-γ (IFN-γ), interleukin (IL)-4, and IL-10 were assessed using real-time PCR, while IFN-γ/IL-4(Th1/Th2), IFN-γ/IL-10(Th1/Treg), and IL-4/IL-10(Th2/Treg) ratios were made by dividing their exact values. In the PHA-stimulated group, GSH and IFN-γ/IL-4 levels were markedly diminished, but other variables were significantly elevated compared to the control group. Khellin and visnagin significantly declined the levels of cell proliferation, MDA, MDA/GSH ratio, and NO production. Khellin and visnagin concentration-dependently diminished IFN-γ and IL-4 levels and increased IL-10 levels compared to the PHA-stimulated group. Two higher concentrations of khellin and visnagin (30 and 100μM) considerably diminished the IFN-γ, IFN-γ/IL-10, and IL-4/IL-10 values compared to the PHA-stimulated group. However, 100µM of khellin and visnagin significantly increased GSH level compared to the PHA-stimulated group. In PHA-stimulated lymphocytes, representing Th2 dominant allergic diseases, khellin and visnagin provides more specific anti-oxidant, anti-inflammatory, and immunomodulatory functions than dexamethasone. In addition, the effects of khellin were more prominent than visnagin.

Cationic cellulose nanocrystals as sustainable green material for multi biological applications via ξ potential

The present study aims to disclose the activity of cationic cellulose nanocrystals (CNCs) as a promising multifunctional green nanomaterial with applications in biological aspects. The basic reason behind multifunctional behavior is zeta potential and size distribution of nano biopolymers; exhibit a remarkable physical and biological activity compared to normal molecules. The preliminary characterized studied using absorption spectral analysis showed strong absorption peak indicating that spectrum curves can be screen by UV spectra at wavelength range 200–400nm. Ultrastructural studies (SEM-EDS and TEM), manifest that CNCs are elliptical particles in shape. Also, TEM show CNCs are the ideal illustration of zero-dimensional (0-D) NPs, less than 5.1 nm in diameter with Cationic charge and similar results in size distribution by TEM. Nonetheless, developed as antioxidant activity IC50 was 1467 ± 25.9 µg/mL, antimicrobial activity tested G−ve strains, but not affected on tested G+ve strains and tested fungi. Evaluating toxicity effect of cationic CNCs against human blood erythrocytes (RBCs) and Lymphocyte Proliferation and the end point evaluate by comet assay, which proven no cytotoxic effect. Also, a high dose 500 µg/mL of CNCs highly significant (p < 0.05) reduction in cell viability of Caco-2 cancer cells after 24 h. incubation time, whereas the IC50 was 1884 ± 19.46 µg/mL. Moreover, genotoxic assay indicates Caco-2 cells cause apoptosis with no fragmentation in DNA. Undoubtedly, the obtained results brought about by the interaction of layers carrying opposing charges. Additionally, there is a balance between hydrophilic contact and electrostatic attraction. That emphasizes how the cationic CNCs have excellent potential for use as antioxidants, antimicrobials, and anticancer agents.

Methods to Assess Proliferation of Stimulated Human Lymphocytes In Vitro: A Narrative Review.

The ability to monitor lymphocyte responses is critical for developing our understanding of the immune response in humans. In the current clinical setting, relying on the metabolic incorporation of [3H] thymidine into cellular DNA via a lymphocyte proliferation test (LPT) is the only method that is routinely performed to determine cell proliferation. However, techniques that measure DNA synthesis with a radioactive material such as [3H] thymidine are intrinsically more sensitive to the different stages of the cell cycle, which could lead to over-analyses and the subsequent inaccurate interpretation of the information provided. With cell proliferation assays, the output should preferably provide a direct and accurate measurement of the number of actively dividing cells, regardless of the stimuli properties or length of exposure. In fact, an ideal technique should have the capacity to measure lymphocyte responses on both a quantitative level, i.e., cumulative magnitude of lymphoproliferative response, and a qualitative level, i.e., phenotypical and functional characterization of stimulated immune cells. There are many LPT alternatives currently available to measure various aspects of cell proliferation. Of the nine techniques discussed, we noted that the majority of these LPT alternatives measure lymphocyte proliferation using flow cytometry. Across some of these alternatives, the covalent labelling of cells with a high fluorescence intensity and low variance with minimal cell toxicity while maximizing the number of detectable cell divisions or magnitude of proliferation was achieved. Herein, we review the performance of these different LPT alternatives and address their compatibility with the [3H] thymidine LPT so as to identify the "best" alternative to the [3H] thymidine LPT.

Ipecac root extracts and isolated circular peptides differentially suppress inflammatory immune response characterised by proliferation, activation and degranulation capacity of human lymphocytes in vitro.

Circular peptides are attractive lead compounds for drug development; this study investigates the immunomodulatory effects of defined root powder extracts and isolated peptides (called cyclotides) from Carapichea ipecacuanha (Brot.) L. Andersson ('ipecac'). Changes in the viability, proliferation and function of activated human primary T cells were analysed using flow cytometry-based assays. Three distinct peptide-enriched extracts of pulverised ipecac root material were prepared via C18 solid-phase extraction and analysed by reversed-phase HPLC and mass spectrometry. These extracts induced caspase 3/7 dependent apoptosis, thus leading to a suppressed proliferation of activated T cells and a reduction of the number of cells in the G2 phase. Furthermore, the stimulated T cells had a lower activation potential and a reduced degranulation capacity after treatment with ipecac extracts. Six different cyclotides were isolated from C. ipecacuanha and an T cell proliferation inhibiting effect was determined. Furthermore, the degranulation capacity of the T cells was diminished specifically by some cyclotides. In contrast to kalata B1 and its analog T20K, secretion of IL-2 and IFN- γ was not affected by any of the caripe cyclotides. The findings add to our increased understanding of the immunomodulating effects of cyclotides, and may provide a basis for the use of ipecac extracts for immunomodulation in conditions associated with an exessive immune responses.

Human Omental Mesothelial Cells Impart an Immunomodulatory Landscape Impeding B- and T-Cell Activation

Mesothelial cells form the mesothelium, a simple epithelium lining the walls of serous cavities and the surface of visceral organs. Although mesothelial cells are phenotypically well characterized, their immunoregulatory properties remain largely unknown, with only two studies reporting their capacity to inhibit T cells through TGF-β and their consumption of L-arginine by arginase-1. Whether human mesothelial cells can suppress other immune cells and possess additional leukosuppressive mechanisms, remain to be addressed to better delineate their therapeutic potential for cell therapy. Herein, we generated secretomes from omental mesothelial cells (OMC) and assess their capacity to inhibit lymphocytes proliferation, suppress activated T and B cells, as well as to modify macrophage activation markers. The secretome from mesenchymal stromal cells (MSC) served as a control of immuno-suppression. Although OMC and MSC were phenotypically divergent, their cytokine secretion patterns as well as expression of inflammatory and immunomodulary genes were similar. As such, OMC- and MSC-derived secretomes (OMC-S and MSC-S) both polarized RAW 264.7 macrophages towards a M2-like anti-inflammatory phenotype and suppressed mouse and human lymphocytes proliferation. OMC-S displayed a strong ability to suppress mouse- and human-activated CD19+/CD25+ B cells as compared to MSC-S. The lymphosuppressive activity of the OMC-S could be significantly counteracted either by SB-431542, an inhibitor of TGFβ and activin signaling pathways, or with a monoclonal antibody against the TGFβ1, β2, and β3 isoforms. A strong blockade of the OMC-S-mediated lymphosuppressive activity was achieved using L-NMMA, a specific inhibitor of nitric oxide synthase (NOS). Taken together, our results suggest that OMC are potent immunomodulators.

Crocin restores the balance of Th1/Th2 immune cell response in ConA-treated human lymphocytes.

Following antigen stimulation, naive CD4+ T cells differentiate into different T helper (Th) subsets characterized by lineage-specific transcriptional factors and cytokines. The balance between cytokines from Th1 and Th2 cells is disrupted in autoimmune disorders, asthma, and allergic reactions. Crocin, the major carotenoid of saffron, has anti-inflammatory properties. We investigated crocin modifying effects on the human lymphocytes proliferation and Th1/Th2 balance as a possible mechanism of its anti-inflammatory effects. The human peripheral blood mononuclear cells were isolated using Ficoll density gradient centrifugation. MTT was used to evaluate the effect of 72-h treatment with different concentrations of crocin with or without ConA on lymphocytes proliferation. INF-γ/IL-4 cytokine secretion and T-bet/GATA-3 transcription factor expression ratios (as indicators of Th1/Th2 response status) were measured in non-stimulated and ConA-stimulated cells in the presence or absence of crocin byELISA and RT-qPCR methods, respectively. The results showed crocin at a concentration of 50μM and higher was toxic for human lymphocytes, and at a non-toxic concentration of 25µM, it did not affect cell proliferation. The ratio of T-bet/GATA-3 and INF-γ/IL-4 was higher in the culture supernatant of ConA-stimulated cells compared to non-stimulated ones. Crocin-treated cells showed slightly lower T-bet/GATA-3 and INF-γ/IL-4 ratios compared to untreated cells. Crocin (25μM) was also able to restore the increased ratio of Th1/Th2 immune response induced by ConA. Crocin can alleviate inflammatory-stimulant effects of ConA on human lymphocytes by decreasing T-bet/GATA-3 and INF-γ/IL-4 ratios, which are indicative of restoring the balance of Th1/Th2 responses.

Performance evaluation of two antigen-extracted xenogeneic ostein and experimental study on repairing skull defects in rats

To evaluate the physical and chemical properties, immunogenicity, and osteogenesis of two antigen-extracted xenogeneic bone scaffolds-decalcified bone matrix (DBM) and calcined bone. By removing the inorganic and organic components of adult pig femus, xenogeneic DBM and calcined bone were prepared respectively. The density and pH value of the two materials were measured and calculated, the material morphology and pore diameter were observed by scanning electron microscope, and the surface contact angle was measured by automatic contact angle measuring instrument. The safety, osteogenic activity, and immunogenicity of the two materials were evaluated by cytotoxicity test, osteoblast proliferation test, DNA residue test, and human peripheral blood lymphocyte proliferation test. The two materials were implanted into the 5 mm full-thickness skull defect of 6-week-old male Sprague Dawley rats (the blank control group was not implanted with materials). The materials were taken at 4 and 8 weeks after operation, the repair effect of the materials on the rat skull was observed and evaluated by gross observation, Micro-CT scanning, and HE staining observation. Compared with calcined bone, DBM has lower density and poor hydrophilicity; the pH value of the two materials was 5.5-6.1, and the pore diameter was 160-800 μm. The two materials were non-cytotoxic and could promote the proliferation of osteoblasts. The absorbance ( A) values of osteoblast proliferation at 1, 4, and 7 days in the DBM group were significantly higher than those in the calcined bone group ( P<0.05). The DNA residues of the two materials were much lower than 50 ng/mg dry weight, and neither of them could stimulate the proliferation and differentiation of human peripheral blood lymphocytes. The results of animal experiments in vivo showed that the bone volume/total volume (BV/TV) in DBM group and calcined bone group were significantly higher than that in blank control group at 4 weeks after operation ( P<0.05), and that in calcined bone group was significantly higher than that in DBM group ( P<0.05); at 8 weeks after operation, there was no significant difference in BV/TV between groups ( P>0.05). HE staining showed that at 4 and 8 weeks after operation, the defect in the blank control group was filled with fibrous connective tissue, the defect was obvious, and no bone growth was found; the defect in DBM group and calcined bone group had been repaired to varying degrees, and a large number of new bone formation could be seen. The material degradability of DBM group was better than that of calcined bone group. The physical and chemical properties and degradability of the two kinds of xenogeneic bone scaffolds were slightly different, both of them have no immunogenicity and can promote the repair and reconstruction of skull defects in rats.

Immunomodulatory Potentials of Winged Bean (Psophocarpus tetragonolobus) Bioactive Compounds on Human Lymphocyte Proliferation

Winged bean (Psophocarpus tetragonolobus) has been reported to consist of many bioactive compounds that can improve the human immune system. Food preparation using heat treatment applied typically can change the bioactive properties of the bean. These studies' main aims were to analyze antioxidants activity and immunomodulatory effect of young winged bean pods and mature winged beans, boiled or canned on human lymphocytes, representing the immune system. The samples were extracted using three-stage maceration methods with n-hexane, ethyl acetate, and water. The extracts were cultured with lymphocyte cells using various concentrations representing normal consumption. IL-2 representing cell proliferation was analyzed using ELISA. Cell marker proteins CD4+, CD8+, CD3+, CD19, and CD16/56 were analyzed using a flowcytometer. The highest antioxidants activity was on the water extract of raw mature bean (7.2175±0.4794 mg AAE/g). The boiling process increased young winged bean anti-oxidant activity (P&lt;0.05), but decreases the anti-oxidant activity of the mature bean (P&lt;0.05). The highest proliferation indexes were obtained from water extracts of both boiled (2.13) and canned mature bean (2.12). Water extracts of all samples increased expressions of IL-2, CD4+, CD8+, CD3+, CD19 and CD16/56 on the cell surface. Boiled young winged bean pods have the best activity in increasing CD19 marker. Canned mature bean was effective in increasing CD16/56 expression. Boiling and canning of both young and mature winged beans can increase the immune system as shown by the immune parameter analyzed.

Rabbit antithymocyte globulin induces human lymphocyte activation, proliferation, and apoptosis in the absence of complement: an experimental study.

Rabbit antithymocyte globulin (rATG) has become the first choice for induction therapy in HLA-presensitized patients undergoing organ transplantation. Meanwhile, complement inhibitors have been approved for preventing or treating antibody-mediated rejection in these patients. The biological effects of rATG on lymphocytes in cases of complement deficiency or significant inhibition are not yet clear. We measured lymphocyte activation, proliferation, and apoptosis in response to rATG treatment in the absence of complement. T-cell subsets were analyzed transcriptomically features to rATG stimulation. Activation-related phenotypes on T cells were determined in patients after rATG administration. We found that rATG treatment led to lymphocyte activation and proliferation in vitro without the addition of complement. A dose-dependent apoptosis in rATG-treated lymphocytes was detected, which was partially caspase-3-dependent but Fas/FasL-independent. T cells were more sensitive to rATG stimulation than were non-T cells. Both CD4+ T cells and CD8+ T cells upregulated a series of genes related to cell activation, cytokine production and apoptosis to rATG stimulation. CD69 and CD25 levels in surviving T cells were increased in patients after rATG administration. These findings indicate that rATG can stimulate lymphocyte activation, proliferation, and apoptosis in the absence of complement. Biologic effects of rATG other than complement-dependent cytotoxicity need to be concerned.

Lack of Effect of Human Chorionic Gonadotropin in Mixed Lymphocyte Reaction in Xenotransplantation

It has been speculated that the immunomodulation associated with pregnancy, e.g., decreasing pro-inflammatory cytokines, increasing anti-inflammatory cytokines, upregulation of T regulatory cells (Tregs), is in part due to the effect of human chorionic gonadotropin (hCG). In this study, we tested the effect of hCG on proliferation of human peripheral blood mononuclear cells (PBMCs) stimulated by irradiated pig PBMCs. Mixed lymphocyte reaction (MLR) was carried out with human PBMCs as responders and irradiated wild-type pig PBMCs as stimulators, with or without hCG. The spontaneous mean proliferation of CD3+T cells was 7% and, when stimulated by phytohemagglutinin (PHA) was 43%. When stimulated with irradiated wild-type pig PBMCs, CD3+T cell proliferation was 18%. When hCG (at concentrations of 100 IU/ml, 500 IU/ml, and 1,000 IU/ml) was added to the MLR, the proliferation of CD3+T lymphocytes was 20%, 20%, and 18%, respectively. hCG also had no effect on the proliferation of CD4+T and CD8+T cells. hCG does not suppress human lymphocyte proliferation stimulated by wild-type pig PBMCs in MLR (unless this is related to an increased number of Tregs, which was not tested in this study).

Human Adipose Tissue-Derived Stromal Cells Suppress Human, but Not Murine Lymphocyte Proliferation, via Indoleamine 2,3-Dioxygenase Activity.

Over recent years, mesenchymal stromal cells (MSC) have gained immense attraction in immunotherapy, regenerative medicine and tissue engineering. MSC microenvironment modulation occurs through synergy of direct cell–cell contact, and secreted soluble factors and extracellular vesicles (EV). MSC-derived EV have been suggested as cell-free immunomodulatory alternative to MSC; however, previous findings have challenged this. Furthermore, recent data suggest that evaluating the mechanism of action of human MSC (hMSC) in animal models might promote adverse immune reactions or lack of functionality due to xeno-incompatibilities. In this study, we first assessed the immunomodulatory strength of different human MSC sources on in vitro stimulated T cells and compared this to interferon-gamma (IFNγ) primed MSC conditioned medium (CM) and EV. Second, we addressed the main molecular mechanisms, and third, we assessed the MSC in vitro immunosuppressive effect across interspecies barriers. We identified human adipose tissue-derived stromal cells (ASC) with strongest immunomodulatory strength, followed by bone marrow (BM) and cord blood-derived MSC (CB). Whilst CM from primed ASC managed to exert analogous effects as their cellular counterpart, EV derived thereof did not, reproducing previous findings. IFNγ-induced indoleamine 2,3-dioxygenase (IDO) activity was identified as key mechanism to suppress human lymphocyte proliferation, as in the presence of the IDO inhibitor epacadostat (Epac) a stimulation of proliferation was seen. In addition, we revealed MSC immunosuppressive effects to be species-specific, because human cells failed to suppress murine lymphocyte proliferation. In summary, ASC were the strongest immunomodulators with the IDO-kynurenine pathway being key within the human system. Importantly, the in vitro lack of interspecies immunomodulatory strength suggests that preclinical data need to be carefully interpreted especially when considering a possible translation to clinical field.

Hepatoprotective Activities of Colocasia esculenta (L.) Schottin Mice Model with Liver Injury Induced by Paracetamol

This paper uses the model of experimental mouse liver damage with paracetamol to evaluate the liver protective effects of the methanol extract (Colocasia esculenta (L.) Schott) (MCE). After 8 days, the hepatoprotective activities of MCE in mice (damaged by paracetamol) at doses of 500, 1,000 and 2,000 mg/kg/day proved effective as the AST enzyme content decreased by 6.98, 22.84 and 26.59%, respectively; and ALT decreased by 53.17, 56.46 and 57.93%, respectively. MCE at a dose of 1,000 mg/kg/day had a protective effect equivalent to that of silymarin (used in liver treatment) at a dose of 50 mg/kg/day and MCE at a dose of 2,000 mg/kg/day had better effect. Observation of the microscopic liver tissue cross section also revealed that the mice treated with MCE of C. esculenta at doses of 1,000 and 2,000 mg/kg/day showed significantly improvement in their liver tissues compared to the non-treated control group.&#x0D; Keywords:&#x0D; Colocasia esculenta, hepatoprotective, paracetamol.&#x0D; References&#x0D; [1] S. Shahani. Evaluation of hepatoprotective efficacy of APCL-A poly herbal formulation in vivo in rats, Indian Drugs. 36(1999) 628-631.[2] Y. Cui, X. Yang, X. Lu, J. Chen, Y. Zhao. Protective effects of polyphenols-enriched extract from Huangshan Maofeng green tea against CCl4-induced liver injury in mice, Chemico- Biological Interactions 220 (5) (2014) 75-83. https://doi.org/10.1016/j.cbi.2014.06.018 [3] K.C. Choi, W.T. Chung, J.K. Kwon, J.Y. Yu, Y.S. Jang, S.M. Park, S.Y. Lee, J.C. Lee. Inhibitory effects of quercetin on aflatoxin B1 induced hepatic damage in mice, Food Chemical Toxicology, 48 (10) (2010) 2747-2753 . https://doi.org/10.1016/j.fct.2010.07.001[4] E.S. Sabina, J. Samue, S.R. Ramya, S. Patel, N. Mandal, P. Preety, P.P. Mishra, M.K. Rasool. Hepatoprotective and antioxidant potential of Spirulina fusiformis on acetaminophen induced hepatotoxicity in mice, International Journal of Integrative Biology 6 (1) (2009) 1-5. http://ijib.classicrus.com/.../1501.pdf[5] Pham Hoang Ho. Vietnamese plants, episode III. Young Publishing House, (1999), pp. 353 (in Vietnamese).[6] C.O. Eleazu, M. Iroaganachi, K.C. Eleazu. Ameliorative potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiaca L.) on the relative tissue weights ofstreptozotocin-induced diabetic rats. Journal of Diabetes Research, 197 (2013), https://doi.org/10.1155/2013/160964.[7] R.C. Cambie, L.R. Ferguson. Potential functional foods in the traditional Maori diet. Mutation Research Letters 523–524 (2003) 109-117. https://doi.org/10.1016/s0027-5107(02)00344-5[8] C.L. Abraham, K. Yoshinori, T. Masakuni, I. Hironori, O. Hirosuke, T. Hajime. Flavonoid glycosides in the shoot system of Okinawa Taumu (Colocasia esculenta S). Food Chemistry 119 (2010) 630- 635. https://doi.org/10.1016/j.foodchem.2009.07.004[9] P.J. Bouic, D. Etsebeth, R.W. Liebenberg, C.F. Albrecht, K. Pegel, J.P.P. Van. Beta sitosterol and beta sitosterol glycoside stimulate human peripheral blood lymphocyte proliferation: Implications for their use as an immunomodulatory vitamin combination. International Journal of Immuno-pharmacology 18 (12) (1996) 693-700. https://doi.org/10.1016/S0192-0561(97)85551-8.[10] Vo Van Chi. Dictionary of Vietnamese medicinal plants. Medical Publishing House (1997), pp. 871-873 (in Vietnamese).[11] Do Trung Dam. Method of determining drug toxicity. Medical Publishing House, Hanoi (2014), pp. 11-137 (in Vietnamese). [12] J.T. Litchfield, F. Wilcoxon. A simplified method of evaluating dose-effect experiments, Journal of Pharmcology and Experimental Therapeutics, 96 (2) (1949) 99-113. PMID: 18152921 [13] Doan Thi Nhu, Do Trung Dam, Pham Duy Mai. Method research of the pharmacological effect of drugs from medicinal herbs, Science and Technics Publishing House, Hanoi (2006), pp. 142 (in Vietnamese).[14] A. Godwin. Histochemical uses of haematoxylin - A Review. JPCS 1 (2011) 24-34. [15] Ho Thi Thanh Huyen, Thai Nguyen Hung Thu, Nguyen Thai An. Some results of plan microscopic studies and chemical composition of Bombax malabaricum DC., Bombacaceae, Proceeding Pharma Indochina VII, 10/2011, The 7th Indochina Conference on Pharmaceutical science, Bangkok, Thai Lan (2011) 270-274.[16] A.N. Chinonyelum, A.P. Uwadiegwu, O.C. Nwachukwu, O. Emmanuel. Evaluation of hepatoprotective activity of Colocasia esculenta (L. Schott) leaves on thioacetamide-induced hepatotoxicity in rats. Pakistan Journal Pharmaceutical Sciences, 28 (6S) (2015) 2237-2241. [17] O.F. Dayo, B.C. Eluke, E.O. Ukaejiofo, O.L. Olayinka, C.I. Johnpaul, O.A.K .Tajudeen, I. Chinwe, L.S. Adetona. Hepatoproactive and haematopoietic modulatory efficacy of leaf extract of Colocasia esculenta in Albino wistar rats. International Journal of Tropical Medicine 12 (3-6) (2017) 35-41. https://doi.org/3923/ijtmed.2017.35.41.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Synthesis and Biological Activity of New 7-Amino-oxazolo[5,4-d]Pyrimidine Derivatives.

The synthesis of a series of novel 7-aminooxazolo[5,4-d]pyrimidines 5, transformations during their synthesis and their physicochemical characteristics have been described. Complete detailed spectral analysis of the intermediates 2–4, the N′-cyanooxazolylacetamidine by-products 7 and final compounds 5 has been carried out using MS, IR, 1D and 2D NMR spectroscopy. Theoretical research was carried out to explain the privileged formation of 7-aminooxazolo[5,4-d]pyrimidines in relation to the possibility of their isomer formation and the related thermodynamic aspects. Additionally, the single-crystal X-ray diffraction analysis for 5h was reported. Ten 7-aminooxazolo[5,4-d]pyrimidines 5 (SCM1–10) were biologically tested in vitro to preliminarily evaluate their immunological, antiviral and anticancer activity. Compounds SCM5 and SCM9 showed the best immunoregulatory profile. The compounds displayed low-toxicity and strongly inhibited phytohemagglutinin A-induced proliferation of human peripheral blood lymphocytes and lipopolysaccharide-induced proliferation of mouse splenocytes. Compound SCM9 caused also a moderate suppression of tumor necrosis factor α (TNF-α) production in a human whole blood culture. Of note, the compounds also inhibited the growth of selected tumor cell lines and inhibited replication of human herpes virus type-1 (HHV-1) virus in A-549 cell line. Molecular investigations showed that the compounds exerted differential changes in expression of signaling proteins in Jurkat and WEHI-231 cell lines. The activity of SCM5 is likely associated with elicitation of cell signaling pathways leading to cell apoptosis. The compounds may be of interest in terms of therapeutic utility as inhibitors of autoimmune disorders, virus replication and antitumor agents.

Effects of beta-endorphin and dynorphin A on in vitro apoptosis in human peripheral blood lymphocytes

Along with functioning in the nerve system, the endogenous opioid peptides as the ligands of mu-, delta-, and kappa-opioid receptors exert multiple effects on immune cells. Moreover, experimental evidence showed that morphine as an exogenous agonist of mu-opioid receptors affects immune cell viability. Such effects were discovered in experiments with cultured cells and laboratory animals. Hence, we studied effects of endogenous opioid peptides dynorphin A and beta-endorphin on viability of human peripheral blood mononuclear cells in vitro. For this, we used samples of peripheral blood cells collected from the fourteen healthy volunteers, who provided with signed informed consent and might request any information regarding the research. Mononuclear cells were collected from the heparinized blood samples according to standard protocol and cultivated in the humid atmosphere for 72 hours. Two μCi 3H-Methyl-thymidine was added into each test tube at 18 hours before the end of the cultivation period. Scintillation counting was performed by using Guardian liquid scintillation analyzer (Wallac, Finland) expressing the data as count per minute. To assess apoptosis, the cells were cultured for 24 hours in similar conditions except for adding radioactive probe. Next, the cells were stained with Annexin V-FITC/7-AAD kit (Beckman Coulter, USA) according to the manufacturer’s instructions for further recording apoptotic cells in flow cytometers BD FACSCalibur (Becton Dickinson, USA) or CytoFLEX S (Beckman Coulter, USA). The lymphocyte gate set by light scatter parameters was shown in typical Annexin V-FITC vs 7-AAD plot followed by counting Annexin V+/7-AADcells. All data were expressed as means ± S.E. Statistical significance was assessed by using Student’s t-test. It was found that physiologic concentrations of mu- and kappa-opioid receptor agonists beta-endorphin and dynorphin A exerted multidirectional effects on proliferation of human peripheral blood lymphocytes. In particular, dynorphin A increased basal proliferation and proliferation in response to suboptimal mitogen stimulation. Moreover, beta-endorphin enhanced effects of mitogen stimulation at suboptimal concentration but profoundly suppressed proliferation in maximally activated cells. The modulating effects of beta-endorphin and dynorphin A on in vitro proliferation are not associated with augmented cell apoptosis.

Cytotoxic Effects of Pistacia khinjuk Seed Extracts on Different Cell Lines and its Mitogenic Effects on Blood Lymphocyte In Vitro

Reports indicated that extract Pistacia khinjuk has anti-inflammatory, antipyretic, antibacterial, and antiviral, in treating of diarrhea and throat infections and has hepatoprotective effects against acetaminophen and carbon tetrachloride. This study was undertaken to investigate the possible cytotoxic effects of methanolic and aqueous seeds extract of P. khinjuk on different tumors (rhabdomyosarcoma [RD] and murine mammary adenocarcinoma [Ahmed-Mohammed-Nahi-2003 (AMN-3)]) and normal cell lines (murine fibroblast) and its mitogenic effects on blood lymphocytes. The cytotoxic effects of P. khinjuk seed extracts were evaluated on two tumor cell lines, RD and murine mammary adenocarcinoma (AMN-3) and one normal cell line, murine fibroblast (L20B). Moreover, the mitogenic effects of the plant extract were studied, on human blood lymphocytes. Both methanolic and aqueous seed extracts of P. khinjuk significantly induced tumor cell lines and the normal cell line proliferation, especially in highest concentrations. The results show that the extracts induced significant increases in human blood lymphocyte proliferation at 72 h. This activity of plant extracts recommends it as a good mitogenic agent in researches; in conclusion, seed extracts of P. khinjuk induced proliferation of all tested cell lines. High concentrations of both aqueous and methanolic seed extracts of P. khinjuk showed mitogenic effects.

Suillus collinitus (Fr.) Kuntze ekstraktlarının insan lenfositlerinin genotoksisitesi ve proliferasyonu üzerindeki etkileri

Cultivated or wild edible mushroom species have traditionally been used by humans for medical purposes for many years. Edible mushrooms have the potential to show different activities due to the numerous bioactive components they contain. In particular, some mushroom species whose regulatory properties have been identified on human immunity are of interest in the scientific world. Considering these characteristics of edible mushroom species, in the present study, it was examined the effects of Suillus collinitus (Fr.) Kuntze, an important edible mushroom species, on human peripheral lymphocytes. For this purpose, acetone and water extracts were obtained from S. collinitus and the effects of these extracts on genotoxicity and proliferation of human lymphocytes were tested by chromosome aberration (CA), micronucleus (MN), nuclear division index (NBI) and mitotic index (MI) analyses. When genotoxicity analyses were examined, it was found that none of the tested extract applications (1-100 mg/L) did not change the CA and MN frequencies statistically (p &amp;gt; 0.05) compared to the negative control group. Proliferation analyses showed that only the maximum concentration (100 mg/L) application of acetone extract of S. collinitus decreased the NBI and MI ratio of the cells at a level of p &amp;lt; 0.05 compared to the negative control group. The obtained results revealed that the acetone and water extracts of S. collinitus, especially the applications at concentrations of 1-50 mg/L, did not show any genotoxic or cytotoxic activity on lymphocytes involved in the human immune system.