Application of Nano-Inspired Scaffolds-Based Biopolymer Hydrogel for Bone and Periodontal Tissue Regeneration.

This review's objectives are to provide an overview of the various kinds of biopolymer hydrogels that are currently used for bone tissue and periodontal tissue regeneration, to list the advantages and disadvantages of using them, to assess how well they might be used for nanoscale fabrication and biofunctionalization, and to describe their production processes and processes for functionalization with active biomolecules. They are applied in conjunction with other materials (such as microparticles (MPs) and nanoparticles (NPs)) and other novel techniques to replicate physiological bone generation more faithfully. Enhancing the biocompatibility of hydrogels created from blends of natural and synthetic biopolymers can result in the creation of the best scaffold match to the extracellular matrix (ECM) for bone and periodontal tissue regeneration. Additionally, adding various nanoparticles can increase the scaffold hydrogel stability and provide a number of biological effects. In this review, the research study of polysaccharide hydrogel as a scaffold will be critical in creating valuable materials for effective bone tissue regeneration, with a future impact predicted in repairing bone defects.

A Single-Center Study of Patients With Synchronous Primary Malignancy: A Case Series.

Multiple primary malignant tumors (MPMT) can be defined as more than two different tumors synchronously or metachronously forming in the same organ or different organs. The incidence of MPMTs varies dramatically between antemortem and postmortem examinations, becoming a serious medical issue. Evidence shows that the overall incidence of MPMTs is between 2.4% and 17%. Double primary malignancy (DPM) is considered the most common type of MPMT. In this case series, we present three cases of MPMT. The first case involved the colon and the breast, the second case involved the colon and the kidney, and the third case involved rectum and kidney.

Relationship Between Loneliness and Hypothyroidism.

Aim This study aimed to assess the relationship between loneliness and hypothyroidism in patients with hypothyroidism and to determine predictors of loneliness. Materials and methods A cross-sectional study was conducted on hypothyroid patients attending the endocrine clinics at Alhada Military Hospital and Prince Mansour Military Hospital, Taif, Saudi Arabia between the period of December 2020 and May 2021. Patients with more than 18 years of hypothyroidism were included and those with other thyroid diseases were excluded as well as those with other comorbidities and psychiatric disorders and those who were living alone. Data were collected using an online pre-structured questionnaire. Results The study included 231 hypothyroid patients with a mean age of 43.34 ± 12.9 years, and 90.9% were females. The majority (96.5%) were taking levothyroxine, and 27.3% were practicing physical activity. Only 2.2% of the participants had a high degree of loneliness, whereas 47.2%, 34.6%, and 16% had low, moderate, and moderately high degrees of loneliness, respectively. Discussion In this study, 2.2% of sampled hypothyroid patients had high (2.2%) or moderately high degrees of loneliness feelings (16%). Duration of hypothyroidism was a significant predictor for high loneliness score.

Improvement of In Vitro Dissolution of the Poor Water-Soluble Amlodipine Drug by Solid Dispersion with Irradiated Polyvinylpyrrolidone.

The aim of this study was to increase both the rates of dissolution and bioavailability of the amlodipine (Amlo) drug. Due to the low cost, high solubility, and amorphous state, polyvinylpyrrolidone (PVP) has been used as a drug carrier in the solid dispersion process. Through applying an irradiation technique, powder of (PVP) is irradiated with six 0-50 kGy irradiation doses. The six irradiated (PVP) samples were characterized using gel permeation chromatography, electron spin resonance, and Fourier transform infrared (FT-IR) spectroscopy. The formulation of six (PVP/Amlo) samples at a ratio of 2:1 wt/wt were characterized using FT-IR spectroscopy and X-ray powder diffraction. In vitro dissolution of (Amlo) drug was assessed in a water solvent at pH 1.2 and pH 7. Results demonstrated that there is a change in the physicochemical properties of irradiated (PVP). FT-IR confirmed that there is an intermolecular H bond between the (Amlo) drug and (PVP) polymer. XRD confirmed that (PVP) changes the crystalline (Amlo) to amorphous amlodipine. Irradiated (PVP) at a dose of 20 kGy released approximately 89% from 40 mg of (Amlo) in 60 s. The in vitro rate of amlodipine dissolution depends on the drug-polymer intermolecular H bond. The rate of (Amlo) dissolution is increased due to the drug-drug intramolecular hydrogen bonding replaced with the drug-polymer intermolecular hydrogen bonding, which reduces the crystal packing. Irradiated (PVP) improved the rate of (Amlo) dissolution compared to unirradiated (PVP).

Tracing insect pests: is there new potential in molecular techniques?

Insects are amongst the greatest pests of agriculture, horticulture and forestry worldwide, inflicting damage and economic costs both directly and by transmitting plant viruses. Many kinds of insects are now resistant or cross-resistant to pesticides. Tracking studies have become very important for combatting insect pests and for better understanding their biology (eg insect population dynamics, movements, feeding behaviour and other ecological interactions). A wide variety of tracing approaches have been used including discriminative, tracer and molecular methods. The perfect technique for insect tracking is the technique that harmonizes with insects' 'normal' biology. Furthermore, the technique should be environmentally safe, cost-effective and easy to use. This paper reviews the current techniques used for insect traceability, documents the advantages and drawbacks of each method, and puts special focus on molecular techniques, including PCR-denaturing gradient gel electrophoresis as a new and promising traceability tool that could provide insects with a unique biological barcode and thus make it possible to trace their movements.

New synthetic strategies for acyclic and cyclic pyrimidinethione nucleosides and their analogues.

Pyrimidinethione nucleosides are effective compounds and have significant and pivotal effects in several fields. New synthetic strategies for many pyrimidinethione nucleosides including acyclic and cyclic derivatives have been reported.

Design, synthesis, molecular docking and anti-hepatocellular carcinoma evaluation of novel acyclic pyridine thioglycosides.

A novel series of acyclic pyridine thioglycosides has been synthesized. Evaluation of the anti proliferative activity of these compounds against HEPG-2 cell lines (liver carcinoma cell lines) shows that most of the compounds have high anti-tumor activities especially 6b, 6c, 7b and 7c. Furthermore, in the modeling study, these compounds showed that they have high binding affinity with thymidylate synthase dihydrofolate reductase (TS-DHFR).

Antimetabolites: Design, synthesis, and cytotoxic evaluation of novel dihydropyridine thioglycosides and pyridine thioglycosides.

A convenient synthesis of a novel series of dihydropyridine and pyridine thioglycosides was developed. The evaluation of anti-proliferative activity against HepG-2 cell lines (liver carcinoma cell lines) shows that most of the compounds have antitumor activity, especially 5b, 5f, 5j, 5n, 7b, 7f, 7j, 7n, 8b, 8f, and 8j. The results of molecular docking reveal that these compounds have high binding affinity by hydrogen bond formation with the binding pocket of thymidylate synthase dihydrofolate reductase (TS-DHFR).

p15(Ink4b) Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The p15(Ink4b) gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India). MATERIALS AND METHODS: p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction, while its subsequent expression analysis was carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA. CONCLUSION: Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

p15(Ink4b) Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The p15(Ink4b) gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study,we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India). MATERIALS AND METHODS: p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction, while its subsequent expression analysis was carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semiquantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA. CONCLUSION: Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.

Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5-hydroxytryptamine

Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.

Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5-hydroxytryptamine

Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.

Field evaluation of two diagnostic antigen tests for Wuchereria bancrofti infection among Indian expatriates in Saudi Arabia.

Two commercially available diagnostic tools (Tro-Bio ELISA and ICT card test) were used to detect circulating filarial antigen of Wuchereria bancrofti infections among Indian expatriate workers in Saudi Arabia. Daytime serum samples collected from 302 individuals (210 men and 92 women) were tested. Night blood surveys for microfilaraemia were restricted to those individuals who became positive for the trop-Bio assay test. The overall prevalence of filarial antigeaemia was 10.6% (32 individuals). Of these 32 antigen positive cases, microfilariae were found in 10 men (31.3%), with a mean microfilarial count of 105 mff/ml. No positive antigen results were found in control sera from 200 native healthy Saudis or from patients with helminthic infections (schistosomiasis, echinicoccosis, hookworm, ascariasis and trichuriasis). All 32 positive sera with the Trop-Bio ELISA showed a positive ICT card reaction (specificity and sensitivity 100%). It is concluded that, in Saudi Arabia and other Gulf states, where a continuous flow of south- and southeastern workers coming from areas endemic for bancroftian filariasis, the ICT card test may be useful in monitoring the potential risk of introducing bacncroftian filariasis to the host countries.

Regulation of interleukin-4 production and cytokine-induced growth potential in peripheral T-cell non-Hodgkin's lymphomas.

The malignant cells in tumour tissues produce cytokines/growth factors that may influence tumour growth, tumour immunogenicity and host immune response. We demonstrate that lymph node cell (LNC) purified neoplastic T cells from CD4+ peripheral T-cell lymphoma (CD4+ PTCL) and CD8+ PTCL spontaneously, and after stimulation with anti-CD3, secreted high amounts of interleukin-4 (IL-4) as compared to LNC-purified CD4+ and CD8+ non-malignant T cells. Furthermore, IL-4 was observed to be the most potent cytokine that induced in vitro proliferation and growth of the malignant T cells. Moreover, malignant T-cell-derived IL-4 secretion was augmented by exogeneous recombinant human interferon-gamma (IFN-gamma) and was profoundly inhibited by IL-2. Because IL-4 was shown to be a locally active cytokine with a wide range of immunoregulatory properties, regulation of IL-4 production by IFN-gamma and IL-2 in malignant T cells may be one of the important parameters to be assessed in the design of anticancer-specific immunotherapy. In summary, we report that malignant T cells produce IL-4, a type 2 cytokine (Th2 cell response) that acts as a growth factor and which may play a critical role in PTCL disease mechanism.

Visceral and cutaneous leishmaniasis comparative ultrastructure of host-parasite interactions.

The comparative ultrastructure of host-parasite interactions is described for the first time in patients with visceral (VL) and cutaneous (CL) leishmaniasis. In patients with VL, the parasite invades the bone marrow (BM) macrophages (Mcs) and neutrophils, while in patients with CL, the parasite invades the dermal fibroblasts in addition to Mcs. The skin Mcs seem to have more lethal effects on the parasite than the BM Mcs; this is possibly due to the presence of numerous melanosomes with acid phosphatase activity in the Mcs digestive vacuole. In patients with high level of VL parasitaemia, the parasite may induce the BM reticulocytes to phagocytose both the parasite and mature erythrocytes, i.e. lost recognition. In patients with low level of VLparasitaemia, the parasite may induce the BM Mcs to be haemophagocytic, i.e. temporarily mimick malignant histiocytosis until the course of treatment. In early stages of CL infection, the cellular infiltrate consists of the monocyte-macrophage system, plasma cells, lymphocytes and fibroblasts; while in the late stages, two types of epithelioid cells (ECs) are added to the infiltrate and are involved in the formation of tuberculous granulomas. Type I ECs thought to produce a granuloma factor, while type II ECs possibly precedes healing by fibrosis. However, the severity of host-parasite interactions seems to depend mainly on species of the parasite, the degree of parasitaemia, the type of infected tissue(s), and the variation of host tissue reaction against the parasite from one patient to another.

Interleukin-8 and granulocyte-macrophage colony-stimulating factor secretion in hematologic malignancies.

Interleukin-8 (LL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are cytokines/hematopoietic growth factor and are important mediators of inflammation and immune resoponse producing pathophysiological changes in human disease. Levels of IL-8 and GM-CSF in circulation of various hematologic diseases are unknown. To demonstrate their importance in lymphoproliferative disorders, we have measured the circulating levels of these two cytokines from patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). IL-8 and GM-CSF levels were determined by highly specific enzyme-linked immunosorbent assays. IL-8 levels were elevated in most patients with B-cell malignancies, B-cell CLL (B-CLL) and B-cell NHL (B-NHL) as well as in patients with HD. However, GM-CSF levels were higher in most patients with NHL (T-NHL and B-NHL) and HD. IL-8 was undetectable in T-cell malignancies (T-CLL and T-NHL), whereas GMCSF was undetectable from CLL (T-CLL and B-CLL). Of interest, IL-8 levels were correlated with white blood cell counts (WBC) in B-cell malignancies (B-CLL and B-NHL) but not in HD. These results suggest that both IL-8 and GMCSF may play an important role in pathophysiological changes in B-NHL and HD. IL-8 may be related with recruitment and activation of neutrophils, whereas, GM-CSF in proliferation and differentiation of hematopoietic progenitor cells and immune response in these malignancies. The clinical status of B-CLL patients in regards to WBC counts appeared to be associated with the serum levels of IL-8.

Peripheral T-cell lymphomas. Immunoregulatory cytokine (interleukin-2, interleukin-4, and interferon-gamma) abnormalities and autologous mixed lymphocyte reaction.

BACKGROUND: Cytokines are the most important secretions of the immune system and have a wide range of immunoregulatory functions in various immune disorders and T-cell malignancy. The authors have determined that characteristic enhanced autologous mixed lymphocyte reaction (AMLR) of the lymph node-derived malignant T-cells from peripheral T-cell lymphomas is a function of the T-cell derived cytokines interleukin (IL)-2, IL-4, and interferon-gamma (IFN-tau). METHODS: Autologous mixed lymphocyte reaction assay was performed by the standard proliferative response (3H-thymidine incorporation), by culturing autologous lymph node-derived or blood-purified T-cells with autologous blood-purified mitomycin-c treated non-T-cells. The production of IL-2, IL-4, and IFN-tau in the AMLR cultures was determined by bioassay or enzyme immunoassays. RESULTS: Enhanced IL-2 and IFN-tau but deficient IL-4 production is the most characteristic and unique feature of the augmented AMLR in peripheral T-cell lymphomas. CONCLUSION: The immunoregulatory aberrations in lymph node-derived malignant T-cells that produce highly elevated IL-2 and IFN-tau but decreased IL-4 during augmented AMLR may play an important role in immune dysfunction in this neoplasm (peripheral T-cell lymphomas).

Circulating levels of cytokines and soluble cytokine receptors in various T-cell malignancies.

BACKGROUND: Cytokines, interleukin (IL)-4, IL-6, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), soluble CD23 (sCD23), and soluble IL-2 receptors (sIL-2R) are mediators of inflammation and immune response. Alterations in immune status of patients with various cancers may result in release of cytokines in circulation. The authors measured the circulating levels of IL-4, IL-6, IFN-gamma, TNF-alpha, sCD23, and sIL-2R from patients with T-cell chronic lymphocytic leukemia (T-CLL), T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphoma (PTCL) to determine their importance in these T-cell disorders. METHODS: IL-4, IL-6, IFN-gamma, TNF-alpha, sCD23, and sIL-2R levels were measured from the serum samples by enzyme-linked immunosorbent assay or bioassay methods. RESULTS: IL-4 levels were higher only in T-CLL, whereas, IFN-gamma and sIL-2R levels were higher in T-CLL and T-ALL. However, IL-6, TNF-alpha, and sCD23 levels were higher in PTCL. CONCLUSIONS: T-cell-derived IL-4 and IFN-gamma in T-CLL may act as an autocrine growth factor for proliferation of neoplastic T-cells. The sIL-2R levels in T-CLL, T-ALL, and PTCL are an indication of the degree of T-cell or immune activation due to concomitant immunologic processes in these disorders. However, IL-6, TNF-alpha, and sCD23 levels may contribute to inflammatory response and provide evidence of monocyte/macrophage, T-cell, or B-cell aberrations in PTCL.

Peripheral T-cell lymphomas - cytokine profile and characteristic interleukin-4 and tumor-necrosis-factor alpha-deficiency.

Because of the recent evidence of involvement of cytokines in the inflammatory processes, cellular proliferation and host defence mechanism, we have measured the in vitro production of interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-6 and tumor necrosis factor-alpha (TNFalpha) from the phenotypically and histologically characterized ten peripheral T cell lymphoma (PTCL) cases. The immunophenotypic study had identified three gammadelta PTCL cases (CD3-CD4+CD8+, one case and CD3+CD4-CD8, two cases). Mononuclear cells obtained from the lymph node cells of PTCL cases, irrespective of histologic type, were found to produce highly elevated levels of IFN-gamma and IL-6 both spontaneously and in response to concanavalin A stimulations. However, IL-4 and TNFalpha production was characteristically decreased from cells obtained from both blood and lymph nodes. IL-4 and TNFalpha have a number of pleiotropic activities in particular stimulation of various immune effector functions. Their deficient production is an important indication of severe immune dysfunction in this disease. However, the meaning of their deficient production is currently unclear. It may be a loss of physiologic regulation within the cytokine network. On the contrary, elevated IFN-gamma and IL-6 production may be important in etiology, inflammatory response or disease pathogenesis.

Visceral leishmaniasis: II. Histiocyte ultrastructure in bone marrow associated with low level of parasitaemia and mimicking malignant histiocytosis.

The ultrastructural features of histiocytes in the bone marrow (BM) were studied in a febrile, splenomegalic and pancytopenic Sudanese patient who was diagnosed by one of us as visceral leishmaniasis (VL) associated with low level of parasitaemia and mimicking malignant histiocytosis (MH). Serial thick (STS) and ultrathin (SUT) sections showed that the BM was hypercellular and markedly infiltrated by large histiocytes with prominent phagocytosis. A thorough examination of various ST and UT section revealed only a single, typical Leishman-Donovan body. At transmission electron microscopy (TEM) level, two principal types of histiocytic cells were identified: Type I, subdivided into two subtypes, were actively phagocytic histiocytes (PH) with large digestive vacuoles and primary lysosomes; type II were nonphagocytic histiocytes (nPH) with primary lysosomes only. The rate of PH to nPH ws 7:2 in plastic STS. The interaction between the PH and ingested cells is described. Both types of cell were morphologically similar to previously described malignant histiocytic cells. However, this study showed a better characterization of PH during VL.