Nanocellulose-Based Passivated-Carbon Quantum Dots (P-CQDs) for Antimicrobial Applications: A Practical Review.

Passivated-carbon quantum dots (P-CQDs) have been attracting great interest as an antimicrobial therapy tool due to their bright fluorescence, lack of toxicity, eco-friendly nature, simple synthetic schemes, and possession of photocatalytic functions comparable to those present in traditional nanometric semiconductors. Besides synthetic precursors, CQDs can be synthesized from a plethora of natural resources including microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC). Converting MCC into NCC is performed chemically via the top-down route, while synthesizing CODs from NCC can be performed via the bottom-up route. Due to the good surface charge status with the NCC precursor, we focused in this review on synthesizing CQDs from nanocelluloses (MCC and NCC) since they could become a potential source for fabricating carbon quantum dots that are affected by pyrolysis temperature. There are several P-CQDs synthesized with a wide spectrum of featured properties, namely functionalized carbon quantum dots (F-CQDs) and passivated carbon quantum dots (P-CQDs). There are two different important P-CQDs, namely 2,2'-ethylenedioxy-bis-ethylamine (EDA-CQDs) and 3-ethoxypropylamine (EPA-CQDs), that have achieved desirable results in the antiviral therapy field. Since NoV is the most common dangerous cause of nonbacterial, acute gastroenteritis outbreaks worldwide, this review deals with NoV in detail. The surficial charge status (SCS) of the P-CQDs plays an important role in their interactions with NoVs. The EDA-CQDs were found to be more effective than EPA-CQDs in inhibiting the NoV binding. This difference may be attributed to their SCS as well as the virus surface. EDA-CQDs with surficial terminal amino (-NH2) groups are positively charged at physiological pH (-NH3+), whereas EPA-CQDs with surficial terminal methyl groups (-CH3) are not charged. Since the NoV particles are negatively charged, they are attracted to the positively charged EDA-CQDs, resulting in enhancing the P-CQDs concentration around the virus particles. The carbon nanotubes (CNTs) were found to be comparable to the P-CQDs in the non-specific binding with NoV capsid proteins, through complementary charges, π-π stacking, and/or hydrophobic interactions.

A Novel Microwave Hot Pressing Machine for Production of Fixed Oils from Different Biopolymeric Structured Tissues.

A microwave hot pressing machine (MHPM) was used to heat the colander to produce fixed oils from each of castor, sunflower, rapeseed, and moringa seed and compared them to those obtained using an ordinary electric hot pressing machine (EHPM). The physical properties, namely the moisture content of seed (MCs), the seed content of fixed oil (Scfo), the yield of the main fixed oil (Ymfo), the yield of recovered fixed oil (Yrfo), extraction loss (EL), six Efficiency of fixed oil extraction (Efoe), specific gravity (SGfo), refractive index (RI) as well as chemical properties, namely iodine number (IN), saponification value (SV), acid value (AV), and the yield of fatty acid (Yfa) of the four oils extracted by the MHPM and EHPM were determined. Chemical constituents of the resultant oil were identified using GC/MS after saponification and methylation processes. The Ymfo and SV obtained using the MHPM were higher than those for the EHPM for all four fixed oils studied. On the other hand, each of the SGfo, RI, IN, AV, and pH of the fixed oils did not alter statistically due to changing the heating tool from electric band heaters into a microwave beam. The qualities of the four fixed oils extracted by the MHPM were very encouraging as a pivot of the industrial fixed oil projects compared to the EHPM. The prominent fatty acid of the castor fixed oil was found to be ricinoleic acid, making up 76.41% and 71.99% contents of oils extracted using the MHPM and EHPM, respectively. In addition, the oleic acid was the prominent fatty acid in each of the fixed oils of sunflower, rapeseed, and moringa species, and its yield by using the MHPM was higher than that for the EHPM. The role of microwave irradiation in facilitating fixed oil extrusion from the biopolymeric structured organelles (lipid bodies) was protruded. Since it was confirmed by the present study that using microwave irradiation is simple, facile, more eco-friendly, cost-effective, retains parent quality of oils, and allows for the warming of bigger machines and spaces, we think it will make an industrial revolution in oil extraction field.

A novel genotype c.1228C>G/c.1448C-1498C (L371V/Rec-NciI) in a 3-year-old child with type 1 Gaucher disease.

Gaucher disease (GD) is an autosomal recessive inborn error of metabolism, resulting from a deficiency of the enzyme glucocerebrosidase, causing an accumulation of the glycolipid glucocerebroside within lysosomes of macrophages in the reticuloendothelial system. Three major clinical forms have been assigned and more than 200 gene mutations have been identified. We herein report a Lebanese boy born with a novel combined mutation L371V/Rec-NciI, who presented with moderate-severe type 1 GD. An overview of the clinical and biomarker improvement following enzyme replacement therapy with imiglucerase is described in a follow-up of 30 months. Imiglucerase seems to be efficacious in decreasing the severity of the disease associated with this mutation. However, a high dose may be required to achieve optimal growth, platelet count, and hemoglobin level.

Alterations of erythrocyte free radical defense system, heart tissue lipid peroxidation, and lipid concentration in streptozotocin-induced diabetic rats under coenzyme Q10 supplementation.

OBJECTIVE: Free radicals play an important role in genesis and development of various chronic diseases and aging. Our objective is to study the effects of coenzyme Q10 (CoQ10) supplementation on erythrocyte antioxidants, heart tissue lipid peroxidation end products and lipid concentration in different age of diabetic rats. METHODS: In this study, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the content of reduced glutathione (GSH) were determined in erythrocytes. The products of lipid peroxidation were determined in the heart tissues of streptozotocin-induced diabetic rats and in healthy rats at 4, 8, and 13-months of age. The above mentioned antioxidant systems of erythrocytes were also determined after supplementation of diabetic and healthy rats with CoQ10. This study was carried out in King Fahad Medical Research Center, Jeddah, Kingdom of Saudi Arabia between 2000 and 2001. RESULTS: In erythrocytes of diabetic rats the activity of GSH-Px was significantly decreased (p<0.001) in all different age groups, whereas the activity of SOD was significantly increased (p<0.001). However, in erythrocyte of streptozotocin-induced diabetic rats, the concentration of GSH and high-density lipoprotein (HDL)-cholesterol were significantly lower than non-diabetic rats. Moreover, the concentration of heart tissue lipid peroxidation end products, and plasma glucose, cholesterol and triacylglycerol were significantly increased (p<0.001) in all age groups of diabetic rats. Daily supplementation with CoQ10 (10 mg/kg body weight, one month) after induction of diabetes to the rats resulted in the following changes: an increase in both erythrocyte GSH concentration and GSH-Px activity, and slightly increases in plasma HDL-cholesterol. However, SOD activity was significantly decreased (p<0.05). In addition, the levels of lipid peroxidation end products, and triacylglycerol were significantly decreased (p<0.05) in diabetic rats supplemented with CoQ10. CONCLUSION: The results of the present study indicated that CoQ10 supplementation helps to prevent clinical complications during the course of the disease in diabetic rats.

Evaluation of efficiency of insulin suppository formulations containing sodium salicylate or sodium cholate in insulin dependent diabetic patients.

Two formulations of insulin suppositories were prepared to contain different amounts of sodium salicylate and sodium cholate as absorption promoters and also of insulin with the purpose of obtaining the most effective formulation in reducing plasma glucose levels after rectal administration to diabetic patients. The results show that insulin suppositories containing 100 mg sodium salicylate and 100 or 200 U of crystalline insulin showed no significant difference in AUC, Cmax and Tmax and both formulations showed significant reduction in plasma glucose level compared to initial values within 1.5-2 h. The results from experiments carried out in health volunteers showed that 100 mg sodium salicylate is the optimum amount to be included in insulin suppositories producing significantly higher Cmax and AUC compared to those produced after rectal administration of insulin suppositories containing 50 or 200 mg sodium salicylate. The results also show that using sodium cholate in 50 mg amount did not produce any significant reduction in plasma glucose levels of insulin dependent diabetic patients given suppositories containing 100 U of insulin, but this amount in suppositories containing 200 U of insulin was able to produce significant (p < 0.05) reduction in plasma glucose level within 1 h which lasted till end of experiment producing Cmax of 29.7 +/- 6.61% at Tmax of 1.5 +/- 0.61 h. On increasing the amount of sodium cholate to 100 mg in the suppositories, a marked (p < 0.01) reduction in plasma glucose level took place and the Cmax increased to 47.7 +/- 12.24% at Tmax of 1.5 +/- 0.63 h. This resulted in AUC of 86.7 +/- 22.4 mg%h which was non significantly higher from that produced after administration of suppositories containing 50 mg sodium cholate and 200 U insulin (62.5 +/- 17.6 mg%h). The results also show that insulin suppositories containing 100 mg sodium cholate and 200 U insulin resulted in a non significant differences in Cmax and AUC from those produced by S.C. injection of insulin (20 U) but significantly (p < 0.001) shorter Tmax. This formulation also shows non significant differences in Tmax and AUC and significantly (p < 0.05) higher Cmax than from those produced after rectal administration of suppositories containing 100 mg of sodium salicylate and same amount of insulin. Further more this formulation produced severe hypoglycemia in control healthy volunteers within 1 h of administration producing Cmax of 57.0 +/- 18.8% at Tmax of 0.75 +/- 0.35 h. The results of this study showed that the formulation containing 100 mg of sodium cholate and 200 U of insulin tested in fasted insulin dependent diabetic patients produced a maximum % reduction in plasma glucose levels (Cmax) of 47.7 +/- 12.24% at tmax of 1.5 +/- 0.63 h compared to Cmax of 50.56 +/- 6.8% at tmax of 2.93 +/- 0.19 h resulted after subcutaneous injection of 20 U insulin. These suppositories produced an area under the curve (AUC) of 87 +/- 22.4 mg%h compared to an AUC of 81 +/- 13.4 mg%h obtained after subcutaneous injection. This formulation of suppositories studied in 7 insulin dependent diabetic patients was found to abolish the 2-h post-prandial significant rise in plasma glucose levels after meal. These results show that these insulin suppositories containing 100 mg of sodium cholate and 200 U of insulin can serve as effective buffer against meal related hyperglycemia. The suppositories were safe, effective, accepted and well tolerated by the tested individuals.

Induction of apoptosis in rat hepatocarcinoma cells by expression of IGF-I antisense c-DNA.

BACKGROUND/AIMS: We have developed a gene therapy strategy based on the observation that insulin-like growth factor I (IGF-I) is necessary for the acquisition and maintenance of the transformed phenotype in hepatocarcinoma. This strategy consists in transfecting the rat hepatoma cell line with an episomal vector expressing the antisense IGF-I c-DNA under the control of the metallothionein I promoter inducible by zinc, decreasing therefore the level of IGF-I in these cells. The transfected clones lost their tumorigenic properties, and were able to induce, in vivo, the regression of an established tumor in syngeneic rats. To understand the loss of tumorigenic properties of these transfected clones, we have quantified, by different approaches, the number of apoptotic cells according to the level of IGF-I expression. METHODS: IGF-I antisense synthesis in transfected cells was stimulated using zinc. We then characterized and quantified apoptosis, in these transfected clones, by morphological and DNA fragmentation analyses, flow cytometry and comet assay. RESULTS: We have demonstrated that IGF-I inhibits the development of apoptosis in parental cells, that the transfected clones are able to restore the spontaneous apoptotic programme, and that apoptosis increases massively when overexpression of IGF-I antisense is caused by zinc stimulation of the metallothionein I promoter. CONCLUSION: The present results allow us to conclude that the level of apoptotic pathway in liver cell lines is directly related to the amount of IGF-I deficiency.

In vitro inhibition of normal human hematopoiesis by marrow CD3+, CD8+, HLA-DR+, HNK1+ lymphocytes.

We previously demonstrated that after allogeneic bone marrow transplantation (BMT) a subset of CD8, HNK1, and DR-positive T lymphocytes are able to inhibit CFU-GM and BFU-E growth with an HLA-DR restriction. In this study we investigated whether these cells, present in normal marrow in low concentration (less than 1%), play the same role. HNK1-positive sorted marrow cells forming rosettes (E+C) were able to inhibit BFU-E and CFU-GM growth when added back to the marrow E-C at a ratio of 1:10 (HNK1+ E+C/E-C) in a range from 40% to 60%. This inhibitory effect was also detected for a cellular ratio of 1:100, which is the normal marrow value for this subset of T cell. HNK1+ DR+-sorted E+C after double-immunofluorescent labeling also showed the same inhibitory activity as the HNK1+ E+C, whereas the negative fraction including all the other E+C had no detectable inhibitory activity. CD3 and CD8 antigens were also present on the membrane of these cells, as demonstrated in two cases by double-immunofluorescent labeling performed with anti-CD3 or anti-CD8 monoclonal antibodies (MoAbs) and HNK1 MoAb, respectively, and subsequent cell sorting. Blocking experiments, performed by adding in culture anti-CD4 and anti-CD8 MoAbs to HNK1+ T cells showed that only the last MoAb was able to prevent inhibition of hematopoietic colony growth. These results confirmed that one subset of CD3+, CD8+, HNK1+, and DR+ T cells was responsible for in vitro inhibition of normal hematopoiesis. In addition, this inhibition was genetically restricted to HLA-class II antigens, since in three co-culture experiments with unrelated bone marrow cells inhibition occurred only when cells with one haplo-identical HLA-DR antigen was added back to the culture. Indeed, this effect was really HLA-DR restricted, since in blocking experiments with different anti-HLA class II MoAbs (anti-DR, anti-DP, and anti-DQ MoAbs) only an anti-HLA-DR MoAb was able to prevent the colony growth inhibition by CD3+ HNK1+, or CD8+ HNK1+ E+C. In conclusion, the CD3+, HNK1+, CD8+, DR+ cells may be the T-cell subset able to inhibit normal hematopoiesis with an HLA-DR restriction.

Functional analysis of CD8 lymphocytes in long-term surviving patients after bone marrow transplantation.

The recovery of T-cell populations after bone marrow transplantation (BMT) is characterized by a persistent expansion of CD8 lymphocytes. Previously, we have shown that beyond 1 year posttransplantation the CD8 lymphocytes consist, to a large extent, of CD8+ HNK1+ cells that suppress, like normal CD8 lymphocytes, immunoglobulin production in vitro. We have further investigated the functional capabilities of CD8 lymphocytes, mostly HNK1+ (from 50 to 77%), in seven long-term BMT patients. As normal, patient CD8 lymphocytes do not suppress (1) phytohemagglutinin (PHA)-induced interleukin 2 (IL2) receptor expression and IL2 responsiveness by normal T cells or (2) the mixed lymphocyte reaction of donor cells. Also as normal, patient CD8 lymphocytes can be activated into potent cytotoxic effectors. Therefore, under the present experimental conditions, the increase in the absolute number of CD8 lymphocytes in the long-term BMT patients is characterized by an expansion of the CD8+ HNK1+-cell subpopulation and a normal suppressor/cytotoxic potential on a per-CD8+ cell basis.